The Relative Occupational Success of Blacks and Whites

macroeconomics, occupational success

ARC: A compact, high-field, fusion nuclear science facility and demonstration power plant with demountable magnets

The affordable, robust, compact (ARC) reactor is the product of a conceptual design study aimed at reducing the size, cost, and complexity of a combined fusion nuclear science facility (FNSF) and demonstration fusion Pilot power plant. ARC is a ∼200–250 MWe tokamak reactor with a major radius of 3.3 m, a minor radius of 1.1 m, and an on-axis magnetic field of 9.2 T. ARC has rare earth barium copper oxide (REBCO) superconducting toroidal field coils, which have joints to enable disassembly. This allows the vacuum vessel to be replaced quickly, mitigating first wall survivability concerns, and permits a single device to test many vacuum vessel designs and divertor materials. The design point has a plasma fusion gain of Q[subscript p] ≈ 13.6, yet is fully non-inductive, with a modest bootstrap fraction of only ∼63%. Thus ARC offers a high power gain with relatively large external control of the current profile. This highly attractive combination is enabled by the ∼23 T peak field on coil achievable with newly available REBCO superconductor technology. External current drive is provided by two innovative inboard RF launchers using 25 MW of lower hybrid and 13.6 MW of ion cyclotron fast wave power. The resulting efficient current drive provides a robust, steady state core plasma far from disruptive limits. ARC uses an all-liquid blanket, consisting of low pressure, slowly flowing fluorine lithium beryllium (FLiBe) molten salt. The liquid blanket is low-risk technology and provides effective neutron moderation and shielding, excellent heat removal, and a tritium breeding ratio ≥ 1.1. The large temperature range over which FLiBe is liquid permits an output blanket temperature of 900 K, single phase fluid cooling, and a high efficiency helium Brayton cycle, which allows for net electricity generation when operating ARC as a Pilot power plant.United States. Department of Energy (Grant DE-FG02-94ER54235)United States. Department of Energy (Grant DE-SC008435)United States. Department of Energy. Office of Fusion Energy Sciences (Grant DE-FC02-93ER54186)National Science Foundation (U.S.) (Grant 1122374

Multipotential stromal cell abundance in cellular bone allograft: comparison with fresh age-matched iliac crest bone and bone marrow aspirate

Aim: To enumerate and characterize multipotential stromal cells (MSCs) in a cellular bone allograft and compare with fresh age-matched iliac crest bone and bone marrow (BM) aspirate. Materials and methods: MSC characterization used functional assays, confocal/scanning electron microscopy and whole-genome microarrays. Resident MSCs were enumerated by flow cytometry following enzymatic extraction. Results: Allograft material contained live osteocytes and proliferative bone-lining cells defined as MSCs by phenotypic and functional capacities. Without cultivation/expansion, the allograft displayed an 'osteoinductive' molecular signature and the presence of CD45-CD271+CD73+CD90+CD105+ MSCs; with a purity over 100-fold that of iliac crest bone. In comparison with BM, MSC numbers enzymatically released from 1 g of cellular allograft were equivalent to approximately 45 ml of BM aspirate. Conclusion: Cellular allograft bone represents a unique nonimmune material rich in MSCs and osteocytes. This osteoinductive graft represents an attractive alternative to autograft bone or composite/synthetic grafts in orthopedics and broader regenerative medicine settings

Single-cell sequencing of iPSC-Dopamine neurons reconstructs disease progression and identifies HDAC4 as a regulator of Parkinson cell phenotypes

Induced pluripotent stem cell (iPSC)-derived dopamine neurons provide an opportunity to model Parkinson’s disease (PD), but neuronal cultures are confounded by asynchronous and heterogeneous appearance of disease phenotypes in vitro. Using high-resolution, single-cell transcriptomic analyses of iPSC-derived dopamine neurons carrying the GBA-N370S PD risk variant, we identified a progressive axis of gene expression variation leading to endoplasmic reticulum stress. Pseudotime analysis of genes differentially expressed (DE) along this axis identified the transcriptional repressor histone deacetylase 4 (HDAC4) as an upstream regulator of disease progression. HDAC4 was mislocalized to the nucleus in PD iPSC-derived dopamine neurons and repressed genes early in the disease axis, leading to late deficits in protein homeostasis. Treatment of iPSC-derived dopamine neurons with HDAC4-modulating compounds upregulated genes early in the DE axis and corrected PD-related cellular phenotypes. Our study demonstrates how single-cell transcriptomics can exploit cellular heterogeneity to reveal disease mechanisms and identify therapeutic targets

Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis

Present investigations suggest that approximately 30% of colorectal cancer (CRC) cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with CRC. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high grade dysplasia were enrolled. Known familial CRC syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE's 1100 short tandem repeat marker set at an average 4 cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with MERLIN analysis package. Linkage analysis revealed three genetic regions with NPL LOD scores ≥ 2.0: Ch. 3q29, LOD 2.61 (p=0.0003); Ch. 4q31.3, LOD 2.13 (p=0.0009); and Ch. 7q31.31, LOD 3.08 (p=0.00008). Affected siblings with increased sharing at the 7q31 locus have an 3.8 year (±3.5) earlier age of CRC onset although this is not statistically significant (p=0.11). No significant linkage was found near genes causing known syndromes or, regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21-q24 region reported to be linked in CRC relative pairs, is supported by our study, albeit a minor peak (LOD 0.9, p=0.02). No known familial cancer genes reside in the 7q31 locus, thus the identified region may contain a novel susceptibility gene responsible for common familial CRC

Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS)

The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188–5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals

Two Chromatin Remodeling Activities Cooperate during Activation of Hormone Responsive Promoters

Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements (HREs) and recruitment of kinases, chromatin remodeling complexes, and coregulators to their target promoters. Here we show that in breast cancer cells the BAF, but not the closely related PBAF complex, is required for progesterone induction of several target genes including MMTV, where it catalyzes localized displacement of histones H2A and H2B and subsequent NF1 binding. PCAF is also needed for induction of progesterone target genes and acetylates histone H3 at K14, an epigenetic mark that interacts with the BAF subunits by anchoring the complex to chromatin. In the absence of PCAF, full loading of target promoters with hormone receptors and BAF is precluded, and induction is compromised. Thus, activation of hormone-responsive promoters requires cooperation of at least two chromatin remodeling activities, BAF and PCAF

Second gene for gonadotropin-releasing hormone in humans

Gonadotropin-releasing hormone (GnRH) is a decapeptide widely known for its role in regulating reproduction by serving as a signal from the hypothalamus to pituitary gonadotropes. In addition to hypothalamic GnRH (GnRH-I), a second GnRH form (pGln-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly; GnRH-II) with unknown function has been localized to the midbrain of many vertebrates. We show here that a gene encoding GnRH-II is expressed in humans and is located on chromosome 20p13, distinct from the GnRH-I gene that is on 8p21-p11.2. The GnRH-II genomic and mRNA structures parallel those of GnRH-I. However, in contrast to GnRH-I, GnRH-II is expressed at significantly higher levels outside the brain (up to 30×), particularly in the kidney, bone marrow, and prostate. The widespread expression of GnRH-II suggests it may have multiple functions. Molecular phylogenetic analysis shows that this second gene is likely the result of a duplication before the appearance of vertebrates, and predicts the existence of a third GnRH form in humans and other vertebrates