Development of a Broad-Spectrum Antiviral Agent with Activity Against Herpesvirus Replication and Gene Expression

Purpose: To evaluate the broad-spectrum antiviral activity of peptide H9 (H9) in vitro in order to gain insight into its underlying molecular mechanisms.Method: Antiviral activity against Herpes simplex virus type 1 (HSV-1) was determined using thiazolyl blue (MTT) assay. Polymerase Chain Reaction (PCR) was employed to assay H9 antiviral activity against human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). The inhibitory effect of H9 on the replication of these viral genes including early genes was assayed by real time-Ppolymerase chain reaction (RT-PCR) and Western blot.Results: H9 possessed significant inhibitory effect on the four different herpesviruses with 50 % inhibitory concentration (IC50) of 1.21 ng/mL (HSV-1). AD169 infection was strongly inhibited with an EC50 value of 0.46 ng/ml. The anti-herpesviral activity of H9 was dose-dependent. The peptide acted primarily during the early stage of infection by detection of the early genes.Conclusion: The results demonstrate that H9 can inhibit the infection of HSV-1, EBV and HCMV. Furthermore, H9 has a broad-spectrum anti-herpesviral effect in vitro based on targeted killing of infected cells expressing genes.Keywords: Antagonist, Trapping receptor/ligand, Broad-spectrum, Anti-herpesvirus, H9 peptide, Gene expressio

Reducing bias in auditory duration reproduction by integrating the reproduced signal

Duration estimation is known to be far from veridical and to differ for sensory estimates and motor reproduction. To investigate how these differential estimates are integrated for estimating or reproducing a duration and to examine sensorimotor biases in duration comparison and reproduction tasks, we compared estimation biases and variances among three different duration estimation tasks: perceptual comparison, motor reproduction, and auditory reproduction (i.e. a combined perceptual-motor task). We found consistent overestimation in both motor and perceptual-motor auditory reproduction tasks, and the least overestimation in the comparison task. More interestingly, compared to pure motor reproduction, the overestimation bias was reduced in the auditory reproduction task, due to the additional reproduced auditory signal. We further manipulated the signal-to-noise ratio (SNR) in the feedback/comparison tones to examine the changes in estimation biases and variances. Considering perceptual and motor biases as two independent components, we applied the reliability-based model, which successfully predicted the biases in auditory reproduction. Our findings thus provide behavioral evidence of how the brain combines motor and perceptual information together to reduce duration estimation biases and improve estimation reliability

Caenorhabditis elegans Operons Contain a Higher Proportion of Genes with Multiple Transcripts and Use 3′ Splice Sites Differentially

RNA splicing generates multiple transcript isoforms from a single gene and enhances the complexity of eukaryotic gene expression. In some eukaryotes, operon exists as an ancient regulatory mechanism of gene expression that requires strict positional and regulatory relationships among its genes. It remains unknown whether operonic genes generate transcript isoforms in a similar manner as non-operonic genes do, the expression of which is less likely limited by their positions and relationships with surrounding genes. We analyzed the number of transcript isoforms of Caenorhabditis elegans operonic genes and found that C. elegans operons contain a much higher proportion of genes with multiple transcript isoforms than non-operonic genes do. For genes that express multiple transcript isoforms, there is no apparent difference between the number of isoforms in operonic and non-operonic genes. C. elegans operonic genes also have a different preference of the 20 most common 3′ splice sites compared to non-operonic genes. Our analyses suggest that C. elegans operons enhance expression complexity by increasing the proportion of genes that express multiple transcript isoforms and maintain splicing efficiency by differential use of common 3′ splice sites

Health-related quality of life as measured with EQ-5D among populations with and without specific chronic conditions: A population-based survey in Shaanxi province, China

© 2013 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. Methods: A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. Results: The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. Conclusion: The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs. © 2013 Tan et al.National Nature Science Foundation (No. 8107239

Membranes, molecules and biophysics: enhancing monocyte derived dendritic cell (MDDC) immunogenicity for improved anti-cancer therapy

Despite great medical advancement in the treatment of cancer, cancer remains a disease of global significance. Chemotherapeutics can be very expensive and drain medical resources at a national level and in some cases the cost of treatment is so great that it prohibits their use by local health authorities. Drug resistance is also a major limiting factor to the successful treatment of cancer with many patients initially responding well but then becoming refractory to treatment with the same drug and in some case may become multi-drug resistant. The immune system is known to be important in the prevention of tumors by eliminating pre-cancerous or cancerous cells. This concept of immune surveillance has largely been super-ceded by the concept of immunoediting whereby the immune system imposes a selective pressure on tumor cells which may either control tumor growth or inadvertently select for tumor cells which have evolved to escape the immune response and which may induce tumor development. Stimulation of the immune system by vaccination offers many benefits in the treatment of cancer. It is highly cost effective and vaccines can be manipulated to include multi-antigens which in some cases may overcome equilibrium (and selective pressure) while also preventing the establishment of reactivated cancer cells, since cancer antigen-specific memory would be induced following the initial vaccination/booster phase. To date studies using vaccination as a treatment for cancer have been a little disappointing, probably due to insufficient level of immunogenicity. In this review we will discuss methods of manipulation of the immune system to increase the anti-cancer activity of dendritic cells in vivo and how monocyte derived dendritic cells may be manipulated ex vivo to provide more robust, patient-specific treatments

Exact vortex solutions in a CP^N Skyrme-Faddeev type model

We consider a four dimensional field theory with target space being CP^N which constitutes a generalization of the usual Skyrme-Faddeev model defined on CP^1. We show that it possesses an integrable sector presenting an infinite number of local conservation laws, which are associated to the hidden symmetries of the zero curvature representation of the theory in loop space. We construct an infinite class of exact solutions for that integrable submodel where the fields are meromorphic functions of the combinations (x^1+i x^2) and (x^3+x^0) of the Cartesian coordinates of four dimensional Minkowski space-time. Among those solutions we have static vortices and also vortices with waves traveling along them with the speed of light. The energy per unity of length of the vortices show an interesting and intricate interaction among the vortices and waves.Comment: 21 pages, plain latex, no figure

High-speed Packet Capture Mechanism Based on Zero-copy in Linux

The development of gigabit-network demand higher standard of the packet capture's efficiency. Traditional network packet capture mechanisms get poor performance when used in gigabit-network. So we proposed a new network packet capture mechanism using zero-copy and POLLING. Through the modification to the bottom-layer, we achieve the packet capture in user space, and bypass the intervention of operating system's kernel. The efficiency of data processing is improved We achieve wire-speed capture rate, and the CPU usage rate is below 10%

Geochemistry of reduced inorganic sulfur, reactive iron, and organic carbon in fluvial and marine surface sediment in the Laizhou Bay region, China

Understanding the geochemical cycling of sulfur in sediments is important because it can have implications for both modern environments (e.g., deterioration of water quality) and interpretation of the ancient past (e.g., sediment C/S ratios can be used as indicators of palaeodepositional environment). This study investigates the geochemical characteristics of sulfur, iron, and organic carbon in fluvial and coastal surface sediments of the Laizhou Bay region, China. A total of 63 sediment samples were taken across the whole Laizhou Bay marine region and the 14 major tidal rivers draining into it. Acid volatile sulfur, chromium (II)-reducible sulfur and elemental sulfur, total organic carbon, and total nitrogen were present in higher concentrations in the fluvial sediment than in the marine sediment of Laizhou Bay. The composition of reduced inorganic sulfur in surface sediments was dominated by acid volatile sulfur and chromium (II)-reducible sulfur. In fluvial sediments, sulfate reduction and formation of reduced inorganic sulfur were controlled by TOC and reactive iron synchronously. High C/S ratios in the marine sediments indicate that the diagenetic processes in Laizhou Bay have been affected by rapid deposition of sediment from the Yellow River in recent decades

A new concept for the combination of optical interferometers and high-resolution spectrographs

The combination of high spatial and spectral resolution in optical astronomy enables new observational approaches to many open problems in stellar and circumstellar astrophysics. However, constructing a high-resolution spectrograph for an interferometer is a costly and time-intensive undertaking. Our aim is to show that, by coupling existing high-resolution spectrographs to existing interferometers, one could observe in the domain of high spectral and spatial resolution, and avoid the construction of a new complex and expensive instrument. We investigate in this article the different challenges which arise from combining an interferometer with a high-resolution spectrograph. The requirements for the different sub-systems are determined, with special attention given to the problems of fringe tracking and dispersion. A concept study for the combination of the VLTI (Very Large Telescope Interferometer) with UVES (UV-Visual Echelle Spectrograph) is carried out, and several other specific instrument pairings are discussed. We show that the proposed combination of an interferometer with a high-resolution spectrograph is indeed feasible with current technology, for a fraction of the cost of building a whole new spectrograph. The impact on the existing instruments and their ongoing programs would be minimal.Comment: 27 pages, 9 figures, Experimental Astronomy; v2: accepted versio