bluuebunny/crossref_metadata_2025 huggingface dataset:
Paroxysmal supraventricular tachycardia in pregnant women and birth outcomes of their children: A population‐based study
Authors: Bánhidy Ferenc , Ács Nándor , Puhó Erzsébet H. , Czeizel Andrew E.
Published: May 2015

The aim of the study was to estimate the possible association of pregnant women with paroxysmal supraventricular tachycardia (PSVT) with the possible risk for adverse birth outcomes, particularly different congenital abnormalities (CAs) in their children. Prospectively and medically recorded PSVT was evaluated in 103 pregnant women who later had offspring with CA (case group) and 149 pregnant women who later delivered newborn infants without CA (control group) and matched to cases in the population‐based data set of the Hungarian Case–Control Surveillance System of Congenital Abnormalities, 1980–1996. Of 252 pregnant women with PSVT, 115 (45.6%) had the onset of this condition before the study pregnancy, that is, their PSVT was a chronic condition, while the rest (N = 137) of PSVT was considered as new onset in the study pregnancy. The comparison of occurrence of PSVT in pregnant women who had offspring with different CA groups and in control mothers showed a higher risk for cardiovascular CAs (adjusted OR with 95% CI: 2.1, 1.1–3.8) explained mainly by secundum atrial septal defect. This association was confirmed in pregnant women with PSVT in the second and/or third gestational month, that is, critical period of cardiovascular CAs. In conclusion PSVT in pregnant women associates with a higher risk of secundum atrial septal defect in their children. © 2015 Wiley Periodicals, Inc.
A Ruthenium(II)–Copper(II) Dyad for the Photocatalytic Oxygenation of Organic Substrates Mediated by Dioxygen Activation
Authors: Iali Wissam , Lanoe Pierre‐Henri , Torelli Stéphane , Jouvenot Damien , Loiseau Frédérique , Lebrun Colette , Hamelin Olivier , Ménage Stéphane
Published: May 2015

Dioxygen activation by copper complexes is a valuable method to achieve oxidation reactions for sustainable chemistry. The development of a catalytic system requires regeneration of the CuI active redox state from CuII. This is usually achieved using extra reducers that can compete with the CuII(O2) oxidizing species, causing a loss of efficiency. An alternative would consist of using a photosensitizer to control the reduction process. Association of a RuII photosensitizing subunit with a CuII pre‐catalytic moiety assembled within a unique entity is shown to fulfill these requirements. In presence of a sacrificial electron donor and light, electron transfer occurs from the RuII center to CuII. In presence of dioxygen, this dyad proved to be efficient for sulfide, phosphine, and alkene catalytic oxygenation. Mechanistic investigations gave evidence about a predominant 3O2 activation pathway by the CuI moiety.
Direct Detection of the Superoxide Anion as a Stable Intermediate in the Electroreduction of Oxygen in a Non‐Aqueous Electrolyte Containing Phenol as a Proton Source
Authors: Peng Zhangquan , Chen Yuhui , Bruce Peter G. , Xu Ye
Published: May 2015

The non‐aqueous Li–air (O2) battery has attracted intensive interest because it can potentially store far more energy than today′s batteries. Presently Li–O2 batteries suffer from parasitic reactions owing to impurities, found in almost all non‐aqueous electrolytes. Impurities include residual protons and protic compounds that can react with oxygen species, such as the superoxide (O2−), a reactive, one‐electron reduction product of oxygen. To avoid the parasitic reactions, it is crucial to have a fundamental understanding of the conditions under which reactive oxygen species are generated in non‐aqueous electrolytes. Herein we report an in situ spectroscopic study of oxygen reduction on gold in a dimethyl sulfoxide electrolyte containing phenol as a proton source. It is shown directly that O2−, not HO2, is the first stable intermediate during the oxygen reduction process to hydrogen peroxide. The unusual stability of O2− is explained using density functional theory (DFT) calculations.
Following the Reaction of Heteroanions inside a {W18O56} Polyoxometalate Nanocage by NMR Spectroscopy and Mass Spectrometry
Authors: Zheng Qi , Vilà‐Nadal Laia , Busche Christoph , Mathieson Jennifer S. , Long De‐Liang , Cronin Leroy
Published: May 2015

By incorporating phosphorus(III)‐based anions into a polyoxometalate cage, a new type of tungsten‐based unconventional Dawson‐like cluster, [W18O56(HPIIIO3)2(H2O)2]8−, was isolated, in which the reaction of the two phosphite anions [HPO3]2− within the {W18O56} cage could be followed spectroscopically. As well as full X‐ray crystallographic analysis, we studied the reactivity of the cluster using both solution‐state NMR spectroscopy and mass spectrometry. These techniques show that the cluster undergoes a structural rearrangement in solution whereby the {HPO3} moieties dimerize to form a weakly interacting (O3PH⋅⋅⋅HPO3) moiety. In the crystalline state the cluster exhibits a thermally triggered oxidation of the two PIII template moieties to form PV centers (phosphite to phosphate), commensurate with the transformation of the cage into a Wells–Dawson {W18O54} cluster.
Kohlenstoff‐Nanopunkte: supramolekulare Elektronendonor‐Akzeptor‐Hybride mit Perylendiimiden
Authors: Strauss Volker , Margraf Johannes T. , Dirian Konstantin , Syrgiannis Zois , Prato Maurizio , Wessendorf Cordula , Hirsch Andreas , Clark Timothy , Guldi Dirk M.
Published: May 2015

