Quasi-static liquid–air drainage in narrow channels with variations in the gap

This paper studies the shape of an air bubble quasi-statically flowing in the longitudinal direction of narrow channels. Two bottom topographies are treated, i.e., linear and quadratic variations of the gap along the transverse direction. This work analyses the main characteristics of the gas–liquid interface with respect to the wedge aspect ratio. From the convergence of asymptotic, numerical and experimental analyses, we found simple dependences for the finger width and total curvature as a function of channel aspect ratio. These results provide simple and general expressions for the pressure drop needed to overcome capillary forces and push the air finger inside the channel

A Cre-lox approach for transient transgene expression in neural precursor cells and long-term tracking of their progeny in vitro and in vivo.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Neural precursor cells (NPCs) can be isolated from various regions of the postnatal central nervous system (CNS). Manipulation of gene expression in these cells offers a promising strategy to manipulate their fate both in vitro and in vivo. In this study, we developed a technique that allows the transient manipulation of single/multiple gene expression in NPCs in vitro, and the long-term tracking of their progeny both in vitro and in vivo. RESULTS: In order to combine the advantages of transient transfection with the long-term tracking of the transfected cells progeny, we developed a new approach based on the cre-lox technology. We first established a fast and reliable protocol to isolate and culture NPCs as monolayer, from the spinal cord of neonatal transgenic Rosa26-YFP cre-reporter mice. These cells could be reliably transfected with single/multiple plasmids by nucleofection. Nucleofection with mono- or bicistronic plasmids containing the Cre recombinase gene resulted in efficient recombination and the long-term expression of the YFP-reporter gene. The transient cre-expression was non-toxic for the transfected cells and did not alter their intrinsic properties. Finally, we demonstrated that cre-transfected cells could be transplanted into the adult brain, where they maintained YFP expression permitting long-term tracking of their migration and differentiation. CONCLUSION: This approach allows single/multiple genes to be manipulated in NPCs, while at the same time allowing long-term tracking of the transfected cells progeny to be analyzed both in vitro and in vivo

Noise-induced behaviors in neural mean field dynamics

The collective behavior of cortical neurons is strongly affected by the presence of noise at the level of individual cells. In order to study these phenomena in large-scale assemblies of neurons, we consider networks of firing-rate neurons with linear intrinsic dynamics and nonlinear coupling, belonging to a few types of cell populations and receiving noisy currents. Asymptotic equations as the number of neurons tends to infinity (mean field equations) are rigorously derived based on a probabilistic approach. These equations are implicit on the probability distribution of the solutions which generally makes their direct analysis difficult. However, in our case, the solutions are Gaussian, and their moments satisfy a closed system of nonlinear ordinary differential equations (ODEs), which are much easier to study than the original stochastic network equations, and the statistics of the empirical process uniformly converge towards the solutions of these ODEs. Based on this description, we analytically and numerically study the influence of noise on the collective behaviors, and compare these asymptotic regimes to simulations of the network. We observe that the mean field equations provide an accurate description of the solutions of the network equations for network sizes as small as a few hundreds of neurons. In particular, we observe that the level of noise in the system qualitatively modifies its collective behavior, producing for instance synchronized oscillations of the whole network, desynchronization of oscillating regimes, and stabilization or destabilization of stationary solutions. These results shed a new light on the role of noise in shaping collective dynamics of neurons, and gives us clues for understanding similar phenomena observed in biological networks

