bluuebunny/crossref_metadata_2025 huggingface dataset:
Compounds based on ultra‐high molecular weight PVC resins for use in automotive applications
Authors: Brookman Robert S. , Mazer Paul , Schmeyer Donald
Published: December 2004

This paper reviews early work done in Japan and leads into recent domestic activities reviewing the current “state of the art.” The authors present original work covering the development of elastomeric PVC compounds for interior and exterior automotive compounds. Compound variations include variations in the molecular weight of the speciality resin component, effect of plasticizer level changes, and the addition of alloying polymers. Physical characteristics such as hardness, specific gravity, torsional modulus, tensile strength, elongation, compression set, and abrasion resistance are measured and reported. Rheology of the compounds are characterized and related to processing ease and compound surface characteristics, smoothness, gloss, etc., and evaluated in light of potential automotive applications. Weatherability for use in automotive exterior trim is discussed.
Improved process control for the plastics industry
Authors: Beauregard Michael R.
Published: December 2004

One of the valuable tools for organizations involved in a total quality improvement effort is statistical process control (SPC). When implementing SPC in their processes, many of these organizations have equated SPC only with X & R control charts. These control charts, though important, may not be the best tool to monitor and control every process. Other charts such as an X, Rw, Rm control chart, which monitors the location of the process outpout, the instantaneous variation, and the process variation over time, may often be a better tool. This is especially true where manufacturing companies are processing materials in batches or using batches of materials such as in polymer production and molding.
Nonprofessional counselors: Revisiting selection and impact issues
Authors: Mitchell C. M. , Davidson William S. , Redner Robin , Blakely Craig , Emshoff James G.
Published: December 2004

Conclusion

In summary, the present study suggests that selection of university undergraduate nonprofessional counselors using paper‐and‐pencil measures had little incremental validity over self‐selection and potential treatment effects. In addition, the results suggest that the training and supervision experience of nonprofessionals clearly can have different impacts on attitudes and satisfaction. In fact, students in the least intensive condition felt quite dissatisfied with their experience and themselves. There is one caveat which should be kept in mind when examining the findings of this study. First, although four of the six conditions had reasonable numbers of students (n ≤ 24), two of the conditions were comparatively small (n = 12). Often, effects were carried by the larger conditions even when the smaller conditions evidenced opposite trends. Finally, results suggest that the setting of the experience can produce different impacts. This study suggests the importance of training intensity, content, and setting — elements which have often been neglected by previous research.
Inhibition of diethyl ether degradation in Rhodococcus sp. strain DEE5151 by glutaraldehyde and ethyl vinyl ether
Authors: Kim Yong-Hak , Engesser Karl-Heinrich
Published: December 2004

Alkyl ether-degrading Rhodococcus sp. strain DEE5151, isolated from activated sewage sludge, has an activity for the oxidation of a variety of alkyl ethers, aralkyl ethers and dibenzyl ether. The whole cell activity for diethyl ether oxidation was effectively inhibited by 2,3-dihydrofurane, ethyl vinyl ether and glutaraldehyde. Glutaraldehyde of less than 30 μM inhibited the activity by a competitive manner with the inhibition constant, KI of 7.07 ± 1.36 μM. The inhibition type became mixed at higher glutaraldehyde concentrations >30 μM, probably due to the inactivation of the cell activity by the Schiff-base formation. Structurally analogous ethyl vinyl ether inhibited the diethyl ether oxidation activity in a mixed manner with decreasing the apparent maximum oxidation rate, , and icreasing the apparent Michaelis–Menten constant, . The mixed type inhibition by ethyl vinyl ether seemed to be introduced not only by the structure similarity with diethyl ether, but also by the reactivity of the vinyl ether with cellular components in the whole cell system.
Functional Anatomy of the Lateral Collateral Ligament Complex of the Elbow: Morphology and Strain
Authors: TAKIGAWA N. , RYU J. , KISH V. L. , KINOSHITA M. , ABE M.
Published: December 2004

The anatomy of the lateral ulnar collateral ligament (LUCL) of the elbow was investigated in 26 fresh frozen cadavers. Two types of insertion of the LUCL were originally described but we found another type which is characterized by a broad single expansion along with a thin membranous fibre. Strain on the LUCL was measured in situ during extension and flexion with the forearm in supination, pronation and neutral. Strain in the proximal fibres started to occur at around 32° flexion and peaked at between 50° and 60° flexion. Strains measured in the distal fibres were smaller in magnitude. Forearm rotation had little effect on strain during extension to flexion. Based on these results, we conclude that the LUCL functions in unison with the annular ligament.
Information sharing and coordination in make‐to‐order supply chains
Authors: Sahin Funda , Robinson E. Powell
Published: December 2004

This research, based on our observations of an industrial vendor–manufacturer relationship, investigates the impact of information sharing and physical flow coordination in a make‐to‐order supply chain. We mathematically model and develop simulation‐based rolling schedule procedures for analyzing the manufacturer's ordering policies, transportation activities, and the vendor's manufacturing and order fulfillment processes under five alternative integration strategies. Our objective is to measure the value of information sharing and system coordination across the strategies, identify whether the source of the benefits come from information sharing or coordination, study the allocation of system benefits among channel members, and analyze the impact of environmental factors on system cost performance. The experimental results indicate a 47.58% cost reduction moving from a traditional supply chain to a fully integrated system. While information sharing reduces costs, the main economic benefit comes from coordinated decision‐making. The savings associated with system integration are not equally allocated among channel members, and vary by strategy. The procedures developed in the research provide economic insight that fosters the sharing of technological and strategic efforts.
Evaluation of postponement structures to accommodate mass customization
Authors: Su Jack C.P. , Chang Yih‐Long , Ferguson Mark
Published: December 2004

