bluuebunny/crossref_metadata_2025 huggingface dataset:
Core–shell biopolymer microspheres for sustained drug release
Authors: Tan Liqing , Jiang Tao , Yang Xiaolan , Li Wei , Pan Lijun , Yu Mingan
Published: December 2014

In this work, a core–shell biopolymer microsphere comprising a carvedilol‐loaded yeast cell wall polysaccharides core surrounded by a silk fibroin shell layer is developed to eliminate the risks of using synthetic polymers for drug encapsulation on human health and to avoid burst release and to prolong the release time. Transmission electron microscopy, Fourier‐transform infrared, confocal laser scanning microscope, and phase contrast microscopy analysis indicate that yeast treated with Tris–HCl containing cetyltrimethylammonium bromide, EDTA, and NaCl could provide much larger space for host drug as compared to plasmolyzed cells because the former can help maintain the original shape of yeast cells. In addition, its permeability barrier is significantly altered and nucleus becomes pyknotic. In contrast, plasmolyzed cells can hardly maintain the rigidity and integrity of their cell walls and will finally end up with cell fragments. SEM observation reveals that the carvedilol‐loaded cells maintain very similar shape and size before and after coating with 0.1% silk fibroin. In vitro release studies show that a drug delivery system using the carvedilol‐loaded cells can achieve a sustained drug release up to 20 days probably due to the electrostatic interaction between the positively charged carvedilol and the negatively charged yeast cells at the pH 7.4 and to the stability of the yeast cell helped by silk fibroin that provides an effective diffusion barrier. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41782.
Total Synthesis of Maoecrystal V
Authors: Zhang Wei‐Bin , Lin Guang , Shao Wen‐Bin , Gong Jian‐Xian , Yang Zhen
Published: December 2014

Maoecrystal V (1) is a novel diterpenoid, which was originally isolated from the leaves of the Chinese medicinal herb Isodon eriocalyx in 2004 by Sun et al.1 It has been found to be selectively cytotoxic towards HeLa cells, with an IC50 value of 20 ng mL−1. Significant research efforts have been devoted to the synthesis of maoecrystal V because of its intriguing biological properties, rarity in nature, and complex structural features. Herein, we describe our recent investigations, which have culminated in the total synthesis of (±)‐maoecrystal V. The current strategy involved three key steps for the successful construction of the key tetrahydrofuran oxa‐bridge skeleton, including a Wessely oxidative dearomatization, a novel intramolecular Diels–Alder reaction, and a RhII‐catalyzed OH insertion reaction.
A fast sensor for in vivo quantification of cytosolic phosphate in Saccharomyces cerevisiae
Authors: Zhang Jinrui , Sassen Tom , ten Pierick Angela , Ras Cor , Heijnen Joseph J. , Wahl Sebastian Aljoscha
Published: December 2014

Eukaryotic metabolism consists of a complex network of enzymatic reactions and transport processes which are distributed over different subcellular compartments. Currently, available metabolite measurement protocols allow to measure metabolite whole cell amounts which hinder progress to describe the in vivo dynamics in different compartments, which are driven by compartment specific concentrations. Phosphate (Pi) is an essential component for: (1) the metabolic balance of upper and lower glycolytic flux; (2) Together with ATP and ADP determines the phosphorylation energy. Especially, the cytosolic Pi has a critical role in disregulation of glycolysis in tps1 knockout. Here we developed a method that enables us to monitor the cytosolic Pi concentration in S. cerevisiae using an equilibrium sensor reaction: maltose + Pi < = > glucose + glucose‐1‐phosphate. The required enzyme, maltose phosphorylase from L. sanfranciscensis was overexpressed in S. cerevisiae. With this reaction in place, the cytosolic Pi concentration was obtained from intracellular glucose, G1P and maltose concentrations. The cytosolic Pi concentration was determined in batch and chemostat (D = 0.1 h−1) conditions, which was 17.88 µmol/gDW and 25.02 µmol/gDW, respectively under Pi‐excess conditions. Under Pi‐limited steady state (D = 0.1 h−1) conditions, the cytosolic Pi concentration dropped to only 17.7% of the cytosolic Pi in Pi‐excess condition (4.42 µmol/gDW vs. 25.02 µmol/gDW). In response to a Pi pulse, the cytosolic Pi increased very rapidly, together with the concentration of sugar phosphates. Main sources of the rapid Pi increase are vacuolar Pi (and not the polyPi), as well as Pi uptake from the extracellular space. The temporal increase of cytosolic Pi increases the driving force of GAPDH reaction of the lower glycolytic reactions. The novel cytosol specific Pi concentration measurements provide new insight into the thermodynamic driving force for ATP hydrolysis, GAPDH reaction, and Pi transport over the plasma and vacuolar membranes. Biotechnol. Bioeng. 2015;112: 1033–1046. © 2014 Wiley Periodicals, Inc.
Stoichiometric model and flux balance analysis for a mixed culture of Leptospirillum ferriphilum and Ferroplasma acidiphilum
Authors: Merino M. P. , Andrews B. A. , Asenjo J. A.
Published: December 2014

The oxidation process of sulfide minerals in natural environments is achieved by microbial communities from the Archaea and Bacteria domains. A metabolic reconstruction of two dominant species, Leptospirillum ferriphilum and Ferroplasma acidiphilum, which are always found together as a mixed culture in this natural environments, was made. The metabolic model, composed of 152 internal reactions and 29 transport reactions, describes the main interactions between these species, assuming that both use ferrous iron as energy source, and F. acidiphilum takes advantage of the organic compounds secreted by L. ferriphilum for chemomixotrophic growth. A first metabolic model for a mixed culture used in bacterial leaching is proposed in this article, which pretends to represent the characteristics of the mixed culture in a simplified manner. It was evaluated with experimental data through flux balance analysis (FBA) using as objective function the maximization of biomass. The growth yields on ferrous iron obtained for each microorganism are consistent with experimental data, and the flux distribution obtained allows understanding of the metabolic capabilities of both microorganisms growing together in a bioleaching process. The model was used to simulate the growth of F. acidiphilum on different substrates, to determine in silico which compounds maximize cell growth, and which are essential. Knockout simulations were carried out for L. ferriphilum and F. acidiphilum metabolic models, predicting key enzymes of central metabolism. The results of this analysis are consistent with experimental data from literature, showing a robust behavior of the metabolic model. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:307–315, 2015
Characterization of the Gene Cluster CYP264B1‐geoA from Sorangium cellulosum So ce56: Biosynthesis of (+)‐Eremophilene and Its Hydroxylation
Authors: Schifrin Alexander , Ly Thuy T. B. , Günnewich Nils , Zapp Josef , Thiel Verena , Schulz Stefan , Hannemann Frank , Khatri Yogan , Bernhardt Rita
Published: December 2014

Terpenoids can be found in almost all forms of life; however, the biosynthesis of bacterial terpenoids has not been intensively studied. This study reports the identification and functional characterization of the gene cluster CYP264B1–geoA from Sorangium cellulosum So ce56. Expression of the enzymes and synthesis of their products for NMR analysis and X‐ray diffraction were carried out by employing an Escherichia coli whole‐cell conversion system that provides the geoA substrate farnesyl pyrophosphate through simultaneous overexpression of the mevalonate pathway genes. The geoA product was identified as a novel sesquiterpene, and assigned NMR signals unambiguously proved that geoA is an (+)‐eremophilene synthase. The very tight binding of (+)‐eremophilene (∼0.40 μM), which is also available in S. cellulosum So ce56, and its oxidation by CYP264B1 suggest that the CYP264B1–geoA gene cluster is required for the biosynthesis of (+)‐eremophilene derivatives.
Supramolecular Encapsulation of Neutral Diazoacetate Esters and Catalyzed 1,3‐Dipolar Cycloaddition Reaction by a Self‐Assembled Hexameric Capsule
Authors: La Sorella Giorgio , Sperni Laura , Strukul Giorgio , Scarso Alessandro
Published: December 2014

Diazoacetate esters proved to be suitable neutral guests for the self‐assembled resorcin[4]arene hexameric capsule. The hydrogen‐bonded supramolecular host catalyzed the 1,3‐dipolar cycloaddition reaction between diazoacetate esters and electron‐poor alkenes such as acrolein, acrylonitrile, predominantly trans‐crotonaldehyde, trans‐2‐hexenal, methyl, and butyl acrylate, which led to the corresponding 4,5‐dihydro‐1H‐pyrazole derivatives. The cycloaddition reaction occurred within the cavity of the capsule. In fact, substantial inhibition of the catalytic activity was observed by employing tetraethylammonium tetrafluoroborate characterized by greater affinity for the hexameric capsule as a competitive guest; its presence inhibited access of the substrates. The 1,3‐dipolar cycloaddition reaction between diazoacetate esters and acrylate esters of different lengths showed a significant degree of substrate selectivity owing to the encapsulation of the reagents before the cycloaddition reaction.
Synthesis of Nanocrystalline CeO2 with High Surface Area by the Taguchi Method and its Application in Methanation
Authors: Nematollahi Behzad , Rezaei Mehran , Nemati Lay Ebrahim
Published: December 2014

Mesoporous nanocrystalline cerium(IV) oxide (CeO2) with high surface area was synthesized by precipitation using a cationic surfactant and employed as support for a nickel catalyst in CO methanation. The preparation factors of CeO2 were optimized by the Taguchi method to achieve a sample with high surface area. The obtained results reveal that the sample prepared under optimized conditions has a mesoporous structure with high surface area and crystallite size. The addition of a surfactant significantly influences the structural properties of CeO2 and improves the specific surface area. The optimized sample was employed as support for a nickel catalyst in CO methanation reaction. The prepared catalyst possessed a high activity compared to a commercial methanation catalyst.
Combustion and Agglomeration Characteristics of the Residue from Corn Stalk‐Based Cellulosic Ethanol
Authors: Ren Qiangqiang , Li Shiyuan , Wang Dongyu , Bao Shaolin , Lu Qinggang
Published: December 2014

Lignocellulose is considered an efficient raw material to produce fuel ethanol. Clean utilization of the solid residue derived from lignocellulose‐based fuel ethanol is important for the biomass‐to‐ethanol production chain. Combustion characteristics of the residue originating from corn stalk‐based cellulosic ethanol are studied in a circulating fluidized bed. Results indicate that circulating fluidized‐bed combustion is an effective and stable way to burn the residue with high moisture content. CO emission during biomass combustion in a circulating fluidized bed is low in the range of several ppm. NO and N2O are the major pollutants during residue combustion. The optimal combustion temperature is limited to avoid agglomeration and reduce pollutant emission. Design data and theoretical support for design and operation of the residue combustion circulating fluidized‐bed boiler are provided.
Stereoselective Synthesis and Physicochemical Properties of Liquid‐Crystal Compounds Possessing a trans‐2,5‐Disubstituted Tetrahydropyran Ring with Negative Dielectric Anisotropy
Authors: Araki Keisuke , Yamamoto Tetsuya , Tanaka Ryoji , Tanaka Saori , Ushioda Makoto , Gotoh Yasuyuki , Yamakawa Tetsu , Inoue Munenori
Published: December 2014

Three stereoselective syntheses and the physicochemical properties of trans,trans‐5‐(4‐ethoxy‐2,3‐difluorophenyl)‐2‐(4‐propylcyclohexyl)tetrahydropyran, which is an important liquid‐crystal compound with a large negative dielectric anisotropy (Δε=−7.3), are described. The key step in the construction of the trans‐2,5‐disubstituted tetrahydropyran ring in the first approach involved a benzylic cation mediated intramolecular olefin cyclization of a 2‐allyloxy‐1‐arylethanol derivative. The second method included the Et2Zn‐induced 1,2‐aryl shift of a bromohydrin obtained from a hetero‐Diels–Alder reaction, followed by stereoselective bromination. The third approach utilized the hetero‐Diels–Alder reaction of trans‐4‐propylcyclohexanecarboxaldehyde and a 2‐aryl‐3‐(trimethylsilyl)oxy‐1,3‐butadiene, followed by stereoselective protonation. From results obtained by using a quantum chemical calculation method, the reason why the target compound shows a large negative Δε value is discussed.
Towards Reaction Control: An Expeditious Access to Racemic 5‐Substituted Tetramates and 5‐Substituted Tetramic Acids from Malimides
Authors: Huang Pei‐Qiang , Ou Wei , Ye Jian‐Liang
Published: December 2014

A versatile and divergent two‐step transformation of malimides to racemic tetramates and tetramic acids is described. The method consists of Grignard reagent addition with malimides to give hemiaminals and concentrated HCl‐promoted chemoselective transformations of the latter. When running the reaction in CH2Cl2 and in the presence of 2.5 molar equiv. of conc. HCl, 5‐alkyltetramates were formed, while in neat conc. HCl, 5‐alkyltetramic acids were obtained. Using this method, a variety of title compounds were prepared in good to excellent yields (82%–99%, and 76%/85%). The work also constitutes a formal racemic total synthesis of reutericyclin. On the basis of the experimental evidences and of a deuterium labeling experiment, a plausible reaction mechanism was proposed. This work thus demonstrated two new types of step economical and chemodivergent transformations starting from malic acid.
Feedback in the brainstem: An excitatory disynaptic pathway for control of whisking
Authors: Matthews David W. , Deschênes Martin , Furuta Takahiro , Moore Jeffrey D. , Wang Fan , Karten Harvey J. , Kleinfeld David
Published: December 2014

Sensorimotor processing relies on hierarchical neuronal circuits to mediate sensory‐driven behaviors. In the mouse vibrissa system, trigeminal brainstem circuits are thought to mediate the first stage of vibrissa scanning control via sensory feedback that provides reflexive protraction in response to stimulation. However, these circuits are not well defined. Here we describe a complete disynaptic sensory receptor‐to‐muscle circuit for positive feedback in vibrissa movement. We identified a novel region of trigeminal brainstem, spinal trigeminal nucleus pars muralis, which contains a class of vGluT2+ excitatory projection neurons involved in vibrissa motor control. Complementary single‐ and dual‐labeling with traditional and virus tracers demonstrate that these neurons both receive primary inputs from vibrissa sensory afferent fibers and send monosynaptic connections to facial nucleus motoneurons that directly innervate vibrissa musculature. These anatomical results suggest a general role of disynaptic architecture in fast positive feedback for motor output that drives active sensation. J. Comp. Neurol. 523:921–942, 2015. © 2014 Wiley Periodicals, Inc.
Baseline Patient Characteristics Predicting Outcome and Attrition in Cognitive Therapy for Social Phobia: Results from a Large Multicentre Trial
Authors: Hoyer Juergen , Wiltink Joerg , Hiller Wolfgang , Miller Robert , Salzer Simone , Sarnowsky Stephan , Stangier Ulrich , Strauss Bernhard , Willutzki Ulrike , Leibing Eric
Published: December 2014

We examined the role of baseline patient characteristics as predictors of outcome (end‐state functioning, response and remission) and attrition for cognitive therapy (CT) in social anxiety disorder (SAD). Beyond socio‐demographic and clinical variables such as symptom severity and comorbidity status, previously neglected patient characteristics (e.g., personality, self‐esteem, shame, interpersonal problems and attachment style) were analysed.

Method

Data came from the CT arm of a multicentre RCT with n = 244 patients having DSM‐IV SAD. CT was conducted according to the manual by Clark and Wells. Severity of SAD was assessed at baseline and end of treatment with the Liebowitz Social Anxiety Scale (LSAS). Multiple linear regression analyses and logistic regression analyses were applied.

Results

Up to 37% of the post‐treatment variance (LSAS) could be explained by all pre‐treatment variables combined. Symptom severity (baseline LSAS) was consistently negatively associated with end‐state functioning and remission, but not with response. Number of comorbid diagnoses was negatively associated with end‐state functioning and response, but not with remission. Self‐esteem was positively associated with higher end‐state functioning and more shame with better response. Attrition could not be significantly predicted.

Conclusions

The results indicate that the initial probability for treatment success mainly depends on severity of disorder and comorbid conditions while other psychological variables are of minor importance, at least on a nomothetic level. This stands in contrast with efforts to arrive at an empirical‐based foundation for differential indication and argues to search for more potent moderators of therapeutic change rather on the process level.

Key Practitioner Message

Personality, self‐esteem, shame, attachment style and interpersonal problems do not or only marginally moderate the effects of interventions in CT of social phobia.

Symptom severity and comorbid diagnoses might affect treatment outcome negatively.

Beyond these two factors, most patients share a similar likelihood of treatment success when treated according to the manual by Clark and Wells.

Copyright © 2014 John Wiley & Sons, Ltd.
Der Eurocode 6 vor der bauaufsichtlichen Einführung
Authors: Schmidt‐Wottrich Jörg , Rast Ronald
Published: December 2014

Das Regelwerk zum Mauerwerksbau befindet sich nach wie vor in einer Umstellungsphase. Die endgültige bauaufsichtliche Einführung des Eurocode 6 zur Bemessung von Mauerwerkskonstruktionen ist ab dem Jahr 2015 vorgesehen. Die Koexistenz von DIN 1053 und Eurocode 6 soll mit der endgültigen bauaufsichtlichen Einführung des Eurocode 6 beendet werden. Bis dahin gelten die bisherigen nationalen Bemessungsnormen weiter. Zusätzlich konnte schon ab Mitte 2012 der Eurocode 6 (EC 6) über eine Gleichwertigkeitserklärung zur Anwendung kommen. Das Nebeneinander beider Normenwerke wirft verschiedene rechtliche Fragen auf, die im Beitrag diskutiert werden.

The Eurocode 6 prior to the final introduction by the building authority – Legal problems during and after the transition period. The rules for masonry construction are still in a transition phase. The final building inspection introduction of Eurocode 6 for the Design of masonry structures is provided from 2015. The coexistence of DIN 1053 and Eurocode 6 should be completed with the final building authority introduction of the Eurocode 6. Until then, the current national design codes shall continue to apply. In addition the Eurocode 6 could be applied on a system of equivalence statement since mid‐2012. The coexistence of both standard works raises several legal issues that will be discussed in the article.
Bemessung von Mauerwerk bei Erdbebenbeanspruchung
Authors: Fehling Ekkehard , Brenker Elena
Published: December 2014

In Mitteleuropa wird der überwiegende Teil der Wohngebäude sowie kleiner und mittlerer Büro‐ und Geschäftshäuser in Mauerwerksbauweise ausgeführt. Auch ein erheblicher Anteil des Gebäudebestands sind Mauerwerksbauten, deren Wände traditionell aus unbewehrtem Mauerwerk bestehen. Durch die Entwicklung der europäischen Normung, besonders im Hinblick auf die Eurocodes 6 und 8, sowie der nationalen Normen in Mitteleuropa wurde auch für Deutschland und die umliegenden Länder die Frage des Erdbebenwiderstands besonders bei Mauerwerksbauten aktuell. Anders als bei Stahlbetonbauwerken kann man nicht einfach durch Einlegen von etwas mehr Bewehrung erhöhte rechnerische Belastungen aufnehmen. Bewehrung in Mauerwerkswänden würde eine komplette Änderung der Bauweise bedingen, bei der eine Reihe der Vorzüge des Bauens mit Mauerwerk geopfert werden müssten. Der vorliegende Beitrag soll nach einer kurzen Beleuchtung der Problematik einen Überblick über Forschungsprojekte der letzten Zeit geben und Lösungsansätze aufzeigen, die auch teilweise die Normung beeinflusst haben. Dabei kommt es nicht nur auf Nachweismöglichkeiten an, die erhöhte Querschnittstragfähigkeiten von Mauerwerk nachweisbar machen, sondern auch auf den Aspekt der Verformungskapazität und des Zusammenwirkens unterschiedlicher Bauteile im Gesamttragwerk.

Design of masonry structures for seismic loading. In Central Europe many residential as well as small and medium office‐ and commercial buildings are built with masonry. Moreover, a major part of existing buildings also has been built in masonry. Typically, the masonry walls consist of unreinforced masonry. For this traditional way of building construction, the development of new national and international codes, especially Eurocode 6 and 8, has given rise to the question of the seismic resistance. Other than with reinforced concrete structures it is not possible to increase the resistance just by placing some more reinforcement. Placing reinforcement into masonry at all would mean a complete change of this traditional way of building so that a lot of advantages of unreinforced masonry might be lost. In this paper, following a brief presentation of the problem, an overview about research that has been conducted in this field during the past years shall be given. Furthermore, proposals for more realistic design checks as well as for developments which have influenced the design codes will be highlighted. In this regard, not only the bearing capacity of masonry cross sections is of importance but also the aspect of deformation capacity and the interaction of different structural members within a building.
Validation of the SCOFF questionnaire for eating disorders in a multiethnic general population sample
Authors: Solmi Francesca , Hatch Stephani L. , Hotopf Matthew , Treasure Janet , Micali Nadia
Published: December 2014

Introduction

This study aimed to validate the SCOFF, an eating disorders (ED) screening questionnaire, in a multiethnic general population sample of adults.

Method

A two‐stage design was employed using the South East London Community Health Study phases I and II data. A total of 1,669 participants were screened using the SCOFF in SELCoHI, and 145 were administrated an ED clinical interview in SELCoHII. We explored the diagnostic validity of the questionnaire restricting to the 145 individuals with the clinical questionnaire.

Results

Sensitivity and specificity of the SCOFF were 53.7 and 93.5%, respectively.