Topological and semantic Web based method for analyzing TGF-β signaling pathways

International audienceTargeting the deleterious effects of Transforming Growth Factor TGF-β without affecting its physiological role is the common goal of therapeutic strategies aiming at curing fibrosis, the final outcome of all chronic liver disease. The pleiotropic effects of TGF-β are linked to the complex nature of its activation and signaling net- works which understanding requires modeling approaches. Our group recently developed a model of TGF-beta signal propagation based on guarded transitions (ref, Andrieux et al, 2014). In this initial work, we explored the combinatorial complexity of cell signaling, developing a discrete formalism based on guarded transitions. We imported the whole database Pathway Interaction Database into a single unified model of signal transduction. We detected 16,000 chains of reactions linking TGF-β to at least one of 159 target genes in the nucleus. The size and complexity of this model place it beyond current understanding. Its analysis requires automated tools for identifying general patterns.Currently, we focus on designing one reasoning method based on Semantic Web technologies for the analysis of signaling pathways. Our method aims at leveraging external domain knowledge represented in biomedical ontologies and linked databases to rank these candidates. We consider a signaling pathway as a set of proteins involved in the respons of a cell to an external stimulus and influencing at least one gene. The underlying reasoning methods are based on graph topological analysis, formal concepts analysis (FCA) and semantic similarity and particularity measures. First, we determine the formal concepts, maximal bi-cliques, between proteins sets and genes. Then, to determine the biological relevance of theses gene clusters, we calculate a similarity score for each cluster based on Wang semantic similarity. Using such approaches, we identify groups of genes sharing signaling networks.Cibler les effets délétères du Transforming Growth Factor, TGF-β, sans affecter son rôle physiologique est l’objectif commun des stratégies thérapeutiques visant à guérir la fibrose, la conséquence finale de toutes les maladies chroniques du foie. Les effets pléiotropiques du TGF-β sont liés à la nature complexe de son activation et du réseaux de signalisation qu’il induit, et dont la compréhension nécessite des approches de modélisation. Notre équipe a développé un modèle de la propagation du signal induit par le TGF-β base ́ sur les transitions gardées. Le développement d’un formalisme discret base ́ sur les transitions gardées permet d’étudier la complexité combinatoire de la signalisation cellulaire. Nous avons formalise ́ l’intégralité de la base de données Pathway Interaction Database en un unique modèle de la propagation du signal. Nous avons détecté 16 000 chaines de réactions reliant le TGF-β à au moins l’un des 159 gènes cibles d’intérêt Pour identifier des propriétés au sein de ces résultats il est nécessaire d’utiliser des outils automatisés.Nous développons actuellement une méthode basée sur le Web sémantique pour l’analyse des voies de signalisation. Cette méthode vise à tirer parti des connaissances de domaine externe représentées dans les ontologies biomédicales et des bases de données pour classer ces candidats. Nous considérons qu’une voie de signalisation est un ensemble des protéines impliquées dans la réaction d’une cellule à un stimulus externe et qui influence au moins un gène. Les méthodes de raisonnement sous-jacentes sont basées sur l’analyse topologique, l’analyse formelle de concepts et les mesures de similarité et de particularité sémantique. Tout d’abord, nous déterminons les concepts formels, c’est-à-dire les bi-cliques maximales, entre les ensembles de protéines et les gènes. Puis, afin de déterminer la pertinence biologique de ces groupes de gènes, nous calculons un score de similarité pour chacun des groupes, base ́ sur la mesure de Wang. La finalité est d’identifier des groupes de gènes similaires influencés par un même ensemble de voies de signalisation

Magnetoelastic modelling in soft nanocrystalline alloys

Magnetoelastic effects in ultra soft nanocrystalline alloys are investigated theoretically and experimentally. From Hc measurements, extraction of magnetoelastic contribution is carried out using a formalism obtained revisiting random anisotropy model (RAM) in the light of domain walls (DW) displacements, our approach based on theoretical investigations on the way of a reversal of a correlated volume (CV) located in the vicinity of a DW. Modelling of magnetoelastic effects shows that even in perfectly relaxed samples, a magnetoelastic contribution exists due to elastic frustration experienced by a CV during its magnetization reversal. Magnitude of this energy is large enough to drive coercivity of samples featuring grain diameter D around 10 nm, which are of major interest for applications

Acceleration of vaccine development by improvement of process understanding - Analysis of the host cell proteome

