bluuebunny/crossref_metadata_2025_split huggingface dataset:
A modified MRP for a production system with the coexistence of MRP and kanbans
Authors: Ding Fong‐Yuen , Yuen Ming‐Nang 
Published: October 2002

AbstractThis paper deals with MRP treatments of the coexistence of MRP and kanban systems. In practical applications, MRP and kanban can both exist in a factory. When a production system contains parts managed by an MRP system and parts managed by a kanban system, MRP needs to have a special way of dealing with those parts managed by the kanban system in order to provide accurate gross demand data for the MRP system.A modified MRP for treating parts ordered through kanbans with the coexistence of MRP and kanbans is proposed. Along with two other existing methods (one by Karmarkar and another by a major tractor company), three methods are compared in a GPSS simulation study.Empirical results regarding inventory and shortages from the simulation study showed that both the proposed modified MRP and Karmarkar's methods of dealing with parts ordered by kanbans performed quite well.This research study suggests two effective lot‐sizing rules to be used in MRP part explosion for kanban‐controlled stages of a production system in which some stages are controlled by kanbans and other stages by MRP releases. The simulation study established empirical evidence for the effectiveness of these two lot sizing rules.
Analysis and design of focused demand chains
Authors: Childerhouse Paul , Aitken James , Towill Denis R. 
Published: October 2002

AbstractThe paper describes the evolution of focused demand chains over an extended period of time as a major UK lighting manufacturer has sought to remain an international player in a fast changing business environment. Analysis and design procedures make use of the concepts of Wickham Skinner and Marshall Fisher to answer the strategic questions “what facilities are required and how should they be laid out to enable the necessary focused demand chains?” and to answer the tactical question “which focused demand chain is appropriate for this product?” The case study then details how the company has been transformed from operating within a traditional supply chain to driving change via the engineering of four focused demand chains. The paper concludes with a comparison of operations enablers, customer choice, and business performance metrics covering the transition period culminating in the current focused demand chain scenario. By matching products to the appropriate value stream there is a consequential reduction in product development time of 75%; manufacturing costs reduction of up to 27%; and up to 95% reduction in delivery lead times.
Article: Contemporary issues in audiology: A hearing scientist's perspective
Authors: Parker David J 
Published: October 2002

AbstractAudiology has developed significantly over the last 30 years leading to better identification and assessment of hearing loss and better habilitation services for both children and adults with congenital or acquired deafness. Advancement in the profession and its services has been largely dependent on the technological development of key methodologies such as the auditory brainstem response and otoacoustic emissions. These methodologies have been used for the identification and assessment of the severity of hearing loss. As a result, these methodologies have underpinned the emergence of service development initiatives such as hearing screening and provision of hearing aids, particularly for newborn babies and young children. This review identifies, describes and evaluates the key methodologies and services involved and presents a hearing scientist's perspective on the developments to date. The aim is to provide state‐of‐the‐art information to those working with children and adults with communication disorders, particularly speech and language therapists.
Complex language functions and subcortical mechanisms: Evidence from Huntington's disease and patients with non‐thalamic subcortical lesions
Authors: Chenery Helen J. , Copland David A. , Murdoch Bruce E. 
Published: October 2002

AbstractThe neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non‐thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non‐thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n =13) were compared with those of an age‐ and education‐matched group of patients with chronic NTS lesions following stroke (n =13) and a non‐neurologically impaired control group (n =13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive‐linguistic battery employed selected subtests from The Test of Language Competence ‐ Expanded, The Test of Word Knowledge and The Word Test ‐ Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p<0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico‐semantic tasks (e.g. the Boston Naming Test and providing definitions), on both single‐word and sentence‐level generative tasks (e.g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non‐thalamic subcortex resulting from either focal neurological insult or a degenerative disease.
The Calcium-Binding Activity of a Vacuole-Associated, Dehydrin-Like Protein Is Regulated by Phosphorylation
Authors: Heyen Bruce J. , Alsheikh Muath K. , Smith Elizabeth A. , Torvik Carl F. , Seals Darren F. , Randall Stephen K. 
Published: October 2002

