bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Antiviral Cytotoxic T-Lymphocyte Epitope for Diverse Arenaviruses
Authors: Oldstone Michael B. A. , Lewicki Hanna , Homann Dirk , Nguyen Christophe , Julien Sylvianne , Gairin Jean Edouard 
Published: July 2002

ABSTRACT

Members of the
Arenaviridae
family have been isolated from mammalian hosts in disparate geographic locations, leading to their grouping as Old World types (i.e., lymphocytic choriomeningitis virus [LCMV], Lassa fever virus [LFV], Mopeia virus, and Mobala virus) and New World types (i.e., Junin, Machupo, Tacaribe, and Sabia viruses) (C. J. Peters, M. J. Buchmeier, P. E. Rollin, and T. G. Ksiazek, p. 1521–1551,
in
B. N. Fields, D. M. Knipe, and P. M. Howley [ed.], Fields virology, 3rd ed., 1996; P. J. Southern, p. 1505–1519,
in
B. N. Fields, D. M. Knipe, and P. M. Howley [ed.], Fields virology, 3rd ed., 1996). Several types in both groups—LFV, Junin, Machupo, and Sabia viruses—cause severe and often lethal human diseases. By sequence comparison, we noted that eight Old World and New World arenaviruses share several amino acids with the nucleoprotein (NP) that consists of amino acids (aa) 118 to 126 (NP 118–126) (RPQASGVYM) of LCMV that comprise the immunodominant cytotoxic T-lymphocyte (CTL) epitope for
H-2

d

mice (32). This L
d
-restricted epitope constituted >97% of the total bulk CTLs produced in the specific antiviral or clonal responses of
H-2

d

BALB mice. NP 118–126 of the Old World arenaviruses LFV, Mopeia virus, and LCMV and the New World arenavirus Sabia virus bound at high affinity to L
d
. The primary
H-2

d

CTL anti-LCMV response as well as that of a CTL clone responsive to LCMV NP 118–126 recognized target cells coated with NP 118–126 peptides derived from LCMV, LFV, and Mopeia virus but not Sabia virus, indicating that a common functional NP epitope exists among Old World arenaviruses. Use of site-specific amino acid exchanges in the NP CTL epitope among these arenaviruses identified amino acids involved in major histocompatibility complex binding and CTL recognition.
The Ribosome Binding Site of Hepatitis C Virus mRNA
Authors: Lytle J. Robin , Wu Lily , Robertson Hugh D. 
Published: July 2002

ABSTRACT
Hepatitis C virus (HCV) infects an estimated 170 million people worldwide, the majority of whom develop a chronic infection which can lead to severe liver disease, and for which no generally effective treatment yet exists. A promising target for treatment is the internal ribosome entry site (IRES) of HCV, a highly conserved domain within a highly variable RNA. Never before have the ribosome binding sites of any IRES domains, cellular or viral, been directly characterized. Here, we reveal that the HCV IRES sequences most closely associated with 80S ribosomes during protein synthesis initiation are a series of discontinuous domains together comprising by far the largest ribosome binding site yet discovered.
Temporal Regulation of Herpes Simplex Virus Type 2 VP22 Expression and Phosphorylation
Authors: Geiss Brian J. , Tavis John E. , Metzger Lisa M. , Leib David A. , Morrison Lynda A. 
Published: July 2002

