bluuebunny/crossref_metadata_2025_split huggingface dataset:
S100A8 causes a shift toward expression of activatory Fcγ receptors on macrophages via toll‐like receptor 4 and regulates Fcγ receptor expression in synovium during chronic experimental arthritis
Authors: van Lent Peter L. , Grevers Lilyanne C. , Schelbergen Rik , Blom Arjen , Geurts Jeroen , Sloetjes Annet , Vogl Thomas , Roth Johannes , van den Berg Wim B. 
Published: July 2010

AbstractObjectiveThe levels of both Fcγ receptor (FcγR) and the alarmins S100A8 and S100A9 are correlated with the development and progression of cartilage destruction during antigen‐induced arthritis (AIA). This study was undertaken to study the active involvement of S100A8, S100A9, and S100A8/S100A9 in FcγR regulation in murine macrophages and synovium during AIA.MethodsRecombinant murine S100A8 (rS100A8) was injected into normal mouse knee joints, and the synovium was isolated for analysis of FcγR messenger RNA (mRNA) expression by reverse transcription–polymerase chain reaction (RT‐PCR). Macrophages, including bone marrow macrophages derived from Toll‐like receptor 4–deficient (TLR‐4−/−) mice, and polymorphonuclear cells (PMNs) were stimulated with S100 proteins, and levels of FcγR mRNA and protein were measured using RT‐PCR and fluorescence‐activated cell sorting analyses. AIA was induced in the knee joints of S100A9‐deficient (S100A9−/−) mice, compared with wild‐type (WT) controls, and the extent of cartilage destruction was determined using immunohistochemical analysis.ResultsIntraarticular injection of rS100A8 into the knee joints of normal mice caused a strong up‐regulation of mRNA levels of activating FcγRI (64‐fold increase) and FcγRIV (256‐fold increase) in the synovium. Stimulation of macrophages with rS100A8 led to significant up‐regulation of mRNA and protein levels of FcγRI and FcγRIV, but not FcγRIII, while the effects of S100A9 or S100A8/S100A9 complexes were less potent. Stimulation of PMNs (32Dcl3 cell line) with S100 proteins had no effect on FcγR expression. Up‐regulation of FcγRI and FcγRIV was abrogated in rS100A8‐stimulated macrophages from TLR‐4−/− mice, indicating that the induction of FcγR expression by S100A8 is mediated by TLR‐4. FcγR expression in the inflamed synovium of S100A9−/− mice was significantly lower on day 14 after arthritis induction when compared with WT controls, and these findings correlated with reduced severity of matrix metalloproteinase–mediated cartilage destruction.ConclusionS100A8 is a strong promoter of activating FcγRI and FcγRIV in macrophages through the activation of TLR‐4, and acts as a regulator of FcγR expression in inflamed synovium in chronic experimental arthritis.
Sustained T cell Rap1 signaling is protective in the collagen‐induced arthritis model of rheumatoid arthritis
Authors: Abreu Joana R. F. , Krausz Sarah , Dontje Wendy , Grabiec Aleksander M. , de Launay Daphne , Nolte Martijn A. , Tak Paul P. , Reedquist Kris A. 
Published: July 2010

AbstractObjectiveDefective activation of T cell receptor–proximal signaling proteins, such as the small GTPase Rap1, is thought to contribute to the pathologic behavior of rheumatoid arthritis (RA) synovial T cells. This study was undertaken to determine whether maintaining Rap1 signaling in murine T cells modifies disease onset or severity in collagen‐induced arthritis (CIA).MethodsCIA experiments were conducted using wild‐type and RapV12‐transgenic mice, which express an active mutant of Rap1 in the T cell compartment. Mice were assessed using macroscopic, microscopic, and radiologic measures, and serum levels of anticollagen antibodies were measured by enzyme‐linked immunosorbent assay. Phenotypic and functional characterization of wild‐type and RapV12‐transgenic T cells under homeostatic conditions and during disease onset was performed by flow cytometry.ResultsDisease incidence and severity, synovial infiltration, joint destruction, and anticollagen antibody production were significantly reduced in RapV12‐transgenic mice. Although the numbers and percentages of CD3+, CD4+, and CD8+ (naive, effector, and memory) T cells, Treg cells, and Th17 cells were equivalent in wild‐type and RapV12‐transgenic mice, a significant decrease in the percentage of tumor necrosis factor α–secreting CD8+ T cells was observed in RapV12‐transgenic mice during CIA. RapV12‐transgenic T cells also inefficiently expressed inducible costimulator and CD40L costimulatory proteins involved in B cell immunoglobulin class switching.ConclusionOur findings indicate that maintenance of T cell Rap1 signaling in murine T cells reduces disease incidence and severity in CIA, which are associated with specific defects in T cell effector function. Therefore, the restoration of Rap1 function in RA synovial T cells may have therapeutic benefit in RA.
Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis
Authors: Barnes Michael G. , Grom Alexei A. , Thompson Susan D. , Griffin Thomas A. , Luyrink Lorie K. , Colbert Robert A. , Glass David N. 
Published: July 2010

