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1.
The focus with which the paper is concerned is the process or task of intervention and, more specifically, the exploration of three (overlapping and interacting) questions pertinent to those who would intervene: What is to be done? How shall we decide what to do? What can guide our actions? In terms of what we will describe as pragmatic pluralism (our response to these questions), we intend this to be read in several different ways and on several different levels. Illustrating the discussion with examples from a number of different case studies, we will talk about pluralism in each of the following features: in the use of specific methods/techniques in the role(s) of the interventionists in the modes of representation employed in the use of different rationalities in the ‘nature’ of the client 相似文献
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Summary The serum activities of aspartate aminotransferase, alanine aminotransferase, -hydroxybutyrate dehydrogenase and creatine phosphokinase have been measured in the African elephant. In general, the values were broadly comparable with those of man except that alanine aminotransferase was much lower and creatine phosphokinase higher. No variation due to age, sex, season or location was observed. 相似文献
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Hessa T Meindl-Beinker NM Bernsel A Kim H Sato Y Lerch-Bader M Nilsson I White SH von Heijne G 《Nature》2007,450(7172):1026-1030
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Wilker EW van Vugt MA Artim SA Huang PH Petersen CP Reinhardt HC Feng Y Sharp PA Sonenberg N White FM Yaffe MB 《Nature》2007,446(7133):329-332
14-3-3 proteins are crucial in a wide variety of cellular responses including cell cycle progression, DNA damage checkpoints and apoptosis. One particular 14-3-3 isoform, sigma, is a p53-responsive gene, the function of which is frequently lost in human tumours, including breast and prostate cancers as a result of either hypermethylation of the 14-3-3sigma promoter or induction of an oestrogen-responsive ubiquitin ligase that specifically targets 14-3-3sigma for proteasomal degradation. Loss of 14-3-3sigma protein occurs not only within the tumours themselves but also in the surrounding pre-dysplastic tissue (so-called field cancerization), indicating that 14-3-3sigma might have an important tumour suppressor function that becomes lost early in the process of tumour evolution. The molecular basis for the tumour suppressor function of 14-3-3sigma is unknown. Here we report a previously unknown function for 14-3-3sigma as a regulator of mitotic translation through its direct mitosis-specific binding to a variety of translation/initiation factors, including eukaryotic initiation factor 4B in a stoichiometric manner. Cells lacking 14-3-3sigma, in marked contrast to normal cells, cannot suppress cap-dependent translation and do not stimulate cap-independent translation during and immediately after mitosis. This defective switch in the mechanism of translation results in reduced mitotic-specific expression of the endogenous internal ribosomal entry site (IRES)-dependent form of the cyclin-dependent kinase Cdk11 (p58 PITSLRE), leading to impaired cytokinesis, loss of Polo-like kinase-1 at the midbody, and the accumulation of binucleate cells. The aberrant mitotic phenotype of 14-3-3sigma-depleted cells can be rescued by forced expression of p58 PITSLRE or by extinguishing cap-dependent translation and increasing cap-independent translation during mitosis by using rapamycin. Our findings show how aberrant mitotic translation in the absence of 14-3-3sigma impairs mitotic exit to generate binucleate cells and provides a potential explanation of how 14-3-3sigma-deficient cells may progress on the path to aneuploidy and tumorigenesis. 相似文献
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Biasing reaction pathways with mechanical force 总被引:1,自引:0,他引:1
During the course of chemical reactions, reactant molecules need to surmount an energy barrier to allow their transformation into products. The energy needed for this process is usually provided by heat, light, pressure or electrical potential, which act either by changing the distribution of the reactants on their ground-state potential energy surface or by moving them onto an excited-state potential energy surface and thereby facilitate movement over the energy barrier. A fundamentally different way of initiating or accelerating a reaction is the use of force to deform reacting molecules along a specific direction of the reaction coordinate. Mechanical force has indeed been shown to activate covalent bonds in polymers, but the usual result is chain scission. Here we show that mechanically sensitive chemical groups make it possible to harness the mechanical forces generated when exposing polymer solutions to ultrasound, and that this allows us to accelerate rearrangement reactions and bias reaction pathways to yield products not obtainable from purely thermal or light-induced reactions. We find that when placed within long polymer strands, the trans and cis isomers of a 1,2-disubstituted benzocyclobutene undergo an ultrasound-induced electrocyclic ring opening in a formally conrotatory and formally disrotatory process, respectively, that yield identical products. This contrasts with reaction initiation by light or heat alone, in which case the isomers follow mutually exclusive pathways to different products. Mechanical forces associated with ultrasound can thus clearly alter the shape of potential energy surfaces so that otherwise forbidden or slow processes proceed under mild conditions, with the directionally specific nature of mechanical forces providing a reaction control that is fundamentally different from that achieved by adjusting chemical or physical parameters. Because rearrangement in our system occurs before chain scission, the effect we describe might allow the development of materials that are activated by mechanical stress fields. 相似文献
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Bedding TR Mosser B Huber D Montalbán J Beck P Christensen-Dalsgaard J Elsworth YP García RA Miglio A Stello D White TR De Ridder J Hekker S Aerts C Barban C Belkacem K Broomhall AM Brown TM Buzasi DL Carrier F Chaplin WJ Di Mauro MP Dupret MA Frandsen S Gilliland RL Goupil MJ Jenkins JM Kallinger T Kawaler S Kjeldsen H Mathur S Noels A Aguirre VS Ventura P 《Nature》2011,471(7340):608-611
Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes. Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies. Here we report observations of gravity-mode period spacings in red giants that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained by the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly ~ 50 seconds) and those that are also burning helium (period spacing ~ 100 to 300 seconds). 相似文献
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Molecular genetic basis of the histo-blood group ABO system 总被引:59,自引:0,他引:59
The histo-blood group ABO, the major human alloantigen system, involves three carbohydrate antigens (ABH). A, B and AB individuals express glycosyltransferase activities converting the H antigen into A or B antigens, whereas O(H) individuals lack such activity. Here we present a molecular basis for the ABO genotypes. The A and B genes differ in a few single-base substitutions, changing four amino-acid residues that may cause differences in A and B transferase specificity. A critical single-base deletion was found in the O gene, which results in an entirely different, inactive protein incapable of modifying the H antigen. 相似文献