Quantitative thermal microscopy using thermoelectric probe in passive mode

International audienceA scanning thermal microscope working in passive mode using a micronic thermocouple probe is presented as a quantitative technique.We show that actual surface temperature distributions of microsystems are measurable under conditions for which most of usual techniques cannot operate. The quantitative aspect relies on the necessity of an appropriate calibration procedure which takes into account of the probe-to-sample thermal interaction prior to any measurement. Besides this consideration that should be treated for any thermal contact probing system, the main advantages of our thermal microscope deal with the temperature available range, the insensitivity to the surface optical parameters, the possibility to image DC, and AC temperature components up to 1 kHz typically and a resolution limit related to near-field behavior

First case of NDM-1 producing Klebsiella pneumoniae in Caribbean islands

Characterize a NDM-1 producing K. pneumoniae isolate recovered from a patient hospitalized in Guadeloupe, French West Indies, after its transfer from CubaMethodsAntibiotic susceptibilities were determined by the disk diffusion method, and E-test. Carbapenemase production was assessed using the Carba NP test. Antibiotic resistance determinants and their surrounding structures were characterized by PCR mapping and DNA sequencing. Transfer of the β-lactam resistance marker was attempted by liquid mating-out assaysResultsHere we reported the first NDM-1 producing enterobacterial isolate recovered from Caribbean islands. This K. pneumoniae isolate belongs to a new sequence type (ST1649). The blaNDM-1 gene together with the aacA4 gene were carried on a self conjugative IncR plasmid of c.a. 80 kb.ConclusionThis study describes the first identification of a NDM-1 producer in Caribbean islands. The uncommon incompatibility group of the blaNDM-1 carrying plasmid and the uncommon ST type of the K. pneumoniae strain suggest a possible local emergence of NDM producers

Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells

International audienceBenzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2*TMEDA (TMEDA = N,N,N',N'-tetramethylethylenediamine, 1 equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3 equiv). Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81, 82, 67 and 42% yields, respectively. These yields are higher (10% more) than those obtained using ZnCl2*TMEDA (0.5 equiv) and LiTMP (1.5 equiv), except in the case of benzoxazole (10% less). The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2 equiv) and Cs2CO3 (2 equiv), and using acetonitrile as solvent (no other ligand) to provide after 24 h reflux the expected N-arylated azoles in yields ranging from 33 to 81%. Using benzotriazole also led to N-arylation products, but in lower 34, 39, 36 and 6% yields, respectively. A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72 h treatment at 10-5 M

Easy grasping location learning from one-shot demonstration

In this paper, we propose a fast learner grasping pipeline able to grasp objects at a specific location few minutes after being taught by an operator. Our motivation is to ease reconfiguration of robot according to a specific task, without any CAD model, nor existing database, nor simulator. We build a CNN pipeline which performs a semantic segmentation of object, and recognizes authorized and prohibited grasping location shown during demonstration. For that we have simplified the input space, created a data augmentation process and proposed a light CNN architecture allowing learning in less than 5 minutes. Validation on a real 7-DOF robot shown good performances (70 to 100% depending on the object), with only a one-shoot operator’s demonstration. Performances remain good when grasping similar unseen objects, and with several objects in the robot’s workspace using few demonstrations. A video highlighting the main aspects can be found at https://www.youtube.com/watch?v=rYCIk6njBo

Progressive Discrete Domains for Implicit Surface Reconstruction

International audienceMany global implicit surface reconstruction algorithms formulate the problem as a volumetric energy minimization, trading data fitting for geometric regularization. As a result, the output surfaces may be located arbitrarily far away from the input samples. This is amplified when considering i) strong regularization terms, ii) sparsely distributed samples or iii) missing data. This breaks the strong assumption commonly used by popular octree-based and triangulation-based approaches that the output surface should be located near the input samples. As these approaches refine during a pre-process, their cells near the input samples, the implicit solver deals with a domain discretization not fully adapted to the final isosurface.We relax this assumption and propose a progressive coarse-to-fine approach that jointly refines the implicit function and its representation domain, through iterating solver, optimization and refinement steps applied to a 3D Delaunay triangulation. There are several advantages to this approach: the discretized domain is adapted near the isosurface and optimized to improve both the solver conditioning and the quality of the output surface mesh contoured via marching tetrahedra

