Search

Shallow clouds remain greatly significant in improving our understanding of the atmosphere. Using the Met Office Unified Model, we compare highly idealised simulations of shallow cumuli with those using more realistic domains, with open lateral boundaries and varying large-scale forcing. We find that the realistic simulations are more capable of representing the cloud field on large spatial scales, and appear to limit the aerosol perturbations leading to impacts on the thermodynamic conditions. Aerosol perturbations lead to changes in the cloud vertical structure, and thermodynamic evolution of the idealised simulations; a central feature of behavior seen previously in idealised simulations. Modelling approaches with open boundaries and time-varying forcing may allow for improved representation of shallow clouds in the atmosphere, and greater understanding of how they may respond to perturbations.

« We shall not cease from explorationAnd the end of all our exploringWill be to arrive where we startedAnd know the place for the first time. » T.S. Eliot, Little Gidding (1942) Les articles réunis dans ce numéro sont, pour la plupart, issus de communications données dans le cadre du séminaire de littérature anglophone organisé par le laboratoire CORPUS de l’Université de Picardie-Jules Verne (UR-UPJV 4295), de 2018 à 2021. L’objet du séminaire était d’étudier la dynamique du retour vers des ...

On September 2, 2020, Powell’s Books, “one of the world’s largest independent bookstores”, based in Portland, Oregon, hosted Ron Rash and Colum McCann on Zoom. At the time, Ron Rash’s new collection, In the Valley: Stories and a Novella based on Serena, had just come out. A virtuosic novelist, poet, and story writer, Rash evokes the beauty and brutality of the land, the relentless tension between past and present. In the ten stories of his new collection, he spins a haunting allegory of the t...

Interstitial fluid flow plays a critical role in tumor cell invasion, yet this role has not been explored extensively in combination with other microenvironmental factors. Here, we establish a novel computational model of three-dimensional breast cancer cell migration to unveil the effect of interstitial fluid flow in the dependence of various extracellular matrix (ECM) physical properties. Our model integrates several principal factors: fluid dynamics, autologous chemotaxis, collagen fiber network structure, ECM stiffness, and cell-fiber and cell-flow interaction. First, independently with an aligned collagen fiber network and interstitial fluid flow, this model is validated by successfully reproducing the cell migration patterns. In the model, the interstitial fluid flow leads to directional symmetry breaking of chemotactic migration and synergizes with the ECM orientation to regulate cell migration. This synergy is universal in both the mesenchymal and the amoeboid migration modes, despite the fact that the cell-ECM interaction are different. Consequently, we construct a cell displacement function depending on these factors. Our cell migration model enables three-dimensional cancer migration prediction, mechanism exploration, and inhibition treatment design in a complex tumor microenvironment.

Contexte : depuis 2006, les etudiants en soins infirmiers sont formes aux gestes et soins d’urgence par la simulation. Cette derniere peut etre source d’insecurite psychologique. But : l’etude vise a explorer les strategies deployees par les formateurs a l’attestation de formation aux gestes et soins d’urgence (AFGSU) pour garantir la securite psychologique des etudiants lors d’une seance de simulation. Methode : une recherche qualitative a ete realisee, dans une approche exploratoire, par entretiens semi-directifs aupres de formateurs AFGSU intervenant en semestre 2. Resultats : les formateurs deploient des strategies de prevention en regard de facteurs de risque d’insecurite psychologique. Lorsque l’etudiant est en insecurite voire en detresse, ils mobilisent des outils de remediation. Ces strategies interviennent aux trois temps de la simulation : le briefing, le scenario et le debriefing. Discussion : en simulation, l’importance des risques psychologiques pour les etudiants doit etre prise en consideration par les formateurs. Les risques doivent etre anticipes des la conception et l’execution des seances de simulation. Conclusion : la gestion des etudiants en detresse psychologique doit-etre mieux abordee en formation de formateur AFGSU.

Background As part of the USDA-Department of Health and Human Services Pregnancy and Birth to 24 Months Project, we conducted systematic reviews (SRs) on topics important for health and nutrition of young children. Objectives The purpose of the present SR was to examine the relation between caregiver feeding practices in children from birth to 24 mo and child weight gain, size, and body composition. Methods A search of articles published from January 1980 to January 2017 in 4 databases identified 8739 references. Nutrition Evidence Systematic Review (NESR) analysts used the Nutrition Evidence Library Risk of Bias Assessment Tool to assess potential bias in the studies, and a Technical Expert Collaborative graded the body of evidence using the NESR grading rubric. Results Twenty-seven articles were included in this review (8 controlled trials, 19 longitudinal cohort studies). Moderate evidence from randomized controlled trials suggests that providing responsive feeding guidance to teach mothers to recognize and respond appropriately to children's hunger and satiety cues can lead to "normal" weight gain and/or "normal" weight status in children aged ≤2 y compared with children whose mothers did not receive responsive feeding guidance. Moderate evidence from longitudinal cohort studies indicates an association between maternal feeding practices and the child's weight status and/or weight gain, but the direction of effect has not been adequately studied. Restrictive feeding practices are associated with increased weight gain and higher weight status, and pressuring feeding practices are associated with decreased weight gain and lower weight status. Evidence suggests that a mother's feeding practices are related to concerns about her child's body weight. Conclusions This review highlights the importance of the interaction between caregivers and infants and toddlers related to child feeding practices on children's weight outcomes. Research is needed on more diverse populations with consistent methodological app-roaches and objective measures.

