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The treadmill walking test with post-exercise pressure measurement can be used as a diagnostic test and could classify peripheral arterial disease of the lower limbs. It can also exclude the diagnosis allowing to raise the possibility of differential diagnoses. In this study, we assessed the feasibility of performing treadmill test by advanced practice nurse to assess suspected lower extremity peripheral artery disease patients.

The tryptophan zipper (Trpzip) is an iconic folding motif of β-hairpin peptides capitalizing on two pairs of cross-strand tryptophans, each stabilized by an aromatic–aromatic stacking in an edge-to-face (EtF) geometry. Yet, the origins and the contribution of this EtF packing to the unique Trpzip stability remain poorly understood. To address this question of structure–stability relationship, a library of Trpzip hairpins was developed by incorporating readily accessible nonproteinogenic tryptophans of varying electron densities. We found that each EtF geometry was, in fact, stabilized by an intricate combination of XH/π interactions. By tuning the π-electron density of Trpfacerings, CH/π interactions are strengthened to gain additional stability. On the contrary, our DFT calculations support the notion that Trpedgemodulations are challenging due to their simultaneous paradoxical engagement as H-bond donors in CH/π and acceptors in NH/π interactions.

Improving our understanding of how the ocean absorbs carbon dioxide is critical to climate change mitigation efforts. We, a group of early career ocean professionals working in Canada, summarize current research and identify steps forward to improve our understanding of the marine carbon sink in Canadian national and offshore waters. We have compiled an extensive collection of reported surface ocean air–sea carbon dioxide exchange values within each of Canada's three adjacent ocean basins. We review the current understanding of air–sea carbon fluxes and identify major challenges limiting our understanding in the Pacific, the Arctic, and the Atlantic Ocean. We focus on ways of reducing uncertainty to inform Canada's carbon stocktake, establish baselines for marine carbon dioxide removal projects, and support efforts to mitigate and adapt to ocean acidification. Future directions recommended by this group include investing in maturing and building capacity in the use of marine carbon sensors, improving ocean biogeochemical models fit-for-purpose in regional and ocean carbon dioxide removal applications, creating transparent and robust monitoring, verification, and reporting protocols for marine carbon dioxide removal, tailoring community-specific approaches to co-generate knowledge with First Nations, and advancing training opportunities for early career ocean professionals in marine carbon science and technology.

Drug resistance and cancer relapse represent significant therapeutic challenges after chemotherapy or immunotherapy, and a major limiting factor for long-term cancer survival. Netrin-1 was initially identified as a neuronal navigation cue but has more recently emerged as an interesting target for cancer therapy, which is currently clinically investigated. We show here that netrin-1 is an independent prognostic marker for clinical progression of breast and ovary cancers. Cancer stem cells (CSCs)/Tumor initiating cells (TICs) are hypothesized to be involved in clinical progression, tumor relapse and resistance. We found a significant correlation between netrin-1 expression and cancer stem cell (CSC) markers levels. We also show in different mice models of resistance to chemotherapies that netrin-1 interference using a therapeutic netrin-1 blocking antibody alleviates resistance to chemotherapy and triggers an efficient delay in tumor relapse and this effect is associated with CSCs loss. We also demonstrate that netrin-1 interference limits tumor resistance to immune checkpoint inhibitor and provide evidence linking this enhanced anti-tumor efficacy to a decreased recruitment of a subtype of myeloid-derived suppressor cells (MDSCs) called polymorphonuclear (PMN)-MDSCs. We have functionally demonstrated that these immune cells promote CSCs features and, consequently, resistance to anti-cancer treatments. Together, these data support the view of both a direct and indirect contribution of netrin-1 to cancer stemness and we propose that this may lead to therapeutic opportunities by combining conventional chemotherapies and immunotherapies with netrin-1 interfering drugs.

The optimal strength of compression needed to prevent post-thrombotic syndrome (PTS) after a proximal deep vein thrombosis (DVT) is debated. We aimed to assess whether 25 mm Hg elastic compression stockings (ECS) are non-inferior to 35 mm Hg ECS in preventing PTS after a DVT.

Le test de Strandness peut permettre de diagnostiquer et de classer l’artériopathie oblitérante des membres inférieurs (AOMI) d’un patient. Dans le contexte du nouveau métier d’infirmière en pratique avancée (IPA) en France, l’objectif était d’évaluer la faisabilité de cet acte par une IPA sur une étude cohorte de patients.

La majorité des intoxications individuelles aiguës au chlore sont liées au mésusage de produits ménagers (association d’un produit chloré et d’un acide) et à une exposition en milieu de piscine (après entretien par choc chloré). Une exposition aiguë au chlore peut être à l’origine d’une intoxication respiratoire, mais aussi cutanée et oculaire. L’atteinte respiratoire est la plus commune et la plus susceptible d’entraîner une intoxication collective, avec une relation dose-dépendante. La durée d’exposition et la concentration en chlore constituent des facteurs importants qui donneront lieu à des tableaux cliniques de gravité variable. Des troubles de la fonction respiratoire peuvent persister plusieurs mois après l’exposition. Il n’y a pas d’antidote ni de traitement spécifique permettant de traiter une intoxication aiguë au chlore : intérêt possible d’une oxygénothérapie ; corticothérapie et béta2mimétiques discutables. Cette revue met en évidence le bénéfice majeur d’une prise en charge préhospitalière avec arrêt rapide de l’exposition (aérer, ventiler, évacuer les personnes exposées sur une zone surélevée, de préférence en extérieur) et propose un protocole de prise en charge aux services de prévention et de santé au travail.

If there is such a thing as a dominant public sphere in post-reform China, its emotional tonality has often been described as overwhelmingly positive, as evidenced by the recent focus on “happiness” campaigns or state-promoted “positive energy.” This special section takes the prevalence of positivity as an invitation to investigate its opposites: what, in an authoritarian context, is the political work of negative affects such as bitterness, fear, shame, indifference, deflation, or trouble? Locating the articles within a broader literature on affect and emotion in anthropology and beyond, this introduction provides an overall framing for the collection. Based on the articles, it depicts the potential of negativity as both disruptive and generative, as affects work through their evaluative and propositional force which induces transformation while often evading repression.

Among the documented consequences of anthropogenic global warming are the increased frequency and duration of marine heatwaves in the global ocean. The literature dedicated to Arctic marine heatwaves corroborates those results, but fails to identify the heat sources and sinks. Because of the numerous feedbacks impacting polar regions, understanding the processes triggering and dissipating those extreme events is particularly important to predict their occurrence in a fast changing ocean. A three‐dimensional regional ice‐ocean numerical model is used to calculate a surface mixed layer heat budget and to investigate mechanisms generating and dissipating marine heatwaves. The majority of the marine heatwaves are onset by surface heat fluxes and decayed by bottom and surface heat fluxes. The dominant processes are spatially and seasonally heterogeneous: lateral heat flux can become the primary process when advecting heat anomalies at the main Arctic gateways or by triggering temperature extremes in winter. Using a Reynolds decomposition, it can be determined that the shoaling of the surface mixed layer induced by ice melt can significantly lengthen and intensify Arctic marine heatwaves. In winter, the analysis of marine heatwaves poses unique challenges, with the long term freshening of the Arctic inducing a positive trend of 0.1°C per decade for the freezing point. Arctic marine heatwaves are expected to keep increasing in duration and intensity due to the increased trend of the primary process, the surface heat flux, and their dissipation by bottom heat flux provides a pathway for heat from the atmosphere to the Arctic subsurface water masses. Extreme warm temperature anomalies in the ocean, called marine heatwaves are becoming more frequent, longer and more intense around the globe. In the Arctic Ocean, the complex links between sea ice, the atmosphere and the ocean could both amplify or hinder the impact of those events. Yet, understanding where the heat comes from and where it goes is critical to anticipate further changes in an already fast‐changing environment. To this aim, we calculate the sources and sinks of heat in a numerical model simulating the ocean and sea ice. Most marine heatwaves in the Arctic are generated by taking atmospheric heat up and disappear when this heat is transferred to the deeper ocean. In doing so, marine heatwaves provide a pathway for heat from the atmosphere to the subsurface ocean. Oceanic circulation can also propagate marine heatwaves along the continental shelf and toward the marginal ice zone. When ice melts, it shoals the upper layer of the ocean, concentrating the atmospheric heat and lengthening and intensifying marine heatwaves. The excess heat stored in the subsurface can be expected to resurface later in the season and will then delay the freezing of new sea ice. A heat budget analysis is applied to a regional ice‐ocean model to determine the dominating drivers of marine heatwaves in the ArcticMarine heatwaves in the Arctic provide a pathway for heat from the atmosphere to the subsurface oceanSea ice melt shoals the surface mixed layer, and this prolongs and intensifies marine heatwaves A heat budget analysis is applied to a regional ice‐ocean model to determine the dominating drivers of marine heatwaves in the Arctic Marine heatwaves in the Arctic provide a pathway for heat from the atmosphere to the subsurface ocean Sea ice melt shoals the surface mixed layer, and this prolongs and intensifies marine heatwaves

Deep eutectic solvents (DESs) have been considered “the organic reaction medium of the century” because they can be used as solvents and active catalysts in chemical reactions. However, experimental and theoretical studies are still needed to provide information on the structures of DESs, the kinetics and thermodynamics properties, the interactions between the DESs and the substrates, the effect of water on the DES supramolecular network and its physicochemical properties, and so forth. This information is very useful to understand the essence of the processes that take place in the catalysis of chemical reactions and, therefore, to help in the design of a DES for a specific reaction and sample. This article shows a systematic study of the impact of DES choline chloride/p-toluenesulfonic acid and DES choline chloride/p-toluenesulfonic acid–water in the aza-Michael addition of arylamines to maleimide to obtain aminopyrrolidine-2,5-dione derivatives. The derivatives are obtained under very mild reaction conditions with good yield. The global reaction is exothermic, spontaneous, permitted by enthalpy, and prohibited for entropy. The calculated potential energy surface shows a reaction mechanism of six steps controlled by enthalpy (except the last step that is controlled by entropy). The water incorporated in the supramolecular DES complex stabilizes the transition states and favors the enthalpy-driven binding. A set of H/D exchange NMR experiments validates the transition state existing in the fourth stage of the mechanism.

It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced prostate cancer. We aimed to prospectively plan a systematic review of randomised controlled trials (RCTs) comparing these radiotherapy approaches.

The design of novel and functional biomimetic foldamers remains a major challenge in creating mimics of native protein structures. Herein, we report the stabilization of a remarkably short β-sheet by incorporating N-(hydroxy)glycine (Hyg) residues into the backbone of peptides. These peptide–peptoid hybrids form unique parallel β-sheet structures by self-assembly upon hydrogenation. Our spectroscopic and crystallographic data suggest that the local conformational perturbations induced by N-(hydroxy)amides are outweighed by a network of strong interstrand hydrogen bonds.

The binding affinity of antibodies to specific antigens stems from a remarkably broad repertoire of hypervariable loops known as complementarity-determining regions (CDRs). While recognizing the pivotal role of the heavy-chain 3 CDRs (CDR-H3s) in maximizing antibody–antigen affinity and specificity, the key structural determinants responsible for their adaptability to diverse loop sequences, lengths, and noncanonical structures are hitherto unknown. To address this question, we achieved a de novo synthesis of bulged CDR-H3 mimics excised from their full antibody context. CD and NMR data revealed that these stable standalone β-hairpin scaffolds are well-folded and retain many of the native bulge CDR-H3 features in water. In particular, the tryptophan residue, highly conserved across CDR-H3 sequences, was found to extend the kinked base of these β-bulges through a combination of stabilizing intramolecular hydrogen bond and CH/π interaction. The structural ensemble consistent with our NMR observations exposed the dynamic nature of residues at the base of the loop, suggesting that β-bulges act as molecular hinges connecting the rigid stem to the more flexible loops of CDR-H3s. We anticipate that this deeper structural understanding of CDR-H3s will lay the foundation to inform the design of antibody drugs broadly and engineer novel CDR-H3 peptide scaffolds as therapeutics.

Alcohol consumption has been linked to increased aggressiveness and to different types of violence. It has been suggested that both the empathic disposition and the executive function (EF) are mediators and moderators of aggression in alcoholic patients and during alcohol intoxication. In this work, we analyze the cognitive-affective profile that mediates or modulates the relationship between alcohol consumption and violence in social drinkers.

Poly(N-isopropylacrylamide) (PNIPAm) is a stimuli-responsive polymer with wide applications as a scaffold in biomedical applications. This study presents the PNIPAm’s thermoresponsive behavior during storage and its stability in potential pharmaceutical formulations as a drug delivery excipient. Therefore, the turbidity curves of linear PNIPAm aqueous solutions are investigated before and after its thermal oxidation under air at 120°C and 130°C. First, PNIPAm aqueous phase separation diagram is determined for unaged polymer and then compared to thermally aged samples at two distinct points (1 and 10% (w/w)). After isothermal aging, the transition temperature has increased with a shift up to 4°C. The correlation between PNIPAm’s chemical structure and phase transition temperature properties is illustrated in terms of chemical modifications, macromolecular changes as well as the polar/non-polar groups balance. It is observed that the water affinity and glass transition temperature (Tg) have increased at the macromolecular level. In addition, chains scissions are highlighted and seem to explain the shift of transition temperature. Chemical changes have revealed the presence of supplementary polar groups induced by aging. This multiscale study suggests a possible mechanism for the partial thermal oxidation based on all the observations.

Elexacaftor–tezacaftor–ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTRvariant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor–tezacaftor–ivacaftor for people with cystic fibrosis without a F508del CFTRvariant in France and to determine CFTRvariant responsiveness to elexacaftor–tezacaftor–ivacaftor based on the observed clinical response.

L’un des principaux objectifs des classifications des troubles du sommeil est d’améliorer la fiabilité inter-évaluateur des diagnostics (ou le degré d’accord sur un diagnostic entre cliniciens). Nous avons réalisé une revue systématique des études de fiabilité des critères diagnostiques des troubles du sommeil des principales classifications internationales utilisées en médecine du sommeil.

Malgré son rôle central dans la sémiologie et les classifications des troubles du sommeil et de l’éveil, il n’existe pas actuellement de consensus sur la définition de la somnolence. Nous proposons d’identifier les différents termes associés à la somnolence dans l’intégralité de la littérature scientifique et de quantifier les relations entre eux à l’aide de techniques de traitement automatique du langage naturel.

Based on the observation of the misuse of ICD-10 to code the diagnoses in the RIM-P (lack of completeness, conformity and diversity), the Technical Agency for information on Hospital Care (ATIH), which provides tools for collecting medical information, conducted two actions in 2016. First, a chapter devoted to the instructions of coding has been written in the methodological guide of production of the RIM-P, second, a variable “type psy” was added to the ICD-10 nomenclature's file framing ICD-10 coding in the RIM-P. The purpose of this study is to describe the quality of diagnosis coding using ICD-10 in the RIM-P in 2015 and 2016.

L’objectif de cette étude est d’évaluer la variabilité de la remontée des certificats de décès en cas de mort suspecte.

To study the interplay of rare outcrossing and metapopulation structure, we focus on the nematode Caenorhabditis elegans. Its remarkably low outcrossing rate is at the extreme end of the spectrum for facultative selfing organisms. At the demographic level, C. elegansnatural populations undergo boom and bust dynamics on ephemeral resources, with the dauer diapause larva acting as the dispersal form. Here we investigate the small-scale genetic structure of C. eleganspopulations in two localities over several years, using 2b restriction-associated DNA sequencing of nearly 1000 individuals. We find a remarkably small number of genome-wide haplotypes, almost exclusively in the homozygous state, confirming the low effective outcrossing rate. Most strikingly, the major haplotypes in a locality remain intact and do not effectively recombine over several years. From the spatial pattern of diversity, we estimate that each subpopulation or deme is seeded by a mean of 3–10 immigrating individuals. Populations are thus formed by clones that compete at two levels, within a subpopulation and at the metapopulation level. We test for the presence of local phenotypic variation in pathogen resistance and dauer larva nictation, which could possibly explain the maintenance of different genotypes by heterogeneous selection in different local environments or lifecycles. This study is the first to address the local spatiotemporal genetic structure of C. eleganson feeding substrates. We conclude that these animals coexist as competing homozygous clones at the smallest population scale as well as in the metapopulation.

