95 research outputs found

    A chemical biological approach to study G protein-coupled receptors: labeling the adenosine A1 receptor using an electrophilic covalent probe

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    G protein-coupled receptors (GPCRs) have been known for decades as attractive drug targets. This has led to the development and approval of many ligands targeting GPCRs. Although ligand binding effects have been studied thoroughly for many GPCRs, there are multiple aspects of GPCR signaling that remain poorly understood. The reasons for this are the difficulties that are encountered upon studying GPCRs, for example, a poor solubility and low expression levels. In this work, we have managed to overcome some of these issues by developing an affinity-based probe for a prototypic GPCR, the adenosine A1 receptor (A1AR). Here, we show the design, synthesis, and biological evaluation of this probe in various biochemical assays, such as SDS-PAGE, confocal microscopy, and chemical proteomics.Toxicolog

    Prevenção da formação de hidratos em gasodutos submarinos

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    Ao longo do processo de transporte do gás natural em gasodutos submarinos até as Unidades de Processamento, a indústria petrolífera pode enfrentar diversos problemas, dentre eles, a formação de hidratos. O ambiente submarino possui condições propicias de pressão (alta) e temperatura (baixa) para que estas estruturas sólidas se formem. Os hidratos são problemas críticos para a garantia de escoamento, pois podem causar entupimento das tubulações, prisão e problemas de acionamento em equipamentos, podem comprometer a produtividade das operações, aumentar custos de produção e consumo de energia, além de gerar danos aos equipamentos e as estruturas, comprometendo a segurança das atividades e em casos mais extremos, causando a paralisação completa da produção. Por isso, faz-se necessário adotar medidas de controle, planejamento e monitoramento das condições termodinâmicas as quais o gás natural está sendo transportado. Neste trabalho são simuladas as condições próximas das reais enfrentadas durante o transporte do gás natural produzido na Unidade de Produção de Petróleo e Gás Natural FPSO Cidade de Vitória até a Unidade de Tratamento de Gás de Cacimbas. Para verificar as propriedades de fluxo do sistema, a temperatura e a pressão de formação dos hidratos, e dimensionar de forma otimizada o uso de métodos químicos (inibidores) e métodos térmicos (aquecedores) de prevenção será utilizado o software HYSYS. Os resultados obtidos comprovam a eficiência do inibidor termodinâmico metanol na prevenção da formação do hidrato e as vazões necessárias para realizar este controle. Além disso, indica-se a quantidade de energia necessária para que um aquecedor elétrico forneça calor suficiente à tubulação para prevenir a formação de hidratos, mostrando que este método térmico pode substituir a injeção do metanol, porém é necessário avaliar o requisito energético, que pode ser elevado. Palavras-chave: transporte de gás natural; escoamento transiente; hidrato; inibidores de hidrato

    Development of an affinity-based probe to profile endogenous human adenosine A3 receptor expression

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    The adenosine A3 receptor (A3AR) is a G protein-coupled receptor (GPCR) that exerts immunomodulatory effects in pathophysiological conditions such as inflammation and cancer. Thus far, studies toward the downstream effects of A3AR activation have yielded contradictory results, thereby motivating the need for further investigations. Various chemical and biological tools have been developed for this purpose, ranging from fluorescent ligands to antibodies. Nevertheless, these probes are limited by their reversible mode of binding, relatively large size, and often low specificity. Therefore, in this work, we have developed a clickable and covalent affinity-based probe (AfBP) to target the human A3AR. Herein, we show validation of the synthesized AfBP in radioligand displacement, SDS-PAGE, and confocal microscopy experiments as well as utilization of the AfBP for the detection of endogenous A3AR expression in flow cytometry experiments. Ultimately, this AfBP will aid future studies toward the expression and function of the A3AR in pathologies.Medicinal Chemistr

    Exploratory research in alternative raw material sources and reformulation for industrial soda-lime-silica glass batch

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    For energy saving and CO2 emissions reduction, in addition to extending the range of suitable raw material sources for glass manufacture, compositional reformulation, and alternative raw materials have been studied in the context of industrial container and float‐type soda‐lime‐silica (SLS) glasses. Lithium, potassium, and boron were applied to modify benchmark glass compositions. Reformulation impacts on key glass properties including the viscosity‐temperature relationship, thermal expansion, liquidus temperature, forming behavior and color. Compared to the benchmark glass, representative of commercial SLS glasses, melting temperatures (taken as temperatures corresponding to log (viscosity/dPa·s) = 2) of reformulated glasses are reduced by 11°C‐55°C. Investigation of four industrial by‐products (seashell waste, eggshell waste, biomass ash, and rice husk ash), and their potential suitability as alternative glass batch raw materials, was also conducted. Seashell waste and biomass ash were successfully introduced into representative green glass formulations

    Effects of composition and phase relations on mechanical properties and crystallisation of silicate glasses

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    Crystallization, mechanical properties and workability are all important for commercialization and optimization of silicate glass compositions. However, the inter-relations of these properties as a function of glass composition have received little investigation. Soda-lime-silica glasses with Na2O-MgO-CaO-Al2O3-SiO2 compositions relevant to commercial glass manufacture were experimentally studied and multiple liquidus temperature and viscosity models were used to complement the experimental results. Liquidus temperatures of the fabricated glasses were measured by the temperature gradient technique, and Rietveld refinements were applied to X-Ray powder diffraction (XRD) data for devitrified glasses, enabling quantitative determination of the crystalline and amorphous fractions and the nature of the crystals. Structural properties were investigated by Raman spectroscopy. Acoustic echography, micro-Vicker’s indentation and single-edge notched bend testing methods were used to measure Young’s moduli, hardness and fracture toughness, respectively. It is shown that it is possible to design lower-melting soda-lime-silica glass compositions without compromising their mechanical and crystallization properties. Unlike Young’s modulus, brittleness is highly responsive to the composition in soda-lime-silica glasses, and notably low brittleness values can be obtained in glasses with compositions in the wollastonite primary phase field: an effect that is more pronounced in the silica primary phase field. The measured bulk crystal fractions of the glasses subjected to devitrification at the lowest possible industrial conditioning temperatures, indicate that soda-lime-silica glass melts can be conditioned close to their liquidus temperatures within the compositional ranges of the primary phase fields of cristobalite, wollastonite or their combinations

    Management of cultural differences under various forms of China–UK higher education strategic alliances

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    International strategic alliances are notorious for their high failure rate. Increased inter-partner conflict resulting from ineffective cross-cultural management is perceived to be one of the key reasons for unsatisfactory alliance performance. Driven by globalization, universities are extending into foreign markets through the establishment of various types of strategic alliances (SAs). Through an empirical investigation, this study reveals that although cultural differences (CDs) exist in China–UK higher education (HE) SAs their impact depends on the structure of the SA. Although cultural conflicts occur more frequently in equity joint ventures than in non-equity modes, the impact of conflict arising from CDs is more serious and significant in non-equity arrangements. Moreover, partners perceive CDs as sources of mutual interest. The findings imply that the negative impact of CDs can be ameliorated to varying degrees depending on the type of China–UK HE SA

    internationalization strategies and policies in second tier higher education institutions

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    This study addresses the major objectives and challenges in the internationalization processes of second-tier higher education institutions. We use the examples of universities of applied sciences in the Netherlands, academic colleges in Israel, and community colleges in Canada to offer a global perspective regarding the internationalization efforts in these types of institutions. Through comprehensive comparative analysis of secondary sources, we identify the trends taking place within these types of higher education institutions in these countries. We find that second-tier institutions tend not to have solidified for themselves tailored internationalization approaches and strategies that are uniquely fitting to their own missions, aims and student populations. This oversight creates a situation whereby such institutions, despite their culturally diverse student populations and the promise they hold to create a unique niche within internationalization discourse, fail to utilize the potential inherent in targeted internationalization strategies
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