1,221 research outputs found
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Reproducibility of cardiac 31P MRS at 7 T
Synopsis
Cardiac PCr/ATP ratios measured by P MRS change in cardiovascular disease giving them value as a biomarker. We scanned 13 healthy
volunteers at 7T, assessing their PCr/ATP with 6 ½ min P CSI scans. These data have better reproducibility than a 30min 3T protocol
previously published by our centre. Repeated PCr/ATP measurements from subjects in this study were not significantly (P=0.83) different.
Measurements were significantly different (P<0.001) from DCM patient data acquired in a previous 7T study using the same coil and pulse
sequence. This data will allow us to plan future 7T P-MRS clinical studies.Funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (Grant No. 098436/Z/12/Z). JE receives a DPhil (PhD) studentship
from the Medical Research Council (UK)
Tumor necrosis Factor (TNF) Bioactivity at the site of an acute cell-Mediated immune response is Preserved in rheumatoid arthritis Patients responding to anti-TNF Therapy
The impact of anti-tumor necrosis factor (TNF) therapies on inducible TNF-dependent activity in humans has never been evaluated in vivo. We aimed to test the hypothesis that patients responding to anti-TNF treatments exhibit attenuated TNF-dependent immune responses at the site of an immune challenge. We developed and validated four context-specific TNF-inducible transcriptional signatures to quantify TNF bioactivity in transcriptomic data. In anti-TNF treated rheumatoid arthritis (RA) patients, we measured the expression of these biosignatures in blood, and in skin biopsies from the site of tuberculin skin tests (TSTs) as a human experimental model of multivariate cell-mediated immune responses. In blood, anti-TNF therapies attenuated TNF bioactivity following ex vivo stimulation. However, at the site of the TST, TNF-inducible gene expression and genome-wide transcriptional changes associated with cell-mediated immune responses were comparable to that of RA patients receiving methotrexate only. These data demonstrate that anti-TNF agents in RA patients do not inhibit inducible TNF activity at the site of an acute inflammatory challenge in vivo, as modeled by the TST. We hypothesize instead that their therapeutic effects are limited to regulating TNF activity in chronic inflammation or by alternative non-canonical pathways
Realistic Standard Model Fermion Mass Relations in Generalized Minimal Supergravity (GmSUGRA)
Grand Unified Theories (GUTs) usually predict wrong Standard Model (SM)
fermion mass relation m_e/m_{\mu} = m_d/m_s toward low energies. To solve this
problem, we consider the Generalized Minimal Supergravity (GmSUGRA) models,
which are GUTs with gravity mediated supersymmetry breaking and higher
dimensional operators. Introducing non-renormalizable terms in the super- and
K\"ahler potentials, we can obtain the correct SM fermion mass relations in the
SU(5) model with GUT Higgs fields in the {\bf 24} and {\bf 75} representations,
and in the SO(10) model. In the latter case the gauge symmetry is broken down
to SU(3)_C X SU(2)_L X SU(2)_R X U(1)_{B-L}, to flipped SU(5)X U(1)_X, or to
SU(3)_C X SU(2)_L X U(1)_1 X U(1)_2. Especially, for the first time we generate
the realistic SM fermion mass relation in GUTs by considering the
high-dimensional operators in the K\"ahler potential.Comment: JHEP style, 29 pages, no figure,references adde
PGB pair production at LHC and ILC as a probe of the topcolor-assisted technicolor models
The topcolor-assisted technicolor (TC2) model predicts some light pseudo
goldstone bosons (PGBs), which may be accessible at the LHC or ILC. In this
work we study the pair productions of the charged or neutral PGBs at the LHC
and ILC. For the productions at the LHC we consider the processes proceeding
through gluon-gluon fusion and quark-antiquark annihilation, while for the
productions at the ILC we consider both the electron-positron collision and the
photon-photon collision. We find that in a large part of parameter space the
production cross sections at both colliders can be quite large compared with
the low standard model backgrounds. Therefore, in future experiments these
productions may be detectable and allow for probing TC2 model.Comment: 26 pages, 16 figures. slight changes in the text; notations for
curves changed; references adde
General Gauge and Anomaly Mediated Supersymmetry Breaking in Grand Unified Theories with Vector-Like Particles
In Grand Unified Theories (GUTs) from orbifold and various string
constructions the generic vector-like particles do not need to form complete
SU(5) or SO(10) representations. To realize them concretely, we present
orbifold SU(5) models, orbifold SO(10) models where the gauge symmetry can be
broken down to flipped SU(5) X U(1)_X or Pati-Salam SU(4)_C X SU(2)_L X SU(2)_R
gauge symmetries, and F-theory SU(5) models. Interestingly, these vector-like
particles can be at the TeV-scale so that the lightest CP-even Higgs boson mass
can be lifted, or play the messenger fields in the Gauge Mediated Supersymmetry
Breaking (GMSB). Considering GMSB, ultraviolet insensitive Anomaly Mediated
Supersymmetry Breaking (AMSB), and the deflected AMSB, we study the general
gaugino mass relations and their indices, which are valid from the GUT scale to
the electroweak scale at one loop, in the SU(5) models, the flipped SU(5) X
U(1)_X models, and the Pati-Salam SU(4)_C X SU(2)_L X SU(2)_R models. In the
deflected AMSB, we also define the new indices for the gaugino mass relations,
and calculate them as well. Using these gaugino mass relations and their
indices, we may probe the messenger fields at intermediate scale in the GMSB
and deflected AMSB, determine the supersymmetry breaking mediation mechanisms,
and distinguish the four-dimensional GUTs, orbifold GUTs, and F-theory GUTs.Comment: RevTex4, 45 pages, 15 tables, version to appear in JHE
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Assessing metabolism and function of normothermically perfused ex vivo livers by multinuclear MR imaging and spectroscopy
Synopsis
Liver transplantation is the only cure for end-stage liver disease. Unfortunately, 20% of patients die waiting for a donor. New techniques for
preserving transplant livers, such as normothermic machine perfusion (NMP), provide an opportunity to utilise ‘marginal’ (currently discarded)
donated livers if their viability can be assessed accurately. We present initial results from a CE-marked NMP system that we adapted for use in
an MRI scanner. We demonstrate the power of NMP-MRI to assess structure and metabolism in a freshly donated pig liver, dynamically over a
10-hour period. Our protocol includes H imaging, P spectroscopy, and hyperpolarised C spectroscopy.This work was funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (Grant No. 098436/Z/12/Z) and by the National
Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)
E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia
Acute lung injury (ALI) is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial-specific lipid, is generated by cardiolipin synthase (CLS1). Here, we show that S.aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S.aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S.aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme. © 2014 The Authors
Flavor Physics in an SO(10) Grand Unified Model
In supersymmetric grand-unified models, the lepton mixing matrix can possibly
affect flavor-changing transitions in the quark sector. We present a detailed
analysis of a model proposed by Chang, Masiero and Murayama, in which the
near-maximal atmospheric neutrino mixing angle governs large new b -> s
transitions. Relating the supersymmetric low-energy parameters to seven new
parameters of this SO(10) GUT model, we perform a correlated study of several
flavor-changing neutral current (FCNC) processes. We find the current bound on
B(tau -> mu gamma) more constraining than B(B -> X_s gamma). The LEP limit on
the lightest Higgs boson mass implies an important lower bound on tan beta,
which in turn limits the size of the new FCNC transitions. Remarkably, the
combined analysis does not rule out large effects in B_s-B_s-bar mixing and we
can easily accomodate the large CP phase in the B_s-B_s-bar system which has
recently been inferred from a global analysis of CDF and DO data. The model
predicts a particle spectrum which is different from the popular Constrained
Minimal Supersymmetric Standard Model (CMSSM). B(tau -> mu gamma) enforces
heavy masses, typically above 1 TeV, for the sfermions of the degenerate first
two generations. However, the ratio of the third-generation and
first-generation sfermion masses is smaller than in the CMSSM and a (dominantly
right-handed) stop with mass below 500 GeV is possible.Comment: 44 pages, 5 figures. Footnote and references added, minor changes,
Fig. 2 corrected; journal versio
Invisible Higgs and Dark Matter
We investigate the possibility that a massive weakly interacting fermion
simultaneously provides for a dominant component of the dark matter relic
density and an invisible decay width of the Higgs boson at the LHC. As a
concrete model realizing such dynamics we consider the minimal walking
technicolor, although our results apply more generally. Taking into account the
constraints from the electroweak precision measurements and current direct
searches for dark matter particles, we find that such scenario is heavily
constrained, and large portions of the parameter space are excluded.Comment: arXiv admin note: text overlap with arXiv:0912.229
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