bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral Effects of Human Immunodeficiency Virus Type 1-Specific Small Interfering RNAs against Targets Conserved in Select Neurotropic Viral Strains
Authors: Dave Rajnish S. , Pomerantz Roger J. 
Published: November 2004

ABSTRACTRNA interference, a natural biological phenomenon mediated by small interfering RNAs (siRNAs), has been demonstrated in recent studies to be an effective strategy against human immunodeficiency virus type 1 (HIV-1). In the present study, we used 21-bp chemically synthesized siRNA duplexes whose sequences were derived from the gp41 gene,nef,tat, andrevregions of viral RNA. These sequences are conserved in select neurotropic strains of HIV-1 (JR-FL, JR-CSF, and YU-2). The designed siRNAs exerted a potent antiviral effect on these HIV-1 strains. The antiviral effect was mediated at the RNA level (as observed by the down-regulation of the HIV-1-specific spliced transcript generating a 1.2-kbp reverse transcription [RT]-PCR product) as well as viral assembly on the cell membrane. Spliced transcripts (apart from the most abundant transcript generating a 1.2-kbp RT-PCR product) arising from an unspliced precursor likely contributed, albeit to a lesser extent, to the antiviral effect. The resultant progeny viruses had infectivities similar to that of input virus. We therefore conclude that these siRNAs interfere with the processing of the unspliced transcripts for the gp41 gene,tat,rev, andnef, eventually affecting viral assembly and leading to the overall inhibition of viral production. Apart from using the gp41 gene as a target, the conservation of each of these targets in the above-mentioned viral strains, as well as several primary isolates, would enable these siRNAs to be used as potent antiviral tools for investigations with cells derived from the central nervous system in order to evaluate their therapeutic potential and assess their utility in inhibiting HIV-1 neuropathogenesis and neuroinvasion.
Intrahepatic Gene Expression during Chronic Hepatitis C Virus Infection in Chimpanzees
Authors: Bigger Catherine B. , Guerra Bernadette , Brasky Kathleen M. , Hubbard Gene , Beard Michael R. , Luxon Bruce A. , Lemon Stanley M. , Lanford Robert E. 
Published: November 2004

ABSTRACTHepatitis C virus (HCV) infections represent a global health problem and are a major contributor to end-stage liver disease including cirrhosis and hepatocellular carcinoma. An improved understanding of the parameters involved in disease progression is needed to develop better therapies and diagnostic markers of disease manifestation. To better understand the dynamics of host gene expression resulting from persistent virus infection, DNA microarray analyses were conducted on livers from 10 chimpanzees persistently infected with HCV. A total of 162 genes were differentially regulated in chronically infected animals compared to uninfected controls. Many genes exhibited a remarkable consistency in changes in expression in the 10 chronically infected animals. A second method of analysis identified 971 genes altered in expression during chronic infection at a 99% confidence level. As with acute-resolving HCV infections, many interferon (IFN)-stimulated genes (ISGs) were transcriptionally elevated, suggesting an ongoing response to IFN and/or double-stranded RNA which is amplified in downstream ISG expression. Thus, persistent infection with HCV results in a complex and partially predictable pattern of gene expression, although the underlying mechanisms regulating the different pathways are not well defined. A single genotype 3-infected animal was available for analysis, and this animal exhibited reduced levels of ISG expression compared to levels of expression with genotype 1 infections and increased expression of a number of genes potentially involved in steatosis. Gene expression data in concert with other observations from HCV infections permit speculation on the regulation of specific aspects of HCV infection.
Evidence and Consequence of Porcine Endogenous Retrovirus Recombination
Authors: Bartosch Birke , Stefanidis Dimitrios , Myers Richard , Weiss Robin , Patience Clive , Takeuchi Yasuhiro 
Published: November 2004

