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Search Results: 1 - 10 of 95283 matches for " Stephen W. Homans "
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RNA Packing Specificity and Folding during Assembly of the Bacteriophage MS2
Ottar Rolfsson,Katerina Toropova,Victoria Morton,Simona Francese,Gabriella Basnak,Gary S. Thompson,Stephen W. Homans,Alison E. Ashcroft,Nicola J. Stonehouse,Neil A. Ranson,Peter G. Stockley
Computational and Mathematical Methods in Medicine , 2008, DOI: 10.1080/17486700802168445
Abstract: Using a combination of biochemistry, mass spectrometry, NMR spectroscopy and cryo-electron microscopy (cryo-EM), we have been able to show that quasi-equivalent conformer switching in the coat protein (CP) of an RNA bacteriophage (MS2) is controlled by a sequence-specific RNA–protein interaction. The RNA component of this complex is an RNA stem-loop encompassing just 19 nts from the phage genomic RNA, which is 3569 nts in length. This binding results in the conversion of a CP dimer from a symmetrical conformation to an asymmetric one. Only when both symmetrical and asymmetrical dimers are present in solution is assembly of the T = 3 phage capsid efficient. This implies that the conformers, we have characterized by NMR correspond to the two distinct quasi-equivalent conformers seen in the 3D structure of the virion. An icosahedrally-averaged single particle cryo-EM reconstruction of the wild-type phage (to ∼9 Å resolution) has revealed icosahedrally ordered density encompassing up to 90% of the single-stranded RNA genome. The RNA is seen with a novel arrangement of two concentric shells, with connections between them along the 5-fold symmetry axes. RNA in the outer shell interacts with each of the 90 CP dimers in the T = 3 capsid and although the density is icosahedrally averaged, there appears to be a different average contact at the different quasi-equivalent protein dimers: precisely the result that would be expected if protein conformer switching is RNA-mediated throughout the assembly pathway. This unprecedented RNA structure provides new constraints for models of viral assembly and we describe experiments aimed at probing these. Together, these results suggest that viral genomic RNA folding is an important factor in efficient assembly, and further suggest that RNAs that could sequester viral CPs but not fold appropriately could act as potent inhibitors of viral assembly.
Dissecting the Fine Details of Assembly of a T?=?3 Phage Capsid
P. G. Stockley,A. E. Ashcroft,S. Francese,G. S. Thompson,N. A. Ranson,A. M. Smith,S. W. Homans,N. J. Stonehouse
Computational and Mathematical Methods in Medicine , 2005, DOI: 10.1080/10273660500149869
Abstract: The RNA bacteriophages represent ideal model systems in which to probe the detailed assembly pathway for the formation of a T = 3 quasi-equivalent capsid. For MS2, the assembly reaction can be probed in vitro using acid disassembled coat protein subunits and a short (19 nt) RNA stem-loop that acts as the translational operator of the replicase gene and leads to sequence-specific sequestration and packaging of the cognate phage RNA in vivo. Reassembly reactions can be initiated by mixing these components at neutral pH. The molecular basis of the sequence-specific RNA–protein interaction is now well understood. Recent NMR studies on the protein demonstrate extensive mobility in the loops of the polypeptide that alter their conformations to form the quasi-equivalent conformers of the final capsid. It seems reasonable to assume that RNA binding results in reduction of this flexibility. However, mass spectrometry suggests that these RNA–protein complexes may only provide one type of quasi-equivalent capsid building block competent to form five-fold axes but not the full shell. Work with longer RNAs suggests that the RNA may actively template the assembly pathway providing a partial explanation of how conformers are selected in the growing shell.
Thermal Stress in HFEF Hot Cell Windows Due to an In-Cell Metal Fire  [PDF]
Charles W. Solbrig, Stephen A. Warmann
World Journal of Nuclear Science and Technology (WJNST) , 2016, DOI: 10.4236/wjnst.2016.61003
Abstract: This work investigates an accident during the pyrochemical extraction of Uranium and Plutonium from PWR spent fuel in an argon atmosphere hot cell. In the accident, the heavy metals (U and Pu) being extracted are accidently exposed to air from a leaky instrument penetration which goes through the cell walls. The extracted pin size pieces of U and Pu metal readily burn when exposed to air. Technicians perform the electrochemical extraction using manipulators through a 4 foot thick hot cell concrete wall which protects them from the radioactivity of the spent fuel. Four foot thick windows placed in the wall allow the technicians to visually control the manipulators. These windows would be exposed to the heat of the metal fire. This analysis determines if the thermal stress caused by the fire would crack the windows and if the heat would degrade the window seals allowing radioactivity to escape from the cell.
Commentary on 'What is the point: will screening mammography save my life?' by Keen and Keen
Stephen W Duffy
BMC Medical Informatics and Decision Making , 2009, DOI: 10.1186/1472-6947-9-19
Abstract: The paper by Keen and Keen [1] presents new estimates of the absolute numbers of breast cancer deaths prevented by mammographic screening. The estimation is carried out by synthesis of a range of estimates of relative risk of breast cancer mortality loosely derived from the randomised trials, SEER data on breast cancer mortality and the proportion of the recent reduction in breast cancer mortality estimated by Berry et al to be owing to mammography [2]. Much is made of the relatively small absolute benefit estimated, and indeed the absolute benefit estimated here is notably smaller than that estimated in a randomised trial, and in an evaluation of service screening [3,4]. In relation to the results and the accompanying discussion, two remarks spring to mind.The first is that the paper rather labours the obvious point that in breast cancer screening, as in primary and secondary prevention generally, one has to apply the intervention to large numbers of healthy subjects in order to benefit the few who are unlucky enough to develop the disease. The same argument can be made of vaccination, cervical screening and many other interventions. If one is in the business of preventive medicine, one has to accept this as a fact of life. The improvements in length of life in recent decades are a combination of two per thousand from one disease, three per thousand from another, and so on.The second point is that the accuracy of the figures arrived at is questionable. From a rather convoluted ecological synthesis of information from different sources, the authors arrive at the finding that 1.8 breast cancer deaths would be prevented by repeatedly screening 1000 women for 15 years. Directly estimating this from empirical randomised trial data gives a figure of approximately 3 per 1000 over ten years [3], and from service screening in Sweden 2.1 per 1,000 [4]. They also estimate that less than 5% of screen-detected cases have their lives saved as a result of the screening. This is c
Case 4
Stephen W. Daunt
University of Toronto Medical Journal , 2002, DOI: 10.5015/utmj.v80i1.849
Abstract:
Case 6
Stephen W. Daunt
University of Toronto Medical Journal , 2003, DOI: 10.5015/utmj.v80i2.790
Abstract:
Prospects for summative evaluation of CAL in higher education
Stephen W. Draper
Research in Learning Technology , 1997, DOI: 10.3402/rlt.v5i1.10549
Abstract: Summative evaluation is evaluation done after software design and production is complete in order to establish its performance and properties. A prototypical case would be the tables produced in the consumer magazine Which? comparing a considerable range of properties of alternative available products (for example, washing machines) that they have measured in their own trials. Thus summative evaluation is not only done after production; it is typically about comparative measurements done to assist decisions concerning purchase.
Reconciliation: The theological challenge
Stephen W Martin
Nederduitse Gereformeerde Teologiese Tydskrif , 2012, DOI: 10.5952/51-3-97
Abstract: This paper argues that reconciliation is the Christian theological response to the challenge presented by a world of atrocities. While commonly articulated as adoctrine, reconciliation is primarily a narrative enacted through liturgy within Christian worship. This liturgy shapes a Christian response to a broken world, but is also provoked and challenged by that world. Within this movement, the church confesses that its practices of reconciliation are both incomplete and anticipatory. And yet these practices participate in the fullness of reconciliation made visible at the coming of the Kingdom. Anticipating this fullness allows Christian theology to articulate parables of reconciliation, and one example of this is South Africa’s own Truth and Reconciliation Commission. The paper concludes with a reflection on what “the parable of the TRC” says back to the church.
BCL-2 AND IAP PROTEINS AS POTENTIAL DRUG TARGETS
Stephen W. Fesik
The Scientific World Journal , 2001, DOI: 10.1100/tsw.2001.129
Abstract:
Power for tests of interaction: effect of raising the Type I error rate
Marshall Stephen W
Epidemiologic Perspectives and Innovations , 2007, DOI: 10.1186/1742-5573-4-4
Abstract: Background Power for assessing interactions during data analysis is often poor in epidemiologic studies. This is because epidemiologic studies are frequently powered primarily to assess main effects only. In light of this, some investigators raise the Type I error rate, thereby increasing power, when testing interactions. However, this is a poor analysis strategy if the study is chronically under-powered (e.g. in a small study) or already adequately powered (e.g. in a very large study). To demonstrate this point, this study quantified the gain in power for testing interactions when the Type I error rate is raised, for a variety of study sizes and types of interaction. Methods Power was computed for the Wald test for interaction, the likelihood ratio test for interaction, and the Breslow-Day test for heterogeneity of the odds ratio. Ten types of interaction, ranging from sub-additive through to super-multiplicative, were investigated in the simple scenario of two binary risk factors. Case-control studies of various sizes were investigated (75 cases & 150 controls, 300 cases & 600 controls, and 1200 cases & 2400 controls). Results The strategy of raising the Type I error rate from 5% to 20% resulted in a useful power gain (a gain of at least 10%, resulting in power of at least 70%) in only 7 of the 27 interaction type/study size scenarios studied (26%). In the other 20 scenarios, power was either already adequate (n = 8; 30%), or else so low that it was still weak (below 70%) even after raising the Type I error rate to 20% (n = 12; 44%). Conclusion Relaxing the Type I error rate did not usefully improve the power for tests of interaction in many of the scenarios studied. In many studies, the small power gains obtained by raising the Type I error will be more than offset by the disadvantage of increased "false positives". I recommend investigators should not routinely raise the Type I error rate when assessing tests of interaction.
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