ABSTRACT
The VP22 protein of herpes simplex virus type 2 (HSV-2) is a major component of the virion tegument. Previous work with HSV-1 indicated that VP22 is phosphorylated during infection, and phosphorylation may play a role in modulating VP22 localization in infected cells. It is not clear, however, when phosphorylation occurs in infected cells or how it is regulated. Less is known about the synthesis and phosphorylation of HSV-2 VP22. To study the complete biosynthetic history of HSV-2 VP22, we generated a monoclonal antibody to the carboxy terminus of VP22. Using immunoprecipitation and Western blot analyses, we show that HSV-2 VP22 can be found in three distinct isoforms in infected cells, two of which are phosphorylated. Like HSV-1 VP22, HSV-2 VP22 is synthesized ca. 4 h after infection, and the isoform later incorporated into virions is hypophosphorylated. In addition, we demonstrate for the first time (i) that newly synthesized VP22 is phosphorylated rapidly after synthesis, (ii) that this phosphorylation occurs in a virus-dependent manner, (iii) that the HSV-2 kinase UL13 is capable of inducing phosphorylation of VP22 in the absence of other viral proteins, (iv) that phosphorylated VP22 is very stable in infected cells, (v) that phosphorylated isoforms of VP22 are gradually dephosphorylated late in infection to produce the virion tegument form, and (vi) that this dephosphorylation occurs independently of viral DNA replication or virion assembly. These results indicate that HSV-2 VP22 is a stable protein that undergoes highly regulated, virus-dependent phosphorylation events in infected cells.
Protection against Tetanus by Needle-Free Inoculation of Adenovirus-Vectored Nasal and Epicutaneous Vaccines
Authors: Shi Zhongkai , Zeng Mingtao , Yang Guang , Siegel Felix , Cain Laura J. , van Kampen Kent R. , Elmets Craig A. , Tang De-Chu C. 
Published: July 2002

ABSTRACT

The effectiveness of vaccination programs would be enhanced greatly through the availability of vaccines that can be administered simply and, preferably, painlessly without the need for timed booster injections. Tetanus is a prime example of a disease that is readily preventable by vaccination but remains a major threat to public health due to the problems associated with administration of the present vaccine. Here we show that a protective immune response against live
Clostridium tetani
infection in mice can be elicited by an adenovirus vector encoding the tetanus toxin C fragment when administered as a nasal or epicutaneous vaccine. The results suggest that these vaccination modalities would be effective needle-free alternatives. This is the first demonstration that absorption of a small number of vectored vaccines into the skin following topical application of a patch can provide protection against live bacteria in a disease setting.
Human Immunodeficiency Virus Type 1 Nef Selectively Associates with a Catalytically Active Subpopulation of p21-Activated Kinase 2 (PAK2) Independently of PAK2 Binding to Nck or β-PIX
Authors: Renkema G. Herma , Manninen Aki , Saksela Kalle 
Published: July 2002

ABSTRACT
We have recently identified the Nef-associated serine-threonine kinase (NAK) as the p21-activated kinase 2 (PAK2). Here we have taken advantage of the possibility to manipulate the functional properties of NAK by transfecting PAK2 cDNA or its mutant derivatives in order to further characterize the Nef-NAK complex. To exclude the possibility that some Nef variants might interact with PAK1 instead of PAK2, we also examined the identity of NAK complexed with divergent human immunodeficiency virus type 1 HIV-1 Nef proteins. All tested Nef proteins, including SF2, NL4-3, BH10, and HAN-2, associated with PAK2 but not with PAK1. By exchanging different regions between these two PAK proteins, the selective ability of PAK2 to associate with Nef could be mapped to the carboxy-terminal part of its regulatory domain. Binding of PAK2 with the adapter protein Nck or β-PIX was found to be dispensable for the assembly of the Nef-PAK2 complex, whereas an intact Cdc42-Rac1 interactive binding motif was required. Most importantly, we found that NAK represented a distinct subpopulation of the total cellular PAK2 characterized by a high specific kinase activity. Thus, although only a small fraction of cellular PAK2 could be found in complex with Nef, NAK represented a major part of cellular PAK2 activity.
Analysis of p53 Inactivation in a Human T-Cell Leukemia Virus Type 1 Tax Transgenic Mouse Model
Authors: Portis Toni , Grossman William J. , Harding John C. , Hess Jay L. , Ratner Lee 
Published: July 2002

