bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Efficacy of Abatacept in Reducing Synovial T Cell Activation by CD1c Myeloid Dendritic Cells Is Overruled by the Stimulatory Effects of T Cell–Activating Cytokines
Authors: Moret F. M. , Bijlsma J. W. J. , Lafeber F. P. J. G. , van Roon J. A. G. 
Published: December 2014

ObjectiveTo investigate whether the potential of abatacept to inhibit vigorous CD1c myeloid dendritic cell (MDC)–driven activation of naive and memory CD4 T cells is abrogated in the presence of T cell–activating cytokines.MethodsCD4 T cell subsets (naive [Tn], central memory [Tcm], and effector memory [Tem] T cells) were isolated from the peripheral blood (PB) of healthy controls and the PB and synovial fluid (SF) of rheumatoid arthritis (RA) patients. CD4 T cells were cocultured with autologous, thymic stromal lymphopoietin (TSLP)–primed CD1c MDCs in the presence or absence of abatacept (CTLA‐4Ig) and/or interleukin‐7 (IL‐7) or IL‐15. Subsequently, T cell proliferation and cytokine production were measured.ResultsThe percentages of each CD4 T cell subset from the circulation of healthy controls and RA patients were comparable and mainly consisted of Tn and Tcm cells, whereas the SF of RA patients mainly consisted of Tcm and Tem cells. Activation of CD4 T cell subsets by TSLP‐primed MDCs from the RA PB was completely blocked by abatacept. Addition of IL‐7 or IL‐15 to the cocultures strongly increased CD4 T cell activation and overruled the inhibitory capacity of abatacept. IL‐7–induced reversal was associated with robust induction of interferon‐γ, tumor necrosis factor α, and IL‐17 secretion. Similarly, CD4 T cell proliferation induced by TSLP‐primed MDCs from the SF of RA patients was strongly blocked by abatacept, but this inhibitory effect was vigorously overruled in the presence of IL‐7.ConclusionThese findings indicate that the presence of T cell–activating cytokines such as IL‐7 or IL‐15 in the joints of RA patients reduces the capacity of abatacept to inhibit MDC‐driven CD4 T cell activation. This mechanism may be one explanation for the partial, and sometimes absent, response to abatacept therapy in a subset of patients.
Entwicklung eines innovativen Kammerquerschnitts für die neue Schleuse Dörverden
Authors: Ebers‐Ernst Jeannette , Herbort Johannes 
Published: December 2014

AbstractNach fast fünfjähriger Bauzeit wurde Ende 2013 die neue Schleuse Dörverden an der Mittelweser für den Verkehr freigegeben. Damit wurde im Bereich der Wasser‐ und Schifffahrtsverwaltung des Bundes (WSV) erstmals eine neuartige Kammerbauweise, bestehend aus einer rückverankerten, überschnittenen Bohrpfahlwand mit Stahlbetonvorsatzschale sowie einer mit Verpresspfählen rückverankerten Unterwasserbetonsohle, realisiert. Der “Baugrubenverbau” wurde als wesentliches Tragelement für das spätere Schleusenbauwerk übernommen. Die Wasserundurchlässigkeit der Schleusenkammer wird durch eine Stahlbetonvorsatzschale realisiert, die gleichzeitig die Schleusenausrüstung aufnimmt. Die Häupter wurden in Massivbauweise geplant. Als Verschlusselement zum Oberwasser dient ein Drucksegment mit Füllmuschel und einseitigem Antrieb. Das Untertor ist als Stemmtor in Faltwerksbauweise ausgebildet. Die Entleerung der Kammer erfolgt über kurze Torumläufe.Der Bericht erörtert die Randbedingungen, Planungsergebnisse und Entscheidungen, die im Zuge des Entwurfsprozesses im Hinblick auf Tragfähigkeit und Gebrauchstauglichkeit, Herstellbarkeit, Wirtschaftlichkeit sowie Nutzungsanforderungen bei einer angestrebten Lebensdauer von 100 Jahren zur Realisierung dieser neuartigen Kammerbauweise geführt haben und zeigt Ansatzpunkte für zukünftige Entwicklungen auf.A novel chamber construction for the new lock in DörverdenAfter almost five years of construction the new lock in Dörverden at the middle Weser was opened to the traffic at the end of 2013. Hereby, a novel chamber construction, consisting of a tied‐back, secant bored pile wall with reinforced concrete facing and a subaqueous concrete floor tied back by tension piles was implemented for the first time in the range of the Federal Waterways and Shipping Administration. The construction pit support system was inherited as a crucial bearing element for the final lock structure. The impermeability of the lock chamber is ensured through a reinforced concrete facing which also holds the lock equipment. The heads were planned as massive construction. A rotary segment gate with single‐sided drive serves as closing element against headwaters. The lower gate is designed as a mitre gate in tiled slab style. The emptying of the chamber is carried out via short circulations of the lock gate.The report discusses the marginal conditions, planning results and decisions as well as the usage requirements for a life expectancy of 100 years, which have led to the development of this novel chamber style, concerning bearing capacity, useability, construction and cost efficiency. Furthermore, the report presents starting points for future developments.
miRNA and Methylation: A Multifaceted Liaison
Authors: Chhabra Ravindresh 
Published: December 2014

