bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superelastic Shape Recovery of Mechanically Twinned 3,5‐Difluorobenzoic Acid Crystals
Authors: Takamizawa Satoshi , Takasaki Yuichi 
Published: February 2015

AbstractGenerally, superelastic behavior cannot be expected in mechanically twinned crystals because there is essentially no strain on the interface that is a driving force for spontaneous shape recovery. However, we found that single crystals of 3,5‐difluorobenzoic acid are superelastic organic crystals under mechanical twinning. The unexpected shape recovery can be explained by molecular distortion on the twinning interface, which suggests a new mechanism for superelasticity in molecular materials.
The Histone Deacetylase Sirtuin 1 Is Reduced in Systemic Sclerosis and Abrogates Fibrotic Responses by Targeting Transforming Growth Factor β Signaling
Authors: Wei Jun , Ghosh Archit K. , Chu Haiyan , Fang Feng , Hinchcliff Monique E. , Wang Jiucun , Marangoni Roberta Goncalves , Varga John 
Published: February 2015

ObjectivePersistent fibroblast activation underlies skin fibrosis in systemic sclerosis (SSc), but the transcriptional and epigenetic mechanisms controlling this process are not well understood. In view of the potent influence of acetylation status governing tissue fibrosis, we undertook this study to investigate the expression of the antiaging deacetylase enzyme sirtuin 1 (SIRT1) in SSc and its effects on fibrotic responses in vitro and in vivo.MethodsTissue expression of SIRTs was interrogated from publicly available genome‐wide expression data sets and by immunohistochemistry. The effects of SIRT1 on modulating fibrotic responses, as well as the underlying mechanisms, were examined in human and mouse fibroblasts in culture and in an experimental fibrosis model in the mouse.ResultsAnalysis of transcriptome data revealed a selective reduction of SIRT1 messenger RNA (mRNA) levels in SSc skin biopsy samples as well as a negative correlation of SIRT1 mRNA with the skin score. Cellular SIRT1 levels were suppressed in normal fibroblasts exposed to hypoxia or platelet‐derived growth factor and were constitutively down‐regulated in SSc fibroblasts. Activation of SIRT1 attenuated fibrotic responses in skin fibroblasts and skin organ cultures, while genetic or pharmacologic inhibition of SIRT1 had profibrotic effects. The antifibrotic effects of SIRT1 were due in part to decreased expression and function of the acetyltransferase p300. In mice, experimentally induced skin fibrosis was accompanied by reduced SIRT1 expression in lesional tissue fibroblasts, and both fibrosis and loss of SIRT1 in these mice were mitigated by treatment with a SIRT1 activator.ConclusionSIRT1 has antifibrotic effects, and its reduced tissue expression in patients with SSc might have a direct causal role in progression of fibrosis. Pharmacologic modulation of SIRT1 in these patients therefore might represent a potential treatment strategy.
Bioactivity in an Aggrecan 32‐mer Fragment Is Mediated via Toll‐like Receptor 2
Authors: Lees Sophie , Golub Suzanne B. , Last Karena , Zeng Weiguang , Jackson David C. , Sutton Philip , Fosang Amanda J. 
Published: February 2015

ObjectiveTo determine whether an aggrecan 32‐mer fragment derived from dual ADAMTS and matrix metalloproteinase (MMP) cleavage in the aggrecan interglobular domain was bioactive and, if so, to elucidate its mechanism of action.MethodsMouse primary chondrocytes, synovial fibroblasts, or peritoneal macrophages, human primary chondrocytes, and cells or cell lines from myeloid differentiation factor 88 (MyD88)–deficient and Toll‐like receptor 2 (TLR‐2)–deficient mice were stimulated with synthetic mouse 32‐mer peptide, human 32‐mer peptide, a 32‐mer scrambled peptide, or native, glycosylated 32‐mer peptide. Cells stimulated with 32‐mer peptide were analyzed for changes in messenger RNA (mRNA) expression by quantitative polymerase chain reaction. Conditioned medium was analyzed for levels of interleukin‐6 protein by an AlphaLISA or for levels of MMP‐3 and MMP‐13 protein by Western blotting. NF‐κB activation was measured in a luciferase reporter assay.ResultsTreatment of mouse cells or cartilage explants with 32‐mer peptide or scrambled peptide revealed that the 32‐mer peptide, but not the scrambled peptide, had antianabolic, procatabolic, and proinflammatory bioactivity in vitro. Chondrocytes, synovial fibroblasts, and macrophages from MyD88‐deficient mice failed to respond to 32‐mer peptide stimulation. A macrophage cell line derived from TLR‐2–deficient mice also failed to respond to 32‐mer peptide stimulation. Stimulation of human chondrocytes with human 32‐mer peptide increased the expression of catabolic markers at the mRNA and protein levels. Mouse and human 32‐mer peptide stimulated NF‐κB activation in a TLR‐2–dependent reporter assay, and the response of chondrocytes from both species to native, glycosylated 32‐mer peptide was similar to the response to synthetic peptides.ConclusionThe aggrecan 32‐mer fragment is a novel endogenous ligand of TLR‐2 with the potential to accelerate cartilage destruction in vivo.
Brief Report: Articular Ankle Fracture Results in Increased Synovitis, Synovial Macrophage Infiltration, and Synovial Fluid Concentrations of Inflammatory Cytokines and Chemokines
Authors: Furman Bridgette D. , Kimmerling Kelly A. , Zura Robert D. , Reilly Rachel M. , Zlowodzki Michal P. , Huebner Janet L. , Kraus Virginia B. , Guilak Farshid , Olson Steven A. 
Published: February 2015

ObjectiveThe inflammatory response following an articular fracture is thought to play a role in the development of posttraumatic arthritis (PTA) but has not been well characterized. The objective of this study was to characterize the acute inflammatory response, both locally and systemically, in joint synovium, synovial fluid (SF), and serum following articular fracture of the ankle. We hypothesized that intraarticular fracture would alter the synovial environment and lead to increased local and systemic inflammation.MethodsSynovial tissue biopsy specimens, SF samples, and serum samples were collected from patients with an acute articular ankle fracture (n = 6). Additional samples (normal, ankle osteoarthritis [OA], and knee OA [n = 6 per group]) were included for comparative analyses. Synovial tissue was assessed for synovitis and macrophage count. SF and serum were assessed for cytokines (interferon‐γ [IFNγ], interleukin‐1β [IL‐1β], IL‐6, IL‐8, IL‐10, IL‐12p70, and tumor necrosis factor α) and chemokines (eotaxin, eotaxin 3, IFNγ‐inducible 10‐kd protein, monocyte chemotactic protein 1 [MCP‐1], MCP‐4, macrophage‐derived chemokine, macrophage inflammatory protein 1β, and thymus and activation–regulated chemokine).ResultsSynovitis scores were significantly higher in ankle fracture tissue compared with normal ankle tissue (P = 0.007), and there was a trend toward an increased abundance of CD68+ macrophages in ankle fracture synovium compared with normal knee synovium (P = 0.06). The concentrations of all cytokines and chemokines were elevated in the SF of patients with ankle fracture compared with those in SF from OA patients with no history of trauma. Only the concentration of IL‐6 was significantly increased in the serum of patients with ankle fracture compared with normal serum (P = 0.027).ConclusionArticular fracture of the ankle increased acute local inflammation, as indicated by increased synovitis, increased macrophage infiltration into synovial tissue, and increased SF concentrations of biomarkers of inflammation. Characterizing the acute response to articular fracture provides insight into the healing process and may help to identify patients who may be at greater risk of PTA.
Microvascular Abnormalities in Adjuvant‐Induced Arthritis: Relationship to Macrovascular Endothelial Function and Markers of Endothelial Activation
Authors: Totoson Perle , Maguin‐Gaté Katy , Nappey Maude , Prati Clément , Wendling Daniel , Demougeot Céline 
Published: February 2015

ObjectiveTo determine the time course of microvascular abnormalities and the link with macrovascular endothelial function and circulating markers of endothelial activation in adjuvant‐induced arthritis (AIA) in rats.MethodsMicrovascular function/structure and mechanics were studied in third‐order mesenteric arteries subjected to flow and/or pressure on day 4 (preclinical arthritis), day 11 (very early arthritis), day 33 (severe disease), and day 90 (when inflammation has resolved) after AIA induction. Macrovascular function was studied in aortic rings, and blood pressure, plasma levels of C‐reactive protein (CRP), intercellular adhesion molecule 1 (ICAM‐1), and vascular cell adhesion molecule 1 (VCAM‐1) were measured at each time point.ResultsMesenteric flow‐mediated vasodilation was significantly reduced from very early arthritis to chronic disease, whereas increased microvascular arterial stiffness was evident only on day 33. Macrovascular endothelial dysfunction was observed only on day 33. Thus, on day 90, whereas rats with AIA recovered normal macrovascular endothelial function, microvascular endothelial function remained impaired. No correlation was found between micro‐ and macrovascular endothelial function throughout the course of arthritis (r = 0.180, P = 0.229). Furthermore, no correlation was found between CRP levels, ICAM‐1 levels, and endothelial function whatever the vascular bed. AIA was not associated with change in blood pressure or VCAM levels.ConclusionOur findings indicate that microvascular endothelial dysfunction occurs earlier than macrovascular endothelial dysfunction and microvascular arterial stiffness during arthritis, suggesting that microvascular endothelial function would be a valuable tool for the early assessment of cardiovascular risk in RA. Neither the ICAM‐1 level nor the CRP level is a good marker of micro‐ or macrovascular endothelial dysfunction.
Glucocorticoid‐Induced Leucine Zipper Governs the Therapeutic Potential of Mesenchymal Stem Cells by Inducing a Switch From Pathogenic to Regulatory Th17 Cells in a Mouse Model of Collagen‐Induced Arthritis
Authors: Luz‐Crawford P. , Tejedor G. , Mausset‐Bonnefont A. L. , Beaulieu E. , Morand E. F. , Jorgensen C. , Noël D. , Djouad F. 
Published: February 2015

ObjectiveMesenchymal stem cells (MSCs) are potent immunosuppressive cells that have shown promise in the treatment of rheumatoid arthritis (RA). Deciphering the intrinsic characteristics of MSCs that correlate with their biologic activity will facilitate their clinical use. Recently, the role of glucocorticoid‐induced leucine zipper (GILZ) in the development of RA has been documented. The aim of this study was to evaluate whether GILZ expression by MSCs may contribute to their therapeutic effect.MethodsMSCs were isolated from GILZ‐deficient (GILZ−/−) mice and wild‐type mice. MSCs (1 × 106 cells) were injected twice via the tail vein into mice with collagen‐induced arthritis (CIA).ResultsIn vitro, we showed that GILZ is a key factor involved in the immunosuppressive potential of MSCs. MSCs derived from GILZ−/− mice did not suppress the proliferation of CD4+ T cells and were less efficient than MSCs derived from WT mice in altering Th17 cell polarization. Thus, we investigated the role of GILZ in an experimental model of arthritis and demonstrated that although WT MSCs significantly reduced paw swelling in arthritic mice, GILZ−/− MSCs did not. Moreover, the magnitude of the effects of GILZ−/− MSCs on Th17 cell frequency was significantly lower than that of WT MSCs. The therapeutic effect of MSCs correlated with the generation of Treg cells bearing the CD4 + RORγt+IL‐17low IL‐10+ signature, and Th17 cell polarization was GILZ dependent.ConclusionThis study demonstrates that GILZ has an essential role in the therapeutic effectiveness of MSCs in arthritis by favoring Th17 cell polarization toward a regulatory phenotype. Therefore, potentiation of GILZ expression in MSCs could represent a means to enhance their therapeutic effect in autoimmune diseases.
A Reactive Oxygen Species–Mediated Loop Maintains Increased Expression of NADPH Oxidases 2 and 4 in Skin Fibroblasts From Patients With Systemic Sclerosis
Authors: Spadoni Tatiana , Svegliati Baroni Silvia , Amico Donatella , Albani Lisa , Moroncini Gianluca , Avvedimento Enrico V. , Gabrielli Armando 
Published: February 2015

ObjectiveReactive oxygen species (ROS) contribute to the pathogenesis of fibrosis in systemic sclerosis (SSc; scleroderma), and NADPH oxidase (NOX) is an important source of ROS. Since the role of single NOX isoforms has not been previously investigated in SSc, this study was undertaken to assess the expression of NOX in SSc fibroblasts compared to normal healthy cells and to analyze their role in cell activation.MethodsExpression of NOX isoforms in dermal fibroblasts from patients with SSc and healthy control subjects was analyzed by real‐time polymerase chain reaction, immunoblotting, and immunofluorescence. NOX isoforms were silenced using small interfering RNA. Production of ROS was measured by fluorometry and confocal microscopy.ResultsScleroderma fibroblasts showed up‐regulation of NOX‐2 and NOX‐4 protein and messenger RNA (mRNA) expression. Treatment of the cells with diphenyleneiodonium, a nonselective inhibitor of flavin‐containing enzymes, and silencing of NOX2 and NOX4 decreased the production of ROS as well as the expression of type I collagen and α‐smooth muscle actin in SSc fibroblasts. ROS generated by NOX‐2 and NOX‐4 were involved in DNA damage and activation of a DNA repair checkpoint. Incubation of healthy control fibroblasts with platelet‐derived growth factor (PDGF) or with IgG isolated from SSc patient serum enhanced the expression of NOX2 and NOX4 mRNA, via ROS, in a time‐dependent manner. Treatment with actinomycin D, a transcription inhibitor, reversed the effects of PDGF stimulation but not the effects of SSc IgG.ConclusionBoth NOX2 and NOX4 generate ROS in SSc fibroblasts and play a critical role in cell activation and DNA damage. Expression of NOX‐2 and NOX‐4 in SSc fibroblasts is maintained by a ROS‐mediated loop.
Semaphorin 4D Contributes to Rheumatoid Arthritis by Inducing Inflammatory Cytokine Production: Pathogenic and Therapeutic Implications
Authors: Yoshida Yuji , Ogata Atsushi , Kang Sujin , Ebina Kousuke , Shi Kenrin , Nojima Satoshi , Kimura Tetsuya , Ito Daisuke , Morimoto Keiko , Nishide Masayuki , Hosokawa Takashi , Hirano Toru , Shima Yoshihito , Narazaki Masashi , Tsuboi Hideki , Saeki Yukihiko , Tomita Tetsuya , Tanaka Toshio , Kumanogoh Atsushi 
Published: February 2015

