Imaging and writing magnetic domains in the non-collinear antiferromagnet Mn3Sn

Non-collinear antiferromagnets are revealing many unexpected phenomena and they became crucial for the field of antiferromagnetic spintronics. To visualize and prepare a well-defined domain structure is of key importance. The spatial magnetic contrast, however, remains extraordinarily difficult to be observed experimentally. Here, we demonstrate a magnetic imaging technique based on a laser induced local thermal gradient combined with detection of the anomalous Nernst effect. We employ this method in one the most actively studied representatives of this class of materials—Mn3Sn. We demonstrate that the observed contrast is of magnetic origin. We further show an algorithm to prepare a well-defined domain pattern at room temperature based on heat assisted recording principle. Our study opens up a prospect to study spintronics phenomena in non-collinear antiferromagnets with spatial resolution

Dynamic Profiling of β-Coronavirus 3CL Mpro Protease Ligand-Binding Sites

β-coronavirus (CoVs) alone has been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a backup against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensable role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide a comprehensive comparison of all nonredundant ligand-binding sites available for SARS-CoV2, SARS-CoV, and MERS-CoV Mpro. Extensive adaptive sampling has been used to investigate structural conservation of ligand-binding sites using Markov state models (MSMs) and compare conformational dynamics employing convolutional variational auto-encoder-based deep learning. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-CoV homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Grey Wolf Optimizer Algorithm for Multi-Objective Optimal Power Flow

This article introduces the Grey Wolf Optimizer (GWO) algorithm, a novel method aimed at tackling the challenges posed by the multi-objective Optimal Power Flow (OPF) problem. Drawing inspiration from the foraging behavior of grey wolves, GWO stands apart from traditional approaches by enhancing initial solutions without relying on gradient data collection from the objective function. In the domain of power system optimization, the OPF problem is widely acknowledged, involving constraints related to generator parameters, valve-point loading, reactive power, and active power. The proposed GWO technique is applied to IEEE 14-bus and 30-bus power systems, targeting four case objectives: minimizing cost with quadratic cost function, minimizing cost with inclusion of valve point, minimizing power loss, and minimizing both cost and losses simultaneously. For the IEEE-14 bus system, which requires meeting a power demand of 259 MW, GWO yields optimal costs of 827.0056 $/hr, 833.4691$/hr, 1083.2410 $/hr, and 852.2255$/hr across the four cases. Similarly, for the IEEE-30 bus system aiming to satisfy a demand of 283.4 MW, GWO achieves optimal costs of 801.8623 $/hr, 825.9321$/hr, 1028.6309 $/hr, and 850.4794$/hr for the respective cases. These optimal results are then compared with existing research outcomes, highlighting the efficiency and cost-effectiveness of the GWO algorithm when juxtaposed with alternative methods for solving the OPF problem

Imaging and writing magnetic domains in the non-collinear antiferromagnet Mn₃Sn

Non-collinear antiferromagnets are revealing many unexpected phenomena and they became crucial for the field of antiferromagnetic spintronics. To visualize and prepare a well-defined domain structure is of key importance. The spatial magnetic contrast, however, remains extraordinarily difficult to be observed experimentally. Here, we demonstrate a magnetic imaging technique based on a laser induced local thermal gradient combined with detection of the anomalous Nernst effect. We employ this method in one the most actively studied representatives of this class of materials-Mn3Sn. We demonstrate that the observed contrast is of magnetic origin. We further show an algorithm to prepare a well-defined domain pattern at room temperature based on heat assisted recording principle. Our study opens up a prospect to study spintronics phenomena in non-collinear antiferromagnets with spatial resolution.publishe

Structural dynamics of the β-coronavirus M^pro protease ligand binding sites

This article is a preprint and has not been certified by peer review. It was eventually published online on 14 June 2021 by American Chemical Society (ACS Publications) as: Cho, E. et al. (2021) 'Dynamic Profiling of β-Coronavirus 3CL Mpro Protease Ligand-Binding Sites', Journal of Chemical Information and Modeling, 61 (6), pp. 3058 - 3073. doi: 10.1021/acs.jcim.1c00449.Data Availability Statement: The trajectories of Mpro simulations and models of the metastable states can be obtained from the corresponding author. Jupyter-notebooks to generate Markov State Models can be downloaded from 10.6084/m9.figshare.14343725bioRxiv posts many COVID19-related papers. A reminder: they have not been formally peer-reviewed and should not guide health-related behavior or be reported in the press as conclusive.β-coronaviruses alone have been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a back-up against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensible role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide a comprehensive comparison of all non-redundant ligand-binding sites available for SARS-CoV2, SARS-CoV and MERS-CoV Mpro. Extensive adaptive sampling has been used to explore conformational dynamics employing convolutional variational auto encoder-based deep learning, and investigates structural conservation of the ligand binding sites using Markov state models across β-coronavirus homologs. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-coronavirus homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor.U.S. Department of Energy, Office of Science, through the Advanced Scientific Computing Research (ASCR), under contract number DEAC05-00OR22725 and the Exascale Computing Project (ECP) (17-SC-20-SC). BI would like to acknowledge the COVID-19 pump-priming grant from the University of Huddersfield for funding computing resources for analysis

Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.Yale-NIH Center for Mendelian GenomicsNational Institutes of Health (NIH)American Heart AssociationHoward Hughes Institut