HPG function in men and women stratified by drug use and HIV status

Most studies of hypothalamic-pituitary-gonadal (HPG) function and depression in illicit drug users focus only on men or do not consider the impact of HIV infection along with drug use. This study investigated relationships between illicit drug use and HIV status with depressive symptoms and HPG function in both men and women. Illicit drug use and HIV status were differentially associated with HPG function and depressive symptoms in men and women. Specifically, free testosterone concentrations were lower in men who use drugs and in women who are HIV positive. Estradiol concentrations were marginally lower in women, but not in men, who are HIV positive. Women and drug users reported the most depressive symptoms; however, impaired HPG function was associated with increased depressive symptoms in men only. Neither HPG function nor depression was impacted in an additive or synergistic manner by both drug use and HIV in either sex. These data indicate that illicit drug use is associated with altered HPG function in men and HIV infection is associated with altered HPG function in women. Furthermore, altered HPG function was associated with depressive symptoms in men, but not in women. Sex specific natural histories of illicit drug use and HIV infection, as they relate to endocrine and mental health, suggest a potential role for sex specific treatments to ameliorate these problems. The present data support recommendations of The National Academy of Science to consider gender differences in medical research

Generic Isolated Horizons and their Applications

Boundary conditions defining a generic isolated horizon are introduced. They generalize the notion available in the existing literature by allowing the horizon to have distortion and angular momentum. Space-times containing a black hole, itself in equilibrium but possibly surrounded by radiation, satisfy these conditions. In spite of this generality, the conditions have rich consequences. They lead to a framework, somewhat analogous to null infinity, for extracting physical information, but now in the \textit{strong} field regions. The framework also generalizes the zeroth and first laws of black hole mechanics to more realistic situations and sheds new light on the `origin' of the first law. Finally, it provides a point of departure for black hole entropy calculations in non-perturbative quantum gravity.Comment: 4 pages, RevTeX. Minor typos were corrected and the fact that, in contrast to Ref [4], isolated horizons are now allowed to have distortion and rotation was clarifie

Degenerate Sectors of the Ashtekar Gravity

This work completes the task of solving locally the Einstein-Ashtekar equations for degenerate data. The two remaining degenerate sectors of the classical 3+1 dimensional theory are considered. First, with all densitized triad vectors linearly dependent and second, with only two independent ones. It is shown how to solve the Einstein-Ashtekar equations completely by suitable gauge fixing and choice of coordinates. Remarkably, the Hamiltonian weakly Poisson commutes with the conditions defining the sectors. The summary of degenerate solutions is given in the Appendix.Comment: 19 pages, late

Black hole entropy calculations based on symmetries

Symmetry based approaches to the black hole entropy problem have a number of attractive features; in particular they are very general and do not depend on the details of the quantization method. However we point out that, of the two available approaches, one faces conceptual problems (also emphasized by others), while the second contains certain technical flaws. We correct these errors and, within the new, improved scheme, calculate the entropy of 3-dimensional black holes. We find that, while the new symmetry vector fields are well-defined on the ``stretched horizon,'' and lead to well-defined Hamiltonians satisfying the expected Lie algebra, they fail to admit a well-defined limit to the horizon. This suggests that, although the formal calculation can be carried out at the classical level, its real, conceptual origin probably lies in the quantum theory.Comment: 14 pages, Latex, CGPG-01/1-

Identification and characterization of a novel ubiquitous nucleolar protein ‘NARR’ encoded by a gene overlapping the rab34 oncogene

There are only few reports on protein products originating from overlapping mammalian genes even though computational predictions suggest that an appreciable fraction of mammalian genes could potentially overlap. Mass spectrometry-based proteomics has now acquired the tools to probe proteins in an unbiased manner, providing direct evidence of the output of the genomic and gene expression machinery. In particular, proteomics can refine gene predictions and discover novel gene-processing events and gene arrangements. Here, we report the mass spectrometric discovery and biochemical validation of the novel protein encoded by a gene overlapping rab34 oncogene. The novel protein is highly conserved in mammals. In humans, it contains 13 distinct Nine-Amino acid Residue-Repeats (NARR) with the consensus sequence PRVIV(S/T)PR in which the serine or threonine residues are phosphorylated during M-phase. NARR is ubiquitously expressed and resides in nucleoli where it colocalizes with ribosomal DNA (rDNA) gene clusters. Its distribution only partially overlaps with upstream binding factor, one of the main regulators of RNA Polymerase I activity, and is entirely uncoupled from it in mitotic cells and upon inhibition of transcription. NARR only partially colocalizes with fibrillarin, the pre-ribosomal RNA-processing protein, positioning NARR in a separate niche within the rDNA cluster

Application of Least Squares with Conditional Equations Method for Railway Track Inventory Using GNSS Observations

Satellite geodetic networks are commonly used in surveying tasks, but they can also be used in mobile surveys. Mobile satellite surveys can be used for trackage inventory, diagnostics and design. The combination of modern technological solutions with the adaptation of research methods known in other fields of science offers an opportunity to acquire highly accurate solutions for railway track inventory. This article presents the effects of work carried out using a mobile surveying platform on which Global Navigation Satellite System (GNSS) receivers were mounted. The satellite observations (surveys) obtained were aligned using one of the methods known from classical land surveying. The records obtained during the surveying campaign on a 246th km railway track section were subjected to alignment. This article provides a description of the surveying campaign necessary to obtain measurement data and a theoretical description of the method employed to align observation results as well as their visualisation. Document type: Articl

Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug–Drug Interactions

ABSTRACT: The hepatic organic anion transporting poly-peptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug−drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors