Intracellular Serotonin Modulates Insulin Secretion from Pancreatic β-Cells by Protein Serotonylation

Non-neuronal, peripheral serotonin deficiency causes diabetes mellitus and identifies an intracellular role for serotonin in the regulation of insulin secretion

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Modeling Computational Limitations in H-Phy and Overlay-NoC Architectures

High performance computing demands constant growth in computational power and services that can be offered by modern supercomputers. It requires technological and designing advances in the multiprocessor internal structures as well as novel computing models considering the very high computing demands. One of the increasingly important requirements of computing platforms is a functionality that allows efficient managing computational resources, i.e., monitor them, restrict an access to some part of the resources, account for computational service, or ensure reliability and quality of service when some resources are broken or disabled. In this paper, we present a new model describing computational limitations for processing tasks on multiprocessor systems. The model is implemented in Hardware-Physical (H-Phy) and Overlay-Network-on-Chip (Overlay-NoC) architectures. Both architectures and the model are described and analyzed. Experimentation system is also presented, together with simulation assumptions, results of research and their study. The paper provides complete models of H-Phy and Overlay-NoC structures with an ability to restrict processing resources

Migration, development and inequality: Eastern Punjabi transnationalism

Drawing on original, ethnographic research in India and the UK, in this article we discuss the impact of transnational activity on the Doaba region of East Punjab, India. We argue that some recent studies have underplayed some of the less progressive consequences of Indian transnationalism. In particular, we contend that they have underestimated the extent of division between transnational migrants and Indian non-migrants and downplayed the relationship between transnationalism and caste inequality. This empirical study of transnationalism, when placed in the context of the dynamic caste relations of East Punjab, supports those who contend that access to international migration is becoming an increasingly significant component of contemporary global social stratification, with the ‘broad’ transnational processes of capitalist globalization driving the ‘narrow’ transnationalism studied here. In this article, we question any straightforwardly progressive relationship between transnationalism and ‘development’ within East Punjab, and suggest that the arguments presented have a resonance beyond northwest India