bluuebunny/crossref_metadata_2025_split huggingface dataset:
17β‐estradiol induces CD40 expression in dendritic cells via MAPK signaling pathways in a minichromosome maintenance protein 6–dependent manner
Authors: Xie Hao , Hua Chunyan , Sun Lin , Zhao Xiaoyin , Fan Hongye , Dou Huan , Sun Lingyun , Hou Yayi 
Published: May 2011

AbstractObjectiveThe human immune system exhibits sexual dimorphism in autoimmune diseases such as systemic lupus erythematosus (SLE). Female sex hormones, including 17β‐estradiol, are strongly implicated in the gender bias in SLE. CD40 is a costimulatory molecule and plays a crucial role in modulating the immune response of effector cells. We have previously shown that 17β‐estradiol up‐regulated CD40 expression and altered minichromosome maintenance protein 6 (MCM6) gene expression in dendritic cells (DCs). The mechanism of the correlation between CD40 and MCM6 in the presence of 17β‐estradiol remains unknown. This study was undertaken to elucidate this mechanism and to explain the role of MCM6 in the gender bias in SLE.MethodsBone marrow–derived DCs transfected with small interfering RNA (siRNA) for MCM6 were treated with 17β‐estradiol in the absence or presence of CpG. The expression levels of costimulatory molecules, activity of MAPKs, and levels of MCM6 protein were measured. Moreover, the functions of DCs, including proliferation, apoptosis, endocytosis, and cytokine production, were analyzed. In addition, levels of messenger RNA for MCM6 were detected in DCs purified from SLE patients.ResultsRegardless of the presence or absence of CpG, 17β‐estradiol induced CD40 expression via the activation of p38 and JNK, but not ERK. The activation of p38 and JNK enhanced MCM6 expression, which then induced CD40 expression. Suppression of MCM6 in DCs abolished the up‐regulation of 17β‐estradiol–induced CD40 expression. Importantly, MCM6 expression was significantly increased in SLE patients compared with healthy controls.ConclusionOur findings indicate that 17β‐estradiol induces CD40 expression in DCs via p38 and JNK MAPKs in an MCM6‐dependent manner. MCM6 may be a critical mediator of sex‐based differences in autoimmune disease.
Vascular endothelial growth factor C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage in mice
Authors: Zhou Quan , Guo Ruolin , Wood Ronald , Boyce Brendan F. , Liang Qianqian , Wang Yong‐Jun , Schwarz Edward M. , Xing Lianping 
Published: May 2011

AbstractObjectiveTo investigate whether the enhancement of joint lymphangiogenesis by injection of vascular endothelial growth factor C (VEGF‐C) adeno‐associated virus (AAV) into the affected joints has therapeutic efficacy in chronic inflammatory arthritis in mice.MethodsTumor necrosis factor–transgenic (TNF‐Tg) mice were used as a model of chronic inflammatory arthritis. Human VEGF‐C was cloned into an AAV expression vector to generate AAV‐VEGF‐C. The joints of TNF‐Tg mice were injected with AAV‐VEGF‐C or AAV‐luciferase (AAV‐Luc) as a control. During the 4 months following injection, magnetic resonance imaging of the joints and lymphatic imaging were performed to assess changes in synovial volume and lymph flow from the joint tissues to local draining lymph nodes. Joint inflammation, bone erosion, and cartilage loss were examined by histologic analyses. Lymphatic vessel formation was assessed using immunohistochemistry.ResultsIntraarticular administration of AAV‐VEGF‐C virus significantly attenuated the increase in synovial volume and increased lymphatic vessel number in the joint sections, as compared with that in control AAV‐Luc–injected joints, during the 4‐month period. This was accompanied by a reduction in the area of inflammation, bone erosion, cartilage loss, and osteoclast numbers. Lymph flow from the joints to local draining lymph nodes was slower in TNF‐Tg mice than in wild‐type littermates, and was significantly improved with AAV‐VEGF‐C treatment.ConclusionIntraarticular injection of AAV‐VEGF‐C increased lymphangiogenesis and improved lymphatic drainage from the inflamed joints of mice, resulting in attenuation of joint tissue damage. Thus, improvement of joint lymphatic function by local administration of lymphatic growth factors represents a new therapeutic approach for chronic inflammatory arthritis.
Systemic sclerosis–related pulmonary hypertension associated with interstitial lung disease: Impact of pulmonary arterial hypertension therapies
Authors: Le Pavec Jérôme , Girgis Reda E. , Lechtzin Noah , Mathai Stephen C. , Launay David , Hummers Laura K. , Zaiman Ari , Sitbon Olivier , Simonneau Gérald , Humbert Marc , Hassoun Paul M. 
Published: May 2011

AbstractObjectivePrecapillary pulmonary hypertension (PH) is an important cause of death in patients with systemic sclerosis (SSc). It can occur in isolation (pulmonary arterial hypertension [PAH]) or in association with interstitial lung disease (ILD). Importantly, the outcomes and efficacy of PAH therapies in patients with SSc‐related PH complicating ILD (PH‐ILD) remain unknown. This study was undertaken to evaluate our experience with PH‐ILD with regard to the efficacy and safety of PAH therapies in this patient cohort.MethodsWe conducted a retrospective analysis of consecutive SSc patients from 2 large referral centers who had PH‐ILD confirmed by right‐sided heart catheterization and who received targeted PAH therapies. World Health Organization (WHO) functional class, 6‐minute walk distance, and hemodynamic parameters were assessed at baseline and after a mean ± SD of 7.7 ± 6.2 months of treatment for PAH. Kaplan‐Meier and Cox proportional hazards models were used to analyze survival and to identify prognostic factors.ResultsSeventy patients were included in the study. No significant changes were observed in WHO functional class, 6‐minute walk distance, or hemodynamic parameters after therapy. The 1‐, 2‐, and 3‐year survival estimates were 71%, 39%, and 21%, respectively. In the multivariate model, worsening oxygenation during followup and reduced renal function were the only significant risk factors for death.ConclusionThis study represents the largest series to date in which the impact of PAH therapies in SSc‐related PH‐ILD was examined. In this cohort, PAH therapies were associated with no clear benefits. Deterioration in oxygenation was an important determinant of long‐term survival. Prospective clinical trials focusing on this group of patients are warranted.
Palladium‐Catalyzed Allyl Cross‐Coupling Reactions with In Situ Generated Organoindium Reagents
Authors: Lee Kooyeon , Kim Hyunseok , Mo Juntae , Lee Phil Ho 
Published: May 2011

AbstractInter‐ and intramolecular palladium‐catalyzed allyl cross‐coupling reactions, using allylindium generated in situ from allyl halides and indium, is demonstrated. Allylindium compounds may be effective nucleophilic coupling partners in palladium‐catalyzed cross‐coupling reactions. A variety of allyl halides, such as allyl iodide, allyl bromide, crotyl bromide, prenyl bromide, geranyl bromide, and 3‐bromocyclohexene afforded the allylic cross‐coupling products in good to excellent yields. Stereochemistry of the double bond is retained in the allylic cross‐coupling reactions. Electrophilic cross‐coupling partners, such as aryl and vinyl halides, dibromoolefin, alkynyl iodide, and aryl and vinyl triflates participate in these reactions. The presence of various substituents, such as n‐butyl, ketal, acetyl, ethoxycarbonyl, nitrile, N‐phenylamido, nitro, and chloride groups on the aromatic ring of electrophilic coupling partners showed little effect on the efficiency of the reactions. The present conditions work equally well for not only intermolecular but also intramolecular palladium‐catalyzed cross‐coupling reactions. These methods provide an efficient synthetic method for the introduction of an allyl group, which can be easily further functionalized to afford an sp2‐ and sp‐hybridized carbon. The present method complements existing synthetic methods as a result of advantageous features such as easy preparation and handling, thermal stability, high reactivity and selectivity, operational simplicity, and low toxicity of allylindium reagents.
Cooperative Activation of Alkyne and Thioamide Functionalities; Direct Catalytic Asymmetric Conjugate Addition of Terminal Alkynes to α,β‐Unsaturated Thioamides
Authors: Yazaki Ryo , Kumagai Naoya , Shibasaki Masakatsu 
Published: May 2011

AbstractA detailed study of the direct catalytic asymmetric conjugate addition of terminal alkynes to α,β‐unsaturated thioamides is described. A soft Lewis acid/hard Brønsted base cooperative catalyst, comprising [Cu(CH3CN)4]PF6, bisphosphine ligand, and Li(OC6H4‐p‐OMe) simultaneously activated both substrates to compensate for the low reactivity of copper alkynylide. A series of control experiments revealed that the intermediate copper‐thioamide enolate functioned as a Brønsted base to generate copper alkynylide from the terminal alkyne, thus driving the catalytic cycle through an efficient proton transfer between substrates. These findings led to the identification of a more convenient catalyst using potassium hexamethyldisilazane (KHMDS) as the Brønsted base, which was particularly effective for the reaction of silylacetylenes. Divergent transformation of the thioamide functionality and a concise enantioselective synthesis of a GPR40 receptor agonist AMG‐837 highlighted the synthetic utility of the present catalysis.
Optimal check up and replacement periods of variable message signs: a case of the Seoul metropolitan transportation center
Authors: Lee Chungwon , Kim Seong W. , Lee Soo‐Beom 
Published: May 2011

AbstractVariable message signs (VMS) are one kind of traffic management facility installed following the “Guidelines on the Standard of Road Structures and Facilities.” VMS are installed and operated within the Intelligent Transport Systems (ITS). However, existing VMS are operated and managed by designers or operators without any consistent criteria on check up and replacement periods. There has been very little research on check up and replacement periods of VMS. This study was to introduce a new methodology to estimate check up and replacement periods of VMS. This study reflected the actual VMS failure data and VMS and Portable Variable Message Signs luminance test results. Consequently, I hope that this study will be a useful reference for VMS and other ITS facilities. Copyright © 2011 John Wiley & Sons, Ltd.
Productivity changes in consideration of accident costs in Seoul's bus industry
Authors: Oh Miyoung , Shon Euiyoung , Kim Sungsoo 
Published: May 2011

AbstractThe Seoul Metropolitan Government has introduced a quasi‐public operational system since the public transport systems were reformed in July 2004. Thus, there has been controversy on moral hazards. A question addressed by researchers of transportation is the extent to which the public transport reforms have led to improvements in efficiency and productivity growth. The directional distance function and the Malmquist Luenberger Index, respectively, were used to investigate the impacts of public transport reforms on efficiency and productivity growth both with and without accident costs in Seoul's bus industry. The data cover 2003 and 2005; 2003 is the pre‐reform year and 2005 is the post‐reform year. It is found that the overall productivity increased a little regardless of the consideration of accident costs; it increased a little bit more in the presence of accident costs. This means that the overall productivity at least did not decrease and the level of service in terms of safety was improved following the public transport reforms. Copyright © 2011 John Wiley & Sons, Ltd.
Stochastic modeling of the equilibrium speed–density relationship
Authors: Wang Haizhong , Ni Daiheng , Chen Qian‐Yong , Li Jia 
Published: May 2011

SUMMARYAs the graphical and mathematical representation of relationships among traffic flow, speed, and density, the fundamental diagram has been the foundation of traffic flow theory and transportation engineering. Underlying the fundamental diagram is the speed–density relationship which was originally documented in Greenshields' seminal work and followed by a variety of equilibrium models over the past 75 years. Observed in these efforts was their deterministic nature striving to pursue two seemingly competing goals: mathematical elegance and empirical accuracy, the former of which is attractive to mathematical modeling of traffic dynamics, and the latter is required if such modeling is meant to be realistic. As a continued effort of such a pursuit, this paper presents a stochastic speed–density model. The motivation is twofold: first, it is desirable to have a model which achieves both goals reasonably and second, the stochastic model can potentially lead to probabilistic traffic flow modeling and prediction which is typically not offered by a macroscopic approach. Copyright © 2011 John Wiley & Sons, Ltd.
Diabetic embryopathy: A role for the epigenome?
Authors: Salbaum J. Michael , Kappen Claudia 
Published: May 2011

AbstractEmbryonic development under adverse conditions, such as maternal diabetes or obesity during pregnancy, constitutes a major risk factor for birth defects, as well as for long‐term health consequences and disease susceptibility in the offspring. While contributions from epigenetic changes have been invoked previously to explain the long‐term changes in terms of developmental programming, we here review how maternal metabolism may directly affect the embryonic epigenome in relationship to teratogenic processes. We consider four epigenetic modalities – DNA methylation, non‐coding RNA, transcription factors, and histone modifications – and their contribution to epigenetic memory, and discuss how epigenomic changes may mediate the altered control of embryonic gene expression brought about by maternal diabetes. In combination, the epigenomic modalities serve to define transcription‐permissive domains of the genome, resulting in distinct epigenomic landscapes in different developmental cell types. We evaluate experimental approaches to characterize the epigenome in adverse pregnancy conditions, highlighting the role of next‐generation sequencing on the technological side, while emphasizing the necessity to study defined cell populations in terms of biologic impact. Finally, we outline the challenges in moving from findings that correlate epigenomics to developmental phenotypes to scenarios that establish teratogenic causality. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.
Chemischer Angriff auf verpresste Anker und Pfähle
Authors: Rigo Ellen , Unterderweide Klaus 
Published: May 2011

AbstractDie für die Herstellung und Ausführung von verpressten Pfählen und Ankern relevanten Regelwerke enthalten für die chemischen Angriffe durch Ammonium‐ und Chloridionen keine konkreten Angaben zur Sicherstellung der Dauerhaftigkeit. Dies führt zu großen Unsicherheiten beim Planer. Mit Hilfe numerischer Simulation wurde unter Berücksichtigung hoher Ammonium‐ und Chloridionenkonzentrationen (150 mg/L NH4+, 2500 mg/L Cl–) die Dauerhaftigkeit von mit Zementleimsuspensionen verpressten Pfählen und Ankern berechnet. Dazu wurde das Programm Transreac genutzt, welches den Transport in porösen Materialien mit der Berechnung der chemischen Reaktionen kombiniert. Es konnte gezeigt werden, dass innerhalb von 100 Jahren eine sehr geringe Schädigung (< 1 mm) hinsichtlich des lösenden Angriffes durch Ammonium zu erwarten ist. Für den Stahlkörper der Pfähle ergibt die Prognose weder durch die pH‐Wert‐Absenkung infolge des lösenden Ammoniumangriffes noch hinsichtlich eines kritischen Chloridgehaltes eine bedeutende Korrosion.Chemical Attack on Grouted Piles and Anchors A Numerical Prognosis of DurabilityWith the aid of numerical simulation, the degradation of grouted piles and anchors in presence of high amounts of ammoniumions (up to 150 mg/L NH4+) and chloride‐ions (up to 2500 mg/L Cl–) was calculated. Given these environmental conditions it can be assumed, that the grout (cement paste with high w/b) is dissolved by the ammonium‐ions, and the steel of the piles and anchors is corroded because of the reduction of the pH‐value and the attack of the chloride‐ions. Until now there is not one technical rule or a code that deals with the durability of piles and anchors that suffer from chemical attack due to ammonium or chloride or both combined. The designers are not sure how to establish the durability in that case. Due to this fact a numerical calculation of combined chemical attack of ammonium‐ions and chloride‐ions is performed for real environmental conditions. For that purpose the numerical model Transreac is used. This model combines the calculation of transport processes in porous materials and the calculation of chemical reactions. The numerical prognosis shows that the grout is not likely to degenerate within 100 years by reason of the attack of ammonium‐ions. Furthermore, there will not be a considerable consumption of steel in the anchor within the given conditions, neither from the decrease in the pH‐value nor from the chloride.
Ein Beitrag zur Berechnung des kriechbedingten Abbaues von Zwangschnittgrößen aus Setzungen
Authors: Strauß Peter 
Published: May 2011

AbstractEs wird ein Rechenverfahren vorgestellt, mit dem der kriechbedingte Abbau von Zwangschnittgrößen für beliebige stetig zunehmende Zeit‐Setzungsverläufe berechnet werden kann. Die primäre Zielsetzung des Verfahrens ist die Bestimmung des quantitativen Kriecheinflusses auf die Setzungsschnittgrößen bei der Nachrechnung bestehender Bauwerke mit bekannten Setzungsverläufen. An einem Beispiel wird die Anwendung des Rechenverfahrens auf einen konkreten Nachweisfall gezeigt.About the Calculation of Creep‐related Relief of Restraint Forces out of SettlementsA method is presented here with which it is possible to calculate the creep‐related relief of restraint forces in sections for any settlement processes that constantly increase over time. The chief aim of this method is to determine the quantitative influence of creep on the settlement forces in sections when analysing existing structures with known settlement patterns. The application of the method of calculation is demonstrated in an example based on a specific case.
Online naphazoline quality control by micellar‐enhanced spectrofluorimetry
Authors: Peralta Cecilia Mariana , Silva Raúl Alejandro , Fernández Liliana Patricia , Masi Adriana Noemí 
Published: May 2011

