bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-Like Receptor 3 Has a Protective Role against West Nile Virus Infection
Authors: Daffis Stephane , Samuel Melanie A. , Suthar Mehul S. , Gale Michael , Diamond Michael S. 
Published: August 2008

ABSTRACT

Protection against West Nile virus (WNV) infection requires rapid viral sensing and the generation of an interferon (IFN) response. Mice lacking IFN regulatory factor 3 (IRF-3) show increased vulnerability to WNV infection with enhanced viral replication and blunted IFN-stimulated gene (ISG) responses. IRF-3 functions downstream of several viral sensors, including Toll-like receptor 3 (TLR3), RIG-I, and MDA5. Cell culture studies suggest that host recognizes WNV in part, through the cytoplasmic helicase RIG-I and to a lesser extent, MDA5, both of which activate ISG expression through IRF-3. However, the role of TLR3 in vivo in recognizing viral RNA and activating antiviral defense pathways has remained controversial. We show here that an absence of TLR3 enhances WNV mortality in mice and increases viral burden in the brain. Compared to congenic wild-type controls, TLR3
−/−
mice showed relatively modest changes in peripheral viral loads. Consistent with this, little difference in multistep viral growth kinetics or IFN-α/β induction was observed between wild-type and TLR3
−/−
fibroblasts, macrophages, and dendritic cells. In contrast, a deficiency of TLR3 was associated with enhanced viral replication in primary cortical neuron cultures and greater WNV infection in central nervous system neurons after intracranial inoculation. Taken together, our data suggest that TLR3 serves a protective role against WNV in part, by restricting replication in neurons.
Identification of a Broad-Spectrum Arenavirus Entry Inhibitor
Authors: Larson Ryan A. , Dai Dongcheng , Hosack Virginia T. , Tan Ying , Bolken Tove’ C. , Hruby Dennis E. , Amberg Sean M. 
Published: August 2008

ABSTRACT

Several arenaviruses, including Lassa virus (LASV), are causative agents of hemorrhagic fever, for which effective therapeutic options are lacking. The LASV envelope glycoprotein (GP) gene was used to generate lentiviral pseudotypes to identify small-molecule inhibitors of viral entry. A benzimidazole derivative with potent antiviral activity was identified from a high-throughput screen utilizing this strategy. Subsequent lead optimization for antiviral activity identified a modified structure, ST-193, with a 50% inhibitory concentration (IC
50
) of 1.6 nM against LASV pseudotypes. ST-193 inhibited pseudotypes generated with other arenavirus envelopes as well, including the remaining four commonly associated with hemorrhagic fever (IC
50
s for Junín, Machupo, Guanarito, and Sabiá were in the 0.2 to 12 nM range) but exhibited no antiviral activity against pseudotypes incorporating either the GP from the LASV-related arenavirus lymphocytic choriomeningitis virus (LCMV) or the unrelated G protein from vesicular stomatitis virus, at concentrations of up to 10 μM. Determinants of ST-193 sensitivity were mapped through a combination of LASV-LCMV domain-swapping experiments, genetic selection of viral variants, and site-directed mutagenesis. Taken together, these studies demonstrate that sensitivity to ST-193 is dictated by a segment of about 30 amino acids within the GP2 subunit. This region includes the carboxy-terminal region of the ectodomain and the predicted transmembrane domain of the envelope protein, revealing a novel antiviral target within the arenavirus envelope GP.
Epstein-Barr Virus Encodes Three Bona Fide Ubiquitin-Specific Proteases
Authors: Sompallae Ramakrishna , Gastaldello Stefano , Hildebrand Sebastian , Zinin Nikolay , Hassink Gerco , Lindsten Kristina , Haas Juergen , Persson Bengt , Masucci Maria G. 
Published: August 2008

