Functional single-cell analysis of T-cell activation by supported lipid bilayer-tethered ligands on arrays of nanowells

Supported lipid bilayers are an important biomolecular tool for characterizing immunological synapses. Immobilized bilayers presenting tethered ligands on planar substrates have yielded both spatio-temporal and structural insights into how T cell receptors (TCRs) reorganize during the initial formation of synapses upon recognition of peptide antigens bound to major histocompatibility complex (MHC) molecules. The prototypical configuration of these assays, however, limits the extent to which the kinetics and structure of the supramolecular activation clusters of the synapse (that occur in seconds or minutes) can be related to subsequent complex cellular responses, such as cytokine secretion and proliferation, occurring over hours to days. Here we describe a new method that allows correlative measures of both attributes with single-cell resolution by using immobilized lipid bilayers and tethered ligands on the surface of dense arrays of subnanoliter wells. This modification allows each nanowell to function as an artificial antigen-presenting cell (APC), and the synapses formed upon contact can be imaged by fluorescence microscopy. We show that the lipid bilayers remain stable and mobile on the surface of the PDMS, and that modifying the ligands tethered to the bilayer alters the structure of the resulting synapses in expected ways. Finally, we demonstrate that this approach allows the subsequent characterization of secreted cytokines from the activated human T cell clones by microengraving in both antigen- and pan-specific manners. This new technique should allow detailed investigations on how biophysical and structural aspects of the synapse influence the activation of individual T cells and their complex functional responses.National Institute of Allergy and Infectious Diseases (U.S.) (5P01AI045757)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051

Optimisation du bruit de fond et de la réponse des détecteurs sphériques à gaz pour la recherche de matière noire légère

The spherical proportional counters have been used by the NEWS-G collaboration since 2013 for dark matter search with the SEDINE detector installed at the Laboratoire Souterrain de Modane. This first detector allowed for establishing a new limit on the WIMP-nucleon cross section for WIMPs of mass less than 0.6 GeV/c². Since then, the collaboration has been working on the development of a new detector. This thesis focuses on two improved aspects of the second detector. The study of the background observed by SEDINE led to the conclusion that it is dominated by the presence of Pb²¹⁰ decay chain on the surfaces and in the materials making up the detector and its shielding. This allowed for the selection of materials and manufacturing methods to reduce the background noise of the next detector. The second development concerns the detector anode. Placed in the center of the sphere, the anode ensures the formation of the signal. The latest developments show the ability of this component to ensure the detection of single electrons while being stable and with good resolution. This study made it possible to develop a new generation of detector which will be installed at SNOLAB in 2020.Les compteurs proportionnels sphériques sont utilisés pour la recherche de matière noire par la collaboration NEWS-G depuis 2013 avec le détecteur SEDINE installé au Laboratoire Souterrain de Modane. Ce premier détecteur a permis d'établir une nouvelle limite de la section efficace d'interaction WIMP-nucléon pour des WIMPs de masse inférieur à 0.6 GeV/c². Depuis, la collaboration travail à la mise au point d'un nouveau détecteur. Cette thèse se concentre sur deux aspects améliorés pour le second détecteur. L'étude du bruit de fond observé par SEDINE a permis de conclure que celui-ci est dominé par le présence de la chaine de désintégration du Pb²¹⁰ sur les surfaces et dans le matériaux composant le détecteur et son blindage. Ceci a permis de sélectionner des matériaux et des procédés de fabrication permettant de réduire le bruit de fond du prochain détecteur. Le second développement concerne l'anode du détecteur. Placée au centre de la sphère, l'anode assure la formation du signal. Les derniers développements montrent la capacité de ce composant à assurer la détection d'électrons uniques en étant stable et avec une bonne résolution

Estimación del periodo dominante del suelo, una herramienta en la gestión local de riesgos geológicos

The analysis of the risks of microseisms for the obtaining of dominant periods of the soil, is a wealthy tool in the urban planning and in the local management of risks, mainly in cases of seisms. The investigation had as objective the elaboration of the map of dominant periods of soils for the city of San Cristobal (western Cuba), using the analysis of microseism as main method. The reached results allowed to subdivide the city in to five zones according to the behavior of the dominant period of the soil. Particularly the zone with dominant period of the soil superior in two seconds, is the most favorable zone for the amplification of the seismic waves in the city. The obtained seismic microzoning is a tool for the consult in the future urban ordering and in the local administration of geological risks.El análisis de los registros de microsismos para la obtención de periodos dominantes del suelo, es una valiosa herramienta en la planificación urbana y en la gestión local de riesgos, fundamentalmente frente a sismos. La investigación tuvo como objetivo la elaboración del mapa de periodos dominantes del suelo para la ciudad de San Cristóbal (Cuba occidental), empleando el análisis de microsismos como método principal. Los resultados alcanzados permitieron subdividir la ciudad en cinco zonas de acuerdo al comportamiento de periodo dominante del suelo. En particular la zona con periodo dominante superior a dos segundos, es la más favorable para la amplificación de las ondas sísmicas en la cuidad. La microzonación sísmica obtenida constituye una herramienta de consulta en el futuro ordenamiento urbano y en la gestión local de riesgos geológicos

