bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection against anti–citrullinated protein antibody–positive rheumatoid arthritis is predominantly associated with HLA–DRB1*1301: A meta‐analysis of HLA–DRB1 associations with anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis in four European populations
Authors: van der Woude Diane , Lie Benedicte A. , Lundström Emeli , Balsa Alejandro , Feitsma Anouk L. , Houwing‐Duistermaat Jeanine J. , Verduijn Willem , Nordang Gry B. N. , Alfredsson Lars , Klareskog Lars , Pascual‐Salcedo Dora , Gonzalez‐Gay Miguel A. , Lopez‐Nevot Miguel A. , Valero Fernando , Roep Bart O. , Huizinga Tom W. J. , Kvien Tore K. , Martín Javier , Padyukov Leonid , de Vries René R. P. , Toes René E. M. 
Published: January 2010

AbstractObjectiveThe protective effect of HLA–DRB1 alleles on the development of rheumatoid arthritis (RA) is poorly understood. The aim of this study was to perform a meta‐analysis of 4 European populations to investigate which HLA–DRB1 alleles are associated with protection in anti–citrullinated protein antibody (ACPA)–positive RA and ACPA‐negative RA.MethodsData for >2,800 patients and >3,000 control subjects for whom information on HLA–DRB1 typing and ACPA status was available were collected from 4 European countries: Norway, Sweden, The Netherlands, and Spain. The odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with the different HLA–DRB1 alleles were analyzed in a combined meta‐analysis focused on protective alleles and classifications. The analysis of ACPA‐positive RA was stratified for the shared epitope (SE) alleles, to correct for skewing due to this association.ResultsIn ACPA‐positive RA, the only alleles that conveyed protection after stratification for SE were HLA–DRB1*13 alleles (OR 0.54 [95% CI 0.38–0.77]). The protective effect of the allele classifications based on the DERAA and D70 sequences was no longer present after exclusion of DRB1*13 (for D70, OR 0.97 [95% CI 0.75–1.25]), indicating that DRB1*13, rather than the DERAA or D70 sequence as such, is associated with protection. Among the DRB1*13 alleles, only DRB1*1301 was associated with protection (OR 0.24 [95% CI 0.09–0.59]). Protection appeared to follow a north‐to‐south gradient, with the strongest association in northern European countries. In ACPA‐negative RA, there were no robust associations with HLA–DRB1 alleles.ConclusionOur data do not support any of the classifications of protective alleles and indicate that protection against ACPA‐positive RA is predominantly associated with HLA–DRB1*1301.
Expanding the phenotypic spectrum of lupus erythematosus in Aicardi‐Goutières syndrome
Authors: Ramantani Georgia , Kohlhase Jürgen , Hertzberg Christoph , Innes A. Micheil , Engel Kerstin , Hunger Susan , Borozdin Wiktor , Mah Jean K. , Ungerath Kristina , Walkenhorst Hartmut , Richardt Hans‐Helmut , Buckard Johannes , Bevot Andrea , Siegel Corinna , von Stülpnagel Celina , Ikonomidou Chrysanthy , Thomas Kara , Proud Virginia , Niemann Frank , Wieczorek Dagmar , Häusler Martin , Niggemann Pascal , Baltaci Volkan , Conrad Karsten , Lebon Pierre , Lee‐Kirsch Min Ae 
Published: January 2010

