NRC Institute for Biological Sciences

Ottawa, Canada

NRC Institute for Biological Sciences

Ottawa, Canada
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News Article | December 9, 2016

WINNIPEG, MB--(Marketwired - December 09, 2016) - 3D Signatures Inc. (TSX VENTURE: DXD) (the "Company" or "3DS") is pleased to announce two additional strategic appointments to its Board of Directors and its Clinical and Scientific Advisory Board respectively. Helen Stevenson, Founder and Chief Executive Officer of Reformulary Group Inc., has been appointed to the Company's Board of Directors. Dr. Ian Smith, will be stepping down from the Board of Directors and will be joining the Company's Clinical and Scientific Advisory Board ("CSAB"). Both appointments will help shape 3DS' clinical priorities and its path towards commercial success. Helen Stevenson is Founder and Chief Executive Officer of Reformulary Group Inc., a company dedicated to helping manage prescription drug costs for employer drug plans while promoting better patient health outcomes. Ms. Stevenson was formerly Executive Officer of Canada's largest provincial drug program, the Ontario Public Drug Program by Order-In-Council, as well as Assistant Deputy Minister at the Ontario Ministry of Health and Long-Term Care. Ms. Stevenson led two major transformations in the prescription drug system; first with Ontario's Bill 102 (2006) and, more recently, with the Province's generic pricing reforms (2010). In addition, she led many of Ontario's drug system initiatives, including the Drugs for Rare Diseases Framework, Ontario Narcotics Strategy, Ontario Citizens' Council, MedsCheck medication review program, Compassionate Access Program, Competitive Agreements Framework, and the Drug Innovation Fund. Ms. Stevenson is a member of the Board of Trustees of the Auto Sector Retiree Health Care Trust, and a former member of the Board of North York General Hospital. Widely recognized as a champion of value-based pricing and outcomes, 3DS will greatly benefit from Ms. Stevenson's unique experience in managing healthcare budgets at both the government level and for private payers -- two stakeholder groups that will be beneficiaries of 3DS' value-based personalized medicine strategies. Ms. Stevenson brings a unique biopharma perspective on advancing novel therapeutics with physicians and payers, which will be instrumental when addressing the industry's need for personalized and appropriate use of cancer therapies, a central focus for 3DS as it aims to rapidly commercialize a new class of biomarkers and companion diagnostics for a variety of cancers and dementia. Dr. Ian Smith was an inaugural and invaluable member of 3DS' Board of Directors. He shares founder Dr. Sabine Mai's vision for advancing the personalization of medicine and is now an esteemed member the Company's Clinical and Scientific Advisory Board. Dr. Smith is currently the Chairman of the Centre for Imaging Technology Commercialization. His past research and commercialization achievements include significant success in the field of magnetic resonance imaging. Dr. Smith is a former Director General of the NRC Institute for Biological Sciences in Ottawa, and founder and Director General of the Institute for Biodiagnostics, in Winnipeg. He is a passionate advocate for the advancement of diagnostics for the early detection and treatment of disease, and successfully started nine companies (such as Novadaq and IMRIS), with a present value of $2.5 billion with more than 300 employees in Canada and worldwide. From 2001 to 2016, he served as a Member of the Manitoba Premier's Economic Advisory Council. He was appointed Officer of the Order of Canada in 2008 for his leadership in the advancement, development and commercialization of Canada's diagnostic technologies, notably magnetic resonance imaging, in the field of health care. In addition, Dr. Smith received the 2008 Outstanding Achievement Award of the Public Service of Canada, presented to individuals who have displayed long-term excellence throughout their careers in Canada's public service. He was awarded the Queen's Gold (2002) and Diamond (2012) Jubilee Medals for his contributions. Dr. Smith is widely recognized as a successful pioneer and creator of value for med tech companies with a disciplined scientific and business acumen that was critical to 3DS as is formed the Board, management team and early strategic priorities. As a member of the CSAB, he will make important contributions including leveraging his imaging expertise and professional network, so that 3DS can complete the development of its proprietary TeloView™ software. Upon completion, TeloView™ will comprise a fully automated, scalable and end-to-end solution for 3DS' clinical lab partners to submit 3D images and generate and deliver personalized medical reports. "We are honored to welcome Dr. Smith to our Clinical and Scientific Advisory Board and Ms. Stevenson to our Board of Directors. Dr. Smith is a renowned scientist who will continue to be invaluable in guiding the development of this entirely new class of minimally invasive biomarkers," said John Swift, Chairman of 3D Signatures Inc. "Ms. Stevenson is a significant new addition to our team who brings strategic experience both at the government level and within private industry, in addition to her global networks and deep biopharma insights which will be of great benefit to the Company as we rapidly move towards commercialization," he remarked. Helen Stevenson's appointment to the Board of Directors is pending approval from the TSX Venture Exchange. The Company has granted 210,000 incentive stock options (the "Options") to directors, officers and employees of 3DS, at an exercise price of $0.76 per share. The Options are exercisable for a ten-year period from the date of grant, December 9, 2016, and vest as follows: 135,000 options at the date of grant and 75,000 twelve months later. A total of 4,647,956 options are now issued and outstanding and 24,827 remain for future issuance. The Options are granted pursuant to the Company's stock option plan, which was most recently approved by the shareholders of the Company at the annual general meeting of shareholders held on February 29, 2016. 3DS (TSX VENTURE: DXD) is a personalized medicine company with a proprietary software platform based on the three-dimensional analysis of chromosomal signatures. The technology is well developed and supported by 16 clinical studies on over 1,500 patients on 13 different cancers and Alzheimer's disease. Depending on the desired application, the technology can measure the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is designed to predict the course of disease and to personalize treatment for the individual patient. For more information, visit the Company's new website at This news release includes forward-looking statements that are subject to risks and uncertainties. Forward-looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of the Company to be materially different from the historical results or from any future results expressed or implied by such forward-looking statements. All statements within, other than statements of historical fact, are to be considered forward looking. In particular, the Company's statements that it expects to benefit greatly from its association with the individuals named in this news release is forward-looking information. Although 3DS believes the expectations expressed in such forward-looking statements are based on reasonable assumptions, such statements are not guarantees of future performance and actual results or developments may differ materially from those in forward-looking statements. Risk factors that could cause actual results or outcomes to differ materially from the results expressed or implied by forward-looking information include, among other things: market demand; technological changes that could impact the Company's existing products or the Company's ability to develop and commercialize future products; competition; existing governmental legislation and regulations and changes in, or the failure to comply with, governmental legislation and regulations; the ability to manage operating expenses, which may adversely affect the Company's financial condition; the Company's ability to successfully maintain and enforce its intellectual property rights and defend third-party claims of infringement of their intellectual property rights; adverse results or unexpected delays in clinical trials; changes in laws, general economic and business conditions; and changes in the regulatory regime. There can be no assurances that such statements will prove accurate and, therefore, readers are advised to rely on their own evaluation of such uncertainties. We do not assume any obligation to update any forward-looking statements. Neither the TSX Venture Exchange nor its Regulation Service Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

