The technology based on the time domain reflectometry of the coaxial cable and its application

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Comparison of techniques for handling missing covariate data within prognostic modelling studies: a simulation study

Background: There is no consensus on the most appropriate approach to handle missing covariate data within prognostic modelling studies. Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model. Methods: Datasets were generated to resemble the skewed distributions seen in a motivating breast cancer example. Multivariate missing data were imposed on four covariates using four different mechanisms; missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and a combination of all three mechanisms. Five amounts of incomplete cases from 5% to 75% were considered. Complete case analysis (CC), single imputation (SI) and five multiple imputation (MI) techniques available within the R statistical software were investigated: a) data augmentation (DA) approach assuming a multivariate normal distribution, b) DA assuming a general location model, c) regression switching imputation, d) regression switching with predictive mean matching (MICE-PMM) and e) flexible additive imputation models. A Cox proportional hazards model was fitted and appropriate estimates for the regression coefficients and model performance measures were obtained. Results: Performing a CC analysis produced unbiased regression estimates, but inflated standard errors, which affected the significance of the covariates in the model with 25% or more missingness. Using SI, underestimated the variability; resulting in poor coverage even with 10% missingness. Of the MI approaches, applying MICE-PMM produced, in general, the least biased estimates and better coverage for the incomplete covariates and better model performance for all mechanisms. However, this MI approach still produced biased regression coefficient estimates for the incomplete skewed continuous covariates when 50% or more cases had missing data imposed with a MCAR, MAR or combined mechanism. When the missingness depended on the incomplete covariates, i.e. MNAR, estimates were biased with more than 10% incomplete cases for all MI approaches. Conclusion: The results from this simulation study suggest that performing MICE-PMM may be the preferred MI approach provided that less than 50% of the cases have missing data and the missing data are not MNAR

Identification of a Novel Marine Fish Virus, Singapore Grouper Iridovirus-Encoded MicroRNAs Expressed in Grouper Cells by Solexa Sequencing

BACKGROUND: MicroRNAs (miRNAs) are ubiquitous non-coding RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies has revealed that viruses can also encode miRNAs, which are proposed to be involved in viral replication and persistence, cell-mediated antiviral immune response, angiogenesis, and cell cycle regulation. Singapore grouper iridovirus (SGIV) is a pathogenic iridovirus that has severely affected grouper aquaculture in China and Southeast Asia. Comprehensive knowledge about the related miRNAs during SGIV infection is helpful for understanding the infection and the pathogenic mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether SGIV encoded miRNAs during infection, a small RNA library derived from SGIV-infected grouper (GP) cells was constructed and sequenced by Illumina/Solexa deep-sequencing technology. We recovered 6,802,977 usable reads, of which 34,400 represented small RNA sequences encoded by SGIV. Sixteen novel SGIV-encoded miRNAs were identified by a computational pipeline, including a miRNA that shared a similar sequence to herpesvirus miRNA HSV2-miR-H4-5p, which suggests miRNAs are conserved in far related viruses. Generally, these 16 miRNAs are dispersed throughout the SGIV genome, whereas three are located within the ORF057L region. Some SGIV-encoded miRNAs showed marked sequence and length heterogeneity at their 3' and/or 5' end that could modulate their functions. Expression levels and potential biological activities of these viral miRNAs were examined by stem-loop quantitative RT-PCR and luciferase reporter assay, respectively, and 11 of these viral miRNAs were present and functional in SGIV-infected GP cells. CONCLUSIONS: Our study provided a genome-wide view of miRNA production for iridoviruses and identified 16 novel viral miRNAs. To the best of our knowledge, this is the first experimental demonstration of miRNAs encoded by aquatic animal viruses. The results provide a useful resource for further in-depth studies on SGIV infection and iridovirus pathogenesis

Pathogenic Connexin-31 Forms Constitutively Active Hemichannels to Promote Necrotic Cell Death

Mutations in Connexin-31 (Cx31) are associated with multiple human diseases including erythrokeratodermia variabilis (EKV). The molecular action of Cx31 pathogenic mutants remains largely elusive. We report here that expression of EKV pathogenic mutant Cx31R42P induces cell death with necrotic characteristics. Inhibition of hemichannel activity by a connexin hemichannel inhibitor or high extracellular calcium suppresses Cx31R42P-induced cell death. Expression of Cx31R42P induces ER stress resulting in reactive oxygen species (ROS) production, in turn, to regulate gating of Cx31R42P hemichannels and Cx31R42P induced cell death. Moreover, Cx31R42P hemichannels play an important role in mediating ATP release from the cell. In contrast, no hemichannel activity was detected with cells expressing wildtype Cx31. Together, the results suggest that Cx31R42P forms constitutively active hemichannels to promote necrotic cell death. The Cx31R42P active hemichannels are likely resulted by an ER stress mediated ROS overproduction. The study identifies a mechanism of EKV pathogenesis induced by a Cx31 mutant and provides a new avenue for potential treatment strategy of the disease

Peripheral Arterial and Venous Response to Tilt Test after a 60-Day Bedrest with and without Countermeasures (ES-IBREP)

We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures on arterial and venous response to tilt. Methods: Twenty-one males: 7 control (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow velocity and leg vascular resistance (FRI), the portal vein section (PV), the flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius (Gast), and saphenous (Saph) vein sections were measured by echography and Doppler ultrasonography. Arterial and venous parameters were measured at 3-min pre-tilt in the supine position, and at 1 min before the end of the tilt. Results: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb groups (not significant) but remained stable in the RVE gr. FRI dropped in the Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV decreased less in the Con and Herb groups but remained unchanged in the RVE gr. MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in the RVE gr. Gast section significantly increased more in the Con gr only, whereas Tib section increased more in the Con and Herb groups but not in the RVE gr. The percent change in Saph section was similar at pre- and post-HDBR tilt. Conclusion: In the Con gr, vasoconstriction was reduced in leg and splanchnic areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast distension whereas only RVE had a protective effect on the Tib

Adenylyl Cyclases 1 and 8 Initiate a Presynaptic Homeostatic Response to Ethanol Treatment

BACKGROUND:Although ethanol exerts widespread action in the brain, only recently has progress been made in understanding the specific events occurring at the synapse during ethanol exposure. Mice deficient in the calcium-stimulated adenylyl cyclases, AC1 and AC8 (DKO), demonstrate increased sedation duration and impaired phosphorylation by protein kinase A (PKA) following acute ethanol treatment. While not direct targets for ethanol, we hypothesize that these cyclases initiate a homeostatic presynaptic response by PKA to reactivate neurons from ethanol-mediated inhibition. METHODOLOGY/PRINCIPAL FINDINGS:Here, we have used phosphoproteomic techniques and identified several presynaptic proteins that are phosphorylated in the brains of wild type mice (WT) after ethanol exposure, including synapsin, a known PKA target. Phosphorylation of synapsins I and II, as well as phosphorylation of non-PKA targets, such as, eukaryotic elongation factor-2 (eEF-2) and dynamin is significantly impaired in the brains of DKO mice. This deficit is primarily driven by AC1, as AC1-deficient, but not AC8-deficient mice also demonstrate significant reductions in phosphorylation of synapsin and eEF-2 in cortical and hippocampal tissues. DKO mice have a reduced pool of functional recycling vesicles and fewer active terminals as measured by FM1-43 uptake compared to WT controls, which may be a contributing factor to the impaired presynaptic response to ethanol treatment. CONCLUSIONS/SIGNIFICANCE:These data demonstrate that calcium-stimulated AC-dependent PKA activation in the presynaptic terminal, primarily driven by AC1, is a critical event in the reactivation of neurons following ethanol-induced activity blockade

Morphology and photoluminescence study of titania nanoparticles

Titania nanoparticles are prepared by sol–gel chemistry with a poly(ethylene oxide) methyl ether methacrylate-block-poly(dimethylsiloxane)-block-poly(ethylene oxide) methyl ether methacrylate triblock copolymer acting as the templating agent. The sol–gel components—hydrochloric acid, titanium tetraisopropoxide, and triblock copolymer—are varied to investigate their effect on the resulting titania morphology. An increased titania precursor or polymer content yields smaller primary titania structures. Microbeam grazing incidence small-angle X-ray scattering measurements, which are analyzed with a unified fit model, reveal information about the titania structure sizes. These small structures could not be observed via the used microscopy techniques. The interplay among the sol–gel components via our triblock copolymer results in different sized titania nanoparticles with higher packing densities. Smaller sized titania particles, (∼13–20 nm in diameter) in the range of exciton diffusion length, are formed by 2% by weight polymer and show good crystallinity with less surface defects and high oxygen vacancies