bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of Aryl Halide to Alkyl Halide: Reductive Elimination of Alkylhalide from Alkylpalladium Halides Containing syn‐β‐Hydrogen Atoms
Authors: Hao Wei , Wei Junnian , Geng Weizhi , Zhang Wen‐Xiong , Xi Zhenfeng
Published: November 2014

β‐Hydride abstraction is a well‐accepted elementary step for catalytic cycles in organometallic chemistry. It is usually anticipated that alkylpalladium halides containing syn‐β‐hydrogen atoms will undergo β‐hydride abstraction to afford the Heck‐type products. However, this study discloses that the above general knowledge is only conditionally correct. Our experimental results demonstrate that the reductive elimination of alkylhalides from alkylpalladium halides containing syn‐β‐hydrogen atoms may surpass the β‐hydride abstraction or even become exclusive in certain cases.
Controlled Formation of Polymer Nanocapsules with High Diffusion‐Barrier Properties and Prediction of Encapsulation Efficiency
Authors: Hofmeister Ines , Landfester Katharina , Taden Andreas
Published: October 2014

Polymer nanocapsules with high diffusion‐barrier performance were designed following simple thermodynamic considerations. Hindered diffusion of the enclosed material leads to high encapsulation efficiencies (EEs), which was demonstrated based on the encapsulation of highly volatile compounds of different chemical natures. Low interactions between core and shell materials are key factors to achieve phase separation and a high diffusion barrier of the resulting polymeric shell. These interactions can be characterized and quantified using the Hansen solubility parameters. A systematic study of our copolymer system revealed a linear relationship between the Hansen parameter for hydrogen bonding (δh) and encapsulation efficiencies which enables the prediction of encapsulated amounts for any material. Furthermore EEs of poorly encapsulated materials can be increased by mixing them with a mediator compound to give lower overall δh values.
Nitrimines as Reagents for Metal‐Free Formal C(sp2)–C(sp2) Cross‐Coupling Reactions
Authors: Angeles‐Dunham Veronica V. , Nickerson David M. , Ray Devin M. , Mattson Anita E.
Published: November 2014

Nitrimines are employed as powerful reagents for metal‐free formal C(sp2)–C(sp2) cross‐coupling reactions. The new chemical process is tolerant of a wide array of nitrimine and heterocyclic coupling partners giving rise to the corresponding di‐ or trisubstituted alkenes, typically in high yield and with high stereoselectivity. This method is ideal for the metal‐free construction of heterocycle‐containing drug targets, such as phenprocoumon.
The Mechanisms of Rectification in Au|Molecule|Au Devices Based on Langmuir–Blodgett Monolayers of Iron(III) and Copper(II) Surfactants
Authors: Wickramasinghe Lanka D. , Mazumder Shivnath , Gonawala Sunalee , Perera Meeghage Madusanka , Baydoun Habib , Thapa Bishnu , Li Li , Xie Lingxiao , Mao Guangzhao , Zhou Zhixian , Schlegel H. Bernhard , Verani Cláudio N.
Published: November 2014

Langmuir–Blodgett films of metallosurfactants were used in Au|molecule|Au devices to investigate the mechanisms of current rectification.
Preparation of a new polymer‐dispersed liquid crystal film by using phthalocyanine‐functional photocurable copolymer
Authors: Mert Humeyra , Dinçer Hatice , Çalışkan Emel , Şen Betül Nur , Gürsel Yeşim Hepuzer
Published: October 2014

A new, asymmetrical zinc phthalocyanine (aZnPc)‐functional photocurable copolymer was prepared by the combination of atom transfer radical polymerization and copper (I)‐catalyzed azide‐alkyne cyclo‐addition (CuAAC) click reaction and used as polymer matrix of polymer dispersed liquid crystal (PDLC) film. For this purpose, aZnPc was prepared through statistical condensation of 4‐tert‐butylphthalonitrile and 4‐pent‐4‐ynyloxyphthalonitrile. Double CuAAC click reaction between azido‐functional poly(methyl methacrylate‐co‐2‐(2‐bromoisobutyryloxy)‐ethyl methacrylate), terminal alkynyl‐substituted aZnPc, and 4‐ethynyl‐N,N‐dimethyl aniline yielded photocurable aZnPc‐functional copolymer. Thereby, synthesized copolymer was crosslinked in the presence of liquid crystalline mesogen 4′‐(octyloxy)‐4‐biphenylcarbonitrile by ultraviolet irradiation using benzophenone as initiator and ethylene glycol dimethacrylate as difunctional crosslinker. Thermal and optical properties of PDLC film were investigated by using differential scanning calorimetry and polarized optical microscopy. Smectic A liquid crystal mesophases were observed in both PDLC film and its mesogenic component 4′‐(octyloxy)‐4‐biphenylcarbonitrile. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41574.
Electrospun dendritic ZnO nanofibers and its photocatalysis application
Authors: Li Jianing , Cheng Zhiqiang , Liu Mengzhu , Zhang Mingyue , Hu Meijuan , Zhang Li , Jiang Haifeng , Li Junfeng
Published: October 2014

