bluuebunny/crossref_metadata_2025_split huggingface dataset:
cis
-Acting Elements Required for Efficient Packaging of Brome Mosaic Virus RNA3 in Barley Protoplasts
Authors: Asmira Damayanti Tri , Tsukaguchi Satoshi , Mise Kazuyuki , Okuno Tetsuro 
Published: August 2003

ABSTRACT
Brome mosaic virus (BMV) is a positive-sense RNA plant virus, the tripartite genomic RNAs of which are separately packaged into virions. RNA3 is copackaged with subgenomic RNA4. In barley protoplasts coinoculated with RNA1 and RNA2, an RNA3 mutant with a 69-nucleotide (nt) deletion in the 3′-proximal region of the 3a open reading frame (ORF) was very poorly packaged compared with other RNA3 mutants and wild-type RNA3, despite their comparable accumulation in the absence of coat protein. Computer analysis of RNA secondary structure predicted two stem-loop (SL) structures (i.e., SL-I and SL-II) in the 69-nt region. Disruption of SL-II, but not of SL-I, significantly reduced RNA3 packaging. A chimeric BMV RNA3 (B3Cmp), with the BMV 3a ORF replacing that of cucumber mosaic virus (CMV), was packaged negligibly, whereas RNA4 was packaged efficiently. Replacement of the 3′-proximal region of the CMV 3a ORF in B3Cmp with the 3′-proximal region of the BMV 3a ORF significantly improved packaging efficiency, and the disruption of SL-II in the substituted BMV 3a ORF region greatly reduced packaging efficiency. These results suggest that the 3′-proximal region of the BMV 3a ORF, especially SL-II predicted between nt 904 and 933, plays an important role in the packaging of BMV RNA3 in vivo. Furthermore, the efficient packaging of RNA4 without RNA3 in B3Cmp-infected cells implies the presence of an element in the 3a ORF of BMV RNA3 that regulates the copackaging of RNA3 and RNA4.
Nedd4 Regulates Egress of Ebola Virus-Like Particles from Host Cells
Authors: Yasuda Jiro , Nakao Mitsuyoshi , Kawaoka Yoshihiro , Shida Hisatoshi 
Published: August 2003

ABSTRACT
Ebola virus budding is mediated by two proline-rich motifs, PPxY and PTAP, within the viral matrix protein VP40. We have previously shown that a Nedd4-like protein BUL1, but not Nedd4, positively regulates budding of type D retrovirus Mason-Pfizer monkey virus (J. Yasuda, E. Hunter, M. Nakao, and H. Shida, EMBO Rep. 3:636-640, 2002). Here, we report that the cellular E3 ubiquitin ligase Nedd4 regulates budding of VP40-induced virus-like particles (VLPs) through interaction with the PPxY motif. Mutation of the active site cysteine (C894A), resulting in abrogation of ubiquitin ligase activity, impaired the function of Nedd4 on budding. In addition, the WW domains of Nedd4 are essential for binding to the viral PPxY motif, and a small fragment of Nedd4 containing only WW domains significantly inhibited Ebola VLP budding in a dominant-negative manner. Our findings suggest that the viruses containing PPxY as an L-domain motif specifically use E3 in the process of virus budding. We also examined the effects of overexpression of Tsg101 and its mutant. As expected, Tsg101 enhanced VP40-induced VLP release, and TsgΔC, which lacks its C-terminal half, inhibited VLP release. These results indicate that Nedd4, together with Tsg101, plays an important role in Ebola virus budding.
Assorted Mutations in the Envelope Gene of Simian Immunodeficiency Virus Lead to Loss of Neutralization Resistance against Antibodies Representing a Broad Spectrum of Specificities
Authors: Johnson Welkin E. , Sanford Hannah , Schwall Linda , Burton Dennis R. , Parren Paul W. H. I. , Robinson James E. , Desrosiers Ronald C. 
Published: August 2003

