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Leuven, Belgium

The Leuven Faculty of Theology and Religious Studies, was a branch of the Catholic University of Leuven. The faculty traces its history back to its founding in 1432, however it was abolished in 1797 due to the French Revolution. The current faculty was established in 1834, as a part of the Catholic University of Leuven. Following the Belgian Revolution of 1830, which has established the freedom of teaching, this New Catholic University was founded in 1834 in Mechelen by the private initiative of the Belgian bishops. In 1967 the faculty was divided into Flemish and French speaking departments, and they exist today as two separate faculties. Wikipedia.


Vandenbosch G.A.E.,Catholic University of Leuven
IEEE Antennas and Propagation Magazine | Year: 2012

The session of the EurAAP Working Group on Software convened at EuCAP last year should be considered a startup event. It was the first time that the working group established really close cooperation with software vendors in a mutual effort. The goal was to discuss the future of computational electromagnetics. This year, the immediate goal was to organize a session - with time reserved for discussion - between the antennas and propagation software and design research community, on the one hand, and the software vendors, on the other hand. The idea was to fi gure out whether it would be possible to establish a kind of common roadmap, by mutual consent, for the further development and use of numerical techniques and software tools. It is obvious that the input for this roadmap should partially come from the antennas-and-propagation software and designer community, since they are the fi nal customers of the software. Source


Vermeersch P.M.,Catholic University of Leuven
Quaternary International | Year: 2011

In the Benelux, the Federmesser population of the Allerød period seems to have disappeared at the onset of the Younger Dryas, which was a period of very cold conditions. The Ahrensburgian, a new group of people, occupied and expanded in the lowland and the higher country probably on a seasonal basis, during winter in the lowlands, and during the summer in the southern highland. In the Benelux, it can be defined typologically as an industry with numerous Zonhoven points, a variable number of Ahrensburgian points, numerous end scrapers and burins and no microburin technique. The origin of the Ahrensburgian remains fully unclear. We suggest that the Benelux Ahrensburgian is older than the north European one. At the end of the Younger Dryas and early Preboreal the whole Benelux, northern France, the dry southern North Sea and Southern England was used by Ahrensburgian groups. The late Ahrensburgian groups gave birth to the early Mesolithic and a continuous occupation of the Benelux. © 2010 Elsevier Ltd and INQUA. Source


Visnjic Kastalli I.,ESADE Business School | Visnjic Kastalli I.,University of Cambridge | Van Looy B.,Catholic University of Leuven | Van Looy B.,University of Twente
Journal of Operations Management | Year: 2013

As manufacturing businesses operate in an ever more competitive, global economy where products are easily commoditized, innovating by adding services to the core product offering has become a popular strategy. Contrary to the economic benefits expected, recent findings pinpoint implementation hurdles that lead to a potential performance decline, the so-called 'servitization paradox'. In this paper, we analyze this paradox by disentangling the value creation and value appropriation processes of 44 national subsidiaries of a global manufacturing firm turned product-service provider, in the 2001-2007 period. Our findings show that the firm under study is able to successfully transcend the inherent substitution of products by services and to enact complementary sales dynamics between the two activities. Moreover, labor-intensive services such as maintenance, which imply higher levels of customer proximity, further enhance product sales. Empirical results also reveal a positive yet non-linear relationship between the scale of service activities and profitability: while initial levels of servicing result in a steep increase in profitability, a period of relative decline is observed before the positive relationship between the scale of services and profitability re-emerges. These findings suggest the presence of initial short-term gains but also indicate the existence of a 'profitability' hurdle; profitable growth seems feasible only to the extent that investments in service capability are translated into economies of scale. In helping to clarify the performance implications of service innovation, our findings suggest pathways to sustainable growth through servitization for manufacturing firms. © 2013 Elsevier B.V. Source


Diehl M.,Catholic University of Leuven | Amrit R.,University of Wisconsin - Madison | Rawlings J.B.,University of Wisconsin - Madison
IEEE Transactions on Automatic Control | Year: 2011

Standard model predictive control (MPC) yields an asymptotically stable steady-state solution using the following procedure. Given a dynamic model, a steady state of interest is selected, a stage cost is defined that measures deviation from this selected steady state, the controller cost function is a summation of this stage cost over a time horizon, and the optimal cost is shown to be a Lyapunov function for the closed-loop system. In this technical note, the stage cost is an arbitrary economic objective, which may not depend on a steady state, and the optimal cost is not a Lyapunov function for the closed-loop system. For a class of nonlinear systems and economic stage costs, this technical note constructs a suitable Lyapunov function, and the optimal steady-state solution of the economic stage cost is an asymptotically stable solution of the closed-loop system under economic MPC. Both finite and infinite horizons are treated. The class of nonlinear systems is defined by satisfaction of a strong duality property of the steady-state problem. This class includes linear systems with convex stage costs, generalizing previous stability results [1] and providing a Lyapunov function for economic MPC or MPC with an unreachable setpoint and a linear model. A nonlinear chemical reactor example is provided illustrating these points. © 2006 IEEE. Source


Lange C.,Catholic University of Leuven
Nature Reviews Neurology | Year: 2016

Brain function critically relies on blood vessels to supply oxygen and nutrients, to establish a barrier for neurotoxic substances, and to clear waste products. The archetypal vascular endothelial growth factor, VEGF, arose in evolution as a signal affecting neural cells, but was later co-opted by blood vessels to regulate vascular function. Consequently, VEGF represents an attractive target to modulate brain function at the neurovascular interface. On the one hand, VEGF is neuroprotective, through direct effects on neural cells and their progenitors and indirect effects on brain perfusion. In accordance, preclinical studies show beneficial effects of VEGF administration in neurodegenerative diseases, peripheral neuropathies and epilepsy. On the other hand, pathologically elevated VEGF levels enhance vessel permeability and leakage, and disrupt blood–brain barrier integrity, as in demyelinating diseases, for which blockade of VEGF may be beneficial. Here, we summarize current knowledge on the role and therapeutic potential of VEGF in neurological diseases. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Source


Everingham M.,University of Leeds | Van Gool L.,Catholic University of Leuven | Williams C.K.I.,University of Edinburgh | Winn J.,Microsoft | Zisserman A.,University of Oxford
International Journal of Computer Vision | Year: 2010

The Pascal Visual Object Classes (VOC) challenge is a benchmark in visual object category recognition and detection, providing the vision and machine learning communities with a standard dataset of images and annotation, and standard evaluation procedures. Organised annually from 2005 to present, the challenge and its associated dataset has become accepted as the benchmark for object detection. This paper describes the dataset and evaluation procedure. We review the state-of-the-art in evaluated methods for both classification and detection, analyse whether the methods are statistically different, what they are learning from the images (e.g. the object or its context), and what the methods find easy or confuse. The paper concludes with lessons learnt in the three year history of the challenge, and proposes directions for future improvement and extension. © 2009 Springer Science+Business Media, LLC. Source


Two-photon absorption (TPA) efficiency - scale corrected - as a function of the number of effective electrons, Neff, for the N-core organometallics dendrimers reported by Roberts et. al. (1, 2, 3; spheres); which are two orders of magnitude more efficient than the N-core organic dendrimers (G0, G1, G2; hexagons) used for comparison. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Valev V.K.,Catholic University of Leuven
Langmuir | Year: 2012

Because of its high surface and interface sensitivity, the nonlinear optical technique of second harmonic generation (SHG) is a designated method for investigating nanostructured metal surfaces. Indeed, the latter present a high surface-to-volume ratio, but even more importantly, they can exhibit strong near-field enhancements or "hot spots". Hot spots often appear as a result of geometric features on the nanoscale or surface plasmon resonances, which are collective electron oscillations on the surface that, on the nanoscale, can readily be excited by light. In the last 10 years, near-field hot spots have been responsible for dramatic developments in the field of nano-optics. In this Feature Article, the influence of hot spots on the SHG response of nanostructured metal surfaces is discussed on both the microscopic and macroscopic levels. On the microscopic level, the nanostructured metal surfaces were characterized by scanning SHG microscopy, complemented by rigorous numerical simulations of the near-field and of the local electric currents at the fundamental frequency. On the macroscopic level, SHG-circular dichroism and magnetization-induced SHG characterization techniques were employed. © 2012 American Chemical Society. Source


Dewachter I.,Catholic University of Leuven
Molecular neurodegeneration | Year: 2014

The amyloid cascade hypothesis has been the prevailing hypothesis in Alzheimer's Disease research, although the final and most wanted proof i.e. fully successful anti-amyloid clinical trials in patients, is still lacking. This may require a better in depth understanding of the cascade. Particularly, the exact toxic forms of Aβ and Tau, the molecular link between them and their respective contributions to the disease process need to be identified in detail. Although the lack of final proof has raised substantial criticism on the hypothesis per se, accumulating experimental evidence in in vitro models, in vivo models and from biomarkers analysis in patients supports the amyloid cascade and particularly Aβ-induced Tau-pathology, which is the focus of this review. We here discuss available models that recapitulate Aβ-induced Tau-pathology and review some potential underlying mechanisms. The availability and diversity of these models that mimic the amyloid cascade partially or more complete, provide tools to study remaining questions, which are crucial for development of therapeutic strategies for Alzheimer's Disease. Source


Rossion B.,Catholic University of Leuven
Trends in Cognitive Sciences | Year: 2014

Electrophysiological recordings on the human scalp provide a wealth of information about the temporal dynamics and nature of face perception at a global level of brain organization. The time window between 100 and 200. ms witnesses the transition between low-level and high-level vision, an N170 component correlating with conscious interpretation of a visual stimulus as a face. This face representation is rapidly refined as information accumulates during this time window, allowing the individualization of faces. To improve the sensitivity and objectivity of face perception measures, it is increasingly important to go beyond transient visual stimulation by recording electrophysiological responses at periodic frequency rates. This approach has recently provided face perception thresholds and the first objective signature of integration of facial parts in the human brain. © 2014 Elsevier Ltd. Source


Baeck M.,Catholic University of Louvain | Goossens A.,Catholic University of Leuven
Contact Dermatitis | Year: 2012

Background. Corticosteroids (CS), anti-inflammatory drugs also widely used to treat various allergic diseases, may themselves give rise to immediate and delayed allergic hypersensitivity reactions. Objectives. To realise an appropriate diagnostic work-up in order to determine the CS-allergic patient's sensitization/tolerance profile and define the potential replacement agents that can still be tolerated. Methods. Analysis of the patch test results and concomitant (cross-) reaction patterns obtained with 315 corticosteroid-allergic patients, as well as molecular modelling of molecules. Results. Proposal of a simplified classification of corticosteroids as to their allergenic properties into 3 groups, determination of two patient profiles according to steric and electrostatic properties of the molecules. Conclusion. Practical information to the medical profession in order to detect and manage such reactions is provided. © 2011 John Wiley & Sons A/S. Source


Vandenbosch G.A.E.,Catholic University of Leuven
IEEE Transactions on Antennas and Propagation | Year: 2012

A rigorous relation is derived between any local change of the volume of an electrically small radiating device and the lower bound of its radiation Q factor. The relation concerns the actual volume and not the circumscribing volume. This means that also (incremental) changes in volume can be studied where the circumscribing volume remains the same. The relation clearly proves that any arbitrary increase in volume decreases the Q, and any arbitrary reduction in volume increases the Q. When directly applied to volumes embedded within a sphere, it is almost trivial to rigorously prove the well-known fact that the full sphere provides the absolute minimal Q. The communication ends with a simple analytical proof of the limit as introduced by Thal for dipole type spherical TM modes. To the knowledge of the author, these explicit relations between Q factor and occupied volume have not been described in literature yet. © 2011 IEEE. Source


Rex S.,Catholic University of Leuven
Current Opinion in Critical Care | Year: 2012

PURPOSE OF REVIEW: To summarize and highlight recent advances in the understanding and management of burn injuries. RECENT FINDINGS: The review focuses on topics which are of particular relevance for critical care practitioners involved in burn care: resuscitation, management of infection and sepsis, epidemiology and outcome, and organization and costs of burn care. SUMMARY: While being the mainstay of early survival in burn victims, various aspects of burn resuscitation are still contentious and highlighted in this review. In particular, several strategies to overcome the repeatedly observed 'fluid creep' in burn patients are discussed, including the use of computerized resuscitation algorithms and the administration of colloids. Sepsis and multiorgan failure have become the major causes of death in patients surviving the initial phase of burn shock. Various aspects of sepsis management are reviewed, amongst which diagnosis, antibiotic treatment and prophylaxis. Recent epidemiologic data allow to identify risk factors associated with mortality as these are potentially amenable to targeted prevention and therapy. Examples are acute kidney injury and sepsis. The overview is completed by recent findings on organization and costs of burn care, including the adherence to referral criteria and the main determinants of cost. Copyright © 2012 Lippincott Williams & Wilkins. Source


Tack J.,Catholic University of Leuven | Talley N.J.,University of Newcastle
Nature Reviews Gastroenterology and Hepatology | Year: 2013

Dyspepsia refers to a heterogeneous group of symptoms that are localized in the epigastric region. Typical dyspeptic symptoms include postprandial fullness, early satiation, epigastric pain and epigastric burning, but other upper gastrointestinal symptoms such as nausea, belching or abdominal bloating often occur. Functional dyspepsia is defined as the presence of dyspeptic symptoms in the absence of an organic cause that readily explains them. The Rome III consensus proposed the subdivision of functional dyspepsia into postprandial distress syndrome (PDS), characterized by postprandial fullness and early satiation, and epigastric pain syndrome (EPS), characterized by epigastric pain or burning. Epidemiological studies in the USA and Europe confirmed the presence of both subgroups, with good separation between EPS and PDS. By contrast, other studies have found major overlap between EPS and PDS in patients with functional dyspepsia in specialist care centres in Europe and Asia. Preliminary pathophysiological studies suggest that PDS might be characterized by a higher prevalence of impaired gastric accommodation than EPS and raised duodenal eosinophil counts. Whether different treatment approaches are needed for EPS and PDS is currently unclear; only acotiamide, a new drug for the treatment of functional dyspepsia, has been found to be efficacious in PDS but not in EPS. Further randomized controlled trials testing treatment response by subgroup are urgently needed. © 2013 Macmillan Publishers Limited. All rights reserved. Source


Bouillon R.,Catholic University of Leuven
Pediatric endocrinology reviews : PER | Year: 2013

Even one century after its discovery, there are still many gaps in the understanding of the vitamin D endocrine system. Inactivation of the vitamin D receptor (VDR) or the enzymes metabolizing its ligand (especially Cyp27bl) in mice has clearly demonstrated that the active form of vitamin D [1,25(OH)2D] is essential to stimulate calcium absorption in the gut during normal/low calcium intake, and as a consequence, that 1,25(OH)2D is required to maintain normal serum calcium, bone and growth plate homeostasis. These findings have resulted in clear clinical guidelines for the treatment of vitamin D-related bone diseases of infants, children and adults. Tissue-specific VDR or Cyp27b1 deletion in mice has also proven to be useful to define the precise role of 1,25(OH)2D action in cells belonging to the intestine, bone, growth plate and also to many non-classical target tissues. Indeed, experimental findings show that 1,25(OH)2D has numerous extraskeletal effects, and observational studies in man demonstrate that disturbances in the vitamin D pathway are associated with major human diseases such as cancer, infections, autoimmune diseases, cardiovascular and metabolic diseases, muscle function, reproduction and neurocognitive disorders. We will compare the findings in VDR- and Cyp27bi-null mice with findings in man to elucidate what is presently understood of the vitamin D endocrine system and to identify the still outstanding questions. Source


Deborggraeve S.,Institute of Tropical Medicine | Deborggraeve S.,Catholic University of Leuven | Buscher P.,Institute of Tropical Medicine
The Lancet Infectious Diseases | Year: 2010

Sleeping sickness, or human African trypanosomiasis, is a vector-borne disease caused by two subspecies of the protozoan parasite Trypanosoma brucei, and is geographically restricted to sub-Saharan Africa. Although the disease causes major public-health and socioeconomic problems among affected populations, sleeping sickness is one of the world's most neglected diseases. Within the rapidly evolving field of biotechnology, many molecular diagnostics have been developed to detect the parasite. These range from conventional, high-tech, and low-tech PCR formats (eg, isothermal nucleic-acid-amplification techniques), to direct visualisation of the parasite's nucleic acids by fluorescent probes. Besides reviewing the most important molecular diagnostics available, we discuss their current role in diagnosis and disease control. Although powerful, molecular diagnostics are confined to research settings and do not reach the patient or national control programmes. The current formats are not applicable to field conditions, and simplification, standardisation, and proper test evaluation in the target setting should be the main focus for future development. © 2010 Elsevier Ltd. All rights reserved. Source


Van Calster B.,Catholic University of Leuven | Vickers A.J.,Sloan Kettering Cancer Center
Medical Decision Making | Year: 2015

Decision-analytic measures to assess clinical utility of prediction models and diagnostic tests incorporate the relative clinical consequences of true and false positives without the need for external information such as monetary costs. Net Benefit is a commonly used metric that weights the relative consequences in terms of the risk threshold at which a patient would opt for treatment. Theoretical results demonstrate that clinical utility is affected by a model';s calibration, the extent to which estimated risks correspond to observed event rates. We analyzed the effects of different types of miscalibration on Net Benefit and investigated whether and under what circumstances miscalibration can make a model clinically harmful. Clinical harm is defined as a lower Net Benefit compared with classifying all patients as positive or negative by default. We used simulated data to investigate the effect of overestimation, underestimation, overfitting (estimated risks too extreme), and underfitting (estimated risks too close to baseline risk) on Net Benefit for different choices of the risk threshold. In accordance with theory, we observed that miscalibration always reduced Net Benefit. Harm was sometimes observed when models underestimated risk at a threshold below the event rate (as in underestimation and overfitting) or overestimated risk at a threshold above event rate (as in overestimation and overfitting). Underfitting never resulted in a harmful model. The impact of miscalibration decreased with increasing discrimination. Net Benefit was less sensitive to miscalibration for risk thresholds close to the event rate than for other thresholds. We illustrate these findings with examples from the literature and with a case study on testicular cancer diagnosis. Our findings strengthen the importance of obtaining calibrated risk models. © The Author(s) 2014. Source


Schoofs L.,Catholic University of Leuven
Advances in Experimental Medicine and Biology | Year: 2010

Drosophila melanogaster is since decades the most important invertebrate model. With the publishing of the genome sequence, Drosophila also became a pioneer in (neuro)peptide research. Neuropeptides represent a major group of signaling molecules that outnumber all other types of neurotransmitters/ modulators and hormones. By means of bioinformatics 119 (neuro)peptide precursor genes have been predicted from the Drosophila genome. Using the neuropeptidomics technology 46 neuropeptides derived from 19 of these precursors could be biochemically characterized. At the cellular level, neuropeptides usually exert their action by binding to membrane receptors, many of which belong to the family of G-protein coupled receptors or GPCRs. Such receptors are the major target for many contemporary drugs. In this chapter, we will describe the identification, localization and functional characterization of neuropeptide-receptor pairs in Drosophila melanogaster. © 2010 Landes Bioscience and Springer Science+Business Media. Source


Colinet H.,Catholic University of Leuven
Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology | Year: 2011

This study examined the impact of fluctuating thermal regimes (FTRs) on cold tolerance of the polyphagous beetle Alphitobius diaperinus. Daily pulses of elevated temperatures can provide breaks in chronic cold stress, potentially allowing for physiological recovery and improving survival. Perturbations in central metabolism appear to be a common physiological response in insects exposed to low temperatures. It has been suggested that energy supplies, which may be depleted during cold exposure, can be regenerated during the warming pulses of FTRs. This study tested the assumption that chronic cold stress may induce ATP depletion and that recovery during FTR warming pulses may allow re-establishment of ATP supplies. In this study, A. diaperinus were exposed to cold stress under different thermal regimes (constant or fluctuating). The results did not confirm the aforementioned assumption. No cold-induced ATP depletion was observed. The lowest ATP levels were repeatedly detected in the untreated controls. The data show that homoeostasis of ATP is lost when adults A. diaperinus are exposed to cold stress, whatever thermal regime (constant or fluctuating). ATP accumulation may be viewed as a symptom of a production/consumption imbalance under cold stress conditions. Periodic short (2-h) warming pulses clearly improved cold survival. Cellular homeostasis, however, probably requires a longer recovery period to be fully restored. © 2011 Elsevier Inc. Source


Farre R.,Catholic University of Leuven | Farre R.,CIBER ISCIII
Neurogastroenterology and Motility | Year: 2013

Background: Gastro-esophageal reflux disease (GERD) is very prevalent and has a high burden on health security system costs. Nevertheless, pathophysiology is complex and not well-understood. Several mechanisms have been proposed: decreased salivation, impaired esophageal clearance, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations (TLESRs), increased acid, and pepsin secretion, pyloric incompetence provoking duodeno-gastro-esophageal reflux of bile acids and trypsin. Independent of the relevance of each mechanism, the ultimate phenomenon is that mucosal epithelium is exposed for a longer time to agents as acid and pepsin or is in contact to luminal agents not commonly present in gastric refluxate as trypsin or bile acids. This leads to a visible damage of the epithelium (erosive esophagitis -EE) or impairing mucosal integrity without any sign of macroscopic alteration as occurs in non-erosive reflux disease (NERD). Luminal factors are not the only responsible for such impairment; more recent data indicate that endogenous factors may also play a role. Purpose: This review will update the most recent findings on the putative pathophysiological mechanisms and specially will focus on the role of esophageal mucosal integrity in GERD. Methodologies used for the evaluation of mucosal integrity, its relevance in EE and NERD, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed. Gastro-esophageal reflux disease (GERD) is very prevalent. Nevertheless, pathophysiology is complex and not well understood. Several mechanisms have been proposed but the ultimate phenomenon is that mucosal epithelium is most of the times abnormally exposed to luminal agents leading to an impaired mucosal integrity. Methodologies used for the evaluation of mucosal integrity, its relevance in erosive esophagitis and non-erosive reflux disease, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed. © 2013 John Wiley & Sons Ltd. Source


Glanzel W.,Catholic University of Leuven
Profesional de la Informacion | Year: 2012

This study gives an overview of the process of clustering scientific disciplines using hybrid methods, detecting and labelling emerging topics and analysing the results using bibliometrics methods. The hybrid clustering techniques are based on biblographic coupling and text-mining and 'core documents', and cross-citation links are used to identify emerging fields. The collaboration network of those countries that proved to be most active in the underlying disciplines, in combination with a set of standard indicators, form the groundwork for the bibliometric analysis of the detected emerging research topics. Source


Panieri E.,University of Turin | Santoro M.M.,Catholic University of Leuven
Cellular and Molecular Life Sciences | Year: 2015

The purpose of this review is to provide an overview of redox mechanisms, sources and antioxidants that control signaling events in ECs. In particular, we describe which molecules are involved in redox signaling and how they influence the relationship between ECs and other vascular component with regard to angiogenesis. Recent and new tools to investigate physiological ROS signaling will be also discussed. Such findings are providing an overview of the ROS biology relevant for endothelial cells in the context of normal and pathological angiogenic conditions. © 2015 Springer Basel. Source


Schoonheydt R.A.,Catholic University of Leuven
Applied Clay Science | Year: 2014

Clay minerals are layered materials that lend themselves naturally to film formation. In these films the clay mineral layers are oriented horizontally on the substrate. There are four techniques for film formation: (1) casting; (2) spin coating; (3) layer-by-layer assemblage; and (4) the Langmuir-Blodgett technique. The principles of each technique are described. When molecules are organized in the interlayer space of the clay minerals, the films carry a functionality and are called functional hybrid clay mineral films. These functionalities may be (1) sensing of adsorbed molecules; (2) nonlinear optical properties; (3) energy transfer; (4) electron transfer; and (5) magnetism. The expression of functionality depends on the functionality of a molecule, on the degree of organization of these molecules in the interlayer space and on the degree of organization of the clay mineral layers in the films. This is illustrated with examples from the literature for each of the 4 methods of film formation. © 2014 Elsevier B.V. Source


De Strooper B.,Center for the Biology of Disease | De Strooper B.,Catholic University of Leuven | De Strooper B.,University College London
Cell | Year: 2014

γ-Secretase proteases have been associated with pathology in Alzheimer disease (AD), but we are just beginning to understand their basic mechanisms and physiological roles. A negative drug trial with a broad spectrum γ-secretase inhibitor in AD patients has severely dampened enthusiasm for the potential of pursuing γ-secretase research therapeutically. This pessimism is unwarranted: analysis of available information presented here demonstrates significant confounds for interpreting the outcome of the trial and argues that the major lessons pertain to broad knowledge gaps that are imperative to fill. ©2014 Elsevier Inc. Source


Roga W.,Jagiellonian University | Fannes M.,Catholic University of Leuven | Zyczkowski K.,Jagiellonian University
Physical Review Letters | Year: 2010

The mutual information between the sender of a classical message encoded in quantum carriers and a receiver is fundamentally limited by the Holevo quantity. Using strong subadditivity of entropy, we prove that the Holevo quantity is not larger than an exchange entropy. This implies an upper bound for coherent information. Moreover, restricting our attention to classical information, we bound the transmission distance between probability distributions by their entropic distance, which is a concave function of their Hellinger distance. © 2010 The American Physical Society. Source


Pipeleers G.,Catholic University of Leuven | Moore K.L.,Colorado School of Mines
IEEE Transactions on Automatic Control | Year: 2012

When iterative learning control (ILC) is applied to improve a system's tracking performance, the trial-invariant reference input is typically known or contained in a prescribed set of signals. To account for this knowledge, we propose a novel ILC structure that only responds to a given set of trial-invariant inputs. The controllers are called reduced-order ILCs as their order is less than the discrete-time trial length. Exploiting all knowledge available on the input signals is instrumental in facing the fundamental performance limitations in ILC: an ILC is bound to amplify trial-varying inputs and reducing this trial-varying performance degradation invokes a slower learning transient. We present a novel optimal ILC design strategy that allows for a quantitative and systematic analysis of this tradeoff. The merit of reduced-order ILCs in view of this tradeoff is demonstrated by numerical results. © 2011 IEEE. Source


Xia C.,Nanjing University | Chen P.F.,Nanjing University | Keppens R.,Catholic University of Leuven
Astrophysical Journal Letters | Year: 2012

Starting from a realistically sheared magnetic arcade connecting the chromospheric, transition region to coronal plasma, we simulate the in situ formation and sustained growth of a quiescent prominence in the solar corona. Contrary to previous works, our model captures all phases of the prominence formation, including the loss of thermal equilibrium, its successive growth in height and width to macroscopic dimensions, and the gradual bending of the arched loops into dipped loops, as a result of the mass accumulation. Our 2.5 dimensional, fully thermodynamically and magnetohydrodynamically consistent model mimics the magnetic topology of normal-polarity prominences above a photospheric neutral line, and results in a curtain-like prominence above the neutral line through which the ultimately dipped magnetic field lines protrude at a finite angle. The formation results from concentrated heating in the chromosphere, followed by plasma evaporation and later rapid condensation in the corona due to thermal instability, as verified by linear instability criteria. Concentrated heating in the lower atmosphere evaporates plasma from below to accumulate at the top of coronal loops and supply mass to the later prominence constantly. This is the first evaporation-condensation model study where we can demonstrate how the formed prominence stays in a force balanced state, which can be compared to the Kippenhahn-Schlüter type magnetohydrostatic model, all in a finite low-beta corona. © 2012. The American Astronomical Society. All rights reserved.. Source


Lapenta G.,Catholic University of Leuven | Markidis S.,KTH Royal Institute of Technology | Goldman M.V.,University of Colorado at Boulder | Newman D.L.,University of Colorado at Boulder
Nature Physics | Year: 2015

The primary target of the Magnetospheric MultiScale (MMS) mission is the electron-scale diffusion layer around reconnection sites. Here we study where these regions are found in full three-dimensional simulations. In two dimensions the sites of electron diffusion, defined as the regions where magnetic topology changes and electrons move with respect to the magnetic field lines, are located near the reconnection site. But in three dimensions we find that the reconnection exhaust far from the primary reconnection site also becomes host to secondary reconnection sites. Four diagnostics are used to demonstrate the point: the direct observation of topology impossible without secondary reconnection, the direct measurement of topological field line breakage, the measurement of electron jets emerging from secondary reconnection regions, and the violation of the frozen-in condition. We conclude that secondary reconnection occurs in a large part of the exhaust, providing many more chances for MMS to find itself in the right region to hit its target. © 2015 Macmillan Publishers Limited. Source


Mccormick M.K.,Smithsonian Environmental Research Center | Jacquemyn H.,Catholic University of Leuven
New Phytologist | Year: 2014

Summary: The distribution and abundance of orchid populations depend on a suite of biological and ecological factors, including seed production and dispersal, availability of mycorrhizal fungi and appropriate environmental conditions, with the weighting of these factors depending on the spatial scale considered. Disentangling the factors determining successful orchid establishment represents a major challenge, involving seed germination experiments, molecular techniques and assessment of environmental conditions. Identification of fungi from large-scale surveys of mycorrhizal associations in a range of orchid species has shown that mycorrhizal fungi may be widespread and occur in varied habitats. Further, a meta-analysis of seed introduction experiments revealed similar seed germination in occupied and unoccupied habitat patches. Orchid rarity was also unrelated to mycorrhizal specificity. Nonetheless, seed germination within sites appears to depend on both biotic and abiotic conditions. In the few cases that have been examined, coexisting orchids have distinct mycorrhizal communities and show strong spatial segregation, suggesting that mycorrhizal fungi are important drivers of niche partitioning and contribute to orchid coexistence. A broader investigation of orchid mycorrhizal fungus distribution in the soil, coupled with fungus and recruitment mapping, is needed to translate fungal abundance to orchid population dynamics and may lead to better orchid conservation. © 2013 New Phytologist Trust. Source


de Wit J.,Center for the Biology of Disease | de Wit J.,Catholic University of Leuven | Ghosh A.,Roche Holding AG
Trends in Neurosciences | Year: 2014

