HSV-2 Infection of Human Genital Epithelial Cells Upregulates TLR9 Expression Through the SP1/JNK Signaling Pathway

It is known that herpes simplex virus type 2 (HSV-2) triggers the activation of Toll-like receptor (TLR) 9 signaling pathway and the consequent production of antiviral cytokines in dendritic cells. However, the impact of HSV-2 infection on TLR9 expression and signaling in genital epithelial cells, the primary HSV-2 targets, has yet to be determined. In the current study, by using both human genital epithelial cell lines and primary genital epithelial cells as models, we found that HSV-2 infection enhances TLR9 expression at both mRNA and protein levels. Such enhancement is virus replication-dependent and CpG-independent, while the HSV-2-mediated upregulation of TLR9 does not activate TLR9 signaling pathway. Mechanistically, a SP1 binding site on TLR9 promoter appears to be essential for HSV-2-induced TLR9 transactivation. Upon HSV-2 infection, SP1 translocates from the cytoplasm to the nucleus, and consequently binds to TLR9 promoter. By using specific inhibitors, the JNK signaling pathway is shown to be involved in the HSV-2-induced TLR9 transactivation, while HSV-2 infection increases the phosphorylation but not the total level of JNK. In agreement, antagonism of JNK signaling pathway inhibits the HSV-2-induced SP1 nuclear translocation. Taken together, our study demonstrates that HSV-2 infection of human genital epithelial cells promotes TLR9 expression through SP1/JNK signaling pathway. Findings in this study provide insights into HSV-2-host interactions and potential targets for immune intervention

Interacting Generalised Cosmic Chaplygin gas in Loop quantum cosmology: A singularity free universe

In this work we investigate the background dynamics when dark energy is coupled to dark matter with a suitable interaction in the universe described by Loop quantum cosmology. Dark energy in the form of Generalised Cosmic Chaplygin gas is considered. A suitable interaction between dark energy and dark matter is taken into account in order to at least alleviate (if not solve) the cosmic coincidence problem. The dynamical system of equations is solved numerically and a stable scaling solution is obtained. A significant attempt towards the solution of the cosmic coincidence problem is taken. The statefinder parameters are also calculated to classify the dark energy model. Graphs and phase diagrams are drawn to study the variations of these parameters. It is seen that the background dynamics of Generalised Cosmic Chaplygin gas is completely consistent with the notion of an accelerated expansion in the late universe. From the graphs, generalised cosmic Chaplygin gas is identified as a dark fluid with a lesser negative pressure compared to Modified Chaplygin gas, thus supporting a 'No Big Rip' cosmology. It has also been shown that in this model the universe follows the power law form of expansion around the critical point, which is consistent with the known results. Future singularities that may be formed in this model as an ultimate fate of the universe has been studied in detail. It was found that the model is completely free from any types of future singularities.Comment: 10 pages, 10 figures. arXiv admin note: text overlap with arXiv:1109.1481, arXiv:1102.275

Strategically Equivalent Contests

Using a two-player Tullock-type contest, we show that intuitively and structurally different contests can be strategically equivalent. Strategically equivalent contests generate the same best response functions and, as a result, the same equilibrium efforts. However, strategically equivalent contests may yield different equilibrium payoffs. We propose a simple two-step procedure to identify strategically equivalent contests. Using this procedure, we identify contests that are strategically equivalent to the original Tullock contest, and provide new examples of strategically equivalent contests. Finally, we discuss possible contest design applications and avenues for future theoretical and empirical research

RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase.

Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. The mechanism by which AID triggers SHM and CSR has been explained by two distinct models. In the DNA deamination model, AID converts cytidine bases in DNA into uridine. The uridine is recognized by the DNA repair system, which produces DNA strand breakages and point mutations. In the alternative model, RNA edited by AID is responsible for triggering CSR and SHM. However, RNA deamination by AID has not been demonstrated. Here we found that C-to-T and G-to-A mutations accumulated in hepatitis B virus (HBV) nucleocapsid DNA when AID was expressed in HBV-replicating hepatic cell lines. AID expression caused C-to-T mutations in the nucleocapsid DNA of RNase H-defective HBV, which does not produce plus-strand viral DNA. Furthermore, the RT-PCR products of nucleocapsid viral RNA from AID-expressing cells exhibited significant C-to-T mutations, whereas viral RNAs outside the nucleocapsid did not accumulate C-to-U mutations. Moreover, AID was packaged within the nucleocapsid by forming a ribonucleoprotein complex with HBV RNA and the HBV polymerase protein. The encapsidation of the AID protein with viral RNA and DNA provides an efficient environment for evaluating AID's RNA and DNA deamination activities. A bona fide RNA-editing enzyme, apolipoprotein B mRNA editing catalytic polypeptide 1, induced a similar level of C-to-U mutations in nucleocapsid RNA as AID. Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV

Theory of free space coupling to high-Q whispering gallery modes

A theoretical study of free space coupling to high-Q whispering gallery modes both in circular and deformed microcavities are presented. In the case of a circular cavity, both analytical solutions and asymptotic formulas are derived. The coupling efficiencies at different coupling regimes for cylinder incoming wave are discussed, and the maximum efficiency is estimated for the practical Gaussian beam excitation. In the case of a deformed cavity, the coupling efficiency can be higher if the excitation beam can match the intrinsic emission well and the radiation loss can be tuned by adjusting the degree of deformation. Employing an abstract model of slightly deformed cavity, we found that the asymmetric and peak like line shapes instead of the Lorentz-shape dip are universal in transmission spectra due to multi-mode interference, and the coupling efficiency can not be estimated from the absolute depth of the dip. Our results provide guidelines for free space coupling in experiments, suggesting that the high-Q ARCs can be efficiently excited through free space which will stimulate further experiments and applications of WGMs based on free space coupling.Comment: 8 pages, 4 figure

Imprecise probabilistic estimation of design floods with epistemic uncertainties

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.An imprecise probabilistic framework for design flood estimation is proposed on the basis of the Dempster-Shafer theory to handle different epistemic uncertainties from data, probability distribution functions and probability distribution parameters. These uncertainties are incorporated in cost-benefit analysis to generate the lower and upper bounds of the total cost for flood control, thus presenting improved information for decision making on design floods. Within the total cost bounds, a new robustness criterion is proposed to select a design flood that can tolerate higher levels of uncertainty. A variance decomposition approach is used to quantify individual and interactive impacts of the uncertainty sources on total cost. Results from three case studies, with 127-, 104- and 54-year flood data sets respectively, show that the imprecise probabilistic approach effectively combines aleatory and epistemic uncertainties from the various sources and provides upper and lower bounds of the total cost. Between the total cost and the robustness of design floods, a clear trade-off which is beyond the information that can be provided by the conventional minimum cost criterion is identified. The interactions among data, distributions and parameters have a much higher contribution than parameters to the estimate of the total cost. It is found that the contributions of the various uncertainty sources and their interactions vary with different flood magnitude, but remain roughly the same with different return periods. This study demonstrates that the proposed methodology can effectively incorporate epistemic uncertainties in cost-benefit analysis of design floods.This study was supported by the National Natural Science Foundation of China (Grant No. 51320105010 and 51279021). The first author gratefully acknowledges the financial support provided by the China Scholarship Council. The authors are deeply indebted to editors, Dr Francesco Serinaldi and another anonymous reviewer for their valuable time and constructive suggestions that greatly improved the quality of this paper. The data of Three Gorges were obtained from the China Three Gorges Corporation. The data of Biliu were obtained from the Biliu reservoir administration. The data of Harbin were obtained from the Harbin hydrology bureau. These data are available as in Supporting Information Data Set which includes Data Set S1, Data Set S2 and Data Set S3. Data Set S1 corresponds to Three Gorges; Data Set S2 corresponds to Biliu; Data Set S3 corresponds to Harbin

Information seeking, use, and decision making

YesIn this paper we explored three areas: decision making and information seeking, the relationship between information seeking and uncertainty, and the role of expertise in influencing information use. This was undertaken in the context of a qualitative study into decision making in the initial stages of emergency response to major incidents. The research took an interpretive approach in which activity theory is used as an analytical framework. The research provides further evidence that the context of the activity and individual differences influence the choice of decision mode and associated information behavior. We also established that information is often not used to resolve uncertainty in decision making and indeed information is often sought and used after the decision is made to justify the decision. Finally, we point to the significance of both expertise and confidence in understanding information behavior. The contribution of the research to existing theoretical frameworks is discussed and a modified version of Wilson's problem-solving model is proposed

Standardised framework for quantitative analysisof fibrillation dynamics

The analysis of complex mechanisms underlying ventricular fibrillation (VF) and atrial fibrillation (AF) requires sophisticatedtools for studying spatio-temporal action potential (AP) propagation dynamics. However, fibrillation analysis tools are oftencustom-made or proprietary, and vary between research groups. With no optimal standardised framework for analysis, resultsfrom different studies have led to disparate findings. Given the technical gap, here we present a comprehensive framework andset of principles for quantifying properties of wavefront dynamics in phase-processed data recorded during myocardial fibrillationwith potentiometric dyes. Phase transformation of the fibrillatory data is particularly useful for identifying self-perpetuating spiralwaves or rotational drivers (RDs) rotating around a phase singularity (PS). RDs have been implicated in sustaining fibrillation,and thus accurate localisation and quantification of RDs is crucial for understanding specific fibrillatory mechanisms. In thiswork, we assess how variation of analysis parameters and thresholds in the tracking of PSs and quantification of RDs couldresult in different interpretations of the underlying fibrillation mechanism. These techniques have been described and appliedto experimental AF and VF data, and AF simulations, and examples are provided from each of these data sets to demonstratethe range of fibrillatory behaviours and adaptability of these tools. The presented methodologies are available as an opensource software and offer an off-the-shelf research toolkit for quantifying and analysing fibrillatory mechanisms

Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules

Cytoplasmic dynein is a dimeric AAA+ motor protein that performs critical roles in eukaryotic cells by moving along microtubules using ATP. Here using cryo-electron microscopy we directly observe the structure of Dictyostelium discoideum dynein dimers on microtubules at near-physiological ATP concentrations. They display remarkable flexibility at a hinge close to the microtubule binding domain (the stalkhead) producing a wide range of head positions. About half the molecules have the two heads separated from one another, with both leading and trailing motors attached to the microtubule. The other half have the two heads and stalks closely superposed in a front-to-back arrangement of the AAA+ rings, suggesting specific contact between the heads. All stalks point towards the microtubule minus end. Mean stalk angles depend on the separation between their stalkheads, which allows estimation of inter-head tension. These findings provide a structural framework for understanding dynein’s directionality and unusual stepping behaviour

Iron Supported On Bioinspired Green Silica for Water Remediation

Iron has been used previously in water decontamination, either unsupported or supported on clays, polymers, carbons or ceramics such as silica. However, the reported synthesis procedures are tedious, lengthy (involving various steps), and either utilise or produce toxic chemicals. Herein, the use of a simple, rapid, bio-inspired green synthesis method is reported to prepare, for the first time a family of iron supported green nanosilica materials (Fe@GN) to create new technological solutions for water remediation. In particular, Fe@GN were employed for the removal of arsenate ions as a model for potentially toxic elements in aqueous solution. Several characterization techniques were used to study the physical, structural and chemical properties of the new Fe@GN. When evaluated as an adsorption platform for the removal of arsenate ions, Fe@GN exhibited high adsorption capacity (69 mg of As/g of Fe@GN) with superior kinetics (reaching ~35mg As/g sorbent/hr) – threefold higher than the highest removal rates reported to date. Moreover, a method was developed to regenerate the Fe@GN allowing for full recovery and reuse of the adsorbent in subsequent extractions; strongly highlighting the potential technological benefits of these new green materials