ABSTRACT

The genetic nature and biological effects of recombination between porcine endogenous retroviruses (PERV) were studied. An infectious molecular clone was generated from a high-titer, human-tropic PERV isolate, PERV-A 14/220 (B. A. Oldmixon, et al. J. Virol.
76:
3045-3048, 2002; T. A. Ericsson et al. Proc. Natl. Acad. Sci. USA
100:
6759-6764, 2003). To analyze this sequence and 15 available full-length PERV nucleotide sequences, we developed a sequence comparison program, LOHA
TM
to calculate local sequence homology between two sequences. This analysis determined that PERV-A 14/220 arose by homologous recombination of a PERV-C genome replacing an 850-bp region around the
pol
-
env
junction with that of a PERV-A sequence. This 850-bp PERV-A sequence encompasses the
env
receptor binding domain, thereby conferring a wide host range including human cells. In addition, we determined that multiple regions derived from PERV-C are responsible for the increased infectious titer of PERV-A 14/220. Thus, a single recombination event may be a fast and effective way to generate high-titer, potentially harmful PERV. Further, local homology and phylogenetic analyses between 16 full-length sequences revealed evidence for other recombination events in the past that give rise to other PERV genomes that possess the PERV-A, but not the PERV-B,
env
gene. These results indicate that PERV-A
env
is more prone to recombination with heterogeneous backbone genomes than PERV-B
env
. Such recombination events that generate more active PERV-A appear to occur in pigs rather frequently, which increases the potential risk of zoonotic PERV transmission. In this context, pigs lacking non-human-tropic PERV-C would be more suitable as donor animals for clinical xenotransplantation.
Experimental Infection of NOD/SCID Mice Reconstituted with Human CD34
+
Cells with Epstein-Barr Virus
Authors: Islas-Ohlmayer Miguel , Padgett-Thomas Angela , Domiati-Saad Rana , Melkus Michael W. , Cravens Petra D. , Martin Maria del P. , Netto George , Garcia J. Victor 
Published: November 2004

ABSTRACT

Epstein-Barr virus (EBV)-induced lymphoproliferative disease is an important complication in the context of immune deficiency. Impaired T-cell immunity allows the outgrowth of transformed cells with the subsequent production of predominantly B-cell lymphomas. Currently there is no in vivo model that can adequately recapitulate EBV infection and its association with B-cell lymphomas. NOD/SCID mice engrafted with human CD34
+
cells and reconstituted mainly with human B lymphocytes may serve as a useful xenograft model to study EBV infection and pathogenesis. We therefore infected reconstituted mice with EBV. High levels of viral DNA were detected in the peripheral blood of all infected mice. All infected mice lost weight and showed decreased activity levels. Infected mice presented large visible tumors in multiple organs, most prominently in the spleen. These tumors stained positive for human CD79a, CD20, CD30, and EBV-encoded RNAs and were light chain restricted. Their characterization is consistent with that of large cell immunoblastic lymphoma. In addition, tumor cells expressed EBNA1, LMP1, and LMP2a mRNAs, which is consistent with a type II latency program. EBV
+
lymphoblastoid cell lines expressing human CD45, CD19, CD21, CD23, CD5, and CD30 were readily established from the bone marrow and spleens of infected animals. Finally, we also demonstrate that infection with an enhanced green fluorescent protein (EGFP)-tagged virus can be monitored by the detection of infected EGFP
+
cells and EGFP
+
tumors. These data demonstrate that NOD/SCID mice that are reconstituted with human CD34
+
cells are susceptible to infection by EBV and accurately recapitulate important aspects of EBV pathogenesis.
Fitness Costs Limit Viral Escape from Cytotoxic T Lymphocytes at a Structurally Constrained Epitope
Authors: Peyerl Fred W. , Bazick Heidi S. , Newberg Michael H. , Barouch Dan H. , Sodroski Joseph , Letvin Norman L. 
Published: November 2004

ABSTRACTThe intense selection pressure exerted by virus-specific cytotoxic T lymphocytes (CTL) on replicating human immunodeficiency virus and simian immunodeficiency virus results in the accumulation of CTL epitope mutations. It has been assumed that fitness costs can limit the evolution of CTL epitope mutations. However, only a limited number of studies have carefully examined this possibility. To explore the fitness costs associated with viral escape from p11C, C-M-specific CTL, we constructed a panel of viruses encoding point mutations at each position of the entire p11C, C-M epitope. Amino acid substitutions at positions 3, 4, 5, 6, 7, and 9 of the epitope significantly impaired virus replication by altering virus production and Gag protein expression as well as by destabilizing mature cores. Amino acid substitutions at position 2 of the epitope were tolerated but required reversion or additional compensatory mutations to generate replication-competent viruses. Finally, while amino acid substitutions at positions 1 and 8 of the p11C, C-M epitope were functionally tolerated, these substitutions were recognized by p11C, C-M-specific CTL and therefore provided no selection advantage for the virus. Together, these data suggest that limited sequence variation is tolerated by the region of the capsid encoding the p11C, C-M epitope and therefore that only a very limited number of mutations can allow successful viral escape from the p11C, C-M-specific CTL response.
Inhibition of Parainfluenza Virus Type 3 and Newcastle Disease Virus Hemagglutinin-Neuraminidase Receptor Binding: Effect of Receptor Avidity and Steric Hindrance at the Inhibitor Binding Sites
Authors: Porotto Matteo , Murrell Matthew , Greengard Olga , Lawrence Michael C. , McKimm-Breschkin Jennifer L. , Moscona Anne 
Published: November 2004