Faire l’état des lieux des pratiques et de la rédaction des certificats de décès par les instituts médicolégaux, notamment en cas de suicide, dans la perspective de la mise en place d’un volet complémentaire du certificat de décès.

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This paper deals with polymer-fuel interaction focusing on specific effects of biofuels on polyethylene (PE) in automotive applications. The practical objective is to develop a predictable approach for durability of polyethylene tanks in contact of ethanol based or biofuel based fuels. In the case of ethanol, the main consequence on PE durability is a reduction of the rate of stabilizer extraction; this latter phenomenon can be modeled by first order kinetics with a rate constant that obeys the Arrhenius equation. Concerning biodiesels, the study was focused on soy and rapeseed methyl ester which were compared to methyl oleate and methyl linoleate used as model compounds. Here, PE-fuel interactions can be described as well as physical interaction, linked to the oil penetration into the polymer, as chemical interaction linked to an eventual co-oxidation of PE and oil. Both aspects were investigated. Concerning biofuel transport in PE, it appeared that the oil diffusivity depends only of temperature and oil molar mass. Some aspects of the temperature dependence of the oil solubility in PE are discussed. About chemical interaction between oil and PE, it was put in evidence that unsaturated fatty esters promote and accelerate PE oxidation. A co-oxidation kinetic model was proposed to describe this process.

In the frame of minor actinide transmutation, americium can be diluted in UO2and (U, Pu)O2fuels burned in fast neutron reactors. The first mandatory step to foresee the influence of Am on the in-reactor behavior of transmutation targets or fuel is to have fundamental knowledge of the Am–O binary system and, in particular, of the AmO2–xphase. In this study, we coupled HT-XRD (high-temperature X-ray diffraction) experiments with CALPHAD thermodynamic modeling to provide new insights into the structural properties and phase equilibria in the AmO2–x–AmO1.61+x–Am2O3domain. Because of this approach, we were able for the first time to assess the relationships between temperature, lattice parameter, and hypostoichiometry for fcc AmO2–x. We showed the presence of a hyperstoichiometric existence domain for the bcc AmO1.61+xphase and the absence of a miscibility gap in the fcc AmO2–xphase, contrary to previous representations of the phase diagram. Finally, with the new experimental data, a new CALPHAD thermodynamic model of the Am–O system was developed, and an improved version of the phase diagram is presented.

Local-regional recurrence for patients with ≥pT3 disease after radical cystectomy is a significant problem. Chemotherapy has not been shown to reduce the risk of local-regional recurrences in randomized prospective trials, and salvage therapies for local-regional failure are rarely successful. There is promising evidence, particularly from a recent Egyptian NCI trial, that radiation therapy plus chemotherapy can significantly reduce local recurrences compared to chemotherapy alone, and that this improvement in local-regional control may translate to meaningful improvements in disease-free and overall survival with acceptable toxicity. In light of the high rates of local failure following cystectomy for locally advanced disease and the progress that has been made in identifying patients at high risk of failure and the patterns of failure in the pelvis, the NCCN guidelines were revised in 2016 to include post-operative radiotherapy as an option to consider for patients with ≥pT3 disease. Despite advances in our understanding of the problem of local-regional failure after cystectomy and the potential role of adjuvant radiotherapy, the question of whether adjuvant radiotherapy should have a defined role for patients with locally advanced urothelial carcinoma has not yet been determined. The results of the NRG, European, Indian, and Egyptian trials on adjuvant radiotherapy are eagerly awaited. While none of these trials on their own may provide definitive conclusions, their aggregate outcomes will help clarify whether this treatment should have a role in the management of patients with locally advanced bladder cancer.

