bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of MAPKs and NF‐κB in tumor necrosis factor α–induced vascular cell adhesion molecule 1 expression in human rheumatoid arthritis synovial fibroblasts
Authors: Luo Shue‐Fen , Fang Rou‐Yi , Hsieh Hsi‐Lung , Chi Pei‐Ling , Lin Chih‐Chung , Hsiao Li‐Der , Wu Chi‐Chuan , Wang Jong‐Shyan , Yang Chuen‐Mao 
Published: December 2009

AbstractObjectiveTo investigate the roles of MAPKs and NF‐κB in tumor necrosis factor α (TNFα)–induced expression of vascular cell adhesion molecule 1 (VCAM‐1) in human rheumatoid arthritis synovial fibroblasts (RASFs).MethodsHuman RASFs were isolated from synovial tissue obtained from patients with RA who underwent knee or hip surgery. The involvement of MAPKs and NF‐κB in TNFα‐induced VCAM‐1 expression was investigated using pharmacologic inhibitors and transfection with short hairpin RNA (shRNA) and measured using Western blot, reverse transcriptase–polymerase chain reaction, and gene promoter assay. NF‐κB translocation was determined by Western blot and immunofluorescence staining. The functional activity of VCAM‐1 was evaluated by lymphocyte adhesion assay.ResultsTNFα‐induced VCAM‐1 expression, phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK, and translocation of NF‐κB were attenuated by the inhibitors of MEK‐1/2 (U0126), p38 (SB202190), JNK (SP600125), and NF‐κB (helenalin) or by transfection with their respective shRNA. TNFα‐stimulated translocation of NF‐κB into the nucleus and NF‐κB promoter activity were blocked by Bay11‐7082, but not by U0126, SB202190, or SP600125. VCAM‐1 promoter activity was enhanced by TNFα in RASFs transfected with VCAM‐1‐Luc, and this promoter activity was inhibited by Bay11‐7082, U0126, SB202190, and SP600125. Moreover, up‐regulation of VCAM‐1 increased the adhesion of lymphocytes to the RASF monolayer, and this adhesion was attenuated by pretreatment with helenalin, U0126, SP600125, or SB202190 prior to exposure to TNFα or by anti–VCAM‐1 antibody before the addition of lymphocytes.ConclusionIn RASFs, TNFα‐induced VCAM‐1 expression is mediated through activation of the p42/p44 MAPK, p38 MAPK, JNK, and NF‐κB pathways. These results provide new insights into the mechanisms underlying cytokine‐initiated joint inflammation in RA and may inspire new targeted therapeutic approaches.
Inhibition of NF‐κB signaling by fasudil as a potential therapeutic strategy for rheumatoid arthritis
Authors: Okamoto Hiroshi , Yoshio Taku , Kaneko Hirotaka , Yamanaka Hisashi 
Published: December 2009

AbstractObjectiveRheumatoid arthritis (RA) is the most common systemic autoimmune disease and is characterized mainly by symmetric polyarticular joint disorders. The pathologic processes are mediated by a number of cytokines, chemokines, cell adhesion molecules, and matrix metalloproteinases. The expression of most of these molecules is controlled at the transcriptional level. In addition, activation of NF‐κB is involved in RA pathogenesis. This study was performed to explore the role of a novel serine/threonine kinase inhibitor, fasudil, in the control of the NF‐κB activation pathway and to investigate the therapeutic effects of fasudil on arthritis development in a rat model of RA.MethodsFibroblast‐like synoviocytes (FLS) from RA patients and human endothelial cells (ECs) were established and maintained. To study the role of fasudil on cytokine expression, various cytokines expressed in the RA FLS and human ECs were measured by enzyme‐linked immunosorbent assay following stimulation of the cells with interleukin‐1β (IL‐1β) in the presence of various concentrations of fasudil. The role of fasudil on NF‐κB activation was studied using a reporter gene assay, Western blotting of IκBα, immunofluorescence analysis of the p65 subunit of NF‐κB, and electrophoretic mobility shift assay. The in vivo effects of fasudil on arthritis were studied in a rat adjuvant‐induced arthritis (AIA) model.ResultsFasudil inhibited cytokine expression in RA FLS and human ECs and also inhibited the activation of ECs, in a dose‐dependent manner. Fasudil inhibited IL‐1β–induced activation of NF‐κB independent of the inhibition of IκBα degradation and nuclear translocation of NF‐κB, and inhibited IL‐1β–induced DNA binding of NF‐κB. Finally, in vivo, fasudil ameliorated arthritis in rats with AIA, without any adverse effects.ConclusionSerine/threonine kinase inhibitor fasudil inhibits the development of arthritis in a rat model of RA, and also inhibits the NF‐κB signaling required for binding of NF‐κB to specific DNA sequences through, for example, the phosphorylation of p65, suggesting that a specific target of fasudil might be a novel NF‐κB kinase. Thus, fasudil serves as a novel strategy for the treatment of RA.
Muscle resident macrophages control the immune cell reaction in a mouse model of notexin‐induced myoinjury
Authors: Brigitte Madly , Schilte Clementine , Plonquet Anne , Baba‐Amer Yasmine , Henri Adeline , Charlier Caroline , Tajbakhsh Shahragim , Albert Matthew , Gherardi Romain K. , Chrétien Fabrice 
Published: December 2009