ABSTRACT
Zanamivir (4-guanidino-Neu5Ac2en [4-GU-DANA]) inhibits not only the neuraminidase activity but also the receptor interaction of the human parainfluenza virus type 3 (HPIV3) hemagglutinin-neuraminidase (HN), blocking receptor binding and subsequent fusion promotion. All activities of the HPIV3 variant ZM1 HN (T193I/I567V) are less sensitive to 4-GU-DANA's effects. The T193I mutation in HN confers both increased receptor binding and increased neuraminidase activity, as well as reduced sensitivities of both activities to 4-GU-DANA inhibition, consistent with a single site on the HN molecule carrying out both catalysis and binding. We now provide evidence that the HPIV3 variant's resistance to receptor-binding inhibition by 4-GU-DANA is related to a reduced affinity of the HN receptor-binding site for this compound as well as to an increase in the avidity of HN for the receptor. Newcastle disease virus (NDV) HN and HPIV3 HN respond differently to inhibition in ways that suggest a fundamental distinction between them. NDV HN-receptor binding is less sensitive than HPIV3 HN-receptor binding to 4-GU-DANA, while its neuraminidase activity is highly sensitive. Both HPIV3 and NDV HNs are sensitive to receptor-binding inhibition by the smaller molecule DANA. However, for NDV HN, some receptor binding cannot be inhibited. These data are consistent with the presence in NDV HN of a second receptor-binding site that is devoid of enzyme activity and has a negligible, if any, affinity for 4-GU-DANA. Avidity for the receptor contributes to resistance by allowing the receptor to compete effectively with inhibitors for interaction with HN, while the further determinant of resistance is the reduced binding of the inhibitor molecule to the binding pocket on HN. Based upon our data and recent three-dimensional structural information on the HPIV3 and NDV HNs, we propose mechanisms for the observed sensitivity and resistance of HN to receptor-binding inhibition and discuss the implications of these mechanisms for the distribution of HN functions.
Genetic Screen for Monitoring Severe Acute Respiratory Syndrome Coronavirus 3C-Like Protease
Authors: Parera Mariona , Clotet Bonaventura , Martinez Miguel Angel 
Published: November 2004

ABSTRACT

A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome. Site-specific proteolysis plays a critical role in regulating a number of cellular and viral processes. Since the main protease of SCoV, also termed 3C-like protease, is an attractive target for drug therapy, we have developed a safe, simple, and rapid genetic screen assay to monitor the activity of the SCoV 3C-like protease. This genetic system is based on the bacteriophage lambda regulatory circuit, in which the viral repressor cI is specifically cleaved to initiate the lysogenic-to-lytic switch. A specific target for the SCoV 3C-like protease, P1/P2 (SAVLQ/SGFRK), was inserted into the lambda phage cI repressor. The target specificity of the SCoV P1/P2 repressor was evaluated by coexpression of this repressor with a chemically synthesized SCoV 3C-like protease gene construct. Upon infection of
Escherichia coli
cells containing the two plasmids encoding the cI. SCoV P1/P2-cro and the β-galactosidase-SCoV 3C-like protease constructs, lambda phage replicated up to 2,000-fold more efficiently than in cells that did not express the SCoV 3C-like protease. This simple and highly specific assay can be used to monitor the activity of the SCoV 3C-like protease, and it has the potential to be used for screening specific inhibitors.
Sports related maxillofacial injuries: the first maxillofacial trauma database in Switzerland
Authors: Exadaktylos A K , Eggensperger N M , Eggli S , Smolka K M , Zimmermann H , Iizuka T 
Published: November 2004

