2,087 research outputs found
Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation
Prolonged ingestion of a cholesterol- or saturated fatty acid-enriched diet induces chronic, often systemic, auto-inflammatory responses resulting in significant health problems worldwide. In vivo information regarding the local and direct inflammatory effect of these dietary components in the intestine and, in particular, on the intestinal epithelium is lacking. Here we report that both mice and zebrafish exposed to high-fat (HFDs) or high-cholesterol (HCDs) diets develop acute innate inflammatory responses within hours, reflected in the localized interleukin-1β-dependent accumulation of myeloid cells in the intestine. Acute HCD-induced intestinal inflammation is dependent on cholesterol uptake via Niemann-Pick C1-like 1 and inflammasome activation involving apoptosis-associated Speck-like protein containing a caspase recruitment domain, which leads to Caspase-1 activity in intestinal epithelial cells. Extended exposure to HCD results in localized, inflammation-dependent, functional dysregulation as well as systemic pathologies. Our model suggests that dietary cholesterol initiates intestinal inflammation in epithelial cells
Goldstini
Supersymmetric phenomenology has been largely bound to the hypothesis that
supersymmetry breaking originates from a single source. In this paper, we relax
this underlying assumption and consider a multiplicity of sectors which
independently break supersymmetry, thus yielding a corresponding multiplicity
of goldstini. While one linear combination of goldstini is eaten via the
super-Higgs mechanism, the orthogonal combinations remain in the spectrum as
physical degrees of freedom. Interestingly, supergravity effects induce a
universal tree-level mass for the goldstini which is exactly twice the
gravitino mass. Since visible sector fields can couple dominantly to the
goldstini rather than the gravitino, this framework allows for substantial
departures from conventional supersymmetric phenomenology. In fact, this even
occurs when a conventional mediation scheme is augmented by additional
supersymmetry breaking sectors which are fully sequestered. We discuss a number
of striking collider signatures, including various novel decay modes for the
lightest observable-sector supersymmetric particle, gravitinoless
gauge-mediated spectra, and events with multiple displaced vertices. We also
describe goldstini cosmology and the possibility of goldstini dark matter.Comment: 14 pages, 7 figures; references adde
Cosmological vacuum selection and metastable susy breaking
We study gauge mediation in a wide class of O'Raifeartaigh type models where
supersymmetry breaking metastable vacuum is created by gravity and/or quantum
corrections. We examine their thermal evolution in the early universe and the
conditions under which the susy breaking vacuum can be selected. It is
demonstrated that thermalization typically makes the metastable supersymmetry
breaking cosmologically disfavoured but this is not always the case. Initial
conditions with the spurion displaced from the symmetric thermal minimum and a
small coupling to the messenger sector can result in the realization of the
susy breaking vacuum even if the reheating temperature is high. We show that
this can be achieved without jeopardizing the low energy phenomenology. In
addition, we have found that deforming the models by a supersymmetric mass term
for messengers in such a way that the susy breaking minimum and the susy
preserving minima are all far away from the origin does not change the
conclusions. The basic observations are expected to hold also in the case of
models with an anomalous U(1) group.Comment: 28 pages, 4 figures, plain Latex, journal versio
A genome-wide association study identifies protein quantitative trait loci (pQTLs)
There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al
Electroweak Baryogenesis and Dark Matter with an approximate R-symmetry
It is well known that R-symmetric models dramatically alleviate the SUSY
flavor and CP problems. We study particular modifications of existing
R-symmetric models which share the solution to the above problems, and have
interesting consequences for electroweak baryogenesis and the Dark Matter (DM)
content of the universe. In particular, we find that it is naturally possible
to have a strongly first-order electroweak phase transition while
simultaneously relaxing the tension with EDM experiments. The R-symmetry (and
its small breaking) implies that the gauginos (and the neutralino LSP) are
pseudo-Dirac fermions, which is relevant for both baryogenesis and DM. The
singlet superpartner of the U(1)_Y pseudo-Dirac gaugino plays a prominent role
in making the electroweak phase transition strongly first-order. The
pseudo-Dirac nature of the LSP allows it to behave similarly to a Dirac
particle during freeze-out, but like a Majorana particle for annihilation today
and in scattering against nuclei, thus being consistent with current
constraints. Assuming a standard cosmology, it is possible to simultaneously
have a strongly first-order phase transition conducive to baryogenesis and have
the LSP provide the full DM relic abundance, in part of the allowed parameter
space. However, other possibilities for DM also exist, which are discussed. It
is expected that upcoming direct DM searches as well as neutrino signals from
DM annihilation in the Sun will be sensitive to this class of models.
Interesting collider and Gravity-wave signals are also briefly discussed.Comment: 50 pages, 10 figure
Flavor Mediation Delivers Natural SUSY
If supersymmetry (SUSY) solves the hierarchy problem, then naturalness
considerations coupled with recent LHC bounds require non-trivial superpartner
flavor structures. Such "Natural SUSY" models exhibit a large mass hierarchy
between scalars of the third and first two generations as well as degeneracy
(or alignment) among the first two generations. In this work, we show how this
specific beyond the standard model (SM) flavor structure can be tied directly
to SM flavor via "Flavor Mediation". The SM contains an anomaly-free SU(3)
flavor symmetry, broken only by Yukawa couplings. By gauging this flavor
symmetry in addition to SM gauge symmetries, we can mediate SUSY breaking via
(Higgsed) gauge mediation. This automatically delivers a natural SUSY spectrum.
Third-generation scalar masses are suppressed due to the dominant breaking of
the flavor gauge symmetry in the top direction. More subtly, the
first-two-generation scalars remain highly degenerate due to a custodial U(2)
symmetry, where the SU(2) factor arises because SU(3) is rank two. This
custodial symmetry is broken only at order (m_c/m_t)^2. SUSY gauge coupling
unification predictions are preserved, since no new charged matter is
introduced, the SM gauge structure is unaltered, and the flavor symmetry treats
all matter multiplets equally. Moreover, the uniqueness of the anomaly-free
SU(3) flavor group makes possible a number of concrete predictions for the
superpartner spectrum.Comment: 17 pages, 7 figures, 2 tables. v2 references added, minor changes to
flavor constraints and a little discussion adde
Direct Mediation and Metastable Supersymmetry Breaking for SO(10)
We examine a metastable Macroscopic SO(N) SQCD model of
Intriligator, Seiberg and Shih (ISS). We introduce various baryon and meson
deformations, including multitrace operators and explore embedding an SO(10)
parent of the standard model into two weakly gauged flavour sectors. Direct
fundamental messengers and the symmetric pseudo-modulus messenger mediate SUSY
breaking to the MSSM. Gaugino and sfermion masses are computed and compared for
each deformation type. We also explore reducing the rank of the magnetic quark
matrix of the ISS model and find an additional fundamental messenger.Comment: 43 pages, Latex. Version to appear in JHEP
Assessing the psychometric and ecometric properties of neighborhood scales using adolescent survey data from urban and rural Scotland
This work was supported by NHS Health Scotland and the University of St Andrews.Background: Despite the well-established need for specific measurement instruments to examine the relationship between neighborhood conditions and adolescent well-being outcomes, few studies have developed scales to measure features of the neighborhoods in which adolescents reside. Moreover, measures of neighborhood features may be operationalised differently by adolescents living in different levels of urban/rurality. This has not been addressed in previous studies. The objectives of this study were to: 1) establish instruments to measure adolescent neighborhood features at both the individual and neighborhood level, 2) assess their psychometric and ecometric properties, 3) test for invariance by urban/rurality, and 4) generate neighborhood level scores for use in further analysis. Methods: Data were from the Scottish 2010 Health Behaviour in School-aged Children Survey, which included an over-sample of rural adolescents. The survey responses of interest came from questions designed to capture different facets of the local area in which each respondent resided. Intermediate data zones were used as proxies for neighborhoods. Internal consistency was evaluated by Cronbach’s alpha. Invariance was examined using confirmatory factor analysis. Multilevel models were used to estimate ecometric properties and generate neighborhood scores. Results: Two constructs labeled neighborhood social cohesion and neighborhood disorder were identified. Adjustment was made to the originally specified model to improve model fit and measures of invariance. At the individual level, reliability was .760 for social cohesion and .765 for disorder, and between .524 and .571 for both constructs at the neighborhood level. Individuals in rural areas experienced greater neighborhood social cohesion and lower levels of neighborhood disorder compared with those in urban areas. Conclusions: The scales are appropriate for measuring neighborhood characteristics experienced by adolescents across urban and rural Scotland, and can be used in future studies of neighborhoods and health. However, trade-offs between neighborhood sample size and reliability must be considered.Publisher PDFPeer reviewe
Theoretical and practical convergence of a self-adaptive penalty algorithm for constrained global optimization
This paper proposes a self-adaptive penalty function and presents a penalty-based algorithm for solving nonsmooth and nonconvex constrained optimization problems. We prove that the general constrained optimization problem is equivalent to a bound constrained problem in the sense that they have the same global solutions. The global minimizer of the penalty function subject to a set of bound constraints may be obtained by a population-based meta-heuristic. Further, a hybrid self-adaptive penalty firefly algorithm, with a local intensification search, is designed, and its convergence analysis is established. The numerical experiments and a comparison with other penalty-based approaches show the effectiveness of the new self-adaptive penalty algorithm in solving constrained global optimization problems.The authors would like to thank the referees, the Associate Editor
and the Editor-in-Chief for their valuable comments and suggestions to improve the paper.
This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT
- Funda¸c˜ao para a Ciˆencia e Tecnologia within the projects UID/CEC/00319/2013 and
UID/MAT/00013/2013.info:eu-repo/semantics/publishedVersio
A Complete Model of Low-Scale Gauge Mediation
Recent signs of a Standard Model-like Higgs at 125 GeV point towards large
A-terms in the MSSM. This presents special challenges for gauge mediation,
which by itself predicts vanishing A-terms at the messenger scale. In this
paper, we review the general problems that arise when extending gauge mediation
to achieve large A-terms, and the mechanisms that exist to overcome them. Using
these mechanisms, we construct weakly-coupled models of low-scale gauge
mediation with extended Higgs-messenger couplings that generate large A-terms
at the messenger scale and viable mu/B_mu-terms. Our models are simple,
economical, and complete realizations of supersymmetry at the weak scale.Comment: 33 pages; v2: refs added, minor change
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