Towards computational prediction of microRNA function and activity

While it has been established that microRNAs (miRNAs) play key roles throughout development and are dysregulated in many human pathologies, the specific processes and pathways regulated by individual miRNAs are mostly unknown. Here, we use computational target predictions in order to automatically infer the processes affected by human miRNAs. Our approach improves upon standard statistical tools by addressing specific characteristics of miRNA regulation. Our analysis is based on a novel compendium of experimentally verified miRNA-pathway and miRNA-process associations that we constructed, which can be a useful resource by itself. Our method also predicts novel miRNA-regulated pathways, refines the annotation of miRNAs for which only crude functions are known, and assigns differential functions to miRNAs with closely related sequences. Applying our approach to groups of co-expressed genes allows us to identify miRNAs and genomic miRNA clusters with functional importance in specific stages of early human development. A full list of the predicted mRNA functions is available at http://acgt.cs.tau.ac.il/fame/

Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection

Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal maturation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell differentiation. Finally, this novel transcriptional cascade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells

Towards Scalable, Accurate, and Usable Simulations of Distributed Applications and Systems

The study of parallel and distributed applications and platforms, whether in the cluster, grid, peer-to-peer, volunteer, or cloud computing domain, often mandates empirical evaluation of proposed algorithm and system solutions via simulation. Unlike direct experimentation via an application deployment on a real-world testbed, simulation enables fully repeatable and configurable experiments that can often be conducted quickly for arbitrary hypothetical scenarios. In spite of these promises, current simulation practice is often not conducive to obtaining scientifically sound results. State-of-the-art simulators are often not validated and their accuracy is unknown. Furthermore, due to the lack of accepted simulation frameworks and of transparent simulation methodologies, published simulation results are rarely reproducible. We highlight recent advances made in the context of the SimGrid simulation framework in a view to addressing this predicament across the aforementioned domains. These advances, which pertain both to science and engineering, together lead to unprecedented combinations of simulation accuracy and scalability, allowing the user to trade off one for the other. They also enhance simulation usability and reusability so as to promote an Open Science approach for simulation-based research in the field.L'étude de systèmes et applications parallèles et distribués, qu'il s'agisse de clusters, de grilles, de systèmes pair-à-pair de volunteer computing, ou de cloud, demandent souvent l'évaluation empirique par simulation des algorithmes et solutions proposés. Contrairement à l'expérimentation directe par déploiement d'applications sur des plates-formes réelles, la simulation permet des expériences reproductibles pouvant être menée rapidement sur n'importe quel scénario hypothétique. Malgré ces avantages théoriques, les pratiques actuelles en matière de simulation ne permettent souvent pas d'obtenir des résultats scientifiquement éprouvés. Les simulateurs classiques sont trop souvent validés et leur réalisme n'est pas démontré. De plus, le manque d'environnements de simulation communément acceptés et de méthodologies classiques de simulation font que les résultats publiés grâce à cette approche sont rarement reproductibles par la communauté. Nous présentons dans cet article les avancées récentes dans le contexte de l'environnement SimGrid pour répondre à ces difficultés. Ces avancées, comprenant à la fois des aspects techniques et scientifiques, rendent possible une combinaison inégalée de réalisme et précision de simulation et d'extensibilité. Cela permet aux utilisateurs de choisir le grain des modèles utilisés pour ses simulations en fonction de ses besoins de réalisme et d'extensibilité. Les travaux présentés ici améliorent également l'utilisabilité et la réutilisabilité de façon à promouvoir l'approche d'Open Science pour les recherches basées sur la simulation dans notre domaine

Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Reduction of epithelial cell–cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial–mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications

X-chromosome and kidney function:evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.</p