Wir beschreiben die Bildung eines Ladungstransferkomplexes mit elektronendonierenden Kohlenstoff‐Nanopunkten (CNDs; carbon nanodots) und Perylendiimiden (PDIs) als Elektronenakzeptoren. Die Funktionalisierung der PDIs wurde so gewählt, dass sie mit den CNDs sowohl elektrostatisch durch gegensätzlich geladene Kopfgruppen als auch durch π‐π‐Stapelung über ausgedehnte π‐Systeme in Wechselwirkung treten können. Der Beitrag der elektrostatischen Wechselwirkungen wurde durch Referenzexperimente bestätigt, in denen weniger starke Wechselwirkungen mit negativ geladenen PDI‐Kopfgruppen gefunden wurden als bei den gleichen PDIs mit positiv geladenen Kopfgruppen. Die elektronischen Wechselwirkungen zwischen den beiden Komponenten wurden im Grundzustand und im angeregten Zustand durch komplementäre Absorptions‐ und Fluoreszenztitrationsexperimente mit Bindungskonstanten in der Größenordnung von 8×104 M−1 (25 L g−1) quantifiziert. Die Untersuchungen wurden durch selektive Anregung der beiden Komponenten in ultraschnellen Pump‐Probe‐Experimenten abgerundet, bei denen ein ladungsgetrennter Zustand mit 210 ps nachgewiesen wurde.
Barium‐Mediated Cross‐Dehydrocoupling of Hydrosilanes with Amines: A Theoretical and Experimental Approach
Authors: Bellini Clément , Carpentier Jean‐François , Tobisch Sven , Sarazin Yann
Published: May 2015

Alkaline‐earth (most prominently barium) complexes of the type [Ae{N(SiMe3)2}2⋅(THF)x] and [{N^N}Ae{N(SiMe3)2}⋅(THF)x] are very active and productive precatalysts (TON=396, TOF up to 3600 h−1; Ca<Sr<Ba) for NH/HSi cross‐dehydrocoupling, with excellent chemoselectivity in the reaction of (di)amines with (di)hydrosilanes. Experimental and DFT investigations revealed that the reactions proceed by nucleophilic attack of a metal amide at the incoming silane and subsequent turnover‐limiting hydrogen transfer to the metal center.
Organocatalytic Asymmetric 1,6‐Addition/1,4‐Addition Sequence to 2,4‐Dienals for the Synthesis of Chiral Chromans
Authors: Poulsen Pernille H. , Feu Karla Santos , Paz Bruno Matos , Jensen Frank , Jørgensen Karl Anker
Published: May 2015

A novel asymmetric organocatalytic 1,6‐addition/1,4‐addition sequence to 2,4‐dienals is described. Based on a 1,6‐Friedel–Crafts/1,4‐oxa‐Michael cascade, the organocatalyst directs the reaction of hydroxyarenes with a vinylogous iminium‐ion intermediate to give only one out of four possible regioisomers, thus providing optically active chromans in high yields and 94–99 % ee. Furthermore, several transformations are presented, including the formation of an optically active macrocyclic lactam. Finally, the mechanism for the novel reaction is discussed based on computational studies.
Amphiphilic Organic–Inorganic Hybrid Zeotype Aluminosilicate like a Nanoporous Crystallized Langmuir–Blodgett Film
Authors: Ikeda Takuji , Hiyoshi Norihito , Matsuura Shun‐ichi , Kodaira Tetsuya , Nakaoka Takuma , Irisa Ami , Kawano Miki , Yamamoto Katsutoshi
Published: May 2015

A new organic–inorganic hybrid zeotype compound with amphiphilic one‐dimensional nanopore and aluminosilicate composition was developed. The framework structure is composed of double aluminosilicate layers and 12‐ring nanopores; a hydrophilic layer pillared by Q2 silicon atom species and a lipophilic layer pillared by phenylene groups are alternately stacked, and 12‐ring nanopores perpendicularly penetrate the layers. The framework topology looks similar to that of an AFI‐type zeolite but possesses a quasi‐multidimensional pore structure consisting of a 12‐ring channel and intersecting small pores equivalent to 8‐rings. The hybrid material with alternately laminated lipophilic and hydrophilic nanospaces can be assumed as a crystallized Langmuir–Blodgett film. It demonstrates microporous adsorption for both hydrophilic and lipophilic adsorptives, and its outer surface tightly adsorbs lysozyme whose molecular size is much larger than its micropore opening. Our results suggest the possibility of designing porous adsorbent with high amphipathicity.
The Organocatalytic Asymmetric Prins Cyclization
Authors: Tsui Gavin Chit , Liu Luping , List Benjamin
Published: May 2015

We describe here the design and development of an organocatalytic Prins cyclization. In the presence of a confined chiral imidodiphosphoric acid catalyst, salicylaldehydes react with 3‐methyl‐3‐buten‐1‐ol to afford highly functionalized 4‐methylenetetrahydropyrans in excellent regio‐ and enantioselectivity. The extreme steric demand of the acid catalyst is key for the success of this transformation.
Multivalent Polymer Nanocomplex Targeting Endosomal Receptor of Immune Cells for Enhanced Antitumor and Systemic Memory Response
Authors: Kim Sun‐Young , Heo Min Beom , Hwang Geum‐Sook , Jung Youngae , Choi Do Yeol , Park Yeong‐Min , Lim Yong Taik
Published: May 2015

We have designed and synthesized linear polymer‐based nanoconjugates and nanocomplexes bearing multivalent immunostimulatory ligands and also demonstrated that the synthetic multivalent nanocomplexes led to an enhanced stimulation of immune cells in vitro and antitumor and systemic immune memory response in vivo. We have developed hyaluronic acid (HA)‐based multivalent nanoconjugates and nanocomplexes for enhanced immunostimulation through the combination of multivalent immune adjuvants with CpG ODNs (as a TLR9 ligand) and cationic poly(L‐lysine) (PLL; for the enhancement of cellular uptake). The multivalent HA‐CpG nanoconjugate efficiently stimulated the antigen‐presenting cells and the multivalent PLL/HA‐CpG nanocomplex also led to an enhanced cellular uptake as well as continuous stimulation of endosomal TLR9. The mice vaccinated with dendritic cells treated with the multivalent nanocomplex exhibited tumor growth inhibition as well as a strong antitumor memory response.
A Versatile Room‐Temperature Route to Di‐ and Trisubstituted Allenes Using Flow‐Generated Diazo Compounds
Authors: Poh Jian‐Siang , Tran Duc N. , Battilocchio Claudio , Hawkins Joel M. , Ley Steven V.
Published: May 2015

