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Small molecule FKBP inhibitors were prepared with inhibitory activity ranging from micromolar to nanomolar. The design of these inhibitors derives from a structural analysis of the substrates for FKBP and cyclophilin. As a consequence of this analysis two key observations were made, namely: (1) amino ketone moieties are suitable as FKBP recognition elements at the P1-P1' site and (2) the P3'-P4' site will accept a trans-olefin as a suitable mimetic of a peptide moiety. The preparation of these non-peptide inhibitors is readily accomplished by a protocol which includes the synthesis of chiral propargylic amines and their subsequent conversion into vinyl zirconium reagents.

An electrostatic trapping scheme for use in the study of light-induced dissociation of molecular ions is outlined. We present a detailed description of the electrostatic reflection storage device and specifically demonstrate its use in the preparation of a vibrationally cold ensemble of deuterium hydride (HD + ) ions. By interacting an intense femtosecond laser with this target and detecting neutral fragmentation products, we are able to elucidate previously inaccessible dissociation dynamics for fundamental diatomics in intense laser fields. In this context, we present new results of intense field dissociation of HD + which are interpreted in terms of recent theoretical calculations.

A number of governmental and nongovernmental organizations have made significant efforts to encourage the development of artificial intelligence in line with a series of aspirational concepts such as transparency, interpretability, explainability, and accountability. The difficulty at present, however, is that these concepts exist at a fairly abstract level, whereas in order for them to have the tangible effects desired they need to become more concrete and specific. This article undertakes precisely this process of concretisation, mapping how the different concepts interrelate and what in particular they each require in order to move from being high-level aspirations to detailed and enforceable requirements. We argue that the key concept in this process is accountability, since unless an entity can be held accountable for compliance with the other concepts, and indeed more generally, those concepts cannot do the work required of them. There is a variety of taxonomies of accountability in the literature. However, at the core of each account appears to be a sense of “answerability”; a need to explain or to give an account. It is this ability to call an entity to account which provides the impetus for each of the other concepts and helps us to understand what they must each require.

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