Ripples and Grains Segregation on Unpaved Road

Ripples or corrugations are common phenomena observed in unpaved roads in less developed countries or regions. They cause several damages in vehicles leading to increased maintenance and product costs. In this paper, we present a computational study about the so-called washboard roads. Also, we study grain segregation on unpaved roads. Our simulations have been performed by the Discrete Element Method (DEM). In our model, the grains are regarded as soft disks. The grains are subjected to a gravitational field and both translational and rotational movements are allowed. The results show that wheels' of different sizes, weights and moving with different velocities can change corrugations amplitude and wavelength. Our results also show that some wavelength values are related to specific wheels' speed intervals. Segregation has been studied in roads formed by three distinct grain diameters distribution. We observed that the phenomenon is more evident for higher grain size dispersion

Machine learning for target discovery in drug development.

The discovery of macromolecular targets for bioactive agents is currently a bottleneck for the informed design of chemical probes and drug leads. Typically, activity profiling against genetically manipulated cell lines or chemical proteomics is pursued to shed light on their biology and deconvolute drug-target networks. By taking advantage of the ever-growing wealth of publicly available bioactivity data, learning algorithms now provide an attractive means to generate statistically motivated research hypotheses and thereby prioritize biochemical screens. Here, we highlight recent successes in machine intelligence for target identification and discuss challenges and opportunities for drug discovery.T.R. is an Investigador Auxiliar supported by FCT Portugal (CEECIND/00887/2017). T.R. acknowledges the H2020 (TWINN-2017 ACORN, Grant 807281) and FCT/FEDER (02/SAICT/2017, Grant 28333) for funding. G.J.L.B. is a Royal Society University Research Fellow (URF\R\180019) and a FCT Investigator (IF/00624/2015)

IBP study:Idanha-a-Nova/Pt blood pressure study

Objetivos: Determinar a prevalência de Hipertensão Arterial na população adulta do concelho de Idanha-a-Nova, assim como verificar as suas taxas de tratamento e controlo e discriminar quais os fatores de risco associados. Métodos: Trata-se de um estudo transversal, analítico, observacional e prospetivo que se realizou nas várias freguesias do concelho, sendo a amostra constituída por 992 indivíduos, dos quais 52,4% são do género feminino e 47,6% do masculino, com idades compreendidas entre os 18 e 95 anos. A recolha de dados decorreu entre junho e julho de 2013, tendo consistido na avaliação dos valores de pressão arterial e realizadas três avaliações com um intervalo regular de 5 minutos. Resultados: A prevalência de Hipertensão Arterial encontrada foi de 51,0%, dos quais 25,7% eram do género feminino e 25,3% do masculino. Aferiu-se ainda que, do total de inquiridos, 30,7% afirmou tomar medicação anti-hipertensora, sendo que destes 49,8% apresentava os valores de pressão arterial dentro dos níveis de normalidade. Dos fatores de risco encontrados verificou-se que os mais predominantes foram a história familiar de Hipertensão Arterial e a dislipidémia, com prevalências de 36,0% e 35,2%, respetivamente. Conclusões: Verifica- -se uma elevada prevalência de Hipertensão Arterial no concelho estudadoABSTRACT: Objectives: To determine the prevalence of Arterial Hypertension in the adult population of the municipality of Idanha-a-Nova, as well as to verify its treatment and control rates, and to discriminate which are the associated risk factors. Methods: It is a cross-sectional, analytic, observational and prospective study which was performed in each of the various townships, forming a base sample of 992 individuals, of which 52,4% are female, and 47,6% are male, between 18 and 95 years of age. Data collection was performed between June and July of 2013, consisting of the evaluation of arterial pressure values, for this purpose three evaluations were performed with a regular interval of 5 minutes. Results: The prevalence of Arterial Hypertension found was of 51,0%, of which 25,7% were female and 25,3% male. It was also confirmed that, out of the total of inquired individuals, 30,7% stated to take Anti-Hypertension medication, and out of these, 49,8% showed normal levels of blood pressure. Within the risk factors found the most predominant ones were Arterial Hypertension family history and Dyslipidemia, reaching values of 36,0% and 35,2%, respectively. Conclusions: The study shows elevated values of Arterial Hypertension in the county of Idanha.info:eu-repo/semantics/publishedVersio

