3,640 research outputs found

    Strategic use of nickel(0)-catalyzed enyne–epoxide reductive coupling toward the synthesis of (−)-cyatha-3,12-diene

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    Various situations are explored in which the nickel(0)-catalyzed enyne–epoxide reductive coupling was utilized to access key intermediates toward the total synthesis of (−)-cyatha-3,12-diene (1). Enantioenriched 3,5-dien-1-ols with a variety of functionality were obtained in a straightforward manner from easily accessible 1,3-enynes and terminal epoxides.National Institute of General Medical Sciences (U.S.) (GM-063755)Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra

    Development of a fluorescent three‐hybrid system for the identification of protein‐protein associators

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    The chemically‐induced dimerization of proteins is fundamental to many key regulatory pathways. A number of natural products exert their downstream effect through the stabilization of a protein complex, either by direct binding to two distinct protein partners or via an allosteric mechanism. Here, we report a bacterial three‐hybrid system, with dual life/death and fluorescent reporters, which detects protein association and is compatible with high‐throughput screening. We use rapamycin mediated mTOR‐FKBP12 (mammalian target of rapamycin—FK506 Binding Protein 12 kDa) dimerization to validate this platform; the addition of rapamycin results in the association of these target proteins, leading to the expression of two essential life/death reporter genes and a fluorescent signal. We further used this system to quantify the activity of rapamycin by utilizing the fluorescent readout, exemplifying its potential in screening and for ranking large in vivo libraries for compounds that upregulate the association of any two given proteins

    Ladder Polyether Synthesis via Epoxide-Opening Cascades Directed by a Disappearing Trimethylsilyl Group

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    Epoxide-opening cascades offer the potential to construct complex polyether natural products expeditiously and in a manner that emulates the biogenesis proposed for these compounds. Herein we provide a full account of our development of a strategy that addresses several important challenges of such cascades. The centerpiece of the method is a trimethylsilyl (SiMe[subscript 3]) group that serves several purposes and leaves no trace of itself by the time the cascade has come to an end. The main function of the SiMe[subscript 3] group is to dictate the regioselectivity of epoxide opening. This strategy is the only general method of effecting endo-selective cascades under basic conditions.Johnson & Johnson (Fellowship)Boehringer Ingelheim Pharmaceuticals (Fellowship)US-UK Fulbright Commissio

    Kanter Revisited: Gender, Power and (In)visibility

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    This paper revisits Kanter's (1977) seminal work Men and Women of the Corporation, rereading her account of numerical advantage and disadvantage through a poststructuralist lens which exposes hidden dimensions of gendered power. This lens is captured in the ‘(In)visibility Vortex’ (Lewis and Simpson, 2010) which highlights struggles and tensions around the norm through processes of preservation and concealment within the norm as well as dynamics of revealing, exposure and disappearance as features of the margins. The study draws on developments in feminist theorizing, specially around visibility, invisibility and power, to facilitate this rereading. In so doing, the author demonstrate that while Kanter retreated from explanations based on the gendering of organizations or from recognition of gendered power, these dynamics can be identified in her text. The authors suggest that rereading classic texts can surface dimensions of organizations that have contemporary significance and can inform future research

    Still room for improvement? The educational experiences of looked after children in Scotland

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    In this chapter Kirstie Maclean and Graham Connelly present an analysis of joined-up thinking in Scotland from both social services and education perspectives

    Technical standards for respiratory oscillometry : test loads for calibration and verification

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    It has been brought to our attention that there is ambiguity in the ERS technical standards for respiratory oscillometry, specifically regarding the use of test loads for calibration and verification. Here it is worth making a distinction between recommendations for manufacturers versus users. We recognise that a standardised reactive test load has not been established for calibration or verification. This is an active research area, driven by the poor comparability in reactance which remains across devices

    On a conjecture of R. L. Graham

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    HYDROGEOLOGY OF BUTLER VALLEY, ARIZONA: AN ARTIFICIAL RECHARGE AND GROUND-WATER STORAGE PREFEASIBILITY STUDY

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    Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author
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