Impact of circulating bacterial DNA in long-term glucose homeostasis in non-diabetic patients with HIV infection: cohort study

In HIV-infected patients, the damage in the gut mucosal immune system is not completely restored after antiretroviral therapy (ART). It results in microbial translocation, which could influence the immune and inflammatory response. We aimed at investigating the long-term impact of bacterial-DNA translocation (bactDNA) on glucose homeostasis in an HIV population. This was a cohort study in HIV-infected patients whereby inclusion criteria were: patients with age >18 years, ART-naïve or on effective ART (<50 HIV-1 RNA copies/mL) and without diabetes or chronic hepatitis C. Primary outcome was the change in HbA1c (%). Explanatory variables at baseline were: bactDNA (qualitatively detected in blood samples by PCR [broad-range PCR] and gene 16SrRNA - prokaryote), ART exposure, HOMA-R and a dynamic test HOMACIGMA [continuous infusion of glucose with model assessment], hepatic steatosis (hepatic triglyceride content - 1H-MRS), visceral fat / subcutaneous ratio and inflammatory markers. Fifty-four men (age 43.2 ± 8.3 years, BMI 24.9 ± 3 kg/m2, mean duration of HIV infection of 8.1 ± 5.3 years) were included. Baseline HbA1c was 4.4 ± 0.4% and baseline presence of BactDNA in six patients. After 8.5 ± 0.5 years of follow-up, change in HbA1c was 1.5 ± 0.47% in patients with BactDNA vs 0.87 ± 0.3% in the rest of the sample p < 0.001. The change in Hba1c was also influenced by protease inhibitors exposure, but not by baseline indices of insulin resistance, body composition, hepatic steatosis, inflammatory markers or anthropometric changes. In non-diabetic patients with HIV infection, baseline bacterial translocation and PI exposure time were the only factors associated with long-term impaired glucose homeostasis

Empleo del software Sunny Design Web con vistas a dimensionar el sistema conectado a Red en la Universidad Técnica de Manabí

La energía eléctrica generada a partir de fuentes de energía renovables presenta la ventaja de brindar una autosuficiencia que no solo conduce a una mejora del medio ambiente sino también incrementa la rentabilidad de una instalación. Siendo conscientes de estas ventajas, este trabajo investigativo se orientó al estudio energético y económico de un proyecto que, a partir de fuentes renovables de energía en el esquema de generación distribuida, es decir se realizó el dimensionamiento de una Unidad de Producción de Autoconsumo (UPAC) para la Universidad Técnica de Manabí (UTM). Además, se realizó una evaluación energética para encontrar oportunidades de racionalización de consumos de energía; como caso práctico el sistema de iluminación pública del campus universitario. En este caso específico se realiza el análisis con el empleo del software Sunny Design Web, brindándose los resultados alcanzados

Entanglement renormalization and boundary critical phenomena

The multiscale entanglement renormalization ansatz is applied to the study of boundary critical phenomena. We compute averages of local operators as a function of the distance from the boundary and the surface contribution to the ground state energy. Furthermore, assuming a uniform tensor structure, we show that the multiscale entanglement renormalization ansatz implies an exact relation between bulk and boundary critical exponents known to exist for boundary critical systems.Comment: 6 pages, 4 figures; for a related work see arXiv:0912.164

The Circadian Deadenylase Nocturnin Is Necessary for Stabilization of the iNOS mRNA in Mice

Nocturnin is a member of the CCR4 deadenylase family, and its expression is under circadian control with peak levels at night. Because it can remove poly(A) tails from mRNAs, it is presumed to play a role in post-transcriptional control of circadian gene expression, but its target mRNAs are not known. Here we demonstrate that Nocturnin expression is acutely induced by the endotoxin lipopolysaccharide (LPS). Mouse embryo fibroblasts (MEFs) lacking Nocturnin exhibit normal patterns of acute induction of TNFα and iNOS mRNAs during the first three hours following LPS treatment, but by 24 hours, while TNFα mRNA levels are indistinguishable from WT cells, iNOS message is significantly reduced 20-fold. Accordingly, analysis of the stability of the mRNAs showed that loss of Nocturnin causes a significant decrease in the half-life of the iNOS mRNA (t1/2 = 3.3 hours in Nocturnin knockout MEFs vs. 12.4 hours in wild type MEFs), while having no effect on the TNFα message. Furthermore, mice lacking Nocturnin lose the normal nighttime peak of hepatic iNOS mRNA, and have improved survival following LPS injection. These data suggest that Nocturnin has a novel stabilizing activity that plays an important role in the circadian response to inflammatory signals

Pesticides and health: A review of evidence on health effects, valuation of risks, and benefit‐cost analysis

In this paper, we provide reviews of recent scientific findings on health effects and preference valuation of health risks related to pesticides, and the role of benefit‐cost analysis in policies related to pesticides. Our reviews reveal that whereas the focus of the health literature has been on individuals with direct exposure to pesticides, e.g. farmers, the literature on preference elicitation has focused on those with indirect exposure, e.g. consumers. Our discussion of pesticides policies emphasizes the need to clarify the rationale for regulation and the role of risk perceptions in benefit‐cost analysis, and stress the importance of inter‐disciplinary research in this area

The Scrounge-atron: a phased approach to the Advanced Hydrotest Facility utilizing proton radiography

The Department of Energy has initiated its Stockpile Stewardship and Management Program (SSMP) to provide a single, integrated technical program for maintaining the continued safety and reliability of the nation's nuclear weapons stockpile in the absence of nuclear testing. Consistent with the SSMP, the Advanced Hydrotest Facility (AHF) has been conceived to provide improved radiographic imaging with multiple axes and multiple time frames. The AHF would be used to better understand the evolution of nuclear weapon primary implosion shape under normal and accident scenarios. There are three fundamental technologies currently under consideration for use on the AHF. These include linear induction acceleration, inductive-adder pulsed-power technology (both technologies using high current electron beams to produce an intense X-ray beam) and high-energy proton accelerators to produce a proton beam. The Scrounge-atron (a proton synchrotron) was conceived to be a relatively low cost demonstration of the viability of the third technology using bursts of energetic protons, magnetic lenses, and particle detectors to produce the radiographic image. In order for the Scrounge-atron to provide information useful for the AHF technology decision, the accelerator would have to be built as quickly and as economically as possible. These conditions can be met by "scrounging" parts from decommissioned accelerators across the country, especially the Main Ring at Fermilab. The Scrounge-atron is designed to meet the baseline parameters for single axis proton radiography: a 20 GeV proton beam of ten pulses, 10 degrees protons each, spaced 250 ns apart. (2 refs)

Solving patients with rare diseases through programmatic reanalysis of genome-phenome data

Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP’s Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics

Molecular, phenotypic, and sample-associated data to describe pluripotent stem cell lines and derivatives

The use of induced pluripotent stem cells (iPSC) derived from independent patients and sources holds considerable promise to improve the understanding of development and disease. However, optimized use of iPSC depends on our ability to develop methods to efficiently qualify cell lines and protocols, monitor genetic stability, and evaluate self-renewal and differentiation potential. To accomplish these goals, 57 stem cell lines from 10 laboratories were differentiated to 7 different states, resulting in 248 analyzed samples. Cell lines were differentiated and characterized at a central laboratory using standardized cell culture methodologies, protocols, and metadata descriptors. Stem cell and derived differentiated lines were characterized using RNA-seq, miRNA-seq, copy number arrays, DNA methylation arrays, flow cytometry, and molecular histology. All materials, including raw data, metadata, analysis and processing code, and methodological and provenance documentation are publicly available for re-use and interactive exploration at https://www.synapse.org/pcbc. The goal is to provide data that can improve our ability to robustly and reproducibly use human pluripotent stem cells to understand development and disease