bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of temperature‐induced hERG channel blockade variation by drugs
Authors: Kauthale Rahul R. , Dadarkar Shruta S. , Husain Raghib , Karande Vikas V. , Gatne Madhumanjiri M. 
Published: October 2014

AbstractDrug‐induced QT prolongation has been reported in humans and animals. This potentially lethal effect can be induced by drugs interacting with a cardiac potassium channel, namely hERG (human ether‐a go‐go‐related gene) leading to arrhythmia ortorsade de pointes(TdP). Hence,in vitroevaluation of therapeutics for their effects on the rapid delayed rectifier current (IKr) mediated by the K+ion channel encoded by hERG is a valuable tool for identifying potential arrhythmic side effects during drug safety testing. Our objective was to evaluate the temperature‐induced hERG channel blockade variation by human and veterinary drugs using the IonFlux 16 system. A panel of eight drugs was tested for IKrinhibition at both ambient (23 °C) and physiological (37 °C) temperatures at various concentrations using IonFlux 16, an automated patch clamp system. Our results established that both amiodarone (IC50 = 0.56 μM at 23 °C and 0.30 μM at 37 °C) and β‐estradiol (IC50 = 24.72 μM at 23 °C and 8.17 μM at 37 °C) showed a dose‐dependent IKrblockade with a higher blockade at 37 °C. Whereas, blockade of IKrby both ivermectin (IC50 = 12.52 μM at 23 °C and 24.41 μM at 37 °C) and frusemide (IC50 = 12.58 μM at 23 °C and 25.55 μM at 37 °C) showed a dose‐dependent IKrblockade with a lower blockade at 37 °C. Gentamicin, enrofloxacin, xylazine and albendazole did not block IKrat both the assessed temperatures. Collectively, these results demonstrate that the effect of temperature variation should be taken into consideration during the evaluation of test drugs for their hERG channel blockade potential. Copyright © 2014 John Wiley & Sons, Ltd.
Organ‐specific distribution of gold nanoparticles by their surface functionalization
Authors: Lee Jong Kwon , Kim Tae Sung , Bae Ji Young , Jung A. Young , Lee Sang Min , Seok Ji Hyun , Roh Hang Sik , Song Chi Won , Choi Mi Jin , Jeong Jinyoung , Chung Bong Hyun , Lee Yun‐Geon , Jeong Jayoung , Cho Wan‐Seob 
Published: October 2014

AbstractThe behavior and fate of intravenously (i.v.) injected nanoparticles (NPs) can be controlled by several physicochemical factors including size, shape and surface charge. To evaluate the role of surface charge on distribution of NPs, we used neutral‐charged 15‐nm‐sized polyethylene glycol‐coated gold nanoparticles (AuNPPEG) as a core NP and carboxyl or amine groups were conjugated to AuNPPEG to generate negative (AuNPCOOH) or positive AuNP (AuNPNH2), respectively. Each type of AuNP was i.v. injected into mice (1 mg kg–1) and the concentration of Au was measured in different organs at 30 min, 4, 24 h, 7, 14 days, 1, 3 and 6 months post‐injection. The organ distribution also showed the higher deposition rate depending on their functional groups: AuNPPEG for mesenteric lymph node, kidney, brain and testis; AuNPCOOH for liver; AuNPNH2 for spleen, lung and heart. The blood circulation time and the major excretion route were different depending on their functional groups. In conclusion, functional groups conjugated on the surface of AuNPs produce differences in blood kinetics, organ distribution and elimination pattern which can be important information for directing NPs to specific organs or improving the kinetic properties. Copyright © 2014 John Wiley & Sons, Ltd.
Long‐term exposures to di‐n‐butyl phthalate inhibit body growth and impair gonad development in juvenile Murray rainbowfish (Melanotaenia fluviatilis)
Authors: Bhatia Harpreet , Kumar Anupama , Chapman John C. , McLaughlin Mike J. 
Published: October 2014