The function of neural circuits depends on the precise connectivity between populations of neurons. Increasing evidence indicates that disruptions in excitatory or inhibitory synapse formation or function lead to excitation/inhibition (E/I) imbalances and contribute to neurodevelopmental and psychiatric disorders. Leucine-rich repeat (LRR)-containing surface proteins have emerged as key organizers of excitatory and inhibitory synapses. Distinct LRR proteins are expressed in different cell types and interact with key pre- and postsynaptic proteins. These protein interaction networks allow LRR proteins to coordinate pre- and postsynaptic elements during synapse formation and differentiation, pathway-specific synapse development, and synaptic plasticity. LRR proteins, therefore, play a critical role in organizing synaptic connections into functional neural circuits, and their dysfunction may contribute to neuropsychiatric disorders. © 2014 Elsevier Ltd. Source


Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. We investigated whether the anti-pre-cancer activities assigned to curcumin are mediated through an anti-oxidant and DNA-protecting mechanism. Patients with oral leukoplakia, oral submucous fibrosis or lichen planus, and healthy individuals (n = 25 for each group) aged 17-50 years were selected. Salivary and serum oxidative markers such as malonaldehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were measured just prior to the intake of curcumin, after one week of curcumin intake and following clinical cure of precancerous lesions. Serum and salivary vitamins C and E showed increases, while MDA and 8-OHdG levels showed decreases in patients with oral leukoplakia, submucous fibrosis and lichen planus after intake of curcumin for all categories of precancerous lesions. The changes in these values were observed to be statistically significant after clinical cure of the disease (P < 0.05). The five-point rating scale for pain, as well as lesion size in oral leukoplakia, submucous fibrosis and lichen planus, improved significantly (P < 0.05). In addition, in submucous fibrosis, mouth opening (P < 0.05) recovered significantly. In oral leukoplakia, submucous fibrosis and lichen planus, the levels of serum and salivary vitamins C and E increased significantly, while MDA and 8-OHdG levels decreased after 131(15), 211(17), and 191(18) days, respectively. Values for serum and salivary vitamins C and E showed a significant decrease in oral leukoplakia, submucous fibrosis and lichen planus, in contrast to healthy individuals, but increased significantly in all groups subsequent to curcumin administration after clinical cure of lesions. Based on these results, we can conclude that curcumin mediates its anti-pre-cancer activities by increasing levels of vitamins C and E, and preventing lipid peroxidation and DNA damage. Source


Rutgeerts P.J.,Catholic University of Leuven
Digestive Diseases | Year: 2011

At onset, Crohn's disease (CD) is characterized by transmural inflammation with mucosal ulcerations. In its earliest phase the lesions are mainly aphthous ulcers. The ulcers then become larger, a nodular pattern develops and penetration of the deep ulcers leads to fistulas and collagen deposition to fibrotic strictures. The best model to study the earliest lesions in CD is the postoperative recurrence situation where these early lesions recur within weeks to months after surgery. CD recurrence is triggered by the fecal contents of the gut since temporary diversion prevents the recurrence of bowel inflammation. With the development of newer techniques, such as microarray analysis of total mucosal gene expression and molecular analysis of gut content and mucosal microbiome, this model will allow to shed light on the earliest pathogenic features of CD. Copyright © 2011 S. Karger AG, Basel. Source


Wakai T.,University of Massachusetts Amherst | Vanderheyden V.,Catholic University of Leuven | Fissore R.A.,University of Massachusetts Amherst
Cold Spring Harbor Perspectives in Biology | Year: 2011

Changes in the intracellular concentration of calcium ([Ca2+]i) represent a vital signaling mechanism enabling communication among cells and between cells and the environment. The initiation of embryo development depends on a [Ca2+]i increase(s) in the egg, which is generally induced during fertilization. The [Ca2+]i increase signals egg activation, which is the first stage in embryo development, and that consist of biochemical and structural changes that transform eggs into zygotes. The spatiotemporal patterns of [Ca2+]i at fertilization show variability, most likely reflecting adaptations to fertilizing conditions and to the duration of embryonic cell cycles. In mammals, the focus of this review, the fertilization [Ca2+]i signal displays unique properties in that it is initiated after gamete fusion by release of a sperm-derived factor and by periodic and extended [Ca2+]i responses. Here, we will discuss the events of egg activation regulated by increases in [Ca2+]i, the possible downstream targets that effect these egg activation events, and the property and identity of molecules both in sperm and eggs that underpin the initiation and persistence of the [Ca2+]i responses in these species. © 2011 Cold Spring Harbor Laboratory Press. Source


Schroeder M.C.,Baylor College of Medicine | Halder G.,Baylor College of Medicine | Halder G.,University of Houston | Halder G.,Catholic University of Leuven
Seminars in Cell and Developmental Biology | Year: 2012

The Hippo signaling pathway is an evolutionarily conserved mediator of growth control, cell fate decisions and stem cell identity. At the heart of the pathway is a kinase cascade that is reminiscent of other signaling pathways, but recent studies indicate that the Hippo pathway is unique in that it is regulated by cellular architecture and the mechanical properties of the environment. The Hippo pathway may thus serve as a sensor of tissue structure and mechanical tension, integrating information regarding the size and shape of an organ into cellular behavior, such as whether or not to proliferate. In this review we summarize recent discoveries regarding the regulation of the Hippo pathway by cellular polarity, cell junctions, and the cytoskeleton and discuss how these data inform the study of development and disease. © 2012 Elsevier Ltd. Source


Aerts S.,Catholic University of Leuven
Current Topics in Developmental Biology | Year: 2012

Transcription factors (TFs) are key proteins that decode the information in our genome to express a precise and unique set of proteins and RNA molecules in each cell type in our body. These factors play a pivotal role in all biological processes, including the determination of a cell's fate during development and the maintenance of a cell's physiological function. To achieve this, a TF binds to specific DNA sequences in the noncoding part of the genome, recruits chromatin modifiers and cofactors, and directs the transcription initiation rate of its "target genes." Therefore, a key challenge in deciphering a transcriptional switch is to identify the direct target genes of the master regulators that control the switch, the cis-regulatory elements implementing (auto-)regulatory loops, and the target genes of all the TFs in the downstream regulatory network. A better knowledge of a TF's targetome during specification and differentiation of a particular cell type will generate mechanistic insight into its developmental program. Here, I review computational strategies and methods to predict transcriptional targets by genome-wide searches for TF binding sites using position weight matrices, motif clusters, phylogenetic footprinting, chromatin binding and accessibility data, enhancer classification, motif enrichment, and gene expression signatures. © 2012 Elsevier Inc. Source


Wagemans J.,Catholic University of Leuven
i-Perception | Year: 2011

Experimental psycho-aesthetics-the science aimed at understanding the factors that determine aesthetic experience-is reviewed briefly as background to describe the Parallellepipeda project, a cross-over project between artists and scientists in Leuven. In particular, I sketch how it started and developed further, with close interactions between the participating artists and scientists. A few examples of specific research projects are mentioned to illustrate the kind of research questions we address and the methodological approach we have taken. We often found an effect of providing participants with additional information, a difference between novice and expert participants, and a shift with increasing experience with an artwork, in the direction of tolerating more complexity and acquiring more order from it. By establishing more connections between parts of an artwork and more associations to the artwork, it becomes a stronger Gestalt, which is more easily mastered by the viewer and leads to increased appreciation. In the final part of the paper, I extract some general lessons from the project regarding a possible new way of doing psycho-aesthetics research, which is able to solve some of the problems of traditional experimental psycho-aesthetics (eg, trade-off between experimental control and ecological validity). © 2011 J Wagemans. Source


Gmeiner F.,Nikhef | Honecker G.,Catholic University of Leuven
Nuclear Physics B | Year: 2010

We perform a complete analysis of one-loop threshold corrections to the gauge couplings of fractional D6-branes. This includes besides SU (N) also symplectic, orthogonal and massless Abelian gauge factors and the full computation of contributions from discrete and continuous Wilson lines and brane displacements. Two classes of globally consistent supersymmetric compactifications with Standard Model spectra on T6 / Z6 and T6 / Z6 ′ are presented in detail with the latter exhibiting the potential of supersymmetry breaking via a hidden sector gaugino condensate. The T6 / Z6 ′ Standard Models are completely classified, and it turns out that out of 768 distinct D6-brane configurations only 16 different sets of massless spectra and ten distinct values of gauge couplings at one-loop arise. The gauge threshold corrections enhance the diversity to 196 nonequivalent models. © 2009 Elsevier B.V. All rights reserved. Source


Peeters T.L.,Catholic University of Leuven
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2015

Purpose of Review: To summarize the recent findings. Recent Findings: Studies of changes in the plasma levels confirm the earlier concepts, but offer little proof of causal effect. It is increasingly realized that peptides produced in the gut have a paracrine role or an indirect effect via the gut-brain axis. Interest in prokinetic peptide agonists remains high despite the failure of two candidate drugs, but relamorelin and camicinal offer new hope. Summary: We review the original studies published since January 2013 on peptides produced in the gut and with an effect on gastrointestinal motility. © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source


Sansen W.,Catholic University of Leuven
Digest of Technical Papers - IEEE International Solid-State Circuits Conference | Year: 2015

The most important application of ICs, today, is most probably the lnternet-of-Things. It involves sensor nodes and communications at the lowest-possible power levels. Similar low power levels are required for the next-generation smart-phones as images and video become increasing requirements, in phone, body-worn, and automotive applications. Whatever technology is used, portability requires reduced power consumption. © 2015 IEEE. Source


Ca2+ is the most omnipresent pollutant on earth, in higher concentrations a real threat to all living cells. When [Ca2+]i rises above 100nM (=resting level), excess Ca2+ needs to be confined in the SER and mitochondria, or extruded by the different Ca2+-ATPases. The evolutionary origin of eggs and sperm cells has a crucial, yet often overlooked link with Ca2+-homeostasis. Because there is no goal whatsoever in evolution, gametes did neither originate "with the purpose" of generating a progeny nor of increasing fitness by introducing meiosis. The explanation may simply be that females "invented the trick" to extrude eggs from their body as an escape strategy for getting rid of toxic excess Ca2+ resulting from a sex-hormone driven increased influx into particular cells and tissues. The production of Ca2+-rich milk, seminal fluid in males and all secreted proteins by eukaryotic cells may be similarly explained. This view necessitates an upgrade of the role of the RER-Golgi system in extruding Ca2+. In the context of insect metamorphosis, it has recently been (re)discovered that (some isoforms of) Ca2+-ATPases act as membrane receptors for some types of lipophilic ligands, in particular for endogenous farnesol-like sesquiterpenoids (FLS) and, perhaps, for some steroid hormones as well. A novel paradigm, tentatively named "Calcigender" emerges. Its essence is: gender-specific physiotypes ensue from differential Ca2+-homeostasis enabled by genetic differences, farnesol/FLS and sex hormones. Apparently the body of reproducing females gets temporarily more poisoned by Ca2+ than the male one, a selective benefit rather than a disadvantage. © 2014 The Authors. Source


Van Houdt R.,Belgian Nuclear Research Center | Michiels C.W.,Catholic University of Leuven
Journal of Applied Microbiology | Year: 2010

The ability of many bacteria to adhere to surfaces and to form biofilms has major implications in a variety of industries including the food industry, where biofilms create a persistent source of contamination. The formation of a biofilm is determined not only by the nature of the attachment surface, but also by the characteristics of the bacterial cell and by environmental factors. This review focuses on the features of the bacterial cell surface such as flagella, surface appendages and polysaccharides that play a role in this process, in particular for bacteria linked to food-processing environments. In addition, some aspects of the attachment surface, biofilm control and eradication will be highlighted. © 2010 The Society for Applied Microbiology. Source


Hagemeijer A.,Catholic University of Leuven | Graux C.,University Hospital
Genes Chromosomes and Cancer | Year: 2010

T-cell acute lymphoblastic leukemia (T-ALL) is the result of multiple oncogenic insults of thymocytes. Recently, new ABL1 fusion genes have been identified that provide proliferation and survival advantage to lymphoblasts. These are the NUP214-ABL1 fusion gene, on amplified episomes, the unique case of EML1-ABL1 fusion due to a cryptic t(9;14)(q34;q32) and the seldom reported BCR-ABL1 and ETV6-ABL1 chimeric genes. The most frequent and strictly associated with T-ALL is the NUP214-ABL1 fusion identified in 6% of cases, in both children and adults. Patients present with classical T-ALL features. Cytogenetically, the fusion is cryptic but seen by FISH on amplified episomes or more rarely as a small hsr. The ABL1 fusion is a late event associated with other genetic alterations like NOTCH1 activating mutation, deletion of CDKN2A locus, and ectopic expression of TLX1 or TLX3. The mechanism of activation of the NUP214-ABL1 protein is unique and requires localization at the nucleopore complex and interaction with other nuclear pore proteins for crossphosphorylation and constitutive kinase activity. The ABL1 fusion proteins are sensitive to tyrosine kinase inhibitors, which can be included in future treatment strategy. © 2010 Wiley-Liss, Inc. Source


Hertog T.,Catholic University of Leuven
Journal of Cosmology and Astroparticle Physics | Year: 2014

The quantum state of the universe combined with the structure of the landscape potential implies a prior that specifies predictions for observations. We compute the prior for CMB related observables given by the no-boundary wave function (NBWF) in a landscape model that includes a range of inflationary patches representative of relatively simple single-field models. In this landscape the NBWF predicts our classical cosmological background emerges from a region of eternal inflation associated with a plateau-like potential. The spectra of primordial fluctuations on observable scales are characteristic of concave potentials, in excellent agreement with the Planck data. By contrast, alternative theories of initial conditions that strongly favor inflation at high values of the potential are disfavored by observations in this landscape. Source


Gommes C.J.,University of Liege | Gommes C.J.,Catholic University of Leuven
Journal of Applied Crystallography | Year: 2013

Small-angle scattering of X-rays (SAXS) or neutrons is one of the few experimental methods currently available for the in situ analysis of phenomena in mesoporous materials at the mesoscopic scale. In the case of disordered mesoporous materials, however, the main difficulty of the method lies in the data analysis. A stochastic model is presented, which enables one to reconstruct the three-dimensional nanostructure of liquids confined in disordered mesopores starting from small-angle scattering data. This so-called plurigaussian model is a multi-phase generalization of clipped Gaussian random field models. Its potential is illustrated through the synchrotron SAXS analysis of a gel permeated with a critical nitrobenzene/hexane solution that is progressively cooled below its consolute temperature. The reconstruction brings to light a wetting transition whereby the nanostructure of the pore-filling liquids passes from wetting layers that uniformly cover the solid phase of the gel to plugs that locally occlude the pores. Using the plurigaussian model, the dewetting phenomenon is analyzed quantitatively at the nanometre scale in terms of changing specific interface areas, contact angle and specific length of the triple line. Copyright © International Union of Crystallography 2013. Source


Mestdagh A.,Center for Care Research and Consultancy | Hansen B.,Catholic University of Leuven
Social Psychiatry and Psychiatric Epidemiology | Year: 2014

Purpose: The aim of this review is to identify consistent themes among the qualitative literature on stigma as experienced by patients with schizophrenia receiving community mental health care. With the treatment focus of schizophrenia nowadays shifting more and more towards community-based mental health care, professionals need to be aware of the increased vulnerability of their clients in their social environment as a result of stigma towards their disease. In-depth knowledge on stigma is critical in order to offer a dignifying community mental health care. Methods: A systematic search of the qualitative literature in Web of Science, PubMed, PsycINFO and Francis was performed to review the subjective experiences and ideas on stigma in outpatients with schizophrenia. Results: Three major themes were identified in 18 studies and need to be taken into consideration when implementing an adequate community mental health care: (i) the continuing existence of stigma inherent in the health care setting, (ii) the importance of relational aspects of stigma encounters in daily life and (iii) the significance of the behavioural aspects related to previous stigma experiences and beliefs among patients. Conclusions: Despite much effort in community treatment, patients still experience stigma and discrimination. Community mental health care professionals should not only be aware of structural problems in mental health care, but should also pay considerable attention towards the relational and behavioural aspects in their clients' life concerning stigma. Furthermore, they have the crucial role in the community to raise awareness about stigma in order to increase their clients' acceptance in society. © 2013 Springer-Verlag Berlin Heidelberg. Source


Simoens S.,Catholic University of Leuven
Expert Review of Pharmacoeconomics and Outcomes Research | Year: 2014

As part of a health technology assessment, economic evaluation of health technologies for rare diseases poses specific challenges given that such technologies are rarely cost-effective. Therefore, conventional economic evaluation techniques appear to be less relevant to health technologies for rare diseases. However, the definition of health technology assessment points to multi-criteria decision analysis by stating that a health technology needs to be assessed against multiple criteria in order to pronounce a judgement about the value of the health technology. Thus, this editorial argues that a full health technology assessment which uses a multi-criteria decision analysis framework to evaluate the value of a technology can be applied to health technologies for rare diseases. Past experiences demonstrate that the specific characteristics of health technologies for rare diseases can fit in the conventional health technology assessment paradigm by means of multi-criteria decision analysis. © 2014 Informa UK, Ltd. Source


Devreese K.,Ghent University | Hoylaerts M.F.,Catholic University of Leuven
Clinical Chemistry | Year: 2010

BACKGROUND: The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. Its diagnosis is based on clinical and laboratory criteria, defined by strict guidelines. The original clinical and laboratory criteria for the identification of APS patients were published in 1999, in the so-called Sapporo criteria. In 2006 these criteria were revised, and recently more precise guidelines for analysis of the lupus anticoagulant have been provided. However, several questions related to the diagnosis of APS remain unanswered. CONTENT: In addition to providing a historical perspective, this review covers several challenges in the diagnosis of APS with respect to clinical and laboratory features, while highlighting pathogenic pathways of the syndrome. We discuss ongoing dilemmas in the diagnosis of this complex disease. Although antiphospholipid antibodies are found in association with various clinical manifestations, the older established clinical criteria were not substantively altered in the 2006 update. Several laboratory tests recommended in the latest criteria, including phospholipid-dependent coagulation tests for the detection of the lupus anticoagulant and ELISAs for measuring anticardiolipin and β2-glycoprotein I antibodies, still show methodological and diagnostic shortcomings. In addition, antiphospholipid antibodies have been described against other antigens, but their clinical role remains uncertain. CONCLUSIONS: Despite updated APS criteria, diagnosis of this syndrome remains challenging. Further research on clinically relevant antibodies and standardization of their detection are needed to improve clinical risk assessment in APS. © 2010 American Association for Clinical Chemistry. Source


Aupers S.,Catholic University of Leuven
Public Understanding of Science | Year: 2015

Conspiracy theories are immensely popular today, yet in the social sciences they are often dismissed as “irrational,” “bad science,” or “religious belief.” In this study, we take a cultural sociological approach and argue that this persistent disqualification is a form of “boundary work” that obscures rather than clarifies how and why conspiracy theorists challenge the epistemic authority of science. Based on a qualitative study of the Dutch conspiracy milieu, we distinguish three critiques that are motivated by encounters with scientific experts in everyday life: the alleged dogmatism of modern science, the intimate relation of scientific knowledge production with vested interests, and the exclusion of lay knowledge by scientific experts forming a global “power elite.” Given their critique that resonates with social scientific understandings of science, it is concluded that conspiracy theorists compete with (social) scientists in complex battles for epistemic authority in a broader field of knowledge contestation. © The Author(s) 2014 Source


Afanas'ev V.V.,Catholic University of Leuven
Advances in Condensed Matter Physics | Year: 2014

Evolution of the electron energy band alignment at interfaces between different semiconductors and wide-gap oxide insulators is examined using the internal photoemission spectroscopy, which is based on observations of optically-induced electron (or hole) transitions across the semiconductor/ insulator barrier. Interfaces of various semiconductors ranging from the conventional silicon to the high-mobility Ge-based (Ge, Si1-xGex, Ge1-xSnx) and AIIIBV group (GaAs, InxGa1-xAs, InAs, GaP, InP, GaSb, InSb) materials were studied revealing several general trends in the evolution of band offsets. It is found that in the oxides of metals with cation radii larger than ≈0.7 Å, the oxide valence band top remains nearly at the same energy (±0.2 eV) irrespective of the cation sort. Using this result, it becomes possible to predict the interface band alignment between oxides and semiconductors as well as between dissimilar insulating oxides on the basis of the oxide bandgap width which are also affected by crystallization. By contrast, oxides of light elements, for example, Be, Mg, Al, Si, and Sc exhibit significant shifts of the valence band top. General trends in band lineup variations caused by a change in the composition of semiconductor photoemission material are also revealed. © 2014 Valeri V. Afanas'ev. Source


Maoz D.,Tel Aviv University | Mannucci F.,National institute for astrophysics | Nelemans G.,Radboud University Nijmegen | Nelemans G.,Catholic University of Leuven
Annual Review of Astronomy and Astrophysics | Year: 2014

Type Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and end points of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a nondegenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of SN Ia sites pre- and postexplosion from analysis of the explosions themselves and from the measurement of event rates. The recent nearby and well-studied event, SN 2011fe, has been particularly revealing. The observational results are not yet conclusive and sometimes prone to competing theoretical interpretations. Nevertheless, it appears that DD progenitors, long considered the underdog option, could be behind some, if not all, SNe Ia. We point to some directions that may lead to future progress. Copyright © 2014 by Annual Reviews. Source


Vandereycken W.,Catholic University of Leuven
European Eating Disorders Review | Year: 2011

Eating disorders belong to the broad category of self-harming behaviours which may be acquired in a social learning process of imitation, identification and competition. Hence, we should question the possible dangers or unwanted side-effects in treating patients together within a common therapeutic setting. But little is known about the frequency and extent of possibly negative influences of treatment in a group format, the so-called risk of 'peer contagion' in group therapy and/or inpatient treatment. We review in this paper the rather scarce literature on this subject in order to stimulate more critical thinking and systematic research. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association. Source


Reynaert P.,Catholic University of Leuven
IEEE Microwave Magazine | Year: 2011

Integration is the key for reducing the cost of electronic circuits. Just like any other circuit, radio frequency (RF) circuits also obey this law. The feasibility of integrating voltage-controlled oscillator (VCO), low-noise amplifiers (LNAs), transmitters, and receivers in complimentary metal-oxide-semiconductor (CMOS) is obvious when looking at publications and state-of-the-art wireless products. Integrating an RF power amplifier (PA) in CMOS is less obvious. This is no surprise; the low supply voltage of CMOS contradicts with high output power, and the rather larger input and output capacitances of CMOS contradict with high gain. But CMOS has one major advantage compared to any other technology: one can integrate a lot of transistors and easily increase complexity. One should recognize and use this strength when aiming for integrated CMOS PAs. © 2011 IEEE. Source


Degens H.,Manchester Metropolitan University | Gayan-Ramirez G.,Catholic University of Leuven | Van Hees H.W.H.,Radboud University Nijmegen
American Journal of Respiratory and Critical Care Medicine | Year: 2015

Smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). Patients with COPD commonly suffer from skeletal muscle dysfunction, and it has been suggested that cigarette smoke exposure contributes to the development of skeletal muscle dysfunction even before overt pulmonary pathology. This review summarizes the evidence that muscles of nonsymptomatic smokers are weaker and less fatigue resistant than those of nonsmokers. Although physical inactivity of many smokers contributes to some alterations observed in skeletal muscle, exposure to cigarette smoke per se can also induce skeletal muscle dysfunction. Cigarette smoke constituents and systemic inflammatory mediators enhance proteolysis and inhibit protein synthesis, leading to loss of muscle mass. Reduced skeletal muscle contractile endurance in smokers may result from impaired oxygen delivery to the mitochondria and ability of the mitochondria to generate ATP due to interaction of carbon monoxide with hemoglobin, myoglobin, and components of the respiratory chain. Besides hampering contractile function, smoking may have immediate beneficial effects on motor skills, which are attributable to nicotine. In contrast to pulmonary pathology, many of the effects of smoking on skeletal muscle are most likely reversible by smoking cessation. Copyright © 2015 by the American Thoracic Society. Source


van Gool S.,Catholic University of Leuven
Immunotherapy | Year: 2013

Evaluation of: Lasky JL 3rd, Panosyan EH, Plant A et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas. Anticancer Res. 33, 2047-2056 (2013). Immunotherapy for children and adults with high-grade glioma (HGG) is an emerging innovative treatment approach, which aims at stimulating the body's own immune system against HGG by using autologous dendritic cells pulsed with autologous tumor lysate as a therapeutic vaccine. This is the third report on immunotherapy for HGG in children, bringing additional knowledge and experience to the scientific community. However, at the same time, this and other manuscripts urge for the next step in treatment development. Source


Husson S.J.,Catholic University of Leuven
WormBook : the online review of C. elegans biology | Year: 2012

C. elegans is used extensively as a model system in the neurosciences due to its well defined nervous system. However, the seeming simplicity of this nervous system in anatomical structure and neuronal connectivity, at least compared to higher animals, underlies a rich diversity of behaviors. The usefulness of the worm in genome-wide mutagenesis or RNAi screens, where thousands of strains are assessed for phenotype, emphasizes the need for computational methods for automated parameterization of generated behaviors. In addition, behaviors can be modulated upon external cues like temperature, O(subscript)2(/subscript) and CO(subscript)2(/subscript) concentrations, mechanosensory and chemosensory inputs. Different machine vision tools have been developed to aid researchers in their efforts to inventory and characterize defined behavioral "outputs". Here we aim at providing an overview of different worm-tracking packages or video analysis tools designed to quantify different aspects of locomotion such as the occurrence of directional changes (turns, omega bends), curvature of the sinusoidal shape (amplitude, body bend angles) and velocity (speed, backward or forward movement). Source


Hendrickx S.,Catholic University of Leuven
Molecular Psychiatry | Year: 2015

In 1998, we proposed deep brain stimulation as a last-resort treatment option for patients suffering from severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, 24 OCD patients were included in a long-term follow-up study to evaluate the effects of electrical stimulation in the anterior limbs of the internal capsule (ALIC) and bed nucleus of the stria terminalis (BST). We find that electrical stimulation in the ALIC/BST area is safe and significantly decreases obsessions, compulsions, and associated anxiety and depressive symptoms, and improves global functioning in a blinded crossover trial (n=17), after 4 years (n=18), and at last follow-up (up to 171 months, n=24). Moreover, our data indicate that BST may be a better stimulation target compared with ALIC to alleviate OCD symptoms. We conclude that electrical stimulation in BST is a promising therapeutic option for otherwise treatment-resistant OCD patients.Molecular Psychiatry advance online publication, 25 August 2015; doi:10.1038/mp.2015.124. © 2015 Macmillan Publishers Limited Source


Boeckxstaens G.E.,Catholic University of Leuven
Best Practice and Research: Clinical Gastroenterology | Year: 2010

The gastro-oesophageal junction is a specialised segment of the gut designed to prevent reflux of gastric contents into the oesophagus. This task is fulfilled by two structures, i.e. the lower oesophageal sphincter and the crural diaphragm, which generate a high pressure zone. Especially during low pressure at the junction, as in case of long-lasting transient lower oesophageal sphincter relaxations, reflux can occur but mainly if a positive pressure gradient exists between stomach and the oesphagogastric junction. Although patients with gastro-oesophageal reflux disease have increased oesophageal acid exposure compared to controls, the number of transient relaxations is not increased compared to healthy controls. Instead, the risk to have acid reflux is at least doubled in patients, especially in those with a hiatal hernia, most likely as a result of the supradiaphragmatic position of the acid pocket. In hiatal hernia patients, the acid pocket is indeed often trapped in the hernia above the diaphragm. Which factors exactly determine the physical composition (liquid or gas) and the proximal extent of the refluxate however requires further research. © 2010 Elsevier Ltd. All rights reserved. Source


van Aelst L.N.L.,Catholic University of Leuven
Circulation Research | Year: 2014

METHODS AND RESULTS:: OGN expression is associated with collagen deposition and scar formation in mouse and human MI. Absence of OGN in mice resulted in significantly increased rupture-related mortality with tissue disruption, intramyocardial bleeding and increased cardiac dysfunction, despite equal infarct sizes. Surviving OGN null mice had greater infarct expansion in comparison to WT mice due to impaired collagen fibrillogenesis and maturation in the infarcts as revealed by electron microscopy and collagen polarization. Absence of OGN did not affect cardiomyocyte hypertrophy in the remodeling remote myocardium. In cultured fibroblasts, OGN knockdown or supplementation did not alter TGF-ß signaling. Adenoviral overexpression of OGN in WT mice significantly improved collagen quality, thereby blunting cardiac dilatation and dysfunction following MI. In OGN null mice, adenoviral overexpression of OGN was unable to prevent rupture-related mortality due to insufficiently restoring OGN protein levels in the heart. Finally, circulating OGN levels in heart failure patients were significantly increased in the patients with a previous history of myocardial infarction compared to those with non-ischemic heart failure and correlated with survival, left ventricular volumes and other markers of fibrosis.RATIONALE:: To maintain cardiac mechanical and structural integrity after an ischemic insult, profound alterations occur within the extracellular matrix. Osteoglycin (OGN) is a small leucine-rich proteoglycan previously described as a marker of cardiac hypertrophy.OBJECTIVE:: To establish whether OGN may play a role in cardiac integrity and function after myocardial infarction (MI).CONCLUSIONS:: Increased OGN expression in the infarct scar promotes proper collagen maturation and protects against cardiac disruption and adverse remodeling following MI. In human heart failure, OGN is a promising biomarker for ischemic heart failure. © 2014 American Heart Association, Inc. Source


Van Den Berghe G.,Catholic University of Leuven
Nature Reviews Endocrinology | Year: 2012

Hyperglycaemia during critical illness unequivocally correlates with adverse outcome. Three proof-of-concept randomized controlled trials have shown that preventing hyperglycaemia in patients admitted to the intensive care unit (ICU) reduces organ failure and mortality. A subsequent multicentre, randomized controlled trial found that targeting normoglycaemia in this patient population does not affect organ function differently than targeting an intermediate glucose level (7.8-10.0 mmol/l). However, an intermediate glucose target evoked less hypoglycaemia and, for currently unexplained reasons, also fewer deaths than a normoglycaemic target. Moreover, tolerating a caloric deficit, rather than providing nutrients parenterally, accelerated recovery from critical illness in the presence of normoglycaemia. Whether macronutrient restriction renders moderate hyperglycaemia less harmful remains to be investigated. Hence, if adequate monitoring tools and expertise are available, normoglycaemia remains the only proven effective target for insulin treatment of hyperglycaemia in ICU patients. However, if these conditions are not fulfilled in clinical practice, is an intermediate target range preferable? In the absence of hard evidence, common sense supports such an intermediate blood glucose target. © 2012 Macmillan Publishers Limited. All rights reserved. Source


