http://web.stanford.edu/group/brunet/Cell1999

Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor

Convergence of Probability Measures. By P. Billingsley. Chichester, Sussex, Wiley, 1968. xii, 253 p. 9 1/4“. 117s.

Convergence of Probability Measures

Mitogen-activated protein kinases (MAPKs) are important signal transducing enzymes, unique to eukaryotes, that are involved in many facets of cellular regulation. Initial research concentrated on defining the components and organization of MAPK signalling cascades, but recent studies have begun to shed light on the physiological functions of these cascades in the control of gene expression, cell proliferation and programmed cell death.

/pdf/mammalian-map-kinase-signalling-cascades-2wtn4qrixr.pdf

Mammalian MAP kinase signalling cascades

Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death. Cancer cells have adapted these pathways, allowing tumours to survive and even grow under hypoxic conditions, and tumour hypoxia is associated with poor prognosis and resistance to radiation therapy. Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting.

Hypoxia — a key regulatory factor in tumour growth

Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation

Let P be a probability distribution on R d (equipped with an Euclidean norm). Let r,s > 0 and assume (�n)n�1 is an (asymptotically) L r (P)-optimal sequence of n-quantizers. In this paper we investigate the asymptotic behavior of the maximal radius sequence induced by the sequence (�n)n�1 and defined to be for every n ≥ 1, �(�n) = max{|a|, a ∈ �n}. We show that if card(supp(P)) is infinite, the maximal radius sequence goes to sup{|x|,x ∈ supp(P)} as n goes to infinity. We then give the rate of convergence for two c lasses of distributions with unbounded support : distributions with exponential tails a nd distributions with polynomial tails.

/pdf/asymptotics-of-the-maximal-radius-of-an-l-r-optimal-sequence-2g7ubb9m1q.pdf

Asymptotics of the maximal radius of an L r -optimal sequence of quantizers

Lysosomotropic agents such as sunitinib, lapatinib, and chloroquine belong to a drug family that is being used more frequently to treat advanced cancers. Sunitinib is standard care for metastatic renal cell carcinomas (mRCC) and lapatinib is used for trastuzumab/pertuzumab-refractory cancers. However, patients ineluctably relapse with a delay varying from a few months to a few years. To improve reactivity prior to relapse it is essential to identify the mechanisms leading to such variability. We showed previously that sunitinib became sequestered in lysosomes because of its basic pKa. Methods: Modifications to gene expression in response to sunitinib and in sunitinib resistant cells were analyzed by transcriptomic and proteomic analysis. ROS production was evaluated by FACS. Nuclear Factor kappa B (NFkB)-dependent transcriptional regulation of inflammatory gene expression was evaluated with a reporter gene. Correlation of CXCL5 with survival was analyzed with an online available data base (TCGA) and using a cohort of patients enrolled in the SUVEGIL clinical trial (NCT00943839). Results: We now show that sunitinib sequestration in lysosomes induced an incomplete autophagic process leading to activation of the NFkB inflammatory pathway. We defined a subset of inflammatory cytokines that were up-regulated by the drug either after an acute or chronic stimulus. One of the most up-regulated genes in sunitinib-resistant cells was the CXCL5 cytokine. CXCL5 was also induced in RCC by chloroquine and in a model of HER2 positive breast cancer cell lines after acute or chronic treatment with lapatinib. CXCL5 correlated to shorter survival in RCC and to the most aggressive forms of breast cancers. The levels of CXCL5 present in the plasma of patients treated with sunitinib were predictive of the efficacy of sunitinib but not of the VEGF-directed antibody bevacizumab. Conclusion: This translational study identified CXCL5 as a biomarker of efficacy of lysosomotropic drugs, a potential asset for personalized medicine.

https://hal.archives-ouvertes.fr/hal-02454449/document

Resistance to lysosomotropic drugs used to treat kidney and breast cancers involves autophagy and inflammation and converges in inducing CXCL5.

We consider one dimensional probability distributions μ having a continuous and positive probability density function. We find the asymptotic of the size and the mass of the Voronoi cells and we prove that the local distortion associated with stationary or optimal quantizers is asymptotically uniform. Numerical simulations and computations illustrate the theoretical results and lead to the design of some good-fit test for the stationary equilibria.

http://www.proba.jussieu.fr/dw/lib/exe/fetch.php?media=users:delattre:sta-120029827.pdf

Local Distortion and μ-Mass of the Cells of One Dimensional Asymptotically Optimal Quantizers

We study a two armed-bandit algorithm with penalty. We show the convergence of the algorithm and establish the rate of convergence. For some choices of the parameters, we obtain a central limit theorem in which the limit distribution is characterized as the unique stationary distribution of a discontinuous Markov process.

Gilles Pagès

Papers

Asymptotics of the maximal radius of an L r -optimal sequence of quantizers

Resistance to lysosomotropic drugs used to treat kidney and breast cancers involves autophagy and inflammation and converges in inducing CXCL5.

Local Distortion and μ-Mass of the Cells of One Dimensional Asymptotically Optimal Quantizers

A penalized bandit algorithm

On the critical points of the 1-dimensional competitive learning vector quantization algorithm.