bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA in Czech adult patients with autoimmune diabetes mellitus: comparison with Czech children with type 1 diabetes and patients with type 2 diabetes
Authors: Cerna M. , Novota P. , Kolostova K. , Cejkova P. , Zdarsky E. , Novakova D. , Kucera P. , Novak J. , Andel M. 
Published: December 2003

SummaryType 1 diabetes results from an autoimmune insulitis, associated with HLA class II alleles. The evidence about HLA allele association is not clear in patients diagnosed after 35 years of age. In this study we have analyzed HLA alleles of DQB1 and DRB1 genes by sequence specific primer (SSP)‐PCR technique in adult patients with disease onset after 35 years of age. Two hundred and eighty‐one patients were divided into three groups according to the insulin therapy, the level of C peptide (CP), and GAD antibodies (anti‐GAD). Group 1 (type 1 diabetes in adults) was characterized by CP less than 200 pmol/L and anti‐GAD more or less than 50 ng/mL (n = 80). All of them had insulin therapy within 6 months after diagnosis. Group 2 latent autoimmune diabetes mellitus in adults (LADA) was defined by a minimum 6‐month‐long phase after diagnosis without insulin therapy, and was characterized by CP more than 200 pmol/L and anti‐GAD more than 50 ng/mL (n = 70). Group 3 (type 2 diabetes) was characterized by CP more than 200 pmol/L and anti‐GAD less than 50 ng/mL (n = 131). None ever had insulin therapy. In group 1, there was increased frequency of DRB1*04 (45.0% vs. controls 14.1%, OR = 5.0,P < 0.0005) and DQB1*0302 alleles (43.3% vs. controls 11.1%, OR = 6.1,P < 0.00005). There was increased frequency of DRB1*03 and DQB1*0201, and decreased frequency of DQB1*0602 (3.3% vs. controls 20.2%), but it was not significant. In group 2, there was a significantly increased frequency of DRB1*03 only (50.0% vs. controls 21.2%, OR = 3.7,P < 0.05). Compared with children with type 1 diabetes and adults with type 2 diabetes (group 3), we conclude that the presence of predisposing DQB1 alleles in adults with type 1 diabetes decreases with the age, probably due to environmental factors. Only the DRB1*03, but not the DQB1 gene, becomes the main predisposing allele in LADA patients. These findings suggest that the presence of HLA‐DQB1*0302 identifies patients at high risk of requiring insulin treatment. Type 1 diabetes mellitus (DM) in children or adults may have partly different immunogenetic etiopathogenesis than LADA.
Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma
Authors: Howell W. M. , Turner S. J. , Theaker J. M. , Bateman A. C. 
Published: December 2003

SummaryCutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which exposure to UV light is the most important risk factor. Several lines of evidence suggest that CMM patients develop an immune response to their tumours, although, in most cases, anti‐tumour immune responses are insufficient to abrogate tumour development. Polymorphism in genes regulating the immune response and cell growth may result in increased susceptibility to and/or poorer prognosis in certain individuals. In this study, we addressed whether single nucleotide polymorphisms (SNPs) associated with differential expression of selected pro‐ and anti‐inflammatory cytokines and growth factors [interleukin (IL)‐1β−35 and −511, IL‐2 −330, IL‐4 −590, IL‐6 −174, IL‐8 −251, interferon (IFN)‐γ+874 and transforming growth factor (TGF)β1 +915] or as markers of candidate cytokine genes (IL‐12 +1188) are associated with susceptibility to or known prognostic indicators (e.g. initial tumour growth phase, Breslow thickness, mitotic count in vertical growth phase tumours, tumour regression) in CMM. One hundred and sixty‐nine British caucasian CMM patients and 261 controls were included in the study and all SNPs were genotyped by ARMS–PCR. No SNP genotypes or alleles showed significant associations with CMM susceptibility and only the IL‐1β−511 TT genotype was associated with thinner invasive tumours at presentation, as assessed by Breslow thickness at the clinically significant cut‐off point of 1.5 mm [occurring in 2/51 (3.9%) thicker vs. 14/78 (17.9%) thinner tumours (P = 0.03; relative risk = 0.29 (95% confidence interval 0.05–0.95)]. These findings suggest that — with the possible exception of IL‐1β— genetic variation associated with differential expression of the selected pro‐ and anti‐inflammatory cytokines is unlikely to play a major role in susceptibility to and prognosis in CMM.
Coeliac disease: investigation of proposed causal variants in the CTLA4 gene region
Authors: King A. L. , Moodie S. J. , Fraser J. S. , Curtis D. , Reid E. , Dearlove A. M. , Ciclitira P. J. 
Published: December 2003

