278 research outputs found
Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice
Activating signal cointegrator 2 (ASC-2), a cancer-amplified transcriptional coactivator of nuclear receptors and many other transcription factors, contains two LXXLL-type nuclear receptor interaction domains. Interestingly, the second LXXLL motif is highly specific to the liver X receptors (LXRs). In cotransfection, DN2, an ASC-2 fragment encompassing this motif, exerts a potent dominant-negative effect on transactivation by LXRs, which is rescued by ectopic coexpression of the full-length ASC-2 but not by other LXXLL-type coactivators, such as SRC-1 and TRAP220. In contrast, DN2/m, in which the LXXLL motif is mutated to LXXAA to abolish the interactions with LXRs, is without any effect. Accordingly, expression of DN2, but not DN2/m, in transgenic mice results in phenotypes that are highly homologous to those previously observed with LXRalpha(-/-) mice, including a rapid accumulation of large amounts of cholesterol and down-regulation of the known lipid-metabolizing target genes of LXRalpha in the liver upon being fed a high-cholesterol diet. These results identify ASC-2 as a physiologically important transcriptional coactivator of LXRs and demonstrate its pivotal role in the liver lipid metabolism.open1136sciescopu
Higgs production in CP-violating supersymmetric cascade decays: probing the `open hole' at the Large Hadron Collider
A benchmark CP-violating supersymmetric scenario (known as 'CPX-scenario' in
the literature) is studied in the context of the Large Hadron Collider (LHC).
It is shown that the LHC, with low to moderate accumulated luminosity, will be
able to probe the existing `hole' in the - plane, which
cannot be ruled out by the LEP data. We explore the parameter space with
cascade decay of third generation squarks and gluino with CP-violating decay
branching fractions. We propose a multi-channel analysis to probe this
parameter space some of which are background free at an integrated luminosity
of 5-10 fb. Specially, multi-lepton final states (3\l,\, 4\l and like
sign di-lepton) are almost background free and have reach for the
corresponding signals with very early data of LHC for both 14 TeV and 7 TeV
center of mass energy.Comment: 24 pages, 9 figures, references added as in the journal versio
CP violation Beyond the MSSM: Baryogenesis and Electric Dipole Moments
We study electroweak baryogenesis and electric dipole moments in the presence
of the two leading-order, non-renormalizable operators in the Higgs sector of
the MSSM. Significant qualitative and quantitative differences from MSSM
baryogenesis arise due to the presence of new CP-violating phases and to the
relaxation of constraints on the supersymmetric spectrum (in particular, both
stops can be light). We find: (1) spontaneous baryogenesis, driven by a change
in the phase of the Higgs vevs across the bubble wall, becomes possible; (2)
the top and stop CP-violating sources can become effective; (3) baryogenesis is
viable in larger parts of parameter space, alleviating the well-known
fine-tuning associated with MSSM baryogenesis. Nevertheless, electric dipole
moments should be measured if experimental sensitivities are improved by about
one order of magnitude.Comment: 33 pages, 6 figure
Baryon Washout, Electroweak Phase Transition, and Perturbation Theory
We analyze the conventional perturbative treatment of sphaleron-induced
baryon number washout relevant for electroweak baryogenesis and show that it is
not gauge-independent due to the failure of consistently implementing the
Nielsen identities order-by-order in perturbation theory. We provide a
gauge-independent criterion for baryon number preservation in place of the
conventional (gauge-dependent) criterion needed for successful electroweak
baryogenesis. We also review the arguments leading to the preservation
criterion and analyze several sources of theoretical uncertainties in obtaining
a numerical bound. In various beyond the standard model scenarios, a realistic
perturbative treatment will likely require knowledge of the complete two-loop
finite temperature effective potential and the one-loop sphaleron rate.Comment: 25 pages, 9 figures; v2 minor typos correcte
Systematic review of studies examining transtibial prosthetic socket pressures with changes in device alignment
Suitable lower-limb prosthetic sockets must provide an adequate distribution of the pressures created from standing and ambulation. A systematic search for articles reporting socket pressure changes in response to device alignment perturbation was carried out, identifying 11 studies. These were then evaluated using the American Academy of Orthotists and Prosthetists guidelines for a state-of-the-science review. Each study used a design where participants acted as their own controls. Results were available for 52 individuals and 5 forms of alignment perturbation. Four studies were rated as having moderate internal and external validity, the remainder were considered to have low validity. Significant limitations in study design, reporting quality and in representation of results and the suitability of calculations of statistical significance were evident across articles. Despite the high inhomogeneity of study designs, moderate evidence supports repeatable changes in pressure distribution for specific induced changes in component alignment. However, there also appears to be a significant individual component to alignment responses. Future studies should aim to include greater detail in the presentation of results to better support later meta-analyses
Much Ado About the TPP’s Effect on Pharmaceuticals
Ocular antigens are sequestered behind the blood-retina barrier and the ocular environment protects ocular tissues from autoimmune attack. The signals required to activate autoreactive T cells and allow them to cause disease in the eye remain in part unclear. In particular, the consequences of peripheral presentation of ocular antigens are not fully understood. We examined peripheral expression and presentation of ocular neo-self-antigen in transgenic mice expressing hen egg lysozyme (HEL) under a retina-specific promoter. High levels of HEL were expressed in the eye compared to low expression throughout the lymphoid system. Adoptively transferred naïve HEL-specific CD4+ T cells proliferated in the eye draining lymph nodes, but did not induce uveitis. By contrast, systemic infection with a murine cytomegalovirus (MCMV) engineered to express HEL induced extensive proliferation of transferred naïve CD4+ T cells, and significant uveoretinitis. In this model, wild-type MCMV, lacking HEL, did not induce overt uveitis, suggesting that disease is mediated by antigen-specific peripherally activated CD4+ T cells that infiltrate the retina. Our results demonstrate that retinal antigen is presented to T cells in the periphery under physiological conditions. However, when the same antigen is presented during viral infection, antigen-specific T cells access the retina and autoimmune uveitis ensues
Randomized Clinical Trial of Laparoscopic Versus Open Repair of the Perforated Peptic Ulcer: The LAMA Trial
Background: Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open appr
Electroweak phase transitions in the secluded U(1)-prime-extended MSSM
The electroweak phase transition (EWPT) in the secluded--extended MSSM
(sMSSM) is studied. Using the effective potential at zero and finite
temperatures, we search for the non-MSSM-like EWPT in which the light stop mass
is larger than the top quark mass. Scanning the parameters relevant to the
EWPT, the upper limits of the Higgs boson masses, which are consistent with the
strong first order EWPT, are derived. For the lightest CP-even and -odd Higgs
bosons, we find GeV and GeV, respectively. In the
sMSSM, the tree-level CP violation is possible by the complex soft
supersymmetry breaking masses. It is observed that such a CP-violating effect
does not spoil the strong first order EWPT for the typical parameter sets.Comment: 29 pages,15 figures, JHEP style; accepted for publication in JHE
The Higgs sector of the munuSSM and collider physics
The SSM is a supersymmetric standard model that accounts for light
neutrino masses and solves the problem of the MSSM by simply using
right-handed neutrino superfields. Since this mechanism breaks R-parity, a
peculiar structure for the mass matrices is generated. The neutral Higgses are
mixed with the right- and left-handed sneutrinos producing 88 neutral
scalar mass matrices. We analyse the Higgs sector of the SSM in detail,
with special emphasis in possible signals at colliders. After studying in
general the decays of the Higges, we focus on those processes that are genuine
of the SSM, and could serve to distinguish it from other supersymmetric
models. In particular, we present viable benchmark points for LHC searches. For
example, we find decays of a MSSM-like Higgs into two lightest neutralinos,
with the latter decaying inside the detector leading to displaced vertices, and
producing final states with 4 and 8 -jets plus missing energy. Final states
with leptons and missing energy are also found.Comment: Final version to appear in JHEP. The discussion on signals at
colliders, expanded. 33 pages, 8 figures and 9 table
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