AbstractThe aim of the present study was to evaluate whether long‐term exposures to environmentally relevant concentrations of di‐n‐butyl phthalate (DnBP) disrupt the reproduction‐based endpoints in juvenile Murray rainbowfish (Melanotaenia fluviatilis). Fish were exposed to 5, 15 or 50 µg l−1 DnBP for 30, 60 and 90 days each, and the effects on survival, body growth, whole‐body concentrations of sex steroid hormones and gonadal development were investigated. The lowest observed effective concentration to affect the condition factor after 90 days was 5 µg l−1. Complete feminization of the gonad was noted in fish exposed to 5 µg l−1 for 90 days and to 15 and 50 µg l−1 of DnBP for 30 or 60 days. After 90 days of exposure to DnBP, the ovaries were regressed and immature as opposed to the control fish which were in early‐vitellogenic stage. Testes, present only in fish exposed to 5 µg l−1 of DnBP for 30 or 60 days, were immature in comparison to the control fish that contained testes in the mid‐spermatogenic phase. The E2/11‐KT ratio was significantly higher only after exposures to 5 µg l−1 DnBP for 90 days and 50 µg l−1 DnBP for 30 days. Our data suggest that exposures to 5 µg l−1 DnBP for 30 days did not have profound effects on body growth and gonadal differentiation of fish. However, 30 days of exposure to 15 µg l−1 could interfere with the gonad development and to 50 µg l−1 could compromise the hormonal profile of juvenile fish. Copyright © 2014 John Wiley & Sons, Ltd.
Extracellular matrix‐immobilized nanotopographical substrates for enhanced myogenic differentiation
Authors: Lee Eunjee A. , Jung Giyoung , Im Sung Gap , Hwang Nathaniel S. 
Published: October 2014

AbstractExtracellular matrix (ECM) components such as fibronectin (FN) and laminin (LMN) play prominent roles in controlling cellular behaviors. Many attempts have been made to explore cellular behaviors on combinatorial ECM arrays in high‐throughput systems. However these studies were limited to physical adsorption of ECM, which does not guarantee a lasting effect of ECM in vitro. Here, we demonstrate ECM immobilization on polyurethane acrylate (PUA) substrate fabricated in 24 well‐plate platforms to effectively differentiate C2C12. Our study demonstrate that co‐immobilization of FN and LMN was found to enhance myogenic differentiation of C2C12 cells compared to single immobilization of either FN or LMN alone. Furthermore, utilizing nano‐imprint lithography technique, 300 nm and 5 µm line‐patterned substrates were fabricated on 24‐well plates. FN and LMN co‐immobilized substrates with line‐patterns additionally provided the directionality for mimicking musculoskeletal structure and enhanced the myogenic differentiation. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1258–1266, 2015.
Removal of algae from biological cultures: a challenge for electrocoagulation?
Authors: Souza Fernanda L , Cotillas Salvador , Saéz Cristina , Cañizares Pablo , Lanza Marcos RV , Seco Aurora , Rodrigo Manuel A 
Published: October 2014

AbstractBACKGROUNDIn the search for novel technologies for the treatment of urban wastewater, combined anaerobic–algae membrane bioreactors have become a very interesting choice. Recovery of algae produced in these reactors has become the key point to obtain a good economic efficiency with this technology. In this work, electrocoagulation is studied as an alternative for the coarse removal of algae from a biological culture.RESULTSResults demonstrate that the electrochemical technology is a suitable technology for this purpose allowing the removal of more than 90% of the algae without modifying significantly the pH and with an operating cost below 0.04 € m−3. The same general trends are observed for applied current charge and current density supplied when aluminum or iron are used as electrodes although aluminum was much more efficient.CONCLUSIONSThe dose of coagulant reagents required is very low, indicating that coagulant generated in the process is very efficiently used. The best results in terms of algae and turbidity removals are obtained operating at low current densities with aluminum electrodes. According to pH and z‐potential values, insoluble metal hydroxide and anion M(OH)4− seems to be the primary coagulation species involved in the electrocoagulation process. © 2014 Society of Chemical Industry
Evaluation of microvasculature at the auditory midbrain–the benefits of sectioning at a tangential angle
Authors: So Edmund Cheung , Lu Hui‐Pin , Hsing Chung Hsi , Wu Sheng Nan , Chang Yu‐Kai , Poon Paul W.F. 
Published: October 2014

ABSTRACTVascular remodeling in the brain occurs as a plastic change following neural over‐activity. The auditory midbrain (or inferior colliculus, IC) is an ideal place to study sound‐induced vascular changes because it is the brain's most vascularized structure and it is tonotopically organized. However, its micro‐vascular pattern remains poorly understood. Since the IC is a sphere‐like structure, the histological assessment of vasculature could depend on the angle of sectioning. Here, we studied the effects of cutting the IC at different angles on microvascular assessment, specifically: micro‐vascular density and the shape of microvascular lumen. Photomicrographs were taken from 5 µm toluidine blue‐stained histological sections obtained at two angles of sectioning: (a) the conventional coronal sectioning, and (b) a novel “tangential” sectioning (tangential to the dorso‐medial surface of the IC). Results showed that the tangential sections, in comparison with the coronal sections, yielded (a) a higher count of micro‐vascular density and (b) a higher proportion of round‐shaped micro‐vascular lumens. This discrepancy in results between two cut angles is likely related to the spatial pattern of blood vessels supplying the IC. We propose that the tangential sectioning should be adopted as standard for the accurate study of microvasculature in the IC. Microsc. Res. Tech. 78:105–110, 2015. © 2014 Wiley Periodicals, Inc.
Relations between the Local Chromatic Number and Its Directed Version
Authors: Simonyi Gábor , Tardos Gábor , Zsbán Ambrus 
Published: October 2014

