bluuebunny/crossref_metadata_2025 huggingface dataset:
Classical latent variable models for medical research
Authors: Rabe-Hesketh Sophia , Skrondal Anders
Published: September 2007

Latent variable models are commonly used in medical statistics, although often not referred to under this name. In this paper we describe classical latent variable models such as factor analysis, item response theory, latent class models and structural equation models. Their usefulness in medical research is demonstrated using real data. Examples include measurement of forced expiratory flow, measurement of physical disability, diagnosis of myocardial infarction and modelling the determinants of clients' satisfaction with counsellors' interviews.
A Foundation for the Internationalization of the Academic Self
Authors: Sanderson Gavin
Published: September 2007

This article identifies the limitations of contemporary organizational theory on the internationalization of higher education in guiding and supporting internationalization activities at the level of the academic Self. A way forward is provided through Cranton's notion of authenticity in teaching in higher education, which presents a platform for understanding the academic Self through critically reflective and self-reflective processes. Cranton's work is then expanded using the concept of cosmopolitanism to enhance the potential for individual teachers to internationalize their personal and professional outlooks. In sum, this article highlights the importance of the exhortation from Socrates to know thyself as a precondition to better understand Others. Furthermore, the article provides the fundamental underpinnings of a conceptual framework for the internationalization of the academic Self.
Asian Students' Voices: An Empirical Study of Asian Students' Learning Experiences at a New Zealand University
Authors: Campbell Jacqui , Li Mingsheng
Published: September 2007

More than 85% of the international students in New Zealand are Asian in origin. The level of satisfaction of Asian international students with their learning experiences in New Zealand has been of enormous concern for the New Zealand export education industry. The results of this current research, based on a qualitative research study conducted at a New Zealand tertiary institution, provide a critical summary of some important and yet challenging issues in teaching Asian students. This study found that Asian students were overall satisfied with their learning experiences at the university in terms of educational quality, program offering, and learning support. Asian students' voices and narratives on which this research was based have challenged some of our taken-for-granted education traditions, norms, and practices. Characterizing these challenges are language difficulties and cultural differences as intercultural communication barriers, unfamiliar patterns of classroom interactions, lack of knowledge of academic norms and conventions, inadequate learning support, difficulties in making friends with domestic students, and lack of sense of belonging, all these combining to affect Asian students' perceptions and levels of satisfaction with their learning experiences at the university. The study suggests that it is important that lecturers and host institutions are professionally responsible to equip Asian students with adequate knowledge of academic discourses and to help them transcend the culturally framed borders and subjectivities. To meet these challenges, it is important to review and adapt our pedagogical practices and to realign them to the needs of both local and international students.
Loneliness and International Students: An Australian Study
Authors: Sawir Erlenawati , Marginson Simon , Deumert Ana , Nyland Chris , Ramia Gaby
Published: September 2007

In a study of international student security, consisting of 200 intensive interviews with students, resident onshore in Australia, it was found that two thirds of the group had experienced problems of loneliness and/or isolation, especially in the early months. According to Weiss, students experience both personal loneliness because of the loss of contact with families and social loneliness because of the loss of networks. Both forms of loneliness are at times exacerbated by their experiences in institutional sites. The article discusses the coping mechanisms that students use. It identifies a third kind of loneliness experienced by international students, cultural loneliness , triggered by the absence of the preferred cultural and/or linguistic environment. This can affect even students with adequate personal and social support. Thus, same-culture networks are often crucial for international students. Yet same-culture networks are not a universal panacea: They cannot substitute for adequate pastoral care by universities or ensure satisfactory engagement with local cultures, so some causes of cultural loneliness often remain. The article concludes that the creation of stronger bonds between international and local students in the educational setting, helping international students to remake their own cultural maps on their own terms, is key to a forward move on loneliness.
Moving Beyond Gender to Discover Differences in Sensitivity to Disempowering Acts
Authors: Young Angela M. , Vance Charles M. , Harris Claudia
Published: September 2007

The purpose of this study is to examine levels of perceived offensiveness based on observations of disempowering acts and to identify any differences in perceptions based on gender, ethnicity, and a social context in which respondents held majority versus minority status. Gender emerged as a strong determinant of differences in levels of perceived offensiveness, with women reporting higher levels of perceived offensiveness when viewing disempowering acts than did men. However, when comparing groups of the same ethnicity (i.e., African American) on differences in perceived offensiveness based on social context, social context had a significant effect on perceptions, and men, not women, reported higher levels of perceived offensiveness.
Examining the Link Between Diversity and Firm Performance
Authors: Roberson Quinetta M. , Hyeon Jeong Park
Published: September 2007

Given the scarcity of empirical research on the impact of diversity on organizational performance, the authors used longitudinal data for 100 firms to test hypotheses related to the effects of diversity reputation and leader racial diversity on firm financial outcomes. The results showed a positive relationship between diversity reputation and book-to-market equity and a curvilinear, U-shaped relationship among leader diversity and revenues, net income, and book-to-market equity. The analyses suggest that economic benefits generated from diversity reputation may primarily derive from capital rather than product markets. Furthermore, firm performance declines with increases in the representation of racial minorities in leadership up to a point, beyond which further increases in diversity are associated with increases in performance.
Perceived Dissimilarity and Perspective Taking Within Work Teams
Authors: Williams Helen M. , Parker Sharon K. , Turner Nick
Published: September 2007

