bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epitope Determinants of a Chimpanzee Fab Antibody That Efficiently Cross-Neutralizes Dengue Type 1 and Type 2 Viruses Map to Inside and in Close Proximity to Fusion Loop of the Dengue Type 2 Virus Envelope Glycoprotein
Authors: Goncalvez Ana P. , Purcell Robert H. , Lai Ching-Juh 
Published: November 2004

ABSTRACT

The epitope determinants of chimpanzee Fab antibody 1A5, which have been shown to be broadly reactive to flaviviruses and efficient for cross-neutralization of dengue virus type 1 and type 2 (DENV-1 and DENV-2), were studied by analysis of DENV-2 antigenic variants. Sequence analysis showed that one antigenic variant contained a Gly-to-Val substitution at position 106 within the flavivirus-conserved fusion peptide loop of the envelope protein (E), and another variant contained a His-to-Gln substitution at position 317 in E. Substitution of Gly
106
Val in DENV-2 E reduced the binding affinity of Fab 1A5 by approximately 80-fold, whereas substitution of His
317
Gln had little or no effect on antibody binding compared to the parental virus. Treatment of DENV-2 with β-mercaptoethanol abolished binding of Fab 1A5, indicating that disulfide bridges were required for the structural integrity of the Fab 1A5 epitope. Binding of Fab 1A5 to DENV-2 was competed by an oligopeptide containing the fusion peptide sequence as shown by competition enzyme-linked immunosorbent assay. Both DENV-2 antigenic variants were shown to be attenuated, or at least similar to the parental virus, when evaluated for growth in cultured cells or for neurovirulence in mice. Fab 1A5 inhibited low pH-induced membrane fusion of mosquito C6/36 cells infected with DENV-1 or DENV-2, as detected by reduced syncytium formation. Both substitutions in DENV-2 E lowered the pH threshold for membrane fusion, as measured in a fusion-from-within assay. In the three-dimensional structure of E, Gly
106
in domain II and His
317
in domain III of the opposite E monomer were spatially close. From the locations of these amino acids, Fab 1A5 appears to recognize a novel epitope that has not been mapped before with a flavivirus monoclonal antibody.
Immunogenicity and Protection Efficacy of Replication-Deficient Influenza A Viruses with Altered NS1 Genes
Authors: Ferko Boris , Stasakova Jana , Romanova Julia , Kittel Christian , Sereinig Sabine , Katinger Hermann , Egorov Andrej 
Published: November 2004

ABSTRACT

We explored the immunogenic properties of influenza A viruses with altered NS1 genes (NS1 mutant viruses). NS1 mutant viruses expressing NS1 proteins with an impaired RNA-binding function or insertion of a longer foreign sequence did not replicate in murine lungs but still were capable of inducing a Th1-type immune response resulting in significant titers of virus-specific serum and mucosal immunoglobulin G2 (IgG2) and IgA, but with lower titers of IgG1. In contrast, replicating viruses elicited high titers of serum and mucosal IgG1 but less serum IgA. Replication-deficient NS1 mutant viruses induced a rapid local release of proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-6. Moreover, these viruses also elicited markedly higher levels of IFN-α/β in serum than the wild-type virus. Comparable numbers of virus-specific primary CD8
+
T cells were determined in all of the groups of immunized mice. The most rapid onset of the recall CD8
+
-T-cell response upon the wild-type virus challenge was detected in mice primed with NS1 mutant viruses eliciting high levels of cytokines. It is noteworthy that there was one NS1 mutant virus encoding NS1 protein with a deletion of 40 amino acids predominantly in the RNA-binding domain that induced the highest levels of IFN-α/β, IL-6 and IL-1β after infection. Mice that were immunized with this virus were completely protected from the challenge infection. These findings indicate that a targeted modification of the RNA-binding domain of the NS1 protein is a valuable technique to generate replication-deficient, but immunogenic influenza virus vaccines.
Lentiviral Vectors Interfering with Virus-Induced CD4 Down-Modulation Potently Block Human Immunodeficiency Virus Type 1 Replication in Primary Lymphocytes
Authors: Pham Hang M. , Argañaraz Enrique R. , Groschel Bettina , Trono Didier , Lama Juan 
Published: November 2004

