bluuebunny/crossref_metadata_2025_split huggingface dataset:
Citrulline‐Specific Th1 Cells Are Increased in Rheumatoid Arthritis and Their Frequency Is Influenced by Disease Duration and Therapy
Authors: James Eddie A. , Rieck Mary , Pieper Jennifer , Gebe John A. , Yue Betty B. , Tatum Megan , Peda Melissa , Sandin Charlotta , Klareskog Lars , Malmström Vivianne , Buckner Jane H. 
Published: March 2014

ObjectiveRheumatoid arthritis (RA) is thought to be a T cell–mediated disease, based on its strong association with HLA class II alleles, clinical responsiveness to T cell–directed therapies, and the presence of CD4+ T cells in rheumatoid joints. The presence of anti–citrullinated protein antibodies (ACPAs) in RA serum and the association of these antibodies with HLA–DR4 alleles implicate citrulline‐specific autoreactive T cells in the development and progression of RA. The goal of this study was to determine the characteristics and specificity of autoreactive T cell responses in RA.MethodsWe developed a panel of HLA–DRB1*04:01 tetramers, selecting citrullinated peptides from synovial antigens and verifying their immunogenicity in DRB1*04:01‐transgenic mice. Seven tetramers were used to examine the ex vivo frequency and surface phenotype of citrulline‐specific (Cit‐specific) T cells in patients with RA and healthy subjects with DRB1*04:01 haplotypes, using a magnetic enrichment procedure.ResultsCit‐specific T cells were detectable in peripheral blood samples from both healthy subjects and RA patients. In comparison to healthy subjects, RA patients had significantly higher frequencies of Cit‐specific T cells, and a greater proportion of these cells displayed a Th1 memory phenotype. Among RA patients, the frequency of Cit‐specific T cells was highest within the first 5 years after diagnosis of RA and was decreased in patients taking biologic agents, irrespective of disease duration.ConclusionThese findings link the presence of ACPAs in RA with Th1 cells specific for citrullinated epitopes and provide tools for disease‐specific immunomonitoring of autoreactive T cells.
Interleukin‐23 Mediates the Intestinal Response to Microbial β‐1,3‐Glucan and the Development of Spondyloarthritis Pathology in SKG Mice
Authors: Benham Helen , Rehaume Linda M. , Hasnain Sumaira Z. , Velasco Jared , Baillet Athan C. , Ruutu Merja , Kikly Kristine , Wang Ran , Tseng Hsu‐Wen , Thomas Gethin P. , Brown Matthew A. , Strutton Geoffrey , McGuckin Michael A. , Thomas Ranjeny 
Published: March 2014

ObjectiveSpondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin‐23 (IL‐23) receptor signaling in the development of SpA and IBD, and IL‐23 overexpression in mice is sufficient for enthesitis, driven by entheseal‐resident T cells. However, in genetically prone individuals, it is not clear where IL‐23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL‐23 production and its role in SpA pathogenesis in BALB/c ZAP‐70W163C–mutant (SKG) mice injected intraperitoneally with β‐1,3‐glucan (curdlan).MethodsEight weeks after curdlan injection in wild‐type or IL‐17A−/− SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti–IL‐23 or anti–IL‐22. Cytokine production and endoplasmic reticulum (ER) stress were determined in affected organs.ResultsIn curdlan‐treated SKG mice, arthritis, enthesitis, and ileitis were IL‐23 dependent. Enthesitis was specifically dependent on IL‐17A and IL‐22. IL‐23 was induced in the ileum, where it amplified ER stress, goblet cell dysfunction, and proinflammatory cytokine production. IL‐17A was pathogenic, while IL‐22 was protective against ileitis. IL‐22+CD3− innate‐like cells were increased in lamina propria mononuclear cells of ileitis‐resistant BALB/c mice, which developed ileitis after curdlan injection and anti–IL‐22.ConclusionIn response to systemic β‐1,3‐glucan, intestinal IL‐23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL‐17/IL‐22–dependent enthesitis. Innate IL‐22 production promotes ileal tolerance.
Supramolecular Proteoglycan Aggregate Mimics: Cyclodextrin‐Assisted Biodegradable Polymer Assemblies for Electrostatic‐Driven Drug Delivery
Authors: Szente Lajos , Puskás István , Csabai Katalin , Fenyvesi Éva 
Published: March 2014