ABSTRACT
Manipulation of the ubiquitin proteasome system (UPS) is emerging as a common theme in viral pathogenesis. Some viruses have been shown to encode functional homologs of UPS enzymes, suggesting that a systematic identification of these products may provide new insights into virus-host cell interactions. Ubiquitin-specific proteases, collectively known as deubiquitinating enzymes (DUBs), regulate the activity of the UPS by hydrolyzing ubiquitin peptide or isopeptide bonds. The prediction of viral DUBs based on sequence similarity with known enzymes is hampered by the diversity of viral genomes. In this study sequence alignments, pattern searches, and hidden Markov models were developed for the conserved C- and H-boxes of the known DUB families and used to search the open reading frames (ORFs) of Epstein-Barr virus (EBV), a large gammaherpesvirus that has been implicated in the pathogenesis of a broad spectrum of human malignancies of lymphoid and epithelial cell origin. The searches identified a limited number of EBV ORFs that contain putative DUB catalytic domains. DUB activity was confirmed by functional assays and mutation analysis for three high scoring candidates, supporting the usefulness of this bioinformatics approach in predicting distant homologues of cellular enzymes.
Hepatitis C Virus-Specific T-Cell Gamma Interferon and Proliferative Responses Are More Common in Perihepatic Lymph Nodes than in Peripheral Blood or Liver
Authors: Moonka Dilip , Milkovich Kimberly A. , Rodriguez Benigno , Abouljoud Marwan , Lederman Michael M. , Anthony Donald D. 
Published: August 2008

ABSTRACTThe activation state, differentiation state, and functions of liver lymphocytes and perihepatic lymph nodes during chronic hepatitis C virus (HCV) infection are not well understood. Here, we performed phenotypic and functional analyses of freshly prepared lymphocytes isolated from the livers, perihepatic lymph nodes, and peripheral blood compartments of chronic HCV-infected and disease control subjects with end-stage liver disease undergoing liver transplantation. We measured lymphocyte subset frequency and memory T-cell gamma interferon (IFN-γ) and proliferative responses to HCV peptide and control viral antigens in direct ex vivo assays. We found higher frequencies of CD4 cells in the lymph node compartment than in the other compartments for both HCV-infected and disease control subjects. Lymph node CD4 and CD8 cells less commonly expressed the terminal differentiation marker CD57, a finding consistent with an earlier differentiation state. In HCV-infected subjects, HCV-specific IFN-γ-producing and proliferative responses were commonly observed in the lymph node fraction, while they were uncommonly observed in the peripheral blood or liver fractions. In contrast, control viral CD4 protein antigen and CD8 peptide antigen-specific IFN-γ responses were commonly observed in the periphery and uncommonly observed in the lymph nodes of these same subjects. These findings are consistent with a selective defect in HCV-specific T-cell effector function or distribution in patients with advanced chronic HCV infection. The high frequency of HCV-reactive T cells in perihepatic lymph nodes indicates that a failure to generate or sustain T-lymphocyte HCV reactivity is not responsible for the paucity of functional cells even in end-stage liver disease.
Nef Can Enhance the Infectivity of Receptor-Pseudotyped Human Immunodeficiency Virus Type 1 Particles
Authors: Pizzato Massimo , Popova Elena , Göttlinger Heinrich G. 
Published: August 2008

ABSTRACT
Nef is an accessory protein of human immunodeficiency virus type 1 (HIV-1) that enhances the infectivity of progeny virions when expressed in virus-producing cells. The requirement for Nef for optimal infectivity is, at least in part, determined by the envelope (Env) glycoprotein, because it can be eliminated by pseudotyping HIV-1 particles with pH-dependent Env proteins. To investigate the role of Env in the function of Nef, we have examined the effect of Nef on the infectivity of Env-deficient HIV-1 particles pseudotyped with viral receptors for cells expressing cognate Env proteins. We found that Nef significantly enhances the infectivity of CD4-chemokine receptor pseudotypes for cells expressing HIV-1 Env. Nef also increased the infectivity of HIV-1 particles pseudotyped with Tva, the receptor for subgroup A Rous sarcoma virus (RSV-A), even though Nef had no effect if the pH-dependent Env protein of RSV-A was used for pseudotyping. However, Nef does not always enhance viral infectivity if the normal orientation of the Env-receptor interaction is reversed, because the entry of Env-deficient HIV-1 into cells expressing the vesicular stomatitis virus G protein was unaffected by Nef. Together, our results demonstrate that the presence of a viral Env protein during virus production is not required for the ability of Nef to increase viral infectivity. Furthermore, since the infectivity of Tva pseudotypes was blocked by inhibitors of endosomal acidification, we conclude that low-pH-dependent entry does not always bypass the requirement for Nef.
Differential Modulation of prM Cleavage, Extracellular Particle Distribution, and Virus Infectivity by Conserved Residues at Nonfurin Consensus Positions of the Dengue Virus pr-M Junction
Authors: Junjhon Jiraphan , Lausumpao Matthawee , Supasa Sunpetchuda , Noisakran Sansanee , Songjaeng Adisak , Saraithong Prakaimuk , Chaichoun Kridsada , Utaipat Utaiwan , Keelapang Poonsook , Kanjanahaluethai Amornrat , Puttikhunt Chunya , Kasinrerk Watchara , Malasit Prida , Sittisombut Nopporn 
Published: August 2008

