Optimizing high redshift galaxy surveys for environmental information

We investigate the performance of group finding algorithms that reconstruct galaxy groups from the positional information of tracer galaxies that are observed in redshift surveys carried out with multiplexed spectrographs. We use mock light-cones produced by the L-Galaxies semi-analytic model of galaxy evolution in which the underlying reality is known. We particularly focus on the performance at high redshift, and how this is affected by choices of the mass of the tracer galaxies (largely equivalent to their co-moving number density) and the (assumed random) sampling rate of these tracers. We first however compare two different approaches to group finding as applied at low redshift, and conclude that these are broadly comparable. For simplicity we adopt just one of these, "Friends-of-Friends" (FoF) as the basis for our study at high redshift. We introduce 12 science metrics that are designed to quantify the performance of the group-finder as relevant for a wide range of science investigations with a group catalogue. These metrics examine the quality of the recovered group catalogue, the median halo masses of different richness structures, the scatter in dark matter halo mass and how successful the group-finder classifies singletons, centrals and satellites. We analyze how these metrics vary with the limiting stellar mass and random sampling rate of the tracer galaxies, allowing quantification of the various trade-offs between different possible survey designs. Finally, we look at the impact of these same design parameters on the relative "costs" in observation time of the survey using as an example the potential MOONRISE survey using the MOONS instrument.ERC STF

Higgs and Dark Matter Hints of an Oasis in the Desert

Recent LHC results suggest a standard model (SM)-like Higgs boson in the vicinity of 125 GeV with no clear indications yet of physics beyond the SM. At the same time, the SM is incomplete, since additional dynamics are required to accommodate cosmological dark matter (DM). In this paper we show that interactions between weak scale DM and the Higgs which are strong enough to yield a thermal relic abundance consistent with observation can easily destabilize the electroweak vacuum or drive the theory into a non-perturbative regime at a low scale. As a consequence, new physics--beyond the DM itself--must enter at a cutoff well below the Planck scale and in some cases as low as O(10 - 1000 TeV), a range relevant to indirect probes of flavor and CP violation. In addition, this cutoff is correlated with the DM mass and scattering cross-section in a parameter space which will be probed experimentally in the near term. Specifically, we consider the SM plus additional spin 0 or 1/2 states with singlet, triplet, or doublet electroweak quantum numbers and quartic or Yukawa couplings to the Higgs boson. We derive explicit expressions for the full two-loop RGEs and one-loop threshold corrections for these theories.Comment: 29 pages, 13 figure

Low Scale Flavor Gauge Symmetries

We study the possibility of gauging the Standard Model flavor group. Anomaly cancellation leads to the addition of fermions whose mass is inversely proportional to the known fermion masses. In this case all flavor violating effects turn out to be controlled roughly by the Standard Model Yukawa, suppressing transitions for the light generations. Due to the inverted hierarchy the scale of new gauge flavor bosons could be as low as the electroweak scale without violating any existing bound but accessible at the Tevatron and the LHC. The mechanism of flavor protection potentially provides an alternative to Minimal Flavor Violation, with flavor violating effects suppressed by hierarchy of scales rather than couplings.Comment: 24 pages + appendices; v2) Refs. added and numerical examples improved. Results unchanged; v3) small typos in appendix B correcte

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program

Adding 5-hydroxytryptamine receptor type 3 antagonists may reduce drug-induced nausea in poor insight obsessive-compulsive patients taking off-label doses of selective serotonin reuptake inhibitors: a 52-week follow-up case report

Poor-insight obsessive-compulsive disorder (PI-OCD) is a severe form of OCD where the 'typically obsessive' features of intrusive, 'egodystonic' feelings and thoughts are absent. PI-OCD is difficult to treat, often requiring very high doses of serotonergic drugs as well as antipsychotic augmentation. When this occurs, unpleasant side effects as nausea are common, eventually further reducing compliance to medication and increasing the need for pharmacological alternatives. We present the case of a PI-OCD patient who developed severe nausea after response to off-label doses of the selective serotonin reuptake inhibitor (SSRI), fluoxetine. Drug choices are discussed, providing pharmacodynamic rationales and hypotheses along with reports of rating scale scores, administered within a follow-up period of 52 weeks. A slight reduction of fluoxetine dose, augmentation with mirtazapine and a switch from amisulpride to olanzapine led to resolution of nausea while preserving the anti-OCD therapeutic effect. Mirtazapine and olanzapine have already been suggested for OCD treatment, although a lack of evidence exists about their role in the course of PI-OCD. Both mirtazapine and olanzapine also act as 5-hydroxytryptamine receptor type 3 (5-HT3) blockers, making them preferred choices especially in cases of drug-induced nausea