AbstractObjectiveTo explore biologic correlates to age at onset in patients with juvenile idiopathic arthritis (JIA) using peripheral blood mononuclear cell (PBMC) gene expression analysis.MethodsPBMCs were isolated from 56 healthy controls and 104 patients with recent‐onset JIA (39 with persistent oligoarticular JIA, 45 with rheumatoid factor–negative polyarticular JIA, and 20 with systemic JIA). RNA was amplified and labeled using NuGEN Ovation, and gene expression was assessed with Affymetrix HG‐U133 Plus 2.0 GeneChips.ResultsA total of 832 probe sets revealed gene expression differences (false discovery rate 5%) in PBMCs from children with oligoarticular JIA whose disease began before age 6 years (early‐onset disease) compared with those whose disease began at or after age 6 years (late‐onset disease). In patients with early‐onset disease, there was greater expression of genes related to B cells and less expression of genes related to cells of the myeloid lineage. Support vector machine analyses identified samples from patients with early‐ or late‐onset oligoarticular JIA (with 97% accuracy) or from patients with early‐ or late‐onset polyarticular JIA (with 89% accuracy), but not from patients with systemic JIA or healthy controls. Principal components analysis showed that age at onset was the major classifier of samples from patients with oligoarticular JIA and patients with polyarticular JIA.ConclusionPBMC gene expression analysis reveals biologic differences between patients with early‐and late‐onset JIA, independent of classification based on the number of joints involved. These data suggest that age at onset may be an important parameter to consider in JIA classification. Furthermore, pathologic mechanisms may vary with age at onset, and understanding these processes may lead to improved treatment of JIA.
No evidence of association between anti–tumor necrosis factor treatment and mortality in patients with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register
Authors: Lunt Mark , Watson Kath D. , Dixon William G. ,   British Society for Rheumatology Biologics Register Control Centre Consortium, Symmons Deborah P. M. , Hyrich Kimme L. ,   British Society for Rheumatology Biologics Register
Published: July 2010

AbstractObjectiveTo study the association between anti–tumor necrosis factor (anti‐TNF) therapy and mortality in a national cohort of patients with rheumatoid arthritis.MethodsWe prospectively followed up 12,672 patients who were beginning anti‐TNF therapy and 3,522 biologic‐naive patients receiving disease‐modifying antirheumatic drugs (DMARDs) until either July 31, 2008, or death, whichever occurred first. Notification of death and cause of death was received from the UK National Death Register. Mortality was compared using Cox proportional hazards models. Inverse probability of treatment weighting was used to adjust for the confounding effects of baseline differences between groups, including age, sex, disease severity, disability, and comorbidity. Missing baseline data were accounted for using multiple imputation.ResultsWhen compared with the DMARD cohort, the anti‐TNF cohort was younger (median age 57 years versus 61 years), had greater disease activity (median Disease Activity Score in 28 joints 6.6 versus 5.1), and had greater disability (median Health Assessment Questionnaire score 2.1 versus 1.6). Patients in the DMARD cohort were more likely to have a history of myocardial infarction (4.8% versus 3.1%) and chronic obstructive pulmonary disease (8.1% versus 4.8%) but were less likely to have had depression (16.5% versus 18.9%). There were 9,445 and 50,803 person‐years of followup in the DMARD and anti‐TNF cohorts, respectively, during which time 204 DMARD‐treated and 856 anti‐TNF–treated patients died. The weighted mortality hazard ratios in the anti‐TNF cohort were as follows: all‐cause 0.86 (95% confidence interval [95% CI] 0.64–1.16), circulatory disease 0.73 (95% CI 0.44–1.23), neoplasm 0.65 (95% CI 0.39–1.09), and respiratory disease 0.81 (95% CI 0.36–1.83).ConclusionOur results indicate that, compared with standard DMARD therapy, treatment with anti‐TNF therapies was not associated with an increase in mortality.
Expanded T cell receptor Vβ–restricted T cells from patients with sporadic inclusion body myositis are proinflammatory and cytotoxic CD28null T cells
Authors: Pandya Jayesh M. , Fasth Andreas E. R. , Zong Mei , Arnardottir Snjolaug , Dani Lara , Lindroos Eva , Malmström Vivianne , Lundberg Ingrid E. 
Published: July 2010

AbstractObjectiveSporadic inclusion body myositis (IBM) is characterized by T cell infiltrates in muscle tissue, but their functional role is unclear. Systemic signs of inflammation are lacking, and the absence of beneficial effects following immunosuppression has challenged the notion of a role for the immune system. This study was undertaken to investigate the phenotype and functionality of T cells, specifically a subset of proinflammatory, cytotoxic, and apoptosis‐resistant T cells defined as CD28null T cells, in the pathogenesis of sporadic IBM.MethodsA cohort of 27 patients with sporadic IBM was analyzed for the frequency of circulating and muscle‐infiltrating CD28null T cells. The T cell receptor (TCR) Vβ usage was determined using flow cytometry and immunohistochemistry. Anti‐CD3–stimulated peripheral blood mononuclear cells were analyzed for intracellular interferon‐γ and cytotoxic potential by flow cytometry.ResultsWe found striking accumulations of both CD8+CD28null and CD4+CD28null T cells, which represented the TCR Vβ–expanded T cells in sporadic IBM. Such CD28null T cells were abundant both in the inflamed muscle tissue and in the circulation. Although the specific TCR Vβ expansions varied between patients, both CD8+CD28null and CD4+CD28null T cells consistently displayed a highly proinflammatory and cytotoxic potential.ConclusionOur results suggest that CD28null T cell expansions represent the previously described expanded T cell subsets in sporadic IBM, and their proinflammatory capacity and presence in both muscle tissue and the circulation may imply a role of immune activation in sporadic IBM. In addition, CD4+CD28null T cells may exert cytotoxic effects directly on muscle fibers due to a cytotoxic potential similar to that in CD8+ T cells.
Participatory design of a health informatics system for rural health practitioners and disadvantaged women
Authors: Lustria Mia Liza A. , Kazmer Michelle M. , Glueckauf Robert L. , Hawkins Robert P. , Randeree Ebrahim , Rosario Ivee B. , McLaughlin Casey , Redmond Sarah 
Published: July 2010

AbstractWhile advances in highly targeted therapies and increased use of mammogram services have contributed to the overall decline of breast cancer deaths in the United States, these benefits have not been distributed equitably. Less educated, poor, rural, non‐Hispanic African American women have poorer access to cancer services and are less likely to have had a mammogram than are urban women. Lack of physician recommendations and perceived barriers in accessing diagnostic services are major factors that hinder the uptake of regular mammograms in rural communities. This article reports results of formative research conducted as part of a larger study focused on the participatory development of an electronic reminder system for breast cancer screening. The article discusses insights gained from focus groups with rural patients and clinicians about their information needs, breast cancer screening behaviors, barriers to care, and mammography referral practices.
Analyzing URL queries
Authors: Lee Wei Meng , Sanderson Mark 
Published: July 2010

AbstractThis study investigated a relatively unexamined query type, queries composed of URLs. The extent, variation, and user click‐through behavior was examined to determine the intent behind URL queries. The study made use of a search log from which URL queries were identified and selected for both qualitative and quantitative analyses. It was found that URL queries accounted for ∼17% of the sample. There were statistically significant differences between URL queries and non‐URL queries in the following attributes: mean query length; mean number of tokens per query; and mean number of clicks per query. Users issuing such queries clicked on fewer result list items higher up the ranking compared to non‐URL queries. Classification indicated that nearly 86% of queries were navigational in intent with informational and transactional queries representing about 7% of URL queries each. This is in contrast to past research that suggested that URL queries were 100% navigational. The conclusions of this study are that URL queries are relatively common and that simply returning the page that matches a user's URL is not an optimal strategy.
Geospatial identification of optimal straw‐to‐energy conversion sites in the Pacific Northwest
Authors: Mueller‐Warrant George W. , Banowetz Gary M. , Whittaker Gerald W. 
Published: July 2010

AbstractPrevious attempts to develop straw‐based bioenergy systems have stumbled at costs of transporting this low‐density resource to large‐scale, centralized facilities. Success in developing small‐scale, distributed technologies (e.g. syngas or pyrolysis bio‐oil) that reduce these costs will depend on closely matching system requirements to spatial distribution of available straw. We analyzed straw distribution in the Pacific Northwest to identify optimal sites for facilities ranging from a pilot plant currently under development to larger ones of previous studies. Sites for plants with capacities of 1, 10, or 100 million kg straw y‐1 were identified using a ‘lowest‐hanging‐fruit’ iterative siting process in which the location of maximum density of straw over an appropriately sized neighborhood was identified, distance from that point necessary to include desired quantity of straw measured, straw assigned to that plant removed from the raster, and the process repeated until all available straw had been assigned. Compared to K‐means, our new method sited the first 44% of plants at superior locations in terms of local straw density (i.e. lower transportation costs) and the next 39% at equivalent locations. K‐means produced better locations for the final 17% of plants along with superior average results. For the smallest facilities at locations defined by 3‐year average available straw density, 1.2 km buffers were adequate to provide straw for the first 10% of plants, with twice that distance sufficient for the first 70%. For the largest plants, 12 km buffers satisfied the first 10% of plants, with 24 km buffers satisfying the first 60%. Buffer distances exceeded 68 km for the final 20% of the largest plants. Siting patterns for the smallest plants were more evenly distributed than larger ones, suggesting that farm‐scale technology may be more politically appealing. Smaller plants, however, suffered from higher year‐to‐year variability in straw supply within pre‐defined distances. Published in 2010 by John Wiley & Sons, Ltd.
A conceptual framework for siting biorefineries in the Canadian Prairies
Authors: Luk Jason , Fernandes Henrique , Kumar Amit 
Published: July 2010

AbstractEthanol is increasingly used as a means to reduce gasoline consumption. As a result, it has also attracted analysis of its economic, social, and environmental merit. In order for the ethanol production industry to continue to expand, these issues must be confronted in future development. Although technological development is often relied upon, carefully considered ethanol refinery siting also mitigates some of these concerns. Five alternative siting locations were selected in the western Canadian Prairies. These were evaluated using 12 criteria which represent regional resources, economic conditions, government support, or social indicators. The criteria were weighted to represent the perspectives of two stakeholders. The Preference Ranking Organization Method for Enrichment and Evaluations (PROMETHEE) method was applied to this data, ranking the alternative sites. Several future scenarios were created to analyze the sensitivity of the results to both statistical data and subjective inputs. The rankings proved to be robust, and varied little in the different scenarios. Southern Alberta had an advantage with a high ethanol byproduct demand, education level, and ethanol demand. Southern Manitoba benefitted from the lowest labor and miscellaneous costs, due to higher unemployment. Saskatchewan suffers from low byproduct demand and a decrease in water availability while having a heated economy which increases costs. In addition, Saskatchewan as a whole is currently the leader in ethanol production, resulting in less net demand, reduced access to government incentives, and more local competition. Southern Alberta and Southern Manitoba are the optimal regions for future ethanol biorefinery, where as the Saskatchewan locations are the least attractive. © 2010 Society of Chemical Industry and John Wiley & Sons, Ltd
Dynamische Zustandsbewertung einer Verbundbrücke: Beobachtung äußerer und nichtlinearer Einflüsse auf die modalen Eigenschaften
Authors: Bungard Volker , Mahowald Jean , Waldmann Danièle , Maas Stefan , Zürbes Arno 
Published: July 2010

AbstractBei der Anwendung dynamischer Untersuchungsmethoden zur Zustandsbewertung von Ingenieurbauwerken aus Stahl‐ und Spannbeton sowie Verbundbau spielen Veränderungen von Rand‐ und Umweltbedingungen auf die modalen Parameter eine wesentliche Rolle. Während man diese im Laborexperiment weitest gehend überwachen bzw. ausschließen kann, sind sie bei in‐situ Versuchen nur schwer zu kontrollieren. Am Beispiel einer Verbundbrücke soll demonstriert werden, welche Größenordnung die Veränderung von Randbedingungen (z. B. Veränderung von anregenden Kräften) und Umwelteinflüsse (z. B. Temperatur) auf die dynamischen Parameter einer in‐situ Struktur haben können. Die Größenordnung dieser Veränderungen wird mit Veränderungen, die aus wirklichen Strukturschäden resultieren können, verglichen und bewertet.Dynamic Condition Assessment of a Composite Bridge: Investigation of External and Nonlinear Influences on the Modal PropertiesUsing dynamic investigation methods to assess the state of civil constructions like reinforced and prestressed concrete structures as well as composite structures, changes in boundary conditions and environmental influences play a decisive role. Under laboratory conditions it is possible to control respectively to exclude these influences but it is not always possible to control and to exclude them when testing in‐situ. By means of dynamic measurements which are conducted on a composite bridge, possible changes in dynamic properties resulting from changes in the amplitude of the excitation force and resulting from changes in the temperature conditions are demonstrated. The dimension of these changes is compared with changes in modal properties resulting from real structural defects and structural damages.
Rapid characterization of N‐linked glycans from secreted and gel‐purified monoclonal antibodies using MALDI‐ToF mass spectrometry
Authors: Hansen Rasmus , Dickson Alan J. , Goodacre Royston , Stephens Gill M. , Sellick Christopher A. 
Published: July 2010

AbstractRecombinant monoclonal antibodies (MAbs) are increasingly being used for therapeutic use and correct glycosylation of these MAbs is essential for their correct function. Glycosylation profiles are host cell‐ and antibody class‐dependent and can change over culture time and environmental conditions. Therefore, rapid monitoring of glycan addition/status is of great importance for process validity. We describe two workflows of generally applicability for glycan profiling of purified and gel‐purified MAbs produced in NS0 and CHO cells, in which small‐scale antibody purification and buffer exchange is combined with PNGase F glycan cleavage and graphite HyperCarb desalting. MALDI‐ToF mass spectrometry is used for sensitive detection of glycan forms, with the ability to confirm glycan structures by selective ion fragmentation. Both workflows are rapid, technically simple and amenable to automation, and use in multi‐well formats. Biotechnol. Bioeng. 2010;107: 902–908. © 2010 Wiley Periodicals, Inc.
Controlling Amyloid‐β Peptide(1–42) Oligomerization and Toxicity by Fluorinated Nanoparticles
Authors: Saraiva Ana M. , Cardoso Isabel , Pereira M. Carmo , Coelho Manuel A. N. , Saraiva Maria João , Möhwald Helmuth , Brezesinski Gerald 
Published: July 2010

AbstractThe amyloid‐β peptide (Aβ) is a major fibrillar component of neuritic plaques in Alzheimer's disease brains and is related to the pathogenesis of the disease. Soluble oligomers that precede fibril formation have been proposed as the main neurotoxic species that contributes to neurodegeneration and dementia. We hypothesize that oligomerization and cytotoxicity can be repressed by nanoparticles (NPs) that induce conformational changes in Aβ42. We show here that fluorinated and hydrogenated NPs with different abilities to change Aβ42 conformation influence oligomerization as assessed by atomic force microscopy, immunoblot and SDS‐PAGE. Fluorinated NPs, which promote an increase in α‐helical content, exert an antioligomeric effect, whereas hydrogenated analogues do not and lead to aggregation. Cytotoxicity assays confirmed our hypothesis by indicating that the conformational conversion of Aβ42 into an α‐helical‐enriched secondary structure also has antiapoptotic activity, thereby increasing the viability of cells treated with oligomeric species.