Obtenção de filmes híbridos orgânico-inorgânicos a partir de óleo de mamona e teos

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Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors.

Abstract Objectives We evaluated the emergence of mutations associated to integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in HIV-1 infected patients treated with this drug class. Methods Emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under-INSTI and before-INSTI treatment) were evaluated in 107 INSTI-naive patients (19 drug-naive and 88 drug-experienced) with two plasma genotypic resistance tests available: one before and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associated with the integrase evolution under INSTI treatment. Results Patients were mainly infected by B subtype (72.0%). 87 patients were treated with raltegravir, 13 with dolutegravir and 7 with elvitegravir. Before INSTI treatment, one patient harboured the major INSTI-RM R263 K, and three patients the accessory INSTI-RMs T97A. Under INSTI treatment, the emergence of ≥1 INSTI-RM was found in 39 (36.4%) patients. The major INSTI-RMs which emerged more frequently were: N155H (17.8%), G140S (8.4%), Y143R (7.5%), Q148H (6.5%), Y143C (4.7%). Concerning integrase evolution, a higher genetic distance was found in patients with ≥1 INSTI-RM compared to those without emergence of resistance (0.024 [0.012-0.036] vs. 0.015 [0.009-0.024], p = 0.018). This higher integrase evolution was significantly associated with a longer duration of HIV-1 infection, a higher number of past regimens and non-B subtypes. Conclusions Our findings confirmed that in INSTI-naive patients, major INSTI-RMs occur very rarely. Under INSTI treatment, selection of drug-resistance follows the typical drug-resistance pathways; a higher evolution characterizes integrase sequences developing drug-resistance compared to those without any resistance

Anisotropy in Turbulent Flows and in Turbulent Transport

We discuss the problem of anisotropy and intermittency in statistical theory of high Reynolds-number turbulence (and turbulent transport). We present a detailed description of the new tools that allow effective data analysis and systematic theoretical studies such as to separate isotropic from anisotropic aspects of turbulent statistical fluctuations. Employing the invariance of the equations of fluid mechanics to all rotations, we show how to decompose the (tensorial) statistical objects in terms of the irreducible representation of the SO(3) symmetry group. For the case of turbulent advection of passive scalar or vector fields, this decomposition allows rigorous statements to be made: (i) the scaling exponents are universal, (ii) the isotropic scaling exponents are always leading, (iii) the anisotropic scaling exponents form a discrete spectrum which is strictly increasing as a function of the anisotropic degree. Next we explain how to apply the SO(3) decomposition to the statistical Navier-Stokes theory. We show how to extract information about the scaling behavior in the isotropic sector. Doing so furnishes a systematic way to assess the universality of the scaling exponents in this sector, clarifying the anisotropic origin of the many measurements that claimed the opposite. A systematic analysis of Direct Numerical Simulations and of experiments provides a strong support to the proposition that also for the non-linear problem there exists foliation of the statistical theory into sectors of the symmetry group. The exponents appear universal in each sector, and again strictly increasing as a function of the anisotropic degreee.Comment: 150 pages, 26 figures, submitted to Phys. Re

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche’s Endocannabinoid System Projects

: The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs. The pursuit of new therapeutic agents has been enhanced by the creation of specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, and the establishment of biomarkers for target engagement. By fusing medicinal chemistry with chemical biology in a comprehensive, translational end-to-end drug discovery strategy, we have expedited the development of novel therapeutics. Additionally, this strategy promises to foster highly productive partnerships between industry and academia, as will be illustrated through various examples

HIV Testing and Diagnosis Rates in Kiev, Ukraine: April 2013-March 2014

Data from Ukraine on risk factors for HIV acquisition are limited. We describe the characteristics of individuals testing for HIV in the main testing centres of the Ukrainian capital Kiev, including HIV risk factors, testing rates, and positivity rates. As part of a larger study to estimate HIV incidence within Kiev City, we included questions on possible risk factors for HIV acquisition and testing history to existing systems in 4 infectious disease clinics. Data were provided by the person requesting an HIV test using a handheld electronic tablet. All persons (≥16 yrs) presenting for an HIV test April 2013-March 2014 were included. Rates per 100,000 were calculated using region-specific denominators for Kiev. During the study period 6370 individuals tested for HIV, equivalent to a testing rate of 293.2 per 100,000. Of these, 467 (7.8%) were HIV-positive, with the highest proportion positive among 31-35 year olds (11.2%), males (9.4%), people who inject drugs (PWID) (17.9%) and men who have sex with men (MSM) (24.1%). Using published population size estimates of MSM, diagnosis rates for MSM ranged from 490.6 to 1548.3/100,000. A higher proportion of heterosexual women compared to heterosexual men reported contact with PWID, (16% vs. 4.7%) suggesting a bridging in risk between PWID and their sexual partners. Collection of HIV risk factor information in Kiev, essential for the purposes of developing effective HIV prevention and response tools, is feasible. The high percentage of MSM among those testing positive for HIV, may indicate a significant level of undisclosed sex between men in national figures