Development of diamond tracking detectors for high luminosity experiments at the LHC

Tracking detectors have become an important ingredient in high energy physics experiments. In order to survive the harsh detection environment of the LHC, trackers need to have special properties. They must be radiation hard, provide fast collection of charge, be as thin as possible and remove heat from readout electronics. The unique properties of diamond allow it to fulfil these requirements. Further, recent progress in the production of chemical vapour deposited diamond makes large surface area detectors now realistic. We propose a development programme which improves the charge collection properties of diamond, studies the radiation hardness of the material, designs various tracking devices, develops low noise, radiation hard electronics to read out the detectors and applies diamond as a thermal management tool for the LHC

Extração do aroma de bacuri e sua utilização como flavorizante em iogurte natural.

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Revealing cytotoxic substructures in molecules using deep learning

In drug development, late stage toxicity issues of a compound are the main cause of failure in clinical trials. In silico methods are therefore of high importance to guide the early design process to reduce time, costs and animal testing. Technical advances and the ever growing amount of available toxicity data enabled machine learning, especially neural networks, to impact the field of predictive toxicology. In this study, cytotoxicity prediction, one of the earliest handles in drug discovery, is investigated using a deep learning approach trained on a highly consistent in-house data set of over 34,000 compounds with a share of less than 5% of cytotoxic molecules. The model reached a balanced accuracy of over 70%, similar to previously reported studies using Random Forest. Albeit yielding good results, neural networks are often described as a black box lacking deeper mechanistic understanding of the underlying model. To overcome this absence of interpretability, a Deep Taylor Decomposition method is investigated to identify substructures that may be responsible for the cytotoxic effects, the so-called toxicophores. Furthermore, this study introduces cytotoxicity maps which provide a visual structural interpretation of the relevance of these substructures. Using this approach could be helpful in drug development to predict the potential toxicity of a compound as well as to generate new insights into the toxic mechanism. Moreover, it could also help to de-risk and optimize compounds

Discrimination of natural colors in anomalous trichromacy and the effects of EnChroma and Vino filters

It is still unclear how well anomalous trichromats discriminate natural colors and whether commercial spectral filters improve performance in these conditions. We show that anomalous trichromats have good color discrimination with colors drawn from natural environments. It is only about 14% poorer, on average, than normal trichromats in our sample of thirteen anomalous trichromats. No measurable effect of the filters on discrimination was found, even after 8 hours of continuous use. Computations of cone and post-receptoral signals show only a modest increase in medium-to-long-wavelength difference signals, which may explain the absent effect of the filters.Fundação para a Ciência e a Tecnologia (UIDB/FIS/04650/2020); Fundação para a Ciência e a Tecnologia/Fundo Social Europeu (2020.05785.BD

Literatura infanto-juvenil brasileira e o novo modelo familiar: análise da recepção do livro “Meus dois pais”

Um novo núcleo familiar, o de casais do mesmo sexo, passou a ser reconhecido pela primeira vez pelo IBGE no Censo Demográfico 2000-2010, entre as chamadas famílias reconstituídas após a separação ou a morte de um dos cônjuges. As famílias reconstituídas representaram 16,3% do total de famílias no Brasil, aqui entendidas as famílias tradicionais constituídas por marido, mulher e filhos. Entre os 16,3%, existem 60 mil casais do mesmo sexo, grande parte com filhos – crianças ou adolescentes. Este trabalho avalia a recepção da obra Meus Dois Pais, de Walcyr Carrasco, por alunos do ensino fundamental de uma escola pública do Distrito Federal. O livro aborda as dificuldades de um garoto para aceitar o pai e o seu companheiro homoafetivo. O estudo foi baseado na Teoria da Recepção, para a qual a obra apenas se completa a partir da intervenção do leitor, que chega até ela trazendo sua história pessoal e a do momento em que vive. Foi realizada uma pesquisa de campo com o grupo infantil, que permitiu a discussão do tema em relação às referências levantadas. Os resultados apresentados permitiram concluir que, de modo geral, o novo núcleo familiar brasileiro, constituído de dois pais ou duas mães, ainda é visto com estranheza e receio pela maioria dos alunos. Há uma pequena parte, no entanto, que o aceita com naturalidade

Coleta de germoplasma de bacuri (Platonia insignis Mart.) na Amazônia I. Microrregião campos do Marajó (Soure/Salvaterra).

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Reverse-Design toward Optimized Labeled Chemical Probes – Examples from the Endocannabinoid System

Labeled chemical probes are of utmost importance to bring drugs from the laboratory through the clinic and ultimately to market. They support and impact all research and discovery phases: target verification and validation; assay development; lead optimization; and biomarker engagement in the context of preclinical studies and human trials. Probes should display high potency and selectivity as well as fulfill specific criteria in connection with absorption, distribution, metabolism, excretion and toxicology (ADMET) profile. Progress in fields such as imaging and proteomics increased the need for specialized probes to support drug discovery. Labeled probes carrying an additional reporter group are valuable tools to meet specific application requirements, but pose significant challenges in design and construction. In the reverse-design approach, small molecules previously optimized in medicinal chemistry programs form the basis for the generation of such high-quality probes. We discuss the reverse design concept for the generation of labeled probes targeting the endocannabinoid system (ECS), a complex lipid signaling network that plays a key role in many human health and disease conditions. The examples highlighted include diverse reporter units for a range of applications. In several cases the reported probes were the product of mutually rewarding and highly cross-fertilizing collaborations among academic and industry research programs, a strategy that can serve as a blueprint for future probe generation efforts

Identification of a novel benzimidazole pyrazolone scaffold that inhibits KDM4 lysine demethylases and reduces proliferation of prostate cancer cells

Human lysine demethylase (KDM) enzymes (KDM1-7) constitute an emerging class of therapeutic targets, with activities that support growth and development of metastatic disease. By interacting with and co-activating the androgen receptor, the KDM4 subfamily (KDM4A-E) promotes aggressive phenotypes of prostate cancer (PCa). Knockdown of KDM4 expression or inhibition of KDM4 enzyme activity reduces the proliferation of PCa cell lines and highlights inhibition of lysine demethylation as a possible therapeutic method for PCa treatment. To address this possibility, we screened the ChemBioNet small molecule library for inhibitors of the human KDM4E isoform and identified several compounds with IC50 values in the low micromolar range. Two hits, validated as active by an orthogonal enzyme-linked immunosorbent assay, displayed moderate selectivity toward the KDM4 subfamily and exhibited antiproliferative effects in cellular models of PCa. These compounds were further characterized by their ability to maintain the transcriptionally silent histone H3 tri-methyl K9 epigenetic mark at subcytotoxic concentrations. Taken together, these efforts identify and validate a hydroxyquinoline scaffold and a novel benzimidazole pyrazolone scaffold as tractable for entry into hit-to-lead chemical optimization campaigns