Vincent K.,University of Ottawa | Tauskela J.S.,NRC Institute for Biological Sciences | Thivierge J.-P.,University of Ottawa
Frontiers in Computational Neuroscience | Year: 2012

Neuronal avalanches are a ubiquitous form of activity characterized by spontaneous bursts whose size distribution follows a power-law. Recent theoretical models have replicated power-law avalanches by assuming the presence of functionally feedforward connections (FFCs) in the underlying dynamics of the system. Accordingly, avalanches are generated by a feedforward chain of activation that persists despite being embedded in a larger, massively recurrent circuit. However, it is unclear to what extent networks of living neurons that exhibit power-law avalanches rely on FFCs. Here, we employed a computational approach to reconstruct the functional connectivity of cultured cortical neurons plated on multielectrode arrays, and investigated whether pharmacologically-induced alterations in avalanche dynamics are accompanied by changes in FFCs. This approach begins by extracting a functional network of directed links between pairs of neurons, and then evaluates the strength of FFCs using Schur decomposition. In a first step, we examined the ability of this approach to extract FFCs from simulated spiking neurons. The strength of FFCs obtained in strictly feedforward networks diminished monotonically as links were gradually rewired at random. Next, we estimated the FFCs of spontaneously active cortical neuron cultures in the presence of either a control medium, a GABAA receptor antagonist (PTX), or an AMPA receptor antagonist combined with an NMDA receptor antagonist (APV/DNQX). The distribution of avalanche sizes in these cultures was modulated by this pharmacology, with a shallower power-law under PTX (due to the prominence of larger avalanches) and a steeper power-law under APV/DNQX (due to avalanches recruiting fewer neurons) relative to control cultures. The strength of FFCs increased in networks after application of PTX, consistent with an amplification of feed forward activity during avalanches. Conversely, FFCs decreased after application of APV/DNQX, consistent with fading feed forward activation. The observed alterations in FFCs provide experimental support for recent theoretical work linking power-law avalanches to the feed forward organization of functional connections in local neuronal circuits. © 2012 Vincent, Tauskela and Thivierge.

