Patterns of Duality in N=1 SUSY Gauge Theories

We study the patterns in the duality of a wide class of N=1 supersymmetric gauge theories in four dimensions. We present many new generalizations of the classic duality models of Kutasov and Schwimmer, which have themselves been generalized numerous times in works of Intriligator, Leigh and the present authors. All of these models contain one or two fields in a two-index tensor representation, along with fields in the defining representation. The superpotential for the two-index tensor(s) resembles A_k or D_k singularity forms, generalized from numbers to matrices. Looking at the ensemble of these models, classifying them by superpotential, gauge group, and ``level'' -- for terminology we appeal to the architecture of a typical European-style theatre -- we identify emerging patterns and note numerous interesting puzzles.Comment: 34 pages, 4 figures, uses harvmac and table

Deconfinement transition and string tensions in SU(4) Yang-Mills Theory

We present results from numerical lattice calculations of SU(4) Yang-Mills theory. This work has two goals: to determine the order of the finite temperature deconfinement transition on an $N_t = 6$ lattice and to study the string tensions between static charges in the irreducible representations of SU(4). Motivated by Pisarski and Tytgat's argument that a second-order SU($\infty$) deconfinement transition would explain some features of the SU(3) and QCD transitions, we confirm older results on a coarser, $N_t = 4$, lattice. We see a clear two-phase coexistence signal, characteristic of a first-order transition, at $8/g^2 = 10.79$ on a $6\times 20^3$ lattice, on which we also compute a latent heat of $\Delta\epsilon\approx 0.6 \epsilon_{SB}$. Computing Polyakov loop correlation functions we calculate the string tension at finite temperature in the confined phase between fundamental charges, $\sigma_1$, between diquark charges, $\sigma_2$, and between adjoint charges $\sigma_4$. We find that $1 < \sigma_2/\sigma_1 < 2$, and our result for the adjoint string tension $\sigma_4$ is consistent with string breaking.Comment: 10 pages with included figures. For version 2: New calculation and discussion of latent heat added; 2 new figures and 1 new table. Typo in abstract corrected for v3. To appear in Physical Review

The Saturn Ring Skimmer Mission Concept: The next step to explore Saturn's rings, atmosphere, interior, and inner magnetosphere

The innovative Saturn Ring Skimmer mission concept enables a wide range of investigations that address fundamental questions about Saturn and its rings, as well as giant planets and astrophysical disk systems in general. This mission would provide new insights into the dynamical processes that operate in astrophysical disk systems by observing individual particles in Saturn's rings for the first time. The Ring Skimmer would also constrain the origin, history, and fate of Saturn's rings by determining their compositional evolution and material transport rates. In addition, the Ring Skimmer would reveal how the rings, magnetosphere, and planet operate as an inter-connected system by making direct measurements of the ring's atmosphere, Saturn's inner magnetosphere and the material owing from the rings into the planet. At the same time, this mission would clarify the dynamical processes operating in the planet's visible atmosphere and deep interior by making extensive high-resolution observations of cloud features and repeated measurements of the planet's extremely dynamic gravitational field. Given the scientific potential of this basic mission concept, we advocate that it be studied in depth as a potential option for the New Frontiers program.Comment: White paper submitted to the Planetary Science and Astrobiology Decadal Survey (submission #420

The Saturn Ring Skimmer Mission Concept: The next step to explore Saturn's rings, atmosphere, interior and inner magnetosphere

The innovative Saturn Ring Skimmer mission concept enables a wide range of investigations that address fundamental questions about Saturn and its rings, as well as giant planets and astrophysical disk systems in general. This mission would provide new insights into the dynamical processes that operate in astrophysical disk systems by observing individual particles in Saturn's rings for the first time. The Ring Skimmer would also constrain the origin, history, and fate of Saturn's rings by determining their compositional evolution and material transport rates. In addition, the Ring Skimmer would reveal how the rings, magnetosphere, and planet operate as an inter-connected system by making direct measurements of the ring's atmosphere, Saturn's inner magnetosphere and the material owing from the rings into the planet. At the same time, this mission would clarify the dynamical processes operating in the planet's visible atmosphere and deep interior by making extensive high-resolution observations of cloud features and repeated measurements of the planet's extremely dynamic gravitational field. Given the scientific potential of this basic mission concept, we advocate that it be studied in depth as a potential option for the New Frontiers program

Incidence of nonvalvular atrial fibrillation and oral anticoagulant prescribing in England, 2009 to 2019: A cohort study.