Background:With the increase in the amount of medical data handled by emergency units, advances in computerisation have become necessary. New computer technology should have a major influence on accident analysis and prevention and the quality of research in the future.Objectives:To investigate the occurrence of sports related maxillofacial injuries using a newly installed relational database. To establish the first sports trauma database in Switzerland.Methods:The Qualicare databank was used to prospectively review 57 248 case histories of patients treated in the Department of Emergency Medicine between January 2000 and December 2002. Pre-defined key words were used to collect data on sports related maxillofacial injuries.Results:A total of 750 patients with maxillofacial injuries were identified. Ninety (12%) were sports related maxillofacial fractures. Most (27%) were sustained during skiing and snowboarding, 22% during team sports such as soccer or ice hockey, and 21% were from cycling accidents. Sixty eight per cent of the cyclists, 50% of the ice hockey players and soccer players, and 48% of the skiers and snowboarders had isolated fractures of the midface. Fractures of the mandible were noted predominantly in contact sports.Conclusions:Computerisation of trauma and emergency units and the introduction of customised software can significantly reduce the workload of researchers and doctors. The effective use of new computer technology should have a considerable influence on research and the quality of future prospective and retrospective studies.
Three year follow up of a self certification system for the assessment of fitness to dive in Scotland
Authors: Glen S 
Published: November 2004

Background:The need for routine medical examinations of sport divers in the Scottish Sub-Aqua Club (Scot-SAC) was revised in March 2000, and a new system using a self administered screening questionnaire was developed to allow divers to be assessed when necessary by doctors with diving medicine experience.Objective:To assess the effect of the new medical system on medical referee workload, diver exclusion rates, and diving incident frequency.Methods:All divers were required to complete a questionnaire to screen for conditions that might affect fitness to dive. Divers answering “Yes” to any of the questions had their medical background assessed by a diving doctor, and, if necessary, received a clinical examination or investigation. The rate of diver exclusions based on the questionnaire response was recorded in conjunction with analysis of the incident reports.Results:The number of forms requiring review by diving doctors increased from 1.2% to 5.7% (p<0.0001, 95% confidence interval (CI) −0.06 to −0.03) in the year after the introduction of the new medical system and gradually increased in subsequent years to 7.7% (p<0.0001, 95% CI −0.08 to −0.05). The number of divers failing to be certified fit to dive increased slightly from 0.7% to 1.0% after one year (p  =  0.26, 95% CI −0.01 to 0.00) and subsequently to 2.0% (p  =  0.0003, 95% CI 0.02 to −0.01) after three years. Most divers were certified fit to dive on the basis of the questionnaire alone, and only 0.9% required objective investigation (such as exercise testing or echocardiography). Analysis of the incidents during three years of follow up confirmed that no incident occurred because of an undetected pre-existing medical condition. Two incidents involved divers with hypertension, but both had received medical examinations and investigation based on their responses to the questionnaire.Conclusion:The new self administered questionnaire system appears to be an effective screening tool for the detection of divers requiring detailed assessment by doctors with diving medicine experience.
Exercise following a sport induced concussion
Authors: Gall B , Parkhouse W S , Goodman D 
Published: November 2004

Objective:To determine if an athlete’s capacity to perform exercise is impaired following concussion and whether this would be reflected by an altered heart rate response.Methods:Of the 14 concussed athletes, nine missed playing time as a direct result of their concussion and five did not. The concussed athletes performed an exercise protocol on a cycle ergometer within 72 hours of being asymptomatic at rest and a second test at 5 days following the previous assessment. Matched controls (n = 14) were tested using the same time line. The exercise protocol consisted of a 2 minute warm up, 10 minute, low−moderate intensity, steady state exercise session, and a high intensity interval protocol. The interval protocol consisted of a 40 second high intensity bout, followed by a 40 second rest period. This protocol continued until the participant had reached volitional fatigue.Results:The number of exercise bouts completed was not significantly different from their matched controls. However, concussed athletes who missed playing time had a significantly higher heart rate during the steady state exercise session. During this same period, they also exhibited a greater rise in heart rate over time.Conclusion:These findings indicate that exercise capacity is unaffected in concussed athletes who are asymptomatic at rest. However, their heart rate response to submaximal exercise is increased.
TEMPORAL LOGICS FOR COMMUNICATING SEQUENTIAL AGENTS: I
Authors: LODAYA KAMAL , RAMANUJAM R. , THIAGARAJAN P.S. 
Published: November 2004

