Statistical inference across time scales

We investigate statistical inference across time scales. We take as toy model the estimation of the intensity of a discretely observed compound Poisson process with symmetric Bernoulli jumps. We have data at different time scales: microscopic, intermediate and macroscopic. We quantify the smooth statistical transition from a microscopic Poissonian regime to a macroscopic Gaussian regime. The classical quadratic variation estimator is efficient in both microscopic and macroscopic scales but surprisingly shows a substantial loss of information in the intermediate scale that can be explicitly related to the sampling rate. We discuss the implications of these findings beyond this idealised framework.Comment: 29 pages, 2 figure

Existence of Weak Solutions for the Unsteady Interaction of a Viscous Fluid with an Elastic Plate

International audienceWe consider a three--dimensional viscous incompressible fluid governed by the Navier--Stokes equations, interacting with an elastic plate located on one part of the fluid boundary. We do not neglect the deformation of the fluid domain which consequently depends on the displacement of the structure. The purpose of this work is to study the solutions of this unsteady fluid--structure interaction problem, as the coefficient modeling the viscoelasticity (resp. the rotatory inertia) of the plate tends to zero. As a consequence, we obtain the existence of at least one weak solution for the limit problem (Navier--Stokes equation coupled with a plate in flexion) as long as the structure does not touch the bottom of the fluid cavity

Mouse Natural Killer (NK) Cells Express the Nerve Growth Factor Receptor TrkA, which Is Dynamically Regulated

Background: Nerve growth factor (NGF) is a neurotrophin crucial for the development and survival of neurons. It also acts on cells of the immune system which express the NGF receptors TrkA and p75 NTR and can be produced by them. However, mouse NK cells have not yet been studied in this context. Methodology/Principal Findings: We used cell culture, flow cytometry, confocal microscopy and ELISA assays to investigate the expression of NGF receptors by NK cells and their secretion of NGF. We show that resting NK cells express TrkA and that the expression is different on NK cell subpopulations defined by the relative presence of CD27 and CD11b. Expression of TrkA is dramatically increased in IL-2-activated NK cells. The p75 NTR is expressed only on a very low percentage of NK cells. Functionally, NGF moderately inhibits NK cell degranulation, but does not influence proliferation or cytokine production. NK cells do not produce NGF. Conclusions/Significance: We demonstrate for the first time that mouse NK cells express the NGF receptor TrkA and tha

Qualitätskriterien transdisziplinärer Forschung : ein Leitfaden für die formative Evaluation von Forschungsprojekten

Transdisziplinäre Forschung befasst sich mit lebensweltlichen Problemstellungen. Bei der Forschungsarbeit müssen Experten/innen aus verschiedenen Fächern bzw. Disziplinen und aus der Praxis zusammenwirken, um die komplexe Problematik umfassend behandeln zu können. Diese Vielfalt, die besondere Formen der Kooperation, der Differenzierung und Integration, Methoden und Theorien impliziert, bringt es mit sich, dass gängige, bei der fachbezogenen Bewertung hinreichende Verfahren der Evaluation und der Qualitätssicherung nicht unmittelbar auf solche Forschungsvorhaben übertragen werden können. Diesem Mangel an Kriterien und Methoden der Evaluation begegnet Evalunet, das Evaluationsnetzwerk für transdisziplinäre Forschung, mit dem vorgelegten Leitfaden für die Forschungspraxis, der vor allem ausführlich beschriebene Qualitätskriterien enthält und ebenso Aussagen zu methodischen und Verfahrensfragen macht. Er ist aus der empirischen Auswertung konkreter transdisziplinärer Forschungsprojekte und unter Mithilfe zahlreicher Experten und Expertinnen aus verschiedenen Fachrichtungen entstanden. Der Leitfaden dient dem Zweck der Evaluation von transdisziplinären Forschungsprojekten, wobei dieses Instrument auf den Aspekt des Lernens aus dem Evaluationsvorgang (formative Evaluation) zugeschnitten ist und bei der Aus- und Bewertung auf einen Diskurs setzt (diskursive Evaluation). Neben einer Evaluierung mittels der ausführlich beschriebenen Detailkriterien ist auch eine weniger aufwändige Evaluation mit Hilfe einer Kriterienauswahl (Basiskriterien) möglich. Die Qualitätskriterien können auch für die Konzipierung neuer transdisziplinärer Forschungsvorhaben genutzt werden.Transdisciplinary research projects investigate problems from everyday life. Experts from various disciplines and practitioners from the practical field in question have to co-operate to cope with the problem appropriately. Multiple forms of co-operation, differentiation and integration, methods and theories are significant for such projects. So conventional methods of disciplinary evaluation cannot be transferred and applied directly. In this situation, Evalunet, the Network for Transdisciplinary Evaluation, offers this guide, which provides researchers with very detailed evaluation criteria and descriptions of evaluation methods and practices. The criteria and procedures were identified in an empirical process by evaluating a number of transdisciplinary research projects. In this process, the Evalunet team was supported by numerous experts from various research areas. The main purpose of the guide is to provide guidance for the evaluation of transdisciplinary research projects. The criteria mainly support discursive evaluation processes that initiate learning processes for researchers and evaluators (formative evaluation). A set with a reduced number of criteria (Basiskriterien) offers a basic procedure for the evaluation, while the larger set with more detailed criteria (Detailkriterien) provides explanations and assistance in making a judgement. Criteria can also be used for conceiving and constructing new research projects