Hannelien V.,Rega Institute for Medical Research | Karel G.,Catholic University of Leuven | Jo V.D.,Rega Institute for Medical Research | Sofie S.,Rega Institute for Medical Research
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2012

Chronic inflammation may increase the risk to develop cancer, for instance esophagitis or gastritis may lead to development of esophageal or gastric cancer, respectively. The key molecules attracting leukocytes to local inflammatory sites are chemokines. We here provide a systematic review on the impact of CXC chemokines (binding the receptors CXCR1, CXCR2, CXCR3 and CXCR4) on the transition of chronic inflammation in the upper gastrointestinal tract to neoplasia. CXCR2 ligands, including GRO-α,β,γ/CXCL1,2,3, ENA-78/CXCL5 and IL-8/CXCL8 chemoattract pro-tumoral neutrophils. In addition, angiogenic CXCR2 ligands stimulate the formation of new blood vessels, facilitating tumor progression. The CXCR4 ligand SDF-1/CXCL12 also promotes tumor development by stimulating angiogenesis and by favoring metastasis of CXCR4-positive tumor cells to distant organs producing SDF-1/CXCL12. Furthermore, these angiogenic chemokines also directly enhance tumor cell survival and proliferation. In contrast, the CXCR3 ligands Mig/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 are angiostatic and attract anti-tumoral T lymphocytes and may therefore mediate tumor growth retardation and regression. Thus, chemokines exert diverging, sometimes dual roles in tumor biology as described for esophageal and gastric cancer. Therefore extensive research is needed to completely unravel the complex chemokine code in specific cancers. Possibly, chemokine-targeted cancer therapy will have to be adapted to the individual's chemokine profile. © 2011 Elsevier B.V. Source


Albertsen P.C.,University of Connecticut Health Center | Klotz L.,University of Toronto | Tombal B.,Catholic University of Leuven | Grady J.,University of Connecticut Health Center | And 2 more authors.
European Urology | Year: 2014

Background Androgen deprivation therapy (ADT) is associated with increased cardiovascular morbidity. Objective To determine whether cardiovascular morbidity differs following initiation of gonadotropin-releasing hormone (GnRH) agonists compared with an antagonist. Design, setting, and participants Pooled data from six phase 3 prospective randomized trials that recruited 2328 men between 2005 and 2012 to compare the efficacy of GnRH agonists against an antagonist. Men recruited had pathologically confirmed prostate cancer, an Eastern Cooperative Oncology Group score <2, a minimum life expectancy of 12 mo, and were naïve to ADT. Men were excluded if they had a prolonged baseline QT/corrected QT interval, other risk factors for heart failure, hypokalemia or a family history of long QT syndrome, or had another cancer diagnosed within 5 yr. Intervention Men were randomized to receive a GnRH agonist or an antagonist for either 3-7 mo (n = 642) or 12 mo (n = 1686). Treatment groups were balanced for common baseline characteristics. Outcome measurements and statistical analysis Event analysis was based on death from any cause or cardiac events. Data documenting adverse experiences were classified based on the Medical Dictionary for Regulatory Activities. The following conditions defined a cardiac event: arterial embolic or thrombotic events, hemorrhagic or ischemic cerebrovascular conditions, myocardial infarction, and other ischemic heart disease. Kaplan-Meier curves and log-rank tests were used to compare time to a cardiovascular event or death. Results and limitations Among men with preexisting cardiovascular disease, the risk of cardiac events within 1 yr of initiating therapy was significantly lower among men treated with a GnRH antagonist compared with GnRH agonists (hazard ratio: 0.44; 95% confidence interval, 0.26-0.74; p = 0.002). Since our analysis is post hoc, our findings should only be interpreted as hypothesis generating. Conclusions GnRH antagonists appear to halve the number of cardiac events experienced by men with preexisting cardiovascular disease during the first year of ADT when compared to GnRH agonists. © 2013 European Association of Urology. Source


To compare the subgingival microbiota around two differently designed implant systems that were in function for more than 12 years in a randomised split-mouth study design, and to compare the outcome with natural dentition. A total of 18 partially edentulous patients received at least two TiOblast™ (Astra Tech) and two Brånemark (Nobel Biocare) implants following a split-mouth design. At the last follow-up visit, periodontal parameters (probing depth, bleeding on probing and plaque) were recorded and intraoral radiographs were taken to calculate bone loss. Subgingival plaque samples were collected for culture, qPCR and checkerboard DNA-DNA hybridisation analysis. These data were related to implant design and bone loss. This study setup allowed a comparison of 34 Astra Tech (Impl A) with 32 Brånemark (Impl B) implants. During the 12-year follow up, five patients dropped out. One Brånemark implant was lost before abutment connection in a dropout patient. Mean bone loss between loading and year 12 was 0.7 mm (range: -0.8-5.8) (Impl A), and 0.4 mm (range: -1.1-4.1) (Impl B). No significant microbiological differences (qualitative and quantitative) could be observed between both implant types. Compared to teeth, subgingival plaque samples from implants did not reach the concentration of pathogens, even after 12 years of function. These data show that both implant systems (with differences in macro-design and surface characteristics), in patients with good oral hygiene and a stable periodontal condition, can maintain a successful treatment outcome without significant subgingival microbiological differences after 12 years of loading. The presence of periodontopathogens did not necessarily result in bone loss. Source


Rial A.,Catholic University of Leuven | Danezis G.,Microsoft
Proceedings of the ACM Conference on Computer and Communications Security | Year: 2011

Smart grid proposals threaten user privacy by potentially disclosing fine-grained consumption data to utility providers, primarily for time-of-use billing, but also for profiling, settlement, forecasting, tariff and energy efficiency advice. We propose a privacy-preserving protocol for general calculations on fine-grained meter readings, while keeping the use of tamper evident meters to a strict minimum. We allow users to perform and prove the correctness of computations based on readings on their own devices, without disclosing any fine grained consumption. Applying the protocols to time-of-use billing is particularly simple and efficient, but we also support a wider variety of tariff policies. Cryptographic proofs and multiple implementations are used to show the proposed protocols are secure and efficient. © 2011 ACM. Source


Vandecaetsbeek I.,Catholic University of Leuven
Cold Spring Harbor perspectives in biology | Year: 2011

The various splice variants of the three SERCA- and the two SPCA-pump genes in higher vertebrates encode P-type ATPases of the P(2A) group found respectively in the membranes of the endoplasmic reticulum and the secretory pathway. Of these, SERCA2b and SPCA1a represent the housekeeping isoforms. The SERCA2b form is characterized by a luminal carboxy terminus imposing a higher affinity for cytosolic Ca(2+) compared to the other SERCAs. This is mediated by intramembrane and luminal interactions of this extension with the pump. Other known affinity modulators like phospholamban and sarcolipin decrease the affinity for Ca(2+). The number of proteins reported to interact with SERCA is rapidly growing. Here, we limit the discussion to those for which the interaction site with the ATPase is specified: HAX-1, calumenin, histidine-rich Ca(2+)-binding protein, and indirectly calreticulin, calnexin, and ERp57. The role of the phylogenetically older and structurally simpler SPCAs as transporters of Ca(2+), but also of Mn(2+), is also addressed. Source


Cornelis F.M.,Catholic University of Leuven
Discovery medicine | Year: 2011

Osteoarthritis is the most common chronic musculoskeletal disorder. Although osteoarthritis is a multifactorial disease, it is known to have a significant genetic contribution. Identified genes so far, contributing to the prevalence and progression of the disease, belong to signaling pathways such as the bone morphogenetic protein and the wingless-type signaling families. These pathways are important during development and appear to be reactivated in postnatal joint homeostasis and repair. Among the most consistently associated genes, so far, are GDF5 and FRZB, which were both originally identified from a chondrogenic extract of articular cartilage. We focus on the functional aspects of these susceptibility genes and summarize recent evidence, obtained in specific animal models, for their possible roles in osteoarthritis. These data support the view that all tissues within the joint may contribute to osteoarthritis and that pathways important in skeletal development are also involved in the disease processes thereby presenting attractive therapeutic targets. Source


Schmidbaur H.,TU Munich | Schmidbaur H.,King Abdulaziz University | Raubenheimer H.G.,Stellenbosch University | Dobrzanska L.,Catholic University of Leuven
Chemical Society Reviews | Year: 2014

In the first part of this review, the characteristics of Au-H bonds in gold hydrides are reviewed including the data of recently prepared stable organometallic complexes with gold(i) and gold(iii) centers. In the second part, the reports are summarized where authors have tried to provide evidence for hydrogen bonds to gold of the type Au⋯H-X. Such interactions have been proposed for gold atoms in the Au(-i), Au(0), Au(i), and Au(iii) oxidation states as hydrogen bonding acceptors and H-X units with X = O, N, C as donors, based on both experimental and quantum chemistry studies. To complement these findings, the literature was screened for examples with similar molecular geometries, for which such bonding has not yet been considered. In the discussion of the results, the recently issued IUPAC definitions of hydrogen bonding and the currently accepted description of agostic interactions have been used as guidelines to rank the Au⋯H-X interactions in this broad range of weak chemical bonding. From the available data it appears that all the intra- and intermolecular Au⋯H-X contacts are associated with very low binding energies and non-specific directionality. To date, the energetics have not been estimated, because there are no thermochemical and very limited IR/Raman and temperature-dependent NMR data that can be used as reliable references. Where conspicuous structural or spectroscopic effects have been observed, explanations other than hydrogen bonding Au⋯H-X can also be advanced in most cases. Although numerous examples of short Au⋯H-X contacts exist in the literature, it seems, at this stage, that these probably make only very minor contributions to the energy of a given system and have only a marginal influence on molecular conformations which so far have most often attracted researchers to this topic. Further, more dedicated investigations will be necessary before well founded conclusions can be drawn. © 2014 The Royal Society of Chemistry. Source


Delcroix M.,Catholic University of Leuven
European Respiratory Review | Year: 2013

The rationale for the use of pulmonary arterial hypertension-targeted drugs in chronic thromboembolic pulmonary hypertension is based on four bundles of evidence, as follows: 1) the pathobiology of the disease, with a distal component of pre-capillary arteriopathy that is very similar to pulmonary arterial hypertension; 2) the inoperability of some patients, and the persistence or recurrence of pulmonary hypertension after pulmonary endarterectomy in others; 3) the short-term efficacy and safety of pulmonary arterial hypertension-targeted drugs in these patients; and 4) their potential effect on survival. Chronic thromboembolic pulmonary hypertension is essentially a surgical disease, curable by pulmonary endarterectomy, with acceptable procedural mortality in experienced centres. Patient selection for surgery is extremely complex and results in 30-50% of patients considered inoperable. A large clinical experience has been built up with endothelin receptor antagonists and phosphodiesterase-5 inhibitors, while evidence from controlled trials is running far behind schedule. More recently, a randomised controlled trial with the guanylate cyclase stimulator, riociguat, achieved its target and showed haemodynamic, as well as functional, improvements within 4 months of therapy. The place of this therapy in the therapeutic arsenal needs to be further defined, but should be strictly limited to inoperable patients. © ERS 2013. Source


Lijnen H.R.,Catholic University of Leuven
Thrombosis Research | Year: 2011

Obesity is a common disorder, and related diseases such as diabetes, atherosclerosis, hypertension, cardiovascular disease and cancer are a major cause of mortality and morbidity in Westerntype societies. Development of obesity is associated with extensive modifications in adipose tissue involving adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems cooperate in these processes. Adipogenesis is tightly associated with angiogenesis, as shown by the findings that adipose tissue expiants trigger blood vessel formation, whereas in turn adipose tissue endothelial cells promote preadipocyte differentiation. A nutritionally induced obesity model in transgenic mice has been used extensively to study the role of the fibrinolytic and MMP systems and of angiogenesis in the development of obesity. Most studies support a role of these systems in adipogenesis and obesity, and suggest that their modulation may affect development of adipose tissue. Such models have also shown that treatment of obese female mice with estrogens has the potential to improve obesity, insulin resistance and glucose intolerance, via decreased expression of lipogenic genes. Thus, murine models of obesity have been very useful tools to study mechanisms of adipose tissue development, as well as effects of hormonal therapy. © 2010 Elsevier B.V. All rights reserved. Source


Tkachenko A.,Catholic University of Leuven
Astronomy and Astrophysics | Year: 2015

Context. The currently operating space missions, as well as those that will be launched in the near future, will deliver high-quality data for millions of stellar objects. Since the majority of stellar astrophysical applications still (at least partly) rely on spectroscopic data, an efficient tool for the analysis of medium- to high-resolution spectroscopy is needed. Aims. We aim at developing an efficient software package for the analysis of medium- to high-resolution spectroscopy of single stars and those in binary systems. The major requirements are that the code should have a high performance, represent the state-of-the-art analysis tool, and provide accurate determinations of atmospheric parameters and chemical compositions for different types of stars. Methods. We use the method of atmosphere models and spectrum synthesis, which is one of the most commonly used approaches for the analysis of stellar spectra. Our Grid Search in Stellar Parameters (gssp) code makes use of the Message Passing Interface (OpenMPI) implementation, which makes it possible to run in parallel mode. The method is first tested on the simulated data and is then applied to the spectra of real stellar objects. Results. The majority of test runs on the simulated data were successful in that we were able to recover the initially assumed sets of atmospheric parameters. We experimentally find the limits in signal-to-noise ratios of the input spectra, below which the final set of parameters is significantly affected by the noise. Application of the gssp package to the spectra of three Kepler stars, KIC-11285625, KIC-6352430, and KIC-4931738, was also largely successful. We found an overall agreement of the final sets of the fundamental parameters with the original studies. For KIC-6352430, we found that dependence of the light dilution factor on wavelength cannot be ignored, as it has a significant impact on the determination of the atmospheric parameters of this binary system. Conclusions. The gssp software package is a compilation of three individual program modules suitable for spectrum analysis of single stars and individual binary components. The code is highly effective and can be used for spectrum analysis of large samples of stars. © ESO, 2015. Source


Pitman A.,University College London | Krysinska K.,Catholic University of Leuven | Osborn D.,University College London | King M.,University College London
The Lancet | Year: 2012

Suicide is second to only accidental death as the leading cause of mortality in young men across the world. Although suicide rates for young men have fallen in some high-income and middle-income countries since the 1990s, wider mortality measures indicate that rates remain high in specifi c regions, ethnic groups, and socioeconomic groups within those nations where rates have fallen, and that young men account for a substantial proportion of the economic cost of suicide. High-lethality methods of suicide are preferred by young men: hanging and fi rearms in high-income countries, pesticide poisoning in the Indian subcontinent, and charcoal-burning in east Asia. Risk factors for young men include psychiatric illness, substance misuse, lower socioeconomic status, rural residence, and single marital status. Population-level factors include unemployment, social deprivation, and media reporting of suicide. Few interventions to reduce suicides in young men have been assessed. Eff orts to change help-seeking behaviour and to restrict access to frequently used methods hold the most promise. Source


Gebuis T.,Catholic University of Leuven
Psychophysiology | Year: 2012

Nonsymbolic number and its continuous visual properties are confounded in everyday life: When number changes, its continuous visual properties also change. It could therefore be efficient to rely on the visual properties to judge number. The current consensus, however, holds that number is processed independent of its visual properties. In this study, we pitched these two opposing theories against each other. We used electroencephalography to look at the components suggested to process number. The first experiment showed that number and visual cues affect the N1 and/or the P2 component. To disentangle number and visual processes, we controlled the visual cues in the second experiment. Now, no number-related effects were present. When the data were reorganized according to visual cue instead of number size, N1 and P2 effects emerged. These results argue against the idea that number is processed independent of its continuous visual variables. Copyright © 2012 Society for Psychophysiological Research. Source


Vandenbosch G.A.E.,Catholic University of Leuven
IEEE Transactions on Antennas and Propagation | Year: 2013

In part I, closed form expressions were derived in time domain to calculate the electric and magnetic field energy around a device and the energy radiated by the device. In part II, these expressions are applied to cases important in practice: pulses finite in time domain, and sinusoidal regime. The time domain expressions are able to provide a deeper physical insight compared to the previously derived equivalent expressions in frequency domain. The solution proposed by Gustafsson and Jonsson to solve the issue of 'negative energies' can be interpreted based on them. This leads to an upgraded calculation of Q factors. The new expressions are illustrated through numerical calculations for the two most basic radiator types: dipoles and loops. © 1963-2012 IEEE. Source


Vandenbosch G.A.E.,Catholic University of Leuven
IEEE Transactions on Antennas and Propagation | Year: 2013

Closed form expressions are derived in time domain to calculate the electric and magnetic energy linked to the electromagnetic field surrounding an electromagnetic device. The expressions are rigorous, general, and explicit in terms of the time dependent currents flowing on the device. They are computationally very efficient since they involve integrals solely over the device generating the field. The expressions can also be applied to and interpreted in frequency domain. This will lead to a new interpretation of stored energy in the frequency domain. © 1963-2012 IEEE. Source


Fraisl P.,Vesalius Research Center | Fraisl P.,Catholic University of Leuven
Experimental Cell Research | Year: 2013

With every heart beat blood rushes through a complex network of tubes to deliver essential ingredients of life, oxygen and nutrients. Consequently, this network of blood vessels is an indispensable part of vertebrate physiology. Its organization and architecture is highly dynamic in its form and function. Understanding how blood vessels develop, a process referred to as angiogenesis, is equally important as to know how they function considering that failure or misalignment of this process results in disorder and disease, in many cases of which death is inevitable. Much has been learned about the angiogenic process and the critical contributors of blood vessel function. A central determinant is oxygen, an evident contributor given the fact that oxygen delivery is a primary feature of blood vessel function. Not only is oxygen however essential for mitochondrial energy production, it also serves as a key molecule in various biochemical reactions, such as the formation of nitric oxide (NO), on its part a critical regulator of vascular tone and vessel homeostasis. Hence, oxygen abundance relates to the production of NO, and NO in turn regulates oxygen delivery and consumption. Given the importance of the intrinsic link these two molecules exert on angiogenesis and vessel function; this review shall highlight our current understanding on how these two molecules cooperate to form blood vessels. © 2013 Elsevier Inc. Source


Wouters M.M.,Catholic University of Leuven
Neurogastroenterology and Motility | Year: 2011

Genome wide association studies and meta-analyses identified risk factors related to epithelial integrity of the intestinal barrier, innate immune responses and autophagy in inflammatory bowel disorder (IBD) and celiac disease. Irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder (FGID), coexists and shares common, although milder, features with IBD and celiac disease. Although our knowledge on genetic variability in IBS symptom generation is very limited, smaller scale studies attempt to provide insight in the mechanisms underlying IBS. Camilleri et al. identified associations for susceptibility loci in inflammatory and epithelial barrier genes with colonic transit in lower FGID. Their report is the first descriptive study to assess potential genetic factors involved in motor function. Further exploration of genetic variation in IBS will be crucial to unravel its' pathogenesis. © 2011 Blackwell Publishing Ltd. Source


Cox N.L.J.,Catholic University of Leuven | Patat F.,Hemisphere
Astronomy and Astrophysics | Year: 2014

Context. Supernovae (SNe) offer a unique opportunity to study physical properties, small-scale structure, and complex organic chemistry of the interstellar medium (ISM) in different galaxies. Aims. Interstellar absorption features, such as atomic and molecular lines as well as diffuse interstellar bands (DIBs), can be used to study the physical properties of extra-galactic diffuse interstellar clouds. Methods. We used optical high-resolution spectroscopy to study the properties of the ISM in the SN 2008fp host galaxy, ESO 428-G14. The properties of intervening dust were investigated via spectropolarimetry. Results. The spectra of SN 2008fp reveal a complex of diffuse atomic clouds at radial velocities in line with the systematic velocities of the host galaxy. In addition, a translucent (AV ∼ 1.5 mag) cloud is detected at a heliocentric velocity of 1770 km s-1 (redshifted by 70 km s-1 with respect to the system velocity). This cold dense cloud is rich in dense atomic gas tracers, molecules, as well as DIBs. We have detected both C2 and C3 for the first time in a galaxy beyond the Local Group. The CN (0, 0) band-line ratios are consistent with an excitation temperature of T = 2.9 ± 0.4 K. The interstellar polarisation law deviates significantly from what is observed in the Galaxy, indicating substantial differences in the host dust/size composition. No variations over a period of about one month are observed in any of the ISM tracers. Conclusions. The lack of variability in the extra-galactic absorption line profiles implies that the absorbing material is not circumstellar and thus not directly affected by the SN event. It also shows that there are no significant density variation in the small-scale structure of the molecular cloud down to 100 AU. C2 is used to probe the cold diffuse ISM density and temperature. Here we also use observations of CN in a distant galaxies, though for now still in a limited way, for in situ measurements of the cosmic background radiation temperature. © 2014 ESO. Source


Madry H.,Saarland University | Luyten F.P.,Catholic University of Leuven | Facchini A.,Laboratorio Of Immunoreumatologia E Rigenerazione Tissutale
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2012

Purpose: Early OA primarily affects articular cartilage and involves the entire joint, including the subchondral bone, synovial membrane, menisci and periarticular structures. The aim of this review is to highlight the molecular basis and histopathological features of early OA. Methods: Selective review of literature. Results: Risk factors for developing early OA include, but are not limited to, a genetic predisposition, mechanical factors such as axial malalignment, and aging. In early OA, the articular cartilage surface is progressively becoming discontinuous, showing fibrillation and vertical fissures that extend not deeper than into the mid-zone of the articular cartilage, reflective of OARSI grades 1.0-3.0. Early changes in the subchondral bone comprise a progressive increase in subchondral plate and subarticular spongiosa thickness. Early OA affects not only the articular cartilage and the subchondral bone but also other structures of the joint, such as the menisci, the synovial membrane, the joint capsule, ligaments, muscles and the infrapatellar fat pad. Genetic markers or marker combinations may become useful in the future to identify early OA and patients at risk. Conclusion: The high socioeconomic impact of OA suggests that a better insight into the mechanisms of early OA may be a key to develop more targeted reconstructive therapies at this first stage of the disease. Level of evidence: Systematic review, Level II. © 2011 Springer-Verlag. Source


Guillaume F.,Catholic University of Leuven
Journal of Computational Finance | Year: 2012

This paper provides a multivariate Sato model for multivariate option pricing where the asset log-returns are expressed as Sato time-changed Brownian motions and where the time change is the weighted sum of a common and an idiosyncratic component. The main advantage of this model is that it allows us to replicate univariate option prices in both the strike and time-to-maturity dimensions. In particular, it is able to fit both the univariate option surfaces and the asset logreturn dependence structures with high precision for the period from June 2008 to October 2009 – a time frame that includes the credit crisis. © 2012, Incisive Media Ltd. All Rights Reserved. Source


Engelhardt N.,University of California at Santa Barbara | Hertog T.,Catholic University of Leuven | Horowitz G.T.,University of California at Santa Barbara
Physical Review Letters | Year: 2014

To gain insight into the quantum nature of cosmological singularities, we study anisotropic Kasner solutions in gauge-gravity duality. The dual description of the bulk evolution towards the singularity involves N=4 super Yang-Mills theory on the expanding branch of deformed de Sitter space and is well defined. We compute two-point correlators of Yang-Mills operators of large dimensions using spacelike geodesics anchored on the boundary. The correlators show a strong signature of the singularity around horizon scales and decay at large boundary separation at different rates in different directions. More generally, the boundary evolution exhibits a process of particle creation similar to that in inflation. This leads us to conjecture that information on the quantum nature of cosmological singularities is encoded in long-wavelength features of the boundary wave function. © 2014 American Physical Society. Source


Cornelissen V.A.,Catholic University of Leuven
Journal of the American Heart Association | Year: 2013

We conducted meta-analyses examining the effects of endurance, dynamic resistance, combined endurance and resistance training, and isometric resistance training on resting blood pressure (BP) in adults. The aims were to quantify and compare BP changes for each training modality and identify patient subgroups exhibiting the largest BP changes. Randomized controlled trials lasting ≥4 weeks investigating the effects of exercise on BP in healthy adults (age ≥18 years) and published in a peer-reviewed journal up to February 2012 were included. Random effects models were used for analyses, with data reported as weighted means and 95% confidence interval. We included 93 trials, involving 105 endurance, 29 dynamic resistance, 14 combined, and 5 isometric resistance groups, totaling 5223 participants (3401 exercise and 1822 control). Systolic BP (SBP) was reduced after endurance (-3.5 mm Hg [confidence limits -4.6 to -2.3]), dynamic resistance (-1.8 mm Hg [-3.7 to -0.011]), and isometric resistance (-10.9 mm Hg [-14.5 to -7.4]) but not after combined training. Reductions in diastolic BP (DBP) were observed after endurance (-2.5 mm Hg [-3.2 to -1.7]), dynamic resistance (-3.2 mm Hg [-4.5 to -2.0]), isometric resistance (-6.2 mm Hg [-10.3 to -2.0]), and combined (-2.2 mm Hg [-3.9 to -0.48]) training. BP reductions after endurance training were greater (P<0.0001) in 26 study groups of hypertensive subjects (-8.3 [-10.7 to -6.0]/-5.2 [-6.8 to -3.4] mm Hg) than in 50 groups of prehypertensive subjects (-2.1 [-3.3 to -0.83]/-1.7 [-2.7 to -0.68]) and 29 groups of subjects with normal BP levels (-0.75 [-2.2 to +0.69]/-1.1 [-2.2 to -0.068]). BP reductions after dynamic resistance training were largest for prehypertensive participants (-4.0 [-7.4 to -0.5]/-3.8 [-5.7 to -1.9] mm Hg) compared with patients with hypertension or normal BP. Endurance, dynamic resistance, and isometric resistance training lower SBP and DBP, whereas combined training lowers only DBP. Data from a small number of isometric resistance training studies suggest this form of training has the potential for the largest reductions in SBP. Source


Willems P.,Catholic University of Leuven | Willems P.,Vrije Universiteit Brussel
Journal of Hydrology | Year: 2013

Design parameters for urban drainage systems in Belgium have been revised. The revision involves extrapolation of the design rainfall statistics, taking into account the current knowledge on future climate change trends till 2100. Uncertainties in these trend projections have been assessed after statistically analysing and downscaling a broad ensemble set of 44 regional and 69 global climate model runs. Climate change scenarios were developed, tailored for the application of urban drainage impact analysis. By means of a further advanced quantile perturbation method, a 100-year 10-min historical rainfall series was perturbed for each climate change scenario. The perturbations were based on the empirical frequency distributions for the lower return periods, and calibrated extreme value distributions for the higher return periods.Based on the climate scenarios and perturbed historical rainfall series, changes in intensity-duration-frequency (IDF) statistics and design storms have been derived. It was shown that the 10-year design storm intensity can increase up to about 50% by the end of this century. Or, systems currently designed for a 20-year return period of flooding, might flood with a mean recurrence interval of - in order of magnitude - 5. years by the end of the century. Based on a continuous reservoir simulation approach, changes in overflow frequency of storage facilities have been quantified for a wide range of storage capacities and infiltration/throughflow rates. It is found that increase in storage capacity of 11-51% is required to keep the overflow frequency to the current level. © 2013 Elsevier B.V. Source


Belderbos R.,Catholic University of Leuven
Journal of Product Innovation Management | Year: 2010

The present study analyzes the impact of firms' technological strategies on their financial performance. Technology strategies are defined by making a distinction between explorative and exploitative as well as collaborative and solitary technological activities. Several hypotheses are tested on a panel data set (1996-2003) of 168 research and development (R&D)-intensive firms based in Japan, the United States, and Europe and situated in five different industries (i.e., chemicals, pharmaceuticals, information and communication technologies [ICT], electronics, and nonelectrical machinery). This study's analyses confirm the existence of an inverted U-shape relationship between the share of explorative technological activities and financial performance. In addition, firms engaging more intensively in collaboration perform relatively stronger in explorative activities. At the same time, a negative relationship is observed between the share of collaborative technological activities and a firm's market value. This negative relationship is most pronounced in collaborative activities of an exploratory nature. Overall, these findings suggest that the value appropriation complexities of collaborative technological activities may offset their valueenhancing potential. © 2010 Product Development & Management Association. Source


Verhaeghe J.,Catholic University of Leuven
European Journal of Contraception and Reproductive Health Care | Year: 2010

Objective The metabolic syndrome (MS) is a set of five cardiovascular and metabolic risk factors: elevated waist circumference, fasting plasma glucose, triglycerides and blood pressure; and reduced HDL-cholesterol. The prevalence of the MS is rising worldwide, and is linked to two diagnoses in young women: polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM). MethodsThis narrative review focuses on hormonal contraceptive choices available for women in Europe with features of the MS. ResultsThe levonorgestrel- intrauterine system and progestogen-only pills containing desogestrel or levonorgestrel have no significant effects on MS parameters. Combined oestrogen-progestogen methods do not appear to increase waist circumference or the incidence of glucose intolerance in women with PCOS or a history of GDM; their effect on HDL-cholesterol and triglycerides is comparable with that observed in women without the MS, while the effect on blood pressure remains inconclusive. The etonogestrel implant does not affect body weight, triglycerides and blood pressure but mildly reduces insulin sensitivity and HDL-cholesterol in healthy women. Depot medroxyprogesterone acetate increases body weight and truncal fat deposition, and lowers glucose tolerance in women with previous GDM. ConclusionsLow-dose hormonal contraception is safe for many women with the MS, but high-dose progestogens must be avoided. © 2010 The European Society of Contraception and Reproductive Health. Source


Pipeleers G.,Catholic University of Leuven | Moore K.L.,Colorado School of Mines
IEEE Transactions on Automatic Control | Year: 2014

While iterative learning control (ILC) and repetitive control (RC) have much ground in common, they fundamentally differ in the initial conditions at each repetition. This difference has lead to distinct analysis techniques, hereby clouding the interrelations between both control strategies. To facilitate the transfer of results, this paper presents a unified approach to ILC and RC. Both control problems are formulated in the trial domain using so-called system lifting. For a given system, the corresponding ILC and RC trial-domain models differ, and a thorough system theoretic analysis and comparison of these models is performed. To illustrate the value of a unified formulation of ILC and RC, the analysis of the most commonly used ILC and RC structures is harmonized. This analysis reveals central differences and similarities between various stability, monotonic convergence and steady-state performance conditions. © 1963-2012 IEEE. Source