On the Nexus Between CSR Practices, ESG Performance, and Asymmetric information

The purpose of this paper is to test the relationship of CSR practice­–asymmetry information and ESG performance–asymmetry information. We conjecture that there might be a particular role where the disclosure of non-financial information is deemed useful in truncating the level of asymmetry information. Using the data from two different countries, Indonesia (Asia) and Portugal (Europe), we extracted 37 companies with time period of observation ranges from 2012 to 2016. To manifest the empirical test, we use CSR report (CSR_Rep), CSR committee (CSR_com), CSR assurance (CSR_ass) and GRI adoption as the proxies of CSR practice, while the proxies of ESG performance are represented by Environmental (ENVscr), Social (SOCscr), and Governance (GOVscr) pillar scores as obtained from Thomson Reuters ASSET4 database. Bid-ask spread is used as the surrogate indicator of asymmetry information. The empirical test reveals that only variable GRI and SOCscr show negative and significant association with bid-ask spread. Whilst, the remaining variables of CSR practice (CSR_rep, CSR_com, CSR_ass), and ESG performance (ENVscr and GOVscr) are negatively associated with asymmetry information (Spread) but statistically insignificant. Our results suggest that CSR practice and ESG performance are weakly associated with asymmetry information, in which most of CSR practices and ESG performance need a time lag to allow them to be value relevant information in mitigating the level of asymmetry information

Adaptive Optimization of Chemical Reactions with Minimal Experimental Information

Optimizing reaction conditions depends on expert chemistry knowledge and laborious exploration of reaction parameters. To automate this task and augment chemical intuition, we here report a computational tool to navigate search spaces. Our approach (LabMate.ML) integrates random sampling of 0.03%–0.04% of all search space as input data with an interpretable, adaptive machine-learning algorithm. LabMate.ML can optimize many real-valued and categorical reaction parameters simultaneously, with minimal computational resources and time. In nine prospective proof-of-concept studies pursuing distinctive objectives, we demonstrate how LabMate.ML can identify optimal goal-oriented conditions for several different chemistries and substrates. Double-blind competitions and the conducted expert surveys reveal that its performance is competitive with that of human experts. LabMate.ML does not require specialized hardware, affords quantitative and interpretable reactivity insights, and autonomously formalizes chemical intuition, thereby providing an innovative framework for informed, automated experiment selection toward the democratization of synthetic chemistry.D.R. is a Swiss National Science Foundation Fellow (grant nos. P2EZP3_168827 and P300P2_177833). E.A.H. is supported by the Herchel Smith Fellowship awarded by Williams College. G.J.L.B. is a Royal Society URF (URF\R\180019). T.R. is an Investigador Auxiliar supported by FCT Portugal (CEECIND/00887/2017). T.R. acknowledges the H2020 (TWINN-2017 ACORN, grant no. 807281), FCT/FEDER (02/SAICT/2017, grant no. 28333). D.R. acknowledges the MIT-IBM Watson AI Lab and the MIT SenseTime coalition for funding. The authors are extremely grateful to several colleagues for suggesting Ugi reaction conditions, and to Prof. R. Langer and Prof. G. Traverso, who provided invaluable comments on the research and manuscript. The authors are indebted to Prof. R. Moreira for access to the CEM microwave reactor; Dr. F. Corzana for technical assistance with HRMS; and the 13 graduate students, 17 postdoctoral researchers, and eight principal investigators across Austria, Denmark, Portugal, Spain, the United Kingdom, and the United States who took part in the survey. We thank R. Rodrigues for help in producing Figure 1. The survey was approved by the iMM and MIT (COUHES protocol 1809514426). The authors also thank the four anonymous reviewers for their most insightful comments.info:eu-repo/semantics/publishedVersio

A ROTULAGEM COMO INSTRUMENTO DE EFETIVAÇÃO DO DIREITO DE LIBERDADE DE ESCOLHA DO CONSUMIDOR

A informação é um direito básico do consumidor, derivado de princípios constitucionais e explicitamente relatado no Código de Defesa do Consumidor (CDC). Com essa diretriz clara que ilumina as relações de consumo, este artigo tem por objetivo geral analisar a rotulagem dos produtos como meio para a efetivação dos direitos básicos do consumidor à informação e à liberdade de escolha. Seus objetivos específicos consistem em descrever os direitos básicos do consumidor derivados do texto constitucional e previstos no CDC; demonstrar a relevância do direito de informação do consumidor e do consectário dever de informar do fornecedor de produtos; e analisar a função dos rótulos dos produtos para a efetivação do direito de informação e do direito de escolha do consumidor. Este estudo utilizou-se do método dedutivo e de pesquisa bibliográfica. Concluiu-se que os rótulos precisam ser adequados, suficientes, verídicos e claros para que possam transmitir informação digna ao consumidor, influenciando, com isso, no seu direito de escolha

Computational advances in combating colloidal aggregation in drug discovery.