In order to meet increasing customer demands for more diverse product offerings, firms are revising their supply chain structures to accommodate mass customization. The revised structures often involve delaying the delivery of the products until after the customer orders arrive, termed time postponement (TP), or delaying the differentiation of the products until later production stages, termed form postponement (FP). We develop models representing possible implementations of the TP and FP structures and compare their performance in total supply chain cost and expected customer waiting times. We find that once the number of different products increases above some threshold level, the TP structure is preferred under both performance metrics.

For the most general model, a numerical experiment was designed to investigate how different factors affect the performance of the TP and FP structures. Through this experiment we show that higher arrival time and process time variations make the FP structure more favorable while increases in the number of products and higher interest rates make the TP structure more favorable. We also offer guidance to managers using either structure on where to allocate resources for performance improvement. For example, to improve the customer waiting times under the FP structure, increasing the coverage of the generic component and reducing the number of products provide larger benefits than reducing the variability of the arrival and process times.
Impact of HIV seropositivity on graft and patient survival after cadaveric renal transplantation in the United States in the pre highly active antiretroviral therapy (HAART) era: an historical cohort analysis of the United States Renal Data System
Authors: Swanson S.J. , Kirk A.D. , Ko C.W. , Jones C.A. , Agodoa L.Y. , Abbott K.C. , Swanson S.J. , Kirk A.D. , Ko C.W. , Jones C.A. , Agodoa L.Y. , Abbott K.C.
Published: December 2004

Abstract: Background.National statistics are presented for patient survival and graft survival in patients seropositive for the human immunodeficiency virus (HIV+) at the time of renal transplantation in the era prior to highly active antiretroviral therapy (HAART). Methods. Historical cohort analysis of 63, 210 cadaveric solitary renal transplant recipients with valid HIV serology entries in the United States Renal Data System (USRDS) from 1 January 1987 to 30 June 1997. The medical evidence form was also used for additional variables but, because of fewer available values, was analyzed in a separate model. Outcomes were patient characteristics and survival associated with HIV+ status. Results. Thirty‐two patients (0.05%) in the study period were HIV+ at transplant. HIV+ patients were comparable to the national renal transplant population in terms of gender and ethnic distribution but were younger and had younger donors and better HLA matching than the USRDS population. Patient and graft three‐year survival were significantly reduced in HIV+ recipients (53% graft, 83% patient survival) relative to the USRDS population (73% and 88%, respectively). In multivariate analysis, HIV+ status was independently associated with patient mortality and decreased graft survival in recipients of cadaveric kidney transplants. Conclusions. This analysis was retrospective and may underestimate the number of HIV+ patients transplanted in the United States. Although the clinical details of patient selection for transplant were unknown, these results show HIV+ patients can have successful outcomes after cadaveric renal transplantation, although outcomes are significantly different from HIV– recipients.
Copper in solidified copper smelter slags
Authors: Jalkanen Heikki , Vehviläinen Jouni , Poijärvi Jaakko
Published: December 2004

An appreciable amount of copper is slagged in high‐grade matte smelting and converting. The major part of copper lost in slag is recovered through slag‐cleaning operations. Copper losses in slag are of two main types: copper is either dissolved in molten slag as cuprous oxide (or as sulphide) or forms a mechanical dispersion in slag. For slag cleaning by froth flotation, mineralogy and morphology of solidified slag as well as chemical composition of copper‐bearing phases are of great interest. These phenomena are reviewed and discussed in this paper.
Computer simulation of growth and coarsening of Laves phase in a modified 12% chromium steel
Authors: Bjärbo Anders
Published: December 2004

The growth and coarsening of Laves phase at 600 and 650°C in a modified 12% chromium steel was simulated. The simulation, which was carried out with the program package DICTRA, is based on the assumption that thermodynamic equilibrium is established locally at the moving phase interface. The diffusion data was taken from a multicomponent diffusion data bank, MOB. The simulations were compared with experiments and the agreement between simulation and experiments is good.
Meltdown behaviour of pellets reduced in a laboratory reduction furnace
Authors: Gustavsson Joel , Hahlin Pär , Jönsson Pär
Published: December 2004

The meltdown behaviour of pellets reduced under different conditions in a reduction under load furnace has been examined. The pellet type, temperature increase rate, the gas flow and the applied load over the crucible were varied between trials. Samples from 12 trials interrupted just before meltdown were studied under an optical microscope and it was found that all iron oxides in the samples were reduced to iron. After the etching of the samples the carbon content was estimated. The carbon content differs within the samples as well as between the samples. A correlation exists between the average carbon content in a sample and the meltdown temperature. Some differences in the iron structure and the carbon content between the crucible wall and the crucible centre are discussed. Because no big difference in carbon content was found between the crucible wall and the crucible centre most of the carbon in the samples probably dissolves in the metal by a gas reaction where CO gas forms carbon and CO2.
Development of informatics tools for complex gene systems: Killer‐Cell immunoglobulin‐like receptor genes
Authors: Bradshaw D. , Schammel C.M. , Posch P. , Steiner N.K. , Hurley C.K.
Published: December 2004