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL). The HTLV-1 Tax protein has been strongly linked to oncogenesis and is considered to be the transforming protein of this virus. A Tax transgenic mouse model was utilized to study the contribution of p53 inactivation to Tax-mediated tumorigenesis. These mice develop primary, peripheral tumors consisting of large granular lymphocytic (LGL) cells, which also infiltrate the lymph nodes, bone marrow, spleen, liver, and lungs. Primary Tax-induced tumors and tumor-derived cell lines exhibited functional inactivation of the p53 apoptotic pathway; such tumors and tumor cell lines were resistant to an apoptosis-inducing stimulus. In contrast,
p53
mutations in tumors were found to be associated with secondary organ infiltration. Three of four identified mutations inhibited transactivation and apoptosis induction activities in vitro. Furthermore, experiments which involved mating Tax transgenic mice with p53-deficient mice demonstrated minimal acceleration in initial tumor formation, but significantly accelerated disease progression and death in mice heterozygous for
p53
. These studies suggest that functional inactivation of p53 by HTLV-1 Tax, whether by mutation or another mechanism, is not critical for initial tumor formation, but contributes to late-stage tumor progression.
Exchange of the Basic Domain of Human Immunodeficiency Virus Type 1 Rev for a Polyarginine Stretch Expands the RNA Binding Specificity, and a Minimal Arginine Cluster Is Required for Optimal RRE RNA Binding Affinity, Nuclear Accumulation, and
trans
-Activation
Authors: Nam Yong-Suk , Petrovic Ana , Jeong Kyu-Shik , Venkatesan Sundararajan 
Published: July 2002

ABSTRACT
The Rev regulatory protein of human immunodeficiency virus (HIV) facilitates the nuclear export of unspliced and partially spliced HIV RNAs. Using a Rev:MS2 phage coat protein fusion that could be targeted to bind and activate the Rev-responsive element (RRE) RNA or heterologous MS2 phage operator RNA, we analyzed the role(s) of the arginine-rich RNA binding domain in RNA binding and transactivation. The arginine-rich domain could be functionally replaced by a stretch of nine arginines. However, polyarginine substitutions expanded the RNA binding specificity of the resultant mutant Rev protein. Polyarginine insertions in place of residues 24 to 60 that excised the RNA binding and oligomerization domains of Rev preserved the activation for MS2 RNA, but not for the RRE. A nine-arginine insertion outside of the natural context of the Rev nuclear localization signal domain was incompatible with activation of either RNA target. Insertions of fewer than eight arginines impaired RRE activation. Interrupted lysine clusters and disruption of the arginine stretch with lysine or neutral residues resulted in a similar phenotype. Some of these mutants with a null phenotype for RRE activated the heterologous MS2 RNA target. Under steady-state conditions, mutants that preserved the Rev response for RRE RNA localized to the nuclei; those with poor or no Rev response accumulated mostly in the cytoplasm. Many of the cytoplasmically resident derivatives became nuclear when leptomycin B (LMB) treatment inhibited nuclear export of nuclear export signal-containing proteins. Mutants that had a null activation potential for either RNA target were particularly resistant to LMB treatment. Abbreviated nuclear residence times and differences in RRE binding affinity may have compromised their activation potential for RRE. High-affinity binding to MS2 RNA through the intact coat protein was sufficient to overcome the short nuclear residence times and to facilitate MS2 activation by some derivatives.
AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Reevaluation of Neutralizing Antibody Levels Elicited by a Protective and a Nonprotective Vaccine after Removal of Antisubstrate Cell Antibodies
Authors: Giannecchini Simone , Del Mauro Daniela , Matteucci Donatella , Bendinelli Mauro 
Published: July 2002

ABSTRACT
In the feline immunodeficiency virus system, immunization with a fixed-infected-cell vaccine conferred protection against virulent homologous challenge but the immune effectors involved remained elusive. In particular, few or no neutralizing antibodies were detected in sera from vaccinated cats. Here we show that, when preadsorbed with selected feline cells, the same sera revealed clearly evident virus-neutralizing activity. Because high titers of neutralizing antibody in cell-adsorbed sera from 23 cats immunized with fixed-infected-cell or whole-inactivated-virus vaccines correlated with protection, it is likely that they were more important for protection than formerly realized. In vitro, the fixed-cell vaccine efficiently removed neutralizing antibody from immune sera while the whole-inactivated-virus vaccine was much less effective.
Long-Term Circulation of Vaccine-Derived Poliovirus That Causes Paralytic Disease
Authors: Cherkasova Elena A. , Korotkova Ekaterina A. , Yakovenko Maria L. , Ivanova Olga E. , Eremeeva Tatyana P. , Chumakov Konstantin M. , Agol Vadim I. 
Published: July 2002

