bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Proteins from Human Monocytes Bind to Dengue 4 Virus Minus-Strand 3′ Untranslated Region RNA
Authors: Yocupicio-Monroy Rosa Martha E. , Medina Fernando , Reyes-del Valle Jorge , del Angel Rosa M. 
Published: February 2003

ABSTRACT
The synthesis of plus and minus RNA strands of several RNA viruses requires as a first step the interaction of some viral regulatory sequences with cellular and viral proteins. The dengue 4 virus genome, a single-stranded, positive-polarity RNA, is flanked by two untranslated regions (UTR) located in the 5′ and 3′ ends. The 3′UTR in the minus-strand RNA [3′UTR (−)] has been thought to function as a promoter for the synthesis of plus-strand RNA. To study the initial interaction between this 3′UTR and cellular and viral proteins, mobility shift assays were performed, and four ribonucleoprotein complexes (I through IV) were formed when uninfected and infected U937 cells (human monocyte cell line) interacted with the 3′UTR (−) of dengue 4 virus. Cross-linking assays with RNAs containing the complete 3′UTR (−) (nucleotides [nt] 101 to 1) or a partial sequence from nt 101 to 45 and nt 44 to 1 resulted in specific binding of some cellular proteins. Supermobility shift and immunoprecipitation assays demonstrated that the La protein forms part of these complexes. To determine the region in the 3′ UTR that interacted with the La protein, two deletion mutants were generated. The mutant (del-96), with a deletion of nt 96 to 101, was unable to interact with the La protein, suggesting that La interacted with the 5′ portion of the 3′UTR (−). Complex I, which was the main ribonucleoprotein complex formed with the 3′UTR (−) and which had the fastest electrophoretic migration, contained proteins such as calreticulin and protein disulfide isomerase, which constitute important components of the endoplasmic reticulum.
Temperature-Dependent Conformational Changes in Herpes Simplex Virus ICP4 That Affect Transcription Activation
Authors: Compel Peter , DeLuca Neal A. 
Published: February 2003

ABSTRACT
The C-terminal 500 amino acids of herpes simplex virus type 1 ICP4 are required for full activator function and viral growth and are known to participate in interactions consistent with the role of ICP4 as an activator of transcription. Oligonucleotide mutagenesis was used to target stretches of amino acids that are conserved with the ICP4 analogs of other alphaherpesviruses and were also predicted to be exposed on the surface of the molecule. Seven mutants were isolated that possessed one to three amino acid changes to the residue alanine in four regions between residues 1000 and 1200. The mutants generated were analyzed first in transfection assays and subsequently after introduction into the viral genome. A number of phenotypes representing different degrees of functional impairment were observed. In transient assays conducted at 37°C, mutant M2 was indistinguishable from wild-type ICP4. Mutants M6 and M7 were marginally impaired. M3, M4, and M5 were more significantly impaired but still able to activate transcription, and M1 was completely impaired. In the context of the viral genome, M1, M3, and M7 were found to be temperature sensitive for growth. All three overproduced immediate-early (IE) proteins at the nonpermissive temperature (NPT). M3 and M7 produced early but not late proteins, and M1 produced neither early nor late proteins, at the NPT. The ICP4 proteins synthesized by all of the mutants tested were able to bind to specific ICP4 binding sites in electrophoretic mobility shift experiments. However, the DNA-protein complexes formed with the ICP4 from M1, M3, or M7 produced at the NPT possessed altered mobility. These complexes were not supershifted by a monoclonal antibody that recognizes an epitope in the C terminus; however, they were supershifted by a monoclonal antibody that recognizes the N terminus. The results suggest that the mutant forms of ICP4, while able to bind to DNA, are conformationally altered at the NPT, thus impairing the ability of the protein to activate transcription to different extents. The complete lack of ICP4 function characteristic of the M1 protein, and the inability of all the mutants to attenuate IE gene expression, suggest that the mutations additionally affect functions of the N terminus to different extents.
The Power of High‐Throughput Experimentation in Homogeneous Catalysis Research for Fine Chemicals
Authors: Vries Johannes G. de , Vries André H.M. de 
Published: February 2003