AbstractObjectiveAicardi‐Goutières syndrome (AGS) is an early‐onset encephalopathy resembling congenital viral infection that is characterized by basal ganglia calcifications, loss of white matter, cerebrospinal fluid (CSF) lymphocytosis, and elevated interferon‐α levels in the CSF. Studies have shown that AGS is an autosomal‐recessive disease linked to mutations in 5 genes, encoding the 3′‐repair DNA exonuclease 1 (TREX1), the 3 subunits of ribonuclease H2 (RNASEH2A–C), and sterile alpha motif domain and HD domain–containing protein 1 (SAMHD1). In this study we further characterized the phenotypic spectrum of this disease.MethodsClinical and laboratory data were obtained from 26 patients fulfilling the clinical diagnostic criteria for AGS. Genomic DNA was screened for mutations in all 5 AGS genes by direct sequencing, and sera were analyzed for autoantibodies.ResultsIn 20 patients with AGS, 20 mutations, 12 of which were novel, were identified in all 5 AGS genes. Clinical and laboratory investigations revealed a high prevalence of features (some not previously described in patients with AGS) that are commonly seen in patients with systemic lupus erythematosus (SLE), such as thrombocytopenia, leukocytopenia, antinuclear antibodies, erythematous lesions, oral ulcers, and arthritis, which were observed in 12 (60%) of 20 patients with AGS. Moreover, the coexistence of AGS and SLE, was for the first time, demonstrated in 2 patients with molecularly proven AGS.ConclusionThese findings expand the phenotypic spectrum of lupus erythematosus in AGS and provide further insight into its disease mechanisms by showing that activation of the innate immune system as a result of inherited defects in nucleic acid metabolism could lead to systemic autoimmunity.
Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice
Authors: Ramanujam Meera , Bethunaickan Ramalingam , Huang Weiqing , Tao Haiou , Madaio Michael P. , Davidson Anne 
Published: January 2010

AbstractObjectiveTo determine whether BAFF or combined BAFF/APRIL blockade is effective in a mouse model of systemic lupus erythematosus (SLE) nephritis characterized by rapidly progressive glomerulosclerosis.MethodsNZM2410 mice at early and late stages of SLE nephritis were treated with a short course of BAFF‐R‐Ig or TACI‐Ig fusion protein. Proteinuria and serologic profile were evaluated every 2 weeks. Immunohistochemical, flow cytometric, and enzyme‐linked immunospot analyses of the spleen, kidney, and bone marrow were performed after 8 weeks and after 33 weeks.ResultsA short course of selective blockade of BAFF alone was sufficient to prevent and treat SLE nephritis in NZM2410 mice, despite the formation of pathogenic autoantibodies. Decreases in spleen size and B cell depletion persisted for more than 33 weeks after treatment and resulted in secondary decreases in CD4 memory T cell formation and activation of splenic and peripheral monocytes. Immune complex deposition in the kidneys was dissociated from renal damage and from activation of renal endothelial and resident dendritic cells.ConclusionSelective blockade of BAFF alone, which resulted in B cell depletion and splenic collapse, was sufficient to prevent and treat the disease in this model of noninflammatory SLE nephritis. This shows that the inflammatory microenvironment may be a determinant of the outcome of B cell modulation strategies.
Strategies to enhance cell growth and achieve high‐level oil production of a Chlorella vulgaris isolate
Authors: Chen Chun‐Yen , Yeh Kuei‐Ling , Su Huei‐Meei , Lo Yung‐Chung , Chen Wen‐Ming , Chang Jo‐Shu 
Published: January 2010

AbstractThe autotrophic growth of an oil‐rich indigenous microalgal isolate, identified as Chlorella vulgaris CC, was promoted by using engineering strategies to obtain the microalgal oil for biodiesel synthesis. Illumination with a light/dark cycle of 14/10 (i.e., 14 h light‐on and 10 h light‐off) resulted in a high overall oil production rate (voil) of 9.78 mg/L/day and a high electricity conversion efficiency (Ec) of 23.7 mg cell/kw h. When using a NaHCO3 concentration of 1,500 mg/L as carbon source, the voil and Ec were maximal at 100 mg/L/day and 128 mg/kw h, respectively. A Monod type model was used to describe the microalgal growth kinetics with an estimated maximum specific growth rate (μmax) of 0.605 day−1 and a half saturation coefficient (Ks) of 124.9 mg/L. An optimal nitrogen source (KNO3) concentration of 625 mg/L could further enhance the microalgal biomass and oil production, leading to a nearly 6.19 fold increase in voil value. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Rationally engineered biotransformation of p‐nitrophenol
Authors: Mattozzi Matthew de la Peña , Keasling Jay D. 
Published: January 2010

