bluuebunny/crossref_metadata_2025 huggingface dataset:
Web credibility assessment: Conceptualization, operationalization, variability, and models
Authors: Choi Wonchan , Stvilia Besiki
Published: May 2015

This article reviews theoretical and empirical studies on information credibility, with particular questions as to how scholars have conceptualized credibility, which is known as a multifaceted concept with underlying dimensions; how credibility has been operationalized and measured in empirical studies, especially in the web context; what are the important user characteristics that contribute to the variability of web credibility assessment; and how the process of web credibility assessment has been theorized. An agenda for future research on information credibility is also discussed.
Unlocking Inter‐ to Non‐Penetrating Frameworks Using Steric Influences on Spacers for CO2 Adsorption
Authors: Huang Sheng‐Li , Zhang Wen‐Hua , Ling Yun , Ng Seik Weng , Luo He‐Kuan , Hor T. S. Andy
Published: May 2015

Four porous coordination networks have been synthesized from 1,4‐benzenedicarboxylate with Cl, Br, I, and NO2 substituents whose different spatial differences are sufficient to influence the coordination mode of adjacent carboxyl moieties to unlock an inter‐penetrating framework to give isostructural structures. Their size and polarity differences account for the diverging CO2 adsorption performances.
Antiparallel Self‐Association of a γ,α‐Hybrid Peptide: More Relevance of Weak Interactions
Authors: Venugopalan Paloth , Kishore Raghuvansh
Published: May 2015

To learn how a preorganized peptide‐based molecular template, together with diverse weak non‐covalent interactions, leads to an effective self‐association, we investigated the conformational characteristics of a simple γ,α‐hybrid model peptide, Boc‐γ‐Abz‐Gly‐OMe. The single‐crystal X‐ray diffraction analysis revealed the existence of a fully extended β‐strand‐like structure stabilized by two non‐conventional C−H⋅⋅⋅O=C intramolecular H‐bonds. The 2D 1H NMR ROESY experiment led us to propose that the flat topology of the urethane‐γ‐Abz‐amide moiety is predominantly preserved in a non‐polar environment. The self‐association of the energetically more favorable antiparallel β‐strand‐mimic in solid‐state engenders an unusual ‘flight of stairs’ fabricated through face‐to‐face and edge‐to‐edge Ar⋅⋅⋅Ar interactions. In conjunction with FT‐IR spectroscopic analysis in chloroform, we highlight that conformationally semi‐rigid γ‐Abz foldamer in appositely designed peptides may encourage unusual β‐strand or β‐sheet‐like self‐association and supramolecular organization stabilized via weak attractive forces.
Processing of Written Irony in Autism Spectrum Disorder: An Eye‐Movement Study
Authors: Au‐Yeung Sheena K. , Kaakinen Johanna K. , Liversedge Simon P. , Benson Valerie
Published: May 2015

Previous research has suggested that individuals with Autism Spectrum Disorders (ASD) have difficulties understanding others communicative intent and with using contextual information to correctly interpret irony. We recorded the eye movements of typically developing (TD) adults ASD adults when they read statements that could either be interpreted as ironic or non‐ironic depending on the context of the passage. Participants with ASD performed as well as TD controls in their comprehension accuracy for speaker's statements in both ironic and non‐ironic conditions. Eye movement data showed that for both participant groups, total reading times were longer for the critical region containing the speaker's statement and a subsequent sentence restating the context in the ironic condition compared to the non‐ironic condition. The results suggest that more effortful processing is required in both ASD and TD participants for ironic compared with literal non‐ironic statements, and that individuals with ASD were able to use contextual information to infer a non‐literal interpretation of ironic text. Individuals with ASD, however, spent more time overall than TD controls rereading the passages, to a similar degree across both ironic and non‐ironic conditions, suggesting that they either take longer to construct a coherent discourse representation of the text, or that they take longer to make the decision that their representation of the text is reasonable based on their knowledge of the world. Autism Res 2015, 8: 749–760. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Review cyclic peptides on a merry‐go‐round; towards drug design
Authors: Tapeinou Anthi , Matsoukas Minos‐Timotheos , Simal Carmen , Tselios Theodore
Published: May 2015

Peptides and proteins are attractive initial leads for the rational design of bioactive molecules. Several natural cyclic peptides have recently emerged as templates for drug design due to their resistance to chemical or enzymatic hydrolysis and high selectivity to receptors. The development of practical protocols that mimic the power of nature's strategies remains paramount for the advancement of novel peptide‐based drugs. The de novo design of peptide mimetics (nonpeptide molecules or cyclic peptides) for the synthesis of linear or cyclic peptides has enhanced the progress of therapeutics and diverse areas of science and technology. In the case of metabolically unstable peptide ligands, the rational design and synthesis of cyclic peptide analogues has turned into an alternative approach for improved biological activity. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 453–461, 2015.
Self‐assembled penetratin‐deferasirox micelles as potential carriers for hydrophobic drug delivery
Authors: Goswami Dibakar , Vitorino Hector Aguilar , Machini M. Teresa , Espósito Breno P.
Published: May 2015

