bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Anion Gap and Blood Pressure in the National Health and Nutrition Examination Survey
Authors: Taylor Eric N. , Forman John P. , Farwell Wildon R.
Published: June 2007

Increased production of organic acid can result in an elevated serum anion gap and may play a role in the development of hypertension. We studied the cross-sectional associations between anion gap and blood pressure and between serum bicarbonate and blood pressure in the 1999-2000 and 2001-2002 National Health and Nutrition Examination Surveys. We included 5043 adult participants who were not taking antihypertensive medications or diuretics and who denied hypertension, cardiovascular disease, diabetes, and other diseases. Linear regression was used to adjust for age, race, body mass index, creatinine, albumin, and other factors. Sample weights were used to produce weighted regression parameters. In the lowest quintile of anion gap, mean values of sodium, chloride, and bicarbonate were 139 mEq/L, 105 mEq/L, and 25 mEq/L, respectively. In the highest quintile, mean values of sodium, chloride, and bicarbonate were 140 mEq/L, 101 mEq/L, and 22 mEq/L, respectively. Mean blood pressure was 118/72 mm Hg. After multivariable adjustment, participants in the highest quintile of anion gap had systolic blood pressure 3.73 mm Hg higher (95% CI: 1.83 to 5.63 mm Hg;
P
for trend: <0.01) than participants in the lowest quintile. Participants in the highest quintile of bicarbonate had systolic blood pressure 2.73 mm Hg lower (95% CI: 1.26 to 4.20 mm Hg;
P
for trend: <0.01) than participants in the lowest quintile. No associations were observed between anion gap or bicarbonate and diastolic blood pressure. The results were unchanged after excluding participants with estimated glomerular filtration rate <60 cc/min per 1.73 m
2
. The anion gap is independently associated with higher blood pressure. Further research is needed to elucidate the relation between organic acid and hypertension.
Restorative Justice at Work: Examining the Impact of Restorative Justice Resolutions on Juvenile Recidivism
Authors: Rodriguez Nancy
Published: June 2007

Programs with restorative justice ideals attempt to incorporate victims and community members into the administration of justice. Although these programs have become increasingly popular, only a few programs in the United States have been the focus of prior studies. Using official juvenile court data from an urban, metropolitan area, this study finds that juveniles who participated in a restorative justice program were less likely to recidivate than juveniles in a comparison group. Also, gender and prior offenses indirectly influence recidivism in important ways. Girls and offenders with minimal criminal history records exhibit the most success from participating in such programs. Findings demonstrate the importance of examining additive and interactive effects in restorative justice research.
Wrongful Conviction
Authors: Ramsey Robert J. , Frank James
Published: June 2007

Drawing on a sample of 798 Ohio criminal justice professionals (police, prosecutors, defense attorneys, judges), the authors examine respondents' perceptions regarding the frequency of system errors (i.e., professional error and misconduct suggested by previous research to be associated with wrongful conviction), and wrongful felony conviction. Results indicate that respondents perceive system errors to occur more than infrequently but less than moderately frequent. Respondents also perceive that wrongful felony conviction occurs in their own jurisdictions in .5% to 1% of all felony cases, and in the United States in 1% to 3% of all felony cases. Respondents, however, specify an acceptable rate of wrongful conviction to be less than .5%. Findings thus indicate that criminal justice professionals perceive an unacceptable frequency of wrongful conviction and associated system errors and suggest that programs aimed at reducing system errors and improving professional conduct would be broadly accepted among criminal justice professionals.
Perceptions of Punishment
Authors: Tewksbury Richard , Lees Matthew B.
Published: June 2007

Sex offender registries (SORs) are a societal response to serious and presumably dangerous criminal offenders. Existing research on registries has focused on demographic overviews of registrants, assessments of registrants' recidivism, accuracy and completeness of listed information, and collateral consequences for registrants. The present research assesses the perceptions of registrants regarding the value of SORs as a tool to enhance community awareness and promote public safety. In addition, this study examines offenders' perceptions of the strengths and weaknesses of registry format and structure and suggestions for improvement. Results show that registrants see significant potential for registries but seriously question the efficacy and efficiency of how registries are currently constructed and used.
At-Risk Girls and Delinquency
Authors: Davis Carla P.
Published: June 2007

Through fieldwork and in-depth interviews examining the careers of adolescent girls in the juvenile justice system, this article reveals some of the interaction processes by which challenges to parental authority may facilitate contact, entry, and movement through the system. Parents or guardians act as informal agents of control until a breakdown in family solidarity prompts appeal to more formal measures of control. These findings suggest the continuing significance of status offenses in the arrest and incarceration of girls. The 1974 Juvenile Justice and Delinquency Prevention Act restrained courts from responding vigorously to status-type offenses. This article illustrates how families, in their interactions with authorities, have negotiated alternative methods for dealing with troublesome teenage girls.
Epithet or Endearment? Examining Reactions Among Those of the African Diaspora to an Ethnic Epithet
Authors: Motley Carol M. , Craig-Henderson Kellina M.
Published: June 2007