AbstractAn operon encoding enzymes responsible for degradation of the EPA priority contaminant para‐nitrophenol (PNP) from Pseudomonas sp. ENV2030 contains more genes than would appear to be necessary to mineralize PNP. To determine some necessary genes for PNP degradation, the genes encoding the proposed enzymes in the degradation pathway (pnpADEC) were assembled into a broad‐host‐range, BioBricks‐compatible vector under the control of a constitutive promoter. These were introduced into Escherichia coli DH10b and two Pseudomonas putida strains, one with a knockout of the aromatic transport TtgB and the parent with the native transporter. The engineered strains were assayed for PNP removal. E. coli DH10b harboring several versions of the refactored pathway was able to remove PNP from the medium up to a concentration of 0.2 mM; above which PNP was toxic to E. coli. A strain of P. putida harboring the PNP pathway genes was capable of removing PNP from the medium up to 0.5 mM. When P. putida harboring the native PNP degradation cluster was exposed to PNP, pnpADEC were induced, and the resulting production of β‐ketoadipate from PNP induced expression of its chromosomal degradation pathway (pcaIJF). In contrast, pnpADEC were expressed constitutively from the refactored constructs because none of the regulatory genes found in the native PNP degradation cluster were included. Although P. putida harboring the refactored construct was incapable of growing exclusively on PNP as a carbon source, evidence that the engineered pathway was functional was demonstrated by the induced expression of chromosomal pcaIJF. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Paracoccus denitrificans for the effluent recycling during continuous denitrification of liquid food
Authors: Tippkötter Nils , Roikaew Wipa , Ulber Roland , Hoffmann Alexander , Denzler Hans‐Jörg , Buchholz Heinrich 
Published: January 2010

AbstractNitrate is an undesirable component of several foods. A typical case of contamination with high nitrate contents is whey concentrate, containing nitrate in concentrations up to 25 l. The microbiological removal of nitrate by Paracoccus denitrificans under formation of harmless nitrogen in combination with a cell retention reactor is described here. Focus lies on the resource‐conserving design of a microbal denitrification process. Two methods are compared. The application of polyvinyl alcohol‐immobilized cells, which can be applied several times in whey feed, is compared with the implementation of a two step denitrification system. First, the whey concentrate's nitrate is removed by ion exchange and subsequently the eluent regenerated by microorganisms under their retention by crossflow filtration. Nitrite and nitrate concentrations were determined by reflectometric color measurement with a commercially available Reflectoquant® device. Correction factors for these media had to be determined. During the pilot development, bioreactors from 4 to 250 mg·L−1 and crossflow units with membrane areas from 0.02 to 0.80 m2 were examined. Based on the results of the pilot plants, a scaling for the exemplary process of denitrifying 1,000 tons per day is discussed. © 2010 American Institute of Chemical Engineers Biotechnol. Prog. 2010
Cellular level models as tools for cytokine design
Authors: Radhakrishnan Mala L. , Tidor Bruce 
Published: January 2010

AbstractCytokines and growth factors are critical regulators that connect intracellular and extracellular environments through binding to specific cell‐surface receptors. They regulate a wide variety of immunological, growth, and inflammatory response processes. The overall signal initiated by a population of cytokine molecules over long time periods is controlled by the subtle interplay of binding, signaling, and trafficking kinetics. Building on the work of others, we abstract a simple kinetic model that captures relevant features from cytokine systems as well as related growth factor systems. We explore a large range of potential biochemical behaviors, through systematic examination of the model's parameter space. Different rates for the same reaction topology lead to a dramatic range of biochemical network properties and outcomes. Evolution might productively explore varied and different portions of parameter space to create beneficial behaviors, and effective human therapeutic intervention might be achieved through altering network kinetic properties. Quantitative analysis of the results reveals the basis for tensions among a number of different network characteristics. For example, strong binding of cytokine to receptor can increase short‐term receptor activation and signal initiation but decrease long‐term signaling due to internalization and degradation. Further analysis reveals the role of specific biochemical processes in modulating such tensions. For instance, the kinetics of cytokine binding and receptor activation modulate whether ligand–receptor dissociation can generally occur before signal initiation or receptor internalization. Beyond analysis, the same models and model behaviors provide an important basis for the design of more potent cytokine therapeutics by providing insight into how binding kinetics affect ligand potency. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Alternating current electric field effects on neural stem cell viability and differentiation
Authors: Matos Marvi A. , Cicerone Marcus T. 
Published: January 2010

