B-L Cosmic Strings in Heterotic Standard Models

E_{8} X E_{8} heterotic string and M-theory, when compactified on smooth Calabi-Yau manifolds with SU(4) vector bundles, can give rise to softly broken N=1 supersymmetric theories with the exact matter spectrum of the MSSM, including three right-handed neutrinos and one Higgs-Higgs conjugate pair of supermultiplets. These vacua have the SU(3)_{C} X SU(2)_{L} X U(1)_{Y} gauge group of the standard model augmented by an additional gauged U(1)_{B-L}. Their minimal content requires that the B-L symmetry be spontaneously broken by a vacuum expectation value of at least one right-handed sneutrino. The soft supersymmetry breaking operators can induce radiative breaking of the B-L gauge symmetry with an acceptable B-L/electroweak hierarchy. In this paper, it is shown that U(1)_{B-L} cosmic strings occur in this context, potentially with both bosonic and fermionic superconductivity. We present a numerical analysis that demonstrates that boson condensates can, in principle, form for theories of this type. However, the weak Yukawa and gauge couplings of the right-handed sneutrino suggests that bosonic superconductivity will not occur in the simplest vacua in this context. The electroweak phase transition also disallows fermion superconductivity, although substantial bound state fermion currents can exist.Comment: 41 pages, 5 figure

Introduction: Rethinking the Impact of the Inter-American Human Rights System

This chapter introduces the central themes of the book and argues that the Inter-American Human Rights System (IAHRS) is activated by political actors and institutions in ways that transcend traditional compliance perspectives and that have the potential to meaningfully alter politics and provoke positive domestic human rights change. The chapter identifies key gaps in existing human rights scholarship, particularly in relation to the IAHRS, and outlines three core perspectives on the System’s impact on human rights. It offers a synthesis of the key findings of the volume, and provides reflections on the future prospects of the System by locating it in its broader global context

Low diversity Cryptococcus neoformans variety grubii multilocus sequence types from Thailand are consistent with an ancestral African origin.

Published versio

Equivalence and noninferiority trials – are they viable alternatives for registration of new drugs? (III)

The scientific community's reliance on active-controlled trials is steadily increasing, as widespread agreement emerges concerning the role of these trials as viable alternatives to placebo trials. These trials present substantial challenges with regard to design and interpretation as their complexity increases, and the potential need for larger sample sizes impacts the cost and time variables of the drug development process. The potential efficacy and safety benefits derived from these trials may never be demonstrated by other methods. Active-controlled trials can develop valuable data to inform both prescribers and patients about the dose- and time-dependent actions of any new drug and can contribute to the management and communication of risks associated with the relevant therapeutic products

The Mating Type Locus (MAT) and Sexual Reproduction of Cryptococcus heveanensis: Insights into the Evolution of Sex and Sex-Determining Chromosomal Regions in Fungi

Mating in basidiomycetous fungi is often controlled by two unlinked, multiallelic loci encoding homeodomain transcription factors or pheromones/pheromone receptors. In contrast to this tetrapolar organization, Cryptococcus neoformans/Cryptococcus gattii have a bipolar mating system, and a single biallelic locus governs sexual reproduction. The C. neoformans MAT locus is unusually large (>100 kb), contains >20 genes, and enhances virulence. Previous comparative genomic studies provided insights into how this unusual MAT locus might have evolved involving gene acquisitions into two unlinked loci and fusion into one contiguous locus, converting an ancestral tetrapolar system to a bipolar one. Here we tested this model by studying Cryptococcus heveanensis, a sister species to the pathogenic Cryptococcus species complex. An extant sexual cycle was discovered; co-incubating fertile isolates results in the teleomorph (Kwoniella heveanensis) with dikaryotic hyphae, clamp connections, septate basidia, and basidiospores. To characterize the C. heveanensis MAT locus, a fosmid library was screened with C. neoformans/C. gattii MAT genes. Positive fosmids were sequenced and assembled to generate two large probably unlinked MAT gene clusters: one corresponding to the homeodomain locus and the other to the pheromone/receptor locus. Strikingly, two divergent homeodomain genes (SXI1, SXI2) are present, similar to the bE/bW Ustilago maydis paradigm, suggesting one or the other homeodomain gene was recently lost in C. neoformans/C. gattii. Sequencing MAT genes from other C. heveanensis isolates revealed a multiallelic homeodomain locus and at least a biallelic pheromone/receptor locus, similar to known tetrapolar species. Taken together, these studies reveal an extant C. heveanensis sexual cycle, define the structure of its MAT locus consistent with tetrapolar mating, and support the proposed evolutionary model for the bipolar Cryptococcus MAT locus revealing transitions in sexuality concomitant with emergence of a pathogenic clade. These studies provide insight into convergent processes that independently punctuated evolution of sex-determining loci and sex chromosomes in fungi, plants, and animals

