1,587 research outputs found
A Web Semântica e a Educação
Esse artigo discute a construção e aplicação de ontologias parasistemas educacionais baseados na Web. A Web existente hoje com umnúmero exponencial de páginas e de acessos exige uma mudança significativanos modelos de busca e entendimento dos conteúdos disponibilizados baseadoem páginas “estruturadas”, que utilizam ferramentas interativas eautomáticas, onde máquinas participam efetivamente interagindo entre si.Diversos domínios do conhecimento poderão fazer uso deste novo recurso,como sistemas educacionais. Esta “nova” web é denominada Web Semânticae utiliza ontologias para obter uma especificação formal, explícita ecompartilhada de conceitos
A Web Semântica e a Educação
Esse artigo discute a construção e aplicação de ontologias parasistemas educacionais baseados na Web. A Web existente hoje com umnúmero exponencial de páginas e de acessos exige uma mudança significativanos modelos de busca e entendimento dos conteúdos disponibilizados baseadoem páginas “estruturadas”, que utilizam ferramentas interativas eautomáticas, onde máquinas participam efetivamente interagindo entre si.Diversos domínios do conhecimento poderão fazer uso deste novo recurso,como sistemas educacionais. Esta “nova” web é denominada Web Semânticae utiliza ontologias para obter uma especificação formal, explícita ecompartilhada de conceitos
A Web Semântica e a Educação
Esse artigo discute a construção e aplicação de ontologias parasistemas educacionais baseados na Web. A Web existente hoje com umnúmero exponencial de páginas e de acessos exige uma mudança significativanos modelos de busca e entendimento dos conteúdos disponibilizados baseadoem páginas “estruturadas”, que utilizam ferramentas interativas eautomáticas, onde máquinas participam efetivamente interagindo entre si.Diversos domínios do conhecimento poderão fazer uso deste novo recurso,como sistemas educacionais. Esta “nova” web é denominada Web Semânticae utiliza ontologias para obter uma especificação formal, explícita ecompartilhada de conceitos
Crescimento de mudas de mamoeiro 'Formosa' em substratos com utilização de composto orgânico superfosfato simples
Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
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