ABSTRACT
In the generation of flavivirus particles, an internal cleavage of the envelope glycoprotein prM by furin is required for the acquisition of infectivity. Unlike cleavage of the prM of other flaviviruses, cleavage of dengue virus prM is incomplete in many cell lines; the partial cleavage reflects the influence of residues at furin nonconsensus positions of the pr-M junction, as flaviviruses share basic residues at positions P1, P2, and P4, recognized by furin. In this study, viruses harboring the alanine-scanning and other multiple-point mutations of the pr-M junction were generated, employing a dengue virus background that exhibited 60 to 70% prM cleavage and a preponderance of virion-sized extracellular particles. Analysis of prM and its cleavage products in viable mutants revealed a cleavage-suppressive effect at the conserved P3 Glu residue, as well as the cleavage-augmenting effects at the P5 Arg and P6 His residues, indicating an interplay between opposing modulatory influences mediated by these residues on the cleavage of the pr-M junction. Changes in the prM cleavage level were associated with altered proportions of extracellular virions and subviral particles; mutants with reduced cleavage were enriched with subviral particles and prM-containing virions, whereas the mutant with enhanced cleavage was deprived of these particles. Alterations of virus multiplication were detected in mutants with reduced prM cleavage and were correlated with their low specific infectivities. These findings define the functional roles of charged residues located adjacent to the furin consensus sequence in the cleavage of dengue virus prM and provide plausible mechanisms by which the reduction in the pr-M junction cleavability may affect virus replication.
Enhancement of Human Immunodeficiency Virus (HIV)-Specific CD8+T Cells in Cerebrospinal Fluid Compared to Those in Blood among Antiretroviral Therapy-Naïve HIV-Positive Subjects
Authors: Sadagopal Shanmugalakshmi , Lorey Shelly L. , Barnett Louise , Basham Rebecca , Lebo Laurie , Erdem Husamettin , Haman Kirsten , Avison Malcolm , Waddell Kevin , Haas David W. , Kalams Spyros A. 
Published: August 2008

ABSTRACTDuring untreated human immunodeficiency virus type 1 (HIV-1) infection, virus-specific CD8+T cells partially control HIV replication in peripheral lymphoid tissues, but host mechanisms of HIV control in the central nervous system (CNS) are incompletely understood. We characterized HIV-specific CD8+T cells in cerebrospinal fluid (CSF) and peripheral blood among seven HIV-positive antiretroviral therapy-naïve subjects. All had grossly normal brain magnetic resonance imaging and spectroscopy and normal neuropsychometric testing. Frequencies of epitope-specific CD8+T cells by direct tetramer staining were on average 2.4-fold higher in CSF than in blood (P= 0.0004), while HIV RNA concentrations were lower. Cells from CSF were readily expanded ex vivo and responded to a broader range of HIV-specific human leukocyte antigen class I restricted optimal peptides than did expanded cells from blood. HIV-specific CD8+T cells, in contrast to total CD8+T cells, in CSF and blood were at comparable maturation states, as assessed by CD45RO and CCR7 staining. The strong relationship between higher T-cell frequencies and lower levels of viral antigen in CSF could be the result of increased migration to and/or preferential expansion of HIV-specific T cells within the CNS. This suggests an important role for HIV-specific CD8+T cells in control of intrathecal viral replication.
Open Reading Frame 2, Encoded by the Latency-Related Gene of Bovine Herpesvirus 1, Has Antiapoptotic Activity in Transiently Transfected Neuroblastoma Cells
Authors: Shen Wenwen , Jones Clinton 
Published: August 2008

