4,224 research outputs found

    Comparison of total body water estimates from O-18 and bioelectrical response prediction equations

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    Identification of an indirect, rapid means to measure total body water (TBW) during space flight may aid in quantifying hydration status and assist in countermeasure development. Bioelectrical response testing and hydrostatic weighing were performed on 27 subjects who ingested O-18, a naturally occurring isotope of oxygen, to measure true TBW. TBW estimates from three bioelectrical response prediction equations and fat-free mass (FFM) were compared to TBW measured from O-18. A repeated measures MANOVA with post-hoc Dunnett's Test indicated a significant (p less than 0.05) difference between TBW estimates from two of the three bioelectrical response prediction equations and O-18. TBW estimates from FFM and the Kushner & Schoeller (1986) equation yielded results that were similar to those given by O-18. Strong correlations existed between each prediction method and O-18; however, standard errors, identified through regression analyses, were higher for the bioelectrical response prediction equations compared to those derived from FFM. These findings suggest (1) the Kushner & Schoeller (1986) equation may provide a valid measure of TBW, (2) other TBW prediction equations need to be identified that have variability similar to that of FFM, and (3) bioelectrical estimates of TBW may prove valuable in quantifying hydration status during space flight

    Artificial Multienzyme Scaffolds: Pursuing in Vitro Substrate Channeling with an Overview of Current Progress

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    Artificial multienzyme scaffolds are being developed for in vitro cascaded biocatalytic activity and, in particular, accessing substrate channeling. This review covers progress in this field over t..

    Constitutive alzheimer\u27s-type tau epitopes in a neuritogenic rat CNS cell line

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    Paired helical filaments (PHFs) of Alzheimer\u27s disease (AD) largely comprise hyperphosphorylated forms of the cytoskeletal protein tau. AD-type tau phosphoepitopes, detected by various monoclonal antibodies, are absent from normal adult neurons, but recent studies have shown that their expression may contribute to neuritogenesis and axon differentiation in the developing nervous system. Therefore, we have examined a brain nerve cell line that is spontaneously neuritogenic for possible expression of AD-type tau epitopes. The neuritogenic rat brain cell line B103 was found to constitutively produce two AD-related epitopes of tau, detected by cellular immunofluorescence studies with the PHF-1 and Alz-50 monoclonal antibodies. Biochemical studies showed that the antibodies bound to proteins within the molecular weight range expected for phosphorylated tau isoforms. Further verification was established by use of tau antisense oligomers, which eliminated cellular immunofluorescence due to the AD-related monoclonals and polyclonal anti-tau but did not eliminate fluorescence due to anti-tubulin. Cells treated with tau antisense were not neurite-free. Neurites that remained, however, were abnormal, generally short and wavy in appearance. Cellular distribution of the tau epitopes was found to be particularly interesting. Alz-50 recognized only cytoplasmic tau whereas PHF-1 recognized nuclear tau as well as cytoplasmic. Thus, the two epitopes are morphologically segregated within the cell. Because subcellular segregation of tau is compromised in Alzheimer\u27s disease, mechanisms that segregate AD-type phosphotau epitopes in B103 cells may have relevance to this neurodegenerative disorder

    Multiscaffold DNA Origami Nanoparticle Waveguides

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    DNA origami templated self-assembly has shown its potential in creating rationally designed nanophotonic devices in a parallel and repeatable manner. In this investigation, we employ a multiscaffold DNA origami approach to fabricate linear waveguides of 10 nm diameter gold nanoparticles. This approach provides independent control over nanoparticle separation and spatial arrangement. The waveguides were characterized using atomic force microscopy and far-field polarization spectroscopy. This work provides a path toward large-scale plasmonic circuitry

    Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites.

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    Voltage-gated sodium (NaV) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic NaV channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects on NaChBac function and nearly identical anesthetizing effects on tadpole mobility. Using quantitative analysis by 19F-NMR saturation transfer difference spectroscopy, we reveal strong intermolecular cross-relaxation rate constants between 4-fluoropropofol and four different regions of NaChBac, including the activation gate and selectivity filter in the pore, the voltage sensing domain, and the S4-S5 linker. Unlike volatile anesthetics, 4-fluoropropofol does not bind to the extracellular interface of the pore domain. Collectively, our results show that propofol inhibits NaChBac at multiple sites, likely with distinct modes of action. This study provides a molecular basis for understanding the net inhibitory action of propofol on NaV channels. © 2018 Wang et al

    Space-Time Clustering and Correlations of Major Earthquakes

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    Earthquake occurrence in nature is thought to result from correlated elastic stresses, leading to clustering in space and time. We show that occurrence of major earthquakes in California correlates with time intervals when fluctuations in small earthquakes are suppressed relative to the long term average. We estimate a probability of less than 1% that this coincidence is due to random clustering.Comment: 5 pages, 3 figures. Submitted to PR

    Is the association between optimistic cardiovascular risk perceptions and lower rates of cardiovascular disease mortality explained by biomarkers of systemic inflammation or endothelial function? A case-cohort study

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    <p>Abstract</p> <p>Background</p> <p>More optimistic perceptions of cardiovascular disease risk are associated with substantively lower rates of cardiovascular death among men. It remains unknown whether this association represents causality (i.e. perception leads to actions/conditions that influence cardiovascular disease occurrence) or residual confounding by unmeasured factors that associate with risk perceptions and with physiological processes that promote cardiovascular disease (i.e. inflammation or endothelial dysfunction).</p> <p>Purpose</p> <p>To evaluate whether previously unmeasured biological markers of inflammation or endothelial dysregulation confound the observed association between cardiovascular disease risk perceptions and cardiovascular disease outcomes;</p> <p>Methods</p> <p>We conducted a nested case-cohort study among community-dwelling men from Southeastern New England (USA) who were interviewed between 1989 and 1990 as part of the Pawtucket Heart Health Program. We measured C-reactive protein (CRP) and Vascular Endothelial Growth Factor (VEGF) levels from stored sera for a random sample of the parent cohort (control sample, n = 127) and all cases of cardiovascular death observed through 2005 (case sample, n = 44). We evaluated potential confounding using stratified analyses and logistic regression modeling.</p> <p>Results</p> <p>Optimistic ratings of risk associated with lower odds of dying from cardiovascular causes among men (OR = 0.39, 95% CI = 0.17, 0.91). Neither CRP nor VEGF confounded these findings.</p> <p>Conclusions</p> <p>The strong cardio-protective association between optimistic ratings of cardiovascular disease risk and lower rates of cardiovascular mortality among men is not confounded by baseline biomarkers of systemic inflammation or endothelial dysfunction.</p

    A damage model based on failure threshold weakening

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    A variety of studies have modeled the physics of material deformation and damage as examples of generalized phase transitions, involving either critical phenomena or spinodal nucleation. Here we study a model for frictional sliding with long range interactions and recurrent damage that is parameterized by a process of damage and partial healing during sliding. We introduce a failure threshold weakening parameter into the cellular-automaton slider-block model which allows blocks to fail at a reduced failure threshold for all subsequent failures during an event. We show that a critical point is reached beyond which the probability of a system-wide event scales with this weakening parameter. We provide a mapping to the percolation transition, and show that the values of the scaling exponents approach the values for mean-field percolation (spinodal nucleation) as lattice size LL is increased for fixed RR. We also examine the effect of the weakening parameter on the frequency-magnitude scaling relationship and the ergodic behavior of the model
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