Although scholars throughout the social sciences have considered cultural differences among individuals in the African Diaspora, there is little marketplace research examining differences among these peoples. The present research was conducted to better understand how varying identities and cultural group norms influence attitudes, language, communications, and consumption patterns in reactions to the socially explosive epithet nigger. Qualitative research was conducted involving a series of in-depth interviews with people of the African Diaspora who were living in the United States. Analysis of interview data suggests the prominent influence of respondents' culture of origin in their knowledge structures, affective reactions, and expressed contingencies for use. In general, findings from this research reveal the multiple meanings and usage of the term nigger and its derivatives among peoples of the African Diaspora.
Dating Across Race
Authors: Wilson Shauna B. , McIntosh William D. , Insana Salvatore P.
Published: June 2007

The purpose of this study was to determine the factors associated with Black Americans' dating preferences. Two hundred profiles of Black individuals in the United States (100 men and 100 women) were accessed on the Internet dating site Match.com. Fourteen demographic and personal variables were correlated with willingness to date Whites, Hispanics, Native Americans, and Asians, as well as other Blacks. Blacks willing to interracially date tended to be male, young, and/or attractive, tended to smoke, abstain from exercise, and either definitely or possibly wanted children. Willingness to date intraracially was related to living in any geographical region except the West, being a nonsmoker, and being sure of either wanting or not wanting children. Factors unrelated to dating preference included having or not having children, education, political standpoint, religion, body type, and drinking habits. Both mate selection theory and exchange theory were applied in interpreting results.
What They Came With
Authors: Irobi Esiaba
Published: June 2007

This article identifies what was on the continent as festival and ritual performance forms before the Europeans arrived and what the Africans who survived the Atlantic sea crossing came with as “performative literacies” to the Brave New World. The article then examines how these cultural texts and phenomenological deposits have given us hybridized and syncretized aesthetic infrastructures that interrogate the theologies of supremacy often associated with Whiteness and other manifestations of Western cultural and intellectual hegemony. The article then asks, “Does the body have a memory?” and answers by examining how “translocated” indigenous African kinaesthetic intelligence informs the aesthetics of ritual, festive, and carnival performances in the Caribbean, North and South America, the Middle East, and Europe, including Candomble, Voudun, Santeria, Lucumi, Mardi Gras, Oshun, John Konnu, and hip hop, but the focus is on the Omabe Festival Drama of Nsukka-Igbo in Nigeria and the Carnival phenomenon from the Caribbean.
What Is Africana Critical Theory or Black Existential Philosophy?
Authors: Bassey Magnus O.
Published: June 2007

In this article, the author argues that Africana critical theory or Black existential philosophy is the philosophical discourse that critiques domination and affirms the empowerment of Black people in the world. However, although Africana critical theory shares similar concerns and themes such as existence, consciousness, trepidation, meaninglessness, hopelessness, fear, despair, servility, and abasement with European existentialism, there are important distinctions between them. For example, although European existentialism is, as Gordon says, “predicated on the uniqueness of the individual as well as on a universalist conception of humans and their obligation to self,” Africana critical theory or Black existential philosophy is predicated on the liberation of all Black people in the world from oppression.
Bridging the Gap
Authors: Langmia Kehbuma , Durham Eric
Published: June 2007

This study stands as a progressive attempt to investigate the intercultural communicative dynamic between African and African American college students enrolled in historically Black colleges and universities. As these two distinct cultures share more of the same space, it becomes increasingly pertinent to evaluate and understand the ways in which perception and stereotype affect intercultural interactions. Utilizing focus group sessions, various cultural nuances and stereotypical perceptions of each culture are candidly discussed. A combination of Hans-Georg Gadamer's phenomenology and Martin Buber's dialogue act as the theoretical lenses that organize the invaluable data collected from a focus group discussion. The underlying significance of this study is that the African diaspora created two distinct cultures that currently experience dissonance that may have otherwise not existed.
Modeling and Simulation in Service-Oriented Software Development
Authors: Tsai W.T. , Zhibin Cao  , Xiao Wei  , Paul Ray , Qian Huang  , Xin Sun
Published: June 2007

Recently, Service-Oriented Architecture (SOA) has received significant attention. SOA simulation can play an important role in SOA software development as it can be used to verify the SOA application models and to demonstrate runtime and collaborative behaviors of the SOA applications. SOA simulation differs from traditional simulation as it emphasizes on reusability, collaborative behaviors, and its unique model-driven development. This paper focuses on these issues and illustrates how these can be achieved.
A Petri Net-based Approach for Automated Goal-Driven Web Service Composition
Authors: Zhovtobryukh Dmytro
Published: June 2007

The major factor driving the development of contemporary information services, and in particular Web services, is the need for added value. The creation of a huge variety of complex, value-added, although rarely used services seems a bulky approach, whose efficiency is at least questionable. An excellent alternative is the composition of ready-made, more general and simple services for creation of complex value-added functionality on-demand. However, to be really effective such composition has to be real-time, automatic, reliable, and allow thorough customization of the service functionality with respect to user demands and preferences. In this paper we propose a service composition approach based on a Petri nets modeling technique. The approach facilitates automatic and goal-driven creation of composite Web services
Modeling and Simulation of QoS-aware Web Service Selection for Provider Profit Maximization
Authors: Tsesmetzis Dimitrios , Roussaki Ioanna , Sykas Efstathios
Published: June 2007

Web Services (WSs) are a new breed of web application that is gaining momentum. One of the research challenges it brings along is the establishment of an interoperable semantic framework suitable to represent not only the functional, but also the non-functional features of WSs, i.e. their Quality-of-Service (QoS), which in most cases are not included in the WS description. Nevertheless, integrating QoS features in WS profiles is to the advantage of both users and providers, as it supports QoS-aware WS selection and composition addressing the user's QoS requirements, while enabling WS providers to increase their profits. The purpose of this paper is twofold. On the one hand, it aims to present a QoS ontology framework adequate for WS provision. On the other hand, it studies the problem of providers that receive concurrent requests of numerous customers for WSs demonstrating different bandwidth and price properties. It introduces the “Selective Multiple Choice Knapsack Problem” that aims to identify the services that should be delivered to the customers in order to maximize the provider's profit, subject to maximum bandwidth constraints on the server side. Thus, the QoS-awareness in this version of this problem is limited to the consideration of two QoS parameters: service bandwidth and cost. The problem is solved by a proposed algorithm that has been empirically evaluated via numerous experiments.
Quality of Service Measures of Mobile Ad-hoc Wireless Network using Energy Consumption Mitigation with Asynchronous Inactivity Periods
Authors: Mavromoustakis Constandinos X. , Karatza Helen D.
Published: June 2007

Improper power management in a wireless network can substantially degrade the Quality of Service (QoS) and increase the overall energy consumed. This can further lead to network partitioning problems, which denote inefficiency in hosting multimedia applications. Current scheduling approaches for energy conservation save energy by allowing either periodic “idling” or high latencies, which are unable to host delay-sensitive multimedia applications. Delay-sensitive applications need to have an end-to-end path with energy availability. In this paper, an on-demand scheme is proposed based on each node's self-scheduling energy management, suitable for hosting delay-sensitive traffic. A sleep history characterization for the traffic is modeled, affecting the overall idle or inactive/sleep duration in a way that enables energy conservation. Through simulation, the QoS of the proposed scheme is evaluated by using two different routing schemes. These schemes prove that the overall energy savings during delay-sensitive transmissions using asynchronous (non-periodic) sleep time is significantly higher than the synchronous (periodic). Experimental results depict the scheme's efficiency with respect to the underlying routing protocol used, to manage nodes' energy on a self-tuned mode.
A Pipeline Virtual Service Pre-Scheduling Pattern and its Application in Astronomy Data Processing
Authors: Man Wang  , Zhihui Du  , Zhili Cheng  , Suihui Zhu
Published: June 2007

Based on Open Grid Services Architecture (OGSA), the concept and the formal model of Pipeline Virtual Service (PVS) are proposed and presented in this paper. PVS is used to model a special type of grid workflow composed of a group of services that can be executed as a pipeline. A PVS Pre-Scheduling Pattern is described in detail, which can overlap the execution time of a PVS with the time of generating and optimizing the scheduling solution pool. The Pattern includes two independent components, the solution generating component (GenFunc) and the solution execution component (ExeFunc). GenFunc can take advantage of the powerful computing potential of grid environment to find the optimal or a near optimal scheduling solution, while ExeFunc can select a suitable scheduling solution and put a PVS into running as soon as possible. Two corresponding algorithms, SODGen and SODExe, are also developed. The analytic and simulation results show that the PVS Pre-Scheduling Pattern can not only balance the scheduling cost and scheduling precision, save the scheduling time greatly, but also reduce the execution time through selecting the optimized solution. A prototype is designed and implemented for a large scale astronomy data processing center. The early engineering evaluation experiments show that the PVS Pre-Scheduling Pattern is feasible, efficient, and flexible in real astronomy data processing.
Multinomial and Compound Multinomial Error Models for Tests With Complex Item Scoring
Authors: Lee Won-Chan
Published: June 2007

This article introduces a multinomial error model, which models an examinee's test scores obtained over repeated measurements of an assessment that consists of polytomously scored items. A compound multinomial error model is also introduced for situations in which items are stratified according to content categories and/or prespecified numbers of score points. The multinomial and compound multinomial models are implemented in this article for estimating conditional standard errors of measurement and reliability. The applicability of the multinomial and compound multinomial models is illustrated with two real data examples. The first example considers test scores obtained from polytomous items only, and the second example contains test scores from a mixture of dichotomous and polytomous items. A simulation study is conducted to examine the amount and pattern of bias in the estimated conditional standard errors of measurement. Index terms: multinomial model, compound multinomial model, standard errors of measurement, reliability, scale scores
A Method for Estimating Classification Consistency Indices for Two Equated Forms
Authors: Hyun Sook Yi  , Kim Seonghoon , Brennan Robert L.
Published: June 2007

Large-scale testing programs involving classification decisions typically have multiple forms available and conduct equating to ensure cut-score comparability across forms. A test developer might be interested in the extent to which an examinee who happens to take a particular form would have a consistent classification decision if he or she had taken an equated alternate form. In this article, classification consistency indices directly applicable to equating contexts are introduced, and procedures for estimating these indices are presented under three equating designs: the single-group design, the random-groups design, and the common-item nonequivalent-groups design. Two families of psychometric models (item response theory models and beta-binomial models) are introduced, focusing on the procedures for estimating conditional score distributions and ability distributions. Two empirical analyses are provided to illustrate the use of the methodology under the common-item nonequivalent-groups design and the random-groups design, using item response theory models and beta-binomial models.
Performance of DIMTEST- and NOHARM-Based Statistics for Testing Unidimensionality
Authors: Finch Holmes , Habing Brian
Published: June 2007

This Monte Carlo study compares the ability of the parametric bootstrap version of DIMTEST with three goodness-of-fit tests calculated from a fitted NOHARM model to detect violations of the assumption of unidimensionality in testing data. The effectiveness of the procedures was evaluated for different numbers of items, numbers of examinees, correlations between underlying ability dimensions, skewness of underlying ability distributions, and the presence or absence of a guessing parameter. In the absence of guessing, DIMTEST and the NOHARM-based statistics had similar power, with the χ2 statistic having a very low Type I error rate. In the presence of guessing, however, two of the NOHARM-based statistics had unacceptably high Type I error rates, while the third performed similarly to DIMTEST. Given this inflated error rate, the study compares the empirical powers after adjusting for the discrepancy in Type I error rates.
Assessing Dimensionality by Maximizing H Coefficient–Based Objective Functions
Authors: van Abswoude Alexandra A. H. , Vermunt Jeroen K. , Hemker Bas T.
Published: June 2007

Mokken scale analysis can be used for scaling under nonparametric item response theory models. The results may, however, not reflect the underlying dimensionality of data. Various features of Mokken scale analysis—the H coefficient, Mokken scale conditions, and algorithms—may explain this result. In this article, three new H-based objective functions with slight reformulations of Mokken scale analysis in the unidimensional and multidimensional cases are introduced. Deterministic and stochastic nonhierarchical clustering algorithms reduced the probability of obtaining suboptimal solutions. A simulation study investigated whether these methods can determine the dimensionality structure of data sets that vary with respect to item discrimination, item difficulty, number of items per trait, and numbers of observations per test. Furthermore, it was investigated whether deterministic and stochastic algorithms can generate approximately global optimal solutions. The method based on the average within-scale Hi combined with a stochastic nonhierarchical clustering algorithm was the most successful in dimensionality assessment.
Criminal Investigation Enforcement Activities and Taxpayer Noncompliance
Authors: Dubin Jeffrey A.
Published: June 2007

This article tests empirically whether measurable activities of the IRS Criminal Investigation Division (CI) affect taxpayer compliance. The analysis is based on a state-level cross-section for the time period 1988 through 2001. First, it finds that CI activities have a measurable and significant effect on voluntary compliance. Second, it concludes that the mix of sentenced cases (for tax and money laundering violations) is not a significant determinant of tax compliance. Third, it finds that incarceration and probation (rather than fines) have the most influence on taxpayers. Simulations using the estimated models show that the direct effect of doubling the audit rate on assessed tax collections (reported amounts and additional taxes and penalties) is $21.7 billion. Doubling CI tax and money laundering sentences is forecast to increase assessed collections by $16.0 billion. It estimates the general deterrence or spillover effects from either audit or CI activities to be approximately 95 percent.
Accounting for Spatial Error Correlation in the 2004 Presidential Popular Vote
Authors: Lacombe Donald J. , Shaughnessy Timothy M.
Published: June 2007

One problem with describing election vote shares using ordinary least squares (OLS) is that it ignores the possible presence of spatial error correlation, whereby the errors are correlated in a systematic manner over space. This omission can bias OLS standard errors. We examine the 2004 presidential county vote outcome using OLS and a spatial error model (SEM) that accounts for spatial autocorrelation in the error structure. We find that spatial error correlation is present, that the SEM is superior to OLS for making inferences, and that several factors deemed important to the 2004 election outcome are not significant once the spatial error autocorrelation is taken into account.
Competitive Governments, Globalization, and Equalization Grants
Authors: Breton Albert , Fraschini Angela
Published: June 2007

The competition that permeates the public sector acts as a force to discipline public sector actors. But it also serves to build links between the volume of goods and services supplied by public bodies and the prices that citizens must pay for them. Globalization, by permitting a greater mobility of capital, makes it possible for larger business corporations to become more effective oligopsonists when bargaining with governments for the goods and services they need, thus weakening the links between the things provided to citizens and the prices the latter must pay. Equalization payments, by permitting more effective intergovernmental competition, reduce the negative effects of globalization on the links that competition forges.
Developing a research culture in the undergraduate curriculum
Authors: Garde-Hansen Joanne , Calvert Ben
Published: June 2007

A great deal of value is placed on student research within universities, exemplified by the prominent role of the dissertation or extended written work at the end of many programmes, and the more general benefits of embedding research-based learning into a curriculum in order to develop higher-order learning. This article reports on a collaborative problem-based learning (PBL) activity undertaken by staff and students to run an undergraduate conference for first year students on how to develop a research culture. The aim is to better understand how students undertake research and how a research culture might be inculcated much earlier in undergraduate programmes.
Integrating web-delivered problem-based learning scenarios to the curriculum
Authors: Gossman Peter , Stewart Terry , Jaspers Marlene , Chapman Bruce
Published: June 2007

This article reports on a small-scale research project (n=56) that investigated student educational gain. For the purposes of this study, gain is defined as an increase in the score that students obtain for pre/post intervention tests. Students received authentic exposure to the process via a web-delivered problem-based scenario. The students were randomly allocated to case and control groups. No statistically significant differences in educational gain were recorded between the two groups. However, the research highlights the requirement to fully integrate problem-based learning (PBL) work into a curriculum. It also confirms findings from other research that students engage well with PBL and enjoy the learning process using this methodology.
Investigating the baseline skills of research students using a competency-based self-assessment method
Authors: Bromley Anthony P. , Boran James R. , Myddelton William A.
Published: June 2007

Recent government-led initiatives are changing the nature of the UK PhD to support the greater development of transferable skills. There are similar initiatives internationally. A key requirement and challenge is to effectively assess the `baseline' skills of a cohort on entry to a research programme and then monitor their progress in personal development. This article describes an innovative methodology that combines competence model and training needs analysis theory to create an effective self-assessment tool: the Development Needs Analysis (DNA), for collection of baseline data. The DNA provides a means for effective self-assessment of skills, and is capable of highlighting particular needs of students grouped by, for example, date of birth and home vs. overseas status. The methodology is broadly applicable in determination of the baseline skills of students and allows practitioners to tailor learning and teaching to the requirements of a cohort.
Using text messaging to support administrative communication in higher education
Authors: Naismith Laura
Published: June 2007

To be effective in higher education, text messaging must be effectively integrated into both the student and staff experience. These user groups provided input into the design of StudyLink, an email to text message service. A small-scale trial was conducted over a period of two academic terms to investigate the feasibility of using this system in a real educational setting. Students reported high satisfaction with the quantity and content of the text messages and tutors reported changes in behaviour that were directly attributable to the use of text messaging. Administrative staff members were able to integrate this service into their current means of communicating with students, though there were some difficulties in composing appropriate text messages. Students were able to effectively receive and act on text messages, but ambiguities introduced with sending text messages were not resolved.
Visions and Voices: Indigent Persons Living With HIV in the Southern United States Use Photovoice to Create Knowledge, Develop Partnerships, and Take Action
Authors: Rhodes Scott D. , Hergenrather Kenneth C. , Wilkin Aimee M. , Jolly Christine
Published: June 2007

Little is known about the experiences of persons living with HIV/AIDS (PLWHA) in some regions of the United States that are disproportionately affected by HIV/AIDS. “Visions and Voices: HIV in the 21st Century” was an exploratory study to gain insight into the life experiences of 15 indigent PLWHA. The study used photovoice to uncover the realities of living with HIV/AIDS though photographic documentation and Freirean-based critical dialogue and facilitate a process for PLWHA to reach local community members and leaders, policy makers, and advocates to develop plans of action and effect change. From the participants' photographs and words, seven themes emerged and were presented during a community forum. Three main outcomes occurred, including a participant-developed and locally funded gallery exhibition to address HIV/AIDS misinformation and stigma; a new partnership with the public health department to use PLWHA in their prevention programming; and increased community efforts to address substance use.
Neutrophils efficiently cross-prime naive T cells in vivo
Authors: Beauvillain Céline , Delneste Yves , Scotet Mari , Peres Audrey , Gascan Hugues , Guermonprez Pierre , Barnaba Vincenzo , Jeannin Pascale
Published: June 2007

Neutrophils are professional phagocytes that migrate early, in high number, to the infection sites. Our study has analyzed how neutrophils cross-present antigens and influence CD8+ T-cell responses. By using highly purified neutrophils from peritoneal exudates and bone marrow, we have shown that neutrophils cross-present ovalbumin to a CD8+ T-cell hybridoma and to naive CD8+ T cells from OT1 transgenic mice. Cross-presentation by neutrophils was TAP and proteasome dependent and was as efficient as in macrophages. Moreover, it actually occurred earlier than in professional antigen-presenting cells. Peritoneal exudate neutrophils from mice injected intraperitoneally with ovalbumin also cross-presented ovalbumin, proving that neutrophils take up and present exogenous antigens into major histocompatibility complex I (MHC I) molecules in vivo. We then evaluated the in vivo influence of antigen cross-presentation by neutrophils on CD8+ T-cell response using β2-microglobulin-deficient mice transferred with OT1 CD8+ T cells and injected with ovalbumin-pulsed neutrophils. Four days after neutrophil injection, OT1 cells proliferated and expressed effector functions (IFN-γ production and cytolysis). They also responded efficiently to a rechallenge with ovalbumin-pulsed dendritic cells in CFA. These data are the first demonstration that neutrophils cross-prime CD8+ T cells in vivo and suggest that they may constitute, together with professional antigen-presenting cells, an attractive target to induce cytotoxic T cells in vaccines.
A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias
Authors: Karp Judith E. , Ricklis Rebecca M. , Balakrishnan Kumudha , Briel Janet , Greer Jacqueline , Gore Steven D. , Smith B. Douglas , McDevitt Michael A. , Carraway Hetty , Levis Mark J. , Gandhi Varsha
Published: June 2007

Clofarabine has shown impressive response rates in patients with acute leukemias. In vitro investigations with clofarabine in combination with cyclophosphamide in primary cells have demonstrated synergistic cytotoxicity and inhibition of DNA repair. Based on these clinical and laboratory observations, we designed a mechanism-based combination protocol with clofarabine and cyclophosphamide for patients with relapsed acute leukemias. Eighteen patients were treated with cyclophosphamide (200 mg/m2) alone on day 0 and with clofarabine plus cyclophosphamide on day 1. Clinical responses, toxicity, DNA damage measured as H2AX phosphorylation, and accumulation of clofarabine triphosphate (TP) were analyzed. At dose level 1 (20 mg/m2 clofarabine + cyclophosphamide, 6 patients) and dose level 0 (10 mg/m2 clofarabine + cyclophosphamide, 12 patients) overall response rates were 50% and 30%, respectively, with responses in 4 (67%) of 6 patients with refractory acute lymphoblastic leukemia. Dose-limiting toxicity occurred at dose level 1 with prolonged marrow aplasia. Four (22%) patients died from prolonged aplasia (1), fungal pneumonia (1), or multiorgan failure (2). In 12 of 13 patient samples, increased DNA damage (γH2AX) was observed with clofarabine and cyclophosphamide compared with cyclophosphamide alone. In conclusion, pharmacodynamic end points along with clinical results suggest usefulness of this combination strategy, whereas toxicity data suggest reduction in chemotherapeutic intensity. This clinical trial is registered with the National Cancer Institute's PDQ at www.clinicaltrials.gov as no. JHOC-J0561.
Transcriptome changes and cAMP oscillations in an archaeal cell cycle
Authors: Baumann Anke , Lange Christian , Soppa Jörg
Published: June 2007

Background

The cell cycle of all organisms includes mass increase by a factor of two, replication of the genetic material, segregation of the genome to different parts of the cell, and cell division into two daughter cells. It is tightly regulated and typically includes cell cycle-specific oscillations of the levels of transcripts, proteins, protein modifications, and signaling molecules. Until now cell cycle-specific transcriptome changes have been described for four eukaryotic species ranging from yeast to human, but only for two prokaryotic species. Similarly, oscillations of small signaling molecules have been identified in very few eukaryotic species, but not in any prokaryote.

Results

A synchronization procedure for the archaeon Halobacterium salinarum was optimized, so that nearly 100% of all cells divide in a time interval that is 1/4th of the generation time of exponentially growing cells. The method was used to characterize cell cycle-dependent transcriptome changes using a genome-wide DNA microarray. The transcript levels of 87 genes were found to be cell cycle-regulated, corresponding to 3% of all genes. They could be clustered into seven groups with different transcript level profiles. Cluster-specific sequence motifs were detected around the start of the genes that are predicted to be involved in cell cycle-specific transcriptional regulation. Notably, many cell cycle genes that have oscillating transcript levels in eukaryotes are not regulated on the transcriptional level in H. salinarum.

Synchronized cultures were also used to identify putative small signaling molecules. H. salinarum was found to contain a basal cAMP concentration of 200 μM, considerably higher than that of yeast. The cAMP concentration is shortly induced directly prior to and after cell division, and thus cAMP probably is an important signal for cell cycle progression.

Conclusion

The analysis of cell cycle-specific transcriptome changes of H. salinarum allowed to identify a strategy of transcript level regulation that is different from all previously characterized species. The transcript levels of only 3% of all genes are regulated, a fraction that is considerably lower than has been reported for four eukaryotic species (6% – 28%) and for the bacterium C. crescentus (19%).

It was shown that cAMP is present in significant concentrations in an archaeon, and the phylogenetic profile of the adenylate cyclase indicates that this signaling molecule is widely distributed in archaea. The occurrence of cell cycle-dependent oscillations of the cAMP concentration in an archaeon and in several eukaryotic species indicates that cAMP level changes might be a phylogenetically old signal for cell cycle progression.
Glycosylation, transport, and complex formation of palmitoyl protein thioesterase 1 (PPT1) – distinct characteristics in neurons
Authors: Lyly Annina , von Schantz Carina , Salonen Tarja , Kopra Outi , Saarela Jani , Jauhiainen Matti , Kyttälä Aija , Jalanko Anu
Published: June 2007

Background

Neuronal ceroid lipofuscinoses (NCLs) are collectively the most common type of recessively inherited childhood encephalopathies. The most severe form of NCL, infantile neuronal ceroid lipofuscinosis (INCL), is caused by mutations in the CLN1 gene, resulting in a deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). The deficiency of PPT1 causes a specific death of neocortical neurons by a mechanism, which is currently unclear. To understand the function of PPT1 in more detail, we have further analyzed the basic properties of the protein, especially focusing on possible differences in non-neuronal and neuronal cells.

Results

Our study shows that the N-glycosylation of N197 and N232, but not N212, is essential for PPT1's activity and intracellular transport. Deglycosylation of overexpressed PPT1 produced in neurons and fibroblasts demonstrates differentially modified PPT1 in different cell types. Furthermore, antibody internalization assays showed differences in PPT1 transport when compared with a thoroughly characterized lysosomal enzyme aspartylglucosaminidase (AGA), an important observation potentially influencing therapeutic strategies. PPT1 was also demonstrated to form oligomers by size-exclusion chromatography and co-immunoprecipitation assays. Finally, the consequences of disease mutations were analyzed in the perspective of our new results, suggesting that the mutations increase both the degree of glycosylation of PPT1 and its ability to form complexes.

Conclusion

Our current study describes novel properties for PPT1. We observe differences in PPT1 processing and trafficking in neuronal and non-neuronal cells, and describe for the first time the ability of PPT1 to form complexes. Understanding the basic characteristics of PPT1 is fundamental in order to clarify the molecular pathogenesis behind neurodegeneration in INCL.
A complex and punctate distribution of three eukaryotic genes derived by lateral gene transfer
Authors: Rogers Matthew B , Watkins Russell F , Harper James T , Durnford Dion G , Gray Michael W , Keeling Patrick J
Published: June 2007

Background

Lateral gene transfer is increasingly invoked to explain phylogenetic results that conflict with our understanding of organismal relationships. In eukaryotes, the most common observation interpreted in this way is the appearance of a bacterial gene (one that is not clearly derived from the mitochondrion or plastid) in a eukaryotic nuclear genome. Ideally such an observation would involve a single eukaryote or a small group of related eukaryotes encoding a gene from a specific bacterial lineage.

Results

Here we show that several apparently simple cases of lateral transfer are actually more complex than they originally appeared: in these instances we find that two or more distantly related eukaryotic groups share the same bacterial gene, resulting in a punctate distribution. Specifically, we describe phylogenies of three core carbon metabolic enzymes: transketolase, glyceraldehyde-3-phosphate dehydrogenase and ribulose-5-phosphate-3-epimerase. Phylogenetic trees of each of these enzymes includes a strongly-supported clade consisting of several eukaryotes that are distantly related at the organismal level, but whose enzymes are apparently all derived from the same lateral transfer. With less sampling any one of these examples would appear to be a simple case of bacterium-to-eukaryote lateral transfer; taken together, their evolutionary histories cannot be so simple. The distributions of these genes may represent ancient paralogy events or genes that have been transferred from bacteria to an ancient ancestor of the eukaryotes that retain them. They may alternatively have been transferred laterally from a bacterium to a single eukaryotic lineage and subsequently transferred between distantly related eukaryotes.

Conclusion

Determining how complex the distribution of a transferred gene is depends on the sampling available. These results show that seemingly simple cases may be revealed to be more complex with greater sampling, suggesting many bacterial genes found in eukaryotic genomes may have a punctate distribution.
Evaluating the performance of commercial whole-genome marker sets for capturing common genetic variation
Authors: Mägi Reedik , Pfeufer Arne , Nelis Mari , Montpetit Alexandre , Metspalu Andres , Remm Maido
Published: June 2007

Background

New technologies have enabled genome-wide association studies to be conducted with hundreds of thousands of genotyped SNPs. Several different first-generation genome-wide panels of SNPs have been commercialized. The total amount of common genetic variation is still unknown; however, the coverage of commercial panels can be evaluated against reference population samples genotyped by the International HapMap project. Less information is available about coverage in samples from other populations.

Results

In this study we compare four commercial panels: the HumanHap 300 and HumanHap 550 Array Sets from the Illumina Infinium series and the Mapping 100 K and Mapping 500 K Array Sets from the Affymetrix GeneChip series. Tagging performance is compared among HapMap CEPH (CEU), Asian (JPT, CHB) and Yoruba (YRI) population samples. It is also evaluated in an Estonian population sample with more than 1000 individuals genotyped in two 500-kbp ENCODE regions of chromosome 2: ENr112 on 2p16.3 and ENr131 on 2p37.1.

Conclusion

We found that in a non-reference Caucasian population, commercial SNP panels provide levels of coverage similar to those in the HapMap CEPH population sample. We present the proportions of universal and population-specific SNPs in all the commercial platforms studied.
Evolutionary implications of inversions that have caused intra-strand parity in DNA
Authors: Okamura Kohji , Wei John , Scherer Stephen W
Published: June 2007

Background

Chargaff's rule of DNA base composition, stating that DNA comprises equal amounts of adenine and thymine (%A = %T) and of guanine and cytosine (%C = %G), is well known because it was fundamental to the conception of the Watson-Crick model of DNA structure. His second parity rule stating that the base proportions of double-stranded DNA are also reflected in single-stranded DNA (%A = %T, %C = %G) is more obscure, likely because its biological basis and significance are still unresolved. Within each strand, the symmetry of single nucleotide composition extends even further, being demonstrated in the balance of di-, tri-, and multi-nucleotides with their respective complementary oligonucleotides.

Results

Here, we propose that inversions are sufficient to account for the symmetry within each single-stranded DNA. Human mitochondrial DNA does not demonstrate such intra-strand parity, and we consider how its different functional drivers may relate to our theory. This concept is supported by the recent observation that inversions occur frequently.

Conclusion

Along with chromosomal duplications, inversions must have been shaping the architecture of genomes since the origin of life.
Re-annotation and re-analysis of the Campylobacter jejuni NCTC11168 genome sequence
Authors: Gundogdu Ozan , Bentley Stephen D , Holden Matt T , Parkhill Julian , Dorrell Nick , Wren Brendan W
Published: June 2007

Background

Campylobacter jejuni is the leading bacterial cause of human gastroenteritis in the developed world. To improve our understanding of this important human pathogen, the C. jejuni NCTC11168 genome was sequenced and published in 2000. The original annotation was a milestone in Campylobacter research, but is outdated. We now describe the complete re-annotation and re-analysis of the C. jejuni NCTC11168 genome using current database information, novel tools and annotation techniques not used during the original annotation.

Results

Re-annotation was carried out using sequence database searches such as FASTA, along with programs such as TMHMM for additional support. The re-annotation also utilises sequence data from additional Campylobacter strains and species not available during the original annotation. Re-annotation was accompanied by a full literature search that was incorporated into the updated EMBL file [EMBL: AL111168]. The C. jejuni NCTC11168 re-annotation reduced the total number of coding sequences from 1654 to 1643, of which 90.0% have additional information regarding the identification of new motifs and/or relevant literature. Re-annotation has led to 18.2% of coding sequence product functions being revised.

Conclusions

Major updates were made to genes involved in the biosynthesis of important surface structures such as lipooligosaccharide, capsule and both O- and N-linked glycosylation. This re-annotation will be a key resource for Campylobacter research and will also provide a prototype for the re-annotation and re-interpretation of other bacterial genomes.
Autocorrelation analysis reveals widespread spatial biases in microarray experiments
Authors: Koren Amnon , Tirosh Itay , Barkai Naama
Published: June 2007

Background

DNA microarrays provide the ability to interrogate multiple genes in a single experiment and have revolutionized genomic research. However, the microarray technology suffers from various forms of biases and relatively low reproducibility. A particular source of false data has been described, in which non-random placement of gene probes on the microarray surface is associated with spurious correlations between genes.

Results

In order to assess the prevalence of this effect and better understand its origins, we applied an autocorrelation analysis of the relationship between chromosomal position and expression level to a database of over 2000 individual yeast microarray experiments. We show that at least 60% of these experiments exhibit spurious chromosomal position-dependent gene correlations, which nonetheless appear in a stochastic manner within each experimental dataset. Using computer simulations, we show that large spatial biases caused in the microarray hybridization step and independently of printing procedures can exclusively account for the observed spurious correlations, in contrast to previous suggestions. Our data suggest that such biases may generate more than 15% false data per experiment. Importantly, spatial biases are expected to occur regardless of microarray design and over a wide range of microarray platforms, organisms and experimental procedures.

Conclusions

Spatial biases comprise a major source of noise in microarray studies; revision of routine experimental practices and normalizations to account for these biases may significantly and comprehensively improve the quality of new as well as existing DNA microarray data.