AbstractmiRNAs and DNA methylation are both critical regulators of gene expression. Aberration in miRNA expression or DNA methylation is a causal factor for numerous pathological conditions. DNA methylation can inhibit the transcription of miRNAs, just like coding genes, by methylating the CpG islands in the promoter regions of miRNAs. Conversely, certain miRNAs can directly target DNA methyltransferases and bring about their inhibition, thereby affecting the whole genome methylation pattern. Recently, methylation patterns have also been revealed in mRNA. Surprisingly, the two most commonly studied methylation states in mRNA (m6A and m5C) are found to be enriched in 3′‐UTRs (untranslated regions), the target site for the majority of miRNAs. Whereas m5C is reported to stabilise mRNA, m6A has a destabilising effect on mRNA. However, the effect of mRNA methylation on its interaction with miRNAs is largely unexplored. The review highlights the complex interplay between microRNA and methylation at DNA and mRNA level.
Engineering Transaminase for Stability Enhancement and Site‐Specific Immobilization through Multiple Noncanonical Amino Acids Incorporation
Authors: Deepankumar Kanagavel , Nadarajan Saravanan Prabhu , Mathew Sam , Lee Sun‐Gu , Yoo Tae Hyeon , Hong Eun Young , Kim Byung‐Gee , Yun Hyungdon 
Published: December 2014

AbstractIn general, conventional enzyme engineering utilizes 20 canonical amino acids to alter and improve the functional properties of proteins such as stability, and activity. In this study, we utilized the noncanonical amino acid incorporation technique to enhance the functional properties of ω‐transaminase (ω‐TA). Herein, we enhanced the stability of ω‐TA by residue‐specific incorporation of (4R)‐fluoroproline [(4R)‐FP] and successfully immobilized onto chitosan or polystyrene (PS) beads with site‐specifically incorporated L‐3,4‐dihydroxyphenylalanine (DOPA) moiety. The immobilization of ω‐TAdopa and ω‐TAdp[(4R)‐FP] onto PS beads showed excellent reusability for 10 cycles in the kinetic resolution of chiral amines. Compared to the ω‐TAdopa, the ω‐TAdp[(4R)‐FP] immobilized onto PS beads exerted more stability that can serve as suitable biocatalyst for the asymmetric synthesis of chiral amines.
Highly Efficient, Conjugated‐Polymer‐Based Nano‐Photosensitizers for Selectively Targeted Two‐Photon Photodynamic Therapy and Imaging of Cancer Cells
Authors: Shen Xiaoqin , Li Shuang , Li Lin , Yao Shao Q. , Xu Qing‐Hua 
Published: December 2014