ABSTRACTCD4 down-modulation is essential for the production of human immunodeficiency virus (HIV) infectious particles. Disease progression correlates with enhanced viral induced CD4 down-modulation, and a subset of long-term nonprogressors carry viruses defective in this function. Despite multiple pieces of evidence highlighting the importance of this function in viral pathogenesis in vivo, to date, HIV-induced CD4 down-modulation has not been used as a target for intervention. We describe here HIV-based vectors that deliver truncated CD4 molecules resistant to down-modulation by the viral products Nef and Vpu. Infection of cells previously transduced with these vectors proceeded normally, and viral particles were released in normal amounts. However, the infectivity of the released virions was reduced 1,000-fold. Lentiviral vectors expressing truncated CD4 molecules were efficient at blocking HIV-1 infectivity and replication in several cell lines and in CD4-positive primary lymphocytes. The findings presented here provide proof-of-principle that approaches targeting the virus-induced CD4 down-modulation may constitute the basis for novel anti-HIV therapies.
Requirement of Heat Shock Protein 90 for Human Hepatitis B Virus Reverse Transcriptase Function
Authors: Hu Jianming , Flores Dafna , Toft David , Wang Xingtai , Nguyen David 
Published: November 2004

ABSTRACT
The initiation of reverse transcription and nucleocapsid assembly in hepatitis B virus (HBV) depends on the specific recognition of an RNA signal (the packaging signal, ε) on the pregenomic RNA (pgRNA) by the viral reverse transcriptase (RT). RT-ε interaction in the duck hepatitis B virus (DHBV) was recently shown to require the molecular chaperone complex, the heat shock protein 90 (Hsp90). However, the requirement for RT-ε interaction in the human HBV has remained unknown due to the inability to obtain a purified RT protein active in specific ε binding. We now report that Hsp90 is also required for HBV RT-ε interaction. Inhibition of Hsp90 led to diminished HBV pgRNA packaging into nucleocapsids in cells, which depends on RT-ε interaction. Furthermore, using truncated HBV RT proteins purified from bacteria and five purified Hsp90 chaperone factors, we have developed an in vitro RT-ε binding assay. Our results demonstrate that Hsp90, in a dynamic process that was dependent on ATP hydrolysis, facilitated RT-ε interaction in HBV, as in DHBV. Specific ε binding required sequences from both the amino-terminal terminal protein and the carboxy-terminal RT domain. Only the cognate HBV ε, but not the DHBV ε, could bind the HBV RT proteins. Furthermore, the internal bulge, but not the apical loop, of ε was required for RT binding. The establishment of a defined in vitro reconstitution system has now paved the way for future biochemical and structural studies to elucidate the mechanisms of RT-ε interaction and chaperone activation.
JNK Regulates the Release of Proapoptotic Mitochondrial Factors in Reovirus-Infected Cells
Authors: Clarke Penny , Meintzer Suzanne M. , Wang Yibing , Moffitt Lisa A. , Richardson-Burns Sarah M. , Johnson Gary L. , Tyler Kenneth L. 
Published: November 2004

ABSTRACT
Reovirus-induced apoptosis is associated with activation of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) and the JNK-associated transcription factor c-Jun. Here we show that reovirus-induced apoptosis and activation of caspase 3 are inhibited in cells deficient in MEK kinase 1, an upstream activator of JNK in reovirus-infected cells. Inhibition of JNK activity following reovirus infection delays the release of proapoptotic mitochondrial factors and the subsequent onset of apoptosis. In contrast, reovirus-induced apoptosis is not blocked by infection with adenovirus expressing dominant-negative c-Jun, and c-Jun activation does not correlate with apoptosis in reovirus-infected cells. This is the first report demonstrating that JNK is associated with regulation of mitochondrial pathways of apoptosis following viral infection.
Novel Replication-Incompetent Vector Derived from Adenovirus Type 11 (Ad11) for Vaccination and Gene Therapy: Low Seroprevalence and Non-Cross-Reactivity with Ad5
Authors: Holterman Lennart , Vogels Ronald , van der Vlugt Remko , Sieuwerts Martijn , Grimbergen Jos , Kaspers Jorn , Geelen Eric , van der Helm Esmeralda , Lemckert Angelique , Gillissen Gert , Verhaagh Sandra , Custers Jerome , Zuijdgeest David , Berkhout Ben , Bakker Margreet , Quax Paul , Goudsmit Jaap , Havenga Menzo 
Published: November 2004

