Systems with jumps : theory and applications

Introduced in the eigthies, the systems with jumps, also called at the beginning hybrid systems, can efficiently modelize a grea t number of physical systems subject to random jumps in their dynamics . A manoeuvering fighting aircraft, widely studied in th e litterature, is a good illustration of this type of systems . Stability, optimal control and stochastic filtering were the major areas o f study for these models . In fact this modelization results from a combination of three ingredients : diffusion, jumps and deterministi c processes . When restricting ourselves to the first two kinds of processes, we consider models with stochastic diffusions . So, after having introduced the general mathematical representation for such processes, we consider in this article a typica l application in aerospace, the target tracking, to show the significant improvements in performance brought by this approach . When then conclude, after having recalled the various contributions brought by our group on the stochastic diffusions during the last fifteen years .Introduits dans les années quatre vingt, les systèmes à sauts, plus connus à l'origine sous le nom de systèmes hybrides, offrent un cadre mathématique idéal pour l'étude de systèmes physiques caractérisés par des modifications (sauts), brutales et aléatoires de leur dynamique. Un des exemples les plus couramment rencontrés dans la littérature est celui d'un avion de chasse effectuant diverses manoeuvres. La stabilité, la commande optimale et le filtrage stachastique ont été les trois principaux domaines d'études de ces modèles. Cette modélisation résulte en fait d'un mélange de trois constituants élémentaires que sont les processus de diffusion, les processus à sauts et les processus déterministes. En se restreignant aux deux premiers ingrédients, nous parlerons de modèles à diffusions aléatoires. Après avoir introduit la modélisation mathématique de tels processus, nous nous intéressons dans cet article à une application type, la poursuite de trajectoire, afin de montrer les améliorations significatives qu'apporte cette approche. Enfin nous conclurons, non sans avoir rappelé les différents travaux accomplis sur les diffusions aléatoires dans notre groupe, au cours de ces quinze dernières années

Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation

BACKGROUND: Mycoplasmas are the smallest microorganisms capable of self-replication. Our previous studies show that some mycoplasmas are able to induce malignant transformation of host mammalian cells. This malignant transformation is a multistage process with the early infection, reversible and irreversible stages, and similar to human tumor development in nature. The purpose of this study is to explore mechanisms for this malignant transformation. METHODS: To better understand mechanisms for this unique process, we examined gene expression profiles of C3H cells at different stages of the mycoplasma-induced transformation using cDNA microarray technology. A total of 1185 genes involved in oncogenesis, apoptosis, cell growth, cell-cycle regulation, DNA repair, etc. were examined. Differences in the expression of these genes were compared and analyzed using the computer software AtlasImage. RESULTS: Among 1185 genes screened, 135 had aberrant expression at the early infection stage, 252 at the reversible stage and 184 at the irreversible stage. At the early infection stage, genes with increased expression (92 genes) were twice more than those with decreased expression (42 genes). The global gene expression at the reversible stage appeared to be more volatile than that at any other stages but still resembled the profile at the early infection stage. The expression profile at the irreversible stage shows a unique pattern of a wide range of expression levels and an increased number of expressing genes, especially the cancer-related genes. Oncogenes and tumor suppressors are a group of molecules that showed significant changes in expression during the transformation. The majority of these changes occurred in the reversible and irreversible stages. A prolonged infection by mycoplasmas lead to the expression of more cancer related genes at the irreversible stage. CONCLUSION: The results indicate that the expression profiles correspond with the phenotypic features of the cells in the mycoplasma induced transformation process. The early mycoplasma infection stage shares a common phenomenon with many other acute infections, genes with increased expression significantly outnumbering those with decreased expression. The reversible stage is a transition stage between benignancy and malignancy at the molecular level. Aberrant expression of oncogenes and tumor repressors plays a key role in mycoplasma-induced malignant transformation

Subsurface morphology and scaling of lunar impact basins

Impact bombardment during the first billion years after the formation of the Moon produced at least several tens of basins. The Gravity Recovery and Interior Laboratory (GRAIL) mission mapped the gravity field of these impact structures at significantly higher spatial resolution than previous missions, allowing for detailed subsurface and morphological analyses to be made across the entire globe. GRAIL-derived crustal thickness maps were used to define the regions of crustal thinning observed in centers of lunar impact basins, which represents a less unambiguous measure of a basin size than those based on topographic features. The formation of lunar impact basins was modeled numerically by using the iSALE-2D hydrocode, with a large range of impact and target conditions typical for the first billion years of lunar evolution. In the investigated range of impactor and target conditions, the target temperature had the dominant effect on the basin subsurface morphology. Model results were also used to update current impact scaling relationships applicable to the lunar setting (based on assumed target temperature). Our new temperature-dependent impact-scaling relationships provide estimates of impact conditions and transient crater diameters for the majority of impact basins mapped by GRAIL. As the formation of lunar impact basins is associated with the first ~700 Myr of the solar system evolution when the impact flux was considerably larger than the present day, our revised impact scaling relationships can aid further analyses and understanding of the extent of impact bombardment on the Moon and terrestrial planets in the early solar system

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

The deregulated kinase activity of p210-BCR/ABL oncoproteins, hallmark of chronic myelogenous leukaemia (CML), induces and sustains the leukaemic phenotype, and contributes to disease progression. Imatinib mesylate, a BCR/ABL kinase inhibitor, is effective in most of chronic phase CML patients. However, a significant percentage of CML patients develop resistance to imatinib and/or still progresses to blast crisis, a disease stage that is often refractory to imatinib therapy. Furthermore, there is compelling evidence indicating that the CML leukaemia stem cell is also resistant to imatinib. Thus, there is still a need for new drugs that, if combined with imatinib, will decrease the rate of relapse, fully overcome imatinib resistance and prevent blastic transformation of CML. We recently reported that the activity of the tumour suppressor protein phosphatase 2A (PP2A) is markedly inhibited in blast crisis CML patient cells and that molecular or pharmacologic re-activation of PP2A phosphatase led to growth suppression, enhanced apoptosis, impaired clonogenic potential and decreased in vivo leukaemogenesis of imatinib-sensitive and -resistant (T315I included) CML-BC patient cells and/or BCR/ABL+ myeloid progenitor cell lines. Thus, the combination of PP2A phosphatase-activating and BCR/ABL kinase-inhibiting drugs may represent a powerful therapeutic strategy for blast crisis CML patients

Drug Discovery for Duchenne Muscular Dystrophy via Utrophin Promoter Activation Screening

Background: Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. Methodology/Principal Findings: We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. Conclusions/Significance: We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics an

Asthmatics Exhibit Altered Oxylipin Profiles Compared to Healthy Individuals after Subway Air Exposure

Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas

Fusion radar-imagrie en poursuite

La sophistication croissante des mobiles à pister (forte manoeuvrabilité et structures furtives) ainsi que l'émergence des capteurs imageurs sont deux faits récents qui motivent une attention renouvelée dans le domaine de la poursuite. Cet article présente une solution algorithmique originale qui exploite finement la potentialité de cette nouvelle génération de senseurs dans le contexte d'une application de Défense Anti-Aérienne

Recursive Bearings-Only TMA via Unscented Kalman Filter: Cartesian vs. Modified Polar Coordinates

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