Nous étudions la formation et les propriétés des systèmes auto-gravitants à l'aide de simulations numériques à N corps d'effondrements gravitationnels.
Nous effectuons dans un premier temps une ...synthèse des principaux résultats analytiques concernant les équations de Boltzmann sans collisions et de Poisson, qui modélisent les systèmes gravitationnels non collisionnels ainsi que certaines solutions analytiques de ce système couplé d'équations.
Nous présentons ensuite les codes de calcul utilisés pour les simulations. Nous avons parallélisé certains de ces codes, nous introduisons donc le calcul parallèle et la bibliothèque d'échange de message MPI.
Nous exposons enfin les résultats de nos simulations, et leurs analyses. Nous déduisons de ces analyses divers résultats pouvant expliquer différentes caractéristiques des systèmes auto-gravitants ainsi que les conditions initiales nécessaires au déclenchement des instabilités d'Antonov et d'orbites radiales.
H2 formation remains a major issue for the understanding of interstellar physics. We investigate H2 formation in the interstellar medium at the light of the most recent experimental and theoretical ...data. We implemented detailed H2 formation mechanisms on grains surface in the Meudon PDR code : i) Langmuir-Hinshelwood mechanism taking into account the contribution of the different sizes of dust grains in the diffusion processes and ii) the Eley-Rideal mechanism. We show that, thanks to these processes, H2 can be formed even in regions where dust temperature is larger than 25 K. We also show that formation by Eley-Rideal mechanism can be a significant source of heating of the gas. We derive line intensities for various astrophysical conditions. Such an approach results in an enhanced H2 formation rate compared to the standard formation determined by observations in absorption in the UV. We derive some H2 line intensities for isobaric and isochoric models.
The ever increasing size and complexity of data coming from simulations of cosmic structure formation demands equally sophisticated tools for their analysis. During the past decade, the art of object ...finding in these simulations has hence developed into an important discipline itself. A multitude of codes based upon a huge variety of methods and techniques have been spawned yet the question remained as to whether or not they will provide the same (physical) information about the structures of interest. Here we summarize and extent previous work of the "halo finder comparison project": we investigate in detail the (possible) origin of any deviations across finders. To this extent we decipher and discuss differences in halo finding methods, clearly separating them from the disparity in definitions of halo properties. We observe that different codes not only find different numbers of objects leading to a scatter of up to 20 per cent in the halo mass and Vmax function, but also that the particulars of those objects that are identified by all finders differ. The strength of the variation, however, depends on the property studied, e.g. the scatter in position, bulk velocity, mass, and the peak value of the rotation curve is practically below a few per cent, whereas derived quantities such as spin and shape show larger deviations. Our study indicates that the prime contribution to differences in halo properties across codes stems from the distinct particle collection methods and -- to a minor extent -- the particular aspects of how the procedure for removing unbound particles is implemented. We close with a discussion of the relevance and implications of the scatter across different codes for other fields such as semi-analytical galaxy formation models, gravitational lensing, and observables in general.
abridged We present a detailed comparison of fundamental dark matter halo properties retrieved by a substantial number of different halo finders. These codes span a wide range of techniques including ...friends-of-friends (FOF), spherical-overdensity (SO) and phase-space based algorithms. We further introduce a robust (and publicly available) suite of test scenarios that allows halo finder developers to compare the performance of their codes against those presented here. This set includes mock haloes containing various levels and distributions of substructure at a range of resolutions as well as a cosmological simulation of the large-scale structure of the universe. All the halo finding codes tested could successfully recover the spatial location of our mock haloes. They further returned lists of particles (potentially) belonging to the object that led to coinciding values for the maximum of the circular velocity profile and the radius where it is reached. All the finders based in configuration space struggled to recover substructure that was located close to the centre of the host halo and the radial dependence of the mass recovered varies from finder to finder. Those finders based in phase space could resolve central substructure although they found difficulties in accurately recovering its properties. Via a resolution study we found that most of the finders could not reliably recover substructure containing fewer than 30-40 particles. However, also here the phase space finders excelled by resolving substructure down to 10-20 particles. By comparing the halo finders using a high resolution cosmological volume we found that they agree remarkably well on fundamental properties of astrophysical significance (e.g. mass, position, velocity, and peak of the rotation curve).
Glycerolipids constituting the matrix of photosynthetic membranes, from cyanobacteria to chloroplasts of eukaryotic cells, comprise monogalactosyldiacylglycerol, digalactosyldiacylglycerol, ...sulfoquinovosyldiacylglycerol and phosphatidylglycerol. This review covers our current knowledge on the structural and functional features of these lipids in various cellular models, from prokaryotes to eukaryotes. Their relative proportions in thylakoid membranes result from highly regulated and compartmentalized metabolic pathways, with a cooperation, in the case of eukaryotes, of non-plastidic compartments. This review also focuses on the role of each of these thylakoid glycerolipids in stabilizing protein complexes of the photosynthetic machinery, which might be one of the reasons for their fascinating conservation in the course of evolution. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.
