Quebec, Canada
Quebec, Canada

Laval University is the oldest centre of education in Canada , and was the first institution in North America to offer higher education in French. Its main campus is located on the outskirts of the historic city in Quebec City, the capital of the Province of Quebec. The university is ranked among the top ten Canadian universities in terms of research funding. Wikipedia.


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A method for preparing polymers by direct heteroarylation or arylation polycondensation is described herein. The method includes preparing a reaction mixture including at least a monomer to be polymerized, a catalyst and a ligand; heating the reaction mixture; and, optionally, end-capping the reaction mixture.


Patent
Gm Global Technology Operations Llc and Laval University | Date: 2016-07-26

An extended-reach assist device for an assembly task includes a base mechanism and a compliant end-effector. The articulated base mechanism provides one or more passive degrees of freedom. The end-effector is connected to the base mechanism, and has one or more active or passive degrees of freedom collectively configured to react to contact forces with the assist device when completing the dexterous assembly task. A weight of the end-effector is supported by the base mechanism. The end-effector may be optionally configured as a passive device configured to produce a remote center of compliance or as a robot mechanism. A mechanism may actively or passively augment a force applied by the operator. A sensor may detect a signature indicative of successful task completion, e.g., an acoustic, visual, or audio sensor.


Soulet D.,Laval University | Cicchetti F.,Laval University
Molecular Psychiatry | Year: 2011

Huntington's disease (HD) is a devastating and incurable neurodegenerative disorder characterized by progressive cognitive, psychiatric and motor impairments. Although the disease has been seen as a disorder purely of the brain, there is now emerging evidence that abnormalities outside the central nervous system are commonly seen in HD. Indeed, the mutant huntingtin (mHtt) coded for by the abnormal gene in HD is found in every cell type where its presence has been sought. In particular, there are a number of recent observations in HD patients that mHtt interacts with the immune system with accumulating evidence that changes in the immune system may critically contribute to the pathology of HD. However, the nature of this contribution remains unclear, to the extent that it is not even known whether the immune system has a beneficial or detrimental role in HD patients. In this review, we attempt to bring a novel understanding to the interaction of the immune system to HD pathology, thereby shedding light on its potential pathogenic role. As part of this discussion, we revisit the clinical data on the anti-inflammatory drug trials in HD and propose new experimental approaches to interrogate the role of immunity in this currently incurable disorder. © 2011 Macmillan Publishers Limited All rights reserved.


Poirier G.G.,Laval University | Kaufmann S.H.,Mayo Medical School
Clinical Cancer Research | Year: 2012

Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors are undergoing extensive clinical testing for their single-agent activity in homologous recombination (HR)-deficient tumors and ability to enhance the action of certain DNA-damaging agents. Compared with other PARP inhibitors in development, iniparib (4-iodo-3-nitrobenzamide) is notable for its simple structure and the reported ability of its intracellular metabolite 4-iodo-3-nitrosobenzamide to covalently inhibit PARP1 under cell-free conditions. The present preclinical studies were conducted to compare the actions iniparib with the more extensively characterized PARP inhibitors olaparib and veliparib. Experimental Design: The abilities of iniparib, olaparib, and veliparib to (i) selectively induce apoptosis or inhibit colony formation in HR-deficient cell lines, (ii) selectively sensitize HR-proficient cells to topoisomerase I poisons, and (iii) inhibit formation of poly(ADP-ribose) polymer (pADPr) in intact cells were compared. Results: Consistent with earlier reports, olaparib and veliparib selectively induced apoptosis and inhibited colony formation in cells lacking BRCA2 or ATM. Moreover, like earlier generation PARP inhibitors, olaparib and veliparib sensitized cells to the topoisomerase I poisons camptothecin and topotecan. Finally, olaparib and veliparib inhibited formation of pADPr in intact cells. In contrast, iniparib exhibited little or no ability to selectively killHR-deficient cells, sensitize cells to topoisomerase I poisons, or inhibit pADPr formation in situ. In further experiments, iniparib also failed to sensitize cells to cisplatin, gemcitabine, or paclitaxel. Conclusions: While iniparib kills normal and neoplastic cells at high (>40 mmol/L) concentrations, its effects are unlikely to reflect PARP inhibition and should not be used to guide decisions about other PARP inhibitors. ©2012 AACR.


Yousef E.M.,University Of Montre Al | St-Pierre Y.,Laval University | Gaboury L.A.,University Of Montre Al
BMC Cancer | Year: 2014

Background: In 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients. Methods: MMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays. Results: Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse. Conclusions: Differential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes. © 2014 Yousef et al.; licensee BioMed Central Ltd.


Kang J.,Peking University | Rivest S.,Laval University
Endocrine Reviews | Year: 2012

Liver X receptors (LXR) are nuclear receptors that have emerged as key regulators of lipid metabolism. In addition to their functions as cholesterol sensors, LXR have also been found to regulate inflammatory responses in macrophages. Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive cognitive decline associated with inflammation. Evidence indicates that the initiation and progression of AD is linked to aberrant cholesterol metabolism and inflammation. Activation of LXR can regulate neuroinflammation and decrease amyloid-β peptide accumulation. Here, we highlight the role of LXR in orchestrating lipid homeostasis and neuroinflammation in the brain. In addition, diabetes mellitus is also briefly discussed as a significant risk factor for AD because of the appearing beneficial effects of LXR on glucose homeostasis. The ability of LXR to attenuate AD pathology makes them potential therapeutic targets for this neurodegenerative disease. © 2012 by The Endocrine Society.


Cicchetti F.,Laval University
Cell Death and Disease | Year: 2012

Huntington's disease (HD) is a devastating neurodegenerative disorder whose main hallmark is brain atrophy. However, several peripheral organs are considerably affected and their symptoms may, in fact, manifest before those resulting from brain pathology. HD is of genetic origin and caused by a mutation in the huntingtin gene. The mutated protein has detrimental effects on cell survival, but whether the mutation leads to a gain of toxic function or a loss of function of the altered protein is still highly controversial. Most currently used in vitro models have been designed, to a large extent, to investigate the effects of the aggregation process in neuronal-like cells. However, as the pathology involves several other organs, new in vitro models are critically needed to take into account the deleterious effects of mutant huntingtin in peripheral tissues, and thus to identify new targets that could lead to more effective clinical interventions in the early course of the disease. This review aims to present current in vitro models of HD pathology and to discuss the knowledge that has been gained from these studies as well as the new in vitro tools that have been developed, which should reflect the more global view that we now have of the disease. © 2012 Macmillan Publishers Limited.


Popat A.,University of Queensland | Ross B.P.,University of Queensland | Liu J.,University of Queensland | Jambhrunkar S.,University of Queensland | And 3 more authors.
Angewandte Chemie - International Edition | Year: 2012

I want to break free: Mesoporous silica nanoparticles are functionalized with sulfasalazine (SZ; see scheme), a prodrug of 5-aminosalicylic acid (5-ASA) and sulfapyridine, to generate enzyme-responsive nanocarriers. In the presence of the colon-specific enzyme azo-reductase (orange), 5-ASA and sulfapyridine are efficiently released. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Hebert-Dufresne L.,Laval University | Patterson-Lomba O.,Arizona State University | Goerg G.M.,Carnegie Mellon University
Physical Review Letters | Year: 2013

While disease propagation is a main focus of network science, its coevolution with treatment has yet to be studied in this framework. We present a mean-field and stochastic analysis of an epidemic model with antiviral administration and resistance development. We show how this model maps to a coevolutive competition between site and bond percolation featuring hysteresis and both second- and first-order phase transitions. The latter, whose existence on networks is a long-standing question, imply that a microscopic change in infection rate can lead to macroscopic jumps in expected epidemic size. © 2013 American Physical Society.


Jit M.,London School of Hygiene and Tropical Medicine | Jit M.,Public Health England | Brisson M.,Imperial College London | Brisson M.,Laval University | Hutubessy R.,Initiative for Vaccine Research
The Lancet Global Health | Year: 2014

Background: Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specific effects on health and economic costs. We aimed to develop and validate a simple generic model of such effects that could be used and understood in a range of settings with little external support. Methods: We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-effectiveness and health effects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine efficacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-effectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed differences between countries in terms of cost-effectiveness and health effects. Findings: In validation, PRIME reproduced cost-effectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690 000 cases of cervical cancer and 420 000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost effective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200 000 cases of cervical cancer and 100 000 deaths in some of the highest-burden countries. Interpretation: Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions. Funding: WHO. © 2014 World Health Organization.


Crone E.E.,University of Montana | McIntire E.J.B.,Laval University | Brodie J.,University of Montana
Journal of Ecology | Year: 2011

Synchronous, episodic mast seeding is common in plant populations, and is thought to increase plant fitness through economies of scale, such as satiating seed predators, attracting seed dispersers and enhancing pollination success. Although mast seeding is easy to conceptualize, it has been quantified using a number of different metrics that reflect different features of pulsed reproduction. We quantified spatio-temporal patterns of mast seeding across 36 populations of a high-elevation tree, Pinus albicaulis, for which perceived declines in cone production are a conservation concern. We tested for trends in mean cone production through space and time, and documented patterns of mast seeding using six different metrics: coefficient of variation, lag-1 autocorrelation, synchrony, average cone production by individual trees, and the frequency of high cone crops on absolute and relative scales. Overall, we did not detect increasing or decreasing trends in cone production during our study period. Average cone production tended to increase from north-east to south-west. Population-level cone production tended to alternate between high and low years, but overall the coefficient of variation was low for a mast seeding species. Metrics of mast seeding were not concordant across populations. The first principal component describing mast metrics separated populations with frequent high cone crops from those with high coefficients of variation. However, the second principle component was at least somewhat correlated with all metrics of masting, suggesting some ability to separate 'masting' from 'non-masting' populations. In P. albicaulis, spatial variation in mast seeding could reflect differences in site productivity, differences in the importance of satiating generalist seed consumers versus attracting specialist seed dispersers, or recent invasion by an introduced pathogen. Synthesis. Our research reinforces the conclusion that populations form a continuum of strategies between 'masting' versus 'non-masting' extremes. However, because different features of masting do not covary in space, understanding where populations fall along this continuum will depend on the features that are most important for mast seeding in a particular context. © 2011 The Authors. Journal of Ecology © 2011 British Ecological Society.


Zikmund-Fisher B.J.,University of Michigan | Exe N.L.,University of Michigan | Witteman H.O.,Laval University
Journal of Medical Internet Research | Year: 2014

Background: Increasing numbers of patients have direct access to laboratory test results outside of clinical consultations. This offers increased opportunities for both self-management of chronic conditions and advance preparation for clinic visits if patients are able to identify test results that are outside the reference ranges. Objective: Our objective was to assess whether adults can identify laboratory blood test values outside reference ranges when presented in a format similar to some current patient portals implemented within electronic health record (EHR) systems. Methods: In an Internet-administered survey, adults aged 40-70 years, approximately half with diabetes, were asked to imagine that they had type 2 diabetes. They were shown laboratory test results displayed in a standard tabular format. We randomized hemoglobin A1cvalues to be slightly (7.1%) or moderately (8.4%) outside the reference range and randomized other test results to be within or outside their reference ranges (ie, multiple deviations). We assessed (1) whether respondents identified the hemoglobin A1clevel as outside the reference range, (2) how respondents rated glycemic control, and (3) whether they would call their doctor. We also measured numeracy and health literacy. Results: Among the 1817 adult participants, viewing test results with multiple deviations increased the probability of identifying hemoglobin A1cvalues as outside the reference range (participants with diabetes: OR 1.47, 95% CI 1.12-1.92, P=.005; participants without diabetes: OR 1.50, 95% CI 1.13-2.00, P=.005). Both numeracy and health literacy were significant predictors of correctly identifying out-of-range values. For participants with diabetes, numeracy OR 1.32 per unit on a 1-6 scale (95% CI 1.15-1.51, P<.001) and literacy OR 1.59 per unit of a 1-5 scale (95% CI 1.35-1.87, P<.001); for participants without diabetes, numeracy OR 1.36 per unit (95% CI 1.17-1.58, P<.001) and literacy OR 1.33 per unit (95% CI 1.12-1.58, P=.001). Predicted probabilities suggested 77% of higher numeracy and health literacy participants, but only 38% of lower numeracy and literacy participants, could correctly identify the hemoglobin A1clevels as outside the reference range. Correct identification reduced perceived blood glucose control (mean difference 1.68-1.71 points on a 0-10 scale, P<.001). For participants with diabetes, increased health literacy reduced the likelihood of calling one's doctor when hemoglobin A1c=7.1% (OR 0.66 per unit, 95% CI 0.52-0.82, P<.001) and increased numeracy increased intention to call when hemoglobin A1c=8.4% (OR 1.36 per unit, 95% CI 1.10-1.69, P=.005). Conclusions: Limited health literacy and numeracy skills are significant barriers to basic use of laboratory test result data as currently presented in some EHR portals. Regarding contacting their doctor, less numerate and literate participants with diabetes appear insensitive to the hemoglobin A1clevel shown, whereas highly numerate and literate participants with diabetes appear very sensitive. Alternate approaches appear necessary to make test results more meaningful. ©Brian J Zikmund-Fisher, Nicole L Exe, Holly O Witteman.


Beauchemin P.,Laval University | Carruthers R.,UBC MS Clinic
Multiple Sclerosis | Year: 2016

Background: Interleukin-6 (IL6) blockage is a treatment strategy used in many inflammatory conditions. Trials in Neuromyelitis Optica Spectrum Disorder (NMOSD) are ongoing. Secondary auto-immunity affecting the central nervous system (CNS) is well described with some biologic agents, mainly tumor necrosis factor (TNF)-alpha inhibitors. These treatments can also aggravate patients with known multiple sclerosis (MS). Objectives: To describe a case of a patient who developed MS using another biologic, IL6 receptor antibody Tocilizumab. Results: A 48-year-old woman developed MS while on treatment with Tocilizumab for Rheumatoid Arthritis (RA). This is the first published report of this association. It has obvious implications for NMOSD patients receiving anti-IL6 therapy. Development of new white matter lesions suggestive of MS in a patient treated with anti-IL6 therapy might represent an important complication of therapy. Conclusion: This case illustrates that Tocilizumab might cause secondary auto-immunity in CNS. It is important to be aware of this potential complication as anti-IL6 therapy might become an option for the treatment NMOSD. © SAGE Publications.


Marucco F.,Centro Gestione Conservazione Grandi Carnivori | Marucco F.,University of Montana | McIntire E.J.B.,Laval University
Journal of Applied Ecology | Year: 2010

Wolves Canis lupus recently recolonized the Western Alps through dispersal from the Italian Apennines, representing one of several worldwide examples of large carnivores increasing in highly human-dominated landscapes. Understanding and predicting expansion of this population is important for conservation because of its direct impact on livestock and its high level of societal opposition. We built a predictive, spatially explicit, individual-based model to examine wolf population expansion in this fragmented landscape, and livestock depredation risk. We developed the model based on known demographic processes, social structure, behaviour and habitat selection of wolves collected during a 10-year intensive field study of this wolf population. During model validation, our model accurately described the recolonization process within the Italian Alps, correctly predicting wolf pack locations, pack numbers and wolf population size, between 1999 and 2008. We then projected packs and dispersers over the entire Italian Alps for 2013, 2018 and 2023. We predicted 25 packs (95% CI: 19-32) in 2013, 36 (23-47) in 2018 and 49 (29-68) in 2023. The South-Western Alps were the main source for wolves repopulating the Alps from 1999 to 2008. The source area for further successful dispersers will probably shift to the North-Western Alps after 2008, but the large lakes in the Central Alps will probably act as a spatial barrier slowing the wolf expansion. Using the pack presence forecasts, we estimated spatially explicit wolf depredation risk on livestock, allowing tailored local and regional management actions. Synthesis and applications. Our predictive model is novel because we follow the spatio-temporal dynamics of packs, not just population size, which have substantially different requirements and impacts on wolf-human conflicts than wandering dispersers. Our approach enables prioritization of management efforts, including minimizing livestock depredations, identifying important corridors and barriers, and locating future source populations for successful wolf recolonization of the Alps. © 2010 The Authors. Journal compilation © 2010 British Ecological Society.


Gagnon M.-P.,Laval University
PharmacoEconomics | Year: 2014

Health technology assessment (HTA) uses a multidisciplinary approach to answer relevant questions regarding the safety, efficacy, effectiveness and cost-effectiveness of health technologies. There is growing interest in implementing HTA methods at the hospital level because it could facilitate decision-making regarding acquisition, implementation or discontinuation of technologies or interventions within the hospital. First, this article provides an overview of current international experiences and knowledge of hospital-based HTA. Then, it presents the different types of hospital-based HTA, providing examples of each of these models, as well as their strengths and limitations. Finally, it proposes a set of emerging issues that could help inform decision-makers who consider implementing hospital-based HTA, or other stakeholders interested in the field. © 2014, Springer International Publishing Switzerland.


Rangachari M.,Laval University | Kuchroo V.K.,Harvard University
Journal of Autoimmunity | Year: 2013

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in which myelin becomes the target of attack by autoreactive T cells. The immune components of the disease are recapitulated in mice using the experimental autoimmune encephalomyelitis (EAE) model. EAE is classically induced by the immunization of mice with encephalitogenic antigens derived from CNS proteins such as proteolipid protein (PLP), myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG). Immunization of susceptible mouse strains with these antigens will induce autoreactive inflammatory T cell infiltration of the CNS. More recently, the advent of clonal T cell receptor transgenic mice has led to the development of adoptive transfer protocols in which myelin-specific T cells may induce disease upon transfer into naïve recipient animals. When used in concert with gene knockout strains, these protocols are powerful tools by which to dissect the molecular pathways that promote inflammatory T cells responses in the central nervous system (CNS). Further, myelin-antigen-specific transgenic T cells may be cultured invitro under a variety of conditions prior to adoptive transfer, allowing one to study the effects of soluble factors or pharmacologic compounds on T cell pathogenicity. In this review, we describe many of the existing models of EAE, and discuss the contributions that use of these models has made in understanding both T helper cell differentiation and the function of inhibitory T cell receptors. We focus on the step-by-step elucidation of the network of signals required for T helper 17 (Th17) cell differentiation, as well as the molecular dissection of the Tim-3 negative regulatory signaling pathway in Th1 cells. © 2013 Elsevier Ltd.


Neumann M.B.,Eawag - Swiss Federal Institute of Aquatic Science and Technology | Neumann M.B.,Laval University
Science of the Total Environment | Year: 2012

Five sensitivity analysis methods based on derivatives, screening, regression, variance decomposition and entropy are introduced, applied and compared for a model predicting micropollutant degradation in drinking water treatment. The sensitivity analysis objectives considered are factors prioritisation (detecting important factors), factors fixing (detecting non-influential factors) and factors mapping (detecting which factors are responsible for causing pollutant limit exceedances). It is shown how the applicability of methods changes in view of increasing interactions between model factors and increasing non-linearity between the model output and the model factors. A high correlation is observed between the indices obtained for the objectives factors prioritisation and factors mapping due to the positive skewness of the probability distributions of the predicted residual pollutant concentrations. The entropy-based method which uses the Kullback-Leibler divergence is found to be particularly suited when assessing pollutant limit exceedances. © 2012 Elsevier B.V.


Cepeda C.,University of California at Los Angeles | Murphy K.P.S.,Open University Milton Keynes | Parent M.,Laval University | Levine M.S.,University of California at Los Angeles
Progress in Brain Research | Year: 2014

Alterations in dopamine (DA) neurotransmission in Parkinson's disease are well known and widely studied. Much less is known about DA changes that accompany and underlie some of the symptoms of Huntington's disease (HD), a dominant inherited neurodegenerative disorder characterized by chorea, cognitive deficits, and psychiatric disturbances. The cause is an expansion in CAG (glutamine) repeats in the HTT gene. The principal histopathology of HD is the loss of medium-sized spiny neurons (MSNs) and, to a lesser degree, neuronal loss in cerebral cortex, thalamus, hippocampus, and hypothalamus. Neurochemical, electrophysiological, and behavioral studies in HD patients and genetic mouse models suggest biphasic changes in DA neurotransmission. In the early stages, DA neurotransmission is increased leading to hyperkinetic movements that can be alleviated by depleting DA stores. In contrast, in the late stages, DA deficits produce hypokinesia that can be treated by increasing DA function. Alterations in DA neurotransmission affect glutamate receptor modulation and could contribute to excitotoxicity. The mechanisms of DA dysfunction, in particular the increased DA tone in the early stages of the disease, are presently unknown but may include initial upregulation of DA neuron activity caused by the genetic mutation, reduced inhibition resulting from striatal MSN loss, increased excitation from cortical inputs, and DA autoreceptor dysfunction. Targeting both DA and glutamate receptor dysfunction could be the best strategy to treat HD symptoms. © 2014 Elsevier B.V.


Mcintire E.J.B.,Natural Resources Canada | Mcintire E.J.B.,Laval University | Fajardo A.,Austral University of Chile
New Phytologist | Year: 2014

Models describing the biotic drivers that create and maintain biological diversity within trophic levels have focused primarily on negative interactions (i.e. competition), leaving marginal room for positive interactions (i.e. facilitation). We show facilitation to be a ubiquitous driver of biodiversity by first noting that all species use resources and thus change the local biotic or abiotic conditions, altering the available multidimensional niches. This can cause a shift in local species composition, which can cause an increase in beta, and sometimes alpha, diversity. We show that these increases are ubiquitous across ecosystems. These positive effects on diversity occur via a broad host of disparate direct and indirect mechanisms. We identify and unify several of these facilitative mechanisms and discuss why it has been easy to underappreciate the importance of facilitation. We show that net positive effects have a long history of being considered ecologically or evolutionarily unstable, and we present recent evidence of its potential stability. Facilitation goes well beyond the common case of stress amelioration and it probably gains importance as community complexity increases. While biodiversity is, in part, created by species exploiting many niches, many niches are available to exploit only because species create them. New Phytologist © 2013 New Phytologist Trust.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: KBBE.2011.1.1-01 | Award Amount: 7.75M | Year: 2012

In the midst of a climatic change scenario, the genetics of adaptive response in conifers becomes essential to ensure a sustainable management of genetic resources and an effective breeding. Conifers are the target of major tree breeding efforts worldwide. Advances in molecular technologies, such as next-generation DNA sequencing technologies, could have an enormous impact on the rate of progress and achievements made by tree breeding programmes. These new technologies might be used not only to improve our understanding of fundamental conifer biology, but also to address practical problems for the forest industry as well as problems related to the adaptation and management of conifer forests. In this context, ProCoGen will address genome sequencing of two keystone European conifer species. Genome re-sequencing approaches will be used to obtain two reference pine genomes. Comparative genomics and genetic diversity will be closely integrated and linked to targeted functional genomics investigations to identify genes and gene networks that efficiently help to develop or enhance applications related to forest productivity, forest stewardship in response to environmental change or conservation efforts. The development of high-throughput genotyping tools will produce an array of pre-breeding tools to be implemented in forest tree breeding programmes. ProCoGen will also develop comparative studies based on orthologous sequences, genes and markers, which will allow guiding re-sequencing initiatives and exploiting the research accumulated on each of the species under consideration to accelerate the use of genomic tools in diverse species. ProCoGen will integrate fragmented activities developed by European research groups involved in several ongoing international conifer genome initiatives and contribute to strengthening international collaboration with North American initiatives (US and Canada).


Grant
Agency: Cordis | Branch: FP7 | Program: CSA | Phase: ICT-2011.5.6 | Award Amount: 752.51K | Year: 2011

eGovPoliNet sets up an international community in ICT solutions for governance and policy modelling. The international community of researchers and practitioners will share and advance research and insights from practical cases around the world. To achieve this, eGovPoliNet will build on experiences accumulated by leading actors bringing together the innovative knowledge of the field. Capabilities, tools and methods brought forward by academia, ICT industry, highly specialised policy consulting firms, and policy operators and governance experts from governments will be investigated and collected in an international knowledge base. Comparative analyses and descriptions of cases, tools and scientific approaches will complement this knowledge base. Therewith, the currently existing fragmentation across disciplines will be overcome.Functions of eGovPoliNet towards community building, RTD monitoring and comparative analysis will mainly be conducted in an internet-based participatory manner, complemented with regular physical meetings attached to conferences. Community building of experts from academia, industry and public organizations, and other interested stakeholders will be supported by a community portal for knowledge sharing, collaboration, dissemination, and multidisciplinary constituency building in an open environment. eGovPoliNet expertise covers a wide range of aspects for social and professional networking and multidisciplinary constituency building along the axes of technology, participative processes, governance, policy modelling, social simulation and visualisation. Regular physical and virtual meetings with off- and online discussions and comparative studies will contribute to capacity building of the community.Through sharing of approaches and exposing them to the communitys discussions, eGovPoliNet will advance the way research, development and practice is performed worldwide in using ICT solutions for governance and policy modelling.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: BG-09-2016 | Award Amount: 15.49M | Year: 2016

The overall objective of INTAROS is to develop an integrated Arctic Observation System (iAOS) by extending, improving and unifying existing systems in the different regions of the Arctic. INTAROS will have a strong multidisciplinary focus, with tools for integration of data from atmosphere, ocean, cryosphere and terrestrial sciences, provided by institutions in Europe, North America and Asia. Satellite earth observation data plays an increasingly important role in such observing systems, because the amount of EO data for observing the global climate and environment grows year by year. In situ observing systems are much more limited due to logistical constraints and cost limitations. The sparseness of in situ data is therefore the largest gap in the overall observing system. INTAROS will assess strengths and weaknesses of existing observing systems and contribute with innovative solutions to fill some of the critical gaps in the in situ observing network. INTAROS will develop a platform, iAOS, to search for and access data from distributed databases. The evolution into a sustainable Arctic observing system requires coordination, mobilization and cooperation between the existing European and international infrastructures (in-situ and remote including space-based), the modeling communities and relevant stakeholder groups. INTAROS will include development of community-based observing systems, where local knowledge is merged with scientific data. An integrated Arctic Observation System will enable better-informed decisions and better-documented processes within key sectors (e.g. local communities, shipping, tourism, fisheries), in order to strengthen the societal and economic role of the Arctic region and support the EU strategy for the Arctic and related maritime and environmental policies.


Grant
Agency: Cordis | Branch: FP7 | Program: BSG-CSO | Phase: SSH-2007-4.2-01 | Award Amount: 1.06M | Year: 2008

INFOCON is the unique result of extensive consultations and discussions between members of civil society and leading scholars in various disciplines. These consultations have been synthesised into the objectives of the proposed project. The overall objective of the project is to create a better understanding of how Civil Society Organisations (CSOs) representing Transnational Communities (TCs) can help in preventing and resolving conflicts in Europe and the world. Under this overall objective INFOCON strives to attain the following specific objectives: 1. Provide recommendations and strategic tools for CSOs based on the projects results in order to increase the efficiency and involvement of CSOs in the elaboration of policies related to transnational communities and conflicts. 2. Verify past research on TCs and their role in conflicts with the benefit of CSOs experience and their involvement in the research process. It also addresses the current gap between civil society knowledge and academic expertise. 3. Advance the scientific knowledge on the dynamics and current potential role of CSOs in different conflicts by elaborating new and innovative comparisons of TCs across Europe (four cities: Amsterdam, Berlin, Brussels and London) and the world (three regions of origin: Turkey, Kosovo and Great Lakes). 4. Provide conflict-sensitive policy recommendations in order to enhance current conflict policy and to use the leverage and opportunities that transnational community CSOs offer in the field of conflict and peace. 5. Significantly contribute to public debate on the role of TCs in conflicts and conflict policies by large-scale dissemination activities aimed at fostering global communication and connectivity.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: ENV.2009.2.1.6.2 | Award Amount: 1.19M | Year: 2010

The main aim of FoResTTraC is to prepare future coordinated research plans, via a strategic research roadmap, between Europe and North America regarding adaptation of forest trees to climate changes, linking different disciplines: ecology, genetics, genomics and evolution. FoResTTraC brings together a critical mass of research expertise in these disciplines on both sides of the Atlantic with 6 leading European partners, 3 American and 2 Canadian partners. For the time being, large scale genomics projects have been conducted in parallel between North America and Europe, lacking in cooperative exchanges and interactions. The leading institutions coordinating these projects are partners of FoResTTraC to ensure that the current stateofart research is represented in the project. FoResTTraC will deliver a mapping of current research capacity and state of the art research in forest ecosystem genomics, a validated research roadmap regarding adaptation to climate change, a set of joint science plans, a collection of genomic resources preparing future whole genome sequencing of ecologically and economically important tree species. All project outcomes will be validated during the project by a wide group of stakeholders from Europe and North America and will be disseminated widely via the project website and key dissemination.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2008-1-4-05 | Award Amount: 3.08M | Year: 2009

The overall objective of the project is to collect and analyze new data on non-tariff measures (NTMs), particularly on governmental standards and regulations that prescribe the conditions for importing agri-food products into the EU market and into the markets of the main competing players. Furthermore, impacts from EU NTBs on least developing country (LDC) exports are examined. The project will deliver the following results: 1. An analytical framework for defining measures, methods, products and countries. 2. A data base on NTMs in EU, USA, Canada, Japan, China, India, Brazil, Argentina, Australia, Russia and New Zealand. 3. Comparative analyses on the impact of NTMs on agri-food trade of the EU. 4. Policy recommendations from case studies for quantifying NTMs on fruits and vegetables, meat and dairy trade clusters with the EU. 5. Policy recommendations from case studies on the impacts of EU private and public standards in LDCs. 6. Dissemination of project results to key stakeholders. This will be achieved: A. By optimizing complementarities of the project with ongoing NTM research on the TRAINS data base at UNCTAD. B. By organizing the research work in research, database, management and dissemination work packages. C. By developing research methodologies that are innovative and robust, optimizing the direct usefulness of the end results for the end users. D. By proposing a partner consortium that together reunites the relevant needs, for: Scientific excellence and international project experience Appropriate geographic coverage to collect the required data in all countries Linkages and complementarities with ongoing international NTM analyses (UNCTAD, OECD, World Bank, IFPRI) Policy contacts, dialogue and influence Efficient and effective project management E. With a budget of 314.5 person months, 2.372 M EC request, for 19 partners, over 30 months.


Leydig cell steroidogenesis is mainly regulated by LH via increased cAMP production leading to STAR protein activation. STAR is essential for cholesterol shuttling inside mitochondria where steroidogenesis is initiated. Accumulating evidence suggest that persistent organochlorine compounds disrupt testicular function, but the mechanism of action remains poorly characterized. Here we report that in vitro exposure of MA-10 and MLTC-1 Leydig cells to an environmentally relevant mixture of 15 organochlorines impairs steroidogenesis. While having no effect on cell viability and basal steroid production, the organochlorine mixture caused a 50% decrease in cAMP-induced progesterone production. The mixture also reduced cAMP-induced 30 kDa STAR protein by 50% while having no effect on basal STAR protein. Basal or cAMP-induced Star mRNA levels and promoter activity were unaffected by the mixture, indicating that the organochlorine mixture acted at the translational/posttranslational level. Further supporting this is the fact that in COS-7 cells overexpressing STAR, the organochlorine mixture caused a decrease in the 30 kDa form of STAR and an accumulation of the 37 kDa forms. In addition to STAR, we found that the organochlorine mixture also decreases the levels of CYP11A1 and ADXR, two proteins essential for the conversion of cholesterol into pregnenolone. In conclusion, our data show that organochlorine exposure disrupts Leydig cell function by targeting different components of the steroidogenic pathway. © 2014 by the Society for the Study of Reproduction, Inc.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2009-1-2-07 | Award Amount: 4.24M | Year: 2009

A number of studies indicate that the market demand for wood will lead to strong competition between the different wood industry branches. This is especially true in view of a globalised wood market, in which production is characterised by fast structural changes and concentration processes. Competition between different wood industries and the development towards large production units, as well as an often highly diversified forest owner structure, demands a flexible delivery of varying wood quantities and quality. This leads to high cost, which weakens the position of the European wood industry within a global market. In addition, hazardous environmental events, such as wind throws, forest fires or beetle attacks, have increased during the past years. There is strong evidence that hazardous environmental events will become even more frequent, leading to unforeseeable damage in forests and to excessive felling. Increased competition, natural risks and political and economical disturbances within a global market undermine the concept of a steady and predictable long term development of the forest sector. The challenge is to improve existing processes of the wood supply chain to the needs of wood industry under these changing conditions. In order to meet the market demands of an improved and flexible wood supply chain, novel logistic concepts must provide better information assessment on wood resources and enhance optimisation models. The proposed project would provide a better and faster response to the demands of the different wood industry branches, which will lead to an increase in value recovery.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: KBBE.2012.2.2-03 | Award Amount: 14.15M | Year: 2013

The primary goal of PREVIEW is to identify the most efficient lifestyle pattern for the prevention of type-2 diabetes in a population of pre-diabetic overweight or obese individuals. The project comprises two distinct lines of evidence, both embracing European and overseas countries: 1) A multicentre, clinical randomized intervention trial with a total of 2,500 pre-diabetic participants, including children and adolescents, adults and elderly. The duration will be 3 years for the adults and elderly, and 2 years for the children and adolescents. 2) Large population studies using data from all age groups. Focus in both lines of evidence will be on diet (specifically protein and glycemic index) and intensity of physical activity, as well as their interaction with the lifestyle factors, habitual stress and sleeping pattern as well as behavioural, environmental, cultural, and socioeconomic variables. PREVIEW will significantly increase our knowledge on how specific lifestyle factors can help preventing type-2 diabetes. Type-2 diabetes accounts for about 90% of all cases of diabetes, primarily caused by the worldwide obesity epidemic. Diabetes is a costly disease and according to WHO, the direct health care costs of diabetes range from 2.5% to 15% of annual national health care budgets. This worrying trend calls for action and a need for a variety of innovative approaches. PREVIEW aims to be such an innovative attempt including all necessary disciplines and stakeholders, who can contribute to developing new ways for the prevention of this wide-spread life-style related disease. The strategic impact of PREVIEW concerns the massive problems associated with the global diabesity epidemic (obesity and type-2 diabetes) and therefore includes partners from Europe (East, West, North and South) and Australia, New Zealand, and Canada. PREVIEW will thereby contribute to improving health over the life-span of the population in Europe as well as worldwide. Overall the public health and socio-economic impact of PREVIEW is expected to be very significant.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.19 | Award Amount: 9.36M | Year: 2011

Environmental change and particularly amplified global climate change are accelerating in the Arctic. These changes already affect local residents and feedback from the Arctics land surface to the climate system, will have global implications. However, climate change and its impacts are variable throughout the wide environmental and land use envelopes of the Arctic. Unfortunately, the Arctic is generally remote, sparsely populated and research and monitoring activities are more restricted in time and space than elsewhere. This limitation comes when there is a rapidly expanding need for knowledge as well as increasing technological opportunities to make data collection in the field and accessibility more efficient. INTERACT is a network under the auspices of SCANNET, a circumarctic network of terrestrial field bases. INTERACT specifically seeks to build capacity for research and monitoring in the European Arctic and beyond. Partnerships will be established between Station Managers and researchers within Joint Research Activities that will develop more efficient networks of sensors to measure changing environmental conditions and make data storage and accessibility more efficient through a single portal. New communities of researchers will be offered access to Arctic terrestrial infrastructures while local stakeholders as well as major international organisations will be involved in interactions with the infrastructures. This will lead to increased public awareness of environmental change and methods to adapt to them, increased access to information for education at all levels, and input to major international research and assessment programmes.The whole consortium will form a coherent and integrated unit working within a concept of a wide environmental and land use envelopes in which local conditions determine the directions and magnitudes of environmental change whereas the balance and synergies of processes integrated across the whole region have global impacts.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-01-2014 | Award Amount: 6.12M | Year: 2015

Breast tumours are heterogeneous, and result from the complex interplay of multiple lifestyle/environmental and genetic risk factors. Through the EU-funded COGS project, we have identified a large number of germline variants that influence the risk of breast cancer. In combination, these variants can identify women at wide ranges of genetic risk, even in the absence of family history of breast cancer. Given that breast cancer is not one disease, it is now essential to better understand how risk factors act together to influence the development of pathologic-molecular subtypes of breast cancer. The aim of B-CAST is to identify women at moderate to high risk of breast cancer, the subtype of cancer that is most likely to develop and the prognosis of that particular subtype. This will be accomplished through large-scale pathologic-molecular analyses of over 20,000 breast tumours, and the integration of these data with unique resources from existing consortia, including germline, lifestyle/environmental, mammographic breast density, pathologic and clinical data. This information will inform the development of risk prediction and prognostication models that will be validated in longitudinal cohorts and clinical studies, and incorporated into online tools. We will also disseminate this knowledge to relevant stakeholders, and evaluate how to translate it into risk-stratified public health and clinical strategies. The current challenge for optimised prevention, early detection, and treatment decisions for breast cancer is understanding the genetic and lifestyle determinants of risk and prognosis of molecular subtypes. B-CAST will add to this understanding and will have immediate application with benefits to women by providing validated risk and prognostication tools. This will empower women and doctors with knowledge to tailor strategies for prevention and treatment. Ultimately, this work should result in reductions in the occurrence, morbidity and mortality of this disease.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-05-2014 | Award Amount: 6.46M | Year: 2015

Breast cancer affects more than 360,000 women per year in the EU and causes more than 90,000 deaths. Identification of women at high risk of the disease can lead to disease prevention through intensive screening, chemoprevention or prophylactic surgery. Breast cancer risk is determined by a combination of genetic and lifestyle risk factors. The advent of next generation sequencing has opened up the opportunity for testing in many disease genes, and diagnostic gene panel testing is being introduced in many EU countries. However, the cancer risks associated with most variants in most genes are unknown. This leads to a major problem in appropriate counselling and management of women undergoing panel testing. In this project, we aim to build a knowledge base that will allow identification of women at high-risk of breast cancer, in particular through comprehensive evaluation of DNA variants in known and suspected breast cancer genes. We will exploit the huge resources established through the Breast Cancer Association Consortium (BCAC) and ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles). We will expand the existing datasets by sequencing all known breast cancer susceptibility genes in 20,000 breast cancer cases and 20,000 controls from population-based studies, and 10,000 cases from multiple case families. Sequence data will be integrated with in-silico and functional data, with data on other known risk factors, to generate a comprehensive risk model that can provide personalised risk estimates. We will develop online tools to aid the interpretation of gene variants and provide risk estimates in a user-friendly format, to help genetic counsellors and patients worldwide to make informed clinical decisions. We will evaluate the acceptability and utility of comprehensive gene panel testing in the clinical genetics context.


News Article | November 4, 2016
Site: globenewswire.com

PLYMOUTH MEETING, Pa., Nov. 04, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today announced that the Company will participate at the following upcoming investment conferences: Stifel 2016 Healthcare Conference Presentation Dr. Niranjan Sardesai, COO 11:00AM ET, November 15, 2016 Lotte New York Palace, New York, NY 28th Annual Piper Jaffray Healthcare Conference Fireside chat Dr. J. Joseph Kim, President & CEO 11:30AM ET, November 29, 2016 Lotte New York Palace, New York, NY Live and archived versions of the presentation and fireside chat will be available through the “Webcast” tab on Inovio’s home page at www.inovio.com. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended June 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


News Article | November 16, 2016
Site: globenewswire.com

PLYMOUTH MEETING, Pa., Nov. 16, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO), today announced it ranked No. 107 on Deloitte’s Technology Fast 500™, a ranking of the 500 fastest growing technology, media, telecommunications, life sciences and energy tech companies in North America. Technology Fast 500 award winners are selected based on percentage fiscal year revenue growth from 2012 to 2015.  During this period Inovio’s revenue growth reached 885.1%, based on revenue received from grants, partnerships and licensing deals. Dr. J. Joseph Kim, Inovio's President and CEO, said, “We appreciate Deloitte’s recognition of Inovio’s growth based on our advancement of DNA immunotherapies and vaccines for cancers and infectious diseases.  Our growth is fueled by the innovative spirit of our scientists, engineers and business people.  At our company’s core; however, the Inovio team is motivated by our most important value: ‘Patients are waiting.’” “This year’s Fast 500 winners showcase that when organizations are open to diverse perspectives and insights, they are able to create an environment for their employees and investors to see the possibilities and ingenious solutions that might lie ahead,” added Jim Atwell, Deloitte’s national managing partner of the emerging growth practice. “Entrepreneurial environments foster change and innovation within businesses, and we look forward to watching these companies continue to drive change across all sectors.” Deloitte’s Technology Fast 500 provides a ranking of the fastest growing technology, media, telecommunications, life sciences and energy tech companies – both public and private – in North America. Technology Fast 500 award winners are selected based on percentage fiscal year revenue growth from 2012 to 2015. Overall, 2016 Technology Fast 500™ companies achieved revenue growth ranging from 121 percent to 66,661 percent from 2012 to 2015, with median growth of 290 percent. In order to be eligible for Technology Fast 500 recognition, companies must own proprietary intellectual property or technology that is sold to customers in products that contribute to a majority of the company's operating revenues. Companies must have base-year operating revenues of at least $50,000 USD, and current-year operating revenues of at least $5 million USD. Additionally, companies must be in business for a minimum of four years and be headquartered within North America. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including the Zika vaccine GLS-5700, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


News Article | December 21, 2016
Site: marketersmedia.com

Mr. Proulx is a founder of and served as President of Petrolia Oil Corp. from January 2002 to September 17, 2013. He also acted as President and CEO of Puma Exploration Inc. until September 16, 2010, and currently acts as Chairman of Stelmine Canada Ltd. since December 1, 2016. André holds a Master's Degree in Ethnology from Laval University obtained in 1974. The Company welcomes the expertise that Mr. Proulx will bring to its Board of Directors. For clarification, the officers and directors of the Company are now as follows: ON BEHALF OF THE BOARD SIGNED: "Joe DeVries" Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.