ObjectiveSemaphorin 4D (Sema4D)/CD100 has pleiotropic roles in immune activation, angiogenesis, bone metabolism, and neural development. We undertook this study to investigate the role of Sema4D in rheumatoid arthritis (RA).MethodsSoluble Sema4D (sSema4D) levels in serum and synovial fluid were analyzed by enzyme‐linked immunosorbent assay. Cell surface expression and transcripts of Sema4D were analyzed in peripheral blood cells from RA patients, and immunohistochemical staining of Sema4D was performed in RA synovium. Generation of sSema4D was evaluated in an ADAMTS‐4–treated monocytic cell line (THP‐1 cells). The efficacy of anti‐Sema4D antibody was evaluated in mice with collagen‐induced arthritis (CIA).ResultsLevels of sSema4D were elevated in both serum and synovial fluid from RA patients, and disease activity markers were correlated with serum sSema4D levels. Sema4D‐expressing cells also accumulated in RA synovium. Cell surface levels of Sema4D on CD3+ and CD14+ cells from RA patients were reduced, although levels of Sema4D transcripts were unchanged. In addition, ADAMTS‐4 cleaved cell surface Sema4D to generate sSema4D in THP‐1 cells. Soluble Sema4D induced tumor necrosis factor α (TNFα) and interleukin‐6 (IL‐6) production from CD14+ monocytes. IL‐6 and TNFα induced ADAMTS‐4 expression in synovial cells. Treatment with an anti‐Sema4D antibody suppressed arthritis and reduced proinflammatory cytokine production in CIA.ConclusionA positive feedback loop involving sSema4D/IL‐6 and TNFα/ADAMTS‐4 may contribute to the pathogenesis of RA. The inhibition of arthritis by anti‐Sema4D antibody suggests that Sema4D represents a potential therapeutic target for RA.
Rapid induction of omega‐3 fatty acids (EPA) in Nannochloropsis sp. by UV‐C radiation
Authors: Sharma Kalpesh , Schenk Peer M. 
Published: February 2015

ABSTRACTOmega‐3 fatty acids, such as eicosapentaenoic acid (EPA), provide substantial health benefits. As global fish stocks are declining and in some cases are contaminated with heavy metals, there is a need to find more sustainable land‐based sources of these essential fatty acids. The oleaginous microalga Nannochloropsis sp. has been identified as a highly efficient producer of omega‐3 fatty acids. In this study, we present a new process to rapidly induce biosynthesis of essential fatty acids, including EPA in Nannochloropsis sp. BR2. Short exposure to UV‐C at a dose of 100 or 250 mJ/cm2 led to a significant increase in total cellular lipid contents when compared to mock‐treated controls. A low dosage of 100 mJ/cm2 also led to a twofold increase in total EPA content within 24 h that constituted 30% of total fatty acids and up to 12% of total dry weight at higher dosages. UV‐C radiation may find uses as an easily applicable external inducer for large‐scale production of omega‐3 production from microalgae. Biotechnol. Bioeng. 2015;112: 1243–1249. © 2015 Wiley Periodicals, Inc.
From face‐to‐face to distance LMS‐mediated collaborative learning situations with GLUE!
Authors: Alario‐Hoyos Carlos , Gómez‐Sánchez Eduardo , Bote‐Lorenzo Miguel L. , Asensio‐Pérez Juan I. , Vega‐Gorgojo Guillermo , Ruiz‐Calleja Adolfo 
Published: February 2015