AbstractThe use of high‐throughput experimentation (HTE) in homogeneous catalysis research for the production of fine be found within a very short time frame. At the same time, a reliable process can be achieved because extensive time‐to‐market constraints, HTE allows catalytic solutions to be found within a very short time frame. At the same time, a reliable process can be achieved because extensive imisation can be undertaken. We give examples of lead generation and optimisation, and of scope determination, based on our basic research program aimed at developing low‐cost aromatic substitution reactions (C−H activation, Heck and Suzuki reactions). We also give an example of HTE in mechanistic research, which stems from our work on asymmetric hydrogenation with low‐cost monodentate phosphoramidite ligands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Towards the definition and use of a core set of archetypal structures in system dynamics
Authors: Wolstenholme E. F. 
Published: February 2003

AbstractThere has been considerable research in the field of system dynamics over the last decade concerned with defining generic structures and templates by which to classify structures and behavioural insights in dynamic systems. These have appeared both in stock/flow and causal loop terms. This article focuses on generic causal loop structures more commonly known as system archetypes, a profusion of which have now been defined. The purpose of the article is to improve the usefulness of system archetypes both as free standing devices to aid model conceptualisation and as a means of disseminating insights arising from models. In order to achieve this three postulates are made: First, that system archetypes can be usefully condensed down to a more understandable core set of four totally generic archetypes, consisting of the four ways of ordering a pair of reinforcing and balancing feedback loops. These are described, named and current archetypes mapped onto them with specific examples. Second, that for every “problem” archetype there exists a closed loop “solution” archetype. It is suggested that some misunderstandings with current archetypes arise from the fact that they often combine problem and solution links in the same diagram. Third, that each archetype has important characteristics, which are vital to understanding the role of archetypes in assisting systemic thinking. The particular characteristic introduced and highlighted is the concept of organisational boundaries. The article concludes by discussing the importance of the reduced set of archetypes, and organisational boundaries in particular, in explaining some barriers to implementing systemic thinking, using a range of examples encountered by the author in recent consulting practice. Copyright © 2003 John Wiley & Sons, Ltd.
Hopelessness and risk behaviour among adolescents living in high‐poverty inner‐city neighbourhoods
Authors: Bolland John M. 
Published: February 2003

ABSTRACTEthnographic literature on inner‐city life argues that adolescents react to their uncertain futures by abandoning hope, leading them to engage in high levels of risk behaviour. However, few quantitative studies demonstrate this relationship. This study tests this relationship using a survey of 2468 inner‐city adolescents, asking them questions about hopelessness, violent and aggressive behaviour, substance use, sexual behaviour, and accidental injury. Nearly 50% of males and 25% of females had moderate or severe feelings of hopelessness. Moreover, hopelessness predicted of each of the risk behaviours considered. These results suggest that effective prevention and intervention programmes aimed at inner‐city adolescents should target hopelessness by promoting skills that allow them to overcome the limitations of hopelessness.
The relationship between total quality management practices and their effects on firm performance
Authors: Kaynak Hale 
Published: February 2003

AbstractRecent research on total quality management (TQM) has examined the relationships between the practices of quality management and various levels of organizational performance. These studies have produced mixed results, probably because of the nature of the research designs used such as measuring TQM or performance as a single construct. Based on a comprehensive literature review, this study identifies the relationships among TQM practices and examines the direct and indirect effects of these practices on various performance levels. A proposed research model and hypotheses are tested by using cross‐sectional mail survey data collected from firms operating in the US. The test of the structural model supports the proposed hypotheses. The implications of the findings for researchers and practitioners are discussed and further research directions are offered.
Genetic Network Analyzer: qualitative simulation of
genetic regulatory networks
Authors: de Jong Hidde , Geiselmann Johannes , Hernandez Céline , Page Michel 
Published: February 2003

Abstract
Motivation: The study of genetic regulatory networks has received a major impetus from the recent development of experimental techniques allowing the measurement of patterns of gene expression in a massively parallel way. This experimental progress calls for the development of appropriate computer tools for the modeling and simulation of gene regulation processes.
Results: We present Genetic Network Analyzer (GNA), a computer tool for the modeling and simulation of genetic regulatory networks. The tool is based on a qualitative simulation method that employs coarse-grained models of regulatory networks. The use of GNA is illustrated by a case study of the network of genes and interactions regulating the initiation of sporulation in Bacillus subtilis.
Availability: GNA and the model of the sporulation network are available at http://www-helix.inrialpes.fr/gna
Contact: Hidde.de-Jong@inrialpes.fr
* To whom correspondence should be addressed.
Redundancy based detection of sequence polymorphisms in expressed sequence tag data using autoSNP
Authors: Barker Gary , Batley Jacqueline , O’ Sullivan Helen , Edwards Keith J. , Edwards David 
Published: February 2003

