bluuebunny/crossref_metadata_2025 huggingface dataset:
Willingness of Graduate Students in Rehabilitation Counseling to Discuss Sexuality With Clients
Authors: Juergens Maria Helena , Miller Smedema Susan , Berven Norman L.
Published: July 2009

The purpose of this study was to obtain a greater understanding of the willingness of graduate students in rehabilitation counseling to discuss sexuality with clients.This was done by testing a model of factors predicted to influence the willingness of rehabilitation counseling master’s students to discuss sexuality with clients, using path analysis.The results of this study suggest that sexuality knowledge, sexuality education, attitudes toward the sexuality of people with disabilities, and comfort with sexuality affect the willingness of rehabilitation counselors to discuss sexuality with clients, with sexuality knowledge and comfort with sexuality having direct effects on willingness. Understanding the relationships between these variables may facilitate the design of interventions that promote the willingness of rehabilitation counselors to discuss sexuality with clients.
“You’re Not from New York City, You’re from Rotherham”
Authors: Beal Joan C.
Published: July 2009

This paper investigates the use of local accent and dialect features in the performance of Arctic Monkeys, a very successful indie band from Sheffield in the north of England. Previous work on variation in the sung pronunciation of British pop musicians by Trudgill (1983) and Simpson (1999) is reviewed. A qualitative analysis of an Arctic Monkeys performance is carried out to determine the extent to which features of northern and/or more specifically Sheffield English are used by Arctic Monkeys. The results are then discussed within a language-ideological framework, where it is argued that Arctic Monkeys are using features of local accent and dialect to index values such as authenticity and independence from the corporate machine.
Hip-hop in a Post-insular Community
Authors: Clarke Sandra , Hiscock Philip
Published: July 2009

The focus of this article is Gazeebow Unit, an adolescent hip-hop group from Newfoundland, Canada, whose tracks, which date from 2005, are available only online. As white rappers whose language is grounded in vernacular Newfoundland English, their rap raises obvious questions relating to both authenticity and hybridization. Despite the group’s use of local linguistic and semiotic resources to style young working-class Newfoundland male “skeet” identity, their authenticity as both working-class Newfoundlanders and rappers was soon to be publicly contested. Though local language and dialect typically represent “resistance vernaculars” in global hip-hop, the use of vernacular Newfoundland English as a performance register on the part of Gazeebow Unit is shown to be considerably more complex. At one level at least, Gazeebow Unit are engaged in parody, or “strategic inauthenticity,” one ramification of which is to reproduce and reinforce dominant ideologies of social class.
A Prototype Analysis of Gratitude: Varieties of Gratitude Experiences
Authors: Lambert Nathaniel M. , Graham Steven M. , Fincham Frank D.
Published: July 2009

The present research tested the hypothesis that concepts of gratitude are prototypically organized and explored whether lay concepts of gratitude are broader than researchers' concepts of gratitude. In five studies, evidence was found that concepts of gratitude are indeed prototypically organized. In Study 1, participants listed features of gratitude. In Study 2, participants reliably rated the centrality of these features. In Studies 3a and 3b, participants perceived that a hypothetical other was experiencing more gratitude when they read a narrative containing central as opposed to peripheral features. In Study 4, participants remembered more central than peripheral features in gratitude narratives. In Study 5a, participants generated more central than peripheral features when they wrote narratives about a gratitude incident, and in Studies 5a and 5b, participants generated both more specific and more generalized types of gratitude in similar narratives. Throughout, evidence showed that lay conceptions of gratitude are broader than current research definitions.
Clinical findings and recommendations made during home visits by a palliative care specialist physician
Authors: Bush SH , Wearne HJ , Reilly PE , Chacko R , Palmer JL
Published: July 2009

Little has been reported regarding the nature of home visits by palliative care specialist physicians to assist in the management of complex cases. We determined the characteristics, actionable clinical findings and recommendations made during consecutive home visits conducted by a specialist physician for patients registered with a community palliative care service. Patient demographic information and clinical records were reviewed. Ninety-one patients received a total of 104 home and residential facility visits. Median patient age was 59 (Q1—Q3, 43—72). Ten children (under the age of 14) received a total of 15 visits. Seventy-three patients (80%) had a cancer diagnosis. Median visit duration was 60 min (Q1—Q3, 45—60). The major actionable clinical findings were pain (120), gastrointestinal (115), neuropsychiatric (58), mouth and skin (33) and respiratory (29). One-third of recommendations involved changes in analgesia regimen (opioids 67, adjuvants 44). The specialist physician home visit resulted in multiple patient care recommendations. This information may help palliative care programmes improve their care for patients and families in the community.
Cultural ecology: adaptation - retrofitting a concept?
Authors: Head Lesley
Published: July 2009

Adaptation was a core concept of twentieth-century cultural ecology. It is having a new life in the context of debates over climate change, particularly as it becomes more significant in public discourse and policy. In this third and final progress report, I identify ways in which geographers and others are currently using the concept of adaptation, tracing both continuities and discontinuities with its earlier heritage. Three differences that warrant attention are the new mitigation/adaptation binary, the deliberate and conscious nature of climate change adaptation, and the fact that the stimuli to which we are adapting are complex assemblages comprising more-than-climate. To ‘retrofit’ the concept for twenty-first-century conditions, we should avoid the limitations of some past uses, and enhance its operation with new techniques and approaches. I identify four threads in recent geographic research that enhance the retrofit: cultural research around climate; emphasis on everyday practices; attention to the contingencies of scale; and more-than-human/ more-than-nature theoretical conceptualizations.
Procoagulant Behavior and Platelet Microparticle Generation on Nanoporous Alumina
Authors: Ferraz Natalia , Hong Jaan , Karlsson Ott Marjam
Published: July 2009

In the present work, we have investigated platelet microparticle (PMP) generation in whole blood after contact with nanoporous alumina. Alumina membranes with pore sizes of 20 and 200 nm in diameter were incubated with whole blood and the number of PMP in the fluid phase was determined by flow cytometry. The role of the complement system in PMP generation was investigated using an analog of the potent complement inhibitor compstatin. Moreover, the procoagulant activity of the two pore size membranes were compared by measuring thrombin formation. Results indicated that PMP were not present in the fluid phase after whole blood contact with either of the alumina membranes. However, scanning electron microscope micrographs clearly showed the presence of PMP clusters on the 200 nm pore size alumina, while PMP were practically absent on the 20 nm membrane. We probed no influence of complement activation in PMP generation and adhesion and we hypothesize that other specific material-related protein—platelet interactions are taking place. A clear difference in procoagulant activity between the membranes could also be seen, 20 nm alumina showed 100% higher procoagulant activity than 200 nm membrane. By combining surface evaluation and flow cytometry analyses of the fluid phase, we are able to conclude that 200 nm pore size alumina promotes PMP generation and adhesion while the 20 nm membrane does not appreciably cause any release or adhesion of PMP, thus indicating a direct connection between PMP generation and nanoporosity.
Alcohol Consumption and Health Status in Older Adults
Authors: Chen Lucy Y. , Hardy Cindy L.
Published: July 2009

Objective: This longitudinal study examines the relationship of alcohol consumption to mortality and changes in mental and functional health in older adults. Method: In a national population health survey, 4,187 participants aged 50 and older at baseline provided information on alcohol consumption, potential confounders, and follow-up vital status. Logistic regression estimated the odds ratio for mortality, increase in psychological distress, and decline in functional health 10 years later. Results: Compared with lifelong abstainers, light and moderate drinkers were at nonsignificantly lower risk of mortality. Among survivors, alcohol consumption showed no consistent relationship with increases in psychological distress. Occasional and light drinkers had significantly reduced risk of a substantial functional health decline, whereas moderate drinkers had nonsignificantly reduced risk. Discussion: Findings suggest that light-to-moderate alcohol consumption reduces the risk of substantial functional health decline in older middle-aged drinkers.
An Exploratory Study of Individual and Environmental Correlates of Fear of Falling Among Community-Dwelling Seniors
Authors: Filiatrault Johanne , Desrosiers Johanne , Trottier Lise
Published: July 2009

Objective: The objective of this study was to identify individual and environmental correlates of fear of falling among community-dwelling seniors. Method: The study sample involved 288 community-dwelling adults aged 65 years or older going through the normal aging process. Fear of falling and a series of individual and environmental characteristics were measured with a questionnaire during home interviews. Results: Multivariate logistic regression procedures showed that the strongest correlates of fear of falling are gender, support from a spouse or partner, and residential area. Being a female as well as living in a smaller city or rural area were shown to be risk factors for fear of falling, whereas the availability of support from a spouse or partner was a protective factor. Discussion: Findings from this study suggest that researchers should adopt an ecological perspective to understanding the phenomenon of fear of falling among seniors and collect data on a broader range of individual and environmental factors.
Developing a Whole-of-University Approach to Educating for Sustainability
Authors: Mcmillin Jennifer , Dyball Rob
Published: July 2009

Institutions of higher education are poised to play a significant role in the search for a more sustainable future. Most universities are tackling sustainability issues in a compartmentalised manner, sustainability education is confined to specific courses, education is often isolated from research, and neither is likely to be linked to sustainable campus operations. Universities can optimise their role as agents of change with regard to sustainability by adopting a ‘whole-of-university’ approach to sustainability. This approach explicitly links research, educational, operational and outreach activities and engages students in each. By encouraging a collaborative space within the curriculum for students, academics and managers to critically reflect on university's performance with regard to sustainability, many positive benefits ensue, including raising the profile of university's sustainability initiatives; providing solutions to sustainability problems; building trust among students, managers and academics; and providing meaningful learning experiences for students.
Contributions of the American Bahá'í Community to Education for Sustainability
Authors: Podger Dimity
Published: July 2009

UNESCO, the lead agency for the UN Decade of Education for Sustainable Development (DESD), calls for faith organisations to play a role in assisting societal transition towards sustainability through education for sustainability (EfS). However, the interface between sustainability and spirituality, and the insights that faith organisations can provide to efforts to build more sustainable societies, has received little explicit consideration in the broader international institutional EfS discourse. This paper is based on a case study exploring the perspectives and experiences of the American Bahá'í Community as it has engaged with sustainability and EfS frameworks over the past four years. The study found that the faith organisation considers spiritual education and education that develops critical-thinking skills as essential and interconnected aspects of educating for sustainability, and that its perspectives may beneficially be incorporated into the EfS discourse.
A United Nations Decade of Education for Sustainable Development (2005–14)
Authors: Mulà Ingrid , Tilbury Daniella
Published: July 2009

The launch of the United Nations Decade of Education for Sustainable Development (DESD) (2005–2014) was accompanied by a series of high-profile events and celebratory activities across the globe, which raised awareness about the Decade's objectives. Now, as the DESD approaches its mid-term, many stakeholders are asking these questions: What will change as a result of the DESD? What will be its legacy? This article reviews the explicit intentions of the Decade and explores its current and potential contributions. It raises issues about how to assess the progress in education for sustainable development (ESD) during the Decade and questions whether it is possible to effectively evaluate the Decade's impact. It concludes by acknowledging that the success of the DESD will be judged not only by the UN Monitoring and Evaluation mechanisms set in place by UNESCO but also by how the diverse expectations from stakeholders are met.
Toward a New Definition of Health Disparity
Authors: Fink Anne M.
Published: July 2009

In response to federal requests for investigation into measures to eradicate health disparities, a concept analysis of the term health disparity was conducted. Health-related and multidisciplinary literature was reviewed. Multiple terms were explored alone and in combination with no limitations on search date parameters. Findings indicated several definitions of the concept, with the term health care disparity being used interchangeably with the term health disparity . New theoretical and operational definitions, antecedents, characteristics, and consequences of the concept are proffered. Model, borderline, and contrary cases are developed to illustrate the concept. Nursing implications and recommendations for future research are discussed.
Commissioning Legitimacy: The Global Logics of National Violence Commissions in the Twentieth Century
Authors: Keller Matthew R.
Published: July 2009

Based on an analysis of the reports of twenty-eight national-level public commission inquiries into events involving ethno-national violence—drawn from five national contexts and arrayed over the course of the twentieth century—this article demonstrates the strikingly transnational character of these investigatory bodies’ attempts to authoritatively explain episodes of collective violence and to thereby restore governing legitimacy in the wake of violent crises. One of four distinct “logics,” or core explanatory frameworks, each associated with a particular mode of “racial power,” characterized a diverse cross-national pool of violence commission reports during defined periods of the twentieth century. In revealing globally encompassing logics to what has often been framed as a national or case-specific phenomenon, the author shows how global ideational currents compose a key dimension of national political dynamics.
Democracy in the Globalizing Indian City: Engagements of Political Society and the State in Globalizing Mumbai
Authors: Weinstein Liza
Published: July 2009

Transformations under way in Indian cities have begun to alter the opportunities for democratic participation among the urban poor. Highlighting efforts to promote globally oriented urban developments in Mumbai, this article examines the state’s engagement with groups directly impacted by these efforts. Based on ethnographic research and interviews with key stakeholders in the Dharavi Redevelopment Project (DRP), the article traces the character of such engagements over the project’s four-year planning process. It finds that the state undertook an unusually inclusive process, consulting with resident and activist groups at points throughout this period. The article posits that this novel engagement is an unintended consequence of pressures to promote rapid development and ease investor concerns. Situating this case in the recent literature on political shifts in the globalizing Indian city, it concludes that the state may be engaging more with the urban poor than many of these accounts suggest.
Service-Learning by Doing
Authors: Robinson David F. , Lloyd Sherwood Arthur , DePaolo Concetta A.
Published: July 2009

A challenge for undergraduate learning in strategy is that the students lack professional work experiences. Without a rich background of experience, many strategic management topics are difficult to grasp. Our solution has been to develop a strategic management capstone course that combines service-learning and problem-based learning. The experiential design puts students in charge of a consulting company serving struggling local nonprofits and small businesses. By consulting, students have access to strategic decision makers and learn to understand the missions of their organizations. Students acquire a sense of urgency to solve strategic problems and develop a commitment to improving their community. In this article, the authors describe their motivations for the course design and how service-learning enhances the design’s efficacy. In addition, the authors explain the use of a matrix structure for the student consulting company, how the company operates, and the strategic process consultation approach its consultants use. This study also describes the student leadership structure and just-in-time lecture technique that enables the instructor to provide on-demand instruction. The authors conclude by explaining the assessment system of quality checks, presentations, and reflection papers that allows instructors to maintain student learning in a very flexible and student-driven learning system.
Three Models for Short-Term Study Abroad
Authors: Sachau Daniel , Brasher Niel , Fee Scott
Published: July 2009

Nearly 250,000 U.S. college students participate in study abroad programs each year. A growing proportion of students are participating in short-term study abroad programs. Despite the large number of students in these programs, there are relatively few articles that describe how to start or manage a short-term, business-related, study abroad program. With this in mind, this article includes three examples of short-term study abroad programs: the summer semester abroad, the study tour, and the service-learning trip. Benefits of short-term study abroad programs are discussed. The article also includes tips for designing and managing the programs. The article is intended as a resource for faculty who are considering taking students abroad.
Effects of Nonlinearities on the Steady State Dynamic Behavior of Electric Actuated Microcantilever-based Resonators
Authors: Jazar R.N. , Mahinfalah M. , Mahmoudian N. , Rastgaar M.A.
Published: July 2009

This paper presents the dynamic behavior of microcantilever-based microresonators and compares their steady state behavior for polarized and nonpolarized systems at different levels of nonlinearities. A microcantilever, equipped with a time-varying capacitor, makes the microresonator system. The capacitor is activated by a constant polarization voltage, and an alternative actuating voltage. The partial differential equation of motion of the vibrating electrode can be reduced to a highly nonlinear parametric second order ordinary differential equation. The steady state behavior of the microresonator has been analyzed with and without polarization voltage. The main characteristic of the non-polarized model is explained by the stability of the system in parameter plane. A set of stability chart is provided to predict the boundary between the stable and unstable domains. Furthermore, the main characteristic of the polarized model is determination by the period-amplitude relationship of the system. Applying perturbation methods, analytical equations are derived to describe the frequency response of the system, which are suitable to be utilized in parameter study and design.
Optimization of Mechatronic Design Quotient Using Genetic Algorithm in Vibration Controllers for Flexible Beams
Authors: Sun J. , Poo A.N. , Chew C.M. , Ang M.H. , Hong G.S. , De Silva C.W. , Tan K.K.
Published: July 2009

Due to their extensive utilization in engineering designs, various vibration controllers have been investigated with design specifications in mind. The optimization of vibration controller designs is a complicated multi-criteria problem. In this paper, the mechatronic design quotient (MDQ) approach and genetic algorithm (GA) are coupled together to determine this optimal design solution. The MDQ is presented to formulate an evaluation function for the passive vibration controller design of flexible beam structures, and the GA is then used to maximize this function so as to achieve a design solution with the highest MDQ value. For comparison, both the MDQ performance of passive vibration controller design using linear dampers and active vibration controller design using a linear quadratic regulator are provided. The latter is used as the performance benchmark to evaluate the optimal design solution of the former. Experimental results show that the linear dampers design with the proposed method can achieve similar performance to an optimal active controller.
The Pseudospectral Legendre Method for a Class of Singular Boundary Value Problems Arising in Physiology
Authors: Alipanah A. , Razzaghi M. , Dehghan M.
Published: July 2009

This paper presents a computational technique for the solution of a class of nonlinear singular boundary value problems arising in physiology. The approach is based on a pseudospectral Legendre method in which Legendre—Gauss—Lobatto nodes are used to construct the N th degree polynomial interpolation to approximate the solution. The method is easy to implement and yields accurate results. Illustrative examples are included to demonstrate the capability of the proposed method, and a comparison is made with existing methods in the literature.
Sliding Mode Control of a Three-dimensional Overhead Crane
Authors: Almutairi Naif B. , Zribi Mohamed
Published: July 2009

This paper deals with the sliding mode control of a three-dimensional overhead crane. The model of the crane consists of five highly nonlinear second-order ordinary differential equations. The crane is an underactuated system, which makes the design of its controllers intricate. A sliding mode control scheme is proposed for the crane. This scheme, which guarantees the asymptotic stability of the closed-loop system, has two objectives: position regulation and anti-swing control. The performance of the closed-loop system is simulated using MATLAB. The simulation results indicate that the proposed control scheme works well. In addition, the robustness of the controller with respect to uncertainties in the crane parameters is investigated through simulations. It is found that the controller is robust to changes in the parameters. Moreover, since some of the states of the system are not measurable, a Luenberger-type observer is proposed. Simulation of the controlled system using the observer-based sliding mode controller produced good results.
How Safe Are Trick-or-Treaters?
Authors: Chaffin Mark , Levenson Jill , Letourneau Elizabeth , Stern Paul
Published: July 2009

