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151.
In this article, we consider problems with correlated data that can be summarized in a 2 x 2 table with structural zero in one of the off-diagonal cells. Data of this kind sometimes appear in infectious disease studies and two-step procedure studies. Lui (1998, Biometrics54, 706-711) considered confidence interval estimation of rate ratio based on Fieller-type, Wald-type, and logarithmic transformation statistics. We reexamine the same problem under the context of confidence interval construction on false-negative rate ratio in diagnostic performance when combining two diagnostic tests. We propose a score statistic for testing the null hypothesis of nonunity false-negative rate ratio. Score test-based confidence interval construction for false-negative rate ratio will also be discussed. Simulation studies are conducted to compare the performance of the new derived score test statistic and existing statistics for small to moderate sample sizes. In terms of confidence interval construction, our asymptotic score test-based confidence interval estimator possesses significantly shorter expected width with coverage probability being close to the anticipated confidence level. In terms of hypothesis testing, our asymptotic score test procedure has actual type I error rate close to the pre-assigned nominal level. We illustrate our methodologies with real examples from a clinical laboratory study and a cancer study. 相似文献
152.
Padayatti PS Helfand MS Totir MA Carey MP Hujer AM Carey PR Bonomo RA van den Akker F 《Biochemistry》2004,43(4):843-848
Many pathogenic bacteria develop antibiotic resistance by utilizing beta-lactamases to degrade penicillin-like antibiotics. A commonly prescribed mechanism-based inhibitor of beta-lactamases is tazobactam, which can function either irreversibly or in a transient manner. We have demonstrated previously that the reaction between tazobactam and a deacylation deficient variant of SHV-1 beta-lactamase, E166A, could be followed in single crystals using Raman microscopy [Helfand, M. S., et al. (2003) Biochemistry 42, 13386-13392]. The Raman data show that maximal populations of an enamine-like intermediate occur 20-30 min after "soaking in" has commenced. By flash-freezing crystals in this time frame, we were able to trap the enamine species. The resulting 1.63 A resolution crystal structure revealed tazobactam covalently bound in the trans-enamine intermediate state with close to 100% occupancy in the active site. The Raman data also indicated that tazobactam forms a larger population of enamine than sulbactam or clavulanic acid does and that tazobactam's intermediate is also the most long-lived. The crystal structure provides a rationale for this finding since only tazobactam is able to form favorable intra- and intermolecular interactions in the active site that stabilize this trans-enamine intermediate. These interactions involve both the sulfone and triazolyl groups that distinguish tazobactam from clavulanic acid and sulbactam, respectively. The observed stabilization of the transient intermediate of tazobactam is thought to contribute to tazobactam's superior in vitro and in vivo clinical efficacy. Understanding the structural details of differing inhibitor effectiveness can aid the design of improved mechanism-based beta-lactamase inhibitors. 相似文献
153.
Raman crystallography permits the monitoring of chemical events in single-protein crystals in real time. Using a Raman microscope, it is possible to obtain protein Raman spectroscopic data of unprecedented quality and stability. The latter features allow us to obtain the Raman spectrum for small molecules soaking into crystals under normal (nonresonance) Raman conditions. Thus, via an approach utilizing Raman difference spectroscopy, we can quantitate the amount of ligand in the crystal, determine the chemistry of inhibitor-protein interactions, and follow chemical reactions in the active site on the time scale of minutes. While providing unique chemical insights, these data also provide an invaluable guide for determining the conditions for flash-freezing crystals for X-ray crystallographic analysis. In addition, the Raman difference spectra often contain contributions from protein modes due to protein conformational changes occurring upon ligand binding. These features allow us to probe events ranging from small cooperative conformational changes to massive and unexpected secondary structure changes in the crystal. An experimental advantage of Raman crystallography is that the data can be collected from crystals in situ, in sitting or hanging drops, under the conditions used to grow the crystals. 相似文献
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156.
