bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental evaluation of selected electronic document delivery systems
Authors: Morris Anne , Woodfield Julie , Davies J. Eric
Published: March 2008

Reports results of research to test and analyse five different document delivery systems according to request and delivery times, costs, document quality, and coverage. The aim was to evaluate the success of the different systems according to these criteria and to assess their relative value for money. The systems tested were UMI ProQuest Direct, InfoTrac SearchBank, British Library inside, Elsevier Engineering Information EiText and the standard BLDSC service. Two sets of documents were used in the evaluation: one relating to business studies and the other to manufacturing engineering. The full-text database systems provided a more rapid service than e-mailed and faxed delivery options. BLDSC uses the slowest method of delivery. ProQuest Direct and SearchBank were generally reliable. Partial and fragmented delivery of documents was an occasional feature of EiText and British Library inside. The flat rate per document fee charged by BLDSC is at least three times cheaper than either EiText or British Library inside. BLDSC provides the most comprehensive coverage by far in the titles held and the range of subjects. SearchBank and ProQuest Direct offer the least number of titles, across a range of subjects which is broader than EiText but more limited than British Library services. Concludes that the standard BLDSC service still offers extremely good value for money if assessed on document quality, price and coverage. However, if demand for faster document delivery were to increase, then BLDSC would face greater competition albeit in a limited range of material.
Availability, accessibility and demand for recommended books in academic libraries
Authors: Wall Terry , Williams Jan
Published: March 2008

Reports results of a study, undertaken at Cardiff University, of the effect of loan periods on the utilization of short loan books and corroborates these with results of an availability survey. Compares the results with those from a similar survey conducted at Sussex University (Journal of Documentation, 52 (2) Jun 1996, 139-162). Discusses the implications of the results for the conduct of availability surveys and the management of recommended reading collections and notes the potential advantages of electronic provision of short loan materials. Concludes that, if recommended reading resources are to be fully utilized, librarians must ensure not only the ready availability of the material but also the convenience with which it can be used.
Pathways to knowledge
Authors: Slack Frances , Rowley Jennifer
Published: March 2008

Reviews the state of library and information networking and document delivery in Australia, based on the content of the Australian Library and Information Association 5th Biennial Conference and Exhibition, Adelaide, October 1998. Short case studies are presented which cover the co-operative relationships between libraries, users, organizations and publishers to illustrate the diversity of library and information networking and to show that simple user to user models, or publisher to user models, have only limited utility. Focuses on networks, services and databases and publications unique to Australia. Identifies five different types of Australian library networks: Council of Australian University Librarians (CAUL); public library networks; Colleges of Technical and Advanced Further Education (TAFEs); hospital and medical libraries; and co-operating libraries from different sectors. Considers the role of purchasing consortia, such as: the Public Libraries Automated Information Network (PLAIN); database publishing; the National Periodical Service for Schools; national bibliographic networks (notably Australian Bibliographic Network (ABN)); document delivery services offered by the National Library of Australia; access to electronic periodicals at Flinders University of South Australia; and model licences or licence templates (LIBLICENSE Project, National Electronic Site Licensing Initiative (NESLI), Dutch-German Library Joint licensing Principles and Guidelines and International Coalition of Library Consortia (ICOLC)).
Severe digital ischemia–a presenting symptom of malignancy–associated antiphospholipid syndrome
Authors: Grossman A , Gafter-Gvili A , Green H , Ben Aharon I , Stemmer SM , Molad Y , Krause I
Published: March 2008

The association of the antiphospholipid syndrome with malignancy has been extensively reported. Raynaud’s phenomenon has also been reported to be associated with various malignancies. In this report, we describe two patients who presented with severe digital ischemia mimicking Raynaud’s phenomenon. The patients were found to have antiphospholipid syndrome, and upon extensive evaluation, a diagnosis of a malignancy was made. This report highlights the importance of malignancy workup in patients with severe digital ischemia associated with antiphospholipid syndrome.
Hypothyroidism determines the clinical and immunological manifestations of Arabs with lupus
Authors: Al Saleh J , El Sayed M , Jassim V , Mohammed N , Khan N
Published: March 2008

