The Light Stop Scenario from Gauge Mediation

In this paper we embed the light stop scenario, a MSSM framework which explains the baryon asymmetry of the universe through a strong first order electroweak phase transition, in a top-down approach. The required low energy spectrum consists in the light SM-like Higgs, the right-handed stop, the gauginos and the Higgsinos while the remaining scalars are heavy. This spectrum is naturally driven by renormalization group evolution starting from a heavy scalar spectrum at high energies. The latter is obtained through a supersymmetry-breaking mix of gauge mediation, which provides the scalars masses by new gauge interactions, and gravity mediation, which generates gaugino and Higgsino masses. This supersymmetry breaking also explains the \mu\ and B_\mu\ parameters necessary for electroweak breaking and predicts small tri-linear mixing terms A_t in agreement with electroweak baryogenesis requirements. The minimal embedding predicts a Higgs mass around its experimental lower bound and by a small extension higher masses m_H\lesssim 127 GeV can be accommodated.Comment: 20 pages, 3 figures; v2: changes in the conventions; v3: more details on the Higgs mass prediction, version published in JHE

Excluding Electroweak Baryogenesis in the MSSM

In the context of the MSSM the Light Stop Scenario (LSS) is the only region of parameter space that allows for successful Electroweak Baryogenesis (EWBG). This possibility is very phenomenologically attractive, since it allows for the direct production of light stops and could be tested at the LHC. The ATLAS and CMS experiments have recently supplied tantalizing hints for a Higgs boson with a mass of ~ 125 GeV. This Higgs mass severely restricts the parameter space of the LSS, and we discuss the specific predictions made for EWBG in the MSSM. Combining data from all the available ATLAS and CMS Higgs searches reveals a tension with the predictions of EWBG even at this early stage. This allows us to exclude EWBG in the MSSM at greater than (90) 95% confidence level in the (non-)decoupling limit, by examining correlations between different Higgs decay channels. We also examine the exclusion without the assumption of a ~ 125 GeV Higgs. The Higgs searches are still highly constraining, excluding the entire EWBG parameter space at greater than 90% CL except for a small window of m_h ~ 117 - 119 GeV.Comment: 24 Pages, 4 Figures (v3: fixed typos, minor corrections, added references

The Dark Side of the Electroweak Phase Transition

Recent data from cosmic ray experiments may be explained by a new GeV scale of physics. In addition the fine-tuning of supersymmetric models may be alleviated by new O(GeV) states into which the Higgs boson could decay. The presence of these new, light states can affect early universe cosmology. We explore the consequences of a light (~ GeV) scalar on the electroweak phase transition. We find that trilinear interactions between the light state and the Higgs can allow a first order electroweak phase transition and a Higgs mass consistent with experimental bounds, which may allow electroweak baryogenesis to explain the cosmological baryon asymmetry. We show, within the context of a specific supersymmetric model, how the physics responsible for the first order phase transition may also be responsible for the recent cosmic ray excesses of PAMELA, FERMI etc. We consider the production of gravity waves from this transition and the possible detectability at LISA and BBO

Rab-GTPase binding effector protein 2 (RABEP2) is a primed substrate for Glycogen Synthase kinase-3 (GSK3)

Glycogen synthase kinase-3 (GSK3) regulates many physiological processes through phosphorylation of a diverse array of substrates. Inhibitors of GSK3 have been generated as potential therapies in several diseases, however the vital role GSK3 plays in cell biology makes the clinical use of GSK3 inhibitors potentially problematic. A clearer understanding of true physiological and pathophysiological substrates of GSK3 should provide opportunities for more selective, disease specific, manipulation of GSK3. To identify kinetically favourable substrates we performed a GSK3 substrate screen in heart tissue. Rab-GTPase binding effector protein 2 (RABEP2) was identified as a novel GSK3 substrate and GSK3 phosphorylation of RABEP2 at Ser200 was enhanced by prior phosphorylation at Ser204, fitting the known consensus sequence for GSK3 substrates. Both residues are phosphorylated in cells while only Ser200 phosphorylation is reduced following inhibition of GSK3. RABEP2 function was originally identified as a Rab5 binding protein. We did not observe co-localisation of RABEP2 and Rab5 in cells, while ectopic expression of RABEP2 had no effect on endosomal recycling. The work presented identifies RABEP2 as a novel primed substrate of GSK3, and thus a potential biomarker for GSK3 activity, but understanding how phosphorylation regulates RABEP2 function requires more information on physiological roles of RABEP2

Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes

BACKGROUND: GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans. METHODS: Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM. RESULTS: Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P ≥ 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls. CONCLUSION: From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans

Effective field theory and electroweak baryogenesis in the singlet-extended Standard Model

Electroweak baryogenesis is a simple and attractive candidate mechanism for generating the observed baryon asymmetry in the Universe. Its viability is sometimes investigated in terms of an effective field theory of the Standard Model involving higher dimension operators. We investigate the validity of such an effective field theory approach to the problem of identifying electroweak phase transitions strong enough for electroweak baryogenesis to be successful. We identify and discuss some pitfalls of this approach due to the modest hierarchy between mass scales of heavy degrees or freedom and the Higgs, and the possibility of dimensionful couplings violating the decoupling between light and heavy degrees of freedom.Comment: 18 pages + App. 17 figures. v2, References adde

