bluuebunny/crossref_metadata_2025 huggingface dataset:
Sowing the Seeds of Violence in Heterosexual Relationships: Early Adolescents Narrate Compulsory Heterosexuality
Authors: Tolman Deborah L. , Spencer Renée , Rosen‐Reynoso Myra , Porche Michelle V.
Published: March 2003

In this paper, we explore how early adolescents' descriptions of their romantic relationships produce evidence of how precursors to violence are woven into the fabric of such relationships from the very beginning of their experiences of “heterosociality.” We identified Rich's (1983) concept of compulsory heterosexuality as an interpretive framework for analyzing these relationship narratives, examining qualitative data from two samples (combined n= 100) diverse in ethnicity and income to form a dialogue between youth perspectives and theory. We offer adolescents' descriptions, and our interpretations, of several themes, including the conceptualization of boys as sexual predators which normalizes such behaviors, girls' behavior in response to assumed male aggression, and boys' narration of their participation in relational processes which reproduce these beliefs and behaviors.
Computer–Mediated Negotiated Interaction: An Expanded Model
Authors: Smith Bryan
Published: March 2003

This study examines task–based, synchronous computer–mediated communication (CMC) among intermediate–level learners of English. The research specifically explores (a) whether learners engage in negotiated interaction when they encounter new lexical items, (b) whether task type has an effect on the amount of negotiation that transpires, and (c) how this computer–mediated negotiation compares to that noted in the face–to–face literature. Fourteen nonnative–nonnative dyads collaboratively completed 4 communicative tasks using ChatNet, a browser–based chat program. Each dyad completed 2 jigsaw and 2 decision–making tasks, which were each “seeded” with 8 target lexical items. The chatscripts reveal that learners do in fact negotiate for meaning in the CMC environment when nonunderstanding occurs. Furthermore, task type was found to have a definite influence on the extent to which learners engaged in negotiation, but not necessarily in the same way that has been observed in the face–to–face literature. Though the negotiation that occurs in the CMC environment proceeds in ways that are roughly similar to face–to–face negotiation, the observed differences call for a new model of computer–mediated negotiation. This new model is presented as a more accurate tool for describing computer–mediated negotiated interaction than those offered to chart face–to–face negotiation episodes.
Multiple Layers of Meaning in an Oral Proficiency Test: The Complementary Roles of Nonverbal, Paralinguistic, and Verbal Behaviors in Assessment Decisions
Authors: Jenkins Susan , Parra Isabel
Published: March 2003

This study investigated the influence of nonverbal behavior in the context of interactive talk during the assessment of an oral proficiency interview test. The participants were 4 Spanish–speaking and 4 Chinese–speaking international teaching assistants (ITAs). Microanalysis of videotaped tests indicated that interviewees who employed nonverbal behavior considered appropriate by North American evaluators and who negotiated a degree of control over the interview process were able to compensate for perceived weaker linguistic proficiency. Active nonverbal behavior as listeners and turn–takers, together with appropriate paralinguistic features in their talk in interaction, created for the raters an impression of the test taker's interactional competence. This interplay of behaviors ensured high scores for ITAs perceived to be linguistically proficient and low passing scores for those rated as linguistically weaker. The successful test takers in this study were able to modify the power dynamic and to reduce the interview asymmetry. Those participants who framed the interview as a discussion or conversation among peers were more successful than those who framed it as an examination. Implications for oral proficiency testing and ESL instruction are discussed.
Effects of Instruction in an Assignment Completion Strategy on the Homework Performance of Students with Learning Disabilities in General Education Classes
Authors: Hughes Charles A. , Ruhl Kathy L. , Schumaker Jean B. , Deshler Donald D.
Published: March 2003

Homework is an important activity in the lives of school‐aged children, including students with learning disabilities (LD). Characteristics often associated with LD (e.g., poor organizational skills) may adversely impact the rate and quality of homework completion. In this study, a multiple‐probe across‐students design (Horner & Baer, 1978) was used to evaluate the effects of instruction in a comprehensive, independent assignment completion strategy with regard to homework completion rates and the quality of products completed in response to assignments given in general education classrooms. Eight of nine students mastered use of the strategy, and their homework completion rates and the quality of their homework products improved. Associated with these improvements were increases in quarterly grades and teacher ratings of the quality of the assignments. Thus, direct instruction in a comprehensive strategy comprised of organizational behaviors can result in independent completion of more homework by students with LD. Nevertheless, instruction in organizational skills alone appears insufficient to produce a 100 percent submission rate: student motivation to complete assignments and mastery of the skills required, as well as the appropriateness of assignments for students, need to be addressed.
How Should Reading Disabilities be Operationalized? A Survey of Experts
Authors: Speece Deborah L. , Shekitka Lesley
Published: March 2003

In the face of accumulating research and logic, the use of a discrepancy between intelligence and reading achievement test scores is becoming increasingly untenable as a marker of reading disabilities. However, it is not clear what criteria might replace the discrepancy requirement. We surveyed 218 members of journal editorial boards to solicit their opinions on current and proposed definitional components and exclusion criteria. Three components were selected by over two‐thirds of the respondents: reading achievement, phonemic awareness, and treatment validity. However, only 30 percent believed IQ‐reading achievement discrepancy should be a marker. More than 75 percent of the respondents believed exclusion criteria should remain part of the definition. Mental retardation was the most frequently selected exclusion criterion despite rejection of intelligence test scores as a definitional component. Although the findings reflect uncertainty among experts on what elements should comprise a definition, they do signal a willingness to consider new approaches to the conceptually difficult task of defining reading disabilities.
We Talk About It, But Do They Get It?
Authors: Baxter Juliet , Woodward John , Voorhies Jill , Wong Jennifer
Published: March 2003