ABSTRACT
The latency-related (LR) RNA encoded by bovine herpesvirus 1 is abundantly expressed in the trigeminal ganglia of latently infected calves. Expression of LR proteins is necessary for reactivation from latency and the protection of infected neurons from apoptosis. In this study, we demonstrated that an LR-encoded protein, open reading frame 2 (ORF-2), or ORF-2 fusion proteins encoded by alternatively spliced LR transcripts inhibit cold shock or Fas ligand-induced apoptosis in mouse neuroblastoma (neuro-2A) cells. Frameshift mutants of ORF-2 do not inhibit apoptosis, which suggests that protein expression, not LR RNA expression, mediates the antiapoptotic activity of the LR gene in transfected neuro-2A cells.
Genetically Divergent Strains of Feline Immunodeficiency Virus from the Domestic Cat (
Felis catus
) and the African Lion (
Panthera leo
) Share Usage of CD134 and CXCR4 as Entry Receptors
Authors: McEwan William A. , McMonagle Elizabeth L. , Logan Nicola , Serra Rodrigo C. , Kat Pieter , VandeWoude Sue , Hosie Margaret J. , Willett Brian J. 
Published: August 2008

ABSTRACT

The
env
open reading frames of African lion (
Panthera leo
) lentivirus (feline immunodeficiency virus [FIV
Ple
]) subtypes B and E from geographically distinct regions of Africa suggest two distinct ancestries, with FIV
Ple
-E sharing a common ancestor with the domestic cat (
Felis catus
) lentivirus (FIV
Fca)
. Here we demonstrate that FIV
Ple
-E and FIV
Fca
share the use of CD134 (OX40) and CXCR4 as a primary receptor and coreceptor, respectively, and that both lion CD134 and CXCR4 are functional receptors for FIV
Ple
-E. The shared usage of CD134 and CXCR4 by FIV
Fca
and FIV
Ple
-E may have implications for in vivo cell tropism and the pathogenicity of the E subtype among free-ranging lion populations.
The modelling of injectors, pumps and compressors in process simulation
Authors: Martin E.N. 
Published: August 2008

Control engineering studies during the design of an industrial process frequently use simulation methods which require its operation to be represented in mathematical terms. This contribution reviews the salient features of various types of pumps and compressors encountered in such processes and presents models which embody these properties in a form suitable for use on a computer. In general, these represent a compromise between the extremes of simplicity and rigour which has proved satisfactory in this context. Each application should, however, be the subject of engineering judgment on the degree of approximation which will be consistent with the quality of the data available and the objectives for which the simulation is being performed.
Frequency domain solution to the optimum multivariable tracking problem
Authors: Grimble M.J. 
Published: August 2008

A solution is obtained to the infinite time optimal tracking problem for a multivariable system. The derivation is more direct than the usual approach through Parseval's theorem and it relates Hilbert space gradient techniques to the complex frequency domain. where W * : Ln2 (0, ∞) → L m2 (- ∞, ∞). By considering the properties of the impulse response matrix it may be confirmed that the system represented by the operator W * has a response (W*y) (t) existing for negative time, even though y is zero for negative time. It is clear that W * represents a non-causal system.
Threshold fluid logic and its application to knitting machine control
Authors: Burns N.D. , Douglas N.G. 
Published: August 2008

Threshold logic holds many advantages over conventional logic when applied to switching network design. The advantages are greatest when the functions are complex. In such cases threshold logic solutions result in fewer gates and interconnections than purely binary solutions. The application of threshold gates to fluid-logic systems can result in cost savings and performance improvements. Although the logical functions are relatively simple, the use of threshold elements still results in reductions in elements over the purely boolean solution. The success of threshold logic is critically dependent upon the physical structure of the device, its cost, response speed, reliability, etc. Some tentative designs for devices are presented in this paper. Prototypes have been manufactured and during early tests some problems became apparent. Further long term tests are continuing.
Solids-concentration measurement and flow measurement of slurries and sludges using ultrasonic sensors with random data analysis
Authors: Balachandran W. , Beck M.S. 
Published: August 2008