Honey C.J.,Princeton University | Thivierge J.-P.,NRC Institute for Biological Sciences | Sporns O.,Indiana University Bloomington
NeuroImage | Year: 2010

Over the past decade, scientific interest in the properties of large-scale spontaneous neural dynamics has intensified. Concurrently, novel technologies have been developed for characterizing the connective anatomy of intra-regional circuits and inter-regional fiber pathways. It will soon be possible to build computational models that incorporate these newly detailed structural network measurements to make predictions of neural dynamics at multiple scales. Here, we review the practicality and the value of these efforts, while at the same time considering in which cases and to what extent structure does determine neural function. Studies of the healthy brain, of neural development, and of pathology all yield examples of direct correspondences between structural linkage and dynamical correlation. Theoretical arguments further support the notion that brain network topology and spatial embedding should strongly influence network dynamics. Although future models will need to be tested more quantitatively and against a wider range of empirical neurodynamic features, our present large-scale models can already predict the macroscopic pattern of dynamic correlation across the brain. We conclude that as neuroscience grapples with datasets of increasing completeness and complexity, and attempts to relate the structural and functional architectures discovered at different neural scales, the value of computational modeling will continue to grow. © 2010 Elsevier Inc.

Stanimirovic D.B.,NRC Institute for Biological Sciences | Stanimirovic D.B.,University of Ottawa | Friedman A.,Ben - Gurion University of the Negev
Journal of Cerebral Blood Flow and Metabolism | Year: 2012

Pathophysiology of the neurovascular unit (NVU) is commonly seen in neurological diseases. The typical features of NVU pathophysiology include tissue hypoxia, inflammatory and angiogenic activation, as well as initiation of complex molecular interactions between cellular (brain endothelial cells, astroctyes, pericytes, inflammatory cells, and neurons) and acellular (basal lamina) components of the NVU, jointly resulting in increased blood-brain barrier permeability, brain edema, neurovascular uncoupling, and neuronal dysfunction and damage. The evidence of important role of the brain vascular compartment in disease pathogenesis has elicited the debate whether the primary vascular events may be a cause of the neurological disease, as opposed to a mere participant recruited by a primary neuronal origin of pathology? Whereas some hereditary and acquired cerebral angiopathies could be considered a primary cause of neurological symptoms of the disease, the epidemiological studies showing a high degree of comorbidity among vascular disease and dementias, including Alzheimer's disease, as well as migraine and epilepsy, suggested that primary vascular pathology may be etiological factor causing neuronal dysfunction or degeneration in these diseases. This review focuses on recent hypotheses and evidence, suggesting that pathophysiology of the NVU may be initiating trigger for neuronal pathology and subsequent neurological manifestations of the disease. © 2012 ISCBFM All rights reserved.

Qiu H.,NRC Institute for Biological Sciences
PloS one | Year: 2012

Acinetobacter baumannii is an emerging bacterial pathogen that causes nosocomial pneumonia and other infections. Although it is recognized as an increasing threat to immunocompromised patients, the mechanism of host defense against A. baumannii infection remains poorly understood. In this study, we examined the potential role of macrophages in host defense against A. baumannii infection using in vitro macrophage culture and the mouse model of intranasal (i.n.) infection. Large numbers of A. baumannii were taken up by alveolar macrophages in vivo as early as 4 h after i.n. inoculation. By 24 h, the infection induced significant recruitment and activation (enhanced expression of CD80, CD86 and MHC-II) of macrophages into bronchoalveolar spaces. In vitro cell culture studies showed that A. baumannii were phagocytosed by J774A.1 (J774) macrophage-like cells within 10 minutes of co-incubation, and this uptake was microfilament- and microtubule-dependent. Moreover, the viability of phagocytosed bacteria dropped significantly between 24 and 48 h after co-incubation. Infection of J774 cells by A. baumannii resulted in the production of large amounts of proinflammatory cytokines and chemokines, and moderate amounts of nitric oxide (NO). Prior treatment of J774 cells with NO inhibitors significantly suppressed their bactericidal efficacy (P<0.05). Most importantly, in vivo depletion of alveolar macrophages significantly enhanced the susceptibility of mice to i.n. A. baumannii challenge (P<0.01). These results indicate that macrophages may play an important role in early host defense against A. baumannii infection through the efficient phagocytosis and killing of A. baumannii to limit initial pathogen replication and the secretion of proinflammatory cytokines and chemokines for the rapid recruitment of other innate immune cells such as neutrophils.