In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization

The apicomplexan parasite Toxoplasma gondii forms bradyzoite-containing tissue cysts that cause chronic and drug-tolerant infections. However, current in vitro models do not allow long-term culture of these cysts to maturity. Here, we developed a human myotube-based in vitro culture model of functionally mature tissue cysts that are orally infectious to mice and tolerate exposure to a range of antibiotics and temperature stresses. Metabolomic characterization of purified cysts reveals global changes that comprise increased levels of amino acids and decreased abundance of nucleobase- and tricarboxylic acid cycle-associated metabolites. In contrast to fast replicating tachyzoite forms of T. gondii these tissue cysts tolerate exposure to the aconitase inhibitor sodium fluoroacetate. Direct access to persistent stages of T. gondii under defined cell culture conditions will be essential for the dissection of functionally important host-parasite interactions and drug evasion mechanisms. It will also facilitate the identification of new strategies for therapeutic intervention.Peer Reviewe

Quantitative Kinetic Study of the Actin-Bundling Protein L-Plastin and of Its Impact on Actin Turn-Over

BACKGROUND: Initially detected in leukocytes and cancer cells derived from solid tissues, L-plastin/fimbrin belongs to a large family of actin crosslinkers and is considered as a marker for many cancers. Phosphorylation of L-plastin on residue Ser5 increases its F-actin binding activity and is required for L-plastin-mediated cell invasion. METHODOLOGY/PRINCIPAL FINDINGS: To study the kinetics of L-plastin and the impact of L-plastin Ser5 phosphorylation on L-plastin dynamics and actin turn-over in live cells, simian Vero cells were transfected with GFP-coupled WT-L-plastin, Ser5 substitution variants (S5/A, S5/E) or actin and analyzed by fluorescence recovery after photobleaching (FRAP). FRAP data were explored by mathematical modeling to estimate steady-state reaction parameters. We demonstrate that in Vero cell focal adhesions L-plastin undergoes rapid cycles of association/dissociation following a two-binding-state model. Phosphorylation of L-plastin increased its association rates by two-fold, whereas dissociation rates were unaffected. Importantly, L-plastin affected actin turn-over by decreasing the actin dissociation rate by four-fold, increasing thereby the amount of F-actin in the focal adhesions, all these effects being promoted by Ser5 phosphorylation. In MCF-7 breast carcinoma cells, phorbol 12-myristate 13-acetate (PMA) treatment induced L-plastin translocation to de novo actin polymerization sites in ruffling membranes and spike-like structures and highly increased its Ser5 phosphorylation. Both inhibition studies and siRNA knock-down of PKC isozymes pointed to the involvement of the novel PKC-delta isozyme in the PMA-elicited signaling pathway leading to L-plastin Ser5 phosphorylation. Furthermore, the L-plastin contribution to actin dynamics regulation was substantiated by its association with a protein complex comprising cortactin, which is known to be involved in this process. CONCLUSIONS/SIGNIFICANCE: Altogether these findings quantitatively demonstrate for the first time that L-plastin contributes to the fine-tuning of actin turn-over, an activity which is regulated by Ser5 phosphorylation promoting its high affinity binding to the cytoskeleton. In carcinoma cells, PKC-delta signaling pathways appear to link L-plastin phosphorylation to actin polymerization and invasion

Existence of global strong solutions to a beam-fluid interaction system

We study an unsteady non linear fluid-structure interaction problem which is a simplified model to describe blood flow through viscoleastic arteries. We consider a Newtonian incompressible two-dimensional flow described by the Navier-Stokes equations set in an unknown domain depending on the displacement of a structure, which itself satisfies a linear viscoelastic beam equation. The fluid and the structure are fully coupled via interface conditions prescribing the continuity of the velocities at the fluid-structure interface and the action-reaction principle. We prove that strong solutions to this problem are global-in-time. We obtain in particular that contact between the viscoleastic wall and the bottom of the fluid cavity does not occur in finite time. To our knowledge, this is the first occurrence of a no-contact result, but also of existence of strong solutions globally in time, in the frame of interactions between a viscous fluid and a deformable structure

Actin cytoskeleton remodeling at the cancer cell side of the immunological synapse: good, bad, or both?

