Ovarian metabolism of xenobiotics

At birth, the mammalian ovary contains a finite number of primordial follicles, which once depleted, cannot be replaced. Xenobiotic exposures can destroy primordial follicles resulting in premature ovarian failure and, consequently, early entry into menopause. A number of chemical classes can induce premature ovarian failure, including environmental, chemotherapeutic and industrial exposures. While our knowledge on the mechanistic events that occur in the ovary with chemical exposures is increasing, our understanding of the ovary\u27s capacity to metabolize such compounds is less established. This review will focus on three chemicals for which information on ovarian metabolism is known: trichloroethylene, 7,12-dimethylbenz[a]anthracene and 4- vinylcyclohexene. The current state of understanding of ovarian bioactivation and detoxification processes for each will be described

The Sorghum bicolor reference genome: improved assembly, gene annotations, a transcriptome atlas, and signatures of genome organization.

Sorghum bicolor is a drought tolerant C4 grass used for the production of grain, forage, sugar, and lignocellulosic biomass and a genetic model for C4 grasses due to its relatively small genome (approximately 800 Mbp), diploid genetics, diverse germplasm, and colinearity with other C4 grass genomes. In this study, deep sequencing, genetic linkage analysis, and transcriptome data were used to produce and annotate a high-quality reference genome sequence. Reference genome sequence order was improved, 29.6 Mbp of additional sequence was incorporated, the number of genes annotated increased 24% to 34 211, average gene length and N50 increased, and error frequency was reduced 10-fold to 1 per 100 kbp. Subtelomeric repeats with characteristics of Tandem Repeats in Miniature (TRIM) elements were identified at the termini of most chromosomes. Nucleosome occupancy predictions identified nucleosomes positioned immediately downstream of transcription start sites and at different densities across chromosomes. Alignment of more than 50 resequenced genomes from diverse sorghum genotypes to the reference genome identified approximately 7.4 M single nucleotide polymorphisms (SNPs) and 1.9 M indels. Large-scale variant features in euchromatin were identified with periodicities of approximately 25 kbp. A transcriptome atlas of gene expression was constructed from 47 RNA-seq profiles of growing and developed tissues of the major plant organs (roots, leaves, stems, panicles, and seed) collected during the juvenile, vegetative and reproductive phases. Analysis of the transcriptome data indicated that tissue type and protein kinase expression had large influences on transcriptional profile clustering. The updated assembly, annotation, and transcriptome data represent a resource for C4 grass research and crop improvement

A Phase I trial of talazoparib in patients with advanced hematologic malignancies

Aim: The objective of this study was to establish the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of talazoparib. Patients & methods: This Phase I, two-cohort, dose-escalation trial evaluated talazoparib monotherapy in advanced hematologic malignancies (cohort 1: acute myeloid leukemia/myelodysplastic syndrome; cohort 2: chronic lymphocytic leukemia/mantle cell lymphoma). Results: Thirty-three (cohort 1: n = 25; cohort 2: n = 8) patients received talazoparib (0.1-2.0 mg once daily). The MTD was exceeded at 2.0 mg/day in cohort 1 and at 0.9 mg/day in cohort 2. Grade ≥3 adverse events were primarily hematologic. Eighteen (54.5%) patients reported stable disease. Conclusion: Talazoparib is relatively well tolerated in hematologic malignancies, with a similar MTD as in solid tumors, and shows preliminary anti leukemic activity.Clinical trial registration: NCT01399840 (ClinicalTrials.gov)

High voltage pulse cable and connector experience in the kicker systems at SLAC

The SLAC 2-mile linear accelerator uses a wide variety of pulse kicker systems that require high voltage cable and connectors to deliver pulses from the drivers to the magnet loads. Many of the drivers in the SLAC kicker systems use cable lengths up to 80 feet and are required to deliver pulses up to 40 kV, with rise and fall time on the order of 20 ns. Significant pulse degradation from the cable and connector assembly cannot be tolerated. Other drivers are required to deliver up to 80 kV, 20 {mu}s pulses over cables 20 feet long. Several combinations of an applicable high voltage cable and matching connector have been used at SLAC to determine the optimum assembly that meets the necessary specifications and is reliable. 14 refs., 3 figs., 1 tab

Voluntary Medical Male Circumcision: A Qualitative Study Exploring the Challenges of Costing Demand Creation in Eastern and Southern Africa

BACKGROUND: This paper proposes an approach to estimating the costs of demand creation for voluntary medical male circumcision (VMMC) scale-up in 13 countries of eastern and southern Africa. It addresses two key questions: (1) what are the elements of a standardized package for demand creation? And (2) what challenges exist and must be taken into account in estimating the costs of demand creation? METHODS AND FINDINGS: We conducted a key informant study on VMMC demand creation using purposive sampling to recruit seven people who provide technical assistance to government programs and manage budgets for VMMC demand creation. Key informants provided their views on the important elements of VMMC demand creation and the most effective funding allocations across different types of communication approaches (e.g., mass media, small media, outreach/mobilization). The key finding was the wide range of views, suggesting that a standard package of core demand creation elements would not be universally applicable. This underscored the importance of tailoring demand creation strategies and estimates to specific country contexts before estimating costs. The key informant interviews, supplemented by the researchers' field experience, identified these issues to be addressed in future costing exercises: variations in the cost of VMMC demand creation activities by country and program, decisions about the quality and comprehensiveness of programming, and lack of data on critical elements needed to "trigger the decision" among eligible men. CONCLUSIONS: Based on this study's findings, we propose a seven-step methodological approach to estimate the cost of VMMC scale-up in a priority country, based on our key assumptions. However, further work is needed to better understand core components of a demand creation package and how to cost them. Notwithstanding the methodological challenges, estimating the cost of demand creation remains an essential element in deriving estimates of the total costs for VMMC scale-up in eastern and southern Africa

Plasma Physics

Contains reports on five research projects.United States Atomic Energy Commission (Contract AT(30-1)-1842)Project MACAdvanced Research Agency, Department of Defense, under Office of Naval Research Contract Nonr-4102(01

Characterization of the Soluble Nanoparticles Formed through Coulombic Interaction of Bovine Serum Albumin with Anionic Graft Copolymers at Low pH

A static light scattering (SLS) study of bovine serum albumin (BSA) mixtures with two anionic graft copolymers of poly (sodium acrylate-co-sodium 2-acrylamido-2-methyl-1-propanesulphonate)-graft-poly (N, N-dimethylacrylamide), with a high composition in poly (N, N-dimethylacrylamide) (PDMAM) side chains, revealed the formation of oppositely charged complexes, at pH lower than 4.9, the isoelectric point of BSA. The core-corona nanoparticles formed at pH = 3.00, were characterized. Their molecular weight and radius of gyration were determined by SLS, while their hydrodynamic radius was determined by dynamic light scattering. Small angle neutron scattering measurements were used to determine the radius of the insoluble complexes, comprising the core of the particles. The values obtained indicated that their size and aggregation number of the nanoparticles, were smaller when the content of the graft copolymers in neutral PDMAM side chains was higher. Such particles should be interesting drug delivery candidates, if the gastrointestinal tract was to be used

Atomic Resonance and Scattering

Contains research objectives, summary of research and reports on six research projects.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E)National Science Foundation (Grant GP-13633)National Bureau of Standards (Grant NBS(G)-269