bluuebunny/crossref_metadata_2025 huggingface dataset:
The RhoGAP activity of CYK-4/MgcRacGAP functions non-canonically by promoting RhoA activation during cytokinesis
Authors: Zhang Donglei , Glotzer Michael
Published: August 2015

Cytokinesis requires activation of the GTPase RhoA. ECT-2, the exchange factor responsible for RhoA activation, is regulated to ensure spatiotemporal control of contractile ring assembly. Centralspindlin, composed of the Rho family GTPase-activating protein (RhoGAP) MgcRacGAP/CYK-4 and the kinesin MKLP1/ZEN-4, is known to activate ECT-2, but the underlying mechanism is not understood. We report that ECT-2-mediated RhoA activation depends on the ability of CYK-4 to localize to the plasma membrane, bind RhoA, and promote GTP hydrolysis by RhoA. Defects resulting from loss of CYK-4 RhoGAP activity can be rescued by activating mutations in ECT-2 or depletion of RGA-3/4, which functions as a conventional RhoGAP for RhoA. Consistent with CYK-4 RhoGAP activity contributing to GEF activation, the catalytic domains of CYK-4 and ECT-2 directly interact. Thus, counterintuitively, CYK-4 RhoGAP activity promotes RhoA activation. We propose that the most active form of the cytokinetic RhoGEF involves complex formation between ECT-2, centralspindlin and RhoA.
The Role of "Tone at The Top" and Knowledge of Fraud on Auditors’ Professional Skeptical Behavior
Authors: Noviyanti Suzy , Winata Lanita
Published: August 2015

Auditors need to be professionally skeptical when they are conducting an audit. Skeptical behavior is especially needed when there are indications of fraud in the audited entity. Without skepticism, fraud is likely to be overlooked, because fraud is usually concealed by the perpetrators. This experimental study aimed to investigate the influence of skeptical attitude, tone at the top, and knowledge of fraud on auditors’ professional skeptical behavior. The study participants were junior auditors, senior auditors, and auditor supervisors. The analysis led to three key findings in this study. First, skeptical attitude, tone at the top, and the auditor’s knowledge of fraud influenced the skeptical behavior of professional auditors. Second, a high tone at the top of the partner’s style played an important role in maintaining and improving auditors’ professional skeptical behavior, particularly for auditors who had a weak skeptical attitude. This result supported the theory of the attitudes–behavior relationship described by Fazio (1990) in the MODE model. Third, auditors’ knowledge about fraud improved their professional skeptical behavior. However, knowledge of fraud did not influence auditors’ professional behavior if those auditors had weak skeptical attitudes and were supervised by a supervisor with a low tone at the top style.

Keywords: Tone at The Top, The MODE Model, Professional Skepticism, Knowledge of Fraud

To cite this document: Suzy Noviyanti and Lanita Winata, "The Role of "Tone at The Top" and Knowledge of Fraud on Auditors’ Professional Skeptical Behavior", Contemporary Management Research, Vol.11, No.1, pp.55-74, 2015.

Permanent link to this document:
http://dx.doi.org/10.7903/cmr.12239
The formation of graben morphology in the Dead Sea Fault, and its implications
Authors: Ben‐Avraham Zvi , Katsman Regina
Published: August 2015

The Dead Sea Fault (DSF) is a 1000 km long continental transform. It forms a narrow and elongated valley with uplifted shoulders showing an east‐west asymmetry, which is not common in other continental transforms. This topography may have strongly affected the course of human history. Several papers addressed the geomorphology of the DSF, but there is still no consensus with respect to the dominant mechanism of its formation. Our thermomechanical modeling demonstrates that existence of a transform prior to the rifting predefined high strain softening on the faults in the strong upper crust and created a precursor weak zone localizing deformations in the subsequent transtensional period. Together with a slow rate of extension over the Arabian plate, they controlled a narrow asymmetric morphology of the fault. This rift pattern was enhanced by a fast deposition of evaporites from the Sedom Lagoon, which occupied the rift depression for a short time period.
Approximate analytical formulation of radial diffusion and whistler‐induced losses from a preexisting flux peak in the plasmasphere
Authors: Mourenas D. , Artemyev A. V. , Agapitov O. V.
Published: August 2015

Modeling the spatiotemporal evolution of relativistic electron fluxes trapped in the Earth's radiation belts in the presence of radial diffusion coupled with wave‐induced losses should address one important question: how deep can relativistic electrons penetrate into the inner magnetosphere? However, a full modeling requires extensive numerical simulations solving the comprehensive quasi‐linear equations describing pitch angle and radial diffusion of the electron distribution, making it rather difficult to perform parametric studies of the flux behavior. Here we consider the particular situation where a localized flux peak (or storage ring) has been produced at low L < 4 during a period of strong disturbances, through a combination of chorus‐induced energy diffusion (or direct injection) at low L together with enhanced wave‐induced losses and outward radial transport at higher L. Assuming that radial diffusion can be further described as the spatial broadening within the plasmasphere of this preexisting flux peak, simple approximate analytical solutions for the distribution of trapped relativistic electrons are derived. Such a simplified formalism provides a convenient means for easily determining whether radial diffusion actually prevails over atmospheric losses at any particular time for given electron energy E and location L. It is further used to infer favorable conditions for relativistic electron access to the inner belt, providing an explanation for the relative scarcity of such a feat under most circumstances. Comparisons with electron flux measurements on board the Van Allen Probes show a reasonable agreement between a few weeks and 4 months after the formation of a flux peak.
Self‐Assembled Peptide–Polyfluorene Nanocomposites for Biodegradable Organic Electronics
Authors: Khanra Soma , Cipriano Thiago , Lam Thomas , White Tommi A. , Fileti Eudes E. , Alves Wendel A. , Guha Suchismita
Published: August 2015

Based on self‐assembly and mimicking strategies occurring in nature, peptide nanomaterials play a unique role in a new generation of hybrid materials for the electronics of the 21st century. This report describes the functionalization of diphenylalanine (FF)‐based micro/nanostructures with blue‐emitting conducting polymers of the polyfluorene (PF) family. The FF:PF polymer nanocomposites are synthesized by a liquid‐vapor phase method. Electron microscopy images reveal di‐octyl‐substituted PF (PF8) to bind better to the FF micro/nanotubes in comparison with ethyl‐hexyl PF (PF2/6), which influences its optical properties. Molecular dynamics simulations of FF nanotubes with monomeric units of PFs show that PF8 favors greater proximity to the grooves on the surface of the nanotubes due to a higher van der Waals interaction energy compared to PF2/6. The FF:PF nanocomposites are further utilized in light‐emitting diodes. Biodegradability tests from FF:PF8 nanocomposite films show more than 80% weight loss in 2 h by enzymatic action compared to PF8 pristine films, which do not degrade. Self‐assembly of FF nanostructures with organic semiconductors opens up a new generation of biocompatible and biodegradable materials in organic electronics.
Binary and ternary mixtures of liquid crystals with CO2
Authors: de Groen M. , Vlugt T. J. H. , de Loos T. W.
Published: August 2015

Liquid crystals, elongated molecules with a structured liquid phase, may be used as new solvents for CO2 capture. However, no molecule has been found yet with optimal properties. Therefore, mixtures of two liquid crystals and CO2 are investigated. Also, the phase behavior of some binary subsystems of the investigated ternary systems is studied for comparison. In the mixtures investigated, 4,4′‐pentyloxycyanobiphenyl + 4,4′‐heptyloxycyanobiphenyl + CO2 and 4,4′‐propylcyclohexylbenzonitrile + 4,4′‐heptylcyclohexylbenzonitrile + CO2, the nematic phases form a nematic homogeneous solution and the solid phases form an eutectic system, leading to a material with improved properties for CO2 capture. Moreover, the ternary mixture of 4,4′‐propylcyclohexylbenzonitrile + 4,4′‐heptylcyclohexylbenzonitrile + CO2 showed an increased solubility of CO2 compared with the binary subsystems. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2977–2984, 2015
Application of the functional renormalization group method to classical free energy models
Authors: Lue Leo
Published: August 2015

A simple functional renormalization group method is presented to correct the behavior of classical free energy models near the critical point. This approach is applied to the Soave–Redlich–Kwong equation of state to illustrate its ability to better reproduce the phase behavior of simple fluids and to understand the influence of its parameters on the shape of the vapor‐liquid phase diagram. The method is then extended to account for the correlations induced by intramolecular bonds. It is then applied to a first‐order thermodynamic perturbation theory for chain fluids to examine fluids composed of linearly bonded Lennard‐Jones atoms. Unlike previous approaches for applying renormalization group corrections to chain fluids, this is able to accurately reproduce the critical point without predicting an overly flat liquid‐vapor coexistence region. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2985–2992, 2015
Chest circumference and sitting height among children and adolescents from Lhasa, tibet compared to other high altitude populations
Authors: Xi Huanjiu , Chen Zhao , Li Wenhui , Wen Youfeng , Zhang Hailong , Xiao Yanjie , Liu Suwei , Pei Linguo , Zhang Meizhi , Lv Po , Ren Fu , Huang Keqiang , Ye Liping , Li Chunshan , Zhao Liguang
Published: August 2015

Objectives

The adaptation of human beings to a high altitude environment during growth has been reported in several populations but is less known for Tibetans. The objective of this study was to investigate similarities and differences of Tibetans in patterns and characteristics of physical growth and development in comparison to other high altitude populations.

Methods

We measured the stature, weight, chest circumference and sitting height of 2,813 healthy children and adolescents aged 6‐ to 21‐year‐old living at 3,658–4,500 m in Tibet, China, and compared them with published data from other high altitude populations. Eligible participants must have been born and raised in Tibet, and both their parents’ families have to be Tibetan for at least the past three generations.

Results

The physical growth and development of children and adolescents in Tibet and the Andes followed similar patterns, such as delayed growth, short stature and sitting height, and large chest dimensions. Relative to stature, Tibetan sitting heights are similar to Andeans, but chest circumferences are smaller.

Conclusions

Findings from this study reinforce the conclusion that Tibetan and Andean populations have adapted differently to high altitude hypoxia. The physical features of each population may result from unique adaptation to hypoxia, as well as socio‐ecological factors, such as poor nutrition. Am. J. Hum. Biol. 28:197–202, 2016. © 2015 Wiley Periodicals, Inc.
Synthetische Adhäsion von Integrin‐Liposomen als minimales Zellmodell
Authors: Frohnmayer Johannes P. , Brüggemann Dorothea , Eberhard Christian , Neubauer Stefanie , Mollenhauer Christine , Boehm Heike , Kessler Horst , Geiger Benjamin , Spatz Joachim P.
Published: August 2015

Um die mit der Zelladhäsion zusammenhängenden molekularen Signalwege aufzuklären, bieten synthetische Zellen den einzigartigen Vorteil eines gut kontrollierten Modellsystems mit reduzierter molekularer Komplexität. In der vorliegenden Arbeit zeigen wir, dass Liposome mit rekonstituiertem Blutplättchenintegrin αIIbβ3 als adhäsionsvermittelndes Transmembranprotein für ein funktionales, minimales Zellmodell dienen können, um zelluläre Adhäsionsmechanismen in einer definierten Umgebung zu studieren. Die Wechselwirkung dieser synthetischen Zellen mit unterschiedlichen extrazellulären Matrixproteinen wurde mithilfe der Quarzkristallmikrowaage mit Dissipationsanalyse (QCM‐D; quartz crystal microbalance with dissipation monitoring) untersucht. Die Daten zeigten, dass Integrin funktionell in die Lipidvesikel inkorporiert wurde, wodurch die integrinspezifische Adhäsion der hergestellten Liposome auf mit Fibrinogen (Fg) und Fibronektin (Fn) funktionalisierten Oberflächen möglich war. Anschließend konnte das Ablösen der Integrin‐Liposome von diesen Oberflächen bei Zugabe des Peptids GRGDSP eingeleitet werden. Effizienter erfolgte das Ablösen mit unserem neu synthetisierten Peptidmimetikum SN529, das spezifisch Integrin αIIbβ3 blockiert.
Functional polyelectrolyte multilayer assemblies for surfaces with controlled wetting behavior
Authors: Huang Xiayun , Zacharia Nicole S.
Published: August 2015

Controlled wetting at surfaces and interfaces is an important area of research with numerous potential commercial applications. Both superhydrophobicity and superhydrophilicity can be used to enable applications such as self‐cleaning, dropwise condensation, or antifogging. Many strategies for creating such surfaces center around biomimicry, replicating the structure of the lotus leaf, for example. Given the potential impact, creating surfaces with these properties using any number of fabrication is of great interest. One very promising fabrication technique, however, for creating these surfaces is the layer‐by‐layer (LbL)‐directed self‐assembly of polyelectrolytes and other charged materials. LbL is a sequential adsorption technique wherein a surface is exposed to first a solution of one charge and then a solution of the opposite charge. LbL has many advantages, including the ability to incorporate many different types of materials and therefore functionality, the ability to conformally coat substrates of complex geometry, and environmentally friendly aqueous processing. This review describes recent progress in using LbL to create surfaces with controlled wetting. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42767.
CLIPing Staufen to secondary RNA structures: Size and location matter!
Authors: Fernández Moya Sandra M. , Kiebler Michael A.
Published: August 2015

hiCLIP (RNA hybrid and individual‐nucleotide resolution ultraviolet cross‐linking and immunoprecipitation), is a novel technique developed by Sugimoto et al. (2015). Here, the use of different adaptors permits a controlled ligation of the two strands of a RNA duplex allowing the identification of each arm in the duplex upon sequencing. The authors chose a notoriously difficult to study double‐stranded RNA‐binding protein (dsRBP) termed Staufen1, a mammalian homolog of Drosophila Staufen involved in mRNA localization and translational control. Using hiCLIP, they discovered a dominance of intramolecular RNA duplexes compared to the total RNA duplexes identified. Importantly, the authors discovered two different types of intramolecular duplexes in the cell: highly translated mRNAs with long‐range duplexes in their 3′‐UTRs and poorly translated mRNAs with duplexes in their coding region. In conclusion, the authors establish hiCLIP as an important novel technique for the identification of RNA secondary structures that serve as in vivo binding sites for dsRBPs.
Grauhörnchen vs. Eichhörnchen
Authors: Bosch Stefan , Lurz Peter W. W.
Published: August 2015

Mit der Aussetzung nordamerikanischer Grauhörnchen in England, Irland und Norditalien entstand für den bislang einzigen endemischen Hörnchen‐Vertreter in Europa – dem Eichhörnchen – eine völlig neue Konkurrenzsituation. Um die Biologie beider Arten sowie ihre Interaktionen besser zu verstehen und um Schutzstrategien zu entwickeln, wurden viele Aspekte erforscht. Dieser Beitrag gibt eine Übersicht über den komplexen Wettstreit der beiden Hörnchenarten um Ressourcen im Wald. Als Hauptfaktoren des Konkurrenzkampfes gelten die Lebensraumstruktur und das Nahrungsangebot, die beide direkt auf die individuelle Kondition sowie die Fortpflanzung Einfluss nehmen. Auf den britischen Inseln spielt zusätzlich ein Pockenvirus eine Rolle.
Offshore‐Windräder als Mückeninseln
Authors: Kronberg Inge
Published: August 2015

Offshore‐Windparks sind Vorzeigeprojekte der Energiewende. Aus ökologischer Sicht handelt es sich bei den Windrädern um neue Miniatur‐Inseln im Meer, die eine potenzielle Besiedlungsfläche darstellen. Eine kleine Zuckmücke aus dem Pazifik zeigt bespielhaft, wie schnell Arten solche Flächen kolonisieren können.
Herbstspaziergänge: Begegnungen mit Raupen
Authors: Petrischak Hannes
Published: August 2015

Zum Ende des Sommers nimmt die Zahl der Insekten in Wald und Flur deutlich ab. Nur noch wenige Schmetterlinge gaukeln über blütenarme Wiesen. Doch einige häufige Nachtfalter‐Raupen sind gerade im September und Oktober kaum zu übersehen und ermöglichen somit interessante Beobachtungen im Herbst.
Sprung aus der “Höhle des Löwen”
Authors: Sander Johannes
Published: August 2015

Manche Ameisenarten besitzen Schnappfallenkiefer, die ihnen als Multifunktionswerkzeug zur Beutejagd, zur Verteidigung und – wie sich jetzt zeigt – auch zur Flucht dienen.
Mensch und Schwein
Authors: Wuketits Franz M.
Published: August 2015

Der Mensch pflegt zu Schweinen eine ambivalente Beziehung. Er bewundert und verachtet sie zugleich, sie liefern ihm nicht nur Nahrung, sondern sind auch eine sprudelnde Quelle für Metaphern und Schimpfwörter. Schweine zählen zu den ältesten Nutzhaustieren, gelten aber in manchen Kulturen als “unrein”. Nach wie vor ranken sich um diese stattlichen Paarhufer allerlei Missverständnisse.
Time‐course effect of high‐glucose‐induced reactive oxygen species on mitochondrial biogenesis and function in human renal mesangial cells
Authors: Al‐Kafaji Ghada , Sabry Mohamed Abdalla , Skrypnyk Cristina
Published: August 2015

The present study investigated the time‐course effect of high‐glucose‐induced reactive oxygen species (ROS) on mitochondrial biogenesis and function in human renal mesangial cells and the effect of direct inhibition of ROS on mitochondria. The cells were cultured for 1, 4, and 7 days in normal glucose or high glucose in the presence and absence of Mn(III)tetrakis(4‐benzoic acid)porphyrin chloride (MnTBAP) or catalase. Mitochondrial ROS production was assessed by confocal microscope. mtDNA copy number and peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (PGC‐1α), nuclear respiratory factors 1 (NRF‐1), and mitochondrial transcription factor A (TFAM) transcripts were analyzed by real‐time PCR. PGC‐1α, NRF‐1, and TFAM proteins were analyzed by Western blotting. Mitochondrial function was determined by assessing mitochondrial membrane potential and adenosine triphosphate (ATP) levels. High glucose induced significant increases in mitochondrial superoxide and hydrogen peroxide (H2O2) at day 1, which remained significantly elevated at days 4 and 7. The copy number of mtDNA and expression of PGC‐1α, NRF‐1, and TFAM were significantly increased at 1 day in high glucose but were significantly decreased at 4 and 7 days. A progressive decrease in mitochondrial membrane potential was observed at 1, 4, and 7 days in high glucose, and this was associated with decreased ATP levels. Treatment of cells with MnTBAP or catalase during high‐glucose incubation attenuated ROS production and reversed the alterations in mitochondrial biogenesis and function. Increased mitochondrial biogenesis in human renal mesangial cells may be an early adaptive response to high‐glucose‐induced ROS, and prolonged ROS production induced by chronic high glucose decreased mitochondrial biogenesis and impaired mitochondrial function. Protection of mitochondria from high‐glucose‐induced ROS may provide a potential approach to retard the development and progression of diabetic nephropathy.
Chemistry of N,S‐Heterocyclic Carbene and Metallaboratrane Complexes: A New η3‐BCC‐Borataallyl Complex
Authors: Roy Dipak Kumar , De Anangsha , Panda Subhankar , Varghese Babu , Ghosh Sundargopal
Published: August 2015

A high‐yielding synthetic route for the preparation of group 9 metallaboratrane complexes [Cp*MBH(L)2], 1 and 2 (1, M=Rh, 2, M=Ir; L=C7H4NS2) has been developed using [{Cp*MCl2}2] as precursor. This method also permitted the synthesis of an Rh–N,S‐heterocyclic carbene complex, [(Cp*Rh)(L2)(1‐benzothiazol‐2‐ylidene)] (3; L=C7H4NS2) in good yield. The reaction of compound 3 with neutral borane reagents led to the isolation of a novel borataallyl complex [Cp*Rh(L)2B{CH2C(CO2Me)}] (4; L=C7H4NS2). Compound 4 features a rare η3‐interaction between rhodium and the B‐C‐C unit of a vinylborane moiety. Furthermore, with the objective of generating metallaboratranes of other early and late transition metals through a transmetallation approach, reactions of rhoda‐ and irida‐boratrane complexes with metal carbonyl compounds were carried out. Although the objective of isolating such complexes was not achieved, several interesting mixed‐metal complexes [{Cp*Rh}{Re(CO)3}(C7H4NS2)3] (5), [Cp*Rh{Fe2(CO)6}(μ‐CO)S] (6), and [Cp*RhBH(L)2W(CO)5] (7; L=C7H4NS2) have been isolated. All of the new compounds have been characterized in solution by mass spectrometry, IR spectroscopy, and 1H, 11B, and 13C NMR spectroscopies, and the structural types of 4–7 have been unequivocally established by crystallographic analysis.
Proton‐Coupled Electron Transfer Reactions Catalysed by 3 d Metal Complexes
Authors: Siewert Inke
Published: August 2015

Proton‐coupled electron transfer (PCET) reactions are essential for a wide range of natural energy‐conversion reactions and recently, the impact of PCET pathways has been exploited in artificial systems, too. The Minireview highlights PCET reactions catalysed by first‐row transition‐metal complexes, with a focus on the water oxidation, the oxygen reduction, the hydrogen evolution, and the CO2 reduction reaction. Special attention will be paid to systems in which the impact of such pathways is deduced by comparison to systems with “electron‐only”‐transfer pathways.
A Novel Cathode Material for Cathodic Dehalogenation of 1,1‐Dibromo Cyclopropane Derivatives
Authors: Gütz Christoph , Selt Maximilian , Bänziger Markus , Bucher Christoph , Römelt Christina , Hecken Nadine , Gallou Fabrice , Galvão Tomás R. , Waldvogel Siegfried R.
Published: August 2015

Leaded bronze turned out to be an excellent cathode material for the dehalogenation reaction of cyclopropanes without affecting the strained molecular entity. With this particular alloy, beneficial properties of lead cathodes are conserved, whereas the corrosion of cathode is efficiently suppressed. The solvent in the electrolyte determines whether a complete debromination reaction is achieved or if the process can be selectively stopped at the monobromo cyclopropane intermediate. The electroorganic conversion tolerates a variety of functional groups and can be conducted at rather complex substrates like cyclosporine A. This approach allows the sustainable preparation of cyclopropane derivatives.
First Total Synthesis of Trehalose‐Containing Branched Oligosaccharide OSE‐1 of Mycobacterium gordonae (Strain 990)
Authors: Chaube Manishkumar A. , Kulkarni Suvarn S.
Published: August 2015

The first total synthesis of the branched oligosaccharide OSE‐1 of Mycobacterium gordonae (strain 990) is reported. An intramolecular aglycon delivery approach was used for constructing the desymmetrized 1,1′‐α,α‐linked trehalose moiety. A [3+2] glycosylation of the trisaccharide donor and trehalose acceptor furnished the right hand side pentasaccharide. Regioselective O3 glycosylation of L‐rhamnosyl 2,3‐diol allowed expedient synthesis of the left hand side tetrasaccharide. The nonasaccharide was assembled in a highly convergent fashion through a [4+5] glycosylation.
Entwicklung eines Design for End of Life Tools für die Luftfahrtindustrie
Authors: Wimmer Ann‐Kathrin , Salles Ana , Müller Torsten , Elsner Peter
Published: August 2015

Im Rahmen des Projekts Clean Sky wurde ein Ecodesign Guideline Tool für die Luftfahrtindustrie entwickelt. Entsprechend den Zielen des europäischen Beratungsgremiums für die Luft‐ und Raumfahrt (ACARE) wurden zahlreiche luftfahrtspezifische Life Cycle Assessment Daten zu Materialien und Materialkombinationen gesammelt und in ein neu entwickeltes, einfach handhabbares Datenbanktool implementiert. Somit bietet das Tool eine robuste Grundlage für ein drittes Entscheidungskriterium neben Kosten und Gewicht. Das Tool ist auf die End of Life Phase fokussiert, insb. auf Wirtschaftlichkeit, Separation und Recyclingprozesse.
Thermodynamic and kinetic study of the production of oxygenated compounds: Synthesis of 1,1‐diethoxybutane catalyzed by amberlyst‐15
Authors: Rahaman Mehabub , Graça Nuno S. , Pereira Carla S. M. , Rodrigues Alírio E.
Published: August 2015

The aim of the present work is a thermodynamic and kinetic study of the acetalization reaction between butyraldehyde and ethanol to produce the acetal 1,1‐diethoxybutane (DEB). The reaction was catalyzed by the commercial ion‐exchange resin Amberlyst‐15. Through a study of the reaction thermodynamic equilibrium, it was possible to determine the equilibrium constant value as a function of temperature, , and the corresponding thermodynamic parameters, and . Additionally, the standard enthalpy and Gibbs free energy of DEB formation were also calculated, as and , respectively. A mathematical model considering mass‐transfer limitations was used to simulate the batch reactor operation. The parameters estimated for the mathematical model were and . This acetalization reaction presents activation energy of .
4‐Alkylated Silver–N‐Heterocyclic Carbene (NHC) Complexes with Cytotoxic Effects in Leukemia Cells
Authors: Sandtorv Alexander H. , Leitch Calum , Bedringaas Siv Lise , Gjertsen Bjørn Tore , Bjørsvik Hans‐René
Published: August 2015

Computational chemistry has shown that backbone‐alkylated imidazoles ought to be efficient ligands for transition metal catalysts with improved carbene‐to‐metal donation. In this work, such alkylated imidazoles were synthesized and complexed with silver(I) by means of an eight/nine‐step synthetic pathway we devised to access a new class of biologically active silver complexes. The synthesis involves selective iodination of the imidazole backbone, followed by Sonogashira coupling to replace the backbone iodine. The installed alkyne moiety is then subjected to reductive hydrogenation with Pearlman’s catalyst. The imidazole N1 atom is arylated by the palladium‐catalyzed Buchwald N‐arylation method. The imidazole N3 position was then methylated with methyl iodine, whereupon the synthesis was terminated by complexation of the imidazolium salt with silver(I) oxide. The synthetic pathway provided an overall yield of ≈20 %. The resulting complexes were tested in vitro against HL60 and MOLM‐13 leukemic cells, two human‐derived cell lines that model acute myeloid leukemia. The most active compounds exhibiting low IC50 values of 14 and 27 μM, against HL60 and MOLM‐13 cells, respectively. The imidazole side chain was found to be essential for high cytotoxicity, as the imidazole complex bearing a C7 side chain at the 4‐position was four‐ to sixfold more potent than the corresponding imidazole elaborated with a methyl group.
Diagnostic utility of phosphorylated signal transducer and activator of transcription 5 immunostaining in the diagnosis of mammary analogue secretory carcinoma of the salivary gland: A comparative study of salivary gland cancers
Authors: Kawahara Akihiko , Taira Tomoki , Abe Hideyuki , Takase Yorihiko , Kurita Takashi , Sadashima Eiji , Hattori Satoshi , Imamura Ichio , Matsumoto Shinji , Fujisaki Hitomi , Sueyoshi Kazunobu , Akiba Jun , Kage Masayoshi
Published: August 2015

BACKGROUND

Mammary analogue secretory carcinoma (MASC) with an ETS variant gene 6 (ETV6)–neurotrophic tyrosine kinase receptor type 3 (NTRK3) translocation is a newly described type of salivary gland cancer. It is known that overexpression of signal transducer and activator of transcription 5a (STAT5a) occurs in secretory carcinoma of the breast and MASC, and STAT5a expression may be related to the ETV6‐NTRK3 translocation. It was hypothesized that phosphorylated signal transducer and activator of transcription 5 (p‐STAT5) might be specifically expressed in MASC of the salivary gland.

METHODS

The expression of p‐STAT5 and mammaglobin (MMG) was examined with immunohistochemistry (IHC)/immunocytochemistry (ICC) in tissue sections from 58 salivary gland cancers (8 MASCs and 50 other salivary gland cancers) and in cytological smears from 17 salivary gland cancers (7 MASCs with paired histologic samples and 10 other salivary gland cancers).

RESULTS

p‐STAT5 IHC was clearly increased in MASC versus normal salivary gland tissue and other salivary gland cancers. p‐STAT5 expression was found in 7 of 8 MASCs (87.5%) and in none of the 50 other salivary gland cancers (0%) by IHC. On cytology, p‐STAT5 expression was found in all cases of MASC (7 of 7 or 100%) but in none of the 10 other salivary gland cancers (0%) by ICC. The expression rate of MMG by histology and cytology was higher than that of p‐STAT5 in the other salivary gland cancers.

CONCLUSIONS

p‐STAT5 might be useful as a detection marker of MASC in the differential diagnosis of salivary gland cancers, and initial screening with p‐STAT5 IHC/ICC, combined with auxiliary fluorescence in situ hybridization confirmation, is a reliable, economical approach to identifying MASC of the salivary gland. Cancer (Cancer Cytopathol) 2015;123:603–11. © 2015 American Cancer Society.
Numerical simulation of electrocardiograms for full cardiac cycles in healthy and pathological conditions
Authors: Schenone Elisa , Collin Annabelle , Gerbeau Jean‐Frédéric
Published: August 2015

This work is dedicated to the simulation of full cycles of the electrical activity of the heart and the corresponding body surface potential. The model is based on a realistic torso and heart anatomy, including ventricles and atria. One of the specificities of our approach is to model the atria as a surface, which is the kind of data typically provided by medical imaging for thin volumes. The bidomain equations are considered in their usual formulation in the ventricles, and in a surface formulation on the atria. Two ionic models are used: the Courtemanche–Ramirez–Nattel model on the atria and the ‘minimal model for human ventricular action potentials’ by Bueno‐Orovio, Cherry, and Fenton in the ventricles. The heart is weakly coupled to the torso by a Robin boundary condition based on a resistor–capacitor transmission condition. Various electrocardiograms (ECGs) are simulated in healthy and pathological conditions (left and right bundle branch blocks, Bachmann's bundle block, and Wolff–Parkinson–White syndrome). To assess the numerical ECGs, we use several qualitative and quantitative criteria found in the medical literature. Our simulator can also be used to generate the signals measured by a vest of electrodes. This capability is illustrated at the end of the article. Copyright © 2015 John Wiley & Sons, Ltd.
Co‐administration of N‐Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity
Authors: Owumi Solomon E , Andrus James P , Herzenberg Leonard A , Herzenberg Leonore A
Published: August 2015

Preclinical Research

Although acetaminophen (APAP) is an effective analgesic and anti‐pyretic, APAP overdose is the most frequent cause of serious, often lethal, drug‐induced hepatotoxicity. Administration of N‐acetyl cysteine (NAC) within 8 hours of APAP overdose effectively mitigates APAP‐induced hepatotoxicity. Thus, preventing APAP toxicity before it occurs by formulating APAP with NAC is logical and, as we show here in a mouse model, is effective in preventing APAP toxicity. Thus, toxic oral APAP doses sufficient to cause severe widespread liver damage do not cause significant damage when administered concurrently with equal amounts of NAC, that is, in the NAC‐APAP treated animals, hepatic transaminases increase only marginally and liver architecture remains fully intact. Thus, we conclude that concomitant oral dosing with APAP and NAC can provide a convenient and effective way of preventing toxicity associated with large dosage of APAP. From a public health perspective, these findings support the concept that a co‐formulation of APAP plus NAC is a viable over‐the‐counter (OTC) alternative to the current practice of providing APAP OTC and treating APAP toxicity if/when it occurs. In essence, our findings indicate that replacing the current OTC APAP with a safe and functional APAP/NAC formulation could prevent the accidental and intentional APAP toxicity that occurs today. Drug Dev Res 76 : 251‐258, 2015. © 2015 Wiley Periodicals, Inc.
Molecular characterization and follow‐up of five CML patients with new BCR–ABL1 fusion transcripts
Authors: Huet Sarah , Dulucq Stéphanie , Chauveau Aurélie , Ménard Audrey , Chomel Jean‐Claude , Maisonneuve Hervé , Legros Laurence , Perrin Marie‐Claire , Ferrant Emmanuelle , Moreilhon Chimène , Couturier Marie‐Anne , Sujobert Pierre , Magaud Jean‐Pierre , Ugo Valérie , Chabane Kaddour , Raynaud Sophie , Hayette; Sandrine ,   GBMHM (Groupe des Biologistes Moléculaires des Hémopathies Malignes, French Molecular Biology Group in Hematology)
Published: August 2015

We report five chronic myeloid leukaemia (CML) patients in whom we identified and characterized undescribed BCR–ABL1 fusion transcripts. We investigated the precise features of the molecular rearrangements and the minimal residual disease follow‐up for these five patients. Three resulted from new rearrangements between the BCR and ABL1 sequences (the breakpoints being located within BCR exon 13 in two cases and within BCR exon 18 in one case). The other two cases revealed a complex e8‐[ins]‐a2 fusion transcript involving a third partner gene, PRDM12 and SPECC1L, respectively. Moreover, single nucleotide polymorphism‐array analysis performed in the latter two cases showed copy number alterations shared by the two patients, thus identifying genes that were deleted during rearrangement and suggesting their potential role in CML pathogenesis. Interestingly, we highlight that the prognosis of alterations, such as the presence of an e8a2 transcript or the deletion of various genes, which have been controversial, may be definitively erased by the introduction of tyrosine kinase inhibitors (TKIs). © 2015 Wiley Periodicals, Inc.
Projection of climate extremes in the Zhujiang River basin using a regional climate model
Authors: Wu Chuanhao , Huang Guoru
Published: August 2015

Based on the representative concentration pathway (RCP) scenarios, projected changes in climate extremes events in the Zhujiang River basin were investigated using the regional climate model RegCM4.0. Four extreme temperature indices (TXx, TNn, SU30, and TMINmean) and five extreme precipitation indices (Rx1day, Rx5day, SDII, R50mm, and SDII) defined by the Expert Team on Climate Change Detection and Indices (ETCCDI) were used in the investigation. The performance of the model was validated through comparison between observations and simulations for the period 1971–2000. The results show that although RegCM4.0 has certain abilities to reproduce both the spatial distributions of the values of extreme climate indices and their trends in the Zhujiang River basin, there are some large biases in the model results. The model simulates extreme temperatures more accurately than extreme precipitation. Compared to the baseline period 1971–2000, the changes in future (2021–2050 and 2051–2080) climate extremes under the RCP4.5 and RCP8.5 scenarios show very similar patterns, with an increase in extreme temperatures across the entire region and an increase in extreme precipitation in most parts of the region. For the period 2006–2099, a significant warming trend can be expected under both emissions scenarios, especially under the high emissions scenario (RCP8.5). The risk of drought shows statistically significant increasing trends under the RCP8.5 scenario in most parts of the region, especially in the central part of the basin. Meanwhile, more intense rainfall events are expected to occur in most parts of the region, especially in the southern parts of the basin. Furthermore, the increases predicted under the RCP8.5 scenario are more pronounced than those predicted under the RCP4.5 scenario. Overall, our results suggest that the Zhujiang River basin will suffer more natural disasters, such as catastrophic floods, droughts, and heat weaves, in the future.
Relationship between pulp structure breakdown and nutritional value of papaya (Carica papaya) and strawberry (Fragaria x ananassa) nectars using alternative thermal and non‐thermal processing techniques
Authors: Swada Jeffrey G , Keeley Christopher J , Ghane Mohammad A , Engeseth Nicki J
Published: August 2015

BACKGROUND

Papaya and strawberry contain a wide array of nutrients that contribute to human health; however, availability of these fruits is limited due to their short shelf lives and seasonal nature. In this study, the effect of alternative techniques including ultra high temperature (UHT, 20–135 °C, 1–3 s) and irradiation (0–10 kGy) on carotenoid concentration, antioxidant capacity and changes to pulp structure using transmission electron microscopy were determined for papaya and strawberry nectars.

RESULTS

UHT had moderate effects on antioxidant capacity, but the greatest overall release of carotenoids from the pulp matrix (34.2%, 6.26%, 8.31%; β‐cryptoxanthin, β‐carotene, and lycopene, respectively). Irradiation resulted in the greatest increase in antioxidant capacity [19.22 to 24.32 µmol Trolox equivalents kg−1 (papaya), 190.51 to 287.68 µmol Trolox equivalents kg−1 (strawberry)], with moderate effects on carotenoid concentration.

CONCLUSION

This research demonstrates that decreases in nutrient value and antioxidant capacity can result from processing, but that regeneration of these losses can be seen corresponding to the apparent breakdown of pulp structure. © 2015 Society of Chemical Industry
In situ evaluation of the fruit and oil characteristics of the main Lebanese olive germplasm
Authors: Chehade Ali , Bitar Ahmad El , Kadri Aline , Choueiri Elia , Nabbout Rania , Youssef Hiyam , Smeha Maha , Awada Ali , Chami Ziad Al , Dubla Eustachio , Trani Antonio , Mondelli Donato , Famiani Franco
Published: August 2015

BACKGROUND

Very little information is available on the characteristics of the Lebanese olive germplasm. Therefore, the aim of this work was to evaluate the fruit and oil characteristics of the main Lebanese olive varieties (Aayrouni, Abou chawkeh, Baladi, Del and Soury) from two successive crop seasons (2010–2011).

RESULTS

All of the genotypes had medium–high oil content in the fruit, indicating their suitability for oil production; Aayrouni had particularly high values. The variety Abou chawkeh also had a high pulp/pit ratio, which is a very desirable trait in table olives. For all the varieties the values of free fatty acids, peroxide values, absorbances in ultraviolet, fatty acid composition, sterol content and composition and erythrodiol + uvaol content of the oils were within the requirements of the International Olive Council's Trade Standard for extra virgin olive oil. The only exception was for the values of Δ‐7‐stigmastenol in 2011 in Soury and, especially, in Baladi, which were higher than 0.5%. In some cases, stearic and arachidic acids fluctuated around the maximum values allowed.

CONCLUSION

The findings of this study provide a first picture of the main characteristics of olives and oils currently produced in Lebanon. © 2015 Society of Chemical Industry
Development and initial testing of the Penn Parkinson's Daily Activities Questionnaire
Authors: Brennan Laura , Siderowf Andrew , Rubright Jonathan D. , Rick Jacqueline , Dahodwala Nabila , Duda John E. , Hurtig Howard , Stern Matthew , Xie Sharon X. , Rennert Lior , Karlawish Jason , Shea Judy A. , Trojanowski John Q. , Weintraub Daniel
Published: August 2015

Objective

The aim of this work was to describe the development and psychometric analysis of the Penn Parkinson's Daily Activities Questionnaire. The questionnaire is an item response theory‐based tool for rating cognitive instrumental activities of daily living in PD.

Methods

Candidate items for the Penn Parkinson's Daily Activities Questionnaire were developed through literature review and focus groups of patients and knowledgeable informants. Item selection and calibration of item‐response theory parameters were performed using responses from a cohort of PD patients and knowledgeable informants (n = 388). In independent cohorts of PD patients and knowledgeable informants, assessments of test‐retest reliability (n = 50), and construct validity (n = 68) of the questionnaire were subsequently performed. Construct validity was assessed by correlating questionnaire scores with measures of motor function, cognition, an existing activities of daily living measure, and directly observed daily function.

Results

Fifty items were retained in the final questionnaire item bank. Items were excluded owing to redundancy, difficult reading level, and when item‐response theory parameters could not be calculated. Test‐retest reliability was high (intraclass correlation coefficient = 0.97; P < 0.001). The questionnaire correlated strongly with cognition (r = 0.68; P < 0.001) and directly observed daily function (r = 0.87; P < 0.001), but not with motor impairment (r = 0.08; P = 0.53). The questionnaire score accurately discriminated between PD patients with and without dementia (receiver operating characteristic curve = 0.91; 95% confidence interval: 0.85–0.97).

Conclusions

The Penn Parkinson's Daily Activities Questionnaire shows strong evidence of reliability and validity. Item response theory‐based psychometric analysis suggests that this questionnaire can discriminate across a range of daily functions. © 2015 International Parkinson and Movement Disorder Society
Relationship between serum response factor and androgen receptor in prostate cancer
Authors: Prencipe Maria , O'Neill Amanda , O'Hurley Gillian , Nguyen Lan K. , Fabre Aurelie , Bjartell Anders , Gallagher William M. , Morrissey Colm , Kay Elaine W. , Watson R. William
Published: August 2015

BACKGROUND

Serum response factor (SRF) is an important transcription factor in castrate‐resistant prostate cancer (CRPC). Since CRPC is associated with androgen receptor (AR) hypersensitivity, we investigated the relationship between SRF and AR.

MATERIALS AND METHODS

Transcriptional activity was assessed by luciferase assay. Cell proliferation was measured by MTT and flow cytometry. Protein expression in patients was assessed by immunohistochemistry.

RESULTS

To investigate AR involvement in SRF response to androgen, AR expression was down‐regulated using siRNA. This resulted in the abrogation of SRF induction post‐DHT. Moreover, DHT stimulation failed to induce SRF transcriptional activity in AR‐negative PC346 DCC cells, which was only restored following AR over‐expression. Next, SRF expression was down‐regulated by siRNA, resulting in AR increased transcriptional activity in castrate‐resistant LNCaP Abl cells but not in the parental LNCaP. This negative feedback loop in the resistant cells was confirmed by immunohistochemistry which showed a negative correlation between AR and SRF expression in CRPC bone metastases and a positive correlation in androgen‐naïve prostatectomies. Cell proliferation was next assessed following SRF inhibition, demonstrating that SRF inhibition is more effective than AR inhibition in castrate‐resistant cells.

CONCLUSION

Our data support SRF as a promising therapeutic target in combination with current treatments. Prostate 75:1704–1717, 2015. © 2015 Wiley Periodicals, Inc.
Optimal full matching for survival outcomes: a method that merits more widespread use
Authors: Austin Peter C. , Stuart Elizabeth A.
Published: August 2015

Matching on the propensity score is a commonly used analytic method for estimating the effects of treatments on outcomes. Commonly used propensity score matching methods include nearest neighbor matching and nearest neighbor caliper matching. Rosenbaum (1991) proposed an optimal full matching approach, in which matched strata are formed consisting of either one treated subject and at least one control subject or one control subject and at least one treated subject. Full matching has been used rarely in the applied literature. Furthermore, its performance for use with survival outcomes has not been rigorously evaluated. We propose a method to use full matching to estimate the effect of treatment on the hazard of the occurrence of the outcome. An extensive set of Monte Carlo simulations were conducted to examine the performance of optimal full matching with survival analysis. Its performance was compared with that of nearest neighbor matching, nearest neighbor caliper matching, and inverse probability of treatment weighting using the propensity score. Full matching has superior performance compared with that of the two other matching algorithms and had comparable performance with that of inverse probability of treatment weighting using the propensity score. We illustrate the application of full matching with survival outcomes to estimate the effect of statin prescribing at hospital discharge on the hazard of post‐discharge mortality in a large cohort of patients who were discharged from hospital with a diagnosis of acute myocardial infarction. Optimal full matching merits more widespread adoption in medical and epidemiological research. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Diamantartige Kohlenstoffschichten steigern die Effizienz
Authors: Leson Andreas , Englberger Gregor , Hammer Daniel , Makowski Stefan , Meyer Carl‐Friedrich , Leonhard Michael , Scheibe Hans‐Joachim , Weihnacht Volker
Published: August 2015

Steigende Energiepreise sowie zunehmende Folgen des Klimawandels aufgrund der Emission von Treibhausgasen haben die Notwendigkeit zum Energiesparen in den letzten Jahren verstärkt in das öffentliche Bewusstsein gerückt. Für den Einsatz als reibungsmindernde Beschichtung eignen sich insbesondere kohlenstoffbasierte Beschichtungen, die auch DLC‐Schichten genannt werden (DLC = diamond‐like carbon). Dabei sind vor allem wasserstofffreie DLC‐Beschichtungen, die als ta‐C‐Schichten bezeichnet werden, von Interesse, da diese im Vergleich zu Standard‐DLC‐Schichten eine nochmals deutlich gesteigerte Härte und damit Verschleißfestigkeit aufweisen. Zudem zeichnen sich diese Schichten in Kombination mit speziellen Schmierstoffen durch einen teilweise extrem niedrigen Reibungskoeffizienten aus. Die Erzeugung von ta‐C‐Beschichtungen erfolgt aufgrund ihrer besonderen Eigenschaften mit PVD‐Verfahren. So lassen sie sich mit einem lasergesteuerten gepulsten Bogenverfahren, dem sogenannten Laser‐Arc‐Verfahren, herstellen. Dieses zeichnet sich durch eine vergleichsweise hohe Beschichtungsrate sowie eine gute Langzeitstabilität aus und eignet sich daher auch für einen Einsatz in der industriellen Produktion.
A Novel Use of Regional Anesthesia for Spastic Hemiplegia Evaluation and Treatment: A Case Report
Authors: Nagpal Ameet S. , Eckmann Maxim S. , Benfield Jon
Published: August 2015

Spastic hemiplegia is a common sequela of stroke. Spasticity that is not optimally reduced with systemic therapy is often treated with intramuscular botulinum toxin injections. Spastic tone can increase the difficulty of appropriately positioning the patient for botulinum toxin injections, lengthen procedure duration, and increase periprocedural pain. Our patient, a 53‐year‐old woman, was unable to be adequately positioned to receive botulinum toxin injections to her left upper extremity because of challenging flexion synergy posturing and related positional pain. A left interscalene brachial plexus local anesthetic block administered under ultrasound guidance was used to produce both temporary dense muscle relaxation and profound anesthesia, facilitating successful and comfortable botulinum toxin injections in this patient.