A copper‐catalyzed coupling reaction between flow‐generated unstabilized diazo compounds and terminal alkynes provides di‐ and trisubstituted allenes. This extremely mild and rapid transformation is highly tolerant of several functional groups.
DNA‐Encoded Dynamic Combinatorial Chemical Libraries
Authors: Reddavide Francesco V. , Lin Weilin , Lehnert Sarah , Zhang Yixin
Published: May 2015

Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA‐encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal‐to‐noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA‐encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high‐affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA‐templated chemical reactions.
Noncovalent Lone Pair⋅⋅⋅(No‐π!)‐Heteroarene Interactions: The Janus‐Faced Hydroxy Group
Authors: Pavlakos Ilias , Arif Tanzeel , Aliev Abil E. , Motherwell William B. , Tizzard Graham J. , Coles Simon J.
Published: May 2015

A comparative study using NMR spectroscopy and designed top‐pan molecular balances demonstrates that the noncovalent interaction of a hydroxy group with π‐deficient pyrazine and quinoxaline units involves a lone pair–heteroarene interaction which is much stronger and solvent independent when measured relative to the classical π‐facial hydrogen bond to a benzene ring. Alkyl fluorides also prefer the heteroarene rings over the benzene ring. The attractive interaction between a quinoxaline and a terminal alkyne is also stronger than the intramolecular hydrogen bond to an arene.
New strategy to improve acrylic/casein compatibilization in waterborne hybrid nanoparticles
Authors: Picchio Matías L. , Minari Roque J. , Gonzalez Veronica D. G. , Barandiaran María J. , Gugliotta Luis M.
Published: May 2015

The grafting of casein to acrylic polymers is needed to fully exploit the possibilities of hybrid nanoparticles containing such materials. The explored alternative up to now, based on the primary radical formation onto the protein chains through the redox initiation between the casein amino groups and a hydroperoxide, produces a limited degree of compatibilization to guarantee the synergic effect between both components. A novel strategy that overcomes these limitations is presented. The strategy is based on the use of a crosslinkable casein, which in addition to the characteristic grafting capacity by redox initiation with hydroperoxides, contains acrylic groups able to radically polymerize. The degree of grafting of both acrylic and casein is significantly increased by functionalizing casein with varied amounts of pendant propagating points per protein. Moreover, it is observed that the improved degree of compatibility obtained when using the crosslinkable casein considerably enhanced the properties of the acrylic/casein films, such as their mechanical behavior and resistance to both water and organic solvent. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42421.
Nafion‐115/aromatic poly(etherimide) with isopropylidene groups/imidazole membranes for polymer fuel cells
Authors: Iwan Agnieszka , Malinowski Marek , Sikora Andrzej , Tazbir Igor , Pasciak Grzegorz , Grabiec Eugenia
Published: May 2015

Proton exchange membrane fuel cells (PEMFCs) with Pt/C gas diffusion electrodes and graphite single‐serpentine monopolar plates were constructed based on an aromatic poly(etherimide) with isopropylidene groups (PI)/imidazole (Im) and a popular Nafion‐115 matrix. The electrochemical properties of PEMFCs were tested at 25 and 60°C. The maximum power density of 171 mW/cm2 and the maximum current density of 484 mA/cm2 were detected for Nafion‐115/PI membrane. For both constructed PEMFCs the efficiency at 0.6 V was found about 41%. Immersion of Nafion‐115 in PI or PI/Im increased the thermal stability and mechanical properties of membranes. Thermal, mechanical properties and morphology of membranes were characterized by TGA, and AFM techniques including force spectroscopy. Interactions between the components in composite membranes were established by FT‐IR. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42436.
PTPN22 Variant R620W Is Associated With Reduced Toll‐like Receptor 7–Induced Type I Interferon in Systemic Lupus Erythematosus
Authors: Wang Yaya , Ewart David , Crabtree Juliet N. , Yamamoto Ami , Baechler Emily C. , Fazeli Parastoo , Peterson Erik J.
Published: May 2015

Objective

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is associated with an increased risk of systemic lupus erythematosus (SLE). PTPN22 encodes Lyp, and a disease‐associated coding variant bears an R620W substitution (LypW). LypW carriage is associated with impaired production of type I interferon (IFN) by myeloid cells following Toll‐like receptor (TLR) engagement. The aim of this study was to investigate the effects of LypW carriage on TLR signaling in patients with SLE.

Methods

Plasma IFNα concentrations and whole‐blood IFN gene scores were compared in SLE patients who were LypW carriers and those who were noncarriers. TLR‐7 agonist R848–stimulated IFNα and tumor necrosis factor levels, IFN‐dependent gene expression, and STAT‐1 activation were determined in peripheral blood mononuclear cells (PBMCs) and/or plasmacytoid dendritic cells (PDCs) obtained from these patients. The effect of LypW expression on the systemic type I IFN response to R848 stimulation in vivo was assessed in transgenic mice.

Results

Plasma IFNα levels and whole‐blood IFN gene signatures were comparable in SLE patients who were LypW carriers and those who were noncarriers. However, PBMCs from LypW carriers produced less IFNα and showed reduced IFN‐dependent gene up‐regulation and STAT‐1 activation after R848 stimulation. The frequency of PDCs producing IFNα2 and the per‐cell IFNα2 levels were significantly reduced in LypW carriers. LypW‐transgenic mice displayed reduced TLR‐7–induced circulating type I IFN responses.

Conclusion

PDCs from SLE patients carrying the disease‐associated PTPN22 variant LypW showed a reduced capacity for TLR‐7 agonist–induced type I IFN production, even though LypW carriers displayed systemic type I IFN activation comparable with that observed in noncarriers. LypW carriage identifies SLE patients who may harbor defects in TLR‐ and PDC‐dependent host defense or antiinflammatory functions.
Anti–Endothelin Receptor Type A Autoantibodies in Systemic Lupus Erythematosus–Associated Pulmonary Arterial Hypertension
Authors: Guo Li , Li Mengtao , Chen Yi , Wang Qian , Tian Zhuang , Pan Shuming , Zeng Xiaofeng , Ye Shuang
Published: May 2015

Objective

To investigate the role of autoantibodies against endothelin 1 receptor type A (ETRA) in patients with systemic lupus erythematosus (SLE)–associated pulmonary arterial hypertension (PAH) and to examine the possibility that the pathogenesis of this disease is mediated by these autoantibodies.

Methods

ETRA autoantibodies in serum from patients with SLE‐associated PAH and serum from controls (SLE patients without PAH) were detected via a human ETRA epitope peptide–based enzyme‐linked immunosorbent assay. An exploratory cohort of patients with SLE‐associated PAH (n = 76) and an independent validation cohort of patients with SLE‐associated PAH confirmed by right‐sided heart catheterization (RHC) (n = 82) were enrolled. The clinical relevance of ETRA autoantibodies in SLE‐associated PAH was analyzed. The proliferation of vascular smooth muscle cells (SMCs) and the permeability of endothelial cells (ECs) were assessed in vitro in cells stimulated with polyclonal ETRA IgG autoantibodies. Expression of PAH‐related markers, i.e., serotonin transporter, platelet‐derived growth factor receptor β, vascular endothelial growth factor A, and platelet‐derived growth factor B was measured by quantitative polymerase chain reaction. In addition, a suboptimal dose of monocrotaline was used to induce PAH in rats, and the effect of ETRA autoantibodies in vivo was determined using a right ventricular hypertrophy index, pulmonary angiography, and laboratory parameters.

Results

ETRA autoantibodies occurred more frequently in SLE‐associated PAH (41.5%) than in controls (17.1%). There was a significant correlation between ETRA autoantibody titers and pulmonary artery systolic pressure measured by echocardiography (r = 0.2978, P = 0.0038) or pulmonary artery systolic pressure measured by RHC (r = 0.2159, P = 0.0257) in SLE‐associated PAH. ETRA autoantibodies could promote SMC proliferation, disrupt the endothelial barrier, and up‐regulate expression of PAH‐related markers, which could be blocked in the presence of an endothelin receptor antagonist. ETRA autoantibodies aggravated right ventricular hypertrophy and vascular remodeling in vivo.

Conclusion

We identified ETRA autoantibodies as a biomarker of mechanistic relevance in SLE. These autoantibodies may mediate PAH development in SLE.
The W620 Polymorphism in PTPN22 Disrupts Its Interaction With Peptidylarginine Deiminase Type 4 and Enhances Citrullination and NETosis
Authors: Chang Hui‐Hsin , Dwivedi Nishant , Nicholas Anthony P. , Ho I‐Cheng
Published: May 2015

Objective

A C‐to‐T single‐nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase PTPN22 complementary DNA carries the highest risk of rheumatoid arthritis (RA) among all non‐HLA genetic variants. This C1858T SNP converts an arginine (R620) to a tryptophan (W620), but it is unclear why it has such a strong impact on RA, a disease characterized by anti–citrullinated protein antibodies. The aim of this study was to test the hypothesis that PTPN22 regulates protein citrullination.

Methods

The level of citrullinated proteins in immune cells was quantified by Western blotting. The physical interaction between PTPN22 and peptidyl arginine deiminase type 4 (PAD‐4), which is one of the enzymes that catalyzes protein citrullination, was examined by coimmunoprecipitation. Neutrophils were collected from healthy donors carrying the C1858T SNP and healthy donors not carrying this SNP. The formation of neutrophil extracellular traps (NETs) was examined by immunocytochemistry.

Results

PTPN22 physically interacted with PAD‐4, and a deficiency in PTPN22 enhanced protein citrullination. This abnormality was reversed by exogenous wild‐type PTPN22 or catalytically dead mutant PTPN22. The R‐to‐W conversion rendered PTPN22 unable to interact with PAD‐4 and suppress citrullination. The C1858T SNP was associated with hypercitrullination in peripheral blood mononuclear cells and a heightened propensity for spontaneous formation of NETs, which is a PAD‐4–dependent process.

Conclusion

PTPN22 is an inhibitor of PAD‐4 and protein citrullination. This function of PTPN22 is independent of its phosphatase activity but requires R620. Our data not only establish a molecular link between PTPN22 and PAD‐4, but also suggest that the C1858T SNP increases the risk of RA by enhancing protein citrullination and spontaneous formation of NETs.
Brief Report: Association Between Pregnancy Outcomes and Death From Cardiovascular Causes in Parous Women With Systemic Lupus Erythematosus: A Study Using Swedish Population Registries
Authors: Soh May Ching , Nelson‐Piercy Catherine , Dib Fadia , Westgren Magnus , McCowan Lesley , Pasupathy Dharmintra
Published: May 2015

Objective

To determine if maternal placental syndromes (MPS) are associated with an increased risk of death from cardiovascular causes in women with systemic lupus erythematosus (SLE).

Methods

Between 1973 and 2011, women with SLE and a history of pregnancy were identified using linked Swedish population registries. The outcome was death from primarily cardiovascular causes, defined as death from acute coronary syndrome or coronary artery disease, stroke, or peripheral vascular disease. The exposure was MPS, defined as any hypertensive disorders in pregnancy, stillbirth, placental abruption, or delivery of a small‐for‐gestational‐age infant. The association of preterm delivery (delivery at <34 weeks of gestation) with death from cardiovascular causes was also explored. Risk of death from cardiovascular causes was determined using logistic regression, adjusting for the year of first delivery, duration of SLE, number of inpatient admissions, and cardiovascular risk factors.

Results

A total of 3,977 women with SLE had 7,410 pregnancies during the study interval. Death from primarily cardiovascular causes occurred in 44 of the 325 women who died (13.5%). The median age at death from cardiovascular causes was 54 years (interquartile range 48–58 years), and these women were more likely to have had hypertension and renal disease. MPS was associated with an increased risk of death from primarily cardiovascular causes (adjusted odds ratio [OR] 2.19 [95% confidence interval (95% CI) 1.14–4.22]), specifically, a history of placental abruption (adjusted OR 5.78 [95% CI 1.61–20.72]). Delivery at <34 weeks of gestation, particularly when combined with MPS, was also associated with an increased risk of death from primarily cardiovascular causes (adjusted OR 2.49 [95% CI 1.06–5.85]).

Conclusion

MPS in pregnancy is associated with a higher risk of death from primarily cardiovascular causes in women with SLE.
Adverse Events in Connective Tissue Disease–Associated Pulmonary Arterial Hypertension
Authors: Rhee Rennie L. , Gabler Nicole B. , Praestgaard Amy , Merkel Peter A. , Kawut Steven M.
Published: May 2015

Objective

Patients with connective tissue disease (CTD)–associated pulmonary arterial hypertension (PAH) have a poorer prognosis compared to those with idiopathic PAH, but little is known about the differences in treatment‐related adverse events (AEs) and serious adverse events (SAEs) between these groups. This study was undertaken to characterize these differences.

Methods

Individual patient‐level data from 10 randomized controlled trials of therapies for PAH were obtained from the US Food and Drug Administration. Patients diagnosed as having either CTD‐associated PAH or idiopathic PAH were included. A treatment‐by‐diagnosis interaction term was used to examine whether the effect of treatment on occurrence of AEs differed between patients with CTD‐associated PAH and those with idiopathic PAH. Studies were pooled using fixed‐effect models.

Results

The study sample included 2,370 participants: 716 with CTD‐associated PAH and 1,654 with idiopathic PAH. In the active treatment group compared to the placebo group, the risk of AEs was higher among patients with CTD‐associated PAH than among those with idiopathic PAH (odds ratio [OR] 1.57, 95% confidence interval [95% CI] 1.00–2.47 versus OR 0.94, 95% CI 0.69–1.26; P for interaction = 0.061), but there was no difference in the risk of SAEs in analyses adjusted for age, race, sex, hemodynamic findings, and laboratory values. Despite the higher occurrence of AEs in patients with CTD‐associated PAH assigned to active therapy compared to those receiving placebo, the risk of drug discontinuation due to an AE was similar to that in patients with idiopathic PAH assigned to active therapy (P for interaction = 0.27).

Conclusion

Patients with CTD‐associated PAH experienced more treatment‐related AEs compared to those with idiopathic PAH in therapeutic clinical trials. These findings suggest that the overall benefit of advanced therapies for PAH may be attenuated by the greater frequency of AEs.
Inhibition of Inflammation and Bone Erosion by RNA Interference–Mediated Silencing of Heterogeneous Nuclear RNP A2/B1 in Two Experimental Models of Rheumatoid Arthritis
Authors: Herman Sonja , Fischer Anita , Presumey Jessy , Hoffmann Markus , Koenders Marije I. , Escriou Virginie , Apparailly Florence , Steiner Guenter
Published: May 2015

Objective

The nuclear protein heterogeneous nuclear RNP A2/B1 (hnRNP A2/B1) is involved in posttranscriptional regulation of gene expression. It is constitutively expressed in lymphoid organs and highly up‐regulated in the synovial tissue of patients with rheumatoid arthritis (RA), who may also generate autoantibodies to this protein. This study was undertaken to investigate the potential involvement of hnRNP A2/B1 in the pathogenesis of autoimmune arthritis, by silencing hnRNP A2/B1 expression in 2 animal models of RA.

Methods

Collagen‐induced arthritis (CIA) and the K/BxN serum–transfer model were used as animal models of RA. Efficient silencing of hnRNP A2/B1 was achieved using a liposome‐based carrier system for delivery of small interfering RNAs. Expression of hnRNP A2/B1 was analyzed by flow cytometry, reverse transcription–quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The number of osteoclasts was determined by tartrate‐resistant acid phosphatase staining. Cytokine levels and anticollagen antibody levels were measured by enzyme‐linked immunosorbent assay.

Results

Efficient silencing of hnRNP A2/B1 was achieved in all lymphoid organs. In both experimental models, the incidence and severity of arthritis were largely reduced and bone erosion was not detectable as compared to the control groups. Down‐modulation of hnRNP A2/B1 significantly interfered with the production of proinflammatory cytokines from monocyte/macrophages, but not from T cells. Consistent with these findings, production of T cell cytokines was not impaired when cells were restimulated in vitro with type II collagen. Furthermore, levels of anticollagen antibodies were not affected by hnRNP A2/B1 silencing.