While regulatory agencies require stringent product quality and safety to be upheld in biopharmaceutical products, today’s competitive biopharmaceutical market requires short process development times. The demand to accelerate especially the development of vaccines became obvious with the COVID-19 pandemic. By expanding process understanding with the use of process design tools the development time of the purification could be significantly shortened. High throughput experimentation (HTE) provides an automated experimentation platform, which minimizes the amount of used samples and saves experimental time. In this approach, HTE is used to acquire experimental data to regress parameters used as inputs for a chromatographic mechanistic model with the objective to establish an E. coli vaccine purification process development platform for a recombinant subunit vaccine. To provide a generic process development strategy that can be applied to novel antigens, the focus lies on the description of the adsorption behavior of the impurities such as host cell proteins (HCPs) during the capture step. Therefore our approach focuses on the present impurities, in specific the HCPs (Figure 1). When using the same E.coli strain the knowledge regarding the host cell proteins could be transferred to a new product. The first step is the identification of HCPs. Over a thousand HCPs are identified in the E.coli harvest sample investigated by means of mass spectrometry based proteomics. A database containing the properties of these proteins can provide assistance in the decision on chromatography resins suited for the purification process of a new developed antigen. Please click Download on the upper right corner to see the full abstract

Model-based process development for complex vaccine mixtures

The regulations, safety and purity demands are extremely high for vaccine processes and likewise reflected in process development time and cost. Reducing time-to-market is key for pharmaceutical companies, hence saving lives and money, and therefore the need raised for systematic, general and efficient process development strategies (Hanke & Ottens, 2014). Despite the tremendous variation between vaccine purification processes, platform processes for similar types of vaccines could aid to generally accelerate the process development and would be beneficial in terms of knowledge, resources, costs and regulatory aspect. High throughput process development (HTPD) approaches can be used to establish platform processes. HTPD combines high throughput technologies and statistical or mechanistic modeling in an efficient manner. In particular mechanistic models, that aim to describe the real process based upon physical processes occurring, can be of great merit to extend the level of process understanding and thereby support in making decision regarding the process design (Pirrung et al., 2019). Please click Download on the upper right corner to see the full abstract

Alpha-1 antitrypsin deficiency in a French General Hospital: fortuitous detection rather than efficient screening

Introduction: We studied the characteristics of the screening procedure for alpha-1 antitrypsin at Nevers Hospital (France), together with the performance of serum protein gel electrophoresis for the fortuitous detection of patients with deficiency. Material and methods: We carried out a retrospective study of requests for alpha-1 antitrypsin determination referred to the laboratory during 3 years. We compared these requests with the numbers of patients seen at the hospital and requiring screening according to international recommendations. In parallel, we reviewed all the serum protein gel electrophoresis results obtained during the same period. Results: The laboratory received 102 direct requests for alpha-1 antitrypsin determination, whereas more than 1397 patients presented an indication for screening. No case of alpha-1 antitrypsin deficiency was detected among the 102 patients screened. In parallel, 5551 serum protein gel electrophoresis analyses were carried out at the laboratory. A decrease in the size of the alpha-1 globulin fraction was detected in 68 patients. Seventeen of these patients underwent alpha-1 antitrypsin determinations and 14 were found to have alpha-1 antitrypsin deficiency. Conclusion: Alpha-1 antitrypsin deficiency was more frequently detected fortuitously, by electrophoresis, than through efficient screening. The exploration of alpha-1 globulin deficiencies by serum protein gel electrophoresis thus appears to be still a particularly efficient approach to the detection of alpha-1 antitrypsin deficiency and should be carried out systematically. Furthermore, the testing of all patients with an indication for screening according to international recommendations should be encouraged

Approche expérimentale de la tectonique de l'Etna

International audienceL'importance relative de la tectonique régionale et de l'étalement gravitaire sur la stabilité de l'Etna sont étudiés à l'aide de modèles analogiques sable-silicone dimensionnés. Les résultats de cette modélisation montrent notamment que les structures actives observées sur le volcan sont la conséquence d'une interaction entre effets gravitaires et tectonique régionale. En particulier, les composantes décrochantes des failles observées à la fois sur le terrain et sur les modèles réduits sont liés à l'interaction entre le champ de contrainte gravitaire et le champ de contrainte extensif régional. Nous montrons également dans nos modèles que la Valle del Bove, structure majeure du flanc oriental de l'Etna, ne se forme que sous l'influence conjuguée de l'effondrement gravitaire du volcan et du retrait du panneau plongeant ionien suivant des failles majeures