The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test

BACKGROUND: The evolution of alternatively spliced exons (ASEs) is of primary interest because these exons are suggested to be a major source of functional diversity of proteins. Many exon features have been suggested to affect the evolution of ASEs. However, previous studies have relied on the K(A)/K(S )ratio test without taking into consideration information sufficiency (i.e., exon length > 75 bp, cross-species divergence > 5%) of the studied exons, leading to potentially biased interpretations. Furthermore, which exon feature dominates the results of the K(A)/K(S )ratio test and whether multiple exon features have additive effects have remained unexplored. RESULTS: In this study, we collect two different datasets for analysis – the ASE dataset (which includes lineage-specific ASEs and conserved ASEs) and the ACE dataset (which includes only conserved ASEs). We first show that information sufficiency can significantly affect the interpretation of relationship between exons features and the K(A)/K(S )ratio test results. After discarding exons with insufficient information, we use a Boolean method to analyze the relationship between test results and four exon features (namely length, protein domain overlapping, inclusion level, and exonic splicing enhancer (ESE) frequency) for the ASE dataset. We demonstrate that length and protein domain overlapping are dominant factors, and they have similar impacts on test results of ASEs. In addition, despite the weak impacts of inclusion level and ESE motif frequency when considered individually, combination of these two factors still have minor additive effects on test results. However, the ACE dataset shows a slightly different result in that inclusion level has a marginally significant effect on test results. Lineage-specific ASEs may have contributed to the difference. Overall, in both ASEs and ACEs, protein domain overlapping is the most dominant exon feature while ESE frequency is the weakest one in affecting test results. CONCLUSION: The proposed method can easily find additive effects of individual or multiple factors on the K(A)/K(S )ratio test results of exons. Therefore, the system can analyze complex conditions in evolution where multiple features are involved. More factors can also be added into the system to extend the scope of evolutionary analysis of exons. In addition, our method may be useful when orthologous exons can not be found for the K(A)/K(S )ratio test

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit

Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells

Abstract Background Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease. Methods We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from BAL cells and hybridized to an Affymetrix U133A microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we integrated network and gene set enrichment analyses of BAL cell transcriptional profiles. Results Sarcoidosis patients were either non-smokers or former smokers, all had lung involvement and only two were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1500 differentially expressed genes. Several previously described immune mediators, such as interferon gamma, were upregulated in the sarcoidosis subjects. Using an integrative computational approach we constructed a modular network of over 80 gene sets that were highly enriched in patients with sarcoidosis. Many of these pathways mapped to inflammatory and immune-related processes including adaptive immunity, T-cell signaling, graft vs. host disease, interleukin 12, 23 and 17 signaling. Additionally, we uncovered a close association between the proteasome machinery and adaptive immunity, highlighting a potentially important and targetable relationship in the pathobiology of sarcoidosis. Conclusions BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional programs involved in immunity and proteasomal processes. Our findings add to the growing evidence implicating alveolar resident immune effector cells in the pathogenesis of sarcoidosis and identify specific pathways whose activation may modulate disease progression

The effect of acute exercise on glycogen synthesis rate in obese subjects studied by 13C MRS

In obesity, insulin-stimulated glucose uptake in skeletal muscle is decreased. We investigated whether the stimulatory effect of acute exercise on glucose uptake and subsequent glycogen synthesis was normal. The study was performed on 18 healthy volunteers, 9 obese (BMI = 32.6 ± 1.2 kg/m2, mean ± SEM) and 9 lean (BMI = 22.0 ± 0.9 kg/m2), matched for age and gender. All participants underwent a euglycemic hyperinsulinemic clamp, showing reduced glucose uptake in the obese group (P = 0.01), during which they performed a short intense local exercise (single-legged toe lifting). Dynamic glucose incorporation into glycogen in the gastrocnemius muscle before and after exercise was assessed by 13C magnetic resonance spectroscopy combined with infusion of [1-13C]glucose. Blood flow was measured to investigate its potential contribution to glucose uptake. Before exercise, glycogen synthesis rate tended to be lower in obese subjects compared with lean (78 ± 14 vs. 132 ± 24 μmol/kg muscle/min; P = 0.07). Exercise induced highly significant rises in glycogen synthesis rates in both groups, but the increase in obese subjects was reduced compared with lean (112 ± 15 vs. 186 ± 27 μmol/kg muscle/min; P = 0.03), although the relative increase was similar (184 ± 35 vs. 202 ± 51%; P = 0.78). After exercise, blood flow increased equally in both groups, without a temporal relationship with the rate of glycogen synthesis. In conclusion, this study shows a stimulatory effect of a short bout of acute exercise on insulin-induced glycogen synthesis rate that is reduced in absolute values but similar in percentages in obese subjects. These results suggest a shared pathway between insulin- and exercise-induced glucose uptake and subsequent glycogen synthesis