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41.
Alan Burke 《Systemic Practice and Action Research》2006,19(4):351-363
It is argued in this paper that evaluative activities in relation to systems development have traditionally focussed on the financial worth of the product. This approach has excluded the appraisal of important issues such as the process for building the product, the performance of the systems development team, the methods used and the organisational impact of the implemented System. In response to the traditional approach, which is skewed towards quantification techniques, a three stage framework is proposed. The three stages are iterative. The first being concerned with establishing an appropriate focus and resolution level for the evaluation, the second uses a control model to identify relevant outputs, appropriate sensors and comparators and performance criteria. The third is about selecting more sophisticated paradigms for assessing processes and their outputs. It is contended that although the specific focus of this paper is systems development, the framework could be used in any organisational context where products and services are developed and produced. 相似文献
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Genomic alterations in cultured human embryonic stem cells 总被引:22,自引:0,他引:22
Maitra A Arking DE Shivapurkar N Ikeda M Stastny V Kassauei K Sui G Cutler DJ Liu Y Brimble SN Noaksson K Hyllner J Schulz TC Zeng X Freed WJ Crook J Abraham S Colman A Sartipy P Matsui S Carpenter M Gazdar AF Rao M Chakravarti A 《Nature genetics》2005,37(10):1099-1103
Cultured human embryonic stem cell (hESC) lines are an invaluable resource because they provide a uniform and stable genetic system for functional analyses and therapeutic applications. Nevertheless, these dividing cells, like other cells, probably undergo spontaneous mutation at a rate of 10(-9) per nucleotide. Because each mutant has only a few progeny, the overall biological properties of the cell culture are not altered unless a mutation provides a survival or growth advantage. Clonal evolution that leads to emergence of a dominant mutant genotype may potentially affect cellular phenotype as well. We assessed the genomic fidelity of paired early- and late-passage hESC lines in the course of tissue culture. Relative to early-passage lines, eight of nine late-passage hESC lines had one or more genomic alterations commonly observed in human cancers, including aberrations in copy number (45%), mitochondrial DNA sequence (22%) and gene promoter methylation (90%), although the latter was essentially restricted to 2 of 14 promoters examined. The observation that hESC lines maintained in vitro develop genetic and epigenetic alterations implies that periodic monitoring of these lines will be required before they are used in in vivo applications and that some late-passage hESC lines may be unusable for therapeutic purposes. 相似文献
45.
Deposition of 1.88-billion-year-old iron formations as a consequence of rapid crustal growth 总被引:2,自引:0,他引:2
Iron formations are chemical sedimentary rocks comprising layers of iron-rich and silica-rich minerals whose deposition requires anoxic and iron-rich (ferruginous) sea water. Their demise after the rise in atmospheric oxygen by 2.32?billion years (Gyr) ago has been attributed to the removal of dissolved iron through progressive oxidation or sulphidation of the deep ocean. Therefore, a sudden return of voluminous iron formations nearly 500?million years later poses an apparent conundrum. Most late Palaeoproterozoic iron formations are about 1.88?Gyr old and occur in the Superior region of North America. Major iron formations are also preserved in Australia, but these were apparently deposited after the transition to a sulphidic ocean at 1.84?Gyr ago that should have terminated iron formation deposition, implying that they reflect local marine conditions. Here we date zircons in tuff layers to show that iron formations in the Frere Formation of Western Australia are about 1.88?Gyr old, indicating that the deposition of iron formations from two disparate cratons was coeval and probably reflects global ocean chemistry. The sudden reappearance of major iron formations at 1.88?Gyr ago--contemporaneous with peaks in global mafic-ultramafic magmatism, juvenile continental and oceanic crust formation, mantle depletion and volcanogenic massive sulphide formation--suggests deposition of iron formations as a consequence of major mantle activity and rapid crustal growth. Our findings support the idea that enhanced submarine volcanism and hydrothermal activity linked to a peak in mantle melting released large volumes of ferrous iron and other reductants that overwhelmed the sulphate and oxygen reservoirs of the ocean, decoupling atmospheric and seawater redox states, and causing the return of widespread ferruginous conditions. Iron formations formed on clastic-starved coastal shelves where dissolved iron upwelled and mixed with oxygenated surface water. The disappearance of iron formations after this event may reflect waning mafic-ultramafic magmatism and a diminished flux of hydrothermal iron relative to seawater oxidants. 相似文献
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The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design 总被引:1,自引:0,他引:1
Russell RJ Haire LF Stevens DJ Collins PJ Lin YP Blackburn GM Hay AJ Gamblin SJ Skehel JJ 《Nature》2006,443(7107):45-49
The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs. 相似文献
48.
Scientific explanation is a perennial topic in philosophy of science, but the literature has fragmented into specialized discussions in different scientific disciplines. An increasing attention to scientific practice by philosophers is (in part) responsible for this fragmentation and has put pressure on criteria of adequacy for philosophical accounts of explanation, usually demanding some form of pluralism. This commentary examines the arguments offered by Fagan and Woody with respect to explanation and understanding in scientific practice. I begin by scrutinizing Fagan's concept of collaborative explanation, highlighting its distinctive advantages and expressing concern about several of its assumptions. Then I analyze Woody's attempt to reorient discussions of scientific explanation around functional considerations, elaborating on the wider implications of this methodological recommendation. I conclude with reflections on synergies and tensions that emerge when the two papers are juxtaposed and how these draw attention to critical issues that confront ongoing philosophical analyses of scientific explanation. 相似文献
49.
Snodgrass C Tubiana C Vincent JB Sierks H Hviid S Moissl R Boehnhardt H Barbieri C Koschny D Lamy P Rickman H Rodrigo R Carry B Lowry SC Laird RJ Weissman PR Fitzsimmons A Marchi S;OSIRIS team 《Nature》2010,467(7317):814-816
The peculiar object P/2010?A2 was discovered in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010?A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results. The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009. 相似文献
50.
Field GD Gauthier JL Sher A Greschner M Machado TA Jepson LH Shlens J Gunning DE Mathieson K Dabrowski W Paninski L Litke AM Chichilnisky EJ 《Nature》2010,467(7316):673-677
To understand a neural circuit requires knowledge of its connectivity. Here we report measurements of functional connectivity between the input and ouput layers of the macaque retina at single-cell resolution and the implications of these for colour vision. Multi-electrode technology was used to record simultaneously from complete populations of the retinal ganglion cell types (midget, parasol and small bistratified) that transmit high-resolution visual signals to the brain. Fine-grained visual stimulation was used to identify the location, type and strength of the functional input of each cone photoreceptor to each ganglion cell. The populations of ON and OFF midget and parasol cells each sampled the complete population of long- and middle-wavelength-sensitive cones. However, only OFF midget cells frequently received strong input from short-wavelength-sensitive cones. ON and OFF midget cells showed a small non-random tendency to selectively sample from either long- or middle-wavelength-sensitive cones to a degree not explained by clumping in the cone mosaic. These measurements reveal computations in a neural circuit at the elementary resolution of individual neurons. 相似文献