Abstract
A vacuole membrane-associated calcium-binding protein with an apparent mass of 45 kD was purified from celery (Apium graveolens). This protein, VCaB45, is enriched in highly vacuolate tissues and is located within the lumen of vacuoles. Antigenically related proteins are present in many dicotyledonous plants. VCaB45 contains significant amino acid identity with the dehydrin family signature motif, is antigenically related to dehydrins, and has a variety of biochemical properties similar to dehydrins. VCaB45 migrates anomalously in sodium dodecyl sulfate-polyacrylamide gel electrophoresis having an apparent molecular mass of 45 kD. The true mass as determined by matrix-assisted laser-desorption ionization time of flight was 16.45 kD. VCaB45 has two characteristic dissociation constants for calcium of 0.22 ± 0.142 mm and 0.64 ± 0.08 mm, and has an estimated 24.7 ± 11.7 calcium-binding sites per protein. The calcium-binding properties of VCaB45 are modulated by phosphorylation; the phosphorylated protein binds up to 100-fold more calcium than the dephosphorylated protein. VCaB45 is an “in vitro” substrate of casein kinase II (a ubiquitous eukaryotic kinase), the phosphorylation resulting in a partial activation of calcium-binding activity. The vacuole localization, calcium binding, and phosphorylation of VCaB45 suggest potential functions.
Down-regulation of DNA repair in human CD34+progenitor cells corresponds to increased drug sensitivity and apoptotic response
Authors: Buschfort-Papewalis Claudia , Moritz Thomas , Liedert Bernd , Thomale Jürgen 
Published: October 2002

Abstract
Although DNA repair processes have been shown to considerably modulate the cytotoxic effects of alkylating agents, little information is available on the role of these mechanisms in chemotherapy-induced myelosuppression. Therefore, we have analyzed in detail the DNA repair capacity of primary human hematopoietic cells from cord blood (CB) or bone marrow (BM) by 2 functional assays, the immunocytologic assay (ICA) and single-cell gel electrophoresis (comet assay). Besides substantial interindividual differences, we consistently observed significantly lower repair capacity of CD34+ cells in comparison to CD34−, CD19+, or CD33+ cells of the same donor. After exposure to the alkylating agent ethylnitrosourea (EtNU), the comet assay displayed on average twice as many DNA single-strand breaks (SSBs) in CD34+ cells and a tripled half-life of these lesions in comparison to corresponding CD34− cells. Similarly, reduced SSB repair activity in CD34+ cells was detected following melphalan or cisplatin application. When specific antibodies were used to monitor DNA reaction products of these drugs, adduct levels were significantly higher and lesions persisted longer in the CD34+ fraction. To assess the contribution of individual pathways to overall DNA repair, modulators blocking defined steps in repair processes were coapplied with alkylating drugs. Similar “modulation pattern” in corresponding CD34+ and CD34− cell fractions indicated a generalized reduction in DNA repair capacity of CD34+ cells, rather than deficiencies in a specific pathway. Because CD34+ cells also displayed higher frequencies of apoptosis in response to melphalan or cisplatin, these findings may help to explain the myelosuppression after exposure to alkylating agents.
Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia
Authors: Ancliff Phil J. , Gale Rosemary E. , Watts Michael J. , Liesner Ri , Hann Ian M. , Strobel Stephan , Linch David C. 
Published: October 2002

