Model Analysis of Time Reversal Symmetry Test in the Caltech Fe-57 Gamma-Transition Experiment

The CALTECH gamma-transition experiment testing time reversal symmetry via the E2/M1 mulipole mixing ratio of the 122 keV gamma-line in Fe-57 has already been performed in 1977. Extending an earlier analysis in terms of an effective one-body potential, this experiment is now analyzed in terms of effective one boson exchange T-odd P-even nucleon nucleon potentials. Within the model space considered for the Fe-57 nucleus no contribution from isovector rho-type exchange is possible. The bound on the coupling strength phi_A from effective short range axial-vector type exchange induced by the experimental bound on sin(eta) leads to phi_A < 10^{-2}.Comment: 5 pages, RevTex 3.

Inflation, cold dark matter, and the central density problem

A problem with high central densities in dark halos has arisen in the context of LCDM cosmologies with scale-invariant initial power spectra. Although n=1 is often justified by appealing to the inflation scenario, inflationary models with mild deviations from scale-invariance are not uncommon and models with significant running of the spectral index are plausible. Even mild deviations from scale-invariance can be important because halo collapse times and densities depend on the relative amount of small-scale power. We choose several popular models of inflation and work out the ramifications for galaxy central densities. For each model, we calculate its COBE-normalized power spectrum and deduce the implied halo densities using a semi-analytic method calibrated against N-body simulations. We compare our predictions to a sample of dark matter-dominated galaxies using a non-parametric measure of the density. While standard n=1, LCDM halos are overdense by a factor of 6, several of our example inflation+CDM models predict halo densities well within the range preferred by observations. We also show how the presence of massive (0.5 eV) neutrinos may help to alleviate the central density problem even with n=1. We conclude that galaxy central densities may not be as problematic for the CDM paradigm as is sometimes assumed: rather than telling us something about the nature of the dark matter, galaxy rotation curves may be telling us something about inflation and/or neutrinos. An important test of this idea will be an eventual consensus on the value of sigma_8, the rms overdensity on the scale 8 h^-1 Mpc. Our successful models have values of sigma_8 approximately 0.75, which is within the range of recent determinations. Finally, models with n>1 (or sigma_8 > 1) are highly disfavored.Comment: 13 pages, 6 figures. Minor changes made to reflect referee's Comments, error in Eq. (18) corrected, references updated and corrected, conclusions unchanged. Version accepted for publication in Phys. Rev. D, scheduled for 15 August 200

Pharmaceuticals and personal care products in the environment: What are the big questions?

Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.Centro de Investigaciones del Medioambient

Clusters of galaxies: setting the stage

Clusters of galaxies are self-gravitating systems of mass ~10^14-10^15 Msun. They consist of dark matter (~80 %), hot diffuse intracluster plasma (< 20 %) and a small fraction of stars, dust, and cold gas, mostly locked in galaxies. In most clusters, scaling relations between their properties testify that the cluster components are in approximate dynamical equilibrium within the cluster gravitational potential well. However, spatially inhomogeneous thermal and non-thermal emission of the intracluster medium (ICM), observed in some clusters in the X-ray and radio bands, and the kinematic and morphological segregation of galaxies are a signature of non-gravitational processes, ongoing cluster merging and interactions. In the current bottom-up scenario for the formation of cosmic structure, clusters are the most massive nodes of the filamentary large-scale structure of the cosmic web and form by anisotropic and episodic accretion of mass. In this model of the universe dominated by cold dark matter, at the present time most baryons are expected to be in a diffuse component rather than in stars and galaxies; moreover, ~50 % of this diffuse component has temperature ~0.01-1 keV and permeates the filamentary distribution of the dark matter. The temperature of this Warm-Hot Intergalactic Medium (WHIM) increases with the local density and its search in the outer regions of clusters and lower density regions has been the quest of much recent observational effort. Over the last thirty years, an impressive coherent picture of the formation and evolution of cosmic structures has emerged from the intense interplay between observations, theory and numerical experiments. Future efforts will continue to test whether this picture keeps being valid, needs corrections or suffers dramatic failures in its predictive power.Comment: 20 pages, 8 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 2; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Targeting the PD-1/PD-L1 Axis for the Treatment of Non-Small-Cell Lung Cancer

Lung cancer is the leading cause of cancer-specific death among Canadians, with non-small-cell lung cancer (NSCLC) being the most common histologic variant. Despite advances in the understanding of the molecular biology of NSCLC, the survival rate for this malignancy is still poor. It is now understood that, to evade detection and immune clearance, NSCLC tumours overexpress the immunosuppressive checkpoint protein programmed death ligand 1 (PD-L1). Inhibiting the PD-1/PD-L1 axis with monoclonal antibodies has significantly changed the treatment landscape in NSCLC during the last 5 years. Despite evidence of clinical response in some patients, only approximately 20% of patients obtain any durable benefit, and many of the patients who do respond ultimately relapse with drug-resistant disease. The identification of patients who are most likely to benefit from such therapy is therefore important. In the present review, we cover the basics of the PD-1/PD-L1 axis and its clinical significance in NSCLC, biomarkers that are predictive of treatment response, relevant clinical trials of PD-1/PD-L1 blockade completed to date, and proposed mechanisms of acquired therapeutic resistance