bluuebunny/crossref_metadata_2025 huggingface dataset:
Xylochemie – Naturstoffsynthese aus Holz
Authors: Stubba Daniel , Lahm Günther , Geffe Mario , Runyon Jason W. , Arduengo Anthony J. , Opatz Till
Published: October 2015

Die 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

A 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

A 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

Transition‐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

Two 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

The 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

An 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

Objective

Synovial 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.

Methods

Synovial 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.

Results

Lower 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.

Conclusion

These 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

Objective

To determine the contribution of rare variants as genetic modifiers of the expressivity, penetrance, and severity of systemic sclerosis (SSc).

Methods

We 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.

Results

The 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).

Conclusion

ATP8B4 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

Objective

Animal 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).

Methods

We 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.

Results

Among 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.

Conclusion

In 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

Objective

To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs).

Methods

Univariable 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.

Results

Multivariable 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).

Conclusion

Our 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

Objective

To 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.

Methods

We 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.

Results

The 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.

Conclusion

Abnormalities 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

The 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

Background

Ethanol 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.

Methods

Zebrafish 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.

Results

Chronic 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.

Conclusion

These 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

Removal 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.
Effect of EGCG On Fe(III)‐induced conformational transition of silk fibroin, a model of protein related to neurodegenerative diseases
Authors: Xu Lihui , Tu Sidong , Chen Congheng , Zhao Juan , Zhang Yuan , Zhou Ping
Published: October 2015

The abnormal aggregation of amyloid proteins is reported to play a critical role in the etiology of neurodegenerative disorders. Studies have shown that excessive ferric irons are associated with the misfolding of amyloid proteins, and that (‐)‐epigallocatechin gallate (EGCG) is a good metallic ion chelator with inhibitory effect on the aggregation of amyloid proteins. EGCG has been thus considered as a potential drug candidate for the treatment of neurodegenerative diseases. However, the mechanism of action for EGCG in inhibition of aggregation of amyloid proteins is still remaining unclear. Silk fibroin (SF) shares similarities with amyloid proteins in some amino acid sequences and fibrillation kinetics. In this work, therefore, we used SF as a model of protein to investigate the effects of Fe(III) and EGCG on conformational transition by using turbidity assay, thioflavin T (ThT) fluorescence spectroscopy, Raman spectroscopy, and atomic force microscope (AFM). We demonstrated that low concentration of Fe(III) ions promoted the formation of β‐sheet conformers, while high concentration of Fe(III) ions inhibited further aggregation of SF. EGCG could significantly inhibit the conformational transition of SF when induced by Fe(III), and decrease the amount of β‐sheet conformers dose‐dependently. The findings provide important information regarding to EGCG as a potential agent for the prevention and treatment of neurodegenerative diseases. Fe(III) can accelerate the conformation transition of silk fibrion (SF) from random coil into β‐sheet, while (‐)‐epigallocatechin gallate (EGCG) inhibits Fe(III)‐induced β‐sheet aggregation of SF., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 100–107, 2016
Self‐assembly of a peptide with a tandem repeat of the Aβ16‐22 sequence linked by a β turn‐promoting dipeptide sequence
Authors: Sivakama Sundari Chandrasekaran , Bikshapathy Erugurala , Nagaraj Ramakrishnan
Published: October 2015