Small molecule effectors are essential for drug discovery. Specific molecular recognition, reversible binding and dose-dependency are usually key requirements to ensure utility of a novel chemical entity. However, artefactual frequent-hitter and assay interference compounds may divert lead optimization and screening programmes towards attrition-prone chemical matter. Colloidal aggregates are the prime source of false positive readouts, either through protein sequestration or protein-scaffold mimicry. Nevertheless, assessment of colloidal aggregation remains somewhat overlooked and under-appreciated. In this Review, we discuss the impact of aggregation in drug discovery by analysing select examples from the literature and publicly-available datasets. We also examine and comment on technologies used to experimentally identify these potentially problematic entities. We focus on evidence-based computational filters and machine learning algorithms that may be swiftly deployed to flag chemical matter and mitigate the impact of aggregates in discovery programmes. We highlight the tools that can be used to scrutinize libraries, and identify and eliminate these problematic compounds.D.R. is a Swiss National Science Foundation Fellow (Grants P2EZP3_168827 and P300P2_177833). G.J.L.B. is a Royal Society URF (UF110046 and URF/R/180019), an iFCT Investigator (IF/00624/2015), and the recipient of an ERC StG (TagIt, Grant Agreement 676832). T.R. and G.J.L.B. acknowledge Marie Sklodowska-Curie ITN Protein Conjugates (Grant Agreement 675007) for funding. T.R. is a Marie Curie Fellow (Grant Agreement 743640). T.R. acknowledges the H2020 (TWINN-2017 ACORN, Grant Agreement 807281) and POR Lisboa 2020/FEDER (02/SAICT/2017, Grant Agreement Lisboa-01-0145-FEDER-028333) for funding. D.R. acknowledges the MIT-IBM Watson AI Lab and the MIT SenseTime coalition for funding

Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents.

Treatment of cancer is a significant challenge in clinical medicine, and its research is a top priority in chemical biology and drug discovery. Consequently, there is an urgent need for identifying innovative chemotypes capable of modulating unexploited drug targets. The transient receptor potential (TRPs) channels persist scarcely explored as targets, despite intervening in a plethora of pathophysiological events in numerous diseases, including cancer. Both agonists and antagonists have proven capable of evoking phenotype changes leading to either cell death or reduced cell migration. Among these, natural products entail biologically pre-validated and privileged architectures for TRP recognition. Furthermore, several natural products have significantly contributed to our current knowledge on TRP biology. In this Tutorial Review we focus on selected natural products, e.g. capsaicinoids, cannabinoids and terpenes, by highlighting challenges and opportunities in their use as starting points for designing natural product-inspired TRP channel modulators. Importantly, the de-orphanization of natural products as TRP channel ligands may leverage their exploration as viable strategy for developing anticancer therapies. Finally, we foresee that TRP channels may be explored for the selective pharmacodelivery of cytotoxic payloads to diseased tissues, providing an innovative platform in chemical biology and molecular medicine.We thank FCT Portugal (FCT Investigator to G. J. L. B.), the EU (Marie-Curie CIG and Marie-Curie ITN Protein Conjugates to G. J. L. B.), Deutsche Forschungsgemeinschaft (Postdoctoral Fellowship to F. S.), the EPSRC and MRC for funding. G. J. L. B. is a Royal Society University Research Fellow and the recipient of an European Research Council Starting Grant (TagIt)

Traços identitários e confluências da culinária amazonense

O trabalho, fruto de um dos resultados parciais de projeto de pesquisa do Programa Institucional de Bolsas de Iniciação Científica, visa identificar os traços significativos de construção das tradições alimentares do estado do Amazonas. A culinária é uma das mais importantes vertentes culturais de formação de um povo, através dela é possível caracterizar social, econômica, geográfica e antropologicamente os aspectos de determinada cultura. Através da análise do sistema alimentar torna-se possível a compreensão de sua identidade, permitindo conhecer as principais dissonâncias e convergências da composição dos hábitos alimentares e uma tematização sobre essa prática. Nesse sentido, objetiva-se identificar os traços essenciais que compõem a culinária amazonense, as intercorrências e interferências externas e internas da constituição de uma culinária própria e ponderar, a partir da diversidade dessa região, a existência de uma caracterização cultural-alimentar própria, que se utiliza de maneira comum de elementos como a mandioca, o açaí, a castanha do Brasil, o cupuaçu, além do alto consumo de peixes entre outros. Trata-se de um estudo de revisão que demonstra as potencialidades alimentares do estado, compondo um misto de técnicas de preparo, alimentos e costumes alimentares, que pressupõe uma dinamicidade fruto da miscigenação no desenvolvimento da região. Para tal, analisa-se a diversidade da cozinha amazonense a partir da compreensão da herança dos povos Indígenas aliados aos africanos, europeus e árabes, como resultado direto da exploração durante a colonização, da incursão dos jesuítas até a segunda metade do século XVIII, do povo nordestino atraído pela atividade do látex no século XIX e finalmente da abertura dos eixos rodoviários que possibilitaram novos fluxos migratórios. Toda essa convergência, se por um lado contaminou os hábitos culturais dos povos indígenas, do outro lado fomentou a construção de uma cultura alimentar própria do Estado