Conservatoire national des arts et métiers

About: Conservatoire national des arts et métiers is a education organization based out in Paris, France. It is known for research contribution in the topics: Population & Orthogonal frequency-division multiplexing. The organization has 3573 authors who have published 7127 publications receiving 141430 citations. The organization is also known as: CNAM & Conservatoire des arts et métiers.

Dual inhibition of HIV-1 replication by integrase-LEDGF allosteric inhibitors is predominant at the post-integration stage.

Abstract: LEDGF/p75 (LEDGF) is the main cellular cofactor of HIV-1 integrase (IN). It acts as a tethering factor for IN, and targets the integration of HIV in actively transcribed gene regions of chromatin. A recently developed class of IN allosteric inhibitors can inhibit the LEDGF-IN interaction. We describe a new series of IN-LEDGF allosteric inhibitors, the most active of which is Mut101. We determined the crystal structure of Mut101 in complex with IN and showed that the compound binds to the LEDGF-binding pocket, promoting conformational changes of IN which explain at the atomic level the allosteric effect of the IN/LEDGF interaction inhibitor on IN functions. In vitro, Mut101 inhibited both IN-LEDGF interaction and IN strand transfer activity while enhancing IN-IN interaction. Time of addition experiments indicated that Mut101 behaved as an integration inhibitor. Mut101 was fully active on HIV-1 mutants resistant to INSTIs and other classes of anti-HIV drugs, indicative that this compound has a new mode of action. However, we found that Mut101 also displayed a more potent antiretroviral activity at a post-integration step. Infectivity of viral particles produced in presence of Mut101 was severely decreased. This latter effect also required the binding of the compound to the LEDGF-binding pocket. Mut101 has dual anti-HIV-1 activity, at integration and post-integration steps of the viral replication cycle, by binding to a unique target on IN (the LEDGF-binding pocket). The post-integration block of HIV-1 replication in virus-producer cells is the mechanism by which Mut101 is most active as an antiretroviral. To explain this difference between Mut101 antiretroviral activity at integration and post-integration stages, we propose the following model: LEDGF is a nuclear, chromatin-bound protein that is absent in the cytoplasm. Therefore, LEDGF can outcompete compound binding to IN in the nucleus of target cells lowering its antiretroviral activity at integration, but not in the cytoplasm where post-integration production of infectious viral particles takes place.

Determination of an efficient and reliable method for DNA extraction from ticks

Abstract: Molecular detection of pathogenic microorganisms in ticks is based on DNA amplification of the target pathogen; therefore, extraction of DNA from the tick is a major step. In this study, we compared three different tick DNA extraction protocols based on an enzymatic digestion by proteinase K followed by DNA extraction by a commercial kit (method 1), or on mortar crushing, proteinase K digestion and phenol/chloroform DNA extraction (method 2) and fine crushing with a beads beater, proteinase K digestion and DNA extraction using a commercial kit (method 3). The absence of PCR inhibitors and the DNA quality were evaluated by PCR amplification of the tick mitochondrial 16S rRNA gene using tick-specific primers. With method 1, 23/30 (77%) of the samples were extracted; with method 2, 30/31 (97%) of the samples were extracted and with method 3, 30/30 (100%) of the samples were extracted. DNA extraction efficiency using method 3 is significantly higher than DNA extraction efficiency using method 1 (100% versus 77%, P < 0.05). There was no significant difference between methods 2 and 3. Method 3 was however more adapted to cohort studies than method 2. This technique was validated for cohort tick DNA extraction and applicable to the treatment of small samples such as nymphs and soft ticks with 100% efficiency.

Gram: a graph data model and query languages

Abstract: We present a model for data organized as graphs. Regular expressions over the types of the node and edge labels are used to qualify connected subgraphs. An algebraic language based on these regular expressions and supporting a restricted form of recursion is introduced. A natural application of this model and its query language is hypertext querying.

Drag reduction on the 25° slant angle Ahmed reference body using pulsed jets

Abstract: This paper highlights steady and unsteady measurements and flow control results obtained on an Ahmed model with slant angle of 25° in wind tunnel. On this high-drag configuration characterized by a large separation bubble along with energetic streamwise vortices, time-averaged and time-dependent results without control are first presented. The influence of rear-end periodic forcing on the drag coefficient is then investigated using electrically operated magnetic valves in an open-loop control scheme. Four distinct configurations of flow control have been tested: rectangular pulsed jets aligned with the spanwise direction or in winglets configuration on the roof end and rectangular jets or a large open slot at the top of the rear slant. For each configuration, the influence of the forcing parameters (non-dimensional frequency, injected momentum) on the drag coefficient has been studied, along with their impact on the static pressure on both the rear slant and vertical base of the model. Depending on the type and location of pulsed jets actuation, the maximum drag reduction is obtained for increasing injected momentum or well-defined optimal pulsation frequencies.