bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of chondrocyte‐mediated cartilage destruction by S100A8 in experimental murine arthritis
Authors: van Lent P. L. E. M. , Grevers L. C. , Blom A. B. , Arntz O. J. , van de Loo F. A. J. , van der Kraan P. , Abdollahi‐Roodsaz S. , Srikrishna G. , Freeze H. , Sloetjes A. , Nacken W. , Vogl T. , Roth J. , van den Berg W. B. 
Published: November 2008

AbstractObjectiveTo investigate whether S100A8 is actively involved in matrix metalloproteinase (MMP)–mediated chondrocyte activation.MethodsS100A8 and S100A9 proteins were detected in inflamed knee joints from mice with various forms of murine arthritis, using immunolocalization. Murine chondrocyte cell line H4 was stimulated with proinflammatory cytokines or recombinant S100A8. Messenger RNA (mRNA) and protein levels were measured using reverse transcriptase–polymerase chain reaction and intracellular fluorescence‐activated cell sorting (FACS). Breakdown of aggrecan on the pericellular surface of the chondrocytes was measured using VDIPEN and NITEGE antibodies and FACS, and breakdown in patellar cartilage was measured by immunolocalization.ResultsS100A8 and S100A9 proteins were abundantly expressed in and around chondrocytes in inflamed knee joints after induction of antigen‐induced arthritis or onset of spontaneous arthritis in interleukin‐1 (IL‐1) receptor antagonist–knockout mice. Stimulation of chondrocytes by the proinflammatory cytokines tumor necrosis factor α, IL‐1β, IL‐17, and interferon‐γ caused strong up‐regulation of S100A8 mRNA and protein levels and up‐regulation to a lesser extent of S100A9 levels. Stimulation of chondrocytes with S100A8 induced significant up‐regulation of MMP‐2, MMP‐3, MMP‐9, MMP‐13, ADAMTS‐4, and ADAMTS‐5 mRNA levels (up‐regulated 4, 4, 3, 16, 8, and 4 times, respectively). VDIPEN and NITEGE neoepitopes were significantly elevated in a concentration‐dependent manner in chondrocytes treated with 0.2, 1, or 5 μg/ml of S100A8. (VDIPEN levels were elevated 17%, 67%, and 108%, respectively, and NITEGE levels were elevated 8%, 33%, and 67%, respectively.) S100A8 significantly increased the effect of IL‐1β on MMP‐3, MMP‐13, and ADAMTS‐5. Mouse patellae incubated with both IL‐1β and S100A8 had elevated levels of NITEGE within the cartilage matrix when compared with patellae incubated with IL‐1β or S100A8 alone.ConclusionThese findings indicate that S100A8 and S100A9 are found in and around chondrocytes in experimental arthritis. S100A8 up‐regulates and activates MMPs and aggrecanase‐mediated pericellular matrix degradation.
Interleukin‐6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses
Authors: Fujimoto Minoru , Serada Satoshi , Mihara Masahiko , Uchiyama Yasushi , Yoshida Hiroto , Koike Nobuo , Ohsugi Yoshiyuki , Nishikawa Teppei , Ripley Barry , Kimura Akihiro , Kishimoto Tadamitsu , Naka Tetsuji 
Published: November 2008

AbstractObjectiveTo investigate the mechanism of interleukin‐6 (IL‐6) blockade in autoimmune arthritis, by comparing the effect of anti–IL‐6 receptor (anti–IL‐6R) monoclonal antibody (mAb) treatment with the effect of soluble tumor necrosis factor (sTNFR)–Fc fusion protein treatment on T helper cell differentiation in collagen‐induced arthritis (CIA).MethodsDBA/1 mice were immunized with type II collagen (CII) to induce arthritis and were left untreated or were treated with anti‐IL‐6R mAb or TNFR‐Fc. T helper cell differentiation and cytokine expression during the development of arthritis in these mice were analyzed.ResultsImmunization with CII predominantly increased the frequency of Th17 cells rather than Th1 cells. The frequency of FoxP3+ Treg cells was also increased after immunization. Treatment of mice with CIA with anti–IL‐6R mAb on day 0 markedly suppressed the induction of Th17 cells and arthritis development, but treatment with this antibody on day 14 failed to suppress both Th17 differentiation and arthritis. In contrast, treatment of mice with CIA with TNFR‐Fc from day 0 to day 14 suppressed neither Th17 differentiation nor arthritis, but treatment from day 21 to day 35 successfully ameliorated arthritis without inhibiting Th17 induction. Neither antibody treatment increased the frequency of Treg cells.ConclusionOur results indicate that the protective effect of IL‐6 blockade, but not tumor necrosis factor (TNF) blockade, in CIA correlates with the inhibition of Th17 differentiation. Our findings suggest that IL‐6 blockade in rheumatoid arthritis in human is also likely to involve a therapeutic mechanism distinct from that of TNF blockade and thus may represent an alternative therapy for patients in whom the disease is refractory to TNF blockade.
Overexpression of toll‐like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: Toll‐like receptor expression in early and longstanding arthritis
Authors: Ospelt Caroline , Brentano Fabia , Rengel Yvonne , Stanczyk Joanna , Kolling Christoph , Tak Paul P. , Gay Renate E. , Gay Steffen , Kyburz Diego 
Published: November 2008

AbstractObjectiveTo analyze the expression, regulation, and biologic relevance of Toll‐like receptors (TLRs) 1–10 in synovial and skin fibroblasts and to determine the expression levels of TLRs 2, 3, and 4 in synovial tissues from patients with early rheumatoid arthritis (RA), longstanding RA, and osteoarthritis (OA).MethodsExpression of TLRs 1–10 in RA synovial fibroblasts (RASFs), OASFs, and skin fibroblasts was analyzed by real‐time polymerase chain reaction (PCR). Fibroblasts were stimulated with tumor necrosis factor α, interleukin‐1β (IL‐1β), bacterial lipopeptide, poly(I‐C), lipopolysaccharide, and flagellin. Production of IL‐6 was determined by enzyme‐linked immunosorbent assay and induction of TLRs 2–5, matrix metalloproteinases (MMPs) 3 and 13 messenger RNA by real‐time PCR. Expression of TLRs 2–4 in synovial tissues was analyzed by immunohistochemistry.ResultsSynovial fibroblasts expressed TLRs 1–6, but not TLRs 7–10. Among the expressed TLRs, TLR‐3 and TLR‐4 were the most abundant in synovial fibroblasts, and stimulation of synovial fibroblasts with the TLR‐3 ligand poly(I‐C) led to the most pronounced increase in IL‐6, MMP‐3, and MMP‐13. In contrast, skin fibroblasts did not up‐regulate MMP‐3 or MMP‐13 after stimulation with any of the tested stimuli. In synovial tissues from patients with early RA, TLR‐3 and TLR‐4 were highly expressed and were comparable to the levels of patients with longstanding RA. These expression levels were elevated as compared with those in OA.ConclusionOur findings of high expression of TLRs, particularly TLRs 3 and 4, at an early stage of RA and the reactivity of synovial fibroblasts in vitro to TLR ligands suggest that TLR signaling pathways resulting in persistent inflammation and joint destruction are activated early in the disease process.
Modulation of molecular imprints in the antigen‐experienced B cell repertoire by rituximab
Authors: Palanichamy Arumugam , Roll Petra , Theiss Regina , Dörner Thomas , Tony Hans‐Peter 
Published: November 2008

AbstractObjectiveTransient B cell depletion by rituximab has recently gained more importance in the treatment of rheumatic disorders. Nevertheless, little is known about the reemerging B cells. We analyzed dynamic changes in the repopulating B cells, particularly the postswitch B cells, and studied the mutational patterns of Ig genes in antigen‐experienced B cells.MethodsFive patients with active rheumatoid arthritis (RA) were treated with rituximab. In 3 patients, B cell receptor (BCR) gene analysis was performed before treatment and during B cell recovery using genomic DNA. In 2 patients, B cell subsets were studied during the early recovery phase using single‐cell technology. For comparison, immunophenotyping of B cell subsets was performed.ResultsEarly B cell recovery was marked by a relatively expanded population of highly mutated B cells, which were correlated with B cells with a plasmablast phenotype on comparative immunophenotyping. Analysis of the mutational pattern in these cells revealed increased RGYW/WRCY (where R = A/G, Y = C/T, and W = A/T) hotspot targeting (44% before rituximab versus 59% after) and elevated ratios of replacement to silent mutations within the complementarity‐determining regions in Ig genes (1.87 before rituximab versus 2.67 after; P ≤ 0.0025).ConclusionOur findings show that rituximab leads to qualitative changes in the imprints of highly mutated, antigen‐experienced BCRs, representing the result of selection, whereas molecular processes such as Ig V rearrangements are not affected by this treatment.
Inverse association of general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligomeric matrix protein levels
Authors: Chen Hsiang‐Cheng , Shah Svati H. , Li Yi‐Ju , Stabler Thomas V. , Jordan Joanne M. , Kraus Virginia Byers 
Published: November 2008

AbstractObjectiveExtensive joint hypermobility, lower serum cartilage oligomeric matrix protein (COMP) levels, and early‐onset osteoarthritis (OA) are phenotypes of inherited pseudoachondroplasia and multiple epiphyseal dysplasia. However, few studies have evaluated the association between articular hypermobility and primary OA. We undertook the present study to evaluate this association and to test the hypothesis that COMP levels are associated with hypermobility in patients with OA and individuals without OA.MethodsTwo separate cohorts were available for analysis, the CARRIAGE (CARolinas Region Interaction of Aging Genes and Environment) extended family and a subset of the GOGO (Genetics of Generalized Osteoarthritis) sibpair cohort. In the CARRIAGE family, we performed hand and knee examinations and hypermobility evaluations (Beighton criteria) and obtained sera for measurement of COMP and hyaluronan (HA). Data on COMP and HA levels and extensive joint radiographic and hypermobility data were also available for the GOGO cohort.ResultsThe prevalence of hypermobility was 13% in the CARRIAGE family and 5% in the GOGO cohort. In the CARRIAGE family, hypermobility was associated with a significantly reduced prevalence of hand (especially proximal interphalangeal joint) and knee OA and lower mean serum COMP levels, both in the total cohort and in non‐hand‐OA subgroups. These results were further validated in the GOGO subsets without radiographic OA, in which hypermobility was also associated with a significantly reduced mean serum COMP level (P < 0.0001 adjusted for age). Serum HA levels did not differ in relation to hypermobility in either cohort.ConclusionThe present results indicate that there is an inverse relationship between hypermobility and hand and knee OA, and that hypermobility is associated with lower serum COMP levels. Genetic variations of the COMP gene may account for some subgroups of benign joint hypermobility.
Gene–disease relationship discovery based on model-driven data integration and database view definition
Authors: Yilmaz S. , Jonveaux P. , Bicep C. , Pierron L. , Smaïl-Tabbone M. , Devignes M.D. 
Published: November 2008

Abstract
Motivation: Computational methods are widely used to discover gene–disease relationships hidden in vast masses of available genomic and post-genomic data. In most current methods, a similarity measure is calculated between gene annotations and known disease genes or disease descriptions. However, more explicit gene–disease relationships are required for better insights into the molecular bases of diseases, especially for complex multi-gene diseases.
Results: Explicit relationships between genes and diseases are formulated as candidate gene definitions that may include intermediary genes, e.g. orthologous or interacting genes. These definitions guide data modelling in our database approach for gene–disease relationship discovery and are expressed as views which ultimately lead to the retrieval of documented sets of candidate genes. A system called ACGR (Approach for Candidate Gene Retrieval) has been implemented and tested with three case studies including a rare orphan gene disease.
Availability: The ACGR sources are freely available at http://bioinfo.loria.fr/projects/acgr/acgr-software/. See especially the file ‘disease_description’ and the folders ‘Xcollect_scenarios’ and ‘ACGR_views’.
Contact: devignes@loria.fr
Supplementary information: Supplementary data are available at Bioinformatics online.
The Rockwool Group: delivering business growth through culture change
Authors: Geisler Hansen Per , Soerensen Jakob 
Published: November 2008

PurposeThe purpose of this article is to show how The Rockwool Group has undergone an impressive change journey in recent years. Under the leadership of its president and chief executive officer, Eelco van Heel, the business has successfully redefined its strategic objectives, clarified its vision and mission and positively changed its culture to one that focuses firmly on people and values. The aim of this article is to examine the strategic role that HR has played in helping the organization meet its goals.Design/methodology/approachThe case study discusses how managers across the global Rockwool business have been empowered to take on the mantle of change and adapt their own behavior for the good of the wider business. It examines the leadership approach taken to launching the change program and identifies how challenges were overcome in gaining buy‐in from across the organization.FindingsThrough the “Leading People & Brands” program, which encourages managers to mobilize their people to undertake positive change, the Rockwool Group has successfully cascaded responsibility for change throughout the organization.Originality/valueThis case study demonstrates the importance of going beyond simply communicating a new vision to gaining buy‐in from employees. This was achieved at Rockwool by listening and responding to feedback and adapting the launch program so that its message was simpler, understood by all, easy to translate into action and involved managers in its implementation.
Direct marketing and relationships
Authors: Harridge‐March Sally 
Published: November 2008

PurposeThe purpose of this paper is to discuss the complementary effect of relationship marketing and direct marketing and outline the foundations of direct marketing that can be enhanced by relationship marketing principles.Design/methodology/approachThis is a personal viewpoint based on many years of working in, teaching and research of direct and relationship marketing.FindingsThe paper finds that both disciplines of direct marketing and relationship marketing have something of value to the other. The combination of the two strategies can only be of value and benefit to both customers and organisations.Originality/valueThe value of this paper is that it outlines the symbiotic strength of direct marketing and relationship marketing that allows contemporary marketers to utilise the best of both disciplines to establish and maintain strong relationships with their customers
Mapping the profiles of franchisees
Authors: Huang Yu‐an , Phau Ian 
Published: November 2008

PurposeThe purpose of this paper is to investigate franchisees' perception of the value of quality service in the franchise system.Design/methodology/approachTwo dimensions, perceived importance and perceived gaps of the quality of the franchise system, form the anchors of a proposed 2 × 2 franchise system quality (FSQ) matrix. This is empirically tested with 200 Australian franchisees.FindingsThe results reflected a strong evidence of four distinct profiles of franchisees as conceptualized. These results also showed that the more cooperative the franchisees, the better their performance and satisfaction levels with the system. In contrast to existing literature, franchisees who fall in the high‐perceived importance cells of the FSQ matrix have a stronger desire for autonomy.Practical implicationsCooperation between franchisees and franchisors are fundamental to achieve success. It is important to provide resources and assistance to franchisees and these are considered as key success factors. Further, determining the profile of the franchisees allows franchisors to determine the potential Best Buddy who are considered an asset in the franchise system.Research limitations/implicationsA larger sample size should be implored that focuses on specific industries or service sectors. The research can be replicated in other non‐Western contexts to formulate different insights. Cross‐national studies could be conducted to investigate differences between cultures.Originality/valueThe paper addresses the gap in literature by examining franchisees' perception of the value of services provided in a franchise system. The FSQ Matrix is also conceptualized and empirically tested on an Australian sample.
A biomechanical basis for tears of the human acetabular labrum
Authors: Smith C D , Masouros S , Hill A M , Amis A A , Bull A M J 
Published: November 2008

Objective:Acetabular labral tears predominantly affect young patients and are a source of hip pain in the athlete. Four causes of the initiation of labral tears have been proposed; trauma, hypolaxity of the anterior capsule, dysplasia and bony impingement. A further cause could be reduced biomechanical properties in the area most susceptible to tears. However, no work has defined these properties.Design:32 compressive and 32 tensile test samples were harvested from fresh-frozen cadaveric acetabula. The labrum was divided into eight areas to allow comparison around its circumference. Semiconfined compressive testing and tensile testing were performed at a displacement rate of 10 mm/min in a controlled environment of 100% humidity at 37 (SD 1)°C.Setting:Cadaveric study.Results:The mean compressive stiffness was 31.75 (SD 16.7) MPa, and the mean tensile elastic modulus was 24.7 (SD 10.8) MPa. The anterosuperior region had a significantly lower compressive elastic modulus than either of the posterior quadrants (p<0.05) and a significantly lower tensile modulus to the anterioinferior area (p<0.05).Conclusions:The biomechanical properties in the anterosuperior region may be a contributing factor to the initiation of labral tears.
A Clearly Democratic Religious-Zionist Philosophy: The Early Thought of Yeshayahu Leibowitz
Authors: Hellinger Moshe 
Published: November 2008

AbstractIn his early teaching, from the 1920s through the 1950s, Yeshayahu Leibowitz (1903–1994) stands out as one of the most fascinating religious Zionist thinkers. He strives to establish a Jewish democratic state whose democratic aspects will be channeled toward the establishment of an exemplary society, one that can express its religious roots within a modern democratic context.Leibowitz thus attaches enormous importance to democracy in terms of both its political components and its modern Orthodox aspirations. In this respect, he is the most radical spokesman of the Neo-Orthodox notion of Torah with Derekh Eretz, as translated into religious-Zionist terms.
Why Is Thought Linguistic? Ockham's Two Conceptions of the Intellect
Authors: Lenz Martin 
Published: November 2008

AbstractOne of Ockham's fundamental tenets about the human intellect is that its acts constitute a mental language. Although this language of thought shares some of the features of conventional language, thought is commonly considered as prior to conventional language. This paper tries to show that this consensus is seriously challenged in Ockham's early writings. I shall argue that, in claiming the priority of conventional language over mental language, Ockham established a novel explanation of the systematicity of thought—an explanation which anticipates the idea that thought becomes systematic through the acquisition of conventional language.
From an Outsider's Point of View: Lorenzo Valla on the Soul
Authors: Nauta Lodi 
Published: November 2008

AbstractIn his Repastinatio. . . Lorenzo Valla launched a heavy attack on Aristotelian-scholastic thought. While most of this book is devoted to metaphysics, language and argumentation, Valla also incorporates chapters on the soul and natural philosophy. Using as criteria good Latin, common sense and common observation, he rejected much of standard Aristotelian teaching on the soul, replacing the hylopmorphic account of the scholastics by an Augustinian one. In this article his arguments on the soul's autonomy, nobility and independency from the body are studied and analysed. His critique of Aristotle's opinions on natural phenomena as being untrue to what we observe will also be briefly studied. His arguments do not show him always to be deep or consistent thinker, but the critical review of Aristotelian philosophy proceeds from some philosophically interesting assumptions. Moreover, from a broader historical perspective his undermining of Aristotle's authority may be regarded as a contribution to the final demise of the Aristotelian paradigm, even though the humanist critique was just one factor in this process.
Recreating Fatima, Aisha and Marginalized Women in the Early Years of Islam: Assia Djebar's Far from Medina (1991)
Authors: Roded Ruth 
Published: November 2008

AbstractWhen Francophone creative artist Assia Djebar decided to write a semi-fictional work on the early years of Islam, she brought to this endeavor her life experience in the context of Algerian history and French colonial influence. Her writing reveals changing attitudes towards Algerian women and Islam, in response to ongoing events.Far from Medina was influenced by the chain of modern biographies of the Prophet Muhammad produced in English, French and Arabic. Early Islamic feminist endeavors also informed her work. Most fascinating is the dialogue that Djebar seems to have carried out with classical Islamic texts, revealed in the format and style of the book.Djebar proposes that the death of Muhammad, and to a greater extent the death of his daughter Fatima six months later, were turning points in women's roles in Islamic society—taking the Muslims "Far From Medina," where women were strong and stood up for their rights.
Legal Safeguards in Egypt's Petroleum Concession Agreements
Authors: Khatchadourian Minas 
Published: November 2008

This article deals with the concession contracts for the exploration and the production of oil and gas in Egypt. Such tripartite contracts are concluded between the Government of Egypt (GOE) as the host country, a National Oil Company (NOC) as the concession holder and an international oil company (IOC) as the foreign contractor who receives a part of the oil or gas production on a production sharing agreement (PSA). From an Egyptian legal perspective, this contract is qualified as a
State contract
which is supposed to give the Government some exorbitant powers towards its counterparts. However, in order to attract foreign investors into this kind of agreement and encourage international oil companies to explore natural resources, several legal safeguards are incorporated in the concession agreement. Examples of this include placing the contract in the framework of a legislative act, granting the contract a supremacy on any contrary legislation, stabilization clause, adaptation of the contract through renegotiation, arbitration clause, etc.