AbstractThe local chromatic number is a coloring parameter defined as the minimum number of colors that should appear in the most colorful closed neighborhood of a vertex under any proper coloring of the graph. Its directed version is the same when we consider only outneighborhoods in a directed graph. For digraphs with all arcs being present in both directions the two values are obviously equal. Here, we consider oriented graphs. We show the existence of a graph where the directed local chromatic number of all oriented versions of the graph is strictly less than the local chromatic number of the underlying undirected graph. We show that for fractional versions the analogous problem has a different answer: there always exists an orientation for which the directed and undirected values coincide. We also determine the supremum of the possible ratios of these fractional parameters, which turns out to be e, the basis of the natural logarithm.
Substrate‐induced PC12 Cell Differentiation Without Filopodial, Lamellipodial Activity or NGF Stimulationa
Authors: Lamour Guillaume , Souès Sylvie , Hamraoui Ahmed 
Published: October 2014

AbstractNanoscale gradients in energy of adhesion are physical cues from the extracellular environment that can significantly affect cell functions and enhance the neuronal differentiation of PC12 cells. How such surface effects can trigger differentiation and initiate neurite outgrowth, remains to be elucidated. Here we used surface modification, atomic force microscopy and immunofluorescence to analyze PC12 cells. We studied the kinetics of neurites growth under cytochalasin‐B treatment, known as an inhibitor of actin polymerization. We found that neither filopodia nor lamellipodia are involved in detecting the surface effects that induce the differentiation of PC12 cells. This finding suggests that the solution to this problem lies beyond identifying a precise cytoskeleton‐associated cell‐substrate intermediate. Thus, a more comprehensive model is probably required to identify the mechanism by which cell‐substrate interactions are eventually translated into a differentiation signal.
Patients with scans without evidence of dopaminergic deficit: A long‐term follow‐up study
Authors: Batla Amit , Erro Roberto , Stamelou Maria , Schneider Susanne A. , Schwingenschuh Petra , Ganos Christos , Bhatia Kailash P. 
Published: October 2014

ABSTRACTBackgroundWe previously reported on a cohort of dystonic tremor and patients with scans without evidence of dopaminergic deficit (SWEDDs). We aim to report the long‐term clinical and imaging follow‐up of these patients.Patients and MethodsPatients with at least 5‐year follow‐up were included. These patients had an asymmetric arm tremor, a previous diagnosis of Parkinson's disease (PD), and a subsequent normal DaTscan. The imaging and clinical follow‐up was done on the clinical basis.ResultsSixteen patients were included. The mean gap between the first and subsequent scans was 5.4 years. Two patients (12.5%) had reduced nigrostriatal uptake on follow‐up DaTscan, whereas 14 continued to have normal dopaminergic imaging.ConclusionThis is the longest follow up of patients with asymmetric rest tremor and normal DaT scans (SWEDDs) reported to date. We show here that only a minority of them show reduced striatonigral uptake over long term follow up.
Prenatal detection of congenital heart disease in a low risk population undergoing first and second trimester screening
Authors: Jørgensen Ditte E. S. , Vejlstrup Niels , Jørgensen Connie , Maroun Lisa Leth , Steensberg Jesper , Hessellund Anette , Jørgensen Finn Stener , Larsen Torben , Shalmi Anne‐Cathrine , Skibsted Lillian , Zingenberg Helle , Ekelund Charlotte , Tabor Ann 
Published: October 2014

AbstractObjectivesThe prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations. Our aim was to evaluate the prenatal detection of CHD in Eastern Denmark.MethodsFetuses and infants diagnosed with CHD in the period 01.01.2008–31.12.2010 were assessed regarding prenatal detection rate and accuracy, as well as correlation with nuchal translucency (NT) thickness.ResultsOut of 86 121 infants, 831 were born with CHD (0.96%). The prenatal detection rate of ‘all CHD’ was 21.3%, of ‘Major CHD’ 47.4%. Full agreement between prenatal and postnatal/autopsy findings was found in 96% of prenatally detected diagnoses. An NT thickness >95th percentile was found in 15.0% fetuses with ‘Major CHD’. Of ‘Major CHDs’ detected prenatally, 77% were picked up at the time of the malformation scan at weeks 18–21.ConclusionsNearly half of ‘Major CHDs’ were detected prenatally. The prenatal cardiac diagnoses showed a high degree of accuracy. Increased NT thickness as a screening tool for CHD performed moderately but is an important high risk group for specialist examination. A minority of the prenatally detected CHDs was identified because of extra scans performed in high risk pregnancies. © 2014 John Wiley & Sons, Ltd.
Influence of branching on the chiral self‐assembly of poly(phenylene ethynylene)
Authors: Steverlynck Joost , Leysen Pieter , Koeckelberghs Guy 
Published: October 2014

ABSTRACTIn this contribution, we report the synthesis of chiral all‐conjugated branched poly(phenylene ethynylenes) with a controlled amount of branching. Subsequently, the self‐assembly of these PPEs is studied by means of UV–vis, fluorescence spectroscopy, and DSC and the influence of branching is investigated. Finally, CD‐spectroscopy is used to study the influence of branching and self‐assembly on the chiral expression of these polymers. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 79–84
Synthesis and characterization of copoly(amide triazole)s derived from d‐Glucose
Authors: Bueno‐Martínez Manuel , Molina‐Pinilla Inmaculada , Hakkou Khalid , Galbis Juan A. 
Published: October 2014

ABSTRACTCopoly(amide triazole)s, abbreviated as PGBMn, have been prepared by copolymerization of 6‐azido‐6‐deoxy‐2,3,4‐tri‐O‐methyl‐N‐(prop‐2‐yn‐1‐yl)‐d‐gluconamide and 6‐azido‐6‐deoxy‐2,3,4‐tri‐O‐benzyl‐N‐(prop‐2‐yn‐1‐yl)‐d‐gluconamide by catalyst‐ and solvent‐free 1,3‐dipolar Huisgen cycloaddition reaction. The resulting copolymers have a diblock or a random distribution of the monomeric units along the polymer chain. Their molecular weights are in the range of 70,000–90,000 and they were characterized by GPC and IR and NMR spectroscopies. Thermal studies revealed them to be amorphous and stable up to 200 °C under nitrogen. Their qualitative solubilities in various solvents and their water sorption have also been investigated. The copolymers are hydrophilic, one of them being water soluble. The in vitro hydrolysis of this copoly(amide triazole) was studied. The degradation study was carried out at 80 °C in buffered solution at pH 10, and was monitored by GPC, and NMR spectroscopy. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 413–421
Structural and biochemical characterization of a metagenome‐derived esterase with a long N‐terminal extension
Authors: Okano Hiroyuki , Hong Xun , Kanaya Eiko , Angkawidjaja Clement , Kanaya Shigenori 
Published: October 2014

AbstractThe genes encoding six novel esterolytic/lipolytic enzymes, termed LC‐Est1∼6, were isolated from a fosmid library of a leaf‐branch compost metagenome by functional screening using tributyrin agar plates. These enzymes greatly vary in size and amino acid sequence. The highest identity between the amino acid sequence of each enzyme and that available from the database varies from 44 to 73%. Of these metagenome‐derived enzymes, LC‐Est1 is characterized by the presence of a long N‐terminal extension (LNTE, residues 26–283) between a putative signal peptide (residues 1–25) and a C‐terminal esterase domain (residues 284–510). A putative esterase from Candidatus Solibacter usitatus (CSu‐Est) is the only protein, which shows the significant amino acid sequence identity (46%) to the entire region of LC‐Est1. To examine whether LC‐Est1 exhibits activity and its LNTE is important for activity and stability of the esterase domain, LC‐Est1 (residues 26–510), LC‐Est1C (residues 284–510), and LC‐Est1C* (residues 304–510) were overproduced in E. coli, purified, and characterized. LC‐Est1C* was only used for structural analysis. The crystal structure of LC‐Est1C* highly resembles that of the catalytic domain of Thermotoga maritima esterase, suggesting that LNTE is not required for folding of the esterase domain. The enzymatic activity of LC‐Est1C was lower than that of LC‐Est1 by 60%, although its substrate specificity was similar to that of LC‐Est1. LC‐Est1C was less stable than LC‐Est1 by 3.3°C. These results suggest that LNTE of LC‐Est1 rather exists as an independent domain but is required for maximal activity and stability of the esterase domain.
D‐AKAP2:PKA RII:PDZK1 ternary complex structure: Insights from the nucleation of a polyvalent scaffold
Authors: Sarma Ganapathy N. , Moody Issa S. , Ilouz Ronit , Phan Ryan H. , Sankaran Banumathi , Hall Randy A. , Taylor Susan S. 
Published: October 2014