A simple and efficient procedure has been developed to fabricate ZnO nanofibers with dendritic structure via electrospinning and subsequent calcination. The spinning solution is prepared by mixing polyvinylpyrrolidone (PVP) and zinc acetate into methanol. From SEM images, it can be observed that the ZnO product has a tendency of dendritic structure. The diameter of the dendritic branch is ∼137 nm. The structure and physicochemical property of the prepared nanofibers are elucidated by TGA, SEM, XRD, FTIR, and PL, respectively. The photoluminescene measurement of the ZnO samples exhibit a broad visible emission band concentrate on around 430–580 nm. Meanwhile, the intensity is related to the content of surface oxygen vacancies, which probably influence photocatalytic activity of ZnO samples. Whereafter, the photocatalytical activity of the ZnO nanofibers is evaluated by quantifying the degradation of methyl blue. The result indicates that ZnO nanofibers annealed at 650°C show an excellent photocatalytic activity. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41627.
Systemanalyse neugotischer Gewölbe
Authors: Piehler Jens , Hansen Michael , Kapphahn Gerd
Published: November 2014

Ab Mitte des 19. Jahrhunderts bis zum Beginn des Ersten Weltkrieges wurden zahlreiche Bauwerke im neugotischen Stil ausgeführt. In der Neugotik wurden die gotischen Bauelemente mit den in der Gründerzeit geforderten Materialeinsparungen gebaut. Diese leichten und sehr dünnwandigen Gewölbe sind oftmals relativ anfällige Tragsysteme. Sie weisen systemimmanente Schadensbilder in Form signifikanter Rissbildungen in den Kappen und Bögen auf. In dem Forschungsprojekt Sicherung neugotischer Gewölbekonstruktionen werden die typischen Schadensbilder neugotischer Gewölbe mit dem Ziel analysiert, möglichst nachhaltige Sanierungsmaßnahmen zu finden. In diesem Rahmen wurden seit 2011 an einem ausgewählten Referenzbauwerk numerische und experimentelle Untersuchungen durchgeführt.

Das dafür erstellte Geometriemodell der Finite‐Elemente‐Simulation basiert auf den Messdaten eines 3D‐Laserscans, in dem alle Imperfektionen der Konstruktion enthalten sind. Für die Kalibrierung dieses numerischen Modells wurde das Systemverhalten im unkritischen Lastbereich mit einem Belastungsversuch experimentell untersucht. In diesem Beitrag werden der Projektrahmen sowie die Durchführung und Auswertung des Belastungsversuchs dargestellt. In weiteren Beiträgen werden die Übertragung geodätischer Messdaten in das numerische Modell und die Berücksichtigung der mit dem Belastungsversuch erzielten Ergebnisse innerhalb einer Simulation behandelt.

System analysis of Neo‐Gothic vaults – Part 1: Preliminary investigations and experimental validation

From the middle of the 19th century until the beginning of World War I, many buildings were built in the Neo‐Gothic style. In this period, Gothic elements were built regarding the former needs to save material. These lightweight and thin vaults are often relatively fragile support systems. They tend to show systemic damages in the form of significant crack patterns in the vault caps and arches. In the research project Preservation of Neo‐Gothic vault structures, typical damages of Neo‐Gothic vaulted structures are analyzed with the objective to find sustainable and rehabilitative measures. In this context, since 2011, numerical and experimental studies have been carried out on a reference structure. Measured values of a 3D laser scanning, including all the imperfections of the structure, provide the basis of the geometry model, created for the finite element simulation. The system behavior was studied experimentally in the non‐critical load range with a load test for the calibration of this numerical model. In this paper, the project framework as well as the implementation and the evaluation of the load test are presented. In further papers, the transfer of the geodetic measurement data to the numerical model and the consideration of the load test results within a simulation will be addressed.
Epidemiology of twinning in the National Birth Defects Prevention Study, 1997 to 2007
Authors: Dawson April L. , Tinker Sarah C. , Jamieson Denise J. , Hobbs Charlotte A. , Rasmussen Sonja A. , Reefhuis Jennita ,   the National Birth Defects Prevention Study
Published: October 2014

Background

Our objective was to evaluate associations between twinning and maternal demographic factors and periconceptional exposures among infants with and without orofacial clefts.

Methods

We used data from the National Birth Defects Prevention Study; 228 twins and 8242 singletons without birth defects (controls), and 117 twins and 2859 singletons with orofacial clefts, born 1997 to 2007, were included in the analyses. Because of the occurrence of twinning due to the use of assisted reproductive technologies, logistic regression models were computed to estimate odds ratios and 95% confidence intervals for each exposure, stratified by fertility treatment use. To evaluate factors by zygosity, we used sex‐pairing data and a simulation approach to estimate the zygosity of like‐sex twin pairs for unassisted conceptions.

Results

Among control mothers who did not use fertility treatments, predictors of twinning included non‐Hispanic black maternal race (adjusted odds ratio, 1.6; 95% confidence interval, 1.0–2.4), and tobacco smoking (adjusted odds ratio, 1.6; 95% confidence interval, 1.1–2.4). Among control mothers who used fertility treatments, older maternal age, higher income, and state of residence were associated with twinning. Associations were generally stronger among mothers of dizygotic (estimated) twins than monozygotic (estimated) twins. Results for mothers of infants with isolated orofacial clefts were similar to those of controls.

Conclusion

We observed an increased twinning frequency with increasing maternal age, but factors such as maternal race/ethnicity and socioeconomic status may also contribute. Among women receiving fertility treatments, factors associated with twinning suggested a relation with treatment specifics (e.g., treatment type and number of embryos implanted) and availability of insurance coverage. Birth Defects Research (Part A) 103:85–99, 2015 © 2014 Wiley Periodicals, Inc.
Does RNA editing compensate for Alu invasion of the primate genome?
Authors: Levanon Erez Y. , Eisenberg Eli
Published: October 2014

One of the distinctive features of the primate genome is the Alu element, a repetitive short interspersed element, over a million highly similar copies of which account for >10% of the genome. A direct consequence of this feature is that primates' transcriptome is highly enriched in long stable dsRNA structures, the preferred target of adenosine deaminases acting on RNAs (ADARs), which are the enzymes catalyzing A‐to‐I RNA editing. Indeed, A‐to‐I editing by ADARs is extremely abundant in primates: over a hundred million editing sites exist in their genomes. However, there are few essential editing sites conserved across mammals that have maintained their editing level despite the radical change in ADAR target landscape. Here, we review and discuss the cost of having an unusual amount of dsRNA and editing in the transcriptome, as well as the opportunities it presents, which might have contributed to the accelerated evolution of the primates.
Corporate Sustainable Development: is ‘Integrated Reporting’ a Legitimation Strategy?
Authors: Lai Alessandro , Melloni Gaia , Stacchezzini Riccardo
Published: October 2014

In the field of sustainability reporting (SR), the so‐called ‘integrated report’ (IR) is gaining momentum. In spite of its voluntary nature, a growing number of firms are adopting IR by participating in the International Integrated Reporting Council (IIRC) Pilot Programme. Stimulated by concerns on the use of SR as a legitimation strategy, the paper investigates whether the decision to adopt an IR stems from the need to repair legitimacy threats. By showing that IR adopters have significantly higher Bloomberg ESG disclosure ratings relative to non‐adopters, we reject the hypothesis of firms adopting IR as a response to a poor rating. Additionally, we show that other proxies of legitimacy pressures (size, leverage, profitability, industry) do not play a role in explaining IR adoption. Overall, our evidence suggests that corporate engagement in IR is not a matter of strategic legitimation. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
A prison mental health in‐reach model informed by assertive community treatment principles: evaluation of its impact on planning during the pre‐release period, community mental health service engagement and reoffending
Authors: McKenna Brian , Skipworth Jeremy , Tapsell Rees , Madell Dominic , Pillai Krishna , Simpson Alexander , Cavney James , Rouse Paul
Published: November 2014

Background

It is well recognised that prisoners with serious mental illness (SMI) are at high risk of poor outcomes on return to the community. Early engagement with mental health services and other community agencies could provide the substrate for reducing risk.

Aim

To evaluate the impact of implementing an assertive community treatment informed prison in‐reach model of care (PMOC) on post‐release engagement with community mental health services and on reoffending rates.

Methods

One hundred and eighty prisoners with SMI released from four prisons in the year before implementation of the PMOC were compared with 170 such prisoners released the year after its implementation.

Results

The assertive prison model of care was associated with more pre‐release contacts with community mental health services and contacts with some social care agencies in some prisons. There were significantly more post‐release community mental health service engagements after implementation of this model (Z = −2.388, p = 0.02). There was a trend towards reduction in reoffending rates after release from some of the prisons (Z = 1.82, p = 0.07).

Conclusions and implications for practice

Assertive community treatment applied to prisoners with mental health problems was superior to ‘treatment as usual’, but more work is needed to ensure that agencies will engage prisoners in pre‐release care. The fact that the model showed some benefits in the absence of any increase in resources suggests that it may be the model per se that is effective. Copyright © 2014 John Wiley & Sons, Ltd.
Voltage‐Dependent Capacitance, Aging Effects, and Failure Indicators of Double‐Layer Capacitors during Lifetime Testing
Authors: Kurzweil Peter , Frenzel Bernhard , Hildebrand Andreas
Published: October 2014

Aging phenomena, which occur during long‐term cycling tests of supercapacitors, complicate the exact determination of comparable capacitance values by using hitherto introduced electrochemical techniques. The gradual degradation of polymer‐bound carbon electrodes during long‐term operation is caused by the destruction of the adhesive layer between the active material and current collector. Based on ten years of testing experience, a reliable voltammetric method is proposed, with which it is possible to distinguish useable capacitance, residual charges caused by chemical aging processes, and mechanical failure causes. The capacitance of electrode–electrolyte interfaces is shown as a function of temperature, frequency, voltage, state‐of‐charge, and the operating conditions.
In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization
Authors: Barskiy Danila A. , Kovtunov Kirill V. , Koptyug Igor V. , He Ping , Groome Kirsten A. , Best Quinn A. , Shi Fan , Goodson Boyd M. , Shchepin Roman V. , Truong Milton L. , Coffey Aaron M. , Waddell Kevin W. , Chekmenev Eduard Y.
Published: November 2014

By using 5.75 and 47.5 mT nuclear magnetic resonance (NMR) spectroscopy, up to 105‐fold sensitivity enhancement through signal amplification by reversible exchange (SABRE) was enabled, and subsecond temporal resolution was used to monitor an exchange reaction that resulted in the buildup and decay of hyperpolarized species after parahydrogen bubbling. We demonstrated the high‐resolution low‐field proton magnetic resonance imaging (MRI) of pyridine in a 47.5 mT magnetic field endowed by SABRE. Molecular imaging (i.e. imaging of dilute hyperpolarized substances rather than the bulk medium) was conducted in two regimes: in situ real‐time MRI of the reaction mixture (in which pyridine was hyperpolarized), and ex situ MRI (in which hyperpolarization decays) of the liquid hyperpolarized product. Low‐field (milli‐Tesla range, e.g. 5.75 and 47.5 mT used in this study) parahydrogen‐enhanced NMR and MRI, which are free from the limitations of high‐field magnetic resonance (including susceptibility‐induced gradients of the static magnetic field at phase interfaces), potentially enables new imaging applications as well as differentiation of hyperpolarized chemical species on demand by exploiting spin manipulations with static and alternating magnetic fields.
Cellulose Amorphization by Swelling in Ionic Liquid/Water Mixtures: A Combined Macroscopic and Second‐Harmonic Microscopy Study
Authors: Glas Daan , Paesen Rik , Depuydt Daphne , Binnemans Koen , Ameloot Marcel , De Vos Dirk E. , Ameloot Rob
Published: October 2014

