bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth in Densely Populated Asia: Implications for Primary Product Exporters
Authors: Anderson Kym , Strutt Anna 
Published: November 2013

AbstractEconomic growth and integration in Asia is rapidly increasing the global economic importance of the region. To the extent that this growth continues and is strongest in natural resource‐poor Asian economies, it will add to global demand for imports of primary products, to the benefit of (especially nearby) resource‐abundant countries. How will global production, consumption and trade patterns change by 2030 in the course of such economic developments and structural changes? We address this question using the GTAP model and Version 8.1 of the 2007 GTAP database, together with supplementary data from a range of sources, to support projections of the global economy from 2007 to 2030 under various scenarios. Factor endowments and real gross domestic product are assumed to grow at exogenous rates, and trade‐related policies are kept unchanged to generate a core baseline, which is compared with an alternative slower growth scenario. We also consider the impact of several policy changes aimed at increasing China's agricultural self‐sufficiency relative to the 2030 baseline. Policy implications for countries of the Asia‐Pacific region are drawn out in the final section.
Thymidine Phosphorylase Regulates the Expression of CXCL10 in Rheumatoid Arthritis Fibroblast‐like Synoviocytes
Authors: Toyoda Yuko , Tabata Sho , Kishi Jun , Kuramoto Takuya , Mitsuhashi Atsushi , Saijo Atsuro , Kawano Hiroshi , Goto Hisatsugu , Aono Yoshinori , Hanibuchi Masaki , Horikawa Hideaki , Nakajima Toshihiro , Furukawa Tatsuhiko , Sone Saburo , Akiyama Shin‐ichi , Nishioka Yasuhiko 
Published: November 2013

ObjectiveThymidine phosphorylase (TP) in rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) is induced by tumor necrosis factor α (TNFα) and other cytokines that have been reported to be major inflammation mediators in RA. We previously demonstrated that TP plays an important role in angiogenesis and tumor growth, invasion, and metastasis. The aim of this study was to investigate whether the role of TP in the pathogenesis of RA is similar to its role in tumors.MethodsIn FLS obtained from 2 patients with RA, the expression of TP, interferon‐γ (IFNγ)–inducible protein 10 (CXCL10), and other cytokines was measured by quantitative real‐time polymerase chain reaction, immunoblotting, and enzyme‐linked immunosorbent assays. Microarray analysis was performed using FLS transfected with TYMP complementary DNA and treated with a TP inhibitor.ResultsThe expression of TP in FLS was up‐regulated by TNFα, interleukin‐1β (IL‐1β), IL‐17, IFNγ, and lipopolysaccharide. Microarray analysis of FLS overexpressing TP identified CXCL10 as a thymidine phosphorylase–related gene. The expression of CXCL10 was induced by TNFα, and this induction was suppressed by TYMP small interfering RNA and TP inhibitor. Furthermore, the combination of TNFα and IFNγ synergistically augmented the expression of TP and CXCL10. TP‐induced CXCL10 expression was suppressed by the antioxidant EUK‐8. In the synovial tissue of patients with RA, TP levels were significantly correlated with CXCL10 expression.ConclusionThe combination of TNFα and IFNγ strongly induced the expression of thymidine phosphorylase in RA FLS. The induction of thymidine phosphorylase enhanced the expression of CXCL10, which may contribute to the Th1 phenotype and bone destruction observed in RA.
Predictors of Clinical Improvement in Rituximab‐Treated Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis
Authors: Aggarwal Rohit , Bandos Andriy , Reed Ann M. , Ascherman Dana P. , Barohn Richard J. , Feldman Brian M. , Miller Frederick W. , Rider Lisa G. , Harris‐Love Michael O. , Levesque Marc C. ,   the RIM Study Group, Oddis Chester V. 
Published: November 2013