Yan H.,Brock University | Chen W.,NRC Institute for Biological Sciences | Chen W.,Brock University
Chemical Society Reviews | Year: 2010

3′,5′-Cyclic diguanylic acid (c-di-GMP) is a naturally occurring small cyclic dinucleotide found in bacteria. There has been a recent surge of interest in the two-component signalling networks involving this molecule. This tutorial review introduces the biosynthesis of c-di-GMP, particularly the conserved domain features involved in its enzymatic synthesis and degradation, cellular functions and phenotypes regulated by c-di-GMP through c-di-GMP-binding proteins. The chemical synthesis and structural studies of c-di-GMP are also summarized. Two potential applications of c-di-GMP, i.e. bacterial biofilm formation and immunostimulation, are surveyed. Recent observations on c-di-GMP-binding riboswitches are also introduced. © 2010 The Royal Society of Chemistry.

Conlan J.W.,NRC Institute for Biological Sciences
Future Microbiology | Year: 2011

Francisella tularensis subsp. tularensis is a facultative intracellular bacterial pathogen of humans and other mammals. Its inhaled infectious dose is very low and can result in very high mortality. Historically, subsp. tularensis was developed as a biological weapon and there are now concerns about its abuse as such by terrorists. A live attenuated vaccine developed pragmatically more than half a century ago from the less virulent holarctica subsp. is the sole prophylactic available, but it remains unlicensed. In recent years several other potential live, killed and subunit vaccine candidates have been developed and tested in mice for their efficacy against respiratory challenge with subsp. tularensis. This article will review these vaccine candidates and the development hurdles they face. © 2011 Future Medicine Ltd.

Baral T.N.,NRC Institute for Biological Sciences
Journal of Biomedicine and Biotechnology | Year: 2010

Trypanosomiasis is one of the major parasitic diseases for which control is still far from reality. The vaccination approaches by using dominant surface proteins have not been successful, mainly due to antigenic variation of the parasite surface coat. On the other hand, the chemotherapeutic drugs in current use for the treatment of this disease are toxic and problems of resistance are increasing (see Kennedy (2004) and Legros et al. (2002)). Therefore, alternative approaches in both treatment and vaccination against trypanosomiasis are needed at this time. To be able to design and develop such alternatives, the biology of this parasite and the host response against the pathogen need to be studied. These two aspects of this disease with few examples of alternative approaches are discussed here. Copyright © 2010 Toya Nath Baral.

That the ring conformation of glycopyranosyl oxacarbenium ions can influence the stereochemical outcome of glycosylation reactions has been postulated for some time. Some new ionization calculations show that the ultimate conformation 4H 3 or 5S 1 of d-glucopyranosyl oxacarbenium ions depends on the initial φH (CH-1-C-1-S +-SCH 3) conformation of anomeric thiosulfonium ions. Evidence is also presented that nucleophile:electrophile hydrogen bonded complexes, 1,6-anhydro-carbenium ions and electron rich carbon nucleophile:oxacarbenium ion complexes are all probably artifacts of neglecting counter ions or nucleophiles in the DFT calculation. All three cationic species are likely important for glycosylation reaction side reactions but not as productive species. © 2012 Elsevier Ltd. All rights reserved.

Whitfield D.M.,NRC Institute for Biological Sciences
Carbohydrate Research | Year: 2012

The Transition State (TS) for any chemical glycosylation reaction is not known with certainty. Both experimental and computational approaches have been limited due to the complexity of the problem. This work describes a preliminary computational ionization approach using density functional theory calculations to arrive at hypothetical TSs. The new TSs contain the glycosyl donor as anomeric triflates, the acceptor as methanol, some CH 2Cl 2 molecules, and a Li + ion promoter. In this computational approach all glycosylations are disassociative in that the C-1-O Tf bond length is greater then 2 Å before any nucleophilic attack. All nucleophilic attack requires some preassociation of the nucleophile with examples of the pre-attack complexation to donor oxygens. These hypothetical models are intended to guide both experimental and computational approaches to finding TSs for glycosylation reactions that can be used to optimize stereoselectivity of glycosylation. © 2012 Elsevier Ltd. All rights reserved.

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