bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication Adherence in Gout: A Systematic Review
Authors: De Vera Mary A. , Marcotte Greg , Rai Sharan , Galo Jessica S. , Bhole Vidula
Published: April 2014

Objective

Recent data suggesting the growing problem of medication nonadherence in gout have called for the need to synthesize the burden, determinants, and impacts of the problem. Our objective was to conduct a systematic review of the literature examining medication adherence among patients with gout in real‐world settings.

Methods

We conducted a search of Medline, Embase, International Pharmaceutical Abstracts, PsycINFO, and CINAHL databases and selected studies of gout patients and medication adherence in real‐world settings. We extracted information on study design, sample size, length of followup, data source (e.g., prescription records versus electronic monitoring versus self‐report), type of nonadherence problem evaluated, adherence measures and reported estimates, and determinants of adherence reported in multivariable analyses.

Results

We included 16 studies that we categorized according to methods used to measure adherence, including electronic prescription records (n = 10), clinical records (n = 1), electronic monitoring devices (n = 1), and self‐report (n = 4). The burden of nonadherence was reported in all studies, and among studies based on electronic prescription records, adherence rates were all below 0.80 and the proportion of adherent patients ranged from 10–46%. Six studies reported on determinants, with older age and having comorbid hypertension consistently shown to be positively associated with better adherence. One study showed the impact of adherence on achieving a serum uric acid target.

Conclusion

With less than half of gout patients in real‐world settings adherent to their treatment, this systematic review highlights the importance of health care professionals discussing adherence to medications during encounters with patients.
Associations of Hydroxychloroquine Use With Lipid Profiles in Rheumatoid Arthritis: Pharmacologic Implications
Authors: Kerr Gail , Aujero Mireille , Richards John , Sayles Harlan , Davis Lisa , Cannon Grant , Caplan Liron , Michaud Kaleb , Mikuls Ted
Published: April 2014

Objective

To evaluate the association of hydroxychloroquine (HCQ) use with lipid profiles in a Veterans Affairs Rheumatoid Arthritis (VARA) cohort.

Methods

Lipid profiles in HCQ users were compared with HCQ nonusers, adjusting for potential confounders (age, sex, race, disease activity, prednisone, disease‐modifying antirheumatic drugs, diabetes mellitus, and statin use). Applying current National Cholesterol Education Program Adult Treatment Panel III (NCEP‐ATP III) guidelines for reduction of cardiovascular disease (CVD) events risk, the frequency of target lipid profiles with HCQ status was evaluated. Varied periods of HCQ exposure were compared to ascertain pharmacologic associations with lipid values. CVDs were compared between HCQ users and nonusers.

Results

In an elderly, predominantly male VARA cohort, 1,011 patients had lipid profiles; 787 patients (77.8%) were white. Statin use was recorded in 11.6% of patients, diabetes mellitus in 33.5%, and CVD in 31.2%. HCQ users (n = 150) were older, had longer rheumatoid arthritis (RA) disease duration, and had lower disease activity. Optimum lipid profiles, including total cholesterol:high‐density lipoprotein (HDL) and HDL:low‐density lipoprotein ratios (P ≤ 0.001), were more frequent in HCQ users, with the exception of HDL (P = 0.165), and persisted in multivariate analyses. Similarly, more HCQ users had NCEP‐ATP III target levels. Varied periods of HCQ exposure suggested lipid changes to occur early, but lost within a year of drug discontinuation. HCQ users had less prevalent CVD.

Conclusion

In RA patients, HCQ use of at least 3 months' duration was associated with better lipid profiles irrespective of disease activity or statin use. Given the increased CVD risks in RA and the relative low cost and toxicity of HCQ, continued use, regardless of treatment regimen, should be considered.
Lithium Titanate Tailored by Cathodically Induced Graphene for an Ultrafast Lithium Ion Battery
Authors: Yang Yingchang , Qiao Binghan , Yang Xuming , Fang Laibing , Pan Chengchi , Song Weixin , Hou Hongshuai , Ji Xiaobo
Published: April 2014

Nonoxidative cathodically induced graphene (CIG) here incorporates conductive agents for Li4Ti5O12 (LTO) anode materials. The tailored LTO/CIG composite is fabricated by controlled hydrolysis of tetrabutyl titanate in the presence of nonoxidative defect‐free cathodically induced graphene (CIG) and oxalic acid in a mixed solvent of ethanol and water, followed by hydrothermal reaction and a calcination treatment. Due to the introduction of defect‐free graphene, the resulting LTO/CIG composite shows an excellent electrical conductivity (1.2 × 10−4 S cm−1) and Li+ diffusion coefficient (1.61 × 10−12 cm2 s−1). As a result, the tuned LTO/CIG composite exhibits outstanding electrochemical performance, including excellent cycling stability (the capacity retention ratios after 500 cycles at 0.5 C is 96.2%) and a remarkable rate capability (162 mAh g−1 at 10C, 126 mAh g−1 at 100 C). A specific energy of 272 Wh kg−1 at power of 136 W kg−1 is observed when cycling against Li‐foil. Even during 36 s of charge/discharge, the specific energy of LTO/CIG composite remains at 166 Wh kg−1.
Electrospun Polyaniline Fibers as Highly Sensitive Room Temperature Chemiresistive Sensors for Ammonia and Nitrogen Dioxide Gases
Authors: Zhang Yuxi , Kim Jae Jin , Chen Di , Tuller Harry L. , Rutledge Gregory C.
Published: April 2014

Electrospun polyaniline (PAni) fibers doped with different levels of (+)‐camphor‐10‐sulfonic acid (HCSA) are fabricated and evaluated as chemiresistive gas sensors. The experimental results, based on both sensitivity and response time, show that doped PAni fibers are excellent ammonia sensors and that undoped PAni fibers are excellent nitrogen dioxide sensors. The fibers exhibit changes in measured resistances up to 60‐fold for ammonia sensing, and more than five orders of magnitude for nitrogen dioxide sensing, with characteristic response times on the order of one minute in both cases. A time‐dependent reaction‐diffusion model is used to extract physical parameters from fitting experimental sensor data. The model is then used to illustrate the selection of optimal material design parameters for gas sensing by nanofibers.
Nanotechnology for the Detection and Therapy of Stroke
Authors: Kyle Stuart , Saha Sikha
Published: April 2014

Over the years, nanotechnology has greatly developed, moving from careful design strategies and synthesis of novel nanostructures to producing them for specific medical and biological applications. The use of nanotechnology in diagnostics, drug delivery, and tissue engineering holds great promise for the treatment of stroke in the future. Nanoparticles are employed to monitor grafted cells upon implantation, or to enhance the imagery of the tissue, which is coupled with a noninvasive imaging modality such as magnetic resonance imaging, computed axial tomography or positron emission tomography scan. Contrast imaging agents used can range from iron oxide, perfluorocarbon, cerium oxide or platinum nanoparticles to quantum dots. The use of nanomaterial scaffolds for neuroregeneration is another area of nanomedicine, which involves the creation of an extracellular matrix mimic that not only serves as a structural support but promotes neuronal growth, inhibits glial differentiation, and controls hemostasis. Promisingly, carbon nanotubes can act as scaffolds for stem cell therapy and functionalizing these scaffolds may enhance their therapeutic potential for treatment of stroke. This Progress Report highlights the recent developments in nanotechnology for the detection and therapy of stroke. Recent advances in the use of nanomaterials as tissue engineering scaffolds for neuroregeneration will also be discussed.
A Shape‐Adaptive Thin‐Film‐Based Approach for 50% High‐Efficiency Energy Generation Through Micro‐Grating Sliding Electrification
Authors: Zhu Guang , Zhou Yu Sheng , Bai Peng , Meng Xian Song , Jing Qingshen , Chen Jun , Wang Zhong Lin
Published: April 2014

Effectively harvesting ambient mechanical energy is the key for realizing self‐powered and autonomous electronics, which addresses limitations of batteries and thus has tremendous applications in sensor networks, wireless devices, and wearable/implantable electronics, etc. Here, a thin‐film‐based micro‐grating triboelectric nanogenerator (MG‐TENG) is developed for high‐efficiency power generation through conversion of mechanical energy. The shape‐adaptive MG‐TENG relies on sliding electrification between complementary micro‐sized arrays of linear grating, which offers a unique and straightforward solution in harnessing energy from relative sliding motion between surfaces. Operating at a sliding velocity of 10 m/s, a MG‐TENG of 60 cm2 in overall area, 0.2 cm3 in volume and 0.6 g in weight can deliver an average output power of 3 W (power density of 50 mW cm−2 and 15 W cm−3) at an overall conversion efficiency of ∼50%, making it a sufficient power supply to regular electronics, such as light bulbs. The scalable and cost‐effective MG‐TENG is practically applicable in not only harvesting various mechanical motions but also possibly power generation at a large scale.
Nano‐Gold as Artificial Enzymes: Hidden Talents
Authors: Lin Youhui , Ren Jinsong , Qu Xiaogang
Published: April 2014

Creating artificial enzymes that mimic the complexity and function of natural systems has been a great challenge for the past two decades. In this Progress Report, the focus is on recently discovered “hidden talents” of gold nanomaterials in artificial enzymes, including mimicking of nuclease, esterase, silicatein, glucose oxidase, peroxidase, catalase, and superoxide dismutase. These unexpected enzyme‐like activities can be ascribed to nano‐gold itself or the functional groups present on surrounding monolayer. Along with introducing the mechanisms of the various enzyme‐like activities, the design and development of gold‐based biomimetic catalysts, the search for efficient modulators, and their potential applications in bionics, biosensing, and biomedical sciences are highlighted. Eventually, it is expected that the rapidly growing interest in gold‐based nanozymes will certainly fuel the excitement and stimulate research in this highly active field.
Impact of Hole Transport Layer Surface Properties on the Morphology of a Polymer‐Fullerene Bulk Heterojunction
Authors: Widjonarko N. Edwin , Schulz Philip , Parilla Philip A. , Perkins Craig L. , Ndione Paul F. , Sigdel Ajaya K. , Olson Dana C. , Ginley David S. , Kahn Antoine , Toney Michael F. , Berry Joseph J.
Published: April 2014

Investigations on the impact of interfacial modification on organic optoelectronic device performance often attribute the improved device performance to the optoelectronic properties of the modifier. A critical assumption of such conclusions is that the organic active layer deposited on top of the modified surface (interface) remains unaltered. Here the validity of this assumption is investigated by examining the impact of substrate surface properties on the morphology of poly(3‐hexylthiophene):1‐(3‐methoxycarbonyl)‐propyl‐1‐phenyl‐[6,6]C61 (P3HT:PCBM) bulk‐heterojunction (BHJ). A set of four nickel oxide and poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hole transport layers (HTL) with contrasting surface properties and performance in organic photovoltaic (OPV) devices is studied. Differences in vertical composition variation and structural morphologies are observed across the samples, but only in the near‐interface region of <∼20 nm. Near‐interface differences in morphology are most closely correlated with surface polarity and surface roughness of the HTL. Surface polarity is more influenced by surface composition than surface roughness and crystal structure. These findings corroborate the previously mentioned conclusions that the differences in device performance observed in solar cells employing these HTLs are dominated by the electronic properties of the HTL/organic photoactive active layer interface and not by unintentional alteration in the BHJ active layer morphology.
Integrating ZnO Microwires with Nanoscale Electrodes Using a Suspended PMMA Ribbon for Studying Reliable Electrical and Electromechanical Properties
Authors: Kim Hakseong , Yun Hoyeol , Yoon Ho Ang , Lee Sang Wook
Published: April 2014

A simple method for making electrical connections to ZnO microwires is reported. By using a suspended poly(methyl methacrylate) (PMMA) ribbon, it is shown that it is possible to electrically contact 1–2 μm diameter ZnO microwires with metal electrodes that are only 90 nm thick. The contact resistances of ZnO microwire‐based electronic devices fabricated by this method are lower than those of devices fabricated by standard electron‐beam lithography and evaporation processes. As one of the possible device applications from this fabrication method, suspended ZnO microwire‐based electromechanical devices are produced and their piezoelectric properties are investigated. Piezoelectric‐induced current is detected when the suspended microwires are induced to vibrate at their resonant frequency. This fabrication method can be readily and generally applied to prepare nanoscale electrodes on micrometer‐sized materials and provides a convenient means for studying their electrical and electromechanical phenomena in a reliable manner.
Cinchona Alkaloids as Organocatalysts in Enantioselective Halofunctionalization of Alkenes and Alkynes
Authors: Zheng Suqing , Schienebeck Casi M. , Zhang Wei , Wang Hao‐Yuan , Tang Weiping
Published: April 2014

Naturally occurring cinchona alkaloids include quinine, quinidine, cinchonine, and cinchonidine. Many of their derivatives are also readily available. This Focus Review summarizes recent applications of cinchona alkaloid derivatives, an important class of organocatalysts, in enantioselective halofunctionalization of alkenes and alkynes. Most successful examples in this area are intramolecular halofunctionalizations, where the nucleophile is tethered with the alkene or alkyne substrate. Only a few catalytic enantioselective intermolecular halofunctionalization of alkenes have been realized. Dimeric cinchona alkaloids are the most frequently used catalysts in asymmetric halofunctionalizations. Most other catalysts have an appended functional group on the C9 position of the cinchona alkaloids. These functional groups include (thio)urea, thiocarbamate, and sulfonamides.
Redox‐Neutral α,β‐Difunctionalization of Cyclic Amines
Authors: Chen Weijie , Kang YoungKu , Wilde Richard G. , Seidel Daniel
Published: April 2014

In contrast to the continuously growing number of methods that allow for the efficient α‐functionalization of amines, few strategies exist that enable the direct functionalization of amines in the β‐position. A general redox‐neutral strategy is outlined for amine β‐functionalization and α,β‐difunctionalization that utilizes enamines generated in situ. This concept is demonstrated in the context of preparing polycyclic N,O‐acetals from simple 1‐(aminomethyl)‐β‐naphthols and 2‐(aminomethyl)‐phenols.
A Molecular Ferroelectric Thin Film of Imidazolium Perchlorate That Shows Superior Electromechanical Coupling
Authors: Zhang Yi , Liu Yuanming , Ye Heng‐Yun , Fu Da‐Wei , Gao Wenxiu , Ma He , Liu Zhiguo , Liu Yunya , Zhang Wen , Li Jiangyu , Yuan Guo‐Liang , Xiong Ren‐Gen
Published: April 2014

Molecular ferroelectric thin films are highly desirable for their easy and environmentally friendly processing, light weight, and mechanical flexibility. A thin film of imidazolium perchlorate processed from aqueous solution is an excellent molecular ferroelectric with high spontaneous polarization, high Curie temperature, low coercivity, and superior electromechanical coupling. These attributes make it a molecular alternative to perovskite ferroelectric films in sensing, actuation, data storage, electro‐optics, and molecular/flexible electronics.
Substrate Templating Guides the Photoinduced Reaction of C60 on Calcite
Authors: Lindner Robert , Rahe Philipp , Kittelmann Markus , Gourdon André , Bechstein Ralf , Kühnle Angelika
Published: April 2014

A substrate‐guided photochemical reaction of C60 fullerenes on calcite, a bulk insulator, investigated by non‐contact atomic force microscopy is presented. The success of the covalent linkage is evident from a shortening of the intermolecular distances, which is clearly expressed by the disappearance of the moiré pattern. Furthermore, UV/Vis spectroscopy and mass spectrometry measurements carried out on thick films demonstrate the ability of our setup for initiating the photoinduced reaction. The irradiation of C60 results in well‐oriented covalently linked domains. The orientation of these domains is dictated by the lattice dimensions of the underlying calcite substrate. Using the lattice mismatch to deliberately steer the direction of the chemical reaction is expected to constitute a general design principle for on‐surface synthesis. This work thus provides a strategy for controlled fabrication of oriented, covalent networks on bulk insulators.
Relationship of Gene Expression in the Injured Human Meniscus to Body Mass Index: A Biologic Connection Between Obesity and Osteoarthritis
Authors: Rai Muhammad Farooq , Patra Debabrata , Sandell Linda J. , Brophy Robert H.
Published: April 2014

Objective

Higher body mass index (BMI) increases the risk of meniscus injury and knee osteoarthritis (OA). However, it is unknown if and how obesity affects meniscus biology. We analyzed transcriptome‐wide gene expression profiles of injured human menisci to test the hypothesis that meniscal gene expression signatures relate to patient BMI.

Methods

Meniscus samples were obtained from patients undergoing arthroscopic partial meniscectomy. Transcriptome‐wide analysis of gene expression followed by validation of selected transcripts by QuantiGene Plex assay was performed. Correlations of gene expression with BMI and relative fold changes (≥1.5‐fold) in 3 BMI categories (lean [BMI 18.5–24.9 kg/m2], overweight [BMI 25.0–29.9 kg/m2], and obese [BMI >30.0 kg/m2]) were analyzed, and integrated functional classifications were probed computationally.

Results

The obese versus overweight comparison resulted in the largest set of differences (565 transcripts) followed by obese versus lean (280 transcripts) and overweight versus lean (125 transcripts). Biologic reproducibility was confirmed by cluster analysis of expressed transcripts. Differentially regulated transcripts represented important functional classifications. Transcripts associated with oxygen transport, calcium ion binding, and cell homeostasis were elevated with BMI, while those related to extracellular matrix deposition, cell migration, and glucosamine metabolic processes were repressed. While these functional classifications may play key roles in cartilage/meniscus homeostasis, failure of extracellular matrix deposition and increase in calcium ion binding likely contribute to OA development following meniscal injury.

Conclusion

Our results indicate greater differences in gene expression between obese and overweight groups than between overweight and lean groups. This may indicate that there is a weight threshold at which injured meniscus responds severely to increased BMI. BMI‐related changes in gene expression present a plausible explanation for the role of meniscal injury in OA development among obese patients.
HLA–B27 Subtype Oligomerization and Intracellular Accumulation Patterns Correlate With Predisposition to Spondyloarthritis
Authors: Jeanty Cindy , Sourisce Adèle , Noteuil Aurélie , Jah Nadège , Wielgosik Aurore , Fert Ingrid , Breban Maxime , André Claudine
Published: April 2014

Objective

Mechanisms underlying the striking association of spondyloarthritis (SpA) with the class I major histocompatibility complex molecule HLA–B27 remain poorly understood. SpA‐like disease develops spontaneously in B*2705‐transgenic rats, in conjunction with high HLA–B27 expression levels. This study was undertaken to examine the effects of increased expression of HLA–B27 alleles that are differentially associated with SpA on oligomerization and intracellular redistribution.

Methods

HeLa cells were transfected with complementary DNA encoding for HLA–B proteins fused to yellow fluorescent protein and/or Renilla luciferase and harvested at an early phase and a later phase of expression. We monitored HLA–B intracellular trafficking and localization by means of microscopy and live‐cell imaging. Bioluminescence resonance energy transfer (BRET) and Western blotting were used to monitor HLA–B oligomerization.

Results

At low expression levels, BRET signals were similarly elevated for all SpA‐associated HLA–B27 alleles tested, but were lower for the nonassociated B*2706. Of note, at higher expression levels, HLA–B27 signals remained steady while signal for HLA–B7 decreased sharply, reaching the level observed for B*2706. This was due at least in part to a decreased oligomer proportion without unfolded protein response outbreak. Such differential behavior was not abrogated by proteasome inhibition. With increased expression, all HLA–B proteins accumulated to a high density in cytoplasmic vesicles with labile form and size. The extent of this phenomenon was closely correlated with the level of association with predisposition to SpA.

Conclusion

To our knowledge, this is the first report of a correlation between the level of predisposition to SpA conferred by HLA–B27 alleles and their biochemical behavior. These findings open new perspectives for understanding the pathogenicity of HLA–B27.
Deletion of the Antiphospholipid Syndrome Autoantigen β2‐Glycoprotein I Potentiates the Lupus Autoimmune Phenotype in a Toll‐like Receptor 7–Mediated Murine Model
Authors: Giannakopoulos Bill , Mirarabshahi Peyman , Qi Miao , Weatherall Chris , Qi Jian Cheng , Tanaka Kumiko , Millar Ewan , Vonthethoff Leon , Gatto Dominique , Spielman Derek , Krilis Steven A.
Published: April 2014

Objective

The BXSB.Yaa mouse strain is a model of systemic lupus erythematosus that is dependent on duplication of the Toll‐like receptor 7 gene. The objective of this study was to systematically describe the amplified autoimmune phenotype observed when the soluble plasma protein β2‐glycoprotein I (β2GPI) gene was deleted in male BXSB.Yaa mice.

Methods

We generated BXSB.Yaa and NZW mouse strains in which the β2GPI gene had been knocked out by backcrossing the wild‐type strains with C57BL/6 β2GPI−/− mice for 10 generations. Sex‐ and age‐matched mice of the various strains were housed under identical conditions and were killed at fixed time intervals. Serum and tissue specimens were collected at various time points. Lupus‐associated autoantibodies, inflammatory cytokines, and the type I interferon (IFN) gene signature were measured. Flow cytometric analyses of lymphocyte populations were performed. The severity of glomerulonephritis was graded by 2 independent renal histopathologists.

Results

Male BXSB.Yaa β2GPI−/− mice developed significant lymphadenopathy and splenomegaly compared with age‐matched controls. Male BXSB.Yaa β2GPI−/− mice also had significantly higher levels of autoantibodies, increased levels of inflammatory cytokines including tumor necrosis factor α, interleukin‐6, and BAFF, and more severe glomerulonephritis. The type I IFN gene signature in male BXSB.Yaa β2GPI−/− mice was significantly higher than that in control mice. Male BXSB.Yaa β2GPI−/− mice also had marked dysregulation of various B cell and T cell populations in the spleens and lymph nodes and a disturbance in apoptotic cell clearance.

Conclusion

Deletion of β2GPI accelerates and potentiates the autoimmune phenotype in male BXSB.Yaa mice.
Brief Report: T Cell Expression of Granulocyte–Macrophage Colony‐Stimulating Factor in Juvenile Arthritis Is Contingent Upon Th17 Plasticity
Authors: Piper Christopher , Pesenacker Anne M. , Bending David , Thirugnanabalan Balathas , Varsani Hemlata , Wedderburn Lucy R. , Nistala Kiran
Published: April 2014

Objective

Granulocyte–macrophage colony stimulating factor (GM‐CSF) is a potent inflammatory mediator that is responsible for recruitment and activation of innate immune cells. Recent data from murine studies have identified Th17 cells as a key source of GM‐CSF and suggest that T cell–derived GM‐CSF is instrumental in the induction of autoimmune disease. The present study was undertaken to analyze the expression of T cell–derived GM‐CSF in the joints of patients with juvenile idiopathic arthritis (JIA) and to investigate the differentiation of Th17 cells and how this relates to GM‐CSF+ T helper cells.

Methods

Synovial fluid (SF) and peripheral blood (PB) samples from 24 patients with JIA were analyzed, by flow cytometry and reverse transcription–polymerase chain reaction, for expression of GM‐CSF and the Th17 marker CD161. A cytokine capture assay was used to purify Th17 cells and test the plasticity of cytokine production in response to interleukin‐12 (IL‐12) and IL‐23.

Results

The frequency of GM‐CSF–producing T helper cells was significantly enriched in SF mononuclear cells compared to PB mononuclear cells from the patients with JIA (24.1% of CD4+ T cells versus 2.9%) and closely correlated with the erythrocyte sedimentation rate (r2 = 0.91, P < 0.001). Synovial GM‐CSF+ T cells were predominantly CD161+ and coexpressed interferon‐γ (IFNγ), but not IL‐17. Culture of Th17 cells in the presence of IL‐12 led to rapid up‐regulation of GM‐CSF and IFNγ, recapitulating the phenotype of GM‐CSF–expressing cells within the joint.

Conclusion

Our results identify a novel outcome of Th17 plasticity in humans that may account for the enrichment of GM‐CSF–expressing T cells in the joints of patients with JIA. The association of GM‐CSF expression with systemic inflammation highlights the potential role of Th17‐related cytokines in the pathology of JIA.
Fucosyltransferase 1 Mediates Angiogenesis in Rheumatoid Arthritis
Authors: Isozaki Takeo , Amin Mohammad A. , Ruth Jeffrey H. , Campbell Phillip L. , Tsou Pei‐Suen , Ha Christine M. , Stinson W. Alex , Domino Steven E. , Koch Alisa E.
Published: April 2014

Objective

To determine the role of α(1,2)‐linked fucosylation of proteins by fucosyltransferase 1 (FUT1) in rheumatoid arthritis (RA) angiogenesis.

Methods

Analysis of α(1,2)‐linked fucosylated proteins in synovial tissue (ST) samples was performed by immunohistologic staining. Expression of α(1,2)‐linked fucosylated angiogenic chemokine in synovial fluid (SF) was determined by immunoprecipitation and lectin blotting. To determine the angiogenic role of α(1,2)‐linked fucosylated proteins in RA, we performed human dermal microvascular endothelial cell (HMVEC) chemotaxis and Matrigel assays using sham‐depleted and α(1,2)‐linked fucosylated protein–depleted RA SF samples. To examine the production of proangiogenic chemokines by FUT1 in HMVECs, cells were transfected with FUT1 sense or antisense oligonucleotides, and enzyme‐linked immunosorbent assay was performed. We then studied mouse lung endothelial cell (EC) chemotaxis using wild‐type and FUT1 gene–deficient mouse lung ECs.

Results

RA ST endothelial cells showed high expression of α(1,2)‐linked fucosylated proteins compared to normal ST. The expression of α(1,2)‐linked fucosylated monocyte chemoattractant protein 1 (MCP‐1)/CCL2 was significantly elevated in RA SF compared with osteoarthritis SF. Depletion of α(1,2)‐linked fucosylated proteins in RA SF induced less HMVEC migration and tube formation than occurred in sham‐depleted RA SF. We found that blocking FUT1 expression in ECs resulted in decreased MCP‐1/CCL2 and RANTES/CCL5 production. Finally, we showed that FUT1 regulates EC migration in response to vascular endothelial cell growth factor.

Conclusion

Our findings indicate that α(1,2)‐linked fucosylation by FUT1 may be an important new target for angiogenic diseases such as RA.
Genome‐Wide Copy Number Variation Analysis Identifies Deletion Variants Associated With Ankylosing Spondylitis
Authors: Jung Seung‐Hyun , Yim Seon‐Hee , Hu Hae‐Jin , Lee Kyu Hoon , Lee Joo‐Hyun , Sheen Dong‐Hyuk , Lim Mi‐Kyoung , Kim Soon‐Young , Park Sung‐Won , Kim So‐Hee , Han Kyudong , Kim Tae‐Hwan , Shim Seung‐Cheol , Chung Yeun‐Jun
Published: April 2014

Objective

To identify ankylosing spondylitis (AS)–associated copy number variations (CNVs) in Korean subjects and their synergistic roles in the development of AS.

Methods

A genome‐wide association study (GWAS) was performed in 309 patients with AS and 309 control subjects, using a copy number variant (CNV) microarray. AS‐associated CNV regions were replicated in 2 independent sets (625 patients and 891 control subjects) by quantitative polymerase chain reaction (PCR) and deletion‐typing PCR.

Results

In the CNV GWAS, 227 CNV regions were shown to be significantly associated with the risk of AS. Of the candidate CNV regions, 9 were successfully replicated in the first replication analysis: 1q32.2 (HHAT), 1p34.2 (BMP8A), 2q31.2 (PRKRA), 6p21.32 (HLA–DPB1), 11q22.1 (CNTN5), 13q13.1 (EEF1DP3), 14q24.2 (RGS6), 16p13.3, and 22q11.1 (IL17RA). The 5 deletion‐type CNV regions, in 1q32.2, 2q31.2, 6p21.32, 13q13.1, and 16p13.3, were associated with an increased risk of AS, and the other 4 CNV regions were protective. In the second replication analysis, 4 CNV regions in 1q32.2, 2q31.2, 6p21.32, and 16p13.3 were replicated. Among patients with CNV regions in ≥4 risk‐increasing loci, the risk was 18.0 times higher than that in patients without any deletions (odds ratio [OR] 17.98, P = 2.3 × 10−7). Among patients with CNV regions in ≥2 protective loci, the risk was 5.2 times lower than that in those without any deletions (OR 0.19, P = 4.0 × 10−10). The additive effects of simultaneous events were shown to be dependent on the frequency of CNV regions. Through deletion‐typing PCR and sequencing, the exact sizes and breakpoint sequences were defined in 4 CNV regions. The mechanism of all 3 deletions was shown to be microhomology‐based nonhomologous end joining.

Conclusion

The results of this study can help to identify pathogenic mechanisms of AS and can easily be applied in the development of algorithms estimating the risk of AS.
Effect of Methotrexate Use and Erythrocyte Methotrexate Polyglutamate on Glycosylated Hemoglobin in Rheumatoid Arthritis
Authors: de Rotte Maurits C. F. J. , de Jong Pascal H. P. , den Boer Ethan , Pluijm Saskia M. F. , Özcan Behiye , Weel Angelique E. A. M. , Lindemans Jan , Hazes Johanna M. W. , de Jonge Robert
Published: April 2014

Objective

To investigate whether methotrexate (MTX) use, as compared to other therapies, and erythrocyte methotrexate polyglutamate (MTXGlu) concentrations are associated with changes in glycosylated hemoglobin (HbA1c) levels in rheumatoid arthritis (RA) patients.

Methods

The derivation cohort consisted of patients selected from the Treatment in the Rotterdam Early Arthritis Cohort who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA. Patients were randomized to 6 treatment arms: triple disease‐modifying antirheumatic drug (DMARD) therapy (consisting of MTX, sulfasalazine, and hydroxychloroquine [HCQ]) + intramuscular (IM) glucocorticoids, triple DMARD therapy + oral glucocorticoids, MTX + oral glucocorticoid therapy, MTX therapy, oral glucocorticoid therapy, and HCQ therapy. HbA1c levels were determined at baseline and at 3 months. Concentrations of erythrocyte MTXGlu1–5 were measured after 3 months of treatment. Within treatment arms, changes in the level of HbA1c were compared by paired t‐test. Associations of MTXGlu concentrations with changes in the level of HbA1c were tested using multiple linear regression analysis, adjusted for age, sex, body mass index, and comedication. Significant associations were validated using data on RA patients taking MTX who were enrolled in the Methotrexate in Rotterdam cohort.

Results

In the derivation cohort, the mean change in HbA1c level after 3 months of treatment was −1.9 mmoles/mole (−0.18%) (P = 0.001). Levels of HbA1c decreased in 4 of the individual treatment groups, as follows: for the triple DMARD therapy + IM glucocorticoids treatment arm, −5.5 mmoles/mole (−0.50%) (P < 0.001), for the triple DMARD therapy + oral glucocorticoids treatment arm, –3.7 mmoles/mole (−0.34%) (P < 0.001), for the MTX treatment arm, −0.8 mmoles/mole (−0.08%) (P = 0.018), and for the HCQ treatment arm, −2.0 mmoles/mole (−0.19%) (P = 0.175). Increased levels of MTXGlu2 (β = −0.20, P = 0.005), MTXGlu3 (β = −0.31, P < 0.001), MTXGlu4 (β = −0.33, P < 0.001) after treatment, MTXGlu5 (β = −0.39, P < 0.001), and total MTXGlu (β = −0.29, P < 0.001) were associated with decreased levels of HBA1c. In the validation cohort, levels of HbA1c were decreased by 2.6 mmoles/mole (0.23%) (P < 0.001) after treatment, and MTXGlu3 was associated with decreased levels of HbA1c (β = −0.26, P = 0.018).

Conclusion

MTX use and higher concentrations of erythrocyte MTXGlu are associated with decreased levels of HbA1c in RA patients. Triple DMARD therapy and HCQ treatment resulted in reduced HbA1c levels, and glucocorticoid treatment resulted in increased levels of HbA1c.
Empirische Analyse sicherheitskritischer Ereignisse in urbanisierten Gebieten
Authors: Fischer Kai , Siebold Uli , Vogelbacher Georg , Häring Ivo , Riedel Werner
Published: April 2014

Sowohl der Schutz kritischer Infrastruktur als auch Verwundbarkeitsanalysen von städtischen Gebieten gewinnen immer mehr an Bedeutung. Gründe dafür sind eine wachsende Urbanisierung und die steigende Zahl neuer Bedrohungsszenarien. Immer mehr Menschen leben in Städten und in Zukunft wird dieser Trend noch zunehmen. Angesichts der wachsenden Bedrohung, wie beispielsweise globalem Terrorismus oder Naturkatastrophen, ist es essenziell, diese außergewöhnlichen Belastungsszenarien im Rahmen der Sicherheitsforschung zu berücksichtigen. Ziel ist hierbei, dass eine Schutzauslegung fester Bestandteil in der Gebäude‐ und Städteplanung wird.

Um urbane Gebiete oder einzelne Gebäude auszulegen, müssen in einem ersten Schritt maßgebende Szenarien als Bemessungsgrundlage definiert werden, um eine schematische Gefährdungs‐ und Risikoanalyse durchzuführen. In diesem Beitrag werden die Resultate einer empirischen Ereignisanalyse vorgestellt. Im Rahmen dieser Analyse wurden sicherheitskritische Ereignisse in städtischen Gebieten mithilfe der “Terrorist Event Database” ermittelt. Die Ergebnisse liefern die Grundlage der empirischen Auswertung und weiterführender quantitativer Risikoanalysen für sicherheitskritische Ereignisse.

Empirical analysis of security critical events in urban areas

Security for critical infrastructure and the vulnerability analysis of urban areas is a topic of growing interest. Reasons for this are a growing urbanization and an increasing number of new hazard scenarios. More and more people are living in urban areas and this trend is set to continue. When faced with the increasing hazards, like global terrorism or natural disasters for example, it is essential to consider these exceptional scenarios in the context of safety and security research. Therefore, it is the aim to integrate protection design as an inherent part of building development and urban planning.

In a first step, a decisive scenario as assessment basis has to be defined to evaluate urban areas or single buildings. This is essential to build a basis for a schematic hazard and risk analysis. In this paper, the results of an empirical event analysis are presented. Within this work security critical events are evaluated using the ”Terrorist Event Database". The results build the basis for the empirical evaluation and pursuing quantitative risk analyses for safety critical scenarios.
Geschichte der Bautechnik: Anmerkungen eines Beratenden Ingenieurs
Authors: Stiglat Klaus
Published: April 2014

Die folgenden kurzen Anmerkungen gelten dem bauenden Ingenieur als einer Kernperson in der neueren Geschichte der Bautechnik; sie entspringen meinem Alltag als selbstständiger, beratender, planender und prüfender Bauingenieur und, parallel dazu, einem viertel Jahrhundert Erfahrung als Schriftleiter von Beton‐ und Stahlbetonbau. Die Zeit seit meinem Ausscheiden aus dem aktiven Beruf 2001 ist weitergegangen, doch grundlegende Fragen zu Entwicklung und Bedeutung unseres Berufes sind unverändert geblieben.

Als Bauingenieure brauchen wir drei Säulen, um als – nicht nur – dienend rechnende, sondern auch schöpferische, erfindende, gestaltende und sichernde Gruppe auf dem Feld der Bautechnik wahrgenommen zu werden. Wir sind bedeutende Mitgestalter der Baukunst, seit der Aufspaltung des Baumeisters in Architekt und Ingenieur. Unser Berufsbild ist hervorragend, es weist jedoch übersehene und vernachlässigte Façetten auf. Davon will ich erzählen.
Einfache Ermittlung von Plattenstärken nach EC2 – Fortschreibung der Grundgleichungen
Authors: Göttlich Peter
Published: April 2014

Auf der Grundlage von [1] werden die dort vorgestellten Gleichungen erweitert, um noch einfachere und effizientere Bemessungshilfen für die Biegeschlankheit von Platten und Balken aus Stahlbeton zu erzeugen. Im Zuge der Bearbeitung erwies es sich als sinnvoll, Platten und Unterzüge getrennt zu behandeln. Im vorliegenden Aufsatz wird der Entwurf von Platten und Kragplatten behandelt.

Simple determination of plate thicknesses according to EC2 – Development of the basic equations

In order to create easier and more efficient dimensioning guidelines for the flexural slenderness of plates and beams made out of reinforced concrete the equations are extended on the basis of [1]. It turned out to be useful to consider plates and downstand beams separately. In the following the design of plates and cantilever plates is discussed.
Wellenbeanspruchung auf hydrodynamisch kompakte Betonstrukturen für Offshore‐Windenergieanlagen
Authors: Schmidt Boso , Marx Steffen , Göhlmann Joachim , Göthel Oliver , Grünberg Jürgen
Published: April 2014

Für die Ermittlung von Wellen‐ und Strömungslasten auf Offshore‐Gründungskonstruktionen wird häufig die Morison‐Gleichung verwendet. Diffraktionseffekte und vertikale Kraftanteile werden von ihr nicht berücksichtigt. Dass dies nicht nur an hydrodynamisch kompakten Gründungsstrukturen zu unsicheren Ergebnissen führen kann, wird durch Vergleichsrechnungen nach Morison sowie mittels CFD‐Methoden an einer Schwergewichtsgründung gezeigt. Für möglichst realistische Wellenzüge werden hierzu maßgebende Wellenparameter aus langjährigen Messzeitreihen bestimmt und in vergleichenden hydrodynamischen Analysen angesetzt. An definierten Punkten der Struktur werden die resultierenden Schubkräfte und Momente beider Verfahren für eine häufig auftretende Welle moderater Abmessungen und eine Extremwelle verglichen. Hierbei werden auch bei im Verhältnis zur Struktur sehr großen Wellen Effekte bei der Umströmung aufgezeigt, welche zu einer signifikanten Erhöhung der Beanspruchung führen. In einer alleinigen Berechnung nach Morison werden diese Effekte nicht detektiert.

Wave loads on hydrodynamically compact concrete structures for offshore wind turbines

Frequently the Morison equation is used to determine wave and current loads on offshore foundations. This approach does not consider diffraction effects and vertical load components. It is demonstrated that it may lead to uncertain results not only for hydrodynamically compact foundation structures by comparative calculations according to Morison equation and CFD methods on a gravity base foundation. Characteristic wave parameters are determined from long measurement time series for realistic wave trains. They are recognized in the comparative calculations. The shear forces and moments resulting from a frequently occurring and an extreme wave are compared for both methods at defined points of the structure. Flow effects which lead to significantly increasing loads can be detected even for very large waves in relation to the structure. These effects are not detected in calculations according to Morison equation.
Elucidating the effects of postinduction glutamine feeding on the growth and productivity of CHO cells
Authors: Sheikholeslami Zahra , Jolicoeur Mario , Henry Olivier
Published: April 2014

Inducible mammalian expression systems are increasingly being used for the production of valuable therapeutics. In such system, maximizing the product yield is achieved by carefully balancing the biomass concentration during the production phase and the specific productivity of the cells. These two factors are largely determined by the availability of nutrients and/or the presence of toxic waste metabolites in the culture environment. Glutamine is one of the most important components of cell culture medium, since this substrate is an important building block and source of energy for biomass and recombinant protein production. Its metabolism, however, ultimately leads to the formation of ammonia, a well known inhibitor of cellular growth and productivity. In this work, we show that nutrient feeding post‐induction can greatly enhance the product yield by alleviating early limitations encountered in batch. Moreover, varying the amount of glutamine in the feed yielded two distinct culture behaviors post‐induction; whereas excess glutamine allowed to reach greater cell concentrations, glutamine‐limited fed‐batch led to increased cell specific productivity. These two conditions also showed distinctive lactate metabolism. To further assess the physiological impact of glutamine levels on the cells, a comparative 13C‐metabolic flux analysis was conducted and a number of key intracellular fluxes were found to be affected by the amount of glutamine present in the feed during the production phase. Such information may provide useful clues for the identification of physiological markers of cell growth and productivity that could further guide the optimization of inducible expression systems. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:535–546, 2014
Modeling of crude oil biodegradation using two phase partitioning bioreactor
Authors: Fakhru'l‐Razi A. , Peyda Mazyar , Ab Karim Ghani Wan Azlina Wan , Abidin Zurina Zainal , Zakaria Mohamad Pauzi , Moeini Hassan
Published: April 2014

In this work, crude oil biodegradation has been optimized in a solid‐liquid two phase partitioning bioreactor (TPPB) by applying a response surface methodology based d‐optimal design. Three key factors including phase ratio, substrate concentration in solid organic phase, and sodium chloride concentration in aqueous phase were taken as independent variables, while the efficiency of the biodegradation of absorbed crude oil on polymer beads was considered to be the dependent variable. Commercial thermoplastic polyurethane (Desmopan®) was used as the solid phase in the TPPB. The designed experiments were carried out batch wise using a mixed acclimatized bacterial consortium. Optimum combinations of key factors with a statistically significant cubic model were used to maximize biodegradation in the TPPB. The validity of the model was successfully verified by the good agreement between the model‐predicted and experimental results. When applying the optimum parameters, gas chromatography‐mass spectrometry showed a significant reduction in n‐alkanes and low molecular weight polycyclic aromatic hydrocarbons. This consequently highlights the practical applicability of TPPB in crude oil biodegradation. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:797–805, 2014
Baceridin, a Cyclic Hexapeptide from an Epiphytic Bacillus Strain, Inhibits the Proteasome
Authors: Niggemann Jutta , Bozko Przemyslaw , Bruns Nicole , Wodtke Anne , Gieseler Marc Timo , Thomas Kevin , Jahns Christine , Nimtz Manfred , Reupke Inge , Brüser Thomas , Auling Georg , Malek Nisar , Kalesse Markus
Published: April 2014

A new cyclic hexapeptide, baceridin (1), was isolated from the culture medium of a plant‐associated Bacillus strain. The structure of 1 was elucidated by HR‐HPLC‐MS and 1D and 2D NMR experiments and confirmed by ESI MS/MS sequence analysis of the corresponding linear hexapeptide 2. The absolute configurations of the amino acid residues were determined after derivatization by GC‐MS and Marfey's method. The cyclopeptide 1 consists partially of nonribosomal‐derived D‐ and allo‐D‐configured amino acids. The order of the D‐ and L‐leucine residues within the sequence cyclo(‐L‐Trp‐D‐Ala‐D‐allo‐Ile‐L‐Val‐D‐Leu‐L‐Leu‐) was assigned by total synthesis of the two possible stereoisomers. Baceridin (1) was tested for antimicrobial and cytotoxic activity and displayed moderate cytotoxicity (1–2 μg mL−1) as well as weak activity against Staphylococcus aureus. However, it was identified to be a proteasome inhibitor that inhibits cell cycle progression and induces apoptosis in tumor cells by a p53‐independent pathway.
Key Mechanistic Insight into the Direct Gas‐Phase Epoxidation of Propylene by the RuO2–CuO–NaCl/SiO2 Catalyst
Authors: Seubsai Anusorn , Zohour Bahman , Noon Daniel , Senkan Selim
Published: April 2014

The discovery of the RuO2–CuO–NaCl/SiO2 catalyst for the direct gas‐phase epoxidation of propylene to propylene oxide created a potentially promising path towards developing a high‐performing catalyst of substantial commercial value and opened a new challenge in catalysis research. In this work, studies following up this discovery are presented to reveal critical insight into the catalytic mechanism on the trimetallic catalyst. Small crystalline CuO particles, in close proximity of RuO2, were determined from temperature‐programmed reduction and high‐resolution transmission electron microscopy studies to be the site for propylene oxide synthesis. In addition, the presence of NaCl was confirmed to suppress the formation of CO2.
CC Coupling of N‐Heterocycles at the fac‐Re(CO)3 Fragment: Synthesis of Pyridylimidazole and Bipyridine Ligands
Authors: Viguri Maialen Espinal , Pérez Julio , Riera Lucía
Published: April 2014

A new family of cationic rhenium tricarbonyl complexes with either two N‐alkylimidazole (N‐RIm) and one pyridine (Py) ligand, or two pyridine and one N‐RIm ligand, [Re(CO)3(N‐RIm)(3−x)(Py)x]+, has been prepared. The reaction of these complexes with a strong base, followed by an oxidant, selectively afforded 2,2’‐pyridylimidazole complexes as the result of intramolecular dehydrogenative CC coupling reactions. For tris(pyridine) complexes [Re(CO)3(Py)3]+ the reaction pattern upon a deprotonation/oxidation sequence is maintained, which allows the generation of complexes with 2,2’‐bipyridine ligands. In the particular combination of two different types of pyridine ligand in the cationic fac‐Re(CO)3 complexes only the cross‐coupling products with asymmetric 2,2’‐bipyridine ligands were obtained; the homocoupling products were not observed.