ABSTRACT

Simian immunodeficiency virus (SIV) of macaques isolate SIVmac239 is highly resistant to neutralization by polyclonal antisera or monoclonal antibodies, a property that it shares with most primary isolates of human immunodeficiency virus type 1 (HIV-1). This resistance is important for the ability of the virus to persist at high levels in vivo. To explore the physical features of the viral envelope complex that contribute to the neutralization-resistant phenotype, we examined a panel of SIVmac239 derivatives for sensitivity to neutralization by a large collection of monoclonal antibodies (MAbs). These MAbs recognize both linear and conformational epitopes throughout the viral envelope proteins. The variant viruses included three derivatives of SIVmac239 with substitutions in specific N-linked glycosylation sites of gp120 and a fourth variant that lacked the100 amino acids that encompass the V1 and V2 loops. Also included in this study was SIVmac316, a variant of SIVmac239 with distributed mutations in
env
that confer significantly increased replicative capacity in tissue macrophages. These viruses were chosen to represent a broad range of neutralization sensitivities based on susceptibility to pooled, SIV-positive plasma. All three of these very different kinds of mutations (amino acid substitutions, elimination of N-glycan attachment sites, and a 100-amino-acid deletion spanning variable loops V1 and V2) dramatically increased sensitivity to neutralization by MAbs from multiple competition groups. Thus, the mutations did not simply expose localized epitopes but rather conferred global increases in neutralization sensitivity. The removal of specific N-glycan attachment sites from V1 and V2 led to increased sensitivity to neutralization by antibodies recognizing epitopes from both within and outside of the V1-V2 sequence. Surprisingly, while most of the mutations that gave rise to increased sensitivity were located in the N-terminal half of gp120 (surface subunit [SU]), the greatest increases in sensitivity were to MAbs recognizing the C-terminal half of gp120 or the ectodomain of gp41 (transmembrane subunit [TM]). This reagent set and information should now be useful for defining the physical, structural, thermodynamic, and kinetic factors that influence relative sensitivity to antibody-mediated neutralization.
Finite Element Analysis of Tire Curing Process
Authors: Tong Jian , Yan Xiangqiao 
Published: August 2003

Curing is one of the most important steps in the tire manufacturing process. During this process, a green tire is formed to the desired shape and the compound is converted to a strong, elastic material to meet tire performance needs. The process of curing is usually accomplished under pressure and an elevated temperature provided by the mold. The curing process is energy consuming and has a strong effect on material properties. To attain an optimal state of cure for different compounds of various dimensions at minimal capital and energy costs requires proper evaluation of the state of cure in a tire. Various numerical models have been proposed to determine the state of cure of rubber compounds in molds. Their applications are limited to simple geometry and boundary conditions. For a tire, which has complex shape and variable boundary conditions and is built from layers of rubber compounds and fiber/rubber composites, the finite element method appears to be an ideal candidate because of its versatility. In this paper, a simulator for the tire curing processes was developed based on the finite element method of an axisymmetric heat transfer problem for composite materials. The anisotropy of heat transfer properties of composite materials, the dependence of properties of rubber compounds on the temperature and/or the extent of cure, the time-varying boundary conditions which include the cooldown of the tire out of the press and the rigorous cure kinetic models are taken into account. The numerical simulation results of a truck tire curing process show that the simulator successfully describes the variation trends in temperature and in state of cure with the tire curing process. It also serves as the core module of an optimization algorithm, which is being developed for the tire curing and rubber formulation designs.
An Initial Study of Direct Relationships between Life-Cycle Modularity and Life-Cycle Cost
Authors: Zhang Y. , Gershenson J. K. 
Published: August 2003

This work shows the relationship between product life-cycle modularity and product life-cycle costs. Previous statements tying increased modularity to improved costs, specifically product retirement costs, motivated this work.The benefits of modularity with respect to product functionality, product development, production, the supply chain, and other life-cycle elements have been expounded by many works in several fields. Increased modularity has been widely considered to lead to decreased costs. Many have stated that, including modular design tradeoffs early in the design process will decrease life-cycle costs. Some even propose the hypothesis that modular architecture will lead to decreased life-cycle costs even if the modules are not made with other life-cycle characteristics specifically in mind. However, this desirable relationship - decreased costs driven by the increased modularity - has never been shown. No research has been done to prove if there exists a relationship between modularity and cost. Many products and research projects have been based on this unproven assumption.This work begins the exploration into whether a relationship exists between life-cycle product modularity and life-cycle cost for a wide range of consumer products and a wide range of life-cycle issues. The purpose of this paper is to expand initial results in this vain to the whole life-cycle for a more comprehensive look. The results of our work differ significantly from conventional thought and are therefore interesting to both the research and application communities. It is our hope that this paper will motivate others to take a second look at the science behind product modularity and its application.
Update on Epidemiology and Therapeutics for Non-Hodgkin’s Lymphoma
Authors: Vose Julie M. , Chiu Brian C.-H. , Cheson Bruce D. , Dancey Janet , Wright John 
Published: August 2003

