A theoretical framework for combining techniques that probe the link between galaxies and dark matter

We develop a theoretical framework that combines measurements of galaxy-galaxy lensing, galaxy clustering, and the galaxy stellar mass function in a self-consistent manner. While considerable effort has been invested in exploring each of these probes individually, attempts to combine them are still in their infancy despite the potential of such combinations to elucidate the galaxy-dark matter connection, to constrain cosmological parameters, and to test the nature of gravity. In this paper, we focus on a theoretical model that describes the galaxy-dark matter connection based on standard halo occupation distribution techniques. Several key modifications enable us to extract additional parameters that determine the stellar-to-halo mass relation and to simultaneously fit data from multiple probes while allowing for independent binning schemes for each probe. In a companion paper, we demonstrate that the model presented here provides an excellent fit to galaxy-galaxy lensing, galaxy clustering, and stellar mass functions measured in the COSMOS survey from z=0.2 to z=1.0. We construct mock catalogs from numerical simulations to investigate the effects of sample variance and covariance on each of the three probes. Finally, we analyze and discuss how trends in each of the three observables impact the derived parameters of the model. In particular, we investigate the various features of the observed galaxy stellar mass function (low-mass slope, plateau, knee, and high-mass cut-off) and show how each feature is related to the underlying relationship between stellar and halo mass. We demonstrate that the observed plateau feature in the stellar mass function at Mstellar~2x10^10 Msun is due to the transition that occurs in the stellar-to-halo mass relation at Mhalo ~ 10^12 Msun from a low-mass power-law regime to a sub-exponential function at higher stellar mass.Comment: 21 pages. Accepted to Ap

The role of the dystrophin glycoprotein complex in muscle cell mechanotransduction

Dystrophin is the central protein of the dystrophin-glycoprotein complex (DGC) in skeletal and heart muscle cells. Dystrophin connects the actin cytoskeleton to the extracellular matrix (ECM). Severing the link between the ECM and the intracellular cytoskeleton has a devastating impact on the homeostasis of skeletal muscle cells, leading to a range of muscular dystrophies. In addition, the loss of a functional DGC leads to progressive dilated cardiomyopathy and premature death. Dystrophin functions as a molecular spring and the DGC plays a critical role in maintaining the integrity of the sarcolemma. Additionally, evidence is accumulating, linking the DGC to mechanosignalling, albeit this role is still less understood. This review article aims at providing an up-to-date perspective on the DGC and its role in mechanotransduction. We first discuss the intricate relationship between muscle cell mechanics and function, before examining the recent research for a role of the dystrophin glycoprotein complex in mechanotransduction and maintaining the biomechanical integrity of muscle cells. Finally, we review the current literature to map out how DGC signalling intersects with mechanical signalling pathways to highlight potential future points of intervention, especially with a focus on cardiomyopathies

Cosmological Constraints from Galaxy Clustering and the Mass-to-Number Ratio of Galaxy Clusters

We place constraints on the average density (Omega_m) and clustering amplitude (sigma_8) of matter using a combination of two measurements from the Sloan Digital Sky Survey: the galaxy two-point correlation function, w_p, and the mass-to-galaxy-number ratio within galaxy clusters, M/N, analogous to cluster M/L ratios. Our w_p measurements are obtained from DR7 while the sample of clusters is the maxBCG sample, with cluster masses derived from weak gravitational lensing. We construct non-linear galaxy bias models using the Halo Occupation Distribution (HOD) to fit both w_p and M/N for different cosmological parameters. HOD models that match the same two-point clustering predict different numbers of galaxies in massive halos when Omega_m or sigma_8 is varied, thereby breaking the degeneracy between cosmology and bias. We demonstrate that this technique yields constraints that are consistent and competitive with current results from cluster abundance studies, even though this technique does not use abundance information. Using w_p and M/N alone, we find Omega_m^0.5*sigma_8=0.465+/-0.026, with individual constraints of Omega_m=0.29+/-0.03 and sigma_8=0.85+/-0.06. Combined with current CMB data, these constraints are Omega_m=0.290+/-0.016 and sigma_8=0.826+/-0.020. All errors are 1-sigma. The systematic uncertainties that the M/N technique are most sensitive to are the amplitude of the bias function of dark matter halos and the possibility of redshift evolution between the SDSS Main sample and the maxBCG sample. Our derived constraints are insensitive to the current level of uncertainties in the halo mass function and in the mass-richness relation of clusters and its scatter, making the M/N technique complementary to cluster abundances as a method for constraining cosmology with future galaxy surveys.Comment: 23 pages, submitted to Ap

K-ATP channel gene expression is induced by urocortin and mediates its cardioprotective effect

Background-Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion.Methods and Results-We have analyzed global changes in gone expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific K-ATP channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia.Conclusions-This is, to our knowledge, the first report of the altered expression of a K-ATP. channel subunit induced by a cardioprotective agent and demonstrates that K-ATP, channel opening is essential for the effect of this novel cardioprotective agent

Energetic Demands of Immature Sea Otters From Birth to Weaning: Implications for Maternal Costs, Reproductive Behavior and Population-Level Trends