Conclusion

The SCOFF showed good levels of specificity but low sensitivity, resulting in a high percentage of false negatives. Given the low sensitivity found in our sample the SCOFF is likely to be a suboptimal measure for the identification of ED in the community. © 2014 The Authors International Journal of Eating Disorders Published by Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:312–316)
The histamine H4‐receptor (H4R) regulates eosinophilic inflammation in ovalbumin‐induced experimental allergic asthma in mice
Authors: Hartwig Christina , Munder Antje , Glage Silke , Wedekind Dirk , Schenk Heiko , Seifert Roland , Neumann Detlef
Published: December 2014

Via the histamine H4‐receptor (H4R), histamine promotes the pathogenesis of experimental allergic asthma in mice. Application of H4R antagonists during sensitization as well as during provocation reduces the severity of the disease. However, the specific cell types functionally expressing H4R in experimental allergic asthma have not been well characterized in vivo. In this study, we identified the cell type(s) responsible for H4R activity in experimental asthma and related physiological mechanisms. Using H4R‐deficient mice, we studied the role of H4R in the sensitization and effector phase. DCs lacking H4R expression during the in vitro sensitization reaction resulted in effector T cells unable to induce an entire eosinophilic inflammation in the lung upon adoptive transfer in vivo. Recipient mice lacking H4R expression, which were adoptively transferred with H4R+/+ T cells polarized in the presence of H4R+/+ DCs, showed reduced signs of inflammation and ameliorated lung function. Here, we provide in vivo evidence that in experimental asthma in mice the H4R specifically regulates activation of DCs during sensitization, while in the effector phase the H4R is active in cells involved in the activation of eosinophils, and possibly other cells. A putative therapy targeting the H4R may be an option for asthma patients developing IL‐5‐dependent eosinophilia.
Hexagonal‐Prism‐Shaped Optical Sensor/Captor for the Optical Recognition and Sequestration of PdII Ions from Urban Mines
Authors: Shenashen Mohamed A. , El‐Safty Sherif A. , Elshehy Emad A. , Khairy Mohamed
Published: December 2014

In this work, we have developed a hexagonal‐prism‐shaped optical sensor/captor (OSC) based on the immobilization of an organic probe into hexagonal, micrometric monoliths of mesoporous aluminosilica scaffolds for the colorimetric monitoring, selective sequestering, and effective recovery of PdII ions from urban mines as a promising technology for industrial applications. In such a solid OSC, H‐type aggregation and face‐to‐face (π–π* stacking) interactions between the heteroatoms‐coordinated organic probe and the active acid sites of the scaffolds lead to the formation of 1D molecular probe assemblies parallel to the interior pore walls. The design patterns of hexagonal‐prism‐shaped and open cylindrical pores (ca. 4 nm) exhibited suitable accommodation to protect the organic probe from extra H‐aggregates, as evidenced by the high affinity of the PdII–probe binding events. The OSC shows evidence of controlled PdII ion assessment in terms of the optical recognition of PdII ions down to sub‐nanomolar concentrations (3.3 × 10–9 mol/L). Our study shows that the developed OSC can be used as an effective tool for urban mining development, particularly for secondary resources in industrial countries.
Copper(I)‐Catalyzed One‐Pot Synthesis of Highly Functionalized Pyrrolidines from Sulfonyl Azides, Alkynes, and Dimethyl 2‐(Phenylamino)maleate
Authors: Ramanathan Devenderan , Pitchumani Kasi
Published: December 2014

An efficient one‐pot synthesis of highly functionalized pyrrolidines by using sulfonyl azides, alkynes, and dimethyl 2‐(phenylamino)maleate catalyzed by copper(I)–Y zeolite under mild reaction conditions was investigated. This cascade process involves an azide–alkyne [3+2] cycloaddition/ring rearrangement/ketenimine formation/intermolecular nucleophilic addition cascade and consequent intramolecular cyclization followed by [1,3]‐H shift. The important advantage of this methodology, which allows selective intramolecular nucleophilic attack of the generated ketenimine carbanion on an ester moiety for the first time, is that the starting materials can be easily prepared.
Inherently Chiral Calix[5]arenes Incorporating an Axially Chiral Binaphthyl Moiety: Synthesis, Structures and Chiral Recognition
Authors: Zhang Wen‐Zhen , Yang Ke , Li Si‐Zhe , Ma Hui , Luo Jun , Wang Kai‐Ping , Chung Wen‐Sheng
Published: December 2014

Inherent chirality was generated by regioselective monoalkylation of 1,3‐substituted calix[5]crown‐6 incorporating an axially chiral BINOL moiety, with ethyl bromoacetate. The resultant diastereomers 4a and 4b, which possess both axial chirality and inherent chirality, were readily separated by column chromatography. Respective hydrolysis afforded diastereomeric acids 5a and 5b. 1H NMR spectra and X‐ray crystallography established that esters 4a and 4b feature a cone‐in conformation, which disappears in the corresponding acids 5a and 5b due to intramolecular hydrogen‐bonding between the carboxyl group and a glycolic oxygen atom. Amino alcohol‐induced fluorescence quenching was observed for 5a and 5b. The highest enantioselectivity, based on the ratio of Stern–Volmer constants KSV(S)/KSV(R), reached 1.90 in the case of 5a with 2‐amino‐1‐phenylethanol (G1), and 5b with phenylalaninol (G2). The highest diastereoselectivity of 1.83, measured by KSV(5a)/KSV(5b), occurs in the case of 5a/5b with (R)‐G2.
Synthesis of Polycyclic Amines through Mild Metal‐Free Tandem Cross‐Dehydrogenative Coupling/Intramolecular Hydroarylation of N‐Aryltetrahydroisoquinolines and Crotonaldehyde
Authors: Wu Xiang , Chen Dian‐Feng , Chen Shu‐Sen , Zhu Yi‐Fan
Published: December 2014

A [4+2] cycloaddition reaction proceeding through tandem cross‐dehydrogenative coupling/intramolecular hydroarylation between N‐aryltetrahydroisoquinolines and crotonaldehyde was developed by virtue of enamine–iminium catalysis, which enabled the rapid construction of ring‐fused tetrahydroquinolines. The first metal‐free catalytic oxidative coupling of γ‐selective C(sp3)–H bonds of crotonaldehyde was realized by using a secondary amine catalyst and 2,3‐dichloro‐5,6‐dicyanoquinone.
Neuropathic pain in a primary care electronic health record database
Authors: Shadd J.D. , Ryan B.L. , Maddocks H.L. , McKay S.D. , Moulin D.E.
Published: December 2014

Background

Neuropathic pain (NP) is common in the adult population but is difficult to study in electronic health record (EHR) databases because it is a symptom rather than a pathologic diagnosis. The first step in studying NP in EHR databases is to develop methods for identifying patients with NP. The objectives of this study were to develop estimates of the prevalence of NP among patients in a primary care EHR database and describe these patients’ demographic characteristics and health‐care utilization.