There has been a growing interest in the use of micelles with nanofiber geometry as nanocarriers for hydrophobic drugs. Here we show that the conjugate of penetratin, a cell‐penetrating peptide (CPP) with blood‐brain barrier (BBB) permeability, and deferasirox (DFX), a hydrophobic iron chelator, self‐assembles to form micelles at a very low concentration (∼15 mg/L). The critical micelle concentration (CMC) was determined, and the micelles were used for solubilizing curcumin, a hydrophobic anti‐neurodegenerative drug, for successful delivery across RBE4 cells, a BBB model. Transmission Electron Microscope images of the curcumin‐loaded micelles confirmed the formation of nanofibers. These results indicate the potential of CPP‐drug conjugates for use as nanocarriers. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 712–719, 2015.
Make decisions that will help you better manage challenges
Authors: McCarthy Claudine
Published: May 2015

KELLEY WALTON, J.D., INSTRUCTOR, SPORTS ADMINISTRATION DEPARTMENT, INTERIM DIRECTOR, PROFESSIONAL MSA PROGRAM, OHIO UNIVERSITY
Bone marrow‐derived stromal cells are more beneficial cell sources for tooth regeneration compared with adipose‐derived stromal cells
Authors: Ye Lanfeng , Chen Lin , Feng Fan , Cui Junhui , Li Kaide , Li Zhiyong , Liu Lei
Published: May 2015

Tooth loss is presently a global epidemic and tooth regeneration is thought to be a feasible and ideal treatment approach. Choice of cell source is a primary concern in tooth regeneration. In this study, the odontogenic differentiation potential of two non‐dental‐derived stem cells, adipose‐derived stromal cells (ADSCs) and bone marrow‐derived stromal cells (BMSCs), were evaluated both in vitro and in vivo. ADSCs and BMSCs were induced in vitro in the presence of tooth germ cell‐conditioned medium (TGC‐CM) prior to implantation into the omentum majus of rats, in combination with inactivated dentin matrix (IDM). Real‐time quantitative polymerase chain reaction (RT‐qPCR) was used to detect the mRNA expression levels of odontogenic‐related genes. Immunofluorescence and immunohistochemical assays were used to detect the protein levels of odontogenic‐specific genes, such as DSP and DMP‐1 both in vitro and in vivo. The results suggest that both ADSCs and BMSCs have odontogenic differentiation potential. However, the odontogenic potential of BMSCs was greater compared with ADSCs, showing that BMSCs are a more appropriate cell source for tooth regeneration.
Triply Hydrogen‐Bond‐Directed Enantioselective Assembly of Pyrrolobenzo‐1,4‐diazine Skeletons with Quaternary Stereocenters
Authors: Shen Xiaoming , Wang Yongtao , Wu Tiandi , Mao Zhenjun , Lin Xufeng
Published: May 2015

Highly efficient synthesis of optically enriched pyrrolobenzo‐1,4‐diazines bearing quaternary stereocenters has been realized through the chiral Brønsted acid‐catalyzed Pictet–Spengler reaction of 2‐(1H‐pyrrol‐1‐yl)anilines and α‐ketoamides in good to excellent yields and enantioselectivities. Computational studies suggest an unprecedented phenomenon whereby the chiral phosphoric acid catalyst employs attractive arene CH⋅⋅⋅N hydrogen bonding to activate the substrate and induce chirality through a triple hydrogen‐bonding interaction.
Catalytic Enantioselective Reaction of α‐Phenylthioacetonitriles with Imines Using Chiral Bis(imidazoline)–Palladium Catalysts
Authors: Kondo Masaru , Kobayashi Natsumi , Hatanaka Tsubasa , Funahashi Yasuhiro , Nakamura Shuichi
Published: May 2015

The catalytic enantioselective reaction of α‐phenylthioacetonitriles with imines has been developed. The reaction of various imines proceeds in good yields and diastereo‐ and enantioselectivities in the presence of chiral bis(imidazoline)–palladium catalysts. The obtained products can be converted into β‐aminonitrile or β‐aminoamide compounds without loss of enantiopurity.
Influence of ageing on the gloss, color, and structure of colored ABS
Authors: Bociąga Elżbieta , Trzaskalska Milena
Published: May 2015

The results of examination of the influence of ageing by UV rays on the gloss, color, and morphology of injection molded parts made of ABS terpolymer with addition of coloring agents in the form of powder and its masterbatch (granulate) based on ABS and PS media are presented in this article. It has been shown that the UV radiation contributes to decrease in the value of gloss and increase in the luminance of moldings and also changes values of parameters a and b, describing the change in parts color, in the direction of red and yellow, which is connected with the degradation of polymer ABS and coloring agents. Ageing process leads to structural changes in polymer, depending on the type of coloring agent. © 2015 Wiley Periodicals, Inc. Col Res Appl, 41, 392–398, 2016
Interference colorimetry of starch granules
Authors: Swatland H. J.
Published: May 2015

Starch granules viewed under a polarizing microscope may exhibit vivid interference colors – how can they be measured? A tilting compensator was used to generate interference colors, they were measured by spectrophotometry (400–700 nm at 10 nm intervals), and the weighted ordinate method was used to calculate chromaticity coordinates. There was a reasonable correspondence between the subjective terms used to describe interference colors, and those used for the CIE diagram. Three different charts of interference colors were measured by fiber‐optics – only one was close to the interference colors of the tilting compensator (r = 0.805 for CIE x, and r = 0.874 for CIE y, both P < 0.005). The spectra of various interference colors were like sine waves, whereas the matching spectra from charts were irregular with occasional peaks or dips. Thus, radically different spectra shared very similar chromaticity coordinates. As anticipated from first principles, the diameter of starch granules had a strong effect on their chromaticity coordinates (from r = 0.78 to r = 0.87, all P < 0.001). © 2015 Wiley Periodicals, Inc. Col Res Appl, 41, 352–357, 2016
Self‐Supporting Metal Nanotube Networks Obtained by Highly Conformal Electroless Plating
Authors: Muench Falk , De Carolis Dario M. , Felix Eva‐Maria , Brötz Joachim , Kunz Ulrike , Kleebe Hans‐Joachim , Ayata Sevda , Trautmann Christina , Ensinger Wolfgang
Published: May 2015

