534 research outputs found
Metodologia para o cálculo do custo de produção de frango de corte - versão 1.
Metodologia: aspectos gerais; Fórmulas e exemplo de cálculo; Tabelas de custo.bitstream/CNPSA/15778/1/publicacao_e5z35p2o.pd
Novel Insights into RAD52’s Structure, Function, and Druggability for Synthetic Lethality and Innovative Anticancer Therapies
Simple Summary Human RAD52 is a non-essential DNA/RNA-binding protein thought to be involved in many DNA repair mechanisms. Initially regarded as having a major role only in error-prone backup DNA repair mechanisms, RAD52 has recently gained attention because its inhibition induces synthetic lethality in cancer cells with an inactivated homologous recombination pathway (for error-free double-strand-break repair). RAD52 is thus a potential target to overcome resistance and unwanted side effects. Unfortunately, researchers still lack detailed structural and mechanistic information on RAD52 and have identified only a limited number of inhibitors, none of which are in the preclinical phase. This review summarizes the current knowledge on RAD52, highlighting the potential of its inhibition. This review also discusses the critical gaps in knowledge and sets out future directions for effective campaigns to discover RAD52 inhibitors. In recent years, the RAD52 protein has been highlighted as a mediator of many DNA repair mechanisms. While RAD52 was initially considered to be a non-essential auxiliary factor, its inhibition has more recently been demonstrated to be synthetically lethal in cancer cells bearing mutations and inactivation of specific intracellular pathways, such as homologous recombination. RAD52 is now recognized as a novel and critical pharmacological target. In this review, we comprehensively describe the available structural and functional information on RAD52. The review highlights the pathways in which RAD52 is involved and the approaches to RAD52 inhibition. We discuss the multifaceted role of this protein, which has a complex, dynamic, and functional 3D superstructural arrangement. This complexity reinforces the need to further investigate and characterize RAD52 to solve a challenging mechanistic puzzle and pave the way for a robust drug discovery campaign
Pinteiros cobertos - estufas para a redução da síndrome ascítica em frangos de corte.
bitstream/item/58545/1/CUsersPiazzonDocuments216.pd
Belief revision and uncertain reasoning
When a new piece of information contradicts a currently held belief, one has to modify the set of beliefs in order to restore its consistency. In the case where it is necessary to give up a belief, some of them are less likely to be abandoned than others. The concept of epistemic entrenchment is used by some AI approaches to explain this fact based on formal properties of the belief set (e. g. , transitivity). Two experiments were designed to test the hypothesis that contrary to such views, (i) belief is naturally represented by degrees rather than in an all-or-nothing manner, (ii) entrenchment is primarily a matter of content and not only a matter of form, and (iii) consequently prior degree of belief is a powerful factor of change. The two experiments used Elio and Pelletier's (1997) paradigm in which participants were presented with full simple deductive arguments whose conclusion was denied, following which they were asked to decide which premise to revise
Utilização de soja tostada para suínos em crescimento e terminação.