AbstractTwo‐photon photodynamic therapy (2P‐PDT) is a promising noninvasive treatment of cancers and other diseases with three‐dimensional selectivity and deep penetration. However, clinical applications of 2P‐PDT are limited by small two‐photon absorption (TPA) cross sections of traditional photosensitizers. The development of folate receptor targeted nano‐photosensitizers based on conjugated polymers is described. In these nano‐photosensitizers, poly{9,9‐bis[6′′‐(bromohexyl)fluorene‐2,7‐ylenevinylene]‐co‐alt‐1,4‐(2,5‐dicyanophenylene)}, which is a conjugated polymer with a large TPA cross section, acts as a two‐photon light‐harvesting material to significantly enhance the two‐photon properties of the doped photosensitizer tetraphenylporphyrin (TPP) through energy transfer. These nanoparticles displayed up to 1020‐fold enhancement in two‐photon excitation emission and about 870‐fold enhancement in the two‐photon‐induced singlet oxygen generation capability of TPP. Surface‐functionalized folic acid groups make these nanoparticles highly selective in targeting and killing KB cancer cells over NIH/3T3 normal cells. The 2P‐PDT activity of these nanoparticles was significantly improved, potentially up to about 1000 times, as implied by the enhancement factors of two‐photon excitation emission and singlet oxygen generation. These nanoparticles could act as novel two‐photon nano‐photosensitizers with combined advantages of low dark cytotoxicity, targeted 2P‐PDT with high selectivity, and simultaneous two‐photon fluorescence imaging capability; these are all required for ideal two‐photon photosensitizers.
Porous Nitrogen‐Doped Carbon Microspheres Derived from Microporous Polymeric Organic Frameworks for High Performance Electric Double‐Layer Capacitors
Authors: Han Jinpeng , Xu Guiyin , Dou Hui , MacFarlane Douglas R. 
Published: December 2014

AbstractThis research presents a simple and efficient method to synthesize porous nitrogen‐doped carbon microspheres (PNCM) by the carbonization of microporous poly(terephthalaldehyde‐pyrrole) organic frameworks (PtpOF). The common KOH activation process is used to tune the porous texture of the PNCM and produce an activated‐PNCM (A‐PNCM). The PNCM and A‐PNCM with specific surface area of 921 and 1303 m2 g−1, respectively, are demonstrated as promising candidates for EDLCs. At a current density of 0.5 A g−1, the specific capacitances of the PNCM and A‐PNCM are 248 and 282 F g−1, respectively. At the relatively high current density of 20 A g−1, the capacitance remaining is 95 and 154 F g−1, respectively. Capacity retention of the A‐PNCM is more than 92 % after 10 000 charge/discharge cycles at a current density of 2 A g−1.
Direct Detection of 17O in [Gd(DOTA)]− by NMR Spectroscopy
Authors: Fusaro Luca , Casella Girolamo , Bagno Alessandro 
Published: December 2014

AbstractThe 17O NMR spectrum of the non‐coordinated carboxyl oxygen in the GdIII–DOTA (DOTA=tetraazacyclododecanetetraacetic acid) complex has been observed experimentally. Its line width is essentially unaffected by paramagnetic relaxation due to gadolinium, and is only affected by the quadrupole pathway. The results are supported by the relevant parameters (hyperfine and quadrupole coupling constants) calculated by relativistic DFT methods. This finding opens up new avenues for investigating the structure and reactivity of paramagnetic GdIII complexes used as contrast agents in magnetic resonance imaging.
Manipulation of Phosphorescence Efficiency of Cyclometalated Iridium Complexes by Substituted o‐Carboranes
Authors: Lee Young Hoon , Park Jihyun , Jo Song‐Jin , Kim Miyoung , Lee Junseong , Lee Sang Uck , Lee Min Hyung 
Published: December 2014

AbstractA series of [(C^N)2Ir(acac)] complexes [{5‐(2‐R‐CB)ppy}2Ir(acac)] (3 a–3 g; acac=acetylacetonate, CB=o‐carboran‐1‐yl, ppy=2‐phenylpyridine; R=H (3 a), Me (3 b), iPr (3 c), iBu (3 d), Ph (3 e), CF3C6H4 (3 f), C6F5 (3 g)) with various 2‐R‐substituted o‐carboranes at the 5‐position in the phenyl ring of the ppy ligand were prepared. X‐ray diffraction studies revealed that the carboranyl CC bond length increases with increasing steric and electron‐withdrawing effects from the 2‐R substituents. Although the absorption and emission wavelengths of the complexes are almost invariant to the change of 2‐R group, the phosphorescence quantum efficiency varies from highly emissive (ΦPL≈0.80 for R=H, alkyl) to poorly emissive (R=aryl) depending on the 2‐R group and the polarity of the medium. Theoretical studies suggest that 1) the almost nonemissive nature of the 2‐aryl‐substituted complexes is mainly attributable to the large contribution to the LUMO in the S1 excited state from an o‐carborane unit and 2) the variation in the CC bond length between the S0 and T1 state structures increases with increasing steric (2‐alkyl) and electronic effects (2‐aryl) of the 2‐R substituent and the polarity of the solvent. The solution‐processed electroluminescence (EL) devices that incorporated 3 b and 3 d as emitters displayed higher performance than the device based on the parent [(ppy)2Ir(acac)] complex. Along with the high phosphorescence efficiency, the bulkiness of the 2‐R‐o‐carborane unit is shown to play an important role in improving device performance.
Heterometallic Complexes with Gold(I) Metalloligands: Self‐Assembly of Helical Dimers Stabilized by Weak Intermolecular Interactions and Solvophobic Effects
Authors: Cámara Verónica , Barquero Natalia , Bautista Delia , Gil‐Rubio Juan , Vicente José 
Published: December 2014

AbstractNew gold(I) alkynyl metalloligands bpylCCAuL, bpyl′CCAuPPh3, and PPN[Au(CCbpyl′)2] (bpyl or bpyl′=2,2′‐bipyridin‐5‐yl or −4‐yl, respectively; L=PMexPh3−x (x=1–3), P(C6H3Me2‐3,5)3, PCy3, XyNC) have been synthesized. Ligands bpylCCH and metalloligands bpylCCAuL (L=PPh3, PMePh2, PCy3, CNXy) react with MX2 (M=Fe, Zn, X=ClO4; M=Co, X=BF4) to give complexes [M(bpylCCZ)3]X2 (Z=H or AuL). In most cases, these complexes are mixtures of fac and mer isomers in a statistical distribution, in both CH2Cl2 and MeCN. However, for L=PPh3, the fac isomer is dominant in MeCN. NMR and ESI‐MS studies, together with the crystal structure of [Co(bpylCCAuPPh3)3](BF4)2, suggest that this solvent dependence is originated by the formation of helical dimers between two fac complexes in MeCN. These dimers are stabilized by solvophobic effects and multiple intermolecular interactions. Complex [Fe(Ph3PAuCCbpdiylCCAuPPh3)3](ClO4)2 (bpdiyl=2,2′‐bipyridin‐5,5′‐diyl) was obtained by reaction of three diauro diethynylbipyridines and Fe(ClO4)2.
Small‐Molecule Inhibitors That Target Protein–Protein Interactions in the RAD51 Family of Recombinases
Authors: Scott Duncan E. , Coyne Anthony G. , Venkitaraman Ashok , Blundell Tom L. , Abell Chris , Hyvönen Marko 
Published: December 2014