This article reports on the last of a series of iterative research studies involving students with learning disabilities in reform mathematics classrooms at the intermediate grade levels. This study reports the findings from a larger, year‐long case study that focused on ways to include students with learning disabilities and other students who are at risk for special education services in classwide discussions of problem solving. The data reported in this article detail the changes in teacher and student discourse over a nine‐week period in one classroom. Sources of data for this study included videotapes, audiotapes, and informal interviews with the teacher, a paraprofessional, and students. A quantitative analysis of the results indicates clear patterns of change in teacher and student discourse. Nonetheless, intentional efforts to include target students in the whole‐class discussions yielded instructional dilemmas that are underdescribed in the mathematics reform literature. Findings from this study have implications for special educators interested in mathematical problem solving, as well as math reformers who value the role of classroom discourse in daily instruction.
Paradigm Lost: Public Administration at Johns Hopkins University, 1884‐96
Authors: Hoffman M. Curtis
Published: March 2003

Between 1884 and 1896, Herbert Baxter Adams, James Bryce, Richard Ely, Albert Shaw, and Woodrow Wilson, participated in one of the first attempts to build a curriculum specifically aimed at educating American public servants. Their approach to curriculum development did not concentrate on government structure or management skills, but on politics, economics, history, law, and ethics. Their efforts reflected a need to justify local administration, public service, and active government in legal, moral, historical, philosophical, and practical terms. More than 100 years later, their efforts seem both awkwardly archaic and curiously relevant.
The Budget‐Minimizing Bureaucrat? Empirical Evidence from the Senior Executive Service
Authors: Dolan Julie
Published: March 2003

In a representative democracy, we assume the populace exerts some control over the actions and outputs of government officials, ensuring they comport with public preferences. However, the growth of the fourth branch of government has created a paradox: Unelected bureaucrats now have the power to affect government decisions (Meier 1993; Rourke 1984; Aberbach, Putnam, and Rockman 1981).

In this article, I rely on two competing theories of bureaucratic behavior‐representative‐bureaucracy theory and Niskanen's budget‐maximization theory‐to assess how well the top ranks of the federal government represent the demands of the citizenry. Focusing on federal‐spending priorities, I assess whether Senior Executive Service (SES) members mirror the attitudes of the populace or are likely to inflate budgets for their own personal gain. Contrary to the popular portrayal of the budget‐maximizing bureaucrat (Niskanen 1971), I find these federal administrators prefer less spending than the public on most broad spending categories, even on issues that fall within their own departments' jurisdictions. As such, it may be time to revise our theories about bureaucratic self‐interest and spending priorities.
Moral Reasoning in the Context of Reform: A Study of Russian Officials
Authors: Stewart Debra W. , Sprinthall Norman A. , Kem Jackie D.
Published: March 2003

This article reports on an exploratory study of ethical reasoning among public administrators in Russia. Survey interviews and focus group follow‐ups with civil servants participating in graduate training programs at the Russian Academy of Public Service provide information about their preferred mode of ethical reasoning; the demographic, attitudinal, organizational, and professional factors associated with that reasoning; and the behavioral choices implied. Using a sample of 113 public officials who represent a broad spectrum of regions in Russia, this study assesses moral reasoning, examines variables associated with alternative models, and compares these responses with findings from studies conducted in Poland and the United States. Based on this exploratory study, we suggest implications for theory, research, and practice.
From Responsiveness to Collaboration: Governance, Citizens, and the Next Generation of Public Administration
Authors: Vigoda Eran
Published: March 2003

The evolution of the New Public Management movement has increased pressure on state bureaucracies to become more responsive to citizens as clients. Without a doubt, this is an important advance in contemporary public administration, which finds itself struggling in an ultradynamic marketplace. However, together with such a welcome change in theory building and in practical culture reconstruction, modern societies still confront a growth in citizens’ passivism; they tend to favor the easy chair of the customer over the sweat and turmoil of participatory involvement. This article has two primary goals: First to establish a theoretically and empirically grounded criticism of the current state of new managerialism, which obscures the significance of citizen action and participation through overstressing the (important) idea of responsiveness. Second, the article proposes some guidelines for the future development of the discipline. This progress is toward enhanced collaboration and partnership among governance and public administration agencies, citizens, and other social players such as the media, academia, and the private and third sectors. The article concludes that, despite the fact that citizens are formal “owners” of the state, ownership will remain a symbolic banner for the governance and public administration–citizen relationship in a representative democracy. The alternative interaction of movement between responsiveness and collaboration is more realistic for the years ahead.
Outcomes–Based Performance Management in the Public Sector: Implications for Government Accountability and Effectiveness
Authors: Heinrich Carolyn J.
Published: March 2003