Abstract: Killer‐cell immunoglobulin‐like receptors (KIRs) are a newly described family of polymorphic and highly homologous genes that have been difficult to classify and characterize. Before comprehensive analyzes of the genes are completed, researchers must struggle with completing the task of classifying and characterizing what is currently known. A collection and alignment of all KIR sequences found in GenBank was created to facilitate oligonucleotide reagent development and to provide an overall picture of this complex gene system. Two methods, a direct measurement of homology and phylogenetic analysis, were used to categorize sequences previously not specifically identified as belonging to a particular locus. The two methods agreed for 64.2% of sequences. A further 22.6% of uncategorized sequences were specified by only one method, although the assignments were consistent. Some sequences (11.3%) could not be assigned to a locus by either method. For one sequence, the two methods disagreed as to the locus assignment (1.9%). The failure to categorize a sequence was usually related to the short length of the sequence and the similarity among KIR loci. The tools developed in this study have been valuable in the analyses of KIR sequences and can be used for any complex gene system.
Genetic and functional studies in multiple sclerosis patients from Martinique attest for a specific and direct role of the HLA‐DR locus in the syndrome
Authors: Quelvennec E. , Bera O. , Cabre P. , Alizadeh M. , Smadja D. , Jugde F. , Edan G. , Semana G.
Published: December 2004

Abstract: Among candidate genes involved in multiple sclerosis (MS) genetic susceptibility, MHC genes and particularly HLA‐DRB1*1501–DQB1*0602 haplotype play a major role. Based on the strong linkage disequilibrium observed in Caucasians between DRB1*1501 and DQB1*0602 alleles, it is still impossible to draw a firm conclusion about the DRB1 or DQB1 locus involvement. In order to address this issue a strategy associating a genetic and a functional approach was conducted in a population of‐non‐Caucasian MS patients. We observed that in Martinicans (55 MS and 100 controls), the DRB1*15 and DRB1*07 alleles were positively associated with the disease. However in Martinicans the most common DRB1*15 subtype was *1503 and not *1501. Moreover, in Martinicans, the frequency of DQB1*0602, found in association with other DRB1 alleles than DRB1*15 (42% of DQB1*0602 haplotypes), was not increased in DRB1*15‐negative MS patients, suggesting a neutral role of DQB1*0602 in MS genetics. In a second step, we demonstrated the capability of the DRB1*1503 allele associated with MS in Martinicans to present the immunodominant autoantigen MBP 85–99 peptide to a DRB1*1501 restricted MBP specific T cell line. Interestingly, structural features of DRB1*1501 or DRB1*1503 molecules are in good fit with the hypothesis that *1501 and *1503 molecules may act similarly in MS development by presenting the same immunodominant MBP peptide. On the whole, our results show a prominent role of the DRB1 locus (DRB1*1501 and/or DRB1*1503 alleles) in the immunodominant MBP 85–99 peptide presentation to genetically different MS patients and suggest a neutral role of the DQB1 encoded molecule in MS susceptibility.
Models for Longitudinal Data with Censored Changepoints
Authors: Jackson Christopher H. , Sharples Linda D.
Published: December 2004

In longitudinal studies of biological markers, different individuals may have different underlying patterns of response. In some applications, a subset of individuals experiences latent events, causing an instantaneous change in the level or slope of the marker trajectory. The paper presents a general mixture of hierarchical longitudinal models for serial biomarkers. Interest centres both on the time of the event and on levels of the biomarker before and after the event. In observational studies where marker series are incomplete, the latent event can be modelled by a survival distribution. Risk factors for the occurrence of the event can be investigated by including covariates in the survival distribution. A combination of Gibbs, Metropolis–Hastings and reversible jump Markov chain Monte Carlo sampling is used to fit the models to serial measurements of forced expiratory volume from lung transplant recipients.
Principal Component Analysis of Landmarks from Reversible Images
Authors: Theobald C. M. , Glasbey C. A. , Horgan G. W. , Robinson C. D.
Published: December 2004

We consider the use of principal component analysis to summarize the variation in labelled landmark data for images which are reversible in the sense that a mirror image may be defined for each image and the original and mirror images may be regarded as equally representative of the population. We examine the effect of including the original and mirror images on a principal component analysis based on the landmark co-ordinates. The inclusion of mirror images is found to lead to a simplified interpretation in which some components measure asymmetry in the images and the remainder depend symmetrically on pairs of co-ordinates. This is illustrated on shape variation in carrots. A second application is to the segmentation of X-ray computed tomography images of sheep to locate the inner boundary of the carcass. It is found that image boundaries can be identified more accurately by modelling them with principal components, and that including mirror images can offer a further improvement in accuracy. Similar arguments apply when a population of images is thought to be invariant under a rotation and may also be relevant when a principal component analysis is applied to descriptive statistics such as Fourier sums.
Evaluation of Trace Evidence in the Form of Multivariate Data
Authors: Aitken C. G. G. , Lucy D.
Published: December 2004

