How does variability in cells aging and growth rates influence the malthus parameter?

The aim of this study is to compare the growth speed of different cell populations measured by their Malthus parameter. We focus on both the age-structured and size-structured equations. A first population (of reference) is composed of cells all aging or growing at the same rate $\bar v$. A second population (with variability) is composed of cells each aging or growing at a rate $v$ drawn according to a non-degenerated distribution $\rho$ with mean $\bar v$. In a first part, analytical answers -- based on the study of an eigenproblem -- are provided for the age-structured model. In a second part, numerical answers -- based on stochastic simulations -- are derived for the size-structured model. It appears numerically that the population with variability proliferates more slowly than the population of reference (for experimentally plausible division rates). The decrease in the Malthus parameter we measure, around 2% for distributions $\rho$ with realistic coefficients of variations around 15-20\%, is determinant since it controls the {\it exponential} growth of the whole population

Nonparametric estimation of the division rate of an age dependent branching process

We study the nonparametric estimation of the branching rate $B(x)$ of a supercritical Bellman-Harris population: a particle with age $x$ has a random lifetime governed by $B(x)$; at its death time, it gives rise to $k \geq 2$ children with lifetimes governed by the same division rate and so on. We observe in continuous time the process over $[0,T]$. Asymptotics are taken as $T \rightarrow \infty$; the data are stochastically dependent and one has to face simultaneously censoring, bias selection and non-ancillarity of the number of observations. In this setting, under appropriate ergodicity properties, we construct a kernel-based estimator of $B(x)$ that achieves the rate of convergence $\exp(-\lambda_B \frac{\beta}{2\beta+1}T)$, where $\lambda_B$ is the Malthus parameter and $\beta >0$ is the smoothness of the function $B(x)$ in a vicinity of $x$. We prove that this rate is optimal in a minimax sense and we relate it explicitly to classical nonparametric models such as density estimation observed on an appropriate (parameter dependent) scale. We also shed some light on the fact that estimation with kernel estimators based on data alive at time $T$ only is not sufficient to obtain optimal rates of convergence, a phenomenon which is specific to nonparametric estimation and that has been observed in other related growth-fragmentation models

Alibaba, un projet d’avenir pour la Wallonie ?

Dans la matinée du mercredi 5 décembre 2018, le gouvernement fédéral vacille. Le Premier ministre doit prendre la parole devant la Chambre, mais ce matin-là, Charles Michel est à l’aéroport de Liège, pour la signature de l’arrivée du géant chinois du commerce en ligne, Alibaba, via sa filiale Cainiao. « Un jour historique », selon lui

8p22 MTUS1 Gene Product ATIP3 Is a Novel Anti-Mitotic Protein Underexpressed in Invasive Breast Carcinoma of Poor Prognosis

BACKGROUND: Breast cancer is a heterogeneous disease that is not totally eradicated by current therapies. The classification of breast tumors into distinct molecular subtypes by gene profiling and immunodetection of surrogate markers has proven useful for tumor prognosis and prediction of effective targeted treatments. The challenge now is to identify molecular biomarkers that may be of functional relevance for personalized therapy of breast tumors with poor outcome that do not respond to available treatments. The Mitochondrial Tumor Suppressor (MTUS1) gene is an interesting candidate whose expression is reduced in colon, pancreas, ovary and oral cancers. The present study investigates the expression and functional effects of MTUS1 gene products in breast cancer. METHODS AND FINDINGS: By means of gene array analysis, real-time RT-PCR and immunohistochemistry, we show here that MTUS1/ATIP3 is significantly down-regulated in a series of 151 infiltrating breast cancer carcinomas as compared to normal breast tissue. Low levels of ATIP3 correlate with high grade of the tumor and the occurrence of distant metastasis. ATIP3 levels are also significantly reduced in triple negative (ER- PR- HER2-) breast carcinomas, a subgroup of highly proliferative tumors with poor outcome and no available targeted therapy. Functional studies indicate that silencing ATIP3 expression by siRNA increases breast cancer cell proliferation. Conversely, restoring endogenous levels of ATIP3 expression leads to reduced cancer cell proliferation, clonogenicity, anchorage-independent growth, and reduces the incidence and size of xenografts grown in vivo. We provide evidence that ATIP3 associates with the microtubule cytoskeleton and localizes at the centrosomes, mitotic spindle and intercellular bridge during cell division. Accordingly, live cell imaging indicates that ATIP3 expression alters the progression of cell division by promoting prolonged metaphase, thereby leading to a reduced number of cells ungergoing active mitosis. CONCLUSIONS: Our results identify for the first time ATIP3 as a novel microtubule-associated protein whose expression is significantly reduced in highly proliferative breast carcinomas of poor clinical outcome. ATIP3 re-expression limits tumor cell proliferation in vitro and in vivo, suggesting that this protein may represent a novel useful biomarker and an interesting candidate for future targeted therapies of aggressive breast cancer

Solutions to a nonlinear Neumann problem in three-dimensional exterior domains

International audienceWe prove the existence of multipeak solutions for an nonlinear elliptic Neumann problem involving nearly critical Sobolev exponent, in three-dimensional exterior domains

Étude comparative de récepteurs aux œstrogènes (aspects moléculaire et cellulaire de la réponse aux œstrogènes et anti-œstrogènes impliqués dans les causes et thérapies du cancer du sein)

