bluuebunny/crossref_metadata_2025 huggingface dataset:
Does breeding a bulldog harm it? Breeding, ethics and harm to animals
Authors: Palmer C
Published: June 2012

It is frequently claimed that breeding animals that we know will have unavoidable health problems is at least prima facie wrong, because it harms the animals concerned. However, if we take ‘harm’ to mean ‘makes worse off’, this claim appears false. Breeding an animal that will have unavoidable health problems does not make any particular individual animal worse off, since an animal bred without such problems would be a different individual animal. Yet, the intuition that there is something ethically wrong about breeding animals — such as purebred pedigree dogs — in ways that seem negatively to affect welfare remains powerful. In this paper, an animal version of what is sometimes called the non-identity problem is explored, along with a number of possible ways of understanding what might be wrong with such breeding practices, if it is not that they harm the animal itself. These possibilities include harms to others, placeholder arguments, non-comparative ideas of harm, an ‘impersonal’ approach, and concerns about human attitudes and dispositions.
Analysis of MLL2 gene in the first Brazilian family with Kabuki syndrome
Authors: Kokitsu‐Nakata Nancy Mizue , Petrin Aline Lourenço , Heard Jason Paul , Vendramini‐Pittoli Siulan , Henkle Laura E , dos Santos Daniela Vera Cruz , Murray Jeffrey Clark , Richieri‐Costa Antonio
Published: June 2012

Most patients with Kabuki syndrome (KS) are the only person in their family with the condition. However, familial cases of KS have been described showing evidence that this syndrome can be inherited as a dominant trait with variable expressivity. We report on two related individuals with facial findings characteristic of KS. The proposita had arched eyebrows, long and upward slanting palpebral fissures, cleft lip and palate, retromicrognathia, brachydactyly of hands and feet, stubby fingers, nail hypoplasia, and prominent finger pads. Her mother had eyebrows with dispersed lateral half, long and upward slanting palpebral fissures, retrognathia, abnormal and posteriorly rotated ears, prominent finger pads, brachydactyly of feet, learning difficulties, and psychomotor development delay. DNA sequencing revealed a novel missense mutation in the MLL2 gene in both the proposita and her mother. The mutation (p.R5432Q) was found in the exon 51, within the SET domain of the gene, which confers methyltransferase activity on the protein. Therefore, the epigenetic and transcriptional regulatory properties of this protein may be altered and this suggests that the mutation is the cause of phenotype observed in both the patient and her mother. The clinical signs and the molecular evidence in this family further support the notion that KS is an autosomal dominant condition with variable expressivity. To our knowledge this is the first report of a Brazilian family with recurrence of this syndrome. © 2012 Wiley Periodicals, Inc.
Pyrolyzed chicken feather fibers for biobased composite reinforcement
Authors: Senoz Erman , Stanzione Joseph F. , Reno Kaleigh H. , Wool Richard P. , Miller Melissa E. N.
Published: June 2012

An environment friendly, green composite design was demonstrated by producing an almost completely biorenewable and affordable material. Mildly pyrolyzed chicken feather fibers (PCFF) were incorporated in acrylated epoxidized soybean oil (AESO) and methacrylated lauric acid (MLAU)‐based thermosetting resin to provide reinforcement in low density and rubbery polymer applications. The mechanical properties of the polymer composite, such as storage modulus, tensile modulus, tensile strength, and fracture energy were directly proportional to the fiber content. Varying the fiber content up to 32 wt % allowed for a wide tuning of mechanical properties (i.e., 20–300 MPa storage modulus and 10–150 MPa range at room temperature). Upon subjecting the CFFs to a strategic pyrolysis thermal history, the formation of isopeptide and ester bonds with limited protein backbone scission resulted in mechanical fiber integrity. Thermally stabilized PCFF have the potential for utilization in composite manufacturing, where typical manufacturing temperatures, especially in thermoplastic extrusion, exceed the untreated biobased fiber degradation temperature (215°C). © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Development of water‐blown bio‐based thermoplastic polyurethane foams using bio‐derived chain extender
Authors: Rashmi Baralu Jagannatha , Rusu Daniela , Prashantha Kalappa , Lacrampe Marie France , Krawczak Patricia
Published: June 2012

Water‐blown bio‐based thermoplastic polyurethane (TPU) formulations were developed to fulfill the requirements of the reactive rotational molding/foaming process. They were prepared using synthetic and bio‐based chain extenders. Foams were prepared by stirring polyether polyol (macrodiol), chain extender (diol), surfactant (silicone oil), chemical blowing agent (distilled water), catalyst, and diisocyanate. The concentration of chain extender, blowing agent, and surfactant were varied and their effects on foaming kinetics, physical, mechanical, and morphological properties of foams were investigated. Density, compressive strength, and modulus of foams decrease with increasing blowing agent concentration and increase with increasing chain extender concentration, but are not significantly affected by changes in surfactant concentration. The foam glass‐transition temperatures increase with increasing blowing agent and chain extender concentrations. The foam cell size slightly increases with increasing blowing agent content and decreases upon surfactant addition (without any dependence on concentration), whereas chain extender concentration has no effect on cell size. Bio‐based 1,3‐propanediol can be used successfully for the preparation TPU foams without sacrificing any properties. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Ultra‐performance liquid chromatography‐tandem mass spectrometry method for the determination of febuxostat in dog plasma and its application to a pharmacokinetic study
Authors: Zhang Tianhong , Sun Yuanpeng , Zhang Peng , Gao Jingmei , Wang Shanshan , He Zhonggui
Published: June 2012

A rapid, sensitive and selective ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for the determination of febuxostat in dog plasma. Using paclitaxel as an internal standard (IS), a simple liquid–liquid extraction method with ethyl acetate was adopted for plasma sample pretreatment. Separation was carried out on an Acquity UPLC BEH C18 column with a mobile phase consisting of acetonitrile and water (containing 0.2% formic acid). The assay was linear in the concentration ranged from 5 to 5000 ng/mL with a lower limit of quantification of 5 ng/mL for febuxostat. The single run analysis was as short as 2.0 min. Finally, the developed method was successfully applied to the pharmacokinetic study of febuxostat tablets following oral administration at a single dose of 40 mg in beagle dogs. Copyright © 2012 John Wiley & Sons, Ltd.
Qualitative detection of illegal drugs (cocaine, heroin and MDMA) in seized street samples based on SFS data and ANN: validation of method
Authors: Mazina Jekaterina , Aleksejev Valeri , Ivkina Tatjana , Kaljurand Mihkel , Poryvkina Larissa
Published: June 2012

In this paper, the validation procedure of spectral fluorescence signature (SFS) method combined with multilayer perceptron artificial neural networks (MLP‐ANNs) for detection of illegal drugs (cocaine, heroin and 3,4‐methylenedioxy‐N‐methylamphetamine) in street samples is proposed. The qualitative information, based on a binary response (detected/not detected), was directly obtained through the response of an expert system. The performance parameters (limit of detection, selectivity/matrix effects, threshold value and robustness) were evaluated according to the requirements for qualitative method. Copyright © 2012 John Wiley & Sons, Ltd.
Genetic predisposition of hand‐foot skin reaction after sorafenib therapy in patients with hepatocellular carcinoma
Authors: Lee Joo Ho , Chung Young‐Hwa , Kim Jeong A. , Shim Ju Hyun , Lee Danbi , Lee Han Chu , Shin Eun‐Soon , Yoon Jung Hwan , Kim Byung Ik , Bae Si Hyun , Koh Kwang Cheol , Park Neung‐Hwa
Published: June 2012

BACKGROUND:

Sorafenib currently sets the new standard for advanced hepatocellular carcinoma (HCC). It has been suggested that Asian patients with HCC have increased susceptibility to hand‐foot skin reaction (HFSR) related to sorafenib therapy. The authors investigated the association between sorafenib‐induced HFSR and genetic polymorphisms in Korean patients with HCC.

METHODS:

For this prospective cohort study, the authors enrolled 59 consecutive patients with intermediate stage HCC from 5 centers in Korea. All patients received sorafenib 400 mg twice daily in combination with transarterial chemoembolization (TACE). Genotyping was performed on a total of 49 single nucleotide polymorphisms (SNPs) in 8 candidate genes (minor allelic frequency ≥5%). Serum levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor‐alpha (TNF‐α) were measured using enzyme‐linked immunosorbent assays before therapy and 1 month after therapy.

RESULTS:

During a median treatment period of 18 months, 55 patients (93%) developed sorafenib‐induced HFSR, including grade 1 reactions in 15 patients, grade 2 reactions in 27 patients, and grade 3 reaction in 13 patients. The SNPs TNF‐α −308GG, VEGF −94GG, VEGF 1991CC, VEGF IVS3‐28CC, and uridine diphosphate glucuronosyltransferase 1 family‐polypeptide A9 (UGT1A9) IVS1‐37431AA were associated significantly with the development of high‐grade (grade 2 or 3) HFSR in univariate analysis (P < .05). In multivariate analysis, the SNPs VEGF 1991CC (odds ratio, 45.7), TNF‐α −308GG (odds ratio, 44.1), and UGT1A9 IVS1‐37431AA (odds ratio, 18.7) were identified as independent risk factors for the development of high‐grade HFSR (P = .01, P = .02, and P = .02, respectively). He serum TNF‐α level measured 1 month after sorafenib therapy was correlated significantly with the development of high‐grade HFSR (odds ratio, 3.56; P = .026).

CONCLUSIONS:

Differences in the incidence of HFSR may have been caused by ethnic differences in genetic polymorphisms of the TNF‐α, VEGF, and UGT1A9 genes, especially in relation to the expression of serum TNF‐α after sorafenib therapy. Cancer 2013. © 2012 American Cancer Society.
“Late” macroendosomes and acidic endosomes in vertebrate motor nerve terminals
Authors: Stewart Richard S. , Teng Haibing , Wilkinson Robert S.
Published: June 2012

Activity at the vertebrate nerve—muscle synapse creates large macroendosomes (MEs) via bulk membrane infolding. Visualized with the endocytic probe FM1‐43, most (94%) of the ∼25 MEs/terminal created by brief (30‐Hz, 18‐second) stimulation dissipate rapidly (∼1 minute) into vesicles. Others, however, remain for hours. Here we study these “late” MEs by using 4D live imaging over a period of ∼1 hour after stimulation. We find that some (51/398 or 13%) disappear spontaneously via exocytosis, releasing their contents into the extracellular milieu. Others (at least 15/1,960 or 1%) fuse or closely associate with a second class of endosomes that take up acidophilic dyes (acidic endosomes [AEs]). AEs are plentiful (∼47/terminal) and exist independent of stimulation. Unlike MEs, which exhibit Brownian motion, AEs exhibit directed motion (average, 83 nm/sec) on microtubules within and among terminal boutons. AEs populate the axon as well, where movement is predominantly retrograde. They share biochemical and immunohistochemical markers (e.g., lysosomal‐associated membrane protein [LAMP‐1]) with lysosomes. Fusion/association of MEs with AEs suggests a sorting/degradation pathway in nerve terminals wherein the role of AEs is similar to that of lysosomes. Based on our data, we propose that MEs serve as sorting endosomes. Thus their contents, which include plasma membrane proteins, vesicle proteins, and extracellular levels of Ca2+, can be targeted either toward the reformation and budding of synaptic vesicles, toward secretion via exocytosis, or toward a degradation process that utilizes AEs either for lysis within the terminal or for transport toward the cell body. J. Comp. Neurol. 520:4275–4293, 2012. © 2012 Wiley Periodicals, Inc.
Tolerant Chalcogenide Cathodes of Membraneless Micro Fuel Cells
Authors: Gago Aldo Saul , Gochi‐Ponce Yadira , Feng Yong‐Jun , Esquivel Juan Pablo , Sabaté Neus , Santander Joaquin , Alonso‐Vante Nicolas
Published: June 2012

The most critical issues to overcome in micro direct methanol fuel cells (μDMFCs) are the lack of tolerance of the platinum cathode and fuel crossover through the polymer membrane. Thus, two novel tolerant cathodes of a membraneless microlaminar‐flow fuel cell (μLFFC), PtxSy and CoSe2, were developed. The multichannel structure of the system was microfabricated in SU‐8 polymer. A commercial platinum cathode served for comparison. When using 5 M CH3OH as the fuel, maximum power densities of 6.5, 4, and 0.23 mW cm−2 were achieved for the μLFFC with Pt, PtxSy, and CoSe2 cathodes, respectively. The PtxSy cathode outperformed Pt in the same fuel cell when using CH3OH at concentrations above 10 M. In a situation where fuel crossover is 100 %, that is, mixing the fuel with the reactant, the maximum power density of the micro fuel cell with Pt decreased by 80 %. However, for PtxSy this decrease corresponded to 35 % and for CoSe2 there was no change in performance. This result is the consequence of the high tolerance of the chalcogenide‐based cathodes. When using 10 M HCOOH and a palladium‐based anode, the μLFFC with a CoSe2 cathode achieved a maxiumum power density of 1.04 mW cm−2. This micro fuel cell does not contain either Nafion membrane or platinum. We report, for the first time, the evaluation of PtxSy‐ and CoSe2‐based cathodes in membraneless micro fuel cells. The results suggest the development of a novel system that is not size restricted and its operation is mainly based on the selectivity of its electrodes.
Analysis, design and implementation of a high‐voltage gain DC‐DC converter
Authors: Lin Bor‐Ren , Tung Chia‐Yu
Published: June 2012

An interleaved DC‐DC converter with soft switching technique is presented. There are two converter modules in the adopted circuit to share the load power. Since the interleaved pulse‐width modulation (PWM) is adopted to control two circuit modules, the ripple currents at input and output sides are naturally reduced. Therefore the input and output capacitances can be reduced. In each circuit module, a conventional boost converter and a voltage doubler configuration with a coupled inductor are connected in series at the output side to achieve high step‐up voltage conversion ratio. Active snubber connected in parallel with boost inductor is adopted to limit voltage stress on active switch and to release the energy stored in the leakage and magnetizing inductances. Since asymmetrical PWM is used to control active switches, the leakage inductance and output capacitance of active switches are resonant in the transition interval. Thus, both active switches can be turned on at zero voltage switching. The resonant inductance and output capacitances at the secondary side of transformer are resonant to achieve zero current switching turn‐off for rectifier diodes. Therefore, the reverse recovery losses of fast recovery diodes are reduced. Finally, experiments based on a laboratory prototype rated at 400 W are presented to verify the effectiveness of the proposed converter. Copyright © 2012 John Wiley & Sons, Ltd.
Gyrokinetic Simulations of the Edge Pedestal in the TEXTOR Tokamak
Authors: Kiviniemi T. , Leerink S. , Heikkinen J.A. , Janhunen S. , Korpilo T.
Published: June 2012

Full‐f gyrokinetic simulations starting from real experimental TEXTOR profiles are shown to include all the physics ingredients to maintain the steep density profile in H‐mode. For L‐mode profiles, strong geodesic acoustic modes (GAMs) are observed together with strongly correlated oscillatory particle fluxes which lead to profile relaxation (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Modeling of Local Edge Plasma Perturbations Induced by a Biased Probe
Authors: Umansky M.V. , Brunner D. , LaBombard B. , Rognlien T. D.
Published: June 2012

The Langmuir probe is a standard diagnostic tool for laboratory plasmas, routinely used for edge plasmas in magnetic fusion devices. However, recent studies on the Alcator C‐Mod tokamak indicate the possibility of a substantial local plasma perturbation by a negatively biased divertor plate target probe under high recycling conditions when the electron temperature is under ∼10 eV. The effects of the probe perturbation of the plasma are studied using the tokamak edge plasma code UEDGE for parameters relevant to Alcator C‐Mod edge. It is found that at sufficiently negative bias voltage, the probe substantially modifies the local plasma characteristics. In particular, this is relevant to the experimentally known “death‐ray” phenomenon, where the plasma pressure near the probe strongly exceeds the upstream value. Certain features of the “death‐ray” phenomenon are reproduced in the modeling, pointing to interplay of plasma and neutrals transport, atomic physics, and sheath heat‐flux boundary conditions (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Effect of Non‐Coulomb Scattering of Relativistic Electrons on the Generation of Runaways in Multicomponent Plasma
Authors: Igitkhanov Yu. L.
Published: June 2012

Highly energetic runaway electrons are able to penetrate the electron shell of partly ionized heavy ions during collisions, for which reason they may be scattered by a positive charge effectively larger than that of a shielded nucleus. This effect increases the Coulomb cross section and can be treated via an effective ion charge Zeff (εkin) that depends on the energy of the incident electrons εkin. The increase of effective charge number with increasing electron energy in multi‐component plasmas renders qualitatively the same result as high Zeff Coulomb plasmas. Since the generation rate of runaways depends on Zeff, its production during the mitigation of disruptions by massive gas injection could in some cases decrease owing to a heavy impurity concentration in the boundary tokamak plasma. This may explain why it has been observed that the runaway's avalanche is suppressed at electron densities below the so‐called “Rosenbluth density” (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electric Field at a Plasma‐Facing Wall for a Two‐Temperature Electron Distribution
Authors: Tomita Y. , Kawamura G. , Ueno M. , Ohno N. , Huang Z.H. , Pan Y.D. , Yan L.W.
Published: June 2012

The floating potential drop and the electric field at a plasma‐facing wall are studied in the case of double electron temperature, where electrons have a double‐Maxwellian velocity distribution and the ion distribution function is modeled by a Maxwellian distribution shifted by the ion sound speed at the sheath entrance. It was quantitatively clarified that the effects between the hot electron component and the ion temperature to the floating wall potential drop, where the higher hot electron component increases the potential drop and the finite ion temperature decreases it. The electric field is almost proportional to the density of the hot component for the case of lower hot component. On the other hand, at the higher hot electron component the electric field has its maximum with respect to the density of the hot component (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Progress with the COGENT Edge Kinetic Code: Collision Operator Options
Authors: Dorf M. A. , Cohen R. H. , Compton J. C. , Dorr M. , Rognlien T. D. , Angus J. , Krasheninnikov S. , Colella P. , Martin D. , McCorquodale P.
Published: June 2012

COGENT is a continuum gyrokinetic code for edge plasmas being developed by the Edge Simulation Laboratory collaboration. The code is distinguished by application of the fourth order conservative discretization, and mapped multiblock grid technology to handle the geometric complexity of the tokamak edge. It is written in v‖‐μ (parallel velocity – magnetic moment) velocity coordinates, and making use of the gyrokinetic Poisson equation for the calculation of a self‐consistent electric potential. In the present manuscript we report on the implementation and initial testing of a succession of increasingly detailed collision operator options, including a simple drag‐diffusion operator in the parallel velocity space, Lorentz collisions, and a linearized model Fokker‐Planck collision operator conserving momentum and energy (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Reduced Electron Models for Edge Simulation
Authors: Cohen R. H. , Dorf M. , Dorr M.
Published: June 2012

We consider the treatment of electrons in kinetic simulations of edge plasmas. A fully kinetic treatment of electrons is expensive because of the short timescales associated with rapid streaming along field lines. Hence we survey a number of reduced options, of varying complexity, with particular attention to the “adiabatic model” commonly used for core plasmas. We note that the adiabatic model is the linear limit of a Boltzmann model, whose nonlinear form is more appropriate for the large potential variations in edge plasmas, and then consider extensions to the Boltzmann model which render it applicable to a plasma which includes end‐loss in the scrape‐off layer (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Efficient and simultaneous generation of hematopoietic and vascular progenitors from human induced pluripotent stem cells
Authors: Park Tea Soon , Zimmerlin Ludovic , Zambidis Elias T.
Published: June 2012

The hematopoietic and vascular lineages are intimately entwined as they arise together from bipotent hemangioblasts and hemogenic endothelial precursors during human embryonic development. In vitro differentiation of human pluripotent stem cells toward these lineages provides opportunities for elucidating the mechanisms of hematopoietic genesis. We previously demonstrated the stepwise in vitro differentiation of human embryonic stem cells (hESC) to definitive erythromyelopoiesis through clonogenic bipotent primitive hemangioblasts. This system recapitulates an orderly hematopoiesis similar to human yolk sac development via the generation of mesodermal‐hematoendothelial progenitor cells that give rise to endothelium followed by embryonic primitive and definitive hematopoietic cells. Here, we report that under modified feeder‐free endothelial culture conditions, multipotent CD34+CD45+ hematopoietic progenitors arise in mass quantities from differentiated hESC and human induced pluripotent stem cells (hiPSC). These hematopoietic progenitors arose directly from adherent endothelial/stromal cell layers in a manner resembling in vivo hematopoiesis from embryonic hemogenic endothelium. Although fibroblast‐derived hiPSC lines were previously found inefficient in hemato‐endothelial differentiation capacity, our culture system also supported robust hiPSC hemato‐vascular differentiation at levels comparable to hESC. We present comparative differentiation results for simultaneously generating hematopoietic and vascular progenitors from both hESC and fibroblast‐hiPSC. This defined, optimized, and low‐density differentiation system will be ideal for direct single‐cell time course studies of the earliest hematopoietic events using time‐lapse videography, or bulk kinetics using flow cytometry analyses on emerging hematopoietic progenitors. © 2012 International Society for Advancement of Cytometry
A new identity dimensional D‐state observer for sensorless drive of permanent‐magnet synchronous motors
Authors: Shinnaka Shinji
Published: June 2012

A new identity dimensionless D‐state observer whose state variables are the stator reaction flux and rotor flux is proposed for the sensorless drive of permanent‐magnet synchronous motors. Furthermore, sufficient conditions are newly and analytically derived for the observer gains that guarantee stable convergence of state variable estimates. Additionally, two new methods for designing observer gain are presented; these methods, the constant and speed‐dependent gain methods, satisfy the derived analytical conditions. The observer gain conditions used in the design methods are validated through extensive numerical experiments. In addition, typical design examples of the observer gains using the proposed design methods are presented. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 181(1): 45–61, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21200
Integrated reproduction of human motion components by motion copying system
Authors: Tsunashima Noboru , Katsura Seiichiro
Published: June 2012

Currently, the development of leading‐edge technology for recording and loading human motion on the basis of haptic information is required in the fields of manufacturing and human support. Human movement is an assembly of motion components. Since human movements should be supported by a robot in real time, it is necessary to integrate the motion components that were saved earlier. Once such motion integration is realized, future technology for use in daily human life can be developed. This paper proposes the integrated reproduction of the decomposed components of human motion by using a motion copying system. This system is the key technology for the realization of the acquisition, saving, and reproduction of real‐world haptic information. By using the proposed method, it is possible not only to achieve expert skill acquisition, skill transfer to robots, and power assist for each motion component, but also to open up new areas of applications. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 181(1): 28–35, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21263
Receptor modulation and functional activation of human CD34+Lin−‐derived immature NK cells in vitro by Mycobacterium bovisBacillus Calmette‐Guerin (BCG)
Authors: Marras Francesco , Bozzano Federica , Bentivoglio Giorgio , Ugolotti Elisabetta , Biassoni Roberto , Moretta Lorenzo , De Maria Andrea
Published: June 2012

It is not yet clear whether immature NK (iNK) cells are bystanders to or rather participate in immune responses to pathogens that may colocalize in areas of NK‐cell maturation such as bone marrow or lymph nodes. Mycobacteria, including Bacillus Calmette‐Guerin (BCG), have been shown to interact with peripheral NK cells and in vivo may colocalize in areas of iNK‐cell development. We studied infection with BCG of human cord blood CD34+Lin−‐derived cultures containing myelomonocytes and iNK cells in vitro. Increased iNK‐cell DNAM‐1 expression, transient natural cytotoxicity receptor modulation, and production of IFN‐γ were observed. Transcriptional receptor modulation was associated to BCG challenge, which determined increased iNK‐cell cytotoxic activity against tumor cell lines and also increased killing of immature dendritic cells (iDCs). No requirement for cell contact was recorded for BCG‐induced iNK‐cell activation, while cytokine production including IL‐18, IL‐10, GM‐CSF, and TGF‐β contributed to the observed effects. Thus, iNK cells are affected by mycobacteria in vitro and may contribute to shaping of adaptive mature innate responses through iDC‐iNK cross‐talk. In addition, iNK‐cell activation by BCG may represent a novel additional mechanism contributing to the effects observed upon BCG administration in vivo.
The Reactions of Thianthrene and Selenanthrene with AlCl3: Coordination Complexes, Radical Ions, and Investigations on the Unique Triple‐Decker Molecule (Thianthrene)32+
Authors: Tjahjanto Rachmat Triandi , Peintinger Michael F. , Bredow Thomas , Beck Johannes
Published: June 2012

The reactions of thianthrene (TA) and selenanthrene (SeA) with AlCl3 were studied in the melt phase and with liquid SO2 as solvent. From neat AlCl3 and TA, the colorless complex [AlCl3(TA)] was isolated as the main product and the dark red salt (TA)3[Al2Cl7]2 as the byproduct. The analogous solvent‐free reaction of selenanthrene and AlCl3 takes a different course as colorless [Al(SeA)3][Al2Cl7]3 is formed in quantitative yield. With SO2 as solvent, both TA and SeA give the black radical salts (TA)2[AlCl4]2 and (SeA)2[AlCl4]2, respectively. In the structure of [AlCl3(TA)], thianthrene acts as a monodentate ligand and coordinates with one S atom to the pyramidal AlCl3 unit. The structure of the (TA)32+ ion is a stack of three almost planar TA molecules in parallel arrangement. [Al(SeA)3]3+ represents a tris‐chelate complex ion with SeA acting as a bidentate ligand and both Se atoms binding to the octahedrally coordinated Al3+ ion. (SeA)2[AlCl4]2 consists of dimers of SeA+ radical ions, which are bound by weak intermolecular Se···Se bonds. Tentative reaction equations are given to explain the unexpected oxidation processes that lead to the radical ions. Quantum chemical calculations were performed on the molecular fragments and on the periodical structures. The trimeric (TA)32+ ion is in the singlet state in accordance with the magnetic properties of (TA)3[Al2Cl7]2, which show a weak temperature‐independent paramagnetism. The ion is bound by long‐range four‐center bonds between the outer two radicals.
Seven‐Membered Intramolecular Hydrogen Bonding of Phenols: Database Analysis and Phloroglucinol Model Compounds
Authors: Castellano Ronald K. , Li Yan , Homan Edwin A. , Lampkins Andrew J. , Marín Iris V. , Abboud Khalil A.
Published: June 2012

