887 research outputs found
Coreceptor affinity for MHC defines peptide specificity requirements for TCR interaction with coagonist peptide-MHC
The Minimal Phantom Sector of the Standard Model: Higgs Phenomenology and Dirac Leptogenesis
We propose the minimal, lepton-number conserving, SU(3)xSU(2)xU(1)
gauge-singlet, or phantom, extension of the Standard Model. The extension is
natural in the sense that all couplings are of O(1) or forbidden due to a
phantom sector global U(1)_D symmetry, and basically imitates the standard
Majorana see-saw mechanism. Spontaneous breaking of the U(1)_D symmetry
triggers consistent electroweak gauge symmetry breaking only if it occurs at a
scale compatible with small Dirac neutrino masses and baryogenesis through
Dirac leptogenesis. Dirac leptogenesis proceeds through the usual
out-of-equilibrium decay scenario, leading to left and right-handed neutrino
asymmetries that do not fully equilibrate after they are produced. The model
contains two physical Higgs bosons and a massless Goldstone boson. The
existence of the Goldstone boson suppresses the Higgs to bb branching ratio and
instead the Higgs bosons will mainly decay to invisible Goldstone and/or to
visible vector boson pairs. In a representative scenario, we estimate that with
30 fb^-1 integrated luminosity, the LHC could discover this invisibly decaying
Higgs, with mass ~120 GeV. At the same time a significantly heavier, partner
Higgs boson with mass ~210 GeV could be found through its vector boson decays.
Electroweak constraints as well as astrophysical and cosmological implications
are analysed and discussed.Comment: 21 pages, 4 figures. Corrected typos and added references. To appear
in JHE
Age-Related Differences in Susceptibility to Carcinogenesis: A Quantitative Analysis of Empirical Animal Bioassay Data
In revising cancer risk assessment guidelines, the U.S. Environmental Protection Agency (EPA) analyzed animal cancer bioassay data over different periods of life. In this article, we report an improved analysis of these data (supplemented with some chemical carcinogenesis observations not included in the U.S. EPA’s original analysis) and animal bioassay studies of ionizing radiation. We use likelihood methods to avoid excluding cases where no tumors were observed in specific groups. We express dosage for animals of different weights on a metabolically consistent basis (concentration in air or food, or per unit body weight to the three-quarters power). Finally, we use a system of dummy variables to represent exposures during fetal, preweaning, and weaning–60-day postnatal periods, yielding separate estimates of relative sensitivity per day of dosing in these intervals. Central estimate results indicate a 5- to 60-fold increased carcinogenic sensitivity in the birth–weaning period per dose ÷ (body weight(0.75)-day) for mutagenic carcinogens and a somewhat smaller increase—centered about 5-fold—for radiation carcinogenesis per gray. Effects were greater in males than in females. We found a similar increased sensitivity in the fetal period for direct-acting nitrosoureas, but no such increased fetal sensitivity was detected for carcinogens requiring metabolic activation. For the birth–weaning period, we found an increased sensitivity for direct administration to the pups similar to that found for indirect exposure via lactation. Radiation experiments indicated that carcinogenic sensitivity is not constant through the “adult” period, but the dosage delivered in 12- to 21-month-old animals appears a few-fold less effective than the comparable dosage delivered in young adults (90–105 days of age)
Constraining noncommutative field theories with holography
An important window to quantum gravity phenomena in low energy noncommutative
(NC) quantum field theories (QFTs) gets represented by a specific form of UV/IR
mixing. Yet another important window to quantum gravity, a holography,
manifests itself in effective QFTs as a distinct UV/IR connection. In matching
these two principles, a useful relationship connecting the UV cutoff
, the IR cutoff and the scale of
noncommutativity , can be obtained. We show that an effective
QFT endowed with both principles may not be capable to fit disparate
experimental bounds simultaneously, like the muon and the masslessness of
the photon. Also, the constraints from the muon preclude any possibility
to observe the birefringence of the vacuum coming from objects at cosmological
distances. On the other hand, in NC theories without the UV completion, where
the perturbative aspect of the theory (obtained by truncating a power series in
) becomes important, a heuristic estimate of the region
where the perturbative expansion is well-defined , gets affected when holography is applied by providing the energy of the
system a -dependent lower limit. This may affect models
which try to infer the scale by using data from low-energy
experiments.Comment: 4 pages, version to be published in JHE
Brief Report: AIP Mutation in Pituitary Adenomas in the 18th Century and Today
From New England Journal of Medicine, Volume 364, issue 1, p.43-50. Copyright © (2011) Massachusetts Medical Society. Reprinted with permission.Gigantism results when a growth hormone–secreting pituitary adenoma is present
before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of
an Irish patient who lived from 1761 to 1783,1-3 he noted an enlarged pituitary
fossa. We extracted DNA from the patient’s teeth and identified a germline mutation
in the aryl hydrocarbon–interacting protein gene (AIP). Four contemporary
Northern Irish families who presented with gigantism, acromegaly, or prolactinoma
have the same mutation and haplotype associated with the mutated gene. Using
coalescent theory, we infer that these persons share a common ancestor who lived
about 57 to 66 generations earlier
Nonequilibrium Dynamics in Noncommutative Spacetime
We study the effects of spacetime noncommutativity on the nonequilibrium
dynamics of particles in a thermal bath. We show that the noncommutative
thermal bath does not suffer from any further IR/UV mixing problem in the sense
that all the finite-temperature non-planar quantities are free from infrared
singularities. We also point out that the combined effect of finite temperature
and noncommutative geometry has a distinct effect on the nonequilibrium
dynamics of particles propagating in a thermal bath: depending on the momentum
of the mode of concern, noncommutative geometry may switch on or switch off
their decay and thermalization. This momentum dependent alternation of the
decay and thermalization rates could have significant impacts on the
nonequilibrium phenomena in the early universe at which spacetime
noncommutativity may be present. Our results suggest a re-examination of some
of the important processes in the early universe such as reheating after
inflation, baryogenesis and the freeze-out of superheavy dark matter
candidates.Comment: 24 pages, 2 figure
Envelope Determinants of Equine Lentiviral Vaccine Protection
Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al
Preventive Digital Mental Health for Children in Primary Schools: Acceptability and Feasibility Study
Background: The incidence of mental health problems in children and adolescents in the United Kingdom has significantly increased in recent years, and more people are in contact with mental health services in Greater Manchester than in other parts of the country. Children and young people spend most of their time at school and with teachers. Therefore, schools and other educational settings may be ideal environments in which to identify those experiencing or those at the risk of developing psychological symptoms and provide timely support for children most at risk of mental health or related problems. Objective: This study aims to test the feasibility of embedding a low-cost, scalable, and innovative digital mental health intervention in schools in the Greater Manchester area. Methods: Two components of a 6-week digital intervention were implemented in a primary school in Greater Manchester: Lexplore, a reading assessment using eye-tracking technology to assess reading ability and detect early atypicality, and Lincus, a digital support and well-being monitoring platform. Results: Of the 115 children approached, 34 (29.6%) consented and took part; of these 34 children, all 34 (100%) completed the baseline Lexplore assessment, and 30 (88%) completed the follow-up. In addition, most children were classified by Lincus as regular (≥1 per week) survey users. Overall, the teaching staff and children found both components of the digital intervention engaging, usable, feasible, and acceptable. Despite the widespread enthusiasm and recognition of the potential added value from staff, we met significant implementation barriers. Conclusions: This study explored the acceptability and feasibility of a digital mental health intervention for schoolchildren. Further work is needed to evaluate the effectiveness of the digital intervention and to understand whether the assessment of reading atypicality using Lexplore can identify those who require additional help and whether they can also be supported by Lincus. This study provides high-quality pilot data and highlights the potential benefits of implementing digital assessment and mental health support tools in a primary school setting
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
Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours
The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the ‘Smallest Region of Overlap of deletions’ in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT–PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics
- …