Abstract

Data on thyroid disease in Arabs with lupus is scarce. We conducted a cross-sectional and retrospective case–control study to report the prevalence of thyroid diseases in 110 Arabs with lupus who attended our Rheumatology Clinic between January 2002 and January 2007, and to delineate the clinical and immunological features of Arabs lupus patients with thyroid diseases. We found hypothyroidism in 15 (13.7%) patients. Overall, 25.6% had elevated thyroid peroxidase antibodies, 14.6% had elevated anti-thyroglobulin antibodies, and 13.7% were positive for both antibodies. Lupus patients with hypothyroidism had a significantly higher frequency of polyarthritis (OR = 9.3, CI: 2.0–41.7, P < 0.001), cutaneous manifestations (OR = 5.6, CI: 2.4–14.3, P < 0.0001), positive anti-thyroglobulin antibodies (OR = 19.9, CI: 8.38–47.4, P < 0.0001), and thyroid peroxidase antibodies (OR = 12.3, CI: 6.27–24.1, P < 0.0001) than lupus patients with normal thyroid function. Furthermore, neuropsychiatric (OR = 0.36, CI: 0.14–0.93, P < 0.05) and hematological (OR = 0.52, CI: 0.29–0.91, P < 0.05) manifestations were significantly lower in patients with hypothyroidism than in euthyroid patients. Surprisingly, the prevalence of anticardiolipin antibody immunoglobulin G (aCL IgG) (OR = 0.34, CI: 0.13–0.86, P < 0.05), lupus anticoagulant (OR = 0.02, CI: 0.001–0.35, P < 0.0001), and anticardiolipin syndrome (OR = 0.02, CI: 0.001–0.43, P < 0.0001) were significantly lower in lupus patients with hypothyroidism than in lupus patients with normal thyroid function. In conclusion, the prevalence of hypothyroidism in Arabs with lupus is comparable to that reported in the literature. Arab lupus patients with hypothyroidism have distinctive clinical and immunological features that differentiate them from euthyroid patients.
E/E' ratio is more sensitive than E/A ratio for detection of left ventricular diastolic dysfunction in systemic lupus erythematosus
Authors: Lee S-W , Park M-C , Park Y-B , Lee S-K
Published: March 2008

Abstract

To investigate whether the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E') (E/E' ratio) can detect left ventricular diastolic dysfunction more sensitively than the ratio of E to mitral peak velocity of late filling (A) (E/A ratio) in systemic lupus erythematosus (SLE). A total of 137 patients with SLE were investigated and compared with 110 age-matched and sex-matched controls retrospectively. Two-dimensional echocardiography and M-mode echocardiography including conventional and tissue Doppler imaging were performed. There were no differences in the left ventricle ejection fractions and the mean E/A ratio between the two groups. However, the mean E/E' ratio of patients was higher than that of the controls (10.4 ± 4.0 vs 7.7 ± 2.1, P < 0.01). Significantly higher left ventricle ejection fractions and lower E/E' ratio were found in patients with systemic lupus erythematosus receiving angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker than those not receiving ( P < 0.05). Our study showed that the E/E' ratio is more sensitive than the E/A ratio for detection of the left ventricle diastolic dysfunction. Furthermore, patients who had received angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment showed significantly better preservation of both systolic and diastolic function of left ventricle in comparison with those who had not received.
The Membrane Proteinase 3 Expression on Neutrophils Was Downregulated After Treatment With Infliximab in Patients With Rheumatoid Arthritis
Authors: Matsumoto Takeshi , Kaneko Toshihiro , Seto Masashi , Wada Hideo , Kobayashi Toshihiko , Nakatani Kaname , Tonomura Harue , Tono Yasutaka , Ohyabu Mariko , Nobori Tsutomu , Shiku Hiroshi , Sudo Akihiro , Uchida Atsumasa , Stearns Kurosawa Deborah J. , Kurosawa Shinichiro
Published: March 2008

Proteinase 3 (PR3) expression on neutrophils was examined in rheumatoid arthritis (RA) patients before and after antitumor necrosis factor (TNF)-α therapy. Membrane PR3 expression from patients with either an infection or RA significantly increased. Membrane PR3 expression on neutrophils from RA patients treated with infliximab (anti-TNF-α antibody) therapy was less than in those without such treatment in a resting state, but the expression later increased after stimulation in vitro. Membrane PR3 expression increased because of the stimulation of TNFα, whereas it was significantly suppressed by plasma or α1-proteinase inhibitor. The condition of patients with RA improved after treatment with infliximab. Membrane PR3 expression on neutrophils in RA patients was downregulated by infliximab. As a result, PR3 might play an important role in the neutrophil-mediated inflammatory reaction in patients with either RA or an infection.
Primary Prevention of Venous Thromboembolism in Long-Term Care: Identifying and Managing the Risk
Authors: Haas Sylvia , Spyropoulos Alex C.
Published: March 2008

Venous thromboembolism (VTE) is a significant, but underestimated, cause of morbidity and mortality in long-term care settings. VTE risk increases significantly with age and is further increased by comorbidities common to this group; however, advancing age and limited mobility alone are insufficient to warrant pharmacological prophylaxis. Recognizing those at increased VTE risk during an acute illness is crucial for appropriate and timely prophylaxis. Warfarin is used for the long-term secondary prevention of VTE, whereas unfractionated and low-molecular-weight heparins are used for primary prophylaxis. The elderly are at increased risk for bleeding complications, because of the high frequency of comorbidities and comedications. Attention to dosing is recommended for those with severely impaired renal function, low body weight, or perceived to be at high bleeding risk. This review addresses the role of risk assessment in the decision of when to provide prophylaxis to an individual in long-term care and highlights key management issues for those prescribed prophylaxis.
“I thought . . . maybe this is my chance”
Authors: Kvam Marit Hoem , Braathen Stine Hellum
Published: March 2008

This article is based on a pilot study conducted in Malawi in 2006 that intended to uncover episodes of violence and abuse against women and girls with disabilities and furthermore to explore the mechanisms behind such acts. The stories of 23 women with disabilities were obtained through in-depth semistructured interviews that covered, among other topics, aspects of sexual abuse experienced by or known to these women. None of the informants reported having been sexually abused during childhood. In adulthood, several had experienced what they themselves defined as sexual abuse: Men came and wanted to “marry” them. When the woman became pregnant, the man disappeared and left her alone. The interviewees were very opinionated regarding this theme and sought both social and political action in this matter, especially a means to enforce men to take economic responsibility for their biological children. The informants stressed that adapted education for women with disabilities would allow them to become more economically independent and be better able to refuse the advances of unserious suitors.
An Exploratory Evaluation of the Contribution of Personality and Childhood Sexual Victimization to the Development of Sexually Abusive Behavior
Authors: Burton David L.
Published: March 2008

Scores on the Millon Adolescent Clinical Inventory (MACI) and the Childhood Trauma Questionnaire (CTQ) were collected from two samples of incarcerated delinquent males: 74 adjudicated sexual abusers and 53 nonsexual abusers. In comparison to non-sexually abusive youths, a larger percentage of the sexually abusive youths indicated a history of childhood sexual victimization. The scores were then entered into a logistic regression to assess the contribution of personality characteristics to a social learning “victim-to-victimizer” etiological model. After controlling for time in treatment, the model correctly classified 76.6% of the youths. The variables that contributed significantly to the social learning model were the CTQ Sexual Abuse and Physical Neglect scales and the Submissive and Forceful scales on the MACI. Research and treatment implications of these findings are discussed.
Untreated ADHD in Adults
Authors: Rasmussen Kirsten , Levander Sten
Published: March 2008

Objective: To analyze sex differences among adult, never-treated patients referred for central stimulant treatment of ADHD. Method: Data for 600 consecutive patients from northern Norway referred for evaluation by an expert team during 7 years were analyzed. General background information, diagnostic and social history, and symptom profiles were compared between previously never-treated men and women. Results: The sex ratio was skewed. Of the previously untreated patients, more than 20% fell outside society's ordinary vocational activities or social benefit system. Most patients had the combined form, one third the inattentive type, and only 2% the hyperactive/impulsive subtype. Abuse and criminality were more common among men, and affective, eating, and somatization disorders were more common among women. Otherwise few sex differences were found. Conclusion: AD/HD symptom intensity and subtypes did not differ between the sexes and was unrelated to age. Symptom intensity was linked with criminality, abuse, and other psychiatric problems, differentially for the two sexes. (J. of Att. Dis. 2009; 12(4) 353-360)
Invariance of Parent Ratings of the ADHD Symptoms in Australian and Malaysian, and North European Australian and Malay Malaysia Children
Authors: Gomez Rapson
Published: March 2008

Objective: This study used the mean and covariance structures analysis approach to examine the equality or invariance of ratings of the 18 ADHD symptoms. Method: 783 Australian and 928 Malaysian parents provided ratings for an ADHD rating scale. Invariance was tested across these groups (Comparison 1), and North European Australian ( n = 623) and Malay Malaysian ( n = 571, Comparison 2) groups. Results: Results indicate support for form and item factor loading invariance; more than half the total number of symptoms showed item intercept invariance, and 14 symptoms showed invariance for error variances. There was invariance for both the factor variances and the covariance, and the latent mean scores for hyperactivity/impulsivity. For inattention latent scores, the Malaysian (Comparison 1) and Malay Malaysian (Comparison 2) groups had higher scores. Conclusion: These results indicate fairly good support for invariance for parent ratings of the ADHD symptoms across the groups compared. (J. of Att. Diss. 2009; 12(5) 422-433)
Percutaneous management of chronic deep venous reflux: review of experimental work and early clinical experience with bioprosthetic valve
Authors: Pavcnik Dusan , Uchida Barry , Kaufman John , Hinds Monica , Keller Frederick S , Rösch Josef
Published: March 2008

Abstract

Lower extremity chronic deep venous insufficiency (CDVI) is common and remains a major health problem worldwide. Selected patients benefited from direct deep vein valve surgical repair or valve transplantation. A major limitation of this approach is that most of the patients are not candidates for these procedures due to obstructions or residual thrombus throughout the vein. The past 15 years have witnessed experimental efforts at catheter-based management of CDVI. This review describes the initial designs and experimental evolution of a mechanical and bioprosthetic venous valve that can be implanted by using a transcatheter technique. These valves consisted of single, double, or triple cusp leaflets made of synthetic or biological materials attached to a carrier or frame. All described devices for percutaneous transcatheter valve placement rely on some form of a vascular stent for valve attachment.
A randomized trial of iloprost in patients with intermittent claudication
Authors: Creager Mark A , Pande Reena L , Hiatt William R
Published: March 2008

Abstract

Prostanoids, which promote vasodilation and reduce platelet aggregation, have been proposed as candidate therapies for intermittent claudication due to peripheral arterial disease (PAD). However, studies of these medications have yielded inconsistent results. This study tested the hypothesis that iloprost, an oral prostacyclin analogue, would improve walking distance and quality of life in patients with intermittent claudication. The study was a multi-center, randomized, double-blind, placebo-controlled trial comparing three doses of oral iloprost (50 μg, 100 μg, or 150 μg twice daily), pentoxifylline, or placebo in 430 patients with intermittent claudication. The primary outcome measure was improvement in absolute claudication distance (ACD) after 6 months. Secondary outcomes included initial claudication distance and quality of life assessment. Placebo increased ACD by 3.3%, and iloprost increased peak ACD by 7.7%, 8.8% and 11.2% at the 50 μg, 100 μg, and 150 μg twice-daily doses, respectively (all insignificant relative to placebo). Pentoxifylline increased ACD by 13.9% relative to placebo ( p = 0.039). Neither iloprost nor pentoxifylline enhanced quality of life. These results indicate that oral iloprost is not effective in improving exercise performance or quality of life in patients with PAD who have intermittent claudication.
Cognitive–Behavioral Theory and Preparation for Professionals at Risk for Trauma Exposure
Authors: Whealin Julia M. , Ruzek Josef I. , Southwick Steven
Published: March 2008

Military personnel, emergency first responders, and others whose work environments include exposure to traumatic events are at risk for developing posttraumatic stress disorder (PTSD). To help prevent negative sequelae, there is a strong need to identify well-operationalized, empirically supported, theoretically framed models of healthy adaptation to potentially traumatic events. Cognitive–behavioral theories (CBTs) describe etiological factors in trauma, guide research that has identified risk for PTSD, and help develop interventions that can effectively reduce posttrauma symptomatology. In this article, the authors draw on CBT and empirical research on post-traumatic stress to propose possible cognitive–behavioral mechanisms in trauma adaptation. They then suggest directions for future research, including areas for prevention interventions for at-risk professionals.
Black Arts and Good Law: Literary Arguments for Racial Justice in the Time of Plessy
Authors: Perry Imani
Published: March 2008

In this article, the author demonstrates how late 19th Century writers who advocated for racial equality used the concepts of symmetry and equality, as represented in the 14th amendment, to argue that racial justice was beautiful — philosophically as well as politically, and to argue for constitutional interpretations which advanced racial justice. This is read as a species of argumentative formalism, nonetheless bearing political goals. In identifying this practice, the author hopes to enrich conversations about the conflict between abstract legal principles, and the belief that law is a product of social and political realities, as it relates to race, by demonstrating that the abstraction of law was appealing and even useful in historic struggles for racial equality.
PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes
Authors: Fong Christine , Rohmer Laurence , Radey Matthew , Wasnick Michael , Brittnacher Mitchell J
Published: March 2008

Background

The conservation of gene order among prokaryotic genomes can provide valuable insight into gene function, protein interactions, or events by which genomes have evolved. Although some tools are available for visualizing and comparing the order of genes between genomes of study, few support an efficient and organized analysis between large numbers of genomes. The Prokaryotic Sequence homology Analysis Tool (PSAT) is a web tool for comparing gene neighborhoods among multiple prokaryotic genomes.

Results

PSAT utilizes a database that is preloaded with gene annotation, BLAST hit results, and gene-clustering scores designed to help identify regions of conserved gene order. Researchers use the PSAT web interface to find a gene of interest in a reference genome and efficiently retrieve the sequence homologs found in other bacterial genomes. The tool generates a graphic of the genomic neighborhood surrounding the selected gene and the corresponding regions for its homologs in each comparison genome. Homologs in each region are color coded to assist users with analyzing gene order among various genomes. In contrast to common comparative analysis methods that filter sequence homolog data based on alignment score cutoffs, PSAT leverages gene context information for homologs, including those with weak alignment scores, enabling a more sensitive analysis. Features for constraining or ordering results are designed to help researchers browse results from large numbers of comparison genomes in an organized manner. PSAT has been demonstrated to be useful for helping to identify gene orthologs and potential functional gene clusters, and detecting genome modifications that may result in loss of function.

Conclusion

PSAT allows researchers to investigate the order of genes within local genomic neighborhoods of multiple genomes. A PSAT web server for public use is available for performing analyses on a growing set of reference genomes through any web browser with no client side software setup or installation required. Source code is freely available to researchers interested in setting up a local version of PSAT for analysis of genomes not available through the public server. Access to the public web server and instructions for obtaining source code can be found at http://www.nwrce.org/psat.
LocateP: Genome-scale subcellular-location predictor for bacterial proteins
Authors: Zhou Miaomiao , Boekhorst Jos , Francke Christof , Siezen Roland J
Published: March 2008

Background

In the past decades, various protein subcellular-location (SCL) predictors have been developed. Most of these predictors, like TMHMM 2.0, SignalP 3.0, PrediSi and Phobius, aim at the identification of one or a few SCLs, whereas others such as CELLO and Psortb.v.2.0 aim at a broader classification. Although these tools and pipelines can achieve a high precision in the accurate prediction of signal peptides and transmembrane helices, they have a much lower accuracy when other sequence characteristics are concerned. For instance, it proved notoriously difficult to identify the fate of proteins carrying a putative type I signal peptidase (SPIase) cleavage site, as many of those proteins are retained in the cell membrane as N-terminally anchored membrane proteins. Moreover, most of the SCL classifiers are based on the classification of the Swiss-Prot database and consequently inherited the inconsistency of that SCL classification. As accurate and detailed SCL prediction on a genome scale is highly desired by experimental researchers, we decided to construct a new SCL prediction pipeline: LocateP.

Results

LocateP combines many of the existing high-precision SCL identifiers with our own newly developed identifiers for specific SCLs. The LocateP pipeline was designed such that it mimics protein targeting and secretion processes. It distinguishes 7 different SCLs within Gram-positive bacteria: intracellular, multi-transmembrane, N-terminally membrane anchored, C-terminally membrane anchored, lipid-anchored, LPxTG-type cell-wall anchored, and secreted/released proteins. Moreover, it distinguishes pathways for Sec- or Tat-dependent secretion and alternative secretion of bacteriocin-like proteins. The pipeline was tested on data sets extracted from literature, including experimental proteomics studies. The tests showed that LocateP performs as well as, or even slightly better than other SCL predictors for some locations and outperforms current tools especially where the N-terminally anchored and the SPIase-cleaved secreted proteins are concerned. Overall, the accuracy of LocateP was always higher than 90%. LocateP was then used to predict the SCLs of all proteins encoded by completed Gram-positive bacterial genomes. The results are stored in the database LocateP-DBhttp://www.cmbi.ru.nl/locatep-db[1].

Conclusion

LocateP is by far the most accurate and detailed protein SCL predictor for Gram-positive bacteria currently available.
Snagger: A user-friendly program for incorporating additional information for tagSNP selection
Authors: Edlund Christopher K , Lee Won H , Li Dalin , Van Den Berg David J , Conti David V
Published: March 2008

Background

There has been considerable effort focused on developing efficient programs for tagging single-nucleotide polymorphisms (SNPs). Many of these programs do not account for potential reduced genomic coverage resulting from genotyping failures nor do they preferentially select SNPs based on functionality, which may be more likely to be biologically important.

Results

We have developed a user-friendly and efficient software program, Snagger, as an extension to the existing open-source software, Haploview, which uses pairwise r
2 linkage disequilibrium between single nucleotide polymorphisms (SNPs) to select tagSNPs. Snagger distinguishes itself from existing SNP selection algorithms, including Tagger, by providing user options that allow for: (1) prioritization of tagSNPs based on certain characteristics, including platform-specific design scores, functionality (i.e., coding status), and chromosomal position, (2) efficient selection of SNPs across multiple populations, (3) selection of tagSNPs outside defined genomic regions to improve coverage and genotyping success, and (4) picking of surrogate tagSNPs that serve as backups for tagSNPs whose failure would result in a significant loss of data. Using HapMap genotype data from ten ENCODE regions and design scores for the Illumina platform, we show similar coverage and design score distribution and fewer total tagSNPs selected by Snagger compared to the web server Tagger.

Conclusion

Snagger improves upon current available tagSNP software packages by providing a means for researchers to select tagSNPs that reliably capture genetic variation across multiple populations while accounting for significant genotyping failure risk and prioritizing on SNP-specific characteristics.
Both selective and neutral processes drive GC content evolution in the human genome
Authors: Pozzoli Uberto , Menozzi Giorgia , Fumagalli Matteo , Cereda Matteo , Comi Giacomo P , Cagliani Rachele , Bresolin Nereo , Sironi Manuela
Published: March 2008

Background

Mammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains. The scientific debate is still open as to whether such compositional heterogeneity is a selected or neutral trait.

Results

Here we analyze SNP allele frequencies, retrotransposon insertion polymorphisms (RIPs), as well as fixed substitutions accumulated in the human lineage since its divergence from chimpanzee to indicate that biased gene conversion (BGC) has been playing a role in within-genome GC content variation. Yet, a distinct contribution to GC content evolution is accounted for by a selective process. Accordingly, we searched for independent evidences that GC content distribution does not conform to neutral expectations. Indeed, after correcting for possible biases, we show that intron GC content and size display isochore-specific correlations.

Conclusion

We consider that the more parsimonious explanation for our results is that GC content is subjected to the action of both weak selection and BGC in the human genome with features such as nucleosome positioning or chromatin conformation possibly representing the final target of selective processes. This view might reconcile previous contrasting findings and add some theoretical background to recent evidences suggesting that GC content domains display different behaviors with respect to highly regulated biological processes such as developmentally-stage related gene expression and programmed replication timing during neural stem cell differentiation.
Influence of leukotriene gene polymorphisms on chronic rhinosinusitis
Authors: Al-Shemari Hasan , Bossé Yohan , Hudson Thomas J , Cabaluna Myrna , Duval Melanie , Lemire Mathieu , Vallee-Smedja Sophie , Frenkiel Saul , Desrosiers Martin
Published: March 2008

Background

Chronic rhinosinusitis (CRS) is increasingly viewed as an inflammatory condition of the sinonasal mucosa interacting with bacteria and/or fungi. However, factors conferring susceptibility to disease remain unknown. Advances in genomics offer powerful tools to explore this disorder. The goal of this study was to evaluate the effect of single nucleotide polymorphisms (SNP) on CRS in a panel of genes related to cysteinyl leukotriene metabolism.

Methods

Severe cases of CRS and postal code match controls were recruited prospectively. A total of 206 cases and 200 controls were available for the present study. Using a candidate gene approach, five genes related to cysteinyl leukotriene metabolism were assessed. For each gene, we selected the maximally informative set of common SNPs (tagSNPs) using the European-derived (CEU) HapMap dataset. These SNPs are in arachidonate 5-lipoxygenase (ALOX5), arachidonate 5-lipoxygenase-activating protein (ALOX5AP), leukotriene C4 synthase (LTC4S), cysteinyl leukotriene receptor 1 (CYSLTR1) and cysteinyl leukotriene receptor 2 (CYSLTR2) genes.

Results

A total of 59 SNPs were genotyped to capture the common genetic variations within these genes. Three SNPs located within the ALOX5, CYSLTR1 and ALOX5AP genes reached the nominal p-value threshold (p < 0.05) for association with CRS. However, none of these SNPs resist multiple testing adjustment.

Conclusion

While these initial results do not support that polymorphsims in genes assessed involved in the leukotriene pathways are contributing to the pathogenesis of CRS, this initial study was not powered to detect polymorphisms with relative risk of 2.0 or less, where we could expect many gene effects for complex diseases to occur. Thus, despite this lack of significant association noted in this study, we believe that validation with external populations and the use of better-powered studies in the future may allow more conclusive findings.
Surveillance study of vector species on board passenger ships, Risk factors related to infestations
Authors: Mouchtouri Varvara A , Anagnostopoulou Rimma , Samanidou-Voyadjoglou Anna , Theodoridou Kalliopi , Hatzoglou Chrissi , Kremastinou Jenny , Hadjichristodoulou Christos
Published: March 2008

Background

Passenger ships provide conditions suitable for the survival and growth of pest populations. Arthropods and rodents can gain access directly from the ships' open spaces, can be carried in shiploads, or can be found on humans or animals as ectoparasites. Vectors on board ships may contaminate stored foods, transmit illness on board, or, introduce diseases in new areas. Pest species, ship areas facilitating infestations, and different risk factors related to infestations were identified in 21 ferries.

Methods

486 traps for insects and rodents were placed in 21 ferries. Archives of Public Health Authorities were reviewed to identify complaints regarding the presence of pest species on board ferries from 1994 to 2004. A detail questionnaire was used to collect data on ship characteristics and pest control practices.

Results

Eighteen ferries were infested with flies (85.7%), 11 with cockroaches (52.3%), three with bedbugs, and one with fleas. Other species had been found on board were ants, spiders, butterflies, beetles, and a lizard. A total of 431 Blattella germanica species were captured in 28 (9.96%) traps, and 84.2% of them were nymphs. One ship was highly infested. Cockroach infestation was negatively associated with ferries in which Hazard Analysis Critical Control Point system was applied to ensure food safety on board (Relative Risk, RR = 0.23, p = 0.03), and positively associated with ferries in which cockroaches were observed by crew (RR = 4.09, p = 0.007), no cockroach monitoring log was kept (RR = 5.00, p = 0.02), and pesticide sprays for domestic use were applied by crew (RR = 4.00, p = 0.05). Cockroach infested ships had higher age (p = 0.03). Neither rats nor mice were found on any ship, but three ferries had been infested with a rodent in the past.

Conclusion

Integrated pest control programs should include continuing monitoring for a variety of pest species in different ship locations; pest control measures should be more persistent in older ships. HACCP system aids in the prevention of cockroach infestations on board.
Improved production of human type II procollagen in the yeast Pichia pastoris in shake flasks by a wireless-controlled fed-batch system
Authors: Ruottinen Maria , Bollok Monika , Kögler Martin , Neubauer Antje , Krause Mirja , Hämäläinen Eija-Riitta , Myllyharju Johanna , Vasala Antti , Neubauer Peter
Published: March 2008

Background

Here we describe a new technical solution for optimization of Pichia pastoris shake flask cultures with the example of production of stable human type II collagen. Production of recombinant proteins in P. pastoris is usually performed by controlling gene expression with the strong AOX1 promoter, which is induced by addition of methanol. Optimization of processes using the AOX1 promoter in P. pastoris is generally done in bioreactors by fed-batch fermentation with a controlled continuous addition of methanol for avoiding methanol toxification and carbon/energy starvation. The development of feeding protocols and the study of AOX1-controlled recombinant protein production have been largely made in shake flasks, although shake flasks have very limited possibilities for measurement and control.

Results

By applying on-line pO2 monitoring we demonstrate that the widely used pulse feeding of methanol results in long phases of methanol exhaustion and consequently low expression of AOX1 controlled genes. Furthermore, we provide a solution to apply the fed-batch strategy in shake flasks. The presented solution applies a wireless feeding unit which can be flexibly positioned and allows the use of computer-controlled feeding profiles.

By using the human collagen II as an example we show that a quasi-continuous feeding profile, being the simplest way of a fed-batch fermentation, results in a higher production level of human collagen II. Moreover, the product has a higher proteolytic stability compared to control cultures due to the increased expression of human collagen prolyl 4-hydroxylase as monitored by mRNA and protein levels.

Conclusion

The recommended standard protocol for methanol addition in shake flasks using pulse feeding is non-optimal and leads to repeated long phases of methanol starvation. The problem can be solved by applying the fed-batch technology. The presented wireless feeding unit, together with an on-line monitoring system offers a flexible, simple, and low-cost solution for initial optimization of the production in shake flasks which can be performed in parallel. By this way the fed-batch strategy can be applied from the early screening steps also in laboratories which do not have access to high-cost and complicated bioreactor systems.
Evaluation of the current knowledge limitations in breast cancer research: a gap analysis
Authors: Thompson Alastair , Brennan Keith , Cox Angela , Gee Julia , Harcourt Diana , Harris Adrian , Harvie Michelle , Holen Ingunn , Howell Anthony , Nicholson Robert , Steel Michael , Streuli Charles ,   Breast Cancer Campaign Gap Analysis Meeting (2 November 2006, London, UK)
Published: March 2008

Background

A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients.

Methods

Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action.

Results

Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds).

Conclusion

Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care.
Analysis of repetitive DNA distribution patterns in the Tribolium castaneum genome
Authors: Wang Suzhi , Lorenzen Marcé D , Beeman Richard W , Brown Susan J
Published: March 2008

Background

Insect genomes vary widely in size, a large fraction of which is often devoted to repetitive DNA. Re-association kinetics indicate that up to 42% of the genome of the red flour beetle, Tribolium castaneum, is repetitive. Analysis of the abundance and distribution of repetitive DNA in the recently sequenced genome of T. castaneum is important for understanding the structure and function of its genome.

Results

Using TRF, TEpipe and RepeatScout we found that approximately 30% of the T. castaneum assembled genome is composed of repetitive DNA. Of this, 17% is found in tandem arrays and the remaining 83% is dispersed, including transposable elements, which in themselves constitute 5-6% of the genome. RepeatScout identified 31 highly repetitive DNA elements with repeat units longer than 100 bp, which constitute 7% of the genome; 65% of these highly repetitive elements and 74% of transposable elements accumulate in regions representing 40% of the assembled genome that is anchored to chromosomes. These regions tend to occur near one end of each chromosome, similar to previously described blocks of pericentric heterochromatin. They contain fewer genes with longer introns, and often correspond with regions of low recombination in the genetic map.

Conclusion

Our study found that transposable elements and other repetitive DNA accumulate in certain regions in the assembled T. castaneum genome. Several lines of evidence suggest these regions are derived from the large blocks of pericentric heterochromatin in T. castaneum chromosomes.
Aquinas on Mental Representation: Concepts and Intentionality
Authors: Brower Jeffrey E. , Brower-Toland Susan
Published: March 2008

This essay explores some of the central aspects of Aquinas's account of mental representation, focusing in particular on his views about the intentionality of concepts (or intelligible species). It begins by demonstrating the need for a new interpretation of his account, showing in particular that the standard interpretations all face insurmountable textual difficulties. It then develops the needed alternative and explains how it avoids the sorts of problems plaguing the standard interpretations. Finally, it draws out the implications of this interpretation with the aim of correcting some persistent misunderstandings of the connection between Aquinas's views and those developed by contemporary philosophers of mind.
Critical Notice of Kit Fine'sModality and Tense: Philosophical Papers
Authors: Forbes Graeme
Published: March 2008

In this critical review I discuss the main themes of the papers in Kit Fine's Modality and Tense: Philosophical Papers. These themes are that modal operators are intelligible in their own right and that actualist quantifiers are to be taken as basic with respect to possibilist quantifiers. I also discuss a previously unpublished paper of Fine's on modality and existence.
The YPWM motif links Antennapedia to the basal transcriptional machinery
Authors: Prince Frédéric , Katsuyama Tomonori , Oshima Yoshiteru , Plaza Serge , Resendez-Perez Diana , Berry Meera , Kurata Shoichiro , Gehring Walter J.
Published: March 2008

HOX genes specify segment identity along the anteroposterior axis of the embryo. They code for transcription factors harbouring the highly conserved homeodomain and a YPWM motif, situated amino terminally to it. Despite their highly diverse functions in vivo, HOX proteins display similar biochemical properties in vitro, raising the question of how this specificity is achieved. In our study, we investigated the importance of the Antennapedia(Antp) YPWM motif for homeotic transformations in adult Drosophila. By ectopic overexpression, the head structures of the fly can be transformed into structures of the second thoracic segment, such as antenna into second leg, head capsule into thorax (notum) and eye into wing. We found that the YPWM motif is absolutely required for the eye-to-wing transformation. Using the yeast two-hybrid system, we were able to identify a novel ANTP-interacting protein, Bric-à-brac interacting protein 2(BIP2), that specifically interacts with the YPWM motif of ANTP in vitro, as well as in vivo, transforming eye to wing tissue. BIP2 is a TATA-binding protein associated factor (also known as dTAFII3) that links ANTP to the basal transcriptional machinery.
Different autonomous myogenic cell populations revealed by ablation of Myf5-expressing cells during mouse embryogenesis
Authors: Gensch Nicole , Borchardt Thilo , Schneider Andre , Riethmacher Dieter , Braun Thomas
Published: March 2008

The development of myogenic cells is mainly determined by expression of two myogenic factors, Myf5 and Myod1 (MyoD), which genetically compensate for each other during embryogenesis. Here, we demonstrate by conditional cell ablation in mice that Myf5 determines a distinct myogenic cell population, which also contains some Myod1-positive cells. Ablation of this lineage uncovers the presence of a second autonomous myogenic lineage, which superseded Myf5-dependent myogenic cells and expressed Myod1. By contrast, ablation of myogenin-expressing cells erased virtually all differentiated muscle cells,indicating that some aspects of the myogenic program are shared by most skeletal muscle cells. We conclude that Myf5 and Myod1 define different cell lineages with distinct contributions to muscle precursor cells and differentiated myotubes. Individual myogenic cell lineages seem to substitute for each other within the developing embryo.
Smt3 is required forDrosophila melanogastermetamorphosis
Authors: Talamillo Ana , Sánchez Jonatan , Cantera Rafael , Pérez Coralia , Martín David , Caminero Eva , Barrio Rosa
Published: March 2008

Sumoylation, the covalent attachment of the small ubiquitin-related modifier SUMO to target proteins, regulates different cellular processes,although its role in the control of development remains unclear. We studied the role of sumoylation during Drosophila development by using RNAi to reduce smt3 mRNA levels in specific tissues. smt3knockdown in the prothoracic gland, which controls key developmental processes through the synthesis and release of ecdysteroids, caused a 4-fold prolongation of larval life and completely blocked the transition from larval to pupal stages. The reduced ecdysteroid titer of smt3 knockdown compared with wild-type larvae explains this phenotype. In fact, after dietary administration of exogenous 20-hydroxyecdysone, knockdown larvae formed pupal cases. The phenotype is not due to massive cell death or degeneration of the prothoracic glands at the time when puparium formation should occur. Knockdown cells show alterations in expression levels and/or the subcellular localisation of enzymes and transcription factors involved in the regulation of ecdysteroid synthesis. In addition, they present reduced intracellular channels and a reduced content of lipid droplets and cholesterol, which could explain the deficit in steroidogenesis. In summary, our study indicates that Smt3 is required for the ecdysteroid synthesis pathway at the time of puparium formation.
Hairpin RNAs derived from RNA polymerase II and polymerase III promoter-directed transgenes are processed differently in plants
Authors: Wang Ming-Bo , Helliwell Christopher A. , Wu Li-Min , Waterhouse Peter M. , Peacock W. James , Dennis Elizabeth S.
Published: March 2008

RNA polymerase III (Pol III) as well as Pol II (35S) promoters are able to drive hairpin RNA (hpRNA) expression and induce target gene silencing in plants. siRNAs of 21 nt are the predominant species in a 35S Pol II line, whereas 24- and/or 22-nucleotide (nt) siRNAs are produced by a Pol III line. The 35S line accumulated the loop of the hpRNA, in contrast to full-length hpRNA in the Pol III line. These suggest that Pol II and Pol III-transcribed hpRNAs are processed by different pathways. One Pol III transgene produced only 24-nt siRNAs but silenced the target gene efficiently, indicating that the 24-nt siRNAs can direct mRNA degradation; specific cleavage was confirmed by 5′ rapid amplification of cDNA ends (RACE). Both Pol II- and Pol III-directed hpRNA transgenes induced cytosine methylation in the target DNA. The extent of methylation is not correlated with the level of 21-nt siRNAs, suggesting that they are not effective inducers of DNA methylation. The promoter of a U6 transgene was significantly methylated, whereas the promoter of the endogenous U6 gene was almost free of cytosine methylation, suggesting that endogenous sequences are more resistant to de novo DNA methylation than are transgene constructs.