Assortative Matching or Exclusionary Hiring? The Impact of Firm Policies on Racial Wage Differences in Brazil

A growing body of research shows that firms' employment and wage-setting policies contribute to wage inequality and pay disparities between groups. We measure the effects of these policies on racial pay differences in Brazil. We find that nonwhites are less likely to work at establishments that pay more to all race groups, a pattern that explains about 20% of the white-nonwhite wage gap for both genders. The pay premiums offered by different employers are also compressed for nonwhites relative to whites, contributing another 5% of the overall gap. We then ask how much of the under-representation of nonwhites at higher-paying workplaces is due to the selective skill mix at these establishments. Using a counterfactual based on the observed skill distribution at each establishment and the nonwhite shares in different skill groups in the local labor market, we conclude that assortative matching accounts for about two-thirds of the under-representation gap for both men and women. The remainder reflects an unexplained preference for white workers at higher-paying establishments. The wage losses associated with unexplained sorting and differential wage setting are largest for nonwhites with the highest levels of general skills, suggesting that the allocative costs of race-based preferences may be relatively large in Brazil

An Insulating Glass Knowledge Base

This report will discuss issues relevant to Insulating Glass (IG) durability performance by presenting the observations and developed conclusions in a logical sequential format. This concluding effort discusses Phase II activities and focuses on beginning to quantifying IG durability issues while continuing the approach presented in the Phase I activities (Appendix 1) which discuss a qualitative assessment of durability issues. Phase II developed a focus around two specific IG design classes previously presented in Phase I of this project. The typical box spacer and thermoplastic spacer design including their Failure Modes and Effect Analysis (FMEA) and Fault Tree diagrams were chosen to address two currently used IG design options with varying components and failure modes. The system failures occur due to failures of components or their interfaces. Efforts to begin quantifying the durability issues focused on the development and delivery of an included computer based IG durability simulation program. The focus/effort to deliver the foundation for a comprehensive IG durability simulation tool is necessary to address advancements needed to meet current and future building envelope energy performance goals. This need is based upon the current lack of IG field failure data and the lengthy field observation time necessary for this data collection. Ultimately, the simulation program is intended to be used by designers throughout the current and future industry supply chain. Its use is intended to advance IG durability as expectations grow around energy conservation and with the growth of embedded technologies as required to meet energy needs. In addition the tool has the immediate benefit of providing insight for research and improvement prioritization. Included in the simulation model presentation are elements and/or methods to address IG materials, design, process, quality, induced stress (environmental and other factors), validation, etc. In addition, acquired data is presented in support of project and model assumptions. Finally, current and suggested testing protocol and procedure for future model validation and IG physical testing are discussed

Galaxy formation in the Planck cosmology - I. Matching the observed evolution of star formation rates, colours and stellar masses

We have updated the Munich galaxy formation model to the Planck first-year cosmology, while modifying the treatment of baryonic processes to reproduce recent data on the abundance and passive fractions of galaxies from z = 3 down to z = 0. Matching these more extensive and more precise observational results requires us to delay the reincorporation of wind ejecta, to lower the surface density threshold for turning cold gas into stars, to eliminate ram-pressure stripping in haloes less massive than ∼1014 M⊙, and to modify our model for radio mode feedback. These changes cure the most obvious failings of our previous models, namely the overly early formation of low-mass galaxies and the overly large fraction of them that are passive at late times. The new model is calibrated to reproduce the observed evolution both of the stellar mass function and of the distribution of star formation rate at each stellar mass. Massive galaxies (log M⋆/M⊙ ≥ 11.0) assemble most of their mass before z = 1 and are predominantly old and passive at z = 0, while lower mass galaxies assemble later and, for log M⋆/M⊙ ≤ 9.5, are still predominantly blue and star forming at z = 0. This phenomenological but physically based model allows the observations to be interpreted in terms of the efficiency of the various processes that control the formation and evolution of galaxies as a function of their stellar mass, gas content, environment and time

Pathogenic variants in the human m(6)A reader YTHDC2 are associated with primary ovarian insufficiency

Primary ovarian insufficiency (POI) affects 1% of women and carries significant medical and psychosocial sequelae. Approximately 10% of POI has a defined genetic cause, with most implicated genes relating to biological processes involved in early fetal ovary development and function. Recently, Ythdc2, an RNA helicase and N6-methyladenosine reader, has emerged as a regulator of meiosis in mice. Here, we describe homozygous pathogenic variants in YTHDC2 in 3 women with early-onset POI from 2 families: C. 2567C>G, p.P856R in the helicase-associated (HA2) domain and c.1129G>T, p.E377*. We demonstrated that YTHDC2 is expressed in the developing human fetal ovary and is upregulated in meiotic germ cells, together with related meiosisassociated factors. The p.P856R variant resulted in a less flexible protein that likely disrupted downstream conformational kinetics of the HA2 domain, whereas the p.E377*variant truncated the helicase core. Taken together, our results reveal that YTHDC2 is a key regulator of meiosis in humans and pathogenic variants within this gene are associated with POI