bitstream/item/58761/1/CUsersPiazzonDocuments168.pd
Isolation and Characterization of Monomeric Human RAD51: A Novel Tool for Investigating Homologous Recombination in Cancer
RAD51 is a key player in the homologous recombination
pathway. Upon DNA damage, RAD51 is transported into the nucleus
by BRCA2, where it can repair DNA double-strand breaks. Due to the
structural complexity and dynamics, researchers have not yet clarified
the mechanistic details of every step of RAD51 recruitment and DNA
repair. RAD51 possesses an intrinsic tendency to form oligomeric
structures, which make it challenging to conduct biochemical and
biophysical investigations. Here, for the first time, we report on the
isolation and characterization of a human monomeric RAD51
recombinant form, obtained through a double mutation, which
preserves the protein’s integrity and functionality. We investigated
different buffers to identify the most suitable condition needed to
definitively stabilize the monomer. The monomer of human RAD51
provides the community with a unique biological tool for investigating
RAD51-mediated homologous recombination, and paves the way for
more reliable structural, mechanistic, and drug discovery studies
Author Correction: Combining CRISPRi and metabolomics for functional annotation of compound libraries
No abstract available
Combining CRISPRi and metabolomics for functional annotation of compound libraries
Molecular profiling of small molecules offers invaluable insights into the function of compounds and allows for hypothesis generation about small-molecule direct targets and secondary effects. However, current profiling methods are limited in either the number of measurable parameters or throughput. Here we developed a multiplexed, unbiased framework that, by linking genetic to drug-induced changes in nearly a thousand metabolites, allows for high-throughput functional annotation of compound libraries in Escherichia coli. First, we generated a reference map of metabolic changes from CRISPR interference (CRISPRi) with 352 genes in all major essential biological processes. Next, on the basis of the comparison of genetic changes with 1,342 drug-induced metabolic changes, we made de novo predictions of compound functionality and revealed antibacterials with unconventional modes of action (MoAs). We show that our framework, combining dynamic gene silencing with metabolomics, can be adapted as a general strategy for comprehensive high-throughput analysis of compound functionality from bacteria to human cell lines
Global Assessment of the SMAP Level-4 Surface and Root-Zone Soil Moisture Product Using Assimilation Diagnostics
The Soil Moisture Active Passive (SMAP) mission Level-4 Soil Moisture (L4_SM) product provides 3-hourly, 9-km resolution, global estimates of surface (0-5 cm) and root-zone (0-100 cm) soil moisture and related land surface variables from 31 March 2015 to present with ~2.5-day latency. The ensemble-based L4_SM algorithm assimilates SMAP brightness temperature (Tb) observations into the Catchment land surface model. This study describes the spatially distributed L4_SM analysis and assesses the observation-minus-forecast (O-F) Tb residuals and the soil moisture and temperature analysis increments. Owing to the climatological rescaling of the Tb observations prior to assimilation, the analysis is essentially unbiased, with global mean values of ~0.37 K for the O-F Tb residuals and practically zero for the soil moisture and temperature increments. There are, however, modest regional (absolute) biases in the O-F residuals (under ~3 K), the soil moisture increments (under ~0.01 cu.m/cu.m), and the surface soil temperature increments (under ~1 K). Typical instantaneous values are ~6 K for O-F residuals, ~0.01 (~0.003) cu.m/cu.m for surface (root-zone) soil moisture increments, and ~0.6 K for surface soil temperature increments. The O-F diagnostics indicate that the actual errors in the system are overestimated in deserts and densely vegetated regions and underestimated in agricultural regions and transition zones between dry and wet climates. The O-F auto-correlations suggest that the SMAP observations are used efficiently in western North America, the Sahel, and Australia, but not in many forested regions and the high northern latitudes. A case study in Australia demonstrates that assimilating SMAP observations successfully corrects short-term errors in the L4_SM rainfall forcing
Optimization of a high work function solution processed vanadium oxide hole-extracting layer for small molecule and polymer organic photovoltaic cells
We report a method of fabricating a high work function, solution processable vanadium oxide (V2Ox(sol)) hole-extracting layer. The atmospheric processing conditions of film preparation have a critical influence on the electronic structure and stoichiometry of the V2Ox(sol), with a direct impact on organic photovoltaic (OPV) cell performance. Combined Kelvin probe (KP) and ultraviolet photoemission spectroscopy (UPS) measurements reveal a high work function, n-type character for the thin films, analogous to previously reported thermally evaporated transition metal oxides. Additional states within the band gap of V2Ox(sol) are observed in the UPS spectra and are demonstrated using X-ray photoelectron spectroscopy (XPS) to be due to the substoichiometric nature of V2Ox(sol). The optimized V2Ox(sol) layer performance is compared directly to bare indium–tin oxide (ITO), poly(ethyleneoxythiophene):poly(styrenesulfonate) (PEDOT:PSS), and thermally evaporated molybdenum oxide (MoOx) interfaces in both small molecule/fullerene and polymer/fullerene structures. OPV cells incorporating V2Ox(sol) are reported to achieve favorable initial cell performance and cell stability attributes
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