Les œstrogènes (E2), via le récepteur aux œstrogènes (ER), contrôlent l expression de nombreux gènes impliqués dans la croissance, la différenciation cellulaire et les fonctions reproductrices. La régulation de ces gènes résulte de la fixation du ER sur une séquence d ADN : Elément de Réponse aux Œstrogènes (ERE). ER joue un rôle majeur dans le cancer du sein, il est donc important de comprendre les mécanismes moléculaires qui modulent in vivo son activité. Nous observons que, comparé à l EREconsensus, les ER présentent une affinité vis-à-vis d un EREimparfait (rtvtgERE), une activité cellulaire et une sensibilité à E2 plus faible. Une étude in vitro du comportement conformationnel, thermodynamique et dynamique des ER a démontré un rôle du réseau électrostatique au sein des ER dans leurs différences de fonctionnalité. Nous avons recherché et comparé l impact de la liaison au ligand sur l activité cellulaire de deux ER : hER et rtERS. La reconstitution de leur mécanisme d action chez la levure a montré que hER est un facteur d activation de la transcription plus puissant que rtERS et qu il est plus sensible à E2. Nous observons aussi que la présence de ligand induit une relocalisation des ER au sein de foci. Une étude cinétique de l activation transcriptionnelle et de la relocalisation subcellulaire des ER en présence de ligand nous pousse à distinguer ces deux aspects. Nous suggérons qu un fort niveau de phosphorylation de ER par les kinases activées en présence de ligand, augmente son caractère anionique conduisant à empêcher sa fixation à l ADN ou à l en dissocier. Ainsi, ER pourrait être recruté par des complexes dans le noyau ou dans le cytoplasme et formé ces foci.Estrogens (E2), through estrogen receptors (ERs), control the expression of a number of genes involved in growth, cellular differentiation and reproductive functions. Regulation of these genes is carried out by the ER binding to a DNA sequence: the Estrogen Responsive Element (ERE). ERs play a major role in breast cancer and therefore it s important to understand the molecular mechanisms which modulate ER activity in vivo. We found that, compared to the consensus ERE, ERs exhibit a lesser affinity for the imperfect ERE (rtvtgERE), cellular activity and E2 sensitivity. An in vitro study on the ERs conformational, thermodynamical and dynamical behaviour has proved that the electrostatic network plays a role in their different functionalities. We researched and compared the impact of the ligands fixation on the cellular activity of two ER: hER and rtERS. The transcriptional mechanism created in yeast allowed us to show that hER is a transcriptional activator which is more potent and more sensitive to E2 than rtERS. We observed that the presence of the ligand induces ER localization within foci. Time curses of the ER transcriptional activation and sub-cellular localization in the presence of ligands lead us to distinguish these two aspects. We suggest that a high phosphorylation level by kinases activated in the presence of ligand increases the ER anionic character tending either to prevent the fixation on the DNA or to increase their dissociation from the DNA. Thus, ERs could be recruited by complexes in the nucleus or cytoplasm and form some foci.LORIENT-BU (561212106) / SudocSudocFranceF

Health effects from heat waves in France: an economic evaluation

International audienceBackground : Scarcity of data on the health impacts and associated economic costs of heat waves may limit the will to invest in adaptation measures. We assessed the economic impact associated with mortality, morbidity, and loss of well-being during heat waves in France between 2015 and 2019.Methods : Health indicators monitored by the French national heat wave plan were used to estimate excess visits to emergency rooms and outpatient clinics and hospitalizations for heat-related causes. Total excess mortality and years of life loss were considered, as well as the size of the population that experienced restricted activity. A cost-of-illness and willingness-to-pay approach was used to account for associated costs.Results : Between 2015 and 2019, the economic impact of selected health effects of heat waves amounts to €25.5 billion, mainly in mortality (€23.2 billion), minor restricted activity days (€2.3 billion), and morbidity (€0.031 billion).Conclusion : The results highlight a significant economic burden on the French health system and the population. A better understanding of the economic impacts of climate change on health is required to alert decision-makers to the urgency of mitigation and to support concrete adaptation actions

Estimating the division rate from indirect measurements of single cells

International audienceIs it possible to estimate the dependence of a growing and dividing population on a given trait in the case where this trait is not directly accessible by experimental measurements, but making use of measurements of another variable? This article adresses this general question for a very recent and popular model describing bacterial growth, the so-called incremental or adder model. In this model, the division rate depends on the increment of size between birth and division, whereas the most accessible trait is the size itself. We prove that estimating the division 10 rate from size measurements is possible, we state a reconstruction formula in a deterministic and then in a statistical setting, and solve numerically the problem on simulated and experimental data. Though this represents a severely ill-posed inverse problem, our numerical results prove to be satisfactory

Estimating the division rate from indirect measurements of single cells

Is it possible to estimate the dependence of a growing and dividing population on a given trait in the case where this trait is not directly accessible by experimental measurements, but making use of measurements of another variable? This article adresses this general question for a very recent and popular model describing bacterial growth, the so-called incremental or adder model. In this model, the division rate depends on the increment of size between birth and division, whereas the most accessible trait is the size itself. We prove that estimating the division 10 rate from size measurements is possible, we state a reconstruction formula in a deterministic and then in a statistical setting, and solve numerically the problem on simulated and experimental data. Though this represents a severely ill-posed inverse problem, our numerical results prove to be satisfactory