ALMA-IMF VIII -- Combination of Interferometric Continuum Images with Single-Dish Surveys and Structural Analysis of Six Protoclusters

We present the combination of ALMA-IMF and single-dish continuum images from the Mustang-2 Galactic Plane Survey (MGPS90) at 3 millimeters and the Bolocam Galactic Plane Survey (BGPS) at 1 millimeter. Six and ten out of the fiffteen ALMA-IMF fields are combined with MGPS90 and BGPS, respectively. The combination is made via the feathering technique. We used the dendrogram algorithm throughout the combined images, and performed further analysis in the six fields with combination in both bands (G012.80, W43-MM1, W43-MM2, W43-MM3, W51-E, W51-IRS2). In these fields, we calculated spectral index maps and used them to separate regions dominated by dust or free-free emission, and then performed further structural analysis. We report the basic physical parameters of the dust-dominated (column densities, masses) and ionized (emission measures, hydrogen ionization photon rates) structures. We also searched for multi-scale relations in the dust-dominated structures across the analyzed fields, finding that the fraction of mass in dendrogram leaves (which we label as "Leaf Mass Eficiency", LME) as a function of molecular gas column density follows a similar trend: a rapid, exponential-like growth, with maximum values approaching 100% in most cases. The observed behaviour of the LME with gas column is tentatively interpreted as an indicator of large star formation activity within the ALMA-IMF protoclusters. W51-E and G012.80 stand out as cases with comparatively large and reduced potential for further star formation, respectively.Comment: Accepted to The Astrophysical Journal Supplemen

In Vivo Islet Protection by a Nuclear Import Inhibitor in a Mouse Model of Type 1 Diabetes

Insulin-dependent Type 1 diabetes (T1D) is a devastating autoimmune disease that destroys beta cells within the pancreatic islets and afflicts over 10 million people worldwide. These patients face life-long risks for blindness, cardiovascular and renal diseases, and complications of insulin treatment. New therapies that protect islets from autoimmune destruction and allow continuing insulin production are needed. Increasing evidence regarding the pathomechanism of T1D indicates that islets are destroyed by the relentless attack by autoreactive immune cells evolving from an aberrant action of the innate, in addition to adaptive, immune system that produces islet-toxic cytokines, chemokines, and other effectors of islet inflammation. We tested the hypothesis that targeting nuclear import of stress-responsive transcription factors evoked by agonist-stimulated innate and adaptive immunity receptors would protect islets from autoimmune destruction.Here we show that a first-in-class inhibitor of nuclear import, cSN50 peptide, affords in vivo islet protection following a 2-day course of intense treatment in NOD mice, which resulted in a diabetes-free state for one year without apparent toxicity. This nuclear import inhibitor precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from autoimmune diabetes-prone, non-obese diabetic (NOD) mice that develop T1D. Moreover, in this widely used model of human T1D we noted attenuation of pro-inflammatory cytokine and chemokine production in immune cells.These results indicate that a novel form of immunotherapy that targets nuclear import can arrest inflammation-driven destruction of insulin-producing beta cells at the site of autoimmune attack within pancreatic islets during the progression of T1D

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Drop formation in shear-thickening granular suspensions

We study droplet formation in granular suspensions by systematically varying the volume fractions (ϕ) and particle diameters (d). For suspensions with water as the suspending liquid, we find three different regimes. For dilute suspensions (ϕ ≤ 45%), drop formation follows the predictions for inertial breakup and exhibits identical dynamics to that of pure water. The breakup is strongly asymmetrical in this case. Only for more concentrated suspensions (ϕ > 45%) does the presence of particles change the dynamics and two other regimes, a symmetrical inertial regime and a Bagnoldian regime, are uncovered. We construct and discuss a phase diagram that allows us to understand and predict the breakup behavior in granular suspensions.Initiative d'excellence de l'Université de Bordeau

Drop formation in shear-thickening granular suspensions

We study droplet formation in granular suspensions by systematically varying the volume fractions (ϕ) and particle diameters (d). For suspensions with water as the suspending liquid, we find three different regimes. For dilute suspensions (ϕ ≤ 45%), drop formation follows the predictions for inertial breakup and exhibits identical dynamics to that of pure water. The breakup is strongly asymmetrical in this case. Only for more concentrated suspensions (ϕ > 45%) does the presence of particles change the dynamics and two other regimes, a symmetrical inertial regime and a Bagnoldian regime, are uncovered. We construct and discuss a phase diagram that allows us to understand and predict the breakup behavior in granular suspensions.Initiative d'excellence de l'Université de Bordeau

Nonuniversality in the Pinch-Off of Yield Stress Fluids: Role of Nonlocal Rheology

The pinch-off behavior of yield stress fluids is investigated using droplet and liquid-bridge breakup experiments. Contrary to expectations, the neck thinning behavior depends strongly on the way the breakup experiment is carried out. This nonuniversal behavior can be explained through an analysis of the thinning dynamics as well as the shapes of the fluid necks. Recent nonlocal models for the rheology of yield stress fluids are found to be compatible with the results presented

Establishing a national research software award

Software development has become an integral part of the scholarly ecosystem, spanning all fields and disciplines. To support the sharing and creation of knowledge in line with open science principles, and particularly to enable the reproducibility of research results, it is crucial to make the source code of research software available, allowing for modification, reuse, and distribution.Recognizing the significance of open-source software contributions in academia, the second French Plan for Open Science, announced by the Minister of Higher Education and Research in 2021, introduced a National Award to promote open-source research software. This award serves multiple objectives: firstly, to highlight the software projects and teams that have devoted time and effort to develop outstanding research software, sometimes for decades, and often with little recognition; secondly, to draw attention to the importance of software as a valuable research output and to inspire new generations of researchers to follow and learn from these examples.We present here an in-depth analysis of the design and implementation of this unique initiative. As a national award established explicitly to foster Open Science practices by the French Minister of Research, it faced the intricate challenge of fairly evaluating open research software across all fields, striving for inclusivity across domains, applications, and participants. We provide a comprehensive report on the results of the first edition, which received 129 high-quality submissions. Additionally, we emphasize the impact of this initiative on the open science landscape, promoting software as a valuable research outcome, on par with publications