ABSTRACTGLUE! is an integration architecture that allows teachers to easily set up an LMS environment with several external tools to carry out complex collaborative learning situations in distance settings. Though its effectiveness in alleviating the burden on teachers of deploying and enacting such situations has been studied elsewhere, there are no studies in the literature analyzing the impact, in terms of learning achievement, of turning traditional face‐to‐face collaborative learning situations into distance LMS‐mediated ones with the support of integration approaches such as the GLUE! architecture. This paper compares the learning achievement in a distance LMS‐mediated collaborative learning situation supported by GLUE! and in the equivalent face‐to‐face in a non‐technological setting. The conclusions of this comparison, along with the fact that GLUE! significantly reduces the set up effort, suggest that GLUE! is a good choice for turning traditional face‐to‐face collaborative learning situations into distance LMS‐mediated ones without significant negative effects in the learning achievement. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:527–536, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21623
CAS and real life problems to learn basic concepts in Linear Algebra course
Authors: Caridade C. M. R. , Encinas A. H. , Martín‐Vaquero J. , Queiruga‐Dios A. 
Published: February 2015

ABSTRACTIn this paper we examine the effect of the use of a Computer Algebra System (CAS) to solve interdisciplinary problems. We have been working for some years in the application of mathematics to different engineering problems, the main reason was to improve the motivation of our students and to make possible for them to connect and apply what they learn in Linear Algebra class to other engineering subjects. We describe a case study with students of Electromechanical and Mechanical Engineering from the Coimbra Institute of Engineering and from Geological and Industrial Engineering students from the University of Salamanca in a Linear Algebra course. The study involves the application of digital image processing to develop the basic skills of Linear Algebra. Furthermore, we include the results of a pre‐test and post‐test control group study using that application in the classroom. The results indicate that the experiences were very enriching for the students in different subjects. We tested at different centers from two different countries with similar results. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:567–577, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21627
Using IBM SPSS modeler to improve undergraduate mathematical modelling competence
Authors: Xiao Xiang , Xu Honglei , Xu Shouzhi 
Published: February 2015

ABSTRACTThis paper is concerned with the problem of improving undergraduate mathematical modelling competence in the current big data world. Firstly, we review the renowned teacher's seven‐step, student's four‐step and a six‐step modelling cycles to explain mathematical modelling competence. The six‐step modelling cycle is also used in Common Core State Standards for Mathematics (CCSSM) in the United States. Based on these previous modelling cycles, we propose a new five‐phase modelling cycle by use of the tool named IBM SPSS Modeler in accordance with Cross Industry Standard Process for Data Mining (CRISP‐DM). A teaching case will be presented to apply these methodologies to undergraduates’ mathematical modelling lessons. It is shown that teachers can use IBM SPSS Modeler to improve student's mathematical modelling competence by understanding and practicing the process of five‐phase modelling. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:603–609, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21632
Predictive Models for Thermal Behavior of Chemicals with Quantitative Structure‐Property Relationships
Authors: Baati Nadia , Nanchen Annik , Stoessel Francis , Meyer Thierry 
Published: February 2015

AbstractMost processes in the chemical industry involve potentially hazardous steps. It is thus of critical importance to perform risk assessments and to know the thermal behavior of the chemicals at stake. A widely used thermal analysis, differential scanning calorimetry, allows verifying if the compounds are stable towards heat or if they decompose above certain temperatures. This information helps setting the appropriate handling and storage conditions for safe operations. The time and resources needed for these experimental investigations would be reduced if the testing phase could be better targeted and guided using reliable predictive methods. This work helps to answer these needs by proposing predictive models for thermal stability based on the quantitative structure‐property relationships method.
An Innovative Approach for Adsorption Column Modeling
Authors: Boyadjiev Christo , Boyadjiev Boyan , Popova‐Krumova Petya , Doichinova Maria 
Published: February 2015

AbstractAn new methody for physical and chemical adsorption modeling in column apparatuses is presented. A convection‐diffusion model is obtained in the approximations of the continua mechanics, where the mathematical point is equivalent to the medium elementary volume which is sufficiently small with respect to the column volume and at the same time sufficiently large with respect to the intermolecular volumes of the medium. The created convection‐diffusion type model allows performing qualitative analysis of the process and obtaining the effect of the velocity radial nonuniformity in the column. An average concentration model is applied for quantitative description of physical and chemical adsorption in the column apparatus. The methods for model equation solutions and model parameter identifications are described.