Abstract
This chapter presents updated information on the trends and patterns of non-Hodgkin’s lymphoma (NHL) diagnoses as well as new information on chemotherapeutic and immunotherapeutic options for NHL treatment.
In Section I, Dr. Brian Chiu summarizes the current knowledge regarding the etiologic factors and patterns of NHL as well as suggests future epidemiologic studies based on these preliminary results.
In Section II, Dr. Bruce Cheson and colleagues outline new chemotherapeutic and small molecule antineoplastic agents with unique mechanisms of action such as protease inhibitors, farnesyl transferase or histone deacetylase inhibitors, and antisense oligonucleotides.
In Section III, Dr. Julie Vose reviews the anti-lymphoma effects of monoclonal antibodies, radioimmunoconjugates, idiotype vaccines, and immunologic enhancing adjuvants with respect to mechanisms of action, clinical trials, and their potential for patient therapy.
Hypercoagulability: Too Many Tests, Too Much Conflicting Data
Authors: Bauer Kenneth A. , Rosendaal Frits R. , Heit John A. 
Published: August 2003

Abstract
It is now possible to identify hereditary and acquired risk factors in a substantial percentage of patients presenting with a venous thrombotic event. The clinician is faced with an ever-growing number of laboratory tests that can be ordered in such patients, and there is considerable uncertainty as to how this information should be utilized in patient management. Some have argued that widespread testing of thrombosis patients for prothrombotic abnormalities such as the factor V Leiden and prothrombin G20210A mutations has been prematurely adopted into clinical practice as there are few data that their identification leads to improved clinical outcomes.
Dr. Rosendaal provides an overview of the epidemiology of venous thrombosis with an emphasis on hereditary and acquired risk factors. The presentation will include information obtained from properly designed case-control studies as well as family studies.
While some have suggested treatment strategies for managing patients with hereditary thrombophilia with prior thrombotic events or for managing patients undergoing procedures associated with increased thrombotic risk, clinical decision making is complicated by the need to assess the risk of recurrence and the likely benefit of prolonged anticoagulation versus the associated bleeding risk. Drs. Bauer, Heit, and Rosendaal discuss their approaches to patient management. Case presentations are used to illustrate the impact of laboratory test results on decisions.
Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis
Authors: Ljungman Per , Brand Ronald , Einsele Hermann , Frassoni Francesco , Niederwieser Dietger , Cordonnier Catherine 
Published: August 2003

AbstractCytomegalovirus (CMV) has been a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). The importance of the recipient's serologic status is paramount. However, the importance of the donor's serologic status in CMV-seropositive recipients is controversial. We analyzed the influence of the donor's CMV status in a large cohort of patients. A total of 7018 patients seropositive for CMV reported to the European Group for Blood and Marrow Transplantation (EBMT) were included; 5910 patients had undergone HLA-identical sibling SCT and 1108 patients had undergone unrelated donor SCT. Univariate and multivariate proportional hazards models were constructed for survival, event-free survival, transplant-related mortality, and relapse incidence. Patients receiving grafts from CMV-seropositive HLA-identical sibling donors had the same survival as patients grafted from seronegative donors (hazard ratio [HR], 1.04; P = .37; 95% confidence interval [CI], 0.95-1.14). However, unrelated donor stem cell (SC) transplant recipients receiving grafts from CMV-seropositive donors had an improved 5-year survival (35% versus 27%; HR = 0.8; P = .006), an improved event-free survival (30% versus 22%; HR = 0.8; P = .01), and a reduced transplant-related mortality (49% versus 62%; HR = 0.7; P &lt; .001). There was no influence on the relapse incidence. The effects of donor CMV status remained in multivariate analyses. The effect of donor status was different among different disease categories. In patients with chronic myelogenous leukemia (CML), T-cell depletion abrogated the beneficial effect of donor status, suggesting that the effect is mediated through transfer of donor immunity. Our data suggest that donor CMV status influences outcome of unrelated SCT. For a CMV-seropositive patient, a seropositive donor might be preferable. (Blood. 2003;102:4255-4260)
Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)–deficient mice
Authors: Massberg Steffen , Grüner Sabine , Konrad Ildiko , Garcia Arguinzonis Maisa I. , Eigenthaler Martin , Hemler Kathrin , Kersting Julia , Schulz Christian , Müller Iris , Besta Felicitas , Nieswandt Bernhard , Heinzmann Ulrich , Walter Ulrich , Gawaz Meinrad 
Published: August 2003