SummaryCoeliac disease (CD) is an immune‐mediated enteropathy triggered by gluten in genetically predisposed individuals. Patients with CD have an increased prevalence of other autoimmune disorders, including type 1 diabetes (T1D) and Graves’ disease (GD). CD shares with these conditions certain HLA susceptibility alleles. A number of studies have also shown association of autoimmune diseases, including CD, with the CD28‐cytotoxic T lymphocyte antigen 4 (CTLA4)‐inducible costimulator (ICOS) region of chromosome 2q33, but until recently the precise causal variant has remained unknown. Recently, it was shown that, in GD, CT60 (+6230G>A), a single nucleotide polymorphism (SNP) at the end of the CTLA4 transcript, is associated with an alteration in the ratio of splice forms of the CTLA4 gene and that this ratio affects disease susceptibility. A similar but weaker association was found with T1D. There is also an independent association of GD and T1D with the SNP MH30 (−23 327G>C), which possibly affects promoter region function.Hypothesizing that CT60 and MH30 may be causal variants in other autoimmune disorders, we investigated these SNPs in CD using 149 family trios and 100 unrelated/unaffected controls. No association was detected with either SNP using both the transmission disequilibrium test (TDT) and case–control methods. Our study appears to have good power to detect moderate genetic effects, but possibly these SNPs exert too weak an effect on risk of CD to have been detected in our sample. Alternatively, the previously noted association of CD with the CTLA4 gene region may be due to different causal variants. Unlike T1D and GD, CD is not a true autoimmune disease, and CD has different associations at the CTLA4 exon 1 SNP +49G>A from all other autoimmune disorders. MH30, CT60, and other SNPs in the region may still warrant further investigation in other CD samples.
Formation and emplacement of the Dolodrook serpentinite body, Lachlan Orogen, Victoria
Authors: Spaggiari C. V. , Gray D. R. , Foster D. A. 
Published: December 2003

Serpentinised peridotite and ultramafic breccia make up an approximately 5 km‐long, 1 km‐wide fault slice within turbidites in the Dolodrook River region of the central Lachlan Orogen. The serpentinite body is surrounded by juvenile, mafic–ultramafic sedimentary rocks with Cambrian limestone olistoliths representative of locally derived debris flows, and Middle to Upper Ordovician black shale, chert, sandstone and mudstone. The antiformal geometry and nature of the ultramafic breccia and mafic–ultramafic sedimentary rocks (Garvey Gully Formation) indicate that the serpentinite body may have been either a former oceanic transform fault zone, a Marianas‐style serpentine seamount or a combination of these. Observations of modern‐day forearc regions show that faulting processes have led to the exposure of serpentinised peridotite horst blocks and serpentine mud volcanoes that have intruded along fault conduits (e.g. Marianas and Izu–Bonin forearcs). At Dolodrook, the structural and metamorphic relationships with the surrounding rocks, and the lithological associations, have much in common with these observations and indicate that Dolodrook may be an ancient, on‐land example of an accreted seamount or oceanic topographic high. Structural relationships, the very low metamorphic grade of all rocks at Dolodrook, and the presence of broken formation developed in not‐fully lithified Middle to Upper Ordovician sandstone and mudstone indicate that the serpentinite body was emplaced at shallow crustal levels within the turbidite wedge (Tabberabbera Zone), possibly as an offscraped topographic high during marginal basin closure. The Dolodrook serpentinite has previously been inferred as part of the Cambrian igneous sequence (‘greenstones’) exposed in the Governor, Mt Wellington and Heathcote Fault Zones, but structural and metamorphic relationships with surrounding rocks, and the Cambrian tectonic setting in which it formed, have remained speculative.
Preoperative serum acid phosphatase and alkaline phosphatase are not predictors of pathological stage and prostate‐specific antigen failure after radical prostatectomy
Authors: San Francisco I.F. , Olumi A.F. , Yoon J.H. , Regan M.M. , DeWolf W.C. 
Published: December 2003

OBJECTIVETo examine the utility and prognostic significance of enzymatic serum acid phosphatase (total acid phosphatase, TAP, and prostatic fraction of acid phosphatase, PFAP) and alkaline phosphatase (ALP) for staging, grading and outcome of patients who underwent radical retropubic prostatectomy (RRP) after the introduction of prostate‐specific antigen (PSA) testing.PATIENTS AND METHODSIn all, 180 consecutive patients with clinically localized prostate cancer who underwent RRP with standard obturator lymph‐node dissection between 1 January 1990 and 31 December 1995 were evaluated. Levels of TAP of > 5.4 IU/L, PFAP of > 1.2 IU/L and ALP of > 120 IU/L were classified as abnormally high. The relationship between abnormally high values and prostate cancer stage, grade and time to recurrence after RRP were calculated. The median follow‐up was 86 months (≈ 7 years).RESULTSOf the 180 patients, information about preoperative TAP, PFAP and ALP were available in 164, 163 and 154, respectively; TAP was abnormal in seven (4%), PFAP in 33 (20%) and ALP in only 13 (8%). None of the markers examined was associated with any variables of disease severity, as measured by pathological stage, Gleason score, perineural invasion, capsular penetration, positive margins, seminal vesicle involvement, and lymph node involvement. Abnormal TAP, PFAP or ALP were not associated with recurrence (P = 0.96, 0.45 and 0.41, respectively). In contrast, a PSA level of > 4 ng/mL was predictive of recurrence after RRP (P < 0.001). In the sample overall, 25 (14%) of the patients had recurrence and only one died from prostate cancer.CONCLUSIONSPreoperative enzymatic serum TAP, PFAP and ALP levels are not predictors of the severity of disease or PSA disease‐free recurrence after RRP.
Minding Animals, Minding Earth: Old Brains, New Bottlenecks
Authors: Bekoff Marc 
Published: December 2003

Abstract. I emphasize the importance of broadening behavioral, ecological, and conservation science into a more integrative, interdisciplinary, socially responsible, compassionate, spiritual, and holistic endeavor. I stress the significance of studies of animal behavior, especially ethological research concerned with animal emotions in which individuals are named and recognized for their own personalities, for helping us to learn not only about the nonhuman animal beings with whom we share Earth but also about who we are and our place in nature. We are best understood in relationship with others. To this end I develop the notions of “minding animals” and “deep ethology.” Animals are sources of wisdom, a way of knowing.We are all citizens of Earth, members of a global community in which intimate reciprocal and beneficent peaceful relationships are mandatory. A world without cruelty and with boundless compassion, respect, grace, humility, spirituality, and love would be a better world in which to live. We have compelling responsibilities for making Earth a better and more peaceful habitat for all beings. It is essential that we do better than our ancestors. We must reflect and step lightly as we “redecorate” nature. Time is not on our side.I plead for the development of heartfelt and holistic science that allows for joy and play. Science need not be suspicious of things it cannot fully understand. We must not avert our eyes or other senses from the eyes and voices of other beings who urgently need our uncompromising and unconditional aid and love. We can do much more than we have done for animals and the Earth.
Decision Making with Uncertain Judgments: A Stochastic Formulation of the Analytic Hierarchy Process*
Authors: Hahn Eugene D. 
Published: December 2003

ABSTRACTIn the analytic hierarchy process (AHP), priorities are derived via a deterministic method, the eigenvalue decomposition. However, judgments may be subject to error. A stochastic characterization of the pairwise comparison judgment task is provided and statistical models are introduced for deriving the underlying priorities. Specifically, a weighted hierarchical multinomial logit model is used to obtain the priorities. Inference is then conducted from the Bayesian viewpoint using Markov chain Monte Carlo methods. The stochastic methods are found to give results that are congruent with those of the eigenvector method in matrices of different sizes and different levels of inconsistency. Moreover, inferential statements can be made about the priorities when the stochastic approach is adopted, and these statements may be of considerable value to a decision maker. The methods described are fully compatible with judgments from the standard version of AHP and can be used to construct a stochastic formulation of it.
Does Knowledge Mediate the Effect of Context on Performance? Some Initial Evidence
Authors: Dröge Cornelia , Claycomb Cindy , Germain Richard 
Published: December 2003

