bluuebunny/crossref_metadata_2025 huggingface dataset:
2‐Carbaborane‐3‐phenyl‐1H‐indoles—Synthesis via McMurry Reaction and Cyclooxygenase (COX) Inhibition Activity
Authors: Laube Markus , Neumann Wilma , Scholz Matthias , Lönnecke Peter , Crews Brenda , Marnett Lawrence J. , Pietzsch Jens , Kniess Torsten , Hey‐Hawkins Evamarie
Published: January 2013

Cyclooxygenase‐2 (COX‐2) inhibitors have been the focus of medicinal chemistry efforts for years, and many compounds that exhibit high selectivity and affinity have been developed. As carbaboranes represent interesting pharmacophores as phenyl mimetics in drug development, this paper presents the synthesis of carbaboranyl derivatives of COX‐2‐selective 2,3‐disubstituted indoles. Despite the lability of carbaboranes under reducing conditions, 2‐carbaborane‐3‐phenyl‐1H‐indoles could be synthesized by McMurry cyclization of the corresponding amides. Whereas the meta‐carbaboranyl‐substituted derivatives lacked COX inhibitory activity, an ortho‐carbaboranyl analogue was active, but showed a selectivity shift toward COX‐1.
GABAergic inputs from direct and indirect striatal projection neurons onto cholinergic interneurons in the primate putamen
Authors: Gonzales Kalynda Kari , Pare Jean‐Francois , Wichmann Thomas , Smith Yoland
Published: January 2013

Striatal cholinergic interneurons (ChIs) are involved in reward‐dependent learning and the regulation of attention. The activity of these neurons is modulated by intrinsic and extrinsic γ‐aminobutyric acid (GABA)ergic and glutamatergic afferents, but the source and relative prevalence of these diverse regulatory inputs remain to be characterized. To address this issue, we performed a quantitative ultrastructural analysis of the GABAergic and glutamatergic innervation of ChIs in the postcommissural putamen of rhesus monkeys. Postembedding immunogold localization of GABA combined with peroxidase immunostaining for choline acetyltransferase showed that 60% of all synaptic inputs to ChIs originate from GABAergic terminals, whereas 21% are from putatively glutamatergic terminals that establish asymmetric synapses, and 19% from other (non‐GABAergic) sources of symmetric synapses. Double pre‐embedding immunoelectron microscopy using substance P and Met‐/Leu‐enkephalin antibodies to label GABAergic terminals from collaterals of “direct” and “indirect” striatal projection neurons, respectively, revealed that 47% of the indirect pathway terminals and 36% of the direct pathway terminals target ChIs. Together, substance P‐ and enkephalin‐positive terminals represent 24% of all synapses onto ChIs in the monkey putamen. These findings show that ChIs receive prominent GABAergic inputs from multiple origins, including a significant contingent from axon collaterals of direct and indirect pathway projection neurons. J. Comp. Neurol. 521:2502–2522, 2013. © 2013 Wiley Periodicals, Inc.
Covalently Cross‐Linked Sulfone Polybenzimidazole Membranes with Poly(Vinylbenzyl Chloride) for Fuel Cell Applications
Authors: Yang Jingshuai , Aili David , Li Qingfeng , Cleemann Lars N. , Jensen Jens Oluf , Bjerrum Niels J. , He Ronghuan
Published: January 2013

Covalently cross‐linked polymer membranes were fabricated from poly(aryl sulfone benzimidazole) (SO2PBI) and poly(vinylbenzyl chloride) (PVBCl) as electrolytes for high‐temperature proton‐exchange‐membrane fuel cells. The cross‐linking imparted organo insolubility and chemical stability against radical attack to the otherwise flexible SO2PBI membranes. Steady phosphoric acid doping of the cross‐linked membranes was achieved at elevated temperatures with little swelling. The acid‐doped membranes exhibited increased mechanical strength compared to both pristine SO2PBI and poly[2,2′‐(m‐phenylene)‐5,5′‐bibenzimidazole] (mPBI). The superior characteristics of the cross‐linked SO2PBI membranes allowed higher acid doping levels and, therefore, higher proton conductivity. Fuel‐cell tests with the cross‐linked membranes demonstrated a high open circuit voltage and improved power performance and durability.
Experimental Study of the Discharge in the Low Pressure Plasma Jet Sputtering System
Authors: Klusoiň J. , Kudrna P. , Kolpaková A. , Picková I. , Hubička Z. , Tichý M.
Published: January 2013

This article reports on experimental study of the discharge in the low pressure plasma jet sputtering system operated in the continuous DC regime of the discharge excitation. Presented measurements were focused on the description of the working pressure impact on the basic discharge characteristics. The pressure dependence of the gas flow velocity from the nozzle was examined by means of Pitot tube. Further an approximate measurement of the discharge current spatial distribution was realized as well. The second half of the article presents results from Langmuir probe measurements under the conditions of low pressures in the range of units of pascals. These conditions are of special importance in some particular applications especially in preparation of thin layers with high crystallinity. Used experimental setup enabled to perform Langmuir probe diagnostic with spatial resolution both in the plasma jet axis direction and in the direction perpendicular to it (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Measurements of Plasma Properties Using the Floating Potential of Emissive Langmuir Probes
Authors: Tierno S.P. , Roibás E. , Doménech‐Garret J.L. , Donoso J.M. , Condo L.
Published: January 2013

The measurement of the plasma potential of unmagnetized Maxwellian plasmas by using the floating potential of emissive Langmuir probes is discussed. The temperature of the probe was monitored in order to estimate the emitted thermoionic electron current and to determine the limits of the strong electron emission regime. Under these ideal conditions, the measurements of the plasma potential of the emissive probe are cross checked against those of collecting Langmuir probes. In agreement with previous works, the current voltage curves of emissive probes show the temperature dependent electron saturation currents. An empirical expression is suggested for the dependence of this saturation current with the probe temperature which recovers the response of collecting probes when the probe is cold. The experimental data indicate that the floating potential of the emissive probe is close to the local plasma potential only when the emitted thermoionic electron current is similar to the electron saturation current. Larger electron emission currents lead to small increments the floating potential over the local plasma potential. Our results suggest that the electron saturation current of a hot emissive probe is composed by the thermal electrons from the plasma and a returned fraction of the thermoionic emitted electrons (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Langmuir Probe Method for Precise Evaluation of the Negative‐Ion Density in Electronegative Gas Discharge Magnetized Plasma
Authors: Popov Tsv. K. , Mitov M. , Bankova A. , Ivanova P. , Dimitrova M. , Rupnik S. , Kovačič J. , Gyergyek T. , Cerček M. , Dias F. M.
Published: January 2013

The paper reports results from Langmuir probe current‐voltage (IV) characteristic measurements in argon and oxygen low‐gas‐pressure magnetized plasma. The plasma was produced in a stainless steel discharge tube with length 1.5 m and diameter 0.17 m with a hot filaments cathode. The wall of the discharge tube was grounded. An axial magnetic field B was created by a solenoid. A platinum cylindrical Langmuir probe with radius R = 5· 10−5 m and length L = 5· 10−3 m was placed axially and radially at the center of the discharge tube in order to perform measurements along and across the magnetic field.

Using the second derivatives of the measured IV probe characteristics, the EEDF in argon and oxygen was evaluated. The derivatives were taken numerically. Measurements in an argon (i.e., in the absence of negative ions) were performed to obtain results for comparison with the measurements in an oxygen gas discharge, where a high density of negative ions is expected.

In the measurements of the second derivatives of the IV characteristics with the probe parallel to the magnetic field in oxygen, a peak appears close to the plasma potential due to the registration of negative ions. In the same time, the electron part of the second derivative was substantially suppressed relatively to the case with the probe oriented perpendicular to the magnetic field. Thus using the appropriate orientation of the probe and a low magnetic field, when the electron part of the second derivative is suppressed, since the negative ion part is not affected by the low magnetic field applied, we can evaluate precisely the negative ion density.

The results from the plasma parameters evaluation (plasma potential, electron and negative ion densities and electron temperatures) are presented and discussed (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of the Probe Electrode on Probe Measurements for Atmospheric Pressure Microwave Plasma Torch
Authors: Ezumi N. , Kodama N. , Akahane K. , Shiozawa S. , Sawada K. , Ohno N.
Published: January 2013

In this study, in order to clarify the influence of a probe electrode during probe measurements of an atmospheric pressure microwave plasma, simultaneous observations of probe current and the change of plasma shape using a high‐speed camera have been done. Fast and random repetitions of attachment and detachment of the plasma torch to the probe electrode have been observed. It is found that the response time is related to ion sound speed. Different behaviors of the plasma torch for a floating metal electrode or an insulator have been observed. Probe current‐voltage characteristics show asymmetric double probe shape (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Infrared imaging as a cancer diagnostic tool: Introducing a new concept of spectral barcodes for identifying molecular changes in colon tumors
Authors: Nallala Jayakrupakar , Piot Olivier , Diebold Marie‐Danièle , Gobinet Cyril , Bouché Olivier , Manfait Michel , Sockalingum Ganesh D.
Published: January 2013

Complementary diagnostic methods to conventional histopathology are under scrutiny for various types of cancers for rapid and molecular level diagnostics. In this perspective, a biophotonic approach based on infrared spectral micro‐imaging combined with multivariate statistical analysis has been implemented on colon tissues. The ability of infrared imaging to investigate the intrinsic biochemical features of cells and tissues has been exploited to develop a new concept of spectral bar coding. To implement this concept, 10 frozen colon tissue samples (five nontumoral and tumoral pairs from five patients) were imaged using infrared spectral micro‐imaging in a nondestructive manner. The spectral images were processed by a multivariate clustering method to identify the histological organization in a label‐free manner. Spectral information from the epithelial components was then automatically recovered on the basis of their intrinsic biochemical composition, and compared using a statistical method (Mann–Whitney U‐test) to construct spectral barcodes specific to each patient. The spectral barcodes representing the discriminant infrared spectral wavenumbers (900–1,800 cm−1) enabled characterization of some of the malignancy‐associated biochemical alterations associated with mucin, nucleotides, carbohydrates, and protein regions. This approach not only allowed the identification of common biochemical alterations among all the colon cancer patients, but also revealed a difference of gradient within individual patients. This new concept of spectral bar coding gives insight into the potential of infrared spectral micro‐imaging as a complementary diagnostic tool to conventional histopathology, for biochemical level understanding of malignancy in colon cancers in an objective and label‐free manner. © 2013 International Society for Advancement of Cytometry
Commentary on ‘Osmotic and stimulant laxatives for the management of childhood constipation’
Authors: Tabbers Merit M. , Benninga Marc A.
Published: January 2013

