bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of State‐of‐the‐Art Classification Techniques for Expert Automobile Insurance Claim Fraud Detection
Authors: Viaene Stijn , Derrig Richard A. , Baesens Bart , Dedene Guido
Published: March 2003

Several state‐of‐the‐art binary classification techniques are experimentally evaluated in the context of expert automobile insurance claim fraud detection. The predictive power of logistic regression, C4.5 decision tree,k‐nearest neighbor, Bayesian learning multilayer perceptron neural network, least‐squares support vector machine, naive Bayes, and tree‐augmented naive Bayes classification is contrasted. For most of these algorithm types, we report on several operationalizations using alternative hyperparameter or design choices. We compare these in terms of mean percentage correctly classified (PCC) and mean area under the receiver operating characteristic (AUROC) curve using a stratified, blocked, ten‐fold cross‐validation experiment. We also contrast algorithm type performance visually by means of the convex hull of the receiver operating characteristic (ROC) curves associated with the alternative operationalizations per algorithm type. The study is based on a data set of 1,399 personal injury protection claims from 1993 accidents collected by the Automobile Insurers Bureau of Massachusetts. To stay as close to real‐life operating conditions as possible, we consider only predictors that are known relatively early in the life of a claim. Furthermore, based on the qualification of each available claim by both a verbal expert assessment of suspicion of fraud and a ten‐point‐scale expert suspicion score, we can compare classification for different target/class encoding schemes. Finally, we also investigate the added value of systematically collecting nonflag predictors for suspicion of fraud modeling purposes. From the observed results, we may state that: (1) independent of the target encoding scheme and the algorithm type, the inclusion of nonflag predictors allows us to significantly boost predictive performance; (2) for all the evaluated scenarios, the performance difference in terms of mean PCC and mean AUROC between many algorithm type operationalizations turns out to be rather small; visual comparison of the algorithm type ROC curve convex hulls also shows limited difference in performance over the range of operating conditions; (3) relatively simple and efficient techniques such as linear logistic regression and linear kernel least‐squares support vector machine classification show excellent overall predictive capabilities, and (smoothed) naive Bayes also performs well; and (4) the C4.5 decision tree operationalization results are rather disappointing; none of the tree operationalizations are capable of attaining mean AUROC performance in line with the best. Visual inspection of the evaluated scenarios reveals that the C4.5 algorithm type ROC curve convex hull is often dominated in large part by most of the other algorithm type hulls.
Firm Size and Growth in the United Kingdom Life Insurance Industry
Authors: Hardwick Philip , Adams Mike
Published: March 2003

This study tests whether the organic growth rates of United Kingdom (UK) life insurance firms are independent of size, as predicted by Gibrat's (1931) Law of Proportionate Effects. Using data for 1987–1996 and the three subperiods, 1987–1990, 1990–1993, and 1993–1996, we find that smaller life insurance firms tended to grow faster than larger ones in the 1987–1990 period and that larger life insurers tended to grow faster than smaller ones in the 1990–1993 and 1993–1996 periods. But over the ten‐year period, we find no significant difference between the growth rates of small and large firms, thus supporting Gibrat's Law as a long‐run tendency in the UK life insurance industry. When we examine firm‐specific determinants of asset growth, we find evidence in 1987–1996 and 1987–1990 that more diversified life insurance firms experienced higher growth rates on average than more specialized life insurers. We also find that the growth of life insurance firms was related to input costs during the 1990–1993 and 1993–1996 subperiods.
Flexible Spending Accounts as Insurance
Authors: Cardon James H. , Showalter Mark H.
Published: March 2003

We model flexible spending accounts (FSAs) as a special type of insurance policy. We prove the following results given losses drawn from a continuous distribution: (1) the optimal election amount, F*, is increasing in the consumer's level of risk aversion; (2) F* is increasing in the level of the maximum loss; If utility is decreasing in absolute risk aversion (DARA), then F* is (3) decreasing in income and (4) increasing in the marginal tax rate.
Interactive Influences of Perceived Social Contexts on the Reading Achievement of Urban Middle Schoolers with Learning Disabilities
Authors: Fleming Jane E. , Cook Thomas D. , Stone C. Addison
Published: March 2003

This study examined the effects of social influences in the lives of an ethnically diverse sample of fifth through eighth grade students with and without learning disabilities (LD) using survey data and academic achievement scores collected in 19 Chicago public schools from 1993–1997. Similarities and differences in student perceptions of school, family, and peer group contexts were examined. In addition, longitudinal data were analyzed using hierarchical linear modeling (HLM) to identify contextual influences on changes in student reading achievement over time. Comparisons of student responses confirm and extend existing findings in the literature concerning the perceptions of students with LD of their social environments. In particular, having a learning disability was associated with consistent, mostly negative, effects on social relations across the contexts of students’ lives, regardless of gender, race, grade, and socioeconomic status. In addition, student perceptions of their friendship groups were found to have small, but significant, effects on their growth in reading achievement over the course of middle school. While students with and without LD had somewhat different views of their social contexts, the processes working within these environments appeared to affect their reading achievement in similar ways. The results suggest that careful attention should be paid to the social contexts of students’ lives when planning academic interventions.
Financial Control in Australian Government Budgeting
Authors: Robinson Marc
Published: March 2003