News Article | December 21, 2016
Site: globenewswire.com

PLYMOUTH MEETING, Pa., Dec. 21, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today announced its DNA-based Zika vaccine (GLS-5700) generated robust antigen-specific antibody responses in a first-in-man, multi-center phase I trial. In initial testing, Zika-naïve subjects in both low dose and high dose vaccine groups demonstrated Zika antigen-specific antibody responses after one or two vaccinations. In addition, the vaccine was well tolerated and no significant safety concerns were noted in any of the 40 subjects out to 14 weeks from initiation of dosing, the latest available data from the study. This phase I, open-label, dose-ranging study of GLS-5700 in healthy adult volunteers is evaluating the safety, tolerability and induction and persistence of Zika specific antibody and T cell responses out to 60 weeks. In preclinical testing Inovio’s Zika vaccine protected animals that had been exposed to the virus from infection, brain damage and death. Dr. J. Joseph Kim, Inovio’s President & CEO, said, “These early clinical results show that Inovio is on track to rapidly develop Zika countermeasures for this disease that has no currently existing vaccine or treatment. Our synthetic vaccine technology allows rapid development of new products, leading Inovio to be the first to create a Zika vaccine, the first to generate preclinical data, the first to initiate human testing, and now first to report positive clinical data.” “We also look forward to completing our second phase I study of 160 subjects in Puerto Rico, where the CDC estimates 25% of the population could be infected with Zika virus by year end. We expect results next year which may provide exploratory signals of vaccine efficacy. Based on these two studies, we plan to meet with regulators to map out the most efficient path forward to bring our Zika vaccine to patients and help mitigate this widespread Zika outbreak that has expanded into the continental United States.” Inovio is developing its Zika vaccine, GLS-5700, with GeneOne Life Science, Inc. (KSE:011000) and academic collaborators from the U.S. and Canada who are also collaborating to advance clinical development of Inovio’s Ebola and MERS vaccines. In addition to the vaccine development, earlier this month, Inovio and The Wistar Institute received an $8.8 million grant from the Bill & Melinda Gates Foundation to develop a DNA-based monoclonal antibody designed to provide fast-acting protection against Zika infection and its debilitating effects. Unlike vaccines, monoclonal antibody-based therapies could provide more immediate protection but do not develop long-term immune memory. An ideal approach would therefore include the co-administration of a dMAb™ product for immediate protection and a DNA vaccine to train the immune system for longer-term, persistent protection against Zika infection. First identified in Uganda, Zika virus subsequently spread to equatorial Asia and over the past two years has rapidly spread through the South Pacific, Hawaii, South America, Central America, and the Caribbean. In 2016, active local mosquito-borne transmission began to occur in North America, specifically confirmed in Florida and reported but awaiting confirmation in Texas. Zika virus is a flavivirus, a family of viruses including yellow fever, dengue, and West Nile virus, which are introduced to people through mosquito bites. Because the Aedes species of mosquitoes that spreads Zika virus is found throughout the world there is concern that Zika will continue to spread to new countries and regions. As of December 2016, 68 countries and territories (including 48 in the Americas) reported continuing mosquito-borne transmission of the Zika virus, compared to 33 countries stated by WHO in their first Zika situation report in February 2016. Unlike other flaviviruses, Zika virus can be sexually transmitted. The most common manifestations of symptomatic Zika virus infection are fever, rash, joint pain, and conjunctivitis. Zika is very strongly associated with and almost certainly causes birth defects, most notably microcephaly, which arises from infection during pregnancy. Microcephaly is the result of incomplete brain development which is manifested as an abnormally small head and severe mental retardation. In adults, Zika virus infection is also associated with Guillain-Barre syndrome, which causes muscle weakness of the limbs and in severe cases may cause almost total paralysis including the inability to breathe. Recent reports suggest Zika may also be associated with other neurological abnormalities and abnormalities in other systems including ocular and cardiac. No vaccine or therapy currently exists for the prevention or treatment of infection of the Zika virus. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including the Zika vaccine GLS-5700, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


PLYMOUTH MEETING, Pa., Feb. 27, 2017 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today announced that its SynCon® WT1 cancer immunotherapy was capable of breaking immune tolerance and inducing neo-antigen-like T cell responses to cause tumor regression in pre-clinical studies. Breaking tolerance has been a major challenge for developing a potent cancer therapy; researchers have tried many other methods and been unsuccessful for decades. Notably, the WT1 antigen is over-expressed in multiple cancer types but not found in most normal tissue, giving it potential to be used as part of a universal cancer vaccine against multiple tumor types. Results of these pre-clinical studies appear in the online edition of Molecular Therapy in a paper entitled, “A novel DNA vaccine platform enhances neo-antigen-like T-cell responses against WT1 to break tolerance and induce anti-tumor immunity,” authored by Inovio and its collaborators at The Wistar Institute. Study results revealed that while mice did not mount an immune response to native mouse WT1 antigens, mice immunized with Inovio’s SynCon WT1 antigen broke tolerance and generated robust neo-antigen-like T cells. Furthermore, the immunized mice exhibited smaller tumors and prolonged survival in a tumor challenge study. SynCon WT1 DNA vaccination also broke tolerance and generated neo-antigen-like T cell immune responses in Rhesus monkeys, a species whose immune system closely resembles that of humans. Inovio’s ability to overcome the immune system’s usual tolerance of WT1 antigen suggests the potential of its SynCon WT1 antigen to tackle any WT1-expressing cancer in humans, which include pancreatic, brain, lung, thyroid, breast, testicular, ovarian, and melanoma. Dr. J. Joseph Kim, Inovio's President and CEO, said, "Our SynCon antigens’ ability to overcome the immune system’s inability to recognize tumor self-antigens is unique and powerful. While we systematically and synthetically mimic the body’s natural process of creating tumor neo-antigens, which possess differentiated but individualized genetic sequences that may then induce an immune response, our ability to break tolerance with broadly prevalent antigens makes our approach more universal across populations. We are pleased to again show such results with an important cancer antigen – in this case, WT1 – and continue to add to our array of promising universal cancer antigens in Inovio’s product development strategy. “To expand on our capabilities and strategy, the power of our differentiated antigens dovetails with our ability to turn cancer tumors from cold to hot by creating a significant presence of antigen-specific CD8+ killer T cells in a target lesion or tumor microenvironment, which we have shown via biopsies in two human studies. These are critical outcomes: although checkpoint inhibitors have raised the bar for treating cancers by neutralizing cancer cells’ inherent ability to switch off T cells that are hunting them, they do not actually generate the antigen-specific killer T cells required to destroy cancer cells. We believe our DNA-based SynCon immunotherapies are the missing link to take immuno-oncology to the next level.” “With these accomplishments we could not be more enthusiastic about two immuno-oncology combination human studies to start in the first half of 2017. MedImmune will combine INO-3112 (also named MEDI0457) with their checkpoint inhibitor molecule in an upcoming clinical study. Inovio is also planning to conduct a combination study for INO-5401 with a checkpoint inhibitor in cancer patients. We previously noted that INO-5401 will include our hTERT SynCon antigen. I am pleased to say that INO-5401 will also include our SynCon antigens for WT1 and PSMA. We believe this product has the potential to be a very powerful universal cancer immunotherapy in combination with different checkpoint inhibitors.” The National Cancer Institute previously highlighted WT1, hTERT and PSMA among a list of attractive cancer antigens, designating them as high priorities for cancer immunotherapy development. WT1 was at the top of the list. The hTERT antigen relates to 85% of cancers and WT1 and PSMA antigens are also widely prevalent in many cancers. Inovio’s synthetically designed antigens use a consensus of human and multiple animal genetic sequences for the same antigen to create a differentiated SynCon® antigen that can be more readily recognized as “foreign” by immune sentries in the patients. This recognition may help overcome the immune system’s tolerance of tumor cells displaying the native or self-antigens generated by the body. Once a significant antigen-specific T cell response is activated, these T cells may then also seek throughout the body and destroy cancer cells expressing the pre-existing natural or native tumor antigens. There are multiple lines of evidence pointing to the potential of INO-5401 in immuno-oncology. Inovio previously reported preclinical data indicating the ability of its PSMA and hTERT tumor-associated SynCon antigens to generate significant antigen-specific killer T cell responses. Inovio is also running an ongoing phase I study of its SynCon hTERT antigen (INO-1400) to assess safety and immunogenicity in over fifty patients with at least one of nine different hTERT-expressing cancers. Our SynCon PSMA antigen is one of two components (along with SynCon PSA) making up INO-5150, which is currently in a phase I study of sixty biochemical-relapse prostate cancer patients. Interim immune responses and safety data from both INO-1400 and INO-5150 studies will be presented at cancer conferences in 2017. Importantly, Inovio has already reported human data characterizing the activation of significant antigen-specific CD8+ killer T cells in patients and their infiltration into lesions and tumors displaying target antigens. These studies of HPV-related precancer (VGX-3100) and cancer (INO-3112) showed a significant presence of activated T cells based on pre and post immunization biopsies. In a controlled phase 2b study for VGX-3100, Inovio also showed statistically significant efficacy in regressing HPV-related cervical dysplasia. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, ApolloBio Corporation, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including the cancer immunotherapy INO-5401, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


News Article | November 9, 2016
Site: globenewswire.com

PLYMOUTH MEETING, Pa., Nov. 09, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today reported financial results for the quarter ended September 30, 2016. The following financial results provide a year-over-year comparison of the third quarter in 2016 and 2015. Total revenue was $12.5 million compared to $24.2 million. Total operating expenses were $32.7 million compared to $20.5 million. The net loss attributable to common stockholders was $20.8 million, or $0.28 per share for the third quarter 2016, compared to net income of $5.6 million, or $0.08 per share in the third quarter of 2015. The decrease in revenue for the comparable periods was primarily due to $15.0 million of revenue recognized in the third quarter 2015 from the up-front payment received from our partnership agreement with MedImmune. Accounting recognition of the remainder of the $27.5 million upfront payment was deferred and will be triggered by future events. The net income achieved during the third quarter 2015 was attributable to the increase in revenue and may not repeat in future quarters. Research and development expenses were $27.0 million compared to $16.1 million for the third quarter ending 2016 and 2015 respectively. The increase was primarily related to increased investment in our product development programs – notably the DARPA funded Ebola program and clinical trial preparations for the initiation of the VGX-3100 phase III study. General and administrative expenses were $5.8 million compared to $4.4 million. As of September 30, 2016, cash and cash equivalents and short-term investments were $119.7 million compared with $163.0 million as of December 31, 2015. There were 74.0 million shares outstanding and 81.8 million fully diluted. During the three months ended September 30, 2016, the Company sold 448,848 shares of common stock under its ATM common stock sales agreement for net proceeds of $4.2 million, with an average price of $9.45 per share. Inovio’s balance sheet and statement of operations are provided below. Form 10-Q providing the complete 2016 Third quarter financial report can be found at: http://ir.inovio.com/secfilings. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including our ability to obtain a release of the clinical hold from the FDA for the proposed phase III clinical program for VGX-3100, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, our ability to advance our portfolio of immuno-oncology products independently, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, our ability to enter into partnerships in conjunction with our research and development programs, evaluation of potential opportunities, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


PLYMOUTH MEETING, Pa., Feb. 13, 2017 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today announced that it has entered into a collaboration and license agreement providing ApolloBio Corporation (NEEQ:430187) with the exclusive right to develop and commercialize VGX-3100, Inovio’s DNA immunotherapy product designed to treat pre-cancers caused by human papillomavirus (HPV), within Greater China (China, Hong Kong, Macao, Taiwan). The agreement provides for potential inclusion of the Republic of Korea three years following the effective date. Under the collaboration and license agreement, Inovio will receive $15 million in upfront and near term payments comprising an initial $3 million signing fee and a $12 million milestone upon lifting of the VGX-3100 phase 3 pre-initiation clinical hold by the FDA. Under a separate equity agreement, ApolloBio will invest in Inovio common stock subsequent to lifting of the clinical hold at a volume weighted average price encompassing a trading period prior to and following the lifting of the clinical hold. The aggregate investment, which is expected to be completed in the first half of 2017, will not exceed $35 million and may be a lower amount such that ApolloBio will not be the largest shareholder in Inovio. ApolloBio will fund all clinical development costs within the licensed territory, and will pay Inovio up to $20 million based upon the achievement of certain regulatory milestones in the US, China and Korea, and double digit royalties on net sales of VGX-3100. The agreements are subject to People’s Republic of China (PRC) corporate and regulatory approvals, and payments are subject to PRC currency approvals. This collaboration on VGX-3100 encompasses the treatment and/or prevention of pre-cancerous HPV infections and HPV-driven dysplasias, and excludes HPV-driven cancers and all combinations of VGX-3100 with other immunostimulants. Dr. J. Joseph Kim, Inovio’s President and Chief Executive Officer, said, “As Inovio continues to focus on the path to regulatory approvals and commercialization strategies in the U.S. and European countries, this agreement opens up Greater China for our lead program and first phase III product. We believe that ApolloBio is a strong partner that brings significant capabilities and expertise relating to product development, the Chinese regulatory landscape, and the healthcare market in China.” Dr. Weiping Yang, Chief Executive Officer of ApolloBio Corporation, said, “We are delighted to begin 2017 with a strategic collaboration with Inovio. VGX-3100 is the world’s first therapeutic vaccine being developed for HPV pre-cancers. This collaboration, license and equity investment marks our determination to introduce late stage innovative new drugs to meet severely unmet medical needs within the Greater China region.” VGX-3100 is an HPV-specific immunotherapy that is being developed as a non-surgical treatment for high-grade cervical dysplasia and related underlying persistent HPV infection. VGX-3100 works in vivo to activate functional, antigen-specific, CD-8 T-cells to clear persistent HPV 16/18 infection and cause regression of pre-cancerous cervical dysplasia. In a phase II trial, VGX-3100 demonstrated clinical efficacy and was generally well tolerated, without the side effects and obstetric risks associated with surgical excision. VGX-3100 is a first-in-class HPV-specific immunotherapy that targets the underlying cause of cervical dysplasia, providing an opportunity for women to reduce their risk of cervical cancer without undergoing an invasive surgical procedure. HPV is the most common sexually transmitted infection and is the main cause of cervical cancer, which kills more than 250,000 women every year worldwide. Among the 300 million women currently infected with HPV, 500,000 will be diagnosed with cervical cancer each year. Two types of HPV (HPV 16 and HPV 18) cause 70% of cervical cancer cases. High-grade cervical dysplasia is also caused by persistent HPV infection and is a pre-cancerous condition that can progress to cervical cancer if left untreated. Globally the number of high-grade cervical dysplasia cases is estimated to be in the range of 10 million. Currently there are no approved medical treatments for persistent HPV infection or cervical dysplasia. The primary treatment for high-grade cervical dysplasia is surgical excision of the pre-cancerous lesion and a margin of healthy cervical tissue. Because surgical excision does not treat the underlying HPV infection that causes cervical dysplasia, there is a 10-16% risk of disease recurrence. Women with persistent HPV infection after surgical excision remain at high risk for cervical cancer. In addition, surgical treatment is associated with pain and cramping, and a risk for post-surgical bleeding, infection, and pre-term delivery and miscarriages during future pregnancies. ApolloBio Corporation (NEEQ:430187) is a leading Chinese biomedical company committed to research and development of innovative new medicines, accessing such new medicines through in-licensing, and additionally providing medical services. ApolloBio Corp. is focused on pharmaceutical products with significant market potential in China in the three major fields of oncology, liver disease, and cardio-cerebrovascular disease; providing efficient access for American biomedical companies to enter into the Chinese market; and aiming to bring the newest and best medicines across the globe to the Chinese people. For more information, visit www.apollobio.com. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including the agreements with ApolloBio, our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including the timing of the lifting of the VGX-3100 phase 3 pre-initiation clinical hold, receipt of by ApolloBio of corporate and PRC regulatory approvals, uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including VGX-3100, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that the approvals required under the ApolloBio agreements will be obtained, that VGX-3100 or any other product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies for VGX-3100 will be supportive of regulatory approvals required to market licensed products, including in Greater China, or that any of the forward-looking information provided herein will be proven accurate.


PLYMOUTH MEETING, Pa., Nov. 25, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) announced today that further to the voluntary delisting of Genetronics Biomedical Corporation, a predecessor of the Company, from the Toronto Stock Exchange on January 17, 2003, it has applied to the British Columbia Securities Commission and Ontario Securities Commission for a decision that it is no longer a reporting issuer for the purposes of British Columbia and Ontario securities law. The outcome of this application will not affect Inovio’s listing on the NASDAQ stock exchange nor its reporting obligations with the US Securities and Exchange Commission. If an order that the Company is not a reporting issuer in British Columbia and Ontario is granted by the securities regulatory authorities from such jurisdictions, the Company will no longer be a reporting issuer in any jurisdiction of Canada and will no longer be required to file financial statements and other continuous disclosure documents with Canadian securities regulatory authorities. In this regard, Canadian security holders will continue to have access to all financial statements and other continuous disclosure documents required to be filed by the Company under United States securities laws. All reports of the Company filed with the US Securities and Exchange Commission are available at www.sec.gov as well as on the Company’s website at www.inovio.com. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs,  the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


Significant immune responses observed in 100% of Zika-vaccinated subjects and 98% of MERS-vaccinated human subjects in separate phase I studies  PLYMOUTH MEETING, Pa., Feb. 23, 2017 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today announced that Dr. David B. Weiner, Inovio’s co-founder, presented positive clinical data on Inovio’s DNA-based vaccines against MERS (Middle East Respiratory Syndrome) (GLS-5300) and Zika (GLS-5700) at the Coalition for Epidemic Preparedness Innovation (CEPI)’s 1st Scientific Meeting on “Vaccines Against Emerging Infections - A Global Insurance” in Paris, France. Dr. J. Joseph Kim, Inovio’s CEO, said: “Advancing DNA vaccine technology for broadly applicable, rapid response against infectious diseases of epidemic potential is one of Inovio’s priorities. We quickly designed and manufactured vaccines for two recent emerging infectious pathogens, MERS CoV and Zika, and these products join our Ebola program in generating significant immune responses with a favorable safety profile in phase I studies. We are pleased to see CEPI moving forward on its vision for proactive and accelerated vaccine development for epidemic threats and to contribute to their first scientific meeting.” Officially launched at the World Economic Forum in Davos in January, 2017, CEPI received an initial $460 million from the governments of Germany, Japan and Norway, plus the Bill & Melinda Gates Foundation and Wellcome Trust, as part of a drive to bring together a total of $1 billion to fund and support its goal of stimulating, financing and coordinating the advancement of safe, effective and affordable vaccines. Dr. Weiner noted that in a phase I MERS study, after a three dose vaccine regimen with GLS-5300, high levels of binding antibodies were measured (ELISA) in 92% (57 of 62) of evaluated subjects. Even two doses or a single dose of vaccine generated a robust antibody response in 84% (52 of 62) or 44% (27 of 62) of evaluated subjects, respectively. Significant antigen-specific cytotoxic T-lymphocyte (CTL) responses were also observed. Importantly, all but one evaluated vaccinated subject or 98% (61 of 62) generated an antibody and/or T cell response against the MERS vaccine. Generation of MERS antigen-specific antibody and T cell responses is believed to be important for generating immediate and long-lasting protection against the disease. The vaccine was well tolerated and no significant safety concerns were noted to date. These interim data from the first set of evaluated subjects were from a fully enrolled phase I study of 75 healthy volunteers. Inovio and GeneOne Life Science Inc. (KSE: 011000) are co-developing Inovio’s GLS-5300 in partnership with the Walter Reed Army Institute of Research in Maryland, where the trial was conducted. This trial represents the first and still only MERS vaccine to be tested in humans for this disease that has no approved vaccines or treatments. In preclinical studies of GLS-5300 (data published in the peer reviewed journal Science Translational Medicine, 2015), 100% of vaccinated Rhesus macaques were protected from symptoms of MERS when exposed to the live MERS virus. The animals also generated strong antibody and T-cell responses. Since the virus was first identified in Saudi Arabia in 2012, the World Health Organization has reported almost 2,000 MERS infections and nearly 700 deaths worldwide. Twenty seven countries have reported cases, including Korea where an outbreak in the summer of 2015 resulted in 186 cases and 38 deaths. While the SARS epidemic in 2003 killed 10% of those infected, SARS-related MERS has killed about 36% of people who contracted this communicable virus. Dr. Weiner also highlighted that in a phase I Zika study, after a three dose vaccine regimen with GLS-5700, high levels of binding antibodies were measured (ELISA) in 100% (39 of 39) of evaluated subjects. Moreover, two doses or a single dose of vaccine generated a robust antibody response in 82% (32 of 39) or 40% (16 of 40) of evaluated subjects, respectively. T cell immune responses are currently being evaluated. The vaccine was well tolerated and no significant safety concerns were noted. These preliminary data are from a fully enrolled phase I study of 40 healthy volunteers. Inovio and GeneOne are co-developing GLS-5700. This trial represents the first Zika vaccine to be tested in humans for this disease that has no approved vaccines or treatments and also the first human clinical data reported with a Zika vaccine documenting the induction of immune responses following vaccination. Preclinical data published in the peer-reviewed journal npg Vaccines (2016) showed that GLS-5700 generated single-dose protection in 100% of animals against neurologic or testicular effects of the Zika virus.     Dr. Scott White, Inovio’s Vice President of Infectious Disease Clinical Development, will also present this Zika data on Friday, February 24th at the “First International Conference on Zika Virus,” a worldwide forum sponsored by the American Society of Tropical Medicine and Hygiene in Washington, D.C. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, ApolloBio Corporation, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including the MERS vaccine GLS-5300 or Zika vaccine GLS-5700, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


Article published in npj Vaccines demonstrates that DNA vaccine protected 100% of animals from Zika infection after exposure to the virus PLYMOUTH MEETING, Pa., Nov. 10, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today announced that Inovio and its collaborators have published results in Nature Partner Journals (npj) Vaccines demonstrating that its Zika DNA vaccine (GLS-5700) protected animals from infection, brain damage and death. In this study 100% of GLS-5700 vaccinated animals were protected from Zika infection after exposure to the virus. In addition, vaccinated mice were protected from degeneration in the cerebral cortex and hippocampal areas of the brain while unvaccinated mice showed significant degeneration of the brain after Zika infection. Prior preclinical studies have tested potential Zika vaccine candidates in animal models involving normal mice and non-human primates that are naturally resistant to Zika. While providing useful immunology data, they cannot provide relevant evidence of an effective means of controlling the spread or medical impacts of this disease by vaccination. In addition to reporting immunogenicity in such Zika-resistant species, this paper represents the first published research to also analyze a Zika vaccine using the special transgenic murine strain A129 lacking interferon alpha and beta receptors (IFNAR-/-), making them highly susceptible to Zika infection and disease. Taking this extra step provided data on how vaccine-generated immune responses could protect against a lethal viral challenge and demonstrates the benefit a Zika vaccine might provide in people. Dr. J. Joseph Kim, President and CEO of Inovio, said, “We clearly demonstrated the power and speed of our product development platform when we and our collaborators moved our Zika vaccine from the bench to human clinical studies in less than six months, a vaccine industry record. We’re pleased to now build further evidence of the potential utility of our product.” “Our results support the critical importance of immune responses for both preventing infection as well as ameliorating disease caused by the Zika virus,” said lead researcher David B. Weiner, Ph.D., Executive Vice President and Director of the Vaccine Center at The Wistar Institute and the W.W. Smith Charitable Trust Professor in Cancer Research at Wistar. Dr. Weiner is also a member of Inovio’s board of directors and chairs its scientific advisory board. “As the threat of Zika continues, these results further encourage the study of this vaccine as a preventative approach for protecting humans.” This study demonstrated that Inovio’s synthetic DNA vaccine expressed antigens specific to Zika and generated robust antigen-specific and neutralizing antibody and T cell responses in mouse and non-human primate models. Moreover, the study also demonstrated that GLS-5700 provided protection against the disease and death in Zika-susceptible A129 transgenic mice while also being neuroprotective, meaning the disease was unable to spread to the brain. This is especially important given the risk that babies born with the disease have of developing microcephaly, a birth defect resulting in an abnormally small head and that may prevent the brain from developing properly. This Zika vaccine was developed in a collaboration between Inovio Pharmaceuticals, Inc., The Wistar Institute, and GeneOne Life Science Inc. and is currently in two human clinical studies. Inovio expects to report phase I data before the end of this year from the first 40-subject study being conducted in Miami, Philadelphia and Quebec City. In August, the companies initiated a second study of GLS-5700 in 160 subjects in Puerto Rico. The CDC estimates that Zika will infect more than 25 percent of the Puerto Rican population by the end of the year, providing the potential for this study’s placebo control design to provide exploratory signals of vaccine efficacy in 2017. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including the Zika vaccine GLS-5700, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


Grant Provides Funding to Help Prepare New Zika Therapy for Human Trials Inovio Already in Two Human Trials for its Preventive Zika Vaccine PLYMOUTH MEETING, Pa. & PHILADELPHIA, Dec. 01, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) announced today that it has been awarded a $6.1 million sub-grant through The Wistar Institute to develop a DNA-based monoclonal antibody designed to provide a fast-acting treatment against Zika infection and its debilitating effects. The goal of this program, which is funded by a grant to The Wistar Institute from the Bill & Melinda Gates Foundation, is for the researchers to develop a Zika dMAb® therapy ready for human clinical trials in less than two years. There is no approved therapeutic or vaccine for Zika infection, presenting a major unmet medical need given that the World Health Organization estimates that more than two billion people are directly at risk for infection. Importantly, infection with the Zika virus during pregnancy can cause a pattern of birth defects including microcephaly. This new DNA-based monoclonal antibody technology has properties that best fit a response to address a Zika outbreak in that dMAb products can be designed and manufactured expediently on a large scale using common fermentation technology, are thermal-stable, and may be used as a therapy to provide more rapid protection from or limit the spread of Zika infection. Unlike vaccines, monoclonal antibody-based therapies could provide more immediate protection but do not develop long term immune memory. An ideal approach would therefore include the administration of a dMAb product for immediate protection and a DNA vaccine to train the immune system for longer-term, persistent protection against Zika infection. Inovio’s optimized DNA-based immunotherapy platform is uniquely positioned to target both immediate therapy through delivery of dMAb products as well as long-term immunity via DNA vaccination. Dr. J. Joseph Kim, President & CEO of Inovio, said, “As the leader in DNA-based immunotherapy and vaccine products, with our lead program poised to enter phase III study in the near term, we are also excited to expand our powerful technology platform to develop these new dMAb products. We thank the Gates Foundation for their confidence in the Inovio/Wistar team to develop this new type of medicine to address an emerging infectious disease like Zika. This grant marks the fourth major grant in the past couple of years backing the development of Inovio’s dMAb technology. Past grants include two from DARPA totaling over $56 million − one for dMAb products for Ebola and one for dMAb products for universal flu and antibiotic resistant bacteria − as well as one from the NIH for dMAb products for treating HIV infection.” Dr. David B. Weiner, Wistar’s Executive Vice President, Director of its Vaccine Center, and the W. W. Smith Charitable Trust Endowed Professorship in Cancer Research, is the principal investigator of this grant. Other collaborators on the award include Humabs Biomed and GeneOne Life Sciences. Dr. Weiner said, “Our team has strong expertise in DNA immunotherapy development, design and delivery technology as well as molecular immunology (The Wistar Institute) and DNA production and clinical studies including device & delivery development (Inovio Pharmaceuticals) and DNA studies in non-human primates. Our collaborative team skillset includes monoclonal antibody discovery (Humabs) and validation, and extensive experience working with in vivo infectious disease models and challenges (Wistar & Humab). Each group will perform experiments and provide essential reagents to other groups within the consortium. The team is experienced with translation from preclinical studies to the clinic.” In support of its dMAb technology, the Inovio/Wistar team reported earlier this year that its dMAb product for another emerging infectious disease, Chikungunya (CHKV), provided durable 100% protection in mice. In this study, a single intramuscular injection of a dMAb product protected mice from a lethal dose of the virus. The protection expressed by these dMAb antibodies was very rapid, with 100% survival in mice challenged with lethal disease as early as two days after dMAb product administration. In comparison, vaccine-driven protection can take weeks to months to reach peak efficacy levels, but provides better long term protection compared to a dMAb product. This published study demonstrates that an Inovio dMAb product and DNA vaccine could be used as an ideal combination to provide both rapid short-term as well as long-term protection. Inovio is the only organization to report such results in any disease using a DNA-based monoclonal antibody, with published preclinical data in dengue and HIV as well, and is also developing dMAb products for treating MERS, influenza, MRSA, RSV, Ebola and cancers. Inovio is advancing two trials for its DNA-based Zika vaccine. It expects to have preliminary results by year end for its U.S./Canada study. In Puerto Rico, where the CDC estimates Zika will infect more than 25% of the population by year end, Inovio’s second study employs a placebo control design that may provide exploratory signals of vaccine efficacy. The company expects to meet with regulators next year to determine the most efficient path forward to develop its Zika vaccine and help mitigate this widespread Zika outbreak that has now expanded into the continental United States. Unlike conventional monoclonal technology, which involves constructing protein-based antibodies and manufacturing them in cell culture in a complex and costly process, Inovio’s patent-protected DNA-based monoclonal antibody technology encodes the DNA sequence for a specific monoclonal antibody in a highly optimized plasmid, which would be delivered directly into a subject’s arm using electroporation. Cells in the body would then produce the encoded monoclonal antibody molecules, with intended functional activity including high antigen-binding and neutralization capabilities against the targeted disease. Monoclonal antibodies offer the benefit of inducing a rapid onset of the immune response. Overall, Inovio’s dMAb technology may provide clear advantages over conventional monoclonal antibody technology, including faster development, easier product manufacturing, and more favorable pharmacokinetics. The current monoclonal antibody product market is well over $50 billion. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including the Zika vaccine GLS-5700, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


TORONTO, ON--(Marketwired - February 08, 2017) - Wesdome Gold Mines Ltd. ("Wesdome" or the "Company") (TSX: WDO) is pleased to provide an update of underground drilling progress at its 100% owned Kiena Mine Complex, in Val d'Or, Quebec. Since the last update on November 15, 2016, a fourth drill has been added on the 960 metre level (Figure 1), 29 drill holes have been completed and assay results have been received for 21 drill holes (Table 1). The new drilling continues to trace the Kiena Deep mineralized system along an altered and deformed north north west trending ("NNW") basalt-komatiite contact zone. To date, it has been traced 550 metres NNW along strike and over a depth range of 400 metres. It remains open at depth and along trend. Wesdome continues its accelerated drilling program with the goal of determining the extent, continuity and geometry of the Kiena Deep gold system. 1. Major step out holes extending trend to a tested length of 550m: * The geometry of these zones is not clearly understood at this point. Further drilling is required to interpret true widths. Assay intervals include values cut to an arbitrary, historic 1 oz/ton or 34.28 g/t Mr. Duncan Middlemiss, President and CEO, commented "Drilling results have been accelerated with the goal of delineating and defining this significant new find as quickly and efficiently as possible. This set of Kiena Deep drill results continues to deliver grades substantially higher than the historic production grade profile at Kiena of 4.5 g/t. We are also very encouraged by step out holes confirming mineralization now tested along 550 metres of strike length, indicating a potential large new gold system. Furthermore, in the Company's efforts to accelerate our advanced exploration at Kiena, we are pleased to announce the appointment of Marc-André Pelletier as Vice President of Quebec Operations, who will be based full time at the Kiena Complex. Marc-André has over 20 years' experience in underground gold mining in Canada, and will be working closely with our geologic team to evaluate ramp development. On behalf of management and the board, I would like to welcome him to the Wesdome team." Drilling continues to identify two styles of mineralization spatially related to a basalt-komatiite (ultramafic) contact zone that trends NNW. There are likely multiple zones which remain only partially defined and are open. The full extent of the mineralized system has not been delineated. It has been traced 550 m along the contact area trend between depths 1,000 and 1,400 m and remains open. Step out holes 6146 and 6147 are of significant interest as these holes have intersected quality grade over wide widths some 150 metres north, and 250 metres south along trend of the known mineralized system, which remains open (Figure 1). Four drills are operating on levels 670m, 770m, 910m and 960m. Challenging drilling conditions in the deformed and altered contact area have been addressed with a combination of bits, drill assemblies and specialized drilling reagents. The experience obtained in these conditions and the additional drill added to the 960m level has resulted in improved success in attaining the desired targets. Shorter holes with better attack angles will continue to accelerate results. The accelerated drilling is designed to delineate the potential size of the Kiena Deep gold system and define its internal geometry as quickly and efficiently as possible. Confidence in internal grade and continuity will de-risk a decision to initiate ramp development to provide definition drilling and access to Kiena Deep as soon as possible. The Company intends to continue the drilling campaign with four underground drills. Ongoing evaluation for the requirement of enhanced drill platforms will determine the timing of underground ramp development, as the location of this infrastructure is dependent upon drilling results currently being generated. The Company is very encouraged by the continued exploration results at Kiena and the potential to re-establish production at this fully permitted facility. As a result, we are pleased to announce the appointment of Marc-Andre Pelletier as Wesdome's Vice-President of Operations for Quebec in charge of the Kiena Mine Advanced Exploration Program. Marc-Andre is an experienced professional mining engineer who was most recently Vice-President of Operations at St Andrew Goldfields Ltd. Prior to Marc-Andre's tenure at St Andrew's he was employed by Barrick Gold Corporation from 2001-2009 elevating to the position of Mine Superintendent at Barrick's Williams Mine. Prior to his Barrick experience Marc-Andre worked extensively in Quebec in progressive technical roles. Throughout his career Marc-Andre has dedicated himself to achieving safety, production, and costs targets. He is a graduate of Laval University in mining engineering and is a resident of Rouyn-Noranda, Quebec. The Kiena Mine Complex is a fully permitted, integrated mining and milling infrastructure which includes a 930 metre production shaft and 2,000 tonne per day capacity mill. From 1981 to 2013 the mine produced 1.75 million ounces of gold from 12.5 million tonnes at a grade of 4.5 g/t. The bulk of this production came from the S-50 Zone between depths of 100 and 1,000 metres. In 2013, operations were suspended due to a combination of declining gold prices and lack of developed reserves. The infrastructure has been well preserved on care and maintenance status. The technical and scientific disclosure in this press release has been prepared and approved by Marc Ducharme, P. Geo., Chief Exploration Geologist of Wesdome and "Qualified Person" as defined by National Instrument 43-101 disclosure standards. Analytical work was performed by Techni-Lab (ActLabs) of Ste-Germaine-Boulé (Quebec), a certified commercial laboratory (SCC Accredited Lab #707). Sample preparation was done at Techni-Lab (ActLabs) in Val d'Or (Quebec) and assaying was done by fire assay methods at Techni-Lab (ActLabs) laboratory in Ste-Germaine-Boulé (Quebec). In addition to laboratory internal duplicates, standards and blanks, the geology department inserts blind duplicates, standards and blanks into the sample stream at a frequency of one in twenty to monitor quality control. Wesdome Gold Mines is in its 29th year of continuous gold mining operations in Canada. The Company is 100% Canadian focused with a pipeline of projects in various stages of development. The Eagle River Complex in Wawa, Ontario is currently producing gold from two mines, the Eagle River Underground Mine and the Mishi Open pit, from a central mill. Wesdome is actively exploring its brownfields asset, the Kiena Complex in Val d'Or, Quebec. The Kiena Complex is a fully permitted former mine with a 930 metre shaft and 2,000 tonne per day mill. The Company has further upside at its Moss Lake gold deposit, located 100 kilometres west of Thunder Bay, Ontario, which is being explored and evaluated to be developed in the appropriate gold price environment. The Company has approximately 130 million shares issued and outstanding and trades on the Toronto Stock Exchange under the symbol "WDO." This news release contains "forward-looking information" which may include, but is not limited to, statements with respect to the future financial or operating performance of the Company and its projects. Often, but not always, forward-looking statements can be identified by the use of words such as "plans", "expects", "is expected", "budget", "scheduled", "estimates", "forecasts", "intends", "anticipates", or "believes" or variations (including negative variations) of such words and phrases, or state that certain actions, events or results "may", "could", "would", "might" or "will" be taken, occur or be achieved. Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of the Company to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking statements contained herein are made as of the date of this press release and the Company disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or results or otherwise. There can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. The Company undertakes no obligation to update forward-looking statements if circumstances, management's estimates or opinions should change, except as required by securities legislation. Accordingly, the reader is cautioned not to place undue reliance on forward-looking statements. Image Available: http://www.marketwire.com/library/MwGo/2017/2/8/11G129706/Images/feb8Fig_PlanView3_DDH-Traces_PR-Feb2017-5e89cb57d43887bdb32f3bb4046d95e5.jpg Image Available: http://www.marketwire.com/library/MwGo/2017/2/8/11G129706/Images/Kiena_Deep_3D_DDH_Isometric_View1e_All-81016611f3f58eefb6309b20b66d468f.jpg Image Available: http://www.marketwire.com/library/MwGo/2017/2/8/11G129706/Images/Kiena_Deep_3D_DDH_Isometric_Zoomed_View-e1eebb849060b7b29f8371b39c860f70.jpg


News Article | October 26, 2016
Site: globenewswire.com

PLYMOUTH MEETING, Pa., Oct. 26, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) announced today that it will host a conference call and live webcast to discuss its 2016 third quarter financial results and provide a corporate update on Wednesday, November 9, 2016 at 8:30 a.m. ET. A live and archived version of the audio presentation will be available online at http://www.investorcalendar.com/IC/CEPage.asp?ID=175403 as well as through the "Webcast" tab on Inovio's home page at www.inovio.com. This is a listen-only event but will include a live Q&A with analysts. A replay of the conference call will be accessible two hours after the call at 877-660-6853 (domestic) or 1-201-612-7415 (international) using passcode 13648359. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including the Zika vaccine GLS-5700, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended June 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


News Article | December 21, 2016
Site: www.accesswire.com

VANCOUVER, BC / ACCESSWIRE / December 21, 2016 / Petrichor Energy Inc. (FSE: YQN) (OTC PINK: ODEFF) (TSX-V: PTP) (the "Company" or "PTP") announces that it has appointed André Proulx to the Board of Directors, who will take the place of Richard Switzer, who has resigned. The Board thanks Mr. Switzer for his service as a director for the past ten years. Mr. Proulx is a founder of and served as President of Petrolia Oil Corp. from January 2002 to September 17, 2013. He also acted as President and CEO of Puma Exploration Inc. until September 16, 2010, and currently acts as Chairman of Stelmine Canada Ltd. since December 1, 2016. André holds a Master's Degree in Ethnology from Laval University obtained in 1974. The Company welcomes the expertise that Mr. Proulx will bring to its Board of Directors. For clarification, the officers and directors of the Company are now as follows: ON BEHALF OF THE BOARD SIGNED: "Joe DeVries" Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.


OTTAWA, ONTARIO--(Marketwired - Nov. 7, 2016) - Media are invited to a photo op as the Canadian Museum of Nature is graced by a Royal Couple on Monday, Nov. 7 at 2 p.m., with a visit from Norway's Crown Prince Haakon and Crown Princess Mette-Marit. The couple will preside over the opening of a special photo exhibition and symposium about the Arctic, which is coordinated by Laval University, ArcticNet and the Royal Norwegian Embassy. Prince Haakon and Princess Mette-Marit are in Canada from Nov. 7 to 10, when they will also travel to Toronto and St. John's. Their visit will reinforce the bilateral connections between Canada and Norway, highlight common interests in the Arctic and promote business collaboration. The young and dynamic Royal Couple have a keen interest in the Arctic and sustainability of the North. The temporary special exhibit, On Thin Ice, is about the "Lance", a Norwegian research vessel that entrapped itself in sea ice for a year to study how ice forms and changes, all to better understand the impact of climate change. The Royal couple actually visited the ship in action on the ice during its mission. The Symposium, from 1:30 to 4:45 p.m. features two panel presentations about Canadian and Norwegian research in the Arctic. The Canadian Museum of Nature is Canada's national museum of natural history and natural sciences. The museum provides evidence-based insights, inspiring experiences and meaningful engagement with nature's past, present and future. It achieves this through scientific research, a 10.5 million specimen collection, education programs, signature and travelling exhibitions, and a dynamic web site, nature.ca. The museum's Centre for Arctic Knowledge and Exploration provides leadership for understanding Arctic ecosystems. In June 2017, in recognition of Canada's 150th anniversary the museum will open the Canada Goose Arctic Gallery.


News Article | October 26, 2016
Site: www.newscientist.com

It’s a bold claim. Two astronomers think they have spotted messages from not just one extraterrestrial civilisation, but 234 of them. The news has sparked a lively debate in the field as other astronomers think the claim is premature and are working fast to get to the bottom of the signals. In 2012, Ermanno Borra at Laval University in Quebec suggested that an extraterrestrial civilisation might use a laser as a means of interstellar communication. If the little green men simply flashed a laser toward the Earth like a strobe light, we would see periodic bursts of light hidden in the spectrum of their host star. They would be incredibly faint and rapid, but a mathematical analysis could uncover them. “The kind of energy needed to generate this signal is not crazy,” says Borra. In fact, Borra showed that technology we have on Earth today – specifically the Helios laser at the Lawrence Livermore National Laboratory – could generate that kind of signal, should we want to reveal ourselves to the cosmos. With this in mind, Borra’s graduate student Eric Trottier combed through 2.5 million stars recorded by the Sloan Digital Sky Survey in search of such a signal. He found it, down to the exact shape, in 234 stars. The overwhelming majority of those stars are in the same spectral class as the sun, which Borra says supports his hypothesis that this signature must be the result of extraterrestrial intelligent life. And with the data in hand, he thinks that 234 distinct civilisations are beaming pulses of the same periodicity (roughly 1.65 picoseconds) toward the Earth. Borra and Trottier ruled out other possible explanations for the pattern, like rapid pulsations in the atmospheres of the stars themselves and rotational transitions in molecules. “We have to follow a scientific approach, not an emotional one,” says Borra. “But intuitively – my emotion speaks now – I strongly suspect that it’s an ETI signal.” Other astronomers think that Borra’s intuition might have run away with him. “They don’t consider every natural possibility and jump prematurely to the supernatural – so to speak – conclusion,” says Peter Plavchan at Missouri State University in Springfield. “I think it’s way too premature to do that.” “There is perhaps no bolder claim that one could make in observational astrophysics than the discovery of intelligent life beyond the Earth,” says Andrew Siemion, the director of the SETI Research Centre at the University of California Berkeley. “It’s an incredibly profound subject—and of course that’s why many of us devote our lives to the field and put so much energy into trying to answer these questions. But you can’t make such definitive statements about detections unless you’ve exhausted every possible means of follow-up.” So that’s exactly what the Breakthrough Listen Initiative—a project headed by Siemion that searches for signs of intelligent life beyond Earth—will do. The team plans to observe several stars from Borra’s sample with the 2.4-meter Automated Planet Finder telescope at the Lick Observatory in California. Borra is excited to see that others are taking the reins. “At this stage, the signal is so strange, that although our detailed analysis seems to indicate that it is a real signal, it has to be validated with more work,” he says. Still, the Breakthrough Listen team doesn’t share Borra’s enthusiasm. According to a statement, they have rated the detection as a zero to 1 on the Rio Scale for SETI observations, meaning that it is insignificant. In fact, Siemion thinks the spectral patterns were likely caused by errors in calibration or data analysis. And Plavchan agrees. He points to several steps in the team’s data analysis that “scared him” because they didn’t consider how those steps might affect their results—a red flag in any scientific claim. At the end of the day, the signal probably comes down to a human error, he says. “It’s not a bad idea to look for a signal, it’s just that they didn’t do their homework,” says Plavchan.


PLYMOUTH MEETING, Pa., Dec. 06, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today announced that the International Vaccine Institute (IVI) will provide new funding and support to further advance GLS-5300, Inovio’s vaccine to prevent Middle East Respiratory Syndrome (MERS) virus infection. Inovio is co-developing this vaccine with GeneOne Life Science. IVI will add technical, laboratory and financial support for GLS-5300 clinical trials in Korea. Inovio, GeneOne and its academic collaborators have evaluated GLS-5300 in mice, rhesus macaques and camels. As published in Science Translational Medicine, the vaccine induced robust immune responses in all three species. GLS-5300 has been specifically able to induce 100% protection from a live virus challenge in a rhesus macaque non-human primate study. The results of the non-human primate study supported the conduct of the first phase I clinical trial of 75 healthy volunteers in collaboration with the Walter Reed Army Institute of Research. Dr. J. Joseph Kim, Inovio’s President & CEO and a member of the Board of Trustees of IVI, said, “This collaborative funding is part of a 41 billion Won (USD $34 million) grant publicly pledged in 2015 from the Samsung Foundation to IVI to support the development of a MERS vaccine for emergency use in Korea and internationally. The goal of this funding is to expand clinical testing of GLS-5300 toward emergency use authorization by the Korean government as well as authorities of other countries.” “Inovio’s GLS-5300 remains the only vaccine for MERS in clinical testing. With this support from IVI, Inovio, GeneOne, and our other collaborators can expand GLS-5300 vaccine development in Korea and the US. Our phase I MERS trial in the U.S. is fully enrolled with 75 subjects dosed. We intend to report interim data in early 2017 and publish the full data set in peer reviewed journals. We already published positive non-human primate protection results. After obtaining human safety and immunogenicity data, we may be in position to secure additional external funding as well as approach regulators next year to discuss the path to approval via the “Animal Rule,” Dr. Kim said. Despite the continuing threat of MERS outbreaks, there are no licensed vaccines or treatments for MERS. Since the virus was first identified in Saudi Arabia in 2012, the World Health Organization reports almost 1,900 MERS infections and nearly 700 deaths worldwide. Twenty seven countries have reported cases, including Korea where an outbreak in the summer of 2015 resulted in 186 cases and 38 deaths. While a SARS epidemic in 2003 killed 10% of those infected, MERS has killed about 36% of people who contracted this communicable virus. The International Vaccine Institute (IVI) is the world’s only international organization devoted exclusively to developing and introducing new and improved vaccines to protect the world’s poorest people, especially children in developing countries. Established in 1997, IVI operates as an independent international organization under a treaty signed by 35 countries and the World Health Organization. The Institute conducts research in more than 20 countries of Asia, Africa and Latin America on vaccines against enteric and diarrheal infections, Japanese encephalitis, MERS, and dengue fever, and develops new and improved vaccines at its headquarters in Seoul, Republic of Korea. For more information, please visit http://www.ivi.int. GeneOne is an international company focused on finding gene-based solutions to clinical disease. GeneOne is at the forefront of DNA vaccine and DNA-based therapeutic development. GeneOne is currently spearheading clinical trials of vaccines for the Zika virus, MERS-CoV, Ebola and other infectious diseases. GeneOne has a rich pipeline of products targeting multiple cancers and diseases of man. GeneOne’s wholly-owned subsidiary VGXI, Inc. (www.vgxii.com) has 15 years of experience in the manufacture of DNA plasmid vaccines and therapeutics and has the distinction of making vaccines for Zika, MERS, and Ebola for use in human clinical trials. GeneOne is headquartered in Seoul, South Korea. For more information, visit www.genels.com. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including the MERS vaccine GLS-5300, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


PLYMOUTH MEETING, Pa., Nov. 21, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today announced that Dr. David B. Weiner, its co-founder, board member and chair of its scientific advisory board, has been selected as a “Top 20 Translational Researcher” for the year 2015 by the editors of Nature Biotechnology magazine. The selection is based on the number of medical innovations that led to patents a researcher was granted in a calendar year. The designation “translational researcher” refers to basic research that can move from the lab bench to become patented medicine. Dr. Weiner’s patented innovations relate to advancing the field of DNA-based immunotherapies targeting challenging infectious diseases and cancers. Over his career he holds more than 100 issued and pending U.S. patents. From 1986 until 2015, Dr. Weiner’s lab was at the University of Pennsylvania, Perelman School of Medicine. In 2016, Dr. Weiner joined The Wistar Institute, the nation’s first independent biomedical research institute, an NCI-designated Cancer Center, and an international leader in cancer, immunology and infectious disease research, as Executive Vice President, Director of its Vaccine Center and the W. W. Smith Charitable Trust Endowed Professorship in Cancer Research. Dr. J. Joseph Kim, Inovio's President and CEO, said, "This award acknowledges David’s innovation and commitment to creating tomorrow’s medicines with a revolutionary technology, DNA-based immunotherapies and vaccines, which Inovio is developing in early and late-stage clinical trials.  While I can say I am personally proud of my association with Dr. Weiner, which is now decades long, I can also say that we at Inovio as a team have tremendous respect and appreciation for his innovation and dedication to this field and congratulate him on this award.” Dr. Weiner is a world-renowned leader in immunology as well as gene vaccines and immunotherapy. In scientific circles he is known as the “father of DNA vaccines.” He has more than 350 peer-reviewed publications in scientific journals, including mainstream publications such as Scientific American, and has been designated by the Institute for Scientific Information as one of the top-cited scientists in the world. An inventor of more than 100 issued and pending U.S. patents, Dr. Weiner has received numerous honors including election as a fellow to the American Association for the Advancement of Science in 2011 and the International Society for Vaccines in 2012. He was the recipient of the NIH Director’s Transformative Research Award and received the Vaccine Industry Excellence Award for Best Academic Research Team in 2015 at the World Vaccine Congress. Dr. Weiner was honored with the prestigious Hilleman Lectureship in 2015 at the Children’s Hospital of Philadelphia Grand Rounds session and received a Stone Family Award from Abramson Cancer Center for his groundbreaking work on DNA vaccines for cancer immune therapy. David Weiner holds a Ph.D. in developmental biology from the University of Cincinnati College of Medicine, an M.S. in biology from the University of Cincinnati, and a B.S. in biology from SUNY at Stony Brook in Stony Brook, N.Y. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


News Article | December 14, 2016
Site: www.marketwired.com

MONTREAL, QUEBEC--(Marketwired - Dec. 14, 2016) - Canadian Metals Inc. (The "Corporation") (CSE:CME) (CSE:CME.CN) is pleased to announce the appointment of Mr. Hubert Vallee as President and CEO of Canadian Metals Inc. in replacement of Mr. Stéphane Leblanc, who will now act as chief investment officer (CIO) and a director of the Corporation. Mr. Vallée graduated from Laval University. He has been a leader in the mining industry for 30 years. He joined Quebec Cartier Mining as Project Engineer and was promoted to Director of Operations for its Pellet Plant in 2001. He managed the Iron Ore Company of Canada's Pellet Plant in Sept-Iles before joining Domtar Inc. as Mill Manager of its pulp mill in Lebel-sur-Quévillon. He joined Consolidated Thompson in 2006 and was one of the key people who made this project happen. After the sale of Consolidated Thompson to Cliffs, Mr. Vallée acted as VP Project Development for Phase II of Bloom Lake operation. He has also been involved as Senior Vice President, Project Development, at Century Iron Mines. From February 2014 he acting as CEO and President of Lamelee Iron Ore Ltd. Mr. Vallée is known for its superior abilities to bring projects on stream cost-effectively through design innovation and management processes, maintaining relationships with stakeholders. Hubert Vallée said: "I'm excited to take the lead of this promising project, I look forward at this great opportunity to move forward with an experienced team and bring this challenging project to the next level. I want to thank Stéphane for his hard work and dedication through the years, which brought the project at this stage and I expect we will continue to collaborate closely together with a common goal in developing this project successfully for shareholders as well as local stakeholders." Stéphane Leblanc, stated, "We congratulate Hubert Vallée on his appointment and welcome him to the Canadian Metals team with great expectations. We are confident that Canadian Metals is well positioned for the next stage of its growth and development. Hubert's combined mix of technical skill and experience makes him the right person to head the Company going forward. Personally it has been a tremendous honour to lead Canadian Metals over the last four years. The Company is now well positioned to eventually become the next North American silicon metal & ferrosilicon producer. I have had the privilege of working with an exceptional group of leaders as we built the foundations for what we hope will become a long-lasting success." Canadian Metals Inc. is focused exclusively on the development of its Langis Project, a high-purity silica deposit located in the province of Quebec. The Company is rapidly positioning itself to eventually become a North American silicon metal & ferrosilicon producer. Certain statements included herein may constitute "forward-looking statements". All statements included in this press release that address future events, conditions or results, including in connection with the pre-feasibility study, its financing, the hybrid flex project, job creation, the investments to complete the project and the potential performance, production and environmental footprint of the silicon plant, are forward-looking statements. These forward-looking statements can be identified by the use of words such as "may", "must", "plan", "believe", "expect", "estimate", "think", "continue", "should", "will", "could", "intend", "anticipate" or "future" or the negative forms thereof or similar variations. These forward-looking statements are based on certain assumptions and analyses made by management in light of their experiences and their perception of historical trends, current conditions and expected future developments, as well as other factors they believe are appropriate in the circumstances. These statements are subject to risks, uncertainties and assumptions, including those mentioned in the Corporation's continuous disclosure documents, which can be found under its profile on SEDAR (www.sedar.com). Many of such risks and uncertainties are outside the control of the Corporation and could cause actual results to differ materially from those expressed or implied by such forward-looking statements. In making such forward-looking statements, management has relied upon a number of material factors and assumptions, on the basis of currently available information, for which there is no insurance that such information will prove accurate. All forward-looking statements are expressly qualified in their entirety by the cautionary statements set forth above. The Corporation is under no obligation, and expressly disclaims any intention or obligation, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as expressly required by applicable law. Neither the CSE nor its Regulation Services Provider accepts responsibility for the adequacy or accuracy of this release.


