1,271 research outputs found

    Reductive cleavage of sulfones and sulfonamides by neutral organic super electron-donor (S.E.D.) reagent

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    The sulfonyl group finds extensive applications in organic and medicinal chemistry both in sulfonamides, popular as robust protecting groups for amines, and in sulfones. Frequently, sulfones are introduced into synthetic schemes to assist particular transformations; further progress along the synthetic route can later require the removal of a sulfone group, and this can be achieved by reductive desulfonylation or, in the special cases of α-halo- or ß-acyloxysulfones, by elimination to an alkene

    A palace fit for the future: Desirability in temporal work

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    Research on the strategic organization of time often assumes that collective efforts are motivated by and oriented toward achieving desirable, although not necessarily well-defined, future states. In situations surrounded by uncertainty where work has to proceed urgently to avoid an impending disaster, however, temporal work is guided by engaging with both desirable and undesirable future outcomes. Drawing on a real-time, in-depth study of the inception of the Restoration and Renewal program of the Palace of Westminster, we investigate how organizational actors develop a strategy for an uncertain and highly contested future while safeguarding ongoing operations in the present and preserving the heritage of the past. Anticipation of undesirable future events played a crucial role in mobilizing collective efforts to move forward. We develop a model of future desirability in temporal work to identify how actors construct, link, and navigate interpretations of desirable and undesirable futures in their attempts to create a viable path of action. By conceptualizing temporal work based on the phenomenological quality of the future, we advance understanding of the strategic organization of time in pluralistic contexts characterized by uncertainty and urgency

    Influence of solvent in controlling peptide−surface interactions

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    Protein binding to surfaces is an important phenomenon in biology and in modern technological applications. Extensive experimental and theoretical research has been focused in recent years on revealing the factors that govern binding affinity to surfaces. Theoretical studies mainly focus on examining the contribution of the individual amino acids or, alternatively, the binding potential energies of the full peptide, which are unable to capture entropic contributions and neglect the dynamic nature of the system. We present here a methodology that involves the combination of nonequilibrium dynamics simulations with strategic mutation of polar residues to reveal the different factors governing the binding free energy of a peptide to a surface. Using a gold-binding peptide as an example, we show that relative binding free energies are a consequence of the balance between strong interactions of the peptide with the surface and the ability for the bulk solvent to stabilize the peptide

    Social impact management through planning and development : Hedonic Psychology and a new approach to tourism in Zanzibar

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    Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2004.Includes bibliographical references (p. 127-130).This study proposes a new approach to tourism planning and development based on three threads in the literature on social impact management: (1) the current approach to tourism studies; (2) the writings and activities of the Aga Khan Trust for Culture; and, (3) the emerging field of Hedonic Psychology. Combining the best efforts of each of these fields -- respectively, understanding the tensions that arise in tourist areas, developing real-world projects, and understanding the psychological drivers of wellbeing -- creates this new approach, which I call the "Hedonic Psychology Approach." To illustrate the application or this approach and to expose the process of planning and development according to this approach, salient features of the Stone Town of Zanzibar are presented, including brief descriptions of the spatial, social, political, and economic conditions of the historic area. Several recommendations are proposed, from improving open space design to maximize interactions among people, to increasing the coordination new development to institutionalize the potential benefits of the new approach.by A. Tell Metzger.M.C.P

    Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons

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    APE1 is an essential endodeoxyribonuclease of the base excision repair pathway that maintains genome stability. It was identified as a pivotal factor favoring tumor progression and chemoresistance through the control of gene expression by a redox-based mechanism. APE1 is overexpressed and serum-secreted in different cancers, representing a prognostic and predictive factor and a promising non-invasive biomarker. Strategies directly targeting APE1 functions led to the identification of inhibitors showing potential therapeutic value, some of which are currently in clinical trials. Interestingly, evidence indicates novel roles of APE1 in RNA metabolism that are still not fully understood, including its activity in processing damaged RNA in chemoresistant phenotypes, regulating onco-miRNA maturation, and oxidized RNA decay. Recent data point out a control role for APE1 in the expression and sorting of onco-miRNAs within secreted extracellular vesicles. This review is focused on giving a portrait of the pros and cons of the last two decades of research aiming at the identification of inhibitors of the redox or DNA-repair functions of APE1 for the definition of novel targeted therapies for cancer. We will discuss the new perspectives in cancer therapy emerging from the unexpected finding of the APE1 role in miRNA processing for personalized therapy

    Computational study on the boundary between the concerted and stepwise mechanism of bimolecular SNAr reactions

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    The text-book mechanism of bimolecular nucleophilic aromatic substitutions (SNAr) reactions is a stepwise process that proceeds via a so-called Meisenheimer intermediate. Only recently the alternative, concerted version of this mechanism has gained acceptance as more and more examples thereof have been reported. But so far only isolated examples of concerted SNAr reactions have been described and a coherent picture of when a SNAr reaction proceeds via a stepwise and when via a concerted mechanism has not yet been established. Here key factors are identified that influence the mechanistic choice of SNAr reactions. Moreover, the electron affinity is used as a simple descriptor to make a prediction on whether a given aryl fluoride substrate favors a concerted or stepwise mechanism
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