bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Motion and Structure Estimation by Fusion of Inertial and Vision Data
Authors: Gemeiner Peter , Einramhof Peter , Vincze Markus
Published: June 2007

For mobile robotics, head gear in augmented reality (AR) applications or computer vision, it is essential to continuously estimate the egomotion and the structure of the environment. This paper presents the system developed in the SmartTracking project, which simultaneously integrates visual and inertial sensors in a combined estimation scheme. The sparse structure estimation is based on the detection of corner features in the environment. From a single known starting position, the system can move into an unknown environment. The vision and inertial data are fused, and the performance of both Unscented Kalman filter and Extended Kalman filter are compared for this task. The filters are designed to handle asynchronous input from visual and inertial sensors, which typically operate at different and possibly varying rates. Additionally, a bank of Extended Kalman filters, one per corner feature, is used to estimate the position and the quality of structure points and to include them into the structure estimation process. The system is demonstrated on a mobile robot executing known motions, such that the estimation of the egomotion in an unknown environment can be compared to ground truth.
Towards Establishing an Integrated System of Quality Assurance in South African Higher Education Libraries
Authors: de Jager Karin
Published: June 2007

Recent demands for evidence of quality and the impact of library services on teaching and research require libraries to demonstrate accountability and responsiveness to a divergent range of user needs. In 2004 the Committee for Higher Education Librarians in South Africa (CHELSA) recognized a need for an agreed set of criteria, standards and models for quality assurance and the critical success factors for self assessment in university libraries. CHELSA therefore established its own Quality Assurance Subcommittee to provide libraries with clear and practical direction in preparing for mandated national higher education quality audits and to operationalize an ongoing process of library performance evaluation according to agreed measures. The author, a member of this Subcommittee, charts the progress towards building consensus and establishing an integrated system and process of quality assurance at South African university libraries on the basis of international standards.
The Challenges Faced by African Libraries and Information Centres in Documenting and Preserving Indigenous Knowledge
Authors: Sithole Jabulani
Published: June 2007

African libraries and information centres are faced with a plethora of challenges in the documentation and communication of indigenous knowledge. These include the lack of financial resources, human capacity, technology shortages and the lack of legal frameworks at national and international level to support the library efforts to document and communicate indigenous knowledge. The fast developing information and communication technologies continue to pose challenges on how best libraries can document and disseminate this oral and community based knowledge to a globally accepted knowledge base. The paper discusses these challenges, looking at some of the lessons learnt and the best practices that have emerged in dealing with them.
Designing and Implementing Business Information Services in the SMME Sector in a Developing Country: the case for Namibia
Authors: Chiware Elisha Rufaro T.
Published: June 2007

This article outlines the development and implementation strategies that can be applied in the deployment of business information services in the small, medium and micro enterprises (SMMEs) sector in Namibia. The paper is based on a doctoral project that was carried out at the University of Pretoria from 2005 to 2007 and looks at the stages of user needs assessment, the design of services and the implementation stage as well as the impact assessment of the services.
Libraries and Women's Participation in Nigerian Politics
Authors: Badawi Ghaji
Published: June 2007

In the history of Nigeria, cultural factors have been a serious source of problems for the development of women politically and have continued to affect the development and prominence of Nigerian women in their roles in politics. The country has governments run by men at all levels, not because there are no women fit to fill the positions but because most women think of political participation as hopeless for them. Among the factors inhibiting women to vote or contest in elections is lack of information about politics and politicians. Because most women in Nigeria dwell in rural areas and their votes are needed to ensure their full participation in politics, there is a need for libraries to find ways in which women can be informed about and encouraged to participate fully in the 2007 election. This paper discusses how libraries in Nigeria are gearing up, and what more they could do, to fully take part in mobilizing women to participate and contest for political offices now and in future.
Intellectual Property, Libraries and Access to Information in Zimbabwe
Authors: Matsika Kathy
Published: June 2007

This paper will address some of the issues affecting access to information and knowledge in Zimbabwe. It will look at the major challenges posed by finances, technology, infrastructure, the Intellectual Property Laws and the Copyright Act, in particular. It will discuss the role of ZIMCOPY, the Reproduction Rights Organization of Zimbabwe, in the information chain in Zimbabwe. It will pay particular attention to what Zimbabwe has done in trying to harness the potential of information and communication technologies (ICTs) in accessing information; the availability of the Internet and constraints of bandwidth. Zimbabwe has more than 70 percent of its population living in the rural areas. The paper will show the attempts that have been made to provide access to information through libraries and similar information centers, in both urban and rural communities of Zimbabwe. It will also refer to the current economic challenges facing Zimbabweans, how this has made information a luxury when set against the daily problems of food provision and survival. Can improved access to information provide answers to some of the immediate problems facing the Zimbabwean society?
Special Section: Block Supervision: Helping to Overcome Potential Disengagement and Stimulate Development in Qualified Group Analysts
Authors: Hanson Wendy
Published: June 2007

This article describes one form of group supervision for group analysts and discusses the experiences of one such group over a four-year period. The importance of supervision which prevents too early or summary closure of understanding in order to make a positive therapeutic outcome is discussed. Group psychotherapy is described as being highly complex, which requires a high tolerance for complexity of understanding and intervention forms in order to be productive. The block format consisting of supervision once a semester over a two-day period is described, as are participant observations and subjective experiences, showing that this format can mirror developmental processes found in psychotherapy groups, manifesting greater group cohesion, empathy and more authentic interaction between the supervision candidates.
Special Section: Group Supervision of Individual Therapy
Authors: Kalai Sarah
Published: June 2007

In the course of my professional evolution as an individual therapist, I often had the experience of supervision in a group. Sometimes it was individual supervision in the presence of a group. Usually it was an occasion for group members to take part in a clinical discussion of the case presented, where one can certainly learn much from listening and reacting to another therapist at work. However, group process was not employed for the purposes of supervision — and the group process is the focus of this article.
Gazing Through the Crystal Ball: Potential Futures for Nursing Research?
Authors: Malinski Violet M.
Published: June 2007

In this column Thomas Cox explores advances in travel and technology that he believes will help to change the face of healthcare and thus nursing practice and research. Within a focus on the coming globalization of healthcare, he proposes a restructuring of nursing into four tiers of practitioners, each with a different focus in providing care, and reframes the meaning of this care, offering a glimpse into the ways nursing research might evolve to parallel changes in practice. He then delineates in some detail the ways the process of conducting research is likely to change given expected advances in computerization. Francelyn Reeder focuses on the pattern changes taking place globally and the philosophical ideas that can assist nurse researchers in recognizing a very broad array of sources of evidence that will help further the discipline and enhance quality of life for all beings and the environment. Integral to her presentation are the ideas that belonging comes before being in the world and that integral evidence is necessary to understand the unfolding life world of all the world's inhabitants.
Professional Values in Nursing Ethics: Essential or Optional in the Global Universe?
Authors: Milton Constance L.
Published: June 2007

For any discipline with a practice component, value priorities are a reflection of choices on what it means to be a member of the discipline. For the recipients of professional nursing services, values reflect owning individual priorities for what is most important in living health and quality of life. In the context of global healthcare, priority has been afforded to disciplinary practices whose values are consistent with those of normative, empirical science. This column begins a discussion of what values guide and ought to guide the discipline and practice of nursing from a nursing theoretical perspective.
The Power of Imagination: Picturing Practice in 2050
Authors: Mitchell Gail J.
Published: June 2007

The practice columns in this 20th anniversary year are focused on how nursing theory-based practice might evolve and unfold in the future. In this column, nurses affiliated with Neuman's systems model and Rogers' science of unitary human beings imagine what nursing practice guided by their respective theories might look in 2050 and beyond.
Human Becoming and 80/20: An Innovative Professional Development Model for Nurses
Authors: Bournes Debra A. , Ferguson-Paré Mary
Published: June 2007

The authors describe a study that evaluated implementation of a professional development model in which nurses spend 80% of their salaried time in direct patient care and 20% of their salaried time on professional development. The professional development time includes focused learning about patient-centered practice guided by the human becoming nursing theory. A qualitative descriptive preproject-process-postproject method and a longitudinal, repeated measures, descriptive-comparative method were used to answer the research questions. Participants were 33 nurses, 11 other nurse leaders and health professionals, and 55 patients and family members. The findings show that on the study unit overtime hours decreased significantly, the education hours were sustained throughout the study period, workload hours per patient day increased significantly, sick time stayed low, patient satisfaction scores increased, staff satisfaction scores were significantly higher than for comparator groups, and turnover was non-existent among study participants in year 2. Average variable direct labor cost increased over time, but the increase was not significantly higher than on the control units. Themes from the interviews with participants are presented. Ongoing evaluation of the model and implications for future research are discussed.
The Theory of Genetic Vulnerability: A Roy Model Exemplar
Authors: Hamilton Rebekah J. , Bowers Barbara J.
Published: June 2007

The purpose of this study was to explore the experience of adult genetic testing. Grounded theory was used to plan, guide, and analyze in-depth interviews with 29 participants. The theory of genetic vulnerability was developed and is composed of five concepts: (a) experiencing the family disease, (b) testing for a mutation, (c) fore-grounding inherited disease risk, (d) responding to knowledge of genetic vulnerability, and (e) altering or avoiding the family experience of inherited disease. Roy's model of adaptation is discussed as a valuable lens through which to test and adapt this theory.
Contraceptive Decision-Making in Military Women
Authors: Chung-Park Min S.
Published: June 2007

The purpose of this study was to explore the experiences of women in the military related to the prevention of pregnancy. Ten single women, ages 19 to 24, volunteered to be participants. They were interviewed over a 12-week period in a private setting at a military clinic. The results of the study were that their decision to use contraception was influenced by their personal goals, family values, perceived support system, and effectiveness of the birth control. These women used contraceptive methods that they felt were right for them. The conclusion of the study was that women in active military duty are in need of reproductive health education, career counseling, and support. Nurses are in a good position to provide these needed services.
`Schizophrenic Person' or `Person with Schizophrenia'?
Authors: Sass Louis A.
Published: June 2007

Most contemporary experts and mental health advocates would reject the term `schizophrenic', whether used as noun or adjective. The terminology they prefer—`person with schizophrenia'—seems safely to nominalize the ailment and set it apart from the afflicted person, treating the disease entity as a foreign body. The present essay does not advocate rejecting the current terminology. It offers a critical perspective on the contemporary consensus by considering three aspects of schizophrenia that current terminology downplays or denies: (1) how schizophrenia may not merely hijack but actually transform the self; (2) how schizophrenic psychosis may grow out of a particular personality orientation, thus representing the culmination of a personal trajectory or mode of being; (3) how schizophrenic modes of being can sometimes involve, often in paradoxical ways, certain forms of intentionality, self-awareness, commitment or even quasi-volitional choice. Several disadvantages of the `person with schizophrenia' formula are considered: (1) conceptual oversimplification of the psychological realities of schizophrenia; (2) forms of stigmatizing inherent in the biomedical disease model; (3) closing down a potential `dialogue with madness'.
Realism, Self-Deception and the Logical Paradox of Repression
Authors: Boag Simon
Published: June 2007

Historically, repression has been considered a cornerstone of psychoanalytic theory. However, explaining how the ego maintains repression without knowing the repressed appears to create a logical paradox of knowing in order not to know. Maze and Henry's realist analysis of the problem provides an important new direction for framing possible solutions. However, their proposed explanation in terms of `affective blocking' is found to be limited with respect to explaining important features of repression, such as the clinical phenomenon of resistance. Alternatively, the present thesis proposes that a solution can be provided in terms of strong partitioning and neural inhibition. The resolution of the paradox hinges upon the recognition that repression inhibits knowledge of knowing the repressed. Implications of this position for understanding self-deception are discussed.
Addressing the multifaceted nature of music education: An activity theory research perspective
Authors: Welch Graham F.
Published: June 2007

This article explores the potential benefits from an application of activity theory to music education research. In particular, the intention is to understand more clearly those possible, potential and actual interrelationships between the constituent elements that comprise the complex reality of the process of music education. Illustrations are provided from an example case study of new, unpublished research into the nature and impact of the introduction of female choristers into an all-male UK cathedral choir.
A conceptual framework for understanding musical performance anxiety
Authors: Papageorgi Ioulia , Hallam Susan , Welch Graham F.
Published: June 2007

Most research on musical performance anxiety has considered this in relation to the internal characteristics of the performer, the extent of their preparedness for the performance, and factors in the immediate performing environment. The approach to its alleviation has generally been clinical in nature. Little research has been situated within an explicit overarching conceptual framework. This article proposes a theoretical framework that portrays anxiety within a musical performance context as a process that has an explicit time dimension (pre-, during- and post-performance). The model illustrates the likely processes that occur once a performer agrees to participate in a particular performance and explains how these might give rise to either maladaptive or adaptive forms of performance anxiety. The potential longer-term effects on the performer are also discussed. A detailed description of the model and the theories behind its development is followed by a consideration of model's implications and potential usefulness for both research and education.
How Much Does It Cost for Cinema to Tell the Truth of Sex? Cinéma Vérité and Sexography
Authors: de Villiers Nicholas
Published: June 2007

As Foucault has shown, the Christian pastoral and modern psychiatry share a concern for sex as the truth of the subject which must be passed through `the endless mill of speech'. But what happens when the Confessional and the Couch come into contact with the Cinema? How does realist, documentary and cinéma vérité film-making modify confessional discourse? In this article, I compare Pier Paolo Pasolini's Love Meetings (Comizi d'amore) (1964) with a pair of documentaries by Wiktor Grodecki on young male prostitutes in Prague ( Body Without Soul (1996) and Not Angels But Angels (1994)), Larry Clark's KIDS (1995), Paul Morrissey's Flesh (1968) and Andy Warhol's Blow Job (1963). I also consider how Jennie Livingston's Paris Is Burning (1990), in its similarity to Grodecki's and Clark's works, also departs from their (implicit) homophobia towards a critique of its own shared cinéma vérité investment in truth-telling.
Gays and Queers: From the Centering to the Decentering of Homosexuality in American Films
Authors: Dean James Joseph
Published: June 2007

This article examines independent cinema's depictions of homosexuality from 1990 to 2000. Using mainstream Hollywood films of the 1990s as the context for their development, I show significant differences in how homosexuality is represented outside mainstream films. Specifically, I divide independent films into two types: gay and lesbian standpoint films, and queer cinema. Gay standpoint films are distinguished by their narrative focus on a gay and lesbian subculture, whereas queer cinema generally depicts representations of a character's sexuality as decentered. I suggest that if we understand gay and lesbian standpoint films as a response to mainstream Hollywood ones that exclude subcultural depictions, then queer cinema can be seen as a challenge to both gay and lesbian standpoint films, and mainstream Hollywood films that center and normalize homosexual identity.
Perspectives on injuries in snowboarders
Authors: McKenna Jim , Hammond Claire
Published: June 2007

Aims: Adopting effective injury prevention practices continues to be problematic within snowboarding and the participation of older individuals is associated with an appreciable injury burden. The Haddon Matrix provides an important framework for developing injury prevention interventions. Since prevention behaviour must `fit' within individual aspirations, our study investigated the meanings and behaviours associated with snowboarding and injury prevention and then applied the findings to the established Haddon Matrix approach.

Methods: Nine, older adult recreational participants living in south-west England each contributed two interviews. These progressively focused on experiences and reflections. Verbatim transcripts were analysed and interpreted using the hermeneutic phenomenological themes of time, space, body and human relations. A further wave of analysis reinterpreted the findings in relation to the Haddon Matrix.

Findings: Snowboarding was conducted within a holiday when participants were seeking happiness by positively re-evaluating their lives. In a frame of connection-and-disconnection , beginners ( time) were concerned with being- on the slopes ( body and space), while more experienced ( body and time) participants blended this with being-in the mountains ( space). Snowboarding is a bumps-and-bruises activity and this guided the limited prevention practices. Importantly, all prevention practices were time- limited, due to a concern for learning-by-doing within a holiday. At home, more experienced boarders paid careful attention to fitness, whereas in the resorts they actively selected the soft, off-piste areas and wore protective clothing to cushion their inevitable falls. Group experiences were associated with heightened injury risks. Being seen and judged by others helped to determine the quality of the snowboarding experience. Treatment was avoided for all but the most severe injuries.

Conclusion: The findings confirm the exploratory value of mixing van Manen's four-dimensional approach with Haddon's well-established injury prevention framework. The diverse subjective meanings associated with snowboarding limit the potential for prevention approaches and suggest that resort-based `injury control' may be more appropriate for addressing the spectrum of prevention in older snowboarders.
Methodological Reflections
Authors: Valentine Christine
Published: June 2007

This article explores the co-constructed nature of interview narratives in the context of a qualitative bereavement study and the implications of adopting a `collaborative paradigm'. This approach encompasses the emotional impact of the interview on the researcher as much as the participant. It considers the importance of and difficulties encountered in engaging with this aspect. It argues that not only is this essential to achieving an ethical stance, but an invaluable methodological tool for enhancing an understanding of one's findings. Only when I was able to `appreciate' the nature and extent of my own part in narrative constructions did I start to `hear' and `appreciate' more fully the meanings that were being shaped. This process was intimately related to the cultivation of an ethical stance, something that cannot be a once and for all position. Rather it develops from an ongoing reflexive engagement with the research endeavour.
Providing Ethics a Space on the Page
Authors: Burke Tracey Kathleen
Published: June 2007

Critics have faulted reports of qualitative research in social work for not adequately describing ethical issues such that readers can evaluate them. This article provides detailed information about the intertwined methodological and ethical considerations of one ethnographic study conducted among Alaska Native people. The article illustrates that editors must allow considerably more space in reports of findings if scholars are to provide full accounts of their qualitative methods and ethics.
Stent-Angioplasty for Internal-to-External Carotid Artery Anastomotic Stenosis: A Case Report
Authors: Lesley Walter S. , Buckley Clifford J.
Published: June 2007

Endosurgical stenting and angioplasty using filter neuroprotection can be safely performed with a durable result for the repair of a cervical internal-to-external carotid artery anastomotic stenosis.
All Patients Benefit Equally From a Supervised Exercise Program for Claudication
Authors: Serracino-Inglott Ferdinand , Owen Gareth , Carter Andrew , Dix Francis , Smyth John Vince , Mohan Irwin V.
Published: June 2007

This study assessed the effect of gender, diabetic status, statin use, smoking, hypertension, cardiac status, and use of cilostazol on the outcome of a supervised exercise program for patients with claudication. Patient risk factors were prospectively recorded in a group of patients who had completed 1 year on a supervised exercise program. In 165 claudicant patients, maximum walking distance increased ( P < .0001) from 67 meters (range, 17-196) to 122 meters (range, 43-409). Quality of life as measured by the Medical Outcome Study Short Form 36 increased ( P < .0001) from a median of 78 (range, 55-110) to 99 (range, 71-154). The improvements in claudication distance, maximal walking distance, and quality of life after the exercise program were not dependent on any of the measured patient factors. Patients referred to exercise programs for claudication are a heterogenous group. Despite this, they benefit equally from such a program.
Endovascular Treatment of a Primary Aortoduodenal Fistula: 2-Year Follow-Up of a Case Report
Authors: Papacharalambous Gerasimos , Skourtis Georgios , Saliveros Apostolos , Karagannidis Dimitrios , Makris Sotirios , Panousis Panagiotis , Ktenidis Kiriakos
Published: June 2007

The purpose is to evaluate the role of endovascular management for primary aortoduodenal fistula in poor surgical risk patients. A 70-year-old-man was admitted at the emergency room of our hospital with recurrent upper-gastrointestinal bleeding. A diagnostic workup was suggestive of a primary aortoduodenal fistula caused by erosion of an infrarenal abdominal aortic aneurysm. Intractable cardiac arrhythmia, recurrent hemorrhage, and poor patient condition were compatible with an exceedingly high surgical risk. The fistula was successfully treated, and gastrointestinal bleeding was eliminated with placement of a Lifepath endoluminal aortoiliac stent graft. At the 21-month follow-up, the patient was not presenting with symptoms and signs of graft infection, and radiologic studies confirmed decreasing aneurysm size without associated signs of local sepsis. Endovascular stent grafts can efficiently arrest massive exsanguination in critically ill patients with primary aortoenteric fistula. The risk of graft infection remains the most serious problem associated with this approach.
Research capacity for everyone? A case study of two academic nursing schools' capacity building strategies
Authors: Green Barbara , Segrott Jeremy , Priest Helena , Rout Amelia , McIvor Mike , Douglas Julie , Flood Yvonne , Morris Sara , Rushton Claire
Published: June 2007

This paper reports the findings of a comparative case-study project which evaluated the development of nursing research capacity in two academic schools in the United Kingdom. The research compared the approaches used, explored the experiences of staff during the implementation process, and identified the outcomes which were achieved. The methods employed were in-depth interviews, focus groups and documentary analysis. A literature review was undertaken to inform the design and conduct of the study (Segrott et al., 2006).

The project's findings are divided into five sections. We begin by discussing the strategies implemented by the two schools, and their overall success. We then examine the wider development of a research culture, explore the problems and challenges experienced, and consider the management and organisation of capacity building. The final theme concerns the role played by the schools' wider institutional and political contexts.

The paper explores the relative strengths of inclusive and exclusive approaches to staff development, and the importance of integrated academic leadership and effective management. The study highlights the need for academic schools to forge strong connections between experienced researchers and novices, as well as between teaching and research activities.
Every-one's business, no-one's responsibility; reporting clinical academic research activity by nurses in the United Kingdom
Authors: Jackson Christine , Butterworth Tony
Published: June 2007

Gathering a complete data set on the clinical academic research activity of nurses in the United Kingdom is presently not possible. The broad range of funding and development agencies, the scholarship awarding bodies and the individual endeavours of nurses are difficult to bring together in a meaningful way. This paper offers an account of the emerging research landscape in the United Kingdom and the devolved nations and provides examples of the research profiles of nurses that illustrates the dispersed nature of nurse activity data. This paper ends by suggesting a solution to data collection based on one of the recently offered recommendations of the United Kingdom Clinical Research Collaboration (UKCRC) in its report `Developing the Best Research Professionals' (2006), and suggests two first steps in developing a strategic approach to making data more complete, useful and accessible.
Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma
Authors: Kuhn Deborah J. , Chen Qing , Voorhees Peter M. , Strader John S. , Shenk Kevin D. , Sun Congcong M. , Demo Susan D. , Bennett Mark K. , van Leeuwen Fijs W. B. , Chanan-Khan Asher A. , Orlowski Robert Z.
Published: June 2007

The proteasome has emerged as an important target for cancer therapy with the approval of bortezomib, a first-in-class, reversible proteasome inhibitor, for relapsed/refractory multiple myeloma (MM). However, many patients have disease that does not respond to bortezomib, whereas others develop resistance, suggesting the need for other inhibitors with enhanced activity. We therefore evaluated a novel, irreversible, epoxomicin-related proteasome inhibitor, carfilzomib. In models of MM, this agent potently bound and specifically inhibited the chymotrypsin-like proteasome and immunoproteasome activities, resulting in accumulation of ubiquitinated substrates. Carfilzomib induced a dose- and time-dependent inhibition of proliferation, ultimately leading to apoptosis. Programmed cell death was associated with activation of c-Jun-N-terminal kinase, mitochondrial membrane depolarization, release of cytochrome c, and activation of both intrinsic and extrinsic caspase pathways. This agent also inhibited proliferation and activated apoptosis in patient-derived MM cells and neoplastic cells from patients with other hematologic malignancies. Importantly, carfilzomib showed increased efficacy compared with bortezomib and was active against bortezomib-resistant MM cell lines and samples from patients with clinical bortezomib resistance. Carfilzomib also overcame resistance to other conventional agents and acted synergistically with dexamethasone to enhance cell death. Taken together, these data provide a rationale for the clinical evaluation of carfilzomib in MM.
Galectins in the tumor endothelium: opportunities for combined cancer therapy
Authors: Thijssen Victor L. J. L. , Poirier Françoise , Baum Linda G. , Griffioen Arjan W.
Published: June 2007

Galectins are emerging as a family of proteins that play an important role in several steps of tumorigenesis. Evidence is accumulating that galectins are expressed by the tumor endothelium, where they contribute to different steps of tumor progression such as immune escape and metastasis. Recent studies have identified an important role for galectins in tumor angiogenesis. Moreover, it has been shown that galectins in the endothelium can be targeted for therapeutic applications. This opens a window of opportunity for the development of tumor-type independent treatment strategies. This review focuses on the expression of galectins in the tumor endothelium, their contribution to tumor progression, and their application in tumor-type independent cancer therapy.
A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche
Authors: Jang Yoon-Young , Sharkis Saul J.
Published: June 2007

A low-oxygenic niche in bone marrow limits reactive oxygen species (ROS) production, thus providing long-term protection for hematopoietic stem cells (HSCs) from ROS stress. Although many approaches have been used to enrich HSCs, none has been designed to isolate primitive HSCs located within the low-oxygenic niche due to difficulties of direct physical access. Here we show that an early HSC population that might reside in the niche can be functionally isolated by taking advantage of the relative intracellular ROS activity. Many attributes of primitive HSCs in the low-oxygenic osteoblastic niche, such as quiescence, and calcium receptor, N-cadherin, Notch1, and p21 are higher in the ROSlow population. Intriguingly, the ROSlow population has a higher self-renewal potential. In contrast, significant HSC exhaustion in the ROShigh population was observed following serial transplantation, and expression of activated p38 mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) was higher in this population. Importantly, treatment with an antioxidant, a p38 inhibitor, or rapamycin was able to restore HSC function in the ROShigh population. Thus, more potent HSCs associated with the low-oxygenic niche can be isolated by selecting for the low level of ROS expression. The ROS-related signaling pathways together with specific characteristics of niche HSCs may serve as targets for beneficial therapies.
Role of the linker region in the expression of Rhizopus oryzae glucoamylase
Authors: Lin Shu-Chuan , Liu Wei-Ting , Liu Shi-Hwei , Chou Wei-I , Hsiung Bor-Kai , Lin I-Ping , Sheu Chia-Chin , Dah-Tsyr Chang Margaret
Published: June 2007

Background

Rhizopus oryzae glucoamylase (Ro GA) consists of three domains: an amino (N)-terminal raw starch-binding domain (SBD), a glycosylated linker domain, and a carboxy (C)-terminal catalytic domain. The 36-amino-acid linker region (residues 132–167) connects the two functional domains, but its structural and functional roles are unclear.

Results

To characterize the linker sequences of Ro GA and its involvement in protein expression, a number of Ro GA variants containing deletions and mutations were constructed and expressed in Saccharomyces cerevisiae. Deletion analyses demonstrate that the linker region, especially within residues 161 to 167, is required for protein expression. In addition, site-directed mutagenesis and deglycosylation studies reveal that the linker region of Ro GA contains both N- and O-linked carbohydrate moieties, and the N-linked oligosaccharides play a major role in the formation of active enzyme. Although the linker segment itself appears to have no ordered secondary structural conformation, the flexible region indeed contributes to the stabilization of functional N- and C-terminal domains.

Conclusion

Our data provide direct evidence that the length, composition, and glycosylation of the interdomain linker play a central role in the structure and function of Ro GA.
Novel and simple transformation algorithm for combining microarray data sets
Authors: Kim Ki-Yeol , Ki Dong Hyuk , Jeong Ha Jin , Jeung Hei-Cheul , Chung Hyun Cheol , Rha Sun Young
Published: June 2007

Background

With microarray technology, variability in experimental environments such as RNA sources, microarray production, or the use of different platforms, can cause bias. Such systematic differences present a substantial obstacle to the analysis of microarray data, resulting in inconsistent and unreliable information. Therefore, one of the most pressing challenges in the field of microarray technology is how to integrate results from different microarray experiments or combine data sets prior to the specific analysis.

Results

Two microarray data sets based on a 17k cDNA microarray system were used, consisting of 82 normal colon mucosa and 72 colorectal cancer tissues. Each data set was prepared from either total RNA or amplified mRNA, and the difference of RNA source between these two data sets was detected by ANOVA (Analysis of variance) model. A simple integration method was introduced which was based on the distributions of gene expression ratios among different microarray data sets. The method transformed gene expression ratios into the form of a reference data set on a gene by gene basis. Hierarchical clustering analysis, density and box plots, and mixture scores with correlation coefficients revealed that the two data sets were well intermingled, indicating that the proposed method minimized the experimental bias. In addition, any RNA source effect was not detected by the proposed transformation method. In the mixed data set, two previously identified subgroups of normal and tumor were well separated, and the efficiency of integration was more prominent in tumor groups than normal groups. The transformation method was slightly more effective when a data set with strong homogeneity in the same experimental group was used as a reference data set.

Conclusion

Proposed method is simple but useful to combine several data sets from different experimental conditions. With this method, biologically useful information can be detectable by applying various analytic methods to the combined data set with increased sample size.
ATM activation accompanies histone H2AX phosphorylation in A549 cells upon exposure to tobacco smoke
Authors: Tanaka Toshiki , Huang Xuan , Jorgensen Ellen , Gietl Diana , Traganos Frank , Darzynkiewicz Zbigniew , Albino Anthony P
Published: June 2007

Background

In response to DNA damage or structural alterations of chromatin, histone H2AX may be phosphorylated on Ser 139 by phosphoinositide 3-kinase related protein kinases (PIKKs) such as ataxia telangiectasia mutated (ATM), ATM-and Rad-3 related (ATR) kinase, or by DNA dependent protein kinase (DNA-PKcs). When DNA damage primarily involves formation of DNA double-strand breaks (DSBs), H2AX is preferentially phosphorylated by ATM rather than by the other PIKKs. We have recently reported that brief exposure of human pulmonary adenocarcinoma A549 cells or normal human bronchial epithelial cells (NHBE) to cigarette smoke (CS) induced phosphorylation of H2AX.

Results

We report here that H2AX phosphorylation in A549 cells induced by CS was accompanied by activation of ATM, as revealed by ATM phosphorylation on Ser 1981 (ATM-S1981P) detected immunocytochemically and by Western blotting. No cell cycle-phase specific differences in kinetics of ATM activation and H2AX phosphorylation were observed. When cells were exposed to CS from cigarettes with different tobacco and filter combinations, the expression levels of ATM-S1981P correlated well with the increase in expression of phosphorylated H2AX (γH2AX) (R = 0.89). In addition, we note that while CS-induced γH2AX expression was localized within discrete foci, the activated ATM was distributed throughout the nucleoplasm.

Conclusion

These data implicate ATM as the PIKK that phosphorylates H2AX in response to DNA damage caused by CS. Based on current understanding of ATM activation, expression and localization, these data would suggest that, in addition to inducing potentially carcinogenic DSB lesions, CS may also trigger other types of DNA lesions and cause chromatin alterations. As checkpoint kinase (Chk) 1, Chk2 and the p53 tumor suppressor gene are known to be phosphorylated by ATM, the present data indicate that exposure to CS may lead to their phosphorylation, with the downstream consequences related to the halt in cell cycle progression and increased propensity to undergo apoptosis. Defining the nature and temporal sequence of molecular events that are disrupted by CS through activation and eventual dysregulation of normal defense mechanisms such as ATM and its downstream effectors may allow a more precise understanding of how CS promotes cancer development.
Identification of genes differentially expressed during larval molting and metamorphosis of Helicoverpa armigera
Authors: Dong Du-Juan , He Hong-Juan , Chai Lian-Qin , Jiang Xiao-Juan , Wang Jin-Xing , Zhao Xiao-Fan
Published: June 2007

Background

Larval molting and metamorphosis are important physiological processes in the life cycle of the holometabolous insect. We used suppression subtractive hybridization (SSH) to identify genes differentially expressed during larval molting and metamorphosis.

Results

We performed SSH between tissues from a variety of developmental stages, including molting 5th and feeding 6th instar larvae, metamorphically committed and feeding 5th instar larvae, and feeding 5th instar and metamorphically committed larvae. One hundred expressed sequence tags (ESTs) were identified and included 73 putative genes with similarity to known genes, and 27 unknown ESTs. SSH results were further characterized by dot blot, Northern blot, and RT-PCR. The expression levels of eleven genes were found to change during larval molting or metamorphosis, suggesting a functional role during these processes.

Conclusion

These results provide a new set of genes expressed specifically during larval molt or metamorphosis that are candidates for further studies into the regulatory mechanisms of those stage-specific genes during larval molt and metamorphosis
The effect of natural selection on the performance of maximum parsimony
Authors: Hang Dehua , Torng Eric , Ofria Charles , Schmidt Thomas M
Published: June 2007

Background

Maximum parsimony is one of the most commonly used and extensively studied phylogeny reconstruction methods. While current evaluation methodologies such as computer simulations provide insight into how well maximum parsimony reconstructs phylogenies, they tell us little about how well maximum parsimony performs on taxa drawn from populations of organisms that evolved subject to natural selection in addition to the random factors of drift and mutation. It is clear that natural selection has a significant impact on Among Site Rate Variation (ASRV) and the rate of accepted substitutions; that is, accepted mutations do not occur with uniform probability along the genome and some substitutions are more likely to occur than other substitutions. However, little is know about how ASRV and non-uniform character substitutions impact the performance of reconstruction methods such as maximum parsimony. To gain insight into these issues, we study how well maximum parsimony performs with data generated by Avida, a digital life platform where populations of digital organisms evolve subject to natural selective pressures.

Results

We first identify conditions where natural selection does affect maximum parsimony's reconstruction accuracy. In general, as we increase the probability that a significant adaptation will occur in an intermediate ancestor, the performance of maximum parsimony improves. In fact, maximum parsimony can correctly reconstruct small 4 taxa trees on data that have received surprisingly many mutations if the intermediate ancestor has received a significant adaptation. We demonstrate that this improved performance of maximum parsimony is attributable more to ASRV than to non-uniform character substitutions.

Conclusion

Maximum parsimony, as well as most other phylogeny reconstruction methods, may perform significantly better on actual biological data than is currently suggested by computer simulation studies because of natural selection. This is largely due to specific sites becoming fixed in the genome that perform functions associated with an improved fitness.
TCF7L2 rs7903146 variant does not associate with smallness for gestational age in the French population
Authors: Cauchi Stéphane , Meyre David , Choquet Hélène , Deghmoun Samia , Durand Emmanuelle , Gaget Stefan , Lecoeur Cécile , Froguel Philippe , Levy-Marchal Claire
Published: June 2007

Background

In adults, the TCF7L2 rs7903146 T allele, commonly associated with type 2 diabetes (T2D), has been also associated with a lower body mass index (BMI) in T2D individuals and with a smaller waist circumference in subjects with impaired glucose tolerance.

Methods

The present association study aimed at analyzing the contribution of the rs7903146 SNP to smallness for gestational age (SGA) and metabolic profiles in subjects with SGA or appropriate for gestational age birth weight (AGA). Two groups of French Caucasian subjects were selected on birth data: SGA (birth weight < 10th percentile; n = 764), and AGA (25th < birth weight < 75th percentile; n = 627). Family-based association tests were also performed in 3,012 subjects from 628 SGA and AGA pedigrees.

Results

The rs7903146 genotypic distributions between AGA (30.7%) and SGA (29.0%) were not statistically different (allelic OR = 0.92 [0.78–1.09], p = 0.34). Family association-based studies did not show a distortion of T allele transmission in SGA subjects (p = 0.52). No significant effect of the T allele was detected on any of the metabolic parameters in the SGA group. However, in the AGA group, trends towards a lower insulin secretion (p = 0.03) and a higher fasting glycaemia (p = 0.002) were detected in carriers of the T allele.

Conclusion

The TCF7L2 rs7903146 variant neither increases the risk for SGA nor modulates birth weight and young adulthood glucose homeostasis in French Caucasian subjects born with SGA.
Mutations in the 3'-untranslated region of GATA4 as molecular hotspots for congenital heart disease (CHD)
Authors: Reamon-Buettner Stella Marie , Cho Si-Hyen , Borlak Juergen
Published: June 2007

Background

The 3'-untranslated region (3'-UTR) of mRNA contains regulatory elements that are essential for the appropriate expression of many genes. These regulatory elements are involved in the control of nuclear transport, polyadenylation status, subcellular targetting as well as rates of translation and degradation of mRNA. Indeed, 3'-UTR mutations have been associated with disease, but frequently this region is not analyzed. To gain insights into congenital heart disease (CHD), we have been analyzing cardiac-specific transcription factor genes, including GATA4, which encodes a zinc finger transcription factor. Germline mutations in the coding region of GATA4 have been associated with septation defects of the human heart, but mutations are rather rare. Previously, we identified 19 somatically-derived zinc finger mutations in diseased tissues of malformed hearts. We now continued our search in the 609 bp 3'-UTR region of GATA4 to explore further molecular avenues leading to CHD.

Methods

By direct sequencing, we analyzed the 3'-UTR of GATA4 in DNA isolated from 68 formalin-fixed explanted hearts with complex cardiac malformations encompassing ventricular, atrial, and atrioventricular septal defects. We also analyzed blood samples of 12 patients with CHD and 100 unrelated healthy individuals.

Results

We identified germline and somatic mutations in the 3'-UTR of GATA4. In the malformed hearts, we found nine frequently occurring sequence alterations and six dbSNPs in the 3'-UTR region of GATA4. Seven of these mutations are predicted to affect RNA folding. We also found further five nonsynonymous mutations in exons 6 and 7 of GATA4. Except for the dbSNPs, analysis of tissue distal to the septation defect failed to detect sequence variations in the same donor, thus suggesting somatic origin and mosaicism of mutations. In a family, we observed c.+119A > T in the 3'-UTR associated with ASD type II.

Conclusion

Our results suggest that somatic GATA4 mutations in the 3'-UTR may provide an additional molecular rationale for CHD.