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Gordon M, Naidoo K, Akobeng AK, Thomas AG. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane Database of Systematic Reviews 2012, Issue 7 Art. No.: CD009118. DOI: 10.1002/14651858.CD009118.pub2 Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentary on ‘Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age’
Authors: Lazzerini Marzia
Published: January 2013

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: De‐Regil L, Suchdev PS, Vist GE, Walleser S, Pena‐Rosas JP. Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. N.: CD008959. DOI: 10.1002/14651858.CD008959.pub2. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Approaches to the Synthesis of a Water‐Soluble Carboxy Nitroxide
Authors: Thomas Komba , Chalmers Benjamin A. , Fairfull‐Smith Kathryn E. , Bottle Steven E.
Published: January 2013

The robust and diversely useful isoindoline nitroxide, 5‐carboxy‐1,1,3,3‐tetramethylisoindolin‐2‐yloxyl (1; CTMIO), has previously been synthesised in low‐to‐moderate yields from phthalic anhydride (3). Recent interest in its biological potential as a potent antioxidant and in other areas has seen an increased demand for its production. Herein, three new synthetic routes to CTMIO are presented and their efficiencies assessed. Two routes, via the nitrile 9 and the formyl compound 11, derive from 5‐bromo‐1,1,3,3‐tetramethylisoindoline (6). The third approach starts from the readily accessible starting material, 4‐methylphthalic anhydride (12), and proceeds by a methylarene oxidation with potassium permanganate. The three new approaches yield CTMIO in comparable overall yields (16–18 %); however, the synthetic efficiency is most improved when employing the nitrile intermediate 9.
On the Origin of E/Z Selectivity in the Modified Julia Olefination – Importance of the Elimination Step
Authors: Robiette Raphaël , Pospíšil Jiří
Published: January 2013

The mechanism and origin of high E selectivity in the modified Julia olefination of aromatic aldehydes have been explored by computational and experimental means. Reversibility of addition and hence selectivity of the formation of sulfinate 5 is very variable and depends on the nature of the sulfone substrate. However, in all cases, elimination occurs through a concerted antiperiplanar and synperiplanar mechanism for sulfinates anti‐5 and syn‐5, respectively. Both syn and anti diastereomeric pathways thus lead preferentially to the (E)‐alkene.
Validation of ground‐motion simulations for historical events using MDoF systems
Authors: Galasso Carmine , Zhong Peng , Zareian Farzin , Iervolino Iunio , Graves Robert W.
Published: January 2013

The study presented in this paper addresses the issue of engineering validation of Graves and Pitarka's (2010) hybrid broadband ground motion simulation methodology with respect to some well‐recorded historical events and considering the response of multiple degrees of freedom (MDoF) systems. Herein, validation encompasses detailed assessment of how similar is, for a given event, the seismic response due to comparable hybrid broadband simulated records and real records. In the first part of this study, in order to investigate the dynamic response of a wide range of buildings, MDoF structures are modeled as elastic continuum systems consisting of a combination of a flexural cantilever beam coupled with a shear cantilever beam. A number of such continuum systems are selected including the following: (1) 16 oscillation periods between 0.1 and 6 s; (2) three shear to flexural deformation ratios to represent respectively shear‐wall structures, dual systems, and moment‐resisting frames; and (3) two stiffness distributions along the height of the systems, that is, uniform and linear. Demand spectra in terms of generalized maximum interstory drift ratio (IDR) and peak floor acceleration (PFA) are derived using simulations and actual recordings for four historical earthquakes, namely, the 1979 Mw 6.5 Imperial Valley earthquake, 1989 Mw 6.8 Loma Prieta earthquake, 1992 Mw 7.2 Landers earthquake, and 1994 Mw 6.7 Northridge earthquake. In the second part, for two nonlinear case study structures, the IDR and PFA distributions over the height and their statistics, are obtained and compared for both recorded and simulated time histories. These structures are steel moment frames designed for high seismic hazard, 20‐story high‐rise and 6‐story low‐rise buildings. The results from this study highlight the similarities and differences between simulated and real records in terms of median and intra‐event standard deviation of logs of seismic demands for MDoF building systems. This general agreement, in a broad range of moderate and long periods, may provide confidence in the use of the simulation methodology for engineering applications, whereas the discrepancies, statistically significant only at short periods, may help in addressing improvements in generation of synthetic records. Copyright © 2013 John Wiley & Sons, Ltd.
Carbon isotopes in the rivers from the Lesser Antilles: origin of the carbonic acid consumed by weathering reactions in the Lesser Antilles
Authors: Rivé Karine , Gaillardet Jerome , Agrinier Pierre , Rad Setareh
Published: January 2013

In this paper, we use carbon isotopes in the dissolved load of rivers from the Lesser Antilles volcanic arc (Guadeloupe, Martinique and Dominica islands) to constrain the source of the carbon dioxide (CO2) involved in the neutralization reactions during water–rock interactions. The δ13C data span a large range of variations, from –19‰ to –5 · 2‰ for DIC (dissolved inorganic carbon) concentrations ranging from 11 μM to 2000 μM. Coupled with major element concentrations, carbon isotopic ratios are interpreted as reflecting a mixture of magmatic CO2 (enriched in heavy carbon (δ13C ≈ –3 · 5‰) and biogenic CO2 produced in soils (enriched in light carbon (δ13C < –17‰)). Carbon isotopes show that, at the regional scale, 23 to 40% of CO2 consumed by weathering reactions is of magmatic origin and is transferred to the river system through aquifers under various thermal regimes. These numbers remain first‐order estimates as the major uncertainty in using carbon isotopes as a source tracer is that carbon isotopes can be fractionated by a number of processes, including soil and river degassing. Chemical weathering is clearly, at least, partly controlled by the input of magmatic CO2, either under hydrothermal (hot) or surficial (cold) weathering regimes.

This study shows that the contribution of magmatic CO2 to chemical weathering is an additional parameter that could explain the high weathering rates of volcanic rocks. The study also shows that a significant part of the carbon degassed from the Earth's interior is not released as CO2 to the atmosphere, but as DIC to the ocean because it interacts with the groundwater system. This study calls for a better understanding of the contributions of deep carbon to the hydrosphere and its influence on the development of the Critical Zone. Copyright © 2013 John Wiley & Sons, Ltd.
Nanism and ephemerism as reasons for a hidden abundance in vernal pool plants: The example of Lepuropetalon spathulatum in Chile
Authors: Alvarez Miguel , San Martín José , Deil Ulrich
Published: January 2013

Minute size (nanism) and short live cycle (ephemerism) are characteristic features of many plants living in seasonal wetlands in Mediterranean biomes. Lepuropetalon (Celastraceae) is a monotypic genus with an antitropical distribution (disjunct in temperate regions of both Americas). L. spathulatum is the smallest vascular plant of Chile, not recorded in herbaria for decades. Its distribution, ecology and phytosociology were studied based on herbarium vouchers and field observations. L. spathulatum occurs in the fringes of vernal pools, on oligotrophic sandy soils and in grazed Acacia caven pseudo‐savannas. Its distribution is linked to the Mediterranean and Submediterranean bioclimates. Associated species are other dwarfish annuals, many of them originating from the Western Palearctic subkingdom and characteristic for the class Isoëto‐Nanojuncetea. Other floristic elements are Chilean endemics and species with a disjunction to California (character species of the Nanojuncetea australis). L. spathulatum is not a rare plant in Chile, but is often overlooked because of its dwarfish and ephemeral habit. Although most populations occurred in secondary habitats and the species can tolerate disturbance, intensification of agriculture, forest plantations and modification of the hydrological conditions may threaten the species in the long term. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A scanning electron microscope study of the stem structure in the West African Cane Palms (Calamoideae)
Authors: Jayeola Adeniyi A. , Thorpe Julian R.
Published: January 2013

The canes of thirteen rattan taxa comprising two Calamus, three Eremospatha, five Laccosperma and three Oncocalamus were studied anatomically by scanning electron microscopy (SEM). Six out of the taxa tagged L. secundiflorum a, b, c; Oncocalamus sp. d, Oncocalmus sp. e and Calamus sp. f were unresolved herbarium voucher specimens many decades old.

SEM photomicrographs revealed cell‐tissue specific differences in anticlinal cell wall of the epidermis, fibrous sheaths, sheath parenchyma and phloem strands, leaf traces, and vessel diam‐ eter. Metaxylem vessel diameters varied between 20–212 µm in the outer peripheral zone and 90–310 µm in the central cylinder, except in L. secundiflorium c where the trend is reversed. Regression analysis of the metaxylem diameter values along radial distance shows large interspecific differences from central to outer cylinder. The weak R2 values (P ≤ 0.5) in nine of the thirteen species suggests that other unmeasured variables contribute to the observed trend. The structure of the unresolved voucher specimens appear to follow the same general trend in the identified specimens suggestive of phenotypic divergence between po‐ pulations brought about by developmental plasti‐ city. The leaf trace observed in Oncocalamus sp. e is unique and deserved to be examined more closely. A simple arithmetical expression indicat‐ ing structural synergy between protoxylem and metaxylem for possible volume ratio balance is included. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantitative and sensory evaluation of malodour retention of fibre types by use of artificial skin, sweat and radiolabelled isovaleric acid
Authors: Hammer Timo R. , Berner‐Dannenmann Nadja , Hoefer Dirk
Published: January 2013