ABSTRACT

Successful implementation of the global poliomyelitis eradication program raises the problem of vaccination against poliomyelitis in the posteradication era. One of the options under consideration envisions completely stopping worldwide the use of the Sabin vaccine. This strategy is based on the assumption that the natural circulation of attenuated strains and their derivatives is strictly limited. Here, we report the characterization of a highly evolved derivative of the Sabin vaccine strain isolated in a case of paralytic poliomyelitis from a 7-month-old immunocompetent baby in an apparently adequately immunized population. Analysis of the genome of this isolate showed that it is a double (type 1-type 2-type 1) vaccine-derived recombinant. The number of mutations accumulated in both the type 1-derived and type 2-derived portions of the recombinant genome suggests that both had diverged from their vaccine predecessors ∼2 years before the onset of the illness. This fact, along with other recent observations, points to the possibility of long-term circulation of Sabin vaccine strain derivatives associated with an increase in their neurovirulence. Comparison of genomic sequences of this and other evolved vaccine-derived isolates reveals some general features of natural poliovirus evolution. They include a very high preponderance and nonrandom distribution of synonymous substitutions, conservation of secondary structures of important
cis
-acting elements of the genome, and an apparently adaptive character of most of the amino acid mutations, with only a few of them occurring in the antigenic determinants. Another interesting feature is a frequent occurrence of tripartite intertypic recombinants with either type 1 or type 3 homotypic genomic ends.
Positive reform of tuna farm diving in South Australia in response to government intervention
Authors: Whyte P , Doolette D J , Gorman D F , Craig D S 
Published: July 2002

OBJECTIVESMuch of the tuna harvested in South Australia since 1990 has involved “farming” techniques requiring the use of divers. From 1993 to 1995, 17 divers from this industry were treated for decompression illness (DCI). In response, the State Government introduced corrective strategies. A decrease in the number of divers presenting for treatment was subsequently recorded. Consequently, the hypothesis was tested that the government intervention resulted in a decrease in the incidence of DCI in the industry and an improved clinical outcome of divers with DCI.METHODSThe incidence of treated DCI in tuna farm divers was estimated from the number of divers with DCI treated and the number of dives undertaken extrapolated from a survey of the industry in 1997–8. General health was measured in the tuna farm diving population by a valid and reliable self assessment questionnaire. The outcome of the divers treated for DCI was analysed with a modified clinical severity scoring system.RESULTSThe apparent incidence of treated DCI has decreased in tuna farm divers since the government intervention. The evidence supports a truly decreased incidence rather than underreporting. The general health of the tuna farm divers was skewed towards the asymptomatic end of the range, although health scores indicative of DCI were reported after 1.7% of the dives that did not result in recognised DCI. The clinical outcome of the divers treated since the intervention has improved, possibly because of earlier recognition of the disease and hence less time spent diving while having DCI.CONCLUSIONSThe government intervention in the tuna industry in South Australia has resulted in a reduced incidence of DCI in the industry.
Are adolescents attempting to buy cigarettes on the internet?
Authors: Unger Jennifer B , Rohrbach Louise Ann , Ribisl Kurt M 
Published: July 2002

OBJECTIVETo assess the prevalence of, and demographic and smoking behaviour correlates of, attempting to purchase cigarettes via the internet among adolescent current smokers.METHODSA representative sample of 17 181 10th and 12th grade California students completed a written questionnaire on tobacco related attitudes and behaviour during the 1999-2000 school year. Logistic regression analyses were used to determine the variables associated with attempting to purchase cigarettes on the internet.RESULTSAmong youth under 18 years of age who were current smokers (n = 1689), 2.2% (95% confidence interval 1.5% to 2.9%) reported attempting to purchase cigarettes on the internet. Attempted internet purchases were more likely among younger respondents, males, frequent smokers, and respondents reporting lower perceived availability of tobacco products from retail and social sources.CONCLUSIONSFew adolescent smokers in California surveyed during the 1999-2000 school year had attempted to obtain cigarettes from the internet. As internet access increases, future studies should examine whether internet cigarette vendors sell to minors and whether adolescents are purchasing cigarettes on the internet.
Optimizing equijoin queries in distributed databases where relations are hash partitioned
Authors: Shasha Dennis , Wang Tsong-Li 
Published: July 2002