Requirements for outcomes–based performance management are increasing performance–evaluation activities at all government levels. Research on public–sector performance management, however, points to problems in the design and management of these systems and questions their effectiveness as policy tools for increasing governmental accountability. In this article, I analyze experimental data and the performance–management experiences of federal job–training programs to estimate the influence of public management and system–design factors on program outcomes and impacts. I assess whether relying on administrative data to measure program (rather than impacts) produces information that might misdirect program managers in their performance–management activities. While the results of empirical analyses confirm that the use of administrative data in performance management is unlikely to produce accurate estimates of true program impacts, they also suggest these data can still generate useful information for public managers about policy levers that can be manipulated to improve organizational performance.
The Reinvention of Public Personnel Administration: An Analysis of the Diffusion of Personnel Management Reforms in the States
Authors: Kellough J. Edward , Selden Sally Coleman
Published: March 2003

Reform is a common theme in American public administration. During the twentieth century at least 12 major administrative reforms have taken place at the federal level and countless others in state and local governments. Frequently, these reforms have addressed the operation of public personnel management systems. Recent efforts associated with the reinventing government movement, for example, have proposed numerous alterations to civil service rules and procedures, and many jurisdictions have implemented significant changes in their personnel practices. This article examines the extent to which these kinds of personnel reforms have been implemented by state governments. A reform index is developed to document the considerable variation among the states in their approach to personnel practices. Several state characteristics are associated with scores on this index, including legislative professionalism, which bears a positive relationship to reform, and the level of unemployment within a state and the proportion of state employees associated with public employee unions, which are both negatively associated with reform.
Exploring Charismatic Leadership in the Public Sector: Measurement and Consequences
Authors: Javidan Mansour , Waldman David A.
Published: March 2003

A survey of more than 203 middle and upper–middle managers that assessed their superiors (N=51) in the Canadian public sector showed that charismatic leadership in such a setting comprises four dimensions: (1) energy and determination; (2) vision; (3) challenge and encouragement; and (4) risk taking. However, such leadership is only modestly related to motivational consequences and is not significantly related to unit performance. We discuss our findings in terms of their theoretical implications for leadership research in general and for the public sector in particular.
Regime Shifts in Asian Equity and Real Estate Markets
Authors: Kallberg Jarl G. , Liu Crocker H. , Pasquariello Paolo
Published: March 2003

This paper applies a new statistical technology for identifying regime shifts to analyze recent data on real estate and equity markets in eight developing Far Eastern countries in the 1992–1998 time period. We find that regime shifts in volatility occur in the summer of 1997; however, most of the regime shifts in returns occur in the spring of 1998. While the clustering of regime breaks does not seem to follow any obvious pattern, the country’s exposure to trade and firm leverage are important. An analysis of Granger causality suggests that, in most cases, equity returns cause real estate returns but the converse is not true. We also find two‐way causality in volatility, suggesting that a common factor drives volatility in these markets. Finally, we provide evidence that the regime shifts generally imply higher relative risk for real estate securities after the estimated breaks.
Market Mechanism Choice and Real Estate Disposition: Search Versus Auction
Authors: Quan Daniel C.
Published: March 2003

We propose a model of mechanism choice in the disposition of real estate assets where we consider two alternatives: a search market and an auction. Within the search framework, we derive an equilibrium whereby buyers incur search costs and sellers incur holding costs for the period during which the property is not sold. In the auction alternative, the seller joins an existing pool of sellers in undertaking a multiple–object auction and pays a commission upon sale. Buyers and sellers freely choose their mechanisms, which in equilibrium are optimal given each group’s conjectures about the mechanism choice of their counterpart. In equilibrium, an agent cannot benefit from deviating from his choice and each agent’s beliefs are consistent with the equilibrium outcome. It is shown that (a) buyers with high search costs will choose auctions because the auction payoff imposes an upper bound on buyers' gains from search, and (b) prices at auctions will be higher. Using vacant lot sales data and a method–of–moment estimator which accounts for the presence of an endogenous discrete mechanism choice variable, we estimated a hedonic regression to detect the price effect. It was determined that, on average, lots sold for $1.44 per square foot more in auctions than in the search market, as predicted by our model.
The Urban Geography of Welfare Reform: Spatial Patterns of Caseload Dynamics in Detroit
Authors: Allard Scott W.
Published: March 2003

Objective. To assess how the characteristics of welfare recipients have varied geographically in the Detroit metropolitan area since the passage of welfare reform in 1996 and how spatial proximity to job opportunities is related to work rates among welfare recipients. Methods. Using administrative data on welfare receipt in the Detroit metropolitan area and data from two employer surveys in Detroit, I examine changes in the welfare caseload between 1992 and 2000 and estimate logit models of the probability that welfare recipients report work earnings in 1998. Results. Although the number of adult welfare recipients in the Detroit metropolitan area declined by over 75 percent between 1992 and 2000, nearly 25,000 households—most residing in the central city—continue to receive welfare. Rates of work among welfare recipients are positively related to the accessibility of employment opportunities. Conclusions. My results indicate that support services and programs in the coming years will have to fit a caseload that is changing both qualitatively and geographically. Further, consistent with the most current spatial mismatch research, my findings show that greater access to job opportunities leads to greater rates of reported work earnings among welfare recipients.
Gender and the Internet*
Authors: Ono Hiroshi , Zavodny Madeline
Published: March 2003

Objective.This article examines whether there are differences in men's and women's use of the Internet and whether any such gender gaps have changed in recent years.

Methods.We use data from several surveys during the period 1997–2001 to show trends in Internet usage and to estimate regression models of Internet usage that control for individuals’ socioeconomic characteristics.

Results.Women were significantly less likely than men to use the Internet at all in the mid‐1990s, but this gender gap in being online disappeared by 2000. However, once online, women remain less frequent and less intense users of the Internet.

Conclusions.There is little reason for concern about sex inequalities in Internet access and usage now, but gender differences in frequency and intensity of Internet usage remain.
Are Subsidiaries More Prone to Pollute? New Evidence from the EPA's Toxics Release Inventory*
Authors: Grant Don , Jones Andrew W.
Published: March 2003

Objective. Some scholars fear that because firms are no longer liable for the hazardous activities of their subsidiaries, the latter are under less corporate pressure to limit their pollution. However, researchers have yet to examine the environmental performance of subsidiaries. This reflects a more general failure on their part to test the effects different organizations have on pollution.

Methods. To begin to remedy this situation, we use data from the EPA's Toxics Release Inventory to determine whether subsidiaries emit pollutants at a higher rate than other facilities in the chemical industry.

Results. We find that subsidiaries have significantly higher emission rates than other facilities after controlling for several relevant factors.

Conclusions. Results suggest how recent research on the structural determinants of environmental degradation might be advanced by focusing on the effects of specific organizational forms.
Pass‐through and Exposure
Authors: Bodnar Gordon M. , Dumas Bernard , Marston Richard C.
Published: March 2003

Firms differ in the extent to which they “pass through” changes in exchange rates into foreign currency prices and in their “exposure” to exchange rates—the responsiveness of their profits to changes in exchange rates. Because pricing affects profitability, a firm's pass‐through and exposure should be related. This paper develops models of exporting firms under imperfect competition to study these related phenomena. From these models we derive the optimal pass‐through decisions and the resulting exchange rate exposure. The models are estimated on eight Japanese export industries using both the price data pass‐through and financial data for exposure.
Government Ownership of Banks
Authors: La Porta Rafael , Lopez‐De‐Silanes Florencio , Shleifer Andrei
Published: March 2003

We assemble data on government ownership of banks around the world. The data show that such ownership is large and pervasive, and higher in countries with low levels of per capita income, backward financial systems, interventionist and inefficient governments, and poor protection of property rights. Higher government ownership of banks in 1970 is associated with slower subsequent financial development and lower growth of per capita income and productivity. This evidence supports “political” theories of the effects of government ownership of firms.
Range‐Based Estimation of Stochastic Volatility Models
Authors: Alizadeh Sassan , Brandt Michael W. , Diebold Francis X.
Published: March 2003

We propose using the price range in the estimation of stochastic volatility models. We show theoretically, numerically, and empirically that range‐based volatility proxies are not only highly efficient, but also approximately Gaussian and robust to microstructure noise. Hence range‐based Gaussian quasi‐maximum likelihood estimation produces highly efficient estimates of stochastic volatility models and extractions of latent volatility. We use our method to examine the dynamics of daily exchange rate volatility and find the evidence points strongly toward two‐factor models with one highly persistent factor and one quickly mean‐reverting factor.
The Quiet Period Goes out with a Bang
Authors: Bradley Daniel J. , Jordan Bradford D. , Ritter Jay R.
Published: March 2003

We examine the expiration of the IPO quiet period, which occurs after the 25th calendar day following the offering. For IPOs during 1996 to 2000, we find that analyst coverage is initiated immediately for 76 percent of these firms, almost always with a favorable rating. Initiated firms experience a five‐day abnormal return of 4.1 percent versus 0.1 percent for firms with no coverage. The abnormal returns are concentrated in the days just before the quiet period expires. Abnormal returns are much larger when coverage is initiated by multiple analysts. It does not matter whether a recommendation comes from the lead underwriter or not.
New Evidence on the Market for Directors: Board Membership and Pennsylvania Senate Bill 1310
Authors: Coles Jeffrey L. , Hoi Chun‐Keung
Published: March 2003

We examine the relation between a board' decision to reject antitakeover provisions of Pennsylvania Senate Bill 1310 and subsequent labor market opportunities of those same board members. Compared to directors retaining all provisions, directors rejecting all protective provisions of SB1310 are three times as likely to gain additional external directorships and are 30 percent more likely to retain their internal slot on the board of that same Pennsylvania company. For external board seats, the results are driven by nonexecutive directors who are not members of the management team; for internal board seats, the results are driven by executive directors.
Inoculation of Plasmids Encoding Japanese Encephalitis Virus PrM-E Proteins with Colloidal Gold Elicits a Protective Immune Response in BALB/c Mice
Authors: Zhao Zijiang , Wakita Takaji , Yasui Kotaro
Published: March 2003

We established a simple and effective method for DNA immunization against Japanese encephalitis virus (JEV) infection with plasmids encoding the viral PrM and E proteins and colloidal gold. Inoculation of plasmids mixed with colloidal gold induced the production of specific anti-JEV antibodies and a protective response against JEV challenge in BALB/c mice. When we compared the efficacy of different inoculation routes, the intravenous and intradermal inoculation routes were found to elicit stronger and more sustained neutralizing immune responses than intramuscular or intraperitoneal injection. After being inoculated twice, mice were found to resist challenge with 100,000 times the 50% lethal dose (LD50) of JEV (Beijing-1 strain) even when immunized with a relatively small dose of 0.5 μg of plasmid DNA. Protective passive immunity was also observed in SCID mice following transfer of splenocytes or serum from plasmid DNA- and colloidal gold-immunized BALB/c mice. The SCID mice resisted challenge with 100 times the LD50of JEV. Analysis of histological sections detected expression of proteins encoded by plasmid DNA in the tissues of intravenously, intradermally, and intramuscularly inoculated mice 3 days after inoculation. DNA immunization with colloidal gold elicited encoded protein expression in splenocytes and might enhance immune responses in intravenously inoculated mice. This approach could be exploited to develop a novel DNA vaccine.
A NONLINEAR DYNAMICS PERSPECTIVE OF WOLFRAM'S NEW KIND OF SCIENCE PART I: THRESHOLD OF COMPLEXITY
Authors: CHUA LEON O. , YOON SOOK , DOGARU RADU
Published: March 2003

This tutorial provides a nonlinear dynamics perspective to Wolfram's monumental work on A New Kind of Science. By mapping a Boolean local Rule, or truth table, onto the point attractors of a specially tailored nonlinear dynamical system, we show how some of Wolfram's empirical observations can be justified on firm ground. The advantage of this new approach for studying Cellular Automata phenomena is that it is based on concepts from nonlinear dynamics and attractors where many fuzzy concepts introduced by Wolfram via brute force observations can be defined and justified via mathematical analysis. The main result of Part I is the introduction of a fundamental concept called linear separability and a complexity index κ for each local Rule which characterizes the intrinsic geometrical structure of an induced "Boolean cube" in three-dimensional Euclidean space. In particular, Wolfram's seductive idea of a "threshold of complexity" is identified with the class of local Rules having a complexity index equal to 2.
A random effects nonlinear regression model for analysis of environmental contamination data
Authors: Otani Keiko , Ohtaki Megu , Watanabe Shaw
Published: March 2003

The purpose of this study is to examine the relationship between dioxin concentration in humans and their living environmental factors such as diet or residential district. We develop a nonlinear random effects regression model based on a pharmacokinetic model that explains dioxin accumulation in the human body. The model takes into consideration two points: individual differences in dioxin intake and historical exposure to dioxins. We apply the model to data collected by the Japanese Ministry of Health, Labour and Welfare. Copyright © 2003 John Wiley & Sons, Ltd.
Applied personality psychology: lessons learned from the IWO field
Authors: De Fruyt Filip , Salgado Jesús F.
Published: March 2003

The industrial, work, and organizational (IWO) psychology domain might corroborate on new insights developed within the fundamental personality area, but also, vice versa, the personality field should also build upon applied research on individual differences. It is our conviction that these two fields developed too independently in the past. A selective number of issues and themes that cross the personality–IWO bridge are discussed that can be addressed in future research or implemented in professional practice, including processes explaining trait–performance relationships, trait assessment in the workplace, variable versus person centred approaches towards personality description, personality of teams and groups, and finally maladaptive personality functioning. Copyright © 2003 John Wiley & Sons, Ltd.
DLA‐DRB1 polymorphisms in dogs defined by sequence‐specific oligonucleotide probes (SSOP)
Authors: Kennedy L.J. , Carter S.D. , Barnes A. , Bell S. , Bennett D. , Ollier B. , Thomson W.
Published: March 2003

To date, DNA sequences for 29 dog DLA‐DRB1 alleles have been reported. However, no data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether there is interbreed variation of allele distribution. We have addressed this by establishing a molecular based sequence‐specific oligonucleotide probing (SSOP) method to identify all of the known broad DRB1 types and we have used this to type a random panel of dogs. A series of oligonucleotide probes were designed to detect known polymorphisms in the three DRB1 hypervariable regions, together with two distinctive motifs in other regions of exon 2. This set of probes enabled us to assign broad DRB1 types. Two hundred and eighteen dogs were SSOP typed for DRB1. All but 4 of the published DLA‐DRB1 alleles were identified in these animals. Interbreed variation in both allele distributions and allele frequencies were observed, which may be useful in the study of genetic variation between breeds. This variation also has implications for the selection of control groups for studies aimed at identifying MHC associations with disease susceptibility in the dog.
Intronic sequence motifs of HLA‐DQB1 are shared between humans, apes and old world monkeys, but a retroviral LTR element (DQLTR3) is human specific
Authors: Donner H. , Tönjes R.R. , Bontrop R.E. , Kurth R. , Usadel K.H. , Badenhoop K.
Published: March 2003

Long terminal repeats (LTRs) of the human endogenous retrovirus K (HERV‐K) family have been found at several sites within the human genome, of which one is located in the vicinity of HLA‐DQB1. Since this DQLTR3 is only present on some haplotypes, we performed a linkage analysis in 130 Caucasian families. In order to date the integration event we also investigated the presence of this DQLTR3 in apes and old world monkeys. Additionally, we sequenced the adjacent region of DQLTR3‐positive and ‐negative haplotypes in humans, apes and old world monkeys to elucidate their evolution. Linkage analysis revealed a differential integration of DQLTR3 on specific HLA‐DQ haploypes: there was a high frequency of this LTR on haplotypes containing HLA‐DQB1*0302 (0.96) and a moderate frequency on HLA‐DQB1*0402 (0.78), HLA‐DQB1*0303 (0.44), HLA‐DQB1*0502 (0.38) and HLA‐DQB1*0301 (0.35). HLA‐DQB1*0201 (0.18), HLA‐DQB1*0503 (0.15), HLA‐DQB1*0603 (0.15), HLA‐DQB1*0602 (0.04), HLA‐DQB1*0501 (0.03) and HLA‐DQB1*0604 were rarely positive or devoid of DQLTR3. In apes and old world primates there was no DQLTR3 rendering it a human specific insertion. Sequence analysis of the adjacent region showed two different motifs in humans corresponding to either presence or absence of DQLTR3. Two different motifs were observed within three sequences of Macaca mulatta: One motif is closely related to the sequence from Macaca nemestrina and Macaca fascicularis whereas the other sequence is more closely related with that of Papio papio and Cercopithecus aethiops. Therefore the analysis of retroviral elements as well as intronic sequences of MHC‐DQB1 could help to clarify the evolution of this gene region as well the phylogenic relationship between humans, apes and old world monkeys.
HLA‐DMA and HLA‐DMB alleles in German patients with type 1 diabetes mellitus
Authors: Siegmund T. , Donner H. , Braun J. , Usadel K.H. , Badenhoop K.
Published: March 2003

The HLA‐DMA and HLA‐DMB genes are located in the HLA‐D region between DQ and DP. Four variants of DMA (DMA*0101–0104) and five of the DMB (DMB*0101–0105) have so far been identified. HLA‐DM molecules are required in the process of peptide loading to HLA class II antigens, both regulating the dissociation of class II‐associated invariant chain peptides (CLIP) and the subsequent binding of exogenous peptides to HLA class II molecules. In order to investigate the immunogenetic heterogeneity within the HLA‐D susceptibility region, we analysed the distribution of DMA alleles in 125 patients with type 1 diabetes mellitus and 90 healthy controls, and of DMB alleles in 102 patients and 89 healthy controls. Patients and controls were all from central Germany. The polymerase chain reaction (PCR) amplified products were purified and separated on a 10% polyacrylamide gel electrophoresis. Among the four recognized DMA alleles, DMA*0102 was significantly less frequent (12% vs. 28.9%, P<0.01) in patients with type 1 diabetes mellitus. DMB*0101 (70.6% vs. 97.8%, P<5.5×10−3) was also reduced in frequency compared to controls. Comparing patients and controls positive for the type 1 diabetes high‐risk markers we found a significant association between DMA*0102 and DQA*0501 (9.5% vs. 39.1%, P<0.02), as well as DMB*0101 and DQA*0501 (62.5% vs. 96.2%, P<0.03). In conclusion, DMA*0102 and DMB*0101 contribute to genetic protection to type 1 diabetes mellitus in individuals with high‐risk DQA markers in the German population.
High‐resolution typing for HLA‐DRB1*15 and ‐DRB1*16 by fluorescence‐marked sequence‐specific priming (TaqMan assay)
Authors: Tremmel M. , Opelz G. , Mytilineos J.
Published: March 2003

Sequence‐specific primed polymerase chain reaction (PCR‐SSP) is widely used in HLA laboratories. The TaqMan method, which is described here for high‐resolution typing of HLA‐DRB1*15 and ‐DRB1*16, does not require elaborate and time‐consuming post‐PCR detection steps. In this one‐tube assay, conventional PCR‐SSP and fluorescence detection of the amplicon with a doubly labeled fluorescent probe are combined: a fluorogenic hybridization probe (FHP) labeled with a spectral resolvable fluorescent reporter dye (FAM or TET) at its 5′ terminus and a common quencher dye (TAMRA) at its 3′ terminus is cleaved by the 5′ nuclease activity of Taq DNA polymerase only if the target sequence is amplified. An increase of fluorescence intensity indicates a successful amplification. For high‐resolution typing of HLA‐DRB1*15 and ‐DRB1*16 alleles we designed two FHPs and 14 specific primer mixes (7 for DR15 and 7 for DR16). Amplification of the specific sequence was detected by a FAM‐labeled FHP, whereas amplification of the internal control was detected by a TET‐labeled FHP. We were able to type all heterozygous DRB1*15/DRB1*16 subtype combinations. For evaluation, 60 HLA‐DRB1*15‐positive and 40 HLA‐DRB1*16‐positive individuals were typed and the results were compared with conventional PCR‐SSP DR15/16 subtyping. There were no discrepancies between the two methods. The TaqMan method is an alternative to conventional PCR‐SSP typing which is suitable for routine use in HLA laboratories.
Significant associations of HLA‐B*5101 and B*5108, and lack of association of class II alleles with Behçet’s disease in Italian patients
Authors: Kera J. , Mizuki N. , Ota M. , Katsuyama Y. , Pivetti‐Pezzi P. , Ohno S. , Inoko H.
Published: March 2003

Behçet’s disease has been known to be strongly associated with human leukocyte antigen (HLA) B51, one of the split antigens of HLA‐B5. An increased incidence of HLA‐B51 in the patient group has also been reported in an Italian population. Since the B51 antigen has been recently identified to comprise nine alleles, B*5101–B*5109, we performed HLA‐B51 allele genotyping by the polymerase chain reaction‐sequencing based typing (PCR‐SBT) method as well as serological HLA‐A and ‐B typing among 21 Italian patients with Behçet’s disease in order to investigate whether there is any correlation of one particular B51‐associated allele with Behçet’s disease. In addition, HLA class II genotyping was performed by the PCR‐restriction fragment length polymorphism (RFLP) method. As a result, only the phenotype frequency of the B51 antigen was found to be significantly increased in the patient group as compared to the ethnically matched control group by the corrected P‐value analysis (71.4% in patients vs. 17.9% in controls; χ2=14.26, Pc=0.0042, R.R.=11.5). In the B51 allele genotyping, 11 out of 15 B51‐positive patients were B*5101 and the remaining four were B*5108, whereas all of 5 normal controls were B*5101, showing significant association of each allele with Behçet’s disease. No significant difference was observed between the patient and control groups in the HLA class II allelic distribution. This study revealed a strong association of Behçet’s disease in Italian with B*5108 as well as B*5101, providing important insight into the molecular mechanism underlying an HLA association with Behçet’s disease.
NRAMP1 gene polymorphisms in patients with rheumatoid arthritis
Authors: Singal D.P. , Li J. , Zhu Y. , Zhang G.
Published: March 2003

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with HLA‐DR genes that share amino acid sequence motif QKRAA/QRRAA from position 70 to 74 in the third hypervariable region of DR1 molecule. The contribution of HLA in RA is however about 37%, suggesting a role for other genes. One such candidate is the gene that encodes natural resistance‐associated macrophage protein (NRAMP1), which plays a crucial role in inflammation and tissue destruction. In the present study, we examined the role of NRAMP1 gene polymorphisms in susceptibility to RA. The results show that variation at position 543 in exon 15, which involves substitution of negatively charged aspartic acid (D) by uncharged asparagine (N), and the deletion of TGTG in the 3′ UTR may confer protection from development of RA.
HLA haplotypes are associated with differential susceptibility to Trypanosoma cruzi infection
Authors: Nieto A. , Beraún Y. , Callado M.D. , Caballero A. , Alonso A. , González A. , Martín J.
Published: March 2003

We explored a possible role of HLA class II genes in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease in a rural mestizo population from Arequipa (Southern Peru). HLA‐DRB1 and DQB1 polymorphisms were determined in 85 seropositive (asymptomatic, n=52; cardiomyopathic, n=33) and 87 seronegative individuals. We observed that the DRB1*14‐DQB1*0301 haplotype correlates with not having T. cruzi infection in a highly endemic area (OR=0.26 (0.12–0.63); Pc=0.01). This protective association is a dominant trait. We found no differences in the allelic or haplotypic distributions we examined between asymptomatic and cardiomyopathic patients in this population. Our data offer indirect but compelling evidence that polymorphism in HLA region is involved in a differential susceptibility to T. cruzi chronic infection.
A porcine cell surface receptor identified by monoclonal antibodies to SWC3 is a member of the signal regulatory protein family and associates with protein‐tyrosine phosphatase SHP‐1
Authors: Alvarez B. , Sánchez C. , Bullido R. , Marina A. , Lunney J. , Alonso F. , Ezquerra A. , Domínguez J.
Published: March 2003

SWC3 was defined at the First International Swine CD Workshop as a specific myelomonocytic antigen of 230 kDa with mAbs 74‐22‐15, 6F3 and DH59B. In this report, we describe two new mAbs (BL1H7 and BA1C11) that react selectively with granulocytes, monocytes and macrophages. These monoclonal antibodies (mAbs) recognize a molecule in the range of 90–115 kDa in immunoprecipitation and/or Western blotting analyses. Two‐colour FACS analyses showed that the distribution of BL1H7 and BA1C11 antigens was identical to that of SWC3. Moreover, in this assay, mAb 74‐22‐15 appeared to partially block the binding of mAbs BL1H7 and BA1C11, suggesting that all these mAbs reacted with the same or spatially close epitopes. Cross‐blocking analyses indicated that it was the case with mAbs 74‐22‐15 and BL1H7. Immunoprecipitation experiments with mAbs 74‐22‐15, BL1H7 and BA1C11, followed by immunoblotting with mAb BL1H7 confirmed that all three mAbs recognize the same molecule. Analysis of the N‐terminal sequence carried out on the affinity purified protein revealed homology with members of signal regulatory protein (SIRP) family. Like other members of this family, after treatment with sodium pervanadate, SWC3 became phosphorylated in tyrosines, and associated with the protein‐tyrosine phosphatase SHP‐1.
HLA‐DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis
Authors: Naruse T.K. , Matsuzawa Y. , Ota M. , Katsuyama Y. , Matsumori A. , Hara M. , Nagai S. , Morimoto S. , Sasayama S. , Inoko H.
Published: March 2003

Cardiac sarcoidosis occurs in 1–5% of sarcoidosis patients. We previously reported a significant increase of the uncommon TNFA (tumor necrosis factor α) allele, TNFA2 with cardiac sarcoidosis in Japanese. In order to precisely localize the susceptible locus for cardiac sarcoidosis within the HLA region, genetic polymorphisms of classical HLA genes, non‐classical HLA class II genes such as HLA‐DMA and ‐DMB genes and several genes involved in the class I‐mediated antigen presentation pathway (TAP1, TAP2, LMP2 and LMP7) were investigated. Further, association analyses using four polymorphic microsatellite markers located around the TAP1 and TNFA genes were also carried out. As a result, HLA‐DQB1*0601 was found to be the most significantly associated allele, being more significantly increased than TNFA2. No significant increase of the DR52‐associated DRB1 alleles (DRB1*03, 05, 06 and 08), which was suggested to be primarily associated with lung sarcoidosis, was observed in cardiac sarcoidosis. A primary role of DQB1*0601 in determination of the susceptibility to cardiac sarcoidosis was supported by association analysis using four polymorphic microsatellite markers, in which only the TAP1 microsatellite locus, the nearest marker to the DQB1 gene among the microsatellites tested, displayed a significant positive association with cardiac sarcoidosis. On the other hand, the HLA‐DQB1*0501‐DQA1*0101‐DRB1*0101‐B7 haplotype showed a negative association with the disease, as similarly observed in lung sarcoidosis. Thus, molecular mechanism for controlling the development of the disease related to HLA molecules are different between cardiac and lung sarcoidosis, whereas thoses for conferring a resistant trait may be similar to each other.
Nucleotide sequence of a new Fc gamma receptor IIIB allele that codes for a neutrophil antigen
Authors: Watanabe Y. , Shimada E. , Fujiwara K. , Niihara H. , Shimano K. , Mitsunaga S. , Tadokoro K. , Juji T.
Published: March 2003

A new allele of the human neutrophil antigen (HNA) system (tentatively called NA2M) was discovered and its nucleotide sequence was determined. NA2M differs in a single nucleotide (193G→A) from FCGR3B*2(NA2), resulting in an amino acid change (54Glu→Lys). The frequency of the NA2M gene in the Japanese population was estimated to be 0.008. Granulocytes of individuals possessing NA2M reacted with HNA‐1b(NA2)‐specific monoclonal antibody (TAG2) in the GIFT assay (
Note).
New polymorphic microsatellite markers in the human MHC class II region
Authors: Matsuzaka Y. , Makino S. , Nakajima K. , Tomizawa M. , Oka A. , Kimura M. , Bahram S. , Tamiya G , Inoko H.
Published: March 2003

The human major histocompatibility complex (MHC) class II region spans approximately 1.1 Mb and presently contains over 30 functional genes. Susceptibility loci to numerous diseases, mainly of autoimmune nature are known to map to the this region, as assessed by associations with particular HLA class II alleles. However, it has been difficult to precisely localize these susceptibility loci to a single gene, for example DQB1 or DRB1, due to the tight linkage disequilibrium observed in the HLA class II region. To facilitate disease mapping within this region, we have analyzed 2∼5 bases short tandem repeats (microsatellites) in this same region. A total of 494 microsatellites were identified from the genomic sequence of the HLA class II region. These consist of 158 di‐, 65 tri‐, 163 tetra‐, and 108 penta‐nucleotide repeats, out of which four were located within the coding sequence of expressed genes (Daxx, BING1, RXRB and COL11A2). Twenty‐two repeats were selected as polymorphic markers due to their high (average) number of alleles (8.9) as well as their high polymorphic content value (PIC) (0.58). These novel polymorphic microsatellites will provide useful genetic markers in HLA‐related research, such as genetic mapping of HLA class II‐associated diseases, transplantation matching, population genetics, identification of recombination hot spots as well as linkage disequilibrium studies.
Three newly identified HLA‐B alleles: B*5124, B*5306, B*5307 and confirmation of B*0809 and B*5606
Authors: Anholts J.D.H. , Kemps‐Mols B. , Verduijn W. , Oudshoorn M. , Schreuder G.M.Th.
Published: March 2003

Abstract: Five HLA‐B sequences are described which have been detected as irregular patterns during routine molecular typing. Sequencing of HLA‐B exon 2 and 3, both heterozygous and after group specific amplification, revealed three new HLA‐B alleles: B*5124, B*5306 and B*5307, whereas the sequences of B*0809 and B*5606 were confirmed. Serological typing showed that B*0809 is expressed as a regular B8, B*5124 as a regular B51, B*5306 as a B51/B53‐like variant and B*5606 as a B‘blank’‐Bw6.
Novel HLA‐B alleles identified in potential marrow donors: B*3917, B*1405 and B*3528
Authors: Gourley I.S. , Kearns J. , Hou J. , Wu J. , Bassinger S. , Montoya G.D. , McKeen M. , Birkos S. , Williams T.M. , Kamoun M.
Published: March 2003

Abstract: Sequence‐specific oligonucleotide probe hybridization and sequence‐specific primer polymerase chain reaction (PCR) typing of volunteer bone marrow donors suggested the presence of variants of known HLA‐B alleles in five individuals. PCR products encompassing HLA‐B locus exons 1 through 3 were prepared and subcloned. Three African‐American individuals had a novel HLA‐B*39 allele (B*3917), and another African‐American was found to have a novel HLA‐B*14 allele (B*1405). In a third individual of Hispanic origin, a novel HLA‐B*35 allele (B*3528) was identified. These findings further illustrate the substantial genetic variation present at the HLA‐B locus within human populations.