Quantitative full-colour transmitted light microscopy and dyes for concentration mapping and measurement of diffusion coefficients in microfluidic architectures

International audienceA simple and versatile methodology has been developed for the simultaneous measurement of multiple concentration profiles of colourants in transparent microfluidic systems, using a conventional transmitted light microscope, a digital colour (RGB) camera and numerical image processing combined with multicomponent analysis. Rigorous application of the Beer-Lambert law would require monochromatic probe conditions, but in spite of the broad spectral bandwidths of the three colour channels of the camera, a linear relation between the measured optical density and dye concentration is established under certain conditions. An optimised collection of dye solutions for the quantitative optical microscopic characterisation of microfluidic devices is proposed. Using the methodology for optical concentration measurement we then implement and validate a simplified and robust method for the microfluidic measurement of diffusion coefficients using an H-filter architecture. It consists of measuring the ratio of the concentrations of the two output channels of the H-filter. It enables facile determination of the diffusion coefficient, even for non-fluorescent molecules and nanoparticles, and is compatible with non-optical detection of the analyte

Impact of radiotherapy in the management of locally advanced extrahepatic cholangiocarcinoma

BACKGROUND: Optimal therapy for patients with unresectable locally advanced extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the role of radiotherapy in the management of such tumors. METHODS: We retrospectively reviewed the charts of patients treated in our institution with conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent chemotherapy. RESULTS: Thirty patients were included: 24 with a primary tumor (group 1) and 6 with a local relapse (group 2). Toxicity was low. Among 25 patients assessable for EBRT response, we observed 9 complete responses, 4 partial responses, 10 stabilisations, and 2 progressions. The median follow-up was 12 months. Twenty out of 30 patients (66%) experienced a relapse, which was metastatic in 75% of cases in the whole series, 87% in group 1, 60% in group 2 (p = 0.25). Twenty-eight patients (93%) died of relapse or disease complications. Median overall survivals in the whole group and in group 1 or 2 were respectively 12, 11 and 21 months (p = 0.11). The 1-year and 3-year progression-free survivals were respectively 38% and 16% in the whole series; 31% and 11% in group 1, 67% and 33% in group 2 (p = 0.35). CONCLUSION: EBRT seems efficient to treat ULAC, with acceptable toxicity. For primary disease, the high rate of metastatic relapse suggests to limit EBRT to non-progressive patients after induction chemotherapy

Inducing micromechanical motion by optical excitation of a single quantum dot

Hybrid quantum optomechanical systems1 interface a macroscopic mechanical degree of freedom with a single two-level system such as a single spin2–4, a superconducting qubit5–7 or a single optical emitter8–12. Recently, hybrid systems operating in the microwave domain have witnessed impressive progress13,14. Concurrently, only a few experimental approaches have successfully addressed hybrid systems in the optical domain, demonstrating that macroscopic motion can modulate the two-level system transition energy9,10,15. However, the reciprocal effect, corresponding to the backaction of a single quantum system on a macroscopic mechanical resonator, has remained elusive. In contrast to an optical cavity, a two-level system operates with no more than a single energy quantum. Hence, it requires a much stronger hybrid coupling rate compared to cavity optomechanical systems1,16. Here, we build on the large strain coupling between an oscillating microwire and a single embedded quantum dot9. We resonantly drive the quantum dot’s exciton using a laser modulated at the mechanical frequency. State-dependent strain then results in a time-dependent mechanical force that actuates microwire motion. This force is almost three orders of magnitude larger than the radiation pressure produced by the photon flux interacting with the quantum dot. In principle, the state-dependent force could constitute a strategy to coherently encode the quantum dot quantum state onto a mechanical degree of freedom1

Stratégies démographiques des poissons des rivières françaises : premiers résultats

