Chinese investment in North Africa should be viewed as an opportunity not a threat

LSE’s Chris Alden and Faten Aggard Clerx of ECDPM urge North African leaders to think of a smart solution that would allow them to derive the full benefit from Chinese investments

Four Ways to Fit an Ion Channel Model

© 2019 Biophysical Society Mathematical models of ionic currents are used to study the electrophysiology of the heart, brain, gut, and several other organs. Increasingly, these models are being used predictively in the clinic, for example, to predict the risks and results of genetic mutations, pharmacological treatments, or surgical procedures. These safety-critical applications depend on accurate characterization of the underlying ionic currents. Four different methods can be found in the literature to fit voltage-sensitive ion channel models to whole-cell current measurements: method 1, fitting model equations directly to time-constant, steady-state, and I-V summary curves; method 2, fitting by comparing simulated versions of these summary curves to their experimental counterparts; method 3, fitting to the current traces themselves from a range of protocols; and method 4, fitting to a single current trace from a short and rapidly fluctuating voltage-clamp protocol. We compare these methods using a set of experiments in which hERG1a current was measured in nine Chinese hamster ovary cells. In each cell, the same sequence of fitting protocols was applied, as well as an independent validation protocol. We show that methods 3 and 4 provide the best predictions on the independent validation set and that short, rapidly fluctuating protocols like that used in method 4 can replace much longer conventional protocols without loss of predictive ability. Although data for method 2 are most readily available from the literature, we find it performs poorly compared to methods 3 and 4 both in accuracy of predictions and computational efficiency. Our results demonstrate how novel experimental and computational approaches can improve the quality of model predictions in safety-critical applications

Gevolgen van de aanleg van Rijksweg73-Zuid voor de zeggekorfslak en de kwaliteit van de elzenbroekbossen in het Swalmdal

De directie Zuid van het ministerie van Landbouw, Natuurbeheer en Visserij heeft Alterra verzocht, ten behoeve van de behandeling van de ontheffingsaanvraag voor het A73-tracédeel Swalmen in het kader van de Natuurbeschermingswet/Habitatrichtlijn ingediend door Rijkswaterstaat, onderzoek te verrichten naar de kwaliteit van de informatie die in de aanvraag van Rijkswaterstaat is gebruikt over het voorkomen van de zeggekorfslak in het Swalmdal, en de mogelijke directe of indirecte effecten van het A73-tracédeel door of direct langs het Swalmdal op de daar voorkomende populaties van de zeggekorfslak. In dit rapport wordt verslag gedaan van de bevindingen van dit onderzoek

Multi-scale modeling and variability in cardiac cellular electrophysiology

Cardiac rhythm is the result of interactions between millions of heart muscle cells. Genetic, molecular and functional factors are involved on the cellular, tissue and organ level. Multi-scale computer models are used to study this complex interplay of processes on various levels. This dissertation introduces a software application that makes these models more versatile and easier to use. It also presents results on the effects of genetic mutations and natural variability on ion channel function in heart muscle cells. These results improve our understanding of the mechanisms of the heart and can serve as a catalyst for studies on cardiac arrhythmias

Modulation of angiogenesis during adipose tissue development in murine models of obesity.

peer reviewedDevelopment of vasculature and mRNA expression of 17 pro- or antiangiogenic factors were studied during adipose tissue development in nutritionally induced or genetically determined murine obesity models. Subcutaneous (SC) and gonadal (GON) fat pads were harvested from male C57Bl/6 mice kept on standard chow [standard fat diet (SFD)] or on high-fat diet for 0-15 wk and from male ob/ob mice kept on SFD. Ob/ob mice and C57Bl/6 mice on high-fat diet had significantly larger SC and GON fat pads, accompanied by significantly higher blood content, increased total blood vessel volume, and higher number of proliferating cells. mRNA and protein levels of angiopoietin (Ang)-1 were down-regulated, whereas those of thrombospondin-1 were up-regulated in developing adipose tissue in both obesity models. Ang-1 mRNA levels correlated negatively with adipose tissue weight in the early phase of nutritionally induced obesity as well as in genetically determined obesity. Placental growth factor and Ang-2 expression were increased in SC adipose tissue of ob/ob mice, and thrombospondin-2 was increased in both their SC and GON fat pads. mRNA levels of vascular endothelial growth factor (VEGF)-A isoforms VEGF-B, VEGF-C, VEGF receptor-1, -2, and -3, and neuropilin-1 were not markedly modulated by obesity. This modulation of angiogenic factors during development of adipose tissue supports their important functional role in obesity

