13 research outputs found
Um modelo para a construção de base de conhecimentos sobre projetos nas organizações, suportado por ferramentas colaborativas
A utilização de ferramentas de colaboração para o gerenciamento de bases de conhecimento permite que as organizações possam armazenar e disseminar o conhecimento produzido nos projetos de maneira efetiva, aliando as modernas soluções de tecnologia de informação aos conceitos de gestão do conhecimento e gerenciamento de projetos, beneficiando-as da manutenção e utilização memória organizacional através da utilização de modelos especificadas e possibilitando, assim, a obtenção de vantagens competitivas. Assim, este artigo tem por objetivo apresentar um modelo para a construção de uma base de conhecimentos as lições aprendidas no gerenciamento de projetos baseado no guia PMBOK (Um Guia do Conhecimento em Gerenciamento de Projetos), suportado por ferramentas colaborativas e fundamentos de gestão do conhecimento.Sociedad Argentina de Informática e Investigación Operativ
Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients with Hypertrophic Cardiomyopathy
Background - Pathogenic variants in MYBPC3, encoding cardiac MyBP-C, are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique MYBPC3 variants and relatively small genotyped HCM cohorts have precluded detailed genotype-phenotype correlations. Methods - Patients with HCM and MYBPC3 variants were identified from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Variant types and locations were analyzed, morphologic severity was assessed, and time-event analysis was performed (composite clinical outcome of sudden death, class III/IV heart failure, LVAD/transplant, atrial fibrillation). For selected missense variants falling in enriched domains, myofilament localization and degradation rates were measured in vitro. Results - Among 4,756 genotyped HCM patients in SHaRe, 1,316 patients were identified with adjudicated pathogenic truncating (N=234 unique variants, 1047 patients) or non-truncating (N=22 unique variants, 191 patients) variants in MYBPC3. Truncating variants were evenly dispersed throughout the gene, and hypertrophy severity and outcomes were not associated with variant location (grouped by 5' - 3' quartiles or by founder variant subgroup). Non-truncating pathogenic variants clustered in the C3, C6, and C10 domains (18 of 22, 82%, p<0.001 vs. gnomAD common variants) and were associated with similar hypertrophy severity and adverse event rates as observed with truncating variants. MyBP-C with variants in the C3, C6, and C10 domains was expressed in rat ventricular myocytes. C10 mutant MyBP-C failed to incorporate into myofilaments and degradation rates were accelerated by ~90%, while C3 and C6 mutant MyBP-C incorporated normally with degradation rate similar to wild-type. Conclusions - Truncating variants account for 91% of MYBPC3 pathogenic variants and cause similar clinical severity and outcomes regardless of location, consistent with locus-independent loss-of-function. Non-truncating MYBPC3 pathogenic variants are regionally clustered, and a subset also cause loss-of-function through failure of myofilament incorporation and rapid degradation. Cardiac morphology and clinical outcomes are similar in patients with truncating vs. non-truncating variants
Experimental comparative study of the histotoxicity of poly(lactic-co-glycolic acid) copolymer and poly(lactic-co-glycolic acid)-poly(isoprene) blend
Current treatments of craniosynostosis rely on the application of metal springs for cranial bone deviation. However, those metal springs demand a second surgical procedure for their removal. An attractive alternative would be the substitution of metal for bioresorbable polymers in the composition of the springs. The addition of poly(isoprene), PI, to poly(lactic-co-glycolic acid), PLGA, produces a polymeric blend with partial miscibility and distinct mechanical behavior that may benefit the patient recover. It is necessary to compare the histotoxicity of PLGA/PI to that presented by PLGA. In order to verify the histological behavior of the blend, 46 male Wistar rats (Rattus norvegicus, albino strain) underwent implantation of PLGA or PLGA/PI in the skull and were allocated into subgroups by timing of euthanasia (15, 30, 60, or 90 days). After euthanasia, the skull was removed and the histotoxicity was assessed histopathologically. The PLGA/PI blend showed greater histotoxicity in animals euthanized at 60 days, although in this period the histotoxicity of the PLGA/PI blend was similar to that of the PLGA copolymer at 15 days. Despite the instability of histological response, presented in different periods of observation, the results obtained in long-term show that the material has high potential for studies in craniosynostosis treatment
Recommended from our members
An Unbiased Screen Identified the Hsp70-BAG3 Complex as a Regulator of Myosin-Binding Protein C3.
Variants in the gene myosin-binding protein C3 (MYBPC3) account for approximately 50% of familial hypertrophic cardiomyopathy (HCM), leading to reduced levels of myosin-binding protein C3 (MyBP-C), the protein product made by gene MYBPC3. Elucidation of the pathways that regulate MyBP-C protein homeostasis could uncover new therapeutic strategies. Toward this goal, we screened a library of 2,426 bioactive compounds and identified JG98, an allosteric modulator of heat shock protein 70 that inhibits interaction with Bcl-2-associated athanogene (BAG) domain co-chaperones. JG98 reduces MyBP-C protein levels. Furthermore, genetic reduction of BAG3 phenocopies treatment with JG-98 by reducing MYBP-C protein levels.. Thus, an unbiased compound screen identified the heat shock protein 70-BAG3 complex as a regulator of MyBP-C stability