Methods

This was a retrospective cohort study of de‐identified data from a 5‐year period (2005–2010) from 23 general practitioners (GPs) in 10 primary care practices in southwestern Ontario, Canada. International Classification of Diseases version 9 (ICD‐9) diagnostic codes and medication prescriptions were used to identify patients with certain and probable NP.

Results

Different methods produced prevalence estimates ranging from 1.5% (for certain NP in the epidemiologically rigorous period cohort) to 11.2% (for certain NP + probable NP in the more inclusive database cohort). Patients in the NP groups had more GP visits, specialist referrals and analgesic prescriptions than patients without NP.

Conclusion

This study represents a step towards being able to utilize EHR databases to study NP by proposing methods to identify patients with certain and probable NP in a primary care EHR database. Validation against a gold standard is the next step.
Transcriptional profiling identifies physicochemical properties of nanomaterials that are determinants of the in vivo pulmonary response
Authors: Halappanavar Sabina , Saber Anne Thoustrup , Decan Nathalie , Jensen Keld Alstrup , Wu Dongmei , Jacobsen Nicklas Raun , Guo Charles , Rogowski Jacob , Koponen Ismo K. , Levin Marcus , Madsen Anne Mette , Atluri Rambabu , Snitka Valentinas , Birkedal Renie K. , Rickerby David , Williams Andrew , Wallin Håkan , Yauk Carole L. , Vogel Ulla
Published: December 2014

We applied transcriptional profiling to elucidate the mechanisms associated with pulmonary responses to titanium dioxide (TiO2) nanoparticles (NPs) of different sizes and surface coatings, and to determine if these responses are modified by NP size, surface area, surface modification, and embedding in paint matrices. Adult C57BL/6 mice were exposed via single intratracheal instillations to free forms of TiO2NPs (10, 20.6, or 38 nm in diameter) with different surface coatings, or TiO2NPs embedded in paint matrices. Controls were exposed to dispersion medium devoid of NPs. TiO2NPs were characterized for size, surface area, chemical impurities, and agglomeration state in the exposure medium. Pulmonary transcriptional profiles were generated using microarrays from tissues collected one and 28 d postexposure. Property‐specific pathway effects were identified. Pulmonary protein levels of specific inflammatory cytokines and chemokines were confirmed by ELISA. The data were collapsed to 659 differentially expressed genes (P ≤ 0.05; fold change ≥ 1.5). Unsupervised hierarchical clustering of these genes revealed that TiO2NPs clustered mainly by postexposure timepoint followed by particle type. A pathway‐based meta‐analysis showed that the combination of smaller size, large deposited surface area, and surface amidation contributes to TiO2NP gene expression response. Embedding of TiO2NP in paint dampens the overall transcriptional effects. The magnitude of the expression changes associated with pulmonary inflammation differed across all particles; however, the underlying pathway perturbations leading to inflammation were similar, suggesting a generalized mechanism‐of‐action for all TiO2NPs. Thus, transcriptional profiling is an effective tool to determine the property‐specific biological/toxicity responses induced by nanomaterials. Environ. Mol. Mutagen. 56:245–264, 2015. © 2014 Wiley Periodicals, Inc.
Gender-Specific Differences in the Skeletal Response to Continuous PTH in Mice Lacking the IGF1 Receptor in Mature Osteoblasts
Authors: Babey Muriel , Wang Yongmei , Kubota Takuo , Fong Chak , Menendez Alicia , ElAlieh Hashem Z , Bikle Daniel D
Published: December 2014

The primary goal of this study was to determine whether the IGF1R in mature osteoblasts and osteocytes was required for the catabolic actions of continuous parathyroid hormone (cPTH). Igf1r was deleted from male and female FVN/B mice by breeding with mice expressing cre recombinase under control of the osteocalcin promoter (0CNIgfr1-/-). Littermates lacking the cre recombinase served as controls. PTH, 60 μg/kg/d, was administered continuously by Alzet minipumps for 4 weeks. Blood was obtained for indices of calcium metabolism. The femurs were examined by micro-computed tomography for structure, immunohistochemistry for IGF1R expression, histomorphometry for bone formation rates (BFR), mRNA levels by qPCR, and bone marrow stromal cell cultures (BMSC) for alkaline phosphatase activity (ALP+), mineralization, and osteoblast-induced osteoclastogenesis. Whereas cPTH led to a reduction in trabecular bone volume/tissue volume (BV/TV) and cortical thickness in the control females, no change was found in the control males. Although trabecular BV/TV and cortical thickness were reduced in the 0CNIgfr1-/- mice of both sexes, no further reduction after cPTH was found in the females, unlike the reduction in males. BFR was stimulated by cPTH in the controls but blocked by Igf1r deletion in the females. The 0CNIgfr1-/- male mice showed a partial response. ALP+ and mineralized colony formation were higher in BMSC from control males than from control females. These markers were increased by cPTH in both sexes, but BMSC from male 0CNIgfr1-/- also were increased by cPTH, unlike those from female 0CNIgfr1-/-. cPTH stimulated receptor activator of NF-κB ligand (RANKL) and decreased osteoprotegerin and alkaline phosphatase expression more in control female bone than in control male bone. Deletion of Igf1r blocked these effects of cPTH in the female but not in the male. However, PTH stimulation of osteoblast-driven osteoclastogenesis was blocked by deleting Igfr1 in both sexes. We conclude that cPTH is catabolic in female but not male mice. Moreover, IGF1 signaling plays a greater role in the skeletal actions of cPTH in the female mouse than in the male mouse, which may underlie the sex differences in the response to cPTH. © 2015 American Society for Bone and Mineral Research.
Elastic behavior of weakly cemented contact
Authors: Langlois V.
Published: December 2014