International audienceThe analysis of the biological, morphological and food characteristics of 35 French species leads to distinguish two main strategies. The first one gathers 11 species with a short life span and which maximize the survival of juveniles. Within it, cold water species with a long reproduction lifetime and thermophilous species with a relatively stronger fertility can be distinguished. Their diets are essentially made of insects- plankton and insects-fishes. In the second group, no care is given to juveniles; relative fertilities are higher and inversely correlated to the number of reproduction cycles. 10 species are omnivorous with a grass-wastes tendancy, and 4 species eat strictly fishes. The canonical analysis of correspondances shows that these biological characteristics are sufficuent to understand most of the longitudinal zonation.L'analyse des caractéristiques biologiques et morpho-alimentaires de 35 espèces françaises permet de distinguer 2 stratégies principales. La première rassemble 11 espèces à faible longévité et maximisant la survie des jeunes. En son sein, on distingue des espèces d'eau froide à longue durée de vie pré-reproductrice et des espèces thermophiles à fécondité relativement plus forte. Leurs régimes alimentaires sont essentiellement du type insectivore-planctonophage et insectivore-ichtyophage. Dans le second groupe, aucun soin n'est apporté aux jeunes ; les fécondités relatives sont plus fortes et inversement corrélées avec le nombre de cycles de reproduction. 10 espèces sont des omnivores à tendance herbivore-détritivore et 4 des ichtyophages stricts. L'analyse canonique des correspondances démontre que ces caractéristiques biologiques rendent compte de l'essentiel de la zonation longitudinale

Gene expression profiling of patient‐derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: implications for individualized medicine efforts

Abstract c‐MYC controls more than 15% of genes responsible for proliferation, differentiation, and cellular metabolism in pancreatic as well as other cancers making this transcription factor a prime target for treating patients. The transcriptome of 55 patient‐derived xenografts show that 30% of them share an exacerbated expression profile of MYC transcriptional targets (MYC‐high). This cohort is characterized by a high level of Ki67 staining, a lower differentiation state, and a shorter survival time compared to the MYC‐low subgroup. To define classifier expression signature, we selected a group of 10 MYC target transcripts which expression is increased in the MYC‐high group and six transcripts increased in the MYC‐low group. We validated the ability of these markers panel to identify MYC‐high patient‐derived xenografts from both: discovery and validation cohorts as well as primary cell cultures from the same patients. We then showed that cells from MYC‐high patients are more sensitive to JQ1 treatment compared to MYC‐low cells, in monolayer, 3D cultured spheroids and in vivo xenografted tumors, due to cell cycle arrest followed by apoptosis. Therefore, these results provide new markers and potentially novel therapeutic modalities for distinct subgroups of pancreatic tumors and may find application to the future management of these patients within the setting of individualized medicine clinics

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BackgroundHistologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.MethodsThis was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0–4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0–2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.FindingsOf 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44–63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33–91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62–0·81) for histology, 0·76 (0·70–0·83) for LSM-VCTE, 0·74 (0·64–0·82) for FIB-4, and 0·70 (0·63–0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.InterpretationSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases

Mécanismes de photoionisation et de phototransfert d'électron en solution

Nous avons étudié l'apport de la spectrométrie Raman de résonance résolue dans le temps à la compréhension des processus de transfert d'électron photoinduit en solution pour deux types de réactions modèles : la photoionisation de deux amines aromatiques et la photoréduction de la 4,4'-bipyridine par deux amines aliphatiques. L'objectif majeur de ce travail était la caractérisation expérimentale de paires d'ions intermédiaires dont la présence est prédite par les cinétiques obtenues par spectroscopies électroniques. L'étude de la photoionisation des amines aromatiques n'a conduit à aucune caractérisation spectroscopique de la présence de paires d'ions, les différences structurales entre l'ion libre et l'ion engagé dans la paire étant trop faibles pour être discernables. Cependant, l'ensemble des données obtenues par Raman de résonance et absorption transitoire a permis de mieux comprendre les processus de photoionisation en solution et notamment les phénomènes observables à temps courts. De plus, l'analyse structurale du premier état excité singulet des deux amines a été réalisées à partir des spectres Raman de résonnance enregistrés pour plusieurs dérivés isotopiques. Les résultats suggèrent une structure plane symétrique, ne présentant pas de distorsion quinoïdale, l'excitation étant localisée sur la partie cyclique des molécules. L'étude de la photoréduction de 44BPY a permis de mettre en évidence de manière directe la présence de paires d'ions. L'anion de 44BPY présent dans le CIP possède des fréquences Raman différentes de celles de l'anion libre, au contraire de l'anion engagé dans la SSIP. La réactivité de ces paires d'ions a été étudiée afin de mieux comprendre l'influence du solvant et notamment des liaisons hydrogène entre solutés et solvant sur la dynamique réactionnelle de la paire.LILLE1-BU (590092102) / SudocSudocFranceF

