Structural equation modeling (SEM) is a versatile tool for conducting a wide range of multivariate statistical analyses, including multiple regression, mediation analysis, moderation analysis, and analyses of variance and covariance. Two specialized uses of SEM that appear frequently in communication research are confirmatory factor analysis (CFA) and path analysis. Confirmatory factor analysis specifies one or more unobserved constructs, or latent factors, that a number of observed indicators define. This analysis is useful for validating the composition of multiple-item indexes or scales. The other common use of structural equation modeling, path analysis, estimates correlation and regression paths among structural nodes, which may include both observed variables and latent factors. When path analysis includes latent factors, the definition of those factors is equivalent to CFA and is the basis of a measurement model. The specification of paths among latent factors and observed variables constitutes a structural model. Whatever the intended use of SEM in communication research, it should be based on careful theoretical considerations. General ApproachA set of variables have an observed covariance matrix, which accounts for all the relationships among the variables. A structural regression model that estimates all covariance paths among the variables will reproduce the covariance matrix exactly but is unlikely to resolve a theoretical understanding of how the variables relate. The aim of SEM is to define a parsimonious regression model that specifies theoretically consistent paths among variables.To the extent that model paths reflect established theory, the model will generally have good external validity.
Gold surfaces modified with thiol-derivatized DNA duplexes have been investigated as a function of applied electrochemical potential via atomic force microscopy (EC-AFM). At open circuit, monolayers of well-packed DNA helices form with a film depth of 45(3) Å. On the basis of the anisotropic dimensions of these 15 base pair duplexes (20 Å in diameter versus 50 Å in length), this corresponds to an average ∼45° orientation of the helical axis with respect to the gold surface. Under potential control, the monolayer thickness (and therefore the orientation of the helices) changes dramatically with applied potential. At potentials negative of ∼0.45 V (versus a Ag wire quasi-reference electrode) film thicknesses of ∼55 Å are observed, whereas at more positive potentials the monolayer thickness drops to a limiting value of ∼20 Å. These results are consistent with a morphology change in which the helices either stand straight up or lie flat down on the metal surface, depending on the electrode potential relative to the potential of zero charge (pzc). This voltage-induced morphology change is reversible and effectively constitutes a nanoscale mechanical “switch”.
In this study, the safety, tolerability, and pharmacokinetics of intravenous (i.v.)-to oral-dose regimens of voriconazole were evaluated with a group of 42 healthy men, 41 of whom completed the study. Two cohorts of subjects participated in the study. Cohort 1 (n ؍ 28) took part in two study periods, each consisting of 14 days separated by a minimum 7-day washout. In one of the periods, 14 subjects received 6 mg/kg i. 1-fold increases in C max and AUC , respectively. Similarly, a 2-fold increase in oral dosing resulted in 2.8-and 3.9-fold increases in C max and AUC , respectively. The mean values for C max observed following oral dosing were lower than those obtained after i.v. administration, ranging from 62.7 to 89.6% of the i.v. value. After the switch from i.v. to oral dosing, most subjects achieved steady state by day 4, and mean minimum concentrations in plasma remained above clinically important MICs. The pharmacokinetic profiles for saliva followed a pattern similar to those observed for plasma; there was a highly significant correlation between plasma and saliva voriconazole concentrations (P < 0.0001). Voriconazole was well tolerated; the most commonly reported adverse events in voriconazole-treated subjects were mild to moderate headache, rash, and abnormal vision. Visual function tests detected no further abnormalities during voriconazole treatment.
As major consumers of heterotrophic bacteria and phytoplankton, microzooplankton are a critical link in aquatic foodwebs. Here, we show that a major marine microflagellate grazer is infected by a giant virus, Cafeteria roenbergensis virus (CroV), which has the largest genome of any described marine virus (≈730 kb of doublestranded DNA). The central 618-kb coding part of this AT-rich genome contains 544 predicted protein-coding genes; putative early and late promoter motifs have been detected and assigned to 191 and 72 of them, respectively, and at least 274 genes were expressed during infection. The diverse coding potential of CroV includes predicted translation factors, DNA repair enzymes such as DNA mismatch repair protein MutS and two photolyases, multiple ubiquitin pathway components, four intein elements, and 22 tRNAs. Many genes including isoleucyl-tRNA synthetase, eIF-2γ, and an Elp3-like histone acetyltransferase are usually not found in viruses. We also discovered a 38-kb genomic region of putative bacterial origin, which encodes several predicted carbohydrate metabolizing enzymes, including an entire pathway for the biosynthesis of 3-deoxy-D-manno-octulosonate, a key component of the outer membrane in Gram-negative bacteria. Phylogenetic analysis indicates that CroV is a nucleocytoplasmic large DNA virus, with Acanthamoeba polyphaga mimivirus as its closest relative, although less than one-third of the genes of CroV have homologs in Mimivirus. CroV is a highly complex marine virus and the only virus studied in genetic detail that infects one of the major groups of predators in the oceans.
The genus Coccolithovirus is a recently discovered group of viruses that infect the globally important marine calcifying microalga Emiliania huxleyi. Among the 472 predicted genes of the 407,339-base pair genome are a variety of unexpected genes, most notably those involved in biosynthesis of ceramide, a sphingolipid known to induce apoptosis. Uniquely for algal viruses, it also contains six RNA polymerase subunits and a novel promoter, suggesting this virus encodes its own transcription machinery. Microarray transcriptomic analysis reveals that 65% of the predicted virus-encoded genes are expressed during lytic infection of E. huxleyi.
These results show that sildenafil is a well tolerated and effective oral therapy for male erectile dysfunction with no established organic cause and may represent a new class of peripherally acting drug for the treatment of this condition.
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