Stoks R.,Catholic University of Leuven | Crdoba-Aguilar A.,National Autonomous University of Mexico
Annual Review of Entomology | Year: 2012

Most insects have a complex life cycle with ecologically different larval and adult stages. We present an ontogenetic perspective to analyze and summarize the complex life cycle of Odonata within an evolutionary ecology framework. Morphological, physiological, and behavioral pathways that generate carry-over effects across the aquatic egg and larval stages and the terrestrial adult stage are identified. We also highlight several mechanisms that can decouple life stages including compensatory mechanisms at the larval and adult stages, stressful and stochastic events during metamorphosis, and stressful environmental conditions at the adult stage that may overrule effects of environmental conditions in the preceding stage. We consider the implications of these findings for the evolution, selection, and fitness of odonates; underline the role of the identified numerical and carry-over effects in shaping population and metapopulation dynamics and the community structure across habitat boundaries; and discuss implications for applied conservation issues. © 2012 by Annual Reviews. All rights reserved. Source


Saio T.,Rutgers University | Guan X.,Rutgers University | Rossi P.,Rutgers University | Economou A.,Catholic University of Leuven | And 2 more authors.
Science | Year: 2014

Molecular chaperones prevent aggregation and misfolding of proteins, but scarcity of structural data has impeded an understanding of the recognition and antiaggregation mechanisms. We report the solution structure, dynamics, and energetics of three trigger factor (TF) chaperone molecules in complex with alkaline phosphatase (PhoA) captured in the unfolded state. Our data show that TF uses multiple sites to bind to several regions of the PhoA substrate protein primarily through hydrophobic contacts. Nuclear magnetic resonance (NMR) relaxation experiments show that TF interacts with PhoA in a highly dynamic fashion, but as the number and length of the PhoA regions engaged by TF increase, a more stable complex gradually emerges. Multivalent binding keeps the substrate protein in an extended, unfolded conformation. The results show how molecular chaperones recognize unfolded polypeptides and, by acting as unfoldases and holdases, prevent the aggregation and premature (mis)folding of unfolded proteins. Source


Lapenta G.,Catholic University of Leuven | Bettarini L.,Royal Observatory of Belgium
Geophysical Research Letters | Year: 2011

We report a 3D magnetohydrodynamics simulation that studies the formation of dipolarization fronts during magnetotail reconnection. The crucial new feature uncovered in the present 3D simulation is that the process of reconnection produces flux ropes developing within the reconnection region. These flux ropes are unstable to the kink mode and introduce a spontaneous structure in the dawn-dusk direction. The dipolarization fronts forming downstream of reconnection are strongly affected by the kinking ropes. At the fronts, a density gradient is present with opposite direction to that of the acceleration field and leads to an interchange instability. We present evidence for a causal link where the perturbations of the kinking flux ropes with their natural and well defined scales drive and select the scales for the interchange mode in the dipolarization fronts. The results of the simulation are validated against measured structures observed by the THEMIS mission. Copyright 2011 by the American Geophysical Union. Source


Tuytelaars T.,Catholic University of Leuven
Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition | Year: 2010

Local features or image patches have become a standard tool in computer vision, with numerous application domains. Roughly speaking, two different types of patch-based image representations can be distinguished: interest points, such as corners or blobs, whose position, scale and shape are computed by a feature detector algorithm, and dense sampling, where patches of fixed size and shape are placed on a regular grid (possibly repeated over multiple scales). Interest points focus on 'interesting' locations in the image and include various degrees of viewpoint and illumination invariance, resulting in better repeatability scores. Dense sampling, on the other hand, gives a better coverage of the image, a constant amount of features per image area, and simple spatial relations between features. In this paper, we propose a hybrid scheme, which we call dense interest points, where we start from densely sampled patches yet optimize their position and scale parameters locally. We investigate whether doing so it is possible to get the best of both worlds. ©2010 IEEE. Source


Vansteenkiste J.F.,Catholic University of Leuven
Future Oncology | Year: 2014

The anaplastic lymphoma kinase (ALK) gene plays a key role in the pathogenesis of selected tumors, including non-small-cell lung cancer (NSCLC). Patients with ALK-rearranged NSCLC are initially sensitive to the ALK inhibitor crizotinib but eventually become resistant, limiting its therapeutic potential. Ceritinib is an oral second-generation ALK inhibitor with greater preclinical antitumor potency than crizotinib in ALK-positive NSCLC. A Phase I trial of ceritinib in ALK-positive tumors demonstrated good activity in patients with advanced NSCLC, including those who had progressed on crizotinib. Adverse events are similar to those seen with other ALK tyrosine kinase inhibitors and are generally manageable. Ongoing trials are evaluating ceritinib in patients with ALK-rearranged NSCLC treated with prior chemotherapy and/or crizotinib. © 2014 Future Medicine Ltd. Source


Koerber P.,Catholic University of Leuven
Fortschritte der Physik | Year: 2011

In these lectures we review Generalized Complex Geometry and discuss two main applications to string theory: the description of supersymmetric flux compactifications and the supersymmetric embedding of D-branes. We start by reviewing G-structures, and in particular SU(3)-structure and its torsion classes, before extending to Generalized Complex Geometry. We then discuss the supersymmetry conditions of type II supergravity in terms of differential conditions on pure spinors, and finally introduce generalized calibrations to describe D-branes. As examples we discuss in some detail AdS4 compactifications, which play a role as the geometric duals in the AdS4/CFT3-correspondence. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Mandemakers W.,Catholic University of Leuven
Cold Spring Harbor Protocols | Year: 2014

Here we describe a method to purify corticospinal motor neurons (CSMNs). It combines the versatility of retrograde labeling with the advantages of immunopanning. Rat cortices with CSMNs that have been labeled with cholera toxin beta (CTB) are dissected and dissociated, and the CSMNs are specifically purified via immunopanning with an anti-CTB antibody. We show the efficacy of this method in early rat pups by purifying CSMNs to >99% purity. The method can be used to highly purify any neuronal cell type whose projections can be selectively labeled via retrograde tracing. © 2014 Cold Spring Harbor Laboratory Press. Source


Abanin D.A.,University of Geneva | De Roeck W.,Catholic University of Leuven | Huveneers F.,University of Paris Dauphine
Physical Review Letters | Year: 2015

We derive general bounds on the linear response energy absorption rates of periodically driven many-body systems of spins or fermions on a lattice. We show that, for systems with local interactions, the energy absorption rate decays exponentially as a function of driving frequency in any number of spatial dimensions. These results imply that topological many-body states in periodically driven systems, although generally metastable, can have very long lifetimes. We discuss applications to other problems, including the decay of highly energetic excitations in cold atomic and solid-state systems. © 2015 American Physical Society. Source


Peeters J.,Catholic University of Leuven | Muller J.-F.,Belgian Institute for Space Aeronomy
Physical Chemistry Chemical Physics | Year: 2010

A consistent body of experimental evidence from work of other groups is presented in support of the novel, theoretically based, isoprene oxidation mechanism we recently proposed to rationalize the unexpectedly high OH concentrations observed over areas with high isoprene emissions. Some explicit or implicit criticisms on the new mechanism are addressed. A particular photochemical mechanism is newly proposed for the OH-regenerating photolysis of the crucial hydroperoxy-methyl-butenals (HPALDs), formed by isomerisation of the initial isoprene hydroxy-peroxy radicals, that rationalizes a quantum yield close to 1. A similar photolysis mechanism of the resulting photolabile peroxy-acid-aldehydes (PACALDs) is shown to generate ample additional OH. Global modeling demonstrates the major importance of the new chemistry for the oxidizing capacity of the atmosphere over continents. The globally averaged yield of the HPALDs in the oxidation of isoprene by OH is estimated to be of the order of 0.6. The isomerisation reactions of isoprene peroxy radicals are found to result in modelled [OH] increases in the planetary boundary layer by up to a factor of 3, in agreement with the reported observations as in the Amazon basin. © the Owner Societies 2010. Source


Van Calster B.,Catholic University of Leuven
Journal of the American Society for Information Science and Technology | Year: 2012

The way in which scientific publications are picked up by the research community can vary. Some articles become instantly cited, whereas others go unnoticed for some time before they are discovered or rediscovered. Papers with delayed recognition have also been labeled "sleeping beauties." I briefly discuss an extreme case of a sleeping beauty. Peirce's short note in Science in 1884 shows a remarkable increase in citations since around 2000. The note received less than 1 citation per year in the decades prior to 2000, 3.5 citations per year in the 2000s, and 10.4 in the 2010s. This increase was seen in several domains, most notably meteorology, medical prediction research, and economics. The paper outlines formulas to evaluate a binary prediction system for a binary outcome. This citation increase in various domains may be attributed to a widespread, growing research focus on mathematical prediction systems and the evaluation thereof. Several recently suggested evaluation measures essentially reinvented or extended Peirce's 120-year-old ideas. © 2012 ASIS&T. Source


Pedersen S.F.,Copenhagen University | Klausen T.K.,Copenhagen University | Nilius B.,Catholic University of Leuven
Acta Physiologica | Year: 2015

The volume-regulated anion channel (VRAC) plays a pivotal role in cell volume regulation in essentially all cell types studied. Additionally, VRAC appears to contribute importantly to a wide range of other cellular functions and pathological events, including cell motility, cell proliferation, apoptosis and excitotoxic glutamate release in stroke. Although biophysically, pharmacologically and functionally thoroughly described, VRAC has until very recently remained a genetic orphan. The search for the molecular identity of VRAC has been long and has yielded multiple potential candidates, all of which eventually turned out to have properties not fully compatible with those of VRAC. Recently, two groups have independently identified the protein leucine-rich repeats containing 8A (LRRC8A), belonging to family of proteins (LRRC8A-E) distantly related to pannexins, as the likely pore-forming subunit of VRAC. In this brief review, we summarize the history of the discovery of VRAC, outline its basic biophysical and pharmacological properties, link these to several cellular functions in which VRAC appears to play important roles, and sketch the amazing search for the molecular identity of this channel. Finally, we describe properties of the LRRC8 proteins, highlight some features of the LRRC8A knockout mouse and discuss the impact of the discovery of LRRC8 as VRAC on future research. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. Source


Van Der Bruggen B.,Catholic University of Leuven
Industrial and Engineering Chemistry Research | Year: 2013

One of the suggestions made by Enrico Drioli to the membrane community for many years is to work on a radical change from conventional separation and conversion methods to membrane-based separation methods, making use of integrated systems combining a range of membrane separation processes. This paper looks back at these ideas, taking a joint paper written by myself with Efrem Curcio and Enrico Drioli and published in 2004, as a reference. Three processes were central in this paper: the use of nanofiltration for fractionation, membrane distillation, and membrane contactors combined with crystallization as membrane crystallizers. The objective of this paper is to monitor the progress in these three aspects of the proposed overall integrated process. This is done based on the literature and our own expertise. The intention is not to focus on a new and limited subset of results but to evaluate the overall idea of process integration one decade after being proposed. Based on this, it is concluded that the required fractionation in nanofiltration appears to be possible by process engineering rather than membrane engineering. Membrane distillation is today in a clear exponential growth phase and has emerged from research laboratories into larger scale applications, although most still in desalination whereas the potential is larger. Membrane crystallization remains an undiscovered process for many, in spite of its proven technical performance and interest in the scientific literature. © 2013 American Chemical Society. Source


Ghaye B.,Catholic University of Leuven
JBR-BTR | Year: 2013

Lung cancer is the leading cause of death related to cancer. Fifteen to thirty percent of patients with a localized lung cancer are actually inoperable as they present with poor general condition, limited cardiopulmonary function, or a too high surgical risk. Therefore, minimally invasive treatments are needed and percutaneous ablation seems an attractive option. Thermal ablation can be performed by delivering heat (radiofrequency, microwave, laser) or cold (cryotherapy) through a needle inserted into the tumor under CT guidance. The ideal lesion is less than 2 or 3 cm in diameter. Success of percutaneous thermal ablation appears to be close to those of surgery for localized lung cancer. Nevertheless studies are still needed to definitely assess the role of ablation compared to other emerging techniques, as stereotactic radiotherapy as well as potential synergy with other treatments. Source


Mandemakers W.,Catholic University of Leuven
Cold Spring Harbor Protocols | Year: 2014

Immunopanning of viable neurons requires availability of an antibody directed against a neuronal surface epitope that is specific for a neuron type of interest (e.g., corticospinal motor neurons [CSMNs]) and that is able to immobilize only neurons of interest from a dissociated brain suspension on a culture dish. However, few, if any, neuron type-specific monoclonal antibodies have been developed. Panning antibodies have not been characterized for CSMNs. To circumvent this issue, we developed a method to retrograde label CSMNs with a cholera toxin B subunit (CTB) tracer that localizes to the plasma membrane only of labeled CSMNs. The main objective of this procedure is to provide CSMNs with a surface marker that can be used to immunopan only the labeled CSMNs by using a CTB-specific antibody. © 2014 Cold Spring Harbor Laboratory Press. Source


Janssens S.,Catholic University of Leuven
Annual Review of Medicine | Year: 2010

Progenitor cells residing in bone marrow, adipose tissue, and skeletal muscle or circulating in the blood are capable of improving myocardial function in preclinical models. In contrast, early clinical studies using bone marrow cells have shown mixed results and reflect our incomplete understanding of underlying mechanisms. Recent identification of various cardiac precursor cells has suggested an endogenous reservoir for cell-based repair. However, confronted with massive cardiac cell loss, inventive strategies and enabling technologies are required to mobilize or deliver functionally competent progenitor cells to sites of injury or to effectively stimulate endogenous repair. We review our present knowledge in this promising and rapidly evolving development in cardiovascular medicine and highlight obstacles as well as opportunities. © 2010 by Annual Reviews All rights reserved. Source


Maes W.H.,Ghent University | Verbist B.,Catholic University of Leuven
Renewable and Sustainable Energy Reviews | Year: 2012

Although 40% of the global population relies on traditional biomass use, mainly firewood and charcoal, for cooking, traditional biomass has received very little attention in the current biomass debate, because of its considered primitive and unsustainable nature. In this review, we discuss how the sustainability of household cooking in developing countries can be improved. Indoor air pollution due to incomplete combustion of traditional biomass causes the death of 1.45 million people every year, mainly of women and children, who also carry the heavy burden of fuelwood collection. In addition, charcoal production and combustion is responsible for very high greenhouse gas emissions per unit of energy. On the other hand, fuelwood production and trade is of vital importance for local economies and serves as safety net for the poorest people. Moreover, fuelwood collection is not a driver of deforestation and global fuelwood shortage will not occur, despite local problems of fuelwood provision. There are two distinct policy alternatives to increase the sustainability of cooking in developing countries. The first option is to climb the energy ladder and to switch from solid fuels to fossil fuels (LPG or kerosene), biogas or electricity. As this largely avoids the severe health damages of traditional biomass use, this option is considered the most desirable by numerous countries and by international organizations. However, as most developing countries are far away from meeting the necessary requirements, related to infrastructure, economics and local culture, expecting a large-scale switch to liquid fuels or electricity is unrealistic. In that case, the second policy option, increasing the sustainability of the current traditional biomass system, must be considered. This can be realized by an integrated approach, in which national and regional fuelwood policies are adapted, improved systems for charcoal production are implied and improved stoves, in combination with chimneys, are distributed. © 2012 Elsevier Ltd. All right reserved. Source


Blanckaert N.,Catholic University of Leuven
Clinical Chemistry and Laboratory Medicine | Year: 2010

Both technological advances and economic drivers have led to major changes in clinical laboratories across the world, with vastly improved testing productivity. However, the production process capability advances have far outpaced the clinical pathologists' success in assuring optimal test utilization and interpretation. While productivity of 'commodity' testing increases, our healthcare value productivity decreases. Such developments constitute a serious threat to our clinical pathology specialty, not only because pathologists may lose direct control of the commodity testing production activities, but also because the present evolution exposes a failure of our core clinical activities, the pathologist's knowledge processes that translate 'commodity' results into medical outcomes optimization. At a time when a revolution in health care organization is inescapable in the years ahead, clinical pathology must proceed from a merely reactive strategy (to fulfill the 'more with less' demands) to a proactive strategy where we build excellence and visibility in knowledge services on a strong foothold of operational excellence. Based on a Strengths-Weaknesses-Opportunities-Threats analysis, we argue that clinical pathology should safeguard and expand its healthcare value productivity by assuming leadership in building integrated laboratory services networks. We also suggest that the core knowledge processes deserve a system approach, for example, by applying a risk-based quality management system. © 2010 by Walter de Gruyter, Berlin, New York. Source


Hondeghem L.M.,Catholic University of Leuven
Journal of Cardiovascular Pharmacology | Year: 2013

Domperidone (antinausea/vomiting agent) was recently shown by several groups to increase sudden cardiac death (SCD). Drug-induced disturbances of cardiac repolarization may be a major mechanism. METHODS AND RESULTS: Experiments were executed in isolated female rabbit hearts perfused for 150 minutes with domperidone 30, 60, or 100 nM. Domperidone significantly prolonged the action potential duration: +9% at 30 nM, +32% at 60 nM, and +48% at 100 nM. Domperidone induced significant disturbances of repolarization in 83% of hearts at 60 nM and in 100% at 100 nM, including early afterdepolarizations and polymorphic ventricular tachycardia. Maximum therapeutic free drug plasma concentration of domperidone (19 nM) yields a safety index of only ∼2.5, that is, 12-fold below the accepted minimum. Gastrointestinal benefits and risks for SCD were derived from the literature. The defined daily dose of domperidone (30 mg/day) fails to show unequivocal gastrointestinal benefits beyond a placebo effect. In contrast, 5 of 5 population-based studies show that oral domperidone significantly increases the odds ratio for SCD to 2.8 (1.53-6.21) and it increases sharply above 30 mg/day. CONCLUSIONS: Because domperidone has placebo-like benefits but is associated with increased SCD and a narrow safety margin, it should not be used in medicine. Copyright © 2013 by Lippincott Williams & Wilkins. Source


Mitchell A.J.,Royal Infirmary | Vancampfort D.,Catholic University of Leuven | Sweers K.,University Psychiatric Center Katholieke | Van Winkel R.,University Psychiatric Center Katholieke | And 2 more authors.
Schizophrenia Bulletin | Year: 2013

Individuals with schizophrenia have high levels of medical comorbidity and cardiovascular risk factors. The presence of 3 or more specific factors is indicative of metabolic syndrome, which is a significant influence upon future morbidity and mortality. We aimed to clarify the prevalence and predictors of metabolic syndrome (MetS) in adults with schizophrenia and related disorders, accounting for subgroup differences. A PRISMA systematic search, appraisal, and meta-analysis were conducted of 126 analyses in 77 publications (n = 25 692). The overall rate of MetS was 32.5% (95% CI = 30.1%-35.0%), and there were only minor differences according to the different definitions of MetS, treatment setting (inpatient vs outpatient), by country of origin and no appreciable difference between males and females. Older age had a modest influence on the rate of MetS (adjusted R2 =. 20; P <. 0001), but the strongest influence was of illness duration (adjusted R2 =. 35; P <. 0001). At a study level, waist size was most useful in predicting high rate of MetS with a sensitivity of 79.4% and a specificity of 78.8%. Sensitivity and specificity of high blood pressure, high triglycerides, high glucose and low high-density lipoprotein, and age (>38 y) are shown in supplementary appendix 2 online. Regarding prescribed antipsychotic medication, highest rates were seen in those prescribed clozapine (51.9%) and lowest rates of MetS in those who were unmedicated (20.2%). Present findings strongly support the notion that patients with schizophrenia should be considered a high-risk group. Patients with schizophrenia should receive regular monitoring and adequate treatment of cardio-metabolic risk factors. © 2013 The Author. Source


Valluru R.,Montpellier SupAgro | Van den Ende W.,Catholic University of Leuven
Plant Science | Year: 2011

Myo-inositol is a versatile compound that generates diversified derivatives upon phosphorylation by lipid-dependent and -independent pathways. Phosphatidylinositols form one such group of myo-inositol derivatives that act both as membrane structural lipid molecules and as signals. The significance of these compounds lies in their dual functions as signals as well as key metabolites under stress. Several stress- and non-stress related pathways regulated by phosphatidylinositol isoforms and associated enzymes, kinases and phosphatases, appear to function in parallel to coordinatively adapt growth and stress responses in plants. Recent evidence also postulates their crucial roles in nuclear functions as they interact with the key players of chromatin structure, yet other nuclear functions remain largely unknown. Phosphatidylinositol monophosphate 5-kinase interacts with and represses a cytosolic neutral invertase, a key enzyme of sugar metabolism suggesting a crosstalk between lipid and sugar signaling. Besides phosphatidylinositol, myo-inositol derived galactinol and associated raffinose-family oligosaccharides are emerging as antioxidants and putative signaling compounds too. Importantly, myo-inositol polyphosphate 5-phosphatase (5PTase) acts, depending on sugar status, as a positive or negative regulator of a global energy sensor, SnRK1. This implies that both myo-inositol- and sugar-derived (e.g. trehalose 6-phosphate) molecules form part of a broad regulatory network with SnRK1 as the central regulator. Recently, it was shown that the transcription factor bZIP11 also takes part in this network. Moreover, a functional coordination between neutral invertase and hexokinase is emerging as a sweet network that contributes to oxidative stress homeostasis in plants. In this review, we focus on myo-inositol, its direct and more downstream derivatives (galactinol, raffinose), and the contribution of their associated networks to plant stress tolerance. © 2011 Elsevier Ireland Ltd. Source


Van Houdt S.,Catholic University of Leuven
BMC health services research | Year: 2013

Care pathways are widely used in hospitals for a structured and detailed planning of the care process. There is a growing interest in extending care pathways into primary care to improve quality of care by increasing care coordination. Evidence is sparse about the relationship between care pathways and care coordination.The multi-level framework explores care coordination across organizations and states that (inter)organizational mechanisms have an effect on the relationships between healthcare professionals, resulting in quality and efficiency of care.The aim of this study was to assess the extent to which care pathways support or create elements of the multi-level framework necessary to improve care coordination across the primary-hospital care continuum. This study is an in-depth analysis of five existing local community projects located in four different regions in Flanders (Belgium) to determine whether the available empirical evidence supported or refuted the theoretical expectations from the multi-level framework. Data were gathered using mixed methods, including structured face-to-face interviews, participant observations, documentation and a focus group. Multiple cases were analyzed performing a cross case synthesis to strengthen the results. The development of a care pathway across the primary-hospital care continuum, supported by a step-by-step scenario, led to the use of existing and newly constructed structures, data monitoring and the development of information tools. The construction and use of these inter-organizational mechanisms had a positive effect on exchanging information, formulating and sharing goals, defining and knowing each other's roles, expectations and competences and building qualitative relationships. Care pathways across the primary-hospital care continuum enhance the components of care coordination. Source


Bobev N.,Catholic University of Leuven | El-Showk S.,CERN | El-Showk S.,CNRS Theoretical and High Energy Physics | Mazac D.,Perimeter Institute for Theoretical Physics | Paulos M.F.,CERN
Physical Review Letters | Year: 2015

We implement the conformal bootstrap program for three dimensional conformal field theories with N=2 supersymmetry and find universal constraints on the spectrum of operator dimensions in these theories. By studying the bounds on the dimension of the first scalar appearing in the operator product expansion of a chiral and an antichiral primary, we find a kink at the expected location of the critical three dimensional N=2 Wess-Zumino model, which can be thought of as a supersymmetric analog of the critical Ising model. Focusing on this kink, we determine, to high accuracy, the low-lying spectrum of operator dimensions of the theory, as well as the stress-tensor two-point function. We find that the latter is in an excellent agreement with an exact computation. © 2015 authors. Published by the American Physical Society Source


Van Den Mooter G.,Catholic University of Leuven
Drug Discovery Today: Technologies | Year: 2012

The use of amorphous solid dispersions is an interesting strategy to increase the bioavailability of poorly soluble drugs by improving their rate and extent of dissolution. Lack of understanding of the physical chemistry and their in vivo behavior still hamper full breakthrough in pharmaceutical industry. This paper aims to review aspects like the amorphous state, manufacturing, characterization and biopharmaceutical testing to better understand the strength and weakness of this formulation strategy. © 2011 Elsevier Ltd. All rights reserved. Source


Lapenta G.,Catholic University of Leuven
Journal of Computational Physics | Year: 2011

A new method for the simulation of plasma materials interactions is presented. The method is based on the particle in cell technique for the description of the plasma and on the immersed boundary method for the description of the interactions between materials and plasma particles. A technique to adapt the local number of particles and grid adaptation are used to reduce the truncation error and the noise of the simulations, to increase the accuracy per unit cost. In the present work, the computational method is verified against known results. Finally, the simulation method is applied to a number of specific examples of practical scientific and engineering interest. © 2011 Elsevier Inc. Source


Verbeeck G.,University of Arts | Hens H.,Catholic University of Leuven
Building and Environment | Year: 2010

Traditionally, life cycle assessment (LCA) is mostly concerned with product design and hardly considers large systems, such as buildings, as a whole. Though, by limiting LCA to building materials or building components, boundary conditions, such as thermal comfort and indoor air quality, cannot be taken into account. The life cycle inventory (LCI) model presented in this paper forms part of a global methodology that combines advanced optimisation techniques, LCI and cost-benefit assessment to optimise low energy buildings simultaneously for energy, environmental impact and costs without neglecting the boundary conditions for thermal comfort, indoor air quality and legal requirements for energy performance. This paper first outlines the goal and scope of the LCI. Then, the partial inventory models as well as the overall building inventory model are presented. Finally, the LCI results are shown and discussed for one reference dwelling for the context of Belgium. © 2009 Elsevier Ltd. All rights reserved. Source


Verbeeck G.,University of Arts | Hens H.,Catholic University of Leuven
Building and Environment | Year: 2010

A companion paper presented the life cycle inventory (LCI) calculation model for buildings as a whole, developed within a global methodology to optimise low energy buildings simultaneously for energy, environmental impact and costs without neglecting the boundary conditions for thermal comfort and indoor air quality. This paper presents the results of a contribution analysis of the life cycle inventory of four typical Belgian residential buildings. The analysis shows the relative small importance of the embodied energy of a building compared to the energy consumption during the usage phase. This conclusion is even more valid when comparing the embodied energy of energy saving measures with the energy savings they realise. In most studied cases, the extra embodied energy for energy saving measures is gained back by the savings in less than 2 years. Only extremely low energy buildings might have a total embodied energy higher than the energy use of the utilisation phase. However, the sum of both remains small and the energy savings realised with these dwellings are large, compared to the energy consumption of average dwellings. © 2009 Elsevier Ltd. All rights reserved. Source


Reynders E.,Catholic University of Leuven
Journal of the Acoustical Society of America | Year: 2014

A probabilistic framework is developed for quantifying the combined effect of uncertain parameters in sound insulation measurements, such as test sample dimensions, room properties, and loudspeaker positions, on the sound insulation values. The joint probability distribution of the uncertain parameters is constructed from the available information by means of a maximum entropy approach. The resulting sound insulation predictions are fully compatible with the available information but otherwise maximally conservative, so that the robustness of the predictions is guaranteed. Fundamental insight in the inherent uncertainty of the measurement procedure for airborne sound insulation is obtained by combining the method with detailed numerical simulations of the measurement procedure for single and double walls. The resulting uncertainty levels are very large, especially in the lowest frequency bands, and agree with experimental results. Furthermore, the probability distribution of the band-averaged sound reduction index of modally sparse walls can be of bimodal form. © 2014 Acoustical Society of America. Source


Spaepen S.,Catholic University of Leuven
Cold Spring Harbor perspectives in biology | Year: 2011

Microbial synthesis of the phytohormone auxin has been known for a long time. This property is best documented for bacteria that interact with plants because bacterial auxin can cause interference with the many plant developmental processes regulated by auxin. Auxin biosynthesis in bacteria can occur via multiple pathways as has been observed in plants. There is also increasing evidence that indole-3-acetic acid (IAA), the major naturally occurring auxin, is a signaling molecule in microorganisms because IAA affects gene expression in some microorganisms. Therefore, IAA can act as a reciprocal signaling molecule in microbe-plant interactions. Interest in microbial synthesis of auxin is also increasing in yet another recently discovered property of auxin in Arabidopsis. Down-regulation of auxin signaling is part of the plant defense system against phytopathogenic bacteria. Exogenous application of auxin, e.g., produced by the pathogen, enhances susceptibility to the bacterial pathogen. Source


Purpose: The purpose of this paper is to offer and test a theoretical framework that can be used to identify different styles of peer reporting, and explain why police officers and labour inspectors (do not) report peers' misconduct. Design/methodology/approach: A conceptual framework is developed that identifies underlying mechanisms of peer reporting. It aims to be an alternative for the blue code of silence literature and the general whistleblowing studies, which have a number of disadvantages. This newly developed framework is then tested in a qualitative research project in the police and the labour inspection in a West-European country. Findings: This paper concludes that, in the four agencies, the individualistic type of keeping silent is often preferred when confronted with colleagues' misbehaviour, but in exceptional situations respondents decide to report colleagues' misbehaviour to their boss in a fatalistic or individualistic way. This can probably be explained by the low group (and, thus, fatalistic or individualistic) working context. As for the police, the respondents are "case officers" who are solely responsible for the success of their investigations. As for the labour inspection, the respondents enjoy wide discretion and autonomy in their investigations. In the labour inspections a hierarchical silence code can be found among inspectors with low seniority. Research limitations/implications: This qualitative study is an exploratory study, aimed at theory-building by developing hypotheses which need to be tested in future research. It is not aimed at making generalisations to other police agencies or labour inspections. Practical implications: Grid group cultural theory could inspire practitioners who want to implement whistleblowing policies by recommending that whistleblowing measures, to be effective, should be adapted to organisational characteristics and the prevalent whistleblowing behaviour. Originality/value: This paper offers a new theoretical framework to analyse and explain peer reporting in the police and other professional groups; not only enriching the police culture literature, but also enabling comparative research. © Emerald Group Publishing Limited. Source


