bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZAP‐70 Genotype Disrupts the Relationship Between Microbiota and Host, Leading to Spondyloarthritis and Ileitis in SKG Mice
Authors: Rehaume Linda M. , Mondot Stanislas , Aguirre de Cárcer Daniel , Velasco Jared , Benham Helen , Hasnain Sumaira Z. , Bowman Jaclyn , Ruutu Merja , Hansbro Philip M. , McGuckin Michael A. , Morrison Mark , Thomas Ranjeny 
Published: July 2014

ObjectiveThe spondyloarthritides share genetic susceptibility, interleukin‐23 (IL‐23) dependence, and the involvement of microbiota. The aim of the current study was to elucidate how host genetics influence gut microbiota and the relationship between microbiota and organ inflammation in spondyloarthritides.MethodsBALB/c ZAP‐70W163C–mutant (SKG) mice, Toll‐like receptor 4 (TLR‐4)–deficient SKG mice, and wild‐type BALB/c mice were housed under specific pathogen–free conditions. SKG and wild‐type BALB/c mice were maintained under germ‐free conditions, and some of these mice were recolonized with altered Schaedler flora. All of the mice were injected intraperitoneally with microbial β‐1,3‐glucan (curdlan). Arthritis, spondylitis, and ileitis were assessed histologically. Microbiome composition was analyzed in serial fecal samples obtained from mice that were co‐housed beginning at the time of weaning, using 454 pyrosequencing. Infiltrating cells and cytokines in the peritoneal cavity were measured by flow cytometry and enzyme‐linked immunosorbent assay. Cytokine, endoplasmic reticulum (ER) stress marker, and tight junction protein transcription was measured by quantitative real‐time polymerase chain reaction.ResultsMicrobiota content and response to curdlan varied according to whether T cell receptor signal strength was normal or was impaired due to the ZAP‐70W163C mutation. Curdlan triggered acute inflammation regardless of the presence of the SKG allele or microbiota. However, no or limited microbiota content attenuated the severity of arthritis. In contrast, ileal IL‐23 expression, ER stress, lymph node IL‐17A production, goblet cell loss, and ileitis development were microbiota‐dependent. Ileitis but not arthritis was suppressed by microbiota transfer upon co‐housing SKG mice with wild‐type BALB/c mice, as well as by TLR‐4 deficiency.ConclusionThe interaction between immunogenetic background and host microbiota leads to an IL‐23–dependent loss of mucosal function, triggering ileitis in response to curdlan.
Role of Toll‐like Receptors 2 and 4 in Mediating Endothelial Dysfunction and Arterial Remodeling in Primary Arterial Antiphospholipid Syndrome
Authors: Benhamou Ygal , Bellien Jeremy , Armengol Guillaume , Brakenhielm Ebba , Adriouch Sahil , Iacob Michele , Remy‐Jouet Isabelle , Le Cam‐Duchez Véronique , Monteil Christelle , Renet Sylvanie , Jouen Fabienne , Drouot Laurent , Menard Jean‐François , Borg Jeanne‐Yvonne , Thuillez Christian , Boyer Olivier , Levesque Hervé , Richard Vincent , Joannidès Robinson 
Published: July 2014

ObjectiveTo assess the role of Toll‐like receptors (TLRs) in antiphospholipid antibody (aPL)–mediated vascular abnormalities in patients with primary arterial antiphospholipid syndrome (APS).MethodsForty‐eight subjects participated in the study. Arterial function and structure and TLR pathway activation were determined in patients with primary arterial APS and matched controls. The pathogenic effects of aPL isolated from patients were assessed in wild‐type (WT) and TLR‐knockout mice.ResultsAPS patients had endothelial dysfunction, arterial stiffening, and hypertrophy, as evidenced by decreased brachial artery endothelium‐dependent flow‐mediated dilation (FMD) and increased aortic pulse wave velocity and carotid intima‐media thickness (IMT), as compared with controls. Plasma samples from APS patients revealed decreased nitric oxide (NO) availability and a pro‐oxidative, proinflammatory, and prothrombotic state illustrated by a decrease in nitrite and an increase in lipid peroxidation, tumor necrosis factor α levels, and tissue factor (TF) levels. Furthermore, TLR pathway activation was found in APS patients with increased TLR‐2 and TLR‐4 messenger RNA expression and increased protein levels of the activated TLR transduction protein interleukin‐1 receptor–associated kinase 1 in peripheral blood mononuclear cells. Moreover, agonist‐stimulated cell‐surface expression of TLR‐2 and TLR‐4 in circulating monocytes was higher in APS patients than in controls. These changes were positively associated with IMT and negatively associated with FMD. Finally, aPL injection decreased mesenteric endothelium‐dependent relaxation and increased TF expression in WT mice but not in TLR‐2– or TLR‐4–knockout mice.ConclusionThis translational study supports the notion that TLR‐2 and TLR‐4 play a role in mediating vascular abnormalities in patients with primary arterial APS. TLRs thus constitute a promising pharmacologic target for preventing cardiovascular complications in APS.
Dual‐Specificity Phosphatase 5 Attenuates Autoimmune Arthritis in Mice via Reciprocal Regulation of the Th17/Treg Cell Balance and Inhibition of Osteoclastogenesis
Authors: Moon Su‐Jin , Lim Mi‐Ae , Park Jin‐Sil , Byun Jae‐Kyeong , Kim Sung‐Min , Park Mi‐Kyung , Kim Eun‐Kyung , Moon Young‐Mee , Min Jun‐Ki , Ahn Sung‐Min , Park Sung‐Hwan , Cho Mi‐La 
Published: July 2014

ObjectiveDual‐specificity phosphatase 5 (DUSP‐5) is a phosphatase that specifically dephosphorylates both phosphoserine and phosphotyrosine residues of MAPK. The dysregulated activation of MAPK contributes to the pathogenesis of rheumatoid arthritis. This study was undertaken to investigate the therapeutic potential of DUSP‐5 in preventing the development of autoimmune arthritis in an animal model.MethodsAutoimmune arthritis was induced in DBA/1J mice by immunization with type II collagen (CII). Eight days after CII immunization, the mice were injected intravenously with pcDNA–DUSP5 or mock vector, and electroporation was performed. The serum concentration of anti‐CII antibodies was measured by enzyme‐linked immunosorbent assay. Histologic analysis of the joints was performed using Safranin O, toluidine blue, and immunohistochemical staining. The expression of transcription factors was analyzed by immunostaining and Western blotting. The frequencies of interleukin‐17–producing CD4+ Th17 cells and CD4+CD25+Foxp3+ Treg cells were analyzed by flow cytometry.ResultsIn DUSP5‐overexpressing mice, the severity of arthritis, as indicated by the clinical arthritis score and the extent of histologic inflammation and cartilage damage, was attenuated. The pcDNA–DUSP5–injected mice had lower circulating levels of total and CII‐specific IgG, IgG1, and IgG2a. The Th17 cell population frequency was decreased and the Treg cell frequency was increased in the spleens of the DUSP5‐treated group. The reciprocal regulation of Th17 and Treg cells in vivo was associated with attenuated activity of pSTAT‐3 and pERK, and with increased activity of pSTAT‐5. DUSP5 overexpression suppressed joint damage through down‐regulation of pro‐osteoclastogenic molecules.ConclusionThe antiarthritic properties of DUSP‐5 are associated with its reciprocal regulation of Th17 and Treg cells and its inhibition of ERK activity.
Rituximab for the Treatment of Relapses in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Miloslavsky E. M. , Specks U. , Merkel P. A. , Seo P. , Spiera R. , Langford C. A. , Hoffman G. S. , Kallenberg C. G. M. , St.Clair E. W. , Tchao N. K. , Viviano L. , Ding L. , Iklé D. , Villarreal M. , Jepson B. , Brunetta P. , Allen N. B. , Fervenza F. C. , Geetha D. , Keogh K. , Kissin E. Y. , Monach P. A. , Peikert T. , Stegeman C. , Ytterberg S. R. , Stone J. H. ,   for the Rituximab in ANCA‐Associated Vasculitis–Immune Tolerance Network Research Group
Published: July 2014

ObjectiveDisease relapses are frequent in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). This study was undertaken to evaluate outcomes in patients with AAV who are re‐treated with rituximab (RTX) and prednisone for severe disease relapses.MethodsThe Rituximab in AAV trial was a randomized, double‐blind, placebo‐controlled trial comparing the rates of remission induction among patients treated with RTX (n = 99) and patients treated with cyclophosphamide (CYC) followed by azathioprine (AZA) (n = 98). Prednisone was tapered to discontinuation after 5.5 months. After remission was achieved, patients who experienced a severe disease relapse between months 6 and 18 were eligible to receive RTX and prednisone on an open‐label basis according to a prespecified protocol. Investigators remained blinded with regard to the original treatment assignment.ResultsTwenty‐six patients received RTX for disease relapse after remission had initially been achieved with their originally assigned treatment. Fifteen of these patients were initially randomized to receive RTX and 11 to receive CYC/AZA. Thirteen (87%) of the patients originally assigned to receive RTX and 10 (91%) originally assigned to receive CYC/AZA achieved remission again with open‐label RTX (an overall percentage of 88%). In half of the patients treated with open‐label RTX, prednisone could be discontinued entirely. Patients in this cohort experienced fewer adverse events compared to the overall study population (4.7 adverse events per patient‐year versus 11.8 adverse events per patient‐year).ConclusionRe‐treatment of AAV relapses with RTX and glucocorticoids appears to be a safe and effective strategy, regardless of previous treatment.
Peroxisome Proliferator–Activated Receptor γ Coactivator 1α and FoxO3A Mediate Chondroprotection by AMP‐Activated Protein Kinase
Authors: Zhao Xianling , Petursson Freyr , Viollet Benoit , Lotz Martin , Terkeltaub Robert , Liu‐Bryan Ru 
Published: July 2014

ObjectiveAMP‐activated protein kinase (AMPK) inhibits chondrocyte procatabolic responses to inflammation and biomechanical injury. This study was undertaken to test the hypothesis that peroxisome proliferator–activated receptor γ coactivator 1α (PGC‐1α) and FoxO3A, 2 major AMPK downstream targets, mediate the chondroprotective effect of AMPK activation.MethodsWe assessed the activity of AMPKα (threonine 172 phosphorylation) and the expression of PGC‐1α and FoxO3A in human chondrocytes and AMPKα1‐ or AMPKα2‐knockout mouse chondrocytes by Western blotting, and in mouse knee cartilage by immunohistochemistry. We also knocked down or overexpressed PGC‐1α and FoxO3A by small interfering RNA or plasmid DNA transfection, respectively. We assessed mitochondrial superoxide generation using MitoSOX Red.ResultsExpression of PGC‐1α and FoxO3A was enhanced by pharmacologic AMPK activator A‐769662 but impaired in AMPKα1−/− or AMPKα2−/− mouse chondrocytes. Reduced expression of PGC‐1α and FoxO3A was observed in mouse knee instability–induced osteoarthritis (OA) cartilage and in aged C57BL/6 mouse knee cartilage. Knockdown of PGC‐1α and FoxO3A enhanced, but limited the ability of A‐769662 to inhibit, phosphorylation of p65 NF‐κB (Ser536) and procatabolic responses induced by inflammatory cytokines. Forced expression of PGC‐1α and FoxO3A induced increased expression of superoxide dismutase 2 (SOD2) and catalase, but A‐769662 failed to increase the expression of SOD2 and catalase in either PGC‐1α– or FoxO3A‐knockdown chondrocytes. Last, menadione‐induced superoxide generation was inhibited by AMPK pharmacologic activators and by overexpression of PGC‐1α or FoxO3A.ConclusionPGC‐1α and FoxO3A limit oxidative stress and at least partially mediate the capacity of AMPK activity to block procatabolic responses in chondrocytes, and therefore have the potential to inhibit the progression of cartilage damage in OA.
Consensus guidelines for enhanced recovery after gastrectomy
Authors: Mortensen K , Nilsson M , Slim K , Schäfer M , Mariette C , Braga M , Carli F , Demartines N , Griffin S M , Lassen K ,   Enhanced Recovery After Surgery (ERAS®) Group, Dejong C H C , Fearon K C F , Ljungqvist O , Lobo D N , Revhaug A 
Published: July 2014

AbstractBackgroundApplication of evidence-based perioperative care protocols reduces complication rates, accelerates recovery and shortens hospital stay. Presently, there are no comprehensive guidelines for perioperative care for gastrectomy.MethodsAn international working group within the Enhanced Recovery After Surgery (ERAS®) Society assembled an evidence-based comprehensive framework for optimal perioperative care for patients undergoing gastrectomy. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system and were discussed until consensus was reached within the group. The quality of evidence was rated ‘high’, ‘moderate’, ‘low’ or ‘very low’. Recommendations were graded as ‘strong’ or ‘weak’.ResultsThe available evidence has been summarized and recommendations are given for 25 items, eight of which contain procedure-specific evidence. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations.ConclusionThe present evidence-based framework provides comprehensive advice on optimal perioperative care for the patient undergoing gastrectomy and facilitates multi-institutional prospective cohort registries and adequately powered randomized trials for further research.
The moderating role of gift recipients' attachment orientations on givers' gift‐giving perceptions
Authors: Nguyen Hieu P. , Munch James M. 
Published: July 2014

ABSTRACTRomantic gift‐giving perceptions in dyadic relationships are examined in this research as informed by attachment theory. In two studies, we investigate the moderating role of the recipient's attachment orientation on the giver's gift‐giving perceptions and the mechanism through which the interaction between the giver's and recipient's attachment orientations influence gift‐giving perceptions. We show that the recipient's attachment orientation could accentuate or attenuate the impact of the giver's attachment orientation on gift‐giving perceptions and that this effect is carried through the giver's satisfaction with the relationship. We provide implications for future research and practitioners. Copyright © 2014 John Wiley & Sons, Ltd.
Acute Toxicity, Bioactivity, and Enantioselective Behavior with Tissue Distribution in Rabbits of Myclobutanil Enantiomers
Authors: Sun Mingjing , Liu Donghui , Qiu Xinxu , Zhou Qian , Shen Zhigang , Wang Peng , Zhou Zhiqiang 
Published: July 2014

ABSTRACTThe enantioselective bioactivity against pathogens (Cercospora arachidicola, Fulvia fulva, and Phytophthora infestans) and acute toxicity to Daphnia magna of the fungicide myclobutanil enantiomers were studied. The (+)‐enantiomer in an antimicrobial activity test was about 1.79–1.96 times more active than the (–)‐enantiomer. In the toxicity assay, the calculated 24‐h LC50 values of the (–)‐form, rac‐form and (+)‐form were 16.88, 13.17, and 11.91 mg/L, and the 48‐h LC50 values were 10.15, 9.24, and 5.48 mg/L, respectively, showing that (+)‐myclobutanil was more toxic. Meanwhile, the enantioselective metabolism of myclobutanil enantiomers following a single intravenous (i.v.) administration was investigated in rabbits. Total plasma clearance value (CL) of the (+)‐enantiomer was 1.68‐fold higher than its antipode. Significant differences in pharmacokinetics parameters between the two enantiomers indicated that the high bioactive (+)‐enantiomer was preferentially metabolized and eliminated in plasma. Consistent consequences were found in the tissues (liver, brain, heart, kidney, fat, and muscle), resulting in a relative enrichment of the low‐activity (–)‐myclobutanil. These systemic assessments of the stereoisomers of myclobutanil cannot be used only to investigate environmental and biological behavior, but also have human health implications because of the long persistence of triazole fungicide and enantiomeric enrichment in mammals and humans. Chirality 26:784–789, 2014. © 2014 Wiley Periodicals, Inc.
Large basolateral processes on type II hair cells are novel processing units in mammalian vestibular organs
Authors: Pujol Rémy , Pickett Sarah B. , Nguyen Tot Bui , Stone Jennifer S. 
Published: July 2014

ABSTRACTSensory receptors in the vestibular system (hair cells) encode head movements and drive central motor reflexes that control gaze, body movements, and body orientation. In mammals, type I and II vestibular hair cells are defined by their shape, contacts with vestibular afferent nerves, and membrane conductance. Here we describe unique morphological features of type II vestibular hair cells in mature rodents (mice and gerbils) and bats. These features are cytoplasmic processes that extend laterally from the hair cell base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells vary in shape, size, and branching, with the longest processes extending three to four hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Furthermore, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network among type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3–6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells and suggest that type II hair cells may directly communicate with each other, which has not been described in vertebrates. J. Comp. Neurol. 522:3141–3159, 2014. © 2014 Wiley Periodicals, Inc.
A three step blind approach for improving high performance computing systems' energy performance
Authors: Tsafack Chetsa Ghislain Landry , Lefevrem Laurent , Stolf Patricia 
Published: July 2014

SUMMARYNowadays, there is no doubt that energy consumption has become a limiting factor in the design and operation of high performance computing (HPC) systems. This is evidenced by the rise of efforts both from the academia and the industry to reduce the energy consumption of those systems. Unlike hardware solutions, software initiatives targeting HPC systems' energy consumption reduction despite their effectiveness are often limited for reasons including (1) the program specific nature of the solution proposed; (2) the need of deep understanding of the application task at hand; and (3) proposed solutions are often difficult to use by novices and/or are designed for single task environments. This paper proposes a three step blind system‐wide, application independent, fine‐grain, and easy to use (user friendly) methodology for improving energy performance of HPC systems. The methodology typically breaks into phase detection, phase characterization, and phase identification and system reconfiguration. And it is blind in the sense that it does not require any knowledge from users. It relies upon reconfigurable capabilities offered by the majority of HPC subsystems—including the processor, storage, memory, and communication subsystems—to reduce the overall energy consumption of the system (excluding network equipments) at runtime. We also present an implementation of our methodology through which we demonstrate its effectiveness via static analyses and experiments using benchmarks representative of HPC workloads. The memory becoming one of the most power hungry HPC system this paper also introduces and investigates the relevance of a potential power saving scheme which we refer to as memory size scaling. It is destined to scale the memory size for saving energy in a CPU frequency scaling like fashion. Copyright © 2014 John Wiley & Sons, Ltd.
Failure analysis and tolerance strategies in web service ecosystems
Authors: Liu Yi , Fan Yushun , Huang Keman , Tan Wei 
Published: July 2014

SummaryService‐oriented computing and cloud computing are playing critical roles in supporting business collaboration over the Internet. Thanks to the latest development in computing technologies, various large‐scale, evolving, and rapidly growing service ecosystems emerge. However, service failures greatly hamper the usability and reputation of service ecosystems. In the previous work, service failure is not adequately studied from an ecosystem's perspective. To address this gap, we propose a service failure analysis framework based on a complex network model of service ecosystem. This framework comprises a feature model of failed services and several service failure impact indicators. By applying the framework, empirical analysis of failed service features and failure impact assessment can be implemented more easily and precisely. Moreover, to provide failure tolerance strategies for service ecosystems, a novel composition‐based service substitution method is designed to replace the failed services with functional similar ones, such that the service systems are more robust when a failure occurs. As the new substitution method requires fewer structural data of services, it is more convenient to be applied in present RESTful Representational State Transfer (REST) service environment. Both the framework and the service substitution method are tested on real‐world data set, and their usability and efficiency are demonstrated. Copyright © 2014 John Wiley & Sons, Ltd.
The power of circuit simulations for designing photonic integrated circuits
Authors: Arellano C. , Mingaleev S. F. , Sokolov E. S. , Richter A. 
Published: July 2014

SUMMARYThe emerging of circuit‐level simulators for photonic integrated circuits (PICs) is driven by recent developments in technologies for integration of large‐scale monolithic PICs in both, silicon and InP technologies. For that reason, powerful circuit‐level simulators should be capable to model on the same circuit different types of sub‐components performing photonic, electronic or opto‐electronic, active or passive functions. In comparison with device‐level simulations, the use of realistic circuit‐level abstracted models facilitates rapid functional design without going into technological fabrication details and subsequent design flow. This accelerates the design process and decreases the number of runs to achieve the desired results. Detailed physical modeling remains limited to the design of some specific individual sub‐elements. Large‐scale PICs might comprise several thousands of elements. The circuit‐level abstraction also ensures that the simulation speed to achieve a certain simulation accuracy decreases reasonably slowly with the total number of photonic components in the modeled PIC. In this work, we present our solution for modeling PICs in the framework of the circuit‐level simulation tool VPIcomponentMaker™Photonic Circuits (Carnotstr. 6, 10587, Berlin, Germany, www.VPIphotonics.com). We demonstrate the combination of different simulation approaches in time domain, frequency domain and time‐and‐frequency domain for fast and accurate simulations. We discuss several diverse modeling benefits by means of application examples on silicon photonic PICs. Copyright © 2014 John Wiley & Sons, Ltd.