Abstract
Summary: AutoSNP is a program to detect single nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms (indels) in expressed sequence tag (EST) data. The program uses d2cluster and cap3 to cluster and align EST sequences, and uses redundancy to differentiate between candidate SNPs and sequence errors. Candidate polymorphisms are identified as occurring in multiple reads within an alignment. For each candidate SNP, two measures of confidence are calculated, the redundancy of the polymorphism at a SNP locus and the co segregation of the candidate SNP with other SNPs in the alignment.
Availability: The program was written in PERL and is freely available to non-commercial users by request from the authors.
Contact: dave.edwards@nre.vic.gov.au
* To whom correspondence should be addressed.
IslandPath: aiding detection of genomic islands in prokaryotes
Authors: Hsiao William , Wan Ivan , Jones Steven J. , Brinkman Fiona S. L. 
Published: February 2003

Abstract
Summary: Genomic islands (clusters of genes of potential horizontal origin in a prokaryotic genome) are frequently associated with a particular adaptation of a microbe that is of medical, agricultural or environmental importance, such as antibiotic resistance, pathogen virulence, or metal resistance. While many sequence features associated with such islands have been adopted separately in applications for analysis of genomic islands, including pathogenicity islands, there is no single application that integrates multiple features for island detection. IslandPath is a network service which incorporates multiple DNA signals and genome annotation features into a graphical display of a bacterial or archaeal genome, to aid the detection of genomic islands.
Availability: This application is available at http://www.pathogenomics.sfu.ca/islandpath and the source code is freely available, under GNU public licence, from the authors.
Contact: brinkman@sfu.ca
Supplementary information: An online help file, which includes analyses of the utility of IslandPath, can be found at http://www.pathogenomics.sfu.ca/islandpath/current/islandhelp.html
* To whom correspondence should be addressed.
Transcription Factor YY1 Binds to the Murine Beta Interferon Promoter and Regulates Its Transcriptional Capacity with a Dual Activator/Repressor Role
Authors: Weill Laure , Shestakova Elena , Bonnefoy Eliette 
Published: February 2003

ABSTRACT
The induction of the beta interferon (IFN-β) gene constitutes one of the first responses of the cell to virus infection. Its regulation is achieved through an intricate combination of virus-induced binding of transcription factors and local chromatin remodeling. In this work, we demonstrate that transcription factor YY1, known to interact with histone deacetylases (HDAC) and histone acetyltransferases, has a dual activator/repressor role during the regulation of the IFN-β promoter activity. We show that YY1 specifically binds in vitro and in vivo to the murine IFN-β promoter at positions −90 and −122. Overexpression of YY1 strongly repressed the transcriptional capacity of a stably integrated IFN-β promoter fused to a chloramphenicol acetyltransferase reporter gene as well as the endogenous IFN activity of murine L929 cells via an HDAC activity. Stably integrated IFN-β promoters mutated at the −90 site were no longer repressed by YY1, could no longer be activated by trichostatin A, displayed a retarded postinduction turn off, and a reduced virus-induced activity. Introduction of a mutation at the −122 site did not affect YY1-induced repression, but promoters with this mutation displayed a reduced virus-induced activity. Stably integrated full-length promoters (from position −330 to +20) mutated at both YY1-binding sites displayed extremely reduced promoter activities. We conclude that YY1 has a dual activator/repressor role on IFN-β promoter activity depending on its binding site and time after infection.
Efficient Replication of Hepatitis C Virus Genotype 1a RNAs in Cell Culture
Authors: Blight Keril J. , McKeating Jane A. , Marcotrigiano Joseph , Rice Charles M. 
Published: February 2003