Consider the class of distributed database systems consisting of a set of nodes connected by a high bandwidth network. Each node consists of a processor, a random access memory, and a slower but much larger memory such as a disk. There is no shared memory among the nodes. The data are horizontally partitioned often using a hash function. Such a description characterizes many parallel or distributed database systems that have recently been proposed, both commercial and academic. We study the optimization problem that arises when the query processor must repartition the relations and intermediate results participating in a multijoin query. Using estimates of the sizes of intermediate relations, we show (1) optimum solutions for closed chain queries; (2) the NP-completeness of the optimization problem for star, tree, and general graph queries; and (3) effective heuristics for these hard cases.
Our general approach and many of our results extend to other attribute partitioning schemes, for example, sort-partitioning on attributes, and to partitioned object databases.
Limits to low-latency communication on high-speed networks
Authors: Thekkath Chandramohan A. , Levy Henry M. 
Published: July 2002

The throughput of local area networks is rapidly increasing. For example, the bandwidth of new ATM networks and FDDI token rings is an order of magnitude greater than that of Ethernets. Other network technologies promise a bandwidth increase of yet another order of magnitude in several years. However, in distributed systems, lowered latency rather than increased throughput is often of primary concern. This paper examines the system-level effects of newer high-speed network technologies on low-latency, cross-machine communications.To evaluate a number of influences, both hardware and software, we designed and implemented a new remote procedure call system targeted at providing low latency. We then ported this system to several hardware platforms (DECstation and SPARCstation) with several different networks and controllers (ATM, FDDI, and Ethernet). Comparing these systems allows us to explore the performance impact of alternative designs in the communication system with respect to achieving low latency, e.g., the network, the network controller, the hose architecture and cache system, and the kernel and user-level runtime software.Our RPC system, which achieves substantially reduced call times (170 μseconds on an ATM network using DECstation 5000/200 hosts), allows us to isolate those components of next-generation networks and controllers that still stand in the way of low-latency communication. We demonstrate that new-generation processor technology and software design can reduce small-packet RPC times to near network-imposed limits, making network and controller design more crucial than ever to achieving truly low-latency communication.
Algorithm 719: Multiprecision translation and execution of FORTRAN programs
Authors: Bailey David H. 
Published: July 2002

This paper describes two Fortran utilities for multiprecision computation. The first is a package of Fortran subroutines that perform a variety of arithmetic operations and transcendental functions on floating point numbers of arbitrarily high precision. This package is in some cases over 200 times faster than that of certain other packages that have been developed for this purpose.
The second utility is a translator program, which facilitates the conversion of ordinary Fortran programs to use this package. By means of source directives (special comments) in the original Fortran program, the user declares the precision level and specifies which variables in each subprogram are to be treated as multiprecision. The translator program reads this source program and outputs a program with the appropriate multiprecision subroutine calls.
This translator supports multiprecision integer, real, and complex datatypes. The required array space for multiprecision data types is automatically allocated. In the evaluation of computational expressions, all of the usual conventions for operator precedence and mixed mode operations are upheld. Furthermore, most of the Fortran-77 intrinsics, such as ABS, MOD, NINT, COS, EXP are supported and produce true multiprecision values.
Search strategy and selection function for an inferential relational system
Authors: Minker Jack 
Published: July 2002

An inferential relational system is one in which data in the system consists of both explicit facts and general axioms (or “views”). The general axioms are used together with the explicit facts to derive the facts that are implicit (virtual relations) within the system. A top-down algorithm, as used in artificial intelligence work, is described to develop inferences within the system. The top-down approach starts with the query, a conjunction of relations, to be answered. Either a relational fact solves a given relation in a conjunct, or the relation is replaced by a conjunct of relations which must be solved to solve the given relation. The approach requires that one and only one relation in a conjunction be replaced (or expanded) by the given facts and general axioms. The decision to expand only a single relation is termed a selection function. It is shown for relational systems that such a restriction still guarantees that a solution to the problem will be found if one exists.
The algorithm provides for heuristic direction in the search process. Experimental results are presented which illustrate the techniques. A bookkeeping mechanism is described which permits one to know when subproblems are solved. It further facilitates the outputting of reasons for the deductively found answer in a coherent fashion.