Seven‐membered intramolecular hydrogen bonding (7MHB) arrangements involving phenolic hydroxyl group donors have been investigated through Cambridge Structural Database (CSD) and literature mining, and by the characterization of model compounds. The CSD reveals the numerous H‐bond accepting functional groups that can participate in 7MHB when they are proximal to a phenolic OH, including alcohols, amides, amines, ethers, N‐containing heterocycles, ketones, N‐oxides, phosphates, and phosphane oxides. The HB contacts are defined by Ophenol···N and Ophenol···O distances of ca. 2.7 Å, and two dihedral angles that fall within the range of typical peptide γ‐turns. Two of the identified 7MHB motifs have been readily mapped onto the phloroglucinol (1,3,5‐trihydroxybenzene) scaffold to provide eight model compounds; intramolecular hydrogen bonding involving all three hydroxyl groups is shown to persist in solution and the solid state for the compounds. Intramolecular 7MHB enforces nonplanar conformations that should be useful when designing molecular hosts and catalysts.
Electrochemical Sensor Based on Molecularly Imprinted Polymer Film Prepared with Functional Abietic‐Type Acids as Cross‐Linker for the Determination of Quinine
Authors: Liu Li , Tan Xuecai , Fang Xiaoxue , Sun Yuexin , Lei Fuhou , Huang Zaiyin
Published: June 2012

A novel cross‐linker (functional abietic‐type acids) for preparing highly sensitive, molecularly imprinted sensors was proposed for quinine determination. A MIP film was created on a glassy carbon electrode for determination of quinine using free radical polymerization method. The modification procedure was characterized via electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The interaction between functional monomer and target molecule was observed by UV spectrometric methods. Under the optimal experimental conditions, the peak currents were proportional to the concentrations of quinine in the range from 8.0×10−7 to 2.6×10−4 M with a detection limit of 2.0×10−8 M. Meanwhile the prepared sensor showed sensitive and selective binding sites for quinine. Determination of quinine in tonic water showed good recovery.
An Electrochemical Impedance Immunosensor Based on Gold Nanoparticle‐Modified Electrodes for the Detection of HbA1c in Human Blood
Authors: Liu Guozhen , Iyengar Sridhar G. , Gooding J. Justin
Published: June 2012

A label‐free immunosensor for the detection of HbA1c was developed based on gold nanoparticle (AuNP)‐aryl diazonium salt modified glassy carbon (GC) electrode where transduction is achieved using electrochemical impedance spectroscopy (EIS). GC electrodes were first modified with 4‐aminophenyl (Ph‐NH2) layers to which AuNPs were attached. Thereafter an oligo(ethylene glycol) (OEG‐COOH) species were covalently attached to the remaining free amine groups on the Ph‐NH2 surface. The AuNP surfaces were further modified with Ph‐NH2 followed by attachment of a glycosylated pentapeptide (GPP), an analogon to HbA1c. Exposure of this interface to anti‐HbA1c IgG resulted in a change in charge transfer resistance (Rct) due to the anti‐HbA1c IgG selectively complexing to the surface bound GPP. To detect the amount of HbA1c, a competitive inhibition assay was employed where the surface bound GPP and HbA1c in solution compete for the anti‐HbA1c IgG antibodies. The higher the concentration of HbA1c, the less antibody binds to the sensing interface and the lower the change of Rct. The response of the immunosensor is linear with the HbA1c% of total haemoglobin in the range of 0%–23.3%. This competitive inhibition assay can be used for the detection of HbA1c in human blood. The performance of the immunosensor for detection of HbA1c in human blood is comparable to the clinical laboratory method.
Development and validation of a capillary electrophoresis method for the determination of escitalopram and sensitive quantification of its enantiomeric impurity in formulations
Authors: Deng Xiaolan , De Wolf Joris , Vervoort Ruud , Pamperin Dirk , Adams Erwin , Schepdael Ann Van
Published: June 2012

A rapid capillary zone electrophoresis method has been developed capable of quantifying 0.05% of R‐enantiomer and assaying the main component in escitalopram formulations. Many parameters influencing enantioseparation were investigated, which include chiral selectors, buffer composition and pH, applied voltage, capillary length, temperature, and rinsing procedure. Optimal separation conditions were obtained by using a 25 mM phosphate buffer at pH 7.0, containing 1.6% (w/v) sulfated‐β‐cyclodextrin with short‐end injection at 0.5 psi for 5 s. Online UV detection was performed at 205 nm. A voltage of −20 kV was applied and the capillary temperature was kept at 25°C. Separation was achieved in less than 2 min. The method was further validated, including robustness, stability of the solution, selectivity, linearity (escitalopram from 0.25 μg/mL to 600 μg/mL, y = 1528.3 × +1812.9; R2 = 0.9999), LOD and LOQ (0.08 and 0.25 μg/mL, respectively), precision and accuracy. The proposed method was then applied to the quality control of the bulk sample and tablets of escitalopram (10 mg).
Capillary electrophoretic enantioselective determination of zopiclone and its impurities
Authors: Tonon Milena Araújo , Bonato Pierina Sueli
Published: June 2012