We present a versatile approach for the fabrication of well‐defined networks of interconnected metal nanotubes, which applies electroless plating to ion‐track‐etched polymer templates that enclose designed pore networks. In order to obtain self‐supporting structures, the deposition reactions must be optimized to yield conformal nanoscale metal films on microstructured substrates possessing extensive inner surfaces. Using this route, gold, copper, silver, nickel, and platinum nanotube networks are synthesized. The resulting structures can be handled macroscopically and combine a large surface area with continuous mass transport and conduction pathways, rendering them promising for application in, for example, electrocatalysis and sensing. This potential is demonstrated by employing a gold nanotube network for the amperometric detection of hydrogen peroxide, in which excellent sensitivity, catalyst utilization, and stability is achieved.
Capacitive Deionization using Biomass‐based Microporous Salt‐Templated Heteroatom‐Doped Carbons
Authors: Porada Slawomir , Schipper Florian , Aslan Mesut , Antonietti Markus , Presser Volker , Fellinger Tim‐Patrick
Published: May 2015

Microporous carbons are an interesting material for electrochemical applications. In this study, we evaluate several such carbons without/with N or S doping with regard to capacitive deionization. For this purpose, we extent the salt‐templating synthesis towards biomass precursors and S‐doped microporous carbons. The sample with the largest specific surface area (2830 m2 g−1) showed 1.0 wt % N and exhibited a high salt‐sorption capacity of 15.0 mg g−1 at 1.2 V in 5 mM aqueous NaCl. While being a promising material from an equilibrium performance point of view, our study also gives first insights to practical limitations of heteroatom‐doped carbon materials. We show that high heteroatom content may be associated with a low charge efficiency. The latter is a key parameter for capacitive deionization and is defined as the ratio between the amounts of removed salt molecules and electrical charge.
Towards Stronger Coulomb Coupling in an Ultracold Neutral Plasma
Authors: Lyon M. , Bergeson S. D.
Published: May 2015

Ultracold neutral plasmas are strongly coupled Coulomb systems that are generated by photoionizing lasercooled atoms close to the ionization threshold. The strong coupling parameter Γ is limited at times later than ∼100 ns by disorder‐induced heating. A recent simulation predicted that higher values of Γ can be realized in ultracold neutral plasmas if the plasma ions are excited to higher ionization states. In this paper we present recent results from an experiment that increases the strong coupling of an ultracold neutral plasma by promoting the plasma ions to the second ionization state. Using laser‐induced fluorescence we map out the ion velocity distribution of the Ca+ ions in a partially doubly ionized plasma and show that the heating due to the second ionization depends on the timing of the second ionization laser pulses. We compare our results to MD simulations, which estimate that Γ increases from approximately 2.5 to 3.6. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantum Hydrodynamics for Plasmas – a Thomas‐Fermi Theory Perspective
Authors: Michta D. , Graziani F. , Bonitz M.
Published: May 2015

The idea to describe quantum systems within a hydrodynamic framework (quantum hydrodynamics, QHD) goes back to Madelung and Bohm. While such a description is formally exact for a single particle, more recently the concept has been applied to many‐particle systems by Manfredi and Haas [Phys. Rev. B 64, 075316 (2001)] and received high popularity in parts of the quantum plasma community. Thereby, often the applicability limits of these equations are ignored, giving rise to unphysical predictions. Here we demonstrate that modified QHD equations for plasmas can be derived from Thomas‐Fermi theory including gradient corrections. This puts QHD on firm grounds. At the same time this derivation yields a different prefactor, γ = (D – 2/3D), in front of the quantum (Bohm) potential which depends on the system dimensionality D. Our approach allows one to identify the limitations of QHD and to outline systematic improvements. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Chick embryos have the same pattern of hypoxic lower‐brain activation as fetal mammals
Authors: Landry Jeremy P. , Hawkins Connor , Lee Aaron , Coté Alexandra , Balaban Evan , Pompeiano Maria
Published: May 2015

cFos expression (indicating a particular kind of neuronal activation) was examined in embryonic day (E) 18 chick embryos after exposure to 4 h of either normoxia (21% O2), modest hypoxia (15% O2), or medium hypoxia (10% O2). Eight regions of the brainstem and hypothalamus were surveyed, including seven previously shown to respond to hypoxia in late‐gestation mammalian fetuses (Breen et al., 1997; Nitsos and Walker, 1999b). Hypoxia‐related changes in chick embryo brain activation mirrored those found in fetal mammals with the exception of the medullary Raphe, which showed decreased hypoxic activation, compared with no change in mammals. This difference may be explained by the greater anapyrexic responses of chick embryos relative to mammalian fetuses. Activation in the A1/C1 region was examined in more detail to ascertain whether an O2‐sensitive subpopulation of these cells containing heme oxygenase 2 (HMOX2) may drive hypoxic brain responses before the maturation of peripheral O2‐sensing. HMOX2‐positive and ‐negative catecholaminergic cells and interdigitating noncatecholaminergic HMOX2‐positive cells all showed significant changes in cFos expression to hypoxia, with larger population responses seen in the catecholaminergic cells. Hypoxia‐induced activation of lower‐brain regions studied here was significantly better correlated with activation of the nucleus of the solitary tract (NTS) than with that of HMOX2‐containing A1/C1 neurons. Together, these observations suggest that (1) the functional circuitry controlling prenatal brain responses to hypoxia is strongly conserved between birds and mammals, and (2) NTS neurons are a more dominant driving force for prenatal hypoxic cFos brain responses than O2‐sensing A1/C1 neurons. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 64–74, 2016
Development of diagnostic microsatellite markers from whole‐genome sequences ofAmmodramussparrows for assessing admixture in a hybrid zone
Authors: Kovach Adrienne I. , Walsh Jennifer , Ramsdell Jordan , Kelley Thomas W.
Published: May 2015

Studies of hybridization and introgression and, in particular, the identification of admixed individuals in natural populations benefit from the use of diagnostic genetic markers that reliably differentiate pure species from each other and their hybrid forms. Such diagnostic markers are often infrequent in the genomes of closely related species, and genomewide data facilitate their discovery. We used whole‐genome data from Illumina HiSeqS2000 sequencing of two recently diverged (600,000 years) and hybridizing, avian, sister species, the Saltmarsh (Ammodramus caudacutus) and Nelson's (A. nelsoni) Sparrow, to develop a suite of diagnostic markers for high‐resolution identification of pure and admixed individuals. We compared the microsatellite repeat regions identified in the genomes of the two species and selected a subset of 37 loci that differed between the species in repeat number. We screened these loci on 12 pure individuals of each species and report on the 34 that successfully amplified. From these, we developed a panel of the 12 most diagnostic loci, which we evaluated on 96 individuals, including individuals from both allopatric populations and sympatric individuals from the hybrid zone. Using simulations, we evaluated the power of the marker panel for accurate assignments of individuals to their appropriate pure species and hybrid genotypic classes (F1, F2, and backcrosses). The markers proved highly informative for species discrimination and had high accuracy for classifying admixed individuals into their genotypic classes. These markers will aid future investigations of introgressive hybridization in this system and aid conservation efforts aimed at monitoring and preserving pure species. Our approach is transferable to other study systems consisting of closely related and incipient species.
Capillary electrophoresis for rapid identification of monoclonal antibodies for routine application in hospital
Authors: Jaccoulet Emmanuel , Smadja Claire , Prognon Patrice , Taverna Myriam
Published: May 2015

mAbs are widely used in cancer therapy. Their compounding, performed just before their administration to patients, is executed in a production unit of the hospital. Identification of these drugs, individually prepared in bags for infusion before patient administration, is of paramount importance to detect potential mistakes during compounding stage. A fast and reliable analytical method based on CZE combined to a cationic capillary coating (hexadimethrine bromide) was developed for identification of the most widely used compounded therapeutic for cancer therapy (bevacizumab, cetuximab, rituximab, and trastuzumab). Considering the high structural and physico‐chemical similarities of these mAbs, an extensive optimization of the BGE composition has been performed. The addition of perchlorate ions and polysorbate in the BGE greatly increased the resolution. To validate the method, an internal standard was used and the relative migration times (RTm) were estimated. Very satisfactory RSDs of the RTm for rituximab (0.76%), cetuximab (0.46%), bevacizumab (0.31%), and trastuzumab (0.60%) were obtained. The intraday and interday RSD of the method were less than 0.32 and 1.3%, respectively for RTm. Significant differences between theses RTms have been demonstrated allowing mAbs identification. Finally, accurate mAbs identification has been demonstrated by a blind test.
Evaluation on the external environment cost of pig‐breeding with different size in sichuan province of China
Authors: Zhengtao He , Jue Peng
Published: May 2015

In this article, pig manure treatment methods and technical levels in households were considered, and the market value method and the treatment cost approach were applied to estimate the external environmental cost (EEC) of pig‐farming with different scales quantitatively, reflecting the impacts of pig farming on the environment. Results show that the total EEC for medium‐scale farms is lower than that of range breeding and small‐scale farms. Its data envelopment analysis overall effective years are most, and its average scale efficiency and comprehensive efficiency are the highest, and its unit EEC is the minimal among the four scales. Therefore, range breeding should be narrowed, but the medium‐scale breeding should be moderately encouraged and developed. This is in line with Chinese policy and planning of developing livestock and poultry industry in moderate scale. © 2015 American Institute of Chemical Engineers Environ Prog, 34: 1488–1496, 2015
Throughput, energy efficiency and interference characterisation of 802.11ac
Authors: Zeng Yunze , Pathak Parth H. , Mohapatra Prasant
Published: May 2015

This paper is the first of its kind in presenting a detailed characterisation of IEEE 802.11ac using real experiments. 802.11ac is the latest Wireless Local Area Network (WLAN) standard that is rapidly being adapted because of its potential to deliver very high throughput. The throughput increase in 802.11ac can be attributed to three factors—larger channel width (80/160 MHz), support for denser modulation (256 Quadrature Amplitude Modulation (QAM)) and increased number of spatial streams for Multiple‐input Multiple‐output (MIMO). We provide an experiment evaluation of these factors and their impact using a real 802.11ac testbed. Our findings provide numerous insights on benefits and challenges associated with using 802.11ac in practice.

Because utilisation of larger channel width is one of the most significant changes in 802.11ac, we focus our study on understanding its impact on energy efficiency and interference. Using experiments, we show that utilising larger channel width is in general less energy efficient because of its higher power consumption in idle listening mode. Increasing the number of MIMO spatial streams is comparatively more energy efficient for achieving the same percentage increase in throughput. We also show that 802.11ac link witnesses severe unfairness issues when it coexists with legacy 802.11. We provide a detailed analysis to show how medium access in heterogeneous channel width environment leads to the unfairness issues. We believe that these and many other findings presented in this work will help in understanding and resolving various performance issues of next generation WLANs. Copyright © 2015 John Wiley & Sons, Ltd.
The taste enhancer divanillin: a review on sources and enzymatic generation
Authors: Krings Ulrich , Esparan Vida , Berger Ralf G.
Published: May 2015

Dehydrodivanillin, the symmetrical dimer of vanillin, is a taste enhancer which imparts pleasant impressions of creaminess to food. Found in vanilla pods in traces only, a co‐substrate independent dimerization of vanillin, conducted in a co‐solvent system to improve the solubility of vanillin, was developed using iso‐active fungal laccases from Meripilus giganteus, Agaricus bisporus and Funalia trogii. The yields were compared with a peroxidase from Marasmius scorodonius (MsP2) and the reference enzyme horseradish peroxidase (HRP), both supplied with hydrogen peroxide. Using laccase catalysis, the kinetically preferred reaction product, 5,5'‐dehydrodivanillin, rapidly reached saturation and precipitated in situ, thus shifting the reaction equilibrium to the product. Yields of > 95 % were obtained with the high‐redox‐potential laccase of Funalia trogii, while HRP gave 18 %. Copyright © 2015 John Wiley & Sons, Ltd.
Mechanism of cell integration on biomaterial implant surfaces in the presence of bacterial contamination
Authors: Yue Chongxia , van der Mei Henny C. , Kuijer Roel , Busscher Henk J. , Rochford Edward T. J.
Published: May 2015

Bacterial contamination during biomaterial implantation is often unavoidable, yielding a combat between cells and bacteria. Here we aim to determine the modulatory function of bacterial components on stem‐cell, fibroblast, and osteoblast adhesion to a titanium alloy, including the role of toll‐like‐receptors (TLRs). Presence of heat‐sacrificed Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa induced dose and cell‐type dependent responses. Stem‐cells were most sensitive to bacterial presence, demonstrating decreased adhesion number yet increased adhesion effort with a relatively large focal adhesion contact area. Blocking TLRs had no effect on stem‐cell adhesion in presence of S. aureus, but blocking both TLR2 and TLR4 induced an increased adhesion effort in presence of E. coli. Neither lipopolysaccharide, lipoteichoic acid, nor bacterial DNA provoked the same cell response as did whole bacteria. Herewith we suggest a new mechanism as to how biomaterials are integrated by cells despite the unavoidable presence of bacterial contamination. Stimulation of host cell integration of implant surfaces may open a new window to design new biomaterials with enhanced healing, thereby reducing the risk of biomaterial‐associated infection of both “hardware‐based” implants as well as of tissue‐engineered constructs, known to suffer from similarly high infection risks as currently prevailing in “hardware‐based” implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3590–3598, 2015.
Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH)
Authors: Dong Bingzi , Endo Itsuro , Ohnishi Yukiyo , Kondo Takeshi , Hasegawa Tomoka , Amizuka Norio , Kiyonari Hiroshi , Shioi Go , Abe Masahiro , Fukumoto Seiji , Matsumoto Toshio
Published: May 2015

Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and hypercalciuria, similar to the clinical features of hypoparathyroidism. The current treatment of ADH is similar to the other forms of hypoparathyroidism, using active vitamin D3 or parathyroid hormone (PTH). However, these treatments aggravate hypercalciuria and renal calcification. Thus, new therapeutic strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR, and may be effective for the treatment of ADH caused by activating mutations of CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR harboring activating mutations in the extracellular and transmembrane domains in vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442 suppressed the hypersensitivity to extracellular Ca2+ of HEK cells transfected with the CaSR gene with activating mutations in the extracellular and transmembrane domains. We then selected two activating mutations locating in the extracellular (C129S) and transmembrane (A843E) domains, and generated two strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment in vivo increased urinary cAMP excretion, improved serum and urinary calcium and phosphate levels by stimulating endogenous PTH secretion, and prevented renal calcification. In contrast, PTH(1-34) treatment normalized serum calcium and phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock-in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK-5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD) in these mice. These results demonstrate that calcilytics can reverse almost all the phenotypes of ADH including hypercalciuria and renal calcification, and suggest that calcilytics can become a novel therapeutic agent for ADH. © 2015 American Society for Bone and Mineral Research.
Implementation of extended Lagrangian dynamics in GROMACS for polarizable simulations using the classical Drude oscillator model
Authors: Lemkul Justin A. , Roux Benoît , van der Spoel David , MacKerell Alexander D.
Published: May 2015

Explicit treatment of electronic polarization in empirical force fields used for molecular dynamics simulations represents an important advancement in simulation methodology. A straightforward means of treating electronic polarization in these simulations is the inclusion of Drude oscillators, which are auxiliary, charge‐carrying particles bonded to the cores of atoms in the system. The additional degrees of freedom make these simulations more computationally expensive relative to simulations using traditional fixed‐charge (additive) force fields. Thus, efficient tools are needed for conducting these simulations. Here, we present the implementation of highly scalable algorithms in the GROMACS simulation package that allow for the simulation of polarizable systems using extended Lagrangian dynamics with a dual Nosé–Hoover thermostat as well as simulations using a full self‐consistent field treatment of polarization. The performance of systems of varying size is evaluated, showing that the present code parallelizes efficiently and is the fastest implementation of the extended Lagrangian methods currently available for simulations using the Drude polarizable force field.
Accurate Detection of Hepatitis B Virus G1896A Mutant by Developed Taqman‐ARMS Followed a Strict Control System
Authors: Lu Renfei , Shao Jianguo , Zhou Min , Zhang Hongping , Wu Yueping
Published: May 2015

Background

Hepatitis B virus (HBV) G1896A mutation was associated with HBeAg seronegativity and hepatitis B related acute‐on‐chronic liver failure. In this study, we developed Taqman amplification refractory mutation system (Taqman‐ARMS) and established a strict control system to detect HBV G1896A mutant.

Methods

HBV viral DNA was isolated from 60 patient serum samples, and full‐length HBV genome was cloned. Then, Taqman‐ARMS was used to detect HBV G1896A mutant.

Results

The assay has the sensitivity of 1E+3 IU/ml G1896A template, and 0.1% weak population virus with G1896A could be found in mixtures. Total of all 60 clinical samples random collected were detected by Taqman‐ARMS, the results were consistent with those by DNA sequencing.

Conclusion

The proposed Taqman‐ARMS real‐time PCR method for the detection of G1896A mutation of HBV was rapid, simple, sensitive, specific, and applicable in the clinical setting.
Revisiting Chaos Theorem to Understand the Nature of miRNAs in Response to Drugs of Abuse
Authors: Taki Faten A. , Pan Xiaoping , Zhang Baohong
Published: May 2015

Just like Matryoshka dolls, biological systems follow a hierarchical order that is based on dynamic bidirectional communication among its components. In addition to the convoluted inter‐relationships, the complexity of each component spans several folds. Therefore, it becomes rather challenging to investigate phenotypes resulting from these networks as it requires the integration of reductionistic and holistic approaches. One dynamic system is the transcriptome which comprises a variety of RNA species. Some, like microRNAs, have recently received a lot of attention. miRNAs are very pleiotropic and have been considered as therapeutic and diagnostic candidates in the biomedical fields. In this review, we survey miRNA profiles in response to drugs of abuse (DA) using 118 studies. After providing a summary of miRNAs related to substance use disorders (SUD), general patterns of miRNA signatures are compared among studies for single or multiple drugs of abuse. Then, current challenges and drawbacks in the field are discussed. Finally, we provide support for considering miRNAs as a chaotic system in normal versus disrupted states particularly in SUD and propose an integrative approach for studying and analyzing miRNA data. J. Cell. Physiol. 230: 2857–2868, 2015. © 2015 Wiley Periodicals, Inc.
Evaluation of regional gastrointestinal absorption of edoxaban using the enterion capsule
Authors: Parasrampuria Dolly A. , Kanamaru Taro , Connor Alyson , Wilding Ian , Ogata Koichiro , Shimoto Yoshimasa , Kunitada Satoshi
Published: May 2015

Two studies in healthy subjects assessed the absorption of edoxaban when delivered to specific locations within the gastrointestinal tract using Enterion capsules. In study 1 (single‐dose, 4‐way crossover), 8 participants received edoxaban 60 mg as immediate‐release (IR) tablets (treatment A), as powder formulation delivered to the distal small bowel (treatment B) or ascending colon (treatment C), or as an aqueous suspension delivered to the ascending colon (treatment D). In study 2 (single‐dose, 2‐way crossover), 10 participants received edoxaban 30 mg as IR tablets (treatment E) or in granulate formulation with fumaric acid 50 mg, added to acidify the local gastrointestinal tract and enhance solubility, delivered to the ascending colon (treatment F). Peak and total exposure following targeted drug delivery to the distal gastrointestinal tract were significantly lower than with IR tablet delivery. In study 1, total exposure ratios of treatments B, C, and D compared with A were 14.9%, 7.9%, and 6.1%, respectively. In study 2, relative total exposure was 12.6% for treatment F despite the fumaric acid. Time to peak concentration was longer with higher variability for edoxaban delivered to the distal gastrointestinal tract compared with the IR tablet. These data indicate that edoxaban absorption occurs predominantly in the proximal small intestine.
Population pharmacokinetics of edoxaban and its main metabolite in a dedicated renal impairment study
Authors: Jönsson Siv , Simonsson Ulrika S. H. , Miller Raymond , Karlsson Mats O.
Published: May 2015