The flow velocity is measured by cross- correlating the output signals from two axially spaced ultrasonic sensors, similar to the sensors described in Part 1 of this paper. A meter factor of 0.84 ± 0.02 was observed to calibrate the measured cross- correlation velocity against actual mean flow velocity, for flow of Reynold's number from 3× 10 3 up to 75 × 103. The meter performance was not affected by change in particle size and concentration; small quantities of gas bubbles (up to 5% by volume) do not affect the calibration curve.
Design of closed-loop optimal controllers for systems with shape deterministic inputs
Authors: Grimble M.J. 
Published: August 2008

The design of closed-loop optimal controllers for systems with output-feedback is considered. The disturbance, initial condition and reference signals in the system are assumed to be either deterministic or shape-deterministic or a sum of both, The shape-deterministic signals have a specified time response, but the magnitude of the response is a random variable with known mean and covariance. The performance criterion includes the expectation averaging operator, and the cost is measured over the positive-time interval only. The performance criterion also includes dynamical operators which may be chosen to achieve specified response characteristics. The solution for the closed-loop controller is obtained, for both tracking and regulating problems, in the s-domain. The controller is not, in general, the same as those obtained from either the LQP or LQG optimal-control problems. The advantages of the technique are that output feedback, rather than state-feedback, is used, and both random and deterministic signals are optimised. In other approaches to such problems, there are severe difficulties in defining a performance criterion which is suitable for both deterministic and stochastic signals.
Design of diametral displacement transducer for continuous measurement of the external diameter of a ring under compression at any temperature
Authors: Abdul N.A. 
Published: August 2008

A knowledge of the amount of friction present at the die/ workpiece interface and the basic yield characteristics of a workpiece material are fundamental requirements for any metal-forming analysis to have a useful practical application Coincidentally the property of a ring under compression provides a reliable means of sensing and measuring friction and of determining the basic yield characteristic of the workpiece material under bulk plastic deformation. However, the application of the ring technique requires measurement of axial as well as diametral displacements which - for ease of application and saving on material — should be made continuously, especially for high temperature application. Towards taking maximum advantage of the ring technique, this work presents a design of a special diametral displacement transducer consisting of four cylindrical variable area capacitors for continuous measurement of external diametral displacement of a ring under compression. The transducer, capable of automatically recording the mean of two orthogonal diametral displacements was used at elevated temperature.
Control of medium-term dynamic econometric models: an application to the Cambridge Growth Project model
Authors: van der Ploeg Rick 
Published: August 2008

The latest version of a large-scale multisectoral dynamic model of the UK's economy, developed by the Cambridge Growth Project under direction of Sir Richard Stone, is described. Its dynamic properties, owing to an investment cycle of the order of five or six years, and its main economic properties are analysed thoroughly. The medium- term nature of the model is exploited to formulate a macroeconomic policy for the UK's economy. An understanding of the long- run dynamics of the economy is crucial, since a change in policy today has complicated consequences many years later. A regulation approach is proposed and yields an optimal reflationary mix for steering the economy over the next decade towards its desired target trajectory. The dynamics in the policy ensure satisfactory levels for growth, inflation and unemployment. The industrial implications of the feedback policy are discussed and suggestions for sectoral policy are given.
Frequency limits for gas flow pulsation damping criteria
Authors: Mottram R.C. , Mohammad W.A. 
Published: August 2008

The accuracy of most flowmeters is seriously affected by pulsations, and these must be damped before reliable measurements can be achieved. Damping criteria based on the Hodgson Number have been used for many years in flow measurements made with differential pressure-type flow meters. The objects of this paper are to demonstrate the validity of such criteria in gas flows and to specify their frequency limits. A damping criterion derived from a theoretical analysis applicable to any pulsation waveform is presented. Results of experimental tests carried out with both piston- and siren-type devices, producing pulsations of sinusoidal and non-sinusoidal waveforms in the frequency range of 5-500 Hz, are shown. The results verify that the damping criterion is valid on the Surrey University air flow rig at various pulsation amplitudes and damping volumes at frequencies below 50 Hz. It is suggested that these results are applicable to any gas flow system provided the limiting frequency is such that: (i) The dimensions of the damping chamber are not greater than one-tenth of the pulsation wavelength. (ii) The length of pipe between damping tank and flowmeter should not exceed one-fifth of the pulsation wavelength.