One Loop Predictions of the Finely Tuned SSM

We study the finely tuned SSM, recently proposed by Arkani-Hamed and Dimopoulos, at the one loop level. The runnings of the four gaugino Yukawa couplings, the mu term, the gaugino masses, and the Higgs quartic coupling are computed. The Higgs mass is found to be 130 - 170 GeV for M_s > 10^6 GeV. If the Yukawa coupling constants are measured at the 1% level, this can determine the SUSY breaking scale to within an order of magnitude. Measuring the relationships between the couplings to this accuracy provides a striking signal for this model.Comment: 5 pages, 4 figures; v2: Minor corrections to anomalous dimensions and beta functions. Numerical results are not significantly affected. v3: Minor changes to figures and references, as published in PR

Principles for the post-GWAS functional characterisation of risk loci

Several challenges lie ahead in assigning functionality to susceptibility SNPs. For example, most effect sizes are small relative to effects seen in monogenic diseases, with per allele odds ratios usually ranging from 1.15 to 1.3. It is unclear whether current molecular biology methods have enough resolution to differentiate such small effects. Our objective here is therefore to provide a set of recommendations to optimize the allocation of effort and resources in order maximize the chances of elucidating the functional contribution of specific loci to the disease phenotype. It has been estimated that 88% of currently identified disease-associated SNP are intronic or intergenic. Thus, in this paper we will focus our attention on the analysis of non-coding variants and outline a hierarchical approach for post-GWAS functional studies

Gene regulatory changes underlie developmental plasticity in respiration and aerobic performance in highland deer mice

Phenotypic plasticity can play an important role in the ability of animals to tolerate environmental stress, but the nature and magnitude of plastic responses are often specific to the developmental timing of exposure. Here, we examine changes in gene expression in the diaphragm of highland deer mice (Peromyscus maniculatus) in response to hypoxia exposure at different stages of development. In highland deer mice, developmental plasticity in diaphragm function may mediate changes in several respiratory traits that influence aerobic metabolism and performance under hypoxia. We generated RNAseq data from diaphragm tissue of adult deer mice exposed to (1) life-long hypoxia (before conception to adulthood), (2) post-natal hypoxia (birth to adulthood), (3) adult hypoxia (6–8 weeks only during adulthood) or (4) normoxia. We found five suites of co-regulated genes that are differentially expressed in response to hypoxia, but the patterns of differential expression depend on the developmental timing of exposure. We also identified four transcriptional modules that are associated with important respiratory traits. Many of the genes in these transcriptional modules bear signatures of altitude-related selection, providing an indirect line of evidence that observed changes in gene expression may be adaptive in hypoxic environments. Our results demonstrate the importance of developmental stage in determining the phenotypic response to environmental stressors. Includes supplementary materials

Trends in Resource Utilization by Children with Neurological Impairment in the United States Inpatient Health Care System: A Repeat Cross-Sectional Study

Jay Berry and colleagues report findings from an analysis of hospitalization data in the US, examining the proportion of inpatient resources attributable to care for children with neurological impairment

Jedi public health: Co-creating an identity-safe culture to promote health equity

© 2016 The Authors. The extent to which socially-assigned and culturally mediated social identity affects health depends on contingencies of social identity that vary across and within populations in day-to-day life. These contingencies are structurally rooted and health damaging inasmuch as they activate physiological stress responses. They also have adverse effects on cognition and emotion, undermining self-confidence and diminishing academic performance. This impact reduces opportunities for social mobility, while ensuring those who "beat the odds" pay a physical price for their positive efforts. Recent applications of social identity theory toward closing racial, ethnic, and gender academic achievement gaps through changing features of educational settings, rather than individual students, have proved fruitful. We sought to integrate this evidence with growing social epidemiological evidence that structurally-rooted biopsychosocial processes have population health effects. We explicate an emergent framework, Jedi Public Health (JPH). JPH focuses on changing features of settings in everyday life, rather than individuals, to promote population health equity, a high priority, yet, elusive national public health objective. We call for an expansion and, in some ways, a re-orienting of efforts to eliminate population health inequity. Policies and interventions to remove and replace discrediting cues in everyday settings hold promise for disrupting the repeated physiological stress process activation that fuels population health inequities with potentially wide application.National Institute on Aging (Grant # R01 AG032632)National Institute on Aging (Grant # T32 AG00221