The authors investigate the relationship between employee perceptions of surface- and deep-level dissimilarity and within-team perspective taking. Results suggest that the more dissimilar employees perceive themselves to be from their fellow team members in terms of their work style, the less their perspective taking (i.e., lower positive attributions and empathy). In addition, the authors found that perceived work-style dissimilarity interacted with a contextually salient surface-level attribute (perceived age dissimilarity) such that when perceived work-style dissimilarity was low, perceived age dissimilarity had a stronger negative effect on within-team perspective taking. This study demonstrates the importance of considering perspective taking in their understanding of the effects of dissimilarity within teams and furthers theoretical understanding of the effects of relational demography by testing competing theories undergirding relational demography research.
Evaluation of the design and reliability of three elastomeric and one mechanical infusers
Authors: Ackermann Monique , Maier Stéphanie , Ing Ho , Bonnabry Pascal
Published: September 2007

Background. Disposable elastomeric and mechanical (spring mechanism) infusers with pre-fixed flow rates are principally used for long-term antibiotic therapy, chemotherapy, antiviral therapy, and chronic pain management.

Methods. Three elastomeric pumps and one mechanical infuser pump are evaluated. The design and function are assessed using specific questionnaires elaborated for the pharmaceutical staff, nurses and patients, respectively. Several tests are performed to determine the flow accuracy and the influence of different parameters such as the temperature, the viscosity, the height, and the restrictor variability.

Results. The functional tests show that the perfusion duration is shorter than that specified by the manufacturers, the restrictors are not homogeneous within a batch. However, the temperature of the regulator, the viscosity of the solution, and the height of the reservoir influence the flow rate.

Conclusions. The ideal infuser should be small, light, unnoticeable, easy to fill, well identified and have a flow rate barely affected by external factors. None of the infusers has fulfilled all criteria, therefore the choice of infusers depends upon the nature of the treatment. The tested elastomeric infusers are adequate for 5-fluorouracil, but not for a treatment requiring a stable administration rate.
Low-molecular-weight heparin in cancer-associated thrombosis: treatment, secondary prevention, and survival
Authors: Nishioka Jennifer , Goodin Susan
Published: September 2007

Objectives. Venous thromboembolism (VTE) occurs more frequently in cancer patients than in non-cancer patients and outcomes are poor in patients with both cancer and thrombosis. Patients with cancer who develop thrombosis are more likely to experience a recurrence of VTE and have increased bleeding complications while receiving oral anticoagulant treatment. The purpose of this paper is to discuss the causes and outcomes of thrombosis in cancer patients, the limitations of warfarin therapy, the guidelines and data for the use of low-molecular-weight heparins (LMWHs) in the treatment and secondary prevention of thrombosis in cancer patients, and emerging data regarding survival with the use of LMWH in cancer patients.

Methods. Literature for this paper has been collected using multiple sources, including primary, secondary, and tertiary references. Online searches have been conducted utilizing the PubMed and OVID databases, and abstracts from the Proceedings of the American Society of Clinical Oncology and the American Society of Hematology Annual Meeting and Exhibition. The following key terms were used in the search: cancer, deep vein thrombosis, pulmonary embolism, anticoagulation, LMWHs, guidelines, survival, cost.

Results. The long-term use of LMWHs in the settings of cancer and thrombosis are supported by recent clinical trial evidence that demonstrate their equivalent safety and improved efficacy when compared to oral anticoagulants resulting in their inclusion in current guidelines. Finally, newer studies offer further evidence of improved outcomes with dalteparin and nadroparin, including possible survival benefits.

Conclusions. Treatment with LMWHs has been shown to be more effective than warfarin in the extended treatment of VTE in patients with cancer and is safe in this setting. Use of a LMWH for at least the first 3–6 months of long-term treatment is now considered the standard of care for patients with cancer and is recommended in numerous guidelines. Additionally, further evaluation of the survival benefits of LMWH in cancer patients is warranted.
Liposomal doxorubicin-associated acute hypersensitivity despite appropriate preventive measures
Authors: Chan Alexandre , Shih Vivianne , Chee Kian Tham
Published: September 2007

Liposomal doxorubicin is becoming popular as a chemotherapeutic agent in the treatment of multiple malignancies. This paper describes an episode of hypersensitivity reaction associated with the infusion of liposomal doxorubicin in an ovarian cancer patient, despite preventive measures being undertaken during her first cycle of chemotherapy. Clinicians may overlook the possibility of hypersensitivity reactions associated with liposomal doxorubicin because routine prophylaxis is not provided and reactions are infrequently observed in practice. Close monitoring during the first 15 min of infusion for signs of hypersensitivity should be mandatory for patients receiving their first dose of liposomal doxorubicin. Further research should identify patients who are at risk of experiencing such hypersensitivity.
Long-term stability of sodium folinate in dextrose 5% polyolefin bags at 4°C
Authors: Cadrobbi Julie , Hecq Jean-Daniel , Vanbeckbergen Danielle , Jamart Jacques , Galanti Laurence
Published: September 2007

Objectives. Preparation of intravenous solutions in advance could be an efficient approach to improve quality assurance, security, time management, and cost saving of drug provision. The purpose of this paper is to investigate the stability of sodium folinate solutions at 3.2 mg mL-1 in 5% dextrose polyolefin bags at 48C.

The purpose of this paper is to investigate least 30 days at 4°C, where lower confidence limits of the stability of sodium folinate solutions the results value remain above 90% of the initial conat 3.2 mg mL-1 in 5% dextrose polyolefin bags centration. During this stability period, the pH values at 4°C. of infusions have been observed to decrease slightly

Methods. The stability of five polyolefin bags of solution containing approximately 3.2 mg mL-1 of sodium folinate in 5% dextrose prepared under aseptic conditions and stored at 48C have been studied over 30 days. Sodium folinate concentrations have been measured by highperformance liquid chromatography and the results have been analysed by regression analysis. Solutions have been visually inspected and pH measured.

Results. No colour change or precipitation occurred in the preparations. Based on a shelf-life of 90% residual potency, sodium folinate solutions have been observed to be stable for a period of at least 30 days at 48C, where lower confidence limits of the results value remain above 90% of the initial concentration. During this stability period, the pH values of infusions have been observed to decrease slightly without affecting chromatographic parameters.

Conclusion. Within these limits, sodium folinate in 5% dextrose infusion may be prepared and stored in advance by a centralized intravenous admixture service.
I branching formation in erythroid differentiation is regulated by transcription factor C/EBPα
Authors: Twu Yuh-Ching , Chen Chie-Pein , Hsieh Chuang-Yi , Tzeng Cheng-Hwai , Sun Chien-Feng , Wang Shih-Hsin , Chang Mau-Sun , Yu Lung-Chih
Published: September 2007

The histo-blood group i and I antigens have been characterized as straight and branched repeats of N-acetyllactosamine, respectively, and the conversion of the straight-chain i to the branched-chain I structure on red cells is regulated to occur after birth. It has been demonstrated that the human I locus expresses 3 IGnT transcripts, IGnTA, IGnTB, and IGnTC, and that the last of these is responsible for the I branching formation on red cells. In the present investigation, the K-562 cell line was used as a model to show that the i-to-I transition in erythroid differentiation is determined by the transcription factor CCAAT/enhancer binding protein α (C/EBPα), which enhances transcription of the IGnTC gene, consequently leading to formation of the I antigen. Further investigation suggested that C/EBPα IGnTC-activation activity is modulated at a posttranslational level, and that the phosphorylation status of C/EBPα may have a crucial effect. Results from studies using adult and cord erythropoietic cells agreed with those derived using the K-562 cell model, with lentiviral expression of C/EBPα in CD34+ hemopoietic cells demonstrating the determining role of C/EBPα in the induction of the IGnTC gene as well as in I antigen expression.
PKC ζ–mTOR pathway: a new target for rituximab therapy in follicular lymphoma
Authors: Leseux Ludivine , Laurent Guy , Laurent Camille , Rigo Maxime , Blanc Amandine , Olive Daniel , Bezombes Christine
Published: September 2007

Previous studies have documented that, in malignant B cells, rituximab elicits a complex and not yet totally understood signaling network contributing to its antitumor effect. In this context, we investigated the role of protein kinase C ζ (PKCζ), an atypical PKC isoform, in the cellular response to rituximab. We found that follicular lymphoma cells displayed an increase in PKCζ expression and activity levels, compared with nonmalignant B cells, and that this enzyme was a critical regulator of the classical MAPK module by stimulating Raf-1 kinase activity. PKCζ appeared to be a significant contributor of abnormal mTOR regulation in follicular lymphoma cells through a MAPK-dependent mechanism. Rituximab was found to inhibit the PKCζ/MAPK/mTOR module in these cells but not in other B-cell lymphomas. Importantly, the expression of a constitutively active form of PKCζ resulted in an efficient protection of these cells toward rituximab. Altogether, our study describes a new regulatory component of mTOR pathway in follicular cell lymphoma and demonstrates that PKCζ is a target for rituximab. Therefore, PKCζ could represent an important parameter for rituximab efficacy and a promising target for future targeted therapy in follicular lymphoma.
A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification
Authors: Mueller Dorothee , Bach Christian , Zeisig Deniz , Garcia-Cuellar Maria-Paz , Monroe Sara , Sreekumar Arun , Zhou Rong , Nesvizhskii Alexey , Chinnaiyan Arul , Hess Jay L. , Slany Robert K.
Published: September 2007

Chimeric proteins joining the histone methyltransferase MLL with various fusion partners trigger distinctive lymphoid and myeloid leukemias. Here, we immunopurified proteins associated with ENL, a protein commonly fused to MLL. Identification of these ENL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase II C-terminal domain kinase [RNAPolII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltransferase DOT1L) as well as other frequent MLL partners (AF4, AF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR). The composition of EAP was further verified by coimmunoprecipitation, 2-hybrid analysis, pull-down, and colocalization experiments. Purified EAP showed a histone H3 lysine 79–specific methylase activity, displayed a robust RNAPolII CTD kinase function, and counteracted the effect of the pTEFb inhibitor 5,6-dichloro-benzimidazole-riboside. In vivo, an ENL knock-down diminished genome-wide as well as gene-specific H3K79 dimethylation, reduced global run-on elongation, and inhibited transient transcriptional reporter activity. According to structure-function data, DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. These results suggest a function of ENL in histone modification and transcriptional elongation.
Simultaneous loss of β- and γ-catenin does not perturb hematopoiesis or lymphopoiesis
Authors: Koch Ute , Wilson Anne , Cobas Monica , Kemler Rolf , MacDonald H. Robson , Radtke Freddy
Published: September 2007

Hematopietic stem cells (HSCs) maintain life-long hematopoiesis in the bone marrow via their ability to self-renew and to differentiate into all blood lineages. Although a central role for the canonical wnt signaling pathway has been suggested in HSC self-renewal as well as in the development of B and T cells, conditional deletion of β-catenin (which is considered to be essential for Wnt signaling) has no effect on hematopoiesis or lymphopoiesis. Here, we address whether this discrepancy can be explained by a redundant and compensatory function of γ-catenin, a close homolog of β-catenin. Unexpectedly, we find that combined deficiency of β- and γ-catenin in hematopoietic progenitors does not impair their ability to self-renew and to reconstitute all myeloid, erythroid, and lymphoid lineages, even in competitive mixed chimeras and serial transplantations. These results exclude an essential role for canonical Wnt signaling (as mediated by β- and/or γ-catenin) during hematopoiesis and lymphopoiesis.
Invasive and noninvasive methods for studying pulmonary function in mice
Authors: Glaab Thomas , Taube Christian , Braun Armin , Mitzner Wayne
Published: September 2007

The widespread use of genetically altered mouse models of experimental asthma has stimulated the development of lung function techniques in vivo to characterize the functional results of genetic manipulations. Here, we describe various classical and recent methods of measuring airway responsiveness in vivo including both invasive methodologies in anesthetized, intubated mice (repetitive/non-repetitive assessment of pulmonary resistance (RL) and dynamic compliance (Cdyn); measurement of low-frequency forced oscillations (LFOT)) and noninvasive technologies in conscious animals (head-out body plethysmography; barometric whole-body plethysmography). Outlined are the technical principles, validation and applications as well as the strengths and weaknesses of each methodology. Reviewed is the current set of invasive and noninvasive methods of measuring murine pulmonary function, with particular emphasis on practical considerations that should be considered when applying them for phenotyping in the laboratory mouse.
OntologyWidget – a reusable, embeddable widget for easily locating ontology terms
Authors: Beauheim Catherine C , Wymore Farrell , Nitzberg Michael , Zachariah Zachariah K , Jin Heng , Skene JH Pate , Ball Catherine A , Sherlock Gavin
Published: September 2007

Background

Biomedical ontologies are being widely used to annotate biological data in a computer-accessible, consistent and well-defined manner. However, due to their size and complexity, annotating data with appropriate terms from an ontology is often challenging for experts and non-experts alike, because there exist few tools that allow one to quickly find relevant ontology terms to easily populate a web form.

Results

We have produced a tool, OntologyWidget, which allows users to rapidly search for and browse ontology terms. OntologyWidget can easily be embedded in other web-based applications. OntologyWidget is written using AJAX (Asynchronous JavaScript and XML) and has two related elements. The first is a dynamic auto-complete ontology search feature. As a user enters characters into the search box, the appropriate ontology is queried remotely for terms that match the typed-in text, and the query results populate a drop-down list with all potential matches. Upon selection of a term from the list, the user can locate this term within a generic and dynamic ontology browser, which comprises the second element of the tool. The ontology browser shows the paths from a selected term to the root as well as parent/child tree hierarchies. We have implemented web services at the Stanford Microarray Database (SMD), which provide the OntologyWidget with access to over 40 ontologies from the Open Biological Ontology (OBO) website [1]. Each ontology is updated weekly. Adopters of the OntologyWidget can either use SMD's web services, or elect to rely on their own. Deploying the OntologyWidget can be accomplished in three simple steps: (1) install Apache Tomcat [2] on one's web server, (2) download and install the OntologyWidget servlet stub that provides access to the SMD ontology web services, and (3) create an html (HyperText Markup Language) file that refers to the OntologyWidget using a simple, well-defined format.

Conclusion

We have developed OntologyWidget, an easy-to-use ontology search and display tool that can be used on any web page by creating a simple html description. OntologyWidget provides a rapid auto-complete search function paired with an interactive tree display. We have developed a web service layer that communicates between the web page interface and a database of ontology terms. We currently store 40 of the ontologies from the OBO website [1], as well as a several others. These ontologies are automatically updated on a weekly basis. OntologyWidget can be used in any web-based application to take advantage of the ontologies we provide via web services or any other ontology that is provided elsewhere in the correct format. The full source code for the JavaScript and description of the OntologyWidget is available from http://smd.stanford.edu/ontologyWidget/.
A Bayesian nonparametric method for prediction in EST analysis
Authors: Lijoi Antonio , Mena Ramsés H , Prünster Igor
Published: September 2007

Background

Expressed sequence tags (ESTs) analyses are a fundamental tool for gene identification in organisms. Given a preliminary EST sample from a certain library, several statistical prediction problems arise. In particular, it is of interest to estimate how many new genes can be detected in a future EST sample of given size and also to determine the gene discovery rate: these estimates represent the basis for deciding whether to proceed sequencing the library and, in case of a positive decision, a guideline for selecting the size of the new sample. Such information is also useful for establishing sequencing efficiency in experimental design and for measuring the degree of redundancy of an EST library.

Results

In this work we propose a Bayesian nonparametric approach for tackling statistical problems related to EST surveys. In particular, we provide estimates for: a) the coverage, defined as the proportion of unique genes in the library represented in the given sample of reads; b) the number of new unique genes to be observed in a future sample; c) the discovery rate of new genes as a function of the future sample size. The Bayesian nonparametric model we adopt conveys, in a statistically rigorous way, the available information into prediction. Our proposal has appealing properties over frequentist nonparametric methods, which become unstable when prediction is required for large future samples. EST libraries, previously studied with frequentist methods, are analyzed in detail.

Conclusion

The Bayesian nonparametric approach we undertake yields valuable tools for gene capture and prediction in EST libraries. The estimators we obtain do not feature the kind of drawbacks associated with frequentist estimators and are reliable for any size of the additional sample.
Evolutionary conservation of P-selectin glycoprotein ligand-1 primary structure and function
Authors: Baïsse Bénédicte , Galisson Frédérique , Giraud Sylvain , Schapira Marc , Spertini Olivier
Published: September 2007

Background

P-selectin glycoprotein ligand-1 (PSGL-1) plays a critical role in recruiting leukocytes in inflammatory lesions by mediating leukocyte rolling on selectins. Core-2 O-glycosylation of a N-terminal threonine and sulfation of at least one tyrosine residue of PSGL-1 are required for L- and P-selectin binding. Little information is available on the intra- and inter-species evolution of PSGL-1 primary structure. In addition, the evolutionary conservation of selectin binding site on PSGL-1 has not been previously examined in detail. Therefore, we performed multiple sequence alignment of PSGL-1 amino acid sequences of 14 mammals (human, chimpanzee, rhesus monkey, bovine, pig, rat, tree-shrew, bushbaby, mouse, bat, horse, cat, sheep and dog) and examined mammalian PSGL-1 interactions with human selectins.

Results

A signal peptide was predicted in each sequence and a propeptide cleavage site was found in 9/14 species. PSGL-1 N-terminus is poorly conserved. However, each species exhibits at least one tyrosine sulfation site and, except in horse and dog, a T [D/E]PP [D/E] motif associated to the core-2 O-glycosylation of a N-terminal threonine. A mucin-like domain of 250–280 amino acids long was disclosed in all studied species. It lies between the conserved N-terminal O-glycosylated threonine (Thr-57 in human) and the transmembrane domain, and contains a central region exhibiting a variable number of decameric repeats (DR). Interspecies and intraspecies polymorphisms were observed. Transmembrane and cytoplasmic domain sequences are well conserved. The moesin binding residues that serve as adaptor between PSGL-1 and Syk, and are involved in regulating PSGL-1-dependent rolling on P-selectin are perfectly conserved in all analyzed mammalian sequences. Despite a poor conservation of PSGL-1 N-terminal sequence, CHO cells co-expressing human glycosyltransferases and human, bovine, pig or rat PSGL-1 efficiently rolled on human L- or P-selectin. By contrast, pig or rat neutrophils were much less efficiently recruited than human or bovine neutrophils on human selectins. Horse PSGL-1, glycosylated by human or equine glycosyltransferases, did not interact with P-selectin. In all five species, tyrosine sulfation of PSGL-1 was required for selectin binding.

Conclusion

These observations show that PSGL-1 amino acid sequence of the transmembrane and cytoplasmic domains are well conserved and that, despite a poor conservation of PSGL-1 N-terminus, L- and P-selectin binding sites are evolutionary conserved. Functional assays reveal a critical role for post-translational modifications in regulating mammalian PSGL-1 interactions with selectins.
Optical mapping as a routine tool for bacterial genome sequence finishing
Authors: Latreille Phil , Norton Stacie , Goldman Barry S , Henkhaus John , Miller Nancy , Barbazuk Brad , Bode Helge B , Darby Creg , Du Zijin , Forst Steve , Gaudriault Sophie , Goodner Brad , Goodrich-Blair Heidi , Slater Steven
Published: September 2007

Background

In sequencing the genomes of two Xenorhabdus species, we encountered a large number of sequence repeats and assembly anomalies that stalled finishing efforts. This included a stretch of about 12 Kb that is over 99.9% identical between the plasmid and chromosome of X. nematophila.

Results

Whole genome restriction maps of the sequenced strains were produced through optical mapping technology. These maps allowed rapid resolution of sequence assembly problems, permitted closing of the genome, and allowed correction of a large inversion in a genome assembly that we had considered finished.

Conclusion

Our experience suggests that routine use of optical mapping in bacterial genome sequence finishing is warranted. When combined with data produced through 454 sequencing, an optical map can rapidly and inexpensively generate an ordered and oriented set of contigs to produce a nearly complete genome sequence assembly.
Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion In Vitro
Authors: Ando Tomoaki , Langley Robert R , Wang Yuping , Jordan Paul A , Minagar Alireza , Alexander J Steven , Jennings Merilyn H
Published: September 2007

Background

MAdCAM-1 plays a central role in T-lymphocyte homing to the gut, but its role in chronic liver inflammation remains unknown. Therefore, this study measured MAdCAM-1 expression, regulation, and function in cultured murine hepatic endothelial cells.

Methods

Cultures of hepatic endothelial cells (HEC) were prepared from mice expressing a temperature-sensitive SV40 large T antigen (H-2Kb-tsA58) under the control of an IFN-γ promoter. Time and dose dependent expression of MAdCAM-1 in response to TNF-α, IL-1β and IFN-γ was studied by immunoblotting. Lymphocyte adhesion was studied using α4β7integrin expressing lymphocytes (TK-1) +/- anti-MAdCAM-1 mAb.

Results

TNF-α induced MAdCAM-1 dose-and time-dependently with maximum expression at 20 ng/ml and at 48 hours. IL-1β also induced MAdCAM-1 to a lesser extent compared to TNF-α; IFN-γ did not induce MAdCAM-1. TNF-α significantly increased lymphocyte-endothelial adhesion (P< 0.01), which was reversed by anti-MAdCAM-1 antibody. MAdCAM-1 expression was also reduced by N-acetylcysteine and by two NO donors (SperNO, DETANO) suggesting that hepatic endothelial MAdCAM-1 is oxidant and NO regulated.

Conclusion

MAdCAM-1 is a major determinant of leukocyte recruitment in chronic inflammation and is expressed by HEC in response to IL-1β and TNF-α. This system may provide a useful model for studying inflammatory mechanisms in liver disease and help determine if controlled MAdCAM-1 expression might influence inflammation in liver disease.
Developing a web-based information resource for palliative care: an action-research inspired approach
Authors: Street Annette F , Swift Kathleen , Annells Merilyn , Woodruff Roger , Gliddon Terry , Oakley Anne , Ottman Goetz
Published: September 2007

Background

General Practitioners and community nurses rely on easily accessible, evidence-based online information to guide practice. To date, the methods that underpin the scoping of user-identified online information needs in palliative care have remained under-explored. This paper describes the benefits and challenges of a collaborative approach involving users and experts that informed the first stage of the development of a palliative care website [1].

Method

The action research-inspired methodology included a panel assessment of an existing palliative care website based in Victoria, Australia; a pre-development survey (n = 197) scoping potential audiences and palliative care information needs; working parties conducting a needs analysis about necessary information content for a redeveloped website targeting health professionals and caregivers/patients; an iterative evaluation process involving users and experts; as well as a final evaluation survey (n = 166).

Results

Involving users in the identification of content and links for a palliative care website is time-consuming and requires initial resources, strong networking skills and commitment. However, user participation provided crucial information that led to the widened the scope of the website audience and guided the development and testing of the website. The needs analysis underpinning the project suggests that palliative care peak bodies need to address three distinct audiences (clinicians, allied health professionals as well as patients and their caregivers).

Conclusion

Web developers should pay close attention to the content, language, and accessibility needs of these groups. Given the substantial cost associated with the maintenance of authoritative health information sites, the paper proposes a more collaborative development in which users can be engaged in the definition of content to ensure relevance and responsiveness, and to eliminate unnecessary detail. Access to volunteer networks forms an integral part of such an approach.
Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells
Authors: Shelby Bryan D , LaMarca Heather L , McFerrin Harris E , Nelson Anne B , Lasky Joseph A , Sun Gang , Myatt Leslie , Offermann Margaret K , Morris Cindy A , Sullivan Deborah E
Published: September 2007

Background

Kaposi's sarcoma associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a highly vascularized neoplasm characterized by endothelial-derived spindle-shaped tumor cells. KSHV-infected microvascular endothelial cells demonstrate increased cyclooxygenase-2 (COX-2) expression and KS lesions have high levels of prostaglandin E2 (PGE2), a short-lived eicosanoid dependent on cyclooxygenase activity that has been linked to pathogenesis of other neoplasias. To determine whether increased COX-2 expression and PGE2 production is mediated by the angiogenic and tumorigenic KSHV-encoded G-protein coupled receptor (vGPCR), we developed a recombinant retrovirus to express vGPCR in Human Umbilical Vascular Endothelial Cells (HUVEC).

Results

In the present study, we show that vGPCR-expressing HUVEC exhibit a spindle-like morphology that is characteristic of KS endothelial cells and demonstrate selective induction of PGE2 and COX-2. By treating vGPCR-expressing HUVEC with selective and non-selective COX inhibitors, we show that vGPCR-induced PGE2 production is dependent on the expression of COX-2 but not COX-1.

Conclusion

Taken together, these results demonstrate that vGPCR induces expression of COX-2 and PGE2 that may mediate the paracrine effects of this key viral protein in KS pathogenesis.
Long-term results of radiotherapy for periarthritis of the shoulder: a retrospective evaluation
Authors: Niewald Marcus , Fleckenstein Jochen , Naumann Susanne , Ruebe Christian
Published: September 2007

Background

To evaluate retrospectively the results of radiotherapy for periarthritis of the shoulder

Methods

In 1983–2004, 141 patients were treated, all had attended at least one follow-up examination. 19% had had pain for several weeks, 66% for months and 14% for years. Shoulder motility was impaired in 137/140 patients. Nearly all patients had taken oral analgesics, 81% had undergone physiotherapy, five patients had been operated on, and six had been irradiated. Radiotherapy was applied using regular anterior-posterior opposing portals and Co-60 gamma rays or 4 MV photons. 89% of the patients received a total dose of 6 Gy (dose/fraction of 1 Gy twice weekly, the others had total doses ranging from 4 to 8 Gy. The patients and the referring doctors were given written questionnaires in order to obtain long-term results. The mean duration of follow-up was 6.9 years [0–20 years].

Results

During the first follow-up examination at the end of radiotherapy 56% of the patients reported pain relief and improvement of motility. After in median 4.5 months the values were 69 and 89%, after 3.9 years 73% and 73%, respectively. There were virtually no side effects. In the questionnaires, 69% of the patients reported pain relief directly after radiotherapy, 31% up to 12 weeks after radiotherapy. 56% of the patients stated that pain relief had lasted for "years", in further 12% at least for "months".

Conclusion

Low-dose radiotherapy for periarthropathy of the shoulder was highly effective and yielded long-lasting improvement of pain and motility without side effects.
Impact of intensive care on renal function before graft harvest: results of a monocentric study
Authors: Blasco Valéry , Leone Marc , Bouvenot Julien , Geissler Alain , Albanèse Jacques , Martin Claude
Published: September 2007

Background

The aim of life-support measures in brain-dead donors is to preserve the functional value of their organs. In renal transplantation, serum creatinine level is one of the criteria for graft harvest. The aim of this study was to assess the impact of intensive care on donor renal function through two criteria: preharvesting serum creatinine level above 120 μmol/L and the elevation of serum creatinine level above 20% between intensive care unit (ICU) admission and graft harvest.

Methods

Between 1 January 1999 and 31 December 2005, we performed an observational study on 143 brain-dead donors. ICU chronology, hemodynamic, hematosis, and treatment data were collected for each patient from ICU admission to kidney removal.

Results

Twenty-two percent of the 143 patients had a serum creatinine level above 120 μmol/L before graft harvest. The independent factors revealed by multivariate analysis were the administration of epinephrine (odds ratio [OR]: 4.36, 95% confidence interval [CI]: 1.33 to 14.32; p = 0.015), oliguria (OR: 3.73, 95% CI: 1.22 to 11.36; p = 0.021), acidosis (OR: 3.26, 95% CI: 1.07 to 9.95; p = 0.038), the occurrence of disseminated intravascular coagulation (OR: 3.97, 95% CI: 1.05 to 15.02; p = 0.042), female gender (OR: 0.13, 95% CI: 0.03 to 0.50; p = 0.003), and the administration of desmopressin (OR: 0.12, 95% CI: 0.03 to 0.44; p = 0.002). The incidence of elevated serum creatinine level above 20% between admission and graft harvest was 41%. The independent risk factors were the duration of brain death greater than 24 hours (OR: 2.64, 95% CI: 1.25 to 5.59; p = 0.011) and the volume of mannitol (OR: 2.08, 95% CI: 1.03 to 4.21; p = 0.041).

Conclusion

This study shows that the resuscitation of brain-dead donors impacts on their renal function. The uses of epinephrine and mannitol are associated with impairment of kidney function. It seems that graft harvest should be performed less than 24 hours after brain death diagnosis.
IL-4 promotes the formation of multinucleated giant cells from macrophage precursors by a STAT6-dependent, homotypic mechanism: contribution of E-cadherin
Authors: Moreno Jose L , Mikhailenko Irina , Tondravi Mehrdad M , Keegan Achsah D
Published: September 2007

Multinucleated giant cells (MNG) are central players in the inflammatory response to foreign materials and in adverse responses to implants. IL-4 promotes the formation of MNG from bone marrow-derived precursors in vitro and participates in the development of the foreign body reaction in vivo. Therefore, we investigated the mechanism by which IL-4 promotes formation of MNG and engulfment of foreign bodies. We found that generation of MNG cells by IL-4 was dependent on cell density and expression of STAT6; macrophages derived from STAT6−/− mice were unable to form MNG in response to IL-4. No soluble factors including CCL2 or supernatants from IL-4-treated macrophages compensated for the lack of MNG cells in STAT6−/− cultures. We found that IL-4 must remain present during the full differentiation process and that STAT6+/+ macrophage precursors retained their ability to differentiate into MNG over time. These MNG were able to internalize large particles efficiently, and the mononuclear STAT6−/− macrophages were unable to do so. Furthermore, we found that IL-4 induced expression of E-cadherin and dendritic cell-specific transmembrane protein in a STAT6-dependent manner. E-cadherin expression was critical for the formation of MNG cells by IL-4; an anti-E-cadherin antibody prevented the formation of large MNG. In addition, we found that STAT6−/− progenitors failed to fuse with STAT6+/+, revealing the need for a homotypic interaction. Thus, IL-4 promotes the formation of MNG in a STAT6-dependent manner by regulating cell surface expression of E-cadherin, leading to homotypic cell fusion and the incorporation of large foreign bodies.
Modulation of dendritic cell differentiation by colony-stimulating factor-1: role of phosphatidylinositol 3′-kinase and delayed caspase activation
Authors: Lo Agnes S , Gorak-Stolinska Patricia , Bachy Véronique , Ibrahim Mohammad A , Kemeny David M , Maher John
Published: September 2007

Monocytes acquire a dendritic cell (DC) phenotype when cultured with GM-CSF and IL-4. By contrast, CSF-1 is a potent inducer of monocyte-to-macrophage differentiation. Increasing evidence indicates that DC development is impaired in conditions characterized by CSF-1 overproduction, including pregnancy, trauma, and diverse malignancies. To study this, we have exposed newly established monocyte-derived DC cultures to conditions of CSF-1 excess. As a consequence, differentiation is skewed toward a unique intermediate phenotype, which we have termed DC-M. Such cells exhibit macrophage-like morphology with impaired allostimulatory capacity, altered cytokine production, and a distinctive cell surface immunophenotype. In light of the emerging role of caspase activation during macrophage differentiation, the activity of caspases 3, 8, and 9 was examined in DC and DC-M cultures. It is striking that DC-M cultures exhibit a delayed and progressive increase in activation of all three caspases, associated with depolarization of mitochondrial membrane potential. Furthermore, when DC-M cultures were supplemented with an inhibitor of caspase 8 or caspase 9, impairment of DC differentiation by CSF-1 was counteracted. To investigate upstream regulators of caspase activation in DC-M cultures, experiments were performed using inhibitors of proximal CSF-1 receptor signaling. These studies demonstrated that the PI-3K inhibitors, wortmannin and LY294002, antagonize the ability of CSF-1 to inhibit DC differentiation and to promote caspase activation. Together, these data identify a novel, PI-3K-dependent pathway by which CSF-1 directs delayed caspase activation in monocytes and thereby modulates DC differentiation.
Transcriptional profiling of human monocytes reveals complex changes in the expression pattern of inflammation-related genes in response to the annexin A1-derived peptide Ac1-25
Authors: Lange Carsten , Starrett Diane J , Goetsch Julia , Gerke Volker , Rescher Ursula
Published: September 2007

Annexin A1 is a glucocorticoid-regulated, anti-inflammatory protein, which plays an important role as an endogenous regulator of the inflammatory response. Many of these anti-inflammatory properties are retained in the N-terminal annexin A1 peptide Ac1-25, which is released from the full-length protein by a neutrophil elastase. To elucidate whether the anti-inflammatory activity of the bioactive peptide is solely a result of immediate post-translational effects, which include the shedding of L-selectin or also involve transcriptional changes affecting leukocyte function, we recorded global gene expression changes in human monocytes stimulated with exogenously applied Ac1-25. Applying stringent selection criteria, we show that ∼100 genes are up-regulated, and ∼230 are down-regulated by a factor of at least two in the Ac1-25-treated monocytes. It is important that the profiling reveals that Ac1-25 induces an anti-inflammatory phenotype by down-regulating proinflammatory and up-regulating anti-inflammatory mediators. These effects, elicited by exogenously applied Ac1-25, depend, to different extents, on ERK1/2 and p38 signaling pathways. This identifies the annexin A1 N-terminal peptide as a stimulus, eliciting not only short-term, post-translational effects in human monocytes but also transcriptional changes, defining a more anti-inflammatory profile.
Disease-modifying capability of murine Flt3-ligand DCs in experimental autoimmune encephalomyelitis
Authors: Papenfuss Tracey L , Kithcart Aaron P , Powell Nicole D , McClain Melanie A , Gienapp Ingrid E , Shawler Todd M , Whitacre Caroline C
Published: September 2007

Dendritic cells (DCs) bridge the innate and adaptive immune response, are uniquely capable of priming naïve T cells, and play a critical role in the initiation and regulation of autoimmune and immune-mediated disease. At present, in vivo expansion of DC populations is accomplished primarily through the administration of the recombinant human growth factor fms-like tyrosine kinase 3 ligand (hFL), and in vitro DCs are generated using cytokine cocktails containing GM-CSF ± IL-4. Although hFL has traditionally been used in mice, differences in amino acid sequence and biological activity exist between murine FL (mFL) and hFL, and resultant DC populations differ in phenotype and immunoregulatory functional capabilities. This study developed and characterized mFL-generated DCs and determined the therapeutic capability of mFL DCs in the autoimmune disease experimental autoimmune encephalomyelitis (EAE). Our findings demonstrate that mFL and hFL expand splenic DCs equally in vivo but that mFL-expanded, splenic DCs more closely resemble normal, resting, splenic DCs. In addition, a novel method for generating mFL-derived bone marrow-derived DCs (BM-DCs) was developed, and comparison of mFL with hFL BM-DCs found mFL BM-DCs to be less mature (i.e., lower MHC Class II, CD80, and CD86) than hFL BM-DCs. These immature mFL DCs up-regulated costimulatory molecules in response to maturation stimuli LPS and TNF-α. Mature mFL BM-DCs were immunogenic and exacerbated the clinical disease course of EAE.