ABSTRACT

A novel plasmid-based adenovirus vector system that enables manufacturing of replication-incompetent (ΔE1) adenovirus type 11 (Ad11)-based vectors is described. Ad11 vectors are produced on PER.C6/55K cells yielding high-titer vector batches after purification. Ad11 seroprevalence proves to be significantly lower than that of Ad5, and neutralizing antibody titers against Ad11 are low. Ad11 seroprevalence among human immunodeficiency virus-positive (HIV
+
) individuals is as low as that among HIV
−
individuals, independent of the level of immune suppression. The low level of coinciding seroprevalence between Ad11 and Ad35 in addition to a lack of correlation between high neutralizing antibody titers towards either adenovirus strongly suggest that the limited humoral cross-reactive immunity between these two highly related B viruses appears not to preclude the use of both vectors in the same individual. Ad11 transduces primary cells including smooth muscle cells, synoviocytes, and dendritic cells and cardiovascular tissues with higher efficiency than Ad5. Ad11 and Ad35 appear to have a similar tropism as judged by green fluorescent protein expression levels determined by using a panel of cancer cell lines. In addition, Ad5 preimmunization did not significantly affect Ad11-mediated transduction in C57BL/6 mice. We therefore conclude that the Ad11-based vector represents a novel and useful candidate gene transfer vehicle for vaccination and gene therapy.
Mutation of All Runx (AML1/Core) Sites in the Enhancer of T-Lymphomagenic SL3-3 Murine Leukemia Virus Unmasks a Significant Potential for Myeloid Leukemia Induction and Favors Enhancer Evolution toward Induction of Other Disease Patterns
Authors: Sørensen Karina Dalsgaard , Quintanilla-Martinez Leticia , Kunder Sandra , Schmidt Jörg , Pedersen Finn Skou 
Published: November 2004

ABSTRACTSL3-3 murine leukemia virus is a potent inducer of T-lymphomas in mice. Using inbred NMRI mice, it was previously reported that a mutant of SL3-3 with all enhancer Runx (AML1/core) sites disrupted by 3-bp mutations (SL3-3dm) induces predominantly non-T-cell tumors with severely extended latency (S. Ethelberg, J. Lovmand, J. Schmidt, A. Luz, and F. S. Pedersen, J. Virol.71:7273-7280, 1997). By use of three-color flow cytometry and molecular and histopathological analyses, we have now performed a detailed phenotypic characterization of SL3-3- and SL3-3dm-induced tumors in this mouse strain. All wild-type induced tumors had clonal T-cell receptor β rearrangements, and the vast majority were CD3+CD4+CD8−T-lymphomas. Such a consistent phenotypic pattern is unusual for murine leukemia virus-induced T-lymphomas. The mutant virus induced malignancies of four distinct hematopoietic lineages: myeloid, T lymphoid, B lymphoid, and erythroid. The most common disease was myeloid leukemia with maturation. Thus, mutation of all Runx motifs in the enhancer of SL3-3 severely impedes viral T-lymphomagenicity and thereby discloses a considerable and formerly unappreciated potential of this virus for myeloid leukemia induction. Proviral enhancers with complex structural alterations (deletions, insertions, and/or duplications) were found in most SL3-3dm-induced T-lymphoid tumors and immature myeloid leukemias but not in any cases of myeloid leukemia with maturation, mature B-lymphoma, or erythroleukemia. Altogether, our results indicate that the SL3-3dm enhancer in itself promotes induction of myeloid leukemia with maturation but that structural changes may arise in vivo and redirect viral disease specificity to induction of T-lymphoid or immature myeloid leukemias, which typically develop with moderately shorter latencies.
Detection and Analysis of Six Lizard Adenoviruses by Consensus Primer PCR Provides Further Evidence of a Reptilian Origin for the Atadenoviruses
Authors: Wellehan James F. X. , Johnson April J. , Harrach Balázs , Benkö Mária , Pessier Allan P. , Johnson Calvin M. , Garner Michael M. , Childress April , Jacobson Elliott R. 
Published: November 2004

ABSTRACT

A consensus nested-PCR method was designed for investigation of the DNA polymerase gene of adenoviruses. Gene fragments were amplified and sequenced from six novel adenoviruses from seven lizard species, including four species from which adenoviruses had not previously been reported. Host species included Gila monster, leopard gecko, fat-tail gecko, blue-tongued skink, Tokay gecko, bearded dragon, and mountain chameleon. This is the first sequence information from lizard adenoviruses. Phylogenetic analysis indicated that these viruses belong to the genus
Atadenovirus
, supporting the reptilian origin of atadenoviruses. This PCR method may be useful for obtaining templates for initial sequencing of novel adenoviruses.
Oncogenicity of Virulent Marek's Disease Virus Cloned as Bacterial Artificial Chromosomes
Authors: Petherbridge Lawrence , Brown Andrew C. , Baigent Susan J. , Howes Ken , Sacco Melanie A. , Osterrieder Nikolaus , Nair Venugopal K. 
Published: November 2004