ABSTRACTThis research examines the links among four firm context variables, knowledge, and financial performance. Adopting a knowledge‐based, contingency view of the firm and assuming that strategy's locus is knowledge creation and application, we hypothesize that knowledge completely mediates the effects of context on performance. The results from analyzing 208 manufacturers found a positive relationship between applied knowledge and financial performance, but none between knowledge creation and performance. As for context, production technology routineness and low demand unpredictability were positively related only to greater applied knowledge; high technological turbulence was positively related to both knowledge creation and knowledge application; and firm size had no effect on either knowledge construct. No direct context‐performance relationships were found (i.e., all effects were indirect): knowledge, in particular applied knowledge, completely mediated the impact of context on performance.
Confirmatory Factor Analysis of the End‐User Computing Satisfaction Instrument: Replication within an ERP Domain*
Authors: Somers Toni M. , Nelson Klara , Karimi Jahangir 
Published: December 2003

ABSTRACTOver the past decade, organizations have made significant investments in enterprise resource planning (ERP) systems. The realization of benefits from these investments depends on supporting effective use of information technology (IT) and satisfying IT users. User satisfaction with information systems is one of the most important determinants of the success of those systems. Drawing upon a sample of 407 end users of ERP systems and working within the framework of confirmatory factor analysis (CFA), this study examines the structure and dimensionality, and reliability and validity of the end‐user computing satisfaction (EUCS) instrument posited by Doll and Torkzadeh (1988). In response to Klenke's (1992) motion to cross‐validate management information system (MIS) instruments and to retest the end user computing satisfaction instrument using new data, this study's results, consistent with previous findings, confirm that the EUCS instrument maintains its psychometric stability when applied to users of enterprise resource planning application software. Implications of these results for practice and research are provided.
Multiple Conceptualizations of Small Business Web Use and Benefit*
Authors: Pflughoeft Kurt A. , Ramamurthy K. , Soofi Ehsan S. , Yasai‐Ardekani Masoud , Zahedi Fatemeh (Mariam) 
Published: December 2003

ABSTRACTSmall businesses play an important role in the U.S. economy and there is anecdotal evidence that use of the Web is beneficial to such businesses. There is, however, little systematic analysis of the conditions that lead to successful use of and thereby benefits from the Web for small businesses. Based on the innovation adoption, organizations, and information systems (IS) implementation literature, we identify a set of variables that are related to adoption, use, and benefits of information technology (IT), with particular emphasis on small businesses. These variables are reflective of an organization's contextual characteristics, its IT infrastructure, Web use, and Web benefits. Since the extant research does not suggest a single theoretical model for Web use and benefits in the context of small businesses, we adopt a modeling approach and explore the relationships between “context‐IT‐use‐benefit” (CIUB) through three models—partial‐mediator, reduced partial‐mediator, and mediator. These models posit that the extent of Web use by small businesses and the associated benefits are driven by organizations’ contextual characteristics and their IT infrastructure. They differ in the endogeneity/exogeneity of the extent of IT sophistication, and in the direct/mediated effects of organizational context. We examine whether the relationships between variables identified in the literature hold within the context of these models using two samples of small businesses with national coverage, including various sizes, and representing several industry sectors. The results show that the evidence for patterns of relationships is similar across the two independent samples for two of these models. We highlight the relationships within the reduced partial‐mediator and mediator models for which conclusive evidence are given by both samples. Implications for small business managers and providers of Web‐based technologies are discussed.
The Baculovirus GP64 Protein Mediates Highly Stable Infectivity of a Human Respiratory Syncytial Virus Lacking Its Homologous Transmembrane Glycoproteins
Authors: Oomens A. G. P. , Wertz Gail W. 
Published: December 2003