AbstractSelf‐assembled, noncovalent polymeric biodegradable materials mimicking proteoglycan aggregates were synthesized from inclusion complexes of cationic surfactants with γ‐cyclodextrin and the natural anionic polymer hyaluronan. The amorphous structure of this ternary system was proven by X‐ray diffraction and thermal analysis. Light‐scattering measurements showed that there was a competition between hyaluronic acid and the surfactant for the cyclodextrin cavity. These self‐assembled supramolecular matrices were loaded with both hydrophilic and lipophilic drug substances for dissolution studies. The release of the entrapped drugs was found to be controlled by cations in the surrounding media and by biodegradation. Slow drug release in an ion‐free medium became faster in physiological salt solution in which the macroscopic polymer matrix was disassembled. In contrast, the enzymatic degradation of hyaluronan was hindered in the polymeric matrix. The supramolecular systems consisting of γ‐cyclodextrin as a macrocyclic host, a cationic surfactant guest, and hyaluronic acid as the anionic polymer electrostatically cross‐linked by the inclusion complex of the first two was found to be a novel drug‐delivery system for the controlled release of traditional drugs such as curcumin and ketotifen and proteins such as bovine serum albumin.
Microporous Metal–Organic Frameworks for Gas Separation
Authors: Li Bin , Wang Hailong , Chen Banglin 
Published: March 2014

AbstractMicroporous metal–organic frameworks (MOFs) are comparatively new porous materials. Because the pores within such MOFs can be readily tuned through the interplay of both metal‐containing clusters and organic linkers to induce their size‐selective sieving effects, while the pore surfaces can be straightforwardly functionalized to enforce their different interactions with gas molecules, MOF materials are very promising for gas separation. Furthermore, the high porosities of such materials can enable microporous MOFs with optimized gas separation selectivity and capacity to be targeted. This Focus Review highlights recent significant advances in microporous MOFs for gas separation.
Minimizing fucosylation in insect cell‐derived glycoproteins reduces binding to IgE antibodies from the sera of patients with allergy
Authors: Palmberger Dieter , Ashjaei Kazem , Strell Stephanie , Hoffmann‐Sommergruber Karin , Grabherr Reingard 
Published: March 2014

AbstractThe baculovirus/insect cell system has proven to be a very powerful tool for the expression of several therapeutics. Nevertheless, these products sometimes suffer from reduced biological activity and unwanted side effects. Several studies have demonstrated that glycosylation can greatly influence the structure, function, half‐life, antigenicity and immunogenicity of various glycoproteins. Yet, the glycosylation pattern of insect cell‐derived products is not favorable for many applications. Especially, the presence of core α1,3‐linked fucose bears the risk of causing immediate hypersensitivity reactions in patients with allergy. In this study, we evaluated the impact of fucose residues on the allergenic potential of an insect cell‐expressed vaccine candidate. In order to block the GDP‐L‐fucose de novo synthesis pathway, we integrated the Pseudomonas aeruginosa GDP‐6‐deoxy‐D‐lyxo‐4‐hexulose reductase (RMD) gene into a baculovirus backbone. This virus was then used for the expression of soluble influenza A virus hemagglutinin (HA). Expression studies showed that the co‐expression of RMD did not influence the overall level of recombinant protein secretion. We confirmed the result of our strategy by analyzing PNGase A‐released N‐glycans using MALDI‐TOF‐MS. In order to evaluate the biological impact of defucosylation of influenza HA we tested the binding activity of IgE derived from the sera of patients with allergy to the purified antigen. The non‐fucosylated HA showed a 10‐fold decrease in IgE binding levels as compared to wildtype variants.same article under 10.1002/biot.201400061.
On a novel mechanistic model for simultaneous enzymatic hydrolysis of cellulose and hemicellulose considering morphology
Authors: Zhang Yang , Xu Bingqian , Zhou Wen 
Published: March 2014

ABSTRACTWe develop a novel and general modeling framework for enzymatic hydrolysis of cellulose and hemicellulose simultaneously. Our mechanistic model, for the first time, takes into consideration explicitly the time evolution of morphologies of intertwining cellulose and hemicelluloses within substrate during enzymatic hydrolysis. This morphology evolution is driven by hydrolytic chain fragmentation and solubilization, which is, in return, profoundly affected by the substrate morphology. We represent the substrate morphology as a randomly distributed smallest accessible compartments (SACs) which are described by geometric functions to track total volume and exposed surface substrate materials, including both cellulose and hemicelluloses. Our morphology‐plus‐kinetics approach then couple the time‐dependent morphology with chain fragmentation and solubilization resulted from enzymatic reactions between various bonds in cellulose and hemicelluloses and a mixture (i.e., endo‐, exo‐, and oligomer‐ acting) of cellulases and hemicellulases. In addition, we propose an advanced and generalized site concentration formalism that considers different polysaccharide chain types and different monomer unit types on chains. The resulting ODE system has a substantially reduced size compared to conventional chain concentration formalism. We present numerical simulation results under real enzymatic hydrolysis experimental conditions from literature. The comparisons between the simulation results and the experiment measurements demonstrate effectiveness and wide applicability of the proposed mechanistic model. Biotechnol. Bioeng. 2014;111: 1767–1781. © 2014 Wiley Periodicals, Inc.
Structure–Activity Relationships of Nickel–Hexaaluminates in Reforming Reactions Part I: Controlling Nickel Nanoparticle Growth and Phase Formation
Authors: Roussière Thomas , Schelkle Korwin M. , Titlbach Sven , Wasserschaff Guido , Milanov Andrian , Cox Gerhard , Schwab Ekkehard , Deutschmann Olaf , Schulz Linus , Jentys Andreas , Lercher Johannes , Schunk Stephan A. 
Published: March 2014

AbstractThe controlled synthesis of hexaaluminates ANiyAl12−yO19−δ(A=Ba, La, Sr, andy=0.25, 0.5, 1) is reported by a freeze drying route. This route allows the use of moderate temperatures of approximately 1200 °C to obtain hexaaluminates of high phase purity (>80 wt %) as well as high specific surface areas (10–30 m2 g−1). Under reducing conditions at elevated temperatures, nickel expulsion from the hexaaluminate framework can be observed. High stability of the crystalline phase is observed even if all substitution cations leave the hexaaluminate framework. The moderate calcination temperature of 1200 °C facilitates the reducibility of the Ni–hexaaluminates compared to Ni–hexaaluminates calcined at 1600 °C. SEM and TEM imaging revealed that Ni–hexaaluminates with low Ni loading (y=0.25) and calcined at moderate temperature (1200 °C) lead under reducing atmosphere to the formation of strong textural growth and highly disperse and highly textured Ni0nanoparticles. Nanoparticle growth is associated to surface defect sites occurring on the hexaaluminate platelets.
Methane Coupling Reaction in an Oxy‐Steam Stream through an OH Radical Pathway by using Supported Alkali Metal Catalysts
Authors: Liang Yin , Li Zhikao , Nourdine Mohamed , Shahid Salman , Takanabe Kazuhiro 
Published: March 2014

AbstractA universal reaction mechanism involved in the oxidative coupling of methane (OCM) is demonstrated under oxy‐steam conditions using alkali‐metal‐based catalysts. Rigorous kinetic measurements indicated a reaction mechanism that is consistent with OH radical formation from a H2O–O2 reaction followed by CH activation in CH4 with an OH radical. Thus, the presence of water enhances both the CH4 conversion rate and the C2 selectivity. This OH radical pathway that is selective for the OCM was observed for the catalyst without Mn, which suggests clearly that Mn is not the essential component in a selective OCM catalyst. The experiments with different catalyst compositions revealed that the OH.‐mediated pathway proceeded in the presence of catalysts with different alkali metals (Na, K) and different oxo anions (W, Mo). This difference in catalytic activity for OH radical generation accounts for the different OCM selectivities. As a result, a high C2 yield is achievable by using Na2WO4/SiO2, which catalyzes the OH.‐mediated pathway selectively.
Optimized Dispersion and Stability of Hybrid Fe3O4/Pd Catalysts in Water for Suzuki Coupling Reactions: Impact of Organic Capping Agents
Authors: Woo Hyunje , Lee Kyoungho , Park Kang Hyun 
Published: March 2014

AbstractPd nanoparticles were easily immobilized on Fe3O4 microspheres without any treatment such as functionalization with organic groups. The Fe3O4 microspheres were synthesized by using different capping agents, and the effect of the capping agents on the dispersion stability and catalytic activity of the Fe3O4/Pd composite for Suzuki coupling reactions in water were evaluated. The catalytic activity varied depending on the dispersion stability of Fe3O4/Pd catalysts in water. The Pd nanoparticles immobilized onto Fe3O4 microspheres capped with trisodium citrate showed strong dispersion stability in water over the reaction duration of seven days (at pH 7), high catalytic activity, and recyclability under mild conditions.
Performance and Energy Consumption of Membrane‐Distillation Hybrid Systems for Olefin‐Paraffin Separation
Authors: Pedram Sara , Kaghazchi Tahereh , Ravanchi Maryam Takht 
Published: March 2014

AbstractLight olefin and paraffin are commonly separated by energy‐intensive cryogenic distillation. Membrane/distillation hybrid systems constitute an economical alternative separation process. Different configurations of this hybrid system are studied for olefin‐paraffin separation with emphasis on C3 separation. An approach based on the McCabe‐Thiele method is applied to analyze different process configurations. A facilitated transport membrane is considered as membrane type. Both new column design and augmentation of an existing distillation column by a membrane module are considered. Numerical examples are considered for the separation of propane from propylene through different hybridization shapes with facilitated transport membranes. The energy requirement can be halved using hybrid systems.
Application of a genomic model for high‐dimensional chemometric analysis
Authors: Shen Xia , Li Ying , Rönnegård Lars , Udén Peter , Carlborg Örjan 
Published: March 2014

AbstractThe rapid development of new technologies for large‐scale analysis of genetic variation in the genomes of individuals and populations has presented statistical geneticists with a grand challenge to develop efficient methods for identifying the small proportion of all identified genetic polymorphisms that have effects on traits of interest. To address such a “largepsmalln” problem, we have developed a heteroscedastic effects model (HEM) that has been shown to be powerful in high‐throughput genetic analyses. Here, we describe how this whole‐genome model can also be utilized in chemometric analysis. As a proof of concept, we use HEM to predict analyte concentrations in silage using Fourier transform infrared spectroscopy signals. The results show that HEM often outperforms the classic methods and in addition to this presents a substantial computational advantage in the analyses of such high‐dimensional data. The results thus show the value of taking an interdisciplinary approach to chemometric analysis and indicate that large‐scale genomic models can be a promising new approach for chemometric analysis that deserve to be evaluated more by experts in the field. The software used for our analyses is freely available as an R package athttp://cran.r‐project.org/web/packages/bigRR/. Copyright © 2014 John Wiley & Sons, Ltd.
‘À la Carte’ Peptide Shuttles: Tools to Increase Their Passage across the Blood–Brain Barrier
Authors: Malakoutikhah Morteza , Guixer Bernat , Arranz‐Gibert Pol , Teixidó Meritxell , Giralt Ernest 
Published: March 2014

AbstractNoninvasive methods for efficient drug delivery to the brain is an unmet need. Molecular access to the brain is regulated by the blood–brain barrier (BBB) established by the endothelial cells of brain vessels. Passive diffusion is one of the main mechanisms that organic compounds use to travel through these endothelial cells. This passage across the BBB is determined mainly by certain physicochemical properties of the molecule such as lipophilicity, size, and the presence of hydrogen bond donors and acceptors. One emerging strategy to facilitate the passage of organic compounds across the BBB is the use of peptide shuttles.1 In using this approach the permeability in front the BBB is, clearly, determined by the combined physicochemical properties of both the cargo and the shuttle. Herein we report the synthesis of a series of variations of one of the more efficient peptide shuttles, (N‐MePhe)n. These include diverse structural features such as various backbone stereochemistries or the presence of non‐natural amino acids, including halogenated residues. In several cases, we assessed the BBB permeability of both the shuttles alone and linked to a few cargos. Our results show how factors such as stereochemistry or halogen content influences the passage across the BBB and, more importantly, opens the way to a strategy of peptide shuttles ‘à la carte′, in which a particular fine‐tuned shuttle is used for each specific cargo.
Identification of a characteristic copy number alteration profile by high‐resolution single nucleotide polymorphism arrays associated with metastatic sporadic colorectal cancer
Authors: González‐González María , Fontanillo Celia , Abad María M. , Gutiérrez María L. , Mota Ines , Bengoechea Oscar , Santos‐Briz Ángel , Blanco Oscar , Fonseca Emilio , Ciudad Juana , Fuentes Manuel , De Las Rivas Javier , Alcazar José A. , García Jacinto , Muñoz‐Bellvis Luís , Orfao Alberto , Sayagués José M. 
Published: March 2014

BACKGROUNDMetastatic dissemination is the most frequent cause of death in patients with sporadic colorectal cancer (sCRC). It is believed that the metastatic process is related at least in part to a specific background of genetic alterations accumulated in cells from primary tumors, and the ability to detect such alterations is critical for the identification of patients with sCRC who are at risk of developing metastases.METHODSThe authors used high‐resolution, 500‐K single nucleotide polymorphism arrays to identify copy number alteration profiles present at diagnosis in primary tumors from patients with metastatic (n = 23) versus nonmetastatic (n = 26) sCRC.RESULTSThe results revealed a characteristic pattern of copy number alterations in metastatic sCRC tumors that involved losses of 23 regions at chromosomes 1p, 17p, and 18q, together with gains of 35 regions at chromosomes 7 and 13q.CONCLUSIONSIn line with expectations, the copy number profile investigated involved multiple genes that were associated previously with sCRC (ie, SMAD2) and/or the metastatic process (ie, podocalyxin‐like [PODXL]), and it also was associated with a poorer outcome. Cancer 2014;120:1948–1959. © 2014 American Cancer Society.
Sign Inversion of the Spontaneous Polarization in a “de Vries”‐Type Ferroelectric Liquid Crystal
Authors: Nonnenmacher Dorothee , Lemieux Robert P. , Osipov Mikhail A. , Giesselmann Frank 
Published: March 2014

AbstractIn contrast to common ferroelectric smectic C* liquid crystals, the siloxane‐terminated smectic mesogen E6 is characterized by an unusual temperature variation of the spontaneous polarization. The polarization starts to grow from nearly zero despite the first‐order SmA*‐SmC* transition, and increases faster than linearly over a large temperature interval while the tilt angle rapidly saturates. To study this behavior in more detail, binary mixtures of different concentrations of E6 in the achiral SmC material C8Cl, which has a similar chemical structure, were investigated. Surprisingly, all mixtures show a temperature dependent polarization sign inversion, which shifts towards the SmC*‐SmA* transition with increasing E6 concentration. For the pure E6 the inversion temperature meets the SmA*‐SmC* phase transition temperature. In a second binary mixture with E6 and a conventional material C9–2PhP we found out, that the dependence of the inversion temperature on the concentration of E6 changes qualitatively when the nanosegregation is partially destroyed. A molecular theory of the polarization sign inversion in smectics C* with strong polar intermolecular interactions is developed which enables one to explain the concentration dependence of the inversion temperature in both mixtures.
The Discriminative Stimulus Effects of the Neurotensin NTS1 Receptor Agonist PD149163 in Rats: Stimulus Generalization Testing with Dopamine D1 and D2 Receptor Ligands
Authors: Prus Adam J. , Schuck Candice J. , Rusch Kristoffer R. , Carey Lawrence M. 
Published: March 2014

Abstract

Preclinical Research

Brain‐penetrant neurotensin NTS1 receptor agonists produce antipsychotic drug‐like effects in animal models, including inhibition of conditioned avoidance responding and reversal of psychostimulant‐induced hyperactivity and stereotypy. Allosteric interactions between NTS1 receptors and dopamine D2 receptors may account for some of these antipsychotic effects. In order to determine the role that dopamine receptors may play in the behavioral effects produced by activation of NTS1 receptors, a drug discrimination approach was used in rats to evaluate the potential mediation of NTS1 receptor agonist stimulus effects by dopamine D1 and D2 receptors. Rats were trained to discriminate either the NTS1 receptor agonist PD149163, the D1 receptor agonist SKF81297, or the D2 receptor agonist quinpirole from vehicle in a two choice drug discrimination task. Full stimulus generalization occurred from PD149163 to the typical antipsychotic drug and D2 receptor‐preferring antagonist haloperidol. However, stimulus generalization did not occur from SKF81297 or quinpirole to PD149163. The discriminative cue for SKF91297 and quinpirole was fully blocked the D1 receptor antagonist SCH23390 and the D2/3 receptor antagonist raclopride, respectively. Cross generalization did not occur between SKF91297 and quinpirole. Based on these findings, the stimulus effects of PD149163 may be mediated, in part, through D2 receptor antagonism, but this may only be evident when PD149163 is used as the training drug.