Changes in the variability and periodicity of precipitation in Scotland

This paper analyses the temporal and spatial changes in the amount and variability of rainfall in Scotland. The sequential Mann–Kendall test reveals that total annual precipitation has increased across Scotland since the 1970s with increasing trends in variability beginning between the mid-1960s and the mid-1970s. Whilst temporally consistent increasing trends in precipitation totals prevail in the West, many weather stations in the East have experienced subsequent trend turning points in the following two decades, explaining the larger magnitude of the trends in western Scotland in recent decades. Trend analyses on six measures of rainfall variability indicate an increase in rainfall variability during the period 1961–2000, as measured by the intra-annual variance, the winter to summer precipitation ratio and the annual cumulative sum range, with decreasing trends observed in the number of dry days. Periodicities associated with the North Atlantic Oscillation and the Atlantic Multidecadal Oscillation could explain the observed temporal variability of rainfall

Racial/Ethnic Disparities in Exercise and Dietary Behaviors of Middle-Aged and Older Adults

BackgroundDifferences in health behaviors may be important contributors to racial/ethnic disparities in the health status of adults. Studies to date have not compared whether there are health behavior differences in exercise and dietary behaviors among middle-age and older adults in the four largest racial/ethnic categories.ObjectiveTo investigate racial/ethnic differences in exercise and dietary behaviors of middle-aged and older adults.DesignWe used data from the 2007 California Health Interview Survey. Multivariable logistic regression was used to examine interactions between age and race/ethnicity in predicting two categories of health behaviors. Analyses were conducted adjusting for sociodemographic characteristics, health insurance status, and healthcare utilization.ParticipantsA population-based sample of 33,189 California adults 45 years old and older: 26,522 non-Hispanic whites, 1,686 African American/blacks, 2,565 Asian/Pacific Islanders (1,741 English-proficient; 824 limited English-proficient), and 2,416 Latinos (1,538 English-proficient; 878 limited English-proficient).Main measuresSelf-report leisure-time physical activity (moderate and vigorous) and daily consumption of fruits and vegetables.Key resultsRacial/ethnic minorities generally engaged in less healthy exercise and dietary behaviors than whites, with differences more pronounced in middle adulthood. The disparities were the greatest among English-proficient minorities. Specifically, among middle-aged respondents, all racial/ethnic minorities engaged in less vigorous physical activity than whites (ORs range = 0.28 to 0.73; 95% CI range = 0.16-1.00). Additionally, middle-aged, English-proficient minorities engaged in less moderate physical activity compared to whites (ORs range =0.57 to 0.67; 95% CI range = 0.45-0.79). Furthermore, middle-aged, English-proficient Latinos had a poorer diet than whites (OR = 0.54; 0.39-0.75). Few significant racial/ethnic differences emerged in the exercise and dietary behaviors of older adults.ConclusionsRacial/ethnic disparities in exercise and dietary behaviors are most notable among middle-aged, acculturated minorities. Results highlight the need to promote positive exercise and dietary behaviors during critical preventive ages, when racial/ethnic disparities are large and the potential to prevent chronic disease is great

Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals

Background The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). Results Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p < 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p < 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing. Conclusions These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication