12 research outputs found

    Advancing biological understanding and therapeutics discovery with small-molecule probes

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    Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the NIH launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines but also highlight the need to innovate the science of therapeutic discovery

    The emergence and outcomes of collective action: an institutional and ecosystem approach A emergência e os resultados da ação coletiva: uma abordagem institucional e ecossistêmica

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    Participation in collective action is frequently studied through a community-based analysis, with focus on the social features of the participants and on the ecological features of the managed system. This study addresses the importance of scaling down to household level to understand different individual incentives to collaborate (or not) as well as scaling up to the landscape level to evaluate the ecological outcome of the local forms of collective action. A study of a riparian community of 33 households in the Lower Amazon located between two distinct ecosystems -a privately owned upland forest and a communally owned floodplain- reveals that household-based analysis uncovers how heterogeneity within the community leads to different incentives for participation in the communal floodplain, while systemic analysis reveals that interconnection between the managed ecosystem and adjacent ecosystem influences the decisions to participate as well as the ecological outcomes of the collective actions.<br>A participação numa ação coletiva é estudada com freqüência por meio de uma análise baseada nas comunidades e enfocada nas características sociais dos participantes e nas características ecológicas do sistema manejado. Este estudo refere-se à importância de se limitar a análise ao nível das famílias para compreender os diferentes incentivos individuais que colaboram (ou não), assim como de se ampliar a análise ao nível da esfera territorial a fim de se avaliar o resultado ecológico das formas locais de ação coletiva. Um estudo feito numa comunidade costeira de 33 famílias na Baixa Amazonia situada entre dois ecosistemas diferentes -uma mata/floresta de propriedade privada situada em terras altas e uma planície pluvial pertencente a uma comunidade- revela que a análise baseada nas famílias mostra que a heterogeneidade dentro da comunidade conduz a diferentes incentivos para participar das atividades na planície pluvial. A análise sistêmica, no entanto, mostra que a interconexão entre o ecosistema manejado e o ecosistema adjacente influi nas decisões para participar assim como nos resultados das ações coletivas

    Tumor Immune Escape Mechanisms

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    Silica and other materials as supports in liquid chromatography. Chromatographic tests and their importance for evaluating these supports. Part I

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    Reversed-phase liquid chromatography (RP-HPLC) has become a powerful and widely employed technique in the separation and analysis of a great variety of compounds with different functionalities. The most common type of stationary phase for RP-HPLC consists of nonpolar, hydrophobic organic species (e.g., octyl, octadecyl) attached by siloxane bonds to the surface of a silica support. In the first part of this article, a description of the many beneficial properties that make porous silica the most employed support in RP-HPLC will be presented, starting from the synthesis of silica. It is noteworthy that the chromatographic properties of the final column are strictly correlated to the preparation type. A silica surface possesses a number of attractive properties, but also some drawbacks. Unreacted or residual silanols interact with basic compounds and can induced peak tailing, which means a loss in chromatographic performance. This problem has lead many manufactures to produce stationary phases with reduced silanol activity which improve dramatically the peak shape of basic compounds. In the second part of this review, different approaches are proposed to obtain less reactive stationary phases

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