Conclusion

Our findings suggest that hnRNP A2/B1 has an important role in regulation of the innate immune system, especially at the level of monocyte/macrophage activation. Therefore, down‐modulation of hnRNP A2/B1 seems to affect primarily the effector phase of autoimmune arthritis.
The construction of interdisciplinarity: The development of the knowledge base and programmatic focus of the journal Climatic Change, 1977–2013
Authors: Hellsten Iina , Leydesdorff Loet
Published: May 2015

Climate change as a complex physical and social issue has gained increasing attention in the natural as well as the social sciences. Climate change research has become more interdisciplinary and even transdisciplinary as a typical Mode‐2 science that is also dependent on an application context for its further development. We propose to approach interdisciplinarity as a co‐construction of the knowledge base in the reference patterns and the programmatic focus in the editorials in the core journal of the climate‐change sciences—Climatic Change—during the period 1977–2013. First, we analyze the knowledge base of the journal and map journal–journal relations on the basis of the references in the articles. Second, we follow the development of the programmatic focus by analyzing the semantics in the editorials. We argue that interdisciplinarity is a result of the co‐construction between different agendas: The selection of publications into the knowledge base of the journal, and the adjustment of the programmatic focus to the political context in the editorials. Our results show a widening of the knowledge base from referencing the multidisciplinary journals Nature and Science to citing journals from specialist fields. The programmatic focus follows policy‐oriented issues and incorporates public metaphors.
Controllability of Semilinear Systems of Parabolic Equations with Delay on the State
Authors: Carrasco A. , Leiva Hugo , Merentes N. , Sanchez J. L.
Published: May 2015

In this paper we prove the approximate controllability of the following semilinear system parabolic equations with delay on the state variable

urn:x-wiley:asjc:media:asjc1162:asjc1162-math-0001
where Ω is a bounded domain in
is a n × n non diagonal matrix whose eigenvalues are semi‐simple with non negative real part, the control u belongs to
and B is a n × m matrix. Here τ≥0 is the maximum delay, which is supposed to be finite. We assume that the operator L:L2([−τ,0];Z)→Z is linear and bounded with
and the nonlinear function f:[0,r] × IRn×IRm→IRn is smooth and bounded.
Effects of Video Modeling and Feedback on Mothers' Implementation of Peer‐to‐Peer Manding
Authors: Madzharova Maya S. , Sturmey Peter
Published: May 2015

Children with autism spectrum disorder (ASD) exhibit deficits in appropriate requesting such as manding to peers. Experiment 1 used feedback and modeling to train three mothers to increase manding between three children with ASD and their typical siblings or peers. Video modeling and feedback increased the mother's correct implementation of the treatment but a causal relation was not established over the children's manding. Experiment 2 aimed to address the lack of functional control observed in the children's data using a partial component analysis. For one of the children there was a functional relation between the materials' location, which appeared to act as a motivating operation. When Sam's mother positioned the materials correctly his manding increased. These data indicated that a simple training protocol could be used to train caregivers to implement a complex social skill such as peer‐to‐peer interaction. Copyright © 2015 John Wiley & Sons, Ltd.
A perspective perception on the applications of light‐emitting diodes
Authors: Nair Govind B. , Dhoble S. J.
Published: May 2015

Light‐emitting diodes (LEDs) continue to penetrate the global market; their pervasiveness clearly being felt in such diverse fields as technological, socio‐economic and commercial interests. The multi‐billion dollar LED market is shared by various segments, including office and household lighting, street lighting, the automobile industry, traffic signals, backlighting for hand‐held devices, indoor and outdoor signs and indicators, medicine, communication systems, crop cultivation using artificial light and many more. The technological development of LEDs has undergone many phases in different parts of the world. From the early discovery of luminescence to the invention of highly efficient organic LEDs, researchers have worked with the prime purpose of improving the performance of luminaires. The need to infuse the market with more efficient and cheaper products has been prevalent from the start. LEDs are a result of this uncontrolled desire of researchers to develop superior products that would displace existing products in the market. To understand what led to the current prominence of LEDs, we give a brief historical overview of the field followed by a thorough discussion of the positive features of LEDs. This work includes the basic requirements, advantages and disadvantages of LEDs in a variety of applications. A brief description of the diverse applications of LED in fields such as lighting, indicators and displays, farming, medicine and communication is given. Considerable importance is placed on discussing the possible difficulties that must be overcome before using LEDs in commercial applications. Copyright © 2015 John Wiley & Sons, Ltd.
Resolving the contributions of two cooperative mechanisms to the DNA Binding of AGT
Authors: Melikishvili Manana , Fried Michael G.
Published: May 2015

The O6‐alkylguanine DNA alkyltransferase (AGT) is a DNA repair enzyme that binds DNA with moderate cooperativity. This cooperativity is important for its search for alkylated bases. A structural model of the cooperative complex of AGT with DNA predicts short‐range interactions between nearest protein neighbors and long‐range interactions between proteins separated in the array. DNA substrates ranging from 11bp to 30bp allowed us to use differences in binding stoichiometry to resolve short‐ and long‐range protein contributions to the stability of AGT complexes. We found that the short‐range component of ΔG°coop was nearly independent of DNA length and protein packing density. In contrast the long‐range component oscillated with DNA length, with a period equal to the occluded binding site size (4bp). The amplitude of the long‐range component decayed from ∼−4 kcal/mole of interaction to ∼−1.2 kcal/mol of interaction as the size of cooperative unit increased from 4 to 7 proteins, suggesting a mechanism to limit the size of cooperative clusters. These features allow us to make testable predictions about AGT distributions and interactions with chromatin structures in vivo. © 2015 The Authors Biopolymers Published by Wiley Periodicals, Inc. Biopolymers 103: 509–516, 2015.
Modification of the degree of branching of a beta‐(1,3)‐glucan affects aggregation behavior and activity in an oxidative burst assay
Authors: Magee Andrew S. , Langeslay Ryan R. , Will Paul M. , Danielson Michael E. , Wurst Lindsay R. , Iiams Vanessa A.
Published: May 2015