Amyloid deposits have been found to be abundant in patients with Alzheimer's disease due to fibril formation by the Aβ peptides. Peptide Aβ16‐22, comprising of the seven‐residue segment KLVFFAE, spanning residues 16–22 of the full length Aβ42 peptide, aggregates to form fibrils or other nanostructures in isolation, depending on the conditions of dissolution and incubation. In this study, we have examined the self‐assembly of PAβ, a tandem repeat peptide of the Aβ16‐22 sequence, joined by a β‐turn‐inducing sequence Asn‐Gly. To study the effect of various solvents on the self‐association, hexafluoroisopropanol (HFIP), trifluoroethanol (TFE) and methanol were used. The peptide was also incubated in fibril‐promoting conditions of 20% fluorinated alcohol–water mixtures which form dynamical solvent clusters, as well as in 20% MeOH–water mixture which does not form solvent clusters. Secondary structural studies suggest the presence of β‐structures. Electron microscopic images indicate that fibril formation occurs in a time‐dependent manner, under different conditions of solvent composition. Thioflavin‐T fluorescence studies confirm the presence of amyloid fibrils in the aggregates. Although the insertion of the Asn‐Gly sequence has not facilitated the formation of an ideal Type I’ rigid turn, the intramolecular interactions aid the formation of a flexible β‐turn conformation, with twisted β‐sheets. Interactions between the intermolecular β‐sheets result in the formation of amyloid fibrils. Organic solvents appear to play an important role in modulating self‐assembly of peptide PAβ during fibril formation. Studies on β‐hairpin engineered amyloidogenic peptides could lead to knowledge about suitable conditions for generating a diverse range of polymorphic structures. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 790–803, 2015.
Use of Polyacrylic Acid and Polydimethylsiloxane Mixture for In‐Needle Microextraction of Volatile Aroma Compounds in Essential Oils
Authors: Jeon Hye‐Lim , Son Hyun‐Hwa , Bae Sunyoung , Lee Dong‐Sun
Published: October 2015

A prototype stainless steel needle (Hamilton 90022, 22 gauge, 718 µm o.d., 413 µm i.d., 51 mm length, bevel tip) packed with polyacrylic acid (PAA) and polydimethylsiloxane (PDMS) mixture (7:3 ratio) having a micro‐bore tunnel (290 µm i.d., ca. 61.5 µm thickness, 10 mm length) was newly prepared as a device of headspace in‐needle microextraction (HS‐INME). Design of the needle, optimization of adsorption, desorption parameters, and validation of analytical methods were conducted to evaluate the HS‐INME efficiency for volatile organic compounds. The optimized adsorption conditions were 60 °C for 20 min and desorption conditions were 240 °C for 2 min. The calibration curves showed good linearity with the squared correlation coefficient value (r2) over 0.99. The limit of detection for linalool, (+)‐limonene, and eugenol were 13.5, 10.9, and 9.1 ng while limit of quantification were 45.1, 36.4, and 30.5 ng, respectively. The recovery results showed the acceptable range between 95.6 and 115.3%. The relative standard deviations for intra‐ and inter‐assay showed the values less than 10%. It was applied to analyze seven essential oils for polar and nonpolar volatile aroma compounds successfully. From the results obtained in this study, HS‐INME was advantageous to low cost due to ease of fabrication, reuse without loss of absorbent or reduction of extraction efficiency, and no use of solvent. In conclusion, a needle packed with PAA and PDMS mixture having a micro‐bore tunnel is a new development of INME that may complement the shortcomings of the current headspace extraction methods.
National treatment patterns in patients presenting with Stage IVC head and neck cancer: analysis of the National Cancer Database
Authors: Schwam Zachary G. , Burtness Barbara , Yarbrough Wendell G. , Mehra Saral , Husain Zain , Judson Benjamin L.
Published: October 2015

Head and neck cancer patients presenting with distant metastases are generally considered incurable. Treatment patterns and survival by primary disease site and therapy have not been described. Retrospective cohort analysis of 2525 patients in the National Cancer Database (2003–2006). Kaplan–Meier and Cox proportional hazards analyses were performed. Combined locoregional and systemic therapy was the most common treatment regimen (39.2%), followed by no treatment (23.9%), locoregional (19.0%), and systemic treatment (17.8%). Multivariate analysis demonstrated decreased survival was associated with age 65–79 years hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.14–1.80), Medicaid/uninsured status (HR 1.27, 95% CI 1.13–1.42), Medicare/other government insurance (HR 1.21, 95% 1.07–1.38), treatment at a nonacademic/research program (HR 1.17, 95% CI 1.07–1.27), and Charlson comorbidity score of 1 (HR 1.33, 95% 1.19–1.48). Compared to systemic therapy alone, receiving locoregional and systemic therapy was associated with decreased risk of death (HR 0.73, 95% CI 0.65–0.83). Only 14.6% and 0.6% of patients were recorded as receiving palliative therapy or being enrolled in a clinical trial, respectively. Significant treatment diversity exists in distantly metastatic head and neck cancer. Those who received combination locoregional and systemic therapy were more likely to have improved overall survival, but important factors in treatment selection are unknown. A small proportion of patients was found to receive either palliative therapy or was enrolled in a clinical trial, although these data likely underestimate the true proportions.
Increased risk for colorectal cancer under age 50 in racial and ethnic minorities living in the United States
Authors: Rahman Rubayat , Schmaltz Chester , Jackson Christian S. , Simoes Eduardo J. , Jackson‐Thompson Jeannette , Ibdah Jamal A.
Published: October 2015

Colorectal cancer (CRC) is the second most common cause of cancer death in USA. We analyzed CRC disparities in African Americans, Hispanics, Asians/Pacific Islanders, and American Indians/Alaska Natives compared to non‐Hispanic Whites. Current guidelines recommend screening for CRC beginning at age 50. Using SEER (Surveillance, Epidemiology, and End Results) database 1973–2009 and North American Association of Central Cancer Registries (NAACCR) 1995–2009 dataset, we performed frequency and rate analysis on colorectal cancer demographics and incidence based on race/ethnicity. We also used the SEER database to analyze stage, grade, and survival based on race/ethnicity. Utilizing SEER database, the median age of CRC diagnosis is significantly less in Hispanics (66 years), Asians/Pacific Islanders (68 years), American Indians/Alaska Natives (64 years), and African Americans (64 years) compared to non‐Hispanic whites (72 years). Twelve percent of Asians/Pacific Islanders, 15.4% Hispanics, 16.5% American Indians/Alaska Natives, and 11.9% African Americans with CRC are diagnosed at age <50 years compared to only 6.7% in non‐Hispanic Whites (P < 0.0001). Minority groups have more advanced stages at diagnosis compared to non‐Hispanic Whites. Trend analysis showed age‐adjusted incidence rates of CRC diagnosed under the age of 50 years have significantly increased in all racial and ethnic groups but are stable in African Americans. These results were confirmed through analysis of NAACCR 1995–2009 dataset covering nearly the entire USA. A significantly higher proportion of minority groups in USA with CRC are diagnosed before age 50 compared to non‐Hispanic Whites, documenting that these minority groups are at higher risk for early CRC. Further studies are needed to identify the causes and risk factors responsible for young onset CRC among minority groups and to develop intervention strategies including earlier CRC screening, among others.
Facets of country image and brand equity: Revisiting the role of product categories in country‐of‐origin effect research
Authors: Andéhn Mikael , Nordin Fredrik , Nilsson Mats E.
Published: October 2015

The country‐of‐origin effect is a topic central to the field of international marketing. Country of origin has been found to exert a particularly potent effect on consumer evaluation in situations where there is a strong link between a country and a particular product category. The present study provides further insight into how this particular effect can be understood. Drawing on a novel conceptualization of how country image and product categories interact, this study tested the relative evaluative relevance of product category with respect to estimates of brand equity across a variety of product categories. The findings suggest that facets of a country's image that are more closely related to the evaluation situation exert a greater influence on the evaluation of brands. This result encourages scholars as well as practitioners to re‐evaluate which situations might cause the country of origin effect to hold managerial relevance and paves the way for new paths toward a more comprehensive understanding of the effect. Copyright © 2015 John Wiley & Sons, Ltd.
Molecular Insight into Long‐Wavelength Fluorogenic Dye Design: Hydrogen Bond Induces Activation of a Dormant Acceptor
Authors: Kisin‐Finfer Einat , Redy‐Keisar Orit , Roth Michal , Ben‐Eliyahu Ronen , Shabat Doron
Published: October 2015

The detection of chemical or biological analytes in response to molecular changes relies increasingly on fluorescence methods. Therefore, there is a substantial need for the development of improved fluorogenic dyes. In this study, we demonstrated how an intramolecular hydrogen bond activates a dormant acceptor through a charge induction between phenolic hydrogen and a heteroaryl nitrogen moiety. As a result, a new fluorochrome is produced, and the molecule exhibits a strong fluorescent emission. When the strength of the hydrogen bonding was increased by conformational locking, the obtained dye emitted at longer wavelengths and fluoresced under physiological conditions. The dye was implemented in a turn‐ON system responsive to hydrogen peroxide. The molecular insight provided by this study should assist in the design of fluorescent dyes that are suitable for in vitro and in vivo applications.
Somatostatin 2a receptors are not expressed on functionally identified respiratory neurons in the ventral respiratory column of the rat
Authors: Le Sheng , Turner Anita J. , Parker Lindsay M. , Burke Peter G. , Kumar Natasha N. , Goodchild Ann K. , McMullan Simon
Published: October 2015

Microinjection of somatostatin (SST) causes site‐specific effects on respiratory phase transition, frequency, and amplitude when microinjected into the ventrolateral medulla (VLM) of the anesthetized rat, suggesting selective expression of SST receptors on different functional classes of respiratory neurons. Of the six subtypes of SST receptor, somatostatin 2a (sst2a) is the most prevalent in the VLM, and other investigators have suggested that glutamatergic neurons in the preBötzinger Complex (preBötC) that coexpress neurokinin‐1 receptor (NK1R), SST, and sst2a are critical for the generation of respiratory rhythm. However, quantitative data describing the distribution of sst2a in respiratory compartments other than preBötC, or on functionally identified respiratory neurons, is absent. Here we examine the medullary expression of sst2a with particular reference to glycinergic/expiratory neurons in the Bötzinger Complex (BötC) and NK1R‐immunoreactive/inspiratory neurons in the preBötC. We found robust sst2a expression at all rostrocaudal levels of the VLM, including a large proportion of catecholaminergic neurons, but no colocalization of sst2a and glycine transporter 2 mRNA in the BötC. In the preBötC 54% of sst2a‐immunoreactive neurons were also positive for NK1R. sst2a was not observed in any of 52 dye‐labeled respiratory interneurons, including seven BötC expiratory‐decrementing and 11 preBötC preinspiratory neurons. We conclude that sst2a is not expressed on BötC respiratory neurons and that phasic respiratory activity is a poor predictor of sst2a expression in the preBötC. Therefore, sst2a is unlikely to underlie responses to BötC SST injection, and is sparse or absent on respiratory neurons identified by classical functional criteria. J. Comp. Neurol. 524:1384–1398, 2016. © 2015 Wiley Periodicals, Inc.
High‐Performance Platinum‐Free Dye‐Sensitized Solar Cells with Molybdenum Disulfide Films as Counter Electrodes
Authors: Hussain Sajjad , Shaikh Shoyebmohamad F. , Vikraman Dhanasekaran , Mane Rajaram S. , Joo Oh‐Shim , Naushad Mu , Jung Jongwan
Published: October 2015

By using a radio‐frequency sputtering method, we synthesized large‐area, uniform, and transparent molybdenum disulfide film electrodes (1, 3, 5, and 7 min) on transparent and conducting fluorine‐doped tin oxide (FTO), as ecofriendly, cost‐effective counter electrodes (CE) for dye‐sensitized solar cells (DSSCs). These CEs were used in place of the routinely used expensive platinum CEs for the catalytic reduction of a triiodide electrolyte. The structure and morphology of the MoS2 was analyzed by using Raman spectroscopy, X‐ray diffraction, and X‐ray photoemission spectroscopy measurements and the DSSC characteristics were investigated. An unbroken film of MoS2 was identified on the FTO crystallites from field‐emission scanning electron microscopy. Cyclic voltammetry, electrochemical impedance spectroscopy, and Tafel curve measurements reveal the promise of MoS2 as a CE with a low charge‐transfer resistance, high electrocatalytic activity, and fast reaction kinetics for the reduction of triiodide to iodide. Finally, an optimized transparent MoS2 CE, obtained after 5 min synthesis time, showed a high power‐conversion efficiency of 6.0 %, which comparable to the performance obtained with a Pt CE (6.6 %) when used in TiO2‐based DSCCs, thus signifying the importance of sputtering time on DSSC performance.
The Experience of Caring For or Living with an Individual with an Eating Disorder: A Meta‐Synthesis of Qualitative Studies
Authors: Fox John RE , Dean Madeleine , Whittlesea Anna
Published: October 2015

Eating disorders (ED) has the highest mortality rate of psychiatric disorders and a high incidence of comorbidity. Because of the average age of onset, care typically befalls family members. However, despite the severity of the disorder and the burden placed on the family, research into the caregiving experience is still developing. Studies have shown caregivers of individuals with ED to experience high levels of distress, burden and expressed emotion. Recent theoretical models have underscored the importance of caregivers' responses as a maintenance factor for the ED, and family therapy has proved efficacious. However, the literature pertaining to the experience of family members living with or caring for an individual with an ED has not been systematically reviewed. This review aimed to synthesize qualitative studies relating to the caring experience and its impact, thereby gaining an understanding from the perspective of the individuals themselves. Relevant search terms were utilized to systematically search key databases. Twenty studies, with a total sample of 239 participants, met the inclusion criteria. Nine core themes emerged from the synthesis, forming the basis of an explanatory theory. The ED was found to have a pervasive impact upon family members, mediated by a number of factors. Cognitive appraisals affected the caregiving experience and responses to the individual. The experience of caregiving was continually reappraised leading to a process of adaptation. The majority of studies identified unmet carer needs. The implications of the findings are discussed with reference to existing theoretical models and in terms of clinical practice. Copyright © 2015 John Wiley & Sons, Ltd.

Key Practitioner Messages

Carers experience a significant amount of guilt and distress once they have found out about their loved one's eating disorder.

Across the studies, there were many themes of unmet need for carers.

Siblings have often been overlooked by both clinicians and researchers.

Interventions for people with eating disorders should also acknowledge carers and close family members.
Effectiveness of plasters and textile reinforced mortars for strengthening clay masonry infill walls subjected to combined in‐plane/out‐of‐plane actions / Wirksamkeit von Putz und textilbewehrtem Mörtel bei der Verstärkung von Ausfachungswänden aus Ziegelmauerwerk, die kombinierter Scheiben‐ und Plattenbeanspruchung ausgesetzt sind
Authors: da Porto Francesca , Guidi Giovanni , Verlato Nicolò , Modena Claudio
Published: October 2015

This work presents the results of experimental tests on full‐scale one‐bay, one‐storey reinforced concrete (RC) frames, filled with non‐load‐bearing clay masonry walls. The infill walls were made with clay masonry units characterized by a high percentage of voids and low strength. Such ‘light’ infill walls have shown fragile behaviour during recent earthquakes, due to the combined effects of damage produced by out‐of‐plane seismic action, together with in‐plane deformation of the RC frame.

In this context, various solutions to the problems involved in external reinforcement of ‘light’ infill walls, typically found in existing RC buildings but still used in common construction practice, have recently been developed. These solutions are: i) special lime‐based plaster with geo‐polymer binder; ii) bidirectional composite meshes applied with inorganic matrices, i.e., Textile Reinforced Mortars (TRM); iii) TRM improved by anchorage of the mesh to the RC frame.

For these construction elements, a special set‐up for combined in‐plane/out‐of‐plane cyclic testing, already used for other infill wall types at the University of Padova, was used. In particular, this work describes: a) materials and systems for strengthening infill walls; b) experimental results of infill walls under in‐plane loads; c) effects of out‐of‐plane loads on previously in‐plane damaged infill walls. The final aim was to achieve complete mechanical characterization of infill walls in both original and strengthened conditions, and to validate the effectiveness of the proposed strengthening systems.
Environmental footprint study of mortar, render and plaster formulation / Studie über die Umweltauswirkungen von Mörtel
Authors: Schlegel Thomas , Shtiza Aurela
Published: October 2015

A comparative environmental assessment study focusing on the stages of mortar production and carbonation through hardening has been conducted by the European Lime Association in collaboration with mortar producers from various EU countries on 17 formulations of mortars, renders and plasters. The results of the “cradle‐to‐gate” for mortar and renders indicated that: There are no significant differences between products with low and high lime contents and depending on the lime content in the products, the contribution of the hydrated lime to the different environmental indicators can range between 0 % and about 20 %. However, there are clear differences in the environmental footprints of gypsum or lime based plasters. Based on the plaster composition investigated in this study, it appears that lime based plasters have the lowest environmental footprint for some of the impacts (primary energy consumption, abiotic depletion and water eutrophication), whereas for the remaining indicators the gypsum based plasters have the lowest environmental footprint. Depending on the lime content in the plasters, the contribution of the hydrated lime to the different environmental indicators can vary in a wide range, i. e. between 0 and 40 %.

The differences in the environmental impacts of mortars, renders and plasters produced in integrated or non‐integrated mortar plants are generally rather small The lime carbonation process lowers the overall carbon footprint during the first period of the use phase of the mortars in buildings. This impact shall be taken into account in holistic LCA studies. If not, this leads to a wrong interpretation of the environmental impact of the mortars.
Review consent decree for guidance on assistance animals
Authors: Hope Joan
Published: October 2015

A recently announced consent decree in United States v. University of Nebraska at Kearney, 940 F. Supp. 2d 974 (D. Neb. 2013), could provide guidance to campus officials about policies and procedures to put into place with regard to assistance animals. Jeanne M. Kincaid, Esq., an attorney at Drummond Woodsum, discussed the consent decree with us.
Ruling upholds increased disability accommodations for LSAT
Authors: Sutton Halley
Published: October 2015

On August 7, 2015, U.S. Magistrate Joseph C. Spero upheld most of the recommended rules that an independent council had submitted to the Law School Admission Council regarding best practices for granting students with disabilities sufficient accommodations during the Law School Admission Test. The federal ruling came as a result of the Best Practices Report issued as part of the settlement in Department of Fair Employment and Housing v. The Law School Admission Council. The lawsuit alleged that LSAC violated the Americans with Disabilities Act because individuals with disabilities faced unfair treatment during LSAT testing and did not receive due accommodations.
Expression of the Drosophila homeobox gene, Distal‐less, supports an ancestral role in neural development
Authors: Plavicki Jessica S. , Squirrell Jayne M. , Eliceiri Kevin W. , Boekhoff‐Falk Grace
Published: October 2015

Background: Distal‐less (Dll) encodes a homeodomain transcription factor expressed in developing appendages of organisms throughout metazoan phylogeny. Based on earlier observations in the limbless nematode Caenorhabditis elegans and the primitive chordate amphioxus, it was proposed that Dll had an ancestral function in nervous system development. Consistent with this hypothesis, Dll is necessary for the development of both peripheral and central components of the Drosophila olfactory system. Furthermore, vertebrate homologs of Dll, the Dlx genes, play critical roles in mammalian brain development. Results: Using fluorescent immunohistochemistry of fixed samples and multiphoton microscopy of living Drosophila embryos, we show that Dll is expressed in the embryonic, larval and adult central nervous system and peripheral nervous system (PNS) in embryonic and larval neurons, brain and ventral nerve cord glia, as well as in PNS structures associated with chemosensation. In adult flies, Dll expression is expressed in the optic lobes, central brain regions and the antennal lobes. Conclusions: Characterization of Dll expression in the developing nervous system supports a role of Dll in neural development and function and establishes an important basis for determining the specific functional roles of Dll in Drosophila development and for comparative studies of Drosophila Dll functions with those of its vertebrate counterparts. Developmental Dynamics 245:87–95, 2016. © 2015 Wiley Periodicals, Inc.