bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Dysfunction in Patients with Gynecologic Neoplasms: A Retrospective Pilot Study
Authors: Amsterdam Alison , Krychman Michael L.
Published: June 2006

Introduction

Little is known regarding the impact of a sexual health program on the sexual functioning of patients with a history of a gynecologic malignancy.

Aim

To evaluate as a pilot study the prevalence of common sexual health symptoms and evaluate the effects and compliance with clinical recommendations in gynecologic oncology patients.

Methods

A retrospective cohort study of 259 female cancer patients who attended a survivorship program at an academic medical center from March 1, 2003 through December 31, 2004. Patients received symptomatic treatment recommendations including hormone therapy alternatives, psychosexual counseling, minimally absorbed vaginal estrogen suppositories, and vaginal dilators.

Main Outcome Measures

Patient self-report of the severity of sexual symptomology at follow-up visit.

Results

Ninety-six patients (37%) had gynecologic neoplasms and the most common gynecologic malignancy seen was ovarian (27%). Median age at initial visit was 51 years (range 25–76) and 88 patients (92%) were postmenopausal. The most frequent presenting complaint encountered was dyspareunia (72%), atrophic vaginitis (65%), hypoactive desire (43%), and orgasmic dysfunction (17%). At a median of 6 months (range 0–20), 60 patients (63%) received follow-up, and of them 42 (70%) self-reported improvement in their symptoms.

Conclusions

The establishment of a well-structured sexual health program in a cancer setting can result in a 63% compliance rate with a 70% subjective improvement in sexual health complaints. Further research with objective measures of sexual dysfunction is needed to better evaluate patients’ progress in this setting.
Stability of School Academic Performance Across Subject Areas
Authors: Ma Xin
Published: June 2006

Recent studies on the stability of school academic performance across school subject areas show two weaknesses: a lack of research attention to elementary schools and a lack of adequate statistical adjustments for school characteristics. With data describing elementary students (N = 6,883 students in Grade 6 in 148 schools) from the New Brunswick School Climate Study (NBSCS), the current study examined correlates of academic performance across mathematics, science, reading, and writing among students and among schools, using a multivariate multilevel model with statistical adjustments for student characteristics and school context and climate characteristics. Results indicated that (a) students were differentially successful in different subject areas, (b) schools were differentially effective in different subject areas, and (c) the differential success was more obvious among students than among schools. Findings of this study call for a new type of school programs that aim to ensure that students progress equally in different subject areas and for stronger school policies that systematically coordinate classroom or department practices.
Item Analysis by the Hierarchical Generalized Linear Model
Authors: Kamata Akihito
Published: June 2006

The hierarchical generalized linear model (HGLM) is presented as an explicit, two‐level formulation of a multilevel item response model. In this paper, it is shown that the HGLM is equivalent to the Rasch model and that, characteristic of the HGLM, person ability can be expressed in the form of random effects rather than parameters. The two‐level item analysis model is presented as a latent regression model with person‐characteristic variables. Furthermore, it is shown that the two‐level HGLM model can be extended to a three‐level latent regression model that permits investigation of the variation of students' performance across groups, such as is found in classrooms and schools, and of the interactive effect of person‐and group‐characteristic variables.
Item Selection in Computerized Adaptive Testing: Should More Discriminating Items be Used First?
Authors: Hau Kit‐Tai , Chang Hua‐Hua
Published: June 2006

During computerized adaptive testing (CAT), items are selected continuously according to the test‐taker's estimated ability. The traditional method of attaining the highest efficiency in ability estimation is to select items of maximum Fisher information at the currently estimated ability. Test security has become a problem because high‐discrimination items are more likely to be selected and become overexposed. So, there seems to be a tradeoff between high efficiency in ability estimations and balanced usage of items. This series of four studies with simulated data addressed the dilemma by focusing on the notion of whether more or less discriminating items should be used first in CAT. The first study demonstrated that the common maximum information method with Sympson and Hetter (1985) control resulted in the use of more discriminating items first. The remaining studies showed that using items in the reverse order (i.e., less discriminating items first), as described in Chang and Ying's (1999) stratified method had potential advantages: (a) a more balanced item usage and (b) a relatively stable resultant item pool structure with easy and inexpensive management. This stratified method may have ability‐estimation efficiency better than or close to that of other methods, particularly for operational item pools when retired items cannot be totally replenished with similar highly discriminating items. It is argued that the judicious selection of items, as in the stratified method, is a more active control of item exposure, which can successfully even out the usage of all items.
An Essay on the History and Future of Reliability from the Perspective of Replications
Authors: Brennan Robert L.
Published: June 2006

This article provides a review of some important milestones in the history of reliability, some current issues concerning reliability, and some likely prospects for reliability, from the perspective of one central question: “What constitutes a replication of a measurement procedure?” Special attention is given to the fixed/random aspects of facets that characterize replications.
Current Concerns in Validity Theory
Authors: Kane Michael T.
Published: June 2006

We are at the end of the first century of work on models of educational and psychological measurement and into a new millennium. This certainly seems like an appropriate time for looking backward and looking forward in assessment. Furthermore, a new edition of the Standards for Educational and Psychological Testing (AERA, APA, & NCME, 1999) has been published, and the previous editions of the Standards have served as benchmarks in the development of measurement theory.

This backward glance will be just that, a glance. After a brief historical review focusing mainly on construct validity, the current state of validity theory will be summarized, with an emphasis on the role of arguments in validation. Then how an argument‐based approach might be applied will be examined in regards to two issues in validity theory: the distinction between performance‐based and theory‐based interpretations, and the role of consequences in validation.
Improving Construct Validity With Cognitive Psychology Principles
Authors: Embretson Susan , Gorin Joanna
Published: June 2006

Cognitive psychology principles have been heralded as possibly central to construct validity. In this paper, testing practices are examined in three stages: (a) the past, in which the traditional testing research paradigm left little role for cognitive psychology principles, (b) the present, in which testing research is enhanced by cognitive psychology principles, and (c) the future, for which we predict that cognitive psychology's potential will be fully realized through item design. An extended example of item design by cognitive theory is given to illustrate the principles. A spatial ability test that consists of an object assembly task highlights how cognitive design principles can lead to item generation.
Recentering and Realigning the SAT Score Distributions: How and Why
Authors: Dorans Neil J.
Published: June 2006

The process employed to produce the conversions that take scores from the original SAT scales to recentered scales, in which reference group scores are centered near the midpoint of the score‐reporting range, is laid out. For the purposes of this article, SAT Verbal and SAT Mathematical scores were placed on recentered scales, which have reporting ranges of 920 to 980, means of 950, and standard deviations of 11. (The 920‐to‐980 scale is used in this article to highlight the distinction between it and the old 200‐to‐800 scale. In actuality, recentered scores were reported on a 200‐to‐800 scale.) Recentering was accomplished via a linear transformation of normally distributed scores that were obtained from a continuized, smoothed frequency distribution of original SAT scores that were originally on augmented two‐digit scales (i.e., discrete scores rounded to either 0 or 5 in the third decimal place). These discrete scores were obtained for all students in the 1990 Reference Group using 35 different editions of the SAT spanning October 1988 to June 1990. The performance of this 1990 Reference Group on the original and recentered scales is described. The effects of recentering on scores of individuals and the 1990 Reference Group are also examined. Finally, recentering did not occur solely on the basis of its technical merit. Issues associated with converting recentering from a possibility into a reality are discussed.
Impact of Changing Difficulty on Inferences From the National Assessment of Educational Progress
Authors: Cohen Jon , Snow Stephanie
Published: June 2006

The U.S. Department of Education measures student achievement through the National Assessment of Educational Progress (NAEP). NAEP estimates of population proficiency quantiles are based on a Bayesian multiple‐imputation procedure. This article shows (a) that the resulting estimates depend directly on the mix of item difficulties on the test, and (b) the difficulty of items on the NAEP mathematics exam has increased over time. Does the increasing difficulty of the exam lead to observable changes in student performance over time? This study compared the simulated performance of 1990 examinees on the easier 1990 exam and the more difficult 1996 exam. No significant differences were found. While our results instill confidence that these changes have not impacted the NAEP trend line, our findings are both data‐specific and limited in scope, and NAEP should carefully evaluate future adjustments to the test in this manner.
Outlier Detection in High‐Stakes Certification Testing
Authors: Meijer Rob R.
Published: June 2006

Recent developrnents of person‐Jit analysis in computerized adaptive testing (CAT) are discussed. Methods from stutistical process control are presented that have been proposed to classify an item score pattern as fitting or misjitting the underlying item response theory model in CAT. Most person‐fit research in CAT is restricted to simulated data. In this study, empirical data from a certification test were used, Alternatives are discussed to generate norms so that bounds can be determined to classify an item score pattern as fitting or misfitting. Using bounds determined from a sample of a high‐stakes certification test, the empirical analysis showed that dizerent types of misfit can be distinguished. Further applications using statistical process control methods to detect misfitting item score patterns are discussed.
Measurement Efficiency of Innovative Item Formats in Computer‐Based Testing
Authors: Jodoin Michael G.
Published: June 2006

The psychometric literature provides little empirical evaluation of examinee test data to assess essential psychometric properties of innovative items. In this study, examinee responses to conventional (e.g., multiple choice) and innovative item formats in a computer‐based testing program were analyzed for IRT information with the three‐parameter and graded response models. The innovative item types considered in this study provided more information across all levels of ability than multiple‐choice items. In addition, accurate timing data captured via computer administration were analyzed to consider the relative efficiency of the multiple choice and innovative item types. As with previous research, multiple‐choice items provide more information per unit time. Implications for balancing policy, psychometric, and pragmatic factors in selecting item formats are also discussed.
Two New Statistics to Detect Answer Copying
Authors: Sotaridona Leonardo S. , Meijer Rob R.
Published: June 2006

Two new indices to detect answer copying on a multiple‐choice test—S1 and S2—were proposed. The S1 index is similar to the K index (Holland, 1996) and the K2 index (Sotaridona & Meijer, 2002) but the distribution of the number of matching incorrect answers of the source and the copier is modeled by the Poisson distribution instead of the binomial distribution to improve the detection rate of K and K2. The S2 index was proposed to overcome a limitation of the K and K2 index, namely, their insensitiveness to correct answers copying. The S2 index incorporates the matching correct answers in addition to the matching incorrect answers. A simulation study was conducted to investigate the usefulness of S1 and S2 for 40‐ and 80‐item tests, 100 and 500 sample sizes, and 10%, 20%, 30%, and 40% answer copying. The Type I errors and detection rates of S1 and S2 were compared with those of the K2 and the ω copying index (Wollack, 1997). Results showed that all four indices were able to maintain their Type I errors, with S1 and K2 being slightly conservative compared to S2 and ω. Furthermore, S1 had higher detection rates than K2. The S2 index showed a significant improvement in detection rate compared to K and K2.
The Relationship Between Item Exposure and Test Overlap in Computerized Adaptive Testing
Authors: Chen Shu‐Ying , Ankenmann Robert D. , Spray Judith A.
Published: June 2006

The purpose of this article is to present an analytical derivation for the mathematical form of an average between‐test overlap index as a function of the item exposure index, for fixed‐length computerized adaptive tests (CATs). This algebraic relationship is used to investigate the simultaneous control of item exposure at both the item and test levels. The results indicate that, in fixed‐length CATs, control of the average between‐test overlap is achieved via the mean and variance of the item exposure rates of the items that constitute the CAT item pool. The mean of the item exposure rates is easily manipulated. Control over the variance of the item exposure rates can be achieved via the maximum item exposure rate (rmax). Therefore, item exposure control methods which implement a specification of rmax (e.g., Sympson & Hetter, 1985) provide the most direct control at both the item and test levels.
Constructing a Universal Scale of High School Course Difficulty
Authors: Bassiri Dina , Schulz E. Matthew
Published: June 2006

This study examined the usefulness of applying the Rasch rating scale model (Andrich, 1978) to high school grade data. ACT Assessment test scores (English, Mathematics, Reading, and Science Reasoning) were used as “common items” to adjust for different grading standards in individual high school courses both within and across schools. This scaling approach yielded an ACT Assessment‐adjusted high school grade point average (AA‐HSGPA) on a common scale across high schools and cohorts within a large public university. AA‐HSGPA was a better predictor of first‐year college grade point average (CGPA) than the regular high school grade point average. The best model for predicting CGPA included both the ACT composite score and AA‐HSGPA.
Comparing Multidimensional and Unidimensional Proficiency Classifications: Multidimensional IRT as a Diagnostic Aid
Authors: Walker Cindy M. , Beretvas S. Natasha
Published: June 2006

This research examined the effect of scoring items thought to be multidimensional using a unidimensional model and demonstrated the use of multidimensional item response theory (MIRT) as a diagnostic tool. Using real data from a large‐scale mathematics test, previously shown to function differentially in favor of proficient writers, the difference in proficiency classifications was explored when a two‐versus one‐dimensional confirmatory model was fit. The estimate of ability obtained when using the unidimensional model was considered to represent general mathematical ability. Under the two‐dimensional model, one of the two dimensions was also considered to represent general mathematical ability. The second dimension was considered to represent the ability to communicate in mathematics. The resulting pattern of mismatched proficiency classifications suggested that examinees found to have less mathematics communication ability were more likely to be placed in a lower general mathematics proficiency classification under the unidimensional than multidimensional model. Results and implications are discussed.
Assessing Goodness of Fit of Item Response Theory Models: A Comparison of Traditional and Alternative Procedures
Authors: Stone Clement A. , Zhang Bo
Published: June 2006

Testing the goodness of fit of item response theory (IRT) models is relevant to validating IRT models, and new procedures have been proposed. These alternatives compare observed and expected response frequencies conditional on observed total scores, and use posterior probabilities for responses across θ levels rather than cross‐classifying examinees using point estimates of θ and score responses. This research compared these alternatives with regard to their methods, properties (Type 1 error rates and empirical power), available research, and practical issues (computational demands, treatment of missing data, effects of sample size and sparse data, and available computer programs). Different advantages and disadvantages related to these characteristics are discussed. A simulation study provided additional information about empirical power and Type 1 error rates.
Applying the Liu‐Agresti Estimator of the Cumulative Common Odds Ratio to DIF Detection in Polytomous Items
Authors: Penfield Randall D. , Algina James
Published: June 2006

Liu and Agresti (1996) proposed a Mantel and Haenszel‐type (1959) estimator of a common odds ratio for several 2 × J tables, where the J columns are ordinal levels of a response variable. This article applies the Liu‐Agresti estimator to the case of assessing differential item functioning (DIF) in items having an ordinal response variable. A simulation study was conducted to investigate the accuracy of the Liu‐Agresti estimator in relation to other statistical DIF detection procedures. The results of the simulation study indicate that the Liu‐Agresti estimator is a viable alternative to other DIF detection statistics.
Applications of the Analytically Derived Asymptotic Standard Errors of Item Response Theory Item Parameter Estimates
Authors: Li Yuan H. , Lissitz Robert W.
Published: June 2006

The analytically derived asymptotic standard errors (SEs) of maximum likelihood (ML) item estimates can be approximated by a mathematical function without examinees’ responses to test items, and the empirically determined SEs of marginal maximum likelihood estimation (MMLE)/Bayesian item estimates can be obtained when the same set of items is repeatedly estimated from the simulation (or resampling) test data. The latter method will result in rather stable and accurate SE estimates as the number of replications increases, but requires cumbersome and time‐consuming calculations. Instead of using the empirically determined method, the adequacy of using the analytical‐based method in predicting the SEs for item parameter estimates was examined by comparing results produced from both approaches. The results indicated that the SEs yielded from both approaches were, in most cases, very similar, especially when they were applied to a generalized partial credit model. This finding encourages test practitioners and researchers to apply the analytically asymptotic SEs of item estimates to the context of item‐linking studies, as well as to the method of quantifying the SEs of equating scores for the item response theory (IRT) true‐score method. Three‐dimensional graphical presentation for the analytical SEs of item estimates as the bivariate function of item difficulty together with item discrimination was also provided for a better understanding of several frequently used IRT models.
Effects of Differentially Time‐Consuming Tests on Computer‐Adaptive Test Scores
Authors: Bridgeman Brent , Cline Frederick
Published: June 2006

Time limits on some computer‐adaptive tests (CATs) are such that many examinees have difficulty finishing, and some examinees may be administered tests with more time‐consuming items than others. Results from over 100,000 examinees suggested that about half of the examinees must guess on the final six questions of the analytical section of the Graduate Record Examination if they were to finish before time expires. At the higher‐ability levels, even more guessing was required because the questions administered to higher‐ability examinees were typically more time consuming. Because the scoring model is not designed to cope with extended strings of guesses, substantial errors in ability estimates can be introduced when CATs have strict time limits. Furthermore, examinees who are administered tests with a disproportionate number of time‐consuming items appear to get lower scores than examinees of comparable ability who are administered tests containing items that can be answered more quickly, though the issue is very complex because of the relationship of time and difficulty, and the multidimensionality of the test.
An Interactive Method to Solve Infeasibility in Linear Programming Test Assembling Models
Authors: Huitzing Hiddo A.
Published: June 2006

In optimal assembly of tests from item banks, linear programming (LP) models have proved to be very useful. Assembly by hand has become nearly impossible, but these LP techniques are able to find the best solutions, given the demands and needs of the test to be assembled and the specifics of the item bank from which it is assembled. However, sometimes even LP techniques do not offer an acceptable solution to the test assembler. Infeasibility occurs when the demands are contradictory. These contradictions may be rather complex, especially when stated in terms of LP models. Techniques are described that can solve these infeasibility problems in different manners. The objectives are twofold. First, the assembler is given a helping hand to identify the bottlenecks in the specifications of the LP model. Second, a solution is forced, such that the test assembler is always presented a test as close as possible to the original specifications. These objectives should be realizable both automatically and interactively with the test assembler.
Accuracy of Measurement in the Context of Mathematics National Curriculum Tests in England for Ethnic Minority Pupils and Pupils Who Speak English as an Additional Language
Authors: Lamprianou Iasonas , Boyle Bill
Published: June 2006

Research has suggested that inappropriate or misfitting response patterns may have detrimental effects on the quality and validity of measurement. It has been suggested that factors like language and ethnic background are related to the generation of misfitting response patterns, but the empirical research on this is rather poor. This research analyzes data from three testing cycles of the National Curriculum tests in mathematics in England using the Rasch model. It was found that pupils having English as an additional language and pupils belonging to ethnic minorities are significantly more likely to generate aberrant response patterns. However, within the groups of pupils belonging to ethnic minorities, those who speak English as an additional language are not significantly more likely to generate misfitting response patterns. This may indicate that the ethnic background effect is more significant than the effect of the first language spoken. The results suggest that pupils having English as an additional language and pupils belonging to ethnic minorities are mismeasured significantly more than the remainder of pupils by taking the mathematics National Curriculum tests. More research is needed to generalize the results to other subjects and contexts.
Impact of Fewer Questions per Section on SAT I Scores
Authors: Bridgeman Brent , Trapani Catherine , Curley Edward
Published: June 2006

The impact of allowing more time for each question on the SAT I: Reasoning Test scores was estimated by embedding sections with a reduced number of questions into the standard 30‐minute equating section of two national test administrations. Thus, for example, questions were deleted from a verbal section that contained 35 questions to produce forms that contained 27 or 23 questions. Scores on the 23‐question section could then be compared to scores on the same 23 questions when they were embedded in a section that contained 27 or 35 questions. Similarly, questions were deleted from a 25‐question math section to form sections of 20 and 17 questions. Allowing more time per question had a minimal impact on verbal scores, producing gains of less than 10 points on the 200–800 SAT scale. Gains for the math score were less than 30 points. High‐scoring students tended to benefit more than lower‐scoring students, with extra time creating no increase in scores for students with SAT scores of 400 or lower. Ethnic/racial and gender differences were neither increased nor reduced with extra time.
Exact Small‐Sample Differential Item Functioning Methods for Polytomous Items With Illustration Based on an Attitude Survey
Authors: Meyer J. Patrick , Huynh Huynh , Seaman Michael A.
Published: June 2006

Exact nonparametric procedures have been used to identify the level of differential item functioning (DIF) in binary items. This study explored the use of exact DIF procedures with items scored on a Likert scale. The results from an attitude survey suggest that the large‐sample Cochran‐Mantel‐Haenszel (CMH) procedure identifies more items as statistically significant than two comparable exact nonparametric methods. This finding is consistent with previous findings; however, when items are classified in National Assessment of Educational Progress DIF categories, the results show that the CMH and its exact nonparametric counterparts produce almost identical classifications. Since DIF is often evaluated in terms of statistical and practical significance, this study provides evidence that the large‐sample CMH procedure may be safely used even when the focal group has as few as 76 cases.
A Statistical Test for Detecting Answer Copying on Multiple‐Choice Tests
Authors: van der Linden Wim J. , Sotaridona Leonardo
Published: June 2006

A statistical test for the detection of answer copying on multiple‐choice tests is presented. The test is based on the idea that the answers of examinees to test items may be the result of three possible processes: (1) knowing, (2) guessing, and (3) copying, but that examinees who do not have access to the answers of other examinees can arrive at their answers only through the first two processes. This assumption leads to a distribution for the number of matched incorrect alternatives between the examinee suspected of copying and the examinee believed to be the source that belongs to a family of “shifted binomials.” Power functions for the tests for several sets of parameter values are analyzed. An extension of the test to include matched numbers of correct alternatives would lead to improper statistical hypotheses.
Control and co-ordination in corporate rescue
Authors: Finch Vanessa
Published: June 2006

The Enterprise Act 2002 sought to assist troubled companies by enhancing the rescue-friendliness of the UK insolvency regime. Assessing that regime calls for a focus on: the different roles and control powers of the various parties involved with troubled companies; the essential tasks that a rescue regime has to carry out; and the level of co-ordination that is to be expected between different parties. Key tasks in the furtherance of rescue are: the collectiiig of relevant information; the production of sound judgments and strategies; and the taking of timely actions and decisions. The problems of co-ordination, moreover, vary from task to task. For judges, central challenges in coming years will be not only to protect parties’rights within the new rescue regime but also to use judicial oversight powers to encourage co-ordinated action in pursuit of rescue. An appreciation of the co-ordination issue is central to an understanding of the post-Enterprise Act 2002 regime and the potential of the judges to enhance that regime in its furtherance of rescue.
Positive Natural Selection in the Human Lineage
Authors: Sabeti P. C. , Schaffner S. F. , Fry B. , Lohmueller J. , Varilly P. , Shamovsky O. , Palma A. , Mikkelsen T. S. , Altshuler D. , Lander E. S.
Published: June 2006

Positive natural selection is the force that drives the increase in prevalence of advantageous traits, and it has played a central role in our development as a species. Until recently, the study of natural selection in humans has largely been restricted to comparing individual candidate genes to theoretical expectations. The advent of genome-wide sequence and polymorphism data brings fundamental new tools to the study of natural selection. It is now possible to identify new candidates for selection and to reevaluate previous claims by comparison with empirical distributions of DNA sequence variation across the human genome and among populations. The flood of data and analytical methods, however, raises many new challenges. Here, we review approaches to detect positive natural selection, describe results from recent analyses of genome-wide data, and discuss the prospects and challenges ahead as we expand our understanding of the role of natural selection in shaping the human genome.
The Age of the Taklimakan Desert
Authors: Sun Jimin , Liu Tungsheng
Published: June 2006

The Taklimakan Desert is located in the foreland basin of the Tibetan Plateau. We report here the results of stratigraphic investigations of a 1626-meter-thick sequence with interbedded wind-blown silt from the southern marginal Taklimakan Desert. Because the studied section is located downwind of the desert, the eolian silt accumulation is closely linked to desert formation. Our new evidence indicates that shifting sand dunes prevailed in the Tarim Basin by at least 5.3 million years ago, as they do today. We attribute this event to late Cenozoic climatic deterioration, as well as to changes in atmospheric circulation induced by Tibetan Plateau uplift.
Regulation of B Cell Tolerance by the Lupus Susceptibility Gene
Ly108
Authors: Kumar Kirthi Raman , Li Liunan , Yan Mei , Bhaskarabhatla Madhavi , Mobley Angela B. , Nguyen Charles , Mooney Jill M. , Schatzle John D. , Wakeland Edward K. , Mohan Chandra
Published: June 2006

The susceptibility locus for the autoimmune disease lupus on murine chromosome 1,
Sle1
z
/
Sle1b
z
, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of
Sle1
z
/
Sle1b
z
impairs B cell anergy, receptor revision, and deletion. Members of the
SLAM
costimulatory molecule family constitute prime candidates for

Sle1b
z

, among which the
Ly108.1
isoform of the
Ly108
gene was most highly expressed in immature B cells from lupus-prone B6.
Sle1
z
mice. The normal
Ly108.2
allele, but not the lupus-associated
Ly108.1
allele, was found to sensitize immature B cells to deletion and
RAG
reexpression. As a potential regulator of tolerance checkpoints,
Ly108
may censor self-reactive B cells, hence safeguarding against autoimmunity.
Phosphatized Polar Lobe-Forming Embryos from the Precambrian of Southwest China
Authors: Chen Jun-Yuan , Bottjer David J. , Davidson Eric H. , Dornbos Stephen Q. , Gao Xiang , Yang Yong-Hua , Li Chia-Wei , Li Gang , Wang Xiu-Qiang , Xian Ding-Chang , Wu Hung-Jen , Hwu Yeu-Kuang , Tafforeau Paul
Published: June 2006

In developing embryos of some extant spiralian animals, polar lobe formation is one of the symmetry-breaking mechanisms for segregation of maternal cytoplasmic substances to certain blastomeres and not others. Polar lobe formation leads to unique early cleavage morphologies that include trilobed, J-shaped, and five-lobed structures. Fossil embryos similar to modern lobeforming embryos are recognized from the Precambrian Doushantuo Formation phosphates, Weng'an, Guizhou Province, China. These embryos are abundant and form a developmental sequence comparable to different developing stages observed in lobe-forming embryos of extant spiralians. These data imply that lobe formation is an evolutionarily ancient process of embryonic specification.
Bidirectional Counting of Single Electrons
Authors: Fujisawa Toshimasa , Hayashi Toshiaki , Tomita Ritsuya , Hirayama Yoshiro
Published: June 2006

A bidirectional single-electron counting device is demonstrated. Individual electrons flowing in forward and reverse directions through a double quantum dot are detected with a quantum point contact acting as a charge sensor. A comprehensive statistical analysis in the frequency and time domains and of higher order moments of noise reveals antibunching correlation in single-electron transport through the device itself. The device can also be used to investigate current flow in the attoampere range, which cannot be measured by existing current meters.
Reverse Genetic Generation of Recombinant Zaire Ebola Viruses Containing Disrupted IRF-3 Inhibitory Domains Results in Attenuated Virus Growth In Vitro and Higher Levels of IRF-3 Activation without Inhibiting Viral Transcription or Replication
Authors: Hartman Amy L. , Dover Jason E. , Towner Jonathan S. , Nichol Stuart T.
Published: June 2006

The VP35 protein of Zaire Ebola virus is an essential component of the viral RNA polymerase complex and also functions to antagonize the cellular type I interferon (IFN) response by blocking activation of the transcription factor IRF-3. We previously mapped the IRF-3 inhibitory domain within the C terminus of VP35. In the present study, we show that mutations that disrupt the IRF-3 inhibitory function of VP35 do not disrupt viral transcription/replication, suggesting that the two functions of VP35 are separable. Second, using reverse genetics, we successfully recovered recombinant Ebola viruses containing mutations within the IRF-3 inhibitory domain. Importantly, we show that the recombinant viruses were attenuated for growth in cell culture and that they activated IRF-3 and IRF-3-inducible gene expression at levels higher than that for Ebola virus containing wild-type VP35. In the context of Ebola virus pathogenesis, VP35 may function to limit early IFN-β production and other antiviral signals generated from cells at the primary site of infection, thereby slowing down the host's ability to curb virus replication and induce adaptive immunity.
Protective Immunity against Secondary Poxvirus Infection Is Dependent on Antibody but Not on CD4 or CD8 T-Cell Function
Authors: Panchanathan Vijay , Chaudhri Geeta , Karupiah Gunasegaran
Published: June 2006

Renewed interest in smallpox and the need for safer vaccines have highlighted our lack of understanding of the requirements for protective immunity. Since smallpox has been eradicated, surrogate animal models of closely related orthopoxviruses, such as ectromelia virus, have been used to establish critical roles for CD8 T cells in the control of primary infection. To study the requirements for protection against secondary infection, we have used a prime-challenge regime, in which avirulent ectromelia virus was used to prime mice that were then challenged with virulent ectromelia virus. In contrast to primary infection, T cells are not required for recovery from secondary infection, since gene knockout mice deficient in CD8 T-cell function and wild-type mice acutely depleted of CD4, CD8, or both subsets were fully protected. Protection correlated with effective virus control and generation of neutralizing antibody. Notably, primed mice that lacked B cells, major histocompatibility complex class II, or CD40 succumbed to secondary infection. Thus, antibody is essential, but CD4 or CD8 T cells are not required for recovery from secondary poxvirus infection.
LMP1 Strain Variants: Biological and Molecular Properties
Authors: Mainou Bernardo A. , Raab-Traub Nancy
Published: June 2006