Update on HHV-8-Associated Malignancies

The human herpesvirus 8 (HHV-8) is the oncogenic virus associated with Kaposi’s sarcoma (KS) and lymphoproliferative disorders, namely, primary effusion lymphoma and multicentric Castleman’s disease. KS is among the most common malignancies seen in HIV-infected patients despite the decreased incidence of KS in the era of highly active antiretroviral therapy. Advances in molecular pathology reveal HHV-8 tumorigenesis is mediated through molecular mimicry wherein viral-encoded proteins can activate several cellular signaling cascades while evading immune surveillance. This knowledge has led to the evolution of multiple therapeutic strategies against specific molecular targets. Many such therapeutic modalities have shown activity, but none have proven to be curative. Identifying possible prognostic factors is another active area of research. This review summarizes the recent developments in the fields of virus transmission, molecular biology, and treatment of HHV-8-related neoplasms

A conserved NR5A1-responsive enhancer regulates SRY in testis-determination

International audienceThe Y-linked SRY gene initiates mammalian testis-determination. However, how the expression of SRY is regulated remains elusive. Here, we demonstrate that a conserved steroidogenic factor-1 (SF-1)/NR5A1 binding enhancer is required for appropriate SRY expression to initiate testis-determination in humans. Comparative sequence analysis of SRY 5’ regions in mammals identified an evolutionary conserved SF-1/NR5A1-binding motif within a 250 bp region of open chromatin located 5 kilobases upstream of the SRY transcription start site. Genomic analysis of 46,XY individuals with disrupted testis-determination, including a large multigenerational family, identified unique single-base substitutions of highly conserved residues within the SF-1/NR5A1-binding element. In silico modelling and in vitro assays demonstrate the enhancer properties of the NR5A1 motif. Deletion of this hemizygous element by genome-editing, in a novel in vitro cellular model recapitulating human Sertoli cell formation, resulted in a significant reduction in expression of SRY . Therefore, human NR5A1 acts as a regulatory switch between testis and ovary development by upregulating SRY expression, a role that may predate the eutherian radiation. We show that disruption of an enhancer can phenocopy variants in the coding regions of SRY that cause human testis dysgenesis. Since disease causing variants in enhancers are currently rare, the regulation of gene expression in testis-determination offers a paradigm to define enhancer activity in a key developmental process

MicroRNA-122 Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells and Sensitizes These Cells to Sorafenib*

MicroRNAs are negative regulators of protein coding genes. The liver-specific microRNA-122 (miR-122) is frequently suppressed in primary hepatocellular carcinomas (HCCs). In situ hybridization demonstrated that miR-122 is abundantly expressed in hepatocytes but barely detectable in primary human HCCs. Ectopic expression of miR-122 in nonexpressing HepG2, Hep3B, and SK-Hep-1 cells reversed their tumorigenic properties such as growth, replication potential, clonogenic survival, anchorage-independent growth, migration, invasion, and tumor formation in nude mice. Further, miR-122-expressing HCC cells retained an epithelial phenotype that correlated with reduced Vimentin expression. ADAM10 (a distintegrin and metalloprotease family 10), serum response factor (SRF), and insulin-like growth factor 1 receptor (Igf1R) that promote tumorigenesis were validated as targets of miR-122 and were repressed by the microRNA. Conversely, depletion of the endogenous miR-122 in Huh-7 cells facilitated their tumorigenic properties with concomitant up-regulation of these targets. Expression of SRF or Igf1R partially reversed tumor suppressor function of miR-122. Further, miR-122 impeded angiogenic properties of endothelial cells in vitro. Notably, ADAM10, SRF, and Igf1R were up-regulated in primary human HCCs compared with the matching liver tissue. Co-labeling studies demonstrated exclusive localization of miR-122 in the benign livers, whereas SRF predominantly expressed in HCC. More importantly, growth and clonogenic survival of miR-122-expressing HCC cells were significantly reduced upon treatment with sorafenib, a multi-kinase inhibitor clinically effective against HCC. Collectively, these results suggest that the loss of multifunctional miR-122 contributes to the malignant phenotype of HCC cells, and miR-122 mimetic alone or in combination with anticancer drugs can be a promising therapeutic regimen against liver cancer