Optimal localization patterns in bacterial protein synthesis

In $\textit{Escherichia coli}$ bacterium, the molecular compounds involved in protein synthesis, messenger RNAs (mRNAs) and ribosomes, show marked intracellular localization patterns. Yet a quantitative understanding of the physical principles which would allow one to control protein synthesis by designing, bioengineering, and optimizing these localization patterns is still lacking. In this study, we consider a scenario where a synthetic modification of mRNA reaction-diffusion properties allows for controlling the localization and stoichiometry of mRNAs and polysomes$\mathrm{-}$complexes of multiple ribosomes bound to mRNAs. Our analysis demonstrates that protein synthesis can be controlled, e.g., optimally enhanced or inhibited, by leveraging mRNA spatial localization and stoichiometry only, without resorting to alterations of mRNA expression levels. We identify the physical mechanisms that control the protein-synthesis rate, highlighting the importance of colocalization between mRNAs and freely diffusing ribosomes, and the interplay between polysome stoichiometry and excluded-volume effects due to the DNA nucleoid. The genome-wide, quantitative predictions of our work may allow for a direct verification and implementation in cell-biology experiments, where localization patterns and protein-synthesis rates may be monitored by fluorescence microscopy in single cells and populations

Modélisation de structures en béton armé avec des éléments poutres multifibres

International audienceOn présente dans cette étude la modélisation du comportement de structures en béton armé en utilisant des éléments poutres multifibres. Les modèles du comportement utilisés associent plasticité pour les aciers et endommagement pour le béton. Les structures étudiées sont un poteau soumis à un chargement cyclique 3D, testé au laboratoire ELSA d'Ispra et un bâtiment à deux murs contreventés, testé à la table sismique du laboratoire LNEC à Lisbonne

Theoretical and experimental study of (In,Ga)As/GaP quantum dots

International audience(In,Ga)As/GaP(001) quantum dots (QDs) are grown by molecular beam epitaxy and studied both theoretically and experimentally. The electronic band structure is simulated using a combination of k*p and tight-binding models. These calculations predict an indirect to direct crossover with the In content and the size of the QDs. The optical properties are then studied in a low-In-content range through photoluminescence and time-resolved photoluminescence experiments. It suggests the proximity of two optical transitions of indirect and direct types

Structural and optical properties of (In,Ga)As/GaP quantum dots and (GaAsPN/GaPN) diluted-nitride nanolayers coherently grown onto GaP and Si substrates for photonics and photovoltaics applications

San Francisco, California, United StatesInternational audienceLattice-matched GaP-based nanostructures grown on silicon substrates is a highly rewarded route for coherent integration of photonics and high-efficiency photovoltaic devices onto silicon substrates. We report on the structural and optical properties of selected MBE-grown nanostructures on both GaP substrates and GaP/Si pseudo-substrates. As a first stumbling block, the GaP/Si interface growth has been optimised thanks to a complementary set of thorough structural analyses. Photoluminescence and time-resolved photoluminescence studies of self-assembled (In,Ga)As quantum dots grown on GaP substrate demonstrate a proximity of two different types of optical transitions interpreted as a competition between conduction band states in X and Γ valleys. Structural properties and optical studies of GaAsP(N)/GaP(N) quantum wells coherently grown on GaP substrates and GaP/Si pseudo substrates are reported. Our results are found to be suitable for light emission applications in the datacom segment. Then, possible routes are drawn for larger wavelengths applications, in order to address the chip-to-chip and within-a-chip optical interconnects and the optical telecom segments. Finally, results on GaAsPN/GaP heterostructures and diodes, suitable for PV applications are reporte

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Codèle (une approche de composition de modèles pour la construction de systèmes à grande échelle)

