Parallel single cell analysis on an integrated microfluidic platform for cell trapping, lysis and analysis

We report here a novel and easily scalable microfluidic platform for the parallel analysis of hundreds of individual cells, with controlled single cell trapping, followed by their lysis and subsequent retrieval of the cellular content for on-chip analysis. The device consists of a main channel and an array of shallow side channels connected to the main channel via trapping structures. Cells are individually captured in dam structures by application of a negative pressure from an outlet reservoir, lyzed on site and the cellular content controllably extracted and transported in the individual side channels for on-chip analysis.\u

Geoacoustic inversion in the frequency range 0.8-1.6 kHz with drifting sparse arrays during MREA/BP'07 experiment

In order to evaluate properly the acoustic propagation characteristics in shallow water environments, it is well established that appropriate knowledge of the acoustic properties of the seabottom is required. In the last decade, full-field geoacoustic inversion techniques have been demonstrated to provide adequate methodologies to assess those properties. However, several of the developed techniques may suffer a lack of adequacy to the design of low-frequency active sonar systems (LFAS) for which the assessment of seabottom characteristics are drawn. For instance most matched-field inversion techniques demonstrated so far use acoustical signals at much lower frequencies than those of the sonar. Furthermore, some of the techniques may be difficult to be handled in an "operationally relevant context" since they are based on relatively complex designed systems such as highly instrumented vertical line arrays spanning the whole water column. In this paper, we investigate the potential of medium-frequency acoustical signals (0.8-1.6 kHz) received at several ranges on a field of drifting sparse arrays, eventually reduced to a couple of hydrophones, for spatially-coherent geoacoustic inversion purposes. The experimental datasets of the Maritime Rapid Environmental Assessment MREA/BP'07 sea trial south of Elba Island in the Mediterranean Sea are used to support this study

A dog oviduct-on-a-chip model of serous tubal intraepithelial carcinoma

Ovarian cancer is the fifth cause of cancer-related mortality in women, with an expected 5-year survival rate of only 47%. High-grade serous carcinoma (HGSC), an epithelial cancer phenotype, is the most common malignant ovarian cancer. It is known that the precursors of HGSC originate from secretory epithelial cells within the Fallopian tube, which first develops as serous tubal intraepithelial carcinoma (STIC). Here, we used gene editing by CRISPR-Cas9 to knock out the oncogene p53 in dog oviductal epithelia cultured in a dynamic microfluidic chip to create an in vitro model that recapitulated human STIC. Similar to human STIC, the gene-edited oviduct-on-a-chip, exhibited loss of cell polarization and had reduced ciliation, increased cell atypia and proliferation, with multilayered epithelium, increased Ki67, PAX8 and Myc and decreased PTEN and RB1 mRNA expression. This study provides a biomimetic in vitro model to study STIC progression and to identify potential biomarkers for early detection of HGSC.</p

The Level-0 Muon Trigger for the LHCb Experiment

A very compact architecture has been developed for the first level Muon Trigger of the LHCb experiment that processes 40 millions of proton-proton collisions per second. For each collision, it receives 3.2 kBytes of data and it finds straight tracks within a 1.2 microseconds latency. The trigger implementation is massively parallel, pipelined and fully synchronous with the LHC clock. It relies on 248 high density Field Programable Gate arrays and on the massive use of multigigabit serial link transceivers embedded inside FPGAs.Comment: 33 pages, 16 figures, submitted to NIM

Réalités et enjeux de la participation des femmes dans les essais cliniques sur les antirétroviraux : expérience au Sénégal

De plus en plus d'essais cliniques se déroulent dans les pays du Sud. Contrairement aux pays du Nord, où dans les années 1990 les associations critiquaient l'absence de femmes dans les essais, les femmes sont quatre fois plus nombreuses que les hommes parmi les participants lors du dernier d'entre eux mené à Dakar. Cela rend particulièrement aiguë la question de la survenue de grossesses dans les essais. Ce chapitre analyse cette féminisation des participants aux essais, avec la question de savoir si celle-ci résulte des modalités d'inclusion. Le mode de prise en charge des femmes enceintes dans les essais sera présenté et discuté à partir de l'expérience des femmes, des soignants et des chercheurs. Les problèmes que pose la féminisation des participants aux essais cliniques seront discutés, notamment pour ce qui concerne les limites du dispositif de prise en charge en matière de contraception, les dispositions éthiques exigées et la possibilité de critères d'inclusion basés sur le sexe

Sonoprinting liposomes on tumor spheroids by microbubbles and ultrasound

Ultrasound-triggered drug-loaded microbubbles have great potential for drug delivery due to their ability to locally release drugs and simultaneously enhance their delivery into the target tissue. We have recently shown that upon applying ultrasound, nanoparticle-loaded microbubbles can deposit nanoparticles onto cells grown in 2D monolayers, through a process that we termed "sonoprinting". However, the rigid surfaces on which cell monolayers are typically growing might be a source of acoustic reflections and aspherical microbubble oscillations, which can influence microbubble-cell interactions. In the present study, we aim to reveal whether sonoprinting can also occur in more complex and physiologically relevant tissues, by using free-floating 3D tumor spheroids as a tissue model. We show that both monospheroids (consisting of tumor cells alone) and cospheroids (consisting of tumor cells and fibroblasts, which produce an extracellular matrix) can be sonoprinted. Using doxorubicin-liposome-loaded microbubbles, we show that sonoprinting allows to deposit large amounts of doxorubicin-containing liposomes to the outer cell layers of the spheroids, followed by doxorubicin release into the deeper layers of the spheroids, resulting in a significant reduction in cell viability. Sonoprinting may become an attractive approach to deposit drug patches at the surface of tissues, thereby promoting the delivery of drugs into target tissues

Kinetics of error generation in homologous B-family DNA polymerases

The kinetics of forming a proper Watson–Crick base pair as well incorporating bases opposite furan, an abasic site analog, have been well characterized for the B Family replicative DNA polymerase from bacteriophage T4. Structural studies of these reactions, however, have only been performed with the homologous enzyme from bacteriophage RB69. In this work, the homologous enzymes from RB69 and T4 were compared in parallel reactions to determine the relative abilities of the two polymerases to incorporate correct nucleotides as well as to form improper pairings. The kinetic rates for three different exonuclease mutants for each enzyme were measured for incorporation of an A opposite T and an A opposite furan as well as for the formation of A:C and T:T mismatches. The T4 exonuclease mutants were all ∼2- to 7-fold more efficient than the corresponding RB69 exonuclease mutants depending on whether a T or furan was in the templating position and which exonuclease mutant was used. The rates for mismatch formation by T4 were significantly reduced compared with incorporation opposite furan, much more so than the corresponding RB69 mutant. These results show that there are kinetic differences between the two enzymes but they are not large enough to preclude structural assumptions for T4 DNA polymerase based on the known structure of the RB69 DNA polymerase