Packing and Hausdorff measures of stable trees

In this paper we discuss Hausdorff and packing measures of random continuous trees called stable trees. Stable trees form a specific class of L\'evy trees (introduced by Le Gall and Le Jan in 1998) that contains Aldous's continuum random tree (1991) which corresponds to the Brownian case. We provide results for the whole stable trees and for their level sets that are the sets of points situated at a given distance from the root. We first show that there is no exact packing measure for levels sets. We also prove that non-Brownian stable trees and their level sets have no exact Hausdorff measure with regularly varying gauge function, which continues previous results from a joint work with J-F Le Gall (2006).Comment: 40 page

Atypical KRASG12R Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer

Allele-specific signaling by different KRAS alleles remains poorly understood. The KRASG12R mutation displays uneven prevalence among cancers that harbor the highest occurrence of KRAS mutations: It is rare (∼1%) in lung and colorectal cancers, yet relatively common (∼20%) in pancreatic ductal adenocarcinoma (PDAC), suggesting context-specific properties. We evaluated whether KRASG12R is functionally distinct from the more common KRASG12D- or KRASG12V-mutant proteins (KRASG12D/V). We found that KRASG12D/V but not KRASG12R drives macropinocytosis and that MYC is essential for macropinocytosis in KRASG12D/V- but not KRASG12R-mutant PDAC. Surprisingly, we found that KRASG12R is defective for interaction with a key effector, p110α PI3K (PI3Kα), due to structural perturbations in switch II. Instead, upregulated KRAS-independent PI3Kγ activity was able to support macropinocytosis in KRASG12R-mutant PDAC. Finally, we determined that KRASG12R-mutant PDAC displayed a distinct drug sensitivity profile compared with KRASG12D-mutant PDAC but is still responsive to the combined inhibition of ERK and autophagy. SIGNIFICANCE: We determined that KRASG12R is impaired in activating a key effector, p110α PI3K. As such, KRASG12R is impaired in driving macropinocytosis. However, overexpression of PI3Kγ in PDAC compensates for this deficiency, providing one basis for the prevalence of this otherwise rare KRAS mutant in pancreatic cancer but not other cancers.See related commentary by Falcomatà et al., p. 23.This article is highlighted in the In This Issue feature, p. 1

Matériels associés à l'utilisation des produits explosifs et aux dispositifs d'amorçage

Cet article rédigé par le sous-groupe Matériels associés du GFEE synthétise le travail qu'il a mené. Il a pour vocation d'apporter des compléments d'informations aux utilisateurs, aux responsables sécurité et aux donneurs d'ordre afin d'orienter les prescriptions d'utilisation de ces matériels

Integrative analysis of osmoregulation in yeast Saccharomyces cerevisiae

Similar to other unicellular organisms, yeasts frequently encounter environmental stress such as heat shock, osmotic stress, and nutrition limitations, which challenge their growth potential. To survive, all living cells must be able to adapt to changes in their surrounding environment. A set of adaptive responses is triggered that leads to repair of cellular damage in order to overcome these stress conditions. The aim of this thesis is to determine how yeast cells respond to changes in osmolarity and water activity. Upon hyperosmotic shock, water flows out of the cell, resulting in cell shrinkage, and consequently an increase in the concentrations of all substances present in the cytoplasm. Cells adapt their internal osmolarity by gaining an appropriate cell volume as well as an internal water concentration that is optimal for biochemical processes to recover turgor pressure. Osmoregulation is an active process which is mainly regulated by the High Osmolarity Glycerol (HOG) pathway and controls the cellular water balance. The HOG pathway is one of the four yeast MAP kinase pathways. It conveys the hyper osmolarity stress stimulus into the cell machinery and instigates appropriate responses, including global readjustment of gene expression, changes in translational capacity, transient cell cycle arrest, and accumulation of the compatible solute glycerol. Together, these processes result in osmoadaptation. In this thesis I investigated the quantitative characteristics of osmoregulation in the yeast Saccharomyces cerevisiae. I applied a combination of traditional molecular approaches and frontline technologies for comprehensive and quantitative measurements, such as high throughput experiments, synthetic biology, single cell analysis and mathematical modeling to understand the interdependence and timeline of different osmoadaptation process