ABSTRACT

Baculovirus GP64 is a low-pH-dependent membrane fusion protein required for virus entry and cell-to-cell transmission. Recently, GP64 has generated interest for practical applications in mammalian systems. Here we examined the membrane fusion function of GP64 from
Autographa californica multiple nucleopolyhedrovirus
(Ac
M
NPV) expressed in mammalian cells, as well as its capacity to functionally complement a mammalian virus, human respiratory syncytial virus (HRSV). Both authentic GP64 and GP
64/F
, a chimeric protein in which the GP64 cytoplasmic tail domain was replaced with the 12 C-terminal amino acids of the HRSV fusion (F) protein, induced low-pH-dependent cell-cell fusion when expressed transiently in HEp-2 (human) cells. Levels of surface expression and syncytium formation were substantially higher at 33°C than at 37°C. The open reading frames (ORFs) encoding GP64 or GP
64/F
, along with two marker ORFs encoding green fluorescent protein (GFP) and β-glucuronidase (GUS), were used to replace all three homologous transmembrane glycoprotein ORFs (small hydrophobic SH, attachment G, and F) in a cDNA of HRSV. Infectious viruses were recovered that lacked the HRSV SH, G, and F proteins and expressed instead the GP64 or GP
64/F
protein and the two marker proteins GFP and GUS. The properties of these viruses, designated RSΔ
sh,g,f
/GP64 or RSΔ
sh,g,f
/GP
64/F
, respectively, were compared to a previously described HRSV expressing GFP in place of SH but still containing the wild-type HRSV G and F proteins (RSΔ
sh
[A. G. Oomens, A. G. Megaw, and G. W. Wertz, J. Virol., 77:3785-3798, 2003]). By immunoelectron microscopy, the GP64 and GP
64/F
proteins were shown to incorporate into HRSV-induced filaments at the cell surface. Antibody neutralization, ammonium chloride inhibition, and replication levels in cell culture showed that both GP64 proteins efficiently mediated infectivity of the respective viruses in a temperature-sensitive, low-pH-dependent manner. Furthermore, RSΔ
sh,g,f
/GP64 and RSΔ
sh,g,f
/GP
64/F
replicated to higher levels and had significantly higher stability of infectivity than HRSVs containing the homologous HRSV G and F proteins. Thus, GP64 and a GP64/HRSV F chimeric protein were functional and efficiently complemented an unrelated human virus in mammalian cells, producing stable, infectious virus stocks. These results demonstrate the potential of GP64 for both practical applications requiring stable pseudotypes in mammalian systems and for studies of viral glycoprotein requirements in assembly and pathogenesis.
Evidence for an Essential Catalytic Role of the F10 Protein Kinase in Vaccinia Virus Morphogenesis
Authors: Szajner Patricia , Weisberg Andrea S. , Moss Bernard 
Published: December 2003

ABSTRACT
Temperature-sensitive mutants of vaccinia virus, with genetic changes that map to the open reading frame encoding the F10 protein kinase, exhibit a defect at an early stage of viral morphogenesis. To further study the role of the enzyme, we constructed recombinant vaccinia virus vF10V5i, which expresses inducible V5 epitope-tagged F10 and is dependent on a chemical inducer for plaque formation and replication. In the absence of inducer, viral membrane formation was delayed and crescents and occasional immature forms were detected only late in infection. When the temperature was raised from 37 to 39°C, the block in membrane formation persisted throughout the infection. The increased stringency may be explained by a mild temperature sensitivity of the wild-type F10 kinase, which reduced the activity of the very small amount expressed in the absence of inducer, or by the thermolability of an unphosphorylated kinase substrate or uncomplexed F10-interacting protein. Further analyses demonstrated that tyrosine and threonine phosphorylation of the A17 membrane component was inhibited in the absence of inducer. The phosphorylation defect could be overcome by transfection of plasmids that express wild-type F10, but not by plasmids that express F10 with single amino acid substitutions that abolished catalytic activity. Although the mutated forms of F10 were stable and concentrated in viral factories, only the wild-type protein complemented the assembly and replication defects of vF10V5i in the absence of inducer. These studies provide evidence for an essential catalytic role of the F10 kinase in vaccinia virus morphogenesis.