A model characterizing the population pharmacokinetics (PK) of edoxaban and its major metabolite, M4, following a single oral dose of 15 mg administered to subjects with varying kidney function was developed. Thirty‐two subjects contributed with edoxaban plasma, edoxaban urine, and M4 plasma concentrations. Edoxaban urine concentrations allowed estimation of renal clearance, and high contribution of renal to total clearance enabled estimation of absolute oral bioavailability. A 2‐compartment model with delayed absorption and elimination parameterized as renal clearance linearly related to creatinine clearance (CLcr) and nonrenal clearance forming M4 described edoxaban PK. The PK of M4 was described with a 1‐compartment model. For a typical subject (70 kg; CLcr, 100 mL/min) bioavailability, clearance, and central and peripheral volume of distribution for edoxaban was estimated to 72.3%, 21.0 L/h, 95.4 L, and 54.3 L, respectively. For both edoxaban and M4, the model predicted systemic exposure to increase 57.0%, 35.0%, and 11.6% in a subject having CLcr of 30, 50, and 80 mL/min, respectively, compared with a subject having a CLcr of 100 mL/min. Concentration ratios (M4 over edoxaban) were predicted to vary with time after dose, but with minor influence of kidney function and body weight. Results were in agreement with previous analyses.
Contextual control using a go/no‐go procedure with compound abstract stimuli
Authors: Modenesi Rafael Diego , Debert Paula
Published: May 2015

Contextual control has been described as (1) a five‐term contingency, in which the contextual stimulus exerts conditional control over conditional discriminations, and (2) allowing one stimulus to be a member of different equivalence classes without merging them into one. Matching‐to‐sample is the most commonly employed procedure to produce and study contextual control. The present study evaluated whether the go/no‐go procedure with compound stimuli produces equivalence classes that share stimuli. This procedure does not allow the identification of specific stimulus functions (e.g., contextual, conditional, or discriminative functions). If equivalence classes were established with this procedure, then only the latter part of the contextual control definition (2) would be met. Six undergraduate students participated in the present study. In the training phases, responses to AC, BD, and XY compounds with stimuli from the same classes were reinforced, and responses to AC, BD, and XY compounds with stimuli from different classes were not. In addition, responses to X1A1B1, X1A2B2, X2A1B2, and X2A2B1 compounds were reinforced and responses to the other combinations were not. During the tests, the participants had to respond to new combinations of stimuli compounds YCD to indicate the formation of four equivalence classes that share stimuli: X1A1B1Y1C1D1, X1A2B2Y1C2D2, X2A1B2Y2C1D2, and X2A2B1Y2C2D1. Four of the six participants showed the establishment of these classes. These results indicate that establishing contextual stimulus functions is unnecessary to produce equivalence classes that share stimuli. Therefore, these results are inconsistent with the first part of the definition of contextual control.
Efficient and Facile Synthesis of Substituted Aminothiadiazolylhydrazonoindolin‐2‐ones
Authors: Hassan Alaa A. , Abdel‐Latif Fathy F. , Abdel‐Aziz Mohamed , Mostafa Sara M. , Bräse Stefan , Nieger Martin
Published: May 2015

New series of substituted aminothiadiazolylhydrazonoindolin‐2‐ones were prepared in high yields (89–94%) via the cyclocondensation of thiocarbonohydrazides (1a, 1b, 1c, 1d) with 3‐(dicyanomethylene)‐2‐indolone in (ethanol/piperidine) at room temperature. Explanations of these conversations involve the nucleophilic addition on the dicyanomethylene carbon atom. The structures were established by spectroscopic data and single crystal X‐ray crystallography.
Noise performance and nonlinear distortion of semiconductor laser under two‐tone modulation for use in analog CATV systems
Authors: Mahmoud Safwat W. Z. , Mahmoud Alaa , Ahmed Moustafa
Published: May 2015

We introduce numerical modeling of noise performance and distortion of semiconductor lasers subject to two‐tone modulation according to the National Television Standards Committee NTSC plan for the cable television (CATV) signal transport. The waveform of the laser signal is simulated over wide ranges of the modulation index and placements of the modulation channel. The power and frequency spectra of the relative intensity noise (RIN) are characterized, and the associated second‐order harmonic distortion (2HD), and the second‐order (IMD2) and third‐order intermodulation distortions (IMD3) are calculated. The calculated data are used to predict the measures of the CATV system performance. The dynamic range of linearity of the laser is evaluated in terms of the spurious‐free dynamic range SFDR. We show that under weak modulation, the low‐frequency RIN is constant at −168 dB/Hz regardless the modulation frequency. Within this accepted noise level, IMD2 is 4 dBm higher than 2HD and 10 dBm higher than IMD3. When the modulation index exceeds 25%, the laser emits clipped signals associated with large values of signal distortions. Accepted values of the carrier to noise ratio and distortions correspond to lower modulation index and/or channel frequency. Copyright © 2015 John Wiley & Sons, Ltd.
Transformation of Tourism in Beijing after the 2008 Summer Olympics: An Analysis of the Impacts in 2014
Authors: Singh Neha , Zhou Huiqiong
Published: May 2015

Many countries compete for the opportunity to host the Olympics because of the resulting positive impacts. However, there are also high costs associated with hosting this event. The participants of this study provided insight on how the 2008 Olympics influenced Beijing's tourism industry. This study explores the impacts of hosting the renowned Olympic Games on the transformation of the host city from the supplier perspective. Beijing tourism industry professionals and Beijing residents were considered suppliers and interviewed for the purpose of this study. Collected data reveal that the city of Beijing rapidly developed because of the mega event. Suppliers including Beijing's tourism department, government organizations, hotels, and restaurants have changed their marketing strategies over time because of the impacts of the Olympics. Additionally, Beijing has shifted to promoting a new destination image: fashion and vitality. The present findings will help future host destinations better understand the impacts of hosting the Olympics. Copyright © 2015 John Wiley & Sons, Ltd.
Peptide Dendrimer Functionalized with Amphiphilic Triblock Copolymers: Synthesis and Characterization
Authors: Oledzka Ewa , Sliwerska Patrycja , Sobczak Marcin , Kraska Bartlomiej , Kamysz Wojciech , Nalecz‐Jawecki Grzegorz , Kolodziejski Waclaw
Published: May 2015