We introduce a class of distributed systems called Communicating Sequential Agents (CSAs). Sound and complete axiomatizations are provided for various subclasses using a family of indexed temporal logics. Some of the important features of these logics are: • Both the formulas and the structures for the logics reflect the fact that a system is composed out of a number of participating sequential agents. • Formulas of the logics are interpreted only at local states. • An agent makes a definite assertion about another agent only if it has received — directly or indirectly — some communication from that agent supporting that assertion.
A FAST NEURAL ALGORITHM FOR PRINCIPAL COMPONENT ANALYSIS AND SINGULAR VALUE DECOMPOSITION
Authors: Sirat J. Ariel 
Published: November 2004

We propose a fast neural algorithm to perform Principal Component Analysis (PCA) of a set of examples. It is obtained by simplification of current neural learning rules for PCA. First, we use a single binary neuron to extract a given component by a Hebb-type learning rule (Self-Organized Perceptron). This rule rapidly yields the first principal component. Moreover, as the neuron is binary, convergence is easily interpreted in terms of geometry and trajectory. Then successive components are obtained after projection of examples on the subspace which is supplementary to already learnt components. This avoids mixing the components as in, for example, the “Subspace Method” recently proposed by Oja.11 We have tested this approach on a gaussian distribution of examples: the quality of results is identical to that obtained with methods which diagonalize the correlation matrix computed from the set of examples. A variant of the algorithm is also proposed to perform the Singular Value Decomposition (SVD) which “diagonalizes” an asymmetrical matrix. Performances are as satisfactory as for PCA. Complexity and performances of a VLSI implementation are then estimated from the specifications of the neural VLSI developed in our laboratory. Comparison with hardware implementations of non-neural approaches (SVD) seems to favor neatly the neural approach: the expected speed increase is at least two orders of magnitude for a 100-dimensional SVD calculation.
DESIGN AUTOMATION FOR MULTICHIP MODULE — ISSUES AND STATUS
Authors: CHAN PHILIP C. 
Published: November 2004

In this paper we will review the current state of commercial electronic design automation (EDA) tools for the design of multichip modules. MCM can be classified in terms of its substrate technology. The choice of substrate technology has important implications for the selection of design automation tools. A PCB EDA system seems more appropriate for MCMs with stacked via substrate which closely resembles the through-hole printed circuit board (PCB). A chip layout system may be more appropriate for MCMs with low-cost thin-film silicon substrate which typically uses staircase vias. The cofired ceramic substrate MCM which evolved from the hybrid integrated circuit technology may use the specialized hybrid EDA software packages available for the designing of hybrid integrated circuits. Historically, printed circuit board and integrated circuit design automation software evolved separately. There exists a boundary between the printed circuit board and integrated circuit design automation tools in the physical design hierarchy. This boundary can be an important limitation for the repartitioning of the physical design hierarchy within the MCM. We shall discuss in detail the impact of MCM on various aspects of EDA. In the area of physical design, we must face the traditional placement and routing problem for any high speed design. Problems such as system clock skew and tight timing requirements must be considered. As one push clock frequency higher, one also must consider discontinuities due to vias and bends besides the classical transmission line effect due to long wires. Other traditional physical design problems such as ground and power plane generation, physical design verification and mask tooling must be revisited in the context of various MCM substrate technologies. The thermal aspects of MCM design are strongly influenced by the placement of chips on the MCM substrate. Thermal design is especially important for high density MCMs using the flip-chip mounting technology. Here, the heat must be dissipated through the back of the substrate via thermal pillars or bumps. We still need to deal with the traditional coupled transmission line problems. Due to the small cross section, high performance MCM substrate interconnects are resistive and the transmission lines they form are lossy. Noise is another main problem for MCM design. For high speed MCM with many CMOS buffers, the ground bouncing noise resulting from simultaneous switching of a large number of CMOS drivers must be controlled through proper substrate and package design. We will conclude the paper by comparing existing VLSI and PCB EDA tools for MCM design.