Identifier tous les auto-questionnaires génériques permettant de dépister plusieurs troubles du sommeil existants. Évaluer le contenu en termes de symptômes recherchés afin d’identifier les éléments clés de la sémiologie en médecine du sommeil.

Malgré son rôle central dans la sémiologie et les classifications nosologiques des troubles du sommeil et de l’éveil, il n’existe pas actuellement de consensus sur la définition de la somnolence. Nous proposons d’en étudier les différentes sous-dimensions en évaluant systématiquement les outils conçus pour la mesurer.

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies.

Un mode extrêmement important de vieillissement des matériaux polymères implique une réaction chimique entre les matériaux et l'eau ou l'oxygène présent dans l'environnement. La réaction peut être activée par une élévation de température, une irradiation (UV ou radiations ionisantes) ou un agent chimique jouant, par exemple, le rôle d'amorceur radicalaire. Dans le cas général, la cinétique globale de vieillissement est gouvernée par la diffusion du réactif moléculaire en question et le matériau peut être soumis à un état de contrainte susceptible d'influencer les processus chimiques et diffusionnels, et d'être lui-même influencé par ces derniers. Le présent article passe brièvement en revue les couplages susceptibles d'être rencontrés et les pistes possibles de modélisation. Dans un dernier chapitre, un travail récent portant sur un modèle non empirique de prédiction de durée de vie (à rupture) sous l'effet combiné d'une réaction chimique et d'un état de contrainte (statique) est résumé.

Dans les processus de photo- et de thermo-oxydation des matériaux polymères, les hydroperoxydes (POOH) constituent sans aucun doute l'espèce clé, dont l'accumulation et la décomposition déterminent pour une large part le comportement cinétique. Après un bref rappel des schémas mécanistiques et cinétiques montrant l'importance du rôle des hydroperoxydes, nous analyserons l'influence des conditions d'exposition (température, intensité lumineuse, pression d'oxygène) sur la formation de ces espèces. Les chapitres suivants seront consacrés à l'importance relative des processus uni- et bimoléculaire de décomposition des POOH dans l'amorçage des chaînes d'oxydation, à l'identification de la molécularité de la réaction et à l'utilisation de l'un des deux processus, ou des deux, dans la modélisation cinétique. Nous nous intéresserons également à quelques questions récurrentes sur la coexistence des différents types d'hydroperoxydes : leur décomposition catalysée par des métaux de transition, l'existence éventuelle d'une chimiluminescence induite par leur décomposition, l'intérêt éventuel de leur dosage pour caractériser l'avancement du vieillissement, ainsi que les avantages et les limites des méthodes de dosage courantes.

Graft versus host disease (GvHD), which is the primary complication of allogeneic bone marrow transplantation, can alter the intestinal barrier targeted by activated donor T-cells. Chemical inhibition of the stress protein HSP90 was demonstrated in vitroto inhibit T-cell activation and to modulate endoplasmic reticulum (ER) stress to which intestinal cells are highly susceptible. Since the HSP90 inhibitor 17-allylamino-demethoxygeldanamycin (17AAG) is developed in clinics, we explored here its ability to control intestinal acute GvHD in vivoin two mouse GvHD models (C57BL/6?BALB/c and FVB/N?Lgr5-eGFP), ex vivoin intestine organoids and in vitroin intestinal epithelial cultures. We show that 17AAG decreases GvHD-associated mortality without impairing graft versus leukemia effect. While 17AAG effect in T-cell activation is just moderate at the dose used in vivo,we observe a striking intestinal integrity protection. At the intestine level, the drug promotes the splicing of the transcription factor X-box binding protein 1 (XBP1), which is a key component of the ER stress. This effect is associated with a decrease in intestinal damage and an increase in Lgr5+stem cells, Paneth cells and defensins production. The importance of XBP1 splicing control is further confirmed in cultured cells and organoids of primary intestinal epithelium where XBP1 is either shRNA depleted or inhibited with toyocamycin. In conclusion, 17AAG has a protective effect on the epithelial intestinal barrier in mouse models of acute GvHD. This compound deserves to be tested in the therapeutic control of acute GvHD.

