450 research outputs found
Dynamic sampling schemes for optimal noise learning under multiple nonsmooth constraints
We consider the bilevel optimisation approach proposed by De Los Reyes,
Sch\"onlieb (2013) for learning the optimal parameters in a Total Variation
(TV) denoising model featuring for multiple noise distributions. In
applications, the use of databases (dictionaries) allows an accurate estimation
of the parameters, but reflects in high computational costs due to the size of
the databases and to the nonsmooth nature of the PDE constraints. To overcome
this computational barrier we propose an optimisation algorithm that by
sampling dynamically from the set of constraints and using a quasi-Newton
method, solves the problem accurately and in an efficient way
The gravitino coupling to broken gauge theories applied to the MSSM
We consider gravitino couplings in theories with broken gauge symmetries. In
particular, we compute the single gravitino production cross section in W+ W-
fusion processes. Despite recent claims to the contrary, we show that this
process is always subdominant to gluon fusion processes in the high energy
limit. The full calculation is performed numerically; however, we give analytic
expressions for the cross section in the supersymmetric and electroweak limits.
We also confirm these results with the use of the effective theory of goldstino
interactions.Comment: 26 pages, 4 figure
The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement
Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis
Neutralino versus axion/axino cold dark matter in the 19 parameter SUGRA model
We calculate the relic abundance of thermally produced neutralino cold dark
matter in the general 19 parameter supergravity (SUGRA-19) model. A scan over
GUT scale parameters reveals that models with a bino-like neutralino typically
give rise to a dark matter density \Omega_{\tz_1}h^2\sim 1-1000, i.e. between 1
and 4 orders of magnitude higher than the measured value. Models with higgsino
or wino cold dark matter can yield the correct relic density, but mainly for
neutralino masses around 700-1300 GeV. Models with mixed bino-wino or
bino-higgsino CDM, or models with dominant co-annihilation or A-resonance
annihilation can yield the correct abundance, but such cases are extremely hard
to generate using a general scan over GUT scale parameters; this is indicative
of high fine-tuning of the relic abundance in these cases. Requiring that
m_{\tz_1}\alt 500 GeV (as a rough naturalness requirement) gives rise to a
minimal probably dip in parameter space at the measured CDM abundance. For
comparison, we also scan over mSUGRA space with four free parameters. Finally,
we investigate the Peccei-Quinn augmented MSSM with mixed axion/axino cold dark
matter. In this case, the relic abundance agrees more naturally with the
measured value. In light of our cumulative results, we conclude that future
axion searches should probe much more broadly in axion mass, and deeper into
the axion coupling.Comment: 23 pages including 17 .eps figure
Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?
© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio
A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale
In this era of complete genomes, our knowledge of neuroanatomical circuitry
remains surprisingly sparse. Such knowledge is however critical both for basic
and clinical research into brain function. Here we advocate for a concerted
effort to fill this gap, through systematic, experimental mapping of neural
circuits at a mesoscopic scale of resolution suitable for comprehensive,
brain-wide coverage, using injections of tracers or viral vectors. We detail
the scientific and medical rationale and briefly review existing knowledge and
experimental techniques. We define a set of desiderata, including brain-wide
coverage; validated and extensible experimental techniques suitable for
standardization and automation; centralized, open access data repository;
compatibility with existing resources, and tractability with current
informatics technology. We discuss a hypothetical but tractable plan for mouse,
additional efforts for the macaque, and technique development for human. We
estimate that the mouse connectivity project could be completed within five
years with a comparatively modest budget.Comment: 41 page
Reaction rates and transport in neutron stars
Understanding signals from neutron stars requires knowledge about the
transport inside the star. We review the transport properties and the
underlying reaction rates of dense hadronic and quark matter in the crust and
the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of
Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes,
references updated, overview graphic added in the introduction, improvements
in Sec IV.A.
RAD59 and RAD1 cooperate in translocation formation by single-strand annealing in Saccharomyces cerevisiae
Studies in the budding yeast, Saccharomyces cerevisiae, have demonstrated that a substantial fraction of double-strand break repair following acute radiation exposure involves homologous recombination between repetitive genomic elements. We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically important in this process. We have constructed several rad59 missense alleles to study its function more closely. Characterization of these mutants revealed proportional defects in both translocation formation and spontaneous direct-repeat recombination, which is also thought to occur by SSA. Combining the rad59 missense alleles with a null allele of RAD1, which encodes a subunit of a nuclease required for the removal of non-homologous tails from annealed intermediates, substantially suppressed the low frequency of translocations observed in rad1-null single mutants. These data suggest that at least one role of Rad59 in translocation formation by SSA is supporting the machinery required for cleavage of non-homologous tails
Msh2 Blocks an Alternative Mechanism for Non-Homologous Tail Removal during Single-Strand Annealing in Saccharomyces cerevisiae
Chromosomal translocations are frequently observed in cells exposed to agents that cause DNA double-strand breaks (DSBs), such as ionizing radiation and chemotherapeutic drugs, and are often associated with tumors in mammals. Recently, translocation formation in the budding yeast, Saccharomyces cerevisiae, has been found to occur at high frequencies following the creation of multiple DSBs adjacent to repetitive sequences on non-homologous chromosomes. The genetic control of translocation formation and the chromosome complements of the clones that contain translocations suggest that translocation formation occurs by single-strand annealing (SSA). Among the factors important for translocation formation by SSA is the central mismatch repair (MMR) and homologous recombination (HR) factor, Msh2. Here we describe the effects of several msh2 missense mutations on translocation formation that suggest that Msh2 has separable functions in stabilizing annealed single strands, and removing non-homologous sequences from their ends. Additionally, interactions between the msh2 alleles and a null allele of RAD1, which encodes a subunit of a nuclease critical for the removal of non-homologous tails suggest that Msh2 blocks an alternative mechanism for removing these sequences. These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage
Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron
We report a measurement of the diffractive structure function of
the antiproton obtained from a study of dijet events produced in association
with a leading antiproton in collisions at GeV at the
Fermilab Tevatron. The ratio of at GeV to
obtained from a similar measurement at GeV is compared with
expectations from QCD factorization and with theoretical predictions. We also
report a measurement of the (-Pomeron) and ( of parton in
Pomeron) dependence of at GeV. In the region
, GeV and , is
found to be of the form , which obeys
- factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter
- …