bluuebunny/crossref_metadata_2025 huggingface dataset:
Lorcainide; II. Plasma concentration‐effect relationship
Authors: Meinertz Thomas , Kasper Wolfgang , Kersting Friedrich , Just Hanjörg , Bechtold Heinrich , Jähnchen Eberhard
Published: January 2016

The effects of lorcainide were studied in 17 patients after single doses (2 mg/kg intravenously; 6 mg/min intravenously over 30 to 40 min; 150, 300, and 500 mg orally) and during long‐term antiarrhythmic treatment (200 to 600 mg daily orally). The frequency of ventricular premature contractions (VPCs), the changes in the electrocardiogram (ECG), and the plasma concentration of lorcainide were determined. The widening of the QRS complex observed after single doses of lorcainide mimicked the time course of plasma concentration permitting the construction of linear relationships between both parameters. After oral administration lower plasma concentrations were required to produce the same QRS widening than after intravenous administration. Patients differed considerably in the slopes of these plasma concentration‐effect curves. After repeated intravenous infusions of lorcainide, plasma concentration‐effect relationships were constructed for both antiarrhythmic and ECG effects. During drug infusion higher concentrations of lorcainide were required to induce antiarrhythmic and toxic effects (QRS widening and PQ prolongation) than during the postinfusion period. Whereas during the infusion period the plasma concentration‐effect curves for both effects followed the same slope, during the postinfusion period VPCs were remarkably more sensitive to plasma concentration than the changes in the ECG. Suppression of VPCs during long‐term treatment with lorcainide was accompanied by small changes in the ECG which were related to the dose and plasma concentration of lorcainide. Thus, the lorcainide regimen may be monitored by careful inspection of the ECG.
Drug metabolism in liver disease: Activity of hepatic microsomal metabolizing enzymes
Authors: Farrell G. C. , Cooksley W. G. E. , Powell L. W.
Published: January 2016

The concentration of cytochrome P‐450 and activities of the microsomal enzymes aryl hydrocarbon hydroxylase and ethylmorphine demethylase were measured in hepatic tissue obtained at biopsy from 69 patients. Antipyrine half‐life (AP t½) was measured simultaneously as an in vivo marker of drug metabolism. Values for each index of the drug‐metabolizing system varied greatly, but the mean values in groups of patients with mild hepatitis or inactive cirrhosis did not differ significantly from those of controls. Hepatic cytochrome P‐450 content and aryl hydrocarbon hydroxylase activity were lower in patients with severe hepatitis or active cirrhosis than in controls, but ethylmorphine demethylase activity was unchanged in the patients. Drug ingestion was associated with enhancement of drug‐metabolizing enzymes in all patients but those with severe liver disease; ethylmorphine demethylase activity was enhanced proportionately more than aryl hydrocarbon hydroxylase activity or cytochrome P‐450 concentration. The observation that aryl hydrocarbon hydroxylase and ethylmorphine demethylase activities are influenced to a different extent by liver disease and also by drug ingestion indicates functional heterogeneity of the hepatic microsomal drug‐metabolizing system in man. Correlations between t½ and hepatic drug oxidases were weak, even when allowance was made for variation in liver size. Thus, the rate of drug metabolism in vivo assessed by measuring AP t½ does not appear to be closely related to the activity of some hepatic drug‐metabolizing enzymes.
Verapamil plasma levels and ventricular rate response in patients with atrial fibrillation and flutter
Authors: Dominic Jerome , McAllister R. G. , Kuo Chien-Suu , Reddy C. Pratap , Surawicz Borys
Published: January 2016

The acute effect of verapamil on the ventricular rate in atrial fibrillation and flutter was studied in 15 patients, 13 of whom had heart rate inadequately controlled with digitalis. Plasma concentrations were measured 5 and 10 min after intravenous doses of 0.075 mg/kg and 0.15 mglkg verapamil. In 9 patients who were clinically compensated, the 0.075‐mg dose alone decreased the ventricular rate to under 100/min (responders); in the remaining 6, who had acute congestive heart failure manifested by orthopnea, rales, and pulmonary congestion, ventricular rates were above 100/min after the 0.075‐mg dose (nonresponders). The 6 nonresponders received the 0.15‐mg dose 30 min later. In all, the response was greater when plasma drug concentration rose after the high dose, although the rate decrease was smaller than in the 9 compensated patients who received the low dose. These results can be explained by assuming an antagonism of the verapamil effect by sympathetic stimulation in nonresponders.
A Simple Catalytic Route for Alkyn­ylgermanes
Authors: Rzonsowska Monika , Woźniak Bartosz , Dudziec Beata , Pyziak Jadwiga , Kownacki Ireneusz , Marciniec Bogdan
Published: January 2016

We report a new one‐pot, iridium(I)‐catalyzed direct method for the synthesis of alkynyl‐substituted germanium compounds with various functional groups from commercially available reagents. More than 25 compounds were obtained and spectroscopically characterized. Moreover, detailed DFT calculations were performed to study the mechanism of the catalytic cycle of the germylative coupling. The results confirm our assumptions that the rate‐determining step of the germylative coupling process is the product‐formation step.
Oxidovanadium Complexes of 2,2′‐Bipyridine, 1,10 Phenanthroline, and p‐Nitro‐o‐aminophenol – Radical versus Nonradical States
Authors: Shit Madhusudan , Bera Sachinath , Maity Suvendu , Maji Subrata , Weyhermüller Thomas , Ghosh Prasanta
Published: January 2016

2,2′‐Bipyridine (bpy), 1,10‐phenanthronline (phen) and p‐nitro‐o‐aminophenol (NO2LH2) oxidovanadium complexes of the types [(LONO2–)(VO)(bpy)] (1), [(LONO2–)(VO)(phen)] (2) and [(LONO2–)(VO)(NO2LISQ·–)][NHEt3] (3– NHEt3+; NO2LISQ·– = p‐nitro‐o‐iminobenzosemiquinonate radical) were isolated with (E)‐2‐(3‐hydroxy‐3‐phenyltriaz‐1‐en‐1‐yl)benzoic acid (LONOH2) as a coligand. The single‐crystal X‐ray bond parameters and electron paramagnetic resonance (EPR) spectra authenticated that 1 and 2 are the oxidovanadium(IV) complexes of bpy and phen, whereas 3– is the NO2LISQ·– complex of oxidovanadium(IV) and undergoes reversible one‐electron oxidation and reduction at lower potentials. Density functional theory (DFT) calculations established that the closed‐shell‐singlet (CSS) solution of 3– is unstable owing to open‐shell‐singlet (OSS) perturbation. The CSS → OSS charge‐transfer transition that appears at λ = 632 nm is absent for 1 and 2. Complex 3 is a hybrid of the [(LONO2–)(VO2+)(NO2LIQ)] (NO2LIQ = p‐nitro‐o‐iminobenzoquinone) and [(LONO2–)(VO3+)(NO2LISQ·–)] states, whereas 32– is an oxidovanadium(IV) complex of the type [(LONO2–)(VO2+)(NO2LAP2–)]2– (NO2LAP2– = p‐nitro‐o‐amidophenolato).
Structural and Conformational Study of the O‐Antigenic Portion of the Lipopolysaccharide Isolated from Burkholderia gladioli pv. cocovenenans
Authors: De Felice Antonia , Silipo Alba , Scherlach Kirstin , Ross Claudia , Hertweck Christian , Molinaro Antonio
Published: January 2016

Lipopolysaccharides (LPSs) are virulence factors that are expressed on the cell surface of Gram‐negative bacteria. They represent one of the main traits of bacterial virulence. In this paper, we report the primary structure and the conformational features of the O‐chain from the lipopolysaccharide (LPS) produced by Burkholderia gladioli pv. cocovenenans, a bacterium often associated with the mucoralean fungus Rhizopus microsporus var. oligosporus, which is traditionally used in food fermentations. With the aim of understanding the organization of bacterial cell‐surface components, we isolated and characterized the following O‐antigenic portions of the LPS from B. gladioli pv. cocovenenans: [→2)‐α‐Rha‐(1→2)‐α‐Aco‐(1→2)‐α‐Rha‐(1→4)‐β‐Gal2Me‐(1→]n and [→2)‐α‐Rha‐(1→2)‐α‐Aco‐(1→2)‐α‐Rha‐(1→4)‐β‐Gal‐(1→]n. A distinctive feature of the O‐chain is the presence of methylated sugar residues. This contributes to the creation of