AbstractA‐kinase anchoring proteins (AKAPs) regulate cAMP‐dependent protein kinase (PKA) signaling in space and time. Dual‐specific AKAP2 (D‐AKAP2/AKAP10) binds with high affinity to both RI and RII regulatory subunits of PKA and is anchored to transporters through PDZ domain proteins. Here, we describe a structure of D‐AKAP2 in complex with two interacting partners and the exact mechanism by which a segment that on its own is disordered presents an α‐helix to PKA and a β‐strand to PDZK1. These two motifs nucleate a polyvalent scaffold and show how PKA signaling is linked to the regulation of transporters. Formation of the D‐AKAP2: PKA binary complex is an important first step for high affinity interaction with PDZK1, and the structure reveals important clues toward understanding this phenomenon. In contrast to many other AKAPs, D‐AKAP2 does not interact directly with the membrane protein. Instead, the interaction is facilitated by the C‐terminus of D‐AKAP2, which contains two binding motifs—the D‐AKAP2AKB and the PDZ motif—that are joined by a short linker and only become ordered upon binding to their respective partner signaling proteins. The D‐AKAP2AKB binds to the D/D domain of the R‐subunit and the C‐terminal PDZ motif binds to a PDZ domain (from PDZK1) that serves as a bridging protein to the transporter. This structure also provides insights into the fundamental question of why D‐AKAP2 would exhibit a differential mode of binding to the two PKA isoforms.
MOCVD synthesis of compositionally tuned topological insulator nanowires
Authors: Alegria Loren D. , Yao Nan , Petta Jason R. 
Published: October 2014

Device applications involving topological insulators (TIs) will require the development of scalable methods for fabricating TI samples with sub‐micron dimensions, high quality surfaces, and controlled compositions. Here we use Bi‐, Se‐, and Te‐bearing metalorganic precursors to synthesize TIs in the form of nanowires. Single crystal nanowires can be grown with compositions ranging from Bi2Se3 to Bi2Te3, including the ternary compound Bi2Te2Se. These high quality nanostructured TI compounds are suitable platforms for on‐going searches for Majorana fermions (Mourik et al., Science 336, 1003 (2012) and Cook et al., Rev. B 86, 155431 (2012) [1, 2]).
magnified imageHigh resolution transmission electron microscope image of a Bi2Te3 nanoribbon.(© 2014 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Towards a high‐resolution regional reanalysis for the European CORDEX domain
Authors: Bollmeyer C. , Keller J. D. , Ohlwein C. , Wahl S. , Crewell S. , Friederichs P. , Hense A. , Keune J. , Kneifel S. , Pscheidt I. , Redl S. , Steinke S. 
Published: October 2014

Atmospheric reanalyses covering the European region are mainly available as part of relatively coarse global reanalyses. The aim of this article is to present the development and evaluation of a next generation regional reanalysis for the European CORDEX EUR‐11 domain with a horizontal grid spacing of approximately 6 km. In this context, a reanalysis is understood to be an assimilation of heterogeneous observations with a physical model such as a numerical weather prediction (NWP) model. The reanalysis system presented here is based on the NWP model COSMO by the German Meteorological Service (Deutscher Wetterdienst) using a continuous nudging scheme. In order to assess the added value of data assimilation, a dynamical downscaling experiment has been conducted, i.e. an identical model set‐up but without data assimilation. Both systems have been evaluated for a 1 year test period, employing standard measures such as analysis increments, biases, or log‐odds ratios, as well as tests for distributional characteristics. An important aspect is the evaluation from different perspectives and with independent measurements such as satellite infrared brightness temperatures using forward operators, integrated water vapour from GPS stations, and ceilometer cloud cover. It can be shown that the reanalysis better resolves local extreme events; this is basically an effect of the higher spatio‐temporal resolution, as known from dynamical downscaling approaches. However, an important criterion for regional reanalyses is the coherence with independent observations of high temporal and spatial resolution, resulting in significant improvement over dynamical downscaling. The system is intended to become operational within a year, continuously reprocessing and evaluating longer time periods. The reanalysis data are planned to become available to the research community within a year.