Carlos Bustos Desmond Mac-Leod Carey René Thouvenot Pierre Gouzerh 《Inorganica chimica acta》2010,363(15):4262-4268
A series of aryldiazenido polyoxomolybdates of the type (nBu4N)2[Mo5O13(OMe)4(NNAr){Na(MeOH)}] (Ar = C6F5, 1; Ar = O2N-o-C6H4, 2; Ar = O2N-m-C6H4, 3; Ar = O2N-p-C6H4, 4a; Ar = (O2N)2-o,p-C6H3, 5) have been obtained by controlled degradation of the parent compounds (nBu4N)3[Mo6O18(NNAr)] with NaOH in methanol. They have been characterized by elemental analysis and UV-Vis and IR spectroscopy. In addition, 4a has been characterized by 95Mo NMR spectroscopy and the crystal structure of (nBu4N)2[Mo5O13(OMe)4(NNC6H4-p-NO2){Na(H2O))]·H2O (4b) has been determined by X-ray diffraction. The molecular structure of the anion of 4b features a lacunary Lindqvist-type anion [Mo5O13(OMe)4(NNC6H4-p-NO2)]3− interacting with a sodium cation through the four terminal axial oxygen atoms. The 1:1 sodium complexes react with BaCl2 and BiCl3 to yield 2:1 complexes which have been isolated as (nBu4N)4[Ba{Mo5O13(OMe)4(NNAr)}2] (Ar = C6F5, 6; Ar = O2N-p-C6H4, 7) and (nBu4N)3[Bi{Mo5O13(OMe)4(NNAr)}2] (Ar = C6F5, 8; Ar = O2N-p-C6H4, 9). X-ray crystallography analysis of 9·Me2CO has shown that the tetradentate [Mo5O13(OMe)4(N2C6H4-p-NO2)]3− anions provide a square-antiprismatic environment for Bi. In contrast, IR spectroscopy provides evidence for a square-prismatic environment of Ba in 6 and 7. In acetonitrile-methanol mixed solvent, [Mo5O13(OMe)4(NNAr)]3− and [PW11O39]7−, generated in situ by alkaline degradation of their respective parents, [Mo6O18(NNAr)]3− and [PW12O40]3−, react together to give the Keggin-type diazenido compounds (nBu4N)4[PW11O39(MoNNAr)] (Ar = O2N-o-C6H4, 10; Ar = O2N-m-C6H4, 11; Ar = O2N-p-C6H4, 12), which have been characterized by 31P and 183W NMR spectroscopy. 相似文献
157.
The chemokine receptor CCR5 came into worldwide prominence a decade ago when it was identified as one of the major coreceptors for HIV infectivity. However, subsequent studies suggested an important modulatory role for CCR5 in the inflammatory response. Specifically, CCR5 has been reported to directly regulate T cell function in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes. Moreover, T cell-mediated immune responses are proposed to be critical in the pathogenesis of autoimmune and viral liver diseases, and recent clinical and experimental studies have also implicated CCR5 in the pathogenesis of autoimmune and viral liver diseases. Therefore, in this brief review, we highlight the evidence that supports an important role of CCR5 in the pathophysiology of T cell-mediated liver diseases with specific emphasis on autoimmune and viral liver diseases. 相似文献
158.
Wittenburg H Lyons MA Li R Kurtz U Wang X Mössner J Churchill GA Carey MC Paigen B 《Journal of lipid research》2006,47(8):1780-1790
To identify additional loci that influence lipoprotein cholesterol levels, we performed quantitative trait locus (QTL) mapping in offspring of PERA/EiJxI/LnJ and PERA/EiJxDBA/2J intercrosses and in a combined data set from both crosses after 8 weeks of consumption of a high fat-diet. Most QTLs identified were concordant with homologous chromosomal regions that were associated with lipoprotein levels in human studies. We detected significant new loci for HDL cholesterol levels on chromosome (Chr) 5 (Hdlq34) and for non-HDL cholesterol levels on Chrs 15 (Nhdlq9) and 16 (Nhdlq10). In addition, the analysis of combined data sets identified a QTL for HDL cholesterol on Chr 17 that was shared between both crosses; lower HDL cholesterol levels were conferred by strain PERA. This QTL colocalized with a shared QTL for cholesterol gallstone formation detected in the same crosses. Haplotype analysis narrowed this QTL, and sequencing of the candidate genes Abcg5 and Abcg8 confirmed shared alleles in strains I/LnJ and DBA/2J that differed from the alleles in strain PERA/EiJ. In conclusion, our analysis furthers the knowledge of genetic determinants of lipoprotein cholesterol levels in inbred mice and substantiates the hypothesis that polymorphisms of Abcg5/Abcg8 contribute to individual variation in both plasma HDL cholesterol levels and susceptibility to cholesterol gallstone formation. 相似文献
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160.
Population trends associated with skin peptide defenses against chytridiomycosis in Australian frogs
Many species of amphibians in the wet tropics of Australia have experienced population declines linked with the emergence
of a skin-invasive chytrid fungus, Batrachochytrium dendrobatidis. An innate defense, antimicrobial peptides produced by granular glands in the skin, may protect some species from disease.
Here we present evidence that supports this hypothesis. We tested ten synthesized peptides produced by Australian species,
and natural peptide mixtures from five Queensland rainforest species. Natural mixtures and most peptides tested in isolation
inhibited growth of B. dendrobatidis in vitro. The three most active peptides (caerin 1.9, maculatin 1.1, and caerin 1.1) were found in the secretions of non-declining
species (Litoria chloris, L. caerulea, and L. genimaculata). Although the possession of a potent isolated antimicrobial peptide does not guarantee protection from infection, non-declining
species (L. lesueuri and L. genimaculata) inhabiting the rainforest of Queensland possess mixtures of peptides that may be more protective than those of the species
occurring in the same habitat that have recently experienced population declines associated with chytridiomycosis (L. nannotis, L. rheocola, and Nyctimystes dayi). This study demonstrates that in vitro effectiveness of skin peptides correlates with the degree of decline in the face
of an emerging pathogen. Further research is needed to assess whether this non-specific immune defense may be useful in predicting
disease susceptibility in other species. 相似文献