Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes – NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases

Properties of continuous Fourier extension of the discrete cosine transform and its multidimensional generalization

A versatile method is described for the practical computation of the discrete Fourier transforms (DFT) of a continuous function $g(t)$ given by its values $g_{j}$ at the points of a uniform grid $F_{N}$ generated by conjugacy classes of elements of finite adjoint order $N$ in the fundamental region $F$ of compact semisimple Lie groups. The present implementation of the method is for the groups SU(2), when $F$ is reduced to a one-dimensional segment, and for $SU(2)\times ... \times SU(2)$ in multidimensional cases. This simplest case turns out to result in a transform known as discrete cosine transform (DCT), which is often considered to be simply a specific type of the standard DFT. Here we show that the DCT is very different from the standard DFT when the properties of the continuous extensions of these two discrete transforms from the discrete grid points $t_j; j=0,1, ... N$ to all points $t \in F$ are considered. (A) Unlike the continuous extension of the DFT, the continuous extension of (the inverse) DCT, called CEDCT, closely approximates $g(t)$ between the grid points $t_j$. (B) For increasing $N$, the derivative of CEDCT converges to the derivative of $g(t)$. And (C), for CEDCT the principle of locality is valid. Finally, we use the continuous extension of 2-dimensional DCT to illustrate its potential for interpolation, as well as for the data compression of 2D images.Comment: submitted to JMP on April 3, 2003; still waiting for the referee's Repor

NbSe3: Effect of Uniaxial Stress on the Threshold Field and Fermiology

We have measured the effect of uniaxial stress on the threshold field ET for the motion of the upper CDW in NbSe3. ET exhibits a critical behavior, ET ~ (1 - e/ec)^g, wher e is the strain, and ec is about 2.6% and g ~ 1.2. This ecpression remains valid over more than two decades of ET, up to the highest fields of about 1.5keV/m. Neither g nor ec is very sensitive to the impurity concentraction. The CDW transition temperature Tp decreases linearly with e at a rate dTp/de = -10K/%, and it does not show any anomaly near ec. Shubnikov de-Haas measurements show that the extremal area of the Fermi surface decreases with increasing strain. The results suggest that there is an intimate relationship between pinning of the upper CDW and the Fermiology of NbSe3.Comment: 4 pages, 5 figure

Infrared Spectroscopy of Quantum Crossbars

Infrared (IR) spectroscopy can be used as an important and effective tool for probing periodic networks of quantum wires or nanotubes (quantum crossbars, QCB) at finite frequencies far from the Luttinger liquid fixed point. Plasmon excitations in QCB may be involved in resonance diffraction of incident electromagnetic waves and in optical absorption in the IR part of the spectrum. Direct absorption of external electric field in QCB strongly depends on the direction of the wave vector ${\bf q}.$ This results in two types of $1D\to 2D$ dimensional crossover with varying angle of an incident wave or its frequency. In the case of QCB interacting with semiconductor substrate, capacitive contact between them does not destroy the Luttinger liquid character of the long wave QCB excitations. However, the dielectric losses on a substrate surface are significantly changed due to appearance of additional Landau damping. The latter is initiated by diffraction processes on QCB superlattice and manifests itself as strong but narrow absorption peaks lying below the damping region of an isolated substrate.SubmiComment: Submitted to Phys. Rev.

Adapting SAM for CDF

The CDF and D0 experiments probe the high-energy frontier and as they do so have accumulated hundreds of Terabytes of data on the way to petabytes of data over the next two years. The experiments have made a commitment to use the developing Grid based on the SAM system to handle these data. The D0 SAM has been extended for use in CDF as common patterns of design emerged to meet the similar requirements of these experiments. The process by which the merger was achieved is explained with particular emphasis on lessons learned concerning the database design patterns plus realization of the use cases.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 4 pages, pdf format, TUAT00

Wave packet propagation by the Faber polynomial approximation in electrodynamics of passive media

Maxwell's equations for propagation of electromagnetic waves in dispersive and absorptive (passive) media are represented in the form of the Schr\"odinger equation $i\partial \Psi/\partial t = {H}\Psi$, where ${H}$ is a linear differential operator (Hamiltonian) acting on a multi-dimensional vector $\Psi$ composed of the electromagnetic fields and auxiliary matter fields describing the medium response. In this representation, the initial value problem is solved by applying the fundamental solution $\exp(-itH)$ to the initial field configuration. The Faber polynomial approximation of the fundamental solution is used to develop a numerical algorithm for propagation of broad band wave packets in passive media. The action of the Hamiltonian on the wave function $\Psi$ is approximated by the Fourier grid pseudospectral method. The algorithm is global in time, meaning that the entire propagation can be carried out in just a few time steps. A typical time step is much larger than that in finite differencing schemes, $\Delta t_F \gg \|H\|^{-1}$. The accuracy and stability of the algorithm is analyzed. The Faber propagation method is compared with the Lanczos-Arnoldi propagation method with an example of scattering of broad band laser pulses on a periodic grating made of a dielectric whose dispersive properties are described by the Rocard-Powels-Debye model. The Faber algorithm is shown to be more efficient. The Courant limit for time stepping, $\Delta t_C \sim \|H\|^{-1}$, is exceeded at least in 3000 times in the Faber propagation scheme.Comment: Latex, 17 pages, 4 figures (separate png files); to appear in J. Comput. Phy

