bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neoliberal American Dream as Daydream
Authors: Morgen Sandra , Gonzales Lisa
Published: May 2008

Despite the efforts of its supporters to cast welfare `reform' in the United States as a successful achievement of neoliberal public policy, we argue that among low-income people who have received public assistance, counter-hegemonic interpretations and `possibilities' coexist with, texture and sometimes, challenge hegemonic assumptions about poverty, the state, motherhood and relations of power. Paying attention to these counter-hegemonic perspectives reveals ideological and political possibilities that are foreclosed when neoliberal hegemony is theorized as seamless and complete, rather than partial and vulnerable to disruption. That neoliberalism must be actively produced helps to explain the powerful processes that subject poor women and men, more intensely than many others, to practices and discourses designed to shape compliance with neoliberalism.
Recognition and Importance of Forced Exhalation on the Measurement of Intraabdominal Pressure: A Subgroup Analysis From a Prospective Cohort Study on the Incidence of Abdominal Compartment Syndrome in Medical Patients
Authors: Hongyan Liang  , Daugherty Elizabeth L. , Taichman Darren , Hansen-Flaschen John , Fuchs Barry D.
Published: May 2008

Intraabdominal pressure is measured conventionally at end-expiration; however, the significance of forced exhalation on this measurement has not been evaluated previously. Using data from a previous prospective cohort study of the incidence of intraabdominal hypertension and abdominal compartment syndrome in medical intensive care unit patients, the authors evaluated 65 strip-chart recordings obtained from 28 patients who had measurements of intraabdominal pressure and airway pressures taken simultaneously. Forced exhalation was identified by a rise in intraabdominal pressure during exhalation. Forced exhalation was observed in 4 patients; with a mean intraabdominal pressure increase of 14.3 ± 1.3 mm Hg at end-exhalation, compared with a decrease of −2.5 ± 1.2 mm Hg in 24 patients without forced exhalation and absolute pressures of 28.0 ± 6.6 versus 13.8 ± 3.9 mm Hg ( P < .001). However, there was no difference in end-inspiratory values. Forced exhalation is not uncommon in acutely ill, mechanically ventilated medical intensive care unit patients and may increase intraabdominal pressure significantly to values that exceed the diagnostic threshold for abdominal compartment syndrome.
Redefining the Brain Drain
Authors: Zweig David , Fung Chung Siu , Han Donglin
Published: May 2008

For many years, China's government worried about the ‘brain drain’. But beginning in 1992, China began to encourage students settled abroad to return for short visits and en-gage in various programmes on the Chinese mainland. Then, in 2001, the government adopted a new policy, encouraging overseas mainlanders to contribute to China's modernisation, even if they stayed abroad, and outlining various ways they could help China. This policy mirrors the strategies of other countries who encourage ‘brain circulation’ and develop a ‘diaspora option’ in order to overcome the loss of talented people. But what forms does this assistance take? Why do people contribute to China's modernisation while remaining abroad? What are the characteristics of those who ‘serve China’, as compared to those who do not? We employ data from a survey in Silicon Valley, as well as two Web-based surveys carried out in Canada and the US with mainland Chinese academics to answer these questions.
Coping with a Giant
Authors: Intarakumnerd Patarapong , Fujita Mai
Published: May 2008

This article focuses on how sectoral systems of innovation and production in the same industry but across countries may evolve differently after facing similar threats and opportunities caused by the same external factor. To elaborate on this, we will use the case of evolution of the automotive sectors in Thailand and Vietnam, and their dynamics and transformation when they are facing threats and opportunities from their fierce competitor, China. The findings illustrate that different sectoral systems of innovation and production evolve differently. The direction and the pace of evolution depends very much on existing absorptive capabilities of agents, strength of their linkages, and their process of collective learning to withstand the threats and exploit opportunities.
Science and Technology Policy in South Africa
Authors: Kaplan Dave
Published: May 2008

This article provides a high-level review of the performance of the S&T system in South Africa. All the indicators suggest that, at a high level, performance has not been strong. This is despite the fact that more resources have been devoted to S&T and that there has been extensive policy experimentation. The argument advanced is that the key factor explaining this weak performance is poor provision of skilled labour. The article critically examines the recent OECD review of S&T in South Africa in this light. Finally, the article examines the proposed future direction of S&T policy in South Africa as reflected in the twenty-year plan of the Department of Science and Technology. The plan is highly ambitious, considerably expanding the scope of S&T policy and projects. While it recognises the critical importance of increasing high-level skills for innovation, it fails to give adequate recognition to the fact that this will take time. Accordingly, new projects will need to be undertaken after, and not contemporaneously with, the expansion in the supply of skills.
Patient perception of bodily functions in multiple sclerosis: gait and visual function are the most valuable
Authors: Heesen C , Böhm J , Reich C , Kasper J , Goebel M , Gold SM
Published: May 2008

Multiple sclerosis is a heterogeneous disease with varying clinical picture. There have been substantial efforts to develop outcome measurements for therapeutic interventions but very few studies have addressed the value of bodily functions from the patient perspective. In a randomly selected cohort of early (<5 years, n = 84) and longer lasting disease courses (>15 years, n = 82) patients we asked for a weighting of 13 bodily functions and compared results with actual disability as measured by the United Kingdom Disability Scale. Lower limb function was given the highest priority in both patient groups followed by visual functioning and cognition especially in longer lasting MS. Actual disability did not correlate with the given priorities indicating that experienced deficits do not influence the subjective ratings of bodily functions. These results underline that ambulation-focused scales in MS represent a key dimension from the patient perspective. Visual functioning should be taken more into account.
Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis
Authors: Knudsen S , Jennum PJ , Korsholm K , Sheikh SP , Gammeltoft S , Frederiksen JL
Published: May 2008

There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system has been reported in MS case reports with attacks of hypothalamic lesions, undetectable cerebrospinal fluid (CSF) hcrt-1 and hypersomnia, but not found during remission in small samples. Finally, daytime sleepiness, the major symptom of narcolepsy, is reported in several MS populations, and there are case reports of co-existent narcolepsy and MS. However, it is unknown whether hcrt-1 and daytime sleepiness generally change during MS attacks. We therefore analyzed whether daytime sleepiness (using the Epworth Sleepiness Scale (ESS)) and CSF hcrt-1 levels differed between MS attack and remission, in 48 consecutively referred patients with relapsing–remitting MS (RRMS) or monosymptomatic optic neuritis (MON). Twenty-seven patients were in attack and 21 in remission. ESS was normal both during attacks (5.4 ± 3.0) and remission (5.8 ± 2.6), and mean CSF hcrt-1 was normal (456 ± 41 pg/ml). No statistically significant differences were found between attack and remission. MRI scans revealed no hypothalamic lesions. The results show that the hypocretin system is intact and sleepiness is not typical in RRMS and MON without hypothalamic lesions on MRI.
Is the treatment effect of IFN-β restored after the disappearance of neutralizing antibodies?
Authors: Sorensen PS , Koch-Henriksen N , Flachs EM , Bendtzen K
Published: May 2008

Objective

To establish whether multiple sclerosis (MS) patients, who have lost the therapeutic effect of interferon-beta (IFN-β) owing to neutralizing antibodies (NAbs) and subsequently revert from a NAb-positive to a NAb-negative state under continued IFN-β-1b therapy, regain clinical effect after reversion.

Background

Several studies have shown that a significant proportion of patients treated with IFN-β develop NAbs that hamper or abolish the therapeutic effect of IFN-β. However, some patients, who become NAb-positive under treatment with IFN-β-1b, may revert to a NAb-negative state under continuous treatment.

Methods

We identified 40 patients from the Danish IFN protocol, who fulfilled the criteria: NAb-positive status for at least 12 months followed by reversion to NAb-negative state for at least 12 months. For comparison, we included 64 matching cases that had remained NAb-negative during an observation time of at least 36 months. The two groups were clinically and demographically alike. We measured NAb-neutralizing capacity using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. A patient was defined as NAb-positive after two consecutive blood tests separated by at least 6 months. Reversion to a NAb-negative state required at least two consecutive negative tests. To allow for the confounding effect of time we employed a mixed Poisson model.

Results

Patients who had been NAb-positive and reverted to a NAb-negative state regained treatment effect with the relapse rate as before the NAb-positive period adjusting for the effect of time, and the relapse rate was the same as in the permanently NAb-negative patients in corresponding time periods. The relapse rate ratio comparing the NAb-positive with the NAb-negative periods was 1.98 (95% confidence interval: 1.32–2.97).

Conclusion

Under NAb-positive periods, the clinical effect of IFN-β was abolished. When NAbs disappeared spontaneously under continued treatment, patients regained the full effect of INF-β-1b therapy with no negative carry-over effect from the previous NAb-positive period.
Hull-Spence Behavior Theory as a paradigm for consumer behavior
Authors: Rossiter John R. , Foxall Gordon R.
Published: May 2008

In this paper, which takes a much broader perspective than is now usual, we state the case for the return to a grand, all-encompassing theory of the type that was popular initially in consumer behavior. This theory, a paradigm really, is Hull-Spence Behavior Theory (HSBT). The theory is introduced here in detail with reference to consumer behavior. HSBT is shown to be a very generally applicable theory, not just `middle range', with a rich set of variables that can accommodate the new micro-phenomena toward which our field has gravitated. As a grand theory, HSBT provides the `context' necessary to fully understand, explain, and predict consumer behavior.
Writing Russell Belk: excess all areas
Authors: Brown Stephen , Schau Hope Jensen
Published: May 2008