With the arrival of accrual accounting and “accrual output budgeting,” there have been huge changes in the mechanism of central financial control in the budget‐dependent Australian public sector. This article outlines and evaluates these changes. The new parliamentary appropriations arrangements are discussed, as is the increased role played by nonappropriated departmental “own‐source” funding. The shift of emphasis from legislative to administrative financial controls is noted and analyzed. Consideration is given to the implications of this shift of emphasis, and of the increased complexity of the financial control framework, for fiscal transparency and democratic accountability.
The Impact of Communication Strategy on Launching New Products: The Moderating Role of Product Innovativeness
Authors: Lee Yikuan , Colarelli O'Connor Gina
Published: March 2003

Academic literature is filled with debate on whether product innovativeness positively impacts new product performance (NPP) because of increasing competitive advantage or negatively impacts performance due to consumers' fears of novel technology and resultant resistance to adopt. This study investigates this issue by modeling product innovativeness as a moderator that influences the relationship between communication strategy and new product performance. The authors emphasize that the impact of innovativeness to producers is different from that to consumers and that the differences have strategic impact when commercializing highly innovative products. Product innovativeness is conceptualized as multidimensional, and each dimension is tested separately. Four dimensions of innovativeness are explored—product newness to the firm, market newness to the firm, product superiority to the customer, and adoption difficulty for the customer.

In this study, communication strategy is comprised of preannouncement strategy and advertising strategy. First, the relationship between whether or not a preannouncement is offered and NPP is explored. Then three types of preannouncement messages (customer education, anticipation creation, and market preemption) are investigated. Advertising strategy is characterized by whether the advertisement campaign at the time of launch was based primarily on emotional or functional appeals.

Using empirical results from 284 surveys of product managers, the authors find that the relationship between communication strategy and NPP is moderated by innovativeness, and that the relationships differ not only by degree but also by type of innovativeness. Implications for research and practice are discussed.
The Ombudsman Revisited: Thirty Years of Hawaiian Experience
Authors: Hill Larry B.
Published: March 2003

This article examines the classical, or real, ombudsman. Unlike quasi ombudsmen, which are bureaucratic control mechanisms subject to executive leaders or agency administrators, real ombudsmen are operationally independent officials of the legislative branch. In 1969, the state of Hawaii was the first to create a real ombudsman. Although Iowa, Nebraska, Alaska, and Arizona have since followed Hawaii's lead, no intensive, long‐term study of American ombudsmen has yet been published. This article examines the ombudsman as a monitor of Hawaii's bureaucracies and considers the extent to which the office has become institutionalized over the past 30 years. Nearly 75,000 citizens have had their complaints investigated by the ombudsman, and more than one‐fifth of them were rectified, that is, the agency reversed its original action. This study indicates that the classical ombudsman can become institutionalized in the United States. The findings have policy implications as jurisdictions at the federal, state, and local levels consider the creation of ombudsmen or quasi ombudsmen.
Government Responses to Terrorism: Critical Views of Their Impacts on People and Public Administration
Authors: Haque M. Shamsul
Published: March 2003

Following the tragic, massive terrorist attacks on the United States in September 2001, many antiterrorist laws, policies, and institutions have emerged to wage war on terrorism. These antiterrorist initiatives have major consequences for individuals, societies, and nations all over the world. Although controversies have proliferated with regard to the implications of counterterrorism for people’s basic rights, the debate remains fragmented and often unfocused. This article examines the critical impact of new antiterrorist initiatives on the fundamental rights and responsibilities of citizens and others, with special reference to public administration.
Issues of Federalism in Response to Terrorism
Authors: Kincaid John , Cole Richard L.
Published: March 2003

The terrorist attacks of September 11, 2001, provoked, among other reactions, considerable commentary about the future of American federalism, particularly predictions of administrative centralization. To assess the potential impact of terrorism on U.S. intergovernmental relations and the ways the federal system should respond, members of the American Political Science Association’s Section on Federalism and Intergovernmental Relations were surveyed in late 2001. Generally, these federalism scholars believe the September 11 terrorism will have little effect on intergovernmental relations or on the U.S. Supreme Court’s state–friendly jurisprudence, and the surge in public trust and confidence in the federal government will be short–lived. The scholars tend to support a highly federalized response to terrorism, but with intergovernmental cooperation. Partisan differences among the scholars on policy options, however, mirror the party differences in Congress and the resurgence of “politics as usual” less than a year after September 11, 2001.
Consequences and Costs of Closing a Publicly Funded Methadone Maintenance Clinic
Authors: Alexandre Pierre Kebreau , Salome Helena J. , French Michael T. , Rivers James E. , McCoy Clyde B.
Published: March 2003

Objective. We examine volunteering to support the relief effort after the bombing of the Murrah Federal Building. We address two issues: (1) how widespread was volunteering and what forms did it take, and (2) does Wilson and Musick’s (1997a) “integrated theory of volunteer work” help to explain variation in volunteering in this disaster situation? Methods. We use data from the 1996 Oklahoma City Survey (OKC Survey). The 1996 OKC Survey is based on a random sample of the adult population of Oklahoma City and was administered 10 months after the bombing. Results. Nearly 75 percent of the sample respondents volunteered to support the relief effort in at least one way; giving money and donating nonprofessional goods or services were the two most prevalent volunteer activities. Socioeconomic status, knowing someone killed or injured in the bombing, belonging to voluntary organizations before the bombing, and being affiliated with a religious denomination were predictors of volunteering, depending on the type of volunteer activity considered. Conclusions. The magnitude of volunteering after the Murrah Building bombing was in line with volunteer efforts after other disasters. The integrated theory of volunteer work is a useful framework for studying volunteering after disasters.
Do Banks Provide Financial Slack?
Authors: Hadlock Charles J. , James Christopher M.
Published: March 2003

We study the decision to choose bank debt rather than public securities in a firm's marginal financing choice. Using a sample of 500 firms over the 1980 to 1993 time period, we find that firms are relatively more likely to choose bank loans when variables that measure asymmetric information problems are elevated. The sensitivity of the likelihood of choosing bank debt to information problems is greater for firms with no public debt outstanding. These results are consistent with the hypothesis that banks help alleviate asymmetric information problems and that firms weigh these information benefits against a wide range of contracting costs when choosing bank financing.
Effects of Corporate Diversification on Productivity
Authors: Schoar Antoinette
Published: March 2003

Using plant‐level observations from the Longitudinal Research Database I show that conglomerates are more productive than stand‐alone firms at a given point in time. Dynamically, however, firms that diversify experience a net reduction in productivity. While the acquired plants increase productivity, incumbent plants suffer. Moreover, stock prices track firm productivity and this tracking is equally strong for diversified and stand‐alone firms. Therefore, lower transparency of conglomerates is unlikely to explain the discrepancy between productivity and stock prices on average. Finally, I offer some evidence that this discrepancy may arise because conglomerates dissipate rents in the form of higher wages.
Policy Developments for Workplace Gender Equity in a Global Era: The Importance of the EU in the UK
Authors: WALBY SYLVIA
Published: March 2003

abstract This article asks whether attempts to achieve gender equity in the workplace are limited by globalization. On the one hand, globalization has been seen to curtail ambitions for equity in employment because of the increased power of global capital as compared with labor, including within the state. On the other hand, there are two counter tendencies. One is the modernization of the gender regime, which has restructured gender inequalities and developed new political constituencies among women, and the other is the development of new polities, in particular the European Union, in response to the perceived challenge of globalization. I investigate the impact of these crosscutting changes on policies aimed at gender equity in the workplace in the UK. I consider data on changes in gender equity in the workplace and developments in employment policy, especially increased education and the changing regulation of working time and equal opportunities policies. The article concludes that globalization does not lead to the weakening of all polities, that the EU has become increasingly powerful in the context of globalization, and that despite the weakening of labor, the increased education of women and the increased articulation of women's political voices has led to improvements in some dimensions of the position of some women in employment.
FAMILY NONUNIVERSAL Z′ AND b → sγ DECAY
Authors: SEVER RAMAZAN , AYDEMIR AYTEKIN
Published: March 2003

We have calculated the branching ratio and CP asymmetry of B → Xsγ decay within the family nonuniversal Z′ models. We have established certain bounds on the model parameters using the present experimental bounds. We also comment on the role of family nonuniversality in the hadronic decay modes of the B meson.
EXPERIMENTAL EVIDENCE FOR SPATIOTEMPORAL STABILITY AND CONTROL OF A ONE-WAY OPEN CML
Authors: IMAI TAKUYA , KONISHI KEIJI , KOKAME HIDEKI , HIRATA KENTARO
Published: March 2003

We present an experimental evidence for spatiotemporal stability of a real one-way open coupled map lattice implemented by electronic circuits. Furthermore, it is shown that the decentralized delayed feedback control method can suppress the spatial instability and the spatiotemporal chaos in the coupled map lattice circuits.
Tactile sensory function in the forearm of the monotreme Tachyglossus aculeatus
Authors: Mahns David A. , Coleman Gordon T. , Ashwell Ken W.S. , Rowe Mark J.
Published: March 2003

Peripheral tactile neural mechanisms in the forepaw of the echidna (Tachyglossus aculeatus, from the order Monotremata) were investigated to establish the extent of correspondence or divergence that has emerged over the widely different evolutionary paths taken by monotreme and placental mammals. Electrophysiological recordings were made in anesthetized echidnas from 29 single tactile sensory nerve fibers isolated in fine strands of the median or ulnar nerves of the forearm. Controlled tactile stimuli were applied to the forepaw glabrous skin to classify fibers, initially, into two broad divisions, according to their responses to static skin displacement. One displayed slowly adapting (SA) response properties, and the other showed a selective sensitivity to the dynamic components of the skin displacement. The SA class was made up of low‐threshold SA fibers and other less sensitive SA fibers, and the purely dynamically sensitive tactile fibers could be subdivided according to vibrotactile sensitivity and receptive field characteristics into a rapidly adapting (RA) class, sensitive to low‐frequency (≤50‐Hz) vibration, that resembled a corresponding RA class in placental species, and another class, sensitive to a broader range of vibrotactile frequencies (∼50–300 Hz), that may represent a monotreme equivalent of the Pacinian corpuscle (PC)‐related fiber class of placental mammals. The differential tactile sensitivity of the three principal fiber classes and their individual coding characteristics, determined by quantitative stimulus‐response analysis, indicate, first, that this triad of fiber classes can subserve high‐acuity tactile signalling from the echidna footpad and, second, that peripheral tactile sensory mechanisms are highly conserved across evolutionarily divergent mammalian orders. J. Comp. Neurol. 459:173–185, 2003. © 2003 Wiley‐Liss, Inc.
A statistical method for judging synergism: application to an endocrine disruptor animal experiment
Authors: Matsunaga Nobuhito , Kanno Jun , Yoshimura Isao
Published: March 2003

This article proposes a statistical method for judging whether or not the combined action of chemicals is synergistic, being focused on the case in which two or more endocrine disruptors are made to act simultaneously. After defining synergism, the synergistic relation of two chemicals is formulated for a higher response than that expected under an exchangeable relation between them. Using this formulation as a basis, we then rationalize the triangular design for an animal experiment in which all dose settings are controlled within a triangle domain that prescribes the sum of doses of simultaneously applied chemicals less than a certain level. In addition, a statistical test is proposed for judging the synergism among chemicals used in animal experiments, i.e. the test evaluates the discrepancy between the observed mean response from simultaneous administration groups of chemicals and an estimated response under the null hypothesis of zero interaction based on data from single administration groups. Finally, test performance is examined using a simulation study and a case study—the rodent uterotrophic assay. The simulation study revealed that the test is not superior in power to the standard analysis of variance test based on a linear model with interaction term, yet robust in the sense that type I errors under variance heterogeneity were better controlled using Welch correction than the analysis of variance test. The application of the proposed statistical test to an animal experiment is considered acceptable based on results. Copyright © 2003 John Wiley & Sons, Ltd.
HLA‐A, ‐B, ‐C polymorphism in a UK Ashkenazi Jewish potential bone marrow donor population
Authors: Cox S.T. , Marsh S.G.E. , Scott I. , Clayton J. , Argüello J.R. , McWhinnie A.J. , Prokupek B. , Holman R. , Madrigal J.A. , Little A.‐M.
Published: March 2003

To further our knowledge of HLA polymorphism in different ethnic populations and to increase the number of full HLA class I typed potential bone marrow donors on the Anthony Nolan Bone Marrow Trust register, HLA‐A, ‐B and ‐C polymorphism was characterised in 412 Ashkenazi Jewish potential donors. Serological typings and limited molecular analysis was performed for HLA‐A and ‐B, and molecular typings were performed for HLA‐C. Gene and haplotype frequencies were calculated using the maximum likelihood method and compared with UK Caucasoid and other Jewish populations. While the specificities identified were in general overlapping with the UK Caucasoid data, a difference in the frequencies of individual specificities was observed. For example, HLA‐B62, a common serotype found in the UK Caucasoid population, is almost absent in the Ashkenazim. HLA‐A, ‐C, ‐B haplotype frequencies also differ between the two populations with A26‐Cw*1203‐B38 and A24‐Cw*04‐B35 significant in the Ashkenazim, whilst A1‐Cw*07‐B8, a common Caucasoid haplotype, was found to be less frequent. Overall the results for the UK Ashkenazi population were most similar to previous reports on Polish/Russian Jews.
Characterization of a novel HLA‐A2 variant, A*02012, in the Southern Thai‐Muslim population
Authors: Scheltinga S.A. , Van Der Zwan A.‐W. , Mongkolsuk T. , Sujirachato K. , Chiewsilp P. , Tilanus M.G.J.
Published: March 2003

Southern Thai Muslims (STM) – from Nakon Si Thammarat, whose ancestors come mainly from Malaysia – constitute more than half of all Thai Muslims which, in total, represent approximately 10% of the country’s population. The most common A2 subtypes in STM were A*0203 (n=15), A*0201 (n=8) and A*0207 (n=7). In this study, samples with unexpected amplification patterns were sequenced. Three individuals were indicative of a novel A2 allele, now known as A*02012
Note.
Association of tumor necrosis factor receptor 2 (TNFR2) polymorphism with susceptibility to systemic lupus erythematosus
Authors: Komata T. , Tsuchiya N. , Matsushita M. , Hagiwara K. , Tokunaga K.
Published: March 2003

Multiple genetic as well as environmental factors are considered to be involved in the development of systemic lupus erythematosus (SLE). A number of previous studies have suggested a possible role for tumor necrosis factor (TNF) in the pathogenesis of SLE. In addition, one of the candidate loci suggested by the genome‐wide linkage analysis corresponds to the chromosomal position encompassing the TNF receptor 2 gene (TNFR2). The purpose of this study was to analyze the polymorphism of TNFR2 and its possible association with the susceptibility to SLE, using the case‐control association analysis. Polymorphism screening of the exons containing previously reported nonsynonymous base substitutions was carried out by the polymerase chain reaction (PCR)‐single strand conformation polymorphism (SSCP) method, using genomic DNA from 81 Japanese patients with SLE and 207 healthy individuals. Two alleles were present in exon 6, coding for methionine (196M) and arginine (196R) at position 196. 30 of 81 patients (37.0%) with SLE were positive for the 196R allele, which was significantly more frequent compared with 39 of 207 healthy individuals (18.8%) (χ2=10.6, df=1, P=0.001, odds ratio=2.53, 95% CI: 1.45–4.43). Genotype analysis revealed that the presence of one 196R allele was sufficient for rendering susceptibility. The association of 196R allele with SLE was independent from that of HLA‐DRB1*1501. In conclusion, the TNFR2 196R allele was found to be significantly associated with the susceptibility to SLE in the Japanese population. Further population and functional studies will be of particular importance to establish TNFR2 as one of the susceptibility genes to SLE.
There is more to HLA‐C than exons 2 and 3: sequencing of exons 1, 4 and 5
Authors: Van Der Vlies S.A. , Voorter C.E.M. , Van Den Berg‐Loonen E.M.
Published: March 2003

HLA‐C was shown to be a highly polymorphic gene which can be accurately typed for by sequencing methodologies. Most HLA‐C sequence‐based typing protocols described so far are based on analysis of sequence data of exons 2 and 3. Nonetheless, exons 1, 4 and 5 also contain nucleotide substitutions which contribute to the polymorphisms of the HLA‐C locus. Ten alleles contain polymorphic positions in exons 1, 4 and 5, Cw*0701/06, Cw*12021/2, Cw*15051/2, Cw*1701/02, and Cw*1801/02. Here we describe a reliable solid‐phase sequence‐based typing strategy for sequencing exons 1, 4 and 5, which is an extended protocol of our previous HLA‐C study. A panel of 16 individuals, carrying 27 different Cw‐alleles, was typed for exons 1, 4 and 5 to check the newly designed primers. No allelic dropout or preferential amplification was noticed in these individuals. The panel was also sequenced in order to check the known polymorphisms present in exons 1, 4 and 5. For exon 5 the sequences of the alleles Cw*0302, *0501 and *07011 did not correspond with the published data. In addition, exons 1, 4 and 5 were sequence‐based typing typed in 28, 17 and 59 individuals, respectively. Two new alleles were detected which contain polymorphic positions outside exons 2 and 3, Cw*07012 and Cw*1703. The unknown sequence data of exons 1, 4 and 5 of the alleles Cw*02024, *0308, *1506 and *16041 were elucidated. The described high‐resolution sequence‐based typing protocol for sequencing exons 1, 4 and 5 will be a valuable tool to study the HLA‐C locus for polymorphisms outside exons 2 and 3 and for identification of the presently known HLA‐C alleles with polymorphic positions in these exons.
Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis
Authors: Takashige N. , Naruse T.K. , Matsumori A. , Hara M. , Nagai S. , Morimoto S. , Hiramitsu S. , Sasayama S. , Inoko H.
Published: March 2003

Many studies have previously confirmed high TNFα (tumor necrosis factor‐alpha) production in sarcoidosis, and have shown that TNFα plays an important role in granuloma formation. We investigated TNFA and TNFB (lymphotoxin‐alpha) gene polymorphisms in 26 cardiac sarcoidosis patients of Japanese origin. These studies revealed a significant increase in the more uncommon TNFA2 allele in the patient group, suggesting that the TNFA gene controls the genetic susceptibility to cardiac sarcoidosis.
A nucleotide deletion in exon 4 is responsible for an HLA‐A null allele (A*0105N)
Authors: Poli F. , Bianchi P. , Scalamogna M. , Crespiatico L. , Ghidoli N. , Puglisi G. , Sirchia G.
Published: March 2003

We report herein the identification of a new HLA‐A null allele. This allele, A*0105N, was detected during histocompatibility testing of a cord blood donor and the respective mother. Serologic typing results contrasted those obtained with DNA typing that alone showed the presence of HLA‐A*01. ThisA*0105N was due to a nucleotide deletion in exon 4 that altered the reading frame, causing a premature termination Note.
Nucleotide sequence of a new HLA‐DQB1 allele, DQB1*03033
Authors: Schranz P. , Renz M. , Seelig R. , Seelig H.P.
Published: March 2003

HLA‐genotyping by sequencing of the corresponding polymerase chain reaction (PCR) product allow the identification of a new HLA‐DQB1 allele, DQB1*03033. To confirm the finding the entire exon 2 was sequenced Note.
Role of anchor residues in peptide binding to three HLA‐A26 molecules
Authors: Yamada N. , Ishikawa Y. , Dumrese T. , Tokunaga K. , Juji T. , Nagatani T. , Miwa K. , Rammensee H.‐G. , Takiguchi M.
Published: March 2003

To investigate the role of anchor residues in HLA‐A26 binding peptides, we analyzed the binding of various peptides to three HLA‐A26 molecules using the HLA class I stabilization assay. Of twenty nonamer peptides carrying anchors at P2 and P9, 3, 6 and 3 peptides bound to HLA‐A*2601, HLA‐A*2602 and HLA‐A*2603, respectively. The peptide EVIPMFSAL bound most strongly to these three HLA‐A26 molecules. Analysis using mutants of this peptide at P1, P2 or P9 showed that acidic amino acids at P1 and five hydrophobic residues (Val, Thr, Ile, Leu and Phe) at P2 are anchor residues for the three HLA‐A26 molecules while with exception of positively charged amino acids, a broad range of amino acids function as P9 anchor residues. These anchors were further evaluated using 38 nonamer peptides carrying anchor residues at P1, P2 and P9. Nineteen of these peptides bound to at least one HLA‐A26 molecule. The frequency of HLA‐A26 binding peptides was higher for peptides carrying all three anchor residues than for peptides carrying only P2 and P9 anchor residues. These results indicate that in addition to P2 and P9 anchors, the P1 anchor plays an important role in peptide binding to three HLA‐A26 molecules.
Two DR2‐associated novel alleles arose from the silent mutation of codon 72: DRB1*16012, DRB5*01012
Authors: Lin Y.‐S. , Tang T.F. , Ng J. , Hartzman R.J. , Hurley C.K.
Published: March 2003

Two DRB1*02‐associated alleles, DRB1*16012 and DRB5*01012, are described. Both alleles carry the same silent substitution at codon 72.
The HLA dictionary 1999: a summary of HLA‐A, ‐B, ‐C, ‐DRB1/3/4/5, ‐DQB1 alleles and their association with serologically defined HLA‐A, ‐B, ‐C, ‐DR and ‐DQ antigens
Authors: Schreuder G.M.tH. , Hurley C.K. , Marsh S.G.E. , Lau M. , Maiers M. , Kollman C. , Noreen H.
Published: March 2003

This report presents serologic equivalents of 90 HLA‐A, 190 HLA‐B and 145 HLA‐DRB1 alleles. The equivalents cover over 70% of the presently identified HLA‐A, ‐B and ‐DRB1 alleles. The dictionary is an update of the one published in 1997 and now also includes equivalents for HLA‐C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize information obtained by the WHO HLA Nomenclature Committee, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP) and by individual laboratories. In addition, a listing is provided of alleles which are expressed as antigens with serologic reaction patterns that differ from the well‐established HLA specificities and that often lack official WHO nomenclature. The provided equivalents will be useful in guiding searches for unrelated donors in which patients and/or potential donors are typed by either serology or DNA‐based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. Some guidelines are provided for the use of appropriate WHO HLA nomenclature for serological typings and for generic and allele specific typings obtained with molecular methods. The tables with HLA equivalents and the questionnaire for submission of serology on poorly identified alleles will also be available at the WMDA web page: www.bmdw.org/wmda.
DR2 antigens are associated with severity of disease in toxic oil syndrome (TOS)
Authors: Cárdaba B. , Ezendam J. , Gallardo S. , Del Pozo V. , Izquierdo M. , Martín C. , Cortegano I. , Aceituno E. , Rojo M. , Arrieta I. , Palomino P. , Posada M. , Lahoz C.
Published: March 2003

Toxic oil syndrome (TOS) was an epidemic which broke out in Spain in 1981, caused by the ingestion of rapeseed oil denatured with 2% aniline and sold illegally as edible oil. More than 20,000 people were affected and mortality rate was 8.4%. Genetic susceptibility appears to be involved in the pathology of this disease. Several reports have described association between the chronic stage of the disease and DR‐DQ antigens (DR3, DR4, DR2 and DQ8). In the present work, we have reassessed the HLA class II antigens in a well‐designed case‐control study. Triplets of subjects (n=265) composed by chronic patients (n=117), non‐affected family members (n=71) and non‐related controls (n=77) were studied. Also, HLA class II antigens were analyzed in patients who had died from TOS (n=34) and in TOS control patients who died from other non‐TOS related causes (n=13). Regarding surviving patients no significant association was found between HLA and disease. In contrast, an increase in phenotypic frequency of DR2 antigen, was found in patients who had died from TOS (73.5%) compared with the whole study group: TOS‐affected alive patients (25.6%, corrected P<0.001), non‐affected family members (28.5%, corrected P<0.001), non‐related controls (23.9%, corrected P<0.001) and dead controls (38.4%, P=0.03).
Identification of the novel allele HLA‐A*6813 in two members of a family of Syrian origin: implications for bone marrow transplantation
Authors: Elsner H.‐A. , Pastucha L.T. , Rebmann V. , Grosse‐Wilde H. , Blasczyk R.
Published: March 2003

The identification of the new allele HLA‐A*6813, which was found in a woman of Syrian origin and her son, is described. In the sequence analysis the new allele differs from A*68011 by positions 259 (A>G) and 261 (C>G) in exon 2. As the structure is thus identical to the HLA‐A consensus sequence it is likely that the new allele originated by gene conversion. At the protein level, the new allele has one amino acid difference from A*6801 (Asn63Glu), which results in a distinct banding pattern in one dimensional‐isoelectric focusing. Amino acid residue 63 contributes to the formation of pocket A and B and is thus important for peptide binding. A*6813 was serologically detectable only by two of six polyclonal, but by three monoclonal antisera. The restricted serological A68 activity may be explained by altered peptide binding as presented peptides can affect the serological recognition of major histocompatibility complex (MHC) class I molecules. Moreover, our findings suggest that a possible mismatch with the other known A*68 variants may impair clinical outcome of bone marrow transplantation( Note).
Large‐scale DNA‐based typing of HLA‐A and HLA‐B at low resolution is highly accurate specific and reliable
Authors: Hurley C.K. , Maiers M. , Ng J. , Wagage D. , Hegland J. , Baisch J. , Endres R. , Fernandez‐Vina M. , Heine U. , Hsu S. , Kamoun M. , Mitsuishi Y. , Monos D. , Noreen H. , Perlee L. , Rodriguez‐Marino S. , Smith A. , Stastny P. , Trucco M. , Yang S.Y. , Yu N. , Holsten R. , Hartzman R.J. , Setterholm M.
Published: March 2003

DNA‐based typing of HLA class I alleles of the HLA‐A and HLA‐B loci using sequence‐specific oligonucleotide primers and/or probes has been used for the large‐scale typing of individuals for the National Marrow Donor Program® unrelated donor registry. Typing was performed by 16 laboratories at a low level of resolution (e.g. A*01, B*07). The results of blinded quality control analysis for the first 12 months of the project show the typing to be highly accurate, specific and reliable. The total error rate based on 11,545 HLA‐A and 11,428 HLA‐B assignments was 1.1% for HLA‐A and 1.9% for HLA‐B. This level of accuracy is particularly remarkable because the quality control samples could not be distinguished from 64,180 donor samples tested at the same time by the laboratories.
A unique second donor splice site in the intron 5 sequence of the HLA‐A*11 alleles results in a class I transcript encoding a molecule with an elongated cytoplasmic domain
Authors: Tijssen H.J. , Sistermans E.A. , Joosten I.
Published: March 2003

Full‐length cDNA sequencing of the A*1103 allele revealed an insertion of 18 bp between exon 5 and 6. We hypothesized that this could be the result of alternative splicing. Sequencing of intron‐5 of A*1101, *1102 and *1103 alleles demonstrated that this 18‐bp insertion consisted of the 5′‐end of intron 5, concluded by a second in‐frame donor splice site. Alignment of the 5′‐end intron 5 sequence of A*1101–3 with that of A*0101, *0201 and 0301 revealed a unique polymorphism at position 17 of the intron (A to G) that created this second donor splice site. To exclude the possibility of an Epstein‐Barr virus (EBV)‐induced event, reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis was performed on both peripheral blood mononuclear cells (PBMC) and EBV‐transformed b‐LcL’s of several A*11‐positive individuals, using primers spanning exons 5 and 6. Without exception, both cell types revealed two products for A*11. Densitometric analysis using EBV‐transformed b‐LcL’s and PBMC indicated a ratio of approximately 4:1 in favor of the alternative splice product. Notably, except for the A*11’s none of the other A‐locus alleles yields this alternative splice product. Translation of this product will result in a protein that has an additional 6 amino acids in its cytoplasmic domain. This introduces a negative charge just behind the basic anchor residues of the cytoplasmic segment and results in the loss of the single potential protein kinase C phosphorylation site ( Note).
HLA‐DRB1 and DQB1 genotypes in patients with insulin‐dependent neonatal diabetes mellitus. A study of 13 cases
Authors: Marquis E. , Le Monnier de Gouville I. , Bouvattier C. , Robert J.J. , Junien C. , Charron D. , Hors J. , Diatloff‐Zito C.
Published: March 2003

Insulin‐dependent neonatal diabetes mellitus (NDM) is a rare form of diabetes with a heterogeneous genetic background. The HLA‐DRB1 and DQB1 genotypes were determined for 13 patients with NDM, from 9 unrelated families. Four patients had permanent NDM (PNDM) and 9 patients had transient NDM (TNDM). No excess of HLA susceptibility markers for type 1 diabetes (IDDM) was observed in this series of patients, whatever the forms of diabetes PNDM or TNDM. Paternal isodisomy of chromosome 6 was observed in two TNDM cases. These observations are consistent with the current hypothesis that there is a recessive susceptibility gene, at least in the transient form of the disease, unlinked to the MHC locus on chromosome 6. Although established in a short series, our results do not support an additive role of IDDM1 in the progression of the disease.
CDw149 antibodies recognize a clustered subset of CD47 molecules associated with cytoplasmic signaling molecules
Authors: Drbal K. , Černý J. , Angelisová P. , Hilgert I. , Cebecauer M. , Šinkora J. , Hořejší V.
Published: March 2003

One of the recently described antigens broadly expressed on human leukocytes is CDw149, which was defined at the 6th Human Leukocyte Differentiation Antigen (HLDA) Workshop by means of 2 monoclonal antibodies (mAbs). Molecular characterization of this antigen has been lacking. In the present study we demonstrate that these anti‐CDw149 mAbs actually recognize a clustered subset of a well‐defined membrane protein, CD47, also known as integrin‐associated protein (IAP). This clustered subset is present on leukocytes but not erythrocytes. The anti‐CDw149 mAbs bind with only low affinity to a monomeric (unclustered) subset of CD47 but with high avidity to the CD47 clusters. A fraction of CD47 is associated with large complexes containing cytoplasmic signaling molecules (Src family kinases and heterotrimeric G‐proteins) similar to glycosphingolipid‐enriched microdomains (GEMs), which may explain the previously described signaling capacity of CD47. The low‐affinity anti‐CD47 mAbs may be useful tools targeting specific receptor complexes involved in cell activation. Specific reactivity of low‐affinity mAbs with clustered subsets of cell surface antigens may more generally explain the nature of poorly defined “activation forms” or activation neoepitopes described previously for several cell surface molecules.
A point mutation in β2‐microglobulin results in loss of epitope expression
Authors: Dimaano C. , Nguyen T. , Ahmed A. , Abel E. , Schultz C.S. , Nieto M.C.
Published: March 2003

Acknowledgments:

This work was supported by a National Institutes of Health‐Minority Biomedical Research Support (MBRS) grant (S06 GM48135).

A common tool in studying the structure and function of major histocompatibility complex: (MHC) class I is the generation and analysis of β2‐microglobulin (β2m) mutations. β2m has been shown to affect proper class I antigen presentation at the level of structural functionality. Many studies characterizing β2m function in class I presentation have used antibody‐based assays. Monitoring the effect of β2m mutation on antibody epitope expression, therefore, is essential in being able to truly characterize the impact of a mutant interaction between β2m and class I. Here we describe a mutant β2m molecule, β2m #32, that in association with class I loses reactivity with the human β2m‐specific monoclonal antibody, BBM.1. However, the BBM.1 epitope remains intact when β2m #32 is free from class I association.
MICA 5.1 allele is a susceptibility marker for psoriasis in the Korean population
Authors: Choi H.B. , Han H. , Youn J.I. , Kim T.Y. , Kim T.G.
Published: March 2003

In order to investigate the possibility that the MICA gene is involved in the pathogenesis of psoriasis, microsatellite polymorphism in the transmembrane region of MICA was studied in 138 Korean patients with psoriasis and compared with 126 healthy controls. The MICA 5.1 microsatellite allele, consisting of 5.1 repetitions of GCT/AGC, showed significantly higher frequencies in all patients and in patients with type I psoriasis than in the controls. HLA‐A30‐B13‐Cw*0602‐MICA 5.1 and A1‐B37‐Cw*0602‐MICA 5.1 were found to be an extended haplotype associated with psoriasis. Our results suggest that the MICA 5.1 allele might be a genetic marker related to the early onset of psoriasis and play a secondary role to the HLA‐Cw*0602 gene or an unknown causative gene closely linked to HLA‐Cw*0602 in the genetic susceptibility to psoriasis.
A close relationship of triplet repeat polymorphism in MHC class I chain‐related gene A (MICA) to the disease susceptibility and behavior in ulcerative colitis
Authors: Sugimura K. , Ota M. , Matsuzawa J. , Katsuyama Y. , Ishizuka K. , Mochizuki T. , Mizuki N. , Seki S.S. , Honma T. , Inoko H. , Asakura H.
Published: March 2003

Major histocompatibility complex (MHC) class I chain‐related gene A (MICA) has been found near the HLA‐B gene. The MICA molecule is exclusively expressed on gastrointestinal epithelium and recognized by intestinal epithelial γδ T cells, where it exhibits a triplet repeat polymorphism in the transmembrane region. We investigated the possible correlation between MICA genetic polymorphism and ulcerative colitis (UC). Eighty‐three patients with UC and 132 unrelated controls were included in this study. All subjects were Japanese. A triplet repeat polymorphism in the transmembrane region of the MICA was determined by direct sequencing procedures after amplification by a polymerase chain reaction. A significantly higher allele and phenotype frequencies of MICA A6 allele were observed in patients with UC than controls (allele frequency: Pc=0.000011, phenotype frequency: Pc=0.0049 odds ratio=2.62). A6 homozygous patients with UC showed significantly earlier onset of UC than patients without the A6 allele (Pc=0.0042). Phenotypes of MICA A6 allele in Japanese are closely related to the disease susceptibility and behavior in UC. Examinations of MICA polymorphism in other ethnic groups may provide important information about the locus of primary responsible gene for UC.
Stratification analysis of MICA triplet repeat polymorphisms and HLA antigens associated with ulcerative colitis in Japanese
Authors: Seki S.S. , Sugimura K. , Ota M. , Matsuzawa J. , Katsuyama Y. , Ishizuka K. , Mochizuki T. , Suzuki K. , Yoneyama O. , Mizuki N. , Honma T. , Inoko H. , Asakura H.
Published: March 2003

Abstract: We previously reported a conserved haplotype of HLA B52‐DR2 and a significantly high frequency of the major histocompatibility complex (MHC) class I chain‐related gene A (MICA) transmembrane‐short tandem repeat (TM‐STR) 6 allele in Japanese patients with ulcerative colitis (UC). To examine the predominance of the MICA TM‐STR 6 allele as a marker of the susceptibility to UC within the susceptible haplotype, the association of each allele with UC was estimated following stratification of the patients to control for any possible confounding effects of other alleles positively associated with UC. Sixty‐four patients with UC and 236 unrelated healthy controls were included in this study. All subjects were Japanese. HLA‐A, ‐B, ‐C, and ‐DR antigens were determined serologically. A triplet repeat polymorphism of the MICA was determined by direct sequencing. To control for the effect of linkage disequilibrium, Mantel‐Haenszel weighed odds ratios were calculated. Significantly higher phenotype frequencies of B52, MICA TM‐STR 6, and DR2 were observed in patients with UC. Linkage disequilibria among alleles associated with UC revealed that a B52 –MICA TM‐STR 6 – DR2 haplotype was conserved in patients with UC, as in controls. When the association of HLA‐B52 was estimated after patient stratification for the possible confounding effect of MICA TM‐STR 6 or DR2, a strong significant association of B52 with UC was still observed. In contrast, no association with UC was observed for MICA TM‐STR 6 or DR2, after stratification of the possible confounding effect of HLA‐B52. These results imply that the significant increase in MICA TM‐STR 6 in Japanese patients with UC is attributable to linkage disequilibrium with HLA‐B52.
Distribution of CCR5‐Δ32 and CCR2–64I alleles in an Argentine Amerindian population
Authors: Mangano A. , Theiler G. , Sala L. , Capucchio M. , Fainboim L. , Sen L.
Published: March 2003

Abstract: In order to evaluate the frequency distributions of CCR5‐Δ32 and CCR2–64I polymorphisms in an Amerindian population, we tested a total of 42 Chiriguanos individuals that are aboriginal inhabitants of the north west of Argentina. Only one carried the CCR5‐Δ32 allele (0.0238), while 17 out of 35 carried the CCR2–64I mutation, including one homozygous for the mutated allele (0.2571). Although the cohort studied is considered highly endogamic, the HLA genotyping revealed that 8 out of 42 subjects had a gene flow from Caucasian populations. The only heterozygous CCR5+/Δ32 found and three heterozygous CCR2+/64I belonged to the admix group. In conclusion, the protective deletion CCR5‐Δ32 is practically absent in Chiriguanos whereas the CCR2–64I allele is highly frequent.
A new HLA‐Cw allele (Cw*1510), identified in a French Caucasian individual
Authors: Tamouza R. , Schaeffer V. , Marzais F. , Poirier J.C. , Fortier C. , Ramasawmy R. , Sghiri R. , Krishnamoorthy R. , Toubert A. , Charron D.
Published: March 2003

Abstract: A novel HLA‐Cw*15 allele, Cw*1510, found in a French Caucasian bone marrow recipient is described. Nucleotide sequence of the new variant is identical to the common Cw*15021 DNA sequences except nucleotides at positions 32 and 61 of exon 2. While the first difference is silent, the second cause substitution of an Histidine by an Arginine at amino acid position 21 of the α1 heavy chain domain.