Scleroglucan is a β‐(1,3)‐glucan which is highly branched at the 6‐position with a single glucose residue. Acid hydrolysis of a high molecular weight scleroglucan gave a medium molecular weight, freely soluble material. Linkage analysis by the partially methylated alditol acetate method showed that the solubilized material had 30% branching. When the material was subjected to partial Smith degradations, the percent branching was reduced accordingly to 12% or 17%. After the percent branching was reduced, the average molecular weight of the samples increased considerably, indicating the assembly of higher ordered aggregate structures. An aggregate number distribution analysis was applied to confirm the higher aggregated structures. These aggregated structures gave the material significantly enhanced activity in an in vitro oxidative burst assay compared to the highly branched material. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 665–674, 2015.
Comparative pharmacokinetic profiles of five poorly soluble pulchinenosides in different formulations from Pulsatilla chinensis saponins extracts for enhanced bioavailability
Authors: Huang Jun , Liu Yali , Li Xiang , Song Yonggui , Li Wei , Liu Kuangyi , Su Dan , Feng Yulin , Yang Shilin
Published: May 2015

Pulsatilla chinensis, a traditional Chinese medicine (TCM), has been used for treating amoebic diseases, vaginal trichomoniasis and bacterial infections over a long history. Now growing attention has been attracted to its antitumor activities. The purpose of this work was to compare the pharmacokinetic profiles of pulchinenosides in different formulations and to improve their oral bioavailability. Extracts of P. chinensis saponins were prepared for PRS‐Na (salt forming), PRS‐HPβCD (hydroxypropyl‐β‐cyclodextrin inclusion complex), PRS‐O/W (oil‐in‐water emulsion) and PRS‐silica (micronization), respectively. A simpler and more durable LC‐MS/MS method was developed in this study for quantitative analysis of pulsatilla sapoin D, B7, B10, B11 and sapoin PD simultaneously. The four formulations enhanced saponins oral bioavailability to varying degrees, as PRS‐HPβCD > PRS‐silica > PRS‐O/W > PRS‐Na, which indicated that water‐soluble preparations can obviously improve the solubility of saponins, and are helpful to increase bioavailability. In particular, hydroxypropyl‐β‐cyclodextrin inclusion complex was the most effective way to promote absorption of saponins, raising the F values (bioavailability) >20 times. Therefore, P. chinensis saponin molecules can be slowly released by emulsion and micronization, which can avoid the enormous Cmax appearing in HPβCD, considering the pharmacokinetics profiles. However, appropriate pharmacokinetic parameters were observed in PRS‐Na, although the F value was minimum among the four preparations. Copyright © 2015 John Wiley & Sons, Ltd.
Multiple and aggressive pulmonary vein transcatheter interventions as bridge to transplantation in primary diffuse pulmonary vein stenosis
Authors: Bonello Béatrice , Trivedi Kalyani R. , Fraisse Alain
Published: May 2015

Primary diffuse congenital pulmonary vein stenosis (PDPVS) is a severe condition with poor prognosis. No therapeutic strategy has been found to be effective in its management to date. We report the case of a premature child with severe PDPVS who underwent multiple transcatheter interventions as bridge to heart–lung transplantation. © 2015 Wiley Periodicals, Inc.
One‐year clinical outcomes after sirolimus‐eluting coronary stent implantation in diabetics enrolled in the worldwide e‐SELECT registry
Authors: Bartorelli Antonio L. , Egidy Assenza Gabriele , Abizaid Alexandre , Banning Adrian , Džavík Vladimír , Ellis Stephen , Gao Runlin , Holmes David , Ho Jeong Myung , Legrand Victor , Neumann Franz‐Josef , Spaulding Christian , Worthley Stephen G. , Urban Philip ,   for the e‐SELECT Investigators
Published: May 2015

Background

Diabetes mellitus has worse outcome after percutaneous coronary intervention.

Aim

We assessed stent thrombosis (ST), major adverse cardiac events (MACE), and major bleeding rates at 1 year after implantation of sirolimus‐eluting stents (SES) in patients with diabetes mellitus in a large multicenter registry.

Methods

From May 2006 to April 2008, 15,147 unselected consecutive patients were enrolled at 320 centers in 56 countries in a prospective, observational registry after implantation of ≥ 1 SES. Source data were verified in 20% randomly chosen patients at > 100 sites. Adverse events were adjudicated by an independent Clinical Event Committee.

Results

Complete follow‐up at 1 year was obtained in 13,693 (92%) patients, 4,577 (30%) of whom were diabetics. Within diabetics, 1,238 (9%) were insulin‐treated diabetics (ITD). Diabetics were older (64 vs. 62 years, P < 0.001), with higher incidence of major coronary risk factors, co‐morbidities, and triple‐vessel coronary artery disease. Coronary lesions had smaller reference vessel diameter (2.88 ± 0.46 vs. 2.93 ± 0.45 mm, P < 0.001) and were more often heavily calcified (26.1% vs. 22.6%, P < 0.001). At 1 year, diabetics had higher MACE rate (6.8% vs. 3.9%, P < 0.001) driven by ITD (10.6% vs. 5.5%, P < 0.001). Finally, diabetics had significant increase in ST (1.7% vs. 0.7%, P < 0.001), principally owing to ITD (3.4% vs. 1.1%, P < 0.001). There was an overall low risk of major bleeding during follow‐up, without significant difference among subgroups.