AbstractPlatelet adhesion and activation at the vascular wall are the initial steps leading to arterial thrombosis and vascular occlusion. Prostacyclin and nitric oxide inhibit platelet adhesion, acting via cyclic adenosine monophosphate (cAMP)– and cyclic guanosine monophosphate (cGMP)–dependent protein kinases. A major downstream target for both cAMP- and cGMP-dependent protein kinases is the vasodilator-stimulated phosphoprotein (VASP). To test the significance of VASP for the regulation of platelet adhesion in vivo, we studied platelet–vessel wall interactions using VASP-deficient (VASP–/–) mice. Under physiologic conditions, platelet adhesion to endothelial cells was significantly enhanced in VASP null mutants when compared with wild-type mice (P &lt; .05). Platelet recruitment in VASP null mice involved P-selectin and the fibrinogen receptor glycoprotein IIb-IIIa (GPIIb-IIIa). Under pathophysiologic conditions, the loss of VASP increased platelet adhesion to the postischemic intestinal microvasculature, to the atherosclerotic endothelium of ApoE-deficient mice, and to the subendothelial matrix following endothelial denudation (P &lt; .05 vs wild type). Importantly, platelet adhesion in VASP null mutants was unresponsive to nitric oxide. These data show for the first time in vivo that VASP is involved in down-regulation of platelet adhesion to the vascular wall under both physiologic and pathophysiologic conditions.
ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells
Authors: Tamura Tomohiko , Kong Hee Jeong , Tunyaplin Chainarong , Tsujimura Hideki , Calame Kathryn , Ozato Keiko 
Published: August 2003

AbstractInterferon consensus sequence binding protein/interferon regulatory factor 8 (ICSBP/IRF-8) is a transcription factor that controls myeloid cell development. ICSBP-/- mice develop a chronic myelogenous leukemia (CML)-like syndrome. Several observations on patients and mouse models have implicated ICSBP in the pathogenesis of CML. In this paper, we investigated whether ICSBP modulates the growth-promoting activity of Bcr/Abl, the causal oncoprotein for CML. When transformed with p210 Bcr/Abl, ICSBP-/- myeloid progenitor cells lost growth factor dependence and grew in the absence of granulocyte-macrophage colony-stimulating factor. When ICSBP was ectopically expressed, Bcr/Abl-transformed cells underwent complete growth arrest and differentiated into mature, functional macrophages without inhibiting the kinase activity of Bcr/Abl. Providing a mechanistic basis for the growth arrest, ICSBP markedly repressed c-Myc messenger RNA (mRNA)-expression, a downstream target of Bcr/Abl. A further analysis with the ICSBP/estrogen receptor chimera showed that ICSBP repression of c-Myc is indirect and is mediated by another gene(s). We identified Blimp-1 and METS/PE1, potent c-Myc repressors, as direct targets of ICSBP activated in these cells. Consistent with this, ectopic Blimp-1 repressed c-Myc expression and inhibited cell growth. These results indicate that ICSBP inhibits growth of Bcr/Abl-transformed myeloid progenitor cells by activating several genes that interfere with the c-Myc pathway. (Blood. 2003;102:4547-4554)
Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation
Authors: Heimpel Hermann , Anselstetter Volker , Chrobak Ladislav , Denecke Jonas , Einsiedler Beate , Gallmeier Kerstin , Griesshammer Antje , Marquardt Thorsten , Janka-Schaub Gritta , Kron Martina , Kohne Elisabeth 
Published: August 2003