Poly(l‐lysine) dendrimer end‐functionalized with arginine‐6‐oligomer conjugated biodegradable poly(3‐hydroxybutyrate) (PHB)–poly(ethylene glycol) (PEG)–PHB copolymer may be considered a promising macromolecular drug delivery vehicle. To prepare amphiphilic triblock copolymers, bulk ring‐opening polymerization (ROP) of (R,S)‐β‐butyrolactone initiated with poly(ethylene glycol) is carried out. The copolymers are synthesized with a high yield of 90%. The structure and physical–chemical properties of the obtained products are confirmed by hydrogen and carbon nuclear magnetic resonance (1H and 13C NMR), viscosity method, gel permeation chromatography (GPC), matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF), and differential scanning calorimetry (DSC) technique. Furthermore, the cytotoxicity of the synthesized copolymers is evaluated with a bacterial luminescence test and protozoan assay, which show that the obtained copolymers are not cytotoxic. Poly(l‐lysine) dendrimer end‐functionalized with arginine‐6‐oligomer is further covalently bonded to a copolymer using the 1,1'‐carbonyldiimidazole/4‐(dimethylamino)pyridine (CDI/DMAP) coupling method. The presence of a newly formed urethane bond between the peptide dendrimer and the copolymer is confirmed by 1H NMR studies. This novel peptide dendrimer functionalized with an amphiphilic triblock copolymer can be applied as a compatible biodegradable material for drug carrier applications.β‐butyrolactone; biodegradable polymers; drug delivery system; peptide dendrimers; ring‐opening polymerization

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Alginate–Hydroxyapatite Bone Scaffolds with Isotropic or Anisotropic Pore Structure: Material Properties and Biological Behavior
Authors: Porrelli Davide , Travan Andrea , Turco Gianluca , Marsich Eleonora , Borgogna Massimiliano , Paoletti Sergio , Donati Ivan
Published: May 2015

Alginate/hydroxyapatite composites, with isotropic or anisotropic porosity, were developed using two different freezing methods. Morphological analysis highlighted the differences in their three‐dimensional network. Swelling and in vitro degradation studies revealed that both structures are highly hydrophilic and stable. Static compression tests showed that isotropic scaffolds possess higher modulus and toughness than anisotropic ones. Cyclic compression tests revealed that wet scaffolds are able to withstand high deformations with a peculiar shape‐recovery behaviour. In vitro biological tests showed that osteoblast‐like cells proliferate on both types of structures in a comparable manner.
Energy‐aware traffic allocation to optical lightpaths in multilayer core networks
Authors: Foteinos Vassilis , Tsagkaris Kostas , Peloso Pierre , Ciavaglia Laurent , Demestichas Panagiotis
Published: May 2015

The amount of traffic that is generated by users and high‐demanding services is expected to rise dramatically in the forthcoming years. This will unavoidably deteriorate the performance and increase the consumed energy of core networks, thus constraining the growth of Internet. To this effect, multilayer traffic engineering schemes in IP/multiprotocol label switching over dense wavelength division multiplexing networks have been proposed for achieving improved performance and increased energy savings by flexibly allocating traffic to optical lightpaths. In particular, the consumed energy in a router can be minimized if the lightpaths are established so as to traverse a router without electronic processing and conversion of their signal between optical and electrical layer. Accordingly, this paper aims at providing an energy‐aware solution to the problem of traffic allocation to optical lightpaths in multilayer core networks. The problem is first formulated and then a solution based on a heuristic algorithm, called energy‐aware traffic allocation to optical lightpaths (ETAL) is proposed. The efficiency and worthiness of ETAL is validated through numerous scenarios and simulations. The derived results indicate that the proposed algorithm is an efficient traffic engineering solution that exhibits better performance in terms of consumed energy (up to 44%), when compared to other similar traffic allocation schemes. Copyright © 2015 John Wiley & Sons, Ltd.
Preparation and characterization of submicron hybrid magnetic latex particles
Authors: Jamshaid Talha , Tenório‐Neto Ernandes Taveira , Eissa Mohamed , Zine Nadia , El‐Salhi Abdelhamid Errachid , Kunita Marcos Hiroiuqui , Elaissari Abdelhamid
Published: May 2015

Micrometer magnetic hybrid particles are of great interest in biomedical field, and various morphologies have been prepared via encapsulation processes. Regarding submicron, only few processes have been investigated and the most recent one leading to highly magnetic submicron magnetic hybrid particles is based on oil in water magnetic emulsion (MES) transformation. The encapsulation of magnetic iron oxide nanoparticles forming oil in water MES was investigated using different styrene/cross‐linker divinylbenzene volume ratio in the presence of potassium persulfate initiator. The encapsulation performed in this work is basically conducted by using well‐defined oil in water MES as a seed in radical emulsion polymerization. The chemical composition, morphology, iron oxide content, magnetic properties, electrokinetic properties, particle size, and size distribution of the prepared magnetic hybrid particles were examined using various techniques. The desired perfect magnetic core and polymer shell morphology were successfully obtained, and the final magnetic hybrid particles are superparamagnetic in nature and exhibit high iron oxide content (64 wt %). Copyright © 2015 John Wiley & Sons, Ltd.