Positivity Bounds on Higgs-Portal Dark Matter

We consider the positivity bounds for WIMP scalar dark matter with effective Higgs-portal couplings up to dimension-8 operators. Taking the superposed states for Standard Model Higgs and scalar dark matter, we show that the part of the parameter space for the effective couplings, otherwise unconstrained by phenomenological bounds, is ruled out by the positivity bounds on the dimension-8 derivative operators. We find that dark matter relic density, direct and indirect detection and LHC constraints are complementary to the positivity bounds in constraining the effective Higgs-portal couplings. In the effective theory obtained from massive graviton or radion, there appears a correlation between dimension-8 operators and other effective Higgs-portal couplings for which the strong constraint from direct detection can be evaded. Nailing down the parameter space mainly by relic density, direct detection and positivity bounds, we find that there are observable cosmic ray signals coming from the dark matter annihilations into a pair of Higgs bosons, $WW$ or $ZZ$.Comment: 31 pages, 6 figures, v2: one-loop corrections to the positivity bounds added, version to be published in JHE

The SU(2)DSU(2)_D lepton portals for muon g−2g-2, WW boson mass and dark matter

We propose a novel model for lepton flavor and dark matter based on the $SU(2)_D$ gauge symmetry and vector-like leptons in its fundamental representations. We introduce a dark $SU(2)_D$ Higgs doublet and a Higgs bi-doublet for the mass mixing between the vector-like lepton and the lepton. As a result, the seesaw lepton masses are generated and there are sizable one-loop contributions to the muon $g-2$ via the $SU(2)_D$ gauge bosons and the relatively heavy vector-like lepton, as indicated in Fermilab E989. The tree-level mass mixing between the $Z$ boson and the isospin neutral gauge boson of $SU(2)_D$ in our model accounts for the shift in the $W$ boson mass, being consistent with Tevatron CDFII. Finally, we show that the isospin charged gauge boson of $SU(2)_D$ becomes a plausible candidate for dark matter with a small mass splitting tied up to the modified $W$ boson mass, and there is a viable parameter space where the favored corrections to the muon $g-2$ and the $W$ boson mass and the dark matter constraints are simultaneously fulfilled.Comment: 33 pages, 4 figures, v2: references added, v3: version to appear in Phys. Rev.

Genome-Based Construction of the Metabolic Pathways of Orientia tsutsugamushi and Comparative Analysis within the Rickettsiales Order

Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium that belongs to the order of Rickettsiales. Recently, we have reported that O. tsutsugamushi has a unique genomic structure, consisting of highly repetitive sequences, and suggested that it may provide valuable insight into the evolution of intracellular bacteria. Here, we have used genomic information to construct the major metabolic pathways of O. tsutsugamushi and performed a comparative analysis of the metabolic genes and pathways of O. tsutsugamushi with other members of the Rickettsiales order. While O. tsutsugamushi has the largest genome among the members of this order, mainly due to the presence of repeated sequences, its metabolic pathways have been highly streamlined. Overall, the metabolic pathways of O. tsutsugamushi were similar to Rickettsia but there were notable differences in several pathways including carbohydrate metabolism, the TCA cycle, and the synthesis of cell wall components as well as in the transport systems. Our results will provide a useful guide to the postgenomic analysis of O. tsutsugamushi and lead to a better understanding of the virulence and physiology of this intracellular pathogen

Quantitative measurements of C-reactive protein using silicon nanowire arrays

A silicon nanowire-based sensor for biological application showed highly desirable electrical responses to either pH changes or receptor-ligand interactions such as protein disease markers, viruses, and DNA hybridization. Furthermore, because the silicon nanowire can display results in real-time, it may possess superior characteristics for biosensing than those demonstrated in previously studied methods. However, despite its promising potential and advantages, certain process-related limitations of the device, due to its size and material characteristics, need to be addressed. In this article, we suggest possible solutions. We fabricated silicon nanowire using a top-down and low cost micromachining method, and evaluate the sensing of molecules after transfer and surface modifications. Our newly designed method can be used to attach highly ordered nanowires to various substrates, to form a nanowire array device, which needs to follow a series of repetitive steps in conventional fabrication technology based on a vapor-liquid-solid (VLS) method. For evaluation, we demonstrated that our newly fabricated silicon nanowire arrays could detect pH changes as well as streptavidin-biotin binding events. As well as the initial proof-of-principle studies, C-reactive protein binding was measured: electrical signals were changed in a linear fashion with the concentration (1 fM to 1 nM) in PBS containing 1.37 mM of salts. Finally, to address the effects of Debye length, silicon nanowires coupled with antigen proteins underwent electrical signal changes as the salt concentration changed

Unbiased Gene Expression Analysis Implicates the huntingtin Polyglutamine Tract in Extra-mitochondrial Energy Metabolism