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

Sparticle Spectrum of Large Volume Compactification

We examine the large volume compactification of Type IIB string theory or its F theory limit and the associated supersymmetry breakdown and soft terms. It is crucial to incorporate the loop-induced moduli mixing, originating from radiative corrections to the Kahler potential. We show that in the presence of moduli mixing, soft scalar masses generically receive a D-term contribution of the order of the gravitino mass m_{3/2} when the visible sector cycle is stabilized by the D-term potential of an anomalous U(1) gauge symmetry, while the moduli-mediated gaugino masses and A-parameters tend to be of the order of m_{3/2}/8pi^2. It is noticed also that a too large moduli mixing can destabilize the large volume solution by making it a saddle point.Comment: 29 page

Algometry with a clothes peg compared to an electronic pressure algometer: a randomized cross-sectional study in pain patients

<p>Abstract</p> <p>Background</p> <p>Hypersensitivity of the central nervous system is widely present in pain patients and recognized as one of the determinants of chronic pain and disability. Electronic pressure algometry is often used to explore aspects of central hypersensitivity. We hypothesized that a simple pain provocation test with a clothes peg provides information on pain sensitivity that compares meaningfully to that obtained by a well-established electronic pressure algometer. "Clinically meaningful" was defined as a medium (r = 0.3-0.5) or high (r > 0.5) correlation coefficient according to Cohen's conventions.</p> <p>Methods</p> <p>We tested 157 in-patients with different pain types. A calibrated clothes peg was applied for 10 seconds and patients rated the pain intensity on a 0 to 10 numerical rating scale. Pressure pain detection threshold (PPdt) and pressure pain tolerance threshold (PPtt) were measured with a standard electronic algometer. Both methods were performed on both middle fingers and ear lobes. In a subgroup of 47 patients repeatability (test-retest reliability) was calculated.</p> <p>Results</p> <p>Clothes peg values correlated with PPdt values for finger testing with r = -0.54 and for earlobe testing with r = -0.55 (all p-values < 0.001). Clothes peg values also correlated with PPtt values for finger testing with r = -0.55 (p < 0.001). Test-retest reliability (repeatability) showed equally stable results for clothes peg algometry and the electronic algometer (all r-values > 0.89, all p-values < 0.001).</p> <p>Conclusions</p> <p>Information on pain sensitivity provided by a calibrated clothes peg and an established algometer correlate at a clinically meaningful level.</p

Composite GUTs: models and expectations at the LHC

We investigate grand unified theories (GUTs) in scenarios where electroweak (EW) symmetry breaking is triggered by a light composite Higgs, arising as a Nambu-Goldstone boson from a strongly interacting sector. The evolution of the standard model (SM) gauge couplings can be predicted at leading order, if the global symmetry of the composite sector is a simple group G that contains the SM gauge group. It was noticed that, if the right-handed top quark is also composite, precision gauge unification can be achieved. We build minimal consistent models for a composite sector with these properties, thus demonstrating how composite GUTs may represent an alternative to supersymmetric GUTs. Taking into account the new contributions to the EW precision parameters, we compute the Higgs effective potential and prove that it realizes consistently EW symmetry breaking with little fine-tuning. The G group structure and the requirement of proton stability determine the nature of the light composite states accompanying the Higgs and the top quark: a coloured triplet scalar and several vector-like fermions with exotic quantum numbers. We analyse the signatures of these composite partners at hadron colliders: distinctive final states contain multiple top and bottom quarks, either alone or accompanied by a heavy stable charged particle, or by missing transverse energy.Comment: 55 pages, 13 figures, final version to be published in JHE