Schoonjans S.,Catholic University of Leuven
Journal of Pragmatics | Year: 2012

This paper deals with the phenomenon of German complement-taking mental predicates (CTMPs) evolving into particles. The goal is twofold: on the one hand, to get a better view of the situation in present-day German on the basis of a systematic corpus analysis, and on the other hand to discuss the status of the resulting forms. In both cases, the starting point is the analysis of Imo (2006a, 2009a), who briefly deals with this phenomenon in analyzing the uses of the CTMP glauben. The present paper focuses on glauben as well, but other CTMPs, like denken and finden, are also taken into account. © 2012 Elsevier B.V. Source


Schoffski P.,Catholic University of Leuven
Expert Review of Anticancer Therapy | Year: 2012

Patients with advanced metastatic soft tissue sarcoma (STS) have a poor prognosis, and in the last two decades of the 20th century their overall survival has remained unchanged. Improved treatments are needed for these patients and for preventing metastases in earlier stages of disease. Numerous novel agents and new combination regimens are undergoing clinical testing in STS. Some of these agents show promising activity. Pazopanib is one such agent that has undergone Phase II and III evaluations in advanced STS. Pazopanib is a multi-tyrosine kinase inhibitor, blocking various signaling pathways, thereby preventing angiogenesis and metastasis, and inhibiting tumor cell growth and survival. In a Phase II study, pazopanib demonstrated activity in patients with advanced leiomyosarcomas, synovial sarcomas and other eligible STSs. This activity was confirmed in a Phase III trial, where pazopanib significantly extended the median progression-free survival versus placebo in a variety of STS subtypes. © 2012 Expert Reviews Ltd. Source


Pierloot K.,Catholic University of Leuven
International Journal of Quantum Chemistry | Year: 2011

The present contribution provides a "perspective" on the work on transition metal (TM) bonding and spectroscopy by Björn O. Roos, performed by means of the CASPT2 method in the period 1992-2010. After giving a short overview of important nondynamic correlation effects appearing in TM atoms and molecules, ample attention is given to the work on the Cr 2 molecule and to Björn's fascination for multiple bonds in inorganic molecules containing TM. A short description is also given of his contributions to bioinorganic chemistry, with emphasis on the blue copper proteins. © 2011 Wiley Periodicals, Inc. Source


Simoens S.,Catholic University of Leuven
Journal of Clinical Pharmacy and Therapeutics | Year: 2012

What is known and Objective: Economic evaluation is used to assess the value for money of medicines and inform pharmaceutical pricing/reimbursement decisions in many countries. This paper aims to report on estimates of the value for money of medicines in Europe. Methods: Estimated cost-utilities were derived from studies included in the Tufts Medical Center Cost-Effectiveness Analysis Registry between 2000 and 2007. For each study, the following variables were examined: publication year, target population, intervention type, country of patient sample, disease classification, prevention stage, funding source, study perspective, discounting, sensitivity analysis, incremental cost-utility ratio (ICUR) and methodological quality. Results and Discussion: Six hundred and eight ICURs were reported in 231 cost-utility analyses. Around 17.1% of ratios related to medicines that were more effective and less expensive than the comparator; 76.5% related to medicines that improved outcomes, but increased costs; and 6.4% related to medicines that were less effective and more expensive than the comparator. The median ratio was 12 238 € per quality-adjusted life year (QALY). Using threshold values of 20 000 and 50 000 € per QALY, the probability that medicines provided value for money was 58% and 81%, respectively. Preventive medicines studied provided more value for money than curative medicines (P = 0.002). Studies sponsored by industry generated more favourable results than studies sponsored from other sources (P < 0.001). However, no association was observed between the funding source and the methodological quality of economic evaluations. What is new and Conclusion: The evidence base suggests that the majority of medicines provided value for money. Such information informs policy decisions relating to the allocation of scarce health care resources in Europe. © 2011 Blackwell Publishing Ltd. Source


Cosnard G.,Catholic University of Leuven
Diagnostic and Interventional Imaging | Year: 2012

While reviewing major pathological conditions, the radiologist must learn to adapt his technique to the indication and look for multifocal lesions. In conditions involving malformation, transdural cord herniation and diastematomyelia may be discovered late. In vascular diseases, a dural arteriovenous fistula with perimedullary venous drainage is the most common vascular malformation and a source of diagnostic error. On discovering a medullary cavity, the radiologist needs to know when to discount focal distensions of the ependymal canal and how to detect tumoral syringomyelia. In the case of a tumour, he should know the characteristics of common tumours such as astrocytomas, ependymomas, haemangioblastomas and cavernomas. In inflammatory diseases, he should know when a brain examination is required. When faced with images appearing to show a tumour, he should consider the possibility of pseudotumours and in particular of granulomatoses. © 2012 Published by Elsevier Masson SAS on behalf of the Éditions françaises de radiologie. Source


Colinet H.,Catholic University of Leuven | Boivin G.,Agriculture and Agri Food Canada
Biological Control | Year: 2011

Storage at low temperature is a valuable method for increasing the shelf-life of natural enemies such as insect parasitoids. Cold storage is usually performed under sub-optimal temperatures, and therefore it is generally associated with major fitness costs. Tolerance to cold storage is a very plastic trait influenced by a wide range of endogenous (biotic) and exogenous (abiotic) factors experienced before, during, or after cold exposure. In fact, every hierarchical level from inter-species to inter-individuals shows a high plasticity in the response to cold exposure. Mortality represents the ultimate level of a range of sub-lethal perturbations accumulating during chilling. Even if individuals remain alive after cold storage, a reduction of several fitness-related traits may be observed directly, later in development or even in the next generation. The present review focuses on cold storage of insect parasitoids. We first consider the genotypic-based plasticity in cold storage tolerance and the complex network of endogenous and exogenous factors affecting the phenotypic plasticity in cold storage tolerance. We also summarize and examine the wealth of fitness-related traits affected by cold storage in parasitoids. This review provides a comprehensive list of documented factors that must be taken into account when designing cold storage protocols. © 2011 Elsevier Inc. Source


Vlieghe J.,Catholic University of Leuven
Sport, Education and Society | Year: 2013

In this article we try to think in new ways about the educational relevance of physical exercise at school, revisiting a concrete practice that is mostly seen as superseded, namely Swedish gymnastics. A phenomenological analysis of this 'forgotten' discipline will show that physical education might be taken in a very literal sense as the exercising of the body properly. Going against the criticism that this kind of gymnastics necessarily implies the subordination of corporeity to biopolitical regimes, we argue (referring to the work of Canetti and Agamben) that this practice might set physical activity free of any meaning whatsoever, and that it therefore might grant an experience of corporeal democracy. We argue furthermore that on this point Swedish gymnastics is opposed to other activities and especially sport, which have become dominant today. We hope that our analysis can stimulate the debate concerning the activities physical education-curricula should comprise. © 2013 Copyright Taylor and Francis Group, LLC. Source


Van Schaeybroeck B.,Catholic University of Leuven
Physica A: Statistical Mechanics and its Applications | Year: 2013

Motivated by the recent experiments on Bose-Einstein mixtures with tunable interactions we study repulsive weakly interacting Bose mixtures at finite temperature. We obtain phase diagrams using Hartree-Fock theory which are directly applicable to experimentally trapped systems. Almost all features of the diagrams can be characterized using simple physical insights. Our work reveals two surprising effects which are dissimilar to a system at zero temperature. First of all, no pure phases exist, that is, at each point in the trap, particles of both species are always present. Second, even for very weak interspecies repulsion when full mixing is expected, condensate particles of both species may be present in a trap without them being mixed. © 2013 Elsevier B.V. All rights reserved. Source


Clemen C.S.,University of Cologne | Herrmann H.,German Cancer Research Center | Strelkov S.V.,Catholic University of Leuven | Schroder R.,Friedrich - Alexander - University, Erlangen - Nuremberg
Acta Neuropathologica | Year: 2013

The intermediate filament protein desmin is an essential component of the extra-sarcomeric cytoskeleton in muscle cells. This three-dimensional filamentous framework exerts central roles in the structural and functional alignment and anchorage of myofibrils, the positioning of cell organelles and signaling events. Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive, and sporadic myopathies and/or cardiomyopathies with marked phenotypic variability. The disease onset ranges from childhood to late adulthood. The clinical course is progressive and no specific treatment is currently available for this severely disabling disease. The muscle pathology is characterized by desmin-positive protein aggregates and degenerative changes of the myofibrillar apparatus. The molecular pathophysiology of desminopathies is a complex, multilevel issue. In addition to direct effects on the formation and maintenance of the extra-sarcomeric intermediate filament network, mutant desmin affects essential protein interactions, cell signaling cascades, mitochondrial functions, and protein quality control mechanisms. This review summarizes the currently available data on the epidemiology, clinical phenotypes, myopathology, and genetics of desminopathies. In addition, this work provides an overview on the expression, filament formation processes, biomechanical properties, post-translational modifications, interaction partners, subcellular localization, and functions of wild-type and mutant desmin as well as desmin-related cell and animal models. © 2012 Springer-Verlag Berlin Heidelberg. Source


Van Eldere J.,Catholic University of Leuven | Van Eldere J.,University Hospital Leuven | Slack M.P.E.,Public Health England | Ladhani S.,Public Health England | Cripps A.W.,Griffith University
The Lancet Infectious Diseases | Year: 2014

Non-typeable Haemophilus influenzae (NTHi) is a major cause of mucosal infections such as otitis media, sinusitis, conjunctivitis, and exacerbations of chronic obstructive pulmonary disease. In some regions, a strong causal relation links this pathogen with infections of the lower respiratory tract. In the past 20 years, a steady but constant increase has occurred in invasive NTHi worldwide, with perinatal infants, young children, and elderly people most at risk. Individuals with underlying comorbidities are most susceptible and infection is associated with high mortality. β-lactamase production is the predominant mechanism of resistance. However, the emergence and spread of β-lactamase-negative ampicillin-resistant strains in many regions of the world is of substantial concern, potentially necessitating changes to antibiotic treatment guidelines for community-acquired infections of the upper and lower respiratory tract and potentially increasing morbidity associated with invasive NTHi infections. Standardised surveillance protocols and typing methodologies to monitor this emerging pathogen should be implemented. International scientific organisations need to raise the profile of NTHi and to document the pathobiology of this microbe. © 2014 Elsevier Ltd. Source


Moelans N.,Catholic University of Leuven
Acta Materialia | Year: 2011

The aimed properties of the interpolation functions used in quantitative phase-field models for two-phase systems do not extend to multi-phase systems. Therefore, a new type of interpolation functions is introduced that has a zero slope at the equilibrium values of the non-conserved field variables representing the different phases and allows for a thermodynamically consistent interpolation of the free energies. The interpolation functions are applicable for multi-phase-field and multi-order-parameter representations and can be combined with existing quantitative approaches for alloys. A model for polycrystalline, multi-component and multi-phase systems is formulated using the new interpolation functions that accounts in a straightforward way for composition-dependent expressions of the bulk Gibbs energies and diffusion mobilities, and interfacial free energies and mobilities. The numerical accuracy of the approach is analyzed for coarsening and diffusion-controlled parabolic growth in Cu-Sn systems as a function of R/ℓ, with R grain size and ℓ diffuse interface width. © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Source


Evenepoel P.,Catholic University of Leuven | Vervloet M.G.,VU University Amsterdam
Kidney International | Year: 2016

The increased awareness that disorders of phosphorus metabolism occur early in the course of chronic kidney disease fuels interest in early intervention strategies. A post hoc analysis of data from the Modification of Diet in Renal Disease (MDRD) Study questions the clinical relevance of early dietary phosphate restriction, so far considered a mainstay in the prevention and treatment of mineral metabolism disorders. Still, on the basis of available evidence, a cease-fire in the war on dietary phosphate would be premature. © 2016 International Society of Nephrology. Source


Saimoto S.,Queens University | Van Houtte P.,Catholic University of Leuven
Acta Materialia | Year: 2011

A constitutive relation based on crystal plasticity was derived by equating the energy of dislocations required to generate the imposed incremental strain with that which was stored as determined from the flow stress. The dynamic annihilation of created dislocations was accounted for by using a factor to balance the equation. The specific case of Taylor's parabolic relation was reproduced and microstructure-based parameters were explicitly formulated in the proportionality constant usually attributed as empirical in the Hollomon relation. The nearly precise replication of the stress-strain relation using at least two curve-fits for aluminum and its alloys validates the quantitative determination of the mean slip distance. The intersection of the two fits appears to be analogous to Stage II to III transition, which was confirmed by analysis of [1 1 1] and [1 0 0] single-crystal studies taken from the literature. The correlation of the flow stress with inverse mean slip distance and deformation cell size, together with the measured stored work, permitted an insight into this Stage II to III transition. The analysis suggests that dynamic-recovery effect in Stage III may be attributed to the change in mean slip distance pattern due to the evolution of cells. © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Source


Rossi B.,Catholic University of Leuven
Thin-Walled Structures | Year: 2014

Recent years have seen an increase in the use of stainless steel in buildings, mainly owing to its corrosion properties and therefore long service life. Among stainless steels, ferritic and lean duplex grades are characterized by low nickel content resulting in a more cost-stable and economic material compared to austenitic stainless steels. These grades have comparable (or even higher) strength than carbon steel and good corrosion resistance at lower cost. That is why, lately, they have been more often used in structural components. In this paper, attention is first paid to the advantages associated with the use of stainless steel in recent construction projects in view of sustainability. Second, life cycle analysis and the background of the new European standard EN 15804 are introduced, including module D, which allows credits to be taken now for the eventual reuse or recycling of material in the future, at the end-of-life stage. Life cycle inventories of stainless steel products (cold-rolled coils and quarto plate) are presented. Depending on the fraction of material recovered at the end of the lifespan, two potential impacts (Primary Energy Demand and Global Warming Potential) are presented for four grades: 1.4301 (AISI 304) and 1.4401 (AISI 316) austenitic grades, 1.4016 (AISI 430) ferritic grade and 1.4462 (AISI 2205) duplex grade. The influence of module D is underlined. © 2014 Elsevier Ltd. Source


Baeck M.,Catholic University of Louvain | Goossens A.,Catholic University of Leuven
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2012

Background Although unexpected and paradoxical, allergic hypersensitivity to corticosteroids is a common finding, delayed-type reactions being much more frequently encountered than the immediate-type ones. Although the skin is the main sensitization and elicitation route, other routes, amongst them systemic administration of corticosteroids may exceptionally be involved. Objective To determine the frequency, clinical presentation and cross-reactivity patterns for allergic reactions following systemic administration of corticosteroids amongst patients with identified and investigated 'contact allergy' to corticosteroids. Methods We reviewed clinical data, patch test results and sensitization sources in patients who reacted positively to corticosteroids tested in the K.U. Leuven Dermatology department during an 18-year period. Results Sixteen subjects (out of 315 with CS delayed-type hypersensitivity) presented with allergic manifestations due to systemic administration of corticosteroids. Most patients reacted to molecules from the three groups of the recently reappraised classification. Conclusion The reactions observed seem to be in most cases 'systemic contact dermatitis' due to oral or parenteral re-exposure of sensitized individuals with the respective corticosteroids previously applied topically. Moreover, most patients seem to be able to react to any corticosteroid molecules and therefore need a systematic individualized evaluation of their sensitization/tolerance profile. © 2012 John Wiley & Sons A/S. Source


Mathieu C.,Catholic University of Leuven
Diabetes Research and Clinical Practice | Year: 2015

The potential beneficial effects of supplementing vitamin D or treatment with pharmacological doses of vitamin D in the prevention or cure of diseases like type 1 (T1D) or type 2 diabetes (T2D) remains the subject of debate. Data from epidemiological and association studies clearly indicate a correlation between vitamin D deficiency and a higher prevalence of both forms of diabetes. In animal models, vitamin D deficiency predisposes to type 1 and type 2 diabetes, whereas high doses of vitamin D or its active hormonal form, 1,25-dihydroxyvitamin D, prevent disease. Large scale, randomized, blinded prospective studies however, remain lacking. Here we discuss the current literature on a role for vitamin D in diabetes. We propose, in particular, to avoid vitamin D deficiency in individuals at risk of developing T1D or T2D. Applying international guidelines on supplementation of vitamin D using small daily doses of vitamin D (500-1000. IU) may contribute to reduce the burden of diabetes by preventing vitamin D deficiency. Any other recommendations are at present not supported by data. © 2015 Elsevier Ireland Ltd. Source


To prospectively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index, two logistic regression models, and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result. Prospective temporal and external validation of simple ultrasound rules to distinguish benign from malignant adnexal masses. The rules comprised five ultrasonic features (including shape, size, solidity, and results of colour Doppler examination) to predict a malignant tumour (M features) and five to predict a benign tumour (B features). If one or more M features were present in the absence of a B feature, the mass was classified as malignant. If one or more B features were present in the absence of an M feature, it was classified as benign. If both M features and B features were present, or if none of the features was present, the simple rules were inconclusive. 19 ultrasound centres in eight countries. 1938 women with an adnexal mass examined with ultrasound by the principal investigator at each centre with a standardised research protocol. Reference standard Histological classification of the excised adnexal mass as benign or malignant. Diagnostic sensitivity and specificity. Of the 1938 patients with an adnexal mass, 1396 (72%) had benign tumours, 373 (19.2%) had primary invasive tumours, 111 (5.7%) had borderline malignant tumours, and 58 (3%) had metastatic tumours in the ovary. The simple rules yielded a conclusive result in 1501 (77%) masses, for which they resulted in a sensitivity of 92% (95% confidence interval 89% to 94%) and a specificity of 96% (94% to 97%). The corresponding sensitivity and specificity of subjective assessment were 91% (88% to 94%) and 96% (94% to 97%). In the 357 masses for which the simple rules yielded an inconclusive result and with available results of CA-125 measurements, the sensitivities were 89% (83% to 93%) for subjective assessment, 50% (42% to 58%) for the risk of malignancy index, 89% (83% to 93%) for logistic regression model 1, and 82% (75% to 87%) for logistic regression model 2; the corresponding specificities were 78% (72% to 83%), 84% (78% to 88%), 44% (38% to 51%), and 48% (42% to 55%). Use of the simple rules as a triage test and subjective assessment for those masses for which the simple rules yielded an inconclusive result gave a sensitivity of 91% (88% to 93%) and a specificity of 93% (91% to 94%), compared with a sensitivity of 90% (88% to 93%) and a specificity of 93% (91% to 94%) when subjective assessment was used in all masses. The use of the simple rules has the potential to improve the management of women with adnexal masses. In adnexal masses for which the rules yielded an inconclusive result, subjective assessment of ultrasonic findings by an experienced ultrasound examiner was the most accurate diagnostic test; the risk of malignancy index and the two regression models were not useful. Source


Hartle J.,University of California at Santa Barbara | Hertog T.,Catholic University of Leuven
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

In a quantum theory of gravity spacetime behaves classically when quantum probabilities are high for histories of geometry and field that are correlated in time by the Einstein equation. Probabilities follow from the quantum state. This quantum perspective on classicality has important implications. (a) Classical histories are generally available only in limited patches of the configuration space on which the state lives. (b) In a given patch, states generally predict relative probabilities for an ensemble of possible classical histories. (c) In between patches classical predictability breaks down and is replaced by quantum evolution connecting classical histories in different patches. (d) Classical predictability can break down on scales well below the Planck scale, and with no breakdown in the classical equations of motion. We support and illustrate (a)-(d) by calculating the quantum transition across the de Sitter-like throat connecting asymptotically classical, inflating histories in the no-boundary quantum state. This supplies probabilities for how a classical history on one side transitions and branches into a range of classical histories on the opposite side. We also comment on the implications of (a)-(d) for the dynamics of black holes and eternal inflation. © 2015 American Physical Society. Source


Van De Velde M.,Catholic University of Leuven
Current Opinion in Anaesthesiology | Year: 2016

Purpose of review The purpose is to review the neonatal and maternal effects of remifentanil given at induction of general anesthesia for caesarean section and prior to delivery of the baby. Main findings Remifentanil seems to have short-lived respiratory depressant effects in approximately 50% of neonates, requiring short periods of mask ventilation or tactile stimulation of the neonate. Remifentanil produces excellent maternal hemodynamic stability avoiding tachycardia and hypertension, possibly reducing the risk of maternal awareness. Summary Remifentanil can be safely used at induction of general anesthesia provided healthcare workers are available to manage short-lived neonatal depression. © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source


Van Rompuy A.S.,Catholic University of Leuven
Journal of neuropathology and experimental neurology | Year: 2014

Mutations in the parkin gene are the most common cause of early-onset autosomal recessive Parkinson disease (PD). The pathogenic mechanisms of how parkin mutations lead to the development of PD are not fully understood. Studies of cell cultures and of Drosophila have suggested a dominant negative effect for the clinical parkin mutant T240R. Conversely, the neuroprotective capacity of parkin has been widely reported; this suggests that the parkin protein may have a potential therapeutic role in PD. Here, we aimed to develop a novel genetic rodent model of PD by overexpression of T240R-parkin and human wild-type parkin as a control in the dopaminergic neurons of adult rats using adeno-associated viral vectors (rAAV2/8). Surprisingly, we found that overexpression not only of T240R-parkin but also of human wild-type parkin induced progressive and dose-dependent dopaminergic cell death in rats, starting from 8 weeks after injection. This degeneration was specific for parkin because similar overexpressionof enhanced green fluorescent protein did not lead to nigral degeneration. Our results warrant caution to the development of therapeutic strategies for PD based on overexpression of parkin or enhancing parkin activity because this might be deleterious for dopaminergic neurons in the long-term. Source


Bertrand A.,Catholic University of Leuven
2011 18th IEEE Symposium on Communications and Vehicular Technology in the Benelux, SCVT 2011 | Year: 2011

Wireless microphone networks or so-called wireless acoustic sensor networks (WASNs) are a next-generation technology for audio acquisition and processing. As opposed to traditional microphone arrays that sample a sound field only locally, often at large distances from the relevant sound sources, WASNs allow to use many more microphones to cover a large area of interest. However, the design of such WASNs is very challenging, especially for real-time audio acquisition and signal enhancement due to the significant data traffic in the network. There is a need for scalable solutions, both on the signal processing level and on the network-communication level. In this paper, we give an overview of applications and trends in the field of WASNs, and we address the core challenges that need to be tackled. We mainly focus on the signal processing level, and we explain how advances in the area of signal processing can relax the high-demanding constraints on the network layer design. Furthermore, we address the interaction between the application layer and the network layer, and we explain why cross-layer design can be important to improve the performance of WASN applications. © 2011 IEEE. Source


Happaerts S.,Catholic University of Leuven
Environmental Policy and Governance | Year: 2012

Subnational governments (such as provinces, states or regions) are largely ignored in international policy documents on sustainable development, and they are not recognized in multilateral decision-making. Nevertheless, many subnational governments have launched sustainable development policies. This article examines to what extent they take global sustainable development governance into account when doing so. The theoretical framework presents two mechanisms of international influence, building mostly upon the policy convergence literature. That framework is then applied on a comparative policy analysis of five subnational governments: North Holland (the Netherlands), North Rhine-Westphalia (Germany), Wallonia (Belgium), Flanders (Belgium) and Quebec (Canada). The findings show that subnational governments with a distinct territorial identity react differently on international trends from other subnational governments. Flanders and Quebec, which have such an identity, follow the rules and decision-making procedures of the international sustainable development regime, and they translate the norms and principles into their policies. The article also finds that the influence of international policies is determined by the active participation of subnational governments in multilateral decision-making. Finally, it is argued that the legitimacy pressures exerted by international organizations on lower-level governments to adopt certain policies have a varying impact on subnational governments dependent on their domestic context. © 2012 John Wiley & Sons, Ltd and ERP Environment. Source


Calsteren K.V.,Catholic University of Leuven
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | Year: 2010

The paucity of data on fetal effects of prenatal exposure to chemotherapy prompted us to study the transplacental transport of commonly used anticancer agents in a pregnant baboon model. Single or combination chemotherapy with paclitaxel, docetaxel, carboplatin, and trastuzumab was administered to 9 baboons at a mean (SD) gestational age of 117 (26) days (paclitaxel, 100 mg/m2 [n = 2]; docetaxel, 100 mg/m2 [n = 2]; paclitaxel, 175 mg/m2 with carboplatin, area under the curve of 6 at standard dosage [n = 2] and 50% dosage [n = 1]; docetaxel, 75 mg/m2 with carboplatin, area under the curve 6 [n = 1]; and docetaxel, 75 mg/m2 with trastuzumab, 8 mg/kg [n = 1]). Serial fetal and maternal blood samples, amniotic fluid, maternal urine, and fetal and maternal tissue samples were collected for the first 76 hours after drug infusion. Levels of carboplatin were determined by atomic absorption spectrometry, docetaxel and paclitaxel by high-performance liquid chromatography, and trastuzumab by enzyme-linked immunosorbent assay. Fetal plasma concentrations of carboplatin averaged 57.5% (14.2%) of maternal concentrations (n = 7). Fetal plasma concentrations were 1.5% (0.8%) of maternal concentrations (n = 7). Immediately after ending the infusion, paclitaxel was not detectable in fetal tissues, whereas, after 3 hours, fetal tissues contained 15% of maternal tissue concentrations.Docetaxel could not be detected in fetal blood samples (n = 9). In the first 3 hours after docetaxel infusion, fetal tissues contained 5.0% to 50.0% of maternal tissue concentrations, whereas equal fetal and maternal tissue concentrations were found after 26 and 76 hours.The transplacental passages of trastuzumab were 85.0% and 3.0%, 2 and 26 hours after trastuzumab infusion, respectively. After 26 hours, amniotic fluid contained 36.4% of the fetal plasma concentration. Fetal tissue concentrations varied between 5.0% and 14.0% of the maternal concentration. Variable plasma and/or tissue concentrations of taxanes, carboplatin, and trastuzumab were encountered in the fetal compartment. These data are important when cancer treatment is considered during pregnancy and underline the need for long-term follow-up of children after prenatal exposure to these cytotoxic agents. Source


Heusch G.,University of Duisburg - Essen | Ovize M.,Service dExplorations Fonctionnelles Cardiovasculaires | Van De Werf F.,Catholic University of Leuven
Journal of the American College of Cardiology | Year: 2015

The damage inflicted on the myocardium during acute myocardial infarction is the result of 2 processes: ischemia and subsequent reperfusion (ischemia/reperfusion injury). During the last 3 decades, therapies to reduce ischemic injury (mainly reperfusion strategies) have been widely incorporated into clinical practice. The remarkable reduction in death rates achieved with these therapies has resulted in a shift in emphasis from efforts to reduce mortality to a focus on tackling the downstream consequence of survival: post-infarction heart failure. Infarct size is the main determinant of long-term mortality and chronic heart failure, and thus, the possibility of limiting the extent of necrosis during an ST-segment elevation myocardial infarction is of great individual and socioeconomic value. After the great success of therapies to reduce ischemic injury, the time has come to focus efforts on therapies to reduce reperfusion injury, but in the recent few years, few interventions have successfully passed the proof-of-concept stage. In this review, we examine the past, present, and future therapies to reduce ischemia/reperfusion injury. © 2015 American College of Cardiology Foundation. Source


Castryck W.,Catholic University of Leuven
Discrete and Computational Geometry | Year: 2012

We review previous work of (mainly) Koelman, Haase and Schicho, and Poonen and Rodriguez-Villegas on the dual operations of (i) taking the interior hull and (ii) moving out the edges of a two-dimensional lattice polygon. We show how the latter operation naturally gives rise to an algorithm for enumerating lattice polygons by their genus. We then report on an implementation of this algorithm, by means of which we produce the list of all lattice polygons (up to equivalence) whose genus is contained in {1,..,30}. In particular, we obtain the number of inequivalent lattice polygons for each of these genera. As a byproduct, we prove that the minimal possible genus for a lattice 15-gon is 45. © 2011 Springer Science+Business Media, LLC. Source


Bultynck G.,Catholic University of Leuven
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2016

Bone metastases of tumor cells are a common and life-threatening feature of a variety of late-stage cancers, including breast cancers. However, until now, much less has been known about the intrinsic anti-metastatic properties of the bones and how these could be exploited to prevent or treat bone metastases. Very recently, native Cx43 hemichannels present in osteocytes have been identified as important anti-metastatic signaling complexes by establishing high local extracellular ATP levels. Moreover, bisphosphonate drugs, applied as adjuvant therapies in the treatment of breast cancer patients and bone diseases, are known to display anti-metastatic properties. Now, it became clear that these compounds exert their effects through osteocyte Cx43 hemichannels, thereby triggering their opening and promoting ATP release in the extracellular micro-environment. Hence, endogenous osteocyte Cx43 hemichannels emerge as important and promising therapeutic targets for the prevention of bone metastases and/or clinical treatment of bone-metastasized breast cancers. © 2016 Elsevier B.V. Source


Roskams T.,Catholic University of Leuven | Kojiro M.,Kurume University
Seminars in Liver Disease | Year: 2010

Recently, an EastWest consensus on the histopathologic criteria for the diagnosis of high-grade dysplastic nodules (HGDN) versus early hepatocellular carcinoma (HCC) was reached. Next to classical morphologic criteria such as nucleocytoplasmic ratio, thickness of cell plates, mitotic index, and architectural disturbance like acinar structures, one of the most relevant criteria to diagnose early HCC is stromal invasion. Because a structured basement membrane is lacking along the hepatocytes in the liver, invasion cannot be defined as tumor growth through the basement membrane as in other tissues. However, the number of portal tracts that are present in a nodule gradually decrease because the tumoral hepatocytes start to show a destructive invading growth pattern in the mesenchyma/stroma of these portal tracts. This feature of stromal invasion is however sometimes difficult to recognize in needle biopsies because included portal tracts can be absent. Therefore, other diagnostic criteria are necessary. Based on molecular profiling, several additional markers for early malignant HCC have been found recently. Glypican-3, heat shock protein 70, and glutamine synthetase have been already validated and can be used as a panel of stains to confirm the pathologist's histopathologic diagnosis and to solve difficult cases. © 2010 by Thieme Medical Publishers, Inc. Source


