bluuebunny/crossref_metadata_2025 huggingface dataset:
C-Reactive Protein, Interleukin-6, and Soluble Adhesion Molecules as Predictors of Progressive Peripheral Atherosclerosis in the General Population
Authors: Tzoulaki Ioanna , Murray Gordon D. , Lee Amanda J. , Rumley Ann , Lowe Gordon D.O. , Fowkes F. Gerald R.
Published: August 2005

Background—

The relationship between levels of circulating inflammatory markers and risk of progressive atherosclerosis is relatively undetermined. We therefore studied inflammatory markers as predictors of peripheral atherosclerotic progression, measured by the ankle-brachial index (ABI) at 3 consecutive time points over 12 years.

Methods and Results—

The Edinburgh Artery Study is a population cohort study of 1592 men and women aged 55 to 74 years. C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin were measured at baseline. Valid ABI measurements were obtained on 1582, 1081, and 813 participants at baseline and 5-year and 12-year follow-up examinations, respectively. At baseline, a significant trend was found between higher plasma levels of CRP (
P
≤0.05) and increasing severity of peripheral arterial disease (PAD), after adjustment for baseline cardiovascular risk factors. IL-6 at baseline (
P
≤0.001) was associated with progressive atherosclerosis at 5 years (ABI change from baseline), and CRP (
P
≤0.01), IL-6 (
P
≤0.001), and ICAM-1 (
P
≤0.01) were associated with changes at 12 years, independently of baseline ABI, cardiovascular risk factors, and baseline cardiovascular disease. Only IL-6 independently predicted ABI change at 5 years (
P
≤0.01) and 12 years (
P
≤0.05) in analyses of all inflammatory markers simultaneously and adjusted for baseline ABI, cardiovascular risk factors, and cardiovascular disease at baseline.

Conclusions—

These findings suggest that CRP, IL-6, and ICAM-1 are molecular markers associated with atherosclerosis and its progression. IL-6 showed more consistent results and stronger independent predictive value than other inflammatory markers.
Vascular Effects of the Human Extracellular Superoxide Dismutase R213G Variant
Authors: Chu Yi , Alwahdani Abdullah , Iida Shinichiro , Lund Donald D. , Faraci Frank M. , Heistad Donald D.
Published: August 2005

Background—

Extracellular superoxide dismutase (ECSOD) is a major extracellular antioxidant enzyme. We have demonstrated that vascular effects of ECSOD require an intact heparin-binding domain. A common genetic variant with a substitution in the heparin-binding domain (ECSOD
R213G
) was reported recently to be associated with ischemic heart disease. The goal of this study was to examine vascular effects of ECSOD
R213G
.

Methods and Results—

A recombinant adenovirus (Ad) that expresses ECSOD
R213G
was constructed. ECSOD
R213G
and ECSOD proteins bound to collagen type I in vitro, but binding to aorta ex vivo was 10-fold greater with ECSOD than ECSOD
R213G
. Three days after intravenous injection of AdECSOD
R213G
or AdECSOD in spontaneously hypertensive rats (SHR), immunostaining demonstrated binding of ECSOD to carotid arteries and kidneys but minimal binding of ECSOD
R213G
. Binding to aorta and carotid artery was 2.5- to 3-fold greater with ECSOD than ECSOD
R213G
by immunoblotting. Arterial pressure was significantly reduced by AdECSOD but not by AdECSOD
R213G
. Responses to acetylcholine and basal levels of nitric oxide in carotid arteries were impaired in SHR compared with normotensive Wistar-Kyoto rats and were improved after AdECSOD but not AdECSOD
R213G
. Levels of superoxide and nitrotyrosine in aorta were higher in SHR than Wistar-Kyoto rats and were greatly reduced after AdECSOD but not AdECSOD
R213G
.

Conclusions—

In contrast to ECSOD, ECSOD
R213G
has no significant protective effect on arterial pressure, vascular function, or vascular levels of oxidative stress in SHR. These findings may provide a mechanistic basis for association studies that suggest that human beings carrying ECSOD
R213G
are predisposed to vascular diseases.
Contribution of Cyclooxygenase-2 to Elevated Biosynthesis of Thromboxane A
2
and Prostacyclin in Cigarette Smokers
Authors: McAdam Brendan F. , Byrne Daniel , Morrow Jason D. , Oates John A.
Published: August 2005

Background—

Cigarette smoking is highly pathogenic to the vasculature. In smokers, the biosynthesis of both thromboxane (Tx) A
2
and prostacyclin is increased. We hypothesized that the excess in prostacyclin biosynthesis in smokers was derived from the inducible cyclooxygenase-2 (COX-2). We further hypothesized that if the overproduction of prostacyclin in smokers were restraining platelet activation, then inhibition of COX-2 would lead to an increase in the activation of platelets, with a corresponding increase in the biosynthesis of TxA
2
.

Methods and Results—

Smokers and nonsmokers received rofecoxib 25 mg twice daily or placebo for 1 week each in random sequence. The systemic biosynthesis of TxA
2
and prostacyclin was assessed by analysis of their respective urinary metabolites, 11-dehydrothromboxane B
2
(Tx-M) and 2′3-donor–6-keto-PGF
1α
(PGI-M). Serum TxB
2
was measured as an indicator of platelet COX-1 activity. Results are expressed as mean±SE with median and range. The elevated PGI-M in smokers (189±25, median 174, range 85 to 390 pg/mg creatinine) was reduced by rofecoxib to 78±27, median 71.5, range 50 to 135 pg/mg creatinine (
P
=0.002), and in nonsmokers, PGI-M at baseline (115±10, median 107, range 67 to 198 pg/mg creatinine) fell to 56±15, median 50, range 34 to 125 pg/mg creatinine (
P
=0.001) with rofecoxib. The increased excretion of Tx-M in smokers (284±26, median 252, range 200 to 569 pg/mg creatinine) was reduced by 21% to 223±16, median 206, range 154 to 383 pg/mg creatinine by rofecoxib (
P
=0.04) but was not changed in nonsmokers. Levels of serum TxB
2
were not different in smokers and nonsmokers and were unaffected by rofecoxib.

Conclusions—

The increased prostacyclin biosynthesis in smokers is derived largely from the inducible COX-2. COX-2 also contributes to the increased biosynthesis of TxA
2
in smokers, most likely from inflammatory cells.
Current Icing Potential: Algorithm Description and Comparison with Aircraft Observations
Authors: Bernstein Ben C. , McDonough Frank , Politovich Marcia K. , Brown Barbara G. , Ratvasky Thomas P. , Miller Dean R. , Wolff Cory A. , Cunning Gary
Published: August 2005

The “current icing potential” (CIP) algorithm combines satellite, radar, surface, lightning, and pilot-report observations with model output to create a detailed three-dimensional hourly diagnosis of the potential for the existence of icing and supercooled large droplets. It uses a physically based situational approach that is derived from basic and applied cloud physics, combined with forecaster and onboard flight experience from field programs. Both fuzzy logic and decision-tree logic are applied in this context. CIP determines the locations of clouds and precipitation and then estimates the potential for the presence of supercooled liquid water and supercooled large droplets within a given airspace. First developed in the winter of 1997/98, CIP became an operational National Weather Service and Federal Aviation Administration product in 2002, providing real-time diagnoses that allow users to make route-specific decisions to avoid potentially hazardous icing. The CIP algorithm, its individual components, and the logic behind them are described.
An Integrated Assessment of Measured and Modeled Integrated Water Vapor in Switzerland for the Period 2001–03
Authors: Guerova G. , Brockmann E. , Schubiger F. , Morland J. , Mätzler C.
Published: August 2005

In this paper an integrated assessment of the vertically integrated water vapor (IWV) measured by radiosonde, microwave radiometer (MWR), and GPS and modeled by the limited-area mesoscale model of MeteoSwiss is presented. The different IWV measurement techniques are evaluated through intercomparisons of GPS to radiosonde in Payerne, Switzerland, and to the MWR operated at the Institute of Applied Physics at the University of Bern in Switzerland. The validation of the IWV field of the nonhydrostatic mesoscale Alpine Model (aLMo) of MeteoSwiss is performed against 14 GPS sites from the Automated GPS Network of Switzerland (AGNES) in the period of 2001–03. The model forecast and the nudging analysis are evaluated, with special attention paid to the diurnal cycle. The results from the GPS–radiosonde intercomparison are in agreement, but with a bimodal distribution of the day-to-night basis. At 0000 UTC, the bias is negative (−0.4 kg m−2); at 1200 UTC, it is positive (0.9 kg m−2) and the variability increases. The intercomparison of GPS to MWR shows better agreement (0.4 kg m−2), with a small increase of the daytime bias with 0.3 kg m−2. The intercomparison of MWR to the radiosonde gives a bimodal distribution of the bias, with an increase in the standard deviation at the daytime measurement. The relative bias is negative (−3%) at 0000 UTC and is positive (3%) at 1200 UTC. Based on this cross correlation, it can be concluded that the bimodal distribution is a result of radiosonde humidity measurements. Possible reasons are the solar-heating correction or sensor errors. The monthly bias and standard deviation of aLMo exhibit a strong seasonal dependence with a pronounced dry bias during the warm months of May–October 2002. The diurnal IWV cycle in 2001 shows good model performance between 0000 and 0900 UTC but IWV underestimation by up to 1.5 kg m−2 for the rest of the day. In 2002 the diurnal cycle shows a systematic dry bias in both the analysis and forecast that is more pronounced in the analysis. This substantial underestimation of IWV was found to correlate with overestimation of aLMo precipitation, especially light precipitation up to 0.1 mm (6 h)−1 in 2002. There is strong evidence that this underestimation can be related to the dry radiosonde bias in midday summer observations. The aLMo dry bias is about 1.0–1.5 kg m−2 greater in the nudging analysis as compared with the forecast initialized at 0000 UTC.
Impacts of an Extreme Early-Season Freeze Event in the Interior Pacific Northwest (30 October–3 November 2002) on Western Juniper Woodlands
Authors: Knapp Paul A. , Soulé Peter T.
Published: August 2005

In mid-autumn 2002, an exceptional 5-day cold spell affected much of the interior Pacific Northwest, with minimum temperatures averaging 13°C below long-term means (1953–2002). On 31 October, minimum temperature records occurred at 98 of the 106 recording stations, with records lowered in some locations by 9°C. Calculation of recurrence intervals of minimum temperatures shows that 50% of the stations experienced a >500-yr event. The synoptic conditions responsible were the development of a pronounced high pressure ridge over western Canada and an intense low pressure area centered in the Intermountain West that promoted strong northeasterly winds. The cold spell occurred near the end of the growing season for an ecologically critical and dominant tree species of the interior Pacific Northwest—western juniper—and followed an extended period of severe drought. In spring 2003, it became apparent that the cold had caused high rates of tree mortality and canopy dieback in a species that is remarkable for its longevity and resistance to climatic stress. The cold event altered western juniper dominance in some areas, and this alteration may have long-term impacts on water budgets, fire intensities and frequencies, animal species interrelationships, and interspecific competition among plant species.
The Canonical Approach and the Idea of ‘Scripture’
Authors: Poirier John C.
Published: August 2005

Proponents of the canonical approach have used a narrowed understanding of the term ‘Scripture’ as a means of privileging their own hermeneutical programme. But such a understanding is late, and it does not square with how the New Testament’s authority was understood by the writers and the original canonizers of the Christian Bible.
The sermon as a work of art
Authors: Vos Cas
Published: August 2005

In this article, the author looks at how the concept of the sermon as an ‘open work of art’ offers a theoretical basis for preaching as a dynamic-communicative event. Relevant perspectives from a variety of art forms are employed to argue that evoking a life-enhancing religious response is the ultimate objective of the homiletical process.
Familiar Friend or Alien Stranger? On Translating the Bible
Authors: Horrell David G.
Published: August 2005

Looking especially at the NRSV and NIV, and interacting with the recent comments of Earle Ellis in this journal, this essay argues that translations of the Bible should do more justice to aspects of the text that make it less comfortable to pious modern ears: its rootedness in ancient culture, its sometimes awkward style, its patriarchal assumptions, and its occasional vulgarity.
Eunuchs and the Postgender Jesus: Matthew 19.12 and Transgressive Sexualities
Authors: Hester J. David
Published: August 2005

The eunuch of Mt. 19.12 has long been viewed as a symbol of chastity and celibacy. However, a study of ancient perspectives on eunuchs reveals a highly sexed and morally dubious ‘third type of human’ embodying the worst fears of masculine vulnerability and sexual transgression. Many early Christians interpreted Jesus’ instruction literally, imitating their counterparts in other religious traditions who employed castration as an expression of religious devotion. This created difficulties for certain church leaders concerned with appealing to (aristocratic) male converts, and the effort to transform the eunuch into a symbol of masculine askesis was never an easy one.

In this article I problematize the ‘celibate’ eunuch, exploring implications that a symbol of sexual transgression would have for current discussion regarding the proscription of homosexuality in the Church. Fundamental to understanding Mt. 19.12 is the explicit rejection of the heterosexist binary paradigm for understanding the role and importance of sex, sexuality and sexed identity in the ‘kingdom of heaven’.
The Incident of the Withered Fig Tree in Mark 11: A New Source and Redactional Explanation
Authors: Esler Philip F.
Published: August 2005

The two-stage incident of the fig tree in Mk 11.12-14 and 20-25 is almost always interpreted as a Markan redactional feature aimed at symbolising the coming fate of Israel and its Temple. The aim of this article is to challenge this view. Having first exposed the serious weaknesses in the dominant redactional explanation, I propose instead that Mark found the two stages of the incident (Jesus’ cursing of the tree one day and the discovery of its withered condition the next) in an early Jerusalemite source he utilized in parts of Mk 11-14. This source probably formed the early part of one that Theissen, using ‘local colour’ arguments, has already detected underlying Mk 14-16. Mark has retained this difficult incident, probably because of its significance in relating the only miracle Jesus was believed to have worked in his last days, but has struggled in his redaction to make sense of it. He does so not in relation to judgment impending on Jerusalem and the Temple, but in line with his presentation elsewhere in the Gospel of Jesus’ teaching on faith and prayer.
The Conservatives, the Market, and the Common Law
Authors: Feinman Jay M.
Published: August 2005

The common law—the law of contracts, torts, and property—is in the throes of a remarkable transformation. Many changes already have been adopted, and more are in process. The changes are radical and regressive, abandoning the progressive legal developments of the twentieth century, favoring the interests of big business, and animated by an ideology that is opposed to government acting in the public interest.
Corporate Governance and the “Job Loss” Recovery
Authors: Bivens L. Josh , Weller Christian E.
Published: August 2005

The recent recovery continued a trend that started in the mid-1970s of a growing divergence between capital and labor incomes. This trend appears to be largely due to a shift in the balance of corporate governance. A growing concentration of financial assets among institutional investors was juxtaposed by a declining unionization rate. Consequently, institutional investors had the incentives and increasingly the ability to allocate a growing share of corporate resources towards capital, particularly in the form of share repurchases and dividend payouts instead.
(How) Can We Tell if a Greek Apocryphon or Pseudepigraphon has been Translated from Hebrew or Aramaic?
Authors: Davila James R.
Published: August 2005

This article explores a wide range of problems that arise when we try to retrovert a Hebrew or Aramaic original from a Greek text, or even establish that Semitic interference in the text proves it to have been translated from a Semitic original. These problems include the inadequacy of a bipolar scale of ‘literal’ vs. ‘free’ translation technique; the difficulty of distinguishing Semitic grammar from Greek grammar; the possibility of interference from the language of the LXX (including rare grammatical features made popular in liturgy and testimonia) or bilingual interference; and the need to determine, when possible, the language (Hebrew or Aramaic), dialect, and period of the Vorlage. Claims to have retroverted the original texts of lost Semitic documents from Greek texts are found unconvincing, but this article advances a methodology for establishing Semitic interference due to translation from a Semitic Vorlage.
Time, Self and Reified Artefacts
Authors: Knights David , Yakhlef Ali
Published: August 2005

Discursive accounts of time tend to focus on a deconstruction of taken-for-granted notions of clock time, restricted to linear measurable units. By contrast the present article examines some of the discourses and practices deployed by managers in their attempts to control time; in the final instance, it shows how time can be a mystery that escapes such managerial pursuits and preoccupations. More specifically, we draw on Levinas’s ideas on time and the ‘Other’, and use two managerial discourses to illustrate how reification (through the use of technological and institutional artefacts) as attempts to control time tend to result in a proliferation of participation but, equally, an insistence on participation may invoke an intensification of control through reification. Reified relationships invariably result in a perpetual return to the Other, or what we have called participation. However, to varying degrees, our participatory mode is not possible without reification. Yet ‘relationships’ cannot be completely delegated to rationally calculating devices, formal institutions, or markets. Cooperation has its source not in reified forms of rationality (nor of irrationality), but in the human encounter with the Other. The organizational, social order is based on personal relations and personal responsibilities.
Beyond Employment
Authors: Carrasco Cristina , Mayordomo Maribel
Published: August 2005

The compilation of economic statistics, and particularly those relating to labour, directly reflect the prevailing perspective of the economics discipline, and are manifested in abstractions in the form of models entirely and exclusively focused on market production. In the majority of labour surveys and statistics, thus, domestic work is neither economically relevant nor does it even have the status of ‘work’. The aim of this article is to suggest new ways for studying the working time and living time of women and men, on the basis of a non-gendered methodological proposal implemented in the city of Barcelona - a non-androcentric labour force survey that incorporates both domestic and market work.
Managing hospital databases: can large hospitals really protect patient data?
Authors: Lederman Reeva
Published: August 2005

Between 1998 and 2003 a number of European countries, the UK, Canada, Australia and the US all introduced data privacy legislation that sought to comply with the European Data Privacy Directive of 1995 in protecting the privacy of individuals undergoing treatment in large hospitals. In 2004 we find that hospital administrators within these jurisdictions are still struggling to find ways to implement and maintain hospital databases while complying with the given legislation - where compliance seems to require a whole new approach to database management. This research examines the UK Data Protection Act 1998 and considers whether current database management systems allow the EU Directives contained in the Act to be followed in practice. It finds a number of recurrent problems with hospital systems that would make compliance with the Act difficult. These findings have significant implications for hospital information systems development and design.
Parity in computer-based health education: designing culturally relevant Alzheimer’s disease information
Authors: Tarlow Barbara J. , Mahoney Diane F.
Published: August 2005

Disparities that exist for racial and ethnic minority groups in healthcare status and access are compounded in the presence of Alzheimer’s disease (AD). Recent improvements in the diagnosis and care of persons with AD need to be paralleled in minority communities with early recognition and timely evaluation. Innovative information technologies can help reduce health disparities. A qualitative study was conducted with 48 participants: to understand how cultural values influence responses to signs of memory loss and to critique a CD-ROM memory loss educational program for the purpose of tailoring it to better meet the needs and preferences of African American and Chinese American users. Traditions of close family relationships, respect for elderly and the commitment to care, central to both groups, provided the basis for the frequently parallel recommendations for a revised program. Principles of adult education and web-based program design proved essential in developing a culturally relevant program.
Evaluation of a nursing informatics training program shows significant changes in nurses’ perception of their knowledge of information technology
Authors: Bickford Carol J. , Smith Kathleen , Ball Marion J. , Frantz Gerri , Panniers Teresa L. , Newbold Susan K. , Knecht Karen L. , Farish-Hunt Holly , Cortes-Comerer Nhora
Published: August 2005

A survey of nurses attending a Weekend Immersion in Nursing Informatics (WINI) program showed a statistically significant change in the nurses’ perception of information technology (IT) and of their ability to apply IT to affect the quality of patient care. Attendees first identified their level of expertise based on the Informatics Competencies for Nurses at Four Levels of Nursing Practice, and then completed surveys pre- and postprogram attendance to measure their personal assessments of their knowledge and abilities in specific areas of nursing informatics, information technology, and healthcare information systems. Such personal assessments are mandated in the professional standards of nursing informatics practice.
Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells
Authors: Lawrence H. Jeffrey , Christensen Julie , Fong Stephen , Hu Yu-Long , Weissman Irving , Sauvageau Guy , Humphries R. Keith , Largman Corey
Published: August 2005

The homeobox gene Hoxa-9 is normally expressed in primitive bone marrow cells, and overexpression of Hoxa-9 markedly expands hematopoietic stem cells, suggesting a function in early hematopoiesis. We present evidence for major functional defects in Hoxa-9-/- hematopoietic stem cells. Hoxa-9-/- marrow cells have normal numbers of immunophenotypic stem cells (Lin-c-kit+flk-2-Sca-1+ [KLFS] cells). However, sublethally irradiated Hoxa-9-/- mice develop persistent pancytopenia, indicating unusual sensitivity to ionizing irradiation. In competitive transplantation assays, Hoxa-9-/- cells showed an 8-fold reduction in multilineage long-term repopulating ability, a defect not seen in marrow cells deficient for the adjacent Hoxa-10 gene. Single-cell cultures of KLFS cells showed a 4-fold reduction in large high-proliferation potential colonies. In liquid cultures, Hoxa-9-deficient Lin-Sca-1+ cells showed slowed proliferation (a 5-fold reduction in cell numbers at day 8) and delayed emergence of committed progenitors (a 5-fold decrease in colony-forming cells). Slowing of proliferation was accompanied by a delay in myeloid maturation, with a decrease in Gr-1hiMac-1hi cells at the end of the culture. Retroviral transduction with a Hoxa-9 expression vector dramatically enhanced the cytokine-driven proliferation and in vivo engraftment of Hoxa-9-/- marrow cells. Hoxa-9 appears to be specifically required for normal hematopoietic stem cell function both in vitro and in vivo.
A comparative review of estimates of the proportion unchanged genes and the false discovery rate
Authors: Broberg Per
Published: August 2005

Background

In the analysis of microarray data one generally produces a vector of p-values that for each gene give the likelihood of obtaining equally strong evidence of change by pure chance. The distribution of these p-values is a mixture of two components corresponding to the changed genes and the unchanged ones. The focus of this article is how to estimate the proportion unchanged and the false discovery rate (FDR) and how to make inferences based on these concepts. Six published methods for estimating the proportion unchanged genes are reviewed, two alternatives are presented, and all are tested on both simulated and real data. All estimates but one make do without any parametric assumptions concerning the distributions of the p-values. Furthermore, the estimation and use of the FDR and the closely related q-value is illustrated with examples. Five published estimates of the FDR and one new are presented and tested. Implementations in R code are available.

Results

A simulation model based on the distribution of real microarray data plus two real data sets were used to assess the methods. The proposed alternative methods for estimating the proportion unchanged fared very well, and gave evidence of low bias and very low variance. Different methods perform well depending upon whether there are few or many regulated genes. Furthermore, the methods for estimating FDR showed a varying performance, and were sometimes misleading. The new method had a very low error.

Conclusion

The concept of the q-value or false discovery rate is useful in practical research, despite some theoretical and practical shortcomings. However, it seems possible to challenge the performance of the published methods, and there is likely scope for further developing the estimates of the FDR. The new methods provide the scientist with more options to choose a suitable method for any particular experiment. The article advocates the use of the conjoint information regarding false positive and negative rates as well as the proportion unchanged when identifying changed genes.
Genomic multiple sequence alignments: refinement using a genetic algorithm
Authors: Wang Chunlin , Lefkowitz Elliot J
Published: August 2005

Background

Genomic sequence data cannot be fully appreciated in isolation. Comparative genomics – the practice of comparing genomic sequences from different species – plays an increasingly important role in understanding the genotypic differences between species that result in phenotypic differences as well as in revealing patterns of evolutionary relationships. One of the major challenges in comparative genomics is producing a high-quality alignment between two or more related genomic sequences. In recent years, a number of tools have been developed for aligning large genomic sequences. Most utilize heuristic strategies to identify a series of strong sequence similarities, which are then used as anchors to align the regions between the anchor points. The resulting alignment is globally correct, but in many cases is suboptimal locally. We describe a new program, GenAlignRefine, which improves the overall quality of global multiple alignments by using a genetic algorithm to improve local regions of alignment. Regions of low quality are identified, realigned using the program T-Coffee, and then refined using a genetic algorithm. Because a better COFFEE (Consistency based Objective Function For alignmEnt Evaluation) score generally reflects greater alignment quality, the algorithm searches for an alignment that yields a better COFFEE score. To improve the intrinsic slowness of the genetic algorithm, GenAlignRefine was implemented as a parallel, cluster-based program.

Results

We tested the GenAlignRefine algorithm by running it on a Linux cluster to refine sequences from a simulation, as well as refine a multiple alignment of 15 Orthopoxvirus genomic sequences approximately 260,000 nucleotides in length that initially had been aligned by Multi-LAGAN. It took approximately 150 minutes for a 40-processor Linux cluster to optimize some 200 fuzzy (poorly aligned) regions of the orthopoxvirus alignment. Overall sequence identity increased only slightly; but significantly, this occurred at the same time that the overall alignment length decreased – through the removal of gaps – by approximately 200 gapped regions representing roughly 1,300 gaps.

Conclusion

We have implemented a genetic algorithm in parallel mode to optimize multiple genomic sequence alignments initially generated by various alignment tools. Benchmarking experiments showed that the refinement algorithm improved genomic sequence alignments within a reasonable period of time.
The definition of disabling fatigue in children and adolescents
Authors: Fowler Tom , Duthie Pamela , Thapar Anita , Farmer Anne
Published: August 2005

Background

Disabling fatigue is the main illness related reason for prolonged absence from school. Although there are accepted criteria for diagnosing chronic fatigue in adults, it remains uncertain as to how best to define disabling fatigue and Chronic Fatigue Syndrome (CFS) in children and adolescents. In this population-based study, the aim was to identify children who had experienced an episode of disabling fatigue and examine the clinical and demographic differences between those individuals who fulfilled a narrow definition of disabling fatigue and those who fulfilled broader definitions of disabling fatigue.

Methods

Participants (aged 8–17 years) were identified from a population-based twin register. Parent report was used to identify children who had ever experienced a period of disabling fatigue. Standardised telephone interviews were then conducted with the parents of these affected children. Data on clinical and demographic characteristics, including age of onset, gender, days per week affected, hours per day spent resting, absence from school, comorbidity with depression and a global measure of impairment due to the fatigue, were examined. A narrow definition was defined as a minimum of 6 months disabling fatigue plus at least 4 associated symptoms, which is comparable to the operational criteria for CFS in adults. Broader definitions included those with at least 3 months of disabling fatigue and 4 or more of the associated symptoms and those with simply a minimum of 3 months of disabling fatigue. Groups were mutually exclusive.

Results

Questionnaires were returned by 1468 families (65% response rate) and telephone interviews were completed on 99 of the 129 participants (77%) who had experienced fatigue. There were no significant differences in demographic and clinical characteristics or levels of impairment between those who fulfilled the narrower definition and those who fulfilled the broader definitions. The only exception was the reported number of days per week that the child was affected by the fatigue. All groups demonstrated evidence of substantial impairment associated with the fatigue.

Conclusion

Children and adolescents who do not fulfil the current narrow definition of CFS but do suffer from disabling fatigue show comparable and substantial impairment. In primary care settings, a broader definition of disabling fatigue would improve the identification of impaired children and adolescents who require support.
High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss
Authors: Tang Hsiao-Yuan , Xia Anping , Oghalai John S , Pereira Fred A , Alford Raye L
Published: August 2005

Background

Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change inSLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3.

Methods

To further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing.SLC26A5genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of humanSLC26A5were sought using a splice site prediction program from the Berkeley Drosophila Genome Project.

Results

The IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330). Sequence alignment ofSLC26A5orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of humanSLC26A5.

Conclusion

These data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in intron 2 of humanSLC26A5suggests a potential mechanism by which expression of prestin might be maintained in cells carrying theSLC26A5IVS2-2A>G DNA sequence variation. Additional studies are needed to evaluate the effect of the IVS2-2A>G transition on splicing ofSLC26A5transcripts and characterize the hearing status of individuals homozygous for the IVS2-2A>G variant.
Expression of transforming growth factor-beta-1 and p27Kip1 in pancreatic adenocarcinomas: relation with cell-cycle-associated proteins and clinicopathologic characteristics
Authors: Culhaci Nil , Sagol Ozgul , Karademir Sedat , Astarcioglu Huseyin , Astarcioglu Ibrahim , Soyturk Mujde , Oztop Ilhan , Obuz Funda
Published: August 2005

Background

The purpose of our study was to investigate the immunohistochemical expression of TGF-β1 and p27 in pancreatic adenocarcinomas and to compare the findings with the clinicopathological features and survival. We also aimed to evaluate the expression of TGF-β1 and p27 in the context of other cell cycle and proliferation markers such as cyclin D1 and Ki-67.

Methods

We examined TGF-β1 and p27 expression immunohistochemically in 63 cases of invasive ductal adenocarcinoma of the pancreas. Standard streptavidin-biotin immunperoxidase method was used for immunostaining and the stained slides were examined microscopically using semiquantitative criteria.

Results

TGF-β1 stained the cytoplasms of the tumor cells in 43 cases [68.3%]. There was a statistically significant difference among TGF-β1 staining scores in terms of clinicopathologic factors such as blood vessel invasion, stage and distant metastasis [p < 0.05]. Of the 63 tumors evaluated 23 [36.5%] were positive for p27 within the nucleus. An inverse correlation was found between p27 immunoreactivity and grade [p < 0.05]. But no significant correlation was found between p27 and other parameters. Among the patients with survival data 27 patients had RO resections and these cases were considered in survival analysis. In the univariate analysis, neither TGF-β1 nor p27 expression was related with patient survival.

Conclusion

Our findings suggest that in pancreatic carcinoma, TGF-β1 expression is related to tumor growth and metastasis. But it is not associated with cell cycle proteins. p27 expression is reduced in pancreatic adenocarcinomas and decreased protein levels of p27 may play a role in the differentiation of pancreatic cancer.
Complications after cryosurgery with new miniature cryoprobes in long hollow bones: An animal trial
Authors: Popken Frank , Meschede Peter , Erberich Heike , Koy Timmo , Bosse Marfalda , Fischer Jürgen H , Eysel Peer
Published: August 2005

Background

In vitro studies show that new miniature cryoprobes are suitable for cryoablation of bone tissue. The aim of this animal trial on 24 sheep was to examine the perioperative complications, particularly the danger of embolism, of cryoablation when using miniature cryoprobes.

Methods

Cryoablations with 2 freeze-thaw cycles each were carried out in the epiphysis of the right tibia and the metaphysis of the left femur. Pulmonary artery pressure (PAP) and central venous pressure (CVP) were measured. Throughout the intra- and perioperative phase, heart rate and oxygen saturation by pulse oxymetry, blood gas and electrolytes were monitored regularly. Postoperative complications were examined up to 24 weeks postoperativ.

Results

As result, no significant increase of PAP, CVP or heart rate were observed. Blood gases were unremarkable, with pO2 and pCO2 remaining constant throughout the operation. Regarding pH, standard bicarbonate and base excess, only a non-significant shift towards a slight acidosis was seen. There was a mean hemoglobin decrease of 0.5 g/dl. One animal showed postoperative wound infection and wound edge necrosis. No major peri- and postoperative complications associated with cryosurgery of bone were observed, especially regarding clinically relevant pulmonary embolism.

Conclusion

Surgery with new types of miniature cryoprobes appears to be a safe alternative to or a complement to conventional resection of abnormal bone tissue.
Endothelial cell injury by high glucose and heparanase is prevented by insulin, heparin and basic fibroblast growth factor
Authors: Han Juying , Mandal Anil K , Hiebert Linda M
Published: August 2005

Background

Uncontrolled hyperglycemia is the main risk factor in the development of diabetic vascular complications. The endothelial cells are the first cells targeted by hyperglycemia. The mechanism of endothelial injury by high glucose is still poorly understood. Heparanase production, induced by hyperglycemia, and subsequent degradation of heparan sulfate may contribute to endothelial injury. Little is known about endothelial injury by heparanase and possible means of preventing this injury.

Objectives

To determine if high glucose as well as heparanase cause endothelial cell injury and if insulin, heparin and bFGF protect cells from this injury.

Methods

Cultured porcine aortic endothelial cells were treated with high glucose (30 mM) and/or insulin (1 U/ml) and/or heparin (0.5 μ g/ml) and /or basic fibroblast growth factor (bFGF) (1 ng/ml) for seven days. Cells were also treated with heparinase I (0.3 U/ml, the in vitro surrogate heparanase), plus insulin, heparin and bFGF for two days in serum free medium. Endothelial cell injury was evaluated by determining the number of live cells per culture and lactate dehydrogenase (LDH) release into medium expressed as percentage of control.

Results

A significant decrease in live cell number and increase in LDH release was found in endothelial cells treated with high glucose or heparinase I. Insulin and/or heparin and/or bFGF prevented these changes and thus protected cells from injury by high glucose or heparinase I. The protective ability of heparin and bFGF alone or in combination was more evident in cells damaged with heparinase I than high glucose.

Conclusion

Endothelial cells injured by high glucose or heparinase I are protected by a combination of insulin, heparin and bFGF, although protection by heparin and/or bFGF was variable.
Artificial neural networks for diagnosis and survival prediction in colon cancer
Authors: Ahmed Farid E
Published: August 2005

ANNs are nonlinear regression computational devices that have been used for over 45 years in classification and survival prediction in several biomedical systems, including colon cancer. Described in this article is the theory behind the three-layer free forward artificial neural networks with backpropagation error, which is widely used in biomedical fields, and a methodological approach to its application for cancer research, as exemplified by colon cancer. Review of the literature shows that applications of these networks have improved the accuracy of colon cancer classification and survival prediction when compared to other statistical or clinicopathological methods. Accuracy, however, must be exercised when designing, using and publishing biomedical results employing machine-learning devices such as ANNs in worldwide literature in order to enhance confidence in the quality and reliability of reported data.
Screening and identification of differentially expressed transcripts in circulating cells of prostate cancer patients using suppression subtractive hybridization
Authors: Li Xin , Wong Carson , Mysel Ralph , Slobodov Gennady , Metwalli Adam , Kruska Jarrett , Manatt C Scott , Culkin Daniel J , Kropp Bradley P , Lin Hsueh-Kung
Published: August 2005

Background

Tumor metastasis and changes in host immunosurveillance are important components in cancer development. Tumor cell invasion into the bloodstream is an essential step for systemic metastasis. Currently, the detection of tumor cells in the circulation is mainly dependent upon the utilization of known epithelial cell markers. However, expression of these molecules is not limited to cancer patients; healthy people also have a small number of epithelial cells in their circulation. Utilizing these markers to detect circulating tumor cells (CTCs) cannot adequately explain the mechanisms of tumor cell survival or their development of metastatic potential in peripheral blood. The immune system can also evolve along with the cancer, actually promoting or selecting the outgrowth of tumor variants. Unfortunately, both metastasis and immunosurveillance remain mysterious and are debatable because we have yet to define the molecules that participate in these processes. We are interested in identifying the existence of expressed genes, or mRNA species, that are specifically associated with circulating cells of cancer-bearing patients using prostate cancer (PCa) as a model.

Results

We established two comprehensive subtracted cDNA libraries using a molecular technique called suppression subtractive hybridization. This technique selectively amplifies transcripts that are specifically expressed in circulating cells of either PCa patients or healthy men. Following sequencing reaction, we showed that 17 out of 23 (73.9%) sequenced clones did not match any mRNAs in the GenBank database. This result suggests that genes associated with alterations in circulating cells of cancer-bearing patients are largely unknown. Semi-quantitative RT-PCR confirmed that two genes are up-regulated in circulating cells of PCa patients, whereas another two genes are down-regulated in the same patients.

Conclusion

The comprehensive gene expression analysis is capable of identifying differentially expressed genes in circulating cells of healthy men and PCa patients. We did not attempt to enrich specific cell types in this study because phenotypes of CTCs and subsets of leukocytes participating in immunosurveillance remain largely unknown. Continuous studies of these differentially expressed genes will eventually lead us to understand the mechanisms involved in tumor metastasis and immune modulation during cancer development.
A quest for therapeutic antigens in bone and soft tissue sarcoma
Authors: Kawaguchi Satoshi , Wada Takuro , Tsukahara Tomohide , Ida Kazunori , Torigoe Toshihiko , Sato Noriyuki , Yamashita Toshihiko
Published: August 2005

Over the past three decades, there have been remarkable advances in the treatment of bone and soft tissue sarcomas. These include the introduction of adjuvant chemotherapy, establishment of guidelines for adequate surgical margins, and the development of post-excision reconstruction. There have also been advances in the field of immunotherapy against bone and soft tissue sarcomas, which, unfortunately, have received less attention. However, lack of progress in chemotherapy-based treatments for bone and soft tissue sarcomas has reignited interest in immunotherapeutic approaches. Here we summarize current progress in the immunotherapy of bone and soft tissue sarcomas including the strategies utilized to identify tumor-associated antigens, and the design of clinical trials.
Earthquake and Ambient Vibration Monitoring of the Steel-Frame UCLA Factor Building
Authors: Kohler Monica D. , Davis Paul M. , Safak Erdal
Published: August 2005

Dynamic property measurements of the moment-resisting steel-frame University of California, Los Angeles, Factor building are being made to assess how forces are distributed over the building. Fourier amplitude spectra have been calculated from several intervals of ambient vibrations, a 24-hour period of strong winds, and from the 28 March 2003 Encino, California ( ML=2.9), the 3 September 2002 Yorba Linda, California ( ML=4.7), and the 3 November 2002 Central Alaska ( Mw=7.9) earthquakes. Measurements made from the ambient vibration records show that the first-mode frequency of horizontal vibration is between 0.55 and 0.6 Hz. The second horizontal mode has a frequency between 1.6 and 1.9 Hz. In contrast, the first-mode frequencies measured from earthquake data are about 0.05 to 0.1 Hz lower than those corresponding to ambient vibration recordings indicating softening of the soil-structure system as amplitudes become larger. The frequencies revert to pre-earthquake levels within five minutes of the Yorba Linda earthquake. Shaking due to strong winds that occurred during the Encino earthquake dominates the frequency decrease, which correlates in time with the duration of the strong winds. The first shear wave recorded from the Encino and Yorba Linda earthquakes takes about 0.4 sec to travel up the 17-story building.