The ubiquitous herpesvirus Epstein-Barr virus (EBV) is linked to the development of several malignancies, including nasopharyngeal carcinoma. Latent membrane protein 1 (LMP1) is considered the EBV oncogene as it is necessary for EBV-induced transformation of B lymphocytes and is able to transform Rat-1 fibroblasts. LMP1 can activate a wide array of signaling pathways, including phosphatidylinositol 3-kinase (PI3K)-Akt and NF-κB. Six sequence variants of LMP1, termed Alaskan, China 1, China 2, Med+, Med−, and NC, have been identified, and individuals can be infected with multiple variants. The frequencies of detection of these variants differ for various EBV-associated malignancies from different geographic regions. In this study, the biological and signaling properties of the LMP1 variants have been characterized. All of the LMP1 variants transformed Rat-1 fibroblasts, induced increased motility of HFK cells, and induced increased homotypic adhesion of BJAB cells. While all the variants activated the PI3K-Akt signaling pathway to similar extents, the Alaskan, China 1, and Med+ variants had limited binding to the E3 ubiquitin ligase component homologue of Slimb and had slightly enhanced NF-κB signaling. These findings indicate that the signature amino acid changes of the LMP1 variants do not hinder or enhance their in vitro transforming potentials or affect their signaling properties.
Characterization of the RNA Chaperone Activity of Hantavirus Nucleocapsid Protein
Authors: Mir M. A. , Panganiban A. T.
Published: June 2006

Hantaviruses are tripartite negative-sense RNA viruses and members of the
Bunyaviridae
family. The nucleocapsid (N) protein, encoded by the smallest of the three genome segments (S), has nonspecific RNA chaperone activity. This activity results in transient dissociation of misfolded RNA structures, may be required for facilitating correct higher-order RNA structure, and may function in viral genome replication. We carried out a series of experiments to further characterize the ability of N to dissociate RNA duplexes. As might be expected, N dissociated RNA duplexes but not DNA duplexes or RNA-DNA heteroduplexes. The RNA-destabilizing activity of N is ATP independent, has a pH optimum of 7.5, and has an Mg
2+
concentration optimum of 1 to 2 mM. N protein is unable to unwind the RNA duplexes that are completely double stranded. However, in the presence of an adjoining single-stranded region, helix unwinding takes place in the 3′-to-5′ direction through an unknown mechanism. The N protein trimer specifically recognizes and unwinds the terminal panhandle structure in the viral RNA and remains associated with unwound 5′ terminus. We suggest that hantaviral nucleocapsid protein has an active role in hantaviral replication by working cooperatively with viral RNA polymerase. After specific recognition of the panhandle structure by N protein, the unwound 5′ terminus likely remains transiently bound to N protein, creating an opportunity for the viral polymerase to initiate transcription at the accessible 3′ terminus.
A PERK-Like Receptor Kinase Interacts with the Geminivirus Nuclear Shuttle Protein and Potentiates Viral Infection
Authors: Florentino Lilian H. , Santos Anésia A. , Fontenelle Mariana R. , Pinheiro Guilherme L. , Zerbini Francisco M. , Baracat-Pereira Maria C. , Fontes Elizabeth P. B.
Published: June 2006

The nuclear shuttle protein (NSP) from bipartite geminiviruses facilitates the intracellular transport of viral DNA from the nucleus to the cytoplasm and acts in concert with the movement protein (MP) to promote the cell-to-cell spread of the viral DNA. A proline-rich extensin-like receptor protein kinase (PERK) was found to interact specifically with NSP of
Cabbage leaf curl virus
(CaLCuV) and of tomato-infecting geminiviruses through a yeast two-hybrid screening. The PERK-like protein, which we designated NsAK (for NSP-associated kinase), is structurally organized into a proline-rich N-terminal domain, followed by a transmembrane segment and a C-terminal serine/threonine kinase domain. The viral protein interacted stably with defective versions of the NsAK kinase domain, but not with the potentially active enzyme, in an in vitro binding assay. In vitro-translated NsAK enhanced the phosphorylation level of NSP, indicating that NSP functions as a substrate for NsAK. These results demonstrate that NsAK is an authentic serine/threonine kinase and suggest a functional link for NSP-NsAK complex formation. This interpretation was corroborated by in vivo infectivity assays showing that loss of NsAK function reduces the efficiency of CaLCuV infection and attenuates symptom development. Our data implicate NsAK as a positive contributor to geminivirus infection and suggest it may regulate NSP function.
High Rate of Genetic Recombination in Murine Leukemia Virus: Implications for Influencing Proviral Ploidy
Authors: Zhuang Jianling , Mukherjee Sayandip , Ron Yacov , Dougherty Joseph P.
Published: June 2006

A significant difference in the recombination rates between human immunodeficiency virus type 1 (HIV-1) and the gammaretroviruses was previously reported, with the former being 10 to 100 times more recombinogenic. It is possible that preferential copackaging of homodimers in the case of gammaretroviruses, like murine leukemia virus (MLV), led to the underestimation of their rates of recombination. To reexamine the recombination rates for MLV, experiments were performed to control for nonrandom copackaging of viral RNA, and it was found that MLV and HIV-1 exhibit similar crossover rates. The implications for control of proviral ploidy and preferential recombination during minus-strand DNA synthesis are discussed.
Functional Replacement of the RING, B-Box 2, and Coiled-Coil Domains of Tripartite Motif 5α (TRIM5α) by Heterologous TRIM Domains
Authors: Li Xing , Li Yuan , Stremlau Matthew , Yuan Wen , Song Byeongwoon , Perron Michel , Sodroski Joseph
Published: June 2006

Tripartite motif 5α (TRIM5α) restricts some retroviruses, including human immunodeficiency virus type 1 (HIV-1), from infecting the cells of particular species. TRIM5α is a member of the TRIM family of proteins, which contain RING, B-box, coiled-coil (CC), and, in some cases, B30.2(SPRY) domains. Here we investigated the abilities of domains from TRIM proteins (TRIM6, TRIM34, and TRIM21) that do not restrict HIV-1 infection to substitute for the domains of rhesus monkey TRIM5α (TRIM5α
rh
). The RING, B-box 2, and CC domains of the paralogous TRIM6 and TRIM34 proteins functionally replaced the corresponding TRIM5α
rh
domains, allowing HIV-1 restriction. By contrast, similar chimeras containing the components of TRIM21, a slightly more distant relative of TRIM5, did not restrict HIV-1 infection. The TRIM21 B-box 2 domain and its flanking linker regions contributed to the functional defectiveness of these chimeras. All of the chimeric proteins formed trimers. All of the chimeras that restricted HIV-1 infection bound the assembled HIV-1 capsid complexes. These results indicate that heterologous RING, B-box 2, and CC domains from related TRIM proteins can functionally substitute for TRIM5α
rh
domains.
Active Viremia in Rotavirus-Infected Mice
Authors: Blutt Sarah E. , Fenaux Martijn , Warfield Kelly L. , Greenberg Harry B. , Conner Margaret E.
Published: June 2006

Rotavirus circulates extraintestinally in animals used as models for rotavirus infection and in children. Rotavirus infection in mice was used to define host or viral factors that affect rotavirus viremia. Antigenemia was observed with homologous and heterologous rotaviruses, and neither age nor mouse strain genetics altered the occurrence of rotavirus antigenemia or viremia. Rotavirus RNA and infectious virus were present in sera and associated with the plasma fraction of blood in all infected mice. These findings indicate that antigenemia/viremia occurs routinely in rotavirus infections and imply that infectious rotavirus has access to any extraintestinal cell within contact of blood.
Residual Human Immunodeficiency Virus Type 1 Viremia in Some Patients on Antiretroviral Therapy Is Dominated by a Small Number of Invariant Clones Rarely Found in Circulating CD4
+
T Cells
Authors: Bailey Justin R. , Sedaghat Ahmad R. , Kieffer Tara , Brennan Timothy , Lee Patricia K. , Wind-Rotolo Megan , Haggerty Christine M. , Kamireddi Ashrit R. , Liu Yi , Lee Jessica , Persaud Deborah , Gallant Joel E. , Cofrancesco Joseph , Quinn Thomas C. , Wilke Claus O. , Ray Stuart C. , Siliciano Janet D. , Nettles Richard E. , Siliciano Robert F.
Published: June 2006

Antiretroviral therapy can reduce human immunodeficiency virus type 1 (HIV-1) viremia to below the detection limit of ultrasensitive clinical assays (50 copies of HIV-1 RNA/ml). However, latent HIV-1 persists in resting CD4
+
T cells, and low residual levels of free virus are found in the plasma. Limited characterization of this residual viremia has been done because of the low number of virions per sample. Using intensive sampling, we analyzed residual viremia and compared these viruses to latent proviruses in resting CD4
+
T cells in peripheral blood. For each patient, we found some viruses in the plasma that were identical to viruses in resting CD4
+
T cells by
pol
gene sequencing. However, in a majority of patients, the most common viruses in the plasma were rarely found in resting CD4
+
T cells even when the resting cell compartment was analyzed with assays that detect replication-competent viruses. Despite the large diversity of
pol
sequences in resting CD4
+
T cells, the residual viremia was dominated by a homogeneous population of viruses with identical
pol
sequences. In the most extensively studied case, a predominant plasma sequence was also found in analysis of the
env
gene, and linkage by long-distance reverse transcriptase PCR established that these predominant plasma sequences represented a single predominant plasma virus clone. The predominant plasma clones were released for months to years without evident sequence change. Thus, in some patients on antiretroviral therapy, the major mechanism for residual viremia involves prolonged production of a small number of viral clones without evident evolution, possibly by cells other than circulating CD4
+
T cells.