AbstractHeterozygous mutations in neutrophil elastase have been detected in many sporadic cases of congenital neutropenia. However, a convincing pathogenetic mechanism has not been established, and it is unclear whether the effects of the mutant enzyme occur within the cell of production or are paracrine in nature. The healthy father of a patient was demonstrated to be mosaic for his daughter's Cys42Arg elastase mutation. Using semiquantitative polymerase chain reaction, approximately half of his T cells were shown to carry the mutation in contrast to less than 10% of neutrophils. Individual hematopoietic colonies grown from peripheral blood were heterozygous for the mutation or were homozygous wild type. These results demonstrate that precursors containing the mutation are selectively lost during myelopoiesis or fail to develop into neutrophils. This is the first in vivo confirmation of the pathogenic nature of elastase mutations in humans. The normal neutrophil count in the father suggests that the mutant elastase does not have paracrine effects.
Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children
Authors: Kojima Seiji , Ohara Akira , Tsuchida Masahiro , Kudoh Toru , Hanada Ryoji , Okimoto Yuri , Kaneko Takashi , Takano Toshikuni , Ikuta Koichiro , Tsukimoto Ichiro 
Published: October 2002

Abstract
Long-term survivors of acquired aplastic anemia (AA) have an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST). It is uncertain whether the increased survival time simply discloses the natural history of AA as a premalignant disease or whether secondary disease is related to the therapy itself. Between November 1992 and September 1997, 113 AA children with normal cytogenetics at diagnosis were treated with IST using antithymocyte globulin, cyclosporin, and danazol with or without granulocyte colony-stimulating factor (G-CSF). We assessed risk factors for developing MDS/AML by Cox proportional hazards models. Twelve of 113 patients developed MDS between 9 and 81 months following the time of diagnosis, giving a cumulative incidence of 13.7 ± 3.9%. The following cytogenetic abnormalities were observed at the time of diagnosis of MDS: monosomy 7 (6 patients), monosomy7/trisomy21 (1 patient), trisomy 11 (1 patient), del (11) (9?:14) (1 patient), add (9q) (1 patient), add 7 (q 32) (1 patient), and trisomy 9 (1 patient). The number of days of G-CSF therapy and nonresponse to therapy at 6 months were statistically significant risk factors by multivariate analysis. The present study suggests a close relationship between long-term use of G-CSF and secondary MDS in nonresponders to IST.
Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation
Authors: Basu Sunanda , Hodgson George , Katz Melissa , Dunn Ashley R. 
Published: October 2002

AbstractIn steady-state hematopoiesis, G-CSF (granulocyte-colony stimulating factor) regulates the level of neutrophils in the bone marrow and blood. In this study, we have exploited the availability of G-CSF–deficient mice to evaluate the role of G-CSF in steady-state granulopoiesis and the release of granulocytes from marrow into circulation. The thymidine analogue bromodeoxyuridine (BrdU) was used to label dividing bone marrow cells, allowing us to follow the release of granulocytes into circulation. Interestingly, the labeling index and the amount of BrdU incorporated by blast cells in bone marrow was greater in G-CSF–deficient mice than in wild-type mice. In blood, 2 different populations of BrdU-positive granulocytes, BrdUbright and BrdUdim, could be detected. The kinetics of release of the BrdUbright granulocytes from bone marrow into blood was similar in wild-type and G-CSF–deficient mice; however, BrdUdim granulocytes peaked earlier in G-CSF–deficient mice. Our findings suggest that the mean transit time of granulocytes through the postmitotic pool is similar in G-CSF–deficient and control mice, although the transit time through the mitotic pool is reduced in G-CSF–deficient mice. Moreover, the reduced numbers of granulocytes that characterize G-CSF–deficient mice is primarily due to increased apoptosis in cells within the granulocytic lineage. Collectively, our data suggest that at steady state, G-CSF is critical for the survival of granulocytic cells; however, it is dispensable for trafficking of granulocytes from bone marrow into circulation.
Characterization of Kaposi sarcoma–associated herpesvirus/human herpesvirus–8 infection of human vascular endothelial cells: early events
Authors: Dezube Bruce J. , Zambela Maria , Sage David R. , Wang Jian-Feng , Fingeroth Joyce D. 
Published: October 2002