Background Maternal diet during pregnancy and lactation may provide the earliest opportunity to positively influence child food acceptance. Objective Systematic reviews were completed to examine the relation among maternal diet during pregnancy and lactation, amniotic fluid flavor, breast-milk flavor, and children's food acceptability and overall dietary intake. Design A literature search was conducted in 10 databases (e.g., PubMed, Embase, Cochrane, and CINAHL) to identify articles published from January 1980 to June 2017. Data from each included study were extracted, risk of bias assessed, evidence synthesized qualitatively, conclusion statements developed, and strength of the evidence graded. Results Eleven and 15 articles met a priori criteria for inclusion to answer questions related to maternal diet during pregnancy and lactation, respectively. Conclusions Limited but consistent evidence indicates that flavors (alcohol, anise, carrot, garlic) originating from the maternal diet during pregnancy can transfer to and flavor amniotic fluid, and fetal flavor exposure increases acceptance of similarly flavored foods when re-exposed during infancy and potentially childhood. Moderate evidence indicates that flavors originating from the maternal diet during lactation (alcohol, anise/caraway, carrot, eucalyptus, garlic, mint) transmit to and flavor breast milk in a time-dependent manner. Moderate evidence indicates that infants can detect diet-transmitted flavors in breast milk within hours of a single maternal ingestion (alcohol, garlic, vanilla, carrot), within days after repeated maternal ingestion (garlic, carrot juice), and within 1-4 mo postpartum after repeated maternal ingestion (variety of vegetables including carrot) during lactation. Findings may not generalize to all foods and beverages. Conclusions cannot be drawn to describe the relationship between mothers' diet during either pregnancy or lactation and children's overall dietary intake.

The USDA's Nutrition Evidence Systematic Review (NESR) team specializes in conducting systematic reviews (SRs) to inform federal nutrition policy and programs. The NESR's dedicated staff collaborate with leading scientists to answer important food- and nutrition-related public health questions by objectively reviewing, evaluating, and synthesizing research using state-of-the-art methodology. NESR uses a rigorous, protocol-driven methodology that is designed to minimize bias; to ensure availability of SRs that are relevant, timely, and high quality; and to ensure transparency and reproducibility of findings. This article describes the methods used by NESR to conduct a series of SRs on diet and health in infants, toddlers, and women who are pregnant as part of the Pregnancy and Birth to 24 Months Project.

International audience; Small-angle X-ray scattering (SAXS) experiments are important in structural biology because they are solution methods, and do not require crystallization of protein complexes. Structure determination from SAXS data, however, poses some difficulties. Computation of a SAXS profile from a protein model is expensive in CPU time. Hence, rather than directly refining against the data, most computational methods generate a large number of conformers and then filter the structures based on how well they satisfy the SAXS data. To address this issue in an efficient manner, we propose here a Bayesian model for SAXS data and use it to directly drive a Monte Carlo simulation. We show that the automatic weighting of SAXS data is the key to finding optimal structures efficiently. Another key problem with obtaining structures from SAXS data is that proteins are often flexible and the data represents an average over a structural ensemble. To address this issue, we first characterize the stability of the best model with extensive molecular dynamics simulations. We analyse the resulting trajectories further to characterize a dynamic structural ensemble satisfying the SAXS data. The combination of methods is applied to a tandem of domains from the protein PTPN4, which are connected by an unstructured linker. We show that the SAXS data contain information that supports and extends other experimental findings. We also show that the conformation obtained by the Bayesian analysis is stable, but that a minor conformation is present. We propose a mechanism in which the linker may maintain PTPN4 in an inhibited enzymatic state.

The formation and recovery of gaps in the vascular endothelium governs a wide range of physiological and pathological phenomena, from angiogenesis to atherosclerosis and tumor cell extravasation. However, the interplay between the mechanical and signaling processes that drive dynamic behavior in vascular endothelial cells is not well understood. In this study, we propose a chemo-mechanical model to investigate the maintenance of endothelial junctions as dependent on the crosstalk between actomyosin contractility, VE-cadherin bond turnover, and actin polymerization, which mediate the forces exerted on the cell-cell interface. Our theoretical model reveals that active cell tension can stabilize cadherin bonds within an adhesion, but excessive RhoA signaling can drive bond dissociation and junction failure. While Rac1-mediated actin polymerization aids gap closure, high levels of Rac1 may also facilitate junction weakening. Combining the modeling framework with novel experiments, we identify how dynamic rupture and heal cycles emerge and, further, describe why gaps tend to localize at multi-cell contacts. Beyond, our analysis also indicates that a critical balance between RhoA and Rac1 expression is required to maintain junction stability and limit endothelial dysfunction. The model predicts how pharmacological modulation of actin polymerization and cell contractility impacts junction stability, with predictions subsequently validated experimentally. Our proposed framework can help guide the development of therapeutics that target the Rho family of GTPases and downstream active mechanical processes.