PLYMOUTH MEETING, Pa., Nov. 14, 2016 (GLOBE NEWSWIRE) -- Inovio Pharmaceuticals, Inc. (NASDAQ:INO), today announced an interim data analysis showing that its INO-3112 cancer immunotherapy product generated antigen-specific CD8+ killer T cell responses measured both in tumor tissue and in peripheral blood from subjects with head and neck cancer associated with human papillomavirus (HPV). The immunology results show that INO-3112 treatment generated robust HPV16/18 specific CD8+ T cell responses in peripheral blood in four of five subjects who also showed increased T cell activation in resected tumor tissue samples. These four subjects remained disease free in continuing follow-up that ranged from nine to 24 months at the time of analysis. One subject with only minimal increases in T cell immune responses developed progressive disease at 11 months post start of the study. These results were presented November 12th at the 2016 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in National Harbor, Maryland. Dr. J. Joseph Kim, Inovio's President and CEO, said, "In immuno-oncology, it's all about the T cells. We now have evidence in cancer patients that our immunotherapy product can generate antigen-specific CD8+ killer T cell responses in the tumor, a major step forward towards an effective immunotherapy. This study gives us an important opportunity to evaluate a novel treatment approach using a DNA vaccine platform to increase immune activation by generating a robust in-vivo T cell response, especially in the tumor, and potentially decreasing tumor recurrence in HPV positive head and neck cancer patients.” INO-3112, an active immunotherapy targeting HPV 16/18 combined with a DNA plasmid for IL-12 as an immune activator, is designed to activate patients’ immune responses to specifically target and kill HPV associated tumors. This open label phase I/IIa study has fully enrolled twenty-two subjects with HPV-positive head and neck squamous cell carcinoma and is intended to assess the safety, tolerability, and immunogenicity of INO-3112 in two treatment groups. Additionally, the study is evaluating the anti-tumor response and progression free survival of patients. The first group enrolled six subjects who were treated with INO-3112 before and after resection of their tumor. One subject withdrew consent after surgery, leaving five evaluable subjects in this group. All of these subjects received one dose of INO-3112 (averaging 14 days and ranging 7 to 28 days) prior to definitive surgery plus three additional doses post-surgery. The second group enrolled sixteen subjects who received four doses of INO-3112 after at least two months following completion of definitive chemoradiation or surgery and adjuvant chemoradiation therapy. This poster presentation provided immune response and disease free survival data from the first treatment group. CD8+ and FoxP3 T cell expression were evaluated in tumor samples obtained before and after surgery. In addition, ELISpot analysis was performed to determine the number of T cells capable of secreting IFN-γ in response to HPV antigen stimulation. Four of five subjects had robust T cell response as measured by blood ELISpot assay and the same four subjects also showed an average increase of 60% of CD8+ to FoxP3 ratio measured by immunohistochemistry post vaccination, demonstrating increased infiltration of CD8+ T cells as well as reduction of regulatory T cells measured by FoxP3 expression in tumor tissue. These four subjects remained disease free with follow-up ranging from nine to 24 months to date. One subject with only a marginal increase in ELISpot response magnitude to HPV and no increase in CD8+/FoxP3 ratio in tumor tissue post INO-3112 developed progressive disease at 11 months post-treatment. Overall the characteristics of these immune response data mirrored those previously observed in a phase IIb clinical study of VGX-3100 for HPV-associated cervical dysplasia. In that study, strong CD8+ T cell immune responses were positively correlated with achievement of primary and secondary efficacy endpoints. VGX-3100 is the first therapy to demonstrate that activated killer T cells induced in the body have the power to clear neoplastic lesions as well as the virus which caused the disease. Inovio is continuing subject monitoring and comprehensive immune analyses for both cohorts of this study and expects multiple reports of additional data throughout 2017. In August 2015, Inovio licensed INO-3112 to MedImmune, the global biologics research and development arm of AstraZeneca, for an upfront payment of $27.5 million, $700 million in potential development and commercial milestone payments, and royalties on INO-3112 product sales. Human papillomavirus (HPV) is the most common sexually transmitted disease in the United States, currently infecting about 79 million Americans. HPV is known to play a major role in the development of head and neck cancers, which include cancers of the oral cavity, oropharynx, nose/nasal passages and larynx. In 2016 an estimated 48,330 persons will get oral cavity or oropharyngeal cancer in the U.S. New cases of head and neck cancer occur nearly three times more often in men as in women. Incidence rates of head and neck cancers have been on the rise, especially HPV-associated oropharyngeal cancer in men, and are expected to continue growing. Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. We are the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include MedImmune, The Wistar Institute, University of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com. This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines, our expectations regarding our research and development programs and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs, including INO-3112, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, our ability to support our broad pipeline of SynCon® active immunotherapy and vaccine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that the company and its collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2015, our Form 10-Q for the quarter ended September 30, 2016, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.


Ben Amor L.,Laval University | Ben Amor L.,Hotel Dieu Of Levis Research Center
Journal of Affective Disorders | Year: 2012

Background: Over the past few years, prescriptions of antipsychotic medications to children and adolescents have risen significantly. In particular, there is increasing use of second- and third-generation antipsychotic agents. However, numerous studies have shown clinically-relevant adverse effects (such as weight gain, metabolic disorders, prolactin changes, and extrapyramidal symptoms [EPS]) with these therapeutic agents. Moreover, only a few studies have systematically assessed antipsychotics' safety in the pediatric population. The objective of this article is to provide a comparative review of the safety data available for antipsychotic drug use in pediatric populations. Methods: A PubMed/MEDLINE search was performed for clinical studies that assessed the safety and tolerability of first-generation (typical) and second- and third-generation antipsychotics in children and adolescents with schizophrenia or bipolar disorder. Results: At standard doses, olanzapine and risperidone cause significant weight gain and related metabolic complications in patients treated with the medications. Quetiapine and ziprasidone display a better tolerability profile than risperidone and olanzapine in terms of weight gain, glucose metabolism, increases in prolactin levels, and EPS, while aripiprazole seems to be the most weight-neutral. Limitations: Most of the studies reviewed had a small sample size, a relatively short duration, and a mixed diagnosis population. Systematic analyses of antipsychotics' safety in young populations are lacking. Conclusions: The selection of antipsychotics for children and adolescents should include an evaluation of their individual therapeutic benefits, safety profiles, and approval status for use in the pediatric population. Further research of large samples and long-term follow-ups of these patient groups are warranted to help predict/manage the occurrence of adverse effects. © 2012 Elsevier B.V. All rights reserved.


Moruzzi S.,Vita-Salute San Raffaele University | Rijsdijk F.,King's College London | Battaglia M.,Laval University
Journal of Abnormal Child Psychology | Year: 2014

We investigated the etiological relationships between the three ADHD dimensions of Inattentive Problems (INP), Hyperactivity-Impulsivity Problems (HIP) and Sluggish Cognitive Tempo (SCT) as measured by the CBCL 6-18 questionnaire. Multivariate models were applied to 398 twin pairs (374 boys and 422 girls) aged 8 to 17 years (M = 13.06, SD = 2.59) belonging to the population-based Italian Twin Registry. The INP, HIP and SCT problem scores were moderately-to-substantially (range 0.29-0.47) intercorrelated. The best fitting model showed that these 3 dimensions are correlated both at the genetic (correlations' range: 0.65-0.83) and the environmental (correlations: 0.29 and 0.44) levels, but they are also distinct. While SCT showed moderate heritability and large non-shared environmental influences, variance for both INP and HIP was substantially explained by genetic influences. We also found evidence of negative sibling interaction for INP, implying that a given behavior in one twin leads to an opposite behavior in the co-twin. Our results support at the etiological level the findings of previous psychometric and longitudinal studies of ADHD, which yielded evidence of the 3 distinct - albeit correlated - problem dimensions of inattentiveness, hyperactivity-impulsivity, and sluggish cognitive tempo. © 2013 Springer Science+Business Media New York.


Sainsbury F.,John Innes Center | Sainsbury F.,Laval University | Canizares M.C.,University of Malaga | Lomonossoff G.P.,John Innes Center
Annual Review of Phytopathology | Year: 2010

In the 50 years since it was first described, Cowpea mosaic virus (CPMV) has become one of the most intensely studied plant viruses. Research in the past 15 to 20 years has shifted from studying the underlying genetics and structure of the virus to focusing on ways in which it can be exploited in biotechnology. This work led first to the use of virus particles to present peptides, then to the creation of a variety of replicating virus vectors and finally to the development of a highly efficient protein expression system that does not require viral replication. The circle has been completed by the use of the latter system to create empty particles for peptide presentation and other novel uses. The history of CPMV in biotechnology can be likened to an Ouroborus, an ancient symbol depicting a snake or dragon swallowing its own tail, thus forming a circle. © 2010 by Annual Reviews. All rights reserved.


Chaput J.-P.,Ottawa Hospital Research Institute | Bouchard C.,Pennington Biomedical Research Center | Tremblay A.,Laval University
Obesity | Year: 2014

Objective To investigate the relationship between change in sleep duration and long-term visceral adiposity change in adults. Methods A longitudinal analysis was conducted on 293 participants, aged 18-65 years, followed for a mean of 6.0 ± 0.9 years. At baseline and year 6, sleep duration was self-reported and visceral adipose tissue (VAT) assessed using computed tomography. Multivariable modeling was used to examine the association between change in sleep duration and VAT change over the 6-year time period, with adjustments made for age, sex, change in BMI, personal characteristics, energy intake, and physical activity. Results Participants gained an average of 19.2 ± 37.3 cm2 in VAT over the follow-up period. Baseline short (≤6 h/day) and long (≥9 h/day) sleepers gained significantly more VAT than those reporting sleeping 7-8 hours a night (23.4 and 20.2 cm2 vs. 14.1 cm2, respectively, P < 0.05). Using continuous data, we observed that the change in sleep duration was not associated with VAT change. However, a change in sleep duration from ≤6 h/day to 7-8 h/day was associated with 6 cm2 fewer VAT gain after multivariable adjustment (P < 0.05). Conclusions A spontaneous change in sleep duration (from a short to an adequate duration) is independently and inversely associated with long-term VAT accumulation. Copyright © 2014 The Obesity Society.


Bell A.M.,University of Illinois at Urbana - Champaign | Aubin-Horth N.,Laval University
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

Consistent individual differences in behaviour, aka personality, pose several evolutionary questions. For example, it is difficult to explain within-individual consistency in behaviour because behavioural plasticity is often advantageous. In addition, selection erodes heritable behavioural variation that is related to fitness, therefore we wish to know the mechanisms that can maintain between-individual variation in behaviour. In this paper, we argue that whole genome expression data can reveal new insights into the proximate mechanisms underlying personality, as well as its evolutionary consequences. After introducing the basics of whole genome expression analysis, we show how whole genome expression data can be used to understand whether behaviours in different contexts are affected by the same molecular mechanisms. We suggest strategies for using the power of genomics to understand what maintains behavioural variation, to study the evolution of behavioural correlations and to compare personality traits across diverse organisms. © 2010 The Royal Society.


Bouchard C.,Pennington Biomedical Research Center | Tchernof A.,Laval University | Tremblay A.,Laval University
International Journal of Obesity | Year: 2014

Objective:We have previously shown that 24 young lean men (12 pairs of identical twins) subjected to a standardized 353 MJ (84 000 kcal) overfeeding protocol over 100 days exhibited individual differences in body weight and composition gains. The mean (+s.d.) gains in fat mass (FM) and fat-free mass (FFM) were 5.4+1.9 kg and 2.7+1.5 kg for a total body energy (BE) gain of 221+75 MJ, representing 63% of the energy surplus consumed. We report here on the most important baseline correlates of these overfeeding-induced changes with the aim of identifying biomarkers of the response.Results:Baseline maximal oxygen uptake per kg body mass was negatively correlated with gains in weight, FM and BE (all P<0.05). Enzyme activities indicative of skeletal muscle oxidative potential correlated with gains in FM and BE (all P<0.05). Baseline thyroid-stimulating hormone levels in response to thyrotropin-releasing hormone stimulation correlated positively with changes in FM-to-FFM ratio (P<0.05). Plasma concentrations of androstenediol sulfate, dehydroepiandrosterone and 17-hydroxy pregnenolone were negatively correlated with gains in FM and BE (0.01


Courtemanche M.-A.,Laval University | Legare M.-A.,Laval University | Maron L.,CNRS Laboratory of Physics and Chemistry of Nano-Objects | Fontaine F.-G.,Laval University
Journal of the American Chemical Society | Year: 2013

In this work, we report that organocatalyst 1-Bcat-2-PPh2-C 6H4 ((1); cat = catechol) acts as an ambiphilic metal-free system for the reduction of carbon dioxide in presence of hydroboranes (HBR2 = HBcat (catecholborane), HBpin (pinacolborane), 9-BBN (9-borabicyclo[3.3.1]nonane), BH3·SMe2 and BH 3·THF) to generate CH3OBR2 or (CH 3OBO)3, products that can be readily hydrolyzed to methanol. The yields can be as high as 99% with exclusive formation of CH 3OBR2 or (CH3OBO)3 with TON (turnover numbers) and TOF (turnover frequencies) reaching >2950 and 853 h-1, respectively. Furthermore, the catalyst exhibits "living" behavior: once the first loading is consumed, it resumes its activity on adding another loading of reagents. © 2013 American Chemical Society.


Khuong H.T.,Service de Neurochirurgie | Khuong H.T.,Laval University | Midha R.,University of Calgary
Current Neurology and Neuroscience Reports | Year: 2013

Patients with peripheral nerve injuries face unpredictable and often suboptimal functional outcome, even following standard microsurgical nerve repair. The challenge of improving such outcomes following nerve surgical procedures has interested many research teams, in both clinical and fundamental fields. Some innovative treatments are presently being applied to a widening range of patients, whereas others will require further development before translation to human subjects. This article presents several recent advances in emerging therapies at various stages of clinical application. Nerve transfers have been successfully used in clinical settings, but new indications are being described, enlarging the range of patients who might benefit from them. Brief direct nerve electrical stimulation has been shown to improve nerve regeneration and outcome in animal models and in a small cohort of patients. Further clinical trials are warranted to prove the efficacy of this exciting and easily applicable approach. Animal studies also suggest a tremendous potential for stem and precursor cell therapy. Further studies will lead to a better understanding of their mechanisms of action in nerve repair and potential applications for human patients. © 2012 Springer Science+Business Media New York.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: GC.SST.2012.3-1. | Award Amount: 4.16M | Year: 2012

The objective of Modulushca is to achieve the first genuine contribution to the development of interconnected logistics at the European level, in close coordination with North American partners and the international Physical Internet Initiative. The goal of the project is to enable operating with developed iso-modular logistics units of sizes adequate for real modal and co-modal flows of fast-moving consumer goods (FMCG), providing a basis for an interconnected logistics system for 2030. Modulushca integrates five interrelated working fields: (1) developing a vision addressing the user needs for interconnected logistics in the FMCG domain, (2) the development of a set of exchangeable (ISO) modular logistics units providing a building block of smaller units, (3) establishing digital interconnectivity of the units, (4) development of an interconnected logistics operations platform leading to a significant reduction in costs and CO2 emissions that will be (5) demonstrated in two implementation pilots for interconnected solutions. Modulushca will establish a robust and replicable methodology to develop and evaluate solutions for interconnected logistics looking at other elements of the supply chain. Two implementation pilots will be executed integrating key Modulushca developments in significantly different supply chains: (1) a closed pilot evaluating the benefits on a inter-site supply chain addressing handling and transportation of iso-modular logistics units within one company, and (2) an open network pilot will evaluate the impact of iso-modular logistics units in cross docking and transshipment processes. Modulushca efforts will lead to the development of a road map towards a fully interconnected logistics system in 2030. The road map will address the changes and necessary steps to change the logistics system gradually, exploiting progresses in digital, physical and operational interconnectivity, building on current players, assets and infrastructures.


Turmel D.,Laval University | Parker G.,University of Illinois at Urbana - Champaign | Locat J.,Laval University
Earth-Science Reviews | Year: 2016

Wabush Lake is one of the few very well-constrained source-to-sink sedimentary systems in the world that exhibits near-continuous turbidity currents. In this system, approximately 20 million tons of mine tailings are delivered each year to a 40 km2 lake. Multibeam bathymetric surveys of this lake were carried out between 1999 and 2011. In addition, a program of extensive sampling and seismic surveys, an airborne LiDAR survey and a photogrammetric survey were carried out during this period. The objective of this study was to determine the evolution through time of this anthropic source-to-sink system, from the point where sediments exit the slurry pipelines at the head of the system to the distal end and bottom of the Lake. The total volume of the Lake is around 1 × 109 m3.Analysis of subaerial and subaqueous datasets allows the evaluation of disposal strategies on the delta topset and on tailings accumulation. Disposal strategies influence the dynamics of the channels on the topset, thus in turn affecting the accumulation of tailings throughout the lake, as well as the shoreline advancement rate. Subaqueous erosional channels present on the bed of the Lake influence the depositional pattern of tailings as well as their granulometric distribution. These erosional channels are created by the shoreward migration of knickpoints. In some places, this migration can be documented over multiple surveys.Finally, sequential analysis of the 1999, 2004, 2006, 2008 and 2011 surveys has allowed detailed documentation of the infilling of the Lake, including the migration of sediment depocenters, the mechanism of emplacement and the progressive infilling of a series of minibasins. © 2016.Published by Elsevier B.V.


Chaput J.-P.,Eastern Research Group | Despres J.-P.,Quebec Heart Institute | Bouchard C.,Pennington Biomedical Research Center | Tremblay A.,Laval University
International Journal of Obesity | Year: 2012

The objective of this longitudinal, observational study was to verify whether a favorable change in sleep duration over 6 years could impact objective indicators of adiposity in adults aged 18-64 years. Short-duration sleepers (≤6 h per day; n = 43) at baseline were divided into two groups: (i) those who increased their sleep duration to a 'healthy' length of 7-8 h per day at year 6 (mean increase: 1.52±0.66 h per day; n=23); and (ii) those who maintained their short sleep duration habits (mean change:-0.11±0.38 h per day; n = 20). Adult individuals who reported sleeping 7-8 h per day at both baseline and year 6 (n = 173) were used as a control group. Change in adiposity indicators for each sleep-duration group was compared by analysis of covariance. We observed that the two short-sleep-duration groups had similar baseline characteristics. However, short-duration sleepers who maintained their short sleep duration experienced a greater increase in body mass index (BMI) (difference: 1.1±0.36 kg m -2, P<0.05) and fat mass (difference: 2.4±0.64 kg, P<0.05) over the 6-year follow-up period than short-duration sleepers who increased their sleep duration, even after adjustment for relevant covariates. We did not observe any significant difference in adiposity changes between the control group and short-duration sleepers who increased their sleep duration. This study suggests for the first time that shifting sleep duration from a short to a healthier length is associated with an attenuation of fat mass gain.© 2012 Macmillan Publishers Limited. All rights reserved.


News Article | October 26, 2016
Site: www.csmonitor.com

Our search for extraterrestrial signals has always focused on radio, but a new study suggests that aliens may be communicating with Earth via pulsing starlight. Rumor the German shepherd confirms she is paws above the rest No more watching videos at work: Facebook will now default to audio A new study suggests aliens may be trying to make contact with Earth – not through radio broadcasts or UFO flybys, but by the flickering of distant cosmic lights. A small group of stars – just 234 out of the 2.5 million catalogued by the Sloan Digital Sky Survey (SDSS) – are acting strangely. Astronomers have observed these stars exhibiting what’s called “spectral modulation.” In other words, they’re subtly changing color in repeating patterns. Two scientists, both from Laval University in Quebec, suggest that these modulations may have been intentionally created by extraterrestrials. While many in the astronomical community doubt these “signals” were really created by aliens, the theory may expose an oversight in our search for intelligent life elsewhere in the universe. We build vast arrays of radio telescopes in hopes of 'hearing' an alien voice, but what if our interstellar visitors choose to show rather than tell? Our ears, so to speak, have long been open to the possibility of extraterrestrial life – is it time we opened our eyes? In humanity’s ceaseless quest to understand what lies beyond our planet, radio has proven to be an essential tool. Quasars, the oldest and most distant objects in the observable universe, were first discovered by radio surveys in the late 1950s. Early pioneers of the technology, such as Nikola Tesla and Guglielmo Marconi, believed they could make contact with Martian creatures through radio signals. Even today, the search for extraterrestrial life relies heavily on radio. That’s because radio waves can flow through most matter, and scientists have some degree of control over their path. “Some surveys have used lasers and other forms of optical light to communicate, but matter tends to get in the way,” Jeffrey Coughlin, a SETI Institute consultant for NASA’s Kepler Mission, tells The Christian Science Monitor in a phone interview. “There’s not much that can slow down radio waves.” “If there’s another civilization out there that’s at all like us,” he adds, “radio is the best way we know to communicate.” But the Laval University study, authored by astrophysicists Ermanno Borra and Eric Trottier, suggests a different type of communication. It interprets optical anomalies, detected by the SDSS, as alien billboards. “We consider the possibility, predicted in a previous published paper, that the signals are caused by light pulses generated by Extraterrestrial Intelligence [ETI] to make us aware of their existence,” the study reads. “We find that the detected signals have exactly the shape of an ETI signal predicted in the previous publication and are therefore in agreement with this hypothesis.” Drs. Borra and Trottier have acknowledged that the signals could also be caused by “highly peculiar chemical compositions” in a small number of stars, and have called for additional research into the matter. Even still, they have dismissed the chemical theory as “unlikely.” But as the adage goes, extraordinary claims require extraordinary evidence. And according to Dr. Coughlin, Borra and Trottier haven’t yet met that burden. While working on the Kepler exoplanet mission, Coughlin encountered similar “oddball” cases. “But we always find astrophysical explanations for them,” Coughlin says. “There’s no such thing as a perfectly invariable star.” When gamma-ray bursts were first imaged in 1997, Coughlin notes, many people believed they were alien signals. But the astronomer is quick to distinguish his skepticism from dismissal: paired with radio surveys, optical signals can still be quite telling. “I think it’s good to look,” Coughlin says, “but if you’re going to have a dedicated survey, radio is definitely the way to go.”


Ft. Lauderdale, Nov. 21, 2016 (GLOBE NEWSWIRE) -- Earth Science Tech, Inc. (OTC PINK: ETST) ("ETST" or "the Company"), an innovative biotech company focused on hemp cannabinoid research and development, nutraceuticals, pharmaceuticals, and medical devices; has announced that its wholly owned subsidiary, Earth Science Pharmaceutical, Inc., has initiated a clinical prelaunch study for its MSN-2 medical device for the diagnosis of Chlamydia and Gonorrhea in women. The study will involve 60 female patients. The company has also announced that it has elected Dr. Michel Aubé as its new CEO and CSO (Chief Scientific Officer), as well as Nickolas Tabraue as President of both Earth Science Tech, Inc., and its wholly-owned subsidiary Earth Science Pharmaceutical, Inc. This news follows the company’s August 24, 2016 announcement, “ETST Acquired the Assets and Business of BEO-ITS, Inc., a Canadian Biotech Company Specializing in Medical Devices, Tests and Vaccines for Sexually Transmitted Infections and/or Diseases.” This asset purchase agreement of BEO ITS, Inc., which was incorporated under ETST’s new wholly-owned subsidiary, Earth Science Pharmaceutical, Inc., included the employment of its CEO and principal owner, Dr. Aubé as its CEO. “I’m honored and thrilled to be the CEO and CSO of both Earth Science Tech, Inc., and Earth Science Pharmaceutical, Inc., a company focused on the development of medical devices, testing processes, and vaccines for STIs (Sexually Transmitted Infections and/or Diseases).” stated Dr. Aubé. “I am also excited to announce that Earth Science Pharmaceutical has opened a clinical prelaunch study of its MSN-2 medical device for the diagnosis of Chlamydia and Gonorrhea which will allow us to acquire the final data we need to launch the product. I have personally been working with epidemiologist Dr. Lauren Azoulay on this new study, which will involve recruiting 20 women with Chlamydia and 40 women with Gonorrhea from private medical clinics for testing with our new MSN-2 medical device. The protocol, developed by Dr. Azoulay, will allow all physicians to understand the scope and the value of the new device. The protocol, with the results and the analyzed data, will be transmitted to the authorities once finished. This study will help Earth Science Pharmaceutical acquire all the necessary major regulatory approvals including; ISO 13485, FDA, and Health Canada. The results will be combined in a scientific report in the format of a Short Report or Rapid Communication and will be published in a selected scientific journal such the International Journal of STD & AIDS or Sexual Health.” Dr. Aubé went on to say, “This small, but important study will also allow us to begin manufacturing Earth Science Pharmaceutical’s MSN-2 medical device and will provide the molecular diagnostic expertise that we need to market our MSN-2 device in all countries. I believe this data will be the final proof that our easy method for the self-collection of vaginal specimens is accurate for the diagnosis of Gonorrhea.” The accuracy of the MSN-2 medical device for the diagnosis of women with Chlamydia has already been proven via a study of 510 female patients, which showed PCR testing results on paired samples to be identical for 493 (96.6%) of the 510 women. To view this study, visit Evaluation of a Modified Sanitary Napkin as a Sample Self-Collection Device for the Detection of Genital Chlamydial Infection in Women. Using Earth Science Pharmaceutical’s new technology, a woman will be able to comfortably wear the non-invasive MSN-2 medical device (which is similar to a modified sanitary napkin but with a special filter) for 4 consecutive hours (when she is not menstruating), after which she will place the device in a special envelope packaged with the device and send it to a specific laboratory for testing. This new, simple to use technology means a woman will be able to easily take her own sample in the comfort of her home, instead of going to the doctor for an invasive swab, which can engender feelings of intrusion and/or embarrassment. “We will be releasing more details with regards to the MSN-2 medical device shortly”, added Dr. Aubé. “I plan to build this company into a global leader in the development of low cost, non-invasive diagnostic tools, medical devices, and vaccines. We will have many exciting new developments to announce in the near future, pertaining to the medical and pharmaceutical industry as well as CBD (Cannabidiol).” The global market for this type of testing is very large. Worldwide, the population of woman between the ages of 15 and 25 years is estimated to be more than 500,000,000. ETST’s target-market is all sexually active women in this age group, because the health authorities of many countries recommends that they should be tested for Chlamydia infections yearly to preserve their fertility and avoid severe complications such as cervical cancer. Per the World Health Organization, roughly 1 million new STI cases occur every day. Yearly, the number is about 131 million new cases of Chlamydia and 78 million of Gonorrhea. The United States remains the largest medical device market in the world with a market size of around $148 billion, and it is expected to reach $155 billion by 2017. The U.S. market value represented about 43 percent of the global medical device market in 2015. U.S. exports of medical devices in key product categories identified by the Department of Commerce (DOC) exceeded $44 billion in 2015. There are more than 6,500 medical device companies in the United States, mostly small and medium-sized enterprises (SMEs). Read more at https://www.selectusa.gov/medical-technology-industry-united-states. As previously announced, Earth Science Tech, Inc. (ETST) is focused on the science, research and studies of its High-Grade Hemp CBD Oil as a health and wellness, nutraceutical and dietary supplement. Feel free to view some of our Scientific Research and Data on Earth Science Tech (ETST) High Grade Hemp CBD (Cannabidiol) at http://earthsciencetech.com/scientific-research. ETST invites all interested parties to contact the company at info@earthsciencetech.com to secure its "High Grade Hemp CBD (Cannabidiol) Oil" in bulk for wholesale, resale or distribution. From product formulating, mixing, labeling and launching ETST can do it all. ETST is always open to forming new strategic partnerships, joint ventures and/or supplying vendors, resellers and third party distribution companies with its High Grade Hemp CBD (Cannabidiol) Oil/Products at wholesale prices in order to better help supply consumers as well as the health and wellness markets on a large scale. You can view, research and purchase small quantities or bottles of ETST High Grade CBD (Cannabidiol) Rich Hemp Oil and/or Products at http://www.earthsciencetech.com/cbd-rich-hemp-oil. ETST High Grade Hemp CBD is derived 100% from imported Grade-A European industrial hemp. ETST High Grade Hemp CBD Products contain hundreds of micronutrients (phytonutrients). Modern science has identified over 400 phytonutrients in various parts of the industrial hemp plant. These include hundreds of Terpenoids, Essential Oils and Antioxidants but perhaps the most dynamic are a group of compounds called Cannabinoids (phyto-cannabinoids) that are exclusively found in Hemp and one other place; our bodies. There are roughly 80 different phyto-cannabinoids, most prominently CBD, CBC, CBG, CBN, and most likely others yet to be effectively identified. In addition to the cannabinoids present in our industrial Hemp CBD Oil extracts, there are also many other types of natural molecules and “plant” chemical compounds such as amino acids, fatty acids (including omega 3 & 6), vitamins, flavonoids, ketones, nitrogenous compounds, alkanes, alcohols, glycosides, pigments and terpenes among other things. The most common terpenes in our Hemp CBD oils are Beta-caryophyllene, Caryophyllene Oxide, Myrcene, Terpinolene, α Bisabolol, α Pinene, Nerolidol, Ocimene and Phytol. Hemp oil contains more essential fatty acids than any other plant. Humans are designed with a built-in Endocannabinoid System (ECS): Research shows that many scientists believe cannabinoids work synergistically to support the whole human endo-cannabinoid system (internal and natural human cannabinoid system). It is your body's way of communicating with itself and properly regulating the way every other body system functions from your brain to your toes. The Endocannabinoid System (ECS) has shown to control pain sensation, appetite, temperature regulation, stress reactivity, immune function, and sleep as well as other processes. Even more interesting is that muscle and fat tissue also utilize these receptors to control their processes. Consumers should think of the Endocannabinoid System as one of the body's main control and command centers for tweaking your metabolism's ability to react and adapt to the world around it. Like many other nutrients in our diet, Cannabinoids can become exhausted and in need of steady dietary replenishment. Scientific studies and data show that Hemp CBD (Cannabidiol) Oil as well as all micronutrients (phytonutrients) and phyto-cannabinoids found in the oil work in harmony with the human body's own endocannabinoid system making a positive effect for overall wellness. Hemp oil contains CBD -- a non-psychoactive compound of the plant. There are millions of hemp oil consumers around the world and this number is rapidly rising with an increasing number of reports and studies showing a variety of benefits of hemp oil. ETST is focused on the science, research and studies of its High-Grade Hemp CBD Oil as a health and wellness, nutraceutical and dietary supplement. To assure the public that ETST provides the best High Grade Hemp CBD (Cannabidiol) Oil, we continue to focus on providing the public with sound scientific research and keeping the public informed on the progression of studies being done on our Hemp CBD products. ETST has engaged the expertise of a leading USA independent biological company and has been doing scientific research and studies with a University. Science is what will progress the future of ETST High Grade Hemp CBD (Cannabidiol) Oil and its products. Cannabidiol (CBD) is a naturally occurring constituent of industrial hemp oil. It is the most abundant non-psychoactive cannabinoid in hemp and is commonly used as a dietary supplement to support general wellness. ETST hemp derived, high CBD, full-spectrum phyto-cannabinoid oil blends are made from top quality, Grade-A European hemp cultivars, grown in pristine soil in choice European locations. ETST High Grade Hemp CBD oils are constantly analyzed for their purity and purity from potential contaminants. ETST encourages researching cannabidiol (CBD) from reliable informational sources to see what is being investigated and discussed about CBD oil. Numerous properties and benefits of CBD are being investigated at academic research centers in the United States and elsewhere. The FDA has not evaluated the validity or truthfulness of these claims; therefore, we encourage you to review published researches relating to the benefits and properties of CBD hemp oils and other CBD products. ETST High Grade Hemp CBD (Cannabidiol): ETST High Grade Hemp CBD (Cannabidiol) Oil is formulated using a wide array of cutting-edge technologies. ETST's High Grade Hemp CBD Oil is all-natural and derived completely from the federally legal industrial hemp plant. Industrial Hemp (Hemp) is not marijuana and will not get you 'high' and it does not require a medical license of any kind to authorize purchase. It is lab tested multiple times during the manufacturing process, from seed to shelf. This also includes being tested for CBD content, other Cannabinoid content, yeast/mold/fungus, and bacteria like E. coli to ensure safety and top quality. ETST believes that Hemp CBD Oil awareness today is where Omega 3 and Omega 6 fatty acids were 15 to 20 years ago. One of ETST's pertinent objectives is to help consumers Worldwide with their overall wellness through advanced formulations with its High Grade Hemp CBD (Cannabidiol) Oil and other cutting-edge nutraceuticals and dietary supplements. Hemp CBD Oil is poised to be the most renowned and effective natural compound and botanical alternative introduced to the nutritional and dietary supplement industry in decades. Consumers worldwide desperately need more effective and safe botanical alternatives to help them with their overall health and internal wellness. About Earth Science Tech, Inc. (ETST): Earth Science Tech (www.earthsciencetech.com) is a publicly traded (ETST) unique Science based Biotechnology company focused on cutting edge Nutraceuticals, Bioceuticals, Phytoceuticals and Cosmeceuticals for the Health, Wellness and Alternative Medicine Markets to help improve the quality of life for Consumers Worldwide. ETST is also dedicated to providing Natural Alternatives to prescription medications through the use of its cutting edge Nutritional and Dietary Supplements. This may include products such as its High-Grade Hemp CBD (Cannabidiol) Oil, Vitamins, Minerals, Herbs, Botanicals, Personal Care Products, Homeopathies, Functional Foods and other products. These products may be in various formulations and delivery systems including (but not limited to) capsules, tablets, soft gels, chewables, liquids, creams, sprays, powders, and whole herbs. ETST is focused on researching and developing innovative Hemp extracts and to make them accessible Worldwide. ETST plans to be the premier supplier of the highest quality and purity of High Grade Hemp CBD (Cannabidiol) Oil. ETST's primary goal is to advance different High Quality Hemp extracts with a broad profile of Cannabinoids and additional natural molecules found in Industrial Hemp and to identify their distinct properties. The company is dedicated in offering its consumers the finest and purest quality All Natural-Organic Hemp CBD Oil while never compromising on quality. ETST High Grade Hemp CBD (Cannabidiol) Oil is classified as "food based" and therefore perfectly permissible in all 50 states and more than 40 countries. Cannabinoids (Cannabidiol/CBD) are natural constituents of the Hemp plant and CBD is derived from Hemp stalk and seed. Hemp oil is a well-known dietary supplement and the naturally occurring CBD possesses no psychoactive qualities and presents a continuing stream of overwhelming evidence of significant Wellness benefits. With no psychoactive ingredient, Hemp CBD Oil is a ready-for-market Hemp-based Nutraceutical. The United States Food and Drug Administration (FDA) currently considers non-THC hemp based cannabinoids, including CBD, to be "food based" and therefore saleable. These new non-psychoactive CBD-rich hemp oil products that ETST has geared up to market and distribute are beyond reproach. CBD (cannabidiol), a naturally occurring constituent of the Industrial Hemp plant, promotes and supports the nutritional health of aging bodies in particular. Source: US Government Patent #6,630,507 "Cannabinoids as antioxidants and neuroprotectants." ETST does not grow, sell or distribute any substances that violate United States Law or the controlled substance act. ETST does sell and distribute hemp based products. About Earth Science Pharmaceutical: Earth Science Pharmaceutical, Inc. is a wholly owned subsidiary of Earth Science Tech, Inc (ETST). Earth Science Pharmaceutical is focused on becoming a world leader in the development of low cost, non-invasive diagnostic tools, medical devices, testing processes and vaccines for STIs (Sexually Transmitted Infections and/or Diseases). Earth Science Pharmaceutical CEO, Dr. Michel Aubé, a renowned scientist, is committed to help grow ETST in the medical and pharmaceutical industry. About Dr. Michel Aubé: Dr. Michel Aubé has wide-ranging expertise in the life sciences. As a microbiologist he furthered his graduate studies at Laval University, earning a Master’s degree in Molecular and Cell Biology as well as a PhD in Physiology-Endocrinology. In addition, he has 5 years postdoctoral experience in Immunology in three different labs at Montreal University. His scientific research in Sexually Transmitted Infections (STIs), Cancer and Stem Cell biology has been published in several prestigious medical journals. Dr. Aubé has received a number of Awards for Excellence from the Network for environmental health research and childhood diseases. FOOD AND DRUG ADMINISTRATION (FDA) DISCLOSURE: These statements and products have not been evaluated by the FDA and are not intended to diagnose, treat or cure any disease. Always check with your physician before starting a new dietary supplement program. FORWARD LOOKING DISCLAIMER: This release contains forward-looking statements that involve risks and uncertainties. Readers are referred to the Securities and Exchange Commission filings filed by the Company on EDGAR at http://www.sec.gov/edgar.shtml,specifically the most recent reports which identify important risk facts that could cause actual results to differ from those contained in the forward-looking statements. The Company undertakes no obligation to review or confirm analysts' expectations or estimates or to publicly release any revisions to any forward-looking statements. The information contained in this press release should not be construed as any indication of the Company's future stock price, its revenues or results of operations.


News Article | November 14, 2016
Site: www.eurekalert.org

Siblings bear responsibility for the spread of problem behaviors. Adolescents with a delinquent brother or sister are more likely to misuse alcohol and other substances than those without a delinquent sibling. Identifying the exact nature of that influence has proven difficult, because behavior problems in siblings can also be traced to friends, shared genetics and shared experiences with parents. Evidence describing how problem behaviors spread between siblings and across domains has been scarce - until now. Researchers from Florida Atlantic University and a consortium of universities in Quebec, Canada, conducted a first-of-its-kind longitudinal study on identical and fraternal twins to identify the degree to which siblings contribute to the increase in delinquent behavior and alcohol misuse. Results of the study, published in the journal Developmental Psychology, found that siblings play a key role in the escalation of problem behaviors over time, over and above the contributions of genes, friends and parents. The findings offer important clues into why delinquency exacerbates the growth of substance misuse in adolescents. Participants were drawn from the Quebec Newborn Twin Study, an ongoing longitudinal study of twins born between 1995 and 1998 in the greater Montreal area. Data for this study were collected at ages 13 (seventh grade), 14 (eighth grade), and 15 (ninth grade). By examining the spread of problems between twins, the researchers were able to rule out alternative explanations for increases in alcohol misuse, such as parent modeling and an inherited susceptibility to alcohol abuse that can emerge with puberty. "The hypothesis that we were testing is that somehow bad behavior on the part of one sibling -- the 'bad apple' -- spreads not just between siblings but also across domains, so that one sibling's delinquency seems to spoil everything the other sibling does, increasing problems in a host of other areas. In other words, the more delinquent one sibling is the more different problems the other sibling has," said Brett Laursen, Ph.D., lead author, professor, and graduate studies coordinator in FAU's Department of Psychology. "This turns out not to be the case. Instead, we found that problems spread between siblings within problem behavior domains -- one sibling's delinquency affects the other sibling's delinquency. Then, once the teen finds him or herself on the road of greater delinquency, problem behaviors escalate and spread of their own accord into domains such as alcohol use." Thus, problem behaviors spread indirectly between the siblings via a two-step process; first, a problem is shared between twins within a behavioral domain, then second, within each twin the problem grows and spreads across different behavioral domains. Twin sibling influence is a risk factor for illicit substance use, both because substance use by one twin predicts substance use by the other twin, but also because delinquency in one twin predicts delinquency in the other twin, which then gives rise to greater substance use. "Because problem behaviors spread indirectly between siblings, the key take home message from this study is that intervention programs needs to be targeted at specific problem behaviors and not the relationship itself," said Laursen. "It is insufficient and impractical to try to keep siblings apart, advice we often give when we try to separate adolescents from their problematic friends." Findings from this study confirm that sibling resemblance in problem behaviors cannot be entirely explained by genetics or shared environments. "Although parents are often the target of intervention, practitioners would be well advised to focus their efforts on siblings, who are more influential than parents when it comes to substance use and delinquency, and whose influence rivals that of friends," said Laursen. Laursen co-authored the study with Amy C. Hartl, a Ph.D. student at FAU; Frank Vitaro, Ph.D., University of Montreal; Mara Brendgen, Ph.D., University of Quebec at Montreal; Ginette Dionne, Ph.D., Laval University; and Michel Boivin, Ph.D., Laval University and Tomsk State University. Funding for this study was provided by the Social Science and Humanities Research Council of Canada, the Canadian Institutes of Health Research, and the Fonds Québécois de Recherche sur la Société et la Culture.


VANCOUVER, BC--(Marketwired - November 30, 2016) - Integra Gold Corp. (TSX VENTURE: ICG) ( : ICGQF), ("Integra" or the "Company") is pleased to announce the appointment of Mr. Raynald Vézina to its Board of Directors ("Board"). Mr. Vézina, a mining engineer with a long and successful career focussed on mine building and operations in Québec, will join the Board as a non-executive, independent director. George Salamis, Executive Chairman of the Board, commented, "As Integra transitions from an exploration company to an advanced-stage, operations focussed company, the addition of Mr. Vézina, with his background in the construction of underground mines and operations in Québec, make him a great asset to our Board." "Highly regarded within the ranks of the Québec mining industry, Mr. Vézina played an instrumental role during one of Québec's most prolific growth stages for the mining industry, 1980 to 1995. During this period, Mr. Vézina took a lead role in the construction and operation of 8 mines, a monumental feat by any measure. The team at Integra looks forward to Mr. Vézina's input as Integra enters into this next important phase of growth in Québec, both at the Triangle Deposit and elsewhere." Mr. Vézina is a graduate of Laval University's mining engineering program and has served in several executive positions during his 40 year career, both in Québec and abroad. In the 1970s and 1980s, Mr. Vézina held several positions at Falconbridge Limited within the engineering and operations group, including the position of General Superintendent of Operations of the Lac Dufault division, based in Rouyn-Noranda, Québec. Through the 1980s, he held the position of General Manager of the Kiena Gold Mine, long considered to be the sister operation to the Sigma Mine which was acquired, along with the Sigma Mill and historic Lamaque Mine, by Integra in 2014. At the Kiena Gold Mine, Mr. Vézina was involved in the construction of the underground mine and mill complex and went on to supervise gold production at the mine on behalf of its owners Falconbridge Nickel Ltd. and then Placer Dome Inc. In 1988, Mr. Vézina joined the ranks of Cambior Inc. as Senior Vice President of Mining Operations, managing the construction and operation of 8 mines (7 underground and 1 open pit), including 7 in Québec. This period in time, 1980 to 1995, is regarded as one of the largest periods of exponential resource growth and mining expansion in the history of Québec, and Mr. Vézina is widely viewed as being an integral part of that growth. Mr. Vézina is a member of the "Quebec Order of Engineers," a Fellow of the Canadian Institute of Mining and a consultant on mining engineering projects across the globe. Integra Gold is a junior gold exploration company advancing projects in Val-d'Or, Québec, one of the top mining jurisdictions in the world. The Company's primary focus is its high-grade Lamaque South project. In the fall of 2014, Integra completed the accretive acquisition of the Sigma Mill and Mine Complex, a fully permitted 2,200 ton per day mill and tailings facility. With major federal and provincial permits in place, existing infrastructure and significant exploration potential, this acquisition removed major costs and shortened timelines typically associated with mine projects. Integra has raised over $120 million since 2013, at successively higher share prices, despite depressed gold prices. In August 2015, Eldorado Gold Corporation completed a strategic investment in Integra, acquiring 15% of the outstanding common shares. Integra was recently named to the TSX Venture top 50 performers in 2015 and the OTCQX Best 50 award for 2015. ON BEHALF OF THE BOARD OF DIRECTORS Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this news release. Cautionary Note Regarding Forward-Looking Statements: Certain disclosures in this release constitute forward-looking statements, including timing of completion of an updated resource estimate, timing of completion of an updated PEA and completion of the Sigma-Lamaque transaction. In making the forward-looking statements in this release, the Company has applied certain factors and assumptions that are based on the Company's current beliefs as well as assumptions made by and information currently available to the Company, including that the Company is able to obtain any government or other regulatory approvals, that the Company is able to procure personnel, equipment and supplies required for its exploration and development activities in sufficient quantities and on a timely basis and that actual results are consistent with management's expectations. Although the Company considers these assumptions to be reasonable based on information currently available to it, they may prove to be incorrect, and the forward-looking statements in this release are subject to numerous risks, uncertainties and other factors that may cause future results to differ materially from those expressed or implied in such forward-looking statements. Such risk factors include, among others, those matters identified in its continuous disclosure filings, including its most recently filed MD&A. Readers are cautioned not to place undue reliance on forward-looking statements. The Company does not intend, and expressly disclaims any intention or obligation to, update or revise any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law.


News Article | February 27, 2017
Site: www.marketwired.com

VANCOUVER, BC--(Marketwired - February 27, 2017) - Genesis Metals Corp. (the "Company") (TSX VENTURE: GIS) is pleased to announce that it has appointed Éric Lemieux, MSc, PGeo. as a strategic advisor to the company. Éric Lemieux is a professional geologist and mining analyst based in Québec, Canada. Most recently, Éric was a consulting technical advisor with PearTree Securities Inc. of Toronto, a leading provider of flow-through share donation financing services in Canada. Previously he was with Laurentian Bank Securities in Montreal, as a sell-side mining analyst. His coverage included gold, base-metal, diamond and uranium exploration and development issuers as well as unconventional shale oil and gas plays in the Province of Québec. He also acted as an independent consultant to the Québec and New Brunswick Securities Commissions where he was responsible for NI 43-101 compliance. In the 1990's, Éric was a geologist-analyst with the Montreal Exchange and managed previously exploration projects for Cambior, Noranda and SOQUEM. Éric holds two Master's degrees, one in Mineral Economics from the Colorado School of Mines and in another in Metamorphic-Structural Geology from Laval University in Quebec City. The Company has also engaged O&M Partners LLC to assist in non-deal institutional marketing. The New York firm maintains strong relationships with accredited investors and money managers across 22 cities in the United States. Marketing will include group town hall conference calls and follow-up road shows. The Company will pay a total of $18,000 (U.S.) to O&M over a six-month term. 100,000 stock options have been granted to O&M subject to the approval of the TSX Venture Exchange. Genesis also announces that the Company has granted an aggregate of 375,000 stock options to employees and consultants of the Company including O&M Partners. Each stock option entitles the holder to purchase one common share of the Company at a price of CAD $0.20 cents per common share for a period of five years from the grant date. Genesis has completed the acquisition of the Hygrade property from Les Ressources Tectonic Inc and has received acceptance from the TSX Venture Exchange. The property is located within the boundaries of the company's Chevrier project near Chibougamau, Que. ON BEHALF OF THE BOARD OF DIRECTORS Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. Certain disclosure in this release, including statements regarding the intended use of proceeds from the private placement, constitute forward-looking information or statements (collectively, "forward-looking statements") for the purpose of applicable securities laws. In making the forward-looking statements, the Company has applied certain factors and assumptions that are based on the Company's current beliefs as well as assumptions made by and information currently available to the Company, including that the Company is able to obtain any government or other regulatory approvals required to complete the Company's planned exploration and development activities, that the Company is able to procure personnel, equipment and supplies required for its exploration and development activities in sufficient quantities and on a timely basis and that actual results of exploration activities are consistent with management's expectations. Although the Company considers these assumptions to be reasonable based on information currently available to it, they may prove to be incorrect, and the forward-looking statements in this release are subject to numerous risks, uncertainties and other factors that may cause future results to differ materially from those expressed or implied in such forward-looking statements. Such risk factors include, among others, that the Company will be unable to obtain required regulatory approvals on a timely basis or at all, that actual results of the Company's exploration activities will be different than those expected by management and that the Company will be unable to obtain or will experience delays in obtaining any required government approvals or be unable to procure required equipment and supplies in sufficient quantities and on a timely basis. Readers are cautioned not to place undue reliance on forward-looking statements. The Company does not intend, and expressly disclaims any intention or obligation to, update or revise any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law.


News Article | October 26, 2016
Site: www.csmonitor.com

Our search for extraterrestrial signals has always focused on radio, but a new study suggests that aliens may be communicating with Earth via pulsing starlight. Rumor the German shepherd confirms she is paws above the rest No more watching videos at work: Facebook will now default to audio A new study suggests aliens may be trying to make contact with Earth – not through radio broadcasts or UFO flybys, but by the flickering of distant cosmic lights. A small group of stars – just 234 out of the 2.5 million catalogued by the Sloan Digital Sky Survey (SDSS) – are acting strangely. Astronomers have observed these stars exhibiting what’s called “spectral modulation.” In other words, they’re subtly changing color in repeating patterns. Two scientists, both from Laval University in Quebec, suggest that these modulations may have been intentionally created by extraterrestrials. While many in the astronomical community doubt these “signals” were really created by aliens, the theory may expose an oversight in our search for intelligent life elsewhere in the universe. We build vast arrays of radio telescopes in hopes of 'hearing' an alien voice, but what if our interstellar visitors choose to show rather than tell? Our ears, so to speak, have long been open to the possibility of extraterrestrial life – is it time we opened our eyes? In humanity’s ceaseless quest to understand what lies beyond our planet, radio has proven to be an essential tool. Quasars, the oldest and most distant objects in the observable universe, were first discovered by radio surveys in the late 1950s. Early pioneers of the technology, such as Nikola Tesla and Guglielmo Marconi, believed they could make contact with Martian creatures through radio signals. Even today, the search for extraterrestrial life relies heavily on radio. That’s because radio waves can flow through most matter, and scientists have some degree of control over their path. “Some surveys have used lasers and other forms of optical light to communicate, but matter tends to get in the way,” Jeffrey Coughlin, a SETI Institute consultant for NASA’s Kepler Mission, tells The Christian Science Monitor in a phone interview. “There’s not much that can slow down radio waves.” “If there’s another civilization out there that’s at all like us,” he adds, “radio is the best way we know to communicate.” But the Laval University study, authored by astrophysicists Ermanno Borra and Eric Trottier, suggests a different type of communication. It interprets optical anomalies, detected by the SDSS, as alien billboards. “We consider the possibility, predicted in a previous published paper, that the signals are caused by light pulses generated by Extraterrestrial Intelligence [ETI] to make us aware of their existence,” the study reads. “We find that the detected signals have exactly the shape of an ETI signal predicted in the previous publication and are therefore in agreement with this hypothesis.” Drs. Borra and Trottier have acknowledged that the signals could also be caused by “highly peculiar chemical compositions” in a small number of stars, and have called for additional research into the matter. Even still, they have dismissed the chemical theory as “unlikely.” But as the adage goes, extraordinary claims require extraordinary evidence. And according to Dr. Coughlin, Borra and Trottier haven’t yet met that burden. While working on the Kepler exoplanet mission, Coughlin encountered similar “oddball” cases. “But we always find astrophysical explanations for them,” Coughlin says. “There’s no such thing as a perfectly invariable star.” When gamma-ray bursts were first imaged in 1997, Coughlin notes, many people believed they were alien signals. But the astronomer is quick to distinguish his skepticism from dismissal: paired with radio surveys, optical signals can still be quite telling. “I think it’s good to look,” Coughlin says, “but if you’re going to have a dedicated survey, radio is definitely the way to go.”


Nguyen T.-D.,Laval University | Tran T.-H.,Hue University
RSC Advances | Year: 2014

Simultaneous integration of multifunctional properties from different components into a hybrid nanostructure with hierarchical organization is attractive to construct new materials sought for diverse useful applications. This review highlights recent advances in the fabrication of multicomponent organic-conjugated inorganic nanoarchitectures and their potential uses in optical sensing and diagnostic tools. The similarity of the particle sizes, between inorganic hybrids and biomolecules, is the reason they can integrate into new bioconjugated nanocomposites. These multifunctional properties enable such materials to function as dual diagnostic and therapeutic agents in imaging-guided therapy. Deoxyribonucleic acid (DNA)-templated replica approaches for fabricating DNA-functionalized plasmonic nanoarchitectures are discussed to show how incorporation of metal clusters onto helical DNA structures occurs. The resulting helix plasmonic assemblies response enhanced plasmonic properties and circular dichroism signals to external environments, means they can function as highly selective bioprobes. Nanocrystal superlattices are prepared by assembling the uniform colloids by guiding the external magnetic field and solvent evaporation. The highly organized superlattices with long-range ordering exhibit optical properties tuned by external stimuli and, consequently they can be useful for desirable optical sensors and photoswitchable patterns. The efforts discussed in this review are expected to present the structural diversity of promising multifunctional nanoarchitectures for the design of efficient optical sensing and diagnostic tools. © The Royal Society of Chemistry 2014.


Alishahi A.,Gorgan University of Agricultural Sciences and Natural Resources | Aider M.,Laval University
Food and Bioprocess Technology | Year: 2012

There has recently been an increasing interest in seafood products due to the growing awareness of their nutraceutical value. However, marine-based products are highly susceptible to deterioration, mainly because of their high contents of polyunsaturated fatty acids (PUFAs), their high water activity, abundant free amino acids, neutral pH, and the presence of autolytic enzymes. In recent decades, various alternative methods have been developed to address this issue. Among the proposed solutions, chitosan has been highlighted as one of the most promising solutions. Chitosan, a deacetylated derivative of chitin, has attracted high consideration for its nontoxicity, biocompatibility, and biodegradability. Moreover, it is a polymer with versatile functional properties. For this reason, chitosan, which is commercially produced mostly from marine sources (e. g., crustacean shells), has been used to stabilize seafood-based products. In this review, chitosan is highlighted with respect to the various potential applications exploiting its many features, such as antibacterial and antioxidant properties, edible film- and coating-forming ability, the treatment of seafood industry effluent, enhanced gelling properties, micro- and nanocarrier abilities for bioactive compounds, functional foods, and drug compounds from aquaculture and seafood. © 2011 Springer Science+Business Media, LLC.


Dinh C.-T.,Laval University | Seo Y.,KAIST | Nguyen T.-D.,Laval University | Kleitz F.,Laval University | Do T.-O.,Laval University
Angewandte Chemie - International Edition | Year: 2012

Building with nanobricks: Uniform titanate nanodisks with a controlled diameter of 12-35 nm were synthesized by a non-aqueous method. These nanodisks were used for the design of various titanate-based mesoporous hybrids with a high specific surface area and tailored porosity. They could also be used as efficient stabilizers for the synthesis of small, uniform metal nanoparticles that exhibit enhanced catalytic activity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yen H.,Laval University | Seo Y.,KAIST | Kaliaguine S.,Laval University | Kleitz F.,Laval University
Angewandte Chemie - International Edition | Year: 2012

Porosity control: Mixed metal oxides (CuM/CeO2, M=Co, Fe) with tailored porosity were prepared by improved hard templating. These materials were highly active and selective catalysts for low-temperature oxidation of CO in the presence of excess H2 (see picture), a process which is central for the practical use of H2 in proton-exchange membrane fuel cells. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Tran T.-H.,Hue University | Nguyen T.-D.,Laval University
Colloids and Surfaces B: Biointerfaces | Year: 2011

Aqueous-dispersed single and binary noble metal nanocrystals have attracted much attention as key materials in many fields, especially in biomedicine, catalysis, etc. Controlled growth of the metal nuclei allow for the manipulation of uniform morphology of final products. This behavior would tailor their unique physiochemical and electronic properties and follows by their practical applications. This review presents an overall picture of kinetic formation of a particle and then summarizes an overview of recent progress in many research groups concerning aqueous- and/or polyol-based syntheses of many types of aqueous-dispersed single metallic and bimetallic nanocrystals with controlled shape. The main advantages in these synthetic approaches for the shape-controlled metal nanocrystals are simple, versatile, environmentally friendly, low cost, pure and single-crystalline products, and high yield. The formed products can be easily dispersed in water medium and compatible for biotechnological field. Particularly the biomolecule (antibody including protein and/or DNA)-conjugated gold nanocrystals have been utilized as an active agent for a broad range of biomedical applications. We expect that this review will have a high potential towards novel materials fabrication and nanotechnological fields. © 2011.


Bouchard M.,Laval University | Jousselme A.-L.,Canadian Department of National Defence | Dore P.-E.,University of Rennes 1
International Journal of Approximate Reasoning | Year: 2013

In this paper we provide a proof for the positive definiteness of the Jaccard index matrix used as a weighting matrix in the Euclidean distance between belief functions defined in Jousselme et al. [13]. The idea of this proof relies on the decomposition of the matrix into an infinite sum of positive semidefinite matrices. The proof is valid for any size of the frame of discernment but we provide an illustration for a frame of three elements. The Jaccard index matrix being positive definite guaranties that the associated Euclidean distance is a full metric and thus that a null distance between two belief functions implies that these belief functions are strictly identical. Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved.


Morillo C.A.,Hamilton Health Sciences | Verma A.,Southlake Regional Health Center | Connolly S.J.,Hamilton Health Sciences | Kuck K.H.,Asklepios Klinik St Georg | And 6 more authors.
JAMA - Journal of the American Medical Association | Year: 2014

IMPORTANCE: Atrial fibrillation (AF) is the most common rhythm disorder seen in clinical practice. Antiarrhythmic drugs are effective for reduction of recurrence in patients with symptomatic paroxysmal AF. Radiofrequency ablation is an accepted therapy in patients for whom antiarrhythmic drugs have failed; however, its role as a first-line therapy needs further investigation. OBJECTIVE: To compare radiofrequency ablation with antiarrhythmic drugs (standard therapy) in treating patients with paroxysmal AF as a first-line therapy. DESIGN, SETTING, AND PATIENTS: A randomized clinical trial involving 127 treatment-naive patients with paroxysmal AF were randomized at 16 centers in Europe and North America to received either antiarrhythmic therapy or ablation. The first patient was enrolled July 27, 2006; the last patient, January 29, 2010. The last follow-up was February 16, 2012. INTERVENTIONS: Sixty-one patients in the antiarrhythmic drug group and 66 in the radiofrequency ablation group were followed up for 24 months. MAIN OUTCOMES AND MEASURES: The time to the first documented atrial tachyarrhythmia of more than 30 seconds (symptomatic or asymptomatic AF, atrial flutter, or atrial tachycardia), detected by either scheduled or unscheduled electrocardiogram, Holter, transtelephonic monitor, or rhythm strip, was the primary outcome. Secondary outcomes included symptomatic recurrences of atrial tachyarrhythmias and quality of life measures assessed by the EQ-5D tool. RESULTS: Forty-four patients (72.1%) in the antiarrhythmic group and in 36 patients (54.5%) in the ablation group experienced the primary efficacy outcome (hazard ratio [HR], 0.56 [95% CI, 0.35-0.90]; P = .02). For the secondary outcomes, 59% in the drug group and 47% in the ablation group experienced the first recurrence of symptomatic AF, atrial flutter, atrial tachycardia (HR, 0.56 [95% CI, 0.33-0.95]; P = .03). No deaths or strokes were reported in either group; 4 cases of cardiac tamponade were reported in the ablation group. In the standard treatment group, 26 patients (43%) underwent ablation after 1-year. Quality of life was moderately impaired at baseline in both groups and improved at the 1 year follow-up. However, improvement was not significantly different among groups. CONCLUSIONS AND RELEVANCE: Among patients with paroxysmal AF without previous antiarrhythmic drug treatment, radiofrequency ablation compared with antiarrhythmic drugs resulted in a lower rate of recurrent atrial tachyarrhythmias at 2 years. However, recurrence was frequent in both groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00392054 Copyright 2014 American Medical Association. All rights reserved.


Therrien J.-F.,Acopian Center for Conservation Learning | Gauthier G.,Laval University | Korpimaki E.,University of Turku | Bety J.,University of Quebec at Rimouski
Ecology | Year: 2014

Predation has been suggested to be especially important in simple food webs and less productive ecosystems such as the arctic tundra, but very few data are available to evaluate this hypothesis. We examined the hypothesis that avian predators could drive the population dynamics of two cyclic lemming species in the Canadian Arctic. A dense and diverse suite of predatory birds, including the Snowy Owl (Bubo scandiacus), the Rough-legged Hawk (Buteo lagopus), and the Long-tailed Jaeger (Stercorarius longicaudus), inhabits the arctic tundra and prey on collared (Dicrostonyx groenlandicus) and brown (Lemmus trimucronatus) lemmings during the snow-free period. We evaluated the predation pressure exerted by these predators by combining their numerical (variation in breeding and fledgling numbers) and functional (variation in diet and daily consumption rates) responses to variations in lemming densities over the 2004-2010 period. Breeding density and number of fledglings produced by the three main avian predators increased sharply without delay in response to increasing lemming densities. The proportion of collared lemmings in the diet of those predators was high at low lemming density (both species) but decreased as lemming density increased. However, we found little evidence that their daily consumption rates vary in relation to changes in lemming density. Total consumption rate by avian predators initially increased more rapidly for collared lemming but eventually leveled off at a much higher value for brown lemmings, the most abundant species at our site. The combined daily predation rate of avian predators exceeded the maximum daily potential growth rates of both lemming species except at the highest recorded densities for brown lemmings. We thus show, for the first time, that predation pressure exerted without delay by avian predators can limit populations of coexisting lemming species during the snow-free period, and thus, that predation could play a role in the cyclic dynamic of these species in the tundra. © 2014 by the Ecological Society of America.


Fraser D.J.,Concordia University at Montréal | Weir L.K.,Simon Fraser University | Bernatchez L.,Laval University | Hansen M.M.,University of Aarhus | Taylor E.B.,University of British Columbia
Heredity | Year: 2011

What is the extent and scale of local adaptation (LA)? How quickly does LA arise? And what is its underlying molecular basis? Our review and meta-analysis on salmonid fishes estimates the frequency of LA to be ∼55-70%, with local populations having a 1.2 times average fitness advantage relative to foreign populations or to their performance in new environments. Salmonid LA is evident at a variety of spatial scales (for example, few km to gt; 1000 km) and can manifest itself quickly (6-30 generations). As the geographic scale between populations increases, LA is generally more frequent and stronger. Yet the extent of LA in salmonids does not appear to differ from that in other assessed taxa. Moreover, the frequency with which foreign salmonid populations outperform local populations (∼23-35%) suggests that drift, gene flow and plasticity often limit or mediate LA. The relatively few studies based on candidate gene and genomewide analyses have identified footprints of selection at both small and large geographical scales, likely reflecting the specific functional properties of loci and the associated selection regimes (for example, local niche partitioning, pathogens, parasites, photoperiodicity and seasonal timing). The molecular basis of LA in salmonids is still largely unknown, but differential expression at the same few genes is implicated in the convergent evolution of certain phenotypes. Collectively, future research will benefit from an integration of classical and molecular approaches to understand: (i) species differences and how they originate, (ii) variation in adaptation across scales, life stages, population sizes and environmental gradients, and (iii) evolutionary responses to human activities. © 2011 Macmillan Publishers Limited All rights reserved.


Rulten S.L.,University of Sussex | Fisher A.E.O.,University of Sussex | Robert I.,University of Strasbourg | Zuma M.C.,University of Sussex | And 5 more authors.
Molecular Cell | Year: 2011

PARP-3 is a member of the ADP-ribosyl transferase superfamily of unknown function. We show that PARP-3 is stimulated by DNA double-strand breaks (DSBs) in vitro and functions in the same pathway as the poly (ADP-ribose)-binding protein APLF to accelerate chromosomal DNA DSB repair. We implicate PARP-3 in the accumulation of APLF at DSBs and demonstrate that APLF promotes the retention of XRCC4/DNA ligase IV complex in chromatin, suggesting that PARP-3 and APLF accelerate DNA ligation during nonhomologous end-joining (NHEJ). Consistent with this, we show that class switch recombination in Aplf-/- B cells is biased toward microhomology-mediated end-joining, a pathway that operates in the absence of XRCC4/DNA ligase IV, and that the requirement for PARP-3 and APLF for NHEJ is circumvented by overexpression of XRCC4/DNA ligase IV. These data identify molecular roles for PARP-3 and APLF in chromosomal DNA double-strand break repair reactions. © 2011 Elsevier Inc.


Gauthier G.,Laval University | Milot E.,Laval University | Weimerskirch H.,CNRS Chizé Center for Biological Studies
Journal of Animal Ecology | Year: 2010

1. Dispersal is a fundamental but still poorly known process in population dynamics and several hypotheses have been proposed to explain its patterns. We studied natal and breeding dispersal and survival in a long-lived seabird, the wandering albatross (Diomedea exulans L.), and examined several hypotheses concerning dispersal patterns in birds. 2. We applied multi-state capture-recapture models to a 36-year data set (1969-2004) collected at three albatross colonies on Î le de Possession, Crozet Islands. Because the species has biennial reproduction, we introduced unobservable states in the model to account for the absence of individuals in those years. 3. Adults were highly faithful to their nesting colony but colony fidelity, as well as survival rate, differed slightly among colonies (fidelity ranged from 0Æ957 to 0Æ977). Breeding fidelity was highest in the colony where survival was lowest and individuals were not more likely to change colony following a failed breeding attempt than after a successful one. The colony that attracted most dispersers had the lowest density of nesting birds. 4. Philopatry (the probability that young return to breed at a birth site) was generally high but variable among colonies (ranging from 0Æ70 to 0Æ92), and survival of young differed little. Philopatry was highest in the largest colony, where the availability of potential mates was presumably greatest. However, among dispersing individuals, the colony that had the lowest density of nesting individuals, not the largest colony, attracted the most recruits. 5. Although size of the colony influenced the decision to stay or to leave in young, density was most influential in the selection of a new colony among both adult and young dispersers. Our results support the hypothesis that philopatry is the strategy favoured by most recruits and that conspecific attraction can explain variation in the level of philopatry among colonies but not settlement patterns among dispersing individuals. © 2010 The Authors. Journal compilation © 2010 British Ecological Society.


Mease P.J.,Swedish Medical Center | Genovese M.C.,Stanford University | Greenwald M.W.,Desert Medical Advances | Ritchlin C.T.,University of Rochester | And 6 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: We assessed the efficacy and safety of brodalumab, a human monoclonal antibody against interleukin-17 receptor A (IL17RA), in a phase 2, randomized, double-blind, placebo-controlled study involving patients with psoriatic arthritis. METHODS: We randomly assigned patients with active psoriatic arthritis to receive brodalumab (140 or 280 mg subcutaneously) or placebo on day 1 and at weeks 1, 2, 4, 6, 8, and 10. At week 12, patients who had not discontinued their participation in the study were offered open-label brodalumab (280 mg) every 2 weeks. The primary end point was 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 12. RESULTS: Of the 168 patients who underwent randomization (57 in the brodalumab 140-mg group, 56 in the brodalumab 280-mg group, and 55 in the placebo group), 159 completed the double-blind phase and 134 completed 40 weeks of the open-label extension. At week 12, the brodalumab 140-mg and 280-mg groups had higher rates of ACR 20 than the placebo group (37% [P = 0.03] and 39% [P = 0.02], respectively, vs. 18%); they also had higher rates of 50% improvement (ACR 50) (14% [P = 0.05] and 14% [P = 0.05] vs. 4%). Rates of 70% improvement were not significantly higher in the brodalumab groups. Similar degrees of improvement were noted among patients who had received previous biologic therapy and those who had not received such therapy. At week 24, ACR 20 response rates in the brodalumab 140-mg and 280-mg groups were 51% and 64%, respectively, as compared with 44% among patients who switched from placebo to open-label brodalumab; responses were sustained through week 52. At week 12, serious adverse events had occurred in 3% of patients in the brodalumab groups and in 2% of those in the placebo group. CONCLUSIONS: Brodalumab significantly improved response rates among patients with psoriatic arthritis. Larger studies of longer duration are necessary to assess adverse events. Copyright © 2014 Massachusetts Medical Society.


Gagnaire P.-A.,Laval University | Normandeau E.,Laval University | Cote C.,Laval University | Hansen M.M.,University of Aarhus | Bernatchez L.,Laval University
Genetics | Year: 2012

Our understanding of the genetic basis of local adaptation has recently benefited from the increased power to identify functional variants associated with environmental variables at the genome scale. However, it often remains challenging to determine whether locally adaptive alleles are actively maintained at intermediate frequencies by spatially varying selection. Here, we evaluate the extent to which this particular type of balancing selection explains the retention of adaptive genetic variation in the extreme situation of perfect panmixia, using the American eel (Anguilla rostrata) as a model. We first conducted a genome scan between two samples from opposite ends of a latitudinal environmental gradient using 454 sequencing of individually tagged cDNA libraries. Candidate SNPs were then genotyped in 992 individuals from 16 sampling sites at different life stages of the same cohort (including larvae from the Sargasso Sea, glass eels, and 1-year-old individuals) as well as in glass eels of the following cohort. Evidence for spatially varying selection was found at 13 loci showing correlations between allele frequencies and environmental variables across the entire species range. Simulations under a multiple-niche Levene's model using estimated relative fitness values among genotypes rarely predicted a stable polymorphic equilibrium at these loci. Our results suggest that some genetic-by-environment interactions detected in our study arise during the progress toward fixation of a globally advantageous allele with spatially variable effects on fitness. © 2012 by the Genetics Society of America.


Home > Press > Core technology springs from nanoscale rods: Rice University lab turns nanorods into multistate switches with an electron beam Abstract: Rice University scientists have discovered how to subtly change the interior structure of semi-hollow nanorods in a way that alters how they interact with light, and because the changes are reversible, the method could form the basis of a nanoscale switch with enormous potential. "It's not 0-1, it's 1-2-3-4-5-6-7-8-9-10," said Rice materials scientist Emilie Ringe, lead scientist on the project, which is detailed in the American Chemical Society journal Nano Letters. "You can differentiate between multiple plasmonic states in a single particle. That gives you a kind of analog version of quantum states, but on a larger, more accessible scale." Ringe and colleagues used an electron beam to move silver from one location to another inside gold-and-silver nanoparticles, something like a nanoscale Etch A Sketch. The result is a reconfigurable optical switch that may form the basis for a new type of multiple-state computer memory, sensor or catalyst. At about 200 nanometers long, 500 of the metal rods placed end-to-end would span the width of a human hair. However, they are large in comparison with modern integrated circuits. Their multistate capabilities make them more like reprogrammable bar codes than simple memory bits, she said. "No one has been able to reversibly change the shape of a single particle with the level of control we have, so we're really excited about this," Ringe said. Altering a nanoparticle's internal structure also alters its external plasmonic response. Plasmons are the electrical ripples that propagate across the surface of metallic materials when excited by light, and their oscillations can be easily read with a spectrometer -- or even the human eye -- as they interact with visible light. The Rice researchers found they could reconfigure nanoparticle cores with pinpoint precision. That means memories made of nanorods need not be merely on-off, Ringe said, because a particle can be programmed to emit many distinct plasmonic patterns. The discovery came about when Ringe and her team, which manages Rice's advanced electron microscopy lab, were asked by her colleague and co-author Denis Boudreau, a professor at Laval University in Quebec, to characterize hollow nanorods made primarily of gold but containing silver. "Most nanoshells are leaky," Ringe said. "They have pinholes. But we realized these nanorods were defect-free and contained pockets of water that were trapped inside when the particles were synthesized. We thought: We have something here." Ringe and the study's lead author, Rice research scientist Sadegh Yazdi, quickly realized how they might manipulate the water. "Obviously, it's difficult to do chemistry there, because you can't put molecules into a sealed nanoshell. But we could put electrons in," she said. Focusing a subnanometer electron beam on the interior cavity split the water and inserted solvated electrons – free electrons that can exist in a solution. "The electrons reacted directly with silver ions in the water, drawing them to the beam to form silver," Ringe said. The now-silver-poor liquid moved away from the beam, and its silver ions were replenished by a reaction of water-splitting byproducts with the solid silver in other parts of the rod. "We actually were moving silver in the solution, reconfiguring it," she said. "Because it's a closed system, we weren't losing anything and we weren't gaining anything. We were just moving it around, and could do so as many times as we wished." The researchers were then able to map the plasmon-induced near-field properties without disturbing the internal structure -- and that's when they realized the implications of their discovery. "We made different shapes inside the nanorods, and because we specialize in plasmonics, we mapped the plasmons and it turned out to have a very nice effect," Ringe said. "We basically saw different electric-field distributions at different energies for different shapes." Numerical results provided by collaborators Nicolas Large of the University of Texas at San Antonio and George Schatz of Northwestern University helped explain the origin of the modes and how the presence of a water-filled pocket created a multitude of plasmons, she said. The next challenge is to test nanoshells of other shapes and sizes, and to see if there are other ways to activate their switching potentials. Ringe suspects electron beams may remain the best and perhaps only way to catalyze reactions inside particles, and she is hopeful. "Using an electron beam is actually not as technologically irrelevant as you might think," she said. "Electron beams are very easy to generate. And yes, things need to be in vacuum, but other than that, people have generated electron beams for nearly 100 years. I'm sure 40 years ago people were saying, 'You're going to put a laser in a disk reader? That's crazy!' But they managed to do it. "I don't think it's unfeasible to miniaturize electron-beam technology. Humans are good at moving electrons and electricity around. We figured that out a long time ago," Ringe said. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article | October 10, 2016
Site: www.cemag.us

Rice University scientists have discovered how to subtly change the interior structure of semi-hollow nanorods in a way that alters how they interact with light, and because the changes are reversible, the method could form the basis of a nanoscale switch with enormous potential. “It’s not 0-1, it’s 1-2-3-4-5-6-7-8-9-10,” says Rice materials scientist Emilie Ringe, lead scientist on the project, which is detailed in the American Chemical Society journal Nano Letters. “You can differentiate between multiple plasmonic states in a single particle. That gives you a kind of analog version of quantum states, but on a larger, more accessible scale.” Ringe and colleagues used an electron beam to move silver from one location to another inside gold-and-silver nanoparticles, something like a nanoscale Etch A Sketch. The result is a reconfigurable optical switch that may form the basis for a new type of multiple-state computer memory, sensor, or catalyst. At about 200 nanometers long, 500 of the metal rods placed end-to-end would span the width of a human hair. However, they are large in comparison with modern integrated circuits. Their multistate capabilities make them more like reprogrammable bar codes than simple memory bits, she says. “No one has been able to reversibly change the shape of a single particle with the level of control we have, so we’re really excited about this,” Ringe says. Altering a nanoparticle’s internal structure also alters its external plasmonic response. Plasmons are the electrical ripples that propagate across the surface of metallic materials when excited by light, and their oscillations can be easily read with a spectrometer — or even the human eye — as they interact with visible light. The Rice researchers found they could reconfigure nanoparticle cores with pinpoint precision. That means memories made of nanorods need not be merely on-off, Ringe says, because a particle can be programmed to emit many distinct plasmonic patterns. The discovery came about when Ringe and her team, which manages Rice’s advanced electron microscopy lab, were asked by her colleague and co-author Denis Boudreau, a professor at Laval University in Quebec, to characterize hollow nanorods made primarily of gold but containing silver. “Most nanoshells are leaky,” Ringe says. “They have pinholes. But we realized these nanorods were defect-free and contained pockets of water that were trapped inside when the particles were synthesized. We thought: We have something here.” Ringe and the study’s lead author, Rice research scientist Sadegh Yazdi, quickly realized how they might manipulate the water. “Obviously, it’s difficult to do chemistry there, because you can’t put molecules into a sealed nanoshell. But we could put electrons in,” she says. Focusing a subnanometer electron beam on the interior cavity split the water and inserted solvated electrons – free electrons that can exist in a solution. “The electrons reacted directly with silver ions in the water, drawing them to the beam to form silver,” Ringe says. The now-silver-poor liquid moved away from the beam, and its silver ions were replenished by a reaction of water-splitting byproducts with the solid silver in other parts of the rod. “We actually were moving silver in the solution, reconfiguring it,” she says. “Because it’s a closed system, we weren’t losing anything and we weren’t gaining anything. We were just moving it around, and could do so as many times as we wished.” The researchers were then able to map the plasmon-induced near-field properties without disturbing the internal structure — and that’s when they realized the implications of their discovery. “We made different shapes inside the nanorods, and because we specialize in plasmonics, we mapped the plasmons and it turned out to have a very nice effect,” Ringe says. “We basically saw different electric-field distributions at different energies for different shapes.” Numerical results provided by collaborators Nicolas Large of the University of Texas at San Antonio and George Schatz of Northwestern University helped explain the origin of the modes and how the presence of a water-filled pocket created a multitude of plasmons, she said. The next challenge is to test nanoshells of other shapes and sizes, and to see if there are other ways to activate their switching potentials. Ringe suspects electron beams may remain the best and perhaps only way to catalyze reactions inside particles, and she is hopeful. “Using an electron beam is actually not as technologically irrelevant as you might think,” she says. “Electron beams are very easy to generate. And yes, things need to be in vacuum, but other than that, people have generated electron beams for nearly 100 years. I’m sure 40 years ago people were saying, ‘You’re going to put a laser in a disk reader? That’s crazy!’ But they managed to do it. “I don’t think it’s unfeasible to miniaturize electron-beam technology. Humans are good at moving electrons and electricity around. We figured that out a long time ago,” Ringe says. The research should trigger the imaginations of scientists working to create nanoscale machines and processes, she says. “This is a reconfigurable unit that you can access with light,” she says. “Reading something with light is much faster than reading with electrons, so I think this is going to get attention from people who think about dynamic systems and people who think about how to go beyond current nanotechnology. This really opens up a new field.” Co-authors of the paper are graduate student Josée Daniel of Laval University; former Rice postdoctoral researcher Large, now an assistant professor of physics at the University of Texas at San Antonio; and Schatz, a professor of chemistry at Northwestern University. The research was supported by the National Science Foundation, the Quest high performance computing facility at Northwestern University, the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation, the Funds for Research of Quebec — Nature and Technology, and the University of Laval.


News Article | February 27, 2017
Site: www.marketwired.com

TORONTO, ON--(Marketwired - February 27, 2017) - NewCastle Gold Ltd. (TSX: NCA) (NewCastle Gold or the "Company") is pleased to announce the appointment of Jacques McMullen, P. Eng., to the Board of Directors, effective immediately. Mr. McMullen succeeds James (Jim) Gowans, who is stepping down as a director of NewCastle Gold to focus on his role of President and CEO of Arizona Mining Inc. Richard Warke, Executive Chairman of NewCastle Gold, stated, "We would like to thank Jim for his time and contribution to the Board over the past year. He has been a valued member of our team and we wish him all of the best with his current venture. We are excited to welcome Jacques McMullen to the Board and our team. His many years of senior experience in the mining industry will be invaluable to the success of the Castle Mountain project and the Company." With over 35 years of senior management experience in the mining industry, Mr. McMullen has been directly involved with major capital projects including roles in operations, evaluations, and corporate development for several mining companies. He spent the majority of his career working with Barrick Gold Corporation in various senior roles from 1994 to 2012, as well as serving as Director of Highland Gold Mining Ltd., IGE Resources AB, Fire River Gold Corp and Minera S.A. From 2014 to 2016, Mr. McMullen was Director and Chairman of Orvana Minerals. From 2012 to 2016, he was also Principal and Partner, Mines and Metals with BBA, a private engineering firm, and was a non-executive Director on the Board of Directors. He holds a B.Sc. in Applied Sciences (Metallurgy), is a Professional Engineer, and completed a Master's Degree of Applied Sciences in Mineral Processing at Laval University. Mr. McMullen currently serves as an advisor to management at Detour Gold, and is the Principal of J. McMullen & Associates, a privately held consulting company. NewCastle (an augustagroup company) has a 100% interest in the Castle Mountain property in San Bernardino County, California. The Castle Mountain heap leach gold mine produced over one million ounces of gold from 1992 to 2004. The Mine and Reclamation Plan, under which the mine operated, was authorized by the County of San Bernardino as the Lead Agency and remains in effect. Water for the drill programs was accessed from existing patented wells on the Project. An updated NI 43-101 resource for the project was announced December 2, 2015 which includes Measured Mineral Resources of 17.4 million tonnes grading 0.86 g/t gold containing 0.48 million gold ounces, Indicated Mineral Resources of 202.5 million tonnes grading 0.57 g/t gold containing 3.71 million gold ounces along with Inferred Mineral Resources of 40.8 million tonnes grading 0.58 g/t gold and containing 0.76 million gold ounces. The Project hosts a disseminated low sulphidation epithermal system. Gold is primarily hosted by late-stage rhyolite volcanic units within zones of silicification and brecciation associated with northeast-southwest trending/southeast dipping fault structures which are interpreted to have developed within a collapsed caldera environment. Eleven gold domains are represented by both steep and shallow-dipping orientations. Ian R. Cunningham-Dunlop, P. Eng., the Company's Senior Vice President Technical Services, is the designated Qualified Person for this news release within the meaning of NI 43-101. He has reviewed and verified that the technical information contained in this release is accurate and has approved of the written disclosure of the same. Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this news release. This news release contains "forward-looking statements" and "forward-looking information" (collectively, "forward-looking information") within the meaning of applicable Canadian securities legislation. Forward-looking information includes information that relates to, among other things, statements with respect to the completion of the proposed drill program at Castle Mountain, the mineral resource expansion at Castle Mountain and the identification of future expansion targets at Castle Mountain. Forward-looking information is not, and cannot be, a guarantee of future results or events. Forward-looking information is based on, among other things, opinions, assumptions, estimates and analyses that, while considered reasonable by us at the date the forward-looking information is provided, inherently are subject to significant risks, uncertainties, contingencies and other factors that may cause actual results and events to be materially different from those expressed or implied by the forward-looking information. The material factors or assumptions that we identified and were applied by us in drawing conclusions or making forecasts or projections set out in the forward looking information include, but are not limited to that the Company is able to procure personnel, equipment and supplies required for its exploration and development activities in sufficient quantities and on a timely basis and that actual results will be consistent with management's expectations. The risks, uncertainties, contingencies and other factors that may cause actual results to differ materially from those expressed or implied by the forward-looking information may include, but are not limited to, the risks discussed under the heading "Risks" in general to the business of NewCastle in documents filed (or to be filed) with Canadian regulatory authorities. Should one or more risk, uncertainty, contingency or other factor materialize or should any factor or assumption prove incorrect, actual results could vary materially from those expressed or implied in the forward-looking information. Accordingly, the reader should not place undue reliance on forward-looking information. NewCastle does not assume any obligation to update or revise any forward-looking information after the date of this news release or to explain any material difference between subsequent actual events and any forward-looking information, except as required by applicable law.


Dumesnil J.G.,Laval University | Pibarot P.,Laval University | Carabello B.,Veterans Affairs Medical Center
European Heart Journal | Year: 2010

Paradoxical low flow, low gradient, severe aortic stenosis (AS) despite preserved ejection fraction is a recently described clinical entity whereby patients with severe AS on the basis of aortic valve area have a lower than expected gradient in relation to generally accepted values. This mode of presentation of severe AS is relatively frequent (up to 35 of cases) and such patients have a cluster of findings, indicating that they are at a more advanced stage of their disease and have a poorer prognosis if treated medically rather than surgically. Yet, a majority of these patients do not undergo surgery likely due to the fact that the reduced gradient is conducive to an underestimation of the severity of the disease and/or of symptoms. The purpose of this article is to review and further analyse the distinguishing characteristics of this entity and to present its implications with regards to currently accepted guidelines for AS severity.


Aider M.,Laval University | Barbana C.,University of Zaragoza
Trends in Food Science and Technology | Year: 2011

There is a well-recognized connection between the use of plant proteins in functional foods, nutraceuticals and other natural health products and health promotion and disease risk reduction. Plant proteins are largely used in the food industry, and canola/rapeseed proteins are regarded as potential ingredients that may be used as food additives. In this review, the chemical composition (amino acids and protein fractions), production and isolation techniques, functional properties, allergenicity, food applications and potential uses of canola proteins for the production of bioactive compounds are highlighted. © 2010 Elsevier Ltd.


Evans M.L.,Laval University | Dionne M.,Laval University | Miller K.M.,Canadian Department of Fisheries and Oceans | Bernatchez L.,Laval University
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

Major histocompatibility complex (MHC)-dependent mating preferences have been observed across vertebrate taxa and these preferences are expected to promote offspring disease resistance and ultimately, viability. However, little empirical evidence linking MHC-dependent mate choice and fitness is available, particularly in wild populations. Here, we explore the adaptive potential of previously observed patterns of MHC-dependent mate choice in a wild population of Atlantic salmon (Salmo salar) in Que ́bec, Canada, by examining the relationship between MHC genetic variation and adult reproductive success and offspring survival over 3 years of study. While Atlantic salmon choose their mates in order to increase MHC diversity in offspring, adult reproductive success was in fact maximized between pairs exhibiting an intermediate level of MHC dissimilarity. Moreover, patterns of offspring survival between years 0{thorn} and 1{thorn}, and 1{thorn} and 2{thorn} and population genetic structure at the MHC locus relative to microsatellite loci indicate that strong temporal variation in selection is likely to be operating on the MHC. We interpret MHCdependent mate choice for diversity as a likely bet-hedging strategy that maximizes parental fitness in the face of temporally variable and unpredictable natural selection pressures. © 2011 The Royal Society.


Samson J.E.,Laval University | Spinelli S.,CNRS Architecture and Functions of Biological Macromolecules Lab | Cambillau C.,CNRS Architecture and Functions of Biological Macromolecules Lab | Moineau S.,Laval University
Molecular Microbiology | Year: 2013

AbiQ is a phage resistance mechanism found on a native plasmid of Lactococcus lactis that abort virulent phage infections. In this study, we experimentally demonstrate that AbiQ belongs to the recently described type III toxin-antitoxin systems. When overexpressed, the AbiQ protein (ABIQ) is toxic and causes bacterial death in a bacteriostatic manner. Northern and Western blot experiments revealed that the abiQ gene is transcribed and translated constitutively, and its expression is not activated by a phage product. ABIQ is an endoribonuclease that specifically cleaves its cognate antitoxin RNA molecule in vivo. The crystal structure of ABIQ was solved and site-directed mutagenesis identified key amino acids for its anti-phage and/or its RNase function. The AbiQ system is the first lactococcal abortive infection system characterized to date at a structural level. © 2012 Blackwell Publishing Ltd.


Xu H.L.,Jilin University | Chin S.L.,Laval University
Sensors | Year: 2011

Powerful femtosecond laser pulses propagating in transparent materials result in the formation of self-guided structures called filaments. Such filamentation in air can be controlled to occur at a distance as far as a few kilometers, making it ideally suited for remote sensing of pollutants in the atmosphere. On the one hand, the high intensity inside the filaments can induce the fragmentation of all matters in the path of filaments, resulting in the emission of characteristic fluorescence spectra (fingerprints) from the excited fragments, which can be used for the identification of various substances including chemical and biological species. On the other hand, along with the femtosecond laser filamentation, white-light supercontinuum emission in the infrared to UV range is generated, which can be used as an ideal light source for absorption Lidar. In this paper, we present an overview of recent progress concerning remote sensing of the atmosphere using femtosecond laser filamentation. © 2010 by the authors.


Hancock R.,Laval University | Hancock R.,Silesian University of Technology
International Review of Cell and Molecular Biology | Year: 2014

The principles that determine the organization of the nucleus have become clearer in recent years, largely because of new insights into polymer, colloid, and soft-matter science. Macromolecules, together with the giant linear polymers that form the chromosomes, are confined at high concentrations within the nuclear envelope and their interactions are influenced strongly by short-range depletion or entropic forces which are negligible in dilute systems, in addition to the more familiar van der Waals, electrostatic, steric, hydrogen bonding, and hydrophobic forces. The studies described in this volume are consistent with the model that this complex and concentrated mixture of macromolecules is maintained in a delicate equilibrium by quite simple although unsuspected physicochemical principles. The sensitivity of this equilibrium to perturbation may underlie the controversies about the existence of a nuclear matrix or scaffold. In this volume, we underline the importance for cell biologists of being familiar with current work in colloid, polymer, soft matter, and nanoscience. This chapter presents a brief background to the aspects of the nucleus that are considered in detail in subsequent chapters. © 2014 Elsevier Inc.


Daziano R.A.,Cornell University | Bolduc D.,Laval University
Transportation | Year: 2013

In this paper we discuss the specification, covariance structure, estimation, identification, and point-estimate analysis of a logit model with endogenous latent attributes that avoids problems of inconsistency. We show first that the total error term induced by the stochastic latent attributes is heteroskedastic and nonindependent. In addition, we show that the exact identification conditions support the two-stage analysis found in much current work. Second, we set up a Monte Carlo experiment where we compare the finite-sample performance of the point estimates of two alternative methods of estimation, namely frequentist full information maximum simulated likelihood and Bayesian Metropolis Hastings-within-Gibbs sampling. The Monte Carlo study represents a virtual case of travel mode choice. Even though the two estimation methods we analyze are based on different philosophies, both the frequentist and Bayesian methods provide estimators that are asymptotically equivalent. Our results show that both estimators are feasible and offer comparable results with a large enough sample size. However, the Bayesian point estimates outperform maximum likelihood in terms of accuracy, statistical significance, and efficiency when the sample size is low. © 2012 Springer Science+Business Media, LLC.


Daziano R.A.,Laval University | Daziano R.A.,Cornell University | Bolduc D.,Laval University
Transportmetrica A: Transport Science | Year: 2013

In this article we develop, implement and apply a Markov chain Monte Carlo (MCMC) Gibbs sampler for Bayesian estimation of a hybrid choice model (HCM), using stated data on both vehicle purchase decisions and environmental concerns. Our study has two main contributions. The first is the feasibility of the Bayesian estimator we derive. Whereas classical estimation of HCMs is fairly complex, we show that the Bayesian approach for HCMs is methodologically easier to implement than simulated maximum likelihood because the inclusion of latent variables translates into adding independent ordinary regressions; we also find that, using the Bayesian estimates, forecasting and deriving confidence intervals for willingness to pay measures is straightforward. The second is the capacity of HCMs to adapt to practical situations. Our empirical results coincide with a priori expectations, namely that environmentally-conscious consumers are willing to pay more for low-emission vehicles. The model outperforms standard discrete choice models because it not only incorporates pro-environmental preferences but also provides tools to build a profile of environmentally-conscious consumers. © 2013 Copyright Hong Kong Society for Transportation Studies Limited.


Desrochers A.,Laval University | Desrochers A.,Cornell University
Ecology | Year: 2010

Major landscape changes caused by humans may create strong selection pressures and induce rapid evolution in natural populations. In the last 100 years, eastern North America has experienced extensive clear-cutting in boreal areas, while afforestation has occurred in most temperate areas. Based on museum specimens, I show that wings of several boreal forest songbirds and temperate songbirds of non-forest habitats have become more pointed over the last 100 years. In contrast, wings of most temperate forest and earlysuccessional boreal forests species have become less pointed over the same period. In contrast to wing shape, the bill length of most species did not change significantly through time. These results are consistent with the "habitat isolation hypothesis," i.e., songbirds evolved in response to recent changes in the amount of available habitat and associated implications for mobility. Rapid morphological evolution may mitigate, without necessarily preventing, negative consequences of habitat loss caused by humans through direct exploitation or climate change. © 2010 by the Ecological Society of America.


Huang J.,Laval University | Huang J.,Hohai University | Rodrigue D.,Laval University
Materials and Design | Year: 2013

Carbon nanotubes (CNTs), as a reinforcing material, are extensively used in nanocomposites for their high stiffness and high strength. To analyze the mechanical properties of CNT reinforced polymer composites, continuum mechanics combined with finite elements methods (FEMs) is a very effective tool. However, adopting different numerical models will directly affect the computing efficiency. In this work, solid element, shell element and 3-D truss element are separately used to simulate single wall carbon nanotube (SWCNT). In addition, the effects of CNT aspect ratio on the mechanical properties of CNT reinforced polypropylene composites are investigated. As a first approximation, the polypropylene matrix material is assumed to be a linear elastic or an elastic-plastic material, while CNT is assumed to be a linear elastic material. A series of direct tensile numerical tests were carried out to get the elastic modulus of SWCNT/polypropylene composites and the transverse deformations of the composites are determined for the range of conditions tested. © 2013.


Ferrini F.,University of Turin | De Koninck Y.,University of Québec | De Koninck Y.,Laval University
Neural Plasticity | Year: 2013

Microglia-neuron interactions play a crucial role in several neurological disorders characterized by altered neural network excitability, such as epilepsy and neuropathic pain. While a series of potential messengers have been postulated as substrates of the communication between microglia and neurons, including cytokines, purines, prostaglandins, and nitric oxide, the specific links between messengers, microglia, neuronal networks, and diseases have remained elusive. Brain-derived neurotrophic factor (BDNF) released by microglia emerges as an exception in this riddle. Here, we review the current knowledge on the role played by microglial BDNF in controlling neuronal excitability by causing disinhibition. The efforts made by different laboratories during the last decade have collectively provided a robust mechanistic paradigm which elucidates the mechanisms involved in the synthesis and release of BDNF from microglia, the downstream TrkB-mediated signals in neurons, and the biophysical mechanism by which disinhibition occurs, via the downregulation of the K +-Cl- cotransporter KCC2, dysrupting Cl -homeostasis, and hence the strength of G A B A A - and glycine receptor-mediated inhibition. The resulting altered network activity appears to explain several features of the associated pathologies. Targeting the molecular players involved in this canonical signaling pathway may lead to novel therapeutic approach for ameliorating a wide array of neural dysfunctions. © 2013 Francesco Ferrini and Yves De Koninck.


Deschenes J.-D.,Laval University | Giaccari P.,Segelhof 9P | Genest J.,Laval University
Optics Express | Year: 2010

This paper presents a significant advancement in the referencing technique applied to frequency comb spectrometry (cFTS) that we proposed and demonstrated recently. Based on intermediate laser oscillators, it becomes possible to access the full delay range set by the repetition rate of the frequency combs, overcoming the principal limitation observed in the method based on passive optical filters. With this new referencing technique, the maximum spectral resolution given by each comb tooth is achievable and continuous scanning will improve complex reflectometry measurements. We present a demonstration of such a high resolution cFTS system, providing a spectrometry measurement at 100 MHz of resolution (0.003 cm?1) with a spectral signal to noise ratio of 440 for a 2 seconds measurement time. The resulting spectrum is composed of 105 · 103 resolved spectral elements, each corresponding to a single pair of optical modes (one for each combs). To our knowledge, this represents the first cFTS measurement over the full spectral range of the sources in a single shot with resolved individual modes at full resolution. © 2010 Optical Society of America.


Chowdhury S.,King Fahd University of Petroleum and Minerals | Rodriguez M.J.,Laval University | Sadiq R.,University of Sao Paulo
Journal of Hazardous Materials | Year: 2011

Chlorination for drinking water forms various disinfection byproducts (DBPs). Some DBPs are probably linked to human cancer (e.g., bladder, colorectal cancers) and other chronic and sub-chronic effects. This emphasizes the need to understand and characterize DBPs in drinking water and possible risks to human health. In this study, occurrences of DBPs throughout Canada were investigated. Trihalomethanes (THMs) were observed to be highest in Manitoba followed by Nova Scotia and Saskatchewan, while haloacetic acids were highest in Nova Scotia followed by Newfoundland and Labrador. Based on the characterization of DBPs, risk of cancer from exposure to THMs was predicted using ingestion, inhalation and dermal contact pathways of exposure. In Canada, approximately 700 cancer cases may be caused by exposure to THMs in drinking water. Medical expenses associated with these cancer incidents are estimated at some $140 million/year. Expense may be highest in Ontario (∼$47 million/year) followed by Quebec (∼$25 million/year) due to a greater population base. This paper suggests improvements in water treatment, source protection and disinfection processes, and caution in the use of alternative disinfectants to reduce DBPs. Finally, elements are provided to mitigate risks and reduce cost estimates in future studies. © 2011 Elsevier B.V.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: ICT-06-2014 | Award Amount: 3.37M | Year: 2015

The overall objective of the ROAM project is to investigate and demonstrate the use of the orbital angular momentum (OAM) modes of light for communications and networking. Two are the primary objectives. The firs objective is to exploit the use of OAM modes in optical fibres as a disruptive means of increasing optical fibre transmission capacity for short-reach high data density applications. A transmission testbed utilising OAM multiplexing and wavelength division multiplexing (WDM) dimensions will be demonstrated. The target will be a 10x or more capacity increase by employing 10 or more OAM multiplexed channels over a conventional WDM system. The combination of 10x OAM states with 16 wavelength channels will provide a total of 160 multiplexed channels. Full compatibility with legacy technologies will be demonstrated. Speciality fibres will be employed to support OAM modes transmission in the range up to 2 km. The second objective is to exploit the use of OAM domain as a switching resource in conjunctions with the wavelength domain to significantly improve the scalability and the power consumption of the switches in data-centres applications. A 10x improvement of the scalability of the data-centre switches will be targeted with the study and development of an OAM-based switch compatible with the WDM layer. A switch exploiting 10 OAM modes and 16 wavelengths as switching domains will be implemented. The developed two-layer switch will enable a more than 10x reduction of power consumption/Gb/s with respect to the current commercial switches. OAM switch configuration time of 100 ns will be demonstrated, with 8x improvement with respect to commercial switches. The project goals will be enabled by integrated high performance OAM components build on silicon photonics technology. ROAM consortium is composed by three universities, two research institutes, and two large companies, with the required knowledge and infrastructures to satisfy the project objectives.


News Article | November 11, 2016
Site: www.scientificamerican.com

In people who suffer from pain disorders, painful feelings can severely worsen and spread to other regions of the body. Patients who develop chronic pain after surgery, for example, will often feel it coming from the area surrounding the initial injury and even in some parts of the body far from where it originates. New evidence suggests glia, non-neuronal cells in the brain, may be the culprits behind this effect. Glia were once thought to simply be passive, supporting cells for neurons. But scientists now know they are involved in everything from metabolism to neurodegeneration. A growing body of evidence points to their key role in pain. In a study published today in Science, researchers at the Medical University of Vienna report that glia are involved in long-term potentiation (LTP), or the strengthening of synapses, in pain pathways in the spinal cord. Neuroscientists Timothy Bliss and Terje Lømo first described LTP in the hippocampus, a brain area involved in memory, in the 1970s. Since then scientists have been meticulously studying the role this type of synaptic plasticity—the ability of synapses to change in strength—plays in learning and memory. More recently, researchers discovered that LTP could also amplify pain in areas where injuries or inflammation occur. “We sometimes call this a ‘memory trace of pain’ because the painful insult may lead to subsequent hypersensitivity to painful stimuli, and it was clear that synaptic plasticity can play a role here,” says study co-author Jürgen Sandkühler, a neuroscientist also at the Medical University of Vienna. But current models of how LTP works could not explain why discomfort sometimes becomes widespread or experienced in areas a person has never felt it before, he adds. There are two forms of LTP. In one, synapses strengthen when two neurons transmit signals or “fire” closely in time. The other form, which has long been thought to be dependent on the first, occurs when activity in one circuit reinforces connections in nearby, inactive neural pathways. In their latest study Sandkühler and colleagues show that these two forms of potentiation can, with the help of glial cells, happen independently of each other. To test the role of glia in pain circuits, the researchers conducted a series of experiments in rat spinal cord slices and live rats and found that they could induce both types of LTP between two pain-related neurons—even in the absence of each other—by activating two types of glia, microglia and astrocytes. In a key experiment they induced LTP in one rat and transferred its spinal fluid to another rat; they found that this could induce LTP in the new animal. These results were evidence that the molecules released from glial cells were capable of strengthening synapses between pain-related neurons on their own. Ru-Rong Ji, a neurobiologist studying pain at Duke University who was not involved in the study, praises the work, but adds, “It would be nice to correlate this measurement with behavioral changes—if you see that the animal not only shows LTP but also shows enhanced or prolonged pain behavior.” The Sandkühler group’s study is the most recent addition to a growing body of evidence that glia—and the molecules they release—are involved in long-term potentiation in the spinal cord. This is, however, one of the first studies to provide evidence this effect could be transferable across long distances, although more studies are needed to confirm this. For example, an experiment should be able to demonstrate LTP can, with the help of glia, spread throughout the spinal cord of a single animal. This is something Sandkühler and his colleagues are working on now. “The paper is very provocative because it competes with the idea that LTP is really a single synapse thing [and suggests] a more global process,” says Yves De Koninck, a neuroscientist studying synaptic transmission at Laval University in Quebec. He wonders, however, whether the spreading effect is dependent on the level of neural activation, pointing out that the researchers used a strong electrical stimulus to trigger pain-related neurons and activate glial cells in this study. It is possible, he notes, a small amount of activation could lead to strengthening of specific synapses and that the effect starts to spread as activation increases. The biggest implications of these findings is that molecules released from glial cells in response to a painful stimulus could travel away from the injury site, increasing sensitivity to pain in other parts of the body. Sandkühler also believes glia might be involved in similar mechanisms in the brain, which may explain why physical sickness also has cognitive effects. “I think that the significance of this work is that it will open up the new thinking,” says Min Zhou, a pain neuroscientist at the University of Toronto who did not take part in the work. “Now we [will start] to look if any additional mechanisms may contribute to pain-related emotional changes in the brain.”


La V.D.,Laval University | Howell A.B.,Rutgers University | Grenier D.,Laval University
Antimicrobial Agents and Chemotherapy | Year: 2010

A-type cranberry proanthocyanidins (AC-PACs) have recently been reported to be beneficial for human health, especially urinary tract health. The effect of these proanthocyanidins on periodontitis, a destructive disease of tooth-supporting tissues, needs to be investigated. The purpose of this study was to investigate the effects of AC-PACs on various virulence determinants of Porphyromonas gingivalis as well as on the inflammatory response of oral epithelial cells stimulated by this periodontopathogen. We examined the effects of AC-PACs on P. gingivalis growth and biofilm formation, adherence to human oral epithelial cells and proteincoated surfaces, collagenase activity, and invasiveness. We also tested the ability of AC-PACs to modulate the P. gingivalis-induced inflammatory response by human oral epithelial cells. Our results showed that while AC-PACs neutralized all the virulence properties of P. gingivalis in a dose-dependent fashion, they did not interfere with growth. They also inhibited the secretion of interleukin-8 (IL-8) and chemokine (C-C motif) ligand 5 (CCL5) but did not affect the secretion of IL-6 by epithelial cells stimulated with P. gingivalis. This anti-inflammatory effect was associated with reduced activation of the nuclear factor-κB (NF-κB) p65 pathway. AC-PACs may be potentially valuable bioactive molecules for the development of new strategies to treat and prevent P. gingivalis-associated periodontal diseases. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Marette A.,Laval University | Jobin C.,University of Florida
Cell Metabolism | Year: 2015

Gut dysbiosis is associated with development of metabolic syndrome in Tlr5-/- mice, but the underlying mechanism remains unclear. In this issue, Singh et al. (2015) report that augmented SCFA levels play a deleterious role in metabolic syndrome by promoting conversion of SFA to oleate in Tlr5-/- mice via increased liver SCD1expression. © 2015 Elsevier Inc.


Maltais F.,Laval University | Dennis N.,PAREXEL | Chan C.K.N.,University of Toronto
COPD: Journal of Chronic Obstructive Pulmonary Disease | Year: 2013

COPD is progressive and typically begins many years before a definite diagnosis is made. As the rate of decline in lung function may be faster in the initial stages of the disease, early intervention could be beneficial to control symptoms and affect disease progression and outcomes. A systematic review of published literature relating to mild-to-moderate COPD (patients with FEV1 ≥50% predicted) was performed to evaluate the level of impairment and natural history or disease progression over time, and impact of interventions on the outcomes of patients with early-stage disease. Of the 79 published articles included in this analysis, 31 reported randomized controlled trials; the remaining 48 articles reported studies of non-randomized and/or observational design. Nine of the randomized controlled trials were ≥6 months' duration, enabling assessment of outcomes over time. Most of the randomized controlled trials were in patients with moderate COPD (GOLD stage II); few included patients with the mildest stages of the disease (i.e., stage I). The results show that even patients with milder or moderate COPD can have substantial limitations and physical impairment, which worsen over time. Encouragement of smoking cessation, in conjunction with management of symptoms and treating activity limitation and exacerbations by appropriate non-pharmacologic and pharmacologic management at the earliest possible stage, could positively affect the impact and progression of the disease. © 2013 Informa Healthcare USA, Inc.


Provencher S.,Laval University | Granton J.T.,Toronto General Hospital
Canadian Journal of Cardiology | Year: 2015

Because of the complexities of the disease, early recognition and referral of patients with pulmonary arterial hypertension (PAH) to an expert centre is critically important. Advances in our understanding of the pathogenesis of PAH have translated into novel treatment strategies and pharmacotherapies. A supervised rehabilitation program, psychosocial support, and referral to palliative care might lead to improvements in exercise capacity and quality of life. At present the current medical treatments include prostanoids (parenteral, oral, and inhaled), endothelin antagonists, and agents that increase nitric oxide bioavailability. Although these agents all cause pulmonary vasodilation, they have been shown to improve outcome in patients who do not demonstrate an acute vasodilatory response. This suggests that they might also alter the abnormal proliferative vasculopathy that characterizes PAH. These agents have variably led to improvements in exercise capacity, symptoms, hemodynamics, and markers of right ventricular dysfunction. Adopting the principles of a goal-directed approach, most practitioners (and guidelines) advocate sequentially adding treatments until patients achieve a satisfactory clinical response. Emerging data suggest that upfront combination therapy might be superior to monotherapy. For patients who fail to achieve a satisfactory clinical response, parenteral prostanoids remain the medical treatment of choice. Early referral for evaluation of lung transplantation should be considered for patients who continue to demonstrate poor prognostic features or who require advanced medical treatments. © 2015 Canadian Cardiovascular Society.


Liang L.,Jiangnan University | Liang L.,Laval University | Subirade M.,Laval University
Food Chemistry | Year: 2012

The major protein in bovine milk whey, β-lactoglobulin (β-LG), has several binding sites for ligands. Its interactions with folic acid (a hydrophilic compound), resveratrol (amphiphilic) and α-tocopherol (hydrophobic) at neutral and acidic pH and after heating to 85°C were studied using fluorescence quenching. Binding of folic acid occurs in a hydrophobic pocket in the groove between the α-helix and the β-barrel and is disturbed by decreasing the pH from 7.0 to 2.0. Resveratrol binds to the outer surface of β-LG near Trp19-Arg124 to form complexes that are stable at acidic pH. Acidification caused the release of α-tocopherol bound to the internal cavity but had no influence on that bound to a site at the surface of β-LG. The β-LG/folic acid complex was thermally stable. Thermal denaturing improved the affinity of the protein for resveratrol but decreased somewhat its affinity for α-tocopherol. These results should help guide the development of formulations based on β-LG as a carrier of a wide range of bioactive nutrients. © 2011 Elsevier Ltd. All rights reserved.


Luddington I.A.,Mount Allison University | Kaczmarska I.,Mount Allison University | Lovejoy C.,Laval University
PLoS ONE | Year: 2012

DNA barcoding is a molecular tool that exploits a unique DNA sequence of a standardized gene or non-coding region for the species identification of unknown individuals. The investigation into a suitable barcode for diatoms is ongoing and there are several promising candidates including mitochondrial, plastidial and nuclear markers. We analyzed 272 sequences from 76 diatoms species in the orders Thalassiosirales, Lithodesmiales and Cymatosirales, using distance and character based approaches, to assess the applicability of a DNA barcode based on the hypervariable V4 region of the nuclear 18S rRNA gene. We show that the proposed V4 barcode separated ca. 97% of all centric diatom taxa tested using a threshold p-distance of 0.02 and that many problem pairs were further separated using a character based approach. The reliability of amplification, extensive reference library and variability seen in the V4 region make it the most promising candidate to date for a barcode marker for diatoms particularly when combined with DNA character analysis. © 2012 Luddington et al.


Schmitt C.,Nestlé | Turgeon S.L.,Laval University
Advances in Colloid and Interface Science | Year: 2011

Since the pioneering work of Bungenberg de Jong and co-workers on gelatin-acacia gum complex coacervation in the 1920-40s, protein/polysaccharide complexes and coacervates have received increasing research interest in order to broaden the possible food applications. This review focuses on the main research streams followed in this field during the last 12 years regarding: i) the parameters influencing the formation of complexes and coacervates in protein-polysaccharide systems; ii) the characterization of the kinetics of phase separation and multi-scale structure of the complexes and coacervates; and iii) the investigation of the functional properties of complexes and coacervates in food applications. This latter section encompasses various technological aspects, namely: the viscosifying and gelling ability, the foaming and emulsifying ability and finally, the stabilization and release of bioactives or sensitive compounds. © 2010 Elsevier B.V. All rights reserved.


Tsai A.C.,Massachusetts General Hospital | Lucas M.,Laval University | Sania A.,Harvard University | Kim D.,Northeastern University | Kawachi I.,Harvard University
Annals of Internal Medicine | Year: 2014

Background: Suicide is a major public health problem. Current thinking about suicide emphasizes the study of psychiatric, psychological, or biological determinants. Previous work in this area has largely relied on surrogate outcomes or samples enriched for psychiatric morbidity. Objective: To evaluate the relationship between social integration and suicide mortality. Design: Prospective cohort study initiated in 1988. Setting: United States. Participants: 34 901 men aged 40 to 75 years. Measurements: Social integration was measured with a 7-item index that included marital status, social network size, frequency of contact, religious participation, and participation in other social groups. Vital status of study participants was ascertained through 1 February 2012. The primary outcome of interest was suicide mortality, defined as deaths classified with codes E950 to E959 from the International Classification of Diseases, Ninth Revision. Results: Over 708 945 person-years of follow-up, there were 147 suicides. The incidence of suicide decreased with increasing social integration. In a multivariable Cox proportional hazards regression model, the relative hazard of suicide was lowest among participants in the highest (adjusted hazard ratio [AHR], 0.41 [95% CI, 0.24 to 0.69]) and second-highest (AHR, 0.52 [CI, 0.30 to 0.91]) categories of social integration. Three components (marital status, social network size, and religious service attendance) showed the strongest protective associations. Social integration was also inversely associated with all-cause and cardiovascular-related mortality, but accounting for competing causes of death did not substantively alter the findings. Limitations: The study lacked information on participants' mental well-being. Some suicides could have been misclassified as accidental deaths. Conclusion: Men who were socially well-integrated had a more than 2-fold reduced risk for suicide over 24 years of follow-up. © 2014 American College of Physicians.


Guderley H.,Laval University | Portner H.O.,Alfred Wegener Institute for Polar and Marine Research
Canadian Journal of Zoology | Year: 2010

Evolutionary explanations of the adaptive value of animal characteristics are often expressed in energetic terms, but unless they are accompanied by demonstrations of limited energy availability, they remain speculative. In this review, we argue that metabolic power budgeting provides easily testable mechanisms through which energetically efficient attributes could become adaptive. Given each organism's maximal aerobic (and metabolic) capacity, available metabolic power (energy use per unit time) is limited and must be partitioned between different processes. This leads to compromises among the major fitness functions of growth, locomotor activity, and reproductive investment. As examples of such conflicts, we examine the compromise among growth, reproduction, and predator avoidance in scallops, as well as the means whereby thermal limitations on oxygen uptake reflect the geographical distribution limits and associated energetic tradeoffs of temperate zone and polar fishes. These examples show several means whereby the budgeting of aerobic power is implicated in the major fitness trade-offs faced by animals.


Banerji N.,University of California at Santa Barbara | Cowan S.,University of California at Santa Barbara | Leclerc M.,Laval University | Vauthey E.,University of Geneva | Heeger A.J.,University of California at Santa Barbara
Journal of the American Chemical Society | Year: 2010

The nature and time evolution of the primary excitations in the pristine conjugated polymer, PCDTBT, are investigated by femtosecond-resolved fluorescence up-conversion spectroscopy. The extensive study includes data from PCDTBT thin film and from PCDTBT in chlorobenzene solution, compares the fluorescence dynamics for several excitation and emission wavelengths, and is complemented by polarization-sensitive measurements. The results are consistent with the photogeneration of mobile electrons and holes by interband π-π* transitions, which then self-localize within about 100 fs and evolve to a bound singlet exciton state in less than 1 ps. The excitons subsequently undergo successive migrations to lower energy localized states, which exist as a result of disorder. In parallel, there is also slow conformational relaxation of the polymer backbone. While the initial self-localization occurs faster than the time resolution of our experiment, the exciton formation, exciton migration, and conformational changes lead to a progressive relaxation of the inhomogeneously broadened emission spectrum with time constants ranging from about 500 fs to tens of picoseconds. The time scales found here for the relaxation processes in pristine PCDTBT are compared to the time scale (<0.2 ps) previously reported for photoinduced charge transfer in phase-separated PCDTBT:fullerene blends (Phys. Rev. B 2010, 81, 125210). We point out that exciton formation and migration in PCDTBT occur at times much longer than the ultrafast photoinduced electron transfer time in PCDTBT:fullerene blends. This disparity in time scales is not consistent with the commonly proposed idea that photoinduced charge separation occurs after diffusion of the polymer exciton to a fullerene interface. We therefore discuss alternative mechanisms that are consistent with ultrafast charge separation before localization of the primary excitation to form a bound exciton. © 2010 American Chemical Society.


Patent
The University Of Texas System and Laval University | Date: 2013-05-09

According to one aspect, methods for validating plastic scintillating detectors (PSD) for photon dosimetry and applications of same. In some embodiments, the method includes using at least one PSD to obtain at least one dose measurement, determining at least one PSD correction factor suitable for compensation for variations in energy response of the at least one PSD over the energy range of interest, and determining at least one corrected dose measurement based on the at least one PSD correction factor. In some embodiments, the PSD may be incorporated into a wearable article, such as gloves, eyewear and the like, or used for skin surface measurements.


Various embodiments are described herein for a radiation dosimetry apparatus and associated methods for measuring radiation dose. In some embodiments, the apparatus includes multiple scintillating elements for detecting amounts of radiation dose at multiple points within a detection region. Each of the scintillating elements generates light in response to radiation interacting within their volume. A light guide combines the light generated by all of the scintillating elements as well as radiation-induced contaminated optical energy and transmits the combined light to a spectral analysis setup. Multi or hyper-spectral calibration technique allows calculating the dose or dose rate at the positions of the different scintillating elements. The calibration technique isolates the light produced by a given scintillating element from the other scintillating elements as well as any other source of radiation-induced contaminating light.


News Article | November 2, 2016
Site: www.eurekalert.org

Including canola oil in a healthy diet may help reduce abdominal fat in as little as four weeks, according to health researchers. "Visceral, or abdominal, fat increases the risk for cardiovascular disease, and is also associated with increased risk for conditions such as metabolic syndrome and diabetes," said Penny M. Kris-Etherton, Distinguished Professor of Nutrition, Penn State. "Monounsaturated fats in canola oil decrease this fat that has adverse health effects." Kris-Etherton and colleagues found that after one month of adhering to diets that included canola oil, participants had .11 kilograms, or a quarter pound, less belly fat than they did before the diet. They also found that the weight lost from the mid-section did not redistribute elsewhere in the body. The researchers report their results at The Obesity Society's Annual Scientific Meeting today (Nov. 2). "As a general rule, you can't target weight loss to specific body regions," said Kris-Etherton. "But monounsaturated fatty acids seem to specifically target abdominal fat." In order to incorporate canola oil into the diet, Kris-Etherton suggests using it when sautéing foods, in baking, adding it to a smoothie and in salad dressings. Canola oil is high in monounsaturated fatty acids, which have been shown to have beneficial effects on body composition, especially in people with obesity. When participants consumed conventional canola oil or high-oleic acid canola oil for just four weeks, they lost abdominal fat. The researchers tested the effect of five different vegetable oil blends in 101 participants' diets through a controlled study. The subjects were randomly assigned to follow for four weeks each of the treatment oil diets: conventional canola, high-oleic acid canola, high-oleic acid canola with DHA (a type of omega-3 fatty acid), corn/safflower and flax/safflower. After each four-week diet period, participants were given a four-week break before starting the next diet period. The participants consumed two smoothies during the day, which contained the specified treatment oil. The quantity of oil was calculated based on the participant's energy needs. For example, a participant who was on a 3,000-calorie diet would receive 60 grams of the treatment oil per day, providing 18 percent of his or her total dietary energy. Each smoothie would then contain 100 grams of orange sherbet, 100 grams of non-fat milk, 100 grams of frozen unsweetened strawberries and 30 grams of canola oil. A hundred grams is equivalent to roughly three-and-a-half ounces and 30 grams is approximately two tablespoons. The canola oil was carefully incorporated into the test diets so as to not exceed the participants' daily calorie needs. All of the participants had abdominal obesity, or increased waist circumference, and were either at risk for or had metabolic syndrome -- a group of conditions including obesity, type 2 diabetes, high blood pressure, high blood sugar, low HDL (also known as good cholesterol) and excess body fat around the waist. The researchers point out that further studies should be conducted to look at the long-term effects of a diet high in monounsaturated fatty acids, like canola oil. Also contributing to this research were Xiaoran Liu, a doctoral student, Sheila G. West, professor, biobehavioral health and nutritional sciences, Jennifer A. Fleming, instructor and clinical research coordinator, nutritional sciences, and Cindy E. McCrea, graduate student, biobehavioral health, all at Penn State; Benoît Lamarche, professor, nutrition, and Patrick Couture, professor, endocrinology and nephrology, both at Laval University; David J. A. Jenkins, professor, nutritional sciences and medicine, University of Toronto; Shuaihua Pu, a doctoral student, and Peter J. H. Jones, Canada Research Chair in Functional Foods and Nutrition, both at University of Manitoba; and Philip W. Connelly, staff scientist, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto. Agriculture and Agri Food Canada, the Canola Council of Canada, the Dow Agrosciences and Flax Council of Canada and the National Center for Advancing Translational Sciences all supported this research.


News Article | March 2, 2017
Site: www.marketwired.com

MONTREAL, QUEBEC--(Marketwired - March 2, 2017) - Nevado Resources Corporation. (TSX VENTURE:VDO) (the "Company" or "NEVADO") Is pleased to announce the appointment of Mr. Jonathan Lafontaine as President and Chief Executive Officer of Nevado. Mr. Lafontaine has worked in the mining industry for over 15 years and has progressively assumed leadership roles in various mining and exploration organizations, while being associated with high-level discoveries in various products. He is a professional geologist registered in three jurisdictions with a B.Sc. in Geology from Laval University and a M.Sc. In Geology from UNB. Philippe Cloutier Chairman of the Board of Directors "It is with great pleasure that we welcome Mr. Lafontaine to the Corporation. Mr. Lafontaine, with his experience, will bring new ideas and new dynamism, and we believe he is part of the next generation of our industry. In addition, we would like to thank Mr. Sylvain Laberge who has assumed the role of acting president in recent months. " Mr. Mike Curtis resigns as Director of the Corporation, leaving Mr. Lafontaine on the Board of Directors. We would like to thank Mr. Curtis for all the years devoted to the good governance of the Corporation. Nevado Resources Corporation is a Canadian mineral exploration company engaged in the exploration, evaluation and development of gold mining properties. The TSX Venture Exchange does not accept responsibility for the adequacy or accuracy of this press release.


Hammami R.,Laval University | Fernandez B.,Laval University | Lacroix C.,ETH Zurich | Fliss I.,Laval University
Cellular and Molecular Life Sciences | Year: 2013

Bacteriocin production is a widespread phenomenon among bacteria. Bacteriocins hold great promise for the treatment of diseases caused by pathogenic bacteria and could be used in the future as alternatives to existing antibiotics. The anti-infective potential of bacteriocins for inhibiting pathogens has been shown in various food matrices including cheese, meat, and vegetables. However, their inhibition of pathogens in vivo remains unclear and needs more investigation, due mainly to difficulties associated with demonstrating their health benefits. Many bacteriocins produced by established or potential probiotic organisms have been evaluated as potential therapeutic agents and interesting findings have been documented in vitro as well as in a few in vivo studies. Some recent in vivo studies point to the efficacy of bacteriocin-based treatments of human and animal infections. While further investigation remains necessary before the possibilities for bacteriocins in clinical practice can be described more fully, this review provides an overview of their potential applications to human and veterinary health. © 2012 Springer Basel.


Levesque J.,Laval University | Inal K.,University of Waterloo | Neale K.W.,Université de Sherbrooke | Mishra R.K.,General Motors
International Journal of Plasticity | Year: 2010

In this paper, a constitutive framework based on a rate-dependent crystal plasticity theory is employed to simulate the large strain deformation phenomena in hexagonal closed-packed (HCP) metals such as magnesium. The new framework is incorporated into in-house codes. Simulations are performed using the new crystal plasticity model in which crystallographic slip and deformation twinning are the principal deformation mechanisms. Simulations of various stress states (uniaxial tension, uniaxial compression and the so-called ring hoop tension test) for the magnesium alloy AM30 are performed and the results are compared with experimental observations of specimens deformed at 200 °C. Numerical simulations of forming limit diagrams (FLDs) are also performed using the Marciniak-Kuczynski (M-K) approach. With this formulation, the effects of crystallographic slip and deformation twinning on the FLD can be assessed. © 2009 Elsevier Ltd. All rights reserved.


Hone-Blanchet A.,Laval University | Fecteau S.,Laval University | Fecteau S.,Beth Israel Deaconess Medical Center
Neuropharmacology | Year: 2014

Food has both homeostatic and hedonic components, which makes it a potent natural reward. Food related reward could therefore promote an escalation of intake and trigger symptoms associated to withdrawal, suggesting a behavioral parallel with substance abuse. Animal and human theoretical models of food reward and addiction have emerged, raising further interrogations on the validity of a bond between Substance Use Disorders, as clinically categorized in the DSM 5, and food reward. These models propose that highly palatable food items, rich in sugar and/or fat, are overly stimulating to the brain's reward pathways. Moreover, studies have also investigated the possibility of causal link between food reward and the contemporary obesity epidemic, with obesity being potentiated and maintained due to this overwhelming food reward. Although natural rewards are a hot topic in the definition and categorization of Substance Use Disorders, proofs of concept and definite evidence are still inconclusive. This review focuses on available results from experimental studies in animal and human models exploring the concept of food addiction, in an effort to determine if it depicts a specific phenotype and if there is truly a neurobiological similarity between food addiction and Substance Use Disorders. It describes results from sugar, fat and sweet-fat bingeing in rodent models, and behavioral and neurobiological assessments in different human populations. Although pieces of behavioral and neurobiological evidence supporting a food addiction phenotype in animals and humans are interesting, it seems premature to conclude on its validity. © 2014 Elsevier Ltd. All rights reserved.


Hachem S.,University of Waterloo | Duguay C.R.,University of Waterloo | Allard M.,Laval University
Cryosphere | Year: 2012

Obtaining high resolution records of surface temperature from satellite sensors is important in the Arctic because meteorological stations are scarce and widely scattered in those vast and remote regions. Surface temperature is the primary climatic factor that governs the existence, spatial distribution and thermal regime of permafrost which is a major component of the terrestrial cryosphere. Land Surface (skin) Temperatures (LST) derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor aboard the Terra and Aqua satellite platforms provide spatial estimates of near-surface temperature values. In this study, LST values from MODIS are compared to ground-based near-surface air (Tair) and ground surface temperature (GST) measurements obtained from 2000 to 2008 at herbaceous and shrub tundra sites located in the continuous permafrost zone of Northern Québec, Nunavik, Canada, and of the North Slope of Alaska, USA. LSTs (temperatures at the surface materials-atmosphere interface) are found to be better correlated with Tair (1-3 m above the ground) than with available GST (3-5 cm below the ground surface). As Tair is most often used by the permafrost community, this study focused on this parameter. LSTs are in stronger agreement with Tair during the snow cover season than in the snow free season. Combining Aqua and Terra LST-Day and LST-Nigh acquisitions into a mean daily value provides a large number of LST observations and a better overall agreement with Tair. Comparison between mean daily LSTs and mean daily Tair, for all sites and all seasons pooled together yields a very high correlation (R Combining double low line 0.97; mean difference (MD) Combining double low line 1.8 A°C; and standard deviation of MD (SD) Combining double low line 4.0 A°C). The large SD can be explained by the influence of surface heterogeneity within the MODIS 1 km2 grid cells, the presence of undetected clouds and the inherent difference between LST and Tair. Retrieved over several years, MODIS LSTs offer a great potential for monitoring surface temperature changes in high-latitude tundra regions and are a promising source of input data for integration into spatially-distributed permafrost models. © Author(s) 2012.


Goldman A.,Stanford University | Roy J.,Stanford University | Bodenmiller B.,University of Zürich | Wanka S.,University of Zürich | And 4 more authors.
Molecular Cell | Year: 2014

To define a functional network for calcineurin, the conserved Ca2+/calmodulin-regulated phosphatase, we systematically identified its substrates in S. cerevisiae using phosphoproteomics and bioinformatics, followed by copurification and dephosphorylation assays. This study establishes new calcineurin functions and reveals mechanisms that shape calcineurin network evolution. Analyses of closely related yeasts show that many proteins were recently recruited to the network by acquiring a calcineurin-recognition motif. Calcineurin substrates in yeast and mammals are distinct due to network rewiring but, surprisingly, are phosphorylated by similar kinases. We postulate that corecognition of conserved substrate features, including phosphorylation and docking motifs, preserves calcineurin-kinase opposition during evolution. One example we document is a composite docking site that confers substrate recognition by both calcineurin and MAPK. We propose that conserved kinase-phosphatase pairs define the architecture of signaling networks and allow other connections between kinases and phosphatases to develop that establish common regulatory motifs in signaling networks. © 2014 Elsevier Inc.


Belenguer P.,French National Center for Scientific Research | Pellegrini L.,Laval University
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

The studies addressing the molecular mechanisms governing mitochondrial fusion and fission have brought to light a small group of dynamin-like GTPases (Guanosine-Triphosphate hydrolase) as central regulators of mitochondrial morphology and cristae remodeling, apoptosis, calcium signaling, and metabolism. One of them is the mammalian OPA1 (Optic atrophy 1) protein, which resides inside the mitochondrion anchored to the inner membrane and, in a cleaved form, is associated to oligomeric complexes, in the intermembrane space of the organelle. Here, we review the studies that have made OPA1 emerge as the best understood regulator of mitochondrial inner membrane fusion and cristae remodeling. Further, we re-examine the findings behind the recent claim that OPA1 mediates adrenergic control of lipolysis by functioning as a cytosolic A-kinase anchoring protein (AKAP), on the hemimembrane that envelops the lipid droplet. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology. © 2012 Elsevier B.V.


Robey D.,Georgia State University | Anderson C.,University of Nevada, Reno | Raymond B.,Laval University
Journal of the Association of Information Systems | Year: 2013

We begin with a retrospective reflection on the first author's research career, which in large part is devoted to research about the implications of information technology (IT) for organizational change. Although IT has long been associated with organizational change, our historical review of the treatment of technology in organization theory demonstrates how easily the material aspects of organizations can disappear into the backwaters of theory development. This is an unfortunate result since the material characteristics of IT initiatives distinguish them from other organizational change initiatives. Our aim is to restore materiality to studies of IT impact by tracing the reasons for its disappearance and by offering options in which IT's materiality plays a more central theoretical role. We adopt a socio-technical perspective that differs from a strict sociomaterial perspective insofar as we wish to preserve the ontological distinction between material artifacts and their social context of use. Our analysis proceeds using the concept of"affordance" as a relational concept consistent with the socio-technical perspective. We then propose extensions of organizational routines theory that incorporate material artifacts in the generative system known as routines. These contributions exemplify two of the many challenges inherent in adopting materiality as a new research focus in the study of IT's organizational impacts.


Tilmant A.,Laval University | Kinzelbach W.,ETH Zurich
Water Resources Research | Year: 2012

In recent years there has been a renewed interest for water supply enhancement strategies in order to deal with the exploding demand for water in some regions, particularly in Asia and Africa. Within such strategies, reservoirs, especially multipurpose ones, are expected to play a key role in enhancing water security. This renewed impetus for the traditional supply-side approach to water management may indeed contribute to socioeconomic development and poverty reduction if the planning process considers the lessons learned from the past, which led to the recommendations by the World Commission on Dams and other relevant policy initiatives. More specifically, the issues dealing with benefit sharing within an efficient and equitable utilization of water resources are key elements toward the successful development of those river basins. Hence, there is a need for improved coordination and cooperation among water users, sectors, and riparian countries. However, few studies have explicitly tried to quantify, in monetary terms, the economic costs of noncooperation, which we believe to be important information for water managers and policy makers, especially at a time when major developments are planned. In this paper we propose a methodology to assess the economic costs of noncooperation when managing large-scale water resources systems involving multiple reservoirs, and where the dominant uses are hydropower generation and irrigated agriculture. An analysis of the Zambezi River basin, one of the largest river basins in Africa that is likely to see major developments in the coming decades, is carried out. This valuation exercise reveals that the yearly average cost of noncooperation would reach 350 million US$/a, which is 10% of the annual benefits derived from the system.


Le Fouest V.,University Pierre and Marie Curie | Babin M.,Laval University | Tremblay J.-E.,French National Center for Scientific Research
Biogeosciences | Year: 2013

Present and future levels of primary production (PP) in the Arctic Ocean (AO) depend on nutrient inputs to the photic zone via vertical mixing, upwelling and external sources. In this regard, the importance of horizontal river supply relative to oceanic processes is poorly constrained at the pan-Arctic scale. We compiled extensive historical (1954-2012) data on discharge and nutrient concentrations to estimate fluxes of nitrate, soluble reactive phosphate (SRP), silicate, dissolved organic carbon (DOC), dissolved organic nitrogen (DON), particulate organic nitrogen (PON) and particulate organic carbon (POC) from 9 large Arctic rivers and assess their potential impact on the biogeochemistry of shelf waters. Several key points can be emphasized from this analysis. The contribution of riverine nitrate to new PP (PPnew) is very small at the regional scale (< 1% to 6.7%) and negligible at the pan-Arctic scale (< 0.83%), in agreement with recent studies. By consuming all this nitrate, oceanic phytoplankton would be able to use only 14.3% and 8.7-24.5% of the river supply of silicate at the pan-Arctic and regional scales, respectively. Corresponding figures for SRP are 28.9% and 18.6-46%. On the Beaufort and Bering shelves, riverine SRP cannot fulfil phytoplankton requirements. On a seasonal basis, the removal of riverine nitrate, silicate and SRP would be the highest in spring and not in summer when AO shelf waters are nitrogen-limited. Riverine DON is potentially an important nitrogen source for the planktonic ecosystem in summer, when ammonium supplied through the photoammonification of refractory DON (3.9 × 109 mol N) may exceed the combined riverine supply of nitrate and ammonium (3.4 × 109 mol N). Nevertheless, overall nitrogen limitation of AO phytoplankton is expected to persist even when projected increases of riverine DON and nitrate supply are taken into account. This analysis underscores the need to better contrast oceanic nutrient supply processes with the composition and fate of changing riverine nutrient deliveries in future scenarios of plankton community structure, function and production in the coastal AO. © 2013 Author(s).


Molson J.W.,Laval University | Frind E.O.,University of Waterloo
Journal of Contaminant Hydrology | Year: 2012

Protection and sustainability of water supply wells requires the assessment of vulnerability to contamination and the delineation of well capture zones. Capture zones, or more generally, time-of-travel zones corresponding to specific contaminant travel times, are most commonly delineated using advective particle tracking. More recently, the capture probability approach has been used in which a probability of capture of P = 1 is assigned to the well and the growth of a probability-of-capture plume is tracked backward in time using an advective-dispersive transport model. This approach accounts for uncertainty due to local-scale heterogeneities through the use of macrodispersion. In this paper, we develop an alternative approach to capture zone delineation by applying the concept of mean life expectancy E (time remaining before being captured by the well), and we show how life expectancy E is related to capture probability P. Either approach can be used to delineate time-of-travel zones corresponding to specific travel times, as well as the ultimate capture zone. The related concept of mean groundwater age A (time since recharge) can also be applied in the context of defining the vulnerability of a pumped aquifer. In the same way as capture probability, mean life expectancy and groundwater age account for local-scale uncertainty or unresolved heterogeneities through macrodispersion, which standard particle tracking neglects. The approach is tested on 2D and 3D idealized systems, as well as on several watershed-scale well fields within the Regional Municipality of Waterloo, Ontario, Canada. © 2011 Elsevier B.V. All rights reserved.


McClung M.R.,Oregon Osteoporosis Center | Grauer A.,Amgen Inc. | Boonen S.,Catholic University of Leuven | Bolognese M.A.,Bethesda Health Research Center | And 11 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. METHODS: In a phase 2, multicenter, international, randomized, placebo-controlled, parallelgroup, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator - oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 ìg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover. RESULTS: All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups. CONCLUSIONS: In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. © 2014 Massachusetts Medical Society.


Patent
Laval University and Gm Global Technologiy Operations Llc | Date: 2012-10-31

A balance assist system includes a support structure, an assist device, a variable balancing system, and a balancing cable. The variable balancing system is configured for moving a mass in a vertical direction along a Z axis. The variable balancing system includes a balance platform, a lever, and a mobile counterweight. The lever is pivotally attached to the balance platform at a fixed pivot point such that the lever is pivotable at the fixed pivot point about a balance axis. The mobile counterweight is movably disposed on the lever relative to the fixed balance axis and movable between a minimum position and a maximum position. The minimum position corresponds to the mass having a minimum weight such that the mass is statically balanced along the Z axis. Likewise, the maximum position corresponds to the mass having a maximum weight such that the mass is statically balanced along the Z axis.


News Article | April 22, 2016
Site: news.yahoo.com

Now considered the oldest message in a bottle, this post card was thrown into the North Sea in 1906. The oldest message in a bottle spent 108 years, 4 months and 18 days at sea. After being cast into the sea by the Marine Biological Association of the United Kingdom (MBA) in November 1906, the message washed up at Amrum Island, in Germany, on April 17, 2015. This year, Guinness World Records recognized it as the oldest message in a bottle ever found. One of more than 1,000 bottles thrown into the North Sea by marine biologist George Parker Bidder, the bottle was part of a research project on the patterns of ocean currents. More than a century later, a letter containing an original postcard from one of his bottles arrived in the mail at the MBA's Plymouth laboratory in the United Kingdom. [History's 10 Most Overlooked Mysteries] A German woman discovered the bottle while visiting Amrum, one of Germany's North Frisian Islands. The postcard inside promised a reward of 1 shilling (a former unit of currency that was equivalent to 12 pence) for filling in some information and returning the postcard. The MBA was determined to send her the proper reward. "We found an old shilling, I think we got it on eBay," Guy Baker, communications officer at MBA, told the Guardian. "We sent it to her with a letter saying thank you." Bidder's 1906 experiment was a form of what is now called "citizen science." The bottles were reportedly returned at a rate of around 55 percent — largely from fishermen encouraged by the reward — and the marine biologist was able to prove that the North Sea's deep-sea current flowed from east to west. Though this bottle's recent discovery missed its place in Bidder's original research, it now has its own place in history as the Guinness World Record holder for the world's oldest message in a bottle. Messages in bottles have long fascinated the public and researchers alike. Indeed, they've long been fixtures of heartwarming stories. In 2014, a bottle was discovered containing a message written by a young German man during a nature hike on May 17, 1913, Live Science reported. After the discovery, researchers were able to locate his granddaughter and give her a note from her grandfather, whom she'd never met. Another rare find was a message in a bottle found not at sea, but under a rock pile in the Canadian Arctic. Left by American glaciologist Paul T. Walker in 1959, the message described his glacial research and was found by other researchers 54 years later. Walker's message was particularly impactful, as he suffered a stroke during that expedition and died shortly thereafter. "We were reading some of his last words," said Warwick F. Vincent, director of the Center for Northern Studies at Laval University in Canada, and one of the researchers who found the message, as reported by Live Science. Messages can be adrift (or buried) for decades, but some more modern messages in bottles have been discovered as well. For instance, in 2011, a bottle was found on an Australian beach, 6,000 miles (9,600 kilometers) from its origin, 14 years after being cast into the sea — during a cruise in February 1997, retired Texas Tech professor George Tereshkovich had written out a message, placed it in a bottle with his business card, and tossed it into the ocean. "I told the wife what I was going to do," Tereshkovich said in a statement. "She thought I was seasick or something, throwing a note overboard. We continued cruising, and I completely forgot about it." Whether a decade or a century passes, each message in a bottle has a story to tell. Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


Chaput J.-P.,Eastern Research Group | Doucet E.,University of Ottawa | Tremblay A.,Laval University
Obesity Reviews | Year: 2012

Obesity is characterized by the accumulation of excess body fat and can be conceptualized as the physical manifestation of chronic energy excess. An important challenge of today's world is that our so-called obesogenic environment is conducive to the consumption of energy and unfavourable to the expenditure of energy. The modern, computer-dependent, sleep-deprived, physically inactive humans live chronically stressed in a society of food abundance. From a physiological standpoint, the excess weight gain observed in prone individuals is perceived as a normal consequence to a changed environment rather than a pathological process. In other words, weight gain is a sign of our contemporary way of living or a 'collateral damage' in the physiological struggle against modernity. Additionally, substantial body fat loss can complicate appetite control, decrease energy expenditure to a greater extent than predicted, increase the proneness to hypoglycaemia and its related risk towards depressive symptoms, increase the plasma and tissue levels of persistent organic pollutants that promote hormone disruption and metabolic complications, all of which are adaptations that can increase the risk of weight regain. In contrast, body fat gain generally provides the opposite adaptations, emphasizing that obesity may realistically be perceived as an a priori biological adaptation for most individuals. Accordingly, prevention and treatment strategies for obesity should ideally target the main drivers or root causes of body fat gain in order to be able to improve the health of the population. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.


Bourret V.,Laval University | Dionne M.,Service de la Faune Aquatique | Bernatchez L.,Laval University
Molecular Ecology | Year: 2014

Wild populations of Atlantic salmon have declined worldwide. While the causes for this decline may be complex and numerous, increased mortality at sea is predicted to be one of the major contributing factors. Examining the potential changes occurring in the genome-wide composition of populations during this migration has the potential to tease apart some of the factors influencing marine mortality. Here, we genotyped 5568 SNPs in Atlantic salmon populations representing two distinct regional genetic groups and across two cohorts to test for differential allelic and genotypic frequencies between juveniles (smolts) migrating to sea and adults (grilses) returning to freshwater after 1 year at sea. Given the complexity of the traits potentially associated with sea mortality, we contrasted the outcomes of a single-locus FST based genome scan method with a new multilocus framework to test for genetically based differential mortality at sea. While numerous outliers were identified by the single-locus analysis, no evidence for parallel, temporally repeated selection was found. In contrast, the multilocus approach detected repeated patterns of selection for a multilocus group of 34 covarying SNPs in one of the two populations. No significant pattern of selective mortality was detected in the other population, suggesting different causes of mortality among populations. These results first support the hypothesis that selection mainly causes small changes in allele frequencies among many covarying loci rather than a small number of changes in loci with large effects. They also point out that moving away from the a strict 'selective sweep paradigm' towards a multilocus genetics framework may be a more useful approach for studying the genomic signatures of natural selection on complex traits in wild populations. © 2014 John Wiley & Sons Ltd.


Hill R.B.,Johns Hopkins University | Pellegrini L.,Laval University | Pellegrini L.,Mitochondria Biology Laboratory
Seminars in Cell and Developmental Biology | Year: 2010

Rhomboids are an ancient and conserved family of intramembrane-cleaving proteases, a small group of proteolytic enzymes capable of hydrolyzing a peptide bond within a transmembrane helix that anchors a substrate protein to the membrane. Mitochondrial rhomboids evolved in eukaryotes to coordinate a critical aspect of cell biology, the regulation of mitochondrial membranes dynamics. This function appears to have required the emergence of a structural feature that is unique among all other rhomboids: an additional transmembrane helix (TMH) positioned at the N-terminus of six TMHs that form the core proteolytic domain of all prokaryotic and eukaryotic rhomboids. This " 1 + 6" structure, which is shared only among mitochondrial rhomboids, defines a subfamily of rhomboids with the prototypical family member being mammalian Parl. Here, we present the findings that in 11 years have elevated mitochondrial rhomboids as the gatekeepers of mitochondrial dynamics and apoptosis; further, we discuss the aspects of their biology that are bound to introduce new paradigm shifts in our understanding of how the organelle uses this unique type of protease to govern stress, signaling to the nucleus, and other key mitochondrial activities in health and disease. © 2009 Elsevier Ltd.


Fajardo A.,Center for Ecosystem Research in Patagonia | Mcintire E.J.B.,Laval University | Mcintire E.J.B.,Natural Resources Canada
Journal of Ecology | Year: 2012

Altitudinal tree line ecotones (ATE) are among the most sensitive plant formations facing global warming as the altitudinal decrease in temperature is considered the driver controlling the upper elevation limit of tree lines world-wide. In this study, we attempted to answer the following questions: (i) how have the conditions during the last 2-3 centuries affected ATE tree growth (physiology) and recruitment (demography)? and (ii) how strong is synchrony between these two processes at the ATEs? 2. We used spatial sampling grids at different ATEs in two ecosystems on two subcontinents: Nothofagus pumilio in the Andes of Chilean Patagonia (46°SL) and Pinus albicaulis in the Rockies of Western Montana, USA (46°NL). Basal increment cores were extracted from trees to estimate the growth and recruitment date. An annual detrended basal area increment was estimated for each tree and was modelled against elevation and time. Tree growth improved over multiple centuries at all tree lines. Recently (c. 50years), however, improvements are disappearing or reversing. The uppermost tree line trees showed moderate declines in Montana and incipient declines in Patagonia. The declines are most dramatic slightly below current tree line (c. 200m). Tree recruitment patterns showed that tree lines have been moving uphill in both regions until at least 40-70years ago. These movements occurred primarily through abrupt pulses upward with infilling occurring concurrently (Patagonia) or at some time thereafter (Montana). Synchrony between growth and recruitment occurred in the 18th and 19th centuries in both regions. This synchrony was negative in Patagonia and positive in Montana, with varying lag periods. During the 20th century, these patterns of synchrony were lost at all sites. This loss of synchrony suggests that we could be entering a global period in which temperature is no longer the dominant driver of key features of tree lines. Synthesis. Our study shows that at two structurally different tree lines, recent and initial declines in growth and losses of long-term synchrony are occurring in the latter part of the 20th century. These findings are opposite to simplistic expectations of global warming effects on tree line dynamics and call for a model reformulation that uncouples drivers of growth and recruitment. © 2012 The Authors. Journal of Ecology © 2012 British Ecological Society.


Mccairns R.J.S.,University of Helsinki | Mccairns R.J.S.,Laval University | Bernatchez L.,Laval University
Journal of Evolutionary Biology | Year: 2012

The threespine stickleback (Gasterosteus aculeatus) has emerged as an important model organism in evolutionary ecology, largely due to the repeated, parallel evolution of divergent morphotypes found in populations having colonized freshwater habitats. However, morphological divergence following colonization is not a universal phenomenon. We explore this in a large-scale estuarine ecosystem inhabited by two parapatric stickleback demes, each physiologically adapted to divergent osmoregulatory environments (fresh vs. saline waters). Using geometric morphometric analyses of wild-caught individuals, we detected significant differences between demes, in addition to sexual dimorphism, in body shape. However, rearing full-sib families from each deme under controlled, reciprocal salinity conditions revealed no differences between genotypes and highly significant environmental effects. It is also noteworthy that fish from both demes were fully plated, whether found in the wild or reared under reciprocal salinity conditions. Although we found significant heritability for body shape, we also noted significant direct environmental effects for many latent shape variables. Moreover, we found little evidence for diversifying selection acting on body size and shape (Q ST). Nevertheless, uniform compressive variation did exceed neutral expectations, yet despite evidence of both allometry and genetic correlation with body length, we detected no correlated signatures of selection. Taken together, these results suggest that much of the morphological divergence observed in this system is the result of plastic responses to environmental variation rather than adaptive differentiation. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.


Matamoros S.,Laval University | Gras-Leguen C.,University of Nantes | Gras-Leguen C.,Nantes University Hospital Center | Le Vacon F.,Biofortis SAS | And 3 more authors.
Trends in Microbiology | Year: 2013

Throughout the human lifetime, the intestinal microbiota performs vital functions, such as barrier function, metabolic reactions, trophic effects, and maturation of the host's innate and adaptive immune responses. Development of the intestinal microbiota in infants is characterized by rapid and large changes in microbial abundance, diversity, and composition. These changes are influenced by medical, cultural, and environmental factors such as mode of delivery, diet, familial environment, diseases, and therapies used. Thus, it is nearly impossible to define a universal standard for intestinal colonization and development of the intestinal microbiota. This review discusses recent data on the early colonization of the gut by microbial species, development of the intestinal microbiota, and its impact on health. © 2012 Elsevier Ltd.


Lee H.-Y.,Seoul National University | Despres J.-P.,Laval University | Koh K.K.,Gachon University
Atherosclerosis | Year: 2013

Adipose tissue, which has been considered mainly as a site of energy storage and mobilization, is found in many depots throughout the body. Adipose depots may have structural properties such as, for instance, the fat pads located in the hands and feet and the periorbital fat supporting the eyes. Adipose tissue also shows remarkable regional heterogeneity. For instance, substantial differences have been reported in the metabolic properties of visceral (intra-abdominal) vs. subcutaneous adipose depots. Visceral adipose tissue (VAT) has active endocrine and paracrine functions with the secretion of various pro-inflammatory chemokines potentially contributing to the progression of atherosclerosis related with obesity. In addition, adipose depots surrounding the heart, such as epicardial (EAT) and perivascular adipose tissues (PAT) may also exert important roles in the pathogenesis of cardiovascular disease beyond the contribution of VAT due to their close anatomic relationships with vascular structures and myocardium. The purpose of the present review is to outline the current understanding of the pathophysiological links between EAT, PAT and atherosclerotic cardiovascular disease. Also, we discuss the current investigative methods for PAT quantification and discuss the potential impact of PAT on cardiovascular risk prediction. Finally, potential clinical implications of these notions are discussed. © 2013 Elsevier Ireland Ltd.


Jeyaraju D.V.,Laval University | McBride H.M.,University of Ottawa | Hill R.B.,Johns Hopkins University | Pellegrini L.,Laval University
Cell Death and Differentiation | Year: 2011

The mitochondrial rhomboid protease Parl governs apoptosis, morphology, metabolism and might be implicated in Parkinson's disease, but the structural basis of its activity and complex regulation remain unknown. We report the discovery of γ-cleavage, a proteolytic event on the loop connecting the first transmembrane helix (TMH) of Parl to the 6-TMH catalytic rhomboid domain of the protease. This cleavage disrupts the 16 structure that defines every mitochondrial rhomboid and generates a new form of Parl, PROD (Parl-rhomboid-domain). Structure-function analysis of Parl suggests that γ-cleavage could be implicated in eliminating Parl proteolytic activity, and structural modeling of PROD reveals structural conservation with the bacterial rhomboid GlpG. However, unlike bacterial rhomboids, which employ a diad-based mechanism of catalysis, Parl appears to use a conserved mitochondrial rhomboid-specific Asp residue on TMH-5 in a triad-based mechanism of catalysis. This work provides unexpected insights into the structural determinants regulating Parl stability and activity in vivo, and reveals a complex cascade of proteolytic events controlling the function of the protease in the mitochondrion. © 2011 Macmillan Publishers Limited All rights reserved.


Gagnon A.-E.,Laval University | Heimpel G.E.,University of Minnesota | Brodeur J.,University of Montréal
PLoS ONE | Year: 2011

Intraguild predation (IGP) occurs when one predator species attacks another predator species with which it competes for a shared prey species. Despite the apparent omnipresence of intraguild interactions in natural and managed ecosystems, very few studies have quantified rates of IGP in various taxa under field conditions. We used molecular analyses of gut contents to assess the nature and incidence of IGP among four species of coccinellid predators in soybean fields. Over half of the 368 predator individuals collected in soybean contained the DNA of other coccinellid species indicating that IGP was very common at our field site. Furthermore, 13.2% of the sampled individuals contained two and even three other coccinellid species in their gut. The interaction was reciprocal, as each of the four coccinellid species has the capacity to feed on the others. To our knowledge, this study represents the most convincing field evidence of a high prevalence of IGP among predatory arthropods. The finding has important implications for conservation biology and biological control. © 2011 Gagnon et al.


Roberge S.,Laval University | Nicolaides K.H.,King's College | Demers S.,Laval University | Villa P.,University of Helsinki | Bujold E.,Laval University
Ultrasound in Obstetrics and Gynecology | Year: 2013

Objective To compare early vs late administration of low-dose aspirin on the risk of perinatal death and adverse perinatal outcome. Methods Databases were searched for keywords related to aspirin and pregnancy. Only randomized controlled trials that evaluated the prophylactic use of low-dose aspirin (50-150 mg/day) during pregnancy were included. The primary outcome combined fetal and neonatal death. Pooled relative risks (RR) with their 95% CIs were compared according to gestational age at initiation of low-dose aspirin (≤ 16 vs > 16 weeks of gestation). Results Out of 8377 citations, 42 studies (27 222 women) were included. Inclusion criteria were risk factors for pre-eclampsia, including: nulliparity, multiple pregnancy, chronic hypertension, cardiovascular or endocrine disease, prior gestational hypertension or fetal growth restriction, and/or abnormal uterine artery Doppler. When compared with controls, low-dose aspirin started at ≤ 16 weeks' gestation compared with low-dose aspirin started at >16 weeks' gestation was associated with a greater reduction of perinatal death (RR = 0.41 (95% CI, 0.19-0.92) vs 0.93 (95% CI, 0.73-1.19), P = 0.02), pre-eclampsia (RR = 0.47 (95% CI, 0.36-0.62) vs 0.78 (95% CI, 0.61-0.99), P < 0.01), severe pre-eclampsia (RR = 0.18 (95% CI, 0.08-0.41) vs 0.65 (95% CI, 0.40-1.07), P < 0.01), fetal growth restriction (RR = 0.46 (95% CI, 0.33-0.64) vs 0.98 (95% CI, 0.88-1.08), P < 0.001) and preterm birth (RR = 0.35 (95% CI, 0.22-0.57) vs 0.90 (95% CI, 0.83-0.97), P < 0.001). Conclusion Low-dose aspirin initiated at ≤ 16 weeks of gestation is associated with a greater reduction of perinatal death and other adverse perinatal outcomes than when initiated at >16 weeks. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.


Merkle J.A.,Laval University | Fortin D.,Laval University | Morales J.M.,National University of Comahue
Ecology Letters | Year: 2014

The restricted area of space used by most mobile animals is thought to result from fitness-rewarding decisions derived from gaining information about the environment. Yet, assessments of how animals deal with uncertainty using memory have been largely theoretical, and an empirically derived mechanism explaining restricted space use in animals is still lacking. Using a patch-to-patch movement analysis, we investigated predictions of how free-ranging bison (Bison bison) living in a meadow-forest matrix use memory to reduce uncertainty in energy intake rate. Results indicate that bison remembered pertinent information about location and quality of meadows, and they used this information to selectively move to meadows of higher profitability. Moreover, bison chose profitable meadows they had previously visited, and this choice was stronger after visiting a relatively poor quality meadow. Our work demonstrates a link between memory, energy gains and restricted space use while establishing a fitness-based integration of movement, cognitive and spatial ecology. © 2014 John Wiley & Sons Ltd/CNRS.


Tremblay A.,Laval University | Royer M.-M.,Laval University | Chaput J.-P.,Eastern Research Group | Doucet E.,University of Ottawa
International Journal of Obesity | Year: 2013

The decrease in energy expenditure that occurs during weight loss is a process that attenuates over time the impact of a restrictive diet on energy balance up to a point beyond which no further weight loss seems to be possible. For some health professionals, such a diminished energy expenditure is the normal consequence of a progressive decrease in the motivation to exercise over the course of a weight-reducing program. Another explanation of decreased energy needs during weight loss is the decrease in body energy stores (that is, fat mass and muscle mass) and its related obligatory costs of living. Many studies have also documented the existence of adaptive thermogenesis in the context of weight loss, which represents a greater-than-predicted decrease in energy expenditure. In this paper, we pursue the analysis of this phenomenon by demonstrating that an adaptive decrease in thermogenesis can have a major role in the occurrence of resistance to further lose fat in weight-reduced obese individuals. Evidence is also presented to support the idea of greater hunger sensations in individuals displaying more pronounced thermogenic changes. Finally, as the decrease in thermogenesis persists over time, it is also likely associated with a greater predisposition to body-weight regain after weight loss. Globally, these observations suggest that the adaptive reduction in thermogenesis that accompanies a prolonged negative energy balance is a major determinant of the ability to spontaneously lose body fat. © 2013 Macmillan Publishers Limited.


Duquenne P.,Institute National Of Recherche Et Of Securite | Marchand G.,Service Prevention des Risques Chimiques et Biologiques | Duchaine C.,Laval University
Annals of Occupational Hygiene | Year: 2013

Endotoxins are lipopolysaccharides found in the outer membrane of most Gram-negative bacteria and cyanobacteria. Worker exposure to endotoxins has been shown in a number of work situations and is associated with both respiratory and systemic pathologies. The lack of an occupational exposure limit is mainly due to the absence of a standard protocol at the international level for sampling and analyzing airborne endotoxins. The bibliographic review in this article takes an exhaustive look at the current knowledge on measuring airborne endotoxins. It shows that, despite several reference documents at the international level, the methods used to measure endotoxin exposure differ considerably from one laboratory to another. Standardization is necessary to reduce interlaboratory variability and, ultimately, to improve the use of interstudy data. The bibliographic review presents the current status of standardization for airborne endotoxin measurement methods in the workplace and summarizes areas for further research. This article is both a reference document for all operators wishing to use such methods and a working document to build international consensus around the measurement of airborne endotoxins.


Chaput J.-P.,Eastern Research Group | Tremblay A.,Laval University
Obesity Facts | Year: 2012

Objective: To verify whether sleep quantity and quality at baseline predict the magnitude of fat loss in adults subjected to moderate caloric restriction. Methods: A total of 123 overweight and obese men and women (age, 41.1 ± 6.0 years; BMI, 33.2 ± 3.6 kg/m2 (mean ± SD)) underwent a weight loss intervention consisting of a targeted 600-700 kcal/day decrease in energy intake supervised by a dietician. The length of the intervention varied between 15 and 24 weeks. Body fat mass (dual-energy X-ray absorptiometry), sleep quality (total Pittsburgh Sleep Quality Index score) and sleep duration (h/night, self-reported from the Pittsburgh Sleep Quality Index) were assessed at both baseline and at the end of the weight loss program. Results: The mean weight loss over the dietary intervention was 4.5 ± 3.9 kg, 76% of which came from fat stores. Using a multiple linear regression analysis, we observed a significant positive relationship between sleep duration and the loss of body fat, both in absolute (adjusted β = 0.72 kg/h; p < 0.05) as well as in relative terms (adjusted β = 0.77%/h; p < 0.01), after adjusting for age, sex, baseline BMI, length of the intervention, and change in total energy intake. Furthermore, we observed that a better sleep quality at baseline was associated with greater fat mass loss. Conclusion: This study provides evidence that sleeping habits can influence the success of a weight loss intervention and should be taken into consideration when one decides to start a diet. Copyright © 2012 S. Karger GmbH, Freiburg.


Waldron K.,Laval University | Ruel J.-C.,Laval University | Gauthier S.,Natural Resources Canada
Forest Ecology and Management | Year: 2013

In the eastern boreal forest of Quebec (Canada) windthrow is a major natural disturbance, given the long fire cycle interval. Understanding windthrow is essential to ecosystem-based forest management. Dead wood, live trees, and pit-and-mound microtopography are major post-windthrow attributes with known ecological importance. So far, these structural post-windthrow attributes have not been described for this ecosystem. In addition, ecological consequences of salvage logging after windthrow remain unknown, with no specific salvage standard being applied to maintain such attributes and biological legacies. In this study, comparisons were made between salvaged and unsalvaged windthrow to identify which post-windthrow attributes were more greatly affected by harvest operations and to clarify management options. Downed coarse woody debris (downed CWD), snags, live trees, and pits and mounds were characterized. We showed that downed CWD and snags diminished after salvage operations, with a more uniform distribution among decay classes. Pit and mound density was reduced after salvage logging compared to unsalvaged windthrow, with pits being smaller in the salvaged plots. From an ecosystem management perspective, retention patches with dead wood and standing living trees should be kept in salvaged cut-blocks. To minimize salvage operation effects on microtopography, machinery trails should be reduced to a minimum. Also, a certain proportion of windthrow should be exempted from logging operations. © 2012 Elsevier B.V.


Avineri E.,University of the West of England | Avineri E.,Afeka Academic College of Engineering | Owen D.E.,Laval University
Transportation Research Part A: Policy and Practice | Year: 2013

The provision of information about transport-related carbon dioxide (CO2) emissions to the traveler can be seen as an instrument to increase the likelihood of more sustainable choices being made by individuals. However, as transport-related CO2 emissions are largely seen as a 'social' cost rather than a 'private' cost to the individual, the behavioral engagement with and response to information on environmental effects of travel choices may be limited. It is argued that framing, studied in a range of contexts, can be used to enhance the evaluation of choice attributes and promote more sustainable choices. An experiment is reported that examines the effect of valence framing of amounts of CO2 emissions on the perceived differences between alternative amounts. Through the use of positive and negative terms, the information is framed to focus attention either on the potential of a travel mode to provide environmental benefit (positive frame) or on its potential to reduce environmental loss (negative frame). Survey participants' estimates of CO2 amounts were compared for positive and negative framing of the same information using an ordered logit model. The findings imply that negative framing is more effective than positive framing in highlighting differences between CO2 amounts of alternative travel modes and therefore is likely to influence travel-related choices. © 2012 Elsevier Ltd.


Lim S.,Seoul National University | Despres J.-P.,Laval University | Koh K.K.,Gachon University
Circulation Journal | Year: 2011

Obesity has reached epidemic proportions and complications related to obesity contribute substantially to both healthcare costs and mortality. Obesity, particularly when accompanied by an excess of visceral/ectopic fat, is a major risk factor for diseases ranging from insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. The epidemic proportions reached by obesity has made these conditions a global problem in human health. Accordingly, preventive and/or therapeutic interventions should be considered in obese patients. Regular physical activity/exercise has numerous beneficial effects on the cardiometabolic risk profile and on the cardiovascular system. However, our current clinical environment is not designed to provide the regular support needed by patients to help them maintain over the long term their improved physical activity/nutritional habits. Because hypertension, dyslipidemia, hyperinsulinemia, and excess visceral adipose tissue are linked by complex reciprocal molecular interactions, it is logical to expect that targeting an interconnected pathway may provide multiple benefits. At this stage, combined therapy of statins or PPAR agonists and renin-angiotensin-aldosterone system blockers to target multiple therapeutic pathways may optimally improve the cardiometabolic risk profile through both distinct and interrelated mechanisms. In the present article, we will discuss updated novel approaches, including potential multi-targeted intervention strategies, based on underlying pathophysiological processes.


News Article | September 13, 2016
Site: www.materialstoday.com

Returning after 30 years to the historic city of Boston, the 2016 POWDERMET International Conference on Powder Metallurgy and Particulate Materials, and AMPM (Additive Manufacturing with Powder Metallurgy) conferences and Exhibition were held at the Sheraton Boston Hotel, June 5 to June 8. After welcoming nearly 900 attendees from 30 countries at the opening plenary session, MPIF Executive Director C. James Trombino  gave a special greeting and salute to Mike Jaffe, a past president of MPIF, a PM industry veteran of over 50 years and whose teaching demonstrator 'Pop-corn Press' had been a fixture at the MPIF PM short courses for half a century. Trombino also took the opportunity to mention the recent passing of two PM organization leaders: MPIF’s founder and first Executive Director, Kempton H. Roll, and Jonathan Wroe, who was Executive Director of EPMA since 2001. He went on to welcome the presence of the incoming Director of EPMA, Dr Lionel Aboussouan. Trombino then recognized and thanked the Technical program committee and its co-chairmen, Carl Blais, Laval University, Quebec, and Jeff Hamilton, MPG-Cloyes Gear. This article appeared in the July/Aug issue of Metal Powder Report. Log in to your free Materials Today account to download the full article.


Kirchman D.L.,University of Delaware | Cottrell M.T.,University of Delaware | Lovejoy C.,Laval University
Environmental Microbiology | Year: 2010

Bacterial communities in the surface layer of the oceans consist of a few abundant phylotypes and many rare ones, most with unknown ecological functions and unclear roles in biogeochemical processes. To test hypotheses about relationships between abundant and rare phylotypes, we examined bacterial communities in the western Arctic Ocean using pyrosequence data of the V6 region of the 16S rRNA gene. Samples were collected from various locations in the Chukchi Sea, the Beaufort Sea and Franklin Bay in summer and winter. We found that bacterial communities differed between summer and winter at a few locations, but overall there was no significant difference between the two seasons in spite of large differences in biogeochemical properties. The sequence data suggested that abundant phylotypes remained abundant while rare phylotypes remained rare between the two seasons and among the Arctic regions examined here, arguing against the 'seed bank' hypothesis. Phylotype richness was calculated for various bacterial groups defined by sequence similarity or by phylogeny (phyla and proteobacterial classes). Abundant bacterial groups had higher within-group diversity than rare groups, suggesting that the ecological success of a bacterial lineage depends on diversity rather than on the dominance of a few phylotypes. In these Arctic waters, in spite of dramatic variation in several biogeochemical properties, bacterial community structure was remarkably stable over time and among regions, and any variation was due to the abundant phylotypes rather than rare ones. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.


Da Silva A.K.,University of Texas at Austin | Gosselin L.,Laval University
Numerical Heat Transfer; Part A: Applications | Year: 2011

The main goal of this study is to numerically determine a converged optimal heating pattern for the Graetz problem in a two-dimension channel subjected to a discrete heating profile. The heat input is provided by multiple independent heaters, while considering the following conditions: symmetric and asymmetric heating without a conductive wall and symmetric heating with a conductive wall. The optimization process, which was based on the genetic algorithm, shows a strong dependence of the cooling performance on the heating profile which is especially affected at relatively low flow speeds if the wall conduction is not present. If conduction through the wall is considered, the importance of the heating pattern is reduced for relatively thick walls. Results also indicate that asymmetric heating conditions are not recommended when compared with symmetric patterns. Copyright © Taylor & Francis Group, LLC.


Shah M.,Accenture | Marchand M.,Laval University | Corbeil J.,Laval University
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2012

One of the objectives of designing feature selection learning algorithms is to obtain classifiers that depend on a small number of attributes and have verifiable future performance guarantees. There are few, if any, approaches that successfully address the two goals simultaneously. To the best of our knowledge, such algorithms that give theoretical bounds on the future performance have not been proposed so far in the context of the classification of gene expression data. In this work, we investigate the premise of learning a conjunction (or disjunction) of decision stumps in Occam's Razor, Sample Compression, and PAC-Bayes learning settings for identifying a small subset of attributes that can be used to perform reliable classification tasks. We apply the proposed approaches for gene identification from DNA microarray data and compare our results to those of the well-known successful approaches proposed for the task. We show that our algorithm not only finds hypotheses with a much smaller number of genes while giving competitive classification accuracy but also having tight risk guarantees on future performance, unlike other approaches. The proposed approaches are general and extensible in terms of both designing novel algorithms and application to other domains. © 2012 IEEE.


Huang J.,Laval University | Huang J.,Guangxi University of Science and Technology | Rodrigue D.,Laval University
Materials and Design | Year: 2014

Finite element method (FEM) is used to predict the tensile and compressive stress-strain curves of single wall carbon nanotube (SWCNT) reinforced polypropylene (PP) composites. The numerical simulations, using shell and tetrahedron elements, are first carried out to investigate the effect of SWCNT orientation on the mechanical properties of the nano-composites. Second, the Grunfest-Young constitutive equation is selected to determine the effect of strain rate and solve the finite element program to analyze the mechanical behavior of the nano-composites. Third, the effect of SWCNT volume fraction is studied. In all cases, the shear and normal stresses distribution along the nanotube axis are investigated and compared with the macroscopic tensile or compressive stresses on the composites. At the same time, the stresses of the interface between SWCNT and the matrix along the loading direction are analyzed. Finally, the effects of SWCNT orientation, content and strain rate on the strength of the nano-composites are studied. From the results obtained, it was shown that strain rate can substantially affect the tensile and shear stresses of the composites, but do not significantly influence the initial tensile or compressive elastic moduli. This is especially the case for SWCNT orientation angles less than 30° and volume fractions higher than 0.74%. © 2013.


Parent G.J.,Laval University | Plourde S.,Maurice Lamontagne Institute | Turgeon J.,Laval University
Limnology and Oceanography | Year: 2012

Calanus glacialis and Calanus finmarchicus dominate the zooplankton community in the Arctic and North Atlantic, respectively. The vast zone of sympatry between these species, the potential for overlap between reproductive seasons, and the evidence for intermediate values of discriminant traits suggest that these species hybridize. We genotyped 684 individuals from 14 Arctic to Atlantic stations using one mitochondrial (16S) and 10 nuclear loci (microsatellites). Strong genetic differentiation between parental species confidently identified hybrids in areas of sympatry. Hybrid frequency was highly variable among stations and did not covary with mean annual sea surface temperature. In the St. Lawrence Estuary, parental and hybrid genotypes were nonrandomly distributed between depth layers (300-100 m and 100-0 m) and across sampling dates, and hybrids seemed more frequent in July than in May and September. Overall, the bimodal frequency distribution of parental and hybrid genotypes suggests that reproductive barriers limit gene flow between these species. The opportunity for interbreeding is more likely restricted by differences in species reproductive phenology than by dispersal. Hybridization also affects prosome length, a morphological trait widely used to discriminateCalanus species, and thus possibly contributes to species misidentification. Highly introgressed individuals indicate that hybrids are fertile and reproduce, suggesting that hybrid fitness could affect estimates and models of these species population dynamics. This is the first evidence for interspecific hybridization between marine zooplankton species, but similar cases could be uncovered using nuclear genetic markers in groups of closely related and morphologically similar marine zooplankton species. © 2012, by the Association for the Sciences of Limnology and Oceanography, Inc.


Lussier P.,Laval University | Cale J.,University of New South Wales
Aggression and Violent Behavior | Year: 2013

The current study claims that measures of sexual recidivism provide a distorted view of the criminal activity of adult sex offenders. To address this important limitation, the criminal career perspective is presented and key concepts are defined and described. The study also provides an up-to-date review of the scientific literature on various criminal career parameters of the sexual criminal activity of adult sex offenders. Hence, current empirical knowledge on the prevalence, age of onset, frequency, continuity, versatility, and desistance from sex offending is presented. The findings highlight the complexities of the sexual criminal career of adult sex offenders, and most importantly, its dynamic aspect, both of which are not captured by traditional measures of sexual recidivism. The review also underscores the importance of recognizing that sexual offending develops according to a series of stages, that, if not recognized, may lead to the underestimation of risk for some and over-estimation of risk for others. The review provides a framework to stimulate new areas of research as well as policy-development that is not limited to the identification of the "high-risk" convicted sex offenders. © 2013 Elsevier Ltd.


Seifu D.G.,Laval University | Purnama A.,Laval University | Mequanint K.,University of Western Ontario | Mantovani D.,Laval University
Nature Reviews Cardiology | Year: 2013

Vascular occlusion remains the leading cause of death in Western countries, despite advances made in balloon angioplasty and conventional surgical intervention. Vascular surgery, such as CABG surgery, arteriovenous shunts, and the treatment of congenital anomalies of the coronary artery and pulmonary tracts, requires biologically responsive vascular substitutes. Autografts, particularly saphenous vein and internal mammary artery, are the gold-standard grafts used to treat vascular occlusions. Prosthetic grafts have been developed as alternatives to autografts, but their low patency owing to short-term and intermediate-term thrombosis still limits their clinical application. Advances in vascular tissue engineering technology-such as self-assembling cell sheets, as well as scaffold-guided and decellularized-matrix approaches-promise to produce responsive, living conduits with properties similar to those of native tissue. Over the past decade, vascular tissue engineering has become one of the fastest-growing areas of research, and is now showing some success in the clinic. © 2013 Macmillan Publishers Limited.


Legare F.,St Francois dAssise Hospital | Legare F.,Laval University | Thompson-Leduc P.,St Francois dAssise Hospital
Patient Education and Counseling | Year: 2014

Objective: As shared decision makes increasing headway in healthcare policy, it is under more scrutiny. We sought to identify and dispel the most prevalent myths about shared decision making. Methods: In 20 years in the shared decision making field one of the author has repeatedly heard mention of the same barriers to scaling up shared decision making across the healthcare spectrum. We conducted a selective literature review relating to shared decision making to further investigate these commonly perceived barriers and to seek evidence supporting their existence or not. Results: Beliefs about barriers to scaling up shared decision making represent a wide range of historical, cultural, financial and scientific concerns. We found little evidence to support twelve of the most common beliefs about barriers to scaling up shared decision making, and indeed found evidence to the contrary. Conclusion: Our selective review of the literature suggests that twelve of the most commonly perceived barriers to scaling up shared decision making across the healthcare spectrum should be termed myths as they can be dispelled by evidence. Practice implications: Our review confirms that the current debate about shared decision making must not deter policy makers and clinicians from pursuing its scaling up across the healthcare continuum. © 2014 The Authors.


Laplante M.,Laval University | Sabatini D.M.,Whitehead Institute For Biomedical Research | Sabatini D.M.,Howard Hughes Medical Institute | Sabatini D.M.,Massachusetts Institute of Technology
Journal of Cell Science | Year: 2013

The mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates key cellular functions linked to the promotion of cell growth and metabolism. This kinase, which is part of two protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), has a fundamental role in coordinating anabolic and catabolic processes in response to growth factors and nutrients. Of the two mTOR complexes, mTORC1 is by far the best characterized. When active, mTORC1 triggers cell growth and proliferation by promoting protein synthesis, lipid biogenesis, and metabolism, and by reducing autophagy. The fact that mTORC1 deregulation is associated with several human diseases, such as type 2 diabetes, cancer, obesity and neurodegeneration, highlights its importance in the maintenance of cellular homeostasis. Over the last years, several groups observed that mTORC1 inhibition, in addition to reducing protein synthesis, deeply affects gene transcription. Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPARγ, PPARα, HIF1α, YY1-PGC1α and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts. © 2013. Published by The Company of Biologists Ltd.


Laplante M.,Whitehead Institute For Biomedical Research | Laplante M.,Howard Hughes Medical Institute | Laplante M.,Massachusetts Institute of Technology | Laplante M.,Laval University | And 3 more authors.
Cell | Year: 2012

The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation. © 2012 Elsevier Inc.


Gallant A.R.,Laval University | Lundgren J.,University of Missouri - Kansas City | Drapeau V.,Laval University
Obesity Reviews | Year: 2012

The rising prevalence of obesity is a global concern. Eating behaviour and circadian rhythm are proving to be important factors in the aetiology of obesity. The night-eating syndrome (NES) is characterized by increased late-night eating, insomnia, a depressed mood and distress. It is evident that prevalence is higher among weight-related populations than the general community. The exact relationship between this syndrome and obesity remains unclear. The reasons for the discrepancies found in the literature likely include varying diagnostic criteria and a wide range of study population characteristics. NES does not always lead to weight gain in thus certain individuals may be susceptible to night-eating-related weight gain. Weight loss through surgical and behavioural treatments has shown success in diminishing symptoms. The increasing literature associating obesity with circadian imbalances strengthens the link between the NES and obesity. Circadian genes may play a role in this syndrome. This review will examine different aspects of obesity in the context of the NES. © 2012 International Association for the Study of Obesity.


Yu L.,Laval University | Sheng Y.,Laval University | Chiou A.,National Yang Ming University
Optics Express | Year: 2013

For studying the elastic properties of a biconcave red blood cell using the dual-trap optical tweezers without attaching microbeads to the cell, we implemented a three-dimensional finite element simulation of the light scattering and cell's deformation using the coupled electromagnetic and continuum mechanics modules. We built the vector field of the trapping beams, the cell structure layout, the hyperelastic and viscoelastic cell materials, and we reinforced the constraints on the cell constant volume in the simulation. This computation model can be useful for studying the scattering and the other mechanical properties of the biological cells. © 2013 Optical Society of America.


Liu J.,University of Queensland | Yang H.Q.,Shanxi University | Kleitz F.,Laval University | Chen Z.G.,University of Queensland | And 4 more authors.
Advanced Functional Materials | Year: 2012

This contribution describes the preparation of multifunctional yolk-shell nanoparticles (YSNs) consisting of a core of silica spheres and an outer shell based on periodic mesoporous organosilica (PMO) with perpendicularly aligned mesoporous channels. The new yolk-shell hybrid materials were synthesised through a dual mesophase and vesicle soft templating method. The mesostructure of the shell, the dimension of the hollow space (4∼52 nm), and the shell thickness (16∼34 nm) could be adjusted by precise tuning of the synthesis parameters, as evidenced by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen sorption investigations. Various metal nanoparticles (e.g., Au, Pt, and Pd) were encapsulated and confined in the void space between the core and the shell using impregnation and reduction of adequate metal precursors. The selective oxidation of various alcohol substrates was then carried out to illustrate the benefits of such an architecture in catalysis. High conversion (∼100%) and excellent selectivity (∼99%) were obtained over Pd nanoparticles encapsulated in the hybrid PMO yolk-shell structures. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Silva-Villa E.,Laval University | Adamo A.,Max Planck Institute for Astronomy | Bastian N.,Liverpool John Moores University
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2013

Recent observations, aswell as theoretical studies, have suggested that stellar cluster formation may depend on local and global environmental properties. In particular, the fraction of stars that form within long-lived bound clusters(Γ) may depend on environment, with indications that it may be higher in the more extreme environments of high star formation rate density galaxies. How Γ varies has important implications on the use of clusters to determine thestar formation histories of galaxies as well as our understanding of the star formation process itself. Previous studies have estimated Γ over full galaxies, making it difficult to discern the physical cause of the reported variations. Here, we use existing star cluster catalogues and Hubble Space Telescope Wide Field Camera 3 V and I images of the grand design, face-on spiral galaxy M83 in order to see if and how Γ varies within a single galaxy. We find that Γ decreases strongly as a function of galactocentric radius, by a factor of ̃5 over the inner ̃6 kpc, in agreement with recent theoretical predictions and decreasing trends observed in the gas surface density of the galaxy. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Patent
ImStar Therapeutics Inc. and Laval University | Date: 2014-11-25

Provided herein are synthetic analogs of withanolide natural products of formula (I), wherein R1-R4 are as defined herein, and their pharmaceutical uses in treating neurodegenerative diseases.


News Article | October 25, 2016
Site: www.sciencenews.org

Rocky Mountain hikers might need to start packing more bear spray: Climate change may reduce the time that grizzly bears spend in hibernation — leaving them more time to scare the crap out of any humans wandering in their territory. Scientists aren’t really concerned about bear hibernation because of unwary hikers, of course. It’s because hibernation is an important time of year for a grizzly bear. By going into hibernation and suppressing their metabolisms, the bears can reduce the amount of energy they expend by some 85 percent and more easily get through months when food supplies are short and weather is bleak. Plus, this is when pregnant females give birth and start raising their young. Disrupt hibernation time and a bear is set for a bad — and potentially deadly — year. And then there’s the fact that in some places, grizzly bears aren’t doing so well. That’s true in Alberta, Canada, where the bears, already low in number, have been threatened by habitat loss and human hunters and have low reproductive rates. Karine Pigeon of Laval University in Quebec City and colleagues wanted to know whether they should add climate change to that list of threats. But first they needed more information about the factors that drive the bears into and out of their dens. The bears don’t go into or leave hibernation on specific dates (apparently they don’t use our calendar system), so how do they know when it’s time to hibernate? To find out, the team captured 15 male and 58 female grizzly bears from 1999 to 2011 in an area along the Alberta-British Columbia border northwest of Calgary. The bears were weighed and measured and fitted with tracking collars. Because the signals from the collars couldn’t be tracked from inside the bears’ dens, the researchers knew when the animals entered and left hibernation. The scientists also collected information about the local weather and the availability of berries, one of the bears’ preferred foods. No single factor explained the dates on which the grizzlies entered and left hibernation, but some were more important than others, the team reports in the October Behavioral Ecology and Sociobiology. Pregnant females, for instance, entered their dens on average two weeks earlier than males, and the ones that had given birth and had cubs emerged two weeks later. This matched what scientists know about bear denning habits, which are thought to promote the cubs’ safety and development. The end of hibernation tended to be linked to weather and elevation. A bear denning at high elevation in a year in which spring arrived late would stay snug and warm in its den for longer than a grizzly lower down and when spring arrived early. The den entry date, though, wasn’t tied to weather. It was partially linked to the availability of food: When there were plenty of tasty berries available, grizzlies tended to stay out and keep eating. And this is where there’s a problem regarding climate change, the researchers note. Because if longer autumns promote the plentiful production of berries, and earlier springs are bringing milder conditions that prompt bears to leave their dens, then grizzlies may hibernate less. That could have repercussions for females with cubs, the researchers note, because it may lead to smaller, more vulnerable cubs being led out into the open — where humans or other bears could kill them.


McClellan K.A.,McGill University | Avard D.,McGill University | Simard J.,Laval University | Knoppers B.M.,McGill University
European Journal of Human Genetics | Year: 2013

Personalized medicine promises that an individual's genetic information will be increasingly used to prioritize access to health care. Use of genetic information to inform medical decision making, however, raises questions as to whether such use could be inequitable. Using breast cancer genetic risk prediction models as an example, on the surface clinical use of genetic information is consistent with the tools provided by evidence-based medicine, representing a means to equitably distribute limited health-care resources. However, at present, given limitations inherent to the tools themselves, and the mechanisms surrounding their implementation, it becomes clear that reliance on an individual's genetic information as part of medical decision making could serve as a vehicle through which disparities are perpetuated under public and private health-care delivery models. The potential for inequities arising from using genetic information to determine access to health care has been rarely discussed. Yet, it raises legal and ethical questions distinct from those raised surrounding genetic discrimination in employment or access to private insurance. Given the increasing role personalized medicine is forecast to play in the provision of health care, addressing a broader view of what constitutes genetic discrimination, one that occurs along a continuum and includes inequitable access, will be needed during the implementation of new applications based on individual genetic profiles. Only by anticipating and addressing the potential for inequitable access to health care occurring from using genetic information will we move closer to realizing the goal of personalized medicine: to improve the health of individuals. © 2013 Macmillan Publishers Limited. All rights reserved.


Joyal D.,McGill University | Afilalo J.,McGill University | Rinfret S.,Laval University
American Heart Journal | Year: 2010

Background: Chronic total occlusion (CTO) recanalizations remain extremely challenging procedures. With improvements in technology and techniques, success rates for recanalization of CTO continue to improve. However, the clinical benefits of this practice remain unclear. The aim of the study was to determine the effectiveness of CTO recanalization on clinical outcomes. Methods: We performed a systematic review and meta-analysis of published studies comparing CTO recanalization to medical management. Data were extracted in duplicate and analyzed by a random effects model. Results: We did not identify any randomized controlled trials or observational studies comparing CTO recanalization to a planned medical management. We did identify 13 observational studies comparing outcomes after successful vs failed CTO recanalization attempt. These studies encompassed 7,288 patients observed over a weighted average follow-up of 6 years. There were 721 (14.3%) deaths of 5,056 patients after successful CTO recanalization compared to 390 deaths (17.5%) of 2,232 patients after failed CTO recanalization (odds ratio [OR] 0.56, 95% CI 0.43-0.72). Successful recanalization was associated with a significant reduction in subsequent coronary artery bypass graft surgery (CABG) (OR 0.22, 95% CI 0.17-0.27) but not in myocardial infarction (OR 0.74, 95% CI 0.44-1.25) or major adverse cardiac events (OR 0.81, 95% CI 0.55-1.21). In the 6 studies that reported angina status, successful recanalization was associated with a significant reduction in residual/recurrent angina (OR 0.45, 95% CI 0.30-0.67). Conclusions: In highly selected patients considered for CTO recanalization, successful attempts appear to be associated with an improvement in mortality and with a reduction for the need for CABG as compared to failed recanalization. However, given the observational nature of the reviewed evidence, randomized clinical trials are needed to confirm these findings. © 2010, Mosby, Inc. All rights reserved.