Novel alignment technique for LCD-biosensors

Contains fulltext : 13921.pdf (publisher's version ) (Open Access

Comprendre l’activité réflexive des stagiaires en éducation physique à travers leur rapport de stage : entre « théories subjectives » et « répertoire de savoirs professionnels »

Pour provoquer l’écriture réflexive de stagiaires en éducation physique (n =37), une liste de 39 concepts représentatifs des contenus théoriques et didactiques de leur formation initiale leur est présentée. A charge pour eux de commenter leur activité d’enseignement dans le dernier rapport de stage, à lumière de cinq concepts librement choisis. Le corpus de la présente recherche est constitué des 185 récits de cette cohorte. De nature descriptive et interprétative, son but est de répondre à la question : « Qu’écrivent les stagiaires de ce qu’ils font ? ». Les neuf concepts les plus utilisés sont analysés ci-après. Les récits consacrés à l’improvisation structurée, aux allants-de-soi et à l’impossible à supporter soulignent l’appartenance des stagiaires au genre débutant. Les écrits relatifs aux tâches gagnantes et à la relation montrent l’acquisition des compétences et la constitution progressive de leur identité professionnelle.To provoke reflexive writing of pre-service teachers in physical education (n=37), a list of 39 representative concepts of the theoretical and didactic contents of their initial formation's courses is presented to them. The instruction is to comment their activity of education teaching in their training book, in light of five concepts freely chosen among 39. 185 narratives papers establish the sample of this present research with a descriptive and interpretative nature. The aim of this study is to answer the following question: « What the pre-service teachers are capable of writing about their activity in class? ». In other words, this study questions the report in the knowledge of the beginners. The results show that trainees used nine concepts mainly. These nine most used concepts are analyzed below. Narratives dedicated to concepts like « improvisation structurée », « allants de soi », « impossible à supporter » underline the novice teachers relatedness perception of students. Finally this analysis of reflexive writings papers report of the acquisition of the competence and the progressive constitution of professional identity by pre-service teachers

Physiology-based regularization of the electrocardiographic inverse problem

The inverse problem of electrocardiography aims at noninvasively reconstructing electrical activity of the heart from recorded body-surface electrocardiograms. A crucial step is regularization, which deals with ill-posedness of the problem by imposing constraints on the possible solutions. We developed a regularization method that includes electrophysiological input. Body-surface potentials are recorded and a computed tomography scan is performed to obtain the torso-heart geometry. Propagating waveforms originating from several positions at the heart are simulated and used to generate a set of basis vectors representing spatial distributions of potentials on the heart surface. The real heart-surface potentials are then reconstructed from the recorded body-surface potentials by finding a sparse representation in terms of this basis. This method, which we named 'physiology-based regularization' (PBR), was compared to traditional Tikhonov regularization and validated using in vivo recordings in dogs. PBR recovered details of heart-surface electrograms that were lost with traditional regularization, attained higher correlation coefficients and led to improved estimation of recovery times. The best results were obtained by including approximate knowledge about the beat origin in the PBR basis

Models of the cardiac L-type calcium current: a quantitative comparison

The L-type calcium current (ICaL) plays a critical role in cardiac electrophysiology, and models of ICaL are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modelling ICaL have resulted in several competing theories (encoded in mathematical equations). However, the introduction of new models has not typically been accompanied by a data-driven critical comparison with previous work, so that it is unclear where predictions overlap or conflict, or which model is best suited for any particular application. We gathered 71 mammalian ICaL models, compared their structure, and reproduced simulated experiments to show that there is a large variability in their predictions, which was not substantially diminished when grouping by species or other categories. By highlighting the differences in these competing theories, listing major data sources, and providing simulation code, we have laid strong foundations for the development of a consensus model of ICaL