ObjectiveTo identify the clinical and laboratory predictors of clinical improvement in a cohort of myositis patients treated with rituximab.MethodsWe analyzed data for 195 patients with myositis (75 with adult polymyositis [PM], 72 with adult dermatomyositis [DM], and 48 with juvenile DM) in the Rituximab in Myositis trial. Clinical improvement was defined as 20% improvement in at least 3 of the following 6 core set measures of disease activity: physician's and patient's/parent's global assessment of disease activity, manual muscle testing, physical function, muscle enzymes, and extramuscular disease activity. We analyzed the association of the following baseline variables with improvement: myositis clinical subgroup, demographics, myositis damage, clinical and laboratory parameters, core set measures, rituximab treatment, and myositis autoantibodies (antisynthetase, anti–Mi‐2, anti–signal recognition particle, anti–transcription intermediary factor 1γ [TIF‐1γ], anti‐MJ, other autoantibodies, and no autoantibodies). All measures were univariately assessed for association with improvement using time‐to‐event analyses. A multivariable time‐dependent proportional hazards model was used to evaluate the association of individual predictive factors with improvement.ResultsIn the final multivariable model, the presence of an antisynthetase, primarily anti–Jo‐1 (hazard ratio [HR] 3.08, P < 0.01), anti–Mi‐2 (HR 2.5, P < 0.01), or other autoantibody (HR 1.4, P = 0.14) predicted a shorter time to improvement compared to the absence of autoantibodies. A lower physician's global assessment of damage (HR 2.32, P = 0.02) and juvenile DM (versus adult myositis) (HR 2.45, P = 0.01) also predicted improvement. Unlike autoantibody status, the predictive effect of physician's global assessment of damage and juvenile DM diminished by week 20. Rituximab treatment did not affect these associations.ConclusionOur findings indicate that the presence of antisynthetase and anti–Mi‐2 autoantibodies, juvenile DM subset, and lower disease damage strongly predict clinical improvement in patients with refractory myositis.
Features of the Synovium of Individuals at Risk of Developing Rheumatoid Arthritis: Implications for Understanding Preclinical Rheumatoid Arthritis
Authors: de Hair M. J. H. , van de Sande M. G. H. , Ramwadhdoebe T. H. , Hansson M. , Landewé R. , van der Leij C. , Maas M. , Serre G. , van Schaardenburg D. , Klareskog L. , Gerlag D. M. , van Baarsen L. G. M. , Tak P. P. 
Published: November 2013

ObjectiveFindings from previous studies have suggested that subclinical inflammation of the synovium does not coincide with the appearance of rheumatoid arthritis (RA)–specific autoantibodies. This study was undertaken to examine the relationship between the presence of autoantibodies, changes in the synovium, and development of arthritis over time in a markedly larger, prospective study.MethodsFifty‐five individuals who were IgM rheumatoid factor positive and/or anti–citrullinated protein antibody (ACPA) positive (detected by the anti–cyclic citrullinated peptide antibody test) and who were without any evidence of arthritis upon physical examination were included in the study. ACPAs were subsequently also detected using a multiplex chip‐based assay. All individuals underwent magnetic resonance imaging and mini‐arthroscopic synovial biopsy sampling of a knee joint at inclusion and were prospectively followed up. Proportional hazards regression analysis was performed to investigate whether changes in the synovium were associated with the onset of arthritis.ResultsFifteen individuals (27%) developed arthritis after a median followup time of 13 months (interquartile range 6–27 months; range 1–47 months). No overt synovial inflammation was observed, but CD3+ T cell numbers in the biopsy tissue showed a borderline association with subsequent development of clinically manifest arthritis (hazard ratio 2.8, 95% confidence interval [95% CI] 0.9–9.1; P = 0.088). In addition, the presence of CD8+ T cells was associated with ACPA positivity (odds ratio [OR] 16.0, 95% CI 1.7–151.1) and with the total number of ACPAs present (OR 1.4, 95% CI 1.0–1.8).ConclusionThese findings confirm and extend previous results showing the absence of clearcut synovial inflammation in individuals having systemic autoimmunity associated with RA. However, subtle infiltration by synovial T cells may precede the signs and symptoms of arthritis in preclinical RA.
Ultrasound Assessment of Synovial Pathologic Features in Rheumatoid Arthritis Using Comprehensive Multiplane Images of the Second Metacarpophalangeal Joint: Identification of the Components That Are Reliable and Influential on the Global Assessment of the Whole Joint
Authors: Ikeda Kei , Seto Yohei , Narita Akihiro , Kawakami Atsushi , Kawahito Yutaka , Ito Hiromu , Matsushita Isao , Ohno Shigeru , Nishida Keiichiro , Suzuki Takeshi , Kaneko Atsushi , Ogasawara Michihiro , Fukae Jun , Henmi Mihoko , Sumida Takayuki , Kamishima Tamotsu , Koike Takao ,   for the Japan College of Rheumatology Committee for the Standardization of Musculoskeletal Ultrasonography
Published: November 2013