Dirac Neutrino Dark Matter

We investigate the possibility that dark matter is made of heavy Dirac neutrinos with mass in the range [O(1) GeV- a few TeV] and with suppressed but non-zero coupling to the Standard Model Z as well as a coupling to an additional Z' gauge boson. The first part of this paper provides a model-independent analysis for the relic density and direct detection in terms of four main parameters: the mass, the couplings to the Z, to the Z' and to the Higgs. These WIMP candidates arise naturally as Kaluza-Klein states in extra-dimensional models with extended electroweak gauge group SU(2)_L* SU(2)_R * U(1). They can be stable because of Kaluza-Klein parity or of other discrete symmetries related to baryon number for instance, or even, in the low mass and low coupling limits, just because of a phase-space-suppressed decay width. An interesting aspect of warped models is that the extra Z' typically couples only to the third generation, thus avoiding the usual experimental constraints. In the second part of the paper, we illustrate the situation in details in a warped GUT model.Comment: 35 pages, 25 figures; v2: JCAP version; presentation and plots improved, results unchange

Twisted boundary states in c=1 coset conformal field theories

We study the mutual consistency of twisted boundary conditions in the coset conformal field theory G/H. We calculate the overlap of the twisted boundary states of G/H with the untwisted ones, and show that the twisted boundary states are consistently defined in the diagonal modular invariant. The overlap of the twisted boundary states is expressed by the branching functions of a twisted affine Lie algebra. As a check of our argument, we study the diagonal coset theory so(2n)_1 \oplus so(2n)_1/so(2n)_2, which is equivalent with the orbifold S^1/\Z_2. We construct the boundary states twisted by the automorphisms of the unextended Dynkin diagram of so(2n), and show their mutual consistency by identifying their counterpart in the orbifold. For the triality of so(8), the twisted states of the coset theory correspond to neither the Neumann nor the Dirichlet boundary states of the orbifold and yield the conformal boundary states that preserve only the Virasoro algebra.Comment: 44 pages, 1 figure; (v2) minor change in section 2.3, references adde

Hip fracture risk assessment: Artificial neural network outperforms conditional logistic regression in an age- and sex-matched case control study

Copyright @ 2013 Tseng et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background - Osteoporotic hip fractures with a significant morbidity and excess mortality among the elderly have imposed huge health and economic burdens on societies worldwide. In this age- and sex-matched case control study, we examined the risk factors of hip fractures and assessed the fracture risk by conditional logistic regression (CLR) and ensemble artificial neural network (ANN). The performances of these two classifiers were compared. Methods - The study population consisted of 217 pairs (149 women and 68 men) of fractures and controls with an age older than 60 years. All the participants were interviewed with the same standardized questionnaire including questions on 66 risk factors in 12 categories. Univariate CLR analysis was initially conducted to examine the unadjusted odds ratio of all potential risk factors. The significant risk factors were then tested by multivariate analyses. For fracture risk assessment, the participants were randomly divided into modeling and testing datasets for 10-fold cross validation analyses. The predicting models built by CLR and ANN in modeling datasets were applied to testing datasets for generalization study. The performances, including discrimination and calibration, were compared with non-parametric Wilcoxon tests. Results - In univariate CLR analyses, 16 variables achieved significant level, and six of them remained significant in multivariate analyses, including low T score, low BMI, low MMSE score, milk intake, walking difficulty, and significant fall at home. For discrimination, ANN outperformed CLR in both 16- and 6-variable analyses in modeling and testing datasets (p?<?0.005). For calibration, ANN outperformed CLR only in 16-variable analyses in modeling and testing datasets (p?=?0.013 and 0.047, respectively). Conclusions - The risk factors of hip fracture are more personal than environmental. With adequate model construction, ANN may outperform CLR in both discrimination and calibration. ANN seems to have not been developed to its full potential and efforts should be made to improve its performance.National Health Research Institutes in Taiwa

Text Line Segmentation of Historical Documents: a Survey

There is a huge amount of historical documents in libraries and in various National Archives that have not been exploited electronically. Although automatic reading of complete pages remains, in most cases, a long-term objective, tasks such as word spotting, text/image alignment, authentication and extraction of specific fields are in use today. For all these tasks, a major step is document segmentation into text lines. Because of the low quality and the complexity of these documents (background noise, artifacts due to aging, interfering lines),automatic text line segmentation remains an open research field. The objective of this paper is to present a survey of existing methods, developed during the last decade, and dedicated to documents of historical interest.Comment: 25 pages, submitted version, To appear in International Journal on Document Analysis and Recognition, On line version available at http://www.springerlink.com/content/k2813176280456k3