Amorphization of cellulose by swelling in ionic liquid (IL)/water mixtures at room temperature is a suitable alternative to the dissolution–precipitation pretreatment known to facilitate enzymatic digestion. When soaking microcrystalline cellulose in the IL 1‐ethyl‐3‐methylimidazolium acetate containing 20 wt % water, the crystallinity of the cellulose sample is strongly reduced. As less than 4 % of the cellulose dissolves in this mixture, this swelling method makes a precipitation step and subsequent energy‐intensive IL purification redundant. Second‐harmonic generation (SHG) microscopy is used as a structure‐sensitive technique for in situ monitoring of the changes in cellulose crystallinity. Combined optical and SHG observations confirm that in the pure IL complete dissolution takes place, while swelling without dissolution in the optimal IL/water mixture yields a solid cellulose with a significantly reduced crystallinity in a single step.
Synthesis and characterization of 6β‐hydroxyandrosterone and 6β‐hydroxyetiocholanolone conjugated with glucuronic acid
Authors: Kotronoulas Aristotelis , Fabregat Andreu , Alfonso Ignacio , Parella Teodor , Segura Jordi , Ventura Rosa , Joglar Jesús , Pozo Oscar J.
Published: October 2014

The detection of testosterone (T) misuse by doping control laboratories is mainly based on monitoring urinary T phase I metabolites released after enzymatic hydrolysis of the corresponding phase II glucuronide metabolites by gas chromatography (tandem) mass spectrometry (GC‐MS(/MS)) methods. However, this strategy fails to properly determine two recently reported phase II metabolites of T conjugated with glucuronic acid that remained mostly conjugated after the hydrolysis step. These metabolites were identified as glucuronides of 6β‐hydroxyandrosterone (6β‐OH‐And) and 6β‐hydroxyetiocholanolone (6β‐OH‐Etio) but their exact conjugation site remained undetermined. In this study, the four possible glucuronides of 6β‐OH‐And and 6β‐OH‐Etio were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy. Moreover, their chromatographic properties and MS spectra were compared to those obtained for the urine samples collected after administration of T. Results confirmed that the recently reported metabolites were the 3α‐glucuronides of 6β‐OH‐And and 6β‐OH‐Etio. The synthesis and the elucidation of the exact structure of the metabolites presented in this study are crucial steps for the development of analytical methods in order to explore their role in T metabolism and their potential usefulness as biomarkers of T misuse. Copyright © 2014 John Wiley & Sons, Ltd.
Peptide selectivity discriminates NK cells from KIR2DL2‐ and KIR2DL3‐positive individuals
Authors: Cassidy Sorcha , Mukherjee Sayak , Myint Thet Mon , Mbiribindi Berenice , North Helen , Traherne James , Mulder Arend , Claas Frans HJ , Purbhoo Marco A , Das Jayajit , Khakoo Salim I
Published: October 2014

Natural killer cells are controlled by peptide selective inhibitory receptors for MHC class I, including the killer cell immunoglobulin‐like receptors (KIRs). Despite having similar ligands, KIR2DL2 and KIR2DL3 confer different levels of protection to infectious disease. To investigate how changes in peptide repertoire may differentially affect NK cell reactivity, NK cells from KIR2DL2 and KIR2DL3 homozygous donors were tested for activity against different combinations of strong inhibitory (VAPWNSFAL), weak inhibitory (VAPWNSRAL), and antagonist peptide (VAPWNSDAL). KIR2DL3‐positive NK cells were more sensitive to changes in the peptide content of MHC class I than KIR2DL2‐positive NK cells. These differences were observed for the weakly inhibitory peptide VAPWNSRAL in single peptide and double peptide experiments (p < 0.01 and p < 0.03, respectively). More significant differences were observed in experiments using all three peptides (p < 0.0001). Mathematical modeling of the experimental data demonstrated that VAPWNSRAL was dominant over VAPWNSFAL in distinguishing KIR2DL3‐ from KIR2DL2‐positive donors. Donors with different KIR genotypes have different responses to changes in the peptide bound by MHC class I. Differences in the response to the peptide content of MHC class I may be one mechanism underlying the protective effects of different KIR genes against infectious disease.
Gal‐3 regulates the capacity of dendritic cells to promote NKT‐cell‐induced liver injury
Authors: Volarevic Vladislav , Markovic Bojana Simovic , Bojic Sanja , Stojanovic Maja , Nilsson Ulf , Leffler Hakon , Besra Gurdyal S. , Arsenijevic Nebojsa , Paunovic Verica , Trajkovic Vladimir , Lukic Miodrag L.
Published: October 2014

Galectin‐3 (Gal‐3), an endogenous lectin, exhibits pro‐ and anti‐inflammatory effects in various disease conditions. In order to explore the role of Gal‐3 in NKT‐cell‐dependent pathology, we induced hepatitis in C57BL/6 WT and Gal‐3‐deficient mice by using specific ligand for NKT cells: α‐galactosylceramide, glycolipid Ag presented by CD1d. The injection of α‐galactosylceramide significantly enhanced expression of Gal‐3 in liver NKT and dendritic cells (DCs). Genetic deletion or selective inhibition of Gal‐3 (induced by Gal‐3‐inhibitor TD139) abrogated the susceptibility to NKT‐cell‐dependent hepatitis. Blood levels of pro‐inflammatory cytokines (TNF‐α, IFN‐γ, IL‐12) and their production by liver DCs and NKT cells were also downregulated. Genetic deletion or selective inhibition of Gal‐3 alleviated influx of inflammatory CD11c+CD11b+ DCs in the liver and favored tolerogenic phenotype and IL‐10 production of liver NKT and DCs. Deletion of Gal‐3 attenuated the capacity of DCs to support liver damage in the passive transfer experiments and to produce pro‐inflammatory cytokines in vitro. Gal‐3‐deficient DCs failed to optimally stimulate production of pro‐inflammatory cytokines in NKT cells, in vitro and in vivo. In conclusion, Gal‐3 regulates the capacity of DCs to support NKT‐cell‐mediated liver injury, playing an important pro‐inflammatory role in acute liver injury.
Cationic Trialkylphosphates: Synthesis and Transfection Efficacies Compared to Phosphoramidate Analogues
Authors: Le Corre Stéphanie S. , Berchel Mathieu , Le Gall Tony , Haelters Jean‐Pierre , Lehn Pierre , Montier Tristan , Jaffrès Paul‐Alain
Published: October 2014

We report herein the synthesis of a novel family of cationic lipids, characterized by a trimethylammonium headgroup linked through a phosphate function to either two identical or two different lipid chains. The novelty of this study arises from the use of a trialkyl phosphate group to associate the hydrophobic domain to the cationic polar head. The structure of these new cationic lipids, which differs from that of previously reported lipophosphoramidates, is closer to the phospholipids encountered in the plasma membrane, and possesses a phosphocholine polar head. Evaluation of the transfection activity allowed us to compare the efficacy of cationic lipophosphates with that of lipophosphoramidates. These results demonstrate that cationic lipophosphates and lipophosphoramidates having otherwise identical chemical structures exhibit similar transfection efficacies. The second conclusion is that the structure of the lipid domain is a much more important parameter in governing transfection efficacy than the composition of the linker moiety. The best results were obtained with cationic lipophosphates or lipophosphoramidates possessing two different lipid chains, for example one oleyl chain with one phytanyl chain. These nonsymmetric cationic lipids exhibited transfection efficacies that were 10‐ to 200‐fold better than those obtained with Lipofectamine used as a commercial standard.
In vivo genotoxicity of estragole in male F344 rats
Authors: Ding Wei , Levy Dan D. , Bishop Michelle E. , Pearce Mason G. , Davis Kelly J. , Jeffrey Alan M. , Duan Jian‐Dong , Williams Gary M. , White Gene A. , Lyn‐Cook Lascelles E. , Manjanatha Mugimane G.
Published: October 2014

Estragole, a naturally occurring constituent of various herbs and spices, is a rodent liver carcinogen which requires bio‐activation. To further understand the mechanisms underlying its carcinogenicity, genotoxicity was assessed in F344 rats using the comet, micronucleus (MN), and DNA adduct assays together with histopathological analysis. Oxidative damage was measured using human 8‐oxoguanine‐DNA‐N‐glycosylase (hOGG1) and EndonucleaseIII (EndoIII)‐modified comet assays. Results with estragole were compared with the structurally related genotoxic carcinogen, safrole. Groups of seven‐week‐old male F344 rats received corn oil or corn oil containing 300, 600, or 1,000 mg/kg bw estragole and 125, 250, or 450 mg/kg bw safrole by gavage at 0, 24, and 45 hr and terminated at 48 hr. Estragole‐induced dose‐dependent increases in DNA damage following EndoIII or hOGG1 digestion and without enzyme treatment in liver, the cancer target organ. No DNA damage was detected in stomach, the non‐target tissue for cancer. No elevation of MN was observed in reticulocytes sampled from peripheral blood. Comet assays, both without digestion or with either EndoIII or hOGG1 digestion, also detected DNA damage in the liver of safrole‐dosed rats. No DNA damage was detected in stomach, nor was MN elevated in peripheral blood following dosing with safrole suggesting that, as far both safrole and estragole, oxidative damage may contribute to genotoxicity. Taken together, these results implicate multiple mechanisms of estragole genotoxicity. DNA damage arises from chemical‐specific interaction and is also mediated by oxidative species. Environ. Mol. Mutagen. 56:356–365, 2015. © 2014 Crown copyright.
Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish
Authors: Niemuth Nicholas J. , Jordan Renee , Crago Jordan , Blanksma Chad , Johnson Rodney , Klaper Rebecca D.
Published: October 2014

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been found ubiquitously in wastewater and surface waters around the world. A major source of these compounds is incomplete metabolism in humans and subsequent excretion in human waste, resulting in discharge into surface waters by wastewater treatment plant (WWTP) effluent. One pharmaceutical found in particularly high abundance in recent WWTP effluent and surface water studies is metformin, one of the world's most widely prescribed antidiabetic drugs. Interactions between insulin signaling and steroidogenesis suggest potential endocrine-disrupting effects of metformin found in the aquatic environment. Adult fathead minnows (Pimephales promelas) were chronically exposed to metformin for 4 wk, at 40 µg/L, a level similar to the average found in WWTP effluent in Milwaukee, Wisconsin, USA. Genetic endpoints related to metabolism and endocrine function as well as reproduction-related endpoints were examined. Metformin treatment induced significant up-regulation of messenger ribonucleic acid (mRNA) encoding the egg-protein vitellogenin in male fish, an indication of endocrine disruption. The present study, the first to study the effects of environmentally relevant metformin exposure in fathead minnows, demonstrates the need for further study of the endocrine-disrupting effects of metformin in aquatic organisms. Environ Toxicol Chem 2014;9999:1–6. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of SETAC.
The influence of particle size and static magnetic fields on the uptake of magnetic nanoparticles into three dimensional cell‐seeded collagen gel cultures
Authors: Lewis Emily E. L. , Child Hannah W. , Hursthouse Andrew , Stirling David , McCully Mark , Paterson David , Mullin Margaret , Berry Catherine C.
Published: October 2014

Over recent decades there has been and continues to be major advances in the imaging, diagnosis and potential treatment of medical conditions, by the use of magnetic nanoparticles. However, to date the majority of cell delivery studies employ a traditional 2D monolayer culture. This article aims to determine the ability of various sized magnetic nanoparticles to penetrate and travel through a cell seeded collagen gel model, in the presence or absence of a magnetic field. Three different sized (100, 200, and 500 nm) nanoparticles were employed in the study. The results showed cell viability was unaffected by the presence of nanoparticles over a 24‐h test period. The initial uptake of the 100 nm nanoparticle into the collagen gel structure was superior compared to the larger sized nanoparticles under the influence of a magnetic field and incubated for 24 h. Interestingly, it was the 200 nm nanoparticles, which proved to penetrate the gel furthest, under the influence of a magnetic field, during the initial culture stage after 1‐h incubation. © 2014 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1294–1301, 2015.
Risk of Subsequent Fractures and Mortality in Elderly Women and Men with Fragility Fractures with and without Osteoporotic Bone Density: The Dubbo Osteoporosis Epidemiology Study
Authors: Bliuc Dana , Alarkawi Dunia , Nguyen Tuan V , Eisman John A , Center Jacqueline R
Published: October 2014

Half of fragility fractures occur in individuals with nonosteoporotic BMD (BMD T-score > –2.5); however, there is no information on postfracture adverse events of subsequent fracture and mortality for different BMD levels. The objective of this work was to determine the risk and predictors of subsequent fracture and excess mortality following initial fracture according to BMD. The subjects were community-dwelling participants aged 60+ years from the Dubbo Osteoporosis Epidemiology Study with incident fractures followed from 1989 to 2011. The outcome measurements were as follows: risk of subsequent fracture and mortality according to BMD categorized as normal (T-score < –1), osteopenia (T-score ≤ –1 and > –2.5), and osteoporosis (T-score ≤ –2.5). There were 528 low-trauma fractures in women and 187 in men. Of these, 12% occurred in individuals with normal BMD (38 women, 50 men) and 42% in individuals with osteopenia (221 women, 76 men). The relative risk (RR) of subsequent fracture was >2.0-fold for all levels of BMD (normal BMD: 2.0 [1.2 to 3.3] for women and 2.1 [1.2 to 3.8] for men; osteopenia: 2.1 [1.7 to 2.6] for women and 2.5 [1.6 to 4.1] for men; and osteoporosis 3.2 [2.7 to 3.9] for women and 2.1 [1.4 to 3.1] for men. The likelihood of falling and reduced quadriceps strength contributed to subsequent fracture risk in women with normal BMD. By contrast with subsequent fracture risk, postfracture mortality was increased particularly in individuals with low BMD (age-adjusted standardized mortality ratio [SMR] for osteopenia 1.3 [1.1 to 1.7] and 2.2 [1.7 to 2.9] for women and men, respectively, and osteoporosis 1.7 [1.5 to 2.0] and 2.7 [2.0 to 3.6] for women and men, respectively). This study demonstrates the high burden of subsequent fracture in individuals with normal BMD and osteopenia, and excess mortality particularly for those with osteopenia (and osteoporosis). These findings highlight the importance of these fractures and underscore the gap in evidence for benefit of antiosteoporotic treatment for fragility fracture, in those with only mildly low BMD. © 2014 American Society for Bone and Mineral Research.
T Cell–Expressed CD40L Potentiates the Bone Anabolic Activity of Intermittent PTH Treatment
Authors: Robinson Jerid W , Li Jau-Yi , Walker Lindsey D , Tyagi Abdul Malik , Reott Michael A , Yu Mingcan , Adams Jonathan , Weitzmann M Neale , Pacifici Roberto
Published: October 2014

T cells are known to potentiate the bone anabolic activity of intermittent parathyroid hormone (iPTH) treatment. One of the involved mechanisms is increased T cell secretion of Wnt10b, a potent osteogenic Wnt ligand that activates Wnt signaling in stromal cells (SCs). However, additional mechanisms might play a role, including direct interactions between surface receptors expressed by T cells and SCs. Here we show that iPTH failed to promote SC proliferation and differentiation into osteoblasts (OBs) and activate Wnt signaling in SCs of mice with a global or T cell–specific deletion of the T cell costimulatory molecule CD40 ligand (CD40L). Attesting to the relevance of T cell–expressed CD40L, iPTH induced a blunted increase in bone formation and failed to increase trabecular bone volume in CD40L–/– mice and mice with a T cell–specific deletion of CD40L. CD40L null mice exhibited a blunted increase in T cell production of Wnt10b and abrogated CD40 signaling in SCs in response to iPTH treatment. Therefore, expression of the T cell surface receptor CD40L enables iPTH to exert its bone anabolic activity by activating CD40 signaling in SCs and maximally stimulating T cell production of Wnt10b. © 2014 American Society for Bone and Mineral Research.
Sclerostin Inhibition Prevents Spinal Cord Injury-Induced Cancellous Bone Loss
Authors: Beggs Luke A , Ye Fan , Ghosh Payal , Beck Darren T , Conover Christine F , Balaez Alexander , Miller Julie R , Phillips Ean G , Zheng Nigel , Williams Alyssa A , Aguirre JIgnacio , Wronski Thomas J , Bose Prodip K , Borst Stephen E , Yarrow Joshua F
Published: October 2014

Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte-derived glycoprotein that negatively regulates intraskeletal Wnt signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. Our primary purposes were to determine whether a sclerostin antibody (Scl-Ab) prevents hindlimb cancellous bone loss in a rodent SCI model and to compare the effects of a Scl-Ab to that of testosterone-enanthate (TE), an agent that we have previously shown prevents SCI-induced bone loss. Fifty-five (n = 11–19/group) skeletally mature male Sprague-Dawley rats were randomized to receive: (A) SHAM surgery (T8 laminectomy), (B) moderate-severe (250 kilodyne) SCI, (C) 250 kilodyne SCI + TE (7.0 mg/wk, im), or (D) 250 kilodyne SCI + Scl-Ab (25 mg/kg, twice weekly, sc) for 3 weeks. Twenty-one days post-injury, SCI animals exhibited reduced hindlimb cancellous bone volume at the proximal tibia (via μCT and histomorphometry) and distal femur (via μCT), characterized by reduced trabecular number and thickness. SCI also reduced trabecular connectivity and platelike trabecular structures, indicating diminished structural integrity of the remaining cancellous network, and produced deficits in cortical bone (femoral diaphysis) strength. Scl-Ab and TE both prevented SCI-induced cancellous bone loss, albeit via differing mechanisms. Specifically, Scl-Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCI + Scl-Ab and SCI + TE animals, whereas only Scl-Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI-induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl-Ab prevents osteoporosis in the SCI population. © 2014 American Society for Bone and Mineral Research.
N‐methyl‐D‐aspartate receptor channel blockers prevent pentylenetetrazole‐induced convulsions and morphological changes in rat brain neurons
Authors: Zaitsev Aleksey V. , Kim Kira Kh. , Vasilev Dmitry S. , Lukomskaya Nera Ya. , Lavrentyeva Valeria V. , Tumanova Natalia L. , Zhuravin Igor A. , Magazanik Lev G.
Published: October 2014

Alterations in inhibitory and excitatory neurotransmission play a central role in the etiology of epilepsy, with overstimulation of glutamate receptors influencing epileptic activity and corresponding neuronal damage. N‐methyl‐D‐aspartate (NMDA) receptors, which belong to a class of ionotropic glutamate receptors, play a primary role in this process. This study compared the anticonvulsant properties of two NMDA receptor channel blockers, memantine and 1‐phenylcyclohexylamine (IEM‐1921), in a pentylenetetrazole (PTZ) model of seizures in rats and investigated their potencies in preventing PTZ‐induced morphological changes in the brain. The anticonvulsant properties of IEM‐1921 (5 mg/kg) were more pronounced than those of memantine at the same dose. IEM‐1921 and memantine decreased the duration of convulsions by 82% and 37%, respectively. Both compounds were relatively effective at preventing the tonic component of seizures but not myoclonic seizures. Memantine significantly reduced the lethality caused by PTZ‐induced seizures from 42% to 11%, and all animals pretreated with IEM‐1921 survived. Morphological examination of the rat brain 24 hr after administration of PTZ revealed alterations in the morphology of 20–25% of neurons in the neocortex and the hippocampus, potentially induced by excessive glutamate. The expression of the excitatory amino acid transporter 1 protein was increased in the hippocampus of the PTZ‐treated rats. However, dark neurons did not express caspase‐3 and were immunopositive for the neuronal nuclear antigen protein, indicating that these neurons were alive. Both NMDA antagonists prevented neuronal abnormalities in the brain. These results suggest that NMDA receptor channel blockers might be considered possible neuroprotective agents for prolonged seizures or status epilepticus leading to neuronal damage. © 2014 Wiley Periodicals, Inc.
In vitro and in vivo evaluation of heparin mediated growth factor release from tissue‐engineered constructs for anterior cruciate ligament reconstruction
Authors: Leong Natalie L. , Arshi Armin , Kabir Nima , Nazemi Azadeh , Petrigliano Frank A. , Wu Ben M. , McAllister David R.
Published: October 2014

Anterior cruciate ligament (ACL) rupture is a common injury often necessitating surgical treatment with graft reconstruction. Due to limitations associated with current graft options, there is interest in a tissue‐engineered substitute for use in ACL regeneration. While they represent an important step in translation to clinical practice, relatively few in vivo studies have been performed to evaluate tissue‐engineered ACL grafts. In the present study, we immobilized heparin onto electrospun polycaprolactone scaffolds as a means of incorporating basic fibroblast growth factor (bFGF) onto the scaffold. In vitro, we demonstrated that human foreskin fibroblasts (HFFs) cultured on bFGF‐coated scaffolds had significantly greater cell proliferation. In vivo, we implanted electrospun polycaprolactone grafts with and without bFGF into athymic rat knees. We analyzed the regenerated ACL using histological methods up to 16 weeks post‐implantation. Hematoxylin and eosin staining demonstrated infiltration of the grafts with cells, and picrosirius red staining demonstrated aligned collagen fibers. At 16 weeks postop, mechanical testing of the grafts demonstrated that the grafts had approximately 30% the maximum load to failure of the native ACL. However, there were no significant differences observed between the graft groups with or without heparin‐immobilized bFGF. While this study demonstrates the potential of a regenerative medicine approach to treatment of ACL rupture, it also demonstrates that in vitro results do not always predict what will occur in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:229–236, 2015.
Peri‐operative epidural may not be the preferred form of analgesia in select patients undergoing pancreaticoduodenectomy
Authors: Axelrod Trevor M. , Mendez Bernardino M. , Abood Gerard J. , Sinacore James M. , Aranha Gerard V. , Shoup Margo
Published: October 2014

Background and Objectives

Epidural analgesia has become the preferred method of pain management for major abdominal surgery. However, the superior form of analgesia for pancreaticoduodenecomy (PD), with regard to non‐analgesic outcomes, has been debated. In this study, we compare outcomes of epidural and intravenous analgesia for PD and identify pre‐operative factors leading to early epidural discontinuation.

Methods

A retrospective review was performed on 163 patients undergoing PD between 2007 and 2011. We performed regression analyses to measure the predictive success of two groups of analgesia on morbidity and mortality and to identify predictors of epidural failure.

Results

Intravenous analgesia alone was given to 14 (9%) patients and 149 patients (91%) received epidural analgesia alone or in conjunction with intravenous analgesia. Morbidity and mortality were not significantly different between the two groups. Early epidural discontinuation was necessary in 22 patients (15%). Those older than 72 and with a BMI < 20 (n = 5) had their epidural discontinued in 80% of cases compared to 12% not meeting these criteria. However, early epidural discontinuation was not associated with increased morbidity and mortality.

Conclusion

Epidural analgesia may be contraindicated in elderly, underweight patients undergoing PD given their increased risk of epidural‐induced hypotension or malfunction. J. Surg. Oncol. 2015 111:306–310. © 2014 Wiley Periodicals, Inc.
Perineural invasion in oral squamous cell carcinoma: Quantitative subcategorisation of perineural invasion and prognostication
Authors: Aivazian Karina , Ebrahimi Ardalan , Low Tsu‐Hui (Hubert) , Gao Kan , Clifford Anthony , Shannon Kerwin , Clark Jonathan R. , Gupta Ruta
Published: October 2014

Background

Evidence regarding the prognostic value of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) and whether PNI alone warrants consideration of adjuvant therapy is controversial. We evaluated whether histopathological sub‐categorization of PNI improves risk stratification.

Methods

PNI was evaluated for nerve size, number of foci, and distance from the tumor in 318 OSCC patients. Univariable and multivariable analyses were performed, with local failure (LF) and disease‐specific survival (DSS) as the primary endpoints.

Results

PNI did not influence prognosis when classified as absent versus present. In contrast, multifocal PNI was associated with LF (P = 0.049) and decreased DSS (P = 0.043) on multivariable analyses. The size of the involved nerve separated those with multifocal PNI into intermediate (<1 mm) and high‐risk (≥1 mm) groups. Unifocal PNI and distance from the tumor did not influence prognosis. Multifocal PNI was associated with worse prognosis irrespective of post‐operative radiotherapy (PORT).

Conclusions

Multifocal PNI is associated with poor outcomes even with PORT suggesting consideration of therapeutic escalation, particularly with involved nerves ≥1 mm. Unifocal PNI did not affect prognosis even in the absence of PORT, which may not be required if this is the sole risk factor. Prospective validation and testing of these hypotheses is essential before implementation. J. Surg. Oncol. 2015 111:352–358. © 2014 Wiley Periodicals, Inc.
Nanocomposites of Phosphonic‐Acid‐Functionalized Polyethylenes with Inorganic Quantum Dots
Authors: Rünzi Thomas , Baier Moritz C. , Negele Carla , Krumova Marina , Mecking Stefan
Published: November 2014

Insertion of diethyl vinyl phosphonates and free vinyl phosphonic acid, respectively, into [(P^O)Pd(Me)(dmso)] ((P^O) =κ2‐P,O‐Ar2PC6H4SO2O with Ar = 2‐MeOC6H4) (1‐dmso) occurs in a 2,1‐ as well as 1,2‐fashion, to form a four‐and a five‐membered chelate [(P^O)Pd{κ2‐C,O‐CH(P(O)(OR)2)CH2CH3}] and [(P^O)Pd{κ2‐C,O‐CH2CH(P(O)(OR)2)CH3}] (R = H, Et). No decomposition or other reactions of 1 by free phosphonic acid moieties occur. Copolymerization in a pressure reactor by 1‐dmso yields linear random poly(ethylene‐co‐diethyl vinyl phosphonate) and poly(ethylene‐co‐vinyl phosphonic acid). In these copolymerizations, reversible coordination of the phosphonate moieties of free monomer as well as chelate formation by incorporated monomer retards chain growth as also evidenced by relative binding studies of diethyl phosphonate towards 1. Post‐polymerization emulsification of poly(ethylene‐co‐vinyl phosphonic acid) together with CdSe/CdS quantum dots (QDs) yields submicron (ca. 50 nm from dynamic light scattering (DLS) and transmission electron microscopy (TEM)) polymer particles with the QDs embedded in the functionalized polyethylene in a nonaggregated fashion. This embedding benefits the fluorescence behavior in terms of continuous emission and life‐time as revealed by wide‐field fluorescence measurements. These composite particle dispersions are employed as a ″masterbatch” together with an aqueous high density polyethylene (HDPE) dispersion to generate thin films (by spin‐coating) and bulk materials (from the melt), respectively, in which the inorganic nanoparticles remain highly disperse.

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