Depoortere I.,Catholic University of Leuven
Gut | Year: 2014

Recent progress in unravelling the nutrient-sensing mechanisms in the taste buds of the tongue has triggered studies on the existence and role of chemosensory cells in the gut. Indeed, the gastrointestinal tract is the key interface between food and the human body and can sense basic tastes in much the same way as the tongue, through the use of similar G-protein-coupled taste receptors. These receptors 'taste' the luminal content and transmit signals that regulate nutrient transporter expression and nutrient uptake, and also the release of gut hormones and neurotransmitters involved in the regulation of energy and glucose homeostasis. Hence, they play a prominent role in the communication between the lumen, epithelium, smooth muscle cells, afferent nerve fibres and the brain to trigger adaptive responses that affect gastrointestinal function, food intake and glucose metabolism. This review summarises how sensing of nutrients by taste receptors along the gut plays a key role in the process of digestion, and how disturbances or adaptations of these chemosensory signalling pathways may contribute to the induction or resolution of a number of pathological conditions related to diabetes, obesity, or diet-induced symptom generation in irritable bowel syndrome. Targeting these receptors may represent a promising novel route for the treatment of a number of these diseases. Source


Van Den Berghe G.,Catholic University of Leuven
Thyroid | Year: 2014

Conclusions: It is clear that the name "NTI" during critical illness refers to a syndrome with different faces. Tolerating the early "fasting response" to critical illness and its concomitant changes in thyroid hormone parameters appears to be wise and beneficial. This thus applies to the NTI present in the majority of the patients treated in intensive care units. However, the NTI that occurs in prolonged critically ill patients appears different with regard to both its causes and consequences. Future studies should specifically target this selected population of prolonged critically ill patients, and, after excluding iatrogic drug interferences, investigate the effect on outcome of treatment with hypothalamic releasing factors in adequately powered randomized controlled trials.Background: Critically ill patients typically present with low or low-normal plasma thyroxine, low plasma triiodothyronine (T3), increased plasma reverse T3 (rT3) concentrations, in the absence of a rise in thyrotropin (TSH). This constellation is referred to as nonthyroidal illness syndrome (NTI). Although it is long known that the severity of NTI is associated with risk of poor outcomes of critical illness, the causality in this association has not been well investigated.Summary: In this narrative review, the different faces of NTI during critical illness are highlighted. Acute alterations are dominated by changes in thyroid hormone binding, peripheral thyroid hormone uptake, and alterations in the expression and activity of the type-1 and type-3 deiodinases. It was recently shown that at least part of these acute changes are brought about by concomitant macronutrient restriction, and this part appears adaptive and beneficial. However, the face of the NTI in the prolonged phase of critical illness is different, when patients are fully fed but continue to depend on intensive medical care. In that prolonged phase of illness, hypothalamic thyrotropin releasing hormone (TRH) expression is suppressed and explains reduced TSH secretion and whereby reduced thyroidal hormone release. During prolonged critical illness, and in the presence of adequate nutrition, several tissue responses could be interpreted as compensatory to low thyroid hormone availability, such as increased expression of monocarboxylate transporters, upregulation of type-2 deiodinase activity, and increased sensitivity at the receptor level. Infusing hypothalamic releasing factors in these prolonged critically ill patients can reactivate the thyroid axis and induce an anabolic response. © Copyright 2014, Mary Ann Liebert, Inc. Source


Teirlinck P.,Catholic University of Leuven | Spithoven A.,Belgian Science Policy Office
Technovation | Year: 2013

The literature on 'open' innovation emphasises the need to engage in external knowledge relations in order to innovate. Particularly for SMEs, research cooperation and R&D outsourcing can offer possibilities to complement the often limited internal research resources. However, they also bring in their wake requirements in terms of absorptive capacity and managerial skills of the internal R&D personnel. The paper focuses on the different requirements in terms of availability and training of research managers and R&D experts for research cooperation versus R&D outsourcing in SMEs. An empirical analysis of micro-level data provided by the OECD business R&D survey for Belgium reveals that the relation between R&D personnel requirements and research collaboration and R&D outsourcing depends upon the SME size. Therefore, to study this subject appropriately a distinction between very small, small, and medium-sized firms is relevant. Very small firms engage significantly less in research cooperation than medium-sized firms and the propensity to engage in research cooperation is positively associated with the share of PhD holders among the research managers and R&D experts. For R&D outsourcing a lower involvement is noted in medium-sized firms, and the propensity to outsource increases with the formal qualification level of the R&D personnel and with R&D training. Among the SME, small firms are most engaged in research cooperation and in R&D outsourcing. In the case of research cooperation they rely on highly qualified experts. For R&D outsourcing activities both the presence of research managers and R&D experts is important. © 2012 Elsevier Ltd. Source


Srivastava A.K.,Aryabhatta Research Institute of Observational science ARIES | Goossens M.,Catholic University of Leuven
Astrophysical Journal | Year: 2013

We present rare observational evidence of vertical kink oscillations in a laminar and diffused large-scale plasma curtain as observed by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. The X6.9-class flare in active region 11263 on 2011 August 9 induces a global large-scale disturbance that propagates in a narrow lane above the plasma curtain and creates a low density region that appears as a dimming in the observational image data. This large-scale propagating disturbance acts as a non-periodic driver that interacts asymmetrically and obliquely with the top of the plasma curtain and triggers the observed oscillations. In the deeper layers of the curtain, we find evidence of vertical kink oscillations with two periods (795 s and 530 s). On the magnetic surface of the curtain where the density is inhomogeneous due to coronal dimming, non-decaying vertical oscillations are also observed (period 763-896 s). We infer that the global large-scale disturbance triggers vertical kink oscillations in the deeper layers as well as on the surface of the large-scale plasma curtain. The properties of the excited waves strongly depend on the local plasma and magnetic field conditions. © 2013. The American Astronomical Society. All rights reserved. Source


Henquin J.-C.,Catholic University of Leuven
Science Signaling | Year: 2012

Insulin secretion from pancreatic β cells is controlled by nutrients, hormones, and neurotransmitters. Unlike the latter, which work through classic receptors, glucose and most other nutrients do not interact with membrane receptors but must be metabolized by β cells to induce insulin secretion. Studies have revealed the presence of umami and sweet taste receptors and their downstream effectors in β cells. That the receptors are functional was established by the effects of fructose and artificial sweeteners, which induced signals similar to those produced in taste buds of the tongue. These signals mediated an increase in insulin secretion in the presence of glucose. However, the physiological implications of these pathways in insulin secretion are unclear because of the large differences between plasma concentrations of fructose or sweeteners and their effective concentrations in vitro. Source


Taymans J.-M.,Catholic University of Leuven
Biochemical Society Transactions | Year: 2012

LRRK2 (leucine-rich repeat kinase 2) is a large protein encoding multiple functional domains, including two catalytically active domains, a kinase and a GTPase domain. The LRRK2 GTPase belongs to the Ras- GTPase superfamily of GTPases, more specifically to the ROC (Ras of complex proteins) subfamily. Studies with recombinant LRRK2 protein purified from eukaryotic cells have confirmed that LRRK2 binds guanine nucleotides and catalyses the hydrolysis of GTP to GDP. LRRK2 is linked to PD (Parkinson's disease) and GTPase activity is impaired for several PD mutants located in the ROC and COR (C-terminal of ROC) domains, indicating that it is involved in PD pathogenesis. Ras family GTPases are known to function as molecular switches, and several studies have explored this possibility for LRRK2. These studies show that there is interplay between the LRRK2 GTPase function and its kinase function, with most data pointing towards a role for the kinase domain as an upstream regulator of ROC. The GTPase function is therefore a pivotal functionality within the LRRK2-mediated signalling cascade which includes partners encoded by other LRRK2 domains as well as other cellular signalling partners. The present review examines what is known of the enzymatic properties of the LRRK2 GTPase, the interplay between ROC and other LRRK2 domains, and the interplay between ROC and other cellular proteins with the dual goal to understand how LRRK2 GTPase affects cellular functions and point to future research venues. ©The Authors Journal compilation ©2012 Biochemical Society. Source


The past decade has seen a growing interest in evolutionary models that relax the assumption of site-independent evolution for non-coding sequences. While phylogenetic inference using such so-called context-dependent models is currently computationally prohibitive, these models have been shown to yield significant increases in model fit compared to site-independent evolutionary models, which remain the most widely used evolutionary models to study substitution patterns and perform phylogenetic inference. Context-dependent models have been shown to be suited to study the spontaneous deamination of cytosine in mammalian sequences. In this paper, I discuss various approaches presented in recent years to model context-dependent evolution. I start with discussing the empirical research and results that have led to the development of these models. To accurately estimate the context-dependent substitution patterns that arise from these models, accurate sampling of substitution histories under such models is required. Further, appropriate model selection techniques to assess model performance has become more important than ever, given the drastic increase in parameters of context-dependent models and the tendency of older model selection techniques to prefer parameter-rich models. I also present new results on two mammalian datasets (Primate and Laurasiatheria data) to shed a light on so-called lineage-dependent context-dependent evolution. I conclude this paper with a discussion on current challenges in the development of context-dependent modeling approaches. © 2011 Springer Science+Business Media, LLC. Source


Gheorghiu E.,Catholic University of Leuven
Journal of vision | Year: 2012

Evidence that contour-shapes and texture-shapes are processed by different mechanisms included the finding that contour-shape aftereffects are reduced when the adaptation stimulus is a texture made of contours rather than a single contour. This phenomenon has been termed texture-surround suppression of contour-shape, or TSSCS. How does TSSCS operate and over what spatial extent? We measured the postadaptation shift in the apparent shape frequency of a single sinusoidal-shaped contour as a function of the number of contours in the adaptor stimulus. Contours were Gabor strings in which the Gabor orientations were either tangential (snakes) or orthogonal (ladders) to the path of the contour. We found that for extended surrounds, the aftereffect was strongly reduced when the surround contours were the same as the central adaptor contour, but not when the Gabors making up the surround contours were opposite-in-orientation to those of the central adaptor. For near surrounds, the aftereffect in a snake contour was unaffected by same-orientation but strongly suppressed by opposite-orientation surrounds, whereas the aftereffect for a ladder-contour was suppressed equally by both same- and opposite-orientation near surrounds. Finally, the strength of surround suppression decreased gradually with increasing spatial separation between center and surround. These results indicate that there are two components to texture-surround suppression in our shape aftereffect: one that is sensitive to opposite-orientation texture surrounds, operates locally, and disrupts contour-processing; the other that is sensitive to same-orientation texture surrounds, is spatially extended, and prevents the shape of the contour from being processed as a contour. We also demonstrate that the observed shape aftereffects are not due to changes in the apparent shape-frequency of the adaptors or the precision with which their shape-frequency is encoded, indicating that TSSCS is not an instance of crowding. Source


Severijns N.,Catholic University of Leuven
Journal of Physics G: Nuclear and Particle Physics | Year: 2014

The beta-decay process offers unique possibilities for testing the fundamental symmetries of the standard model and searching for non-standard model components in the weak interaction. Here a non-exhaustive review of this field is given highlighting a number of key experiments or recently performed experiments. Also included are new and ongoing developments providing new opportunities for further significant progress in this research field in the era of the large hadron collider. © 2014 IOP Publishing Ltd. Source


Football turf is increasingly used in European soccer competition. Little is known on the rotational torque that players experience on these fields. High rotational torques between the shoe outsole and the sports surface has been correlated with torsional injuries of the lower limb and knee. To evaluate the effect of six parameters that could influence the rotational torque between the shoe outsole and the latest generation football turf. Controlled laboratory study. A testing apparatus was constructed to measure the peak torque generated during a controlled rotation of the foot. Six parameters that could potentially influence the frictional forces, were considered: (1) the sports surface, (2) the shoe outsole cleat design, (3) the weather conditions, (4) the weight, (5) the presence of an impact and (6) the direction of rotation. The football turf without infill showed significantly lower frictional torques than natural grass whereas a football turf with sand/rubber infill had significantly higher torques. Blades were associated with significantly higher torques than studs on natural grass and on one football turf with sand/rubber infill. Dry weather was associated with higher torques only for the football turf without infill. The torque increased linearly and significantly with an increasing vertical load. The rotational torque increased significantly following an impact. Torques on external rotational movements were significantly higher with blades. Important differences in rotational torques are found and could be seen as potential risk factors for torsional injuries of the lower limb. Source


Scagliotti G.V.,University of Turin | Bironzo P.,University of Turin | Vansteenkiste J.F.,Catholic University of Leuven
Cancer Treatment Reviews | Year: 2015

Chemotherapy is currently the standard of care for non-oncogene-driven advanced non-small cell lung cancer (NSCLC). Due to improvements in chemotherapeutic choices and supportive care, patients currently typically undergo multiple lines of chemotherapy as their disease progresses. Although treatments have improved over recent years, limited benefits are seen, especially in patients receiving later-line chemotherapy, as response rates can be low, response duration short and survival poor. Furthermore, only a small percentage of patients derive benefit from later-line therapy, with most experiencing deteriorating quality of life and significant toxicities. More recently, molecular targeted therapies have provided improvements in outcomes. However, these treatments only offer a clear benefit in subsets of tumours harbouring the appropriate genomic alteration (mutation, amplification, translocation). Most of the genomic abnormalities susceptible to therapeutic intervention are detected in adenocarcinoma, mainly in never smokers, while alterations in the genome of other histological subtypes are known but specific agents targeting these alterations have yet to be developed. Thus, the therapeutic management of these subtypes represents an ongoing challenge. Recent advances in immunotherapy have highlighted the potential of immuno-oncology based treatments for NSCLC, offering the potential to provide durable responses and outcomes regardless of histology or mutation status. This review discusses the current unmet medical needs in NSCLC, the limits of current first-line and later-line chemotherapy and targeted agents, and the emergence of new therapeutic strategies. © 2015 Elsevier Ltd. Source


Papavasiliou A.,Catholic University of Leuven | Oren S.S.,University of California at Berkeley
Operations Research | Year: 2013

In this paper we present a unit commitment model for studying the impact of large-scale wind integration in power systems with transmission constraints and system component failures. The model is formulated as a two-stage stochastic program with uncertain wind production in various locations of the network as well as generator and transmission line failures. We present a scenario selection algorithm for selecting and weighing wind power production scenarios and composite element failures, and we provide a parallel dual decomposition algorithm for solving the resulting mixed-integer program. We validate the proposed scenario selection algorithm by demonstrating that it outperforms alternative reserve commitment approaches in a 225 bus model of California with 130 generators and 375 transmission lines. We use our model to quantify day-ahead generator capacity commitment, operating cost impacts, and renewable energy utilization levels for various degrees of wind power integration. We then demonstrate that failing to account for transmission constraints and contingencies can result in significant errors in assessing the economic impacts of renewable energy integration. ©2013 INFORMS. Source


Mehta V.P.,University of Gottingen | Van Der Eycken E.V.,Catholic University of Leuven
Chemical Society Reviews | Year: 2011

Among the fundamental transformations in the field of synthetic organic chemistry, transition-metal-catalyzed reactions provide some of the most attractive methodologies for the formation of C-C and C-heteroatom bonds. As a result, the application of these reactions has increased tremendously during the past decades and cross-coupling reactions became a standard tool for synthetic organic chemists. Furthermore, a tremendous upsurge in the development of new catalysts and ligands, as well as an increased understanding of the mechanisms, has contributed substantially to recent advances in the field. Traditionally, organic reactions are carried out by conductive heating with an external heat source (for example, an oil bath). However, the application of microwave irradiation is a steadily gaining field as an alternative heating mode since its dawn at the end of the last century. This tutorial review focuses on some of the recent developments in the field of cross-coupling reactions assisted by microwave irradiation. © 2011 The Royal Society of Chemistry. Source


Li X.,CAS Dalian Institute of Chemical Physics | Zhang H.,CAS Dalian Institute of Chemical Physics | Mai Z.,CAS Dalian Institute of Chemical Physics | Vankelecom I.,Catholic University of Leuven
Energy and Environmental Science | Year: 2011

The vanadium redox flow battery (VRB) has received wide attention due to its attractive features for large scale energy storage. The key material of a VRB is an ion exchange membrane (IEM) that prevents cross mixing of the positive and negative electrolytes, while still allowing the transport of ions to complete the circuit during the passage of current. This review focuses on all aspects related to IEMs that are of relevance to understand IEMs better. An overview of the general issues of VRBs will be given first, after which the role of the IEM will be outlined together with the material requirements for advanced alternative IEMs. Finally, the recent progress of IEMs in VRBs will be reviewed and directions will be given for the development of next-generation materials. © 2011 The Royal Society of Chemistry. Source


Verschueren K.,Catholic University of Leuven | Koomen H.M.Y.,University of Amsterdam
Attachment and Human Development | Year: 2012

This special issue aims to prompt reflection on the mutual contribution of attachment theory, on the one hand, and teacher-child relationship research, on the other, by bringing together conceptual and empirical contributions taking an attachment perspective on teacher-child relationships. In this introductory article, we contend that the teacher can be regarded as an ad hoc attachment figure with a safe haven and secure base function, although for most children the relationship with the teacher is probably not an attachment bond. Furthermore, we explain how attachment theory and research: (1) shape the way in which "high quality" teacher-child relationships are conceptualized and operationalized; (2) highlight the importance of teacher sensitivity to children's needs, as a central proximal determinant of relationship quality; (3) guide research hypotheses regarding the consequences of teacher-child relationship quality and the intervening mechanisms; and (4) inspire the development of interventions to improve teacher-child relationships. © 2012 Copyright Taylor and Francis Group, LLC. Source


Van Den Bosch L.,Catholic University of Leuven
Journal of Biomedicine and Biotechnology | Year: 2011

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective death of motor neurons in the motor cortex, brainstem, and spinal cord. A large number of rodent models are available that show motor neuron death and a progressive motor phenotype that is more or less reminiscent of what occurs in patients. These rodent models contain genes with spontaneous or induced mutations or (over) express different (mutant) genes. Some of these models have been of great value to delineate potential pathogenic mechanisms that cause and/or modulate selective motor neuron degeneration. In addition, these genetic rodent models play a crucial role in testing and selecting potential therapeutics that can be used to treat ALS and/or other motor neuron disorders. In this paper, we give a systematic overview of the most important genetic rodent models that show motor neuron degeneration and/or develop a motor phenotype. In addition, we discuss the value and limitations of the different models and conclude that it remains a challenge to find more and better rodent models based on mutations in new genes causing ALS. © 2011 L. Van Den Bosch. Source


Desiron H.A.,Catholic University of Leuven
BMC public health | Year: 2011

The primary aim of this review study was to gather evidence on the effectiveness in terms of return to work (RTW) of occupational therapy interventions (OTIs) in rehabilitation patients with non-congenital disorders. A secondary aim was to be able to select the most efficient OTI. A systematic literature review of peer-reviewed papers was conducted using electronic databases (Cinahl, Cochrane Library, Ebsco, Medline (Pubmed), and PsycInfo). The search focussed on randomised controlled trials and cohort studies published in English from 1980 until September 2010. Scientific validity of the studies was assessed. Starting from 1532 papers with pertinent titles, six studies met the quality criteria. Results show systematic reviewing of OTIs on RTW was challenging due to varying populations, different outcome measures, and poor descriptions of methodology. There is evidence that OTIs as part of rehabilitation programs, increase RTW rates, although the methodological evidence of most studies is weak. Analysis of the selected papers indicated that OTIs positively influence RTW; two studies described precisely what the content of their OTI was. In order to identify the added value of OTIs on RTW, studies with well-defined OT intervention protocols are necessary. Source


Bellemans J.,Catholic University of Leuven
Orthopedics | Year: 2011

The so-called "pie crusting" technique using multiple stab incisions is a well-established procedure for correcting tightness of the iliotibial band in the valgus knee. It is, however, not applicable for balancing the medial side in varus knees because of the risk for iatrogenic transsection of the medial collateral ligament (MCL). This article presents our experience with a safer alternative and minimally invasive technique for medial soft tissue balancing, where we make multiple punctures in the MCL using a 19-gauge needle to progressively stretch the MCL until a correct ligament balance is achieved. Our technique requires minimal to no additional soft tissue dissection and can even be performed percutaneously when necessary. This technique, therefore, does not impact the length of the skin or soft tissue incisions. We analyzed 61 cases with varus deformity that were intraoperatively treated using this technique. In 4 other cases, the technique was used as a percutaneous procedure to correct postoperative medial tightness that caused persistent pain on the medial side. The procedure was considered successful when a 2- to 4-mm mediolateral joint line opening was obtained in extension and 2 to 6 mm in flexion. In 62 cases (95%), a progressive correction of medial tightness was achieved according to the above-described criteria. Three cases were overreleased and required compensatory release of the lateral structures and use of a thicker insert. Based on these results, we consider needle puncturing an effective and safe technique for progressive correction of MCL tightness during minimally invasive total knee arthroplasty. Source


Casaer M.P.,Catholic University of Leuven
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2015

PURPOSE OF REVIEW: Muscle wasting is common in severe critical illness. ICU-acquired weakness (ICU-AW) contributes to acute and long-term morbidity and mortality. The question remains whether nutrition therapy in ICU can prevent or attenuate these complications. This review aims at integrating the most recent clinical data in order to answer this important clinical and research question. Clinical evidence was obtained from randomized controlled trials (RCTs). Results from animal experiments and observational studies are referred to when - respectively - providing possible explanatory mechanisms or new hypotheses. RECENT FINDINGS: Although muscle wasting has been reproducibly quantified early in ICU, its relationship with ICU-AW has not yet been convincingly established. All recent RCTs evaluating increased energy/protein intake during ICU week 1 failed to demonstrate a protective effect against ICU-AW or physical function limitations. In one RCT, early parenteral nutrition increased the incidence of ICU-AW. The latter finding might be explained by suppressed autophagy. SUMMARY: Current evidence does not support improved physical function with increased energy/protein provision in the first ICU week. Future RCTs aimed at reducing the burden of ICU-AW and improving long-term function should particularly focus on nutrition beyond the acute phase of critical illness and on non-nutritional interventions such as early mobilization. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source


Gender is seen as the most important factor related to different levels of fear of crime, with women consistently reporting higher levels of fear than men. Several explanations have been elaborated, which largely focus either on the irrationally high level of female fear or (from a feminist perspective) on the impact of differential socialization processes, with women being socialized as fearful subjects compared to 'fearless' men. However, both explanations imply a rather static interpretation of the gender-fear relation. In this paper, the 'doing gender' thesis (West and Zimmerman 1987) is adopted to develop a gender identity scale, using a broad range of attitudes and activities dominantly seen as masculine or feminine in a sample of Belgian adolescents and young adults. The extent to which this gender identity scale is able to explain differences in the level of fear of crime, and may therefore account for the gender gap, is discussed. © The Author 2010. Published by Oxford University Press on behalf of the Centre for Crime and Justice Studies (ISTD). Source


Depoortere I.,Catholic University of Leuven
Current Opinion in Pharmacology | Year: 2012

GPR39 is an orphan GPCR receptor belonging to the ghrelin/motilin receptor subfamily. The receptor is constitutively active and Zn2+ is a physiological agonist of GPR39. The receptor is emerging as an important regulator of gastrointestinal motility and secretion. Although GPR39 does not seem to be involved in the regulation of food intake, contradictory results are available on the role of GPR39 in the regulation of body weight. A well-established stimulatory role for GPR39 has been defined in insulin secretion which makes the receptor an attractive target for the treatment of type 1 or 2 diabetes. GPR39 signaling also inhibits apoptosis and mediates neural synaptic signaling. Novel ligands of GPR39 are warranted to reveal the main physiological role of this receptor. © 2012 Elsevier Ltd. All rights reserved. Source


Gees M.,Catholic University of Leuven
Cold Spring Harbor perspectives in biology | Year: 2010

The 28 mammalian members of the super-family of transient receptor potential (TRP) channels are cation channels, mostly permeable to both monovalent and divalent cations, and can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are widely expressed in a large number of different tissues and cell types, and their biological roles appear to be equally diverse. In general, considered as polymodal cell sensors, they play a much more diverse role than anticipated. Functionally, TRP channels, when activated, cause cell depolarization, which may trigger a plethora of voltage-dependent ion channels. Upon stimulation, Ca2+ permeable TRP channels generate changes in the intracellular Ca2+ concentration, [Ca2+]i, by Ca2+ entry via the plasma membrane. However, more and more evidence is arising that TRP channels are also located in intracellular organelles and serve as intracellular Ca2+ release channels. This review focuses on three major tasks of TRP channels: (1) the function of TRP channels as Ca2+ entry channels; (2) the electrogenic actions of TRPs; and (3) TRPs as Ca2+ release channels in intracellular organelles. Source


Denef F.,Catholic University of Leuven | Moore G.W.,Rutgers University
Journal of High Energy Physics | Year: 2011

We investigate degeneracies of BPS states of D-branes on compact Calabi-Yau manifolds. We develop a factorization formula for BPS indices using attractor flow trees associated to multicentered black hole bound states. This enables us to study background dependence of the BPS spectrum, to compute explicitly exact indices of various nontrivial D-brane systems, and to clarify the subtle relation of Donaldson-Thomas invariants to BPS indices of stable D6-D2-D0 states, realized in supergravity as "hole halos." We introduce a convergent generating function for D4 indices in the large CY volume limit, and prove it can be written as a modular average of its polar part, generalizing the fareytail expansion of the elliptic genus. We show polar states are "split" D6-anti-D6 bound states, and that the partition function factorizes accordingly, leading to a refined version of the OSV conjecture. This differs from the original conjecture in several aspects. In particular we obtain a nontrivial measure factor g-2 top e-K and find factorization requires a cutoff. We show that the main factor determining the cutoff and therefore the error is the existence of "swing states" - D6 states which exist at large radius but do not form stable D6-anti-D6 bound states. We point out a likely breakdown of the OSV conjecture at small gtop (in the large background CY volume limit), due to the surprising phenomenon that for sufficiently large background Kähler moduli, a charge ΛΓ supporting single centered black holes of entropy ~ Λ2S(Γ) also admits two-centered BPS black hole realizations whose entropy grows like Λ3 when Λ → ∞. © SISSA 2011. Source


Van Winkel R.,Maastricht University | Van Winkel R.,Catholic University of Leuven | Kuepper R.,Maastricht University
Annual Review of Clinical Psychology | Year: 2014

Epidemiological studies have shown that the association between cannabis and psychosis is robust and consistent across different samples, with compelling evidence for a dose-response relationship. Because longitudinal work indicates that cannabis use precedes psychotic symptoms, it seems reasonable to assume a causal relationship. However, more work is needed to address the possibility of gene-environment correlation (for example, genetic risk for psychosis causing onset of cannabis use). Moreover, knowledge about underlying biological mechanisms linking cannabis use and psychosis is still relatively limited. In order to understand how cannabis use may lead to an increased risk for psychosis, in the present article we (a) review the epidemiological, neurobiological, and genetic evidence linking cannabinoids and psychosis, (b) assess the quality of the evidence, and finally (c) try to integrate the most robust findings into a neurodevelopmental model of cannabis-induced psychosis and identify the gaps in knowledge that are in need of further investigation. © 2014 by Annual Reviews. Source


Amariti A.,University of California at San Diego | Siani M.,Catholic University of Leuven
Journal of High Energy Physics | Year: 2011

The three dimensional exact R symmetry of N = 2 SCFTs extremizes the partition function localized on a three sphere. Here we verify this statement at weak coupling. We give a detailed analysis for two classes of models. The first one is an SU(N)k gauge theory at large k with both fundamental and adjoint matter fields, while the second is a avored version of the ABJ theory, where the CS levels are large but they do not necessarily sum up to zero. We study in both cases superpotential deformations and compute the R charges at difierent fixed points. When these fixed points are connected by an RG ow we explicitly verify that the free energy, computed from the partition function localized on S3, decreases at the endpoints of the ow between the fixed points, corroborating the conjecture of an F-theorem in three dimensions. © 2011 SISSA. Source


Gheorghiu E.,Catholic University of Leuven
Journal of vision | Year: 2012

Contour-shape coding is color selective (Gheorghiu & Kingdom, 2007a) and surround textures inhibit the processing of contour shapes (Gheorghiu & Kingdom, 2011; Kingdom & Prins, 2009). These two findings raise two questions: (1) is texture-surround suppression of contour shape color selective, and (2) is texture-shape processing color selective? To answer these questions, we measured the shape-frequency aftereffect using contours constructed from strings of Gabors defined along the red-green, blue-yellow, and luminance axes of cardinal color space. The stimuli were either single sinusoidal-shaped contours or textures made of sinusoidal-shaped contours arranged in parallel. We measured aftereffects for (A) single-contour adaptors and single-contour tests defined along the same versus different cardinal directions, (B) texture adaptors and single-contour tests in which the central-adaptor contour/single-contour test and surround adaptor contours were defined along the same versus different cardinal directions, and (C) texture adaptors and texture tests defined along same versus different cardinal directions. We found that color selectivity was most prominent for contour-shape processing, weaker for texture-surround suppression of contour-shape processing, and absent for texture-shape processing. Source


Acar-Burkay S.,Norwegian School of Management | Fennis B.M.,Norwegian School of Management | Warlop L.,Catholic University of Leuven
Journal of Personality and Social Psychology | Year: 2014

Because trust-related issues inherently involve uncertainty, we expected individuals' social-cognitive motivation to manage uncertainty-which is captured by their need for closure-to influence their level of trust in others. Through the results of 6 studies, we showed that higher need for closure was related to more polarized trust judgments (i.e., low trust in distant others and high trust in close others) in the case of both chronic and situational need for closure. Moreover, participants with high need for closure did not revise their level of trust when they received feedback about the trustees' actual trustworthiness, whereas participants with low need for closure did. Overall, our findings indicate that polarized (either high or low, as opposed to moderate) and persistent levels of trust may serve people's seizing and freezing needs for achieving cognitive closure. Source


Silva-Castaneda L.,Catholic University of Leuven
Agriculture and Human Values | Year: 2012

In recent years, new forms of transnational regulation have emerged, filling the void created by the failure of governments and international institutions to effectively regulate transnational corporations. Among the variety of initiatives addressing social and environmental problems, a growing number of certification systems have appeared in various sectors, particularly agrifood. Most initiatives rely on independent third-party certification to verify compliance with a standard, as it is seen as the most credible route for certification. The effects of third-party audits, however, still need to be empirically investigated. This article provides a critical assessment of the notion of 'evidence' which is at the heart of auditing practices. It focuses on the case of the Roundtable on Sustainable Palm Oil (RSPO) and fieldwork carried out in Indonesia, the world's largest producer of palm oil. In this country, some non-governmental organizations decided to participate in the RSPO in order to use this platform to tackle the issue of land conflicts. They managed to include important clauses regarding indigenous and land rights in the RSPO standard. In practice, however, auditors rarely recognize as valid evidence the forms of proof put forward by local communities. As a result, the whole process risks compounding local power imbalances. © 2012 Springer Science+Business Media B.V. Source


Maes C.,Catholic University of Leuven
Physica Scripta | Year: 2012

In contrast to the quite unique entropy concept useful for systems in (local) thermodynamic equilibrium, there is a variety of quite distinct nonequilibrium entropies, reflecting different physical points. We disentangle these entropies as they relate to heat, fluctuations, response, time asymmetry, variational principles, monotonicity, volume contraction or statistical forces. However, not all of those extensions yield state quantities as understood thermodynamically. At the end we sketch how aspects of dynamical activity can take over for obtaining an extended Clausius relation. © 2012 The Royal Swedish Academy of Sciences. Source


The fear-avoidance model advances fear of pain as a key factor in the origins of chronic pain disability. Initial evidence in those with chronic back pain reveals that exposure therapy reduces fear levels, disability, and pain. Despite the success of exposure in the clinic, fundamental research about its underlying mechanisms lags behind. Using a conditioning paradigm with movements as conditioned stimuli (CS) and a painful shock as unconditioned stimuli (US), we investigated the extinction of experimental fear of movement-related pain and pain-related anxiety (respectively induced by predictable and unpredictable pain). Dependent measures were self-reported fear and eyeblink startle. During acquisition, all groups received both predictable and unpredictable training. In the predictable context, one movement (CS+) was consistently followed by the shock-US, but another movement was not (CS-). In the unpredictable context, joystick movements never signaled the shock-US; shock-US were delivered during the intertrial interval (ITI). During extinction, the extinction group continued training in the predictable context but the CS+ movement was no longer reinforced; the context exposure group continued training in the unpredictable context but ITI shock-US were omitted. The control group continued training after the acquisition reinforcement scheme. Results revealed that fear ratings for the CS+ were extinguished in the extinction group but not in the control group. Interestingly, omitting the ITI shocks not only reduced ITI startle responses in the context exposure group compared with the control group, but also reduced the fear ratings and startle responses elicited by the unpredictable CS. The clinical implications of these findings are discussed. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Source


Boonen S.,Catholic University of Leuven
Osteoporosis International | Year: 2010

Osteoporotic fractures are associated with significant morbidity and mortality with an enormous impact on society and the lives of affected individuals. Age and menopause are the two main risk factors for osteoporosis, and women therefore need to be particularly concerned about bone loss at this time. In addition to suffering fracture-associated morbidity, women with prior fractures have an increased risk of future fractures. Young postmen-opausal women who have experienced a fragility fracture therefore face a lifetime of fracture risk. The burden of fractures increases with advancing age, and bone mineral density declines, with women over the age of 80 years having the highest risk of fracture because of their high prevalence of osteoporosis and an increased likelihood of falls. A number of antiosteoporotic agents are available for the treatment of postmenopausal women including bisphosphonates, raloxifene, teriparatide, and strontium ranelate. For osteoporotic drugs to be beneficial in reducing the burden of fractures, they need to be effective against fracture in all age groups of postmen-opausal women. With its dual mode of action, strontium ranelate is the first agent with proven early and sustained antifracture efficacy in all age groups including young postmenopausal women and those over 80 years. Evidence is now available to show that all women, including the elderly, can benefit from treatment to prevent further bone loss and restore lost bone to decrease the risk of further fractures. By implementing procedures to identify those at greatest risk and initiate safe and effective treatments, physicians can significantly improve patients' quality of life. © International Osteoporosis Foundation and National Osteoporosis Foundation 2010. Source


de Boeck P.,University of Amsterdam | Partchev I.,Catholic University of Leuven
Journal of Statistical Software | Year: 2012

A category of item response models is presented with two defining features: they all (i) have a tree representation, and (ii) are members of the family of generalized linear mixed models (GLMM). Because the models are based on trees, they are denoted as IRTree models. The GLMM nature of the models implies that they can all be estimated with the glmer function of the lme4 package in R. The aim of the article is to present four subcategories of models, the first two of which are based on a tree representation for response categories: 1. linear response tree models (e.g., missing response models), 2. nested response tree models (e.g., models for parallel observations regarding item responses such as agreement and certainty), while the last two are based on a tree representation for latent variables: 3. linear latent-variable tree models (e.g., models for change processes), and 4. nested latent-variable tree models (e.g., bi-factor models). The use of the glmer function is illustrated for all four subcategories. Simulated example data sets and two service functions useful in preparing the data for IRTree modeling with glmer are provided in the form of an R package, irtrees. For all four subcategories also a real data application is discussed. Source


Howard H.C.,University Paul Sabatier | Borry P.,Catholic University of Leuven
Genome Medicine | Year: 2013

Background: The advent of direct-to-consumer (DTC) genetic testing (GT) has sparked a number of debates regarding the scientific validity of tests, their broad health and ethical implications for society as well as their legal status. To date, relatively few empirical studies have been published regarding this phenomenon. We conducted a survey of European clinical geneticists to gauge their awareness of, experiences with, and attitudes towards DTC GT.Methods: We invited 300 clinical geneticists from 28 European countries to complete an online questionnaire. Statistical analyses of closed-ended questions were performed using the STATISTICA software package. Answers to open-ended questions were analysed for recurring themes.Results: One hundred and thirty-one clinical geneticists answered our survey (response rate, 44%). Eighty-six percent (110/128) of respondents were aware of DTC GT, and over one-third had been contacted by at least one patient regarding these services. The majority (84%) of respondents did not agree with telephone medical supervision outside of an established doctor-patient relationship. The majority of clinical geneticists also found it unacceptable to provide non-face-to-face medical supervision for: (i) a presymptomatic test for a condition with very high penetrance; (ii) a predictive test for a condition that has a 'medium' penetrance of 50% to 60%; and (iii) carrier testing. For conditions that are neither treatable nor preventable and for disorders with serious health consequences, clinical geneticists were almost unanimous in expressing the unacceptability of offering such genetic tests outside of the traditional healthcare setting, without an established physician-patient relationship and without face-to-face medical supervision.Conclusion: A high percentage of European clinical geneticists are aware of DTC GT and the majority do not agree with the model of provision used by many commercial companies for certain severe or actionable health conditions. Despite this disagreement with the DTC model of provision, >85% of respondents said that they would offer genetic counselling to patients who asked for a consultation after having undergone DTC genetic testing. The understanding of the views and opinions of this expert stakeholder group should be considered in the attempts to shape responsible policy and guidelines for these services. © 2013 Howard and Borry; licensee BioMed Central Ltd. Source


Simoens S.,Catholic University of Leuven
Orphanet Journal of Rare Diseases | Year: 2011

Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b) few alternative health technologies are available; c) third-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions. © 2011 Simoens; licensee BioMed Central Ltd. Source


Van Beek J.T.M.,NXP Semiconductors | Puers R.,Catholic University of Leuven
Journal of Micromechanics and Microengineering | Year: 2012

MEMS-based oscillators are an emerging class of highly miniaturized, batch manufacturable timing devices that can rival the electrical performance of well-established quartz-based oscillators. In this review, a description is given of the key properties of a MEMS resonator that determine the overall performance of a MEMS oscillator. Piezoelectric, capacitive and active resonator transduction methods are compared and their impact on oscillator noise and power dissipation is explained. An overview is given of the performance of MEMS resonators and MEMS-based oscillators that have been demonstrated to date. Mechanisms that affect the frequency stability of the resonator, such as temperature-induced frequency drift, are explained and an overview is given of methods that have been demonstrated to improve the frequency stability. The aforementioned performance indicators of MEMS-based oscillators are benchmarked against established quartz and CMOS technologies. © 2012 IOP Publishing Ltd. Source


Indekeu J.O.,Catholic University of Leuven
Physica A: Statistical Mechanics and its Applications | Year: 2010

Equilibrium wetting phase transitions and critical phenomena are discussed from a phenomenological point of view. The ubiquitous character of the wetting phase transition is illustrated through its occurrence in a variety of condensed matter systems, ranging from classical fluids to superconductors and BoseEinstein condensates. The intriguing behaviour of the three-phase contact line and its line tension, at wetting, is an example of a fundamental problem in this field on which much progress has been made. © 2010 Elsevier B.V. All rights reserved. Source


The liquid/solid interface provides an interesting medium for molecular self-assembly and scanning tunneling microscopy is the preferred technique to analyse the structural features of the surface-supported self-assembled monolayers in this medium. An interesting aspect is the phenomenon of molecular dynamics at the liquid/solid interface. In this mini-review, we report on our efforts and strategies to investigate and even induce molecular dynamics at the liquid/solid interface, bringing insight to various kinds of processes such as conformational, translational and adsorption/desorption dynamics. © Schweizerische Chemische Gesellschaft. Source


Kuijlaars A.B.J.,Catholic University of Leuven | Zhang L.,Fudan University
Communications in Mathematical Physics | Year: 2014

Akemann, Ipsen and Kieburg recently showed that the squared singular values of products of M rectangular random matrices with independent complex Gaussian entries are distributed according to a determinantal point process with a correlation kernel that can be expressed in terms of Meijer G-functions. We show that this point process can be interpreted as a multiple orthogonal polynomial ensemble. We give integral representations for the relevant multiple orthogonal polynomials and a new double contour integral for the correlation kernel, which allows us to find its scaling limits at the origin (hard edge). The limiting kernels generalize the classical Bessel kernels. For M = 2 they coincide with the scaling limits found by Bertola, Gekhtman, and Szmigielski in the Cauchy–Laguerre two-matrix model, which indicates that these kernels represent a new universality class in random matrix theory. © 2014, Springer-Verlag Berlin Heidelberg. Source


Pepermans G.,Catholic University of Leuven
Energy Economics | Year: 2014

This paper assesses to what extent consumers are willing to make use of the features and capabilities offered by smart meters. Via a choice experiment households are offered the choice between a set of smart meters, described by six attributes: impact on the comfort and privacy level, functionality, visibility, cost savings, and investment outlay.We estimate a main effects conditional logit model and a main effects random parameter logit model, including interactions with socio-demographic characteristics. The results show that households have heterogeneous preferences for some attributes but not for others. The estimates are used to assess marginal willingness to pay values. From a policy perspective, our findings suggest that sufficient effort should be devoted to designing the smart metering devices and to informing households. Without careful preparation, a mandatory or voluntary roll-out of smart meters risks to be unsuccessful because device characteristics do not meet consumer needs. © 2014 Elsevier B.V. Source


Kauskot A.,Catholic University of Leuven
Blood | Year: 2013

Platelet endothelial aggregation receptor-1 (PEAR1) participates in platelet aggregation via sustaining αIIbβ3 activation. To investigate the role of PEAR1 in platelet formation, we monitored and manipulated PEAR1 expression in vitro in differentiating human CD34(+) hematopoietic stem cells and in vivo in zebrafish embryos. PEAR1 expression rose during CD34(+) cell differentiation up to megakaryocyte (MK) maturation. Two different lentiviral short hairpin knockdowns of PEAR1 did not affect erythropoiesis in CD34(+) cells, but increased colony-forming unit MK cell numbers twofold vs control in clonogenic assays, without substantially modifying MK maturation. The PEAR1 knockdown resulted in a twofold reduction of the phosphatase and TENsin homolog (PTEN) phosphatase expression and modulated gene expression of several phosphatidylinositol 3-kinase (PI3K)-Akt and Notch pathway genes. In zebrafish, Pear1 expression increased progressively during the first 3 days of embryo development. Both ATG and splice-blocking PEAR1 morpholinos enhanced thrombopoiesis, without affecting erythropoiesis. Western blots of 3-day-old Pear1 knockdown zebrafish revealed elevated Akt phosphorylation, coupled to transcriptional downregulation of the PTEN isoform Ptena. Neutralization by morpholinos of Ptena, but not of Ptenb, phenocopied the Pear1 zebrafish knockdown and triggered enhanced Akt phosphorylation and thrombocyte formation. In summary, this is the first demonstration that PEAR1 influences the PI3K/PTEN pathway, a critical determinant of Akt phosphorylation, itself controlling megakaryopoiesis and thrombopoiesis. Source


Covens K.,Catholic University of Leuven
Blood | Year: 2013

Controversy has arisen about the nature of circulating human CD20(+)CD27(+)CD43(+)CD70(-)CD69(-) B cells. Although originally described as being the human counterpart of murine B-1 B cells, some studies have raised the possibility that these might instead be plasmablasts. In this article, we have further characterized the putative B-1 cells and compared them directly with memory B cells and plasmablasts for several functional characteristics. Spontaneous antibody production of different isotypes as well as the induced production of antigen-specific antibodies after vaccination with a T-cell-dependent antigen did not reveal differences between the putative B-1 cells and genuine CD20(-) plasmablasts. Gene expression profiling of different B-cell subsets positioned the phenotype of putative B-1 cells closer to CD20(-) plasmablasts than to memory B cells. Moreover, putative B-1 cells could be differentiated into CD20(-) plasmablasts and plasma cells in vitro, supporting a pre-plasmablast phenotype. In conclusion, characterization of the putative B-1 cells revealed a functional phenotype and a gene expression profile that corresponds to cells that differentiate into CD20(-) plasmablasts. Our data offer perspectives for the investigation of differentiation of B cells into antibody secreting cells. Source


Kaltwasser P.R.,Catholic University of Leuven
Physica A: Statistical Mechanics and its Applications | Year: 2010

It is traditionally assumed in finance models that the fundamental value of assets is known with certainty. Although this is an appealing simplifying assumption it is by no means based on empirical evidence. A simple heterogeneous agent model of the exchange rate is presented. In the model, traders do not observe the true underlying fundamental exchange rate and as a consequence they base their trades on beliefs about this variable. Despite the fact that only fundamentalist traders operate in the market, the model belongs to the heterogeneous agent literature, as traders have different beliefs about the fundamental rate. © 2009 Elsevier B.V. All rights reserved. Source


Lens epithelium-derived growth factor (LEDGF/p75) is a cellular cofactor of HIV-1 integrase (IN) that interacts with IN through its IN binding domain (IBD) and tethers the viral pre-integration complex to the host cell chromatin. Here we report the generation of a human somatic LEDGF/p75 knockout cell line that allows the study of spreading HIV-1 infection in the absence of LEDGF/p75. By homologous recombination the exons encoding the LEDGF/p75 IBD (exons 11 to 14) were knocked out. In the absence of LEDGF/p75 replication of laboratory HIV-1 strains was severely delayed while clinical HIV-1 isolates were replication-defective. The residual replication was predominantly mediated by the Hepatoma-derived growth factor related protein 2 (HRP-2), the only cellular protein besides LEDGF/p75 that contains an IBD. Importantly, the recently described IN-LEDGF/p75 inhibitors (LEDGINs) remained active even in the absence of LEDGF/p75 by blocking the interaction with the IBD of HRP-2. These results further support the potential of LEDGINs as allosteric integrase inhibitors. Source


Haslam N.,University of Melbourne | Holland E.,University of Melbourne | Kuppens P.,Catholic University of Leuven
Psychological Medicine | Year: 2012

Taxometric research methods were developed by Paul Meehl and colleagues to distinguish between categorical and dimensional models of latent variables. We have conducted a comprehensive review of published taxometric research that included 177 articles, 311 distinct findings and a combined sample of 533 377 participants. Multilevel logistic regression analyses have examined the methodological and substantive variables associated with taxonic (categorical) findings. Although 38.9% of findings were taxonic, these findings were much less frequent in more recent and methodologically stronger studies, and in those reporting comparative fit indices based on simulated comparison data. When these and other possible confounds were statistically controlled, the true prevalence of taxonic findings was estimated at 14%. The domains of normal personality, mood disorders, anxiety disorders, eating disorders, externalizing disorders, and personality disorders (PDs) other than schizotypal yielded little persuasive evidence of taxa. Promising but still not definitive evidence of psychological taxa was confined to the domains of schizotypy, substance use disorders and autism. This review indicates that most latent variables of interest to psychiatrists and personality and clinical psychologists are dimensional, and that many influential taxonic findings of early taxometric research are likely to be spurious. © Cambridge University Press 2011. Source


Declerck P.J.,Catholic University of Leuven
Hamostaseologie | Year: 2011

Thrombin activatable fibrinolysis inhibitor (TAFI) was discovered two decades ago as a consequence of the identification of an unstable carboxypeptidase (CPU), which was formed upon thrombin activation of the respective pro-enzyme (proCPU). The antifibrinolytic function of the activated form (TAFIa, CPU) is directly linked to its capacity to remove C-terminal lysines from the surface of the fibrin clot. No endogenous inhibitors have been identified, but TAFIa activity is regulated by its intrinsic temperature-dependent instability with a half-life of 8 to 15 min at 37°C. A variety of studies have demonstrated a role for TAFI/TAFIa in venous and arterial diseases. In addition, a role in inflammation and cell migration has been shown. Since an elevated level of TAFIa it is a potential risk factor for thrombotic disorders, many inhibitors, both at the level of activation or at the level of activity, have been developed and were proven to exhibit a profibrinolytic effect in animal models. Pharmacologically active inhibitors of the TAFI/TAFIa system may open new ways for the prevention of thrombotic diseases or for the establishment of adjunctive treatments during thrombolytic therapy. © Schattauer 2011. Source


Faria N.R.,Catholic University of Leuven
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

The factors that determine the origin and fate of cross-species transmission events remain unclear for the majority of human pathogens, despite being central for the development of predictive models and assessing the efficacy of prevention strategies. Here, we describe a flexible Bayesian statistical framework to reconstruct virus transmission between different host species based on viral gene sequences, while simultaneously testing and estimating the contribution of several potential predictors of cross-species transmission. Specifically, we use a generalized linear model extension of phylogenetic diffusion to perform Bayesian model averaging over candidate predictors. By further extending this model with branch partitioning, we allow for distinct host transition processes on external and internal branches, thus discriminating between recent cross-species transmissions, many of which are likely to result in dead-end infections, and host shifts that reflect successful onwards transmission in the new host species. Our approach corroborates genetic distance between hosts as a key determinant of both host shifts and cross-species transmissions of rabies virus in North American bats. Furthermore, our results indicate that geographical range overlap is a modest predictor for cross-species transmission, but not for host shifts. Although our evolutionary framework focused on the multi-host reservoir dynamics of bat rabies virus, it is applicable to other pathogens and to other discrete state transition processes. Source


Delcroix M.,Catholic University of Leuven | Howard L.,Imperial College London
European Respiratory Review | Year: 2015

Pulmonary arterial hypertension (PAH) is a debilitating disease that pervades all aspects of a patient’s daily life. It is also increasingly acknowledged that the burden of PAH extends to older patients and carers. Until recently, the adverse effect of disease symptoms on the physical, emotional and social factors governing patient health-related quality of life (HRQoL) remained largely unrecognised. With a shift in therapeutic objectives to longer term improvements and HRQoL benefits, clinical trials now frequently include HRQoL measures as study end-points. Most HRQoL instruments used in patients with PAH are generic or non-disease-specific questionnaires and therefore may not accurately capture PAH disease burden. New PAH-specific HRQoL instruments currently undergoing validation include emPHasis-10 and Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Using various HRQoL measures, pharmacological therapies have been shown to improve HRQoL in patients with PAH. Patients also derive HRQoL benefits from nonpharmacological strategies, which include the emotional support provided by multidisciplinary care and support groups that is fundamental to patient wellbeing. Looking to the future, validated PAH-specific HRQoL instruments together with dedicated guidelines and procedures are essential to support the translation of HRQoL scores to the clinic, thus enabling a holistic treatment approach to the management of patients with PAH. © ERS 2015. Source


Van Veldhoven P.P.,Catholic University of Leuven
Journal of Lipid Research | Year: 2010

In humans, peroxisomes harbor a complex set of enzymes acting on various lipophilic carboxylic acids, organized in two basic pathways, α-oxidation and β-oxidation; the latter pathway can also handle ω-oxidized compounds. Some oxidation products are crucial to human health (primary bile acids and polyunsaturated FAs), whereas other substrates have to be degraded in order to avoid neuropathology at a later age (very long-chain FAs and xenobiotic phytanic acid and pristanic acid). Whereas total absence of peroxisomes is lethal, single peroxisomal protein deficiencies can present with a mild or severe phenotype and are more informative to understand the pathogenic factors. The currently known single protein deficiencies equal about one-fourth of the number of proteins involved in peroxisomal FA metabolism. The biochemical properties of these proteins are highlighted, followed by an overview of the known diseases. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc. Source


Blondeau K.,Catholic University of Leuven
Neurogastroenterology and Motility | Year: 2010

Refractory gastro-esophageal reflux disease (GERD), defined as persistent symptoms despite proton pump inhibitor (PPI) therapy, is an increasingly prevalent condition and is becoming a major challenge for the clinician. Since non-acidic reflux may be associated with symptoms persisting during PPI treatment, the lower esophageal sphincter (LES), the most important barrier protecting against reflux, has become an important target for the treatment of (refractory) GERD. Preclinical research has identified several receptors that are involved in the control of transient lower esophageal sphincter relaxations (TLESRs), the predominant mechanism of both acid and non-acidic reflux events, and several drugs have now been tested in humans. The GABA B agonist baclofen has demonstrated to effectively reduce the rate of TLESRs and the amount of reflux in both GERD patients and healthy volunteers. Nevertheless, the occurrence of central side effects limits its clinical use for the treatment of GERD. Several analogues are being developed to overcome this limitation and have shown promising results. Additionally, metabotropic glutamate receptor 5 (mGluR5) receptor antagonists have shown to reduce both acid and non-acidic reflux in GERD patients and several molecules are currently being evaluated. Although CB 1 antagonists have been shown to reduce TLESRs, they are also associated with central side effects, limiting their clinical applicability. Despite the identification of several potentially interesting drugs, the main challenge for the future remains the reduction of central side effects. Moreover, future studies will need to demonstrate the efficacy of these treatments in patients with refractory GERD. © 2010 Blackwell Publishing Ltd. Source


Verheyden G.S.,Catholic University of Leuven
The Cochrane database of systematic reviews | Year: 2013

Falls are one of the most common medical complications after stroke with a reported incidence of 7% in the first week after stroke onset. Studies investigating falls in the later phase after stroke report an incidence of up to 73% in the first year post-stroke. To evaluate the effectiveness of interventions aimed at preventing falls in people after stroke. We searched the trials registers of the Cochrane Stroke Group (November 2012) and the Cochrane Bone, Joint and Muscle Trauma Group (May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2012, Issue 5, MEDLINE (1950 to May 2012), EMBASE (1980 to May 2012), CINAHL (1982 to May 2012), PsycINFO (1806 to May 2012), AMED (1985 to May 2012) and PEDro (May 2012). We also searched trials registers, checked reference lists and contacted authors. Randomised controlled trials of interventions where the primary or secondary aim was to prevent falls in people after stroke. Review authors independently selected studies for inclusion, assessed trial quality, and extracted data. We used a rate ratio and 95% confidence interval (CI) to compare the rate of falls (e.g. falls per person year) between intervention and control groups. For risk of falling we used a risk ratio and 95% CI based on the number of people falling (fallers) in each group. We pooled results where appropriate. We included 10 studies with a total of 1004 participants. One study evaluated the effect of exercises in the acute and subacute phase after stroke but found no significant difference in rate of falls (rate ratio 0.92, 95% CI 0.45 to 1.90, 95 participants). The pooled result of four studies investigating the effect of exercises on preventing falls in the chronic phase also found no significant difference for rate of falls (rate ratio 0.75, 95% CI 0.41 to 1.38, 412 participants).For number of fallers, one study examined the effect of exercises in the acute and subacute phase after stroke but found no significant difference between the intervention and control group (risk ratio 1.19, 95% CI 0.83 to 1.71, 95 participants). The pooled result of six studies examining the effect of exercises in the chronic phase also found no significant difference in number of fallers between the intervention and control groups (risk ratio 1.02, 95% CI 0.83 to 1.24, 616 participants).The rate of falls and the number of fallers was significantly reduced in two studies evaluating the effect of medication on preventing falls; one study (85 participants) compared vitamin D versus placebo in institutionalised women after stroke with low vitamin D levels, and the other study (79 participants) evaluated alendronate versus alphacalcidol in hospitalised people after stroke.One study provided single lens distance glasses to regular wearers of multifocal glasses. In a subgroup of 46 participants post-stroke there was no significant difference in the rate of falls (rate ratio 1.08, 95% CI 0.52 to 2.25) or the number of fallers between both groups (risk ratio 0.74, 95% CI 0.47 to 1.18). There is currently insufficient evidence that exercises or prescription of single lens glasses to multifocal users prevent falls or decrease the number of people falling after being discharged from rehabilitation following their stroke. Two studies testing vitamin D versus placebo and alendronate versus alphacalcidol found a significant reduction in falls and the number of people falling. However, these findings should be replicated before the results are implemented in clinical practice. Source


Fransen M.,Catholic University of Leuven
Sub-cellular biochemistry | Year: 2013

Human aging is considered as one of the biggest risk factors for the development of multiple diseases such as cancer, type-2 diabetes, and neurodegeneration. In addition, it is widely accepted that these age-related diseases result from a combination of various genetic, lifestyle, and environmental factors. As biological aging is a complex and multifactorial phenomenon, the molecular mechanisms underlying disease initiation and progression are not yet fully understood. However, a significant amount of evidence supports the theory that oxidative stress may act as a primary etiologic factor. Indeed, many signaling components like kinases, phosphatases, and transcription factors are exquisitely sensitive to the cellular redox status, and a chronic or severe disturbance in redox homeostasis can promote cell proliferation or trigger cell death. Now, almost 50 years after their discovery, there is a wealth of evidence that peroxisomes can function as a subcellular source, sink, or target of reactive oxygen and nitrogen molecules. Yet, the possibility that these organelles may act as a signaling platform for a variety of age-related processes has so far been underestimated and largely neglected. In this review, we will critically discuss the possible role of peroxisomes in the human aging process in light of the available data. Source


Desmet V.J.,Catholic University of Leuven | Desmet V.J.,University Hospital St Rafael
Virchows Archiv | Year: 2011

This article focuses on the observation that most hepatic ductular reactions (DRs) have ductal plate (DP)-like patterns. Considering old and recent data, it hypothesizes that in DR, dedifferentiation of hepatocytes in ductular metaplasia may lead to the de novo development of liver stem/progenitor cells (LPCs). The three recognized types of DR are reconsidered, and an additional fourth type, DR type 2B, is added. In DR type 1 whose pattern differs from DP, the pre-existing cholangiocytes multiply and adjust the ductal structure in response tomicro-environmental changes induced by oedema and inflammation. This DR fails to establish new canaliculo-ductular connections. DRs types 2A, 2B and 3 represent progenitor cell-based reactions in DP configuration which establish canaliculo-ductular connections similar to DPs in embryonic and foetal liver development. DR type 2A occurs in periportal areas in chronic cholestatic and inflammatory diseases and is interpreted as a reaction of LPCs, which either pre-exist or derive from dedifferentiated hepatocytes. DR type 2B occurs in centrolobular areas and zones of parenchymal hypoxia, is induced by hypoxia and corresponds to "ductular metaplasia" like type 2A with a presumably similar cellular origin. DR type 3 relates to the well-recognized activation of LPCs that reside in the canals of Hering. All DRs in DP configuration play a role in progression of fibrosis in chronic liver diseases. © Springer-Verlag 2011. Source


Van Oudenhove L.,Catholic University of Leuven
Neurogastroenterology and Motility | Year: 2011

Background Neuroimaging research on gut-brain interactions has greatly improved our understanding of the brain mechanisms involved in processing and perceiving visceral pain in health and functional gastrointestinal disorders (FGID). However, discrepancies in the results of these studies continue to exist, which is at least partially due to the fact that important factors contributing to the intrinsic heterogeneity of symptom-based FGID, including psychological processes and psychiatric comorbidity, are insufficiently integrated in visceral pain neuroimaging research. Purpose This review will defend the thesis that, to increase our understanding of the heterogeneous etiopathogenesis of FGID, visceral pain neuroimaging studies need to be integrated with: (i) epidemiological and behavioral evidence on the influence of psychological processes on visceral pain in health and FGID, and (ii) methodology and evidence from affective, cognitive, and psychiatric neuroimaging studies. To illustrate this point, the somatic pain neuroimaging field will be taken as an example before giving an overview of novel and integrative visceral pain studies in health and FGID. Some limitations of current pain neuroimaging studies will be outlined, before providing a summary of suggestions for moving the visceral pain neuroimaging field forward. © 2011 Blackwell Publishing Ltd. Source


Santoro M.M.,Catholic University of Leuven | Santoro M.M.,Vesalius Research Center
Trends in Endocrinology and Metabolism | Year: 2014

Cell metabolism plays a key role in many essential biological processes. The recent availability of novel technologies and organisms to model cell metabolism in vivo is expanding current knowledge of cell metabolism. In this context, the zebrafish (. Danio rerio) is emerging as a valuable model system to learn about the metabolic routes critical for cellular homeostasis. Here, the most recent methods and studies on cell metabolism are summarized, which support the overall value for the zebrafish model system not only to study metabolism but also metabolic disease states. It is envisioned that this small vertebrate system will help in the understanding of pathogenesis for numerous metabolic-related disorders in humans and in the identification of their therapeutic treatments. © 2014 Elsevier Ltd. Source


Meyers J.,Catholic University of Leuven | Meneveau C.,Johns Hopkins University
Wind Energy | Year: 2012

As wind farms become larger, the asymptotic limit of the 'fully developed', or 'infinite', wind farm has been receiving an increased interest. This limit is relevant for wind farms on flat terrain whose length exceeds the height of the atmospheric boundary layer by over an order of magnitude. Recent computational studies based on large eddy simulation have identified various mean velocity equilibrium layers and have led to parameterizations of the effective roughness height that allow the prediction of the wind velocity at hub height as a function of parameters such as wind turbine spacing and loading factors. In the current paper, we employ this as a tool in making predictions of optimal wind turbine spacing as a function of these parameters, as well as in terms of the ratio of turbine costs to land surface costs. For realistic cost ratios, we find that the optimal average turbine spacing may be considerably higher than that conventionally used in current wind farm implementations. © 2011 John Wiley & Sons, Ltd. Source