Sewage overflows in headwater catchments are critical, mostly not well monitored point sources for many pollutants such as oxygen depleting substances, pharmaceuticals or heavy metals. The outlets are often located at places where no connection to the power grid is available, hence it is often necessary to provide deployed sensors or sampling devices with mobile power sources like car-batteries. In addition, autosamplers or on-line sensors are expensive devices. For these reasons, a proper monitoring strategy, including water quality parameters in these structures is often complicated to implement and from an economical point of view not reasonable. Therefore, we combined two low-budget DIY devices, a modified Zurich sequential sampler for time-discrete rainfall samples and Stream Temperature, Intermittency, and Conductivity loggers (STIC), to build a low-budget monitoring system being able to take time-discrete samples from sewage overflow. Our modified sampler collects 12 samples in a row, with variable volumes from 0.25 to 0.5 L. In each bottle a STIC was implemented. The STICs start to measure a conductivity higher than zero as soon as water starts to flow into the bottle. This allows for a clear assignment between sample and time. We called this sampler the Sewage Overflow Monitoring Sampler (SOMS).Though the probe volume and the time period for sampling is strongly limited, concentration variations, including peak concentrations, in sewage overflows are expected to be measured right at the beginning of an event (first flush) and should be therefore covered by the sampler. First laboratory tests were successful. In the next step the monitoring system will be implemented on a field side.Depending on the scientific question of the study, the SOMS can be complemented in the field by either another STIC logger or a pressure probe. The STIC logger is located at the bottom of the canal. This allows the detection of the duration of the overflow event. By installing a pressure probe the discharge can be approximated as long as gradient and the geometry of the canal is known.

Background There are a lack of disease‐modifying treatments for peanut allergy, which is lifelong in most instances. Oral immunotherapy has remained at the forefront of prospective treatments, though its efficacy is consistently undermined by the risk of adverse reactions and meager sustained effects. Aim This review discusses the current state of oral immunotherapy, its strengths and limitations, and the future of therapeutics for the treatment of peanut allergy. Conclusion The persistence of peanut allergy is currently attributed to reservoirs of peanut‐specific memory B cells and Th2 cells, though the cellular and molecular interplay that facilitates the replenishment of peanut‐specific IgE remains elusive. Uncovering these events will prove critical for identification of novel targets as we forge ahead to a new age of peanut allergy treatment with biotherapeutics.

International audience; H

Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4+ and CD8+ T cells. LDRT elicited predominantly CD4+ cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4+ cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell–infiltrated tumors.Significance:Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4+ effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors.This article is highlighted in the In This Issue feature, p. 1

International audience

Conflicts between RNA Polymerase II transcription and DNA replication are associated with increased DNA damage and genome instability. Nevertheless, how exactly transcription can affect replication progression through genes is not known. Performing a genome-wide analysis of transcription and replication together we found that transcription increases the velocity of replication across long transcribed genes, because transcription reduces chromatin density along long genes. Conversely, transcription progression dictates where replication forks pause and stall in short highly transcribed genes. Sites of replication forks stalling/pausing are associated with increased DNA damage levels, representing bonafide transcription-replication collisions sites. Importantly, these sites overlap with breakpoints of rearrangements identified in cancers. Such rearrangements involving transcription-replication collisions sites can be induced in vitro following treatment with ATM and ATR inhibitors. Altogether, our findings highlight two opposing effects of transcription on replication progression, with positive and negative consequences for replication fork progression and genome instability.

Background IgE production against innocuous food antigens can result in anaphylaxis, a severe life-threatening consequence of allergic reactions. The maintenance of IgE immunity is primarily facilitated by IgG+ memory B cells, as IgE+ memory B cells and IgE+ plasma cells are extremely scarce and short-lived, respectively. Objective Our aim was to investigate the critical requirements for an IgE recall response in peanut allergy. Methods We used a novel human PBMC culture platform, a mouse model of peanut allergy, and various experimental readouts to assess the IgE recall response in the presence and absence of IL-4Rα blockade. Results In human PBMCs, we have demonstrated that blockade of IL-4/IL-13 signaling aborted IgE production after activation of a recall response and skewed the cytokine response away from a dominant type 2 signature. TH2A cells, identified by single-cell RNA sequencing, expanded with peanut stimulation and maintained their pathogenic phenotype in spite of IL-4Rα blockade. In mice with allergy, anti–IL-4Rα provided long-lasting suppression of the IgE recall response beyond antibody treatment and fully protected against anaphylaxis. Conclusion The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.