ABSTRACTAllergic bronchopulmonary aspergillosis (ABPA) is difficult to diagnose; diagnosis relies on clinical, radiological, pathological, and serological criteria. Our aim was to assess the performance of two new commercially available kits and a new in-house assay: an Aspergillus fumigatusenzyme-linked immunosorbent assay (ELISA) IgG kit (Bordier Affinity Products), an AspergillusWestern blotting IgG kit (LDBio Diagnostics), and a new in-house time-resolved fluorometric IgE assay (dissociation-enhanced lanthanide fluorescent immunoassay, or DELFIA) using recombinant proteins from an Aspergillussp. recently developed by our laboratory for ABPA diagnosis in a retrospective study that included 26 cystic fibrosis patients. Aspergillus fumigatus-specific IgG levels measured by a commercial ELISA kit were in accordance with the level of precipitins currently used in our lab. The ELISA kit could accelerate and help standardize ABPA diagnosis. Aspergillus fumigatus-specific IgE levels measured by ImmunoCAP (Phadia) with A. fumigatusM3 antigen and by DELFIA with a purified protein extract of A. fumigatuswere significantly correlated (P< 10-6). The results with recombinant antigens glucose-6-phosphate isomerase and mannitol-1-phosphate dehydrogenase were encouraging but must be confirmed with sera from more patients. The DELFIA is an effective tool that can detect specific IgE against more fungal allergens than can be detected with other commercially available tests.

Décrire les traitements néoadjuvants et adjuvants à la chirurgie du cancer de la prostate (CaP) et la place de la chirurgie dans la récidive après primotraitement.

Today, a range of biotechnological approaches, from somatic embryogenesis to biomolecular research, play an increasingly important role in breeding strategies for oil palm (Elaeis guineensis Jacq.). Clonal micropropagation. Methods of cloning by in vitro culture led to the development of a micropropagation technique for oil palm based on somatic embryogenesis which was tested at the pilot stage on elite genotypes, thus enabling the production of high oil yielding clones. This phase allowed the identification of limiting factors associated with scaling-up, with respect in particular to the scale of mass production required to meet the needs of planters and to the problem of ensuring genetic fidelity in the regenerated plant material. These two concerns led researchers to look further into the underlying physiological and/or molecular mechanisms involved in somatic embryogenesis and the somaclonal variation events induced by the in vitro cloning procedure. Structural and functional genomics. Marker-assisted breeding in oil palm is a long-term multi-stage project including: molecular analysis of genetic diversity in both E. guineensis and E. oleifera germplasms; large scale development of PCR-based microsatellite markers; and parallel development of three genome mapping and QTL detection projects studying key agronomic characters. Post-genomics. In order to tackle the problem of the mantled flowering abnormality, which is induced during the micropropagation process, studies of gene expression have been carried out in tissue cultures as a means of establishing an early clonal conformity testing procedure. It is important to assess what kind of methodology is the most appropriate for clonal conformity testing by comparing RNA, protein and DNA (PCR) based approaches. Parallel studies on genomic DNA methylation changes induced by tissue culture suggest that the latter may play an important role in the determination of the mantled abnormality.

Les patients hémodialysés chroniques (HDC) sont à haut risque de développer une forme grave d’infection à SARS-CoV-2. Ils constituent une population cible pour la vaccination. Toutefois, la réponse vaccinale chez ces patients n’est pas connue.

The oxidation of six (U1–y,Puy)O2–xpowdered samples, with y= 14, 24, 35, 46, 54, and 62 mol %, was studied in situ by high-temperature XRD at different temperatures. The samples were first reduced at 1500 °C to an oxygen to metal ratio (O/M) lower than 2.00. Afterward, the temperature was rapidly decreased to a value between 200 and 800 °C, which was followed by a long isothermal plateau during which diffraction patterns were recorded continuously. We observed structural changes in the material as it oxidized, in some cases passing through a biphasic domain. We discuss the influence of phase separation on the formation of a passive layer and the kinetics of phase transformations. It was found that entering the biphasic fcc1 + fcc2 domain will inhibit the formation of a passive layer. We hypothesize that the reason behind this behavior is the dependence of oxygen diffusion on the concentration of oxygen defects.