ABSTRACTThe aim of this study was to develop a method for online spectrofluorimetric quality control of naphazoline (NPZ) in pharmaceuticals and raw drugs. A combination of a flow‐injection analysis (FIA) system with micellar‐enhanced fluorescence detection is presented as a powerful alternative for the rapid and sensitive analysis of naphazoline. Since NPZ shows low native fluorescence, the use of an anionic surfactant, such as sodium dodecyl sulphate (SDS), provides a considerable enhancement of fluorescence intensity and the nature of the technique allows a possible and easy adaptation to a FIA system. Using λexc = 280 nm and λem = 326 nm, a good linear relationship (LOL) was obtained in the range 0.003–10 µg mL−1 with a detection limit (LOD) of 3 × 10−4 µg mL−1 (s/n = 3). Parameters related to the nature of the analytical signal and to the FIA manifold were optimized. Satisfactory recoveries were obtained in the analysis of commercial pharmaceutical formulations. The proposed method is simple, accurate and allows for high‐speed sampling and considerably shorter analysis times. In addition, it requires inexpensive equipment and reagents and has easy operational conditions and no side effects, thus avoiding environmental pollution through toxic waste. Copyright © 2011 John Wiley & Sons, Ltd.
Study of the interaction between ofloxacin and human serum albumin by spectroscopic methods
Authors: Varlan Aurica , Ionescu Sorana , Hillebrand Mihaela 
Published: May 2011

ABSTRACTThe binding of ofloxacin (OFLX) to human serum albumin (HSA) was investigated by fluorescence and circular dichroism (CD) techniques. The binding parameters have been evaluated by a fluorescence quenching method. Competitive binding measurements were performed in the presence of warfarin and ibuprofen and suggest binding to the warfarin site I of HSA. The distance r between donor (HSA) and acceptor (OFLX) was estimated according to the Forster's theory of non‐radiatiative energy transfer. CD spectra revealed that the binding of OFLX to HSA induced conformational changes in HSA. Molecular docking was performed and shows that for the lowest energy complex OFLX is located in site I of HSA, which correlate to the competitive binding experiments. Copyright © 2011 John Wiley & Sons, Ltd.
Characterization of secondary amide peptide bond isomerization: Thermodynamics and kinetics from 2D NMR spectroscopy
Authors: Zhang Jin , Germann Markus W. 
Published: May 2011

AbstractSecondary amide cis peptide bonds are of even lower abundance than the cis tertiary amide bonds of prolines, yet they are of biochemical importance. Using 2D NMR exchange spectroscopy (EXSY) we investigated the formation of cis peptide bonds in several oligopeptides: Ac‐G‐G‐G‐NH2, Ac‐I‐G‐G‐NH2, Ac‐I‐G‐G‐N‐NH2 and its cyclic form: I‐G‐G‐N in dimethylsulfoxide (DMSO). From the NMR studies, using the amide protons as monitors, an occurrence of 0.13–0.23% of cis bonds was obtained at 296 K. The rate constants for the trans to cis conversion determined from 2D EXSY spectroscopy were 4–9 × 10−3 s−1. Multiple minor conformations were detected for most peptide bonds. From their thermodynamic and kinetic properties the cis isomers are distinguished from minor trans isomers that appear because of an adjacent cis peptide bond. Solvent and sequence effects were investigated utilizing N‐methylacetamide (NMA) and various peptides, which revealed a unique enthalpy profile in DMSO. The cyclization of a tetrapeptide resulted in greatly lowered cis populations and slower isomerization rates compared to its linear counterpart, further highlighting the impact of structural constraints. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 755‐762, 2011.
An evaluation of Poisson–Boltzmann electrostatic free energy calculations through comparison with experimental mutagenesis data
Authors: Gorham Ronald D. , Kieslich Chris A. , Nichols Aaron , Sausman Noriko U. , Foronda Marisse , Morikis Dimitrios 
Published: May 2011

AbstractFor systems involving highly and oppositely charged proteins, electrostatic forces dominate association and contribute to biomolecular complex stability. Using experimental or theoretical alanine‐scanning mutagenesis, it is possible to elucidate the contribution of individual ionizable amino acids to protein association. We evaluated our electrostatic free energy calculations by comparing calculated and experimental data for alanine mutants of five protein complexes. We calculated Poisson–Boltzmann electrostatic free energies based on a thermodynamic cycle, which incorporates association in a reference (Coulombic) and solvated (solution) state, as well as solvation effects. We observe that Coulombic and solvation free energy values correlate with experimental data in highly and oppositely charged systems, but not in systems comprised of similarly charged proteins. We also observe that correlation between solution and experimental free energies is dependent on dielectric coefficient selection for the protein interior. Free energy correlations improve as protein dielectric coefficient increases, suggesting that the protein interior experiences moderate dielectric screening, despite being shielded from solvent. We propose that higher dielectric coefficients may be necessary to more accurately predict protein–protein association. Additionally, our data suggest that Coulombic potential calculations alone may be sufficient to predict relative binding of protein mutants. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 746‐754, 2011.