bluuebunny/crossref_metadata_2025 huggingface dataset:
Catastrophe and the Public Service: A Case Study of the Government Response to the Destruction of the World Trade Center
Authors: Cohen Steven , Eimicke William , Horan Jessica
Published: March 2003

The destruction of the World Trade Center on September 11, 2001, resulted in a rapid response by government to evacuate the area and, in subsequent days, to bring the city back to a semblance of normalcy. This article provides a case study of government action in New York City during and after the World Trade Center catastrophe. What is most striking is the skill and intensity of government’s response to the emergency and the hard work, dedication, and bravery of New York City’s government officials. This article presents government and public service at its finest, under some of the most difficult conditions one can imagine.
An American Dream Unfulfilled: The Limited Mobility of Mexican Americans
Authors: Livingston Gretchen , Kahn Joan R.
Published: March 2003

Objective. We build on past research regarding immigrant group adaptation by examining the wages of first–, second–, and third–generation Mexican–American men and women and empirically evaluating if past theories of immigrant incorporation apply to the Mexican–American case. Methods. We use the 1989 Latino National Political Study and the 1990/1991 Panel Studies of Income Dynamics and OLS regressions to estimate the effects of generation and human capital on wages. Results. Immigrant men and women report lower wages than their second– and third–generation counterparts, but once human capital controls are added, the wage pattern becomes one of steady decline across generations for men, and stagnation or marginal decline across generations for women. Conclusions. Our results generally contest the applicability of linear assimilation hypotheses to the Mexican–American experience, while lending some credence to the selectivity and immigrant optimism hypotheses. Results also indicate the importance of developing more contextualized immigrant adaptation frameworks.
Venture Capital and the Professionalization of Start‐Up Firms: Empirical Evidence
Authors: Hellmann Thomas , Puri Manju
Published: March 2003

This paper examines the impact venture capital can have on the development of new firms. Using a hand‐collected data set on Silicon Valley start‐ups, we find that venture capital is related to a variety of professionalization measures, such as human resource policies, the adoption of stock option plans, and the hiring of a marketing VP. Venture‐capital‐backed companies are also more likely and faster to replace the founder with an outside CEO, both in situations that appear adversarial and those mutually agreed to. The evidence suggests that venture capitalists play roles over and beyond those of traditional financial intermediaries.
Portfolio Choice in the Presence of Personal Illiquid Projects
Authors: Faig Miquel , Shum Pauline
Published: March 2003

Personal projects, such as a private business or the purchase of a home, influence individuals portfolio choice. We conduct a theoretical analysis of this influence when financial assets are required to provide liquidity to personal projects. Due to this liquidity consideration, individuals behave in a more riskaverse fashion when there is a large penalty for discontinuing or underinvesting in the final stages of the projects. In addition, using data from the 1995 Survey of Consumer Finances, we find that households that are saving to invest in their own businesses or in their own homes indeed have significantly safer financial portfolios.
Term Premia and Interest Rate Forecasts in Affine Models
Authors: Duffee Gregory R.
Published: March 2003

The standard class of affine models produces poor forecasts of future Treasury yields. Better forecasts are generated by assuming that yields follow random walks. The failure of these models is driven by one of their key features: Compensation for risk is a multiple of the variance of the risk. Thus risk compensation cannot vary independently of interest rate volatility. I also describe a broader class of models. These aessentially affine‐ models retain the tractability of standard models, but allow compensation for interest rate risk to vary independently of interest rate volatility. This additional flexibility proves useful in forecasting future yields.
Do Conglomerate Firms Allocate Resources Inefficiently Across Industries? Theory and Evidence
Authors: Maksimovic Vojislav , Phillips Gordon
Published: March 2003

We develop a profit‐maximizing neoclassical model of optimal firm size and growth across different industries based on differences in industry fundamentals and firm productivity. In the model, a conglomerate discount is consistent with profit maximization. The model predicts how conglomerate firms will allocate resources across divisions over the business cycle and how their responses to industry shocks will differ from those of single‐segment firms. Using plant level data, we find that growth and investment of conglomerate and single‐segment firms is related to fundamental industry factors and individual segment level productivity. The majority of conglomerate firms exhibit growth across industry segments that is consistent with optimal behavior.
Momentum, Business Cycle, and Time‐varying Expected Returns
Authors: Chordia Tarun , Shivakumar Lakshmanan
Published: March 2003

A growing number of researchers argue that time‐series patterns in returns are due to investor irrationality and thus can be translated into abnormal profits. Continuation of short‐term returns or momentum is one such pattern that has defied any rational explanation and is at odds with market efficiency. This paper shows that profits to momentum strategies can be explained by a set of lagged macroeconomic variables and payoffs to momentum strategies disappear once stock returns are adjusted for their predictability based on these macroeconomic variables. Our results provide a possible role for time‐varying expected returns as an explanation for momentum payoffs.
IPO Market Cycles: Bubbles or Sequential Learning?
Authors: Lowry Michelle , Schwert G. William
Published: March 2003

Both IPO volume and average initial returns are highly autocorrelated. Further, more companies tend to go public following periods of high initial returns. However, we find that the level of average initial returns at the time of filing contains no information about that company's eventual underpricing. Both the cycles in initial returns and the lead‐lag relation between initial returns and IPO volume are predominantly driven by information learned during the registration period. More positive information results in higher initial returns and more companies filing IPOs soon thereafter.
An Empirical Investigation of Continuous‐Time Equity Return Models
Authors: Andersen Torben G. , Benzoni Luca , Lund Jesper
Published: March 2003

This paper extends the class of stochastic volatility diffusions for asset returns to encompass Poisson jumps of time‐varying intensity. We find that any reasonably descriptive continuous‐time model for equity‐index returns must allow for discrete jumps as well as stochastic volatility with a pronounced negative relationship between return and volatility innovations. We also find that the dominant empirical characteristics of the return process appear to be priced by the option market. Our analysis indicates a general correspondence between the evidence extracted from daily equity‐index returns and the stylized features of the corresponding options market prices.
Nasdaq Trading Halts: The Impact of Market Mechanisms on Prices, Trading Activity, and Execution Costs
Authors: Christie William G. , Corwin Shane A. , Harris Jeffrey H.
Published: March 2003

We study the effects of alternative halt and reopening procedures on prices, transaction costs, and trading activity for a sample of news‐related trading halts on Nasdaq. For intraday halts that reopen after only a five‐minute quotation period, inside quoted spreads more than double following halts and volatility increases to more than nine times normal levels. In contrast, halts that reopen the following day with a longer 90‐minute quotation period are associated with insignificant spread effects and significantly dampened volatility effects. These results are consistent with the hypothesis that increased information transmission during the halt results in reduced posthalt uncertainty.
Managerial Turnover and Leverage under a Takeover Threat
Authors: Novaes Walter
Published: March 2003

How do shareholders perceive managers who lever up under a takeover threat? Increasing leverage conveys good news if it reflects management's ability to enhance value. It conveys bad news, though, if inefficient managers are more pressured to lever up than the efficient ones. This paper demonstrates that negative updating may prevail. Managers who lever up to end a takeover threat may thus commit to enhance value and yet increase their chances of being replaced by their shareholders. The model provides implications for the dispersion of intraindustry leverage and for the stock price reaction to debt‐for‐equity exchanges.
The Geography of Equity Listing: Why Do Companies List Abroad?
Authors: Pagano Marco , Röell Ailsa A. , Zechner Josef
Published: March 2003

This paper documents aggregate trends in the foreign listings of companies, and analyzes their distinctive prelisting characteristics and postlisting performance. In 1986–1997, many European companies listed abroad, mainly on U.S. exchanges, while the number of U.S. companies listed in Europe decreased. European companies that cross‐list tend to be large and recently privatized firms, and expand their foreign sales after listing abroad. They differ sharply depending on where they cross‐list: The U.S. exchanges attract high‐tech and export‐oriented companies that expand rapidly without significant leveraging. Companies cross‐listing within Europe do not grow unusually fast, and increase their leverage after cross‐listing.
Tunneling or Value Added? Evidence from Mergers by Korean Business Groups
Authors: Bae Kee‐Hong , Kang Jun‐Koo , Kim Jin‐Mo
Published: March 2003

We examine whether firms belonging to Korean business groups (chaebols) benefit from acquisitions they make or whether such acquisitions provide a way for controlling shareholders to increase their wealth by increasing the value of other group firms (tunneling). We find that when a chaebol‐affiliated firm makes an acquisition, its stock price on average falls. While minority shareholders of a chaebol‐affiliated firm making an acquisition lose, the controlling shareholder of that firm on average benefits because the acquisition enhances the value of other firms in the group. This evidence is consistent with the tunneling hypothesis.
Disentangling the Incentive and Entrenchment Effects of Large Shareholdings
Authors: Claessens Stijn , Djankov Simeon , Fan Joseph P. H. , Lang Larry H. P.
Published: March 2003

This article disentangles the incentive and entrenchment effects of large ownership. Using data for 1,301 publicly traded corporations in eight East Asian economies, we find that firm value increases with the cash‐flow ownership of the largest shareholder, consistent with a positive incentive effect. But firm value falls when the control rights of the largest shareholder exceed its cash‐flow ownership, consistent with an entrenchment effect. Given that concentrated corporate ownership is predominant in most countries, these findings have relevance for corporate governance across the world.
Trade Credit, Financial Intermediary Development, and Industry Growth
Authors: Fisman Raymond , Love Inessa
Published: March 2003

Recent work suggests that financial development is important for economic growth, since financial markets more effectively allocate capital to firms with high value projects. For firms in poorly developed financial markets, implicit borrowing in the form of trade credit may provide an alternative source of funds. We show that industries with higher dependence on trade credit financing exhibit higher rates of growth in countries with weaker financial institutions. Furthermore, consistent with barriers to trade credit access among young firms, we show that most of the effect that we report comes from growth in the size of preexisting firms.
Mapping and Functional Analysis of Interaction Sites within the Cytoplasmic Domains of the Vaccinia Virus A33R and A36R Envelope Proteins
Authors: Ward Brian M. , Weisberg Andrea S. , Moss Bernard
Published: March 2003

Incorporation of the vaccinia virus A36R protein into the outer membrane of intracellular enveloped virions (IEV) is dependent on expression of the A33R protein. Possible interactions of the 200-amino-acid cytoplasmic domain of the A36R protein with itself or with the cytoplasmic domain of the A33R, A34R, B5R, or F12L IEV membrane protein was investigated by using the yeast two-hybrid system. A strong interaction was detected only between the cytoplasmic domains of the A36R and A33R proteins. Upon further analyses, the interaction site was mapped to residues 91 to 111 of the A36R protein. To investigate the role of the A36R:A33R interaction during viral infection, five recombinant vaccinia viruses containing B5R-GFP as a marker were constructed. Four had the full-length A36R gene replaced with various-length C-terminal truncations of A36R, of which two contained residues 91 to 111 and two were missing this region. The fifth recombinant virus had an A33R gene with most of the 40-amino-acid cytoplasmic tail deleted. Residues 91 to 111 of A36R and the cytoplasmic tail of A33R were required for a strong interaction between the two proteins during viral infection and for maximal amounts of A36R protein on IEV. Mutants lacking these regions of A33R or A36R formed IEV that exhibited only short sporadic intracellular movement, displayed no actin tails, and formed small plaques on cell monolayers equivalent to those of an A36R deletion mutant and smaller than those formed by point mutations that specifically abrogate actin tail formation. The A33R interaction site of the A36R protein is highly conserved among orthopoxviruses and may overlap binding sites for cellular proteins needed for microtubular movement and actin tail formation.
Interaction with a Ubiquitin-Like Protein Enhances the Ubiquitination and Degradation of Hepatitis C Virus RNA-Dependent RNA Polymerase
Authors: Gao Lu , Tu Hong , Shi Stephanie T. , Lee Ki-Jeong , Asanaka Miyuki , Hwang Soon B. , Lai Michael M. C.
Published: March 2003

To identify potential cellular regulators of hepatitis C virus (HCV) RNA-dependent RNA polymerase (NS5B), we searched for cellular proteins interacting with NS5B protein by yeast two-hybrid screening of a human hepatocyte cDNA library. We identified a ubiquitin-like protein, hPLIC1 (for human homolog 1 of protein linking intergrin-associated protein and cytoskeleton), which is expressed in the liver (M. F. Kleijnen, A. H. Shih, P. Zhou, S. Kumar, R. E. Soccio, N. L. Kedersha, G. Gill, and P. M. Howley, Mol. Cell 6: 409-419, 2000). In vitro binding assays and in vivo coimmunoprecipitation studies confirmed the interaction between hPLIC1 and NS5B, which occurred through the ubiquitin-associated domain at the C terminus of the hPLIC1 protein. As hPLICs have been shown to physically associate with two E3 ubiquitin protein ligases as well as proteasomes (Kleijnen et al., Mol. Cell 6: 409-419, 2000), we investigated whether the stability and posttranslational modification of NS5B were affected by hPLIC1. A pulse-chase labeling experiment revealed that overexpression of hPLIC1, but not the mutant lacking the NS5B-binding domain, significantly shortened the half-life of NS5B and enhanced the polyubiquitination of NS5B. Furthermore, in Huh7 cells that express an HCV subgenomic replicon, the amounts of both NS5B and the replicon RNA were reduced by overexpression of hPLIC1. Thus, hPLIC1 may be a regulator of HCV RNA replication through interaction with NS5B.
Selective Virus Resistance Conferred by Expression of Borna Disease Virus Nucleocapsid Components
Authors: Geib Till , Sauder Christian , Venturelli Sascha , Hässler Christel , Staeheli Peter , Schwemmle Martin
Published: March 2003

Persistent viral infections can render host cells resistant to superinfection with closely related viruses by largely uncharacterized mechanisms. We present evidence for superinfection exclusion in brains of Borna disease virus (BDV)-infected rats and in persistently infected Vero cells, and we suggest that acquired resistance to BDV is due to unbalanced intracellular levels of viral nucleocapsid components. We observed that expression of BDV protein P, N, or X rendered human cells resistant to subsequent challenge with BDV but not with other RNA viruses, indicating that incorrect stoichiometry of nucleocapsid components selectively blocked the polymerase activity of incoming viruses. Vero cells containing high levels of an untranslatable BDV-N transcript remained virus susceptible, demonstrating that viral protein rather than RNA mediated resistance. Transient overexpression of BDV-P in persistently infected Vero cells was also remarkably effective against BDV, indicating that the intracellular balance of viral nucleocapsid components could serve as a target for future therapeutic antiviral strategies.
Diverse Dengue Type 2 Virus Populations Contain Recombinant and Both Parental Viruses in a Single Mosquito Host
Authors: Craig Scott , Thu Hlaing Myat , Lowry Kym , Wang Xiao-fang , Holmes Edward C. , Aaskov John
Published: March 2003

Envelope (E) protein genes sampled from populations of dengue 2 (DEN-2) virus in individual
Aedes aegypti
mosquitoes and in serum from dengue patients were copied to cDNA, cloned, and sequenced. The nucleotide sequences of the E genes in more than 70% of the clones differed from the consensus sequence for the corresponding virus population at up to 11 sites, and 24 of the 94 clones contained at least one stop codon. Virus populations recovered up to 2 years apart yielded clones with similar polymorphisms in the E gene. For one mosquito, the clones obtained fell into two genotypes. One group of sequences was closely related to those of viruses recovered from dengue patients in the same locality (Yangon, Myanmar) since 1995 and were classified as Asian 1 genotype. The second group were Cosmopolitan genotype viruses which were also circulating in Yangon in 2000 and which were related to DEN-2 viruses sampled from southern China in 1999. Finally, one clone was identified as a recombinant genome composed of portions of these two “parental” genotypes. This is the first report of recombinant and parental dengue viruses in a single host.
A rapidly tunable terahertz‐wave parametric oscillator
Authors: Imai Kazuhiro , Kawase Kodo , Minamide Hiroaki , Ito Hiromasa
Published: March 2003

We have constructed a terahertz‐wave parametric oscillator (TPO) with pulse‐to‐pulse access to random wavelengths, using an optical beam scanner and a confocal optics system (1:1 telescope) to vary the pump light angle of incidence. In addition, we used the TPO in a spectroscopic study of HCl gas in order to test its tunability, and confirmed that the TPO was continuously tunable from 1 to 2 THz and could rapidly access random frequencies in that range. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(4): 18–26, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10060
Automatic extraction of road networks from map images
Authors: Itonaga Wataru , Matsuda Ichiro , Yoneyama Noritaka , Ito Susumu
Published: March 2003

With the advent of sophisticated and diversified car navigation systems in recent years, it is becoming increasingly important to construct a precise and detailed map database. Among map data, road‐network information is a representation of the connection relations of roads by a graph structure, and is one of the most important kinds of information used in route search and guidance, which is the basic function of car navigation systems. At present, much manpower and time are being spent in the preparation of road‐network information, and it is desirable to reduce the labor required by automation using computers. This paper presents a method in which the road network is automatically extracted from map information. First, the road area is extracted from the map image by stochastic relaxation based on the geometrical properties of the road area and the background area. Then, thinning and piecewise‐linear approximation are applied to the road area to extract the road‐network information, which consists of the graphic structure of nodes and links. In this process, the distortion near junctions produced by thinning is corrected, and the nodes are optimally rearranged so that the road network represents the centers of the roads. Then, precise road‐network information is stably extracted. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(4): 62–72, 2003; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/ecjb.10144
Performance of automatic gain adjustment in a shunt active filter intended for installation on power distribution systems
Authors: Jintakosonwit Pichai , Akagi Hirofumi , Fujita Hideaki , Ogasawara Satoshi
Published: March 2003

This paper discusses automatic gain adjustment in a fully‐digital‐controlled shunt active filter intended for installation on power distribution systems. This is the first step in cooperative control of multiple shunt active filters based on voltage detection for harmonic damping throughout power distribution systems. In general, an optimal control gain is equal to the characteristic impedance of a distribution line. However, it is difficult to know the circuit parameters of a real distribution line, which depend strongly on feeder connections, shunt capacitors, and loads. Therefore, the main purpose of the gain adjustment is to help the active filter to damp out harmonic propagation without considering the circuit parameters. Moreover, the gain adjustment can reduce the compensating current and losses in the active filter. The active filter having the function of automatic gain adjustment is experimentally compared to that with a constant gain. Experiment results verify the effectiveness of the active filter having the function of automatic gain adjustment. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 142(4): 56–65, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10094
Immunohistochemical analysis of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in 271 meningiomas correlation with tumor grade and clinical outcome
Authors: Korshunov Andrey , Shishkina Lyudmila , Golanov Andrey
Published: March 2003

Routine pathological examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Numerous efforts have been made for the evaluation of different immunohistochemical assays in meningioma prognosis. We investigated the prognostic significance of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression by immunohistochemical analysis of 271 meningiomas. All tumors were additionally stained for the proliferation markers Ki‐67 and DNA topoisomerase II alpha (TopoIIα). Significant differences between the number of p16INK4a‐, p18INK4c‐ and p21CIP1‐positive cases were noted among the 3 grades of meningiomas. p16INK4a‐ and p21CIP‐positive tumors were found to prevail among benign meningiomas, whereas p18INK4c immunostaining was closely associated to anaplastic meningiomas. The number of p16INK4a‐ and p21CIP‐positive cases was significantly lower in the cohort of recurrent meningiomas. In contrast, p18INK4c‐positive cases were clustered among recurrent meningiomas regardless of tumor grade. Immunoreactivity of p14ARF, p27KIP1 and p73 did not show any differences between meningiomas of various histology and clinical outcomes. Multivariate analysis revealed that only tumor grade and TopoIIα index are independent criteria for predicting meningioma recurrence. Thus, the immunohistochemical assessment of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in meningiomas does not appear to provide prognostically useful information. Further studies are needed to identify more reliable prognostic markers and to address in more detail the role of cell cycle aberrations in these tumors. © 2003 Wiley‐Liss, Inc.
Rapid screening of T‐cell receptor (TCR) variable gene usage by multiplex PCR: Application for assessment of clonal composition
Authors: Akatsuka Y. , Martin E.G. , Madonik A. , Barsoukov A.A. , Hansen J.A.
Published: March 2003

The selection of various T‐cell receptor (TCR) gene families and complex rearrangements during intra‐thymic differentiation provide the basis for the expression of antigen specificity by mature T cells. TCR beta variable (TCRBV) transcripts can be identified by RT‐PCR, but multiple reactions are required to detect all genes of the TCRBV subfamilies. We describe here a multiplex PCR method that amplifies 46 functional genes comparing 23 TCRBV families in 5 reactions where each reaction contains 4 to 7 specific primers together with a single fluorescence‐tagged TCR beta constant region primer. Between 8 and 10 distinct subtypes within each of the 23 TCRBV families can be identified by analysis of the CDR3 length. Multiplex PCR products isolated from agarose gels can be subjected to direct sequencing for confirmation and definitive clonotyping if necessary. The data illustrated here show that the multiplex PCR technique is useful for screening TCRBV usage and can be easily adapted for analysis of clonal composition in T‐cell populations.
Linkage disequilibrium analysis of familial psoriasis: identification of multiple disease‐associated MHC haplotypes
Authors: Jenisch S. , Westphal E. , Nair R.P. , Stuart P. , Voorhees J.J. , Christophers E. , Krönke M. , Elder J.T. , Henseler T.
Published: March 2003

Although psoriasis vulgaris (PsV) is strongly associated with certain human leukocyte antigens, the pathogenetic nature of these associations remains elusive. The objectives of this study were: (i) to determine whether HLA loci directly determine susceptibility or merely serve as markers for the susceptibility allele; and (ii) to identify additional disease‐associated haplotypes. By applying maximum likelihood linkage disequilibrium analysis (LDA) in cases vs. controls, we found the susceptibility gene to be more strongly associated with specific HLA haplotypes than with their component alleles. Stronger linkage disequilibrium between PsV and HLA alleles was detected at HLA‐C and HLA‐B than at DRB1 and DQB1. Parametric linkage analysis accounting for marker‐trait disequilibrium in psoriasis vulgaris pedigrees yielded most significant results for a locus close to HLA‐B and ‐C. Furthermore, we found that susceptibility is linked to at least three different ancestral HLA haplotypes; among them, HLA‐Cw7‐B8‐DRB1*0301‐DQB1*02 is linked to PsV for the first time. These results identify a major PsV susceptibility locus in the immediate vicinity of, but distinct from HLA‐B or HLA‐C, and suggest that multiple disease alleles have arisen during human evolution.
Molecular analysis of HLA class I alleles in the Mexican Seri Indians: implications for their origin
Authors: Infante E. , Olivo A. , Alaez C. , Williams F. , Middleton D. , De la Rosa G. , Pujol M.j. , Durán C. , Navarro J.l. , Gorodezky C.
Published: March 2003

The molecular analysis of HLA class I loci has demonstrated that, although, the genetic profile is restricted in Amerindians, several micropolymorphisms may be important in conferring a biological advantage. We analyzed the HLA‐A and B genetic profile of Seris, a Mexican Indian tribe living in northwestern Mexico in the state of Sonora. There are presently only 619 individuals. Our study included 100 Seris belonging to nine families. HLA‐A and ‐B loci typing was performed by polymerase chain reaction using an amplification refractory mutation system (PCR‐ARMS) on a select group of samples; all of them were typed by polymerase chain reaction using sequence‐specific oliogonuoleotide probes (PCR‐SSOP) at a low‐intermediate resolution level. The correlation between the techniques was 100%. Only five HLA‐A alleles and seven HLA‐B alleles were found. A*0201, A*68, A*31, A*24, B*3501, B*40, B*51, B*3512 and B*15 were present in over 5% of the individuals. B*27052 was detected in 2%. B27 is absent in any other Mexican Indian groups previously studied. The presence of B27 may be the result of a founder effect due to different waves of southward migrations. The B‐locus is more diverse and the prevalent haplotypes were: A*0201‐B*3501, A*0201‐B*40, A*0201‐B*3512, A*31‐B*51, A*68‐B*3501 and A*68‐B*40. This genetic profile is different from the pattern of other Mexicans. The phylogenetic tree suggests that Seris are more closely related to the Warao Indians from Venezuela, who live in a similar ecosystem, and to some groups of Argentina, than they are to the Mexican Lacandones who live in the jungle. These data emphasize the relevance of the interaction between genes and environment.
Gene frequencies of human platelet antigens in the Tunisian population
Authors: Mojaat N. , Halle L. , Proulle V. , Hmida S. , Ben Hamed L. , Boukef K. , Kaplan C.
Published: March 2003

Gene frequencies for the human platelet antigens HPA‐1, ‐3 and ‐5 in the Tunisian population were determined by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) on 93 volunteer blood donors (78 were tested for HPA‐1, 90 for HPA‐3 and 93 for HPA‐5). This study shows the highest frequencies of the HPA‐1b (0.25) and HPA‐5b (0.22) yet recorded. These antigens are considered as markers of a high risk of platelet alloimmunisation in other populations, and for this reason particular attention should be paid in the case of pregnancy or blood transfusion in this population. The 9 base pair deletion located in intron 21 of the GPIIb gene associated with HPA‐3b determinant is present in this population. No individual showed the polymorphism associated with HPA‐1b (T→G at codon 40 of the GPIIIa).
The IL‐4 receptor α‐chain variant Q576R is strongly associated with decreased kidney allograft survival
Authors: Hackstein H. , Klüter H. , Fricke L. , Hoyer J. , Bein G.
Published: March 2003

The involvement of the interleukin‐4 (IL‐4) pathway in B‐lymphocyte activation and induction of a T helper 2 (Th2) cell response prompted us to investigate the influence of a recently described gain‐of function mutation in the IL‐4 receptor α‐chain gene (IL‐4Rα; CD 124) on renal allograft survival. We developed a genotyping assay for the IL‐4Rα variant Q576R and investigated 203 renal transplant patients, all of whom underwent transplantation surgery at a single institution. The overall frequency of the IL‐4Rα variant Q576R in this group was 38.9% (79/203). The Kaplan‐Meier method was used to estimate the graft survival of 156 patients with complete follow‐up time of 24 months. Significantly higher graft survival rates (P=0.012, log‐rank test) were found in patients with the wild‐type IL‐4 receptor (2‐year graft survival 78.8%) as compared to patients with the IL‐4Rα variant Q576R (2‐year graft survival 60.6%). Multifactorial cox regression analysis showed that this effect was independent of HLA matching, sex of donor and recipient, age of recipient, year of transplantation and preformed antibodies (P=0.017). These results indicate a strong association of the IL‐4Rα variant Q576R with kidney allograft loss. Genotyping of kidney allograft recipients for the IL‐4Rα variant may offer a simple method to identify high‐risk patients in the post‐transplantation period.
Analysis of three HLA‐A*3303 binding peptide anchors using an HLA‐A*3303 stabilization assay
Authors: Takiguchi M. , Matsuda T. , Tomiyama H. , Miwa K.
Published: March 2003

The affinity of 232 8‐ to 11‐mer peptides carrying HLA‐A*3303 anchor residues at position 2 (P2) (Ala, Ile, Leu, Val, Phe or Tyr) and the C‐terminus (Arg) was analysed by a stabilization assay using RMA‐S transfectants expressing HLA‐A*3303 and human β2‐microglobulin. One hundred and nineteen of these peptides (51.3%) bound to HLA‐A*3303, confirming that these residues are anchors for HLA‐A*3303. Evaluation of P2 residues demonstrated that binding of peptides with Phe or Tyr at P2 is stronger than that of peptides with aliphatic hydrophobic residues at P2. This was confirmed by analysis of a panel of peptides mutated at P2. Analysis of the C‐terminal mutant peptides showed that substitution of Lys for Arg had minimal influence on binding to HLA‐A*3303. This implies that peptides carrying HLA‐A*1101 anchor residues (Val, Ile, Phe or Tyr at P2 and Lys at the C‐terminus) can bind to HLA‐A*3303. However, such peptides showed lower binding for HLA‐A*3303 than for HLA‐A*1101. Thus, Arg at the C‐terminus is much stronger anchor for HLA‐A*3303 than Lys. The preference for Arg and Lys at the C‐terminus by HLA‐A*1101 and HLA‐A*3303 respectively may be due to sequences of three residues (70, 97 and 114) forming the F‐pocket of these HLA class I molecules. Statistical analysis of 232 peptides further showed a positive effect of negatively charged residues at P1 for peptide binding to HLA‐A*3303. Thus, residues at P1, P2 and the C‐terminus play an important role in peptide binding to HLA‐A*3303.
Polymorphisms in the TNFA promoter region is not associated with palmoplantar pustulosis
Authors: Niizeki H. , Naruse T. , Hashigucci K. , Yokoyama M. , Yamasaki Y. , Akiya K. , Tojo T. , Urushibara T. , Yamazaki Y. , Inoko H. , Nishikawa T.
Published: March 2003

Polymorphisms of the 5′‐flanking promoter/enhancer region of the TNFA gene were determined in 80 Japanese patients with pulmoplantar pustulosis (PPP). The 5′‐flanking region of the TNFA gene from –1107 to –66 was amplified by polymerase chain reaction (PCR) method. Nucleotide sequencing data from the PCR products revealed that 5 single nucleotide polymorphisms at position –1031, –863, –857, –307 and –237. None of the nucleotide substitutions were significantly increased in PPP patients when compared with those in controls. To clarify the linkage among the neighboring genetic marker, we analyzed the association between the polymorphisms in the TNFA promoter region and the NcoI polymorphism in the first intron of the TNFB gene as well as HLA‐DR9. The genotype at –1031C is strongly associated with TNFB1 and negatively associated with TNFB2 which is reported to be associated with PPP. These data indicate that TNFA gene centromeric to TNFB is not associated with PPP and the susceptible gene of PPP is located between TNFB and HLA‐B.
Diversity is demonstrated in class I HLA‐A and HLA‐B alleles in Cameroon, Africa: description of HLA‐A*03012, *2612, *3006 and HLA‐B*1403, *4016, *4703
Authors: Ellis J.M. , Mack S.J. , Leke R.F.G. , Quakyi I. , Johnson A.H. , Hurley C.K.
Published: March 2003

To examine the genetic diversity in west Africa, class I HLA‐A and HLA‐B alleles of 92 unrelated individuals from two areas in the Cameroon, the capital Yaoundé and the village of Etoa, were identified by direct automated DNA sequencing of exons 2 and 3 of the HLA‐B locus alleles and sequence‐specific oligonucleotide probe (SSOP) and/or sequencing of the HLA‐A locus alleles. HLA‐A*2301 (18.7%), A*2902 (10.4%), B*5301 (10.9%), and B*5802 (10.9%) were the most frequently detected alleles, present in at least 10% of the population. A total of 30 HLA‐A locus and 33 HLA‐B locus alleles, including six novel alleles, were detected. The novel alleles were HLA‐A*03012, A*2612, A*3006 and HLA‐B*1403, B*4016, and B*4703. HLA‐B*4703 contains a novel amino acid sequence that is a combination of the first 5 amino acids of the Bw6 epitope and the last 2 residues of the Bw4 epitope. The addition of 6 alleles to the ever‐expanding number of known class I HLA alleles supports our hypothesis that extensive genetic diversity, including previously undescribed alleles, would be observed in this African population. In the Yaoundé population, the allele frequency distribution at the HLA‐A locus is consistent with distributions indicative of balancing selection. Extensive HLA‐A‐B haplotypes were observed in this population suggesting that only a fraction of the Cameroon HLA‐A‐B haplotype diversity has been observed.
The CTLA4/CD28 gene region on chromosome 2q33 confers susceptibility to celiac disease in a way possibly distinct from that of type 1 diabetes and other chronic inflammatory disorders
Authors: Torinsson Naluai Å. , Nilsson S. , Samuelsson L. , Gudjónsdóttir A.H. , Ascher H. , Ek J. , Hallberg B. , Kristiansson B. , Martinsson T. , Nerman O. , Sollid L.M. , Wahlström J.
Published: March 2003

The effect of the gene region on chromosome 2q33 containing the CD28 and the cytotoxic T‐lymphocyte associated (CTLA4) genes has been investigated in several diseases with chronic inflammatory nature. In addition to celiac disease (CD), type I diabetes, Grave’s disease, rheumatoid arthritis and multiple sclerosis have all demonstrated associations to the A/G single nucleotide polymorphism (SNP) in exon 1, position +49 of the CTLA4 gene. The purpose of this study was to investigate this gene region in a genetically homogeneous population consisting of 107 Swedish and Norwegian families with CD using genetic association and linkage methods. We found a significant association with preferential transmission of the A‐allele of the exon 1 +49 polymorphism by using the transmission disequilibrium test (TDT). Suggestive linkage of this region to CD was moreover demonstrated by non‐parametric linkage (NPL) analysis giving a NPL‐score of 2.1. These data strongly indicates that the CTLA4 region is a susceptibility region in CD. Interestingly, of the several chronic inflammatory diseases that exhibit associations to the CTLA4 +49 A/G dimorphism, CD appears to be the only disease associated to the A allele. This suggests that the +49 alleles of the CTLA4 gene are in linkage disequilibrium with two distinct disease predisposing alleles with separate effects. The peculiar association found in the gut disorder CD may possibly relate to the fact that the gastrointestinal immune system, in contrast to the rest of the immune system, aims to establish tolerance to foreign proteins.
Characterization of the B*5002‐Cw*0602‐DRB1*0406‐DQB1*0402 Haplotype: impact on the unrelated‐bone marrow donor search strategy
Authors: Ansart‐Pirenne H. , Dufossé F. , Duval M. , Cracco P. , Jambou M. , Pédron B. , Vilmer E. , Sterkers G.
Published: March 2003

Abstract: Improvements in HLA‐typing by DNA‐based methods now allow accurate genotyping of unrelated bone marrow (UBM) donors and recipients and also definition of haplotypes. In this regard, B*5002 has been predicted in linkage disequilibrium with Cw*0602, DRB1*0406 and DQB1*0402 based on the frequency of allele coexistence. Here, we confirm this assumption by HLA genotyping of four informative families and three unrelated individuals. In the four families, the extended haplotype HLA‐B*5002, ‐Cw*0602, ‐DRB1*0406, DQB1*0402 can be definitely assigned by the mode of heritance. Furthermore, this association of alleles was also found in the three B*5002 unrelated individuals. Knowledge of the frequent linkage disequilibrium of these rare alleles can improve UBM donor search strategies.
Identification and nucleotide sequence of HLA‐A*03013
Authors: Guttridge M.G. , Darke C.
Published: March 2003

Abstract: We have identified a further HLA‐A*03 allele, A*03013, in three unrelated Caucasoid individuals. The allele was initially detected by the polymerase chain reaction using sequence‐specific primers (PCR‐SSP) and was shown to differ from HLA‐A*03011 by a single non‐coding substitution of G to T at position 167 in exon 2 by DNA sequencing. The A*03013 bearing haplotype in one of the three individuals, was HLA‐A*03013, B*07, Cw*0702, DRB1*1101, DRB3*0202, DQA1*05, DQB1*0301. The estimated phenotype and gene frequencies for A*03013 was <0.02% and <0.00007, respectively.
Two new HLA Cw* alleles, Cw*0105 and Cw*1405, detected by sequence based typing
Authors: Bengtsson M. , Danielsson F. , Jansson I.E. , Jidell E. , Johansson U.
Published: March 2003

Abstract: During recent years, the view of the relative importance of the HLA Cw locus has undergone substantial change. From being an HLA locus with both limited polymorphism and biological significance there are now more than a hundred different alleles known and the biological importance of HLA Cw, both as a transplantation antigen and as a receptor for NK cells, is well established. Sequence based typing has been shown to be a powerful tool, especially for HLA Cw typing. Here we describe two new HLA Cw* alleles found during routine typing of potential bone marrow donors and hematological patients. The HLA Cw*0105 differs from Cw*0102 at positions 361 and 368 in exon 3 leading to a Trp to Arg and Cys to Ser substitution, respectively. HLA Cw*1405 differs from Cw*14021 by a single nucleotide substitution at position 368. This mutation results in an amino acid substitution of Phe for Tyr.
No evidence for association of the inducible nitric oxide synthase promoter polymorphism with Trypanosoma cruzi infection
Authors: Calzada J.E. , López‐Nevot M.A. , Beraún Y. , Martín J.
Published: March 2003

Abstract: The purpose of the present study was to address the possible contribution of the (CCTTT)n microsatellite polymorphism in the NOS2 promoter region to the susceptibility to chronic Trypanosoma cruzi infection and to Chagas' disease related cardiomyopathy. We determined the (CCTTT)n genotypes in a sample of 76 serologically positive chagasic individuals and in 78 healthy controls. No statistically significant differences were observed between total chagasic patients and healthy controls with regard to frequency of the (CCTTT)n microsatellite repeat of any given length. Likewise, we found no differences in the distribution of the (CCTTT)n microsatellite repeats between seropositives without manifestations of the disease and those with chagasic cardiomyopathy. Our data suggest that the NOS2 promoter pentanucleotide microsatellite polymorphisms analyzed do not play a major role in the pathogenesis of chronic T. cruzi infection in this Peruvian sample.
Novel HLA‐A locus alleles including A*01012, A*0306, A*0308, A*2616, A*2617, A*3009, A*3206, A*3403, A*3602 and A*6604
Authors: Bradshaw D. , Gans C.P. , Jones P. , Rizzuto G. , Steiner N. , Mitton W. , Ng J. , Koester R. , Hartzman R.J. , Hurley C.K.
Published: March 2003

Abstract: This paper describes 10 novel HLA‐A alleles that have been characterized by DNA sequencing. Seven alleles, A*0308, A*2616, A*3009, A*3206, A*3403, A*3602 and A*6604 carry motifs observed in other HLA‐A alleles, suggesting that gene conversion has created this diversity. The remaining three alleles, A*01012, A*0306 and A*2617, contain polymorphisms not previously found in any “classical” class I allele. All alleles were identified due to unexpected probe hybridization patterns during routine SSOP typing. Exons 2 and 3 of each allele were subsequently characterized by DNA sequencing.
HLA polymorphism in six ethnic groups from Pakistan
Authors: Mohyuddin A. , Ayub Q. , Khaliq S. , Mansoor A. , Mazhar K. , Rehman S. , Mehdi S.Q.
Published: March 2003

Abstract: The extreme polymorphism found at some of the loci of the HLA system has made it an invaluable tool for population genetic analyses. In this study the genetic polymorphism of six Pakistani ethnic groups was investigated at the HLA‐A, ‐B, ‐C, ‐DRB and DQB1 loci using polymerase chain reaction with sequence specific primers. The groups included in this study are the Baloch, Brahui and Sindhi from the south and the Burusho, Kalash and Pathan from the north of Pakistan. The allele frequencies, three‐locus haplotype frequencies for HLA‐A, ‐C, ‐B and HLA‐A, ‐B, ‐DRB1 are given. Variation in the allele and haplotype distribution between the six Pakistani ethnic groups was observed. A phylogenetic tree and correspondence analysis based on HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 allele frequencies revealed the Kalash population to be distinct from the remaining Pakistani populations. The Baloch and Brahui were closely related to one another. The Sindhi were closer to the Pathan and Burusho populations than to the neighboring Baloch and Brahui populations, indicating admixture between the northern and southern populations of Pakistan. A phylogenetic tree and correspondence analysis comparing the Pakistani populations with various other world populations showed that the Pakistani ethnic groups lie within the cluster of Asian Indian populations. The three‐locus haplotypes found in the Pakistani populations suggest an influence from Caucasian and Oriental populations.
B*27 in molecular diagnostics: Impact of new alleles and polymorphism outside exons 2 and 3
Authors: Voorter C.E.M. , Swelsen W.T.N. , Van Den Berg‐Loonen E.M.
Published: March 2003

Abstract: HLA‐B*27 is known to be associated with ankylosing spondylitis and several methods have been applied to determine its presence or absence. In this report two molecular methods were used for detection of B*27. The polymerase chain reaction sequence‐specific primer (PCR‐SSP) method was performed to detect the presence or absence of B*27, whereas the sequence‐based typing method (SBT) was used to identify the B*27 subtype. The PCR‐SSP method used to detect B*27 was updated to enable the detection of all B*27 alleles. The typing results obtained by this method were compared with the serological typings of 262 individuals. Fifty of them were found to be B*27 positive by PCR‐SSP and 46 also showed positive serological reactions with B27‐specific sera. The four discrepancies were the result of the presence of B*2712 in three individuals and B*2715 in one individual; both alleles showed no serological reactions with B27‐specific antisera. With SBT the sequences of exons 1 through 4 were determined to unequivocally assign the B*27 alleles. Eleven different subtypes were detected in 78 individuals, including three new B*27 alleles: B*27054, B*2715 and B*2717. The allele B*27054 showed an allelic drop out when exon 3 was amplified. Three differences with B*27052 were demonstrated; one in exon 1, one in intron 1 and one in intron 2, the latter being responsible for the allelic drop out. The B*2715 allele was serologically not detectable with several B27‐specific sera, but showed Bw4‐positive reactions. The sequence of B*2715 showed two mismatches with B*2704. The sequence of B*2717 showed one mismatch with B*27052 at position 248 (A→T), which was considered to be a conserved position in all B alleles.