The evaluation of measurements on characteristics of trace evidence found at a crime scene and on a suspect is an important part of forensic science. Five methods of assessment for the value of the evidence for multivariate data are described. Two are based on significance tests and three on the evaluation of likelihood ratios. The likelihood ratio which compares the probability of the measurements on the evidence assuming a common source for the crime scene and suspect evidence with the probability of the measurements on the evidence assuming different sources for the crime scene and suspect evidence is a well-documented measure of the value of the evidence. One of the likelihood ratio approaches transforms the data to a univariate projection based on the first principal component. The other two versions of the likelihood ratio for multivariate data account for correlation among the variables and for two levels of variation: that between sources and that within sources. One version assumes that between-source variability is modelled by a multivariate normal distribution; the other version models the variability with a multivariate kernel density estimate. Results are compared from the analysis of measurements on the elemental composition of glass.
Analysis of Longitudinal Multiple-Source Binary Data Using Generalized Estimating Equations
Authors: O’Brien Liam M. , Fitzmaurice Garrett M.
Published: December 2004

We present a multivariate logistic regression model for the joint analysis of longitudinal multiple-source binary data. Longitudinal multiple-source binary data arise when repeated binary measurements are obtained from two or more sources, with each source providing a measure of the same underlying variable. Since the number of responses on each subject is relatively large, the empirical variance estimator performs poorly and cannot be relied on in this setting. Two methods for obtaining a parsimonious within-subject association structure are considered. An additional complication arises with estimation, since maximum likelihood estimation may not be feasible without making unrealistically strong assumptions about third- and higher order moments. To circumvent this, we propose the use of a generalized estimating equations approach. Finally, we present an analysis of multiple-informant data obtained longitudinally from a psychiatric interventional trial that motivated the model developed in the paper.
The effectiveness of randomized complete block design
Authors: Shieh Gwowen , Jan Show‐Li
Published: December 2004

This paper examines the relative efficiency of randomized complete block design as compared with that of completely randomized design. The most widely used measure of relative efficiency considers only the error variances of the two designs, therefore it does not provide the complete information concerning the sensitivity of the experiment in the final results. We study three alternative criteria related to the sensitivity issue and design planning consideration. The proposed relative measures employ the p‐value, Scheffé confidence interval estimation and power of both designs. The distinct feature of this study is the focus on the estimated relative efficiency measures and their relation with the coefficient of partial determination between responses and block effects, given that treatment effects are present in the models. Furthermore, informative visual representations and numerical assessments of various aspects of their properties are also presented.
Recombinant FVIIa in the management of uncontrolled hemorrhage
Authors: O'Connell Niamh M. , Perry David J. , Hodgson Andrew J. , O'Shaughnessy Denise F. , Laffan Michael A. , Smith Owen P.
Published: December 2004

BACKGROUND: Recombinant FVIIa (rFVIIa/NovoSeven) is a novel hemostatic agent originally developed to treat patients with hemophilia who had developed inhibitors. Several case reports have suggested that rFVIIa may be effective in treating patients without a pre‐existing bleeding disorder who have uncontrolled bleeding.

STUDY DESIGN AND METHODS: Data on the efficacy and safety of rFVIIa in the treatment of massive hemorrhage were obtained retrospectively from the NovoSeven extended‐use data collection system.

RESULTS: A total of 40 patients received rFVIIa for uncontrolled bleeding, and in these patients, bleeding stopped or decreased in 32 (80%). Blood product usage was significantly decreased after rFVIIa administration. Thromboembolic events occurred in three patients with additional risk factors for thrombosis. Of 40 patients, 23 (57.5%) died. Bleeding was the direct cause of death in seven cases (all within 24 hr of administration of rFVIIa). The remaining 16 deaths were the result of sepsis, multi‐organ failure, or the underlying disease.

CONCLUSIONS: In this retrospective study of data voluntarily submitted to a web‐based drug surveillance program, we present preliminary results on the use of rFVIIa in nonhemophilia patients with bleeding. Although some efficacy is suggested, there was a high mortality rate from nonhemorrhagic causes. Randomized controlled trials are needed to properly assess the role of rFVIIa in the management of hemorrhage.
Similar levels of infectivity in the blood of mice infected with human‐derived vCJD and GSS strains of transmissible spongiform encephalopathy
Authors: Cervenakova Larisa , Yakovleva Oksana , McKenzie Carroll , Kolchinsky Svetlana , McShane Lisa , Drohan William N. , Brown Paul
Published: December 2004

BACKGROUND: The possible transmission of variant CJD (vCJD) through blood transfusion or use of plasma‐derived products prompted this study comparing infectivity in murine models of vCJD and Gerstmann‐Sträussler‐Scheinker (GSS) disease, a non‐vCJD form of transmissible spongiform encephalopathy (TSE).

STUDY DESIGN AND METHODS: RIII/Fa/Dk (RIII) or Swiss‐Webster (Swiss) mice were inoculated intracerebrally (IC) with mouse‐adapted strains of vCJD or GSS (Fukuoka‐1) of similar infectivity. Groups of RIII mice were euthanized 17 weeks after inoculation (during the incubation period), and another 23 weeks after inoculation (when symptomatic). Blood was collected, separated into components, and inoculated into groups of healthy mice; brains and spleens from all mice were harvested and tested for the presence of PrPres by Western blot using 6H4 MoAb.