Comparison of Molecular Phenotypes of Ductal Carcinoma In Situ and Invasive Breast Cancer

Introduction: At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal-like. However, the prevalence of these phenotypes among cases of ductal carcinoma in situ (DCIS) has not been previously evaluated in detail. The purpose of this study was to compare the prevalence of these distinct molecular subtypes among cases of DCIS and invasive breast cancer. Methods: We constructed tissue microarrays (TMAs) from breast cancers that developed in 2897 women enrolled in the Nurses' Health Study (1976 to 1996). TMA slides were immunostained for oestrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR). Using these immunostain results, cases were grouped into molecularly defined subtypes. Results: The prevalence of the distinct molecular phenotypes differed significantly between DCIS (n = 272) and invasive breast cancers (n = 2249). The luminal A phenotype was significantly more frequent among invasive cancers (73.4%) than among DCIS lesions (62.5%) (p = 0.0002). In contrast, luminal B and HER2 molecular phenotypes were both more frequent among DCIS (13.2% and 13.6%, respectively) as compared with invasive tumours (5.2% and 5.7%, respectively) (p < 0.0001). The basal-like phenotype was more frequent among the invasive cancers (10.9%) than DCIS (7.7%), although this difference was not statistically significant (p = 0.15). High-grade DCIS and invasive tumours were more likely to be HER2 type and basal-like than low- or intermediate-grade lesions. Among invasive tumours, basal-like and HER2 type tumours were more likely to be more than 2 cm in size, high-grade and have nodal involvement compared with luminal A tumours. Conclusion: The major molecular phenotypes previously identified among invasive breast cancers were also identified among cases of DCIS. However, the prevalence of the luminal A, luminal B and HER2 phenotypes differed significantly between DCIS and invasive breast cancers

Variations of Little Higgs Models and their Electroweak Constraints

We calculate the tree-level electroweak precision constraints on a wide class of little Higgs models including: variations of the Littlest Higgs SU(5)/SO(5), SU(6)/Sp(6), and SU(4)^4/SU(3)^4. By performing a global fit to the precision data we find that for generic regions of the parameter space the bound on the symmetry breaking scale f is several TeV, where we have kept the normalization of f constant in the different models. For example, the ``minimal'' implementation of SU(6)/Sp(6) is bounded by f>3.0 TeV throughout most of the parameter space, and SU(4)^4/SU(3)^4 is bounded by f^2 = f_1^2+f_2^2 > (4.2 TeV)^2. In certain models, such as SU(4)^4/SU(3)^4, a large f does not directly imply a large amount of fine tuning since the heavy fermion masses that contribute to the Higgs mass can be lowered below f for a carefully chosen set of parameters. We also find that for certain models (or variations) there exist regions of parameter space in which the bound on f can be lowered into the range 1-2 TeV. These regions are typically characterized by a small mixing between heavy and standard model gauge bosons, and a small (or vanishing) coupling between heavy U(1) gauge bosons and the light fermions. Whether such a region of parameter space is natural or not is ultimately contingent on the UV completion.Comment: 32 pages, 13 figures; revised discussion of SU(4)^4/SU(3)^4 model, bound on f is slightly highe

Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways.

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy

The technologies of isolation: apocalypse and self in Kurosawa Kiyoshi's Kairo

In this investigation of the Japanese film Kairo, I contemplate how the horrors present in the film relate to the issue of self, by examining a number of interlocking motifs. These include thematic foci on disease and technology which are more intimately and inwardly focused that the film's conclusion first appears to suggest. The true horror here, I argue, is ontological: centred on the self and its divorcing from the exterior world, especially founded in an increased use of and reliance on communicative technologies. I contend that these concerns are manifested in Kairo by presenting the spread of technology as disease-like, infecting the city and the individuals who are isolated and imprisoned by their urban environment. Finally, I investigate the meanings of the apocalypse, expounding how it may be read as hopeful for the future rather than indicative of failure or doom

In Vivo, Fatty Acid Translocase (CD36) Critically Regulates Skeletal Muscle Fuel Selection, Exercise Performance, and Training-induced Adaptation of Fatty Acid Oxidation

For ∼40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (−21%) and oxidation (−25%), intramuscular lipids (less than or equal to −31%), and hepatic glycogen (−20%); but muscle glycogen, VO(2max), and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO(2max)) CD36-KO mice, fatty acid transport (−41%), oxidation (−37%), and exercise duration (−44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27–55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84–90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO