bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xylochemie – Naturstoffsynthese aus Holz
Authors: Stubba Daniel , Lahm Günther , Geffe Mario , Runyon Jason W. , Arduengo Anthony J. , Opatz Till 
Published: October 2015

AbstractDie erste Totalsynthese des dimeren Berberin‐Alkaloids Ilicifolin (Ilicifolin B) wird beschrieben. Sein Kohlenstoffgerüst wird dabei aus Ferulasäure, Veratrol und Methanol aufgebaut – Bausteine, die aus Holz als nachwachsendem Rohstoff gewonnen werden können. Die gleiche Strategie wurde für eine formale Totalsynthese von Morphinan‐Alkaloiden genutzt. Die Verwendung von Ausgangsmaterialien auf Holzbasis (Xylochemikalien) anstelle von Petrochemikalien stellt eine nachhaltige Alternative zu klassischen Synthesestrategien dar.
Dioxygen Activation by Non‐Adiabatic Oxidative Addition to a Single Metal Center
Authors: Akturk Eser S. , Yap Glenn P. A. , Theopold Klaus H. 
Published: October 2015

AbstractA chromium(I) dinitrogen complex reacts rapidly with O2 to form the mononuclear dioxo complex [TptBu,MeCrV(O)2] (TptBu,Me=hydrotris(3‐tert‐butyl‐5‐methylpyrazolyl)borate), whereas the analogous reaction with sulfur stops at the persulfido complex [TptBu,MeCrIII(S2)]. The transformation of the putative peroxo intermediate [TptBu,MeCrIII(O2)] (S=3/2) into [TptBu,MeCrV(O)2] (S=1/2) is spin‐forbidden. The minimum‐energy crossing point for the two potential energy surfaces has been identified. Although the dinuclear complex [(TptBu,MeCr)2(μ‐O)2] exists, mechanistic experiments suggest that O2 activation occurs on a single metal center, by an oxidative addition on the quartet surface followed by crossover to the doublet surface.
Non‐Conjugated Polymer Dots with Crosslink‐Enhanced Emission in the Absence of Fluorophore Units
Authors: Zhu Shoujun , Song Yubin , Shao Jieren , Zhao Xiaohuan , Yang Bai 
Published: October 2015

AbstractA new type of fluorescent material is presented, which is called non‐conjugated polymer dots (NCPDs). The NCPDs only possess sub‐fluorophores (which are groups such as CO, CN, NO) instead of typical conjugated fluorophore groups, and thus these materials should not have strong photoluminescence (PL) in the usual sense. Nevertheless, the PL of these sub‐fluorophores can be enhanced by chemical crosslinking or physical immobilization of polymer chains, which is named the crosslink‐enhanced emission (CEE) effect. The significant advances achieved by us and other groups on both experimental and theoretical aspects are discussed, and the covalent‐bond CEE, rigidity‐aggregated CEE, or supramolecular CEE in NCPDs is elaborated. Moreover, synthetic strategies, unique optical properties, and the promise of NCPDs in bio‐related fields, such as bioimaging and drug delivery, are systematically discussed.
Metal‐Catalyzed β‐Functionalization of Michael Acceptors through Reductive Radical Addition Reactions
Authors: Streuff Jan , Gansäuer Andreas 
Published: October 2015

AbstractTransition‐metal‐catalyzed radical reactions are becoming increasingly important in modern organic chemistry. They offer fascinating and unconventional ways for connecting molecular fragments that are often complementary to traditional methods. In particular, reductive radical additions to α,β‐unsaturated compounds have recently gained substantial attention as a result of their broad applicability in organic synthesis. This Minireview critically discusses the recent landmark achievements in this field in context with earlier reports that laid the foundation for today′s developments.
Reverse Engineering of Conjugated Microporous Polymers: Defect Structures of Tetrakis(4‐ethynylphenyl)stannane Networks
Authors: Uptmoor Andrea C. , Freudenberg Jan , Schwäbel S. Thimon , Paulus Fabian , Rominger Frank , Hinkel Felix , Bunz Uwe H. F. 
Published: October 2015

AbstractTwo different conjugated microporous polymers (CMPs) based on tetrakis(4‐ethynylphenyl)stannane as the repeating unit were synthesized and their BET surfaces and thermal properties were investigated. The first direct method to elucidate the molecular structure of the organic linkers between the tin centers by digestion of the CMP is described. Selective cleavage of the tin–carbon bonds with chloroacetic acid afforded the isolated bridging units and provided insight into the surprisingly varied chemical composition of these networks.
Xylochemistry—Making Natural Products Entirely from Wood
Authors: Stubba Daniel , Lahm Günther , Geffe Mario , Runyon Jason W. , Arduengo Anthony J. , Opatz Till 
Published: October 2015

AbstractThe first total synthesis of the dimeric berberine alkaloid ilicifoline (ilicifoline B) is reported. Its carbon skeleton is constructed from ferulic acid, veratrole, and methanol. The synthesis reported herein employs starting materials solely derived from wood. The natural product is thus constructed entirely from renewable resources. The same strategy is applied to a formal total synthesis of morphinan alkaloids. The use of wood‐derived building blocks (xylochemicals) instead of the conventional petrochemicals represents a sustainable alternative to classical synthetic approaches.
Improving the heat‐resistance and toughness performance of phenolic resins by adding a rigid aromatic hyperbranched polyester
Authors: Liu Dan , Wang Hongmei , Jiang Huasheng , Zhou Dapeng 
Published: October 2015

ABSTRACTAn aromatic hyperbranched polyester (AHBP) was synthesized by melt polycondensation from diphenolic acid and characterized by Fourier transform infrared spectrum (FTIR) spectra. The degree of branching (DB) value of AHBP calculated from the 13C‐NMR spectroscopy was 0.67. The number‐average molecular weight (Mn) and weight‐average molecular weight (Mw) of AHBP were 1792 and 4480 g/mol, respectively. Novel phenolic resins modified with AHBP (PR/AHBP) were then prepared, in which AHBP was used as toughener of phenolic resins. The effect of AHBP on the thermal properties of phenolic resins was studied by means of differential scanning calorimetry (DSC), thermal gravimetric analyses (TGA), and heat deformation temperature tests. The modified resins presented higher glass transition temperature (Tg) than the unmodified system due to that the rigid backbone structure of AHBP with a great deal of the benzene ring groups restricted the mobility of the chain segments of macromolecules. The DSC, scanning electron microscopy (SEM) analyses showed that AHBP had good compatibility with phenolic resin, and the modified resins showed ductile fracture. The results of mechanical performance measurements exhibited that the impact strength of PR/AHBP containing 15 wt % AHBP was about 130% higher than that of the neat phenolic resin, suggesting that the toughness of PR/AHBP was significantly improved by the addition of AHBP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42734.
Amelioration of Experimental Autoimmune Arthritis Through Targeting of Synovial Fibroblasts by Intraarticular Delivery of MicroRNAs 140‐3p and 140‐5p
Authors: Peng Jia‐Shiou , Chen Shih‐Yao , Wu Chao‐Liang , Chong Hao‐Earn , Ding Yun‐Chiao , Shiau Ai‐Li , Wang Chrong‐Reen 
Published: October 2015

ObjectiveSynovial fibroblasts (SFs) with aberrant expression of microRNAs (miRNAs) are critical pathogenic regulators in rheumatoid arthritis (RA), and studies analyzing the effect of overexpressing or silencing miRNA expression in arthritis models can contribute to the development of miRNA‐based therapeutic strategies. This study was undertaken to examine the hypothesis that miRNAs 140‐3p and 140‐5p are involved in the pathogenesis of RA, and to determine whether targeting SFs through the intraarticular (IA) delivery of these molecules could ameliorate autoimmune arthritis in mice.MethodsSynovial tissue samples were obtained from patients with RA. In addition, 2 experimental models in mice were used, collagen‐induced arthritis (CIA) and collagen antibody–induced arthritis (CAIA). Overexpression of miRNAs 140‐3p and 140‐5p in SFs and synovial tissue was induced using lentivirus (LV)–mediated transfer of pre‐miR‐140 precursor molecules.ResultsLower expression levels of miR‐140‐3p and miR‐140‐5p were detected in synovial tissue and SFs from patients with RA and from mice in both arthritis models. In mice with CIA and mice with CAIA, the LV‐mediated IA transfer of miR‐140‐3p and miR‐140‐5p ameliorated arthritis, as determined by clinical examination and histopathologic evaluations showing a decrease in SF densities. Overexpression of miRNAs 140‐3p and 140‐5p caused a reduction in expression, with correlated kinetic patterns, of their corresponding target molecules sirtuin 1 and stromal cell–derived factor 1 in the SFs and joints of mice. Transfection of miR‐140‐3p and miR‐140‐5p into SFs increased cell apoptosis, reduced proliferation responses and migration abilities, and verified the concept that miR‐140 expression is regulated by proinflammatory cytokines.ConclusionThese results demonstrate that targeting SFs by IA delivery of miRNAs 140‐3p and 140‐5p can ameliorate autoimmune arthritis. These findings might facilitate the pharmacologic development of molecular‐based therapies in RA.
Identification of Rare Variants in ATP8B4 as a Risk Factor for Systemic Sclerosis by Whole‐Exome Sequencing
Authors: Gao Li , Emond Mary J. , Louie Tin , Cheadle Chris , Berger Alan E. , Rafaels Nicholas , Vergara Candelaria , Kim Yoonhee , Taub Margaret A. , Ruczinski Ingo , Mathai Stephen C. , Rich Stephen S. , Nickerson Deborah A. , Hummers Laura K. , Bamshad Michael J. , Hassoun Paul M. , Mathias Rasika A. ,   the National Heart, Lung, and Blood Institute GO Exome Sequencing Project, Barnes Kathleen C. 
Published: October 2015

ObjectiveTo determine the contribution of rare variants as genetic modifiers of the expressivity, penetrance, and severity of systemic sclerosis (SSc).MethodsWe performed whole‐exome sequencing of 78 European American patients with SSc, including 35 patients without pulmonary arterial hypertension (PAH) and 43 patients with PAH. Association testing of case–control probability for rare variants was performed using the unified sequence kernel association test with optimal kernel weighting and small sample adjustment by comparing all SSc patients with a reference population of 3,179 controls from the Exome Sequencing Project 5,500 exome data set. Replication genotyping was performed in an independent sample of 3,263 patients (415 patients with SSc and 2,848 controls). We conducted expression profiling of messenger RNA from 61 SSc patients (19 without PAH and 42 with PAH) and 41 corresponding controls.ResultsThe ATP8B4 gene was associated with a significant increase in the risk of SSc (P = 2.77 × 10−7). Among the 64 ATP8B4 variants tested, a single missense variant, c.1308C>G (F436L, rs55687265), provided the most compelling evidence of association (P = 9.35 × 10−10, odds ratio [OR] 6.11), which was confirmed in the replication cohort (P = 0.012, OR 1.86) and meta‐analysis (P = 1.92 × 10−7, OR 2.5). Genes involved in E3 ubiquitin‐protein ligase complex (ASB10) and cyclic nucleotide gated channelopathies (CNGB3) as well as HLA–DRB5 and HSPB2 (heat‐shock protein 27) provided additional evidence of association (P < 10−5). Differential ATP8B4 expression was observed among the SSc patients compared to the controls (P = 0.0005).ConclusionATP8B4 may represent a putative genetic risk factor for SSc and pulmonary vascular complications.
Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self‐Controlled Case Series Study
Authors: Wiese Andrew D. , Griffin Marie R. , Stein C. Michael , Mitchel Edward F. , Grijalva Carlos G. 
Published: October 2015

ObjectiveAnimal studies and in vitro human studies suggest that certain opioid analgesics impair crucial immune functions. This study was undertaken to determine whether opioid use is associated with increased risk of serious infection in patients with rheumatoid arthritis (RA).MethodsWe conducted a self‐controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid in 1995–2009. Within‐person comparisons of the risk of hospitalization for serious infection during periods of opioid use versus non‐use were performed using conditional Poisson regression. Fixed confounders were accounted for by design; time‐varying confounders included age and use of disease‐modifying antirheumatic drugs, glucocorticoids, and proton‐pump inhibitors. In additional analyses, risks associated with new opioid use, use of opioids known to have immunosuppressive properties, use of long‐acting opioids, and different opioid dosages were assessed. Sensitivity analyses were performed to account for potential protopathic bias and confounding by indication.ResultsAmong 1,790 patients with RA who had at least 1 hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared to non‐use, with an incidence rate ratio (IRR) of 1.39 (95% confidence interval [95% CI] 1.19–1.62). The incidence rate was also higher during periods of long‐acting opioid use, immunosuppressive opioid use, and new opioid use compared to non‐use (IRR 2.01 [95% CI 1.52–2.66], IRR 1.72 [95% CI 1.33–2.23], and IRR 2.38 [95% CI 1.65–3.42], respectively). Results of sensitivity analyses were consistent with the main findings.ConclusionIn within‐person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalization for serious infection.
Brief Report: Association of Myositis Autoantibodies, Clinical Features, and Environmental Exposures at Illness Onset With Disease Course in Juvenile Myositis
Authors: Habers G. Esther A. , Huber Adam M. , Mamyrova Gulnara , Targoff Ira N. , O'Hanlon Terrance P. , Adams Sharon , Pandey Janardan P. , Boonacker Chantal , van Brussel Marco , Miller Frederick W. , van Royen‐Kerkhof Annet , Rider Lisa G. ,   for the Childhood Myositis Heterogeneity Study Group
Published: October 2015

ObjectiveTo identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs).MethodsUnivariable and multivariable multinomial logistic regression analyses were performed in a large juvenile IIM registry (n = 365) and included demographic characteristics, early clinical features, serum muscle enzyme levels, myositis autoantibodies, environmental exposures, and immunogenetic polymorphisms.ResultsMultivariable associations with chronic or polycyclic courses compared to a monocyclic course included myositis‐specific autoantibodies (multinomial odds ratio [OR] 4.2 and 2.8, respectively), myositis‐associated autoantibodies (multinomial OR 4.8 and 3.5), and a documented infection within 6 months of illness onset (multinomial OR 2.5 and 4.7). A higher overall clinical symptom score at diagnosis was associated with chronic or monocyclic courses compared to a polycyclic course. Furthermore, severe illness onset was associated with a chronic course compared to monocyclic or polycyclic courses (multinomial OR 2.1 and 2.6, respectively), while anti‐p155/140 autoantibodies were associated with chronic or polycyclic courses compared to a monocyclic course (multinomial OR 3.9 and 2.3, respectively). Additional univariable associations of a chronic course compared to a monocyclic course included photosensitivity, V‐sign or shawl sign rashes, and cuticular overgrowth (OR 2.2–3.2). The mean ultraviolet index and highest ultraviolet index in the month before diagnosis were associated with a chronic course compared to a polycyclic course in boys (OR 1.5 and 1.3), while residing in the Northwest was less frequently associated with a chronic course (OR 0.2).ConclusionOur findings indicate that myositis autoantibodies, in particular anti‐p155/140, and a number of early clinical features and environmental exposures are associated with a chronic course in patients with juvenile IIM. These findings suggest that early factors, which are associated with poorer outcomes in juvenile IIM, can be identified.
Prevalence and Responsiveness to Treatment of Lung Abnormalities on Chest Computed Tomography in Patients With Microscopic Polyangiitis: A Multicenter, Longitudinal, Retrospective Study of One Hundred Fifty Consecutive Hospital‐Based Japanese Patients
Authors: Yamagata Mieko , Ikeda Kei , Tsushima Kenji , Iesato Ken , Abe Mitsuhiro , Ito Takashi , Kashiwakuma Daisuke , Kagami Shin‐ichiro , Iwamoto Itsuo , Nakagomi Daiki , Sugiyama Takao , Maruyama Yuichiro , Furuta Shunsuke , Jayne David , Uno Takashi , Tatsumi Koichiro , Nakajima Hiroshi 
Published: October 2015

ObjectiveTo determine the prevalence of lung abnormalities on chest computed tomography (CT) in patients with microscopic polyangiitis (MPA), to assess the responsiveness of such abnormalities to initial treatment, and to assess associations between these abnormalities and patient and disease characteristics and mortality.MethodsWe retrospectively identified 167 consecutive hospital‐based patients with MPA in 3 hospitals in Japan. We longitudinally collected clinical information for 150 of these patients, for whom CT images obtained before treatment were available. We then determined the presence of 22 imaging components of lung abnormalities in these patients.ResultsThe vast majority of patients (97%) had at least 1 lung abnormality on chest CT images, including interstitial lung lesions (66%), airway lesions (66%), pleural lesions (53%), and emphysematous lesions (37%). In multivariate analyses, ground‐glass opacity was associated with the Birmingham Vasculitis Activity Score, whereas 3 of 4 airway lesions were associated with myeloperoxidase–antineutrophil cytoplasmic antibodies. Latent class analysis identified a distinct group of patients with airway‐predominant lung lesions. Airway lesions such as bronchiolitis and bronchovascular bundle thickening were among the components that showed improvement within 3 months of the initial treatment. An idiopathic pulmonary fibrosis pattern was the only chest CT variable that was independently associated with shorter survival.ConclusionAbnormalities in a wide range of anatomic areas, including the whole airway, can be identified in the lungs of patients with MPA before treatment. The prevalence, clustering patterns, and responsiveness to treatment of individual lung abnormalities provide groundwork for informing future studies to understand the pathophysiology of MPA.
Enantioselective Synthesis of 3,5,6‐Substituted Dihydropyranones and Dihydropyridinones using Isothiourea‐Mediated Catalysis
Authors: Stark Daniel G. , Morrill Louis C. , Cordes David B. , Slawin Alexandra M. Z. , O'Riordan Timothy J. C. , Smith Andrew D. 
Published: October 2015

AbstractThe scope of dihydropyranone and dihydropyridinone products accessible by isothiourea‐catalyzed processes has been expanded and explored through the use of 2‐N‐tosyliminoacrylates and 2‐aroylacrylates in a Michael addition‐lactonization/lactamization cascade reaction. Notably, to ensure reproducibility it is essential to use homoanhydrides as ammonium enolate precursors with 2‐aroyl acrylates, while carboxylic acids can be used with 2‐N‐tosyliminoacrylates, delivering a range of 3,5,6‐substituted dihydropyranones and dihydropyridinones with high enantioselectivity (typically >90 % ee). The derivatization of the heterocyclic core of a 3,5,6‐substituted dihydropyranone through hydrogenation is also reported.
Analysis of crosstalk between retinoic acid and sonic hedgehog pathways following ethanol exposure in embryonic zebrafish
Authors: Zhang Chengjin , Anderson Ashley , Cole Gregory J. 
Published: October 2015

BackgroundEthanol is a teratogen affecting numerous regions of the developing nervous system. The present study was undertaken to ascertain whether ethanol independently disrupts distinct signaling pathways or rather disrupts interactive pathways that regulate development of ethanol‐sensitive tissues.MethodsZebrafish embryos were exposed to ethanol in the absence or presence of aldh1a3 or Shh morpholino oligonucleotides (MOs), which disrupt retinoic acid (RA) or sonic hedgehog (Shh) function, respectively. Morphological analysis of ocular or midbrain–hindbrain boundary (MHB) development was conducted, and the ability to rescue ethanol and MO‐induced phenotypes was assessed. In situ hybridization was used to analyze Pax6a expression during ocular development.ResultsChronic ethanol exposure, or combined ethanol and MO treatment, results in perturbed MHB formation and microphthalmia. While RA can rescue the MHB phenotype following ethanol combined with either MO, Shh mRNA is unable to rescue the disrupted MHB with combined ethanol and aldh1a3 MO treatment. RA also is unable to rescue microphthalmia induced by ethanol and Shh MO.ConclusionThese studies demonstrate that while reduction of either RA or Shh signaling produces the same disruption of MHB or ocular development, that can be phenocopied using ethanol combined with either MO, RA overexpression can only rescue disrupted MHB, but not microphthalmia, in combined subthreshold Shh MO and ethanol. Our data suggest that MHB development may involve crosstalk between RA and Shh signaling, while ocular development depends on RA and Shh signaling that both are targets of ethanol in fetal alcohol spectrum disorders but do not depend on a mechanism involving crosstalk. Birth Defects Research (Part A) 103:1046–1057, 2015. © 2015 Wiley Periodicals, Inc.
Inactivation of GDP‐fucose transporter gene (Slc35c1) in CHO cells by ZFNs, TALENs and CRISPR‐Cas9 for production of fucose‐free antibodies
Authors: Chan Kah Fai , Shahreel Wahyu , Wan Corrine , Teo Gavin , Hayati Noor , Tay Shi Jie , Tong Wen Han , Yang Yuansheng , Rudd Pauline M. , Zhang Peiqing , Song Zhiwei 
Published: October 2015

AbstractRemoval of core fucose from N‐glycans attached to human IgG1 significantly enhances its affinity for the receptor FcγRIII and thereby dramatically improves its antibody‐dependent cellular cytotoxicity activity. While previous works have shown that inactivation of fucosyltransferase 8 results in mutants capable of producing fucose‐free antibodies, we report here the use of genome editing techniques, namely ZFNs, TALENs and the CRISPR‐Cas9, to inactivate the GDP‐fucose transporter (SLC35C1) in Chinese hamster ovary (CHO) cells. A FACS approach coupled with a fucose‐specific lectin was developed to rapidly isolate SLC35C1‐deficient cells. Mass spectrometry analysis showed that both EPO‐Fc produced in mutants arising from CHO‐K1 and anti‐Her2 antibody produced in mutants arising from a pre‐existing antibody‐producing CHO‐HER line lacked core fucose. Lack of functional SLC35C1 in these cells does not affect cell growth or antibody productivity. Our data demonstrate that inactivating Slc35c1 gene represents an alternative approach to generate CHO cells for production of fucose‐free antibodies.