AbstractObjectiveSkeletal muscle may be the site of a variety of poorly understood immune reactions, particularly after myofiber injury, which is typically observed in inflammatory myopathies. This study was undertaken to explore both the cell dynamics and functions of resident macrophages and dendritic cells (DCs) in damaged muscle, using a mouse model of notexin‐induced myoinjury to study innate immune cell reactions.MethodsThe myeloid cell reaction to notexin‐induced myoinjury was analyzed by microscopy and flow cytometry. Bone marrow (BM) transplantation studies were used to discriminate resident from exudate monocyte/macrophages. Functional tests included cytokine screening and an alloantigenic mixed leukocyte reaction to assess the antigen‐presenting cell (APC) function. Selective resident macrophage depletion was obtained by injection of diphtheria toxin (DT) into CD11b–DT receptor–transgenic mice transplanted with DT‐insensitive BM.ResultsThe connective tissue surrounding mouse muscle/fascicle tissue (the epimysium/perimysium) after deep muscle injury displayed a resident macrophage population of CD11b+F4/80+CD11c−Ly‐6C−CX3CR1− cells, which concentrated first in the epimysium. These resident macrophages were being used by leukocytes as a centripetal migration pathway, and were found to selectively release 2 chemokines, cytokine‐induced neutrophil chemoattractant and monocyte chemoattractant protein 1, and to crucially contribute to massive recruitment of neutrophils and monocytes from the blood. Early epimysial inflammation consisted of a predominance of Ly‐6ChighCX3CR1lowCD11c− cells that were progressively substituted by Ly‐6ClowCX3CR1high cells displaying an intermediate, rather than high, level of CD11c expression. These CD11cintermediate cells were derived from circulating CCR2+ monocytes, functionally behaved as immature APCs in the absence of alloantigenic challenge, and migrated to draining lymph nodes while acquiring the phenotype of mature DCs (CD11c+Ia+CD80+ cells, corresponding to an inflammatory DC phenotype).ConclusionThe results in this mouse model show that resident macrophages in the muscle epimysium/perimysium orchestrate the innate immune response to myoinjury, which is linked to adaptive immunity through the formation of inflammatory DCs.
Large‐scale magnetic flux concentrations from turbulent stresses
Authors: Brandenburg A. , Kleeorin N. , Rogachevskii I. 
Published: December 2009

AbstractIn this study we provide the first numerical demonstration of the effects of turbulence on the mean Lorentz force and the resulting formation of large‐scale magnetic structures. Using three‐dimensional direct numerical simulations (DNS) of forced turbulence we show that an imposed mean magnetic field leads to a decrease of the turbulent hydromagnetic pressure and tension. This phenomenon is quantified by determining the relevant functions that relate the sum of the turbulent Reynolds and Maxwell stresses with the Maxwell stress of the mean magnetic field. Using such a parameterization, we show by means of two‐dimensional and three‐dimensional mean‐field numerical modelling that an isentropic density stratified layer becomes unstable in the presence of a uniform imposed magnetic field. This large‐scale instability results in the formation of loop‐like magnetic structures which are concentrated at the top of the stratified layer. In three dimensions these structures resemble the appearance of bipolar magnetic regions in the Sun. The results of DNS and mean‐field numerical modelling are in good agreement with theoretical predictions. We discuss our model in the context of a distributed solar dynamo where active regions and sunspots might be rather shallow phenomena (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The use of real options valuation methodology in enhancing the understanding of the impact of climate change on companies
Authors: Tyler Emily , Chivaka Richard 
Published: December 2009

AbstractClimate change has in recent years gathered traction on the business, political and social agenda. From the business perspective, research has shown that climate change impacts on company value are uncertain, significant and strategically important. The challenge therefore is for the business community to apply financial valuation models that support the incorporation of the climate change impacts in strategic planning. However, the commonly used discounted cash flow techniques in capital budgeting are seen as failing to address the high levels of uncertainties inherent in climate change impacts. Real options thinking has been touted as having the potential to enhance understanding of these impacts via its direct handling of uncertainty, although not much research has been done to demonstrate this. Using an illustrative case study, this research presents an argument for introducing the real options approach, a new method for valuing options of future strategic action by companies in a setting that exhibits climate change impacts. The objective of this research is to contribute to the literature on strategic tools for addressing climate change and ultimately offer some management insights that can narrow the gap between finance theory and business practice. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment.
Tag SNP selection using particle swarm optimization
Authors: Chuang Li‐Yeh , Yang Cheng‐San , Ho Chang‐Hsuan , Yang Cheng‐Hong 
Published: December 2009

AbstractSingle nucleotide polymorphisms (SNPs) are the most abundant form of genetic variations amongst species. With the genome‐wide SNP discovery, many genome‐wide association studies are likely to identify multiple genetic variants that are associated with complex diseases. However, genotyping all existing SNPs for a large number of samples is still challenging even though SNP arrays have been developed to facilitate the task. Therefore, it is essential to select only informative SNPs representing the original SNP distributions in the genome (tag SNP selection) for genome‐wide association studies. These SNPs are usually chosen from haplotypes and called haplotype tag SNPs (htSNPs). Accordingly, the scale and cost of genotyping are expected to be largely reduced. We introduce binary particle swarm optimization (BPSO) with local search capability to improve the prediction accuracy of STAMPA. The proposed method does not rely on block partitioning of the genomic region, and consistently identified tag SNPs with higher prediction accuracy than either STAMPA or SVM/STSA. We compared the prediction accuracy and time complexity of BPSO to STAMPA and an SVM‐based (SVM/STSA) method using publicly available data sets. For STAMPA and SVM/STSA, BPSO effective improved prediction accuracy for smaller and larger scale data sets. These results demonstrate that the BPSO method selects tag SNP with higher accuracy no matter the scale of data sets is used. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Accurate control of oxygen level in cells during culture on silicone rubber membranes with application to stem cell differentiation
Authors: Powers Daryl E. , Millman Jeffrey R. , Bonner‐Weir Susan , Rappel Michael J. , Colton Clark K. 
Published: December 2009

AbstractOxygen level in mammalian cell culture is often controlled by placing culture vessels in humidified incubators with a defined gas phase partial pressure of oxygen (pO2gas). Because the cells are consuming oxygen supplied by diffusion, a difference between pO2gas and that experienced by the cells (pO2cell) arises, which is maximal when cells are cultured in vessels with little or no oxygen permeability. Here, we demonstrate theoretically that highly oxygen‐permeable silicone rubber membranes can be used to control pO2cell during culture of cells in monolayers and aggregates much more accurately and can achieve more rapid transient response following a disturbance than on polystyrene and fluorinated ethylene‐propylene copolymer membranes. Cell attachment on silicone rubber was achieved by physical adsorption of fibronectin or Matrigel. We use these membranes for the differentiation of mouse embryonic stem cells to cardiomyocytes and compare the results with culture on polystyrene or on silicone rubber on top of polystyrene. The fraction of cells that are cardiomyocyte‐like increases with decreasing pO2 only when using oxygen‐permeable silicone membrane‐based dishs, which contract on silicone rubber but not polystyrene. The high permeability of silicone rubber results in pO2cell being equal to pO2gas at the tissue‐membrane interface. This, together with geometric information from histological sections, facilitates development of a model from which the pO2 distribution within the resulting aggregates is computed. Silicone rubber membranes have significant advantages over polystyrene in controlling pO2cell, and these results suggest they are a valuable tool for investigating pO2 effects in many applications, such as stem cell differentiation. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Microwave‐based alkali pretreatment of switchgrass and coastal bermudagrass for bioethanol production
Authors: Keshwani Deepak R. , Cheng Jay J. 
Published: December 2009

AbstractSwitchgrass and coastal bermudagrass are promising lignocellulosic feedstocks for bioethanol production. However, pretreatment of lignocelluloses is required to improve production of fermentable sugars from enzymatic hydrolysis. Microwave‐based alkali pretreatment of switchgrass and coastal bermudagrass was investigated in this study. Pretreatments were carried out by immersing the biomass in dilute alkali reagents and exposing the slurry to microwave radiation at 250 W for residence times ranging from 5 to 20 min. Simons' stain method was used to quantify changes in biomass porosity as a result of the pretreatment. Pretreatments were evaluated based on yields of total reducing sugars, glucose, and xylose. An evaluation of different alkalis identified sodium hydroxide as the most effective alkali reagent for microwave‐based pretreatment of switchgrass and coastal bermudagrass. 82% glucose and 63% xylose yields were achieved for switchgrass and 87% glucose and 59% xylose yields were achieved for coastal bermudagrass following enzymatic hydrolysis of biomass pretreated under optimal conditions. Dielectric properties for dilute sodium hydroxide solutions were measured and compared with solid losses, lignin reduction, and reducing sugar levels in hydrolyzates. Results indicate that dielectric loss tangent of alkali solutions is a potential indicator of the severity of microwave‐based pretreatments. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Chemically Induced Cardiomyogenesis of Mouse Embryonic Stem Cells
Authors: Berkessel Albrecht , Seelig Bianca , Schwengberg Silke , Hescheler Jürgen , Sachinidis Agapios 
Published: December 2009

AbstractA transgenic murine embryonic stem (ES) cell lineage expressing enhanced green fluorescent protein (EGFP) under the control of α‐myosine heavy chain (α‐MHC) promoter (pα‐MHC‐EGFP) was used to investigate the effects of (thio)urea and cinchona alkaloid derivatives on cardiomyogenesis. The screening of the compounds yielded cardiomyogenesis inducing substances with good (IV‐5, V‐4) to very good activities (II‐16, IV‐8), as determined by a 50 to 80 % increase in the EGFP fluorescence compared to untreated cells. Time‐dependent screening approaches in which compounds were added at different developmental stages of the ES cells appeared to be of limited suitability for the identification of potential cellular targets.
Pathways and Substrate Specificity of DMSP Catabolism in Marine Bacteria of the Roseobacter Clade
Authors: Dickschat Jeroen S. , Zell Claudia , Brock Nelson L. 
Published: December 2009

AbstractThe volatiles released by Phaeobacter gallaeciensis, Oceanibulbus indolifex and Dinoroseobacter shibae have been investigated by GC‐MS, and several MeSH‐derived sulfur volatiles have been identified. An important sulfur source in the oceans is the algal metabolite dimethylsulfoniopropionate (DMSP). Labelled [2H6]DMSP was fed to the bacteria to investigate the production of volatiles from this compound through the lysis pathway to [2H6]dimethylsulfide or the demethylation pathway to [2H3]‐3‐(methylmercapto)propionic acid and lysis to [2H3]MeSH. [2H6]DMSP was efficiently converted to [2H3]MeSH by all three species. Several DMSP derivatives were synthesised and used in feeding experiments. Strong dealkylation activity was observed for the methylated ethyl methyl sulfoniopropionate and dimethylseleniopropionate, as indicated by the formation of EtSH‐ and MeSeH‐derived volatiles, whereas no volatiles were formed from dimethyltelluriopropionate. In contrast, the dealkylation activity for diethylsulfoniopropionate was strongly reduced, resulting in only small amounts of EtSH‐derived volatiles accompanied by diethyl sulfide in P. gallaeciensis and O. indolifex, while D. shibae produced the related oxidation product diethyl sulfone. The formation of diethyl sulfide and diethyl sulfone requires the lysis pathway, which is not active for [2H6]DMSP. These observations can be explained by a shifted distribution between the two competing pathways due to a blocked dealkylation of ethylated substrates.
Comments on a recently published paper ‘some surprising properties of multivariate curve resolution‐alternating least squares (MCR‐ALS) algorithms’
Authors: Tauler Romà 
Published: December 2009

AbstractSome of the results given in a recently published paper in this journal concerning some surprising properties of the multivariate curve resolution‐alternating least squares (MCR‐ALS) method are discussed. My results showed that the surprising properties of MCR‐ALS refer only to the slow linear convergence properties of ALS algorithms and to rounding error computer calculations. Results obtained by MCR‐ALS for the first data example were correct and no significant differences were observed in the resolved profiles. In the second more complex data example, large rotation ambiguities were present for the spectrum profile of the very minor second component which was not correctly estimated by MCR‐ALS. However, even in this case, the subspaces spanned by the MCR‐ALS solutions were also very close to the correct ones apart from slow convergence properties of the MCR‐ALS algorithm in this case. Copyright © 2009 John Wiley & Sons, Ltd.
A New Zincate‐Mediated Rearrangement Reaction of 2‐(1‐Hydroxyalkyl)‐1‐alkylcyclopropanol
Authors: Nomura Kenichi , Matsubara Seijiro 
Published: December 2009

AbstractA novel rearrangement of 2‐(1‐hydroxyalkyl)‐1‐alkylcyclopropanol has been found. It proceeds in the presence of a catalytic amount of organozinc ate complex to give vic‐diols. The rearrangement can be applied to various types of 2‐(1‐hydroxyalkyl)‐1‐alkylcyclopropanol, which can be easily prepared from the corresponding α,β‐epoxyketones and bis(iodozincio)methane. When bicyclo[13.1.0]pentadecane‐1,15‐diol was treated with the organozinc ate complex, the corresponding 14‐membered cyclic vic‐diol was obtained. Thus, this rearrangement is also useful for changing the ring size of cyclic substrates.
Phenacyl–Thiophene and Quinone Semiconductors Designed for Solution Processability and Air‐Stability in High Mobility n‐Channel Field‐Effect Transistors
Authors: Letizia Joseph A. , Cronin Scott , Ortiz Rocio Ponce , Facchetti Antonio , Ratner Mark A. , Marks Tobin J. 
Published: December 2009

AbstractElectron‐transporting organic semiconductors (n‐channel) for field‐effect transistors (FETs) that are processable in common organic solvents or exhibit air‐stable operation are rare. This investigation addresses both these challenges through rational molecular design and computational predictions of n‐channel FET air‐stability. A series of seven phenacyl–thiophene‐based materials are reported incorporating systematic variations in molecular structure and reduction potential. These compounds are as follows: 5,5′′′‐bis(perfluorophenylcarbonyl)‐2,2′:5′,‐ 2′′:5′′,2′′′‐quaterthiophene (1), 5,5′′′‐bis(phenacyl)‐2,2′:5′,2′′: 5′′,2′′′‐quaterthiophene (2), poly[5,5′′′‐(perfluorophenac‐2‐yl)‐4′,4′′‐dioctyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene) (3), 5,5′′′‐bis(perfluorophenacyl)‐4,4′′′‐dioctyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene (4), 2,7‐bis((5‐perfluorophenacyl)thiophen‐2‐yl)‐9,10‐phenanthrenequinone (5), 2,7‐bis[(5‐phenacyl)thiophen‐2‐yl]‐9,10‐phenanthrenequinone (6), and 2,7‐bis(thiophen‐2‐yl)‐9,10‐phenanthrenequinone, (7). Optical and electrochemical data reveal that phenacyl functionalization significantly depresses the LUMO energies, and introduction of the quinone fragment results in even greater LUMO stabilization. FET measurements reveal that the films of materials 1, 3, 5, and 6 exhibit n‐channel activity. Notably, oligomer 1 exhibits one of the highest μe (up to ≈0.3 cm2 V−1 s−1) values reported to date for a solution‐cast organic semiconductor; one of the first n‐channel polymers, 3, exhibits μe≈10−6 cm2 V−1 s−1 in spin‐cast films (μe=0.02 cm2 V−1 s−1 for drop‐cast 1:3 blend films); and rare air‐stable n‐channel material 5 exhibits n‐channel FET operation with μe=0.015 cm2 V−1 s−1, while maintaining a large Ion:off=106 for a period greater than one year in air. The crystal structures of 1 and 2 reveal close herringbone interplanar π‐stacking distances (3.50 and 3.43 Å, respectively), whereas the structure of the model quinone compound, 7, exhibits 3.48 Å cofacial π‐stacking in a slipped, donor‐acceptor motif.
Targeting Bacterial Membranes: NMR Spectroscopy Characterization of Substrate Recognition and Binding Requirements of D‐Arabinose‐5‐Phosphate Isomerase
Authors: Airoldi Cristina , Sommaruga Silvia , Merlo Silvia , Sperandeo Paola , Cipolla Laura , Polissi Alessandra , Nicotra Francesco 
Published: December 2009

AbstractLipopolysaccharide (LPS) is an essential component of the outer membrane of Gram‐negative bacteria and consists of three elements: lipid A, the core oligosaccharide, and the O‐antigen. The inner‐core region is highly conserved and contains at least one residue of 3‐deoxy‐D‐manno‐octulosonate (Kdo). Arabinose‐5‐phosphate isomerase (API) is an aldo–keto isomerase catalyzing the reversible isomerization of D‐ribulose‐5‐phosphate (Ru5P) to D‐arabinose‐5‐phosphate (A5P), the first step of Kdo biosynthesis. By exploiting saturation transfer difference (STD) NMR spectroscopy, the structural requirements necessary for API substrate recognition and binding were identified, with the aim of designing new API inhibitors. In addition, simple experimental conditions for the STD experiments to perform a fast, robust, and efficient screening of small libraries of potential API inhibitors, allowing the identification of new potential leads, were set up. Due to the essential role of API enzymes in LPS biosynthesis and Gram‐negative bacteria survival, by exploiting these data, a new generation of potent antibacterial drugs could be developed.