ABSTRACT

Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that induces T-cell lymphomas in poultry. We report the construction of bacterial artificial chromosome (BAC) clones of the highly oncogenic RB-1B strain by inserting mini-F vector sequences into the U
S
2 locus. MDV reconstituted from two BAC clones induced rapid-onset lymphomas similar to those induced by the wild-type virus. Virus reconstituted from another BAC clone that showed a 7.7-kbp deletion in the internal and terminal unique long repeat regions was nononcogenic, suggesting that the deleted region may be associated with oncogenicity. The generation of the oncogenic BAC clones of MDV is a significant step in unraveling the oncogenic determinants of this virus.
A TYPE-FREE THEORY OF HALF-MONOTONE INDUCTIVE DEFINITIONS
Authors: KAMEYAMA YUKIYOSHI 
Published: November 2004

This paper studies an extension of inductive definitions in the context of a type-free theory. It is a kind of simultaneous inductive definition of two predicates where the defining formulas are monotone with respect to the first predicate, but not monotone with respect to the second predicate. We call this inductive definition half-monotone in analogy of Allen’s term half-positive. We can regard this definition as a variant of monotone inductive definitions by introducing a refined order between tuples of predicates. We give a general theory for half-monotone inductive definitions in a type-free first-order logic. We then give a realizability interpretation to our theory, and prove its soundness by extending Tatsuta’s technique. The mechanism of half-monotone inductive definitions is shown to be useful in interpreting many theories, including the Logical Theory of Constructions, and Martin-Löf’s Type Theory. We can also formalize the provability relation “a term p is a proof of a proposition P” naturally. As an application of this formalization, several techniques of program/proof-improvement can be formalized in our theory, and we can make use of this fact to develop programs in the paradigm of Constructive Programming. A characteristic point of our approach is that we can extract an optimization program since our theory enjoys the program extraction theorem.
EFFECT OF AN INTRAPERITONEAL INJECTION OF Ca-DTPA AND Zn-DTPA ON ESSENTIAL TRACE METAL CONCENTRATIONS IN RAT PLASMA
Authors: SATO I. , MATSUSAKA N. , KOBAYASHI H. , SUZUKI T. , SERA K. , FUTATSUGAWA S. , NISHIMURA Y. 
Published: November 2004

Ca-DTPA and Zn-DTPA were injected intraperitoneally into rats with a dose of 30 or 300 µmol/kg. The blood was collected from the tail vein just before the injection, 3, 6 and 24 hours after the injection. and centrifuged 10 separate the plasma. These plasma samples were analyzed by PIXE at Nishina Memorial Cyclotron Center. Sodium, potassium, calcium, iron, copper and zinc were detected in the plasma. Ca-DTPA significantly lowered the concentration of zinc, while no significant changes were observed in the other metals. Zn-DTPA did not lower any metal concentrations, but a significant increase of plasma zinc was observed. In conclusion, Ca-DTPA was confirmed to induce hypozincemia, which may be the cause of fetal injuries such as abortion, fetal death and malformation. Zn-DTPA was suggested not to induce any deficiencies of essential metals.
Elemental Concentrations of Atmospheric Aerosols: Seasonal and Daily Changes
Authors: Kasahara M. , Gotoh N. 
Published: November 2004

The micro-analytical technique has made remarkable progress during the last two to three decades. A Particle Induced X-ray Emission(PIXE) is one of the most powerful analytical method. The analysis of atmospheric aerosol is one of the most preferable fields of the PIXE analysis. Applying the PIXE analysis, we have investigated the characteristics of atmospheric aerosols under the various environmental and meteorological conditions. The atmospheric aerosols were continuously sampled every 12 hours for one year from October 1992 to October 1993. The concentrations of gravimetric mass and 15 elements were determined by a microbalance method and the PXIE analysis.respectively. The seasonal change of mass concentration of atmospheric aerosols has commonly two peaks in spring and early winter. The peak in spring is mainly caused by the Kosa dust. The most dominant element was Si and S the coarse and fine particles,respectively. Daily change of elemental concentrations differed according to the origin of each element and the scavenging effect of atmospheric aerosols by rain drops was clearly observed in the time variation of aerosol concentration.
THE NEW LOW ENERGY ION BEAM ANALYSIS FACILITY AT MAPUTO UNIVERSITY
Authors: UTUI R.J. , HOMMAN N.P.O. , MALMQVIST K.G. 
Published: November 2004