ObjectiveThe aim of this pilot study was to provide groundwork that could be utilized to optimize the global ultrasound (US) assessment of the whole joint for synovial pathologic features in patients with rheumatoid arthritis (RA).MethodsUS images of the second metacarpophalangeal joint in 8 predefined imaging planes, comprising regions that comprehensively capture the synovial pathologic features of the whole joint, were obtained from 30 patients with RA. Twelve experienced sonographers evaluated these images at the level of both the individual image and the whole joint, using a visual analog scale (VAS) to assess pathologic severity. Interrater reproducibility of the VAS scores was evaluated with intraclass correlation coefficients (ICCs), and factors that independently influenced the global assessment of the whole joint were identified using multiple linear regression analysis.ResultsA total of 14,276 VAS scores were analyzed. Interrater reproducibility of any eligible VAS assessment of synovial pathologic features was good (ICC 0.65). US assessment of synovial pathologic features in joints with mild inflammation was less reproducible than that in joints with severe inflammation. Although the most severely affected region in a joint did not always represent the average pathologic severity among the 8 regions, global assessment of the whole joint strongly correlated with assessment of the most severely affected region (P < 0.001). Importantly, the standard, midline imaging plane was not the most influential plane on the global assessment of the whole joint. Assessment of synovial fluid accumulation was not reproducible (ICCs 0.20–0.42) and did not substantially influence the global assessment of synovial inflammation (β = 0.06).ConclusionThe results of this study provide a unique data set that could be utilized to optimize the global US assessment of synovial pathologic features of the whole joint in patients with RA.
Spinal Inflammation in the Absence of Sacroiliac Joint Inflammation on Magnetic Resonance Imaging in Patients With Active Nonradiographic Axial Spondyloarthritis
Authors: van der Heijde Désirée , Sieper Joachim , Maksymowych Walter P. , Brown Matthew A. , Lambert Robert G. W. , Rathmann Suchitrita S. , Pangan Aileen L. 
Published: November 2013

ObjectiveTo evaluate the presence of spinal inflammation with and without sacroiliac (SI) joint inflammation on magnetic resonance imaging (MRI) in patients with active nonradiographic axial spondyloarthritis (SpA), and to compare the disease characteristics of these subgroups.MethodsABILITY‐1 is a multicenter, randomized, controlled trial of adalimumab versus placebo in patients with nonradiographic axial SpA classified using the Assessment of SpondyloArthritis international Society axial SpA criteria. Baseline MRIs were centrally scored independently by 2 readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method for the SI joints and the SPARCC 6–discovertebral unit method for the spine. Positive evidence of inflammation on MRI was defined as a SPARCC score of ≥2 for either the SI joints or the spine.ResultsAmong patients with baseline SPARCC scores, 40% had an SI joint score of ≥2 and 52% had a spine score of ≥2. Forty‐nine percent of patients with baseline SI joint scores of <2, and 58% of those with baseline SI joint scores of ≥2, had a spine score of ≥2. Comparison of baseline disease characteristics by baseline SI joint and spine scores showed that a greater proportion of patients in the subgroup with a baseline SPARCC score of ≥2 for both SI joints and spine were male, and patients with spine and SI joint scores of <2 were younger and had shorter symptom duration. SPARCC spine scores correlated with baseline symptom duration, and SI joint scores correlated negatively with the baseline Bath Ankylosing Spondylitis Disease Activity Index, but neither correlated with the baseline Ankylosing Spondylitis Disease Activity Score, total back pain, the patient's global assessment of disease activity, the Bath Ankylosing Spondylitis Functional Index, morning stiffness, nocturnal pain, or C‐reactive protein level.ConclusionAssessment by experienced readers showed that spinal inflammation on MRI might be observed in half of patients with nonradiographic axial SpA without SI joint inflammation.
A novel method for the immobilization of a thermostable fungal chitinase and the properties of the immobilized enzyme
Authors: Prasad Muthu , Palanivelu Peramachi 
Published: November 2013

AbstractThe recombinant thermostable fungal chitinase of Thermomyces lanuginosus was immobilized on the phenyl Sepharose matrix, and the properties of the immobilized chitinase were studied. The immobilized enzyme was optimally active at pH 6.0 and 50 °C and showed improved activity in the acidic range of pH values when compared with the soluble enzyme. The recombinant thermostable immobilized enzyme showed remarkable thermostability at 50 °C by retaining about 45% of the activity for more than 6 H. The KM and Vmax values were 1.3 mM and 4.5 mol/min/mg of protein, respectively. Both the free and immobilized forms of the enzymes were inhibited significantly by Ag+ but behaved similarly to various other metal ions, detergents, and additives. The immobilized enzyme was stable for at least 1 month at 4 °C.
Exploring the transcriptome space of a recombinant BHK cell line through next generation sequencing
Authors: Johnson Kathryn C. , Yongky Andrew , Vishwanathan Nandita , Jacob Nitya M. , Jayapal Karthik P. , Goudar Chetan T. , Karypis George , Hu Wei‐Shou 
Published: November 2013

AbstractBaby Hamster Kidney (BHK) cell lines are used in the production of veterinary vaccines and recombinant proteins. To facilitate transcriptome analysis of BHK cell lines, we embarked on an effort to sequence, assemble, and annotate transcript sequences from a recombinant BHK cell line and Syrian hamster liver and brain. RNA‐seq data were supplemented with 6,170 Sanger ESTs from parental and recombinant BHK lines to generate 221,583 contigs. Annotation by homology to other species, primarily mouse, yielded more than 15,000 unique Ensembl mouse gene IDs with high coverage of KEGG canonical pathways. High coverage of enzymes and isoforms was seen for cell metabolism and N‐glycosylation pathways, areas of highest interest for biopharmaceutical production. With the high sequencing depth in RNA‐seq data, we set out to identify single‐nucleotide variants in the transcripts. A majority of the high‐confidence variants detected in both hamster tissue libraries occurred at a frequency of 50%, indicating their origin as heterozygous germline variants. In contrast, the cell line libraries' variants showed a wide range of occurrence frequency, indicating the presence of a heterogeneous population in cultured cells. The extremely high coverage of transcripts of highly abundant genes in RNA‐seq enabled us to identify low‐frequency variants. Experimental verification through Sanger sequencing confirmed the presence of two variants in the cDNA of a highly expressed gene in the BHK cell line. Furthermore, we detected seven potential missense mutations in the genes of the growth signaling pathways that may have arisen during the cell line derivation process. The development and characterization of a BHK reference transcriptome will facilitate future efforts to understand, monitor, and manipulate BHK cells. Our study on sequencing variants is crucial for improved understanding of the errors inherent in high‐throughput sequencing and to increase the accuracy of variant calling in BHK or other systems. Biotechnol. Bioeng. 2014;111: 770–781. © 2013 Wiley Periodicals, Inc.
Controlled local presentation of matrix proteins in microparticle–laden cell aggregates
Authors: Bernard Abigail B. , Chapman Rebeccah Z. , Anseth Kristi S. 
Published: November 2013

ABSTRACTMulti‐cellular aggregates are found in healthy and diseased tissues, and while cell–cell contact is important for regulating many cell functions, cells also interact, to varying degrees, with extra‐cellular matrix (ECM) proteins. Islets of Langerhans are one such example of cell aggregates in contact with ECM, both at the periphery of the cluster and dispersed throughout. While several studies have investigated the effect of reintroducing contact with ECM proteins on islet cell survival and function, the majority of these experiments only allow contact with the exterior cells. Thus, cell‐culture platforms that enable the study of ECM–cell interactions throughout multi‐cellular aggregates are of interest. Here, local presentation of ECM proteins was achieved using hydrogel microwell arrays to incorporate protein‐laden microparticles during formation of MIN6 β‐cell aggregates. Varying the microparticle seeding density reproducibly controlled the number of microparticles incorporated within three‐dimensional aggregates (i.e., total amount of protein). Further, a relatively uniform spatial distribution of laminin‐ and fibronectin‐coated microparticles was achieved throughout the x‐, y‐, and z‐directions. Multiple ECM proteins were presented to β‐cells in concert by incorporating two distinct populations of microparticles throughout the aggregates. Finally, scaling the microwell device dimensions allowed for the formation of two different sized cell–particle aggregates, ∼80 and 160 µm in diameter. While the total number of microparticles incorporated per aggregate varied with size, the fraction of the aggregate occupied by microparticles was affected only by the microparticle seeding density, indicating that uniform local concentrations of proteins can be preserved while changing the overall aggregate dimensions. Biotechnol. Biotechnol. Bioeng. 2014;111: 1028–1037. © 2013 Wiley Periodicals, Inc.
SunnyTALEN: A second‐generation TALEN system for human genome editing
Authors: Sun Ning , Bao Zehua , Xiong Xiong , Zhao Huimin 
Published: November 2013

ABSTRACTTranscription activator‐like effector nucleases (TALENs) have rapidly emerged as a powerful genome editing tool. The site‐specific DNA double‐strand breaks generated by TALENs in the human chromosome can induce homologous recombination or non‐homologous end joining, resulting in desired genetic modifications. In this study, we report the development of a TALEN variant, SunnyTALEN, with >2.5‐fold improved genome editing efficacy in human cells. The corresponding scaffold increases the rate of genetic modification at all the 13 tested loci of human genome and is compatible with heterodimer TALEN architectures. This enhanced and high‐efficiency TALEN variant represents a novel second‐generation TALEN system and has great potential for biological and therapeutic applications. Biotechnol. Bioeng. 2014;111: 683–691. © 2013 Wiley Periodicals, Inc.
Scaffold‐free formation of a millimeter‐scale multicellular spheroid with an internal cavity from magnetically levitated 3T3 cells that ingested iron oxide‐containing microspheres
Authors: Lee Joon Ho , Hur Won 
Published: November 2013

ABSTRACTThis report describes fabrication of a millimeter‐scale three‐dimensional (3D) multicellular structure with a central cavity based on magnetic levitation of 3T3 cells that had ingested Fe3O4‐containing microcapsules. Magnetically levitated cells initially formed a disc‐shaped cell cluster at the air‐medium interface and transformed into a spheroid (up to 2.8 mm in diameter) after 10‐day incubation under a magnet. Hematoxylin‐and‐eosin‐stained section revealed that an eosinophilic shell of cells enclosed a pale‐staining core of the spheroid. Mitotic or elongated and aligned cells were found at the outer periphery of the shell, while Fe3O4 deposits were distributed in the inner part of the shell. Surgical dissection indicated that the spheroid had a hollow interior filled with a fluid‐state cell suspension. Accordingly, it was demonstrated that magnetically levitated 3T3 cells organized themselves into a tissue‐like spheroid, resulting in core cell death. The spheroid can be used as a 3D tissue model and as building blocks that fused to form a more complicated structure. Biotechnol. Biotechnol. Bioeng. 2014;111: 1038–1047. © 2013 Wiley Periodicals, Inc.
Virtual Scrum: A teaching aid to introduce undergraduate software engineering students to scrum
Authors: Rodriguez Guillermo , Soria Álvaro , Campo Marcelo 
Published: November 2013

ABSTRACTTeaching agile practices is becoming a priority in Software engineering curricula as a result of the increasing use of agile methods (AMs) such as Scrum in the software industry. Limitations in time, scope, and facilities within academic contexts hinder students' hands‐on experience in the use of professional AMs. To enhance students' exposure to Scrum, we have developed Virtual Scrum, an educational virtual world that simulates a Scrum‐based team room through virtual elements such as blackboards, a Web browser, document viewers, charts, and a calendar. A preliminary version of Virtual Scrum was tested with a group of 45 students running a capstone project with and without Virtual Scrum support. Students' feedback showed that Virtual Scrum is a viable and effective tool to implement the different elements in a Scrum team room and to perform activities throughout the Scrum process. © 2013 Wiley Periodicals, Inc. Comput Appl Eng Educ 999: XX–XX, 2013; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21588 © 2013 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:147–156, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21588