Joly Y.,McGill University | Ngueng Feze I.,McGill University | Simard J.,Laval University
BMC Medicine | Year: 2013

Background: Since the late 1980s, genetic discrimination has remained one of the major concerns associated with genetic research and clinical genetics. Europe has adopted a plethora of laws and policies, both at the regional and national levels, to prevent insurers from having access to genetic information for underwriting. Legislators from the United States and the United Kingdom have also felt compelled to adopt protective measures specifically addressing genetics and insurance. But does the available evidence really confirm the popular apprehension about genetic discrimination and the subsequent genetic exceptionalism?Methods: This paper presents the results of a systematic, critical review of over 20 years of genetic discrimination studies in the context of life insurance.Results: The available data clearly document the existence of individual cases of genetic discrimination. The significance of this initial finding is, however, greatly diminished by four observations. First, the methodology used in most of the studies is not sufficiently robust to clearly establish either the prevalence or the impact of discriminatory practices. Second, the current body of evidence was mostly developed around a small number of 'classic' genetic conditions. Third, the heterogeneity and small scope of most of the studies prevents formal statistical analysis of the aggregate results. Fourth, the small number of reported genetic discrimination cases in some studies could indicate that these incidents took place due to occasional errors, rather than the voluntary or planned choice, of the insurers.Conclusion: Important methodological limitations and inconsistencies among the studies considered make it extremely difficult, at the moment, to justify policy action taken on the basis of evidence alone. Nonetheless, other empirical and theoretical factors have emerged (for example, the prevalence and impact of the fear of genetic discrimination among patients and research participants, the (un)importance of genetic information for the commercial viability of the private life insurance industry, and the need to develop more equitable schemes of access to life insurance) that should be considered along with the available evidence of genetic discrimination for a more holistic view of the debate. © 2013 Joly et al; licensee BioMed Central Ltd.


Isabelle M.,Laval University | Gagne J.-P.,Laval University | Gallouzi I.-E.,McGill University | Poirier G.G.,Laval University
Journal of Cell Science | Year: 2012

Poly(ADP-ribose) (pADPr) is a heterogenic molecule synthesised from NAD by poly(ADP-ribose) polymerases (PARPs). Many cellular functions from genome integrity surveillance, cell cycle progression and DNA repair to apoptosis are affected by pADPr through its network of associated proteins. Using quantitative proteomics, we established a temporal map of pADPr-associated complexes upon genotoxic stress. Results suggested a strong pADPr association to many proteins involved in stress granule formation, notably the ras-GAP SH3-binding protein G3BP, as well as in the later phases of alkylation-stress-induced responses. Further investigation with dynamic imaging clearly demonstrated a pADPr-dependent initiation of stress granule assembly originating from the nucleus. The cotransfection of G3BP with poly(ADP-ribose) glycohydrolase (PARG) indicates that pADPr is involved in modulating the nuclear translocation of G3BP. Moreover, a peptide pADPr blot assay of G3BP revealed that pADPr binds to the glycine-arginine-rich domain of G3BP. Thereafter, we established a comprehensive G3BP interactome in the presence of pADPr. Our findings establish a novel function for pADPr in the formation of G3BP-induced stress granules upon genotoxic stress. © 2012.


Lellouche F.,Laval University | Lipes J.,McGill University
Intensive Care Medicine | Year: 2013

High tidal volumes have historically been recommended for mechanically ventilated patients during general anesthesia. High tidal volumes have been shown to increase morbidity and mortality in patients suffering from acute respiratory distress syndrome (ARDS). Barriers exist in implementing a tidal volume reduction strategy related to the inherent difficulty in changing one's practice patterns, to the current need to individualize low tidal volume settings only for a specific subgroup of mechanically ventilated patients (i.e., ARDS patients), the difficulty in determining the predicated body weight (requiring the patient's height and a complex formula). Consequently, a protective ventilation strategy is often under-utilized as a therapeutic option, even in ARDS. Recent data supports the generalization of this strategy prophylactically to almost all mechanically ventilated patients beginning immediately following intubation. Using tools to rapidly and reliably determine the predicted body weight (PBW), as well as the use of automated modes of ventilation are some of the potential solutions to facilitate the practice of protective ventilation and to finally ventilate our patients' lungs in a more gentle fashion to help prevent ARDS. © 2012 Springer-Verlag Berlin Heidelberg and ESICM.


De Serres G.,Laval University | Skowronski D.M.,British Columbia Center for Disease Control | Wu X.W.,MedImmune | Ambrose C.S.,MedImmune
Eurosurveillance | Year: 2013

The test-negative design (TND) is an efficient form of case-control study commonly applied to influenza vaccine effectiveness (VE) estimation. TND validity is predicated on the core assumption that the intervention (vaccine) has no effect on other non-targeted aetiologies resulting in similar illness/disease. Here we verify this core assumption and compare efficacy estimates derived by the TND versus classical per-protocol analysis of four datasets obtained from randomised placebo-controlled clinical trials (RCT) of the live attenuated influenza vaccine (LAIV) in children ≤7 years-old and the elderly ≥60 years-old. We further assess generalisability of the TND approach in two other RCT datasets to evaluate monoclonal antibody in the prevention of respiratory syncytial virus (RSV) hospitalisation. Efficacy estimates and their confidence intervals were virtually identical for per-protocol RCT versus TND analyses of LAIV and also for RSV monoclonal antibody. Neither LAIV nor monoclonal antibodies affected the risk of disease aetiologies that were not specifically targeted by the respective interventions (e.g. other respiratory viruses). This study validates the core assumption of the TND approach for influenza vaccine efficacy estimation and confirms the accuracy and precision of its estimates compared to the gold standard of classic per-protocol RCT analysis of the same data sets. The TND approach is generalisable for other conditions such as RSV for which the core assumption is also met. However, when used in observational studies, the TND, like all designs, still requires assessment for bias and confounding that may exist in the absence of randomised participation and blinded follow-up.


Guitton M.J.,CRULRG | Guitton M.J.,Laval University
Computers in Human Behavior | Year: 2012

With the increasing importance of virtual settings, we observe a complexification of the media used by members of the virtual communities. Using as the model the Star Wars Role-Play community of the virtual environment of Second Life, and a related news-styled blog, the "Galactic News Network", we analysed here the impact of this media complexification on immersion process. Specifically, we analysed how meta-media can act on virtual community behavior, and on the immersive potential of the virtual world. We combined "out-of-world" analysis of the blog, and "in-world" qualitative and quantitative evaluation of meta-media-related social activities. Our results demonstrate that meta-media strongly contribute to reinforce the immersive potential of the virtual setting via several mechanisms: by increasing three parameters of the virtual world (cohesion, coherence, and commitment), by increasing the social density of the virtual community, and by acting on the perceived time factor. The combined "in-world" and "out-of-world" action of the meta-media increases the possibilities of inter-individual connections. The combination of 2D asynchronous media and 3D instantaneous virtual settings in a homogeneous and coherent immersive environment reinforces the immersive potential of the virtual world. Thus, meta-media seem to be a factor of long-term stabilization of social structures in virtual environments. © 2011 Elsevier Ltd. All rights reserved.


Martin J.,Laval University | E. Tremblay J.,Laval University | Price N.M.,McGill University
Biogeosciences | Year: 2012

Assessments of carbon and nitrogen (N) assimilation in Canadian Arctic waters confirmed the large contribution of subsurface chlorophyll maxima (SCM) to total water-column production from spring to late fall. Although SCM communities showed acclimation to low irradiance and greater nitrate (NO3−) availability, their productivity was generally constrained by light and temperature. During spring-early summer, most of the primary production at the SCM was sustained by NO3−, with an average f-ratio (i.e., relative contribution of NO3− uptake to total N uptake) of 0.74 ± 0.26. The seasonal decrease in NO3− availability and irradiance, coupled to the build up of ammonium (NH4+), favoured a transition toward a predominantly regenerative system © 2012 Author(s).


Jit M.,Public Health England | Brisson M.,Laval University | Brisson M.,University of Quebec at Rimouski
PharmacoEconomics | Year: 2011

The number of economic evaluations related to infectious disease topics has increased over the last 2 decades. However, many such evaluations rely on models that do not take into account unique features of infectious diseases that can affect the estimated value of interventions against them. These include their transmissibility from infected to susceptible individuals, the possibility of acquiring natural immunity following recovery from infection and the uncertainties that arise as a result of their complex natural history and epidemiology. Modellers conducting economic evaluations of infectious disease interventions need to know the main features of different types of infectious disease models, the situations in which they should be applied and the effects of model choices on the cost effectiveness of interventions. © 2011 Adis Data Information BV. All rights reserved.


Giguere P.,Laval University | Dudek G.,McGill University
IEEE Transactions on Robotics | Year: 2011

This paper describes a tactile probe designed for surface identification in a context of all-terrain low-velocity mobile robotics. The proposed tactile probe is made of a small metallic rod with a single-axis accelerometer attached near its tip. Surface identification is based on analyzing acceleration patterns induced at the tip of this mechanically robust tactile probe, while it is passively dragged along a surface. A training dataset was collected over ten different indoor and outdoor surfaces. Classification results for an artificial neural network were positive, with an 89.9% and 94.6% success rate for 1- and 4-s time windows of data, respectively. We also demonstrated that the same tactile probe can be used for unsupervised learning of terrains. For 1-s time windows of data, the classification success rate was only reduced to 74.1%. Finally, a blind mobile robot, performing real-time classification of surfaces, demonstrated the feasibility of this tactile probe as a guidance mechanism. © 2011 IEEE.


Biron C.,Laval University | Karanika-Murray M.,Nottingham Trent University
International Journal of Stress Management | Year: 2014

Although the body of evidence showing the effects of psychosocial risks on employees' health and well-being is substantial, effective and sustainable stress prevention remains a thorny and complex issue. Most studies have focused on evaluating the effects of organizational interventions and the results are mixed. Researchers find the evaluation of such actions methodologically challenging, whereas practitioners often find the development and implementation of such actions a complicated matter. One of the reasons for this mixed impact is the lack of attention to contextual and process issues, namely how, when, and why interventions have their effects on outcomes such as mental health, well-being, and organizational performance. This article aims to help researchers and practitioners to improve the development, implementation, and evaluation of organizational initiatives designed to reduce exposure to stress, and to promote well-being and healthy organizations. The authors review recent developments in the literature on process evaluation and propose examples of broader theoretical frameworks that could be used to improve this area. They articulate the essential elements for developing and bridging gaps between theory, methods, and practice. Throughout, the authors provide recommendations for the content, process, and reporting of research on intervention process evaluation. © 2013 American Psychological Association.


Ruilope L.M.,Hospital 12 Of Octubre | Dukat A.,Comenius University | Bohm M.,Saarland University | Lacourciere Y.,Laval University | And 2 more authors.
The Lancet | Year: 2010

Background: LCZ696 is a first-in-class inhibitor of the angiotensin II receptor and neprilysin. We aimed to establish whether the dual actions of LCZ696 lead to further lowering of blood pressure, compared with the angiotensin-receptor blocker valsartan. Methods: 1328 patients aged 18-75 years with mild-to-moderate hypertension were randomly assigned (double-blind) to 8 weeks' treatment in one of eight groups: 100 mg (n=156 patients), 200 mg (n=169), or 400 mg (n=172) LCZ696; 80 mg (n=163), 160 mg (n=166), or 320 mg (n=164) valsartan; 200 mg AHU377 (n=165); or placebo (n=173). The primary endpoint was the mean difference across the three single-dose pairwise comparisons of LCZ696 versus valsartan (100 mg vs 80 mg, 200 mg vs 160 mg, and 400 mg vs 320 mg) in mean sitting diastolic blood pressure during the 8-week treatment period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00549770. Findings: 1215 patients completed the 8-week treatment period. The average reduction in mean sitting diastolic blood pressure across the doses of LCZ696 versus the appropriate comparator dose of valsartan showed significantly greater reductions with LCZ696 (mean reduction: -2·17 mm Hg, 95% CI -3·28 to -1·06; p<0·0001). The reduction in mean sitting diastolic blood pressure was significantly different for 200 mg LCZ696 versus 160 mg valsartan (-2·97 mm Hg, 95% CI -4·88 to -1·07, p=0·0023) and for 400 mg LCZ696 versus 320 mg valsartan (-2·70 mm Hg, -4·61 to -0·80, p=0·0055). LCZ696 was well tolerated and no cases of angio-oedema were reported; only three serious adverse events occurred during the 8-week treatment period, of which none was judged to be related to the study drug, and no patients died. Interpretation: Compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure, which suggests that the drug holds promise for treatment of hypertension and cardiovascular disease. Funding: Novartis. © 2010 Elsevier Ltd. All rights reserved.


Oualkacha K.,McGill University | Rivest L.-P.,Laval University
Biometrika | Year: 2012

This paper investigates the definition and the estimation of the Fréchet mean of a random rigid body motion in p. The sample space SE(p) contains objects M=(R,t) where R is a p×p rotation matrix and t is a p×1 translation vector. This work is motivated by applications in biomechanics where the posture of a joint at a given time is expressed as MSE(3), the rigid body displacement needed to map a system of axes on one segment of the joint to a similar system on the other segment. This posture can also be reported as M-1=(RT,-RTt) by interchanging the role of the two segments. Several definitions of a Fréchet mean for a random motion are proposed using weighted least squares distances. A special emphasis is given to a Fréchet mean that is equivariant with respect to the inverse transform; this means that if P is the Fréchet mean for M then P-1 is the Fréchet mean for M-1, where M is a random SE(p) object. The sampling properties of moment estimators of the Fréchet means are studied in a large concentration setting, where the scatter of the random Ms around their mean value P is small, and as the sample size goes to ∞. Some simple exponential family models for SE(p) data that generalize Downs' (1972) Fisher-von Mises matrix distribution for rotation matrices are introduced and the least squares mean values for these distributions are calculated. Asymptotic comparisons between the estimators presented in this work are carried out for a particular model when p=2. A numerical example involving the motion of the ankle is presented to illustrate the methodology. © 2012 Biometrika Trust.


Guitton M.J.,CRULRG | Guitton M.J.,Laval University
Computers in Human Behavior | Year: 2010

Avatars serve for humans immersed in virtual settings as the interface between real and virtual worlds. The avatar-creation process involves numerous choices, including choice of visual representation, and choices to imbue the character with personality. Here, we hypothesised that these choices are not independent, and that a cross-modal talk may occur between the different components of the avatar identity. Specifically, we investigated whether name properties may be affected by the visual aspect (human vs. non-human) of the avatar. We analyzed names structure of players characters from the popular massively multiplayer online role-playing game (MMORPG) World of Warcraft, which display both human and non-human avatars. We selected 1261 names of characters actively engaged in the in-game and out-game social networks. Analysis of the names revealed that female names presented more variability than male names, and contained systematically more vowels than male names. However, the strategy used to enrich the vowel composition of female names differed between human-like and non-human characters, suggesting that a lesser proximity with human regular appearance was compensated by an increase of "feminization" of the name. Altogether, our results suggest that a cross-modal compensation occurs between name and visual aspect in the creation of socially active avatars. © 2010 Elsevier Ltd. All rights reserved.


Conner M.,University of Leeds | Godin G.,Laval University | Sheeran P.,University of Sheffield | Germain M.,Hema Quebec
Health Psychology | Year: 2013

Objective: The present research assessed the simultaneous effects of four attitude variables (cognitive attitudes, affective attitudes, anticipated negative affective reactions, and anticipated positive affective reactions) in the context of the theory of planned behavior (TPB) on blood-donation intentions and behavior. Methods: Experienced blood donors (N = 1108) completed questionnaires measuring attitude variables plus components of the TPB and a measure of attitudinal ambivalence in relation to giving blood again in the next six months. Records were used to assess whether participants subsequently donated blood again in the six months after completing the questionnaire. The main outcome measures were objectively assessed blood donation and intentions to make an additional donation of blood. Results: Confirmatory factor analysis supported a distinction between cognitive attitudes about giving blood, affective attitudes about giving blood, anticipated negative affective reactions about not giving blood, and anticipated positive affective reactions about giving blood. Multiple regression analyses indicated that perceived behavioral control, anticipated negative affective reactions, cognitive attitude, anticipated positive affective reactions and subjective norms were significant simultaneous predictors of intentions to donate blood. Logistic regression analyses indicated that intentions, perceived behavioral control, and anticipated positive affective reactions were significant, simultaneous predictors of blood donation. Attitudinal ambivalence significantly moderated the effects of cognitive attitudes on intentions, and the effects of anticipated negative affective reactions on both intentions and donation behavior. Conclusion: The findings point to the value of considering different types of attitudes, and anticipated negative affective reaction in particular, for predicting health behaviors. © 2012 American Psychological Association.


News Article | October 5, 2016
Site: www.sciencenews.org

Storied spawning runs of European eels may not be an en masse push to a mating site. Roundabout routes may delay many eels so much that they miss the big event and have to wait to mate until next season. The most extensive reconstructions of individual eel journeys challenge an assumption that Europe’s freshwater eels (Anguilla anguilla) migrate and spawn as a group, says behavioral ecologist David Righton of the Centre for Environment, Fisheries and Aquaculture Science in Lowestoft, England. Eels tagged for the study took so long on their various journeys that tags scheduled to pop off on April 1 — the expected peak of the spawning — found that none of 33 ocean-going eels had yet made it all the way to the Sargasso Sea mating grounds. Calculating routes and speeds indicates that many eels were already too far off-track to reach the mass gathering that season without unrealistic jumps in swimming speed, Righton and an international team argue October 5 in Science Advances. The eel that came the closest to the Sargasso Sea before its tag detached had already traveled almost 10 months and meandered more than 6,900 kilometers, farther than the distance of a direct route. Freshwater eels’ migration and spawning have confounded biologists for centuries. A. anguilla can live for 90 years in rivers, but they don’t reproduce there. Each animal spawns once in its life, swimming out to salt water and largely disappearing from scientific view into the Atlantic Ocean. About a century ago, a researcher deduced from abundant catches of larval eels that freshwater species must migrate to spawn in the Sargasso Sea, a region within the gyre of great swirling currents and named for its abundant Sargassum seaweed.  This mysterious spawning season may actually begin in December and peak February 14, earlier than previously thought, researchers concluded from a fresh look at previous data on larval size. But even now, no scientist has succeeded in collecting adults there, Righton says. In a project named the eeliad, an international collaboration fitted tags on 707 large eels and loosed the fish along the coast of Europe. Many were caught by predators, sometimes human ones. In 2009, researchers reported the basics of tracking the first 1,300 kilometers of the estimated 5,000-kilometer journey (SN Online: 9/24/09). Now, further analysis from temperature and water depth recorded by tags has let researchers plot routes for the 33 eels that made it across the continental shelf and into deeper water. Looking at the end points of the tracking and the distances yet to cover, researchers calculated that for even half the tracked eels to arrive by the peak of spawning, they would have to pick up the pace by an additional 15 to 53 kilometers per day. And that’s taking a direct route, something the eels — contending with ocean currents and navigating by mysterious eel means — had yet to do. With speedups unlikely, the researchers propose that it’s time to rethink the idea that leaving freshwater together in a given autumn means spawning together that same breeding season. North American freshwater eels likewise leave their rivers and swim to the Sargasso Sea but have a shorter oceanic trip, says Mélanie Béguer-Pon of Laval University in Quebec City. A tag study she and colleagues published indicates these eels take a more direct route and should arrive in time for the current spawning season, she says. But she doesn’t rule out the possibility of some untagged slow travelers on her side of the Atlantic, too. A mixed strategy for the European counterparts covering such a great distance “sounds totally reasonable to me,” she says. Julian Dodson, at Laval and a collaborator on the North American tagging project, says it’s difficult for him to understand why evolutionary forces would not have favored more efficiency in slow-swimming European eels. Extra months of migration mean more exposure to predators and more energy depletion as migrating eels don’t feed. But “that’s the thing about eels, always more questions than answers,” he says.


Charansonney O.L.,Center Hospitalier Sud Francilien | Despres J.-P.,Laval University
Nature Reviews Cardiology | Year: 2010

Obesity is a major health challenge facing the modern world. Some evidence points to obesity itself as the main driver of premature mortality. We propose that this view is oversimplified. For example, high levels of physical activity and cardiorespiratory fitness are associated with lower mortality, even in those who are overweight or obese. To address this issue, we combine epidemiological and physiological evidence in a new paradigm that integrates excess calorie intake, sedentary behavior, and a maladaptive response to stress. Human physiology is optimized to allow large distances to be covered on foot every day in order to find enough food to sustain brain metabolism. Furthermore, when the body is immobilized by an injury, it triggers efficient life-saving metabolic and inflammatory responses. Both these critical adaptations are, however, confounded by a sedentary lifestyle. The implications of these issues for clinical trial design and epidemiologic data analysis are discussed in this article. © 2010 Macmillan Publishers Limited. All rights reserved.


Mauermann J.,Laval University | Fradet V.,Laval University | Lacombe L.,Laval University | Dujardin T.,Laval University | And 3 more authors.
European Urology | Year: 2013

Background: Positive surgical margins (PSMs) increase the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), but their impact on hard clinical end points is a topic of ongoing discussion. Objective: To evaluate the influence of solitary PSMs (sPSMs) and multiple PSMs (mPSMs) on important clinical end points. Design, setting, and participants: Data from 1712 patients from the Centre Hospitalier Universitaire de Québec with pT2-4 N0 prostate cancer (PCa) and undetectable prostate-specific antigen after RP were analyzed. Intervention: RP without neoadjuvant or adjuvant treatment. Outcome measurements and statistical analysis: Kaplan-Meier analysis estimated survival functions, and Cox proportional hazards models addressed predictors of clinical end points. Results and limitations: Median follow-up was 74.9 mo. A total of 1121 patients (65.5%) were margin-negative, 281 patients (16.4%) had sPSMs, and 310 patients (18.1%) had mPSMs. A total of 280 patients (16.4%) experienced BCR, and 197 patients (11.5%) were treated with salvage radiotherapy (SRT). Sixty-eight patients (4.0%) received definitive androgen deprivation therapy, 19 patients (1.1%) developed metastatic disease, and 15 patients (0.9%) had castration-resistant PCa (CRPC). Thirteen patients (0.8%) died from PCa, and 194 patients (11.3%) died from other causes. Ten-year Kaplan-Meier estimates for BCR-free survival were 82% for margin-negative patients, 72% for patients with sPSMs, and 59% for patients with mPSMs (p < 0.0001). Time to metastatic disease, CRPC, PCa-specific mortality (PCSM), or all-cause mortality did not differ significantly among the three groups (p = 0.991, p = 0.988, p = 0.889, and p = 0.218, respectively). On multivariable analysis, sPSMs and mPSMs were associated with BCR (hazard ratio [HR]: 1.711; p = 0.001 and HR: 2.075; p < 0.0001), but sPSMs and mPSMs could not predict metastatic disease (p = 0.705 and p = 0.242), CRPC (p = 0.705 and p = 0.224), PCSM (p = 0.972 and p = 0.260), or all-cause death (p = 0.102 and p = 0.067). The major limitation was the retrospective design. Conclusions: In a cohort of patients who received early SRT in 70% of cases upon BCR, sPSMs and mPSMs predicted BCR but not long-term clinical end points. Adjuvant radiotherapy for margin-positive patients might not be justified, as only a minority of patients progressed to end points other than BCR. PCSM was exceeded 15-fold by competing risk mortality. © 2012 Published by Elsevier B.V. on behalf of European Association of Urology.


Bujold E.,Laval University
Seminars in Perinatology | Year: 2010

The objective was to compare national guidelines regarding vaginal birth after cesarean. Along with the American College of Obstetricians and Gynecologists practice bulletin, guidelines from the Royal College of Obstetricians and Gynaecologists and the Society of Obstetricians and Gynecologists of Canada were reviewed and compared. Although the 3 organizations agree on most of the risk factors for uterine rupture and failed vaginal birth after cesarean (VBAC), there were some variances in the recommendations to women with 2 previous cesareans and those who required oxytocin augmentation. A disagreement was also present in regard to the availability and requirement of resources to allow a trial of labor after a previous cesarean. Although concerns could be raised about how the literature is synthesized, the 3 organizations recognized the potential biases in published reports and the lack of randomized trials. © 2010 Elsevier Inc.


Taillon J.,Laval University | Festa-Bianchet M.,Université de Sherbrooke | Cote S.D.,Laval University
Biological Conservation | Year: 2012

Industrial development, expansion of human populations and climate change increasingly affect habitats of migratory species. Effective protection of critical habitats is urgently required because several large migratory species have declined over the last decades. Protection of critical habitats, such as the calving grounds of migratory ungulates, may however require consideration of temporal shifts in spatial location. We assessed changes in the location of calving grounds used by migratory caribou over 35. years by the Rivière-George (RG) herd and 15. years by the Rivière-aux-Feuilles (RAF) herd, in Northern Québec and Labrador, Canada. We also evaluated the proportion of annual calving ground within protected Wildlife Habitats established to protect caribou calving grounds. The annual size and location of calving grounds changed substantially over time: calving ground size remained relatively stable for the RAF but it declined over 85% for the RG. Calving grounds moved 300. km northward in the Ungava peninsula for the RAF and shifted over 230. km back and forth to the Labrador coast for the RG. Despite recent modifications, legally designated Wildlife Habitats in Québec protected less than 20% of the RG and RAF calving grounds. Protection of calving grounds of migratory caribou must consider the dynamic use of space by adult females. We present recommendations on the use of available monitoring data to better protect calving grounds of migratory caribou and critical habitats of large migratory species. © 2011 Elsevier Ltd.


Masse A.,Laval University | Cote S.D.,Laval University
Journal of Wildlife Management | Year: 2012

During winter, ungulates in boreal forests must cope with high energetic costs related to locomotion in deep snow and reduced forage abundance and quality. At high density, ungulates face additional constraints, because heavy browsing reduces availability of woody browse, the main source of forage during winter. Under these severe conditions, large herbivores might forage on alternative food sources likely independent of browsing pressure, such as litterfall or windblown trees. We investigated the influence of alternative food sources on winter habitat selection, by studying female white-tailed deer (Odocoileus virginianus) living in 2 landscapes with contrasted browse abundance, recently logged and regenerated landscapes, in a population at high density and on a large island free of predators. We fitted 21 female white-tailed deer with Global Positioning System (GPS) collars and delineated winter home ranges and core areas. We measured snow conditions in different habitat categories and sampled vegetation in the core areas and in the rest of the home ranges to determine how forage abundance, protective cover, and snow conditions influenced habitat selection within the home range. In both landscapes, deer were less likely to use open habitat categories as snow accumulated on the ground. At a finer scale, deer inhabiting the regenerated landscape intensively used areas where balsam fir cover was intermediate with greater balsam fir browse density than in the rest of the home range. In the recently logged landscape, deer were more likely to be found near edges between clear-cuts and balsam fir stands and in areas where windblown balsam fir trees were present; the latter being the most influential variable. Although balsam fir browse was sparse and mainly out of reach in this landscape, deer increased the use of areas where it was present. Our results offer novel insights into the resource selection processes of northern ungulates, as we showed that access to winter forage, such as woody browse and alternative food sources, depends on climatic conditions and stochastic events, such as abundant compacted snow or windthrows. To compensate for these scarce and unpredictable food supplies, deer selected habitat categories, but mostly areas within those habitat categories, where the likelihood of finding browse, litterfall, and windblown trees was greatest. Copyright © 2011 The Wildlife Society.


Renaut S.,Laval University | Nolte A.W.,Max Planck Institute for Evolutionary Biology | Bernatchez L.,Laval University
Molecular Ecology | Year: 2010

Next-generation sequencing allows the discovery of large numbers of single nucleotide polymorphisms (SNPs) in species where little genomic information was previously available. Here, we assembled, de novo, over 130 mb of non-normalized cDNA using 454 pyrosequencing data from dwarf and normal lake whitefish and backcross hybrids. Our main goals were to gather a large data set of SNP markers, document their distribution within coding regions, evaluate the effect of species divergence on allele frequencies and combine results with previous genomic studies to identify candidate genes underlying the adaptive divergence of lake whitefish. We identified 6094 putative SNPs in 2674 contigs (mean size: 576 bp, range: 101-6116) and 1540 synonymous and 1734 nonsynonymous mutations for a genome-wide non-synonymous to synonymous substitution rate ratio (pN/pS) of 0.37. As expected based on the young age (<15 000 years) of whitefish species pair, the overall level of divergence between them was relatively weak. Yet, 89 SNPs showed pronounced allele frequency differences between sympatric normal and dwarf whitefish. Among these, SNPs in genes annotated to energy metabolic functions were the most abundant and this, in addition to previous experimental data at the gene expression and phenotypic level, brings compelling evidence that genes involved in energy metabolism are prime candidates explaining the adaptive divergence of lake whitefish species pairs. Finally, we unexpectedly identified 44 contigs annotated to transposable elements and these were predominantly composed of backcross hybrids sequences. This indicates an elevated activity of transposable elements, which could potentially contribute to the reduced fitness of hybrids previously documented. © 2010 Blackwell Publishing Ltd.


Desbiens C.,Laval University
Canadian Geographer | Year: 2010

I discuss the methodological challenges that research with Aboriginal women poses in historical geography, especially in Northern Canada. Drawing a parallel between historical geography and contemporary Northern studies, I explore how the predominance of climate change as a framework for funding Arctic research creates an environment where women's specific ways of knowing and connecting with the land are not adequately captured. A gender approach that is sensitive to the issues women face in their communities reveals that their experience of climate change, as well as the concerns they have about it, are inseparable from the other economic and social issues they face. I argue for the development of a feminist research agenda in the North that allows Aboriginal partners to locate themselves in the frameworks that are constructed for producing knowledge. At times letting the project 'fail' may be the surest way to enable the emergence of a locally-driven agenda that addresses the present and future needs of Northern Aboriginal Peoples. © Canadian Association of Geographers.


Konrad J.-M.,Laval University
Geotechnique | Year: 2010

This paper examines the influence of several freeze-thaw cycles on the hydraulic conductivity changes of a glacial till from Péribonka in Quebec, Canada. Samples reconstituted by consolidation of a slurry and by compaction at dry of optimum conditions were subjected to closed freezing and thaw as well as constant-head permeability tests. For saturated consolidated samples, the relationship between the logarithm of hydraulic conductivity and void ratio was linear for both unfrozen and thawed states. At a given void ratio, the increase of the hydraulic conductivity of the thawed soil was larger for compacted and unsaturated samples than for saturated consolidated samples. Actual freeze-thaw-induced hydraulic conductivity changes, however, may be offset by a decrease in void ratio during thaw consolidation. A general framework considering void ratio, water content, stress and hydraulic conductivity relationships is presented for Péribonka glacial till.


This study presents new geochemical data on mafic gneisses from the Renzy terrane (RT), located in the Grenvillian Parautochthonous Belt of western Quebec. This region is of particular interest since it contains one of the rare Ni-Cu-Co massive sulfide deposits ever mined in the Grenville Province. RT mafic gneisses have been divided into 3 groups based mainly on major element compositions, trace element profiles normalized to the primitive mantle, and incompatible trace element ratios. The behaviour of high field strength elements (HFSE) (Ta, Zr, Hf, Ti, Th) and large ion lithophile elements (LILE) (Ba, Rb) are particularly useful for discriminating RT mafic gneisses. Major and trace element compositions of group 1 mafic/ultramafic gneisses are very similar to those of the RT ultramafic sheets; the mafic gneisses are therefore interpreted as melagabbroic sills cogenetic with these sheets. The trace element composition of group 1 mafic gneisses is typical of magmas formed from a previously metasomatized depleted mantle source. These rocks have high Th/Ta ratios and show strong to moderate negative anomalies in Ti, Zr, and Hf on multi-element plots normalized to the primitive mantle. Mafic gneisses of group 2 show geochemical features transitional between extensional and compressional settings. These rocks generally have low concentrations of HFSE and high concentrations of LILE, typical features of mafic rocks formed in a compressional environment; however, some of them are Fe-Ti rich, with minor or no negative anomalies in HFSE and low to moderate concentrations of LILE on multi-element diagrams normalized to primitive mantle, features more typical of an extensional environment. Mafic gneisses of group 3 have a geochemical signature typical of extensional environments or of ocean island basalt (OIB). These gneisses have no negative anomalies in HFSE and have low concentrations of LILE. RT mafic gneisses are similar in composition to mafic granulites in the Bondy gneiss complex in the Central Metasedimentary Belt and to Shawanaga Domain amphibolites from the Central Gneiss Belt, two paleoarc/back-arc environments in the Grenville Province. Based on the contrasting geochemical signatures found in the RT mafic gneisses and the similarities with known arc/back-arc settings in the Grenville Province, we propose that the RT was formed by arc/back-arc magmatic activity most likely associated with a period of arc magmatism along the Proterozoic Laurentian margin. OIB-like mafic gneisses found in the RT are similar to those from the Kipawa region, formed by intraplate continental magmatism in the Parautochthonous Belt of the Grenville Province. © 2010 Elsevier B.V.


Ait-Aissa A.,Laval University | Aider M.,Laval University
International Journal of Food Science and Technology | Year: 2014

Summary: Lactulose is a synthetic disaccharide. It can be obtained from lactose by chemical, enzymatic or by electro-activation synthesis. This review provides the comprehension of lactulose production and its application in medical, pharmaceutical and functional food applications. Lactulose can be used in medical and pharmaceutical applications for the treatment of diseases such as chronic constipation, therapy of portal systemic encephalopathy, inflammatory bowel disease, reducing blood ammonia levels, colon carcinogenesis, tumour prevention and immunology, mineral absorption and for the inhibition of the secondary bile acid formation. However, with the growing interest in functional foods, the use of nondigestible oligosaccharides such as prebiotic ingredients has increased considerably during the recent years. In this context, lactulose as a well-recognised prebiotic offers excellent possibilities to develop new functional foods. It can be added to several foods. © 2013 Institute of Food Science and Technology.


Godin G.,Laval University
The international journal of behavioral nutrition and physical activity | Year: 2011

The promotion of physical activity among an overweight/obese population is an important challenge for clinical practitioners and researchers. In this regard, completing a questionnaire on cognitions could be a simple and easy strategy to increase levels of physical activity. Thus, the aim of the present study was to test the effect of completing a questionnaire based on the Theory of Planned Behavior (TPB) on the level of physical activity. Overall, 452 overweight/obese adults were recruited and randomized to the experimental or control group. At baseline, participants completed a questionnaire on cognitions regarding their participation in leisure-time physical activity (experimental condition) versus a questionnaire on fruit and vegetable consumption (control condition). The questionnaires assessed the TPB variables that are beliefs, attitude, norm, perception of control, intention and a few additional variables from other theories. At three-month follow-up, leisure-time physical activity was self-reported by means of a short questionnaire. An analysis of covariance with baseline physical activity level as covariate was used to verify the effect of the intervention. At follow-up, 373 participants completed the leisure-time physical activity questionnaire. The statistical analysis showed that physical activity participation was greater among participants in the experimental condition than those in the control condition (F(1,370)=6.85, p=.009, d=0.20). Findings indicate that completing a TPB questionnaire has a significant positive impact on subsequent participation in physical activity. Consequently, asking individuals to complete such a questionnaire is a simple, inexpensive and easy strategy to increase the level of physical activity among overweight/obese adults. © 2011 Godin et al; licensee BioMed Central Ltd.


Cavatorta F.,Laval University
British Journal of Middle Eastern Studies | Year: 2015

North Africa has gone through dramatic events since the eruption of the Arab uprisings in Tunisia in late 2010. Despite sharing similar characteristics that were central to the uprisings, they have known different political and institutional trajectories since then. The article provides an appraisal of the contributions to this special issue focusing in particular on the peculiar situation of countries where no genuine democratic change has occurred and where there is little authoritarian continuity as well. © 2014 British Society for Middle Eastern Studies.


Pavey S.A.,Laval University
Molecular Ecology Resources | Year: 2015

Understanding the genetic structure of species is essential for conservation. It is only with this information that managers, academics, user groups and land-use planners can understand the spatial scale of migration and local adaptation, source-sink dynamics and effective population size. Such information is essential for a multitude of applications including delineating management units, balancing management priorities, discovering cryptic species and implementing captive breeding programmes. Species can range from locally adapted by hundreds of metres (Pavey et al.) to complete species panmixia (Côté et al. ). Even more remarkable is that this essential information can be obtained without fully sequenced or annotated genomes, but from mere (putatively) nonfunctional variants. First with allozymes, then microsatellites and now SNPs, this neutral genetic variation carries a wealth of information about migration and drift. For many of us, it may be somewhat difficult to remember our understanding of species conservation before the widespread usage of these useful tools. However most species on earth have yet to give us that 'peek under the curtain'. With the current diversity on earth estimated to be nearly 9 million species (Mora et al. ), we have a long way to go for a comprehensive meta-phylogeographic understanding. A method presented in this issue by Campbell and colleagues (Campbell et al.) is a tool that will accelerate the pace in this area. Genotyping-in-thousands (GT-seq) leverages recent advancements in sequencing technology to save many hours and dollars over previous methods to generate this important neutral genetic information. © 2015 John Wiley & Sons Ltd.


Bareil P.B.,Laval University | Sheng Y.,Laval University
Optics Express | Year: 2010

We analyze the trap stiffness and trapping force potential for a nano-cylindertrapped in the optical tweezers against its axial and lateral shift and tilt associated to the natural Brownian motion. We explain the physical properties of the optical trapping by computing and integrating the radiation stress distribution on the nano-cylinder surfaces using the T-matrix approach. Our computation shows that the force stiffness to the lateral shift is several times higher than that to the axial shift of the nano-cylinder, and lateral torque due to the stress on the side-face is 1-2 orders of magnitude higher than that on the end-faces of a nano-cylinder with the aspect ratio of 2 - 20. The torque due to the stress on the nano-cylinder surface is 2-3 orders of magnitude higher than the spin torque. We explain why a nano-cylinder of low aspect ratio is trapped and aligned normal to the trapping beam axis. © 2010 Optical Society of America.


Saucier L.,Laval University
Meat Science | Year: 2016

Meat is a nutrient-dense food that provides ideal conditions for microbes to grow and defines its perishable nature. Some organisms simply spoil it while others are a threat to our health. In either case, meat must be discarded from the food chain and, being wasted and consequently an environmental burden. Worldwide, more than 20% of the meat produced is either lost or wasted. Hence, coordinated efforts from farm to table are required to improve microbial control as part of our effort towards global sustainability. Also, new antimicrobial systems and technologies arise to better fulfill consumer trends and demands, new lifestyles and markets, but for them to be used to their full extent, it is imperative to understand how they work at the molecular level. Undetected survivors, either as injured, dormant, persister or viable but non-culturable (VBNC) cells, undermine proper risk evaluation and management. © 2016 Elsevier Ltd.


Dallaire F.,Laval University | Dallaire F.,University of Montréal | Dahdah N.,University of Montréal
Journal of the American Society of Echocardiography | Year: 2011

Background: The aim of this study was to find the best model to obtain valid and normally distributed Z scores for coronary artery (CA) diameters in a large, heterogeneous population of healthy children. Methods: Echocardiography was performed on 1,033 healthy children. Several regression models were tested with height, weight, body surface area, and aortic valve diameter. The computed Z scores were tested for normal distribution and stability. Results: CA diameter was best predicted using regression with the square root of body surface area. The weighted least squares method yielded normally distributed and very stable Z-score estimates for all CA segments. In prepubertal children, aortic valve diameter was also a valid predictor of CA diameter. Conclusions: This study shows two valid methods to estimate Z scores for CA size in children of all ages. Such Z scores are important for risk stratification in patients with Kawasaki disease. © 2011 by the American Society of Echocardiography.


Tremblay G.,Laval University | Sheng Y.,Laval University
Optics Express | Year: 2010

The metallic superlens typically shows two peaks in its transfer function related to the long- and the short-range surface plasmon polariton (SPP) modes. These peaks are necessary to amplify the evanescent waves compensating the exponential decays, but enhance the spatial frequencies disproportionally, resulting in strong sidelobes in the image. We propose to design the metallic superlens with close to the cutoff condition of the longrange SPP mode to balance the SPP amplification and the flatness of the transfer function, and thus eliminating the sidelobes in the image. The design experiments for the Al superlens at 193 nm with both the transfermatrix approach and the numerical finite difference in time domain method are shown. © 2010 Optical Society of America.


Jaworska J.,Laval University | Gravel A.,Laval University | Flamand L.,Laval University
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Two distinct human herpesvirus 6 (HHV-6) variants infect humans. HHV-6B is the etiologic agent of roseola and is associated with life-threatening neurological diseases, such as encephalitis, as well as organ transplant failure. The epidemiology and disease association for HHV-6A remain ill-defined. Specific anti-HHV-6 drugs do not exist and classic antiherpes drugs have secondary effects that are often problematic for transplant patients. Clinical trials using IFN were also performed with inconclusive results. We investigated the efficacy of type I IFN (α/β) in controlling HHV-6 infection. We report that cells infected with laboratory strains and primary isolates of HHV-6B are resistant to IFN-α/β antiviral actions as a result of improper IFN-stimulated gene (ISGs) expression. In contrast, HHV-6A-infected cells were responsive to IFN-α/β with pronounced antiviral effects observed. Type II IFN (γ)-signaling was unaltered in cells infected by either variant. The HHV-6B immediate-early 1 (IE1) physically interacts with STAT2 and sequestrates it to the nucleus. As a consequence, IE1B prevents the binding of ISGF3 to IFN-responsive gene promoters, resulting in ISG silencing. In comparison, HHV-6A and its associated IE1 protein displayed marginal ISG inhibitory activity relative to HHV-6B. The ISG inhibitory domain of IE1B mapped to a 41 amino acid region absent from IE1A. Transfer of this IE1B region resulted in a gain of function that conferred ISG inhibitory activity to IE1A. Our work is unique in demonstrating type I IFN signaling defects in HHV-6B-infected cells and highlights a major biological difference between HHV-6 variants.


Hermawan H.,Laval University | Dube D.,Laval University | Mantovani D.,Laval University
Acta Biomaterialia | Year: 2010

Interest in metallic degradable biomaterials research has been growing in the last decade. Both scientific journals and patent databases record a high increase in publications in this area. Biomedical implants with temporary function, such as coronary stents, are the targeted applications for this novel class of biomaterials. It is expected that stents made of degradable biomaterials, named biodegradable stents, will provide a temporary opening into a narrowed arterial vessel until the vessel remodels and will progressively disappear thereafter. Biodegradable stents made of metal have recently been progressed into preclinical tests in humans after their first introduction in early 2000s. By referring to patents and journal publications, this paper reviews the developments in biodegradable stents, with emphasis on those made of metals, starting from the first design ideas to validation testing. © 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Filteau M.,Laval University | Pavey S.A.,Laval University | St-Cyr J.,Laval University | Bernatchez L.,Laval University
Molecular Biology and Evolution | Year: 2013

A functional understanding of processes involved in adaptive divergence is one of the awaiting opportunities afforded by high-throughput transcriptomic technologies. Functional analysis of coexpressed genes has succeeded in the biomedical field in identifying key drivers of disease pathways. However, in ecology and evolutionary biology, functional interpretation of transcriptomic data is still limited. Here, we used Weighted Gene Co-Expression Network Analysis (WGCNA) to identify modules of coexpressed genes in muscle and brain tissue of a lake whitefish backcross progeny. Modules were connected to gradients of known adaptive traits involved in the ecological speciation process between benthic and limnetic ecotypes. Key drivers, that is, hub genes of functional modules related to reproduction, growth, and behavior were identified, and module preservation was assessed in natural populations. Using this approach, we identified modules of coexpressed genes involved in phenotypic divergence and their key drivers, and further identified a module part specifically rewired in the backcross progeny. Functional analysis of transcriptomic data can significantly contribute to the understanding of the mechanisms underlying ecological speciation. Our findings point to bone morphogenetic protein and calcium signaling as common pathways involved in coordinated evolution of trophic behavior, trophic morphology (gill rakers), and reproduction. Results also point to pathways implicating hemoglobins and constitutive stress response (HSP70) governing growth in lake whitefish. © The Author 2013. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.


Iliuta I.,Laval University | Leclerc A.,Laval University | Larachi F.,Laval University
Bioresource Technology | Year: 2010

A new reactor concept of allothermal cyclic multi-compartment fluidized bed steam biomass gasification is proposed and analyzed numerically. The concept combines space and time delocalization to approach an ideal allothermal gasifier. Thermochemical conversion of biomass in periodic time and space sequences of steam biomass gasification and char/biomass combustion is simulated in which the exothermic combustion compartments provide heat into an array of interspersed endothermic steam gasification compartments. This should enhance unit heat integration and thermal efficiency and procure N2-free biosyngas with recourse neither to oxygen addition in steam gasification nor contact between flue and syngas. The dynamic, one-dimensional, multi-component, non-isothermal model developed for this concept accounts for detailed solid and gas flow dynamics whereupon gasification/combustion reaction kinetics, thermal effects and freeboard-zone reactions were tied. Simulations suggest that allothermal operation could be achieved with switch periods in the range of a minute supporting practical feasibility for portable small-scale gasification units. © 2009 Elsevier Ltd. All rights reserved.


Plante M.,Laval University
International Journal of Gynecological Cancer | Year: 2015

Radical trachelectomy is now recognized as a valid treatment option for young women with early-stage cervical cancer with lesions measuring less than 2 cm. However, for women with bulky lesions measuring greater than 2cm, few data are available in the literature to guide management. There are currently 2 options available: either upfront radical trachelectomy or neoadjuvant chemotherapy followed by fertility-preserving surgery. Overall, both options offer very good oncologic outcome; however, the rate of fertility preservation and obstetrical outcome seem superior after neoadjuvant chemotherapy. Advantages and disadvantages of both options are discussed and a thorough literature review is provided. Issues to be further studied are also outlined. © 2015 by IGCS and ESGO.


Xu E.,Laval University | Schwab M.,Laval University | Marette A.,Laval University
Reviews in Endocrine and Metabolic Disorders | Year: 2014

Insulin resistance is a major disorder that links obesity to type 2 diabetes mellitus (T2D). It involves defects in the insulin actions owing to a reduced ability of insulin to trigger key signaling pathways in major metabolic tissues. The pathogenesis of insulin resistance involves several inhibitory molecules that interfere with the tyrosine phosphorylation of the insulin receptor and its downstream effectors. Among those, growing interest has been developed toward the protein tyrosine phosphatases (PTPs), a large family of enzymes that can inactivate crucial signaling effectors in the insulin signaling cascade by dephosphorylating their tyrosine residues. Herein we briefly review the role of several PTPs that have been shown to be implicated in the regulation of insulin action, and then focus on the Src homology 2 (SH2) domain-containing SHP1 and SHP2 enzymes, since recent reports have indicated major roles for these PTPs in the control of insulin action and glucose metabolism. Finally, the therapeutic potential of targeting PTPs for combating insulin resistance and alleviating T2D will be discussed. © 2013 Springer Science+Business Media.