AbstractKaposi sarcoma–associated herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) is causally associated with Kaposi sarcoma (KS). The absence of a cell culture system that effectively reproduces the composite mechanisms governing initiation and maintenance of HHV-8 infection (lytic and latent) in KS endothelial cells, however, has left important questions unanswered. Here, we report a culture system in which the earliest events that accompany HHV-8 infection could be surveyed in primary endothelial cells. Binding of HHV-8 to microvascular dermal endothelial cells (MVDECs) was directly compared with other primary target cells implicated in HHV-8–associated diseases. Virus attachment, fusion, internalization and transport within MVDECs was monitored by electron microscopy. Studies of genome configuration revealed that rapid circularization of the viral DNA occurred on entry, though by 72 hours after infection linear DNAs accumulated and early as well as late lytic RNAs (T1.1, K8.1) could be detected. The latency transcripts (LT1/LT2) were first detected on day 8, demonstrating that both lytic and latent infection were initiated. Although most lytic transcripts accrued until passage, open-reading frame–74 RNAs fluctuated with a fixed periodicity, suggesting that early replication after infection of MVDECs was synchronous.
A monoclonal antibody to vascular endothelial–cadherin inhibits tumor angiogenesis without side effects on endothelial permeability
Authors: Corada Monica , Zanetta Lucia , Orsenigo Fabrizio , Breviario Ferruccio , Lampugnani Maria Grazia , Bernasconi Sergio , Liao Fang , Hicklin Daniel J. , Bohlen Peter , Dejana Elisabetta 
Published: October 2002

AbstractVascular endothelial cadherin (VE-cadherin) is an endothelial-specific, trans-membrane protein that promotes homophilic cell adhesion. Inhibition of VE-cadherin by the blocking monoclonal antibody (mAb) BV13 inhibited angiogenesis and tumor growth in vivo. However, this effect was accompanied by a marked increase in lung and heart permeability. In the present paper, we characterize a different VE-cadherin mAb (BV14) that is able to inhibit angiogenesis without affecting vascular permeability. In vitro studies show that BV14, in contrast to BV13, did not increase paracellular permeability of endothelial monolayers and did not disrupt VE-cadherin clusters at junctions. However, both antibodies could inhibit formation of vascularlike structures in collagen gels and increase migration of endothelial cells into wounded areas. In vivo, BV14 and BV13 were equally active in inhibiting angiogenesis in the mouse cornea and in reducing the growth of hemangioma and C6 glioma. In contrast to BV13, BV14 did not change vascular permeability in all the organs tested and at any dose used. BV14 and BV13 bind to VE-cadherin extracellular repeats EC4 and EC1, respectively. We propose that, in resting vessels, where junctions are stable and well-structured, antibody binding to EC1 but not EC4 disrupts their organization and increases permeability. In contrast, in growing vessels, where endothelial cells are migrating and junctions are weaker, antibody binding to EC4 may be sufficient to disrupt cell-to-cell adhesion and inhibit assembly of new vascular structures.
A humanized non–FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease
Authors: Carpenter Paul A. , Appelbaum Frederick R. , Corey Lawrence , Deeg H. Joachim , Doney Kris , Gooley Theodore , Krueger James , Martin Paul , Pavlovic Sandra , Sanders Jean , Slattery John , Levitt Daniel , Storb Rainer , Woolfrey Ann , Anasetti Claudio 
Published: October 2002