Plusieurs options thérapeutiques sont actuellement possibles pour le traitement du cancer de la prostate. L’IRM prostatique à une place importante pour la détection et le bilan d’extension du cancer de la prostate, mais également dans l’évaluation post-thérapeutique et la détection des récidives tumorales. L’imagerie nucléaire et en particulier le PET/TDM à la choline a également une place indispensable dans cette indication. Nous verrons dans cette revue qu’elle est la part de ces différentes techniques dans l’évaluation post-thérapeutique du cancer de la prostate.

Effectuer une mise au point sur les cancers localisés de la prostate « à faible risque évolutif ». Ces cancers ont été définis à partir des données histologiques, cliniques et biologiques. L’utilisation du taux de PSA a entraîné une migration de stades vers les cancers de la prostate à faible risque, qui représentent actuellement 40 à 50 % des formes diagnostiquées.

The Escherichia coli dapB gene encodes dihydrodipicolinate reductase. This enzyme is part of the diaminopimelate-lysine pathway, and its synthesis is repressed by lysine. The dapB gene was cloned into pBR322 from a transducing lambda bacteriophage, its complete nucleotide sequence established, and the transcriptional start localized. The DNA sequence predicts that the dapB gene codes for a 273-amino acid polypeptide, Mr 28,798. No attenuation-type sequence can be found between the mRNA start and the coding sequence. The dapB promoter signals appear to be weak as compared to RNA polymerase consensus sequences. Nevertheless an efficient in vivo synthesis of beta-galactosidase was obtained when the lac operon was inserted in vitro in the dapB gene, downstream of the dapB regulatory signals. Further studies were performed on an in-frame gene fusion constructed in vitro between the dapB and the lacZ genes. They indicated that repression by lysine is exerted on a DNA region restricted to a 153-base pair fragment with only 102 nontranscribed nucleotides. Finally, dapB gene expression showed a gene dosage effect which suggests that it is not controlled by an element present in limiting amounts in the cell.

Regulation of the Escherichia coli dapD gene involved in diaminopimelate and lysine biosynthesis was unknown as no convenient enzymatic assay was available until recently. This gene was cloned into pBR322 from a lambda transducing phage; its complete nucleotide sequence was established. This sequence shows that the dapD gene is composed of a single cistron encoding a 274-amino acid polypeptide, Mr 30,040. Enzymatic activity measurements show that this gene encodes the tetrahydrodipicolinate N-succinyltransferase which catalyzes the third step of the specific lysine-diaminopimelate pathway. The transcriptional start of the dapD gene was localized; the identified promoter signals are weak compared to those from the E. coli promoter consensus sequence. The dapD gene-coding sequence is followed by a typical rho-independent transcriptional termination sequence. A study using an operon fusion constructed in vitro between the dapD promoter and the galK structural gene indicated that dapD gene expression is repressed by lysine; no attenuation-like sequence can be found to account for this regulation. At the present time, out of the 9 genes involved in diaminopimelate and lysine biosynthesis, 6 are known to be lysine regulated.

The regulation of lysA which encodes the last enzyme for lysine biosynthesis in Escherichia coli, diaminopimelic acid-decarboxylase, was studied by using lysA-lacZ fusions. Our results indicate an absolute requirement for the LysR product for its activation, LysR protein present in a limiting amount which can be titrated by a multicopy plasmid carrying its target site and a negative regulatory role for the LysA protein itself which decreases lysA-lacZ expression 30-fold.

In Escherichia coli, the first enzyme of the diaminopimelate and lysine pathway is dihydrodipicolinate synthetase, which is feedback-inhibited by lysine and encoded by the dapA gene. The location of the dapA gene on the bacterial chromosome has been determined accurately with respect to the neighboring purC and dapE genes. The complete nucleotide sequence and the transcriptional start of the dapA gene were determined. The results show that dapA consists of a single cistron encoding a 292-amino acid polypeptide of 31,372 daltons.

Construire un algorithme de questionnaires à l’entrée d’un centre du sommeil, fiable, court et complet et permettant d’orienter au mieux les sujets avec une plainte du sommeil dans des filières de soins.