The Huntington's disease (HD) CAG repeat, encoding a polymorphic glutamine tract in huntingtin, is inversely correlated with cellular energy level, with alleles over ∼37 repeats leading to the loss of striatal neurons. This early HD neuronal specificity can be modeled by respiratory chain inhibitor 3-nitropropionic acid (3-NP) and, like 3-NP, mutant huntingtin has been proposed to directly influence the mitochondrion, via interaction or decreased PGC-1α expression. We have tested this hypothesis by comparing the gene expression changes due to mutant huntingtin accurately expressed in STHdhQ111/Q111 cells with the changes produced by 3-NP treatment of wild-type striatal cells. In general, the HD mutation did not mimic 3-NP, although both produced a state of energy collapse that was mildly alleviated by the PGC-1α-coregulated nuclear respiratory factor 1 (Nrf-1). Moreover, unlike 3-NP, the HD CAG repeat did not significantly alter mitochondrial pathways in STHdhQ111/Q111 cells, despite decreased Ppargc1a expression. Instead, the HD mutation enriched for processes linked to huntingtin normal function and Nf-κB signaling. Thus, rather than a direct impact on the mitochondrion, the polyglutamine tract may modulate some aspect of huntingtin's activity in extra-mitochondrial energy metabolism. Elucidation of this HD CAG-dependent pathway would spur efforts to achieve energy-based therapeutics in HD

Orientia tsutsugamushi and Comparative Analysis within the Rickettsiales Order

Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium that belongs to the order of Rickettsiales. Recently, we have reported that O. tsutsugamushi has a unique genomic structure, consisting of highly repetitive sequences, and suggested that it may provide valuable insight into the evolution of intracellular bacteria. Here, we have used genomic information to construct the major metabolic pathways of O. tsutsugamushi and performed a comparative analysis of the metabolic genes and pathways of O. tsutsugamushi with other members of the Rickettsiales order. While O. tsutsugamushi has the largest genome among the members of this order, mainly due to the presence of repeated sequences, its metabolic pathways have been highly streamlined. Overall, the metabolic pathways of O. tsutsugamushi were similar to Rickettsia but there were notable differences in several pathways including carbohydrate metabolism, the TCA cycle, and the synthesis of cell wall components as well as in the transport systems. Our results will provide a useful guide to the postgenomic analysis of O. tsutsugamushi and lead to a better understanding of the virulence and physiology of this intracellular pathogen

HD CAGnome: A Search Tool for Huntingtin CAG Repeat Length-Correlated Genes

Background: The length of the huntingtin (HTT) CAG repeat is strongly correlated with both age at onset of Huntington’s disease (HD) symptoms and age at death of HD patients. Dichotomous analysis comparing HD to controls is widely used to study the effects of HTT CAG repeat expansion. However, a potentially more powerful approach is a continuous analysis strategy that takes advantage of all of the different CAG lengths, to capture effects that are expected to be critical to HD pathogenesis. Methodology/Principal Findings We used continuous and dichotomous approaches to analyze microarray gene expression data from 107 human control and HD lymphoblastoid cell lines. Of all probes found to be significant in a continuous analysis by CAG length, only 21.4% were so identified by a dichotomous comparison of HD versus controls. Moreover, of probes significant by dichotomous analysis, only 33.2% were also significant in the continuous analysis. Simulations revealed that the dichotomous approach would require substantially more than 107 samples to either detect 80% of the CAG-length correlated changes revealed by continuous analysis or to reduce the rate of significant differences that are not CAG length-correlated to 20% (n = 133 or n = 206, respectively). Given the superior power of the continuous approach, we calculated the correlation structure between HTT CAG repeat lengths and gene expression levels and created a freely available searchable website, “HD CAGnome,” that allows users to examine continuous relationships between HTT CAG and expression levels of ∼20,000 human genes. Conclusions/Significance: Our results reveal limitations of dichotomous approaches compared to the power of continuous analysis to study a disease where human genotype-phenotype relationships strongly support a role for a continuum of CAG length-dependent changes. The compendium of HTT CAG length-gene expression level relationships found at the HD CAGnome now provides convenient routes for discovery of candidates influenced by the HD mutation

THE EFFECTS OF WEARING SPANDEX GARMENT WITH COMPRESSION BAND ON KINEMATIC VARIABLES DURING A GOLF SWING

The purpose of this study was to investigate how spandex garment with compressive band affects kinematic variables during a golf swing. The X-factor and angular velocity of the club in EG were increased during the down swing phase, whereas the significant changes of other kinematic variables were not found in this study. Thus, the effects of wearing spandex garment with compression band cannot be explained as a function of the kinematic variables of interest. It is clear that wearing spandex garment with compressive band may enhance joint stability, which in turn may affect joint kinetics and muscle activation. This has led to suggestions of the need for further kinetic and EMG analyses to evaluate its function