RESULTS: Levels of 20‐30 infectious doses per mL were present in buffy coat and plasma during both the incubation and symptomatic stages of disease; PLT pellet infectivity was lower (10 ID/mL) and RBCs were not infectious. The disease was transmitted more efficiently by IV than IC inoculation of plasma, but there was no difference observed with inoculation of buffy coat. The incubation period was shorter after IC inoculation of GSS‐ than vCJD‐brain inocula. The amount of PrPres in spleens was similar for both TSE agents, but was slightly lower in brains of vCJD than GSS mice.

CONCLUSION: Infectivity was detected in blood components of mice infected with a human‐derived strain of vCJD during both the preclinical and clinical phases of disease in a similarly low range of concentrations as in mice infected with a human‐derived nonvariant strain (GSS, Fukuoka‐1). Other measures of virulence, including brain infectivity titers, incubation periods, and the accumulation of PrPres in spleens and brains, were also comparable in both experimental models.
Quantitative real‐time detection of parvovirus B19 DNA in plasma
Authors: Koppelman Marco H.G.M. , Cuypers H. Theo M. , Emrich Thomas , Zaaijer Hans L.
Published: December 2004

BACKGROUND:  As of 2004, the European Pharmacopoeia demands that plasma pools for production of anti‐D immunoglobulin should not contain more than 104 IU per mL of parvovirus B19 (B19V) DNA. Hence, before pooling, highly viremic donations have to be identified, and after pooling the level of B19V DNA must be determined. The performance of a new real‐time B19V DNA PCR test (Roche, Mannheim, Germany) was studied, using a DNA extractor (NucliSens, bioMerieux, Boxtel, the Netherlands) for isolation of nucleic acid, and using a DNA quantification test (LightCycler apparatus, Roche, Mannheim, Germany) for amplification and detection.

STUDY DESIGN AND METHODS:  Dilutions of the international B19V DNA standard and reference preparations were tested to determine the precision, linear range, and accuracy of the assay and to calculate the factor for conversion of B19V DNA copies to IUs. The internal control signals, invalid test results, and the effect of cryo‐poor plasma were studied as a measure for robustness. Routine performance was assessed by testing 164 manufacturing pools (not screened for B19V) and 1048 test pools of 480 donations each.

RESULTS:  The copies‐to‐IU conversion factor was calculated to be 3.34 (95% CI, 3.07‐3.63). The assay appears linear between 103 and 107 IU per mL. Between 103 and 105 IU per mL, the test can discriminate samples differing a factor two in B19V DNA content. Overall, 0.78 percent of the test results were invalid. Of 127 B19V DNA negative control plasma samples, 7 were contaminated with low levels of B19V DNA. Of 164 nonscreened manufacturing plasma pools, 92 contained B19V DNA (56%); 13 contained more than 104 IU per mL. Of 503,040 donations, 29 contained more than 5 × 106 IU per mL B19V DNA (1:17,346).

CONCLUSION:  The B19V DNA quantification test (LightCycler, Roche ) is suitable for quantitative, routine, in‐process measurement of B19V DNA levels in plasma pools, using the DNA extractor (NucliSens, bioMerieux) for nucleic acid isolation.
Cord blood units collected at a remote site: a collaborative endeavor to collect umbilical cord blood through the Hawaii Cord Blood Bank and store the units at the Puget Sound Blood Center
Authors: Wada Randal K. , Bradford Andrea , Moogk Margery , Yim Robyn , Strong D. Michael , Drachman Jonathan , Reems Jo Anna
Published: December 2004

BACKGROUND:  Umbilical cord blood is a useful source of hematopoietic stem cells, especially because compared to equivalent HLA‐matched stem cells from unrelated adult donors. A network of community collection sites targeted at particular ethnic groups and serviced by a central processing and storage facility can maximize the genetic diversity of banked cord blood units (CBUs) in a cost‐effective fashion.

STUDY DESIGN AND METHODS:  The present study compared CBUs collected near the Puget Sound Blood Center in Seattle, WA, with those collected in Honolulu, HI, and processed in Seattle. Evaluated variables include collection volume, total nucleated cell count, cellular viability, CD34+ cell count, clonogenic activity, and donor race for a total of 1646 CBUs received from July 1998 through November 2002.

RESULTS:  CBUs from the two sites did not differ with regard to volume or total nucleated cells. Those from Hawaii had significantly longer transit times (p < 0.001) and lower whole cord blood cell viability. However, the numbers of CFU and viable CD34+ cells were not affected by remote collection. CBUs screened from Seattle were largely from Caucasian donors, whereas over 85 percent of those from Honolulu were from donors of Asian‐Pacific Islander or mixed ethnicity.

