Validação numérica do conjunto estrutural asa-fuselagem de um vant biplano

TCC (graduação) - Universidade Federal de Santa Catarina, Campus Joinville, Engenharia Aeroespacial.Este trabalho apresenta a validação estrutural do conjunto asa-fuselagem de um aeromodelo biplano desenvolvido no ano de 2020 pela equipe Nisus Aerodesign para participar da competição Society of Automotive Engineers (SAE) Brasil. Análises estruturais aprofundadas dentro de projetos de engenharia aeroespacial são de extrema importância para otimização financeira e temporal do projeto e nos permite verificar quais os pontos críticos dessas estruturas. Sendo assim, este trabalho busca identificar os principais carregamentos e esforços aos quais o conjunto está submetido durante o voo, além de validar os cálculos estruturais do aeromodelo por meio numérico, e dessa forma legitimando a qualidade do fundamento técnico por parte da equipe quando não havia conhecimento para tal estudo. A metodologia proposta aventa, portanto, uma série de cálculos a serem realizados durante o projeto estrutural desses componentes, que também inclui uma análise estrutural estática usando o Método dos Elementos Finitos (MEF), por meio do programa Ansys Workbench, para verificar o comportamento das estruturas sólidas e compósitas quando submetida a cargas de voo. A partir dos resultados obtidos nas análises numéricas é possível concluir que algumas estruturas estavam superestimadas, tais como as nervuras e as estruturas sanduíches, pois apresentavam elevadas margens de segurança, e decisões de projeto baseadas em teoria foram precipitadas sem o devido estudo de caso. Contudo, os cálculos por parte da equipe estavam correto e apresentam margens de segurança satisfatórias para a eficácia do projeto

Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement

Background: Whole-exome sequencing has identified the causes of several Mendelian diseases by analyzing multiple unrelated cases, but it is more challenging to resolve the cause of extremely rare and suspected Mendelian diseases from individual families. We identified a family quartet with two children, both affected with a previously unreported disease, characterized by progressive muscular weakness and cardiomyopathy, with normal intelligence. During the course of the study, we identified one additional unrelated patient with a comparable phenotype. Methods: We performed whole-genome sequencing (Complete Genomics platform), whole-exome sequencing (Agilent SureSelect exon capture and Illumina Genome Analyzer II platform), SNP genotyping (Illumina HumanHap550 SNP array) and Sanger sequencing on blood samples, as well as RNA-Seq (Illumina HiSeq platform) on transformed lymphoblastoid cell lines. Results: From whole-genome sequence data, we identified RBCK1, a gene encoding an E3 ubiquitin-protein ligase, as the most likely candidate gene, with two protein-truncating mutations in probands in the first family. However, exome data failed to nominate RBCK1 as a candidate gene, due to poor regional coverage. Sanger sequencing identified a private homozygous splice variant in RBCK1 in the proband in the second family, yet SNP genotyping revealed a 1.2Mb copy-neutral region of homozygosity covering RBCK1. RNA-Seq confirmed aberrant splicing of RBCK1 transcripts, resulting in truncated protein products. Conclusions: While the exact mechanism by which these mutations cause disease is unknown, our study represents an example of how the combined use of whole-genome DNA and RNA sequencing can identify a disease-predisposing gene for a novel and extremely rare Mendelian disease

Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival

Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. “Immortality” of most cancer cells is dependent on telomerase, but the role of associated proteins in the endometrium is poorly understood. The Cancer Genome Atlas data highlighted telomere/telomerase associated genes (TTAGs) with prognostic relevance in the endometrium, and a recent in silico study identified a group of TTAGs and proteins as key regulators within a network of dysregulated genes in EC. We characterise relevant telomere/telomerase associated proteins (TTAPs) NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP in the endometrium using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). qPCR data demonstrated altered expression of multiple TTAPs; specifically, increased NOP10 (p = 0.03) and reduced NHP2 (p = 0.01), TERF2 (p = 0.01) and TERF2IP (p < 0.003) in EC relative to post-menopausal endometrium. Notably, we report reduced NHP2 in EC compared to post-menopausal endometrium in qPCR and IHC (p = 0.0001) data; with survival analysis indicating high immunoscore is favourable in EC (p = 0.0006). Our findings indicate a potential prognostic role for TTAPs in EC, particularly NHP2. Further evaluation of the prognostic and functional role of the examined TTAPs is warranted to develop novel treatment strategies

Role of Nucleolin in Endometrial Precancerous Hyperplasia and Carcinogenesis: Ex Vivo and In Silico Study

Endometrial cancer (EC) is the most common gynaecological malignancy. Nucleolin (NCL) is involved in rDNA transcription, cell proliferation, and apoptosis, with high expression associated with worse overall survival (OS) in other adenocarcinomas. Our aims were to assess NCL gene and protein expression and explore the differential expression of NCL-associated genes (NAGs) in endometrial carcinogenesis. Endometrial samples were obtained from 157 women to include healthy, hyperplastic (EH), EC, and metastatic groups. RT-qPCR and immunohistochemistry were employed to assess NCL gene and protein levels. In silico analysis of NAGs in TCGA and GEO datasets was performed, with the prognostic value determined via Human Protein Atlas. NCL mRNA level of EC was lower than in healthy post-menopausal endometrium (p < 0.01). EH samples had lower NCL immuno-expression scores than healthy pre-menopausal (p < 0.001), benign post-menopausal (p < 0.01), and EC (p < 0.0001) samples. Metastatic lesions demonstrated higher NCL quick scores than primary tissue (p = 0.04). Higher NCL Immuno quick scores carried a worse OS in high-grade EC (p = 0.01). Interrogating Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) and Uterine Carcinosarcoma (TCGA-UCS) cohorts revealed NCL to be the most highly upregulated gene in carcinosarcoma, with S100A11, LMNB2, RERG, E2F1 and CCNA2 representing key dysregulated NAGs in EC. Since NCL is implicated in transforming hyperplastic glands into cancer, with further involvement in metastasis, it is suggested to be a promising target for better-informed diagnosis, risk stratification, and management of EC

Usages des modèles spatiaux pour la prospective

International audienceCet article théorique a pour objectif de faire un état de l'art sur l'usage des modèles spatiaux pour la prospective. Dans un premier temps, il présente un bref historique de la convergence implicite entre prospective et géographie. Dans un second temps, il aborde la question du choix du modèle en présentant les critères à prendre en compte. Dans un troisième temps, il présente la validation des modèles comme un moyen d'améliorer la plausibilité des scénarios à travers la combinaison de méthodes d'évaluation. Enfin, si on constate un usage de plus en plus important de modèles spatiaux en prospective, les méthodes évoquées sont loin d'être exhaustives et replacent la géoprospective comme une simple communauté de pratiques et de méthodes ayant un objectif commun : mieux explorer les futurs pour éclairer l'action présente. Au final, il apporte un éclairage sur l'apport des modèles aux démarches prospectives et vise à aider les géographes, les modélisateurs et/ou les prospectivistes à choisir un modèle approprié à leur problématique et à leurs objectifs afin de tirer parti de tous les avantages qu'ils offrent. Il tente également de clarifier certaines confusions sémantiques qui existent autour de l'usage des modèles couplés à des scénarios