AbstractCongenital dyserythropoietic anemia type II (CDA II) is the most frequent type of congenital dyserythropoietic anemia. More than 200 cases have been described, but with the exception of a report by the International CDA II Registry, these reports include only small numbers of cases and no data on the lifetime evolution of the disease. Since 1967, we were able to follow 48 cases of CDA II from 43 families for up to 35 years. All patients exhibit chronic anemia of variable severity requiring regular red cell transfusions only in a minority of children; 60% developed gallstones before the age of 30 years, and 16 patients had cholecystectomy between 8 and 34 years of age. Iron overload was a frequent complication. In 16 cases, iron depletion started between 7 and 36 years. Three patients died from secondary hemochromatosis. Splenectomy, performed in 22 cases, led to moderate increases in hemoglobin values and eliminated the need for transfusions but did not prevent further iron loading. The current recommendation is to consider splenectomy if the anemia compromises patients' performance, and to manage iron overload according to the guidelines derived from patients with thalassemia. (Blood. 2003;102:4576-4581)
Chimerism and cure: hematologic and pathologic correction of murine sickle cell disease
Authors: Kean Leslie S. , Manci Elizabeth A. , Perry Jennifer , Balkan Can , Coley Shana , Holtzclaw David , Adams Andrew B. , Larsen Christian P. , Hsu Lewis L. , Archer David R. 
Published: August 2003

AbstractBone marrow transplantation (BMT) is the only curative therapy for sickle cell disease (SCD). However, the morbidity and mortality related to pretransplantation myeloablative chemotherapy often outweighs the morbidity of SCD itself, thus severely limiting the number of patients eligible for transplantation. Although nonmyeloablative transplantation is expected to reduce the risk of BMT, it will likely result in mixed-chimerism rather than complete replacement with donor stem cells. Clinical application of nonmyeloablative transplantation thus requires knowledge of the effect of mixed chimerism on SCD pathophysiology. We have, therefore, created a panel of transplanted SCD mice that received transplants displaying an array of red blood cell (RBC) and white blood cell (WBC) chimerism. A significant enrichment of RBC over WBC chimerism occurred in these mice, because of the dramatic survival advantage of donor over sickle RBCs in the peripheral blood. Increasing levels of RBC chimerism provided progressive correction of hematologic and pathologic abnormalities. However, sickle bone marrow and splenic hematopoiesis was not corrected until peripheral blood sickle RBCs were fully replaced with donor RBCs. These results have important and unexpected implications for nonmyeloablative BMT for SCD. As the critical hematopoietic organs were not corrected without full RBC replacement, 100% peripheral blood RBC chimerism becomes the most important benchmark for cure after nonmyeloablative BMT. (Blood. 2003;102:4582-4593)
Differential effects of treatment with a small-molecule VLA-4 antagonist before and after onset of relapsing EAE
Authors: Theien Bradley E. , Vanderlugt Carol L. , Nickerson-Nutter Cheryl , Cornebise Mark , Scott Daniel M. , Perper Stuart J. , Whalley Eric T. , Miller Stephen D. 
Published: August 2003

AbstractInteraction of very late antigen-4 (VLA-4) with its ligand vascular cell adhesion molecule-1 (VCAM-1) is required for central nervous system (CNS) migration of encephalitogenic T cells in relapsing experimental autoimmune encephalomyelitis (R-EAE). Anti-VLA-4 monoclonal antibody (mAb) treatment prior to EAE onset inhibits disease induction; however, treatment initiated after the appearance of clinical symptoms increases relapse rates, augments Th1 responses, and enhances epitope spreading perhaps due to the activation of costimulatory signals. To negate the potential costimulatory activity of intact anti-VLA-4, we examined the ability of BIO 5192, a small-molecule VLA-4 antagonist, to regulate active proteolipid protein 139-151 (PLP139-151)-induced R-EAE. BIO 5192 administered one week after peptide priming (ie, before clinical disease onset) delayed the clinical disease onset but led to severe disease exacerbation upon treatment removal. BIO 5192 treatment initiated during disease remission moderately enhanced clinical disease while mice were on treatment and also resulted in posttreatment exacerbation. Interestingly, BIO 5192 treatment begun at the peak of acute disease accelerated entrance into disease remission and inhibited relapses, but treatment removal again exacerbated disease. Enhanced disease was caused by the release of encephalitogenic cells from the periphery and the rapid accumulation of T cells in the CNS. Collectively, these results further demonstrate the complexity of VLA-4/VCAM interactions, particularly in a relapsing-remitting autoimmune disease. (Blood. 2003;102:4464-4471)