Some prokaryotes are known to be specialized in the use of phytoplankton-derived dissolved organic carbon (DOCp) originated by exudation or cell lysis; however, direct quantification measurements are extremely rare. Several studies have described bacterial selectivity based on DOCp quality, but very few have focused on the quantity of DOCp, and the relative importance of each of these variables (for example, quantity versus quality) on prokaryote responses. We applied an adapted version of the MAR-FISH (microautoradiography coupled with catalyzed reporter deposition fluorescence in situ hybridization) protocol using radiolabelled exudates from axenic algal cultures to calculate a specialization index (d’) for large bacterioplankton phylogenetic groups using DOCp from different phytoplankton species and at different concentrations to elucidate to what extent the bacterial response to DOCp is driven by resource quantity (different DOCp concentrations) or by quality (DOCp from different phytoplankton species). All bacterial phylogenetic groups studied had lower d’ at higher DOCp concentration, indicating more generalist behavior at higher resource availabilities. Indeed, at increasing resource concentrations, most bacterial groups incorporated DOCp indiscriminately, regardless of its origin (or quality). At low resource concentrations, only some specialists were able to actively incorporate the various types of organic matter effectively. The variability of bacterial responses to different treatments was systematically higher at varying concentrations than at varying DOCp types, suggesting that, at least for this range of concentrations (10–100 μM), DOCp quantity affects bacterial responses more than quality does. Therefore, resource quantity may be more relevant than resource quality in the bacterial responses to DOCp and affect how bacterioplankton use phytoplankton-derived carbon.The ISME Journal advance online publication, 29 April 2016; doi:10.1038/ismej.2016.66. © 2016 International Society for Microbial Ecology Source


De Roeck W.,Catholic University of Leuven | Huveneers F.,University of Paris Dauphine
Communications in Mathematical Physics | Year: 2014

We consider a quantum lattice system with infinite-dimensional on-site Hilbert space, very similar to the Bose–Hubbard model. We investigate many-body localization in this model, induced by thermal fluctuations rather than disorder in the Hamiltonian. We provide evidence that the Green–Kubo conductivity κ(β), defined as the time-integrated current autocorrelation function, decays faster than any polynomial in the inverse temperature β as β→0. More precisely, we define approximations κτ(β)to κ(β) by integrating the current-current autocorrelation function up to a large but finite time τ and we rigorously show that β-nκβ-m(β) vanishes as β→0, for any n, m∈ such that m−n is sufficiently large. © 2014, Springer-Verlag Berlin Heidelberg. Source


Veyckemans F.,Catholic University of Leuven
Current Opinion in Anaesthesiology | Year: 2010

Purpose of review: Anaesthesia for a child with a muscle disease is always challenging because there is a risk of malignant hyperthermia, rhabdomyolysis or hypermetabolic reaction if a halogenated agent is used. Ongoing progress in genetics helps in clarifying the link between malignant hyperthermia (a calcium channelopathy) and muscle diseases. Recent findings: We provide a summary of the most recent clinical, pathophysiological and genetic information on those risks when the diagnosis is known or suspected preoperatively. Some simple clues are also given to help make a decision in the presence of an infant or child with hypotonia or motor delay but no diagnosis. Summary: Only a few muscle diseases are really associated with a risk of malignant hyperthermia. The risk of rhabdomyolysis is more difficult to clarify and a multicentric database would be useful to evaluate the risk/benefit ratio of all anaesthetic drugs in patients with muscle diseases. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Pauwels R.,Catholic University of Leuven
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2011

Cone-beam CT (CBCT) has shown to be a useful imaging modality for various dentomaxillofacial applications. However, optimization and quality control of dental CBCT devices is hampered due to the lack of an appropriate tool for image quality assessment. To investigate the application of different image quality parameters for CBCT, a prototype polymethyl methacrylate (PMMA) cylindrical phantom with inserts for image quality analysis was developed. Applicability and reproducibility of the phantom were assessed using seven CBCT devices with different scanning protocols. Image quality parameters evaluated were: CT number correlation, contrast resolution, image homogeneity and uniformity, point spread function, and metal artifacts. Deviations of repeated measurements were between 0.0% and 3.3%. Correlation coefficients of CBCT voxel values with CT numbers ranged between 0.68 and 1.00. Contrast-to-noise ratio (CNR) values were much lower for hydroxyapatite (0 < CNR < 7.7) than for air and aluminum (5.0 < CNR < 32.8). Noise values ranged between 35 and 419. The uniformity index was between 3.3% and 11.9%. Full width at half maximum (FWHM) measurements varied between 0.43 mm and 1.07 mm. The increase of mean voxel values surrounding metal objects ranged between 6.7% and 43.0%. Results from preliminary analyses of the prototype quality control phantom showed its potential for routine quality assurance on CBCT. Large differences in image quality performance were seen between CBCT devices. Based on the initial evaluations, the phantom can be optimized and validated. Source


Delheye P.,Catholic University of Leuven
European Journal of Sport Science | Year: 2014

Abstract: This paper analyses the introduction of statistics in the field of gymnastics and its effect on the institutionalisation of physical education as a fully fledged academic discipline. Soon after Belgian independence, Adolphe Quetelet's research already resulted in large-scale anthropometric statistics – indeed, he developed an index that is still being used and is better known under the name of the body mass index. His insights were applied by promoters of gymnastics who wanted to make physical education more scientific. Thus, Clément Lefébure, director of the Ecole Normale de Gymnastique et d'Escrime in Brussels, set up a comparative experiment (with pre- and post-test measurements) by which he intended to show that the ‘rational’ method of Swedish gymnastics produced much better results than the ‘empirical’ method of Belgian/German Turnen. Lefébure's experiment, which was cited internationally but which was also strongly contested by opponents, was one of the factors that led to Swedish gymnastics being officially institutionalised in 1908 at the newly founded Higher Institute of Physical Education of the State University of Ghent, the first institute in the world where students could obtain a doctoral degree in physical education. Although it rested actually on very weak scientific foundations, the bastion of Swedish gymnastics built in Belgium in that pre-war period collapsed only in the 1960s. From then on, sport science could develop fully within the institutes for physical education. © 2014, © 2014 European College of Sport Science. Source


Nilius B.,Catholic University of Leuven
Reviews of physiology, biochemistry and pharmacology | Year: 2013

Spicy food does not only provide an important hedonic input in daily life, but has also been anedoctically associated to beneficial effects on our health. In this context, the discovery of chemesthetic trigeminal receptors and their spicy ligands has provided the mechanistic basis and the pharmacological means to investigate this enticing possibility. This review discusses in molecular terms the connection between the neurophysiology of pungent spices and the "systemic" effects associated to their trigeminality. It commences with a cultural and historical overview on the Western fascination for spices, and, after analysing in detail the mechanisms underlying the trigeminality of food, the main dietary players from the transient receptor potential (TRP) family of cation channels are introduced, also discussing the "alien" distribution of taste receptors outside the oro-pharingeal cavity. The modulation of TRPV1 and TRPA1 by spices is next described, discussing how spicy sensations can be turned into hedonic pungency, and analyzing the mechanistic bases for the health benefits that have been associated to the consumption of spices. These include, in addition to a beneficial modulation of gastro-intestinal and cardio-vascular function, slimming, the optimization of skeletal muscle performance, the reduction of chronic inflammation, and the prevention of metabolic syndrome and diabetes. We conclude by reviewing the role of electrophilic spice constituents on cancer prevention in the light of their action on pro-inflammatory and pro-cancerogenic nuclear factors like NFκB, and on their interaction with the electrophile sensor protein Keap1 and the ensuing Nrf2-mediated transcriptional activity. Spicy compounds have a complex polypharmacology, and just like any other bioactive agent, show a balance of beneficial and bad actions. However, at least for moderate consumption, the balance seems definitely in favour of the positive side, suggesting that a spicy diet, a caveman-era technology, could be seriously considered in addition to caloric control and exercise as a measurement to prevent and control many chronic diseases associate to malnutrition from a Western diet. Source


Volckaert F.A.M.,Catholic University of Leuven
Journal of Sea Research | Year: 2013

The delineation of natural populations has many faces. While a stock relates to a management unit of organisms, the biological concept of a population may relate to a demographic/ecological perspective on interacting organisms or an evolving group of organisms. In addition, it has become increasingly clear that the time and spatial scales of the ecological and evolutionary population have much in common. Evolutionary population models, which are the focus of this paper, harbor independent information on census population size, population dynamics, population history and population connectivity. Fish populations continuously adapt to the changing environmental conditions. However, the impact of and response to fishing, climate and pollution stress are disconnected in time and lead to measurable changes in the genomes. Several new insights have emerged lately, such as the limited but biologically meaningful subtle genetic differentiation, the contribution of population connectivity, the consequences of the very small effective population sizes and the interaction between environment and evolution. This leads to the importance of management of the genetic monitoring of populations, the inclusion of adaptation in management models and the contribution of marine protected areas to guarantee the long term integrity of marine ecosystems. Of immediate significance is the match between stocks and the biological population model. © 2012 Elsevier B.V. Source


Janssens S.P.,Catholic University of Leuven
European Heart Journal | Year: 2011

This editorial refers to 'Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial', by A. Hirsch et al., on page 1736, and 'Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial', by J. Roncalli et al., on page 1748. © The Author 2011. Source


Vandermeulen E.,Catholic University of Leuven
Best Practice and Research: Clinical Anaesthesiology | Year: 2010

As the life expectancy of our Western population progressively increases, so does the prevalence of cardiovascular disease and thus the use of antithrombotic drugs. The use of central neuraxial anaesthesia techniques in patients treated with these drugs is a major clinical problem as the presence of an impaired coagulation has been found to be the most important risk factor contributing to the formation of a spinal haematoma. The growing number of case reports of spinal haematoma has led many national societies of anaesthetists to come up with guidelines. This article presents an overview of current guidelines on the use of regional anaesthetic techniques in patients treated with various anticoagulants and also describes a possible strategy to deal with new antithrombotic drugs that have recently been introduced in some countries or will be shortly in others. © 2009 Elsevier Ltd. All rights reserved. Source


Decramer M.,Catholic University of Leuven | Cooper C.B.,University of California at Los Angeles
Thorax | Year: 2010

Classical belief is that only smoking cessation, and not pharmacotherapy, beneficially affect disease progression in chronic obstructive pulmonary disease (COPD). In recent years, new data on pharmacotherapy of COPD became available that shed new light on this question. The present paper reviews these data critically in an attempt to put them in a proper perspective. The most impressive new data are subgroup analyses of two large-scale long-term trials. With these new data it is now clear that patients in GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) stage II benefit as much from pharmacotherapy as patients in the later stages of the disease. Effects on prebronchodilator and postbronchodilator forced expiratory volume in 1 s (FEV1), health-related quality of life, exacerbations and hospitalisations appear at least as pronounced in GOLD stage II as in the other GOLD stages. In addition, evidence suggestive of an effect on disease progression is available in the sense of an effect on rate of decline of FEV1, and trends for reductions in mortality. Finally, good evidence is available that, in contrast to conventional thinking, decline of FEV 1 occurs at a considerably faster rate in the early stages of the disease. These data together with the high prevalence of co-morbidities from early in the disease onwards provide us with strong suggestive evidence for early intensive intervention in COPD. New trials, particularly demonstrating the detrimental effects of delaying treatment until later in the course of the disease, are required to render the evidence for early intensive intervention irrefutable. Source


Lee J.W.,Catholic University of Leuven
IEEE Transactions on Electron Devices | Year: 2014

An expression is derived for the conversion of the frequency axis of a low-frequency noise spectrum into a depth axis, based on the capture and emission time constant of a random telegraph signal. By connecting the corner frequency of the corresponding Lorentzian spectrum to the measured trapping time constant, the effect of multiphonon relaxation upon tunneling into an oxide trap can be included in a natural way. With this expression, one can derive in a straightforward manner some important trends with respect to the impact of several trap and material parameters on the tunneling depth, both for {\rm SiO}2 and high-κ gate dielectrics. © 1963-2012 IEEE. Source


Kappe C.O.,Christian Doppler Laboratory | Van Der Eycken E.,Catholic University of Leuven
Chemical Society Reviews | Year: 2010

First described almost a decade ago, "click" reactions such as the Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) are widely used today in organic and medicinal chemistry, in the polymer and material science field, and in chemical biology. While most click reactions can be performed at room temperature there are instances where some form of process intensification is required. In this tutorial review, aimed at the synthetic chemistry community, examples of click chemistry carried out under non-classical reaction conditions, such as for example applying microwave heating or continuous flow processing will be highlighted. © 2010 The Royal Society of Chemistry. Source


This article analyses the creation of new human rights by a contemporary transnational agrarian movement, Vía Campesina. It makes the case that the movement's assertion of new rights contributes to shaping a cosmopolitan, multicultural, and anti-hegemonic conception of human rights. It discusses the advantages and constraints of the human rights framework and analyses the creation of new rights by the movement as a way to overcome the limitations of the 'rights master frame'. It concludes with a discussion of some of the challenges involved in the institutionalization of new rights. © The Author(s) 2012. Source


Lories R.,Catholic University of Leuven
Nature Reviews Rheumatology | Year: 2011

The introduction of targeted therapies has dramatically changed the prognosis of patients with chronic joint diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). As control of inflammation, and hence of symptoms of disease, is increasingly achieved, more attention is given towards the long-term consequences of these disorders, to the structural damage in the skeletal tissues and to the resulting disability. In AS, bone remodeling with new cartilage and bone formation leading to ankylosis is a striking feature. Clinically successful TNF antagonists do not inhibit radiographic progression of disease. New insights into the molecules involved in ankylosis (such as bone morphogenetic proteins and Wnts) have suggested that the classical paradigm linking inflammation and ankylosis can be challenged, and new concepts of disease onset and progression, with a focus on cell stress and damage, are rapidly evolving. In RA, inhibition of Wnt signaling and defective osteoblast function have been associated with lack of repair. As restoration of tissue integrity and homeostasis is the ultimate goal of therapy, these findings suggest new roads for therapeutic intervention. For patients with AS or RA, such strategies will be critically dependent on further research that defines individual risk factors and need for interventions. © 2011 Macmillan Publishers Limited. All rights reserved. Source


Billieux J.,Catholic University of Leuven
Current Psychiatry Reviews | Year: 2012

Despite its unambiguous advantages, cellular phone use has been associated with harmful or potentially disturbing behaviors. Problematic use of the mobile phone is considered as an inability to regulate one's use of the mobile phone, which eventually involves negative consequences in daily life (e.g., financial problems). The current article describes what can be considered dysfunctional use of the mobile phone and emphasizes its multifactorial nature. Validated assessment instruments to measure problematic use of the mobile phone are described. The available literature on risk factors for dysfunctional mobile phone use is then reviewed, and a pathways model that integrates the existing literature is proposed. Finally, the assumption is made that dysfunctional use of the mobile phone is part of a spectrum of cyber addictions that encompasses a variety of dysfunctional behaviors and implies involvement in specific online activities (e.g., video games, gambling, social networks, sex-related websites). © 2012 Bentham Science Publishers. Source


Vandenbosch G.A.E.,Catholic University of Leuven
IEEE Transactions on Antennas and Propagation | Year: 2010

New expressions are derived to calculate the reactive energy stored in the electromagnetic field surrounding an electromagnetic device. The resulting expressions are very simple to interpret, completely general, explicit and without approximations in terms of the currents flowing on the device. They are also fast since they involve integrals solely over the device generating the field. The new technique is very feasible to be used in cases where the electric and magnetic reactive energies are important in practice, especially in the case of radiating structures. Used there, they allow to study the effect of the shape of the device on the amount of reactive energy, and thus on the ${\rm Q}$ of the device. The implementation of the new expressions in numerical CAD tools is extremely simple and straightforward. © 2006 IEEE. Source


Carter A.M.,University of Southern Denmark | Pijnenborg R.,Catholic University of Leuven
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2011

It is now possible to view human placentation in an evolutionary context because advances in molecular phylogenetics provide a reliable scenario for the evolution of mammals. Perhaps the most striking finding is the uniqueness of human placenta. The lower primates have non-invasive placentae and even tarsiers and New World monkeys show restricted trophoblast invasion. Moreover, a truly villous placenta occurs only in Old World monkeys and great apes. The two latter groups of haplorhine primates show varying degrees of trophoblast-uterine interaction, including differences in the extent of decidualization, formation and disintegration of a cytotrophoblastic shell, degree of interstitial trophoblast invasion and depth of trophoblast invasion into spiral arteries. Recently, the occurrence of human-like deep invasion was confirmed in gorillas and chimpanzees. As the still enigmatic disease of pre-eclampsia also occurs in these species, such information may reveal the evolutionary roots of this disease of impaired maternal-fetal interaction. © 2010 Elsevier Ltd. All rights reserved. Source


Tack J.,Catholic University of Leuven
Best Practice and Research: Clinical Gastroenterology | Year: 2011

In this article, traditional and novel therapies for chronic constipation are reviewed. Traditional laxatives are effective at inducing bowel movements, but efficacy in long-term management and efficacy on constipation-associated abdominal symptoms are less well established, with the exception of polyethylene glycol, for which long-term studies confirm sustained efficacy. Recently approved drugs include the colonic secretagogue lubiprostone and the 5-HT4 agonist prucalopride. In controlled trials in chronic constipation, these drugs were shown to significantly improve constipation and its associated symptoms, with a favourable safety record. Methylnaltrexone, a subcutaneously administered peripherally acting mu opioid receptor antagonist, has recently been approved for opioid-induced constipation in terminally ill patients. New agents under evaluation include the 5-HT4 agonists velusetrag and naronapride, the guanylate cyclase-C receptor agonist linaclotide and the peripherally acting mu opioid receptor antagonist alvimopan. © 2010 Elsevier Ltd. All rights reserved. Source


Fagard R.,Catholic University of Leuven
Polskie Archiwum Medycyny Wewnetrznej | Year: 2010

The European Society of Hypertension Task Force document on reappraisal of the 2007 European guidelines on hypertension addresses a number of studies published in the last 2 years to estimate their contribution to the expanding knowledge on hypertension. The importance of total cardiovascular risk with inclusion of subclinical cardiac, vascular, and renal organ damage was reemphasized, followed by a critical reappraisal of recommendations for the initiation of antihypertensive drug treatment in patients with high normal blood pressure (BP) and grade 1 hypertension. Whereas there is sufficient evidence for reducing BP below 140/90 mmHg in most hypertensives, the recommendation of previous guidelines to aim at a lower BP in diabetics and in patients at very high cardiovascular risk is not consistently supported by trial evidence. Moreover, the J-curve phenomenon may occur in patients at high cardiovascular risk. With regard to the choice of antihypertensive drugs, the conclusions of the 2007 guidelines that diuretics, angiotensin-converting enzyme inhibitors, calcium antagonists, angiotensin receptor antagonists, and β-blockers are suitable for initiation and maintenance of anti-hypertensive treatment are reinforced. Furthermore, apart from starting with combination therapy in certain conditions, adding a drug from another class to the initially prescribed one is preferred to increasing the dose of the first one. Some of the drug combinations recommended in 2007 are now regarded as more recommendable. In addition to the benefits of antihypertensive treatment in the elderly, the HYVET (Hypertension in the Very Elderly Trial) has shown that antihypertensive treatment also has benefits in octogenarians. The document ends with a number of issues in urgent need to be approached by new trials. Copyright by Medycyna Praktyczna, 2010. Source


Decottignies A.,Catholic University of Leuven
Frontiers in Genetics | Year: 2013

In the presence of functional DNA repair pathways, DNA double-strand breaks (DSBs) are mainly repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR), two conserved pathways that protect cells from aberrant chromosomal rearrangements. During the past two decades however, unusual and presumably distinct DNA end-joining repair activities have been unraveled in NHEJ-deficient cells and these are likely to operate in various chromosomal contexts and species. Most alternative DNA end-joining events reported so far appear to involve microhomologous sequences and are likely to rely on a subset of HR enzymes, namely those responsible for the single-strand annealing mechanism of HR, and on DNA Ligase III. Usually, microhomologies are not initially present at DSB ends and thus need to be unmasked through DNA end resection, a process that can lead to extensive nucleotide loss and is therefore highly mutagenic. In addition to microhomology-mediated end-joining events, recent studies in mammalian cells point toward the existence of a distinct and still ill defined alternative end-joining pathway that does not appear to rely on pre-existing microhomologies and may possibly involve DNA Ligase I. Whether dependent on microhomologies or not, alternative DNA end-joining mechanisms are likely to be highly mutagenic in vivo, being able to drive telomere fusion events and cancer-associated chromosomal translocations in mouse models. In the future, it will be important to better characterize the genetic requirements of these mutagenic alternative mechanisms of DNA end-joining. © 2013 Decottignies. Source


De Cock M.,Catholic University of Leuven
Physical Review Special Topics - Physics Education Research | Year: 2012

In this paper, we examine student success on three variants of a test item given in different representational formats (verbal, pictorial, and graphical), with an isomorphic problem statement. We confirm results from recent papers where it is mentioned that physics students' problem-solving competence can vary with representational format and that solutions can be triggered by particular details of the representation. Previous studies are complemented with a fine grained analysis of solution strategies. We find that students use different problem-solving strategies, depending on the representational format in which the problem is stated. © 2012 American Physical Society. Source


Verreet B.,IMEC | Heremans P.,IMEC | Stesmans A.,Catholic University of Leuven | Rand B.P.,IMEC
Advanced Materials | Year: 2013

Microcrystalline organic films with tunable thickness are produced directly on an indium-tin-oxide substrate, by crystallizing a thin amorphous rubrene film followed by its use as a template for subsequent homoepitaxial growth. These films, with exciton diffusion lengths exceeding 200 nm, produce solar cells with increasing photocurrents at thicknesses up to 400 nm with a fill factor >65%, demonstrating significant potential for microcrystalline organic electronic devices. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Sienaert P.,Catholic University of Leuven
Canadian Journal of Psychiatry | Year: 2011

In this narrative review, the current knowledge base on the efficacy and the practice of electroconvulsive therapy (ECT) is reviewed, and its relevance for the practising psychiatrist is appreciated. In the past decade, several large-scale studies have confirmed the significant superiority of ECT in the treatment of severe and refractory psychiatric conditions, such as major depressive disorder and bipolar disorder. However, the efficacy of ECT is not reflected in current treatment algorithms, where ECT is often reserved as a last resort. However, clinical characteristics, such as the presence of psychotic symptoms, suicidality, or catatonic signs, should prompt the clinician to consider ECT earlier in the treatment course. ECT is a safe procedure, without absolute contraindications for its use. Nevertheless, patients' fears and complaints should be acknowledged, and patients should be adequately informed about expected benefits and possible risks, such as memory problems, that are generally transient. Research focusing on further minimizing memory problems, while maintaining a superior efficacy, is ongoing. Adequate continuation treatment, either pharmacotherapy or continuation ECT, after a successful ECT course is of vital importance to maintain the benefits achieved and should be the focus of future research. Source


Hens H.,Catholic University of Leuven
Energy and Buildings | Year: 2010

Looking to the EU's 20/20/20 program, energy efficient retrofitting will be a key element in the 20% less primary energy in 2020 compared to business as usual. Within that context, field studies that put realizable efficiency in perspective are urgently needed. The dwelling evaluated was built in 1957. In those days energy efficiency was no concern. Houses got no insulation, ventilation was adventitious and heating systems scored badly. The retrofit started in the early eighties, stepwise as to follow the impact of separate measures on heating energy consumed. A solar boiler was installed in 2004. PV followed in 2009. The first 19 years a family of five inhabited the dwelling, then the parents only. Monitoring started in 1978. In the paper, predicted annual energy for space heating is compared with monitored result. The measured data, though showing a net decrease, consistently underscore predictions. Main reason is direct rebound. The benefits of the solar boiler and PV-panels are minimal compared to the energy avoided by better insulation, energy efficient windows, better air-tightness and upgraded ventilation and central heating. However, targeting passive house and zero energy quality is beyond optimal in terms of net present value and not doable in the dwelling. © 2010 Elsevier B.V. All rights reserved. Source


Nesterov Y.,Catholic University of Leuven
Mathematical Programming | Year: 2015

In this paper, we present new methods for black-box convex minimization. They do not need to know in advance the actual level of smoothness of the objective function. Their only essential input parameter is the required accuracy of the solution. At the same time, for each particular problem class they automatically ensure the best possible rate of convergence. We confirm our theoretical results by encouraging numerical experiments, which demonstrate that the fast rate of convergence, typical for the smooth optimization problems, sometimes can be achieved even on nonsmooth problem instances. © 2014, Springer-Verlag Berlin Heidelberg and Mathematical Optimization Society. Source


Speleers H.,Catholic University of Leuven
Computer Aided Geometric Design | Year: 2013

We present the construction of a multivariate normalized B-spline basis for the quadratic C1-continuous spline space defined over a triangulation in Rs (s≥1) with a generalized Powell-Sabin refinement. The basis functions have a local support, they are nonnegative, and they form a partition of unity. The construction can be interpreted geometrically as the determination of a set of s-simplices that must contain a specific set of points. We also propose a family of quasi-interpolants based on this multivariate Powell-Sabin B-spline representation. Their spline coefficients only depend on a set of local function values. The multivariate quasi-interpolants reproduce quadratic polynomials and have an optimal approximation order. © 2012 Elsevier B.V. Source


Van Acker H.,Ghent University | Van Dijck P.,Vlaams Instituut voor Biotechnologie VIB | Van Dijck P.,Catholic University of Leuven | Coenye T.,Ghent University
Trends in Microbiology | Year: 2014

The formation of microbial biofilms is an important reason for failure of antimicrobial therapy. However, the molecular mechanisms underlying the survival of biofilm cells are still not completely understood. In this review we discuss three mechanisms that play an important role in biofilm survival: (i) biofilm-specific protection against oxidative stress; (ii) biofilm-specific expression of efflux pumps; and (iii) protection provided by matrix polysaccharides. We demonstrate that these mechanisms are found both in bacterial and fungal biofilms and are often surprisingly similar between distantly related organisms. In addition, we give an overview of the data that suggests that these mechanisms may not be independent. © 2014 Elsevier Ltd. Source


Kiedrowski G.V.,Ruhr University Bochum | Otto S.,University of Groningen | Herdewijn P.,Catholic University of Leuven
Journal of Systems Chemistry | Year: 2013

It is our utmost pleasure to launch the Journal of Systems Chemistry. What systems chemistry exactly is will be known in a few years from now when one is able to sketch the scope and vision of the field also based on upcoming contributions to our journal. How systems chemistry came up is more easy to tell. In this editorial we therefore focus predominantly on how the term "Systems Chemistry" came into being and how its scope evolved over recent years. It is perhaps not surprising that the term emerged within the communities researching the origin and synthesis of life, as this is probably the most challenging question in Systems Chemistry. The field however encompasses much more than just this subject - it offers a plethora of new opportunities for the discovery of lifelike dynamic signatures in all areas in chemistry © 2010 von Kiedrowski et al. Source


Boeckxstaens G.E.,Catholic University of Leuven
Gastroenterology Clinics of North America | Year: 2014

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases in the Western world, with typical symptoms, such as heartburn, regurgitation, or retrosternal pain, reported by 15% to 20% of the general population. The pathophysiology of GERD is multifactorial. Our understanding of these factors has significantly improved in recent years, with increased understanding of the acid pocket and hiatal hernia and how these factors interact. Although our insight has significantly increased over the past years, more studies are required to better understand symptom generation in GERD, especially in patients with therapy-resistant symptoms. © 2014 Elsevier Inc. Source


Vankelecom H.,Catholic University of Leuven
Current Stem Cell Research and Therapy | Year: 2012

The pituitary gland represents the organism's endocrine hub, integrating central and peripheral inputs to generate the appropriate hormonal signals that govern key physiological processes. To meet the changing endocrine demands, the gland has to flexibly remodel its hormone-producing cell compartment. Mechanisms underlying pituitary cellular plasticity, as well as homeostatic turnover, are poorly understood. Similar to other tissues, resident stem cells may participate in the generation of newborn cells. Although in the past recurrently postulated to exist, pituitary stem cells remained obscure until the quest recently regained momentum, resulting in a surge of studies that designated very strong candidates for the stem/progenitor cell position. The cells identified express stem cell-associated markers and signaling factors, as well as transcriptional regulators that play essential roles during pituitary embryogenesis. They exhibit the stem cell properties of multilineage differentiation and prominent efflux capacity ("side population" phenotype), and display a topographical pattern reminiscent of niche-like configurations. Yet, the stem cell tenet of long-term self-renewal remains to be unequivocally demonstrated. Taken together, pituitary stem cells commence to drop their mask. While their "face" gradually becomes visible, the "character" they play in the pituitary awaits further disclosure. The aim of this review is to highlight the recent progress in pituitary stem/progenitor cell identification by sketching the historical context, describing the new findings with inclusion of critical and cautionary reflections, proposing a tentative stem/progenitor cell model, and pointing out remaining gaps and challenges. The recent acceleration in pituitary stem cell research may announce an exciting era in this endocrine field. © 2012 Bentham Science Publishers. Source


Vankelecom H.,Catholic University of Leuven | Chen J.,Huazhong University of Science and Technology
Molecular and Cellular Endocrinology | Year: 2014

Some 5. years ago, the stem cells of the adult pituitary gland were discovered. Subsequent in-depth characterization revealed expression of several stemness markers and embryo-typical factors. Now, the quest is open to decipher their role in the gland.When and how pituitary stem cells differentiate to contribute to the mature hormone-producing cell populations is not known. New research models support their involvement in cell regeneration after injury in the gland, and suggest a possible role in pituitary tumor formation. From their expression phenotype, pituitary stem cells seem to re-use embryonic developmental programs during the creation of new hormonal cells.Here, we will review the latest progression in the domain of pituitary stem cells, including the uncovering of some new molecular flavors and of the first potential functions. Eventually, we will speculate on their differentiation programs towards hormonal cells, with a particular focus on gonadotropes. © 2013 Elsevier Ireland Ltd. Source