Sea otters (Enhydra lutris) have the highest mass-specific metabolic rate of any marine mammal, which is superimposed on the inherently high costs of reproduction and lactation in adult females. These combined energetic demands have been implicated in the poor body condition and increased mortality of female sea otters nearing the end of lactation along the central California coast. However, the cost of lactation is unknown and currently cannot be directly measured for this marine species in the wild. Here, we quantified the energetic demands of immature sea otters across five developmental stages as a means of assessing the underlying energetic challenges associated with pup rearing that may contribute to poor maternal condition. Activity-specific metabolic rates, daily activity budgets and field metabolic rates (FMR) were determined for each developmental stage. Mean FMR of pre-molt pups was 2.29±0.81 MJ day−1 and increased to 6.16±2.46 and 7.41±3.17 MJ day−1 in post-molt pups and dependent immature animals, respectively. Consequently, daily energy demands of adult females increase 17% by 3 weeks postpartum and continue increasing to 96% above pre-pregnancy levels by the average age of weaning. Our results suggest that the energetics of pup rearing superimposed on small body size, marine living and limited on-board energetic reserves conspire to make female sea otters exceptionally vulnerable to energetic shortfalls. By controlling individual fitness, maternal behavior and pup provisioning strategies, this underlying metabolic challenge appears to be a major factor influencing current population trends in southern sea otters (Enhydra lutris nereis)

Copper modulates zinc metalloproteinase-dependent ectodomain shedding of key signaling and adhesion proteins and promotes the invasion of prostate cancer epithelial cells

A disintegrin and metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs) are zinc metalloproteinases (ZMPs) that catalyse the 'ectodomain shedding' of a range of cell surface proteins including signalling and adhesion molecules. These 'sheddases' are associated with the invasion and metastasis of a range of cancers. Increased serum and tumour tissue levels of copper are also observed in several cancers although little is known about how the metal might promote disease progression at the molecular level. In the current study, we investigated whether copper might regulate the ectodomain shedding of two key cell surface proteins implicated in the invasion and metastasis of prostate cancer, the Notch ligand Jagged1 and the adhesion molecule E-cadherin, and whether the metal was able to influence the invasion of the prostate cancer epithelial cell line PC3. Physiological copper concentrations stimulated the ZMP-mediated proteolysis of Jagged1 and E-cadherin in cell culture models whilst other divalent metals had no effect. Copper-mediated Jagged1 proteolysis was also observed following the pre-treatment of cells with cycloheximide and in a cell-free membrane system, indicating a post-translational mechanism of sheddase activation. Finally, the concentrations of copper that stimulated ZMP-mediated protein shedding also enhanced PC3 invasion; an effect which could be negated using a sheddase inhibitor or copper chelators. Collectively, these data implicate copper as an important factor in promoting prostate cancer cell invasion and indicate that the selective post-translational activation of ZMP-mediated protein shedding might play a role in this process.

Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2)

Càncer d'ovaris; Biomarcadors tumoralsCáncer de ovarios; Biomarcadores tumoralesOvarian cancer; Tumour biomarkersARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

Cosmological Constraints from the Large Scale Weak Lensing of SDSS MaxBCG Clusters

We derive constraints on the matter density \Om and the amplitude of matter clustering \sig8 from measurements of large scale weak lensing (projected separation R=5-30\hmpc) by clusters in the Sloan Digital Sky Survey MaxBCG catalog. The weak lensing signal is proportional to the product of \Om and the cluster-mass correlation function \xicm. With the relation between optical richness and cluster mass constrained by the observed cluster number counts, the predicted lensing signal increases with increasing \Om or \sig8, with mild additional dependence on the assumed scatter between richness and mass. The dependence of the signal on scale and richness partly breaks the degeneracies among these parameters. We incorporate external priors on the richness-mass scatter from comparisons to X-ray data and on the shape of the matter power spectrum from galaxy clustering, and we test our adopted model for \xicm against N-body simulations. Using a Bayesian approach with minimal restrictive priors, we find \sig8(\Om/0.325)^{0.501}=0.828 +/- 0.049, with marginalized constraints of \Om=0.325_{-0.067}^{+0.086} and \sig8=0.828_{-0.097}^{+0.111}, consistent with constraints from other MaxBCG studies that use weak lensing measurements on small scales (R<=2\hmpc). The (\Om,\sig8) constraint is consistent with and orthogonal to the one inferred from WMAP CMB data, reflecting agreement with the structure growth predicted by GR for an LCDM cosmological model. A joint constraint assuming LCDM yields \Om=0.298 +/- 0.020 and \sig8=0.831 +/- 0.020. Our cosmological parameter errors are dominated by the statistical uncertainties of the large scale weak lensing measurements, which should shrink sharply with current and future imaging surveys.Comment: 20 pages, 12 figures, MNRAS Submitted. For a brief video explaining the key result of this paper, see http://www.youtube.com/user/OSUAstronomy, or http://v.youku.com/v_show/id_XNDI3ODA3NzY4.html in countries where YouTube is not accessibl