579 research outputs found
Gerenciamento de processos na industria de moveis
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro TecnologicoA metodologia de gerĂȘnciamento de processos tem sido apontada como uma das armas mais eficazes na agregação de valor aos produtos, permitindo a aplicação em qualquer empresa. Qualidade e Melhoria contĂnua sĂŁo expressĂ”es que sintetizam claramente os objetivos e os resultados desta metodologia, atendendo, pois, as expectativas do meio empresarial. A pesquisa realizada volta-se para a indĂșstria moveleira e propĂ”e, a partir do gerĂȘnciamento de processos, sua atualização tecnolĂłgica, viabilizando maior e melhor produtividade e aparelhando-as para um desempenho mais competitivo. Em função deste propĂłsito e, com o envolvimento de toda a empresa, definem-se e analisam-se os processos crĂticos do sistema de produção, propondo-se soluçÔes voltadas para a busca permanente de satisfação dos clientes internos e externos. Os resultados obtidos atestam e confirmam as vantagens da metodologia de gerĂȘnciamento de processos, abrindo prespectivas para inĂșmeras outras aplicaçÔes em que se constatem a necessidade de utilizar recursos humanos e materiais para gerar satisfação ao cliente e, influĂȘnciar o desempenho do produto no mercado
A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90a
Hsp90α's vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90α was downregulated using the post-transcriptional RNAi strategy (sihsp90α) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90α, 17-AAG and concurrent sihsp90α/17-AAG (combined treatment). Both Hsp90α gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90α, 17-AAG and a combination of sihsp90α/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90α mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG, respectively. The relationship between Hsp90α protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90α inhibition. Both Hsp90α and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90α protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90α protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90α mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90α in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy
ExperiĂȘncias com a mĂșsica vivenciadas pela secretĂĄria municipal de educação e os desafios para a inserção do ensino de mĂșsica nas escolas da rede pĂșblica de UberlĂąndia
Resumo: Este artigo apresenta recorte da pesquisa acerca da implementação do ensino de mĂșsica nos sistemas educacionais de Minas Gerais (regiĂŁo do TriĂąngulo Mineiro) e Santa Catarina. O objetivo principal da pesquisa Ă© compreender açÔes e estratĂ©gias adotadas pelos sistemas na implementação da mĂșsica como conteĂșdo curricular do ensino fundamental. A pesquisa adota orientação Qual-Quan. Os procedimentos metodolĂłgicos incluem levantamento, seleção, descrição e anĂĄlise de documentos oficiais, questionĂĄrio e entrevista. Este texto, de forma especĂfica, analisa reflexos e influĂȘncias das experiĂȘncias musicais na percepção da secretĂĄria municipal de educação sobre estratĂ©gias e desafios para a inserção do ensino de mĂșsica nas escolas municipais de UberlĂąndia.  Palavras-chave: Implementação do ensino de mĂșsica. Gestor pĂșblico. ExperiĂȘncias musicais.  Experiences with music experienced by the Municipal Secretary of Education and the challenges to insert music as compulsory curricular content in municipal schools of Uberlandia.   Abstract: This paper presents parts of a research study on the implementation of music as a compulsory curricular content in the educational systems of Minas Gerais (TriĂąngulo Mineiro region) and Santa Catarina States. The main objective of the research is to understand actions and strategies adopted by each educational system on the implementation of music as curricular content in the primary level of education. The study adopts a mixed-methods orientation. The methodological procedures include collection, selection, description and analysis of official documents, questionnaire and interview. This text, specifically, analyse reflections and possible influence of the musical experiences on the Municipal Secretary of Educationâs perceptions about the strategies and challenges to insert music as compulsory curricular content in primary schools of Uberlandia, Minas Gerais state, Brazil. Keywords: Implementation of music teaching. Public manager. Musical experiences
Activity of bisnaphthalimidopropyl derivatives against trypanosoma brucei.
Current treatments for African trypanosomiasis are either toxic, costly, difficult to administer, or prone to elicit resistance. This study evaluated the activity of bisnaphthalimidopropyl (BNIP) derivatives against Trypanosoma brucei. BNIPDiaminobutane (BNIPDabut), the most active of these compounds, showed in vitro inhibition in the single-unit nanomolar range, similar to the activity in the reference drug pentamidine, and presented low toxicity and adequate metabolic stability. Additionally, using a murine model of acute infection and live imaging, a significant decrease in parasite load in BNIPDabut-treated mice was observed. However, cure was not achieved. BNIPDabut constitutes a new scaffold for antitrypanosomal drugs that deserves further consideration
Plano educacional para uma biblioteca infantojuvenil: projetando açÔes e mediaçÔes
Phylogeny of Parasitic Parabasalia and Free-Living Relatives Inferred from Conventional Markers vs. Rpb1, a Single-Copy Gene
Parabasalia are single-celled eukaryotes (protists) that are mainly comprised of endosymbionts of termites and wood roaches, intestinal commensals, human or veterinary parasites, and free-living species. Phylogenetic comparisons of parabasalids are typically based upon morphological characters and 18S ribosomal RNA gene sequence data (rDNA), while biochemical or molecular studies of parabasalids are limited to a few axenically cultivable parasites. These previous analyses and other studies based on PCR amplification of duplicated protein-coding genes are unable to fully resolve the evolutionary relationships of parabasalids. As a result, genetic studies of Parabasalia lag behind other organisms.Comparing parabasalid EF1α, α-tubulin, enolase and MDH protein-coding genes with information from the Trichomonas vaginalis genome reveals difficulty in resolving the history of species or isolates apart from duplicated genes. A conserved single-copy gene encodes the largest subunit of RNA polymerase II (Rpb1) in T. vaginalis and other eukaryotes. Here we directly sequenced Rpb1 degenerate PCR products from 10 parabasalid genera, including several T. vaginalis isolates and avian isolates, and compared these data by phylogenetic analyses. Rpb1 genes from parabasalids, diplomonads, Parabodo, Diplonema and Percolomonas were all intronless, unlike intron-rich homologs in Naegleria, Jakoba and Malawimonas.The phylogeny of Rpb1 from parasitic and free-living parabasalids, and conserved Rpb1 insertions, support Trichomonadea, Tritrichomonadea, and Hypotrichomonadea as monophyletic groups. These results are consistent with prior analyses of rDNA and GAPDH sequences and ultrastructural data. The Rpb1 phylogenetic tree also resolves species- and isolate-level relationships. These findings, together with the relative ease of Rpb1 isolation, make it an attractive tool for evaluating more extensive relationships within Parabasalia
Inhibitors of trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.
Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Ă
) to gain insight into the potential specificity of the interaction with the BNIP compounds. In conclusion, the search for TcSir2rp1 specific inhibitors may represent a valuable strategy for drug discovery against T. cruzi
Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder
Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity
CropPol: a dynamic, open and global database on crop pollination
Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved
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