States, municipalities, and parole departments have adopted policies banning known sex offenders from Halloween activities, based on the worry that there is unusual risk on these days. The existence of this risk has not been empirically established. National Incident-Base Reporting System crime report data from 1997 through 2005 were used to examine daily population adjusted rates from 67,045 nonfamilial sex crimes against children aged 12 years and less. Halloween rates were compared with expectations based on time, seasonality, and weekday periodicity. Rates did not differ from expectation, no increased rate on or just before Halloween was found, and Halloween incidents did not evidence unusual case characteristics. Findings were invariant across years, both prior to and after these policies became popular. These findings raise questions about the wisdom of diverting law enforcement resources to attend to a problem that does not appear to exist.
OHMM: a Hidden Markov Model accurately predicting the occupancy of a transcription factor with a self-overlapping binding motif
Authors: Drawid Amar , Gupta Nupur , Nagaraj Vijayalakshmi H , Gélinas Céline , Sengupta Anirvan M
Published: July 2009

Background

DNA sequence binding motifs for several important transcription factors happen to be self-overlapping. Many of the current regulatory site identification methods do not explicitly take into account the overlapping sites. Moreover, most methods use arbitrary thresholds and fail to provide a biophysical interpretation of statistical quantities. In addition, commonly used approaches do not include the location of a site with respect to the transcription start site (TSS) in an integrated probabilistic framework while identifying sites. Ignoring these features can lead to inaccurate predictions as well as incorrect design and interpretation of experimental results.

Results

We have developed a tool based on a Hidden Markov Model (HMM) that identifies binding location of transcription factors with preference for self-overlapping DNA motifs by combining the effects of their alternative binding modes. Interpreting HMM parameters as biophysical quantities, this method uses the occupancy probability of a transcription factor on a DNA sequence as the discriminant function, earning the algorithm the name OHMM: O ccupancy via H idden M arkov M odel. OHMM learns the classification threshold by training emission probabilities using unaligned sequences containing known sites and estimating transition probabilities to reflect site density in all promoters in a genome. While identifying sites, it adjusts parameters to model site density changing with the distance from the transcription start site. Moreover, it provides guidance for designing padding sequences in gel shift experiments. In the context of binding sites to transcription factor NF-κB, we find that the occupancy probability predicted by OHMM correlates well with the binding affinity in gel shift experiments. High evolutionary conservation scores and enrichment in experimentally verified regulated genes suggest that NF-κB binding sites predicted by our method are likely to be functional.

Conclusion

Our method deals specifically with identifying locations with multiple overlapping binding sites by computing the local occupancy of the transcription factor. Moreover, considering OHMM as a biophysical model allows us to learn the classification threshold in a principled manner. Another feature of OHMM is that we allow transition probabilities to change with location relative to the TSS. OHMM could be used to predict physical occupancy, and provides guidance for proper design of gel-shift experiments. Based upon our predictions, new insights into NF-κB function and regulation and possible new biological roles of NF-κB were uncovered.
Self-renewal and differentiation capabilities are variable between human embryonic stem cell lines I3, I6 and BG01V
Authors: Tavakoli Tahereh , Xu Xiangru , Derby Eric , Serebryakova Yevgeniya , Reid Yvonne , Rao Mahendra S , Mattson Mark P , Ma Wu
Published: July 2009

Background

A unique and essential property of embryonic stem cells is the ability to self-renew and differentiate into multiple cell lineages. However, the possible differences in proliferation and differentiation capabilities among independently-derived human embryonic stem cells (hESCs) are not well known because of insufficient characterization. To address this question, a side-by-side comparison of 1) the ability to maintain an undifferentiated state and to self-renew under standard conditions; 2) the ability to spontaneously differentiate into three primary embryonic germ lineages in differentiating embryoid bodies; and 3) the responses to directed neural differentiation was made between three NIH registered hES cell lines I3 (TE03), I6 (TE06) and BG01V. Lines I3 and I6 possess normal XX and a normal XY karyotype while BG01V is a variant cell line with an abnormal karyotype derived from the karyotypically normal cell line BG01.

Results

Using immunocytochemistry, flow cytometry, qRT-PCR and MPSS, we found that all three cell lines actively proliferated and expressed similar "stemness" markers including transcription factors POU5F1/Oct3/4 and NANOG, glycolipids SSEA4 and TRA-1-81, and alkaline phosphatase activity. All cell lines differentiated into three embryonic germ lineages in embryoid bodies and into neural cell lineages when cultured in neural differentiation medium. However, a profound variation in colony morphology, growth rate, BrdU incorporation, and relative abundance of gene expression in undifferentiated and differentiated states of the cell lines was observed. Undifferentiated I3 cells grew significantly slower but their differentiation potential was greater than I6 and BG01V. Under the same neural differentiation-promoting conditions, the ability of each cell line to differentiate into neural progenitors varied.

Conclusion

Our comparative analysis provides further evidence for similarities and differences between three hESC lines in self-renewal, and spontaneous and directed differentiation. These differences may be associated with inherited variation in the sex, stage, quality and genetic background of embryos used for hESC line derivation, and/or changes acquired during passaging in culture.
Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals the immunologic facet of oncolytic therapy
Authors: Worschech Andrea , Chen Nanhai , Yu Yong A , Zhang Qian , Pos Zoltan , Weibel Stephanie , Raab Viktoria , Sabatino Marianna , Monaco Alessandro , Liu Hui , Monsurró Vladia , Buller R Mark , Stroncek David F , Wang Ena , Szalay Aladar A , Marincola Francesco M
Published: July 2009

Background

GLV-1h68 is an attenuated recombinant vaccinia virus (VACV) that selectively colonizes established human xenografts inducing their complete regression.

Results

Here, we explored xenograft/VACV/host interactions in vivo adopting organism-specific expression arrays and tumor cell/VACV in vitro comparing VACV replication patterns. There were no clear-cut differences in vitro among responding and non-responding tumors, however, tumor rejection was associated in vivo with activation of interferon-stimulated genes (ISGs) and innate immune host's effector functions (IEFs) correlating with VACV colonization of the xenografts. These signatures precisely reproduce those observed in humans during immune-mediated tissue-specific destruction (TSD) that causes tumor or allograft rejection, autoimmunity or clearance of pathogens. We recently defined these common pathways in the "immunologic constant of rejection" hypothesis (ICR).

Conclusion

This study provides the first prospective validation of a universal mechanism associated with TSD. Thus, xenograft infection by oncolytic VACV, beyond offering a promising therapy of established cancers, may represent a reliable pre-clinical model to test therapeutic strategies aimed at modulating the central pathways leading to TSD; this information may lead to the identification of principles that could refine the treatment of cancer and chronic infection by immune stimulation or autoimmunity and allograft rejection through immune tolerance.
High-throughput next-generation sequencing technologies foster new cutting-edge computing techniques in bioinformatics
Authors: Yang Mary Qu , Athey Brian D , Arabnia Hamid R , Sung Andrew H , Liu Qingzhong , Yang Jack Y , Mao Jinghe , Deng Youping
Published: July 2009

The advent of high-throughput next generation sequencing technologies have fostered enormous potential applications of supercomputing techniques in genome sequencing, epi-genetics, metagenomics, personalized medicine, discovery of non-coding RNAs and protein-binding sites. To this end, the 2008 International Conference on Bioinformatics and Computational Biology (Biocomp) – 2008 World Congress on Computer Science, Computer Engineering and Applied Computing (Worldcomp) was designed to promote synergistic inter/multidisciplinary research and education in response to the current research trends and advances. The conference attracted more than two thousand scientists, medical doctors, engineers, professors and students gathered at Las Vegas, Nevada, USA during July 14–17 and received great success. Supported by International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design (IJCBDD), International Journal of Functional Informatics and Personalized Medicine (IJFIPM) and the leading research laboratories from Harvard, M.I.T., Purdue, UIUC, UCLA, Georgia Tech, UT Austin, U. of Minnesota, U. of Iowa etc, the conference received thousands of research papers. Each submitted paper was reviewed by at least three reviewers and accepted papers were required to satisfy reviewers' comments. Finally, the review board and the committee decided to select only 19 high-quality research papers for inclusion in this supplement to BMC Genomics based on the peer reviews only. The conference committee was very grateful for the Plenary Keynote Lectures given by: Dr. Brian D. Athey (University of Michigan Medical School), Dr. Vladimir N. Uversky (Indiana University School of Medicine), Dr. David A. Patterson (Member of United States National Academy of Sciences and National Academy of Engineering, University of California at Berkeley) and Anousheh Ansari (Prodea Systems, Space Ambassador). The theme of the conference to promote synergistic research and education has been achieved successfully.
Differences in duplication age distributions between human GPCRs and their downstream genes from a network prospective
Authors: Huang Yong , Zheng Ying , Su Zhixi , Gu Xun
Published: July 2009

Background

How gene duplication has influenced the evolution of gene networks is one of the core problems in evolution. Current duplication-divergence theories generally suggested that genes on the periphery of the networks were preferentially retained after gene duplication. However, previous studies were mostly based on gene networks in invertebrate species, and they had the inherent shortcoming of not being able to provide information on how the duplication-divergence process proceeded along the time axis during major speciation events.

Results

In this study, we constructed a model system consisting of human G protein-coupled receptors (GPCRs) and their downstream genes in the GPCR pathways. These two groups of genes offered a natural partition of genes in the peripheral and the backbone layers of the network. Analysis of the age distributions of the duplication events in human GPCRs and "downstream genes" gene families indicated that they both experienced an explosive expansion at the time of early vertebrate emergence. However, we found only GPCR families saw a continued expansion after early vertebrates, mostly prominently in several small subfamilies of GPCRs involved in immune responses and sensory responses.

Conclusion

In general, in the human GPCR model system, we found that the position of a gene in the gene networks has significant influences on the likelihood of fixation of its duplicates. However, for a super gene family, the influence was not uniform among subfamilies. For super families, such as GPCRs, whose gene basis of expression diversity was well established at early vertebrates, continued expansions were mostly prominent in particular small subfamilies mainly involved in lineage-specific functions.
Reverse engineering module networks by PSO-RNN hybrid modeling
Authors: Zhang Yuji , Xuan Jianhua , de los Reyes Benildo G , Clarke Robert , Ressom Habtom W
Published: July 2009

Background

Inferring a gene regulatory network (GRN) from high throughput biological data is often an under-determined problem and is a challenging task due to the following reasons: (1) thousands of genes are involved in one living cell; (2) complex dynamic and nonlinear relationships exist among genes; (3) a substantial amount of noise is involved in the data, and (4) the typical small sample size is very small compared to the number of genes. We hypothesize we can enhance our understanding of gene interactions in important biological processes (differentiation, cell cycle, and development, etc) and improve the inference accuracy of a GRN by (1) incorporating prior biological knowledge into the inference scheme, (2) integrating multiple biological data sources, and (3) decomposing the inference problem into smaller network modules.

Results

This study presents a novel GRN inference method by integrating gene expression data and gene functional category information. The inference is based on module network model that consists of two parts: the module selection part and the network inference part. The former determines the optimal modules through fuzzy c-mean (FCM) clustering and by incorporating gene functional category information, while the latter uses a hybrid of particle swarm optimization and recurrent neural network (PSO-RNN) methods to infer the underlying network between modules. Our method is tested on real data from two studies: the development of rat central nervous system (CNS) and the yeast cell cycle process. The results are evaluated by comparing them to previously published results and gene ontology annotation information.

Conclusion

The reverse engineering of GRNs in time course gene expression data is a major obstacle in system biology due to the limited number of time points. Our experiments demonstrate that the proposed method can address this challenge by: (1) preprocessing gene expression data (e.g. normalization and missing value imputation) to reduce the data noise; (2) clustering genes based on gene expression data and gene functional category information to identify biologically meaningful modules, thereby reducing the dimensionality of the data; (3) modeling GRNs with the PSO-RNN method between the modules to capture their nonlinear and dynamic relationships. The method is shown to lead to biologically meaningful modules and networks among the modules.
A distribution-free convolution model for background correction of oligonucleotide microarray data
Authors: Chen Zhongxue , McGee Monnie , Liu Qingzhong , Kong Megan , Deng Youping , Scheuermann Richard H
Published: July 2009

Introduction

Affymetrix GeneChip® high-density oligonucleotide arrays are widely used in biological and medical research because of production reproducibility, which facilitates the comparison of results between experiment runs. In order to obtain high-level classification and cluster analysis that can be trusted, it is important to perform various pre-processing steps on the probe-level data to control for variability in sample processing and array hybridization. Many proposed preprocessing methods are parametric, in that they assume that the background noise generated by microarray data is a random sample from a statistical distribution, typically a normal distribution. The quality of the final results depends on the validity of such assumptions.

Results

We propose a Distribution Free Convolution Model (DFCM) to circumvent observed deficiencies in meeting and validating distribution assumptions of parametric methods. Knowledge of array structure and the biological function of the probes indicate that the intensities of mismatched (MM) probes that correspond to the smallest perfect match (PM) intensities can be used to estimate the background noise. Specifically, we obtain the smallest q2 percent of the MM intensities that are associated with the lowest q1 percent PM intensities, and use these intensities to estimate background.

Conclusion

Using the Affymetrix Latin Square spike-in experiments, we show that the background noise generated by microarray experiments typically is not well modeled by a single overall normal distribution. We further show that the signal is not exponentially distributed, as is also commonly assumed. Therefore, DFCM has better sensitivity and specificity, as measured by ROC curves and area under the curve (AUC) than MAS 5.0, RMA, RMA with no background correction (RMA-noBG), GCRMA, PLIER, and dChip (MBEI) for preprocessing of Affymetrix microarray data. These results hold for two spike-in data sets and one real data set that were analyzed. Comparisons with other methods on two spike-in data sets and one real data set show that our nonparametric methods are a superior alternative for background correction of Affymetrix data.
Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing
Authors: Wang Xin , Wang Kejun , Radovich Milan , Wang Yue , Wang Guohua , Feng Weixing , Sanford Jeremy R , Liu Yunlong
Published: July 2009

Background

Human genes undergo various patterns of pre-mRNA splicing across different tissues. Such variation is primarily regulated by trans-acting factors that bind on exonic and intronic cis-acting RNA elements (CAEs). Here we report a computational method to mechanistically identify cis-acting RNA elements that contribute to the tissue-specific alternative splicing pattern. This method is an extension of our previous model, SplicingModeler, which predicts the significant CAEs that contribute to the splicing differences between two tissues. In this study, we introduce tissue-specific functional levels estimation step, which allows evaluating regulatory functions of predicted CAEs that are involved in more than two tissues.

Results

Using a publicly available Affymetrix Genechip® Human Exon Array dataset, our method identifies 652 cis-acting RNA elements (CAEs) across 11 human tissues. About one third of predicted CAEs can be mapped to the known RBP (RNA binding protein) binding sites or match with other predicted exonic splicing regulator databases. Interestingly, the vast majority of predicted CAEs are in intronic regulatory regions. A noticeable exception is that many exonic elements are found to regulate the alternative splicing between cerebellum and testes. Most identified elements are found to contribute to the alternative splicing between two tissues, while some are important in multiple tissues. This suggests that genome-wide alternative splicing patterns are regulated by a combination of tissue-specific cis-acting elements and "general elements" whose functional activities are important but differ across multiple tissues.

Conclusion

In this study, we present a model-based computational approach to identify potential cis-acting RNA elements by considering the exon splicing variation as the combinatorial effects of multiple cis-acting regulators. This methodology provides a novel evaluation on the functional levels of cis-acting RNA elements by estimating their tissue-specific functions on various tissues.
Annotating the human genome with Disease Ontology
Authors: Osborne John D , Flatow Jared , Holko Michelle , Lin Simon M , Kibbe Warren A , Zhu Lihua , Danila Maria I , Feng Gang , Chisholm Rex L
Published: July 2009

Background

The human genome has been extensively annotated with Gene Ontology for biological functions, but minimally computationally annotated for diseases.

Results

We used the Unified Medical Language System (UMLS) MetaMap Transfer tool (MMTx) to discover gene-disease relationships from the GeneRIF database. We utilized a comprehensive subset of UMLS, which is disease-focused and structured as a directed acyclic graph (the Disease Ontology), to filter and interpret results from MMTx. The results were validated against the Homayouni gene collection using recall and precision measurements. We compared our results with the widely used Online Mendelian Inheritance in Man (OMIM) annotations.

Conclusion

The validation data set suggests a 91% recall rate and 97% precision rate of disease annotation using GeneRIF, in contrast with a 22% recall and 98% precision using OMIM. Our thesaurus-based approach allows for comparisons to be made between disease containing databases and allows for increased accuracy in disease identification through synonym matching. The much higher recall rate of our approach demonstrates that annotating human genome with Disease Ontology and GeneRIF for diseases dramatically increases the coverage of the disease annotation of human genome.
Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate
Authors: Pinós Tomàs , Barbosa-Desongles Anna , Hurtado Antoni , Santamaria-Martínez Albert , de Torres Inés , Morote Joan , Reventós Jaume , Munell Francina
Published: July 2009

Background

The human Sex Hormone Binding Globulin (SHBG) gene, located at 17p13.1, comprises, at least, two different transcription units regulated by two different promoters. The first transcription unit begins with the exon 1 sequence and is responsible for the production of plasma SHBG by the hepatocytes, while the second begins with an alternative exon 1 sequence, which replaces the exon 1 present in liver transcripts. Alternative exon 1 transcription and translation has only been demonstrated in the testis of transgenic mice containing an 11-kb human SHBG transgene and in the human testis. Our goal has been to further characterize the 5' end of the SHBG gene and analyze the presence of the SHBG alternative transcripts in human prostate tissue and derived cell lines.

Results

Using a combination ofin silicoandin vitrostudies, we have demonstrated that the SHBG gene, along with exon 1 and alternative exon 1 (renamed here exon 1A), contains four additional alternative first exons: the novel exons 1B, 1C, and 1E, and a previously identified exon 1N, which has been further characterized and renamed as exon 1D. We have shown that these four alternative first exons are all spliced to the same 3' splice site of SHBG exon 2, and that exon 1A and the novel exon 1B can be spliced to exon 1. We have also demonstrated the presence of SHBG transcripts beginning with exons 1B, 1C and 1D in prostate tissues and cell lines, as well as in several non-prostatic cell lines. Finally, the alignment of the SHBG mammalian sequences revealed that, while exons 1C, 1D and 1E are very well conserved phylogenetically through non-primate mammal species, exon 1B probably aroused in apes due to a single nucleotide change that generated a new 5' splice site in exon 1B.

Conclusion

The identification of multiple transcription start sites (TSS) upstream of the annotated first exon of human SHBG, and the detection of the alternative transcripts in human prostate, concur with the prediction of the ENCODE (ENCyclopedia of DNA Elements) project, and suggest that the regulation of SHBG is much more complex than previously reported.