CONCLUSION:  These studies demonstrate the feasibility of long‐distance umbilical cord blood banking. Arrange‐ments such as those described here could be used to help target cost‐effective collection from minority popula‐tions and increase the HLA and ethnic diversity for CBUs.
Expression of Transforming Growth Factor‐β Isoforms and Their Receptors in Lepromatous and Tuberculoid Leprosy
Authors: Kiszewski C. A. , Becerril E. , Baquera J. , Aguilar L. D. , Hernández‐Pando R.
Published: December 2004

Leprosy is an infectious disease with two polar forms, tuberculoid leprosy (TT) and lepromatous leprosy (LL), that are characterized by strong cell‐mediated immunity (CMI) and CMI anergy, respectively. Transforming growth factor‐β (TGF‐β) belongs to a family of pleiotropic cytokines (TGF‐β1, TGF‐β2 and TGF‐β3) that participate in the control of cell differentiation and proliferation, as well as tissue repair. This cytokine family is unique because it suppresses CMI. In this study, we compared the expression of the three TGF‐β isoforms and their receptors in skin biopsies from LL and TT patients (LL = 20; TT = 20) using immunohistochemistry and automated morphometry. The percentage of cells immunostained for the three TGF‐β isoforms and cells positive for the three TGF‐β receptors in the inflammatory infiltrate located in the papillary dermis, reticular dermis and periadnexal tissue were significantly higher in LL than that in TT, with macrophages being the most common and strongest immunoreactive cells. Some lymphocytes, fibroblasts, keratinocytes and epithelial cells from sweat glands and hair roots were also positive. In situ reverse‐transcription polymerase chain reaction corroborated the capacity of these cells to synthesize TGF‐β1 and TGF‐β receptor 2. This high expression of TGF‐β isoforms and their receptors could contribute to CMI anergy and other clinical characteristic features of leprosy, like skin atrophy.
Cellular Profile of Cytokine Production in a Patient with Visceral Leishmaniasis: γδ+ T Cells Express Both Type 1 Cytokines and Interleukin‐10
Authors: Lagler H. , Willheim M. , Traunmüller F. , Wahl K. , Winkler H. , Ramharter M. , Graninger W. , Winkler S.
Published: December 2004

The cytokine profile of CD4+, CD8+ T cells, γδ+ T cells and natural killer (NK) cells (CD94+CD3–) was studied in a patient with visceral leishmaniasis (VL). The otherwise healthy, human immunodeficiency virus‐negative patient acquired the disease in Tuscany, Italy. Diagnosis was made by demonstration of high concentrations of antibodies against Leishmania antigens in serum. Flow cytometry for the detection of intracellular interferon‐γ (IFN‐γ), interleukin (IL)‐2, IL‐4, IL‐6, IL‐10, IL‐13 and tumour necrosis factor (TNF)‐α expression in peripheral blood mononuclear cells stimulated with phorbol 12‐myristate 13‐acetate and ionomycin was performed, followed by treatment with liposomal amphotericin B. CD4+ cells were identified as major cytokine‐expressing cells, capable of producing both type 1 and type 2 cytokines. A high frequency of IL‐4‐ and IL‐13‐expressing CD8+ cells was noted. NK cells and γδ+ T cells, thought to be involved in innate host defences against Leishmania, expressed IFN‐γ and TNF‐α. Ten per cent of γδ+ T cells expressed IL‐10, predominantly together with IFN‐γ, suggesting additional immune‐regulatory roles for this T‐cell subset in VL.
Pretransplant Xenogeneic Blood Transfusions Reduce the Humoral Response in a Mouse‐to‐Rat Heart Transplantation Model
Authors: Bersztel A. , Johnsson C. , Björkland A. , Tufveson G.
Published: December 2004

A mouse heart transplanted to a rat is rejected promptly 3 days after transplantation, independent of whether cyclosporin A (CyA) is used as an immunosuppressant or not. Adding a short course of deoxyspergualin (DSG) initially, in addition to continuous CyA treatment, results in long‐term graft survival and permits retransplantation during CyA monotherapy. In this paper, we have explored the possibility of substituting the initial heart transplant with blood transfusions.

Lymphocyte‐enriched blood transfusions combined with CyA and an initial course of DSG proved to lower or eliminate the haemagglutinating antibody titre normally seen in acute vascular xenorejection. The therapy, however, did not prolong the mean survival of the cardiac xenograft, but the same treatment protocol could result in either hyperacute rejection or prolonged survival of up to 11 days.

In conclusion, this and earlier studies propose that a humoral unresponsiveness can be induced if the recipient vascular circulation is exposed to a xenoantigen in a mouse‐to‐rat combination.
Antigen‐Specific T‐Cell Downregulation by Human Dendritic Cells Following Blockade of NF‐κB
Authors: Calder V. L. , Bondeson J. , Brennan F. M. , Foxwell B. M. J. , Feldmann M.
Published: December 2004

Dendritic cells (DCs) are important for presenting antigen to T cells, especially naïve T cells. It has recently been shown that blocking the transcription factor, nuclear factor kappa B (NF‐κB) in human DCs inhibited the mixed leukocyte reaction. The aim of this study was to investigate the effect of blocking NF‐κB in DCs during presentation of antigen to memory T cells in vitro. Peripheral blood monocytes were differentiated into immature DCs with interleukin‐4 (IL‐4) and granulocyte‐macrophage colony‐stimulating factor, and pulsed with an immunogenic tetanus toxoid peptide. Upon maturation, the antigen‐pulsed DCs were highly effective in presenting antigen to autologous T cells. However, stimulation with antigen‐pulsed DCs overexpressing ΙκΒα, the endogenous inhibitor of NF‐κB, led to a significant reduction in T‐cell proliferation, and decreased production of interferon‐γ, IL‐4 and IL‐10, whereas transforming growth factor‐β production was low throughout. There was a significant increase in apoptosis of antigen‐specific T cells, even in the presence of IL‐2, which was not found in resting T cells. Similar findings were observed using a proteasome inhibitor to block NF‐κB. The effective downregulation of antigen‐specific T‐cell responses following blockade of NF‐κB in DCs could be a useful approach for immunomodulating inflammatory T‐cell responses.
Individual and Common Antigen‐Recognition Sites of Liver‐Derived T Cells in Patients with Autoimmune Hepatitis
Authors: Löhr H. F. , Pingel S. , Weyer S. , Fritz T. , Galle P. R.
Published: December 2004