AbstractThe development of small molecules that inhibit protein–protein interactions continues to be a challenge in chemical biology and drug discovery. Herein we report the development of indole‐based fragments that bind in a shallow surface pocket of a humanised surrogate of RAD51. RAD51 is an ATP‐dependent recombinase that plays a key role in the repair of double‐strand DNA breaks. It both self‐associates, forming filament structures with DNA, and interacts with the BRCA2 protein through a common “FxxA” tetrapeptide motif. We elaborated previously identified fragment hits that target the FxxA motif site and developed small‐molecule inhibitors that are approximately 500‐fold more potent than the initial fragments. The lead compounds were shown to compete with the BRCA2‐derived Ac‐FHTA‐NH2 peptide and the self‐association peptide of RAD51, but they had no effect on ATP binding. This study is the first reported elaboration of small‐molecular‐weight fragments against this challenging target.
Dissecting Cooperative Communications in a Protein with a High‐Throughput Single‐Molecule Scalpel
Authors: Yu Zhongbo , Cui Yunxi , Selvam Sangeetha , Ghimire Chiran , Mao Hanbin 
Published: December 2014

AbstractMiscued communication often leads to misfolding and aggregation of the proteins involved in many diseases. Owing to the ensemble average property of conventional techniques, detailed communication diagrams are difficult to obtain. Mechanical unfolding affords an unprecedented perspective on cooperative transitions by observing a protein along a trajectory defined by two mutated cysteine residues. Nevertheless, this approach requires tedious sample preparation at the risk of altering native protein conformations. To address these issues, we applied click chemistry to tether a protein to the two dsDNA handles through primary amines in lysine residues as well as at the N terminus. As a proof of concept, we used laser tweezers to mechanically unfold and refold calmodulin along 36 trajectories, maximally allowed by this strategy in a single batch of protein preparation. Without a priori knowledge of the particular residues to which the double‐stranded DNA handles attach, we used hierarchical cluster analysis to identify 20 major trajectories, according to the size and the pattern of unfolding transitions. We dissected the cooperativity into all‐or‐none and partially cooperative events, which represent strong and weak high‐order interactions in proteins, respectively. Although the overall cooperativity is higher within the N or C lobe than that between the lobes, the all‐or‐none cooperativity is anisotropic among different the unfolding trajectories and becomes relatively more predominant when the size of the protein segments increases. The average cooperativity for all‐or‐none transitions falls within the expected range observed by ensemble techniques, which supports the hypothesis that unfolding of a free protein can be reconstituted from individual trajectories.
Zirconium and Hafnium Twin Monomers for Mixed Oxides
Authors: Schliebe Christian , Gemming Thomas , Noll Julian , Mertens Lutz , Mehring Michael , Seifert Andreas , Spange Stefan , Lang Heinrich 
Published: December 2014

AbstractThe synthesis of Zr and Hf twin monomers of type [M(2‐OCH2cC4H3O)4(x HOCH2cC4H3O)] (3, M=Zr, x=0; 4, M=Hf, x=1) and M[(2‐OCH2‐C6H4O)2(2‐HOCH2‐C6H4OH)] (5, M=Zr; 6, M=Hf) by reacting M(OR)4 (M=Zr, R=nC3H7, 1; M=Hf, R=nC4H9, 2) with 2‐furylmethanol or 2‐hydroxybenzyl alcohol is discussed. Complexes 3–6 were homopolymerized under acidic conditions. Additionally, 5 and 6 were copolymerized with 2,2′‐spirobi[4 H‐1,3,2‐benzodioxasiline] (SBS). Under acidic conditions SBS forms a phenolic resin/SiO2 nanostructured material. The resulting hybrid materials from the homopolymerization of 3–6 and the copolymerized materials from 5 and 6 were characterized by standard solid‐state analytics. The inorganic lattice of the MO2 materials from the homopolymerized complexes 3–6 and SiO2/MO2 from the copolymerization of 5 and 6 with SBS was obtained by air oxidation. The oxide materials were characterized by X‐ray powder diffraction (XRPD) and energy‐dispersive X‐ray analysis, which proved their identity. The inner surface area was determined by N2 adsorption/desorption studies, which revealed surface areas of 100 m2 g−1 for MO2. The mixed oxides SiO2/MO2 were additionally investigated by differential scanning calorimetry and variable‐temperature XRPD to study the thermal behavior. It was found that crystallization of tetragonal MO2 nanoparticles is characteristic within the SiO2 matrix, but higher sintering temperatures caused crystallization of the SiO2 lattice.
Titanium Oxynitride Interlayer to Influence Oxygen Reduction Reaction Activity and Corrosion Stability of Pt and Pt–Ni Alloy
Authors: Tan XueHai , Wang Liya , Zahiri Beniamin , Kohandehghan Alireza , Karpuzov Dimitre , Lotfabad Elmira Memarzadeh , Li Zhi , Eikerling Michael H. , Mitlin David 
Published: December 2014

AbstractA key advancement target for oxygen reduction reaction catalysts is to simultaneously improve both the electrochemical activity and durability. To this end, the efficacy of a new highly conductive support that comprises of a 0.5 nm titanium oxynitride film coated by atomic layer deposition onto an array of carbon nanotubes has been investigated. Support effects for pure platinum and for a platinum (50 at %)/nickel alloy have been considered. Oxynitride induces a downshift in the d‐band center for pure platinum and fundamentally changes the platinum particle size and spatial distribution. This results in major enhancements in activity and corrosion stability relative to an identically synthesized catalyst without the interlayer. Conversely, oxynitride has a minimal effect on the electronic structure and microstructure, and therefore, on the catalytic performance of platinum–nickel. Calculations based on density functional theory add insight with regard to compositional segregation that occurs at the alloy catalyst–support interface.
Serum ferritin and glucose homeostasis: change in the association by glycaemic state
Authors: Aregbesola Alex , Virtanen Jyrki K. , Voutilainen Sari , Mursu Jaakko , Lagundoye Ayodele , Kauhanen Jussi , Tuomainen Tomi‐Pekka 
Published: December 2014

AbstractBackgroundData on the association between body iron and glucose homeostasis by the three glycaemic states are scarce. Thus, we investigated the association between body iron as assessed by a serum ferritin concentration and glucose homeostasis using homeostasis model assessment (HOMA) of insulin resistance (HOMA‐IR) and beta cell function (HOMA‐BcF) in different glycaemic states.MethodsA cross‐sectional analysis was conducted in 2541 men aged 42–60 years in 1984–1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Subjects were classified into the three glycaemic states, normoglycaemia, prediabetes and type 2 diabetes (T2D), by fasting plasma glucose measurements and the information collected at study visit. The association between serum ferritin quartiles and HOMA‐IR and HOMA‐BcF for each glycaemic state was examined by analysis of covariance and linear regression analysis.ResultsThe mean age and serum ferritin concentrations were 53.1 years (standard deviation = 5.7, range = 42.0–61.3 years) and 166.2 µg/L (standard deviation = 141.7, range = 11–960 µg/L), respectively. After multivariable adjustments, a weak and direct association was observed between serum ferritin quartiles and HOMA‐IR in normoglycaemia (P‐trend = 0.001) but a direct association in prediabetes (P‐trend = 0.007) and in T2D (P‐trend = 0.078). In HOMA‐BcF, the association was weak and direct in normoglycaemia (P‐trend = 0.003), direct in prediabetes (P‐trend = 0.005) and inverse in T2D (P‐trend = 0.105). Strongest associations were observed in prediabetes (β = 0.25, 95% confidence interval = 0.14–0.36 and P = 0.004 in HOMA‐IR; β = 0.23, 95% confidence interval = 0.15–0.31 and P = 0.008 in HOMA‐BcF) after a 100‐µg/L increase in serum ferritin (log‐transformed).ConclusionsThese data suggest that both the strength and the direction of the association between body iron stores and glucose homeostasis are dependent on the glycaemic state of the population. Copyright © 2014 John Wiley & Sons, Ltd.