ABSTRACT
Hepatitis C virus (HCV) genotype 1 (subtypes 1a and 1b) is responsible for the majority of treatment-resistant liver disease worldwide. Thus far, efficient HCV RNA replication has been observed only for subgenomic and full-length RNAs derived from genotype 1b isolates. Here, we report the establishment of efficient RNA replication systems for genotype 1a strain H77. Replication of subgenomic and full-length H77 1a RNAs required the highly permissive Huh-7.5 hepatoma subline and adaptive amino acid substitutions in both NS3 and NS5A. Replication could be detected by RNA quantification, fluorescence-activated cell sorting, and metabolic labeling of HCV-specific proteins. Replication efficiencies were similar for subgenomic and full-length RNAs and were most efficient for HCV RNAs lacking heterologous RNA elements. Interestingly, both subtype 1a and 1b NS3 adaptive mutations are surface exposed and present on only one face of the NS3 structure. The cell culture-adapted subtype 1a replicons should be useful for basic replication studies and for antiviral development. These results are also encouraging for the development of adapted replicons for the remaining HCV genotypes.
Mumps Virus Decreases Testosterone Production and Gamma Interferon-Induced Protein 10 Secretion by Human Leydig Cells
Authors: Le Goffic Ronan , Mouchel Thomas , Ruffault Annick , Patard Jean-Jacques , Jégou Bernard , Samson Michel 
Published: February 2003

ABSTRACTMumps virus is responsible for sterility. Here, we show that the mumps virus infects Leydig cells in vitro and totally inhibits testosterone secretion and that ribavirin in mumps virus-infected Leydig cell cultures completely restores testosterone production. Moreover, we show that gamma interferon-induced protein 10 (IP-10) is highly expressed by mumps virus-infected Leydig cells and that ribavirin does not block IP-10 production.
Apoptotic neutrophils in the circulation of patients with glycogen storage disease type 1b (GSD1b)
Authors: Kuijpers Taco W. , Maianski Nikolai A. , Tool Anton T. J. , Smit G. Peter A. , Rake Jan Peter , Roos Dirk , Visser Gepke 
Published: February 2003

AbstractGlycogen storage disease type 1b (GSD1b) is a rare autosomal recessive disorder characterized by hypoglycemia, hepatomegaly, and growth retardation, and associated—for unknown reasons— with neutropenia and neutrophil dysfunction. In 5 GSD1b patients in whom nicotin-amide adenine dinucleotide phosphate–oxidase activity and chemotaxis were defective, we found that the majority of circulating granulocytes bound Annexin-V. The neutrophils showed signs of apoptosis with increased caspase activity, condensed nuclei, and perinuclear clustering of mitochondria to which the proapoptotic Bcl-2 member Bax had translocated already. Granulocyte colony-stimulating factor (G-CSF) addition to in vitro cultures did not rescue the GSD1b neutrophils from apoptosis as occurs with G-CSF–treated control neutrophils. Moreover, the 2 GSD1b patients on G-CSF treatment did not show significantly lower levels of apoptotic neutrophils in the bloodstream. Current understanding of neutrophil apoptosis and the accompanying functional demise suggests that GSD1b granulocytes are dysfunctional because they are apoptotic.
High plasma fibrinogen level is associated with poor clinical outcome in DIC patients
Authors: Wada Hideo , Mori Yoshitaka , Okabayashi Kazuhiro , Gabazza Esteban C , Kushiya Fumihiko , Watanabe Masato , Nishikawa Masakatsu , Shiku Hiroshi , Nobori Tsutomu 
Published: January 2003

AbstractWe measured the plasma level of fibrinogen in 560 patients with disseminated intravascular coagulation (DIC) and evaluated its relationship with outcome and with other hemostatic markers. Forty‐seven percent of patients had >200 mg/dL of plasma fibrinogen and 24% had <100 mg/dl of plasma fibrinogen, suggesting that plasma fibrinogen level is not a sensitive marker for DIC. In our analysis of outcome and plasma fibrinogen levels, the rate of death was high in leukemia/lymphoma patients with high fibrinogen concentration, but no significant difference in outcome was observed in relation to plasma fibrinogen concentration in non‐leukemia/lymphoma patients with DIC. Among patients with leukemia/lymphoma, the frequency of organ failure was markedly high in patients with high plasma levels of fibrinogen. Among patients without leukemia/lymphoma, the frequency of organ failure increased concomitantly with the increase in plasma fibrinogen levels. The international normalized ratio was significantly increased in leukemia/lymphoma patients with low fibrinogen. FDP levels were slightly increased in patients with low fibrinogen. Platelet count was significantly low in patients without leukemia/lymphoma with high fibrinogen. DIC score increased concomitantly with the reduction in plasma fibrinogen levels. Plasma levels of thrombomodulin and tissue factor were significantly high in patients with high fibrinogen levels. Plasma levels of antiplasmin and plasminogen were significantly decreased in patients with low fibrinogen. Plasma levels of plasmin plasmin–inhibitor complex and tissue type plasminogen activator/plasminogen activator inhibitor‐1 complex (PAI‐I) were significantly higher in patients with low fibrinogen than in those with high fibrinogen. Plasma levels of PAI‐I and IL‐6 were significantly higher in patients with high fibrinogen than in those with low fibrinogen. Patients with high fibrinogen levels showed less activation of secondary fibrinolysis, which might explain the occurrence of organ failure and poor outcome. Am. J. Hematol. 72:1–7, 2003. © 2002 Wiley‐Liss, Inc.
Use of oral mucosal neutrophil counts to detect the onset and resolution of profound neutropenia following high‐dose myelosuppressive chemotherapy
Authors: Akpek Gorgun , Knight Robert D. , Wright Daniel G. 
Published: January 2003