Conclusions

In the e‐SELECT registry, diabetics represented 30% of patients undergoing SES implantation and had significantly more co‐morbidities and complex coronary lesions. Although 1‐year follow‐up documented good overall outcome in diabetics, higher ST and MACE rates were observed, mainly driven by ITD. © 2015 Wiley Periodicals, Inc.
When is rotational angiography superior to conventional single‐plane angiography for planning coronary angioplasty?
Authors: Morris Paul D. , Taylor Jane , Boutong Sara , Brett Sarah , Louis Amal , Heppenstall James , Morton Allison C. , Gunn Julian P.
Published: May 2015

Objectives

To investigate the value of rotational coronary angiography (RoCA) in the context of percutaneous coronary intervention (PCI) planning.

Background

As a diagnostic tool, RoCA is associated with decreased patient irradiation and contrast use compared with conventional coronary angiography (CA) and provides superior appreciation of three‐dimensional anatomy. However, its value in PCI remains unknown.

Methods

We studied stable coronary artery disease assessment and PCI planning by interventional cardiologists. Patients underwent either RoCA or conventional CA pre‐PCI for planning. These were compared with the referral CA (all conventional) in terms of quantitative lesion assessment and operator confidence. An independent panel reanalyzed all parameters.

Results

Six operators performed 127 procedures (60 RoCA, 60 conventional CA, and 7 crossed‐over) and assessed 212 lesions. RoCA was associated with a reduction in the number of lesions judged to involve a bifurcation (23 vs. 30 lesions, P < 0.05) and a reduction in the assessment of vessel caliber (2.8 vs. 3.0 mm, P < 0.05). RoCA improved confidence assessing lesion length (P = 0.01), percentage stenosis (P = 0.02), tortuosity (P < 0.04), and proximity to a bifurcation (P = 0.03), particularly in left coronary artery cases. X‐ray dose, contrast agent volume, and procedure duration were not significantly different.

Conclusions

Compared with conventional CA, RoCA augments quantitative lesion assessment, enhances confidence in the assessment of coronary artery disease and the precise details of the proposed procedure, but does not affect X‐ray dose, contrast agent volume, or procedure duration. © 2015 Wiley Periodicals, Inc.
Growth of the atrial septum after amplatzer device closure of atrial septal defects in young children
Authors: Gossett Jeffrey G. , Mansfield Laura , Acevedo Jennifer , Lay Amy S. , Rychlik Karen , Wax David F.
Published: May 2015

Background

Trans‐catheter closure of atrial septal defects (ASD) with the Amplatzer Septal Occluder (ASO) device is safe and effective, but concern over erosions has increased. Devices are placed in growing children but septal growth after ASOs is ill‐defined. Understanding the device relationship to cardiac structures as a child grows may help us understand erosions. Objective: To define (1) how preprocedural septal measurements change after ASO and (2) the effect of somatic growth on these dimensions. Methods: Data were collected retrospectively. Echocardiograms were reviewed and rims measured prior to ASO, immediately after ASO, and at follow‐up. Demographic, procedural and device data were collected. Results: Thirty‐three patients were enrolled; mean age 5.2 ± 3.2 years with 4.0 ± 2.2 years follow‐up. All septal measurements decreased after ASO. Thirty‐one of 33 devices (94%) contacted the aortic root after ASO; all remained in contact at follow‐up with only the IVC rim growing significantly over time. Change in BSA predicted an asymmetric septal growth with increases in superior (P = 0.01) and IVC (P = 0.005) rims and no increase in aortic or AVV rims. No episodes of erosion occurred. Conclusions: ASDs in young children are not central in the septum, but proximate to the aorta. After ASO, the device remains in close proximity to the aorta. With somatic growth, the septum grows asymmetrically, and device position relative to the aorta is constant. Our study was not powered to detect rare serious adverse events such as erosion, but aortic rims were consistently zero and yet no events occurred. © 2015 Wiley Periodicals, Inc.
Highly Active Bimetallic Nickel–Palladium Alloy Nanoparticle Catalyzed Suzuki–Miyaura Reactions
Authors: Rai Rohit Kumar , Gupta Kavita , Behrens Silke , Li Jun , Xu Qiang , Singh Sanjay Kumar
Published: May 2015

A bimetallic Ni–Pd alloy nanoparticle catalyst with a low palladium content (Ni0.90Pd0.10 nanocatalyst) was prepared and its catalytic performance in Suzuki–Miyaura reactions was evaluated along with that of other Ni–Pd nanocatalysts (with varying Ni/Pd molar ratios in the range of ≈0.25–0.75) and the corresponding monometallic, Ni and Pd, analogues. Notably, the bimetallic Ni0.90Pd0.10 alloy nanocatalyst performed exceptionally well for the synthesis of biaryls by employing a wide range of substituted aryl halides and arylboronic acids having electron‐donating and electron‐withdrawing groups, and they exhibited high recyclability in water/ethanol solution at moderate reaction temperatures. Catalyst poisoning tests and leaching experiments inferred the heterogeneous nature of the Ni0.90Pd0.10 nanocatalysts. The significant synergistic interactions between Ni and Pd account for the observed high catalytic efficacy of the Ni0.90Pd0.10 nanocatalyst.
TiO2 with “Fluorine‐Occupied” Surface Oxygen Vacancies and Its Stably Enhanced Photocatalytic Performance
Authors: Xu Liming , Ming Lufei , Chen Feng
Published: May 2015

Oxygen vacancies have a positive effect on the photocatalytic performance of TiO2, but their benefits are deeply limited owing to their inherent lability. To avoid this disadvantage, fluorine atoms were used to “occupy” the surface oxygen vacancies (O vacancies) of TiO2. The “fluorine‐occupied” surface O vacancies maintain the intrinsic nature of the O vacancies, but they are stable under ambient and photocatalytic conditions. TiO2 with “fluorine‐occupied” surface O vacancies give enhanced performance in terms of both photodegradation and photocurrent conversion. The “occupied” strategy used herein holds promise to be a common method for developing O vacancy‐related photocatalysts.