Cytotoxic lymphocytes (CLs), specifically cytotoxic T lymphocytes and natural killer cells, are indispensable guardians of the immune system and orchestrate the recognition and elimination of cancer cells. Upon encountering a cancer cell, CLs establish a specialized cellular junction, known as the immunological synapse that stands as a pivotal determinant for effective cell killing. Extensive research has focused on the presynaptic side of the immunological synapse and elucidated the multiple functions of the CL actin cytoskeleton in synapse formation, organization, regulatory signaling, and lytic activity. In contrast, the postsynaptic (cancer cell) counterpart has remained relatively unexplored. Nevertheless, both indirect and direct evidence has begun to illuminate the significant and profound consequences of cytoskeletal changes within cancer cells on the outcome of the lytic immunological synapse. Here, we explore the understudied role of the cancer cell actin cytoskeleton in modulating the immune response within the immunological synapse. We shed light on the intricate interplay between actin dynamics and the evasion mechanisms employed by cancer cells, thus providing potential routes for future research and envisioning therapeutic interventions targeting the postsynaptic side of the immunological synapse in the realm of cancer immunotherapy. This review article highlights the importance of actin dynamics within the immunological synapse between cytotoxic lymphocytes and cancer cells focusing on the less-explored postsynaptic side of the synapse. It presents emerging evidence that actin dynamics in cancer cells can critically influence the outcome of cytotoxic lymphocyte interactions with cancer cells

Arabidopsis actin-depolymerizing factors (ADFs) 1 and 9 display antagonist activities

AbstractWe provide evidence that one of the 11 Arabidopsis actin-depolymerizing factors (ADFs), namely ADF9, does not display typical F-actin depolymerizing activity. Instead, ADF9 effectively stabilizes actin filaments in vitro and concomitantly bundles actin filaments with the highest efficiency under acidic conditions. Competition experiments show that ADF9 antagonizes ADF1 activity by reducing its ability to potentiate F-actin depolymerization. Accordingly, ectopic expression of ADF1 and ADF9 in tobacco cells has opposite effects. ADF1 severs actin filaments/bundles and promotes actin cytoskeleton disassembly, whereas ADF9 induces the formation of long bundles. Together these data reveal an additional degree of complexity in the comprehension of the biological functions of the ADF family and illustrate that antagonist activities can be displayed by seemingly equivalent actin-binding proteins

Le réseau PENSERA, acteur du développement de structures d’appui pédagogique en France

Le réseau PENSERA (Pédagogie de l’ENseignement Supérieur En Rhône-Alpes) est un réseau qui regroupe les services d’appui pédago-giques de quatre établissements de la région Rhône-Alpes : l’Université Lyon 1, l’Université Grenoble 1, Grenoble INP, et l’ENSAL. L’Université Jean Monnet de St Etienne deviendra prochainement le cinquième membre de ce réseau. Les conseillers pédagogiques concernés se sont engagés dans une dynamique d’échanges et de mutualisation, basée sur des rencontres mensuelles d’une journée, ainsi que sur la co-conception et la co-animation d’actions pédagogiques au service des enseignants de ces établissements. Le nombre de personnes assurant la fonction de « conseiller pédago-gique » dans l’enseignement supérieur en France est en augmentation notable, et la très grande majorité d’entre eux démarre dans cette mis-sion. Notre réseau est donc régulièrement sollicité pour accompagner la mise en place de structures d’appui pédagogique. Ces nombreuses de-mandes nous placent devant une interrogation : comment aider d’autres services à démarrer (ce qui nous rend plus fort collectivement et nous donne de la visibilité) tout en préservant nos forces qui doivent bénéfi-cier en priorité aux enseignants de nos institutions ? Notre réponse se traduit par l’adoption d’une posture responsabili-sante vis-à-vis des demandeurs, qui pourrait se résumer à cette philoso-phie : « quand un homme a faim, mieux vaut lui apprendre à pêcher que de lui donner un poisson » [Confucius]. Le réseau n’a ainsi pas vocation à assurer une prestation de service pour un autre établissement. En re-vanche il soutient la naissance et le développement des structures d’appui pédagogiques en France, notamment en assurant la montée en compétences des personnes chargées d’en assurer l’animation locale-ment. Cette posture, qui se traduit dans les faits par différents types d’actions, est une réponse pertinente au défi qui nous attend du fait du développement croissant de services d’appui pédagogique dans les éta-blissements d’enseignement supérieur en France