Estimación del periodo dominante del suelo, una herramienta en la gestión local de riesgos geológicos

"El análisis de los registros de microsismos para la obtención de periodos dominantes del suelo, es una valiosa herramienta en la planificación urbana y en la gestión local de riesgos, fundamentalmente frente a sismos. La investigación tuvo como objetiv

Silicon micromachined ultrasonic scalpel for the dissection and coagulation of tissue

This work presents a planar, longitudinal mode ultrasonic scalpel microfabricated from monocrystalline silicon wafers. Silicon was selected as the material for the ultrasonic horn due to its high speed of sound and thermal conductivity as well as its low density compared to commonly used titanium based alloys. Combined with a relatively high Young’s modulus, a lighter, more efficient design for the ultrasonic scalpel can be implemented which, due to silicon batch manufacturing, can be fabricated at a lower cost. Transverse displacement of the piezoelectric actuators is coupled into the planar silicon structure and amplified by its horn-like geometry. Using finite element modeling and experimental displacement and velocity data as well as cutting tests, key design parameters have been identified that directly influence the power efficiency and robustness of the device as well as its ease of controllability when driven in resonance. Designs in which the full- and half-wave transverse modes of the transducer are matched or not matched to the natural frequencies of the piezoelectric actuators have been evaluated. The performance of the Si micromachined scalpels has been found to be comparable to existing commercial titanium based ultrasonic scalpels used in surgical operations for efficient dissection of tissue as well as coaptation and coagulation of tissue for hemostasis. Tip displacements (peak-to-peak) of the scalpels in the range of 10–50 μm with velocities ranging from 4 to 11 m/s have been achieved. The frequency of operation is in the range of 50–100 kHz depending on the transverse operating mode and the length of the scalpel. The cutting ability of the micromachined scalpels has been successfully demonstrated on chicken tissue

Les bases de données du GIS Sol : un accès à la connaissance de l’état des sols sur le territoire

National audienceDepuis maintenant presque 20 ans, le GIS Sol conçoit et coordonne les programmes nationaux d’acquisition des données sur les sols. Ainsi, sous son impulsion et grâce aux financements de ses membres, l’unité de service InfoSol de l’INRA a organisé les actions d’inventaire et de surveillance des sols, tout comme la récupération et la sauvegarde de données anciennes ou acquises par différents acteurs (bureaux d’étude, laboratoires) afin de constituer un système d’information unique sur les sols de France. Ces dernières années, le traitement des données et leur mise à disposition se sont accélérés, rendant ainsi possible l’accès à des informations sur les sols. Sont ainsi disponibles et accessibles des données de base sur les sols (ex : nature, distribution) ainsi que des informations sur les teneurs nationales du fond pédogéochimique en divers éléments majeurs (ex : Al, Fe, Ca, K) et traces (ex : As, Cd, Cu, Hg, Ni, Zn) tout comme les concentrations attendues en certaines familles de contaminants organiques persistants dans l’environnement (ex : HAP, PCB, dioxines). Cette intervention fait le bilan de 20 ans d’un dispositif unique en Europe qui a organisé la coopération entre les ministères de l’Agriculture et de l’Ecologie, des instituts de recherche et des agences de l’Etat pour créer et faire prospérer un système d’information sur les sols de France

EXCESS workshop: Descriptions of rising low-energy spectra

International audienceMany low-threshold experiments observe sharply rising event rates of yet unknown origins below a few hundred eV, and larger than expected from known backgrounds. Due to the significant impact of this excess on the dark matter or neutrino sensitivity of these experiments, a collective effort has been started to share the knowledge about the individual observations. For this, the EXCESS Workshop was initiated. In its first iteration in June 2021, ten rare event search collaborations contributed to this initiative via talks and discussions. The contributing collaborations were CONNIE, CRESST, DAMIC, EDELWEISS, MINER, NEWS-G, NUCLEUS, RICOCHET, SENSEI and SuperCDMS. They presented data about their observed energy spectra and known backgrounds together with details about the respective measurements. In this paper, we summarize the presented information and give a comprehensive overview of the similarities and differences between the distinct measurements. The provided data is furthermore publicly available on the workshop’s data repository together with a plotting tool for visualization