The retention of malodours, especially sweat on fabrics, is a widely discussed problem in the textile industry and science. Since a quantitative analysis of the retention of sweat odour molecules on fibres has not been addressed so far, we used liquid scintillation counting to measure the adhesion/dehesion of 14C‐labelled isovaleric acid, a lead substance of sweat odour, to knitted fabrics of comparable textile structure made of pure cotton, wool or polyester. Significant retention differences were detected, with polyester showing the highest release of isovaleric acid after 3 h and 20 h. Fabric finishes with β‐cyclodextrin enhanced odour retention on cotton and polyester considerably. To study local influences of the clothing materials on odour release, we simulated in diffusion chamber cells a fabric/human skin wear situation using an artificial skin with skin‐like composition, topology and mechanical characteristics. Unidirectional transepidermal water vapour release of the skin model modulated the odour retention. Finally, all samples were subjected to a sensory evaluation test with trained panellists using olfactometry and a non‐labelled artificial sweat containing isovaleric acid as lead substance. Again, polyester showed little retention capacities, whereas the cyclodextrin finish enhanced binding of the artificial sweat and thus reduced its perception. The phase II approach revealed that perceived malodour intensity clearly depended on the finish and fibre type. The presented data and methods provide a basis for future optimization of clothes in terms of sweat odour management in their respective end uses, e.g. sport or business activities. Copyright © 2013 John Wiley & Sons, Ltd.
Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma
Authors: Cammà Calogero , Cabibbo Giuseppe , Petta Salvatore , Enea Marco , Iavarone Massimo , Grieco Antonio , Gasbarrini Antonio , Villa Erica , Zavaglia Claudio , Bruno Raffaele , Colombo Massimo , Craxì Antonio
Published: January 2013

The purpose was to assess the cost-effectiveness of sorafenib in the treatment of hepatocellular carcinoma (HCC) patients incorporating current prices and the results of the recent published field practice SOraFenib Italian Assessment (SOFIA) study. We created a Markov Decision Model to evaluate, in a hypothetical cohort of Caucasian male patients, aged 67 years with Barcelona Clinic Liver Cancer (BCLC) C HCC, or BCLC B HCC who were unfit or failed to respond to locoregional therapies, well compensated cirrhosis, and with performance status 0–1 according to Eastern Cooperative Oncology Group (ECOG), the cost-effectiveness of the following strategies: (1) full or dose-adjusted sorafenib for BCLC B and C patients together; (2) full or dose-adjusted sorafenib for BCLC B patients; (3) full or dose-adjusted sorafenib for BCLC C patients. Outcomes include quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). In the base-case analysis dose-adjusted sorafenib was the most effective of the evaluated strategies. For dose-adjusted sorafenib, QALY was 0.44 for BCLC B and C patients together, 0.44 for BCLC C patients, and 0.38 for BCLC B patients. The ICER of dose-adjusted sorafenib compared with BSC was €34,534 per QALY gained for BCLC B and C patients together, €27,916 per QALY gained for BCLC C patients, and €54,881 per QALY gained for BCLC B patients. Results were sensitive to BSC survival rate, and sorafenib treatment duration.

Conclusion:

In daily practice dose-adjusted, but not full-dose, sorafenib is a cost-effective treatment compared to BSC in intermediate and advanced HCC. (Hepatology 2013)
Ammonia detoxification via ureagenesis in rat hepatocytes involves mitochondrial aquaporin-8 channels
Authors: Soria Leandro R. , Marrone Julieta , Calamita Giuseppe , Marinelli Raúl A.
Published: January 2013

Hepatocyte mitochondrial ammonia detoxification via ureagenesis is critical for the prevention of hyperammonemia and hepatic encephalopathy. Aquaporin-8 (AQP8) channels facilitate the membrane transport of ammonia. Because AQP8 is expressed in hepatocyte inner mitochondrial membranes (IMMs), we studied whether mitochondrial AQP8 (mtAQP8) plays a role in ureagenesis from ammonia. Primary cultured rat hepatocytes were transfected with small interfering RNAs (siRNAs) targeting two different regions of the rat AQP8 molecule or with scrambled control siRNA. After 48 hours, the levels of mtAQP8 protein decreased by approximately 80% (

P

< 0.05) without affecting cell viability. mtAQP8 knockdown cells in the presence of ammonium chloride showed a decrease in ureagenesis of approximately 30% (

P

< 0.05). Glucagon strongly stimulated ureagenesis in control hepatocytes (+120%,

P

< 0.05) but induced no significant stimulation in mtAQP8 knockdown cells. Contrarily, mtAQP8 silencing induced no significant change in basal and glucagon-induced ureagenesis when glutamine or alanine was used as a source of nitrogen. Nuclear magnetic resonance studies using 15N-labeled ammonia confirmed that glucagon-induced 15N-labeled urea synthesis was markedly reduced in mtAQP8 knockdown hepatocytes (−90%,

P

< 0.05).

In vivo

studies in rats showed that under glucagon-induced ureagenesis, hepatic mtAQP8 protein expression was markedly up-regulated (+160%,

P

< 0.05). Moreover, transport studies in liver IMM vesicles showed that glucagon increased the diffusional permeability to the ammonia analog [14C]methylamine (+80%,

P

< 0.05).

Conclusion:

Hepatocyte mtAQP8 channels facilitate the mitochondrial uptake of ammonia and its metabolism into urea, mainly under glucagon stimulation. This mechanism may be relevant to hepatic ammonia detoxification and in turn, avoid the deleterious effects of hyperammonemia.
Structure‐based redesign of proteins for minimal T‐cell epitope content
Authors: Choi Yoonjoo , Griswold Karl E. , Bailey‐Kellogg Chris
Published: January 2013

