bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical Devices in Orthopedic Applications
Authors: Long Philip H.
Published: March 2008

Orthopedic medical devices have been extremely successful in restoring mobility, reducing pain, and improving the quality of life for millions of individuals each year. Their success is reflected in the worldwide biomaterials market, in which orthopedic devices dominated sales at approximately $14 billion in 2002. Of this, approximately $12 billion was spent on joint replacements. In spite of their overwhelming benefits and successes, orthopedic medical devices are not without risk of adverse effects. Most adverse joint replacement outcomes are thought to be mediated by degradation products generated by wear and electrochemical corrosion. Infection and flaws in device manufacturing are other noteworthy causes of orthopedic device failure. This article illustrates and discusses the uses, general properties, and limitations (including adverse outcomes) of orthopedic biomaterials, which are fundamental to understanding requirements for improving current orthopedic medical devices.
Pharmacodynamic Monitoring of Molecular-Targeted Agents in the Peripheral Blood of Leukemia Patients Using Flow Cytometry
Authors: Hedley David W. , Chow Sue , Goolsby Charles , Shankey T. Vincent
Published: March 2008

The introduction of specific, molecular-targeted drugs is radically changing cancer treatment. Pharmacodynamics, which measures drug effects on the host, is key during early-phase clinical trials of novel agents to determine the relations between drug dose and target inhibition as well as measure the downstream effects of target inhibition on the cancer. In this article, we describe the application of flow cytometry to the pharmacodynamic monitoring of molecular-targeted agents in leukemia patients. The methods are based on current clinical flow-cytometry applications, with the addition of phosphospecific antibodies to measure the activation states of intracellular signaling elements and the introduction of techniques that maintain drug–target equilibrium during sample preparation. Using this approach, we successfully showed dose-dependent inhibition of c-Kit during a phase I clinical trial treating acute leukemia patients with the novel agent sorafenib. Further refinements identify considerable interpatient variation in signaling activity within leukemic blast populations, suggesting that an individualized approach to treatment based on flow cytometric monitoring might be advantageous. Improvements in sample turnaround offer the potential to introduce real-time pharmacodynamic monitoring during early-phase clinical trials.
Preparation of Medical Devices for Evaluation
Authors: Rousselle Serge , Wicks Joan
Published: March 2008

Preparing and processing medical device implants for evaluation is a relatively high-risk and high-dollar process in which studies get made and endpoints can be lost with no second chance. It is important to customize every aspect of the preparation process to the type of device and the study endpoints. Some standard and proven approaches for a few types of implants are discussed, addressing fixation, special dissection and extraction techniques, preprocessing imaging, trimming techniques, sample processing, embedding media, and cutting and staining options.
Applications of Laser Scanning Cytometry in Immunohistochemistry and Routine Histopathology
Authors: Peterson Richard A. , Krull David L. , Butler Leroy
Published: March 2008

Laser scanning cytometry (LSC) is a powerful tool for qualitative and quantitative analysis of tissue sections in preclinical drug development. LSC combines the strengths of flow cytometry with tissue architecture retention. This technology has been used predominantly with immunofluorescent techniques on cell culture and tissue sections, but recently LSC has shown promise in evaluating chromogenic immunohistochemistry (IHC) and histochemical products in paraffin-embedded and/or frozen tissue sections. Inverted light scatter measurements or a combination of inverted scatter and fluorescence allows automated determination of cell/nuclear counts (e.g., proliferation labeling indices), cell area (e.g., cellular hypertrophy), stromal elements, and labeling intensity (e.g., cytoplasmic/organellar proteins) in chromogen-labeled IHC or histochemical stained sections that correlates well with standard manual quantification methods. Segmentation with autofluorescence or dual immunolabeling facilitates capture of labeling data from specific cell populations. LSC evaluation of HE-stained sections is accomplished using autofluorescence/eosin fluorescence and inverse scatter. A standardized fluorescent approach with archivability, a lack of fluorescence quenching (photobleaching), and amenability to evaluation of multiple markers in a section has been demonstrated using Qdot® nanocrystals. Examples of LSC use in chromogenic IHC, routine histopathology, and Qdot® labeling will be reviewed, and advantages and disadvantages of this technology will be discussed.
An Approach to Achieve Long-Term Expression in Skin Gene Therapy
Authors: Therrien Jean-Philippe , Pfützner Wolfgang , Vogel Jonathan C.
Published: March 2008

For gene therapy purposes, the skin is an attractive organ to target for systemic delivery of therapeutic proteins to treat systemic diseases, skin diseases, or skin cancer. To achieve long-term stable expression of a therapeutic gene in keratinocytes (KC), we have developed an approach using a bicistronic retroviral vector expressing the desired therapeutic gene linked to a selectable marker (multidrug resistant gene, MDR) that is then introduced into KC and fibroblasts (FB) to create genetically modified human skin equivalent (HSE). After grafting the HSE onto immunocompromised mice, topical colchicine treatment is used to select and enrich for genetically modified keratinocyte stem cells (KSC) that express MDR and are resistant to colchicine’s antimitotic effects. Both the apparatus for topical colchicine delivery and the colchicine doses have been optimized for application to human skin. This approach can be validated by systemic delivery of therapeutic factors such as erythropoietin and the antihypertensive atrial natriuretic peptide.
The Truncation-by-Death Problem
Authors: McConnell Sheena , Stuart Elizabeth A. , Devaney Barbara
Published: March 2008

Although experiments are viewed as the gold standard for evaluation, some of their benefits may be lost when, as is common, outcomes are not defined for some sample members. In evaluations of marriage interventions, for example, a key outcome—relationship quality—is undefined when a couple splits up. This article shows how treatment-control differences in mean outcomes can be misleading when outcomes are not defined for everyone and discusses ways to identify the seriousness of the problem. Potential solutions to the problem are described, including approaches that rely on simple treatment-control differences-in-means as well as more complex modeling approaches.
Mixed Results in a Transitional Planning Program for Alternative School Students
Authors: Wolf Elaine M. , Wolf Douglas A.
Published: March 2008

Disciplinary alternative schools have a reputation as gateways to the juvenile and criminal justice systems. The authors conducted an evaluation of an intervention (Strategies for Success) designed to divert seventh-, eighth-, and ninth-grade alternative school students from this gateway. They used propensity score matching and a multivariate random effects model to estimate program impacts and found that the program not only increased attendance rates, at least in the short term, but also increased the likelihood of reassignment to alternative schools. The discussion focuses on possible reasons and solutions for high rates of return to alternative school and for the erosion of program effects.
On the Path to Mediation
Authors: James Lawrence R.
Published: March 2008

A commentary on mediation is presented. The commentary begins with a brief history of the author's interest in mediation. This is followed by some ideas about why there continues to be interest among organizational researchers in mediation. Last, comments are offered on the articles that are the center of attraction.
Gender—a Crucial Neglected Element in the Service Encounter: An Exploratory Study of the Choice of Hotel Masseur or Masseuse
Authors: Poria Yaniv
Published: March 2008

This exploratory study examines consumer preferences for a masseur or masseuse, using qualitative interviews of 52 participants. The findings suggest that gender preferences and the meanings assigned to the consumption experience, a massage, are linked with elements, including (a) the main purpose of the massage, (b) customer gender, (c) massage type, (d) companion to massage, (e) stereotypes of masseur/masseuse, and (f) readiness to be exposed to and touched by a nonfamiliar person of the opposite sex. Findings indicate that preferences are linked to the gender of both the customer and the service provider. It appears that massage is governed by social norms in a male-dominated society. In addition, the perception of the experience as either a health treatment or leisure experience is linked to the legitimacy of preferences for a masseur or masseuse. Implications for hotel management and researchers are suggested, highlighting the interaction between genders in tourism service encounters.
Portuguese Charter Tourists to Long-Haul Destinations: A Travel Motive Segmentation
Authors: Correia Antónia , Silva João Albino , Moço Cláudia
Published: March 2008

This article presents an empirical study of tourist segmentation based on motivations. The present study, exploratory by nature, aims to provide a deeper insight into profiles of Portuguese tourists traveling to Latin American and African destinations. The research was conducted with 1,097 tourists traveling on Air Luxor to long-haul destinations, by means of factor-cluster analysis, followed by a discriminant and a homals analysis. Three market segments were found: adventure, leisure, and social tourism. The research reveals that each of these segments presents a different profile in terms of motivations and in terms of vacation patterns. However, in terms of sociodemographic characteristics, the differences are not so evident. The managerial implications of these findings are highlighted.
The Interactive Effect of Market Competition and Use of MAS Information on Performance: Evidence From the Upscale Hotels
Authors: Patiar Anoop , Mia Lokman
Published: March 2008

This study examined the combined effect of market competition and managers'use of the information (provided by management accounting system, or MAS) on departmental performance in four- and five-star hotels and resorts in Australia. A self-administered postal survey was used to collect the data from Room Department and Food and Beverage Department managers working in large hotels and resorts. Usable questionnaires from 112 department managers working in 56 large hotels and resorts were received. Although the results reveal a significant combined (interaction) effect of market competition and managers' use of the information (provided by MAS) on nonfinancial performance, no such effect was found for the financial performance. In addition, the results indicated that controlling for different demographic variables did not alter the results for nonfinancial and financial performance.
Examination of Various Financial Risk Measures for Lodging Firms
Authors: Lee Seoki
Published: March 2008

Financial researchers, including those concentrating on the lodging industry, use various financial risk measures for their studies. Examples of those risk measures are beta, earnings variability, bankruptcy probability, debt-to-equity ratio and book-to-market ratio. The purpose of this study is, first, to descriptively investigate various financial risk measures used in the lodging financial literature by performing factor analysis and identifying four distinct risk groups. Second, this study examines the predictive ability of the four risk groups for lodging firm performance. The findings of this study suggest that strategic and stock performance risk factors better represent a lodging firm's financial risk than do bankruptcy and firm performance risk factors, and also, ROA than ROE better estimates lodging firm performance in terms of their relationships with financial risk factors.
Weaving relational webs
Authors: Pedwell Carolyn
Published: March 2008

Through illustrating the similarities between embodied practices rooted in different cultural contexts (such as `African' female genital cutting and `Western' cosmetic surgery), feminist theorists seek to reveal the instability of essentialist binaries which distinguish various groups as culturally, ethnically and morally `different'. They also aim to query how the term `culture' is employed differentially on the basis of embodied axes such as race and nation. However, in emphasizing overarching commonalities between practices, feminist cross-cultural comparisons risk collapsing into economies of sameness that elide the complex relations of power through which such practices have been constituted. They can also fix the imagined subjects of these practices in troubling ways. Using the ubiquitous `African' female genital cutting and `Western' cosmetic surgery binary as an example, this article explores the difference it might make to address culturally essentialist constructions of embodied practice with a focus on relationality rather than commonality. As a means to reorient feminist cross-cultural approaches which depend on assertions of similarity or sameness, it argues for the theoretical and pedagogical utility of thinking through relational webs.
Narrative as a site of subject construction
Authors: Kimura Maki
Published: March 2008

The ordeal of `Comfort Women' who were sexually enslaved by the Japanese Imperial Military during the Second World War became widely known in the 1990s through these women's accounts of their experience. Instead of considering their narratives as historical data which reflect the `true' historical past, this article locates them within a broader framework of thinking of narratives. Drawing on the understanding of narrative as a key to the self and the subject which has been developed in narrative research, as well as Judith Butler on interpellation and Gayatri Chakravorty Spivak on subaltern agency, this article argues that the `Comfort Women's' testimonies should not be read one-dimensionally in the light of `truth' and `falsity', but should rather be considered as the site of their subject-formation. Their narratives are where agency concurrently emerges, and `Comfort Women' are thus not powerless victims but are active participants in their creation of their own narratives and their own selves.
`Showing the girl'
Authors: Ferreday Debra
Published: March 2008

This paper examines the cultural phenomenon of `new burlesque', a subculture in which young women take part in striptease performances which invoke the iconic styles and routines associated with mid-20th century cabaret. By reading burlesque websites alongside the celebrity culture and advertising, the article examines how the retro styles of dress and make-up associated with this subculture have circulated through a range of media sites as an alternative mode of femininity. By focusing on the intersections between online fan communities, popular images of burlesque, fashion, and beauty, I argue that burlesque styles involve a reclaiming of traditionally normative sites of identity production and that computer technologies are an extension of the technologies of dress, cosmetics and movements through which femininity is produced. I go on to suggest a re-framing of burlesque as a site of parody and resistance which `troubles' critiques of femininity within both feminist theory and queer theory.
Intersectionality as buzzword
Authors: Davis Kathy
Published: March 2008

Since its inception, the concept of `intersectionality' — the interaction of multiple identities and experiences of exclusion and subordination — has been heralded as one of the most important contributions to feminist scholarship. Despite its popularity, there has been considerable confusion concerning what the concept actually means and how it can or should be applied in feminist inquiry. In this article, I look at the phenomenon of intersectionality's spectacular success within contemporary feminist scholarship, as well as the uncertainties and confusion which it has generated. Drawing upon insights from the sociology of science, I shall show how and why intersectionality could become a feminist success story. I shall argue that, paradoxically, it is precisely the concept's alleged weaknesses — its ambiguity and open-endedness — that were the secrets to its success and, more generally, make it a good feminist theory.
Using radar charts with qualitative evaluation
Authors: Kaczynski Dan , Wood Leigh , Harding Ansie
Published: March 2008

When university academics implement changes in learning, such as introducing blended learning, it is conventional practice to examine and evaluate the impact of the resulting curriculum reform. Judging the worth and impact of an educational development is a complex task involving subtle differences in learning. Qualitative methods to explore these deep processes in learning include using interviews, observations and open-ended questionnaires targeting all stakeholders in the process, such as students, teachers, administration and technical staff. These evaluation tasks generate a mass of raw data that many faculty members in higher education are unaccustomed to analyzing. This article provides a framework using radar charts adapted from the field of organizational development. A modified six-zone radar chart was used to assess the extent of blended learning in order to compare changes in the learning environment. Data collection included interviews, classroom observations and electronic records generated during educational delivery over a 1-year period of time. A purposeful sample of online course data was collected by three participating universities in South Africa, Australia, and the United States.
An investigation of differences in undergraduates' academic use of the internet
Authors: Selwyn Neil
Published: March 2008

Based on survey data from 1222 undergraduate students studying at UK higher education institutions, this article addresses students' engagement with the internet as a source of academic information for their studies. In particular the article explores how academic use of the internet is patterned by a range of potential influences such as students' wider internet use, access and expertise, their year of study, gender, age, ethnic and educational background. Analysis of these data suggests that students' academic internet use is most strongly patterned along the lines of gender and subject-specialism rather than other individual characteristics or differences in technology access or expertise. The article therefore considers how these differences can be addressed by those seeking to encourage ICT-based learning across all sectors of the undergraduate population.
A workshop activity to demonstrate that approaches to learning are influenced by the teaching and learning environment
Authors: Kember David , Leung Doris Y.P. , McNaught Carmel
Published: March 2008

It is important to demonstrate to those taking courses for new teachers that approaches to learning have a relational nature — that they are influenced by the teaching and learning context. This article describes a workshop activity, based on the Revised Study Process Questionnaire. Workshop participants recorded their approaches to learning in two contexts: how they currently studied as postgraduate students, and how they studied in their most disliked undergraduate course. Analysis of the results from this activity indicates that approaches to learning are markedly influenced by the teaching and learning environment. This provides a graphic demonstration to workshop participants of the importance of their teaching, as it will have a strong influence on the quality of learning of their students. The data from the activity give quantitative evidence of the relational nature of approaches to learning. Further, there appears to be a discipline effect operating with the nature of the typical teaching and learning environment in the arts, humanities and social sciences being more conducive to students cultivating a deep approach to learning.
Are students using the 'wrong' style of learning?
Authors: Valiente Carolina
Published: March 2008

The literature on learning styles suggests that although the behaviour of some students may appear different from what is defined as a `high-quality learning process', their conduct does not demonstrate an `inferior' approach to learning. Furthermore, existing and emerging academic literature that associates learning theories with the studies of cultural concerns suggests alternative interpretations that may help to develop a richer multicultural learning and teaching approach within Western higher education institutions (HE). This article brings together elements of the theory on learning styles and some elements of multicultural management theory to introduce interpretations that may apply to the emerging UK multicultural universities. It considers the importance of memorization as a tool for learning, and reveals how motivation, communication and collaborative patterns could work differently in different cultures. The comparison between best known Western learning theory and Confucian principles is expected to increase academics' awareness of international students' background. The discussion helps to understand some of the students' pragmatic reactions to the challenges prompted by their studies in foreign countries.
Integrating progress files into the academic process
Authors: Haigh Jackie
Published: March 2008

A literature review of published case studies reporting progress file implementation was conducted with the intent of discovering how this is being interpreted and implemented in higher education institutions. The three studies found were analysed using an ideal type categorization developed by Clegg and Bradley (2006), that is, professional, academic or employment. All three case studies are examples of academics learning through experience about the process of personal development planning and how this integrates with current educational provision. As this is not a static process, an activity theory perspective may be a more useful framework to research how this understanding develops in a particular context. Currently the progress file is a contested object, which has not yet fulfilled its potential to place the student and their individual learning needs at the centre of the educational process.
Monitoring Multi-Site Damage Growth During Quasi-Static Testing of a Wind Turbine Blade using a Structural Neural System
Authors: Kirikera Goutham R. , Shinde Vishal , Schulz Mark J. , Sundaresan Mannur J. , Hughes Scott , van Dam Jeroen , Nkrumah Francis , Grandhi Gangadhar , Ghoshal Anindya
Published: March 2008

Structural Health Monitoring (SHM) of a wind turbine blade using a Structural Neural System (SNS) is described in this paper. Wind turbine blades are composite structures with complex geometry and sections that are built of different materials. The 3D structure, large size, anisotropic material properties, and the potential for damage to occur anywhere on the blade makes damage detection a significant challenge. A SNS based on acoustic emission (AE) monitoring (passive listening) was developed for practical low cost SHM of large composite structures such as wind turbine blades. The SNS was tested to detect damage initiation and propagation on a 9 m long wind turbine blade during a quasi-static proof test to failure at the National Renewable Energy Laboratory test facility in Golden, Colorado. Twelve piezoelectric sensors were bonded on the surface of the wind turbine blade and connected to form four continuous sensors which were used in the SNS to determine damage locations. Although 12 sensors monitored the wind turbine blade, the SNS produces only two analog output signals; one time signal to determine and locate damage, and a second time signal containing combined AE waveforms. Testing of the wind turbine blade produced some interesting results. After initial emissions due to settling of the blade diminished, damage initiated at one location on the blade. As the load was increased, damage occurred in a sequence at three other locations until there was a catastrophic buckling failure of the blade. The buckling occurred above the design load for the blade, and was due to the carbon spar cap disbonding from the fiberglass shear web under compressive bending stress. The SNS indicated the general area where the damage started and how the damage progressed, which is valuable information for verifying and improving the blade design and the manufacturing procedure. Strain gages on the blade did not provide a clear indication of damage until buckling occurred. A major outcome of this testing was to provide confidence that SHM of large composite structures that have complex geometry and multiple materials is practical using a simple, low cost SNS.
Testing a Tool to Scale Quality of Life Indicators in Tanzania
Authors: Schwarzwalder Alison , Chilangwa Zephania , Patel Ilesh , Burke Andrew , Lynch Matthew
Published: March 2008

A quality of life questionnaire utilizing scaled response codes is created for implementation in a predominantly rural African setting. The authors design a concrete tool using color as a semantic differential as a means to ease semantic shifts and enhance participant comprehension. Although they find a fairly even response distribution and no significant clustering among a sample of questions for which the tool is used, their interviewers report that some groups have more difficulty than others and suggest alternative or complementary approaches. This article describes the authors' experience with the utility of their tool within the parameters of this study.
High-Sensitivity CRP Is Correlated With Neurologic Symptoms and Plaque Instability in Patients With Severe Stenosis of the Carotid Bifurcation
Authors: Papas Theophanis T. , Maltezos Chrysostomos K. , Papanas Nikolaos , Kopadis Georgios , Marakis Joseph , Maltezos Efstratios , Bastounis Elias
Published: March 2008

The aim of this study is to investigate the correlation of high-sensitivity C-reactive protein and E-selectin with clinical manifestations and plaque characteristics in 88 patients (69 with and 19 without neurological symptoms) with high-grade stenosis of the carotid bifurcation who underwent endarterectomy. The grade of stenosis was quantified by duplex ultrasonography and digital subtraction angiography. Preoperatively, serum high-sensitivity C-reactive protein and E-selectin were measured. Postoperatively, carotid plaque morphology was established according to the American Heart Association classification. High-sensitivity C-reactive protein levels were significantly ( P < .001) higher in symptomatic than in asymptomatic patients, as well as in patients with unstable compared with those with stable plaques ( P < .001). Serum high-sensitivity C-reactive protein levels correlated significantly ( P < .05) with macrophage count on the plaque. In conclusion, serum high-sensitivity C-reactive protein levels are associated with presence of neurological symptoms and plaque instability in patients with high-grade stenosis of the carotid bifurcation.
Endovascular Management of an Arteriovenous Fistula and Concomitant Pseudoaneurysm in an Intravenous Drug Abuser
Authors: Sadat Umar , Noor Nadim , See Teikchoon C. , Hayes Paul D.
Published: March 2008

An interesting case of an intravenous drug abuser who had endovascular management of an arteriovenous fistula and concomitant pseudoaneurysm, resulting from recurrent puncture of the femoral artery is reported in this study.
Transnational circulation of Chinese language television dramas
Authors: Ying Zhu
Published: March 2008

In the late 1990s, a wave of dynasty drama serials began to dominate primetime dramatic programming in People's Republic of China (PRC) television, which soon created a viewing frenzy among Chinese audiences around the world. Together with Taiwan's idol drama and Hong Kong's martial arts sagas and contemporary social mobility dramas, by the early 2000s, PRC's dynasty drama had saturated a pan-Chinese media market. Using transnational dramas from the three Chinese language media production centers as a springboard, this article explores two issues concerning the global circulation of Chinese language television dramas: the forces conducive to their transnational circulation and its cultural and economic impact. It utilizes the framework of the `cultural-linguistic market' to analyze the factors enabling the formation of a Chinese cultural-linguistic media and the products viable for the market. It further entertains the question of how the emergence of a Chinese cultural-linguistic market, together with other cultural-linguistic markets, complicates the power dynamic of global cultural flow.
Dual targeting of the proteasome regulates survival and homing in Waldenström macroglobulinemia
Authors: Roccaro Aldo M. , Leleu Xavier , Sacco Antonio , Jia Xiaoying , Melhem Molly , Moreau Anne-Sophie , Ngo Hai T. , Runnels Judith , Azab Abdelkareem , Azab Feda , Burwick Nicholas , Farag Mena , Treon Steven P. , Palladino Michael A. , Hideshima Teru , Chauhan Dharminder , Anderson Kenneth C. , Ghobrial Irene M.
Published: March 2008

Waldenström macroglobulinemia (WM) is an incurable low-grade B-cell lymphoma characterized by high protein turnover. We dissected the biologic role of the proteasome in WM using 2 proteasome inhibitors, NPI-0052 and bortezomib. We found that NPI-0052 inhibited proliferation and induced apoptosis in WM cells, and that the combination of NPI-0052 and bortezomib induced synergistic cytotoxicity in WM cells, leading to inhibition of nuclear translocation of p65NF-κB and synergistic induction of caspases-3, -8, and -9 and PARP cleavage. These 2 agents inhibited the canonical and noncanonical NF-κB pathways and acted synergistically through their differential effect on Akt activity and on chymotrypsin-like, caspaselike, and trypsinlike activities of the proteasome. We demonstrated that NPI-0052–induced cytotoxicity was completely abrogated in an Akt knockdown cell line, indicating that its major activity is mediated through the Akt pathway. Moreover, we demonstrated that NPI-0052 and bortezomib inhibited migration and adhesion in vitro and homing of WM cells in vivo, and overcame resistance induced by mesenchymal cells or by the addition of interleukin-6 in a coculture in vitro system. Theses studies enhance our understanding of the biologic role of the proteasome pathway in WM, and provide the preclinical basis for clinical trials of combinations of proteasome inhibitors in WM.
Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia
Authors: Stegenga Michiel E. , van der Crabben Saskia N. , Blümer Regje M. E. , Levi Marcel , Meijers Joost C. M. , Serlie Mireille J. , Tanck Michael W. T. , Sauerwein Hans P. , van der Poll Tom
Published: March 2008

Type 2 diabetes is associated with altered immune and hemostatic responses. We investigated the selective effects of hyperglycemia and hyperinsulinemia on innate immune, coagulation, and fibrinolytic responses during systemic inflammation. Twenty-four healthy humans were studied for 8 hours during clamp experiments in which either plasma glucose, insulin, both, or none was increased, depending on randomization. Target plasma concentrations were 5 versus 12 mM for glucose, and 100 versus 400 pmol/L for insulin. After 3 hours, 4 ng/kg Escherichia coli endotoxin was injected intravenously to induce a systemic inflammatory and procoagulant response. Endotoxin administration induced cytokine release, activation of neutrophils, endothelium and coagulation, and inhibition of fibrinolysis. Hyperglycemia reduced neutrophil degranulation (plasma elastase levels, P < .001) and exaggerated coagulation (plasma concentrations of thrombin-antithrombin complexes and soluble tissue factor, both P < .001). Hyperinsulinemia attenuated fibrinolytic activity due to elevated plasminogen activator-inhibitor-1 levels (P < .001). Endothelial cell activation markers and cytokine concentrations did not differ between clamps. We conclude that in humans with systemic inflammation induced by intravenous endotoxin administration hyperglycemia impairs neutrophil degranulation and potentiates coagulation, whereas hyperinsulinemia inhibits fibrinolysis. These data suggest that type 2 diabetes patients may be especially vulnerable to prothrombotic events during inflammatory states.
The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells
Authors: Mamani-Matsuda Maria , Cosma Antonio , Weller Sandra , Faili Ahmad , Staib Caroline , Garçon Loïc , Hermine Olivier , Beyne-Rauzy Odile , Fieschi Claire , Pers Jacques-Olivier , Arakelyan Nina , Varet Bruno , Sauvanet Alain , Berger Anne , Paye François , Andrieu Jean-Marie , Michel Marc , Godeau Bertrand , Buffet Pierre , Reynaud Claude-Agnès , Weill Jean-Claude
Published: March 2008

The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG+ cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG+ cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG+ B cells in blood (ie, 50-100 000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell– depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory—long-lived memory B cells and plasma cells—have specific anatomic distributions—spleen and bone marrow—and homeostatic regulation.
A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils
Authors: Munitz Ariel , McBride Melissa L. , Bernstein Joshua S. , Rothenberg Marc E.
Published: March 2008

The accumulation of eosinophils in inflammatory foci is a hallmark characteristic of Th2 inflammation. Nevertheless, the expression of inhibitory receptors such as paired immunoglobulin-like receptor B (PIR-B) and their function regulating eosinophil accumulation have received limited attention. We now report that Pirb was up-regulated in an eosinophil-dependent manner in the lungs of allergen-challenged and interleukin (IL)-13–overexpressing mice. Eosinophils expressed high levels of PIR-B, and Pirb−/− mice displayed increased gastrointestinal eosinophils. Consistent with these findings, PIR-B negatively regulated eotaxin-dependent eosinophil chemotaxis in vivo and in vitro. Surprisingly, Pirb−/− eosinophils and neutrophils had decreased leukotriene B4 (LTB4)–dependent chemotactic responses in vitro. Furthermore, eosinophil accumulation was decreased in a chitin-induced model, partially dependent on LTB4. Mechanistic analysis using a miniphosphoproteomic approach revealed that PIR-B recruits activating kinases after LTB4 but not eotaxin stimulation. Consequently, eotaxin-activated Pirb−/− eosinophils displayed markedly increased extracellular signal-related kinase 1 and 2 (ERK1/2) phosphorylation, whereas LTB4-activated eosinophils had reduced ERK1/2 phosphorylation. We provide multiple lines of evidence supporting a model in which PIR-B displays opposing but potent regulatory functions in granulocyte activation. These data change the conventional wisdom that inhibitory receptors are restricted to inhibitory signals; we therefore propose that a single receptor can have dual functionality in distinct cell types after unique cellular signals.
ProLoc-GO: Utilizing informative Gene Ontology terms for sequence-based prediction of protein subcellular localization
Authors: Huang Wen-Lin , Tung Chun-Wei , Ho Shih-Wen , Hwang Shiow-Fen , Ho Shinn-Ying
Published: March 2008

Background

Gene Ontology (GO) annotation, which describes the function of genes and gene products across species, has recently been used to predict protein subcellular and subnuclear localization. Existing GO-based prediction methods for protein subcellular localization use the known accession numbers of query proteins to obtain their annotated GO terms. An accurate prediction method for predicting subcellular localization of novel proteins without known accession numbers, using only the input sequence, is worth developing.

Results

This study proposes an efficient sequence-based method (named ProLoc-GO) by mining informative GO terms for predicting protein subcellular localization. For each protein, BLAST is used to obtain a homology with a known accession number to the protein for retrieving the GO annotation. A large numbernof all annotated GO terms that have ever appeared are then obtained from a large set of training proteins. A novel genetic algorithm based method (named GOmining) combined with a classifier of support vector machine (SVM) is proposed to simultaneously identify a small numbermout of thenGO terms as input features to SVM, wherem<<n. Theminformative GO terms contain the essential GO terms annotating subcellular compartments such as GO:0005634 (Nucleus), GO:0005737 (Cytoplasm) and GO:0005856 (Cytoskeleton). Two existing data sets SCL12 (human protein with 12 locations) and SCL16 (Eukaryotic proteins with 16 locations) with <25% sequence identity are used to evaluate ProLoc-GO which has been implemented by using a single SVM classifier with them= 44 andm= 60 informative GO terms, respectively. ProLoc-GO using input sequences yields test accuracies of 88.1% and 83.3% for SCL12 and SCL16, respectively, which are significantly better than the SVM-based methods, which achieve < 35% test accuracies using amino acid composition (AAC) with acid pairs and AAC with dipedtide composition. For comparison, ProLoc-GO using known accession numbers of query proteins yields test accuracies of 90.6% and 85.7%, which is also better than Hum-PLoc (85.0%) and Euk-OET-PLoc (83.7%) using ensemble classifiers with hybridization of GO terms and amphiphilic pseudo amino acid composition for SCL12 and SCL16, respectively.

Conclusion

The growth of Gene Ontology in size and popularity has increased the effectiveness of GO-based features. GOmining can serve as a tool for selecting informative GO terms in solving sequence-based prediction problems. The prediction system using ProLoc-GO with input sequences of query proteins for protein subcellular localization has been implemented (see Availability).
Comprehensive transcriptional profiling of prion infection in mouse models reveals networks of responsive genes
Authors: Sorensen Garrett , Medina Sarah , Parchaliuk Debra , Phillipson Clark , Robertson Catherine , Booth Stephanie A
Published: March 2008

Background

Prion infection results in progressive neurodegeneration of the central nervous system invariably resulting in death. The pathological effects of prion diseases in the brain are morphologically well defined, such as gliosis, vacuolation, and the accumulation of disease-specific protease-resistant prion protein (PrPSc). However, the underlying molecular events that lead to the death of neurons are poorly characterised.

Results

In this study cDNA microarrays were used to profile gene expression changes in the brains of two different strains of mice infected with three strains of mouse-adapted scrapie. Extensive data was collected and analyzed, from which we identified a core group of 349 prion-related genes (PRGs) that consistently showed altered expression in mouse models. Gene ontology analysis assigned many of the up-regulated genes to functional groups associated with one of the primary neuropathological features of prion diseases, astrocytosis and gliosis; protein synthesis, inflammation, cell proliferation and lipid metabolism. Using a computational tool, Ingenuity Pathway Analysis (IPA), we were able to build networks of interacting genes from the PRG list. The regulatory cytokine TGFB1, involved in modulating the inflammatory response, was identified as the outstanding interaction partner for many of the PRGs. The majority of genes expressed in neurons were down-regulated; a number of these were involved in regulatory pathways including synapse function, calcium signalling, long-term potentiation and ERK/MAPK signalling. Two down-regulated genes coding for the transcription regulators, EGR1 and CREB1, were also identified as central to interacting networks of genes; these factors are often used as markers of neuronal activity and their deregulation could be key to loss of neuronal function.

Conclusion

These data provides a comprehensive list of genes that are consistently differentially expressed in multiple scrapie infected mouse models. Building networks of interactions between these genes provides a means to understand the complex interplay in the brain during neurodegeneration. Resolving the key regulatory and signaling events that underlie prion pathogenesis will provide targets for the design of novel therapies and the elucidation of biomarkers.
Arsenic-induced changes in the gene expression of lung epithelial L2 cells: implications in carcinogenesis
Authors: Posey Tisha , Weng Tingting , Chen Zhongming , Chintagari Narendranath R , Wang Pengcheng , Jin Nili , Stricker Heidi , Liu Lin
Published: March 2008

Background

Arsenic is a carcinogen that is known to induce cell transformation and tumor formation. Although studies have been performed to examine the modulation of signaling molecules caused by arsenic exposure, the molecular mechanisms by which arsenic causes cancer are still unclear. We hypothesized that arsenic alters gene expression leading to carcinogenesis in the lung.

Results

In this study, we examined global gene expression in response to 0.75 μM arsenic treatment for 1–7 days in a rat lung epithelial cell line (L2) using an in-house 10 k rat DNA microarray. One hundred thirty one genes were identified using the one-class statistical analysis of microarray (SAM) test. Of them, 33 genes had a fold change of ≥ 2 between at least two time points. These genes were then clustered into 5 groups using K-means cluster analysis based on their expression patterns. Seven selected genes, all associated with cancer, were confirmed by real-time PCR. These genes have functions directly or indirectly related to metabolism, glycolysis, cell proliferation and differentiation, and regulation of transcription.

Conclusion

Our findings provide important insight for the future studies of arsenic-mediated lung cancer.
Antidepressant drugs modulate growth factors in cultured cells
Authors: Henkel Andreas W , Sperling Wolfgang , Rotter Andrea , Reulbach Udo , Reichardt Cornelia , Bönsch Dominikus , Maler Juan M , Kornhuber Johannes , Wiltfang Jens
Published: March 2008

Background

Different classes of antidepressant drugs are used as a treatment for depression by activating the catecholinergic system. In addition, depression has been associated with decrease of growth factors, which causes insufficient axonal sprouting and reduced neuronal damage repair. In this study, antidepressant treatments are analyzed in a cell culture system, to study the modulation of growth factors.

Results

We quantified the transcription of several growth factors in three cell lines after application of antidepressant drugs by real time polymerase chain reaction. Antidepressant drugs counteracted against phorbolester-induced deregulation of growth factors in PMA-differentiated neuronal SY5Y cells. We also found indications in a pilot experiment that magnetic stimulation could possibly modify BDNF in the cell culture system.

Conclusion

The antidepressant effects antidepressant drugs might be explained by selective modulation of growth factors, which subsequently affects neuronal plasticity.
Rice Yellow Mottle Virus stress responsive genes from susceptible and tolerant rice genotypes
Authors: Ventelon-Debout Marjolaine , Tranchant-Dubreuil Christine , Nguyen Thi-Thu-Huang , Bangratz Martine , Siré Christelle , Delseny Michel , Brugidou Christophe
Published: March 2008

Background

The effects of viral infection involve concomitant plant gene variations and cellular changes. A simple system is required to assess the complexity of host responses to viral infection. The genome of the Rice yellow mottle virus (RYMV) is a single-stranded RNA with a simple organisation. It is the most well-known monocotyledon virus model. Several studies on its biology, structure and phylogeography have provided a suitable background for further genetic studies. 12 rice chromosome sequences are now available and provide strong support for genomic studies, particularly physical mapping and gene identification.

Results

The present data, obtained through the cDNA-AFLP technique, demonstrate differential responses to RYMV of two different rice cultivars, i.e. susceptible IR64 (Oryza sativa indica), and partially resistant Azucena (O. s. japonica). This RNA profiling provides a new original dataset that will enable us to gain greater insight into the RYMV/rice interaction and the specificity of the host response. Using the SIM4 subroutine, we took the intron/exon structure of the gene into account and mapped 281 RYMV stress responsive (RSR) transcripts on 12 rice chromosomes corresponding to 234 RSR genes. We also mapped previously identified deregulated proteins and genes involved in partial resistance and thus constructed the first global physical map of the RYMV/rice interaction. RSR transcripts on rice chromosomes 4 and 10 were found to be not randomly distributed. Seven genes were identified in the susceptible and partially resistant cultivars, and transcripts were colocalized for these seven genes in both cultivars. During virus infection, many concomitant plant gene expression changes may be associated with host changes caused by the infection process, general stress or defence responses. We noted that some genes (e.g. ABC transporters) were regulated throughout the kinetics of infection and differentiated susceptible and partially resistant hosts.

Conclusion

We enhanced the first RYMV/rice interaction map by combining information from the present study and previous studies on proteins and ESTs regulated during RYMV infection, thus providing a more comprehensive view on genes related to plant responses. This combined map provides a new tool for exploring molecular mechanisms underlying the RYMV/rice interaction.