A new Ion Beam Analysis (IBA) facility which was recently installed in the Department of Physics of the Eduardo Mondlane University of Maputo, Mozambique, is described. The set up is based on a low energy (500 keV) Van de Graaff proton accelerator and is intended to be used in particle induced X-ray emission (PIXE), Rutherford Backscattering (RBS) and nuclear reaction analysis (NRA). Preliminary experiments on beam diagnostics were performed successfully and the followed procedure is described.
A VLSI PARALLEL ARCHITECTURE FOR FUZZY EXPERT SYSTEMS
Authors: CATANIA V. , ASCIA G. 
Published: November 2004

In this paper we present a VLSI fuzzy processor whose main features are a scalable parallel architecture, and the computation of fuzzy inferences based on the α-level set theory, both of which are important in the field of intensive fuzzy computing, as in fuzzy expert systems. A specific analysis is made in the paper, of techniques for the representation of fuzzy sets, in relation to the amount of area occupied and the forms they can assume. From this analysis a solution is extracted and then used for the processor presented in the paper. The architecture of the processor is chosen after the assessment of possible alternatives by analyzing an appropriate probabilistic model. The processor comprises a set of units which work parallelly and asynschronously to process the various rules. The structure is easy to scale up, as an increase in the number of processing units does not produce bottlenecks in performance. The performance obtainable is about 310 KFLIPS, with a clock frequency of 60 Mhz, 8 input variables, either crisp or fuzzy, and an 8-bit resolution.
POST-EDITING THROUGH APPROXIMATION AND GLOBAL CORRECTION
Authors: TAGHVA KAZEM , BORSACK JULIE , BULLARD BRYAN , CONDIT ALLEN 
Published: November 2004

This paper describes a new automatic spelling correction program to deal with OCR generated errors. The method used here is based on three principles: 1. Approximate string matching between the misspellings and the terms occuring in the database as opposed to the entire dictionary 2. Local information obtained from the individual documents 3. The use of a confusion matrix, which contains information inherently specific to the nature of errors caused by the particular OCR device This system is then utilized to process approximately 10,000 pages of OCR generated documents. Among the misspellings discovered by this algorithm, about 87% were corrected.
ASSESSMENT OF BLEEDING PREDISPOSITIONS IN TONSILLECTOMY/ADENOIDECTOMY PATIENTS USING NON-METRIC CLUSTERING
Authors: GORDON HEATHER , PIZZI NICOLINO J. , GERRARD JON M. , SOMORJAI RAY 
Published: November 2004

A questionnaire, designed to assess bleeding predispositions in tonsillectomy and/or adenoidectomy patients, was administered to 236 otherwise healthy children. For comparative purposes, 114 patients with bleeding disorders were also studied. An unsupervised non-metric clustering technique was used in an attempt to classify bleeders against non-bleeders based solely on the responses to the questionnaire. Non-metric techniques are essential for the classification process because of the large number of missing attribute values in the patient data set. As a benchmark, a supervised inductive machine learning strategy was also used to classify the patients. Performance results are compared and contrasted between the techniques across different subsets of the patient data. These techniques are also evaluated as a methodology for determining the relative significance of attributes vis-à-vis the reduction of the dimensionality of a large medical data set. In this investigation, the classification rate achieved using the non-metric technique (73%) was only marginally poorer than the rate using the supervised technique (76%). Moreover, these results were obtained with an accompanying 80% reduction in the number of attributes used to perform the analysis.
LOW VOLTAGE POWER ELECTRONICS
Authors: COBOS J. A. , GARCÍA O. , SEBASTIÁN J. , UCEDA J. 
Published: November 2004

This paper summarizes some of the current solutions to fulfil the requirements of the new low voltage power systems. On one hand, microelectronics evolution demands lower supply voltage. On the other hand, the portability of the new communication systems demands lighter and smaller power electronics. The improvement of the performance of low power and low output voltage converters is carried out in this paper. Topics like power density, efficiency, thermal management, battery life, hard and soft switching, magnetics integration, synchronous rectification and power factor correction affect each other in these kinds of converters. Although all the relations among the previous terms are difficult to assess, this paper reviews some aspects of the current situation.