The protein universe displays a wealth of therapeutically relevant activities, but T‐cell driven immune responses to non‐“self” biological agents present a major impediment to harnessing the full diversity of these molecular functions. Mutagenic T‐cell epitope deletion seeks to mitigate the immune response, but can typically address only a small number of epitopes. Here, we pursue a “bottom‐up” approach that redesigns an entire protein to remain native‐like but contain few if any immunogenic epitopes. We do so by extending the Rosetta flexible‐backbone protein design software with an epitope scoring mechanism and appropriate constraints. The method is benchmarked with a diverse panel of proteins and applied to three targets of therapeutic interest. We show that the deimmunized designs indeed have minimal predicted epitope content and are native‐like in terms of various quality measures, and moreover that they display levels of native sequence recovery comparable to those of non‐deimmunized designs. © 2013 Wiley Periodicals, Inc.
Cardioembolic stroke: Protective effect of a severe internal carotid artery stenosis in a patient with cardiac embolism
Authors: Vicenzini Edoardo , Petolicchio B. , Toscano M. , La Cesa S. , Puledda F. , Lenzi G. L. , Di Piero V.
Published: January 2013

Cardioembolic stroke is generally caused by intracranial artery occlusion. Clots may be identified in the intracranial vessels by means of conventional neuroimaging in the acute phase. High‐resolution ultrasonography may show some features suggestive of cardiac emboli when occluding extracranial carotid arteries. We describe a patient with cardioembolic ischemic stroke in the right hemisphere in whom a left internal carotid artery stenosis paradoxically protected the ipsilateral hemisphere from distal intracranial embolism. The patient also presented multiple acute ischemic embolic lesions in the right middle cerebral artery territory and in the right occipital lobe, which was fed by the posterior cerebral artery, anomally originating from the right carotid siphon. Interestingly, the left internal carotid artery—which showed a severe preexisting stenosis—was occluded by the cardiac clot, whereas the right internal carotid artery only presented a moderate stenosis that had probably allowed the clots to pass. Therefore, the severe left internal carotid artery stenosis may have blocked the cardiac embolus, preventing it from reaching the ipsilateral hemisphere. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 41:22–27, 2013
Cephalothoracopagus janiceps asymmetros twins: Antenatal sonographic diagnosis
Authors: Sharma Dinesh , Jhobta Anupam , Azad J. R. , Dhiman D. S. , Pandith Mansa , Sharma Sanjiv
Published: January 2013

Conjoined twins have been the subject of myth and legend since antiquity because of the rarity and peculiarity of their juxtaposition. Fortunately, modern medical technology and concurrent advancements in surgical techniques provide an opportunity for successful separation and hope of a normal independent existence for these unique children. Antenatal sonography allows timely detection of this condition so that further management may be planned. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 2013
Studies on the metabolism and toxicological detection of glaucine, an isoquinoline alkaloid from Glaucium flavum (Papaveraceae), in rat urine using GC‐MS, LC‐MSn and LC‐high‐resolution MSn
Authors: Meyer Golo M.J. , Meyer Markus R. , Wissenbach Dirk K. , Maurer Hans H.
Published: January 2013

Glaucine ((S)‐5,6,6a,7‐tetrahydro‐1,2,9,10‐tetramethoxy‐6‐methyl‐4H‐dibenzo [de,g]quinoline) is an isoquinoline alkaloid and main component of Glaucium flavum (Papaveraceae). It was described to be consumed as recreational drug alone or in combination with other drugs. Besides this, glaucine is used as therapeutic drug in Bulgaria and other countries as cough suppressant. Currently, there are no data available concerning metabolism and toxicological analysis of glaucine. To study both, glaucine was orally administered to Wistar rats and urine was collected. For metabolism studies, work‐up of urine samples consisted of protein precipitation or enzymatic cleavage followed by solid‐phase extraction. Samples were afterwards measured by liquid chromatography (LC) coupled to low or high‐resolution mass spectrometry (HR‐MS). The phase I and II metabolites were identified by detailed interpretation of the corresponding fragmentations, which were further confirmed by determination of their elemental composition using HR‐MS. From these data, the following metabolic pathways could be proposed: O‐demethylation at position 2, 9 and 10, N‐demethylation, hydroxylation, N‐oxidation and combinations of them as well as glucuronidation and/or sulfation of the phenolic metabolites. For monitoring a glaucine intake in case of abuse or poisoning, the O‐ and N‐demethylated metabolites were the main targets for the gas chromatography‐MS and LC‐MSn screening approaches described by the authors. Both allowed confirming an intake of glaucine in rat urine after a dose of 2 mg/kg body mass corresponding to a common abuser's dose. Copyright © 2013 John Wiley & Sons, Ltd.
Electrokinetic supercharging in CE for the separation and preconcentration of barbiturate drugs in urine samples
Authors: Botello Igor , Borrull Francesc , Calull Marta , Aguilar Carme
Published: January 2013