A capillary electrophoretic enantioselective method with UV detection was developed and validated for the simultaneous quantification of zopiclone enantiomers and its impurities, zopiclone‐N‐oxide enantiomers, and 2‐amino‐5‐chloropyridine, in tablets. The analytes were extracted from the tablets using ACN and were separated in an uncoated fused‐silica capillary (50 μm, 42 cm effective length, 50 cm total length) using 80 mM sodium phosphate buffer pH 2.5 and 5 mM carboxymethyl‐β‐cyclodextrin as running buffer. The analytes and the internal standard (trimethoprim) were detected at 305 and 200 nm, respectively. A voltage of 27 kV was applied and the capillary temperature was maintained at 25°C. All enantiomers were analyzed within 8 min and linear calibration curves over the concentration range of 0.4–0.8 mg mL−1 for each zopiclone enantiomer, 0.8–1.6 μg mL−1 for 2‐amino‐5‐chloropyridine and 0.4–0.8 μg mL−1 for each zopiclone‐N‐oxide enantiomer were obtained. The coefficients of correlation obtained for the linear curves were greater than 0.99. The intra‐day and inter‐day accuracy and precision were lower than 2% for all analytes. This validated method was employed to study the degradation and racemization of zopiclone under stress conditions. This application demonstrated the importance of a stability‐indicating assay method for this drug.
Forensic analysis of mesembrine alkaloids in Sceletium tortuosum by nonaqueous capillary electrophoresis mass spectrometry
Authors: Roscher Jörg , Posch Tjorben Nils , Pütz Michael , Huhn Carolin
Published: June 2012

The consumption of legal and illegal drugs follows an organic trend comparable to the current trend in food consumption. The investigation of such drugs is therefore of interest to characterize the active ingredients of plants and drug preparations. A new method of nonaqueous capillary electrophoresis coupled to mass spectrometry (NACE‐MS) as a powerful tool for the separation of complex alkaloid mixtures in difficult matrices is presented in this study for the analysis of samples of Sceletium tortuosum and drug products called Kanna made thereof. The method was found to be suitable for the investigation of the alkaloid composition and relative quantification of the ingredients. It proved of value to separate a large number of isobaric compounds, most probably including diastereomers, double‐bond isomers, and further structurally closely related compounds. A comparison of plant samples from different vendors, self‐fermented samples, and products ready for consumption was made. The high separation power obtained allowed a better description of the chemotypic differences of plant samples as well as Kanna preparations compared to other methods presented in the literature so far. Thus, the use of the NACE‐MS enables a new perspective on the alkaloid profile of Sceletium species.
Capillary electrophoresis/mass spectrometry relevant to pharmaceutical and biotechnological applications
Authors: Pioch Markus , Bunz Svenja‐Catharina , Neusüß Christian
Published: June 2012

Advanced analytical techniques play a crucial role in the pharmaceutical and biotechnological field. In this context, capillary electrophoresis/mass spectrometry (CE/MS) has attracted attention due to efficient and selective separation in combination with powerful detection allowing identification and detailed characterization. Method developments and applications of CE/MS have been focused on questions not easily accessible by liquid chromatography/mass spectrometry (LC/MS) as the analysis of intact proteins, carbohydrates, and various small molecules, including peptides. Here, recent approaches and applications of CE/MS relevant to (bio)pharmaceuticals are reviewed and discussed to show actual developments and future prospects. Based on other reviews on related subjects covering large parts of previous works, the paper is focused on general ideas and contributions of the last 2 years; for the analysis of glycans, the period is extended back to 2006.
Succinic acid production from n‐alkanes
Authors: Kamzolova Svetlana V. , Vinokurova Natalia G. , Yusupova Alsu I. , Morgunov Igor G.
Published: June 2012

A novel process of production of succinic acid (SA) has been developed, which includes the synthesis of alpha‐ketoglutaric acid by a thiamine‐auxotrophic yeast strain Yarrowia lipolytica VKM Y‐2412 from n‐alkanes and subsequent oxidation of the acid by hydrogen peroxide to SA. The concentration of SA in the culture broth and its yield were found to be 38.8 g/L and 82.45% of n‐alkane consumed, respectively. The isolation procedure involved the extraction of the residual alkanes with the mixture of ethyl acetate and hexane, the decomposition of H2O2 in the filtrate followed by filtrate bleaching and acidification with a mineral acid; the evaporation of filtrate and the ethanol extraction of SA from lyophilized residue. The purity of the SA isolated from the culture liquid filtrate reached 99.5%.
PRIORITY SETTING IN HEALTH CARE: DISENTANGLING RISK AVERSION FROM INEQUALITY AVERSION
Authors: Echazu Luciana , Nocetti Diego
Published: June 2012

In this paper, we introduce a tractable social welfare function that is rich enough to disentangle attitudes towards risk in health outcomes from attitudes towards health inequalities across individuals. Given this preference specification, we evaluate how the introduction of uncertainty over the severity of illness and over the effectiveness of treatments affects the optimal allocation of healthcare resources. We show that the way in which uncertainty affects the optimal allocation within our proposed specification may differ sharply from that in the standard expected utility framework. Copyright © 2012 John Wiley & Sons, Ltd.
Cross‐border Insolvency and Legal Transnationalisation
Authors: Mason Rosalind
Published: June 2012

The last 20 years has seen an explosion of approaches for dealing with an inevitable consequence of globalised markets, that of cross‐border insolvencies. This article places phenomena such as the United Nations Commission on International Trade Law Model Law on Cross‐border Insolvency and Cross‐border Insolvency Agreements (also known as Protocols) within the context of developing laws on international commercial transactions. First, it briefly describes the evolution of the international commercial law (sometimes known as the law merchant) to provide a context to understanding the international commercial responses to the problems created by cross‐border insolvencies. Next, it outlines the range of approaches being adopted by states and multilateral bodies in recent decades to resolve cross‐border insolvency issues. Finally it draws some preliminary conclusions on the potential implication of this transnationalisation process and broader international commercial law perspective, in particular on the capacity of cross‐border insolvency agreements to address cross‐border insolvency issues. Copyright © 2012 John Wiley & Sons, Ltd.
Generation, characterization and potential therapeutic applications of mature and functional hepatocytes from stem cells
Authors: Zhang Zhenzhen , Liu Jianfang , Liu Yang , Li Zheng , Gao Wei‐Qiang , He Zuping
Published: June 2012

Liver cancer is the sixth most common tumor in the world and the majority of patients with this disease usually die within 1 year. The effective treatment for end‐stage liver disease (also known as liver failure), including liver cancer or cirrhosis, is liver transplantation. However, there is a severe shortage of liver donors worldwide, which is the major handicap for the treatment of patients with liver failure. Scarcity of liver donors underscores the urgent need of using stem cell therapy to the end‐stage liver disease. Notably, hepatocytes have recently been generated from hepatic and extra‐hepatic stem cells. We have obtained mature and functional hepatocytes from rat hepatic stem cells. Here, we review the advancements on hepatic differentiation from various stem cells, including hepatic stem cells, embryonic stem cells, the induced pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, and probably spermatogonial stem cells. The advantages, disadvantages, and concerns on differentiation of these stem cells into hepatic cells are highlighted. We further address the methodologies, phenotypes, and functional characterization on the differentiation of numerous stem cells into hepatic cells. Differentiation of stem cells into mature and functional hepatocytes, especially from an extra‐hepatic stem cell source, would circumvent the scarcity of liver donors and human hepatocytes, and most importantly it would offer an ideal and promising source of hepatocytes for cell therapy and tissue engineering in treating liver disease. J. Cell. Physiol. 228: 298–305, 2013. © 2012 Wiley Periodicals, Inc.
Electromagnetic modeling of microstrip reflectarrays using scale changing technique
Authors: Tahir Farooq Ahmad , Aubert Hervé
Published: June 2012

An efficient numerical technique called scale changing technique is applied here for the electromagnetic modeling of microstrip reflectarrays. Based on the partition of the array surface into further planar sub‐domains at various scale levels, this technique allows the computation of the equivalent multiport from the simple cascade of scale changing networks. Each network models accurately the electromagnetic coupling between the various sub‐domains, including the coupling between non‐identical cells in arrays. The high flexibility of the approach associated with advantages of the integral equation formulation renders this original technique powerful and rapid for designing antenna arrays. Because the computation of scale changing networks is mutually independent, processing and memory requirements can be reduced enormously by using multiple processing units. Copyright © 2012 John Wiley & Sons, Ltd.
Relationship between histopathology of pleomorphic adenoma in the parotid gland and recurrence after superficial parotidectomy
Authors: Park Gi Cheol , Cho Kyung‐Ja , Kang Jun , Roh Jong‐Lyel , Choi Seung‐Ho , Kim Sang Yoon , Nam Soon Yuhl
Published: June 2012

Background

This study evaluated the relationships between capsular characteristics and recurrence of parotid pleomorphic adenomas.

Methods

The pathological slides and clinical data of 110 patients that underwent superficial parotidectomy for pleomorphic adenoma in the parotid gland were reviewed retrospectively. The recurrent and non‐recurrent groups comprised 10 and 100 patients, respectively. The two groups were compared with regard to their clinicopathological features, including the capsular characteristics.

Results

Satellite nodules were observed in six of the 10 recurrent group patients (60.0%) but in only 10 of the 100 non‐recurrent group patients (10.0%) (P = 0.001). Five of the recurrent group subjects (50%), but only 11 of the 100 non‐recurrent group subjects (11.0%), had positive resection margins (P = 0.006). Perioperative rupture of the tumor was observed in three recurrent group subjects (30%), but in only four of the non‐recurrent group subjects (4.0%) (P = 0.016). Multivariate analyses showed that the risk of recurrence was more than fivefold higher when satellite nodules were present (P = 0.010) and more than 14‐fold higher when the tumor had ruptured (P = 0.001).

Conclusions

Satellite nodules and tumor rupture increase the risk of recurrence in patients with pleomorphic adenomas treated by superficial parotidectomy. J. Surg. Oncol. 2012; 106: 942–946. © 2012 Wiley Periodicals, Inc.