Russell Belk is one of the most distinguished thought leaders in marketing and consumer research. He is also one of its most distinctive. This paper examines the distinctiveness of Russell Belk's remarkable writing style, arguing that it exemplifies the `academic gothic'. Five characteristically gothic traits are found in his published corpus — excess, monstrosity, irony, supernaturalism, doubling — and the implications for writing marketing research are considered.
Heuristics revisited: implications for marketing research and practice
Authors: Merlo Omar , Lukas Bryan A. , Whitwell Gregory J.
Published: May 2008

The marketing literature has devoted limited attention to the nature and scope of heuristics in marketing theory development and in marketing-related decision-making processes. This is of concern because the use of heuristics can profoundly influence managerial choices and, in turn, the ability of firms to compete. The authors analyze heuristics, first in general terms by providing a review of the concept and its mechanics, and then more specifically by exploring the use of heuristics in the discipline of marketing. The market orientation and marketing concept constructs are discussed as examples of marketing tenets that, over time, have been enriched through the incorporation of heuristics. The following findings are derived from the analysis: heuristics signal the maturing of a theoretical concept; heuristics act as a measure of a discipline's impact; heuristics do not exist in isolation; effective heuristics are balanced and established; and effective heuristics evolve and adapt. Overall, the purpose of this study is to improve the understanding of the value of heuristics to marketing theory and practice and to renew research interest into heuristics in a marketing context.
Can public sector organizations be coherent corporate brands?
Authors: Wæraas Arild
Published: May 2008

This article discusses the potential challenges of introducing corporate branding in public sector organizations. While the corporate branding ideal is to seek a precise and coherent definition of the organizational identity and achieve message consistency in the organization's self-presentation, public organizations are often characterized by contradictory and inconsistent values and multiple identities. This makes the ideal of consistency difficult to achieve. It is argued that public organizations will benefit more from branding on the basis of inconsistent values and multiple identities rather than trying to promote one set of values and one identity at the expense of others.
Institutional Change, Absorptive Capacity, and the Organizational Zone of Inertia
Authors: Godkin Lynn
Published: May 2008

A framework of theoretical propositions is presented as a heuristic to describe the potential linkage between institutional absorptive capacity and organizational inertia. Means through which insight inertia and action inertia might be addressed are presented. A series of propositions and associated literature are presented for illustration. The concept of a zone of inertia is incorporated to facilitate understanding of the variables involved.
An International Pilot Study of Oncology Physicians' Opinions and Practices on Complementary and Alternative Medicine (CAM)
Authors: Lee Richard T. , Hlubocky Fay J. , Hu Je-Jen , Stafford Randall S. , Daugherty Christopher K.
Published: May 2008

Background. In China and Taiwan, Complementary and Alternative Medicine (CAM) therapies such as traditional Chinese medicine have been an option to cancer patients for centuries, whereas in the United States, CAM has been growing in popularity only in the past few decades. Prior research has indicated that the prevalence of CAM use among cancer patients may exceed 80%. Because of a long cultural history of CAM, we hypothesized that oncologists in China and Taiwan (C/T) would communicate and combine CAM with conventional treatments more often than US oncologists. Methods. In 2004-2005, a convenience sample of oncologists from the United States, mainland China, and Taiwan were surveyed regarding their opinions and self-reported practice patterns regarding CAM. Results. A total 95 oncologists returned surveys, providing a 38% response rate. Four out of 5 respondents (78%) felt their medical training was inadequate to use CAM. However, 70% reported they would allow CAM use during active cancer treatment, even in the setting of curable disease. Responding C/T oncologists tended to ask patients more frequently (they ask > 25% of patients) about CAM use and recommended CAM more commonly (recommend to > 10%) to patients than surveyed US oncologists, 55% versus 37% ( P = .09) and 81% versus 53% ( P < .05). Respondents from the United States felt no more prepared for CAM use than C/T respondents, but 70% reported willingness to combine CAM with conventional treatments for curable disease as compared with only 48% ( P < .05) of C/T oncologists. Conclusions. As expected, responding C/T oncologists communicate more often about CAM with patients by asking and recommending CAM. However, contrary to our original hypothesis, C/T oncologists reported a much lower rate of combining CAM with conventional treatment among curable patients than responding US oncologists. Further research is needed to explore, in depth, the reasons for differences in CAM practice patterns among oncologists.
Shedding Light on Vitamin D and Integrative Oncology
Authors: Cantor Ira
Published: May 2008

Studies show an important relationship between vitamin D and malignancies, both in prevention and treatment. The extraskeletal actions of vitamin D relevant to oncology include being proapoptotic, antimetastatic, antiangiogenic, antiinflammatory, prodifferentiating, and immunomodulating. Widespread and severe vitamin D deficiencies exist worldwide. Decreased sun exposure, caused by lifestyle changes, as well as fear of skin cancers, is the main cause of these deficiencies. Recommended daily oral intakes, as well as suggested blood levels, are below optimal levels suggested by studies. Improvement in vitamin D status, through lifestyle changes and supplementation, can be of profound benefit regarding the occurrence and mortality of malignancies.
Predictors of hospitals' organizational climates and nurses' intent to stay in Jordanian hospitals
Authors: Mrayyan Majd T.
Published: May 2008

This paper aimed at studying variables of hospitals' organizational climates and nurses' intent to stay and determine predictors of the two concepts. A survey using a convenience sampling technique was used to collect data. A total of 362 nurses from three types of hospitals were recruited. Farly's Nursing Practice Environment Scale (NPES) was used to assess the organizational climates at Jordanian hospitals (Farly and Nyberg, 1990). McCain's Behavioral Commitment Scale (McCloskey, 1990) was used to measure nurses' intent to stay. Stepwise regression analyses were used to indicate predictors of hospitals' organizational climates and nurses' intent to stay.

Quality of care and professionalism were major variables influenced hospitals' organizational climates. Nurses reported that they plan to keep their jobs for at least two or three years. Nurses' intent to stay, time commitment, types of hospitals and average daily census were predictors of hospitals' organizational climates. Predictors of nurses' intent to stay were hospitals' organizational climates, decision-making style, age and organizational structures.

Managerial interventions that would create supportive work environments are needed to encourage nurses to stay longer at their jobs. These interventions include, but are not limited to, using participative management and supportive leadership, decreasing workload and employing nurses who work on a full-time basis.
Correlation between self-concept and health status aspects in haemodialysis patients at selected hospitals affiliated to Shaheed Beheshti University of Medical Sciences
Authors: Yaghmaie Farideh , Khalafi Ali , Majd Hamid Alavi , Khost Nderh
Published: May 2008

Chronic renal failure (CRF) is an overwhelming disorder affecting physical, psychological and socioeconomic wellbeing of patients. Restoring health is a primary therapeutic goal and interventions are generally directed toward improving their quality of life (QOL). The concept of health is unique for every one and each individual considers it with respect to his/her own criteria. This concept is influenced by different physical, mental and social factors and is termed self-concept.

A descriptive study was conducted to determine the correlation between self-concept quality and aspects of health status in haemodialysis patients referring to hospitals affiliated to Shaheed Beheshti University of Medical Sciences. One-hundred and thirteen patients between 15 and 65 with no history of kidney transplantation and at least one year's experience of haemodialysis, three times a week, participated in the study. A questionnaire in three parts to collect demographic, self-concept and health status data was used. It was validated by content validity index and its reliability was identified by internal consistency and test-retest methods.

Findings showed a significant relation between self-concept and all aspects of health status except treatment and medication.

The correlation between self-concept and health status shows that subjective patients' attitudes affect their own self image with regards to being healthy and running a productive and fruitful life. Thus, in addition to physical disorders resulting from CRF and haemodialysis and social conditions can affect their motivation and life experience.
Accessing elite nurses for research: reflections on the theoretical and practical issues of telephone interviewing
Authors: Harris Ruth , Kelly Daniel , Hunt Jane A , Plant Hilary , Kelley Kate , Richardson Alison , Sitzia John
Published: May 2008

Elite groups are interesting as they frequently are powerful (in terms of position, knowledge and influence) and enjoy considerable authority. It is important, therefore, to involve them in research concerned with understanding social contexts and processes. This is particularly pertinent in healthcare, where considerable strategic development and change are features of everyday practice that may be guided or perceived as being guided, by elites.

This paper evolved from a study investigating the availability and role of nurses whose remit involved leading nursing research and development within acute NHS Trusts in two health regions in Southern England. The study design included telephone interviews with Directors of Nursing Services during which time the researchers engaged in a reflective analysis of their experiences of conducting research with an `elite' group. Important issues identified were the role of gatekeepers, engagement with elites and the use of the telephone interview method in this context. The paper examines these issues and makes a case for involving executive nurses in further research. The paper also offers strategies to help researchers design and implement telephone interview studies successfully to maximise access to the views and experiences of `hard to reach groups', such as elites, while minimising the associated disruption.
Emotion work and the ethics of novice insider research
Authors: Darra Susanne
Published: May 2008

This paper relates to research practice and in particular, it explores the practice of insider research in a study carried out as part of a research training fellowship. The effects of research on the researcher and the researched are discussed and extracts from transcripts and a research diary are used to illustrate ethical dilemmas that may arise from such a study. The role of the novice researcher is central to the discussion and the concept of `emotion work' is used to illustrate the hidden consequences of seemingly innocuous insider research.

The paper contributes to the body of knowledge relating to qualitative research methods, by combining reflection with emotion work and novice insider research. Despite it being largely about the novice researcher studying within her own profession, it raises important points that may be of interest to more experienced researchers working in other domains.
Research and practice hand in hand: the experience of promoting research of benefit to people with learning disabilities from within the NHS
Authors: McBrien Judith
Published: May 2008

The paper describes how clinicians from different disciplines and agencies working with children and adults with learning disabilities have joined forces to promote and conduct research pertinent to this client group. Examples of research projects show how practitioners can improve the evidence base and service delivery. Difficulties for practitioners in conducting research and gaining funding are described, with reference to the recommendations of the Cooksey report (2006).
Vorinostat synergistically potentiates MK-0457 lethality in chronic myelogenous leukemia cells sensitive and resistant to imatinib mesylate
Authors: Dai Yun , Chen Shuang , Venditti Charis A. , Pei Xin-Yan , Nguyen Tri K. , Dent Paul , Grant Steven
Published: May 2008

Interactions between the dual Bcr/Abl and aurora kinase inhibitor MK-0457 and the histone deacetylase inhibitor vorinostat were examined in Bcr/Abl+ leukemia cells, including those resistant to imatinib mesylate (IM), particularly those with the T315I mutation. Coadministration of vorinostat dramatically increased MK-0457 lethality in K562 and LAMA84 cells. Notably, the MK-0457/vorinostat regimen was highly active against primary CD34+ chronic myelogenous leukemia (CML) cells and Ba/F3 cells bearing various Bcr/Abl mutations (ie, T315I, E255K, and M351T), as well as IM-resistant K562 cells exhibiting Bcr/Abl-independent, Lyn-dependent resistance. These events were associated with inactivation and down-regulation of wild-type (wt) and mutated Bcr/Abl (particularly T315I). Moreover, treatment with MK-0457 resulted in accumulation of cells with 4N or more DNA content, whereas coadministration of vorinostat markedly enhanced aurora kinase inhibition by MK-0457, and preferentially killed polyploid cells. Furthermore, vorinostat also interacted with a selective inhibitor of aurora kinase A and B to potentiate apoptosis without modifying Bcr/Abl activity. Finally, vorinostat markedly induced Bim expression, while blockade of Bim induction by siRNA dramatically diminished the capacity of this agent to potentiate MK-0457 lethality. Together, these findings indicate that vorinostat strikingly increases MK-0457 activity against IM-sensitive and -resistant CML cells through inactivation of Bcr/Abl and aurora kinases, as well as by induction of Bim.
Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells
Authors: Laffont Sophie , Seillet Cyril , Ortaldo John , Coudert Jérôme D. , Guéry Jean-Charles
Published: May 2008

Natural killer (NK)–cell alloreactivity is exploited in bone marrow transplantation to improve clinical outcome. Likewise, in solid organ transplantation, it has been recently shown that recipient NK cells may limit alloreactive T-cell responses through their capacity to prevent the persistence of graft-derived allogeneic dendritic cells (DCs). In a model of CD4+ T cell–mediated allogeneic skin graft rejection, we show that the absence of host NK-cell alloreactivity was characterized by enhanced expansion of alloreactive effector T lymphocytes, including Th2 cells, and massive eosinophilic infiltrates in the rejected tissues. In CD8+ T cell–deficient C57BL/6 (H-2b) recipients injected with allogeneic BALB/c (H-2d) DCs, we demonstrated that NK cells expressing the H-2Dd-specific Ly49D activating receptor were implicated in the regulation of alloreactive CD4+ T-cell responses. Moreover, we showed that Ly49D+ CD127− NK cells were recruited within DC draining lymph nodes and rapidly eliminated allogeneic H-2d DCs through the perforin pathway. In normal mice, we further demonstrated that NK cells by quickly eliminating allogeneic DCs strongly inhibited alloreactive CD8+ T-cell responses. Thus, NK cells act as early regulators of alloreactive T-cell priming in allotransplantation through their capacity to kill allogeneic DCs in draining lymph nodes.
Lack of nuclear factor-κB2/p100 causes a RelB-dependent block in early B lymphopoiesis
Authors: Guo Feng , Tänzer Simone , Busslinger Meinrad , Weih Falk
Published: May 2008

Nuclear factor-κB (NF-κB) transcription factors regulate B-cell development and survival. However, whether they also have a role during early steps of B-cell differentiation is largely unclear. Here, we show that constitutive activation of the alternative NF-κB pathway in p100−/− knockin mice resulted in a block of early B-cell development at the transition from the pre–pro-B to the pro–B-cell stage due to enhanced RelB activity. Expression of the essential B-cell transcription factors EBF and in particular Pax5 was reduced in p100−/− B-cell precursors in a RelB-dependent manner, resulting in reduced mRNA levels of B lineage-specific genes. Moreover, enhanced RelB function in p100−/− B-cell precursors was accompanied by increased expression of B lineage–inappropriate genes, such as C/EBPα, correlating with a markedly increased myeloid differentiation potential of p100−/− progenitor B cells. Ectopic expression of Pax5 in hematopoietic progenitors restored early B-cell development in p100−/− bone marrow, suggesting that impaired early B lymphopoiesis in mice lacking the p100 inhibitor may be due to down-regulation of Pax5 expression. Thus, tightly controlled p100 processing and RelB activation is essential for normal B lymphopoiesis and lymphoid/myeloid lineage decision in bone marrow.
Application of the Linux cluster for exhaustive window haplotype analysis using the FBAT and Unphased programs
Authors: Mishima Hiroyuki , Lidral Andrew C , Ni Jun
Published: May 2008

Background

Genetic association studies have been used to map disease-causing genes. A newly introduced statistical method, called exhaustive haplotype association study, analyzes genetic information consisting of different numbers and combinations of DNA sequence variations along a chromosome. Such studies involve a large number of statistical calculations and subsequently high computing power. It is possible to develop parallel algorithms and codes to perform the calculations on a high performance computing (HPC) system. However, most existing commonly-used statistic packages for genetic studies are non-parallel versions. Alternatively, one may use the cutting-edge technology of grid computing and its packages to conduct non-parallel genetic statistical packages on a centralized HPC system or distributed computing systems. In this paper, we report the utilization of a queuing scheduler built on the Grid Engine and run on a Rocks Linux cluster for our genetic statistical studies.

Results

Analysis of both consecutive and combinational window haplotypes was conducted by the FBAT (Laird et al., 2000) and Unphased (Dudbridge, 2003) programs. The dataset consisted of 26 loci from 277 extended families (1484 persons). Using the Rocks Linux cluster with 22 compute-nodes, FBAT jobs performed about 14.4–15.9 times faster, while Unphased jobs performed 1.1–18.6 times faster compared to the accumulated computation duration.

Conclusion

Execution of exhaustive haplotype analysis using non-parallel software packages on a Linux-based system is an effective and efficient approach in terms of cost and performance.
Drug interaction prediction using ontology-driven hypothetical assertion framework for pathway generation followed by numerical simulation
Authors: Arikuma Takeshi , Yoshikawa Sumi , Azuma Ryuzo , Watanabe Kentaro , Matsumura Kazumi , Konagaya Akihiko
Published: May 2008

Background

In accordance with the increasing amount of information concerning individual differences in drug response and molecular interaction, the role ofin silicoprediction of drug interaction on the pathway level is becoming more and more important. However, in view of the interferences for the identification of new drug interactions, most conventional information models of a biological pathway would have limitations. As a reflection of real world biological events triggered by a stimulus, it is important to facilitate the incorporation of known molecular events for inferring (unknown) possible pathways and hypothetic drug interactions. Here, we propose a new Ontology-Driven Hypothetic Assertion (OHA) framework including pathway generation, drug interaction detection, simulation model generation, numerical simulation, and hypothetic assertion. Potential drug interactions are detected from drug metabolic pathways dynamically generated by molecular events triggered after the administration of certain drugs. Numerical simulation enables to estimate the degree of side effects caused by the predicted drug interactions. New hypothetic assertions of the potential drug interactions and simulation are deduced from the Drug Interaction Ontology (DIO) written in Web Ontology Language (OWL).

Results

The concept of the Ontology-Driven Hypothetic Assertion (OHA) framework was demonstrated with known interactions between irinotecan (CPT-11) and ketoconazole. Four drug interactions that involved cytochrome p450 (CYP3A4) and albumin as potential drug interaction proteins were automatically detected from Drug Interaction Ontology (DIO). The effect of the two interactions involving CYP3A4 were quantitatively evaluated with numerical simulation. The co-administration of ketoconazole may increase AUC and Cmax of SN-38(active metabolite of irinotecan) to 108% and 105%, respectively. We also estimates the potential effects of genetic variations: the AUC and Cmax of SN-38 may increase to 208% and 165% respectively with the genetic variation UGT1A1*28/*28 which reduces the expression of UGT1A1 down to 30%.

Conclusion

These results demonstrate that the Ontology-Driven Hypothetic Assertion framework is a promising approach forin silicoprediction of drug interactions. The following future researches for thein silicoprediction of individual differences in the response to the drug and drug interactions after the administration of multiple drugs: expansion of the Drug Interaction Ontology for other drugs, and incorporation of virtual population model for genetic variation analysis, as well as refinement of the pathway generation rules, the drug interaction detection rules, and the numerical simulation models.
Evolutionary conservation of DNA-contact residues in DNA-binding domains
Authors: Chang Yao-Lin , Tsai Huai-Kuang , Kao Cheng-Yan , Chen Yung-Chian , Hu Yuh-Jyh , Yang Jinn-Moon
Published: May 2008

Background

DNA-binding proteins are of utmost importance to gene regulation. The identification of DNA-binding domains is useful for understanding the regulation mechanisms of DNA-binding proteins. In this study, we proposed a method to determine whether a domain or a protein can has DNA binding capability by considering evolutionary conservation of DNA-binding residues.

Results

Our method achieves high precision and recall for 66 families of DNA-binding domains, with a false positive rate less than 5% for 250 non-DNA-binding proteins. In addition, experimental results show that our method is able to identify the different DNA-binding behaviors of proteins in the same SCOP family based on the use of evolutionary conservation of DNA-contact residues.

Conclusion

This study shows the conservation of DNA-contact residues in DNA-binding domains. We conclude that the members in the same subfamily bind DNA specifically and the members in different subfamilies often recognize different DNA targets. Additionally, we observe the co-evolution of DNA-contact residues and interacting DNA base-pairs.
A topological transformation in evolutionary tree search methods based on maximum likelihood combining p-ECR and neighbor joining
Authors: Guo Mao-Zu , Li Jian-Fu , Liu Yang
Published: May 2008

Background

Inference of evolutionary trees using the maximum likelihood principle is NP-hard. Therefore, all practical methods rely on heuristics. The topological transformations often used in heuristics are Nearest Neighbor Interchange (NNI), Subtree Prune and Regraft (SPR) and Tree Bisection and Reconnection (TBR). However, these topological transformations often fall easily into local optima, since there are not many trees accessible in one step from any given tree. Another more exhaustive topological transformation is p-Edge Contraction and Refinement (p-ECR). However, due to its high computation complexity, p-ECR has rarely been used in practice.

Results

To make the p-ECR move more efficient, this paper proposes a new method named p-ECRNJ. The main idea of p-ECRNJ is to use neighbor joining (NJ) to refine the unresolved nodes produced in p-ECR.

Conclusion

Experiments with real datasets show that p-ECRNJ can find better trees than the best known maximum likelihood methods so far and can efficiently improve local topological transforms in reasonable time.
Protein structural class prediction based on an improved statistical strategy
Authors: Gu Fei , Chen Hang , Ni Jun
Published: May 2008

Background

A protein structural class (PSC) belongs to the most basic but important classification in protein structures. The prediction technique of protein structural class has been developing for decades. Two popular indices are the amino-acid-frequency (AAF) based, and amino-acid-arrangement (AAA) with long-term correlation (LTC) – based indices. They were proposed in many works. Both indices have its pros and cons. For example, the AAF index focuses on a statistical analysis, while the AAA-LTC emphasizes the long-term, biological significance. Unfortunately, the datasets used in previous work were not very reliable for a small number of sequences with a high-sequence similarity.

Results

By modifying a statistical strategy, we proposed a new index method that combines probability and information theory together with a long-term correlation. We also proposed a numerically and biologically reliable dataset included more than 5700 sequences with a low sequence similarity. The results showed that the proposed approach has its high accuracy. Comparing with amino acid composition (AAC) index using a distance method, the accuracy of our approach has a 16–20% improvement for re-substitution test and about 6–11% improvement for cross-validation test. The values were about 23% and 15% for the component coupled method (CCM).

Conclusion

A new index method, combining probability and information theory together with a long-term correlation was proposed in this paper. The statistical method was improved significantly based on our new index. The cross validation test was conducted, and the result show the proposed method has a great improvement.
Dimension reduction with redundant gene elimination for tumor classification
Authors: Zeng Xue-Qiang , Li Guo-Zheng , Yang Jack Y , Yang Mary Qu , Wu Geng-Feng
Published: May 2008

Background

Analysis of gene expression data for tumor classification is an important application of bioinformatics methods. But it is hard to analyse gene expression data from DNA microarray experiments by commonly used classifiers, because there are only a few observations but with thousands of measured genes in the data set. Dimension reduction is often used to handle such a high dimensional problem, but it is obscured by the existence of amounts of redundant features in the microarray data set.

Results

Dimension reduction is performed by combing feature extraction with redundant gene elimination for tumor classification. A novel metric of redundancy based on DIScriminative Contribution (DISC) is proposed which estimates the feature similarity by explicitly building a linear classifier on each gene. Compared with the standard linear correlation metric, DISC takes the label information into account and directly estimates the redundancy of the discriminative ability of two given features. Based on the DISC metric, a novel algorithm named REDISC (Redundancy Elimination based on Discriminative Contribution) is proposed, which eliminates redundant genes before feature extraction and promotes performance of dimension reduction. Experimental results on two microarray data sets show that the REDISC algorithm is effective and reliable to improve generalization performance of dimension reduction and hence the used classifier.

Conclusion

Dimension reduction by performing redundant gene elimination before feature extraction is better than that with only feature extraction for tumor classification, and redundant gene elimination in a supervised way is superior to the commonly used unsupervised method like linear correlation coefficients.
Assessment of decorin-binding protein A to the infectivity of Borrelia burgdorferi in the murine models of needle and tick infection
Authors: Blevins Jon S , Hagman Kayla E , Norgard Michael V
Published: May 2008

Background

Decorin-binding proteins (Dbps) A and B ofBorrelia burgdorferi, the agent of Lyme disease, are surface-exposed lipoproteins that presumably bind to the extracellular matrix proteoglycan, decorin.B. burgdorferiinfects various tissues including the bladder, heart, joints, skin and the central nervous system, and the ability ofB. burgdorferito bind decorin has been hypothesized to be important for this disseminatory pathogenic strategy.

Results

To determine the role of DbpBA in the infectious lifecycle ofB. burgdorferi, we created a DbpBA-deficient mutant ofB. burgdorferistrain 297 and compared the infectious phenotype of the mutant to the wild-type strain in the experimental murine model of Lyme borreliosis. The mutant strain exhibited a 4-log decrease in infectivity, relative to the wild-type strain, when needle inoculated into mice. Upon complementation of the DbpBA-mutant strain with DbpA, the wild-type level of infectivity was restored. In addition, we demonstrated that the DbpBA-deficient mutant was able to colonizeIxodes scapularislarval ticks after feeding on infected mice and persist within the ticks during the molt to the nymphal state. Moreover, surprisingly, the DbpBA-mutant strain was capable of being transmitted to naïve mice via tick bite, giving rise to infected mice.

Conclusion

These results suggest that DbpBA is not required for the natural tick-transmission process to mammals, despite inferences from needle-inoculation experiments implying a requirement for DbpBA during mammalian infection. The combined findings also send a cautionary note regarding how results from needle-inoculation experiments with mice should be interpreted.
Senescence marker protein 30 in acute liver failure: validation of a mass spectrometry proteomics assay
Authors: Lv Sa , Wang Jiang-hua , Liu Feng , Gao Yan , Fei Ran , Du Shao-cai , Wei Lai
Published: May 2008

Background

Our previous proteomic study showed that the senescence marker protein (SMP30) is selectively present in the plasma of a murine model of acute liver failure (ALF). The aim of this study was to validate this SMP30 expression in the plasma and liver tissues of mice and humans with ALF.

Methods

After the proteomic analysis of plasma from a murine model of D-galactosamine/lipopolysaccharide (GalN/LPS)-induced ALF by two-dimensional electrophoresis (2-DE) and mass spectrometry, the expression levels of SMP30 in the plasma and liver tissues were validated by western blot and RT-PCR analyses. These results were then confirmed in plasma samples from humans.

Results

These data validate the results of 2-DE, and western blot showed that SMP30 protein levels were only elevated in the plasma of ALF mice. Further analysis revealed that GalN/LPS induced the downregulation of SMP30 protein levels in liver tissues (by approximately 25% and 16% in the GalN/LPS-treated mice and in the treated mice that survived, respectively; P < 0.01). Hepatic SMP30 mRNA levels decreased by about 90% only in the mice that survived the GalN/LPS treatment. Importantly, plasma obtained from patients with ALF also contained higher levels of SMP30, about (3.65 ± 0.34) times those observed in healthy volunteers.

Conclusion

This study shows that SMP30 is not only a potential biomarker for the diagnosis and even prognosis of ALF. It also plays a very important role in a self-protective mechanism in survival and participates in the pathophysiological processes of ALF.
Clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer
Authors: Oh Sung Yong , Kwon Hyuk-Chan , Kim Sung-Hyun , Jang Jin Seok , Kim Min Chan , Kim Kyeong Hee , Han Jin-Yeong , Kim Chung Ock , Kim Su-Jin , Jeong Jin-sook , Kim Hyo-Jin
Published: May 2008

Background

Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.

We immunohistochemically assessed the HIF-1α, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF).

Results

The positive rates of p53 and HIF-1α (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1α were correlated positively with the depth of invasion (P = 0.015, P = 0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (P = 0.010, P = 0.040, respectively). VEGF overexpression was more frequently observed in the old age group (≥ 60 years old) and the intestinal type (P = 0.013, P = 0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF-1α, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1α was observed to be a poor prognostic factor of disease recurrence or progression (P = 0.002).

Conclusion

p53, HIF-1α and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1α expression was a poor prognostic factor of disease recurrence or progression in patients with gastric cancers.
Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model
Authors: Kalliomäki Tuula M , McCallum Gordon , Lunt Sarah Jane , Wells Peter G , Hill Richard P
Published: May 2008

Background

Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model.

Methods

To address this issue, we determined the effects of 6 weekin vivoacute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG) lesions in the transgenic polyomavirus middle T (PyMT) breast cancer mouse model.

Results

We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that thein vivoexposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs), demonstrating a relationship between hypoxia and macrophages in an experimental model.

Conclusion

These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.