•MGDG, DGDG, PG and SQDG are conserved in photosynthetic membranes.•Thylakoid glycerolipid synthesis combines plastid and ER metabolic pathways.•Thylakoid glycerolipids stabilize protein complexes and are critical for PSII function.•Sulfo- and galactoglycerolipids increase in response to phosphate shortage.•SQDG/PG and DGDG/PC ratios are regulated.
IMPORTANCE: Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. ...OBJECTIVE: To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. INTERVENTIONS: Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. MAIN OUTCOMES AND MEASURES: Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. RESULTS: In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 95% CI, 0.51-7.89; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. CONCLUSIONS AND RELEVANCE: Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00457158
Methods to analyze lipidomes have considerably evolved, more and more based on mass spectrometry technics (LC-MS/MS). However, accurate quantifications using these methods require 13C-labeled ...standards for each lipid, which is not feasible because of the very large number of molecules. Thus, quantifications rely on standard molecules representative of a whole class of lipids, which might lead to false estimations of some molecular species. Here, we determined and compared glycerolipid distributions from three different types of cells, two microalgae (Phaeodactylum tricornutum, Nannochloropsis gaditana) and one higher plant (Arabidopsis thaliana), using either LC-MS/MS or Thin Layer Chromatography coupled with Gas Chromatography (TLC-GC), this last approach relying on the precise quantification of the fatty acids present in each glycerolipid class. Our results showed that the glycerolipid distribution was significantly different depending on the method used. How can one reconcile these two analytical methods? Here we propose that the possible bias with MS data can be circumvented by systematically running in tandem with the sample to be analyzed a lipid extract from a qualified control (QC) of each type of cells, previously analyzed by TLC-GC, and used as an external standard to quantify the MS results. As a case study, we applied this method to compare the impact of a nitrogen deficiency on the three types of cells.
Cancer persister cells tolerate anticancer drugs and serve as the founders of acquired resistance and cancer relapse. Here we show that a subpopulation of BRAF
mutant melanoma cells that tolerates ...exposure to BRAF and MEK inhibitors undergoes a reversible remodelling of mRNA translation that evolves in parallel with drug sensitivity. Although this process is associated with a global reduction in protein synthesis, a subset of mRNAs undergoes an increased efficiency in translation. Inhibiting the eIF4A RNA helicase, a component of the eIF4F translation initiation complex, abrogates this selectively increased translation and is lethal to persister cells. Translation remodelling in persister cells coincides with an increased N6-methyladenosine modification in the 5'-untranslated region of some highly translated mRNAs. Combination of eIF4A inhibitor with BRAF and MEK inhibitors effectively inhibits the emergence of persister cells and may represent a new therapeutic strategy to prevent acquired drug resistance.
Emerging evidence indicates that non-mutational drug tolerance mechanisms underlie the survival of residual cancer “persister” cells. Here, we find that BRAF(V600E) mutant melanoma persister cells ...tolerant to BRAF/MEK inhibitors switch their metabolism from glycolysis to oxidative respiration supported by peroxisomal fatty acid β-oxidation (FAO) that is transcriptionally regulated by peroxisome proliferator-activated receptor alpha (PPARα). Knockdown of the key peroxisomal FAO enzyme, acyl-CoA oxidase 1 (ACOX1), as well as treatment with the peroxisomal FAO inhibitor thioridazine, specifically suppresses the oxidative respiration of persister cells and significantly decreases their emergence. Consistently, a combination treatment of BRAF/MEK inhibitors with thioridazine in human-melanoma-bearing mice results in a durable anti-tumor response. In BRAF(V600E) melanoma samples from patients treated with BRAF/MEK inhibitors, higher baseline expression of FAO-related genes and PPARα correlates with patients’ outcomes. These results pave the way for a metabolic strategy to overcome drug resistance.
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•Melanoma persister cells switch from glycolysis to mitochondrial respiration•Fatty acid oxidation (FAO) signature is upregulated in melanoma persister cells•Peroxisomal FAO is mediated by PPARα-ACOX1 axis in persister cells•Peroxisomal FAO inhibition delays the emergence of resistance to targeted therapy
Drug resistance can originate from non-genetic cancer persister cells. Shen et al. discover that peroxisomal lipid metabolism is an “Achilles heel” of melanoma persister cells. Inhibition of this metabolic adaptation significantly improves the efficacy of melanoma-targeted therapy.
In the past 10 years, a deeper understanding of the immune landscape of cancers, including immune evasion processes, has allowed the development of a new class of agents. The reactivation of host ...antitumor immune response offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies.
The advent of programmed cell death protein 1/programmed death ligand-1 immune checkpoint inhibitors (ICIs), both as single agents and in combination with chemotherapy, and more recently, the combination of ICI, anti–programmed cell death protein 1, and anticytotoxic T-lymphocyte antigen 4 antibody, have led to breakthrough therapeutic advances for patients with advanced NSCLC, and to a lesser extent, patients with SCLC. Encouraging activity has recently emerged in pretreated patients with thymic carcinoma (TC). Conversely, in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC, creating a platform for future therapeutic developments in earlier-stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may affect the therapeutic efficacy of these agents.
The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies.
In this article, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice and elucidate future treatment strategies and research priorities.
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