Three barbiturate drugs, barbital, phenobarbital, and secobarbital were separated and analyzed by electrokinetic supercharging. The influence of different parameters on electrokinetic supercharging performance was evaluated using both univariated and multivariated optimization processes. The parameters studied were sample pH, concentration, and length of the leading and terminating electrolytes, electrokinetic injection of the sample and composition and hydrodynamic injection of the solvent plug. The leading electrolyte (50 mM NaCl) was hydrodynamically injected (50 mbar × 120 s) prior to the sample that was adjusted to pH 9.6 and electrokinetically injected at −8.5 kV for 300 s. The terminating electrolyte (100 mM of 2‐(cyclohexylamino) ethanesulphonic acid) was then hydrodynamically injected (50 mbar × 140 s). The results showed that this strategy enhanced detection sensitivity around 1050‐fold compared with normal hydrodynamic injection, providing detection limits ranging between 1.5 and 2.1 ng/mL for standard samples with good repeatability in terms of peak area (values of relative standard deviation, %RSD < 3). The applicability of the optimized method was demonstrated by the analysis of human urine samples spiked with the studied compounds at different concentration levels and further liquid–liquid extraction step. The estimated detection limits obtained in the urine samples extract ranged between 8 and 15 ng/mL.
Fast gas chromatography combined with a high‐speed triple quadrupole mass spectrometer for the analysis of unknown and target citrus essential oil volatiles
Authors: Tranchida Peter Quinto , Zoccali Mariosimone , Franchina Flavio Antonio , Bonaccorsi Ivana , Dugo Paola , Mondello Luigi
Published: January 2013

The present research description is focused on the evaluation of a high‐speed triple quadrupole mass spectrometer, carried out under moderately fast gas chromatography conditions (analysis time: 17 min). The mass spectrometric system is capable of operation under high‐speed GC conditions, in both full‐scan (maximum scan speed: 20 000 amu/s) and multiple reaction monitoring modalities. Furthermore, the triple quadrupole system can generate full scan and multiple reaction monitoring data simultaneously, also in a very rapid manner.

A fast method was developed for the: (i) qualitative analysis of untargeted Citrus essential oil compounds, and (ii) the quali/quantitative analysis of targeted ones, namely three preservatives (o‐phenylphenol, butylated hydroxytoluene, butylated hydroxy‐anisole). The mass spectrometric system generated a more‐than‐sufficient number of data points/peak for both identification and quantification purposes. The level of sensitivity, reached through the multiple‐reaction‐monitoring side of the analysis, widely exceeded the requirements of current legislation. Method validation, related to the targeted analysis, was performed considering precision of retention times, peak areas and ion ratios; limits of detection/quantification, and accuracy were also measured.
Matrix effect in high‐performance liquid chromatography‐tandem mass spectrometry analysis of antibiotics in environmental water samples
Authors: Zhou Jun Liang , Kang Yuehui
Published: January 2013

This paper describes the matrix effect during the analysis of ten antibiotic compounds in water by SPE followed by HPLC‐ESI‐MS/MS. The target analytes were tetracycline, oxytetracycline (tetracyclines), sulfathiazole, sulfamethazine, sulfadiazine (sulfonamides), erythromycin‐H2O, roxithromycine, spiramycin (macrolides), ofloxacin, and norfloxacin (quinolones). The matrix effect was examined for internal standards and the target analytes in five different water matrixes, with signal suppression being increased in the order: ultrapure water, tap water, river water, sewage effluent, and sewage influent. A combined application of the internal standards and matrix‐matched extract calibration was shown to be successful in compensating the matrix effect for the analytes. The procedural recovery of the target compounds in sewage effluents and influents was higher than in river water samples, which was further enhanced by sample acidification to pH 2. The validity of the internal standard based matrix‐matched calibration approach was verified by the standard addition method.
Segmenting Chinese Backpackers by Travel Motivations
Authors: Chen Ganghua , Bao Jigang , Huang Songshan (Sam)
Published: January 2013

This study examined travel motivations of Chinese backpackers and classified Chinese backpackers according to their travel motivations and related demographics. The study identified four motivation factors driving Chinese backpacker travels: social interaction, self‐actualization, destination experience and escape and relaxation. K‐means cluster analysis further identified three distinct Chinese backpacker segments with different travel motivations: self‐actualizers, destination experiencers and social seekers. Explanations and discussions within the background of China's ongoing tremendous social and economic transformation are also provided. Copyright © 2013 John Wiley & Sons, Ltd.
Cochlear implant electrode misplacement: Incidence, evaluation, and management
Authors: Ying Yu‐Lan Mary , Lin Jerry W. , Oghalai John S. , Williamson Robert A.
Published: January 2013

Objectives/Hypothesis:

To review the presentation and management of improper electrode array placement, and to help guide clinical decision‐making.

Study Design:

Retrospective case series.

Methods:

Pediatric and adult cochlear implant patients managed from January 2001 to present whose electrode arrays were not placed properly within the cochlea or extended beyond the cochlea into the internal auditory canal or adjacent structures.

Results:

Four patients, three pediatric and one adult, were identified from over 824 cases (< 1%) managed over the study duration. All cases had normal cochlear anatomy. These cases were initially identified due to poor auditory skill development or absent behavioral responses following implantation, which prompted imaging. Two patients presented several years after surgery. Sites of improper placement included the eustachian tube, vestibule, internal carotid artery canal, and internal auditory canal (IAC). Intraoperative findings and management are reviewed.

Conclusions:

Electrode array malpositioning is a rare, but serious and correctable complication in cochlear implant surgery. A multidisciplinary approach, including prompt audiologic evaluation and imaging, is important, particularly when benefit from the implant is limited or absent. Management of electrode arrays in the IAC may be more challenging. Laryngoscope, 2013
Optical imaging with a high‐resolution microendoscope to identify cholesteatoma of the middle ear
Authors: Levy Lauren L. , Jiang Nancy , Smouha Eric , Richards‐Kortum Rebecca , Sikora Andrew G.
Published: January 2013

Objectives/Hypothesis:

High‐resolution optical imaging is an imaging modality that allows visualization of structural changes in epithelial tissue in real time. Our prior studies using contrast‐enhanced microendoscopy to image squamous cell carcinoma in the head and neck demonstrated that the contrast agent, proflavine, has high affinity for keratinized tissue. Thus, high‐resolution microendoscopy with proflavine provides a potential mechanism to identify ectopic keratin production, such as that associated with cholesteatoma formation, and distinguish between uninvolved mucosa and residual keratin at the time of surgery.