We investigate the elastic behavior of weakly cemented contact. We show that the radial distribution of stresses and the stiffnesses of a cemented contact are governed by the ratio a/RΛ, where R, a, and Λ are, respectively, the grain radius, the contact size, and the ratio of the elastic moduli of cement and grains. Moreover, we show that a cemented contact is always less stiff than a Hertzian contact having a similar size. Finally, we propose accurate approximate expressions of the contact stiffnesses. Copyright © 2014 John Wiley & Sons, Ltd.
Heterogeneous asynchronous time integrators for computational structural dynamics
Authors: Gravouil A. , Combescure A. , Brun M.
Published: December 2014

Computational structural dynamics plays an essential role in the simulation of linear and nonlinear systems. Indeed, the characteristics of the time integration procedure have a critical impact on the feasibility of the calculation. In order to go beyond the classical approach (a unique time integrator and a unique timescale), the pioneer approach of Belytschko and co‐workers consisted in developing mixed implicit–explicit time integrators for structural dynamics. In a first step, the implementation and stability analyses of partitioned integrators with one time step have been achieved for a large class of time integrators. In a second step, the implementation and stability analyses of partitioned integrators with different time steps were studied in detail for particular cases. However, stability results involving different time steps and different time integrators in different parts of the mesh is still an open question in the general case for structural dynamics. The aim of this paper is to propose a state‐of‐the art of heterogeneous (different time schemes) asynchronous (different time steps) time integrators (HATI) for computational structural dynamics. Finally, an alternative approach based on energy considerations (with velocity continuity at the interface) is proposed in order to develop a general class of HATI for structural dynamics. Copyright © 2014 John Wiley & Sons, Ltd.
One Plus One Equals Three
Authors: Lang Marion
Published: December 2014

Any biomedical technique needs to prove its applicability in day‐to‐day research and diagnosis, not only in “hero‐experiments”. And the success of a new imaging method significantly depends on the cost and complexity of the employed instrument with the laser playing a major part in both aspects. This is especially true when ultrashort laser pulses are required which is the case for all nonlinear imaging techniques. In this article, we will discuss the advantages of fiber lasers for integrated instruments and present a new cost‐effective and maintenance‐free fiber laser concept that provides femtosecond pulses at three fixed wavelengths. This allows exciting all conventional fluorescent markers and enables simultaneous multi‐color 2‐photon imaging with short acquisition times.
White LED with Excellent Rendering of Daylight Spectrum
Authors: Kon Tomoya , Kusano Tamio
Published: December 2014

In recent years, white LEDs have been increasingly used to replace conventional lighting sources including fluorescent lights. However, in some specific lighting applications, the use of such LEDs to replace halogen and xenon lights can present certain problems, such as in spectral distribution and the color rendering index (CRI).
United States Physical Therapists' Knowledge About Joint Hypermobility Syndrome Compared with Fibromyalgia and Rheumatoid Arthritis
Authors: Russek Leslie N. , LaShomb Emily A. , Ware Amy M. , Wesner Sarah M. , Westcott Vanessa
Published: December 2014

Background

Joint hypermobility syndrome (JHS) is one of the most common inherited connective tissue disorders. It causes significant pain and disability for all age groups, ranging from developmental delay among children to widespread chronic pain in adults. Experts in JHS assert that the condition is under‐recognized and poorly managed.

Purpose

The aim of this study was to assess US physical therapists' knowledge about JHS compared with other causes of widespread pain and activity limitations: fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis.

Methods

Cross‐sectional, Internet‐based survey of randomly selected members of the American Physical Therapy Association and descriptive statistics were used to explore physical therapists' knowledge about JHS, fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis, and chi square was used to compare knowledge about the different conditions.

Results

The response rate was 15.5% (496). Although 36% recognized the Beighton Scale for assessing joint hypermobility, only 26.8% of respondents were familiar with the Brighton Criteria for diagnosing JHS. Few respondents (11–19%) realized that JHS has extra‐articular features such as anxiety disorder, fatigue, headache, delayed motor development, easy bruising and sleep disturbance. Physical therapists working in environments most likely to see patients with JHS underestimated the likely prevalence in their patient population.

Conclusions

The results suggest that many physical therapists in the United States are not familiar with the diagnostic criteria, prevalence or common clinical presentation of JHS. Copyright © 2014 John Wiley & Sons, Ltd.
Fragmentation behavior of poly(methyl methacrylate) during matrix‐assisted laser desorption/ionization
Authors: Iura Tomomi , Ohtani Hajime
Published: December 2014

RATIONALE

Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) has been widely utilized for the structural characterization of various synthetic polymers. However, polymer sample molecules can occasionally decompose even in the MALDI process depending on the measurement conditions. In this work, the fragmentation behavior of radically polymerized poly(methyl methacrylate) (PMMA) during laser irradiation in MALDI was investigated in detail.

METHODS

Two types of PMMA samples with oligomeric molar mass were examined: Sample A was synthesized with an excess content of a chain transfer reagent to form simple molecules with less labile structures. Sample B was polymerized with a greater amount of a peroxide initiator without any chain transfer reagent, which resulted in the formation of various terminal and chain structures including relatively labile ones. The original components and fragment ions for the PMMA samples were precisely assigned using a high‐resolution MALDI spiral time‐of‐flight MS system. Electrospray ionization MS measurements were also performed for comparison.

RESULTS

The PMMA chains underwent fragmentation during the MALDI process with high laser intensity even for the relatively stable sample A. The fragmentation reactions proceeded mainly through 1,5‐hydrogen rearrangements via a six‐membered intermediate structure. Furthermore, PMMA molecules formed via recombination termination in sample B selectively decomposed during the MALDI‐MS measurements even with low laser intensity.

CONCLUSIONS

It was observed that the fragmentation reactions in the PMMA chains in MALDI with high laser power were generally the same as those in the post‐source decay or collision‐induced dissociation in MALDI‐MS/MS measurements. Even with low laser intensity, less stable structures in the PMMA chain, especially head‐to‐head linkages, were readily decomposed during the MALDI process. Possible fragmentation, therefore, should be considered in the structural characterization of synthetic polymer samples by MALDI‐MS. Copyright © 2014 John Wiley & Sons, Ltd.
Superwetting Surfaces under Different Media: Effects of Surface Topography on Wettability
Authors: Zhang Pengchao , Wang Shasha , Wang Shutao , Jiang Lei
Published: December 2014

Superwetting surfaces in air, such as superhydrophobic and superoleophobic surfaces that are governed by surface chemical compositions and surface topographies, are one of the most extensively studied topics in this field. However, it is not well‐understood how surface topographies affect the behaviors of immiscible liquids and gases under other kinds of media, although it is significant in diverse fields. The main aim of this work is to systematically investigate the wetting behaviors of liquids (water and oil) and gas (air) on silicon surfaces with different topographies (i.e., smooth, micro, nano, and micro‐/nanostructures) under various media (i.e., air, water, and oil). The contact angles, as well as contact‐angle hysteresis, sliding angles, and adhesive forces, were utilized to evaluate the wettability of these surfaces. As a result, the microstructured surfaces typically exhibit high contact‐angle hysteresis, high sliding angles, and high adhesive forces, whereas the micro‐/nanostructured surfaces display low contact‐angle hysteresis, low sliding angles, and low adhesive forces, even if they have high (>150°) and similar contact angles. Furthermore, when transferring the same surface from one kind of medium to another, different superwetting states can be reversibly switched.
Partial characterization of chayotextle starch composites with added polyvinyl alcohol
Authors: Cotonieto‐Morales Montserrat B. , Palma‐Rodríguez Heidi M. , Chavarría‐Hernández Norberto , Hernández‐Uribe Juan P. , Zamudio‐Flores Paul B. , Bello‐Pérez Luis A. , Vargas‐Torres Apolonio
Published: December 2014

Composites of chayotextle starch (ChS), cellulose (C), cellulose nanoparticles (CN), and polyvinyl alcohol (PVOH) were cast and characterized in physicochemical, mechanical, barrier, and morphological studies. Low mechanical property values were observed in ChS composites. In general, the mechanical properties were improved with increased PVOH concentration and with the addition of C or CN. With increased C or CN concentrations in the composite, the melting temperature increased (137.5 to 174°C for increase from 0.8 to 1.2% C), and the melting enthalpy value decreased (12.5 to 3.3 J/g for increase from 0.8 to 1.2% CN). Microphotography revealed that lower concentrations of C or CN improved the ChS and PVOH distribution in the composites. The water vapor permeability (WVP) of the composite decreased in relation to that of control samples with the addition of C and CN. These studies demonstrate that the mechanical, barrier, and functional properties of chayotextle starch composites can be modified with the addition of PVOH, C, or CN.
Modeling the Ripple Effects of IT‐Based Incidents on Interdependent Economic Systems
Authors: Ali Jalal , Santos Joost R.
Published: December 2014

The information technology (IT) sector is one of the most critically utilized infrastructures within the U.S. economic system. The IT sector is vulnerable to man‐made attacks and it is challenging to assess the consequences of disruptions to the production and delivery of essential IT services to other economic systems. In this paper, we developed a dynamic model based on economic input–output analysis to assess time‐varying disruptions on the IT sector over multiple periods. The model is applied in an ex post analysis of an actual denial‐of‐service (DoS) attack scenario on the IT infrastructure to estimate the consequences propagated to interdependent economic systems. The model uses Bureau of Economic Analysis data to simulate the effects of IT‐based incidents and subsequently identify the critically affected economic sectors. Key results of the case study include assessments of ripple effects to vulnerable sectors in the form of inoperability and economic loss measures. An investigation of the DoS attack in year 2000 using the proposed dynamic model revealed significant losses that are consistent with the magnitude of losses from previous studies. Furthermore, the model is capable of depicting the breakdown of losses across various economic sectors, which is a significant improvement relative to previously published results. This research also extends into a multiyear trend analysis (1999–2009) to aid in developing policies for reducing the effects of IT risks across the interdependent sectors of the U.S. economy.
Von der Röhre zum Chip
Authors: Boslau Oliver
Published: December 2014

Auf dem Weg zur Miniaturisierung wird der offensichtliche Einsatz von Vakuumtechnologie immer geringer. Nun kommt sie versteckter, wie z. B. bei der Herstellung von Mikrochips, zur Anwendung. Wie dieser an den Konsumgütern überall abzulesende Trend auch die Forschung und Entwicklung betrifft wird am Beispiel moderner Analytikgeräte gezeigt, in denen immer öfter herkömmliche Photomultiplier (PMT) durch Silizium‐Photomultiplier (SiPM) abgelöst werden.