The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

LE SUBUTEX (DISPENSATION DE LA BUPRENORPHINE EN OFFICINE : ENQUETE DANS LA REGION DE LENS)

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

LE SUBUTEX (DISPENSATION DE LA BUPRENORPHINE EN OFFICINE : ENQUETE DANS LA REGION DE LENS)

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Interest of the preliminary risk analysis method in a central sterile supply department

International audienceIn order to improve its quality-assurance programme based on ISO 9001, the Central Sterile Supply Department of a public university hospital has performed a prospective risk analysis using the Preliminary Risk Analysis method (PRA). The objectives were the achievement of a global risk mapping related to the whole process of sterilising medical devices, and second, the implementation of corrective measures to reduce identified risks

PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences Are Emerging. A Literature Review

International audienceRecently, the development of immunotherapy through the immune checkpoint blockade led to long-lasting responses in several types of cancers that are refractory to conventional treatments, such as melanoma or non-small cell lung cancer. Immunotherapy has also demonstrated significant improvements in various other types of cancers. However, breast cancer remains one of the tumors that have not experienced the explosion of immunotherapy yet. Indeed, breast cancer was traditionally considered as being weakly immunogenic with a lower mutational load compared to other tumor types. In the last few years, anti-PD1/PD-L1 (Programmed death-ligand 1) agents have been evaluated in breast cancer, particularly in the triple negative subtype, with promising results observed when delivered as monotherapy or in combination with conventional treatments. In this review, we will report the results of the most recent studies evaluating immune checkpoint inhibitors in breast cancer. In addition, we will discuss the concomitant development of possible biomarkers, which is required for improving the selection of patients with the highest probability of benefiting from these agents

TLP-based Human Metal Model stress generator and analysis method of ESD generators

International audienceA new setup for generating a Human Metal Model compliant waveform with a TLP is described. To characterize this generator, a new analytical method has been developed, which is applicable to both TLP and HMM and demonstrates fundamental differences between those three types of generators. Results are used to correlate failure levels on active devices

A-loop conformations in KIT^WT and KIT^D816H/V/Y/N mutants.

<p>(<b>a</b>) Cluster analysis of the MD conformations picked every 10 ps over the 96 ns of productive MD simulations were performed on the RMSDs computed for only the A-loop backbone atoms. Five different sets were produced through 5 independent runs of clustering (I–V). The composition of clusters is represented as colored barplots in a logarithmic scale: KIT^WT (gray), KIT^D816V (red) KIT^D816H (green), KIT^D816Y (blue), KIT^D816N (pink). The rank in the concatenated trajectory of the corresponding <i>reference structure</i> is reported in the bottom of each barplot and colored accoring to the population of the group (see below). (<b>b–d</b>). Superposition of the <i>reference structures</i> in each cluster analysis run. The <i>reference structures</i> are drawn as cartoons illustrating the A-loop conformation (<b>b</b>), the relative orientation of the residues Y823 (A-loop) and D792 (C-loop) (<b>c</b>) and the conformation of DFG motif (A-loop) (<b>d</b>). The A-loop is shown as cartoon diagrams, residues Y823 and D792 as sticks, F811 as thick lines; D/H/V/Y/N816 as sphere. The H-bonds are shown by dotted lines. The A-loop conformations observed in all simulated proteins including KIT^WT are shown in grey; conformations detected in all protein but one mutant are distinguished in black or blue; conformations detected only in the mutants are in yellow; the proper conformations of KIT^D816V mutant are in red; characteristic of the pair of mutants, KIT^D816V/Y or KIT^D816V/N are in purple or in pink.</p

Structural organization of KIT.

<p>Stem Cell Factor (SCF) binding on the extracellular domain of KIT induces dimerization. Upon activation, KIT is autophosphorylated at tyrosine residues (magenta balls) that act as binding sites for downstream signaling kinases/mediators. The location of KIT gain-of-function mutations is indicated by residue numbers. Residues V560 and D816 (red balls), positioned in the JMR and in the kinase domain of the cytoplasmic region, are associated with highly malignant cancers. JMR, juxta-membrane region; KD, kinase domain; KID, kinase insert domain.</p

Communication pathways of cytoplasmic region in KIT^WT.

<p>(<b>a</b>) 2D graph of a global topology the inter-residues communications. Residues are represented by points, c<i>ommunication pathways</i> (<i>CPs</i>) are depicted by bold lines and two connected residues by a thin line. Structural fragments involved in <i>Independent Dynamic Segments</i> (<i>IDSs</i>), are labelled as S_i where i = 1, 2, …10. (<b>b</b>) 3D structural mapping of the communication efficiently of KIT residues. The average MD conformation is presented as cartoon. Residues in 2D (<b>a</b>) and 3D (<b>b</b>) representations are coloured from blue through green and yellow to red according to their communication efficiency, estimated as the number of residues to which they are connected by at least one <i>CP</i>. Residues V560, V559, D792, D816 and Y813 are encircled by magenta. Clusters corresponding to protein segments of interest are contoured by dotted lines. 2D and 3D graphs and drawn with Gephi and PyMOL modules incorporated in MONETA.</p