Depuis "toujours", en Génie Logiciel comme dans toutes les ingénieries, afin réduire la complexité et pour améliorer la réutilisation, le produit à construire est divisé en parties construites indépendamment et ensuite assemblées. L'approche récente de l'Ingénierie Dirigée par les Modèles (IDM, ou MDE pour Model-Driven Engineering), fait de même, en proposant "simplement" que les parties à construire et à assembler soient des modèles et non pas des programmes. C'est ainsi que le problème de la composition de modèles est devenu un thème important de l'IDM, et le sujet de cette thèse. En effet, un système logiciel réel est bien trop complexe pour pouvoir être décrit par un seul modèle. De nombreux modèles devront être créés pour le spécifier, soit à divers niveaux d'abstraction, soit selon divers points de vue, soit encore selon des domaines fonctionnels differents et complémentaires. Dans ce travail, nous partons de l'hypothèse que de tels domaines métiers existent. Un domaine est un champ d'expertise avec 1) les savoir-faire et les connaissances capturés et formalisés sous la forme d'un langage de modélisation dédié au domaine (un Domain-Specific Modeling Language (DSML)), et 2) des outils et des environnements supportant le développement d'applications dans ce domaine. Une application, dans un domaine, est décrite par un modèle (conforme au métamodèle du domaine). Dans ce travail, nous faisons aussi l'hypothèse que ces domaines sont exécutables ; les modèles du domaine sont exécutés par une machine virtuelle du domaine. En IDM, comme dans les autres approches du Génie Logiciel, la réutilisation impose que le processus d'assemblage des parties puisse se faire sans avoir à modifier celles-ci, ni bien sur l'environnement qui les a produit ou qui les exécute. Appliqué à notre contexte, cela signifie qu'il faut être capable de composer des modèles sans les modifier et sans modifier ni l'éditeur ni la machine virtuelle du domaine dont ils sont issus. C'est le problème que nous abordons dans notre travail. Nous montrons que pour atteindre cet objectif, il faut d'abord composer les domaines c'est à dire composer leurs métamodèles et leurs machines virtuelles, puis les modèles. Nous montrons dans ce travail comment ces compositions peuvent être réalisées sans modifier les éléments compos és, en utilisant des relations dites horizontales entre les métamodèles, et des liens entre les modèles. Cette approche est validée d'abord par la réalisation d'un certain nombre de domaines composites, et par de nombreuses compositions de modèles opérationnelles. Une partie importante du travail a consisté à définir Codèle, un langage de composition de modèles et de métamodèles, et à réaliser l'environnement d'assistance correspondant. Codèle assiste les ingénieurs pour composer de façon systématique les domaines, et rend automatique ou semi-automatique la composition de tous modèles provenant de ces domaines. Nous présentons l'outil Codèle et nous évaluons son usage dans divers projets.Since "always", in Software Engineering as in all other engineering fields, the product to be built is divided into parts that are independently built and subsequently assembled. This procedure reduces the complexity and improves the reusability of the products built. Model-Driven Engineering (MDE) is a recent engineering initiative that adopts this approach. MDE "simply" proposes that the parts to be built and assembled be models rather than software programs. In this context, the problem of model composition has become an important theme in the MDE domain and constitutes the subject of this thesis. Indeed, a real software system is much too complex to be described in a single model. Multiple models should be created for the system specification. Such models could represent different system abstraction levels, different system view-points, or different and complementary functional domains. In the presented work, we start from the hypothesis that such application domains do exist. A certain domain is a specialised field containing: 1) the know-how and the knowledge captured and formalised via a Domain-Specific Modeling Language (DSML); and 2) tools and environments for supporting the development of applications in the corresponding domain. In a certain domain, an application is described via a model (that conforms to the domain-specific meta-model). In the presented work, we also make the hypothesis that the considered domains are executable - the domain's models are executed by a domain-specific virtual machine. In MDE, as in all other Software Engineering approaches, reutilisation imposes that the assembly process can be performed without having to modify the parts concerned or their production or execution environment. In our context, this means that model composition must be possible without modifying the concerned models and their domain-specific development editor and virtual machine. This is the problem that our work addresses. We show that for reaching this goal we must first compose the concerned domains and then their specific models. In other words, we must first compose the domains' meta-models and virtual machines. In this work, we show how such compositions can be performed without modifying the composed elements, by using horizontal relations between the meta-models and links between the models. This approach is validated via the creation of several composed domains and numerous composed functional models. An important part of this work consisted in defining Codèle - a model and meta-model composition language, and providing the corresponding support environment. Codèle assists engineers in performing system compositions in a systematic manner and renders automatic or semi-automatic all model composition in these domains. We present the Codèle tool and we evaluate its use in various projects.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF