2H-Azirines as electrophiles

2H-Azirines have shown an unusual potential to synthesise aziridines and other types of compounds. Many functionalized aziridines can be produced by addition of O-, S-,N-, C-nucleophiles and hydride to 2H-azirines. This review is designed to give an overview of the reactivity of 2H-azirines as electrophiles along the years and their usefulness in the synthesisof important families of compounds

Desenvolvimento da atenção e da concentração de alunos de 6- 7 anos em contexto de educação não formal - projeto ciência Júnior- ciência para crianças

Caraterísticas como impaciência, agitação, dispersão, entre outras, são encontradas na maior parte das crianças em idade escolar. Estas especificidades, em bastantes casos, chegam a influenciar negativamente o desempenham destas crianças nas atividades escolares. Sendo o Projeto Ciência Júnior – Ciência para crianças (1-3) uma estratégia didática para o ensino das ciências experimentais que tem em conta a necessidade do desenvolvimento de competências como a atenção e a concentração para uma eficiente introdução ao método experimental; tendo como referencial o trabalho de Fonseca (4,5) sobre dificuldades de aprendizagem e partindo da visão sócio-histórica de Luria e Vygotsky (6-8) sobre atenção, o programa referido desenvolveu um trabalho com o objetivo de avaliar e estimular atenção-concentração e a capacidade de autoorganização. Participaram deste programa, 15 alunas com idades compreendidas entre os 6 e os 7 anos de idade, que tendo por base noções desenvolvidas por Piaget e Miranda sobre o jogo (9-10), foram estimuladas pela ordenação e nomeação de ações. Os dados sugerem que formas de autoorganização emergem espontaneamente entre as crianças enquanto jogam e que o perfil de adaptabilidade, e seleção da informação está relacionado com cada etapa do desenvolvimento. Concluímos que a utilização do jogo como método de ensino possibilita aos alunos um momento diferente de aprendizagem onde estes se apresentam motivados e com maior capacidade de seleção de informação. É, portanto, uma boa pista que abre horizontes para aprofundar esta metodologia.info:eu-repo/semantics/publishedVersio

Advances in the synthesis of Homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine. 1-N-phenyl carboxamide derivatives of both enantiomers of 1-azafagomine: leads for the synthesis of active α-Glycosidase inhibitors

- A new expeditious preparation of homochiral (-)-1-azafagomine, and (+)-5-epi-1-azafagomine has been devised. Stoodley´s diastereoselective cycloaddition of dienes bearing a 2,3,4,6-tetraacetyl glucosyl chiral auxiliary to 4-phenyl-1,2,4-triazole-3,5-dione, was merged with Bols protocol for functionalizing alkenes into molecules bearing a glucosyl framework. Homochiral (+)-5-epi-1-azafagomine was synthetized for the first time. Partial reductive cleavage of the phenyltriazolidinone moiety afforded new homochiral 1-N-phenyl carboxamide derivatives of 1-azafagomine. Both enantiomers of these derivatives were synthetized and tested, displaying a very good enzymatic inhibition towards baker´s yeast α-glucosidase. The molecular recognition mechanism of the 1-N-phenyl carboxamide derivative of 1-azafagomine by α-glucosidase from baker´s yeast was studied by molecular modelling. The efficient packing of the aromatic ring of the 1-N-phenyl carboxamide moiety into a hydrophobic sub-site (pocket) in the enzyme´s active site, seems to be responsible for the improved binding affinity in relation to underivatized (-)1-azafagomine and (+)1-azafagomine.We thank FCT for project funding PTDC/QUI/67407/2006 and FCT and FEDER for funding NMR spectrometer Bruker Avance III 400 as part of the National NMR Network. M.N.M. acknowledges the contract research program "Compromisso com a Ciencia" Reference C2008-UMINHO-CQ-03 and access to the Minho University GRIUM cluster

La Mettrie: o projeto da recondução da alma à matéria

Julien Offray de La Mettrie foi um iluminista francês, médico e filósofo do século XVIII. A obra em que apresenta o seu pensamento filosófico estruturado é a Histoire naturelle de l’âme, mas é em l’Homme machine que procura explicar toda a operatividade humana através da matéria. A filosofia de La Mettrie enquadra-se no materialismo e pretende fornecer uma explicação unificada do ser humano em continuidade com aquilo que podemos conhecer da natureza corpórea. La Mettrie pretende reconduzir a alma à matéria provando que o princípio que coloca em movimento um corpo humano é o mesmo que explica as sensações e a complexidade do pensamento intelectual; dessa forma, e por consequência, ficará provado que a alma não é nem a matéria nem os corpos, mas apenas um ente de razão. Para La Mettrie, o estudo da alma humana só pode ser realizado através dos seus efeitos, ou seja, através das propriedades manifestadas nos corpos, e os guias para esse estudo são apenas os sentidos, pois só por eles temos acesso às manifestações da alma nos corpos. O autor afirma que a matéria deverá ser considerada quer como um princípio ativo, possuindo dentro de si mesma a força de se mover e de ser a causa imediata de todas as leis do movimento; quer como um princípio passivo, por possuir em si em potência todas as formas que poderá vir a adquirir. Para o autor, não existe distinção entre a alma racional e a sensível; nem entre a alma e a matéria ou ainda entre a alma e o corpo que ela habita: todas essas realidades são a mesma coisa. A observação da natureza conduz a afirmar que existe uma gradação suave na complexificação da matéria, que a essa complexificação corresponde um aumento de necessidades e que a menos instinto corresponde mais inteligência. O homem é semelhante ao animal: assim o atesta a anatomia comparada dos nossos órgãos. O que nos distingue são essencialmente duas coisas: o maior número de necessidades a satisfazer, resultante de uma maior organização da matéria, e a nossa menor dotação instintiva. A natureza colmata esta dificuldade dotando o homem de pensamento. Assim, constituindo a organização da matéria uma primeira vantagem do homem, a segunda é a instrução. Há, assim, uma proporcionalidade direta entre necessidades e pensamento ao mesmo tempo que existe uma proporcionalidade inversa entre instinto e pensamento. O que complexifica a matéria é a organização e a funcionalidade dos órgãos. As necessidades do organismo são, portanto, efeito dessa complexificação, dessa auto-organização da matéria. Quanto mais necessidades tem o organismo mais meios requer para as satisfazer, sendo o meio por excelência o instinto. Ao ser humano, paradoxalmente com muitas necessidades e pouco instinto, a natureza dotou-o de pensamento que substitui o instinto. Esta é, no entender de La Mettrie, a sua maior descoberta, a saber: aquilo que produz o pensamento é o aumento das necessidades de um organismo e uma simultânea diminuição do instinto.Julien Offray de La Mettrie was an 18th century French enlightenment physician and philosopher. The work in which he presents his structured philosophical thought is Histoire naturelle de l'âme, but it will be through l'Homme machine seeks to explain all human operativity through matter. La Mettrie's philosophy falls under materialism and aims to provide a unified explanation of the human being in continuity with what we can know about corporeal nature. La Mettrie intends to bring the soul back to matter by proving that the principle that sets a human body in motion is the same one that explains sensations and the complexity of intellectual thought, this way, and therefore, for the author is be proven that the soul is neither matter nor body, but only an entity of reason. According to La Mettrie, the study of the human soul can only be accomplished through its effects, that is, through the properties manifested in bodies, and the guides for this study are only the senses, because only they have access to the manifestations of the soul in bodies. The author states that matter should be considered either as an active principle, possessing within itself the power to move and to be the immediate cause of all the laws of motion; or as a passive principle, for possessing within itself in potency all the forms it may come to acquire. Furthermore, La Mettrie argues that there is no distinction between the rational and the sensitive soul; nor between the soul and matter, or even between the soul and the body it inhabits: all these realities are the same. His observation of nature leads him to affirm that there is a smooth gradation in the complexification of matter, to which corresponds an increase in needs that instinct will try to satisfy. To less instinct corresponds to more intelligence, which is the mean nature provides an organized body to satisfy their needs. Man is similar to the animal: as attested by the comparative anatomy of our organs. What distinguishes us? Essentially two things: the greater number of needs to be satisfied, resulting from a greater organization of matter, and our lesser instinctive endowment. How does nature overcome this difficulty? By endowing man with thought. Thus, since the organization of matter constitutes a first advantage of man, the second is instruction. There is thus a direct proportionality between needs and thought while there is an inverse proportionality between instinct and thought. What complexifies matter? The organization and functionality of the organs. The needs of the organism are, therefore, the effect of this complexification, this self-organization of matter. The more needs the organism has, the more means it requires to satisfy them, the mean by excellence is instinct. To the human being, paradoxically with many needs and little instinct, nature has endowed him with thought which replaces instinct.This is La Mettrie's greatest discovery: what produces thought is the increase in an organism's needs and a simultaneous decrease in instinct

Newborn Screening for the Detection of the TP53 R337H Variant and Surveillance for Early Diagnosis of Pediatric Adrenocortical Tumors: Lessons Learned and Way Forward

The incidence of pediatric adrenocortical tumors (ACT) is high in southern Brazil due to the founder TP53 R337H variant. Neonatal screening/surveillance (NSS) for this variant resulted in early ACT detection and improved outcomes. The medical records of children with ACT who did not participate in newborn screening (non-NSS) were reviewed (2012–2018). We compared known prognostic factors between the NSS and non-NSS cohorts and estimated surveillance and treatment costs. Of the 16 non-NSS children with ACT carrying the R337H variant, the disease stages I, II, III, and IV were observed in five, five, one, and five children, respectively. The tumor weight ranged from 22 to 608 g. The 11 NSS children with ACT all had disease stage I and were alive. The median tumor weight, age of diagnosis, and interval between symptoms and diagnosis were 21 g, 1.9 years, and two weeks, respectively, for the NSS cohort and 210 g, 5.2 years, and 15 weeks, respectively, for the non-NSS cohort. The estimated surveillance/screening cost per year of life saved is US$623/patient. NSS is critical for improving the outcome of pediatric ACT in this region. Hence, we strongly advocate for the inclusion of R337H in the state-mandated universal screening and surveillance

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

PubMe

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field