Checking asynchronously communicating components using symbolic transition systems

place des terrasses de l’Agora, F-91000 Évry Cede

in Aqueous Solution from Picosecond Transient Absorption Measurements

molecule

Séparation de charges de molécules aromatiques insérées dans des zéolithes à canaux (application à la formation de clusters d'argent intrazéolithique)

L aptitude des zéolithes à initier spontanément des séparations de charges durables constitue une de leurs propriétés les plus fascinantes. Dans le cadre de cette étude, l adsorption de trois amines aromatiques (phénothiazine, tétraméthyl-p-phénylènediamine et diéthylaniline) possédant un potentiel d ionisation faible (< 7 eV) a été étudiée dans des zéolithes à canaux de types mordénite, ZSM-5 et Ferriérite. Ces échantillons ont été caractérisés par spectroscopie d absorption UV-visible par réflexion diffuse, spectroscopie de diffusion Raman et résonance paramagnétique électronique. Les effets de la largeur des pores et de la longueur de la chaine alkyle portée par la molécule ont ainsi été testés. L ensemble des résultats a mis en évidence le rôle essentiel de l effet du confinement sur le processus d ionisation et sur la stabilisation des états de charges séparées pendant de longues durées. L observation d espèces radicalaires de longues durées de vie s explique par un éloignement des électrons éjectés par rapport au site d ionisation de la molécule (compartimentalisation).Le deuxième enjeu de cette thèse est consacré à l étude d une nouvelle voie de synthèse de nanoclusters d argent au sein du réseau poreux des zéolithes. La formation des clusters est initiée par la réduction de cations Ag+ suite à l ionisation spontanée ou photoinduite d une molécule aromatique donneuse d électron préalablement adsorbée dans les canaux. Les premières étapes de formation de ces nanoclusters d argent ont été identifiées grâce à la spectroscopie d absorption UV-visible résolue en temps et à l utilisation de nanoparticules de zéolithes en solution colloïdale.One of the most intriguing properties of zeolite is their ability to promote spontaneously ionization through mere incorporation of electron donor molecules in their porous framework. In the present work, we describe the sorption of three aromatic amines (phenothiazine, tetramethyl-p-phenylenediamine and diethylaniline) with low ionization potential values (< 7 eV) within the porous void of channel type zeolites. Spectroscopic and modeling results show that molecule incorporation, charge separation and charge recombination differed dramatically among zeolites with respect to channel structure (ferrierite, ZSM-5, mordenite). The ionization rates and ionization yield values demonstrate that a strong synergy exists between the polarization energy of the channel inner space and spatial constraints imposed by the channel topology as well as by molecule steric constraints. The compartmentalization of ejected electron away from the initial site of ionization decreases dramatically the propensity of charge recombination.The second part of this study shows a new way of synthesis for silver nanoclusters into the void space of zeolite. Cluster formation is initiated by Ag+ reduction through spontaneous or laser photolysis ionization of an electron donor molecule previously occluded in the zeolite channel. The first steps of silver cluster formation are identified by using time resolved spectroscopy and zeolite nanoparticles in colloidal solution.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF