bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of Aggregate Utility Using Stochastic Elements of Additive Multiattribute Utility Models
Authors: Moskowitz Herbert , Tang Jen , Lam Peter
Published: June 2007

Conventionally, elements of a multiattribute utility model characterizing a decision maker's preferences, such as attribute weights and attribute utilities, are treated as deterministic, which may be unrealistic because assessment of such elements can be imprecise and erroneous, or differ among a group of individuals. Moreover, attempting to make precise assessments can be time consuming and cognitively demanding. We propose to treat such elements as stochastic variables to account for inconsistency and imprecision in such assessments. Under these assumptions, we develop procedures for computing the probability distribution of aggregate utility for an additive multiattribute utility function (MAUF), based on the Edgeworth expansion. When the distributions of aggregate utility for all alternatives in a decision problem are known, stochastic dominance can then be invoked to filter inferior alternatives. We show that, under certain mild conditions, the aggregate utility distribution approaches normality as the number of attributes increases. Thus, only a few terms from the Edgeworth expansion with a standard normal density as the base function will be sufficient for approximating an aggregate utility distribution in practice. Moreover, the more symmetric the attribute utility distributions, the fewer the attributes to achieve normality. The Edgeworth expansion thus can provide a basis for a computationally viable approach for representing an aggregate utility distribution with imprecisely specified attribute weights and utilities assessments (or differing weights and utilities across individuals). Practical guidelines for using the Edgeworth approximation are given. The proposed methodology is illustrated using a vendor selection problem.
Telecommunications Network Design—Comparison of Alternative Approaches
Authors: Premkumar G. , Chu Chao‐Hsien , Chou Hsinghua
Published: June 2007

The design and development of the network infrastructure to support mission‐critical applications has become a critical and‐complex activity. This study explores the use of genetic algorithms (GA) for network design in the context of degree‐constrained minimal spanning tree (DCMST) problem; compares for small networks the performance of GA with a mathematical model that provides optimal solutions; and for larger networks, compares GA's performance with two heuristic methods—edge exchange and primal algorithm. Two performance measures, solution quality and computation time, are used for evaluation. The algorithms are evaluated on a wide variety of network sizes with both static and dynamic degree constraints on the network nodes. The results indicate that GA provides optimal solutions for small networks. For larger networks it provides better solution quality compared to edge exchange and primal method, but is worse than the two methods in computation time.
A Comparison of Selected Artificial Neural Networks that Help Auditors Evaluate Client Financial Viability
Authors: Etheridge Harlan L. , Sriram Ram S. , Hsu H. Y. Kathy
Published: June 2007

This study compares the performance of three artificial neural network (ANN) approaches—backpropagalion, categorical learning, and probabilistic neural network—as classification tools to assist and support auditor's judgment about a client's continued financial viability into the future (going concern status). ANN performance is compared on the basis of overall error rates and estimated relative costs of misclassificaticn (incorrectly classifying an insolvent firm as solvent versus classifying a solvent firm as insolvent). When only the overall error rate is considered, the probabilistic neural network is the most reliable in classification, followed by backpropagation and categorical learning network. When the estimated relative costs of misclassification are considered, the categorical learning network is the least costly, followed by backpropagation and probabilistic neural network.
Evaluation of Embedded Intelligent Real‐time Systems*
Authors: Grabowski Martha , Sanborn Stephen D.
Published: June 2007

Over the past two decades, questions have surfaced about the effectiveness and contribution of intelligent systems to decision makers in a variety of settings. This paper focuses on the evaluation challenges associated with intelligent real‐time software systems that are embedded in larger host systems. With the proliferation of such systems in operational settings such as aerospace, medical, manufacturing, and transportation systems, increased attention to evaluations of such systems, and to resulting software safety, is warranted. This paper describes one such evaluation and proposes a set of evaluation criteria for embedded intelligent real‐time systems (EIRTS). Implications of the evaluation and the evaluation criteria are discussed.
Effective Design of Products/Services: An Approach Based on Integration of Marketing and Operations Management Decisions*
Authors: Verma Rohit , Thompson Gary M. , Moore William L. , Louviere Jordan J.
Published: June 2007

This paper presents an integrated framework for designing profit‐maximizing products/ services, which can also be produced at reasonable operating difficulty levels. Operating difficulty is represented as a function of product and process attributes, and measures a firm's relative ease or difficulty in meeting customer demand patterns under specified operating conditions. Earlier optimum product design procedures have not considered. operational difficulty. We show that optimum profit, market share, cost, and product profiles are dependent on operating difficulty level. Empirical results from the pizza delivery industry demonstrate the value of the proposed Effective Product/Service Design approach.
A Structural Equation Model of New Product Design and Development*
Authors: Tan Keah Choon
Published: June 2007

This research uses structural equation modeling to analyze the effects of supplier assessment, Just‐In‐Time, and quality management strategies on new product design and development. A survey of senior managers who are members of the American Production and Inventory Control Society in the United States was used to test the relationships between the constructs in the model. In general, the survey results supported the proposed structural equation model. The data showed that supplier assessment and Just‐In‐Time strategies were correlated and affected the quality management strategy used, which in turn influenced the new product design and development strategy. The data also showed that the Just‐In‐Time strategy directly influenced the new product design and development strategy.
Organization Structure from a Loose Coupling Perspective: A Multidimensional Approach*
Authors: Beekun Rafik I. , Glick William H.
Published: June 2007

Organizational theories frequently rely on notions of sharing and dependence among organizational participants, but researchers usually focus on characteristics of the actors themselves instead of the relational patterns among the actors. Loose coupling is one conceptual tool that emphasizes relational patterns. Loose coupling, however, is an abstract metaphor that is simultaneously fertile and ambiguous. This paper develops a rigorous and comprehensive framework that sharpens the theoretical contributions of loose coupling to our understanding of structural relationships. Characteristics of loose coupling capture some important and underexplored features of multidimensional fit and interdependence in organizations. The proposed framework clarifies these theoretical contributions of loose coupling with concepts and equations modified from network analysis. Testable hypotheses are proposed with respect to three key independent variables that may affect patterns of coupling: organization strategy, technology, and environmental turbulence. Additional hypotheses are advanced with respect to the use of the multidimensional approach to loose coupling in studying new organizational forms. Initial psychometric and empirical evidence are presented.
The Effectiveness of Decisional Guidance: An Empirical Evaluation
Authors: Parikh Mihir , Fazlollahi Bijan , Verma Sameer
Published: June 2007

Decisional guidance is defined as how a decision support system (DSS) influences its users as they structure and execute the decision‐making process. It is assumed that decisional guidance has profound effects on decision making, but these effects are understudied and empirically unproven. This paper describes an empirical, laboratory‐experiment‐based evaluation of the effectiveness of deliberate decisional guidance and its four types. We developed and used a comprehensive model consisting of four evaluation criteria: decision quality, user satisfaction, user learning, and decision‐making efficiency. On these criteria, we compared decisional guidance versus no guidance, informative versus suggestive decisional guidance, and predefined versus dynamic decisional guidance. We found that deliberate decisional guidance was more effective on all four criteria; suggestive guidance was more effective in improving decision quality and user satisfaction, and informative guidance was more effective in user learning about the problem domain, whereas dynamic guidance was more effective than predefined guidance in improving decision quality and user learning; and both suggestive guidance and dynamic guidance reduced the decision time.
Opportunism in Capital Budget Recommendations: The Effects of Past Performance and Its Attributions*
Authors: Ho Joanna L. , Vera‐Muñoz Sandra C.
Published: June 2007

This study uses an experiment to examine the separate and combined effects of managers' loss aversion and their causal attributions about their divisions' performance on tendencies to make goal‐incongruent capital budget recommendations. We find that managers' recommendations are biased by their loss aversion. In particular, managers of high‐performing divisions are more likely than managers of low‐performing divisions to propose investments that maximize their division's short‐term profits at the expense of the firm's long‐term value. We also find that managers' recommendations are biased by their causal attributions. In particular, managers are more likely to propose investments that maximize their division's short‐term profits at the expense of the firm's long‐term value when they attribute their division's performance to external causes (e.g., task difficulty or luck) rather than to internal causes (e.g., managerial ability or effort). Further, the effects of causal attributions are greater for managers of high‐performing divisions than for managers of low‐performing divisions. The study's findings are important because loss aversion and causal attributions are often manifested in firms. Thus, they may bias managers' decisions, which in turn may be detrimental to the firms' long‐term value.
The Value of Production Schedule Integration in Supply Chains
Authors: Krajewski Lee , Wei Jerry C.
Published: June 2007

This study explores the value of integrated production schedules for reducing the negative effects of schedule revisions in supply chains involving buyer and supplier firms. A stochastic cost model is developed to evaluate the total supply chain cost with integrated purchasing and scheduling policies. The model minimizes the costs associated with assembly rate adjustment, safety stock, and schedule changes for all supply chain members. Through experimentation, the paper examines the impact of several environmental factors on the value of schedule integration. This study finds that schedule integration can lead to overall cost savings in a supply chain, but some firms may have to absorb costs in excess of those they would incur with independent scheduling. Environments with high inventory holding costs and long supplier lead times may not find it beneficial to adopt an integrated schedule. Forecast effectiveness plays a critical role in realizing the benefits of schedule integration. The paper concludes with suggestions for future research.
Strict Uncertainty: A Criterion for Moderately Pessimistic Decision Makers*
Authors: Ballestero Enrique
Published: June 2007

This paper proposes a decision rule to rank actions under strict uncertainty, the available information being limited to the states of nature, the set of alternative rows, and the consequence of choosing every row if a given state occurs. This rule is suitable to moderately pessimistic individuals and social groups, these agents being neither maximax nor maximin decision makers but people who assume that the best outcome from the action will not occur. For these decision makers the paper shows the existence of a consistent weight system in which one and only one weight is attached to each state of the world under plausible conditions of domination. Most of the traditional axioms are satisfied by the proposed ranking approach. In the frame of disappointment (measured by ranges of column dispersion), the meaning of some controversial postulates used in the literature is explained. The proposed criterion is a departure from Laplace's (1825) rule and from the remaining standard criteria. Only in the special case of equal column dispersion do both Laplace's rule and the proposed weights lead to the same solution.
A Psychometric Evaluation of the Expectations, Perceptions, and Difference‐Scores Generated by the IS‐Adapted SERVQUAL Instrument
Authors: Carr Christopher L.
Published: June 2007

This article describes the results of a study assessing the psychometric properties of the expectations and perceptions‐of‐performance instruments and the difference‐score data contained within the information systems (IS)‐Adapted SERVQUAL measurement paradigm. The central claim of this study is: In order for rational inferences to be made about service expectations, service performance perceptions, or the gap between them, each of the two instruments must exhibit reasonable psychometric properties in isolation before difference‐scores are taken. Analysis of data from a field study (N= 401) through structural equation modeling (SEM) techniques produces empirical evidence indicating that both of the instruments exhibit low psychometric quality and yet the difference‐scores exhibit “psychometric inflation.” That is, the quality of the difference‐score data is in many ways apparently superior to the raw data from both instruments. Negative conclusions are reached as to the efficacy of either individual instrument and, thus, the full IS‐Adapted SERVQUAL paradigm. Questions and prospects for further research in this important area of service quality measurement/management are presented, and a potentially rich future for IS service quality is outlined. It is strongly suggested that future IS service quality research be based on development of a new instrument, grounded in attributes endemic to IS services and developed using the best available development techniques.
User Acceptance Enablers in Individual Decision Making About Technology: Toward an Integrated Model
Authors: Venkatesh Viswanath , Speier Cheri , Morris Michael G.
Published: June 2007

Building on recent unique, yet potentially complementary, approaches to understanding the formation of user perceptions about technology (Venkatesh, 1999; Venkatesh & Speier, 1999), the present work reanalyzes the data from both studies to develop an integrated model of technology acceptance. The integrated model specifically examines the influence of pre‐training and training environment interventions (termed user acceptance enablers) to understand how user perceptions are formed prior to system implementation. The model is then further extended and tested using longitudinal data in a field setting. The results indicate that the integrated model emerged as a better predictor of user behavior when compared to the existing models.
White matter abnormalities in drug‐naïve patients with obsessive–compulsive disorder: a Diffusion Tensor Study before and after citalopram treatment
Authors: Yoo S. Y. , Jang J. H. , Shin Y.‐W. , Kim D. J. , Park H.‐J. , Moon W.‐J. , Chung E. C. , Lee J.‐M. , Kim I. Y. , Kim S. I. , Kwon J. S.
Published: June 2007

Objective:  The aim was to investigate the white matter abnormalities of drug‐naïve patients with obsessive–compulsive disorder (OCD) using diffusion tensor‐imaging and the white matter changes in the patients after pharmacotherapy.

Method:  Thirteen drug‐naïve OCD patients and 13 age‐ and sex‐matched healthy comparison subjects were examined using diffusion tensor‐imaging and structural magnetic resonance imaging. Measurements were made in OCD patients before and after 12 weeks of citalopram treatment.

Results:  Compared with controls, the drug‐naïve OCD patients showed significant increases in fractional anisotropy (FA) in the corpus callosum, the internal capsule and white matter in the area superolateral to the right caudate. The increases in FA were mostly no longer observed in patients after 12 weeks of treatment compared with controls.

Conclusion:  Our findings suggest that white matter alterations are associated with the pathophysiology of OCD, and the abnormalities may be partly reversible with pharmacotherapy.
Spawning period of a southern brown trout population in a highly unpredictable stream
Authors: Gortázar J. , García de Jalón D. , Alonso‐González C. , Vizcaíno P. , Baeza D. , Marchamalo M.
Published: June 2007

Abstract – The spawning period of brown trout (Salmo truttaL.) was studied in the river Castril, southern Spain, by means of redd counts. This mountain stream is located near to the southern limit of the species’ natural distribution range and it shows a highly unpredictable flow regime. The spawning period extended from December to mid‐April and the maximum reproductive activity was in February. These results represent the latest reproduction date and the longest spawning period reported in the literature along the natural distribution range of the species. However, belated spawning in the Castril is congruent with the known latitudinal cline: the lower the latitude, the later the spawning period. Our results, along with a review of the literature on natural populations, also showed that the duration of reproduction is the longer, the lower the latitude. Spawning lasted twice as long in the main stem of the river, which is connected with a reservoir, than in the isolated reaches. These differences may be linked to the influence of the reservoir and to habitat fragmentation. We discuss and support the hypothesis that a long spawning period is an advantage for survival in unpredictable habitats. The belated and protracted spawning period found in river Castril has important implications in fisheries management. A strong research effort is needed in order to fill the critical lack of data on southern brown trout populations.
Intervening in Employee Disputes: How and When Will Managers from China, Japan and the USA Act Differently?
Authors: Brett Jeanne M. , Tinsley Catherine H. , Shapiro Debra L. , Okumura Tetsushi
Published: June 2007

We investigated how third party managers from China, Japan and the USA intervened in employees' disputes. Consistent with predictions, we found (using non-linear HLM analysis) that managers who were superiors to the disputants behaved autocratically and/or decided on conservative (e.g., contract adhering) outcomes; but managers who were peers (especially in China and the USA), generally involved disputants in decision-making and obtained integrative outcomes that went beyond initial contract related mandates. Our results extend prior research and theorizing using the dispositional and constructivist perspectives on culture by introducing norm complexity as an explanation for variations in third party conflict intervention behaviour within one culture.
Importance of Organizational Citizenship Behaviour for Overall Performance Evaluation: Comparing the Role of Task Interdependence in China and the USA
Authors: Bachrach Daniel G. , Wang Hui , Bendoly Elliot , Zhang Shuoyang
Published: June 2007

In a cross-cultural experiment, we examined how task interdependence influences the importance of organizational citizenship behaviour (OCB) in employee performance evaluations in China and the USA. A total of 150 graduate students in China and 154 in the USA (a total of 304), who serve as evaluators, participated in the experiment. Participants were exposed to a task interdependence manipulation and then rated the importance of OCB in their overall performance evaluations of employees. Results support the moderating effects of national culture (both using a country proxy and as a measure of collectivism) on the affects of task interdependence. Although among evaluators from the USA perceptions of the importance of OCB increased as task interdependence increased, the effects of task interdependence were significandy attenuated among evaluators from China. Implications of these results for research and practice are discussed.
Estimating Excess Deaths in Iraq Since the US—British-Led Invasion
Authors: Zeger Scott L.
Published: June 2007

No-one knows how many Iraqis have died as a result of the invasion of their country. Surveys published in The Lancet in 2004 and 2006 estimated the number at 10 times figures previously given. Predictably, they raised a storm of protest. Politicians attacked the surveys; public media gave their own spin. Here Scott Zeger and Elizabeth Johnson, statistical analysts of the surveys, discuss these and other attempts to count the dead, and how statistical messages should be best communicated.
Detecting the Dubious Digits: Benford's Law in Forensic Accounting
Authors: Kumar Kuldeep , Bhattacharya Sukanto
Published: June 2007

Kuldeep Kumar and Sukanto Bhattacharya Introduce an unexpected quality in natural numbers that can help to detect faked data
ILO “PRINCIPLES” ON FREEDOM OF ASSOCIATION: PROSPECTS FOR PROLETARIAN POWER BEYOND THE STATE
Authors: Germanotta Paul
Published: June 2007

The recent publication of the fifth (revised) edition of the Digest of decisions and principles of the International Labor Organization (ILO)'s Committee on Freedom of Association offers an apposite moment to critique a body of widely, but uncritically, referenced global labor norms. Reconstructed without their obscuring phraseology, these rules are easily seen as a code that regularizes the exercise of state violence against workers' associational activities, particularly those that transcend labor's “guerilla fights” with capital and pursue emancipatory objectives. Paradoxically, one of the few social spaces beyond their reach, and beyond the repressive apparatus of the capitalist state generally, is the very sphere in which they are produced, the meta‐bureaucracies of the United Nations (UN) system. The ILO and UN‐system workers, who constitute an often‐overlooked autonomous class formation, toil under unique structural conditions, notably the absence of a global state, which offer great potential as a site for emancipatory proletarian projects on a global scale.
ASSESSING THE PARENT–CHILD RELATIONSHIP IN PARENTING CAPACITY EVALUATIONS: CLINICAL APPLICATIONS OF ATTACHMENT RESEARCH
Authors: Schmidt Fred , Cuttress L. Jane , Lang Jan , Lewandowski Mary Jane , Rawana Jennine S.
Published: June 2007

The lack of an articulated model of parenting competence and the limited use of empirically based assessment procedures is a weakness of current parenting capacity assessment protocols. The current article attempts to address this issue through the application of attachment theory and research in assessing one of the most critical components of parenting capacity assessments: the parent–child relationship. New empirically and attachment‐based assessment tools and procedures, well suited for the assessment of parental fitness, are presented, along with recommended practice guidelines to enhance the assessment of the parent–child relationship in cases of young, maltreated children (under 6 years of age).
Structure‐based Drug Design of Pyrrolidine‐1, 2‐dicarboxamides as a Novel Series of Orally Bioavailable Factor Xa Inhibitors
Authors: Van Huis Chad A. , Bigge Christopher F. , Casimiro‐Garcia Agustin , Cody Wayne L. , Dudley Danette A. , Filipski Kevin J. , Heemstra Ronald J. , Kohrt Jeffrey T. , Narasimhan Lakshmi S. , Schaum Robert P. , Zhang Erli , Bryant John W. , Haarer Staci , Janiczek Nancy , Leadley Robert J. , McClanahan Thomas , Thomas Peterson J. , Welch Kathleen M. , Edmunds Jeremy J.
Published: June 2007

A novel series of pyrrolidine‐1,2‐dicarboxamides was discovered as factor Xa inhibitors using structure‐based drug design. This series consisted of a neutral 4‐chlorophenylurea P1, a biphenylsulfonamide P4 and a d‐proline scaffold (1, IC50 = 18 nm). Optimization of the initial hit resulted in an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC50 = 0.38 nm), which was shown to be efficacious in a canine electrolytic model of thrombosis with minimal bleeding.
The 2006 higher education pay dispute: the reality of partnership rhetoric?
Authors: Novitz Tonia , Villiers Charlotte
Published: June 2007

The rhetoric of partnership appears to have played a central justificatory role in policy change and law reform during the past decade, especially in the field of industrial relations. We investigate in this paper its implications for higher education. We do so in the context of the 2006 pay dispute with reference both to recent developments in the higher education sector and to the legal framework within which the dispute was conducted. We argue that despite the government’s suggestion that this was only a dispute between universities as employers and their employees, its particular version of partnership shaped the contours of the dispute and determined its outcome.
Narratives on Pain and Comfort: Readings from Endings and Beginnings
Authors: Albertson Sandra
Published: June 2007

At age twenty-nine, while a graduate student in computer science at the University of Pennsylvania, Mark Albertson was diagnosed with lymphosarcoma. He died four months later, leaving a wife and two young daughters—Robin, three years old, and Kim, three months. Sandra Albertson, a Quaker, writes about their family’s experience with death and renewal.

The following is reprinted from Sandra Albertson, Endings and Beginnings (New York: Random House, 1980; Ballantine, 1983): chs. 9, 10.
Amino acid substitutions in the S region of hepatitis B virus in sera from patients with acute hepatitis
Authors: Aono Junko , Yotsuyanagi Hiroshi , Miyoshi Hideyuki , Tsutsumi Takeya , Fujie Hajime , Shintani Yoshizumi , Moriya Kyoji , Okuse Chiaki , Suzuki Michihiro , Yasuda Kiyomi , Iino Shiro , Koike Kazuhiko
Published: June 2007

Background:  An increase in the number of acute hepatitis patients with hepatitis B virus (HBV) of non‐indigenous genotypes may reduce the efficacy of vaccination against HBV.

Methods:  We have determined the amino acid (aa) sequences in the major hydrophilic region (MHR) in the S region of HBV in patients with acute hepatitis B and compared those with the ones from HBV strains used for the production of HBV vaccines commercially available in Japan.

Results:  Of 48 patients studied, 11 were infected with genotype A, 11 with genotype B and 26 with genotype C HBV. The aa sequences of the nine genotype A isolates were the same as the aa sequence of J02205 which is used for the production of one of the commercially available recombinant vaccines. The aa sequences of the 11 genotype B isolates differed from the aa sequence of J02205 in two or three amino acids. Of the26 genotype C isolates, 22 had the same aa sequence as X01587 which is used for the production of another recombinant vaccine. The remaining genotype C isolates had aa substitutions at aa131, which have a potential to alter the hydropathy and the three‐dimensional structure of the MHR. The differences among the three current HBV vaccines in aa sequences in the MHR theoretically alter the hydropathy and three‐dimensional structure.

Conclusion:  Our results suggest that the transmission of HBV isolates with different genotypes or with aa substitutions in the MHR might reduce the efficacy of currently available HBV vaccines in the protection of HBV infections.
Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis
Authors: Miyake Yasuhiro , Iwasaki Yoshiaki , Terada Ryo , Onishi Toru , Okamoto Ryoichi , Takaguchi Kouichi , Ikeda Hiroshi , Makino Yasuhiro , Kobashi Haruhiko , Sakaguchi Kohsaku , Shiratori Yasushi
Published: June 2007

Aim:  In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3‐positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians.

Methods:  We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16–79 years).

Results:  Forty‐seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%).

Conclusion:  In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre‐existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without.
Using multileaf collimator interleaf leakage to extract absolute spatial information from electronic portal imaging device images
Authors: Gao Zhanrong , Szanto Janos , Gerig Lee
Published: June 2007

Electronic portal imaging devices (EPIDs) are potentially valuable tools for linear accelerator quality assurance and for measuring and analyzing geometric variations in radiation treatment delivery. Geometric analysis is more robust if referenced against an absolute position such as the isocenter (collimator axis of rotation), allowing the observer to discriminate between various setup errors and jaw or multileaf collimator (MLC) calibration errors. Unfortunately, mechanical instabilities in EPIDs make such analysis difficult. In the present work, we describe how MLC interleaf radiation leakage, hidden in the background of portal images, can be extracted and analyzed to find the field isocenter perpendicular to leaf travel direction. The signal from the interleaf radiation leakage is extracted to provide a precise and accurate determination of the isocenter location in the direction perpendicular to MLC leaf travel. In the direction of leaf travel, the minimization of residuals between planned and measured leaf positions is used to determine the isocenter. This method assumes that leaf positioning errors are randomly distributed. The validity of the method for determining the angular deviation between EPID image grid lines and collimator angle and for determining the known isocenter position is experimentally established.

PACs numbers: 87.53.Oq, 87.53.Xd, 87.57.NK
Post‐implant computed tomography–magnetic resonance prostate image registration using feature line parallelization and normalized mutual information
Authors: Vidakovic Sandra , Jans Hans S. , Alexander Abe , Sloboda Ron S.
Published: June 2007

Post‐implant dosimetry for permanent prostate brachytherapy is typically performed using computed tomography (CT) images, for which the clear visualization of soft tissue structures is problematic. Registration of CT and magnetic resonance (MR) image volumes can improve the definition of all structures of interest (soft tissues, bones, and seeds) in the joint image set. In the present paper, we describe a novel two‐stage rigid‐body registration algorithm that consists of (1) parallelization of straight lines fit to image features running primarily in the superior–inferior (Z) direction, followed by (2) normalized mutual information registration. The first stage serves to fix rotation angles about the anterior–posterior (Y) and left–right (X) directions, and the second stage determines the remaining Z‐axis rotation angle and the X, Y, Z translation values. The new algorithm was applied to CT and 1.5T MR (T2‐weighted and balanced fast‐field echo sequences) axial image sets for three patients acquired four weeks after prostate brachytherapy using seeds. Image features used for the stage 1 parallelization were seed trains in CT and needle tracks and seed voids in MR. Simulated datasets were also created to further investigate algorithm performance. Clinical image volumes were successfully registered using the two‐stage approach to within a root‐mean‐squares (RMS) distance of <1.5 mm, provided that some pubic bone and anterior rectum were included in the registration volume of interest and that no motion artifact was apparent. This level of accuracy is comparable to that obtained for the same clinical datasets using the Procrustes algorithm. Unlike Procrustes, the new algorithm can be almost fully automated, and hence we conclude that its further development for application in post‐implant dosimetry is warranted.

PACS numbers: 87.53.Jw, 87.57.Gg, 87.59.Fm, 87.61.Pk
Polony Multiplex Analysis of Gene Expression (PMAGE) in Mouse Hypertrophic Cardiomyopathy
Authors: Kim Jae Bum , Porreca Gregory J. , Song Lei , Greenway Steven C. , Gorham Joshua M. , Church George M. , Seidman Christine E. , Seidman J. G.
Published: June 2007

We describe a sensitive mRNA profiling technology, PMAGE (for “polony multiplex analysis of gene expression”), which detects messenger RNAs (mRNAs) as rare as one transcript per three cells. PMAGE incorporates an improved ligation-based method to sequence 14-nucleotide tags derived from individual mRNA molecules. One sequence tag from each mRNA molecule is amplified onto a separate 1-micrometer bead, denoted as a polymerase colony or polony, and about 5 million polonies are arrayed in a flow cell for parallel sequencing. Using PMAGE, we identified early transcriptional changes that preceded pathological manifestations of hypertrophic cardiomyopathy in mice carrying a disease-causing mutation. PMAGE provided a comprehensive profile of cardiac mRNAs, including low-abundance mRNAs encoding signaling molecules and transcription factors that are likely to participate in disease pathogenesis.
Response to Comments on "From Plant Traits to Plant Communities: A Statistical Mechanistic Approach to Biodiversity"
Authors: Shipley Bill , Vile Denis , Garnier Éric
Published: June 2007

We maintain that there is no circularity or structural bias in our model that inflates its predictive ability beyond the sampling bias inherent in the
r
2
statistic. When replacing observed average traits by environmental variables, the generality and predictive ability depends on one's empirical ability to predict these average values. Finally, maximizing rather than minimizing entropy given constraints is justified by axioms of information theory and is not an ecological assumption.
Seismic Evidence for Deep-Water Transportation in the Mantle
Authors: Kawakatsu Hitoshi , Watada Shingo
Published: June 2007

We report seismic evidence for the transportation of water into the deep mantle in the subduction zone beneath northeastern Japan. Our data indicate that water is released from the hydrated oceanic crust at shallow depths (<
∼100
kilometers) and then forms a channel of hydrated mantle material on top of the subducting plate that is the pathway for water into the deep mantle. Our result provides direct evidence that shows how water is transported from the ocean to the deep mantle in a cold subduction zone environment.
Monochromatic Electron Photoemission from Diamondoid Monolayers
Authors: Yang W. L. , Fabbri J. D. , Willey T. M. , Lee J. R. I. , Dahl J. E. , Carlson R. M. K. , Schreiner P. R. , Fokin A. A. , Tkachenko B. A. , Fokina N. A. , Meevasana W. , Mannella N. , Tanaka K. , Zhou X. J. , van Buuren T. , Kelly M. A. , Hussain Z. , Melosh N. A. , Shen Z.-X.
Published: June 2007

We found monochromatic electron photoemission from large-area self-assembled monolayers of a functionalized diamondoid, [121]tetramantane-6-thiol. Photoelectron spectra of the diamondoid monolayers exhibited a peak at the low–kinetic energy threshold; up to 68% of all emitted electrons were emitted within this single energy peak. The intensity of the emission peak is indicative of diamondoids being negative electron affinity materials. With an energy distribution width of less than 0.5 electron volts, this source of monochromatic electrons may find application in technologies such as electron microscopy, electron beam lithography, and field-emission flat-panel displays.
Attenuation of Allergic Contact Dermatitis Through the Endocannabinoid System
Authors: Karsak Meliha , Gaffal Evelyn , Date Rahul , Wang-Eckhardt Lihua , Rehnelt Jennifer , Petrosino Stefania , Starowicz Katarzyna , Steuder Regina , Schlicker Eberhard , Cravatt Benjamin , Mechoulam Raphael , Buettner Reinhard , Werner Sabine , Di Marzo Vincenzo , Tüting Thomas , Zimmer Andreas
Published: June 2007

Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity, we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase–deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated allergic inflammation, whereas receptor agonists attenuated inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin and suggest a target for therapeutic intervention.
Detection of Respiratory Viruses and Subtype Identification of Influenza A Viruses by GreeneChipResp Oligonucleotide Microarray
Authors: Quan Phenix-Lan , Palacios Gustavo , Jabado Omar J. , Conlan Sean , Hirschberg David L. , Pozo Francisco , Jack Philippa J. M. , Cisterna Daniel , Renwick Neil , Hui Jeffrey , Drysdale Andrew , Amos-Ritchie Rachel , Baumeister Elsa , Savy Vilma , Lager Kelly M. , Richt Jürgen A. , Boyle David B. , García-Sastre Adolfo , Casas Inmaculada , Perez-Breña Pilar , Briese Thomas , Lipkin W. Ian
Published: June 2007

Acute respiratory infections are significant causes of morbidity, mortality, and economic burden worldwide. An accurate, early differential diagnosis may alter individual clinical management as well as facilitate the recognition of outbreaks that have implications for public health. Here we report on the establishment and validation of a comprehensive and sensitive microarray system for detection of respiratory viruses and subtyping of influenza viruses in clinical materials. Implementation of a set of influenza virus enrichment primers facilitated subtyping of influenza A viruses through the differential recognition of hemagglutinins 1 through 16 and neuraminidases 1 through 9. Twenty-one different respiratory virus species were accurately characterized, including a recently identified novel genetic clade of rhinovirus.
Characterization and Function of Putative Substrate Specificity Domain in Microvirus External Scaffolding Proteins
Authors: Uchiyama Asako , Chen Min , Fane Bentley A.
Published: June 2007

Microviruses (canonical members are bacteriophages φX174, G4, and α3) are T=1 icosahedral virions with an assembly pathway mediated by two scaffolding proteins. The external scaffolding protein D plays a major role during morphogenesis, particularly in icosahedral shell formation. The results of previous studies, conducted with a cloned chimeric external scaffolding gene, suggest that the first α-helix acts as a substrate specificity domain, perhaps mediating the initial coat-external scaffolding protein interaction. However, the expression of a cloned gene could lead to protein concentrations higher than those found in typical infections. Moreover, its induction before infection could alter the timing of the protein's accumulation. Both of these factors could drive or facilitate reactions that may not occur under physiological conditions or before programmed cell lysis. In order to elucidate a more detailed mechanistic model, a chimeric external scaffolding gene was placed directly in the φX174 genome under wild-type transcriptional and translational control, and the chimeric virus, which was not viable on the level of plaque formation, was characterized. The results of the genetic and biochemical analyses indicate that α-helix 1 most likely mediates the nucleation reaction for the formation of the first assembly intermediate containing the external scaffolding protein. Mutants that can more efficiently use the chimeric scaffolding protein were isolated. These second-site mutations appear to act on a kinetic level, shortening the lag phase before virion production, perhaps lowering the critical concentration of the chimeric protein required for a nucleation reaction.
Development of Smallpox Vaccine Candidates with Integrated Interleukin-15 That Demonstrate Superior Immunogenicity, Efficacy, and Safety in Mice
Authors: Perera Liyanage P. , Waldmann Thomas A. , Mosca Joseph D. , Baldwin Nicole , Berzofsky Jay A. , Oh Sang-Kon
Published: June 2007

The potential use of variola virus, the etiological agent of smallpox, as a bioterror agent has heightened the interest in the reinitiation of smallpox vaccination. However, the currently licensed Dryvax vaccine, despite its documented efficacy in eradicating smallpox, is not optimal for the vaccination of contemporary populations with large numbers of individuals with immunodeficiencies because of severe adverse effects that can occur in such individuals. Therefore, the development of safer smallpox vaccines that can match the immunogenicity and efficacy of Dryvax for the vaccination of contemporary populations remains a priority. Using the Wyeth strain of vaccinia virus derived from the Dryvax vaccine, we generated a recombinant Wyeth interleukin-15 (IL-15) with integrated IL-15, a cytokine with potent immunostimulatory functions. The integration of IL-15 into the Wyeth strain resulted in a >1,000-fold reduction in lethality of vaccinated athymic nude mice and induced severalfold-higher cellular and humoral immune responses in wild-type mice that persisted longer than those induced by the parental Wyeth strain. The superior efficacy of Wyeth IL-15 was further demonstrated by the ability of vaccinated mice to fully survive a lethal intranasal challenge of virulent vaccinia virus even 10 months after vaccination, whereas all mice vaccinated with parental Wyeth strain succumbed. By integrating IL-15 into modified vaccinia virus Ankara (MVA), a virus currently under consideration as a substitute for the Dryvax vaccine, we developed a second vaccine candidate (MVA IL-15) with greater immunogenicity and efficacy than Dryvax. Thus, Wyeth IL-15 and MVA IL-15 viruses hold promise as more-efficacious and safe alternatives to the Dryvax vaccine.
Neutralization of Human Papillomavirus with Monoclonal Antibodies Reveals Different Mechanisms of Inhibition
Authors: Day Patricia M. , Thompson Cynthia D. , Buck Christopher B. , Pang Yuk-Ying S. , Lowy Douglas R. , Schiller John T.
Published: June 2007

The mechanisms of human papillomavirus (HPV) neutralization by antibodies are incompletely understood. We have used HPV16 pseudovirus infection of HaCaT cells to analyze how several neutralizing monoclonal antibodies (MAbs) generated against HPV16 L1 interfere with the process of keratinocyte infection. HPV16 capsids normally bind to both the cell surface and extracellular matrix (ECM) of HaCaT cells. Surprisingly, two strongly neutralizing MAbs, V5 and E70, did not prevent attachment of capsids to the cell surface. However, they did block association with the ECM and prevented internalization of cell surface-bound capsids. In contrast, MAb U4 prevented binding to the cell surface but not to the ECM. The epitope recognized by U4 was inaccessible when virions were bound to the cell surface but became accessible after endocytosis, presumably coinciding with receptor detachment. Treatment of capsids with heparin, which is known to interfere with binding to cell surface heparan sulfate proteoglycans (HSPGs), also resulted in HPV16 localization to the ECM. These results suggest that the U4 epitope on the intercapsomeric C-terminal arm is likely to encompass the critical HSPG interaction residues for HPV16, while the V5 and E70 epitopes at the apex of the capsomer overlap the ECM-binding sites. We conclude that neutralizing antibodies can inhibit HPV infection by multiple distinct mechanisms, and understanding these mechanisms can add insight to the HPV entry processes.
Cathepsin B Mediates Cleavage of Herpes Simplex Virus Type 1 Origin Binding Protein (OBP) To Yield OBPC-1, and Cleavage Is Dependent upon Viral DNA Replication
Authors: Link Malen A. , Silva Laurie A. , Schaffer Priscilla A.
Published: June 2007

Although the seven viral proteins required for herpes simplex virus type 1 (HSV-1) DNA replication have been identified, the mechanism by which viral DNA synthesis is regulated is unclear. HSV-1 DNA replication is thought to occur in two stages: origin-dependent DNA replication (stage I) mediated by the origin binding protein (OBP), followed by origin- and OBP-independent DNA replication (stage II). The mechanism that facilitates the switch from stage I to stage II is unknown; however, it must involve the loss of OBP function or OBP itself from the replication initiation complex. Previous studies from this laboratory identified a transcript (UL8.5) and protein (OBPC) that are in frame with and comprise the C terminus of the gene specifying OBP. Because of its DNA binding ability, OBPC has been hypothesized to mediate the switch from stage I to stage II. Here, we identify a second protein (OBPC-2) that is also in frame with the C terminus of OBP but comprises a smaller portion of the protein. We demonstrate that the protein originally identified (OBPC-1) is a cathepsin B-mediated cleavage product of OBP, while OBPC-2 may be the product of the UL8.5 transcript. We further demonstrate that the cleavage of OBP to yield OBPC-1 is dependent upon viral DNA replication. These results suggest that cleavage may be a mechanism by which OBP levels and/or activity are regulated during infection.