AbstractMethods utilizing stem cells hold tremendous promise for tissue engineering applications; however, many issues must be worked out before these therapies can be routinely applied. Utilization of external cues for preimplantation expansion and differentiation offers a potentially viable approach to the use of stem cells in tissue engineering. The studies reported here focus on the response of murine neural stem cells encapsulated in alginate hydrogel beads to alternating current electric fields. Cell viability and differentiation was studied as a function of electric field magnitude and frequency. We applied fields of frequency (0.1–10) Hz, and found a marked peak in neural stem cell viability under oscillatory electric fields with a frequency of 1 Hz. We also found an enhanced propensity for astrocyte differentiation over neuronal differentiation in the 1 Hz cultures, as compared to the other field frequencies we studied. Published 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Optimization of cultivation conditions in spin tubes for Chinese hamster ovary cells producing erythropoietin and the comparison of glycosylation patterns in different cultivation vessels
Authors: Strnad Jure , Brinc Matjaž , Spudić Vatroslav , Jelnikar Nadja , Mirnik Lidija , Čarman Barbara , Kravanja Zdravko 
Published: January 2010

AbstractThis article describes the optimization of cultivation factor settings, that is the shaking rate and working volume in 50 mL spin tubes for a Chinese hamster ovary cell line expressing recombinant human α‐erythropoietin, using a response D‐optimal surface method. The main objectives of the research were, firstly, to determine a setting in which the product titer and product quality attributes in spin tubes are equivalent to those in 250 mL shake flasks in a seven day batch and, secondly, to find a setting in which the product titer is maximal. The model for product titer prediction as a function of shaking rate and working volume in the defined design space was successfully applied to the optimization of cultivation conditions in spin tubes for the tested cell line. Subsequently, validation experiments were carried out simultaneously in spin tubes, shake flasks and bench scale bioreactors to compare cell culture performance parameters such as growth, productivity and product quality attributes in the form of isoform profiles and glycan antennarity structures. The results of the experiments showed that similar cell culture performance and product quality could be achieved in spin tubes when compared to shake flasks. Additionally, bioreactor titers could be reproduced in spin tubes at high shaking rates and low working volumes, but with differing product quality. Cultivation at lower shaking rates in spin tubes and shake flasks produced a glycoprotein with a product quality slightly comparable to that from bioreactors, but with titers being only two thirds. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Recombinant murine growth hormone from E. coli inclusion bodies: Expression, high‐pressure solubilization and refolding, and characterization of activity and structure
Authors: Fradkin Amber Haynes , Boand Carl S. , Eisenberg Stephen P. , Rosendahl Mary S. , Randolph Theodore W. 
Published: January 2010

AbstractWe expressed recombinant murine growth hormone (rmGH) in E. coli as a cost‐effective way to produce large quantities (gram scale) of the protein for use in murine studies of immunogenicity to therapeutic proteins. High hydrostatic pressure was used to achieve high solubility and high refolding yields of rmGH protein produced in E. coli inclusion bodies. A two‐step column purification protocol was used to produce 99% pure monomeric rmGH. Secondary and tertiary structures of purified rmGH were investigated using circular dichroism and 2D‐UV spectroscopy. The purified rmGH produced was found to be biologically active in hypophysectomized rats. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Solvent‐Induced Structural Transition of Self‐Assembled Dipeptide: From Organogels to Microcrystals
Authors: Zhu Pengli , Yan Xuehai , Su Ying , Yang Yang , Li Junbai 
Published: January 2010

AbstractOrganogels that are self‐assembled from simple peptide molecules are an interesting class of nano‐ and mesoscale soft matter with simplicity and functionality. Investigating the precise roles of the organic solvents and their effects on stabilization of the formed organogel is an important topic for the development of low‐molecular‐weight gelators. We report the structural transition of an organogel self‐assembled from a single dipeptide building block, diphenylalanine (L‐Phe‐L‐Phe, FF), in toluene into a flower‐like microcrystal merely by introducing ethanol as a co‐solvent; this provides deeper insights into the phase transition between mesostable gels and thermodynamically stable microcrystals. Multiple characterization techniques were used to reveal the transitions. The results indicate that there are different molecular‐packing modes formed in the gels and in the microcrystals. Further studies show that the co‐solvent, ethanol, which has a higher polarity than toluene, might be involved in the formation of hydrogen bonds during molecular self‐assembly of the dipeptide in mixed solvents, thus leading to the transition of organogels into microcrystals. The structural transformation modulated by the co‐solvent might have a potential implication in controllable molecular self‐assembly.
Mechanism of the Asymmetric Autocatalytic Soai Reaction Studied by Density Functional Theory
Authors: Schiaffino Luca , Ercolani Gianfranco 
Published: January 2010

AbstractThe mechanism of the Soai reaction has been thoroughly investigated at the M05‐2X/6‐31G(d) level of theory, by considering ten energetically distinct paths. The study indicates the fully enantioselective catalytic cycle of the homochiral dimers to be the dominant mechanism. Two other catalytic cycles are shown to both be important for correct understanding of the Soai reaction. These are the catalytic cycle of the heterochiral dimer and the non‐enantioselective catalytic cycle of the homochiral dimers. The former has been proved to be not really competitive with the principal cycle, as required for the Soai reaction to manifest chiral amplification, whereas the latter, which is only slightly competitive with the principal one, nicely explains the experimental enantioselectivity observed in the reaction of 2‐methylpyrimidine‐5‐carbaldehyde. The study has also evidenced the inadequacy of the B3LYP functional for mechanistic investigations of the Soai reaction.
Dipolar Compounds Containing Fluorene and a Heteroaromatic Ring as the Conjugating Bridge for High‐Performance Dye‐Sensitized Solar Cells
Authors: Chen Chih‐Hsin , Hsu Ying‐Chan , Chou Hsien‐Hsin , Thomas K. R. Justin , Lin Jiann T. , Hsu Chao‐Ping 
Published: January 2010

AbstractA novel series of dipolar organic dyes containing diarylamine as the electron donor, 2‐cyanoacrylic acid as the electron acceptor, and fluorene and a heteroaromatic ring as the conjugating bridge have been developed and characterized. These metal‐free dyes exhibited very high molar extinction coefficients in the electronic absorption spectra and have been successfully fabricated as efficient nanocrystalline TiO2 dye‐sensitized solar cells (DSSCs). The solar‐energy‐to‐electricity conversion efficiencies of DSSCs ranged from 4.92 to 6.88 %, which reached 68–96 % of a standard device of N719 fabricated and measured under the same conditions. With a TiO2 film thickness of 6 μm, DSSCs based on these dyes had photocurrents surpassing that of the N719‐based device. DFT computation results on these dyes also provide detailed structural information in connection with their high cell performance.
A phase 2 pilot trial of low‐dose, continuous infusion, or “metronomic” paclitaxel and oral celecoxib in patients with metastatic melanoma
Authors: Bhatt Rupal S. , Merchan Jaime , Parker Robert , Wu Hua‐Kang , Zhang Liang , Seery Virginia , Heymach John V. , Atkins Michael B. , McDermott David , Sukhatme Vikas P. 
Published: January 2010

AbstractBACKGROUND:Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX‐2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM.METHODS:Patients received paclitaxel 10 mg/m2 for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6‐week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study.RESULTS:Twenty patients were enrolled. Twelve of 20 patients (60%) had received ≥2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment‐related grade 3/4 toxicities were limited to catheter‐related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43‐151 days), and the median overall survival was 212 days (95% confidence interval, 147‐811 days).CONCLUSIONS:Low‐dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease. Cancer 2010. © 2010 American Cancer Society.