AbstractSevere neutropenia following cytotoxic, anti‐cancer chemotherapy is well‐known to be associated with an increased risk of infections that may be life‐threatening, particularly if not treated immediately. Consequently, serial measurements of neutrophil counts in peripheral blood are done routinely following the administration of high‐dose myelosuppressive chemotherapy in order to monitor the onset, severity, and duration of iatrogenic neutropenia. We have studied a non‐invasive method of quantifying neutrophils recoverable from the oral mucosa, a normal tissue site of neutrophil turnover, as an alternative approach for monitoring severe, chemotherapy‐induced neutropenia. This method is based on the quantification of fluorochrome‐stained neutrophils present in timed mouthwash specimens. Blood neutrophil (ANC) and mucosal neutrophil counts (MNC) were measured repeatedly in 23 patients who had been treated with dose‐intensive chemotherapy for a variety of indications. All 23 patients developed profound neutropenia (ANC < 100/mm3), and 19 developed neutropenic fever (>101°F) during the 2 weeks following treatment. Nadirs of neutropenia defined by MNC were significantly less prolonged than those defined by the ANC. Furthermore, the onset and resolution of neutropenic fever coincided more precisely with nadirs of neutropenia defined by the MNC than with those defined by the ANC. Our findings indicate that oral mucosal neutrophil counts predict the timing of clinical events associated with neutropenia (e.g., the onset and resolution of fever) with significantly greater accuracy than blood neutrophil counts. Am. J. Hematol. 72:13–19, 2003. © 2002 Wiley‐Liss, Inc.
Rapid diagnosis of invasive pulmonary aspergillosis by quantitative polymerase chain reaction using bronchial lavage fluid
Authors: Kawazu Masahito , Kanda Yoshinobu , Goyama Susumu , Takeshita Masataka , Nannya Yasuhito , Niino Miyuki , Komeno Yukiko , Nakamoto Tetsuya , Kurokawa Mineo , Tsujino Shiho , Ogawa Seishi , Aoki Katsunori , Chiba Shigeru , Motokura Toru , Ohishi Nobuya , Hirai Hisamaru 
Published: January 2003

AbstractPolymerase chain reaction (PCR) is a sensitive method for detection of Aspergillus DNA in bronchoalveolar lavage fluid, but it has not yet been able to distinguish infection from contamination. We have established a technique to quantify Aspergillus DNA using a real‐time PCR method to resolve this problem, and we report herein a successful application of real‐time PCR to diagnose invasive pulmonary aspergillosis by comparing the amount of Aspergillus DNA in bronchial lavage fluid from an affected area to that from an unaffected area. This novel tool will provide rapid, sensitive, and specific diagnosis of pulmonary aspergillosis. Am. J. Hematol. 72:27–30, 2003. © 2002 Wiley‐Liss, Inc.
Thromboembolic complications of cancer: Epidemiology, pathogenesis, diagnosis, and treatment
Authors: Sutherland Douglas E. , Weitz Ilene C. , Liebman Howard A. 
Published: January 2003

AbstractThe association between malignancy and clinical thrombosis has been recognized for nearly 140 years. The purpose of this review is to examine our current understanding of thrombosis as a complication of cancer and cancer therapy. The review includes a discussion of the epidemiology, pathophysiology, diagnosis and treatment. Am. J. Hematol. 72:43–52, 2003. © 2002 Wiley‐Liss, Inc.