AbstractVisilizumab is a humanized anti-CD3 monoclonal antibody characterized by a mutated IgG2 isotype, lack of binding to Fcγ-receptors, and ability to induce apoptosis selectively in activated T cells. To test pharmacokinetics, safety, and immunosuppressive activity of visilizumab, 17 patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD) were enrolled in a phase 1 study. Six patients were given 7 doses of visilizumab (0.25 or 1.0 mg/m2) on days 1, 3, 5, 7, 9, 11, and 13. Because multiple doses of 1 mg/m2 caused delayed visilizumab accumulation and prolonged lymphopenia, the next 11 patients received a single dose of 3.0 mg/m2 on day 1. GVHD improved in all patients; 15 were evaluable through day 42. Multiple dosing resulted in 1 of 6 complete responses (CRs) and 5 partial responses (PRs), but all 6 patients died at a median of 87 days after starting visilizumab therapy. Single dosing resulted in 6 of 9 CRs, 3 PRs, and 7 of 11 patients surviving after 260 to 490 days (median, 359 days; P = .03). There were no allergic reactions and 3 grade 1 acute infusional toxicities. Plasma Epstein-Barr virus (EBV) DNA titers more than 1000 copies/mL and posttransplant lymphoproliferative disease (PTLD) developed in 2 of the first 7 patients. Based on rising EBV DNA titers, 5 of the next 10 patients were given the B cell–specific monoclonal antibody, rituximab. EBV DNA became undetectable and no overt PTLD developed. Visilizumab is well tolerated and has activity in advanced GVHD. A phase 2 study incorporating preemptive therapy for PTLD is warranted to determine the efficacy of visilizumab in GVHD.
Plasminogen activator inhibitor type 2: a regulator of monocyte proliferation and differentiation
Authors: Yu Hong , Maurer Fabienne , Medcalf Robert L. 
Published: October 2002

AbstractWe have explored the role of plasminogen activator inhibitor type 2 (PAI-2) in THP-1 monocyte–like cells. These cells possess a mutation in the PAI-2 gene and do not produce an active PAI-2 protein. Transfection of THP-1 cells with plasmids expressing active PAI-2 reduced the cells' inherent adhesive properties and decreased the rate of cell proliferation. THP-1 cells expressing active PAI-2 also displayed an altered phenotype in response to phorbol ester–induced differentiation that was concomitant with a reduction in CD14 expression. THP-1 cells transfected with a variant PAI-2 containing a mutation in the reactive center (PAI-2Ala380) displayed no noticeable change in any of these parameters, suggesting the involvement of a PAI-2–sensitive serine protease(s). The antiproliferative effect of PAI-2 was attenuated by treating the PAI-2–expressing THP-1 cells with recombinant urokinase (u-PA), suggesting that PAI-2 was disruptive of a u-PA/u-PA receptor signaling pathway initiated on the cell surface. Consistent with this, treatment of wild-type THP-1 cells with recombinant PAI-2 also caused a reduction in cellular proliferation. These results implicate endogenous PAI-2 as a modulator of monocyte adhesion, proliferation, and differentiation.
The DBY gene codes for an HLA-DQ5–restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease
Authors: Vogt Mario H. J. , van den Muijsenberg Joost W. , Goulmy Els , Spierings Eric , Kluck Petra , Kester Michel G. , van Soest Ronald A. , Drijfhout Jan W. , Willemze Roel , Falkenburg J. H. Frederik 
Published: October 2002

AbstractGraft rejection or graft-versus-host (GVH) disease after HLA-identical stem cell transplantation is the result of recognition of minor histocompatibility antigens (mHags) by immunocompetent T lymphocytes from recipient or donor origin, respectively. Cytolytic T lymphocyte (CTL) clones can be isolated during graft rejection and GVH disease to identify mHags and their corresponding genes. Thus far, all human mHags identified appeared to be HLA class I–restricted. Here, we report the characterization of the first human HLA class II–restricted sex-linked mHag involved in GVH disease. Previously, we isolated an HLA-DQ5–restricted CD4+ CTL clone from a male patient with chronic myeloid leukemia who developed acute GVH disease grade III-IV after transplantation of HLA genotypically identical female stem cells. Using a panel of female HLA-DQ5+ EBV cells that we stably transfected with Y chromosome–specific genes, we determined that the HLA class II male-specific mHag (H-Y) was encoded by the Y chromosome–specific gene DBY. The H-Y epitope was localized in the DBY protein using female HLA-DQ5+peripheral blood mononuclear cells loaded with DBY protein fragments. The minimal peptide sequence leading to maximal recognition by the specific HLA-DQ5–restricted CTL clone was characterized as the 12–amino acid sequence HIENFSDIDMGE. Although the epitope differed by 3 amino acids from its X-homolog DBX, only 2 polymorphisms were shown to be essential for recognition by the CTL clone.