Study Design:

Ex vivo imaging of histopathologically confirmed samples of cholesteatoma and uninvolved middle ear epithelium.

Methods:

Seven separate specimens collected from patients who underwent surgical treatment for cholesteatoma were imaged ex vivo with the fiberoptic endoscope after surface staining with proflavine. Following imaging, the specimens were submitted for hematoxylin and eosin staining to allow histopathological correlation.

Results:

Cholesteatoma and surrounding middle ear epithelium have distinct imaging characteristics. Keratin‐bearing areas of cholesteatoma lack nuclei and appear as confluent hyperfluorescence, whereas nuclei are easily visualized in specimens containing normal middle ear epithelium. Hyperfluorescence and loss of cellular detail is the imaging hallmark of keratin, allowing for discrimination of cholesteatoma from normal middle ear epithelium.

Conclusions:

This study demonstrates the feasibility of high‐resolution optical imaging to discriminate cholesteatoma from uninvolved middle ear mucosa based on the unique staining properties of keratin. Use of real‐time imaging may facilitate more complete extirpation of cholesteatoma by identifying areas of residual disease. Laryngoscope, 2012
Furan fatty acids – valuable minor fatty acids in food
Authors: Vetter Walter , Wendlinger Christine
Published: January 2013

Furan fatty acids (F‐acids) are heterocyclic lipid components with a furan moiety in the centre of the molecule. Reports on F‐acids in the literature are rather scarce, although they are considered as particularly valuable food ingredients. F‐acids occur as minor compounds in the lipids of different food samples. Despite the low concentrations, some studies produced evidence that the F‐acids are excellent radical scavengers and thus are able to protect polyunsaturated fatty acids from lipid peroxidation. Accordingly, they may play a currently underrated and largely overlooked positive role in human nutrition. The limited data available result from difficulties in the analysis of these trace compounds. F‐acids in food can hardly be determined without selective enrichment and the use of gas chromatography with mass spectrometry for their determination. The lack of reference standards is a further drawback that hampers the exact assessment of the actual relevance of F‐acids in human nutrition.
Traceability of the palm oil supply chain
Authors: van Duijn Gerrit
Published: January 2013

Palm oil is mainly produced in Malaysia and Indonesia while the main users are India, China, Indonesia and the EU. For most of these users, the supply chain is long and complex, including overseas shipping. Procedures in this supply chain guarantee stepwise traceability as required by food safety regulations. Continuous traceability is usually not achievable. Also the RSPO trace and traceability systems do not improve this. Exception is the Identity Preserved system, however, the high costs and low volume of this system makes it only applicable for niche market products.
Hofmeister Effect of Sodium Halides on the Switching Energetics of Thermoresponsive Polymer Brushes
Authors: Naini Crispin Amiri , Thomas Marc , Franzka Steffen , Frost Sven , Ulbricht Mathias , Hartmann Nils
Published: January 2013

A laser temperature‐jump technique is used to probe the impact of sodium halides on the temperature‐dependent switching kinetics and thermodynamics of poly(N‐isopropylacrylamide) brushes. An analysis on the basis of a two‐state model reveals van't Hoff enthalpy and entropy changes. Sodium halides increase the endothermicity and the entropic gain of the switching process below and above Tc following the Hofmeister series: NaCl > NaBr > NaI. In contrast, enthalpic and entropic changes at Tc remain virtually unaffected. This provides an unprecedented insight into the underlying switching energetics of this classic stimuli‐responsive polymer. Because of its model character, these results represent an essential reference on the way to unpuzzle the molecular driving forces of the Hofmeister effect.
An approximation of stochastic hyperbolic equations: case with Wiener process
Authors: Ashyralyev Allaberen , Akat Muzaffer
Published: January 2013

In the present paper, the two‐step difference scheme for the Cauchy problem for the stochastic hyperbolic equation is presented. The convergence estimate for the solution of the difference scheme is established. In applications, the convergence estimates for the solution of difference schemes for the numerical solution of four problems for hyperbolic equations are obtained. The theoretical statements for the solution of this difference scheme are supported by the results of the numerical experiment. Copyright © 2012 John Wiley & Sons, Ltd.
Existence of stationary solutions in kinetic models with Gaussian thermostats
Authors: Bianca Carlo
Published: January 2013

The thermostatted kinetic framework has been recently proposed in [C. Bianca, Nonlinear Analysis: Real World Applications 13 (2012) 2593‐2608] for the modeling of complex systems in the applied sciences under the action of an external force field that moves out of equilibrium the system. The framework consists in an integro‐differential equation with quadratic nonlinearity coupled with the Gaussian isokinetic thermostat. This paper is concerned with the existence of stationary solutions proof. The main result is gained by fixed point and measure theory arguments. Copyright © 2013 John Wiley & Sons, Ltd.