Autoimmune hepatitis (AIH) is characterized by dense T‐cell infiltrations in the liver tissue, but little is known how T cells influence the pathogenesis. To address this question, the distribution of T‐cell receptor variable β‐chain (TCR Vβ) transcripts of peripheral blood and liver‐infiltrating T cells from previously untreated patients with newly diagnosed acute exacerbated AIH was investigated. Furthermore, the lengths and sequences of complementary‐determining region 3 (CDR3) were studied. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis and CDR3 spectratyping revealed multiple clonal expansions of liver‐infiltrating T cells but not peripheral T cells within various TCR Vβ families. Further analysis of overexpressed TCR Vβ transcripts using TCR β‐chain‐joining element (TCR Jβ)‐specific primers in a nested PCR showed characteristic Vβ/Jβ combinations. Subsequent sequencing of CDR3 regions from PCR products confirmed the clonality of T‐cell expansions and the usage of common and individual CDR3 motifs. In conclusion, the clonality of expanded T cells within the liver tissue during early clinical manifestation of untreated AIH indicated that autoantigen‐specific T cells accumulate at the inflammation site. Individual and common CDR3 motifs argued for predominant epitopes that were recognized by liver‐infiltrating T cells in AIH patients.
Monocyte‐Derived CD1a+ Dendritic Cells Generated in Two Different Culture Systems: Immunophenotypic and Functional Comparison
Authors: Xia C.‐Q. , Kao K. J.
Published: December 2004

Previous studies demonstrated that CD1a+ dendritic cells (DCs) could not be prepared ex vivo without using fetal calf serum (FCS). Recently, we developed a method of using heparin to induce differentiation of human monocytes into CD1a+ DCs without using FCS. In order to determine the potential clinical applicability of heparin‐induced CD1a+ DCs, we conducted this study to compare both types of CD1a+ DCs, immunophenotypically and functionally. Our results showed that the expression of CD1a on heparin‐DCs was lower than that on FCS‐DCs. Both types of DCs expressed similar levels of CD11c, HLA‐DR, CD40, CD83, CD80 and CD86 before and after lipopolysaccharide stimulation. Immature heparin‐DCs and FCS‐DCs had similar phagocytic activities. Heparin‐DCs consistently secreted higher interleukin‐10 (IL‐10) and lesser IL‐12 than FCS‐DCs after activation. Mature heparin‐DCs were slightly more active than mature FCS‐DCs in stimulating the proliferation of allogeneic CD4+ T cells. Both types of mature CD1a+ DCs primed the naïve CD4+ T cells to produce large amount of interferon‐γ (IFN‐γ). However, naïve CD4+ T cells stimulated with FCS‐DCs produced more IFN‐γ, while the naïve CD4+ T cells stimulated with heparin‐DCs produced more IL‐5. The results indicate that both types of CD1a+ DCs do not have identical function in the priming of CD4+ T cells and have minor difference in immunophenotypes.
Potent Influence of Bovine Serum Proteins in Experimental Dendritic Cell‐Based Vaccination Protocols
Authors: Toldbod H. E. , Agger R. , Bolund L. , Hokland M.
Published: December 2004

Typically autologous dendritic cells (DCs) intended for vaccination are generated from bone marrow derived stem cells or blood monocytes, loaded with antigen and introduced into the organism. However, addition of serum to DC culture medium is often necessary. Thus, serum proteins will be taken up and presented by the DCs together with other antigens. If heterologous serum is used, some of the serum proteins might be antigenic and thus induce a strong immune response when introduced in the recipient. We used the murine model of malignant melanoma, B16, to investigate the consequences of addition of fetal calf serum (FCS) to the medium for culturing murine DCs. The results showed that vaccination of mice with DCs cultured in vitro in the presence of FCS but in the absence of extraneous tumour antigens, protected the mice from challenge with B16 tumour cells similarly cultured in FCS. This protection could not be elicited by vaccination with FCS alone. Interestingly, the protective effect of DC vaccination was abolished when the challenging B16 tumour cells were free of serum proteins. Thus, these results show that DCs grown in the presence of FCS are able to induce immunity, which may be mistaken to be tumour immunity.
γδ T Cells and Interleukin‐6 Levels Could Provide Information Regarding the Progression of Human Renal Allograft
Authors: Borel I. Malan , Racca A. , Garcia M. I. , Bailat A. , Quiroga F. , Soutullo A. , Gaite L.
Published: December 2004

