Etude des phénomènes de protonation et de diffusion dans des membranes échangeuses d'anions à base de poly (4-vinylpyridine)

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

HEURISTIC METHODS FOR TEST SEQUENCING IN TELECOMMUNICATION SATELLITES

Colloque avec actes et comité de lecture. internationale.International audienceThe increasing complexity in telecommunication satellite payload design demands new test sequencing approaches to face the induced increase of validation complexity. In such a sequencing problem, each test requires specific payload equipment states at a dedicated temperature range. The industrial objectives are both to reduce the total time of tests and to keep the thermal stability of the payload. For solving this problem, we compare several strategies. The first one consists in packing compatible tests together and run them package after package. The second approach aims at masking the preparation time of tests and considers the sequencing of all tests separately. In this paper, we propose to improve the first approach by optimizing the sequence of compatible tests to reduce the total time. Then, we propose heuristic methods for the second approach. Experiments are conducted on real payload instances and show the respective interest of the two approaches

Constraint programming for planning test campaigns of communications satellites

International audienceThe payload of communications satellites must go through a series of tests to assert their ability to survive in space. Each test involves some equipment of the payload to be active, which has an impact on the temperature of the payload. Sequencing these tests in a way that ensures the thermal stability of the payload and minimizes the overall duration of the test campaign is a very important objective for satellite manufacturers. The problem can be decomposed in two sub-problems corresponding to two objectives: First, the number of distinct configurations necessary to run the tests must be minimized. This can be modeled as packing the tests into configurations, and we introduce a set of implied constraints to improve the lower bound of the model. Second, tests must be sequenced so that the number of times an equipment unit has to be switched on or off is minimized. We model this aspect using the constraint Switch, where a buffer with limited capacity represents the currently active equipment units, and we introduce an improvement of the propagation algorithm for this constraint. We then introduce a search strategy in which we sequentially solve the sub-problems (packing and sequencing). Experiments conducted on real and random instances show the respective interest of our contributions

Apical and basal auxin sources pattern shoot branching in a moss

Shoot branching mechanisms where branches arise in association with leaves – referred to as lateral or axillary branching – evolved by convergence in the sporophyte of vascular plants and the gametophyte of bryophytes, and accompanied independent events of plant architectural diversification. Previously, we showed that three hormonal cues, including auxin, have been recruited independently to co-ordinate branch patterning in flowering plant leafy shoots and moss gametophores (Coudert, Palubicki et al., 2015). Moreover, auxin-mediated apical dominance, which relies on local auxin production, has been proposed as a unifying molecular regulatory mechanism of branch development across land plants. Whilst our previous work in the moss Physcomitrium patens has gathered indirect evidence supporting the notion that auxin synthesized in gametophore apices regulates branch formation at a distance, direct genetic evidence for a role of auxin biosynthesis in gametophore branching control is still lacking. Here, we show that gametophore apex decapitation promotes branch emergence through massive and rapid transcriptional reprogramming of auxin-responsive genes and altering auxin biosynthesis gene activity. Specifically, we identify a subset of P. patens TRYPTOPHAN AMINO-TRANSFERASE (TAR) and YUCCA FLAVIN MONOOXYGENASE-LIKE (YUC) auxin biosynthesis genes expressed in apical and basal regions of the gametophore, and show that they are essential for branch initiation and outgrowth control. Our results demonstrate that local auxin biosynthesis coordinates branch patterning in moss and thus constitutes a shared and ancient feature of shoot architecture control in land plants

Apical dominance control by TAR-YUC-mediated auxin biosynthesis is a deep homology of land plants

International audienceA key aim in biology is to identify which genetic changes contributed to the evolution of form through time. Apical dominance, the inhibitory effect exerted by shoot apices on the initiation or outgrowth of distant lateral buds, is a major regulatory mechanism of plant form.1 Nearly a century of studies in the sporophyte of flowering plants have established the phytohormone auxin as a front-runner in the search for key factors controlling apical dominance,2,3 identifying critical roles for long-range polar auxin transport and local auxin biosynthesis in modulating shoot branching.4-10 A capacity for lateral branching evolved by convergence in the gametophytic shoot of mosses and primed its diversification;11 however, polar auxin transport is relatively unimportant in this developmental process,12 the contribution of auxin biosynthesis genes has not been assessed, and more generally, the extent of conservation in apical dominance regulation within the land plants remains largely unknown. To fill this knowledge gap, we sought to identify genetic determinants of apical dominance in the moss Physcomitrium patens. Here, we show that leafy shoot apex decapitation releases apical dominance through massive and rapid transcriptional reprogramming of auxin-responsive genes and altering auxin biosynthesis gene activity. We pinpoint a subset of P. patens TRYPTOPHAN AMINO-TRANSFERASE (TAR) and YUCCA FLAVIN MONOOXYGENASE-LIKE (YUC) auxin biosynthesis genes expressed in the main and lateral shoot apices and show that they are essential for coordinating branch initiation and outgrowth. Our results demonstrate that local auxin biosynthesis acts as a pivotal regulator of apical dominance in moss and constitutes a shared mechanism underpinning shoot architecture control in land plants

HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancers

Triple negative breast cancers (TNBCs) represent 15–20% of all breast cancers and are associated with higher recurrence and distant metastasis rate. Standard of care for early stage TNBC is anthracyclines combined with cyclophosphamide (AC) followed by taxanes, in the neo‐adjuvant or adjuvant setting. This work aimed to identify predictive biomarkers of AC response in patient‐derived xenograft (PDX) models of TNBC and to validate them in the clinical setting. By gene and protein expression analysis of 39 PDX with different responses to AC, we found that high expression of HORMAD1 was associated with better response to AC. Both gene and protein expression were associated with promoter hypomethylation. In a cohort of 526 breast cancer patients, HORMAD1 was overexpressed in 71% of TNBC. In a second cohort of 186 TNBC patients treated with AC, HORMAD1 expression was associated with longer metastasis‐free survival (MFS). In summary, HORMAD1 overexpression was predictive of an improved response to AC in PDX and is an independent prognostic factor in TNBC patients treated with AC

A large collection of integrated genomically characterized patient‐derived xenografts highlighting the heterogeneity of triple‐negative breast cancer

A large collection of integrated genomically characterized patient‐derived xenografts highlighting the heterogeneity of triple‐negative breast cance

BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers

Topoisomerase I (TOP1) inhibitors trap TOP1 cleavage complexes resulting in DNA double-strand breaks (DSBs) during replication, which are repaired by homologous recombination (HR). Triple-negative breast cancer (TNBC) could be eligible for TOP1 inhibitors given the considerable proportion of tumors with a defect in HR-mediated repair (BRCAness). The TOP1 inhibitor irinotecan was tested in 40 patient-derived xenografts (PDXs) of TNBC. BRCAness was determined with a single-nucleotide polymorphism (SNP) assay, and expression of Schlafen family member 11 (SLFN11) and retinoblastoma transcriptional corepressor 1 (RB1) was evaluated by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry analyses. In addition, the combination of irinotecan and the ataxia telangiectasia and Rad3-related protein (ATR) inhibitor VE-822 was tested in SLFN11-negative PDXs, and two clinical non-camptothecin TOP1 inhibitors (LMP400 and LMP776) were tested. Thirty-eight percent of the TNBC models responded to irinotecan. BRCAness combined with high SLFN11 expression and RB1 loss identified highly sensitive tumors, consistent with the notion that deficiencies in cell cycle checkpoints and DNA repair result in high sensitivity to TOP1 inhibitors. Treatment by the ATR inhibitor VE-822 increased sensitivity to irinotecan in SLFN11-negative PDXs and abolished irinotecan-induced phosphorylation of checkpoint kinase 1 (CHK1). LMP400 (indotecan) and LMP776 (indimitecan) showed high antitumor activity in BRCA1-mutated or BRCAness-positive PDXs. Last, low SLFN11 expression was associated with poor survival in 250 patients with TNBC treated with anthracycline-based chemotherapy. In conclusion, a substantial proportion of TNBC respond to irinotecan. BRCAness, high SLFN11 expression, and RB1 loss are highly predictive of response to irinotecan and the clinical indenoisoquinoline TOP1 inhibitors

Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers

Homologous recombination deficiency is linked with platinum-based chemotherapy response in triple-negative breast cancer (TNBC) but methods to clinically identify these patients are lacking. Here, using patient-derived xenografts of TNBC the authors demonstrate that shallow HRD is predictive of response to platinum-based chemotherapy

PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance

International audienceA significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Here we perform whole exome sequencing and gene expression analysis of matched primary breast tumours and bone metastasis-derived patient-derived xenografts (PDX). Tran-scriptomic analyses reveal enrichment of the G2/M checkpoint and up-regulation of Polo-like kinase 1 (PLK1) in PDX. PLK1 inhibition results in tumour shrinkage in highly proliferating CCND1-driven PDX, including different RB-positive PDX with acquired palbociclib resistance. Mechanistic studies in endocrine resistant cell lines, suggest an ER-independent function of PLK1 in regulating cell proliferation. Finally, in two independent clinical cohorts of ER positive BC, we find a strong association between high expression of PLK1 and a shorter metastases-free survival and poor response to anastrozole. In conclusion, our findings support clinical development of PLK1 inhibitors in patients with advanced CCND1-driven BC, including patients progressing on palbociclib treatment