BACKGROUND: Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, and AF incidence is expected to increase. Guidelines recommend using oral anticoagulants (OACs) to prevent the development of stroke. However, studies have reported the frequent underuse of OACs in AF patients. The objective of this study is to describe nonvalvular atrial fibrillation (NVAF) incidence in England and assess the clinical and socioeconomic factors associated with the underprescribing of OACs. METHODS AND FINDINGS: We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) database to identify patients with NVAF aged ≥18 years and registered in English general practices between 2009 and 2019. Annual incidence rate of NVAF by age, deprivation quintile, and region was estimated. OAC prescribing status was explored for patients at risk for stroke and classified into the following: OAC, aspirin only, or no treatment. We used a multivariable multinomial logistic regression model to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) of the factors associated with OAC or aspirin-only prescribing compared to no treatment in patients with NVAF who are recommended to take OAC. The multivariable regression was adjusted for age, sex, comorbidities, socioeconomic status, baseline treatment, frailty, bleeding risk factors, and takes into account clustering by general practice. Between 2009 and 2019, 12,517,191 patients met the criteria for being at risk of developing NVAF. After a median follow-up of 4.6 years, 192,265 patients had an incident NVAF contributing a total of 647,876 person-years (PYR) of follow-up. The overall age-adjusted incidence of NVAF per 10,000 PYR increased from 20.8 (95% CI: 20.4; 21.1) in 2009 to 25.5 (25.1; 25.9) in 2019. Higher incidence rates were observed for older ages and males. Among NVAF patients eligible for anticoagulation, OAC prescribing rose from 59.8% (95% CI: 59.0; 60.6) in 2009 to 83.2% (95% CI: 83.0; 83.4) in 2019. Several conditions were associated with lower risk of OAC prescribing: dementia [RRR 0.52 (0.47; 0.59)], liver disease 0.58 (0.50; 0.67), malignancy 0.74 (0.72; 0.77), and history of falls 0.82 (0.78; 0.85). Compared to white ethnicity, patients from black and other ethnic minorities were less likely to receive OAC; 0.78 (0.65; 0.94) and 0.76 (0.64; 0.91), respectively. Patients living in the most deprived areas were less likely to receive OAC 0.85 (0.79; 0.91) than patients living in the least deprived areas. Practices located in the East of England were associated with higher risk of prescribing aspirin only over no treatment than practices in London (RRR 1.22; 95% CI 1.02 to 1.45). The main limitation of this study is that these findings depends on accurate recording of conditions by health professionals and the inevitable residual confounding due to lack of data on certain factors that could be associated with under-prescribing of OACs. CONCLUSIONS: The incidence of NVAF increased between 2009 and 2015, before plateauing. Underprescribing of OACs in NVAF is associated with a range of comorbidities, ethnicity, and socioeconomic factors, demonstrating the need for initiatives to reduce inequalities in the care for AF patients

SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease

Mitochondrial acyl-coenzyme A species are emerging as important sources of protein modification and damage. Succinyl-CoA ligase (SCL) deficiency causes a mitochondrial encephalomyopathy of unknown pathomechanism. Here, we show that succinyl-CoA accumulates in cells derived from patients with recessive mutations in the tricarboxylic acid cycle (TCA) gene succinyl-CoA ligase subunit-beta (SUCLA2), causing global protein hyper-succinylation. Using mass spectrometry, we quantify nearly 1,000 protein succinylation sites on 366 proteins from patient-derived fibroblasts and myotubes. Interestingly, hyper-succinylated proteins are distributed across cellular compartments, and many are known targets of the (NAD(+))-dependent desuccinylase SIRT5. To test the contribution of hyper-succinylation to disease progression, we develop a zebrafish model of the SCL deficiency and find that SIRT5 gain-of-function reduces global protein succinylation and improves survival. Thus, increased succinyl-CoA levels contribute to the pathology of SCL deficiency through post-translational modifications. The pathomechanism of succinyl-CoA ligase (SCL) deficiency, a hereditary mitochondrial disease, is not fully understood. Here, the authors show that increased succinyl-CoA levels contribute to SCL pathology by causing global protein hyper-succinylation.Peer reviewe

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

Sex-Biased Expression of MicroRNAs in Schistosoma mansoni

Schistosomiasis is an important neglected tropical disease caused by digenean helminth parasites of the genus Schistosoma. Schistosomes are unusual in that they are dioecious and the adult worms live in the blood system. MicroRNAs play crucial roles during gene regulation and are likely to be important in sex differentiation in dioecious species. Here we characterize 112 microRNAs from adult Schistosoma mansoni individuals, including 84 novel microRNA families, and investigate the expression pattern in different sexes. By deep sequencing, we measured the relative expression levels of conserved and newly identified microRNAs between male and female samples. We observed that 13 microRNAs exhibited sex-biased expression, 10 of which are more abundant in females than in males. Sex chromosomes showed a paucity of female-biased genes, as predicted by theoretical evolutionary models. We propose that the recent emergence of separate sexes in Schistosoma had an effect on the chromosomal distribution and evolution of microRNAs, and that microRNAs are likely to participate in the sex differentiation/maintenance process