Lalonde M.-E.,Laval University | Cheng X.,Laval University | Cote J.,Laval University
Genes and Development | Year: 2014

Histone modifiers like acetyltransferases, methyltransferases, and demethylases are critical regulators of most DNA-based nuclear processes, de facto controlling cell cycle progression and cell fate. These enzymes perform very precise post-translational modifications on specific histone residues, which in turn are recognized by different effector modules/proteins. We now have a better understanding of how these enzymes exhibit such specificity. As they often reside in multisubunit complexes, they use associated factors to target their substrates within chromatin structure and select specific histone mark-bearing nucleosomes. In this review, we cover the current understanding of how histone modifiers select their histone targets. We also explain how different experimental approaches can lead to conflicting results about the histone specificity and function of these enzymes. © 2014 Lalonde et al.


Eid L.,Laval University | Parent M.,Laval University
Frontiers in Neuroanatomy | Year: 2015

The external (GPe) and internal (GPi) segments of the primate globus pallidus receive dopamine (DA) axonal projections arising mainly from the substantia nigra pars compacta and this innervation is here described based on tyrosine hydroxylase (TH) immunohistochemical observations gathered in the squirrel monkey (Saimiri sciureus). At the light microscopic level, unbiased stereological quantification of TH positive (+) axon varicosities reveals a similar density of innervation in the GPe (0.19 ± 0.02 × 106 axon varicosities/mm3 of tissue) and GPi (0.17 ± 0.01 × 106), but regional variations occur in the anteroposterior and dorsoventral axes in both GPe and GPi and along the mediolateral plane in the GPe. Estimation of the neuronal population in the GPe (3.47 ± 0.15 × 103 neurons/mm3) and GPi (2.69 ± 0.18 × 106) yields a mean ratio of, respectively, 28 ± 3 and 68 ± 15 TH+ axon varicosities/pallidal neuron. At the electron microscopic level, TH+ axon varicosities in the GPe appear significantly smaller than those in the GPi and very few TH+ axon varicosities are engaged in synaptic contacts in the GPe (17 ± 3%) and the GPi (15 ± 4%) compared to their unlabeled counterparts (77 ± 6 and 50 ± 12%, respectively). Genuine synaptic contacts made by TH+ axon varicosities in the GPe and GPi are of the symmetrical and asymmetrical type. Such synaptic contacts together with the presence of numerous synaptic vesicles in all TH+ axon varicosities observed in the GPe and GPi support the functionality of the DA pallidal innervation. By virtue of its predominantly volumic mode of action, DA appears to exert a key modulatory effect upon pallidal neurons in concert with the more direct GABAergic inhibitory and glutamatergic excitatory actions of the striatum and subthalamic nucleus. We argue that the DA pallidal innervation plays a major role in the functional organization of the primate basal ganglia under both normal and pathological conditions. © 2015 Eid and Parent.


Lamarche B.,Laval University | Couture P.,Laval University
Current Opinion in Lipidology | Year: 2015

Purpose of Review: Few studies have reviewed the impact of dietary fat and dietary patterns on lipoprotein metabolism. This review intends to provide perspective on this topic, while focusing primarily on the studies that assessed intravascular lipoprotein kinetics in humans using isotope methodologies. Recent Findings: Data suggest that dietary saturated fatty acids slow the clearance of LDL apolipoprotein (apo)B-100 and of apoA-I from the circulation, whereas possibly increasing also apoA-I production. Dietary trans fats reduce the clearance of LDL apoB-100, whereas increasing the clearance of apoA-I. n-3 polyunsaturated fatty acids (PUFAs) intake reduces the production of apoB-48-containing lipoproteins as well as of VLDL apoB-100 and increases their conversion into smaller lipoproteins. Medium-chain triglycerides appear to have no significant effect on lipoprotein kinetics. Finally, Mediterranean diet in the absence of weight loss reduces LDL cholesterol, primarily by enhancing its clearance from the circulation. Summary: Kinetic studies with tracers allow a better appreciation of the impact of specific dietary factors on plasma lipid risk factors. However, additional studies are required to better document the effect of monounsaturated fatty acids, n-6 PUFAs, and of whole diets on lipoprotein metabolism. Copyright © 2015 Wolters Kluwer Health, Inc.


Laprise P.,Laval University
Journal of Biomedicine and Biotechnology | Year: 2011

Defects in apical-basal polarity regulation are associated with tissue overgrowth and tumorogenesis, yet the molecular mechanisms linking epithelial polarity regulators to hyperplasia or neoplasia remain elusive. In addition, exploration of the expression and function of the full complement of proteins required for the polarized architecture of epithelial cells in the context of cancer is awaited. This paper provides an overview of recent studies performed on Drosophila and vertebrates showing that apical polarity proteins of the Crumbs family act to repress tissue growth and epithelial to mesenchymal transition. Thus, these proteins emerge as potential tumor suppressors. Interestingly, analysis of the molecular function of Crumbs proteins reveals a function for these polarity regulators in junctional complexes stability and control of signaling pathways regulating proliferation and apoptosis. Thereby, these studies provide a molecular basis explaining how regulation of epithelial polarity is coupled to tumorogenesis. Copyright © 2011 Patrick Laprise.


Ghazisaeidi A.,Alcatel - Lucent | Rusch L.A.,Laval University
Journal of Lightwave Technology | Year: 2011

We study the efficiency and numerical accuracy of two digital backpropagation schemes for post-compensating SOA-induced nonlinear impairments in the context of coherent receivers for advanced modulated formats. While the classical Runge-Kutta numerical techniques provide almost ideal post-compensation when the receiver sampling time tends to zero, this accuracy diminishes quickly as we approach realistic sampling times. At rates near Nyquist, despite much reduced complexity, our proposed digital filter back propagation technique outperforms Runge-Kutta techniques in terms of root mean square (rms) residual distortion. We quantify rms residual distortion for both methods as sampling time varies. We also examine bit error performance for 16-QAM, as well as the impact of SOA saturation level. We examine robustness to imperfect channel estimation. © 2006 IEEE.


Maltais R.,Laval University | Poirier D.,Laval University
Steroids | Year: 2011

The steroid sulfatase (STS) plays a major role in the regulation of steroid hormone concentrations in several human tissues and target organs and therefore, represents an interesting target to regulate estrogen and androgen levels implicated in different diseases. In this review article, the emphasis is put on STS inhibitors reported in the fruitful 2000-2010 decade, which consolidated the first ones that were previously developed (1990-1999). The inhibitors reviewed are divided into four categories according to the fact that they are sulfamoylated or not or that they have a steroid nucleus or not. Other topics such as function, localization, structure and mechanism as well as applications of STS inhibitors are also briefly discussed to complement the information on this crucial steroidogenic enzyme and its inhibitors. © 2011 Elsevier Inc. All rights reserved.


Bachelor A.,Laval University
Clinical Psychology and Psychotherapy | Year: 2013

To better understand how clients' and therapists' views of the therapeutic alliance differ and overlap, this study investigated, first, the components of the alliance that are relevant to the therapy participants; second, their relationship to post-therapy outcome; and third, the relationships between participants' alliance constructs. To identify participants' views, exploratory factor analyses were performed on clients' (n=176) and therapists' (n=133 observations) ratings of the Working Alliance Inventory (short form), the Helping Alliance Questionnaire and the California Psychotherapy Alliance Scales and conducted both on each measure separately and on the three measures combined. The results of the separate analyses indicated in general poor correspondence between the participant-derived components and each measure's a priori constructs. Results of the joint analyses suggested that clients view the alliance in terms of six basic components (Collaborative Work Relationship, Productive Work, Active Commitment, Bond, Non-disagreement on Goals/Tasks and Confident Progress), five of which were found to predict client-rated and/or therapist-rated post-therapy outcome. Results for therapists suggested four basic components (Collaborative Work Relationship, Therapist Confidence & Dedication, Client Commitment & Confidence, Client Working Ability), of which three predicted post-therapy outcome. Findings of significant, but modest to low moderate, correlations between several client and therapist joint factors suggested that despite similarities, the therapy partners' views of the alliance differ in important ways. Compared with therapists, clients appear to place greater emphasis on helpfulness, joint participation in the work of therapy and negative signs of the alliance. Implications of these findings are discussed. © 2011 John Wiley & Sons, Ltd.


Adjibade P.,Laval University | Mazroui R.,Laval University
Seminars in Cell and Developmental Biology | Year: 2014

The control of mRNA turnover is essential for the cell to rationalize its mRNA content both under physiological conditions and upon stress. Several mechanisms involved in the control of mRNA turnover have been elucidated. These include surveillance mechanisms such as nonsense-mediated decay, non-stop mediated decay and non-go-mediated decay that eliminate aberrant mRNAs, and regulatory mechanisms including AU-mediated decay, GU-mediated decay, and CDE-mediated decay that ensure mRNA plasticity. In general, the mechanisms of RNA decay rely on interactions between specific cis-acting RNA elements and selected RNA-binding proteins that either prevent the degradation of mRNA targets or induce the recruitment of decaying effectors leading to mRNA degradation. Formation of cytoplasmic RNA granules including processing bodies, stress granules, UV granules, and exosome granules have recently emerged as an additional mechanism that control mRNA turnover of selected mRNAs. Here we will review briefly review the main mechanisms that control mRNA decay and highlight possible implication of RNA granules in such mechanisms. © 2014 Elsevier Ltd.


Bilodeau J.-F.,Chu Of Quebec Research Center Chul | Bilodeau J.-F.,Laval University
Placenta | Year: 2014

The abnormally developed placenta is believed to be the pathophysiological cause of preeclampsia (PE). The resulting malperfusion of the placenta in PE can be associated with fluctuations in oxygen levels, leading to oxidative stress. How then do the placenta and the circulatory system of the mother adapt and respond to the increased oxidative challenge associated with PE? Many antioxidant systems have been shown to be upregulated or downregulated in the placenta and/or the maternal circulation during PE. Such altered antioxidant response can lead to increased lipid peroxidation. Oxidation of arachidonoyl residues in phospholipids generates bioactive lipids such as F 2-isoprostanes, which are known vasoconstrictors. The consequences of changes in antioxidant status can also affect signal transduction and enzymatic pathways related to eicosanoid synthesis. © 2013 Published by IFPA and Elsevier Ltd.


Laprise P.,Laval University | Tepass U.,University of Toronto
Trends in Cell Biology | Year: 2011

Apical-basal polarity is a basic organizing principle of epithelial cells. Consequently, defects in polarity are associated with numerous human pathologies, including many forms of cancer. Recent work in Drosophila has identified novel roles for, or has greatly enhanced our understanding of, functional modules within the epithelial polarity network. A series of recent papers have highlighted the key function of the scaffolding protein Bazooka/Par3 as an early polarity landmark, and its crucial role in dynamic segregation of the apical membrane from the adherens junction. Moreover, novel polarity modules have recently been discovered; the Yurt/Coracle group supports the basolateral membrane during a defined time window of development, while a second module, including the kinases LKB1 and AMP-activated protein kinase, is required for polarity when epithelial cells experience metabolic stress. These new findings emphasize unforeseen complexities in the regulation of epithelial polarity, and raise new questions about the mechanisms of epithelial tissue organization and function. © 2011 Elsevier Ltd.


Sapountzi V.,Laval University | Cote J.,Laval University
Cellular and Molecular Life Sciences | Year: 2011

Covalently modifying a protein has proven to be a powerful mechanism of functional regulation. N-epsilon acetylation of lysine residues was initially discovered on histones and has been studied extensively in the context of chromatin and DNA metabolism, such as transcription, replication and repair. However, recent research shows that acetylation is more widespread than initially thought and that it regulates various nuclear as well as cytoplasmic and mitochondrial processes. In this review, we present the multitude of non-histone proteins targeted by lysine acetyltransferases of the large and conserved MYST family, and known functional consequences of this acetylation. Substrates of MYST enzymes include factors involved in transcription, heterochromatin formation and cell cycle, DNA repair proteins, gluconeogenesis enzymes and finally subunits of MYST protein complexes themselves. Discovering novel substrates of MYST proteins is pivotal for the understanding of the diverse functions of these essential acetyltransferases in nuclear processes, signaling, stress response and metabolism. © 2010 Springer Basel AG.


Ollevier T.,Laval University | Keipour H.,Laval University
Topics in Organometallic Chemistry | Year: 2015

Synthetic organic transformations catalyzed by iron complexes have attracted considerable attention because of an enviable list of assets: iron is an ubiquitous, inexpensive, and environmentally benign metal. It has been documented that various chiral iron complexes can be used in many reactions such as oxidation, cyclopropanation, hydrogenation, hydrosilylation, and alkane hydroxylation. This chapter summarizes recent developments, mainly from 2004 to 2014, of enantioselective iron catalysts. © Springer International Publishing Switzerland 2015.


Gagne C.,Laval University | Harnois I.,Laval University
Health Psychology | Year: 2013

Objective: Based on the theory of planned behavior and the structural model of health behavior, the objectives of this study were to verify whether the psychosocial variables of daycare workers (intention, perceived behavioral control, descriptive norm, past behavior) influence preschoolers' physical activity in daycare centers and determine how these psychosocial variables combine with other factors (environmental, sociodemographic, democratic intervention) to explain children's physical activity. Method: Forty-six daycare workers from 20 daycare centers in Quebec, Canada completed a self-reported questionnaire assessing psychosocial and sociodemographic variables. Thirty days later, 242 children wore an accelerometer. A research assistant went to each daycare center to observe the environment and the democratic intervention of daycare workers. Findings: The specific direct determinants of children's overall mean count/15 seconds were intention, descriptive norm, democratic intervention, daycare workers' age, availability of material, and children's age and gender. Conclusion: In order to increase the overall mean count/15 seconds among preschoolers, it would be important to motivate daycare workers to make children move. Strategies likely to help motivate daycare workers to take action are also necessary. It might be interesting to encourage them to use democratic intervention with children. Use of material adapted to the needs of the children that stimulates their intellectual and socioaffective development should also be encouraged. © 2012 the American Psychological Association.


Tardif S.,Laval University | Simard M.,Laval University
International Journal of Alzheimer's Disease | Year: 2011

This literature paper investigated the efficacy of 14 cognitive intervention programs administered to healthy elderly participants. PsycINFO and PubMed databases were searched using the following terms: cognitive training, cognitive stimulation, elderly, and aging. The majority of participants (13/14 studies) were recruited in community. Nine out of 14 studies targeted memory as the principal cognitive function to train or stimulate. Face-name associations, mental imagery, paired associations, and the method of loci were the main techniques taught to participants. Improvements were observed on at least one outcome measure in each study included in this paper. Recommendations to improve cognitive interventions in the healthy elderly are proposed, such as the utilization of more robust experimental designs, the inclusion of measures of generalization of training in daily life, the assessment of instrumental activities of daily living, quality of life, and self-esteem. © 2011 Sarah Tardif and Martine Simard.


17β-Hydroxysteroid dehydrogenases (17β-HSDs) belong to a group of key enzymes involved in the biosynthesis of steroidal hormones by catalyzing the reduction of 17-ketosteroids or the oxidation of 17β-hydroxysteroids. From three members known in the early nineties, the 17β-HSD functional family has grown to 15 members over the last 20 years. This growing number of 17β-HSD isoforms questioned the importance of each member, especially in their implication in estrogen- and androgen-dependent diseases, such as breast and prostate cancers. One of the strategies used to address the physiological importance of 17β-HSDs is to use potent and selective inhibitors. Furthermore, enzyme inhibitors could also be of therapeutic interest by reducing the level of estradiol (E2). Focusing on estrogens, we targeted 17β-HSD types 1 and 7, two enzymes able to transform the weak estrogen estrone (E1) into the potent estrogen E2. The present review article gives a description of different classes of inhibitors of 17β-HSD1 (C6-derivatives of E2, C16-derivatives of E2 as alkylating and dual action compounds, E2-adenosine hybrids, E2-simplified adenosine hybrids, and C16-derivatives of E1 or E2) and of inhibitors of 17β-HSD7, all these inhibitors developed in our laboratory. The chemical structures and inhibitory activity of these steroidal inhibitors, their potential as therapeutic agents, and their use as tools to elucidate the role of these enzymes in particular biological systems will be discussed. Article from the Special issue on Targeted Inhibitors. © 2010 Elsevier Ltd. All rights reserved.


Avvakumov N.,Laval University | Nourani A.,Laval University | Cote J.,Laval University
Molecular Cell | Year: 2011

The many factors that control chromatin biology play key roles in essential nuclear functions like transcription, DNA damage response and repair, recombination, and replication and are critical for proper cell-cycle progression, stem cell renewal, differentiation, and development. These players belong to four broad classes: histone modifiers, chromatin remodelers, histone variants, and histone chaperones. A large number of studies have established the existence of an intricate functional crosstalk between the different factors, not only within a single class but also between different classes. In light of this, while many recent reviews have focused on structure and functions of histone chaperones, the current text highlights novel and striking links that have been established between these proteins and posttranslational modifications of histones and discusses the functional consequences of this crosstalk. These findings feed a current hot question of how cell memory may be maintained through epigenetic mechanisms involving histone chaperones. © 2011 Elsevier Inc.


Peters C.H.,Stanford University | Sachs-Quintana I.T.,Stanford University | Kastrop J.P.,Stanford University | Beaupre S.,Laval University | And 2 more authors.
Advanced Energy Materials | Year: 2011

Organic bulk-heterojunction solar cells comprising poly[N-9'-hepta-decanyl- 2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2', 1',3'-benzothiadiazole) (PCDTBT) are systematically aged and demonstrate lifetimes approaching seven years, which is the longest reported lifetime for polymer solar cells. An experimental set-up is described that is capable of testing large numbers of solar cells, holding each device at its maximum power point while controlling and monitoring the temperature and light intensity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


OBJECTIVES:: Central hemodynamic parameters are better predictors of the cardiovascular burden than peripheral blood pressure (BP). Beta-blockers are known to reduce central BP to a lesser extent than peripheral BP, a hypothesized mechanistic consequence of heart rate (HR) reduction. METHODS:: The association between beta-blocker use, HR and central hemodynamics indices was studied in treated hypertensive participants of the CARTaGENE study using propensity score analyses and multivariate linear regressions. RESULTS:: Of the 20?004 participants, 2575 were treated hypertensive patients with valid pulse wave analysis. Using propensity score analyses, beta-blocker users (n?=?605) were matched to nonusers having similar clinical characteristics with (Model 1) and without (Model 2) adjustment for HR. This resulted in 457 and 510 pairs with adequate balance, except for a HR difference in Model 2 (62.5?±?10.5 vs. 70.4?±?11.5?bpm, p?


Lavoie C.,Laval University
Perspectives in Plant Ecology, Evolution and Systematics | Year: 2013

Plant specimens stored in herbaria are being used as never before to document the impacts of global change on humans and nature. However, published statistics on the use of biological collections are rare, and ecologists lack quantitative data demonstrating the relevance to science of herbarium specimens. I found 382 studies with original data that used herbarium specimens to document biogeographical patterns or environmental changes. Most studies are less than 10 years old, and only 1.4% of the herbarium specimens worldwide have been used to answer biogeographical or environmental questions. The vast majority (82%) of papers dealt with vascular plants, but some studies also used bryophytes, lichens, seaweeds and fungi. The herbarium specimens were collected from all continents, but most of the studies used specimens from North America (40% of studies) or Europe (28%). Many types of researches (conservation, plant disease, plant invasion, pollution, etc.) can be conducted using herbarium specimens. Climate change, and especially phenological reconstructions, are clearly emerging research topics. By group, small herbaria (<100,000 specimens) are consulted as often as very large herbaria (>1,000,000 specimens) for biogeographical and environmental research, but in most cases, only large facilities provide specimens collected worldwide. The median number of specimens per study in papers using computerized collections (15,295) was much higher than for papers that did not include electronic data (226). The use of molecular analyses to investigate herbarium specimens is still relatively unexplored, at least from biogeographical and environmental points of view. Combined with recently developed procedures to correct biases, herbarium specimens might provide in the near future exciting additional spatio-temporal insights that are currently unimaginable. © 2012 Perspectives in Plant Ecology, Evolution and Systematics.


Gauthier-Landry L.,Laval University | Belanger A.,Laval University | Barbier O.,Laval University
Journal of Steroid Biochemistry and Molecular Biology | Year: 2015

In the prostate, approximately 50% of androgens are from adrenal steroids, mainly dehydroepiandrosterone (DHEA), its sulfate and androstenedione. These compounds are converted first into testosterone, and then into the active hormone dihydrotestosterone (DHT). After having activated the androgen receptor (AR), DHT is reduced into androstane-3α-DIOL (3α-DIOL) and androsterone (ADT), which are subsequently converted into 2 inactive and easily excretable metabolites: 3α-DIOL-17glucuronide (3α-DIOL-17G) and ADT-3glucuronide (ADT-3G). The formation of these last derivatives through the glucuronidation reaction involves 2 UDP-glucuronosyltransferase (UGT) enzymes, namely UGT2B15 and UGT2B17. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of these 2 enzymes for the control of androgen homeostasis. We will resume: (i) how UGT2B15 and UGT2B17 contribute to androgen elimination; (ii) how their glucuronidation capacity influences the androgen signaling pathway in prostate cells; (iii) how they contribute to the anti-proliferative properties of AR antagonists in prostate cancer cells; and (iv) how AR and its spliced variants regulate the UGT2B15 and/or UGT2B17 genes expression. Finally, whether the unexploited AR-UGT axis could serve as a prognostic maker or a pharmacological target for novel therapeutics in the treatment of prostate cancer is also discussed. This article is part of a special issue entitled 'Essential role of DHEA'. © 2014 Elsevier Ltd.


Poirier D.,Laval University
Recent Patents on Endocrine, Metabolic and Immune Drug Discovery | Year: 2015

Cancer is a leading cause of death in the population and despite the significant technological advances that have been made over the last years, there is a great need for new and better treatments with fewer side effects. Among the various types, hormone-dependent cancers are stimulated by the presence of certain steroidal hormones such as androgens and estrogens, which act through a nuclear receptor. The use of small molecules to block the biosynthesis (steroidogenesis) or the action of hormones (androgens or estrogens) is a therapeutic approach that has yielded interesting results and whose development continues. This review article emphasizes the patents and patent applications published over the last five years. It deals exclusively with steroid compounds developed as inhibitors of key enzymes (17α-hydroxylase/17,20-lyase, steroid sulfatase, 5α-reductases, aromatase and 17β-hydroxysteroid dehydrogenases) involved in the steroidogenesis and identified as therapeutic targets. Such inhibitors could be used as a drug to reduce the concentration of androgens or estrogens and, consequently, for treating hormone-dependent diseases such as prostate cancer, breast cancer and endometriosis. © 2015 Bentham Science Publishers.


Legagneux P.,Laval University | Fast P.L.F.,University of Quebec at Rimouski | Gauthier G.,Laval University | Bety J.,University of Quebec at Rimouski
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

Despite observational evidence of carry-over effects (COEs, events occurring in one season that produce residual effects on individuals the following seasons), to our knowledge no experimental studies have been carried out to explore how COEs might affect reproductive output. We simulated an environmental perturbation affecting spring-staging migrants to investigate COEs in greater snow geese (Anser caerulescens atlanticus). During three consecutive years, 2037 females captured during spring staging (approx. 3000 km south of their Arctic breeding grounds) were maintained in captivity (with or without access to food) for 0-4 days. Duration of captivity (but not food treatment) negatively affected reproductive success, probably through stress response. Reproductive success was reduced by 45-71% in 2 years, but not in a third year with unusually favourable breeding conditions. This unprecedented manipulation indicates that COEs can have a strong effect on individual reproductive success in long-distance migrants, but that this effect can be partly compensated for by good environmental conditions on the breeding ground. © 2011 The Royal Society.


Courtemanche M.-A.,Laval University | Legare M.-A.,Laval University | Maron L.,INSA Toulouse | Fontaine F.-G.,Laval University
Journal of the American Chemical Society | Year: 2014

The full mechanism of the hydroboration of CO2 by the highly active ambiphilic organocatalyst 1-Bcat-2-PPh2-C6H4 (Bcat = catecholboryl) was determined using computational and experimental methods. The intramolecular Lewis pair was shown to be involved in every step of the stepwise reduction. In contrast to traditional frustrated Lewis pair systems, the lack of steric hindrance around the Lewis basic fragment allows activation of the reducing agent while moderate Lewis acidity/basicity at the active centers promotes catalysis by releasing the reduction products. Simultaneous activation of both the reducing agent and carbon dioxide is the key to efficient catalysis in every reduction step. © 2014 American Chemical Society.


Desmarais C.,Laval University
Journal of speech, language, and hearing research : JSLHR | Year: 2012

In this study, the authors investigated sentence comprehension and spatial working memory abilities in a sample of internationally adopted, postinstitutionalized (PI) children. The authors compared the performance of these PI children with that of an age-matched group of children living with their birth families. They hypothesized that PI children would perform below clinical threshold on tasks of sentence comprehension and that poor sentence comprehension would be associated with poor performance in working memory. Twenty-three PI children and 36 comparison children were administered sentence comprehension and spatial memory tasks from standardized assessments. Some oral sentence comprehension skills and the spatial working memory skills were weaker in the school-age PI children than in the age-matched comparison children. A mediational analysis demonstrated that poor spatial working memory performance partially explains the sentence comprehension differences between the 2 groups. These findings provide valuable information to better plan early intervention and special education for PI children.


n-3 PUFA are receiving growing attention for their therapeutic potential in central nervous system (CNS) disorders. We have recently shown that long-term treatment with DHA alters the physiology of entorhinal cortex (EC) neurons. In the present study, we investigated by patch-clamp the effect of another major dietary n-3 PUFA, α-linolenic acid (LNA), on the intrinsic properties of EC neurons. Mice were chronically exposed to isoenergetic diets deficient in n-3 PUFA or enriched in either DHA or LNA on an equimolar basis. GC analyses revealed an increase in DHA (34%) and a decrease in arachidonic acid (AA, - 23%) in brain fatty acid concentrations after consumption of the DHA-enriched diet. Dietary intake of LNA similarly affected brain fatty acid profiles, but at a lower magnitude (DHA: 23%, AA: - 13%). Compared to the n-3 PUFA-deficient diet, consumption of DHA, but not LNA, induced membrane hyperpolarisation ( -60 to -70 mV), increased cellular capacitance (32%) and spontaneous excitatory postsynaptic current frequency (50%). We propose that the inefficiency of LNA to modulate cellular capacitance was related to its inability to increase the brain DHA:AA ratio over the threshold necessary to up-regulate syntaxin-3 (46%) and translocate drebrin (40% membrane:cytosol ratio). In summary, our present study shows that the increase in brain DHA content following chronic administration of LNA was not sufficient to alter the passive and synaptic properties of EC neurons, compared to direct dietary intake of DHA. These diverging results have important implications for the therapeutic use of n-3 PUFA in CNS disease, favouring the use of preformed DHA.


Lemyre J.-L.,Laval University | Ritcey A.M.,Laval University
Langmuir | Year: 2010

The 1H NMR spectrum of IgepalCO520 in ternary mixtures containing water and cyclohexane shows a complex dependence on water content. This is in part because of rapid exchange between surfactant molecules within the micelles and free surfactant dissolved in the continuous phase. The analysis of this two-state system is further complicated by the fact that the chemical shifts of both free and micellar surfactants vary with micelle size. We demonstrate that the relative quantities of free and micellar surfactants can be determined from the NMR spectra if the data are compared within sample sets of constant micelle size but differing global composition. By fixing micelle size, the spectra of both surfactant states remain constant within a given series and only the relative populations of the free and micellar species change with overall composition. This method of analysis allows for the determination of free surfactant concentration as a function of micelle size. Results are presented for the water/IgepalCO520/cyclohexane system and indicate that the free surfactant concentration is far from negligible and strongly dependent on micelle size. The free surfactant concentration increases with decreasing micelle size, reflecting the lower stability of the smaller micelles. Similar behavior can be expected for other reverse micellar systems based on non-ionic surfactants. © 2010 American Chemical Society.


Naert G.,Laval University | Rivest S.,Laval University
Current Alzheimer Research | Year: 2011

Alzheimer disease (AD) is characterized by a progressive cognitive decline and accumulation of β-amyloid (Aβ) forming senile plaques that are associated with inflammatory molecules and cells. Resident microglia and newly differentiated cells that are derived from the bone marrow are found in the vicinity of Aβ plaques. Although these two types of microglia are not distinguishable by specific markers in the brain, they seem to possess different phenotype and functions. In mouse models of AD, bone marrow-derived microglia (BMDM) have been shown to delay or stop the progression of AD and preventing their recruitment exacerbates the pathology. Transplantation of competent hematopoietic stem cells or their genetic modifications ameliorate cognitive functions, reduce Aβ accumulation and prevent synaptic dysfunctions. Improving the recruitment of genetically-modified BMDM may be considered as a powerful new therapeutic strategy to counteract AD. Here we review the role of microglia subsets in AD and how these cells have a great potential to fight against Aβ accumulation and cognitive impairment. © 2011 Bentham Science Publishers Ltd.


Seigneur J.,Laval University | Timofeev I.,Laval University
Epilepsia | Year: 2011

Purpose: Seizures are associated with a reduction in extracellular Ca 2+ concentration ([Ca2+]o) and an increase in extracellular K+ concentration ([K+]o). The long-range synchrony observed between distant electrodes during seizures is weak. We hypothesized that changes in extracellular ionic conditions during seizures are sufficient to alter synaptic neuronal responses and synchrony in the neocortex. Methods: We obtained in vivo and in vitro electrophysiologic recordings combined with microstimulation from cat/rat neocortical neurons during seizures and seizure-like ionic conditions. In vitro the [K +]o was 2.8, 6.25, 8.0, and 12 mm and the [Ca 2+]o was 1.2 and 0.6 mm. Key Findings: During seizures recorded in vivo, we observed abolition of evoked synaptic responses. In vitro, the membrane potential of both regular-spiking and fast-spiking neurons was depolarized in high [K+]o conditions and hyperpolarized in high [Ca2+]o conditions. During high [K+] o conditions, changes in [Ca2+]o did not affect membrane potential. The synaptic responsiveness of both regular-spiking and fast-spiking neurons was reduced during seizure-like ionic conditions. A reduction in [Ca2+]o to 0.6 mm increased failure rates but did not abolish responses. However, an increase in [K+]o to 12 mm abolished postsynaptic responses, which depended on a blockade in axonal spike propagation. Significance: We conclude that concomitant changes in [K+]o and [Ca2+]o observed during seizures contribute largely to the alterations of synaptic neuronal responses and to the decrease in long-range synchrony during neocortical seizures. © 2010 International League Against Epilepsy.


A new technology, called CRISPR, derived from the immune system of bacteria, uses a Cas9 nuclease and a guided RNA complementary to a 20 nucleotides sequence of a gene to induce double strand DNA breaks. This permits to modify specifically the targeted gene in plant, animal and human cells. Variants of the technique also permit to reduce or increase the expression of a selected gene. This technology may thus be used not only to understand the role of a gene but also to develop therapies for hereditary and acquired diseases. © 2015 médecine/sciences - Inserm.


Moreau A.,University of Québec | Gosselin-Badaroudine P.,University of Québec | Chahine M.,University of Québec | Chahine M.,Laval University
Quarterly Reviews of Biophysics | Year: 2014

The voltage sensitive domain (VSD) is a pivotal structure of voltage-gated ion channels (VGICs) and plays an essential role in the generation of electrochemical signals by neurons, striated muscle cells, and endocrine cells. The VSD is not unique to VGICs. Recent studies have shown that a VSD regulates a phosphatase. Similarly, Hv1, a voltage-sensitive protein that lacks an apparent pore domain, is a self-contained voltage sensor that operates as an H+ channel. VSDs are formed by four transmembrane helices (S1-S4). The S4 helix is positively charged due to the presence of arginine and lysine residues. It is surrounded by two water crevices that extend into the membrane from both the extracellular and intracellular milieus. A hydrophobic septum disrupts communication between these water crevices thus preventing the permeation of ions. The septum is maintained by interactions between the charged residues of the S4 segment and the gating charge transfer center. Mutating the charged residue of the S4 segment allows the water crevices to communicate and generate gating pore or omega pore. Gating pore currents have been reported to underlie several neuronal and striated muscle channelopathies. Depending on which charged residue on the S4 segment is mutated, gating pores are permeant either at depolarized or hyperpolarized voltages. Gating pores are cation selective and seem to converge toward Eisenmann's first or second selectivity sequences. Most gating pores are blocked by guanidine derivatives as well as trivalent and quadrivalent cations. Gating pores can be used to study the movement of the voltage sensor and could serve as targets for novel small therapeutic molecules. © Cambridge University Press 2014.


Kouidmi I.,University of Montréal | Levesque R.C.,Laval University | Paradis-Bleau C.,University of Montréal
Molecular Microbiology | Year: 2014

With antibiotic resistance mechanisms increasing in diversity and spreading among bacterial pathogens, the development of new classes of antibacterial agents against judiciously chosen targets is a high-priority task. The biochemical pathway for peptidoglycan biosynthesis is one of the best sources of antibacterial targets. Within this pathway are the Mur ligases, described in this review as highly suitable targets for the development of new classes of antibacterial agents. The amide ligases MurC, MurD, MurE and MurF function with the same catalytic mechanism and share conserved amino acid regions and structural features that can conceivably be exploited for the design of inhibitors that simultaneously target more than one enzyme. This would provide multi-target antibacterial weapons with minimized likelihood of target-mediated resistance development. © 2014 John Wiley & Sons Ltd.


Bosse Y.,Laval University
Journal of Endocrinology | Year: 2014

Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked. © 2014 Society for Endocrinology.


Grondin S.,Laval University
Attention, Perception, and Psychophysics | Year: 2010

The aim of the present review article is to guide the reader through portions of the human time perception, or temporal processing, literature. After distinguishing the main contemporary issues related to time perception, the article focuses on the main findings and explanations that are available in the literature on explicit judgments about temporal intervals. The review emphasizes studies that are concerned with the processing of intervals lasting a few milliseconds to several seconds and covers studies issuing from either a behavioral or a neuroscience approach. It also discusses the question of whether there is an internal clock (pacemaker counter or oscillator device) that is dedicated to temporal processing and reports the main hypotheses regarding the involvement of biological structures in time perception. © 2010 The Psychonomic Society, Inc.


April J.,Laval University | Hanner R.H.,University of Guelph | Dion-Cote A.-M.,Laval University | Bernatchez L.,Laval University
Molecular Ecology | Year: 2013

Allopatric speciation may be the principal mechanism generating new species. Yet, it remains difficult to judge the generality of this process because few studies have provided evidence that geographic isolation has triggered the development of reproductive isolation over multiple species of a regional fauna. Here, we first combine results from new empirical data sets (7 taxa) and published literature (9 taxa) to show that the eastern Great Lakes drainage represents a multispecies suture zone for glacial lineages of freshwater fishes with variable levels of genetic divergence. Second, we performed amplified fragment length polymorphism analyses among four pairs of lineages. Results indicate that lineages with relatively deep levels of mtDNA 5′ COI (barcode) sequence divergence (>2%) developed strong reproductive barriers, while lineages with lower levels of divergence show weaker reproductive isolation when found in sympatry. This suggests that a threshold of 2% sequence divergence at mtDNA could be used as a first step to flag cryptic species in North American freshwater fishes. By describing different levels of divergence and reproductive isolation in different co-occurring fishes, we offer strong evidence that allopatric speciation has contributed significantly to the diversification of north-eastern American freshwater fishes and confirm that Pleistocene glacial cycles can be viewed as a 'speciation pump' that played a predominant role in generating biodiversity. © 2012 Blackwell Publishing Ltd.


INTRODUCTION: Sleep disturbances are present in approximately 70% of individuals with an anxiety disorder (AD). Treatments for AD may alleviate associated sleep problems, but empirical support for this view is sparse. OBJECTIVE: To assess state of knowledge about the impact of CBT for AD on sleep disturbances. METHOD: Systematic search for clinical trials of CBT for any AD in PsycINFO, MedLine, and Proquest Dissertations and Theses. RESULTS: Of 1205 studies, only 25 (2.07%) reported sleep data. The combined ES of CBT for AD on sleep was 0.527 [95%CI 0.306-0.748], indicating a moderate effect of anxiety treatment on concomitant sleep difficulties. The impact did not significantly differ according to study design, sleep variable or anxiety disorder. CONCLUSIONS: Although substantial amounts of research documented the efficacy of CBT for AD, very few reported its effect on concomitant sleep problems. Current state of knowledge does not permit definitive conclusions and future research is needed.


Nik O.G.,Laval University | Nohair B.,Laval University | Kaliaguine S.,Laval University
Microporous and Mesoporous Materials | Year: 2011

In this work, the grafting reaction of as-synthesized template-free FAU/EMT intergrowth zeolite with 3-aminopropyltriethoxysilane (APTES), 3-aminopropylmethyldiethoxysilane (APMDES), and 3- aminopropyldimethylethoxysilane (APDMES) containing tri-hydrolyzable ethoxy groups (3E), di-hydrolyzable ethoxy groups (2E), and mono-hydrolyzable ethoxy group (1E), respectively, were investigated in solvents expressing different polarities. The grafting reaction via APMDES was studied in n-hexane (HEX), toluene (TOL), t-butanol (TBUT), isopropanol (IPA), isopropanol/water mixture, 95/5 V/V (IPAW), acetone (ACT) and ethanol (ETN) with dielectric constants of 1.88, 2.4, 12.4, 19.9, 19.9, 21, and 24, respectively. The samples grafting with APDMES and APTES was only conducted in TOL and IPA as examples of non-polar and polar solvents, respectively. The samples were characterized using nitrogen sorption at 77 K (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TG), cross polarization magic angle spinning 29Si NMR and 13C NMR (nuclear magnetic resonance) spectroscopy, FTIR and carbon dioxide (CO 2) adsorption. The obtained results showed that the polarity and dielectric constant of the solvent used for grafting aminosilanes on zeolites strongly affect the amounts of grafted amine groups, the surface area and micropore volume, as well as CO 2 adsorptive properties of the resulting materials. Non-polar solvents resulted in larger concentrations of grafted amine groups, lower surface area materials, and lower CO 2 capacity of adsorption. On the contrary, polar solvents resulted in smaller concentrations of amine groups, higher surface area materials, and larger CO 2 capacity of adsorption. The obtained results also showed that the lower the number of ethoxy groups in the aminosilane, the higher the surface area and CO 2 capacity of adsorption of the samples. © 2011 Elsevier Inc. All rights reserved.


Esmaieli K.,Laval University | Hadjigeorgiou J.,University of Toronto | Grenon M.,Laval University
International Journal of Rock Mechanics and Mining Sciences | Year: 2010

This paper uses a case study from Brunswick Mine in Canada to determine a representative elementary volume (REV) of a jointed rock mass in the vicinity of important underground infrastructure. The equivalent geometrical and mechanical property REV sizes were determined based on fracture systems modeling and numerical experiments on a synthetic rock mass. Structural data collected in massive sulphides were used to generate a large fracture system model (FSM), 40m×40m×40m. This FSM was validated and subsequently sampled to procure 40 cubic specimens with a height to width ratio of 2 based on sample width from 0.05 to 10m. The specimens were introduced into a 3D particle flow code (PFC3D) model to create synthetic rock mass (SRM) samples. The geometrical REV of the rock mass was determined based on the number of fractures in each sampled volume (P30) and the volumetric fracture intensity (P32) of the samples. The mechanical REV was estimated based on the uniaxial compressive strength (UCS) and elastic modulus (E) of the synthetic rock mass samples.The REV size of the rock mass was determined based on a series of statistical tests. The T-test was used to assess whether the means of the samples were statistically different from each other and the F-test to compare the calculated variance. Finally, the coefficient of variation, for the synthetic rock mass geometrical and mechanical properties, was plotted against sample size. For this particular site the estimated geometrical REV size of the rock mass was 3.5. m×3.5. m×7. m, while the mechanical property REV size was 7. m×7. m×14. m. Consequently, for engineering purposes the largest volume (7. m×7. m×14. m) can be considered as the REV size for this rock mass. © 2010 Elsevier Ltd.


The results of a search for peculiar astronomical objects using very low resolution spectra obtained with the NASA Orbital Debris Observatory (NODO) 3 m diameter liquid mirror telescope (LMT) are compared with results of spectra obtained with the Sloan Digital Sky Survey (SDSS). The main purpose of this comparison is to verify whether observations taken with this novel type of telescope are reliable. This comparison is important because LMTs are an inexpensive novel type of telescope that is very useful for astronomical surveys, particularly surveys in the time domain, and validation of the data taken with an LMT by comparison with data from a classical telescope will validate their reliability. We start from a published data analysis that classified as peculiar only 206 of the 18,000 astronomical objects observed with the NODO LMT. A total of 29 of these 206 objects were found in the SDSS. The reliability of the NODO data can be seen through the results of the detailed analysis that, in practice, incorrectly identified less than 0.3% of the 18,000 spectra as peculiar objects, most likely because they are variable stars. We conclude that the LMT gave reliable observations, comparable to those that would have been obtained with a telescope using a glass mirror. © 2015. The American Astronomical Society. All rights reserved.


Javidani M.,Laval University | Larouche D.,Laval University
International Materials Reviews | Year: 2014

Excellent thermal conductivity and lower density make Al-Si alloys a suitable alternative for cast iron in the fabrication of engine components. The increase in the maximum operation temperature and pressure of engines necessitates improving the thermomechanical fatigue performance of Al-Si alloys. This paper has two major parts focussing on the use of Al-Si based alloys in cylinder heads and engine blocks. In the first part, the structural stress-strain and material property requirements of cylinder heads are discussed. In addition, the physical and mechanical properties of different competing materials used in the manufacture of engine components are reviewed. The physical metallurgy, solidification sequence and thermal conductivity of Al-Si based alloys are reviewed. Also discussed is the effect of microstructural features on thermomechanical fatigue lifetime. This part also includes an overview of the strengthening mechanisms of cast Al-Si alloys, by dispersed phases and heat treatment. Demands to improve fuel economy and reduce emissions necessitate modifications in the materials and design of engine blocks. Wear resistance and low friction coefficient are the major characteristics required for engine block materials. In the second part, the most promising alternative approaches to manufacturing liner-less Al-Si alloy cylinder blocks are elaborated. © 2014 Institute of Materials.


Rondeau-Gagne S.,Laval University | Neabo J.R.,Laval University | Desroches M.,Laval University | Larouche J.,Laval University | And 2 more authors.
Journal of the American Chemical Society | Year: 2013

Soluble organic nanorods were prepared from phenylacetylene macrocycles using the topochemical polymerization of butadiyne moieties placed both inside and outside the macrocycles' skeletons. Macrocycles containing amide groups were self-assembled in a columnar fashion through the formation of an organogel in ethyl acetate. Upon irradiation with UV light, the Raman signals associated with butadiyne units completely vanished, indicating the creation of covalently linked nanorods. © 2012 American Chemical Society.


Boucher J.-C.,Laval University
American Review of Canadian Studies | Year: 2010

Is the public perception of Canadians influenced by military losses in Afghanistan? Many commentators, academics, and members of the media have taken for granted that growing popular discontent toward Canada's involvement in Afghanistan has been influenced by the human costs of military operations. However, without an empirical examination of the question, such a claim remains assumed. This article assesses the influence of Canada's military casualties suffered in Afghanistan between 2006 and 2010 on Canadian public opinion. In looking at both aggregate and gendered data, I find that mounting military casualties in Kandahar had no significant impact on public opinion. However, in analyzing Canadian public opinion following regional divisions, I find that Quebec's and Alberta's public attitudes were surprisingly casualty-tolerant. Public opposition to the Afghanistan mission in other regions - that is, Ontario, British Columbia, Manitoba/Saskatchewan, and the Atlantic provinces - was shaped to a lesser degree by casualties suffered by the Canadian Forces. © 2010 ACSUS.


Hungr O.,University of British Columbia | Leroueil S.,Laval University | Picarelli L.,The Second University of Naples
Landslides | Year: 2014

The goal of this article is to revise several aspects of the well-known classification of landslides, developed by Varnes (1978). The primary recommendation is to modify the definition of landslide-forming materials, to provide compatibility with accepted geotechnical and geological terminology of rocks and soils. Other, less important modifications of the classification system are suggested, resulting from recent developments of the landslide science. The modified Varnes classification of landslides has 32 landslide types, each of which is backed by a formal definition. The definitions should facilitate backward compatibility of the system as well as possible translation to other languages. Complex landslides are not included as a separate category type, but composite types can be constructed by the user of the classification by combining two or more type names, if advantageous. © 2013 Springer-Verlag Berlin Heidelberg.


Grenon M.,Laval University | Hadjigeorgiou J.,University of Toronto
International Journal of Rock Mechanics and Mining Sciences | Year: 2010

A design module has been developed for integrating slope stability analysis into the data management, ore reserve and pit optimisation processes of an open pit mine. The developed slope stability analysis tools were successfully implemented along the full projected pit model of a surface mine in Canada. Undertaken stability analyses included both kinematic and limit equilibrium stability analysis for bench and interramp design. The developed stability analysis modules employed geographical information systems (GIS) techniques to provide visualization tools and establish stability susceptibility zones along the pit. This approach facilitated the selection of acceptable slope design criteria for the pit. A case study was used to illustrate the developed methodology and tools. This approach led to an improved design for the optimised 3D pit configuration and can facilitate communication between the mine planning and geotechnical groups. This can contribute to a better understanding of the economic impact of the different slope and pit design scenarios. Given that open pit design is an iterative process, the opportunity of having design tools that can readily accommodate the use of updated data and explore different options provide tangible economic benefits. © 2009 Elsevier Ltd. All rights reserved.