We have determined the percentage of αβ and γδ T cells by flow cytometry as well as serum interleukin‐6 (IL‐6) and soluble interleukin‐6 receptor (sIL‐6R) levels by enzyme‐linked immunosorbent assay in kidney allograft recipients with acute, chronic or stable graft evolution. The percentage of CD4 and CD8 T cells in transplanted patients was lower than in the control group (P < 0.001) with the exception of CD8 γδ T cells from patients with stable evolution (P > 0.05). The serum levels of IL‐6 and sIL‐6R in acute and chronic rejection were higher than in the controls (P < 0.05). No differences in IL‐6 levels were observed between the stable evolution and the control groups (P > 0.05). The levels of sIL‐6R were higher in stable evolution patients than in the controls (P < 0.05) and no differences were observed between the chronic and stable evolution patients (P > 0.05). IL‐6 decreased in patients with a favourable evolution, increased in those with an increased renal dysfunction and was maintained when the renal dysfunction was not modified. These results suggest that γδ T cells could participate in renal allograft maintenance and that IL‐6 but not sIL‐6R serum levels may provide a prognostic marker for measuring the evolution of kidney allograft.
The Interaction Defect of Accessory Molecules is Responsible for the Poor Ex Vivo Response to Human Antigens of Mouse T Helper Cells
Authors: Sun Y. , Langnas A. N. , Zhao Y.
Published: December 2004

Mouse T cells fail to respond to xenogeneic pig and human antigens using the direct antigen‐presenting pathway. The poor response by mouse CD8 cells is because of multiple defects in the molecular interactions between mouse CD8 cells and xenogeneic antigen‐presenting cells (APCs). Using human CD4/DR3+, mouse CD4−/major histocompatibility complex (MHC) class II − mice, we investigated the defects in molecular interaction responsible for the poor response to xenogeneic antigens by naïve mouse CD4+ cells. Mouse CD4 cells failed to respond to human leucocyte antigen (HLA)‐DR3 expressed on mouse APCs but developed a strong response to alloantigens, indicating a defect in the interaction between mouse CD4 and HLA‐DR3 molecules. Human CD4+/mouse CD4– mouse T cells respond poorly to human and pig APCs but not allogeneic APCs, indicating that accessory molecular interactions are deficient across highly separated species. Adding mouse interleukin‐2 (IL‐2) to the mixed lymphocyte reaction system did not improve the poor response to human or pig antigens by mouse or human CD4+/mouse CD4– mouse T cells. Therefore, multiple molecular interactions deficient between mouse CD4 cells and human or pig APCs may lead to the poor response to xenogeneic antigens by naïve mouse CD4 cells.
Direct numerical simulation of bedload transport using a local, dynamic boundary condition
Authors: Schmeeckle Mark W. , Nelson Jonathan M.
Published: December 2004

ABSTRACT Temporally and spatially averaged models of bedload transport are inadequate to describe the highly variable nature of particle motion at low transport stages. The primary sources of this variability are the resisting forces to downstream motion resulting from the geometrical relation (pocket friction angle) of a bed grain to the grains that it rests upon, variability of the near‐bed turbulent velocity field and the local modification of this velocity field by upstream, protruding grains. A model of bedload transport is presented that captures these sources of variability by directly integrating the equations of motion of each particle of a simulated mixed grain‐size sediment bed. Experimental data from the velocity field downstream and below the tops of upstream, protruding grains are presented. From these data, an empirical relation for the velocity modification resulting from upstream grains is provided to the bedload model. The temporal variability of near‐bed turbulence is provided by a measured near‐bed time series of velocity over a gravel bed. The distribution of pocket friction angles results as a consequence of directly calculating the initiation and cessation of motion of each particle as a result of the combination of fluid forcing and interaction with other particles. Calculations of bedload flux in a uniform boundary and simulated pocket friction angles agree favourably with previous studies.
Time‐transgressive deposits of repeated depositional sequences within interlobate glaciofluvial (esker) sediments in Köyliö, SW Finland
Authors: Mäkinen Joni
Published: December 2004

ABSTRACT Evidence of conspicuous repeated seasonal to annual deposition of glaciofluvial and glaciolacustrine sequences within a structurally complex interlobate esker segment in SW Finland is presented. The time‐transgressive, overlapping depositional sequences consist of deposits from two successive melt seasons, including three vertically stacked lithofacies associations: (1) massive to stratified coarse gravels = summer deposits; (2) trough and ripple cross‐stratified fine‐grained deposits = autumn to winter deposits; and (3) sandy stratified beds = spring deposits. The depositional environment of each lithofacies association involves a transition from subglacial or submarginal tunnel to a subaqueous re‐entrant environment, which then passes to a proglacial glaciolacustrine environment. The study also presents evidence of headward extension of subglacial tunnel deposits, related to the rapid shifting of a tunnel expansion point during the increasing spring discharge, which occupied the old tunnel exit: this mode of annual deposition has not been reported previously in esker studies. The good preservation of the rhythmic lithofacies associations is suggested as resulting from interlobate depositional conditions associated with rapidly decaying icestreams. Therefore, the depositional model may provide a key to recognizing time‐transgressive interlobate eskers that form an important geomorphological and sedimentological record of meltwater activity during the last deglaciation of the Fennoscandian and Laurentide ice sheets. The identification of time‐transgressive interlobate eskers and associated palaeo‐icestream behaviour is an essential step forward for more accurate models of ice sheet behaviour and palaeoclimatic reconstructions.