Enriching APSI with Validation Capabilities: the KEEN environment and its use in Robotics

This paper presents the KnowledgE ENgineering (KEEN) design support system in which Validation and Verification (V&V) methods are used to strengthen onground development of software for plan-based autonomy. In particular, the paper describes a collection of verification methods, based on Timed Game Automata (TGA), deployed for the design and development of timeline-based Planning and Scheduling (P&S) applications within the APSI-TRF framework. The KEENs V&V functionalities are illustrated describing software development to synthesize plans for a planetary rover

Rho kinase inhibitors for glaucoma treatment - Review

ABSTRACT Glaucoma is a progressive optic neuropathy characterized by the loss of ganglion cells and their axons. A major risk factor for glaucomatous visual field loss is elevated intraocular pressure (IOP), and several studies have shown that lowering IOP reduces the risk of glaucomatous progression. Currently, an increasing number of researches involve Rho kinase inhibitors, which are a new pharmacological class of hypotensive agents specifically targeting the diseased trabecular outflow pathway. Rho kinase inhibitors reduce IOP by increasing aqueous humor drainage through the primary outflow pathway in the eye, which is known as the trabecular meshwork. In addition to improving the outflow facility of the trabecular meshwork, Rho kinase inhibitors also enhance retinal ganglion cell survival after ischemic injury and increase ocular blood flow

Impact of ERT and follow-up of 17 patients from the same family with a mild form of MPS II

Background: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme Iduronate-2- Sulfatase (IDS), leading to progressive accumulation of Glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefits for patients, retarding the natural progression of the disease. Results: The authors evaluated 17 patients from the same family with a mild form of MPS type II; the proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgical complications shortly after the procedure. Nevertheless, subsequent to his tragic death, 16 affected male relatives were detected after biochemical tests identifying the low or absent activity of the IDS enzyme and confirmed by molecular analysis of the IDS gene. Following diagnosis, different options of treatment were chosen: 6 patients started ERT with Elaprase® (Idursulfase) soon after, while the other 10 remained without ERT. Eventually, 4 patients in the latter group began ERT with Hunterase® (Idursulfase Beta). None presented adverse effects to either form of the enzyme. Among the 6 individuals without any ERT, two died of natural causes, after reaching 70 years. Despite the variable phenotype within the same family (mainly heart dysfunctions and carpal tunnel syndrome), all 14 remaining patients were alive with an independent lifestyle. Conclusion: Here, the authors report the variable progress of the disease with and without ERT in a large Brazilian family with a slowly progressive form of MPS II, harboring the same missense variant in the IDS gene

Exploring the Martian Subsurface with Ma_MISS EXOMARS 2022

International audienc

Angiopoietin-1 is required for Schlemm’s canal development in mice and humans

Made available in accordance with publisher's policyPrimary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and is caused by developmental defects in 2 aqueous humor outflow structures, Schlemm’s canal (SC) and the trabecular meshwork. We previously identified loss-of-function mutations in the angiopoietin (ANGPT) receptor TEK in families with PCG and showed that ANGPT/TEK signaling is essential for SC development. Here, we describe roles for the major ANGPT ligands in the development of the aqueous outflow pathway. We determined that ANGPT1 is essential for SC development, and that Angpt1-knockout mice form a severely hypomorphic canal with elevated intraocular pressure. By contrast, ANGPT2 was dispensable, although mice deficient in both Angpt1 and Angpt2 completely lacked SC, indicating that ANGPT2 compensates for the loss of ANGPT1. In addition, we identified 3 human subjects with rare ANGPT1 variants within an international cohort of 284 PCG patients. Loss of function in 2 of the 3 patient alleles was observed by functional analysis of ANGPT1 variants in a combined in silico, in vitro, and in vivo approach, supporting a causative role for ANGPT1 in disease. By linking ANGPT1 with PCG, these results highlight the importance of ANGPT/TEK signaling in glaucoma pathogenesis and identify a candidate target for therapeutic development

A (in)visibilidade da violência psicológica na infância e adolescência no contexto familiar

A violência psicológica na infância e adolescência, no contexto familiar, ainda é pouco estudada. Este artigo tem como objetivo analisar como a violência psicológica na família relatada por crianças e adolescentes tem sido abordada nos estudos acadêmicos, através de revisão de literatura. A metodologia utilizada baseou-se na pesquisa bibliográfica das fontes de informações das bases de dados da LILACS, MEDLINE, SciELO, PubMed e do Portal Capes, nas bases Scopus e PsycInfo. Entre 51 estudos epidemiológicos, 16 desses se mostraram adequados ao objetivo desse artigo e comprovam a alta prevalência deste tipo de violência. Através dessa revisão pode-se perceber que esse tema tem sido mais estudado na literatura internacional do que na brasileira, e que aumentou significativamente sua visibilidade na última década, porém ainda enfrenta dificuldades quanto à definição, conceituação e operacionalidade. Constatou-se que a violência psicológica ao sair da invisibilidade pode colaborar para o aumento da prevenção e da proteção desta natureza de violência.Psychological family violence in childhood and adolescence is still poorly studied, due to difficulties in its definition and detection. This article aims to examine how psychological family violence reported by children and adolescents has been addressed in academic studies, using a literature review (LILACS, MEDLINE, SciELO, PubMed, CAPES Portal, PsycINFO, and SCOPUS databases). Among 51 epidemiological studies, 16 articles met the review's objectives; some of the articles reported a high prevalence of such violence. The study showed that the issue has been studied more in the international literature than in Brazil, which has significantly increased its visibility in the last decade but still faces difficulties involving definition, conceptualization, and operationalization. Eliminating the invisibility of psychological violence in the family could help promote prevention of such violence and protection of children and adolescents

Genetic analysis in posterior polar congenital cataracts

Introdução: A opacidade localizada na capsula posterior do cristalino e chamada de catarata polar posterior e, devido a proximidade do ponto nodal, resulta frequentemente em diminuicao da acuidade visual acentuada. A incidencia de catarata congenita e estimada em um a seis casos por 10.000 nascidos vivos. As cataratas hereditarias correspondem a mais da metade das cataratas congenitas e o padrao de heranca mais comum e o autossomico dominante. Objetivos: Fazer a analise clinica e genetica de uma familia com catarata congenita polar posterior. Metodos: Foram examinados 44 membros de uma familia com catarata congenita polar posterior, incluindo historia familiar, exame clinico geral e oftalmologico. Sangue periferico foi colhido com consentimento para analise genetica. O DNA foi extraido e amplificado em reacoes de PCR com marcadores polimorficos localizados proximos aos loci previamente descritos para catarata polar posterior. Apos a exclusao dessas regioes, um mapeamento de todo o genoma humano foi realizado pela utilizacao de um painel de marcadores polimorficos com intervalos de 20 cM (Research Genetics). Resultados: O locus da doenca nesta familia nao se mostrou ligado a nenhum dos loci previamente descritos para catarata polar posterior nos cromossomos 1, 11, 16 e 20. Observou-se ligacao no cromossomo 10q25. A analise do haplotipo com mais marcadores na regiao localizou o gene da doenca em um intervalo de 14cM entre os marcadores D10S1680 e D10S467, no qual o gene PITX3 estava incluido. No sequenciamento das regioes codificadoras do gene PITX3, uma duplicacao de 17 pares de bases no exon 3 foi encontrada. Essa mutacao leva a uma mudanca na sequencia codificadora do gene, alterando os 82 aminoacidos do terminal C e interrompendo a funcao da proteina. Conclusoes: 0 presente estudo identificou um novo papel para o gene PITX3 como responsavel pelo desenvolvimento da catarata congenita polar posterior. A mutacao encontrada neste foi previamente descrito em um paciente com disgenesia do segmento anterior. A diferenca do fenotipo desta familia previamente descrita deve resultar de um gene modificador. A identificacao de genes causadores de formas hereditarias de catarata congenita aumenta o nosso conhecimento sobre a cataratogenese e sobre a fisiologia do cristalino. A maior importancia deste assunto deve-se ao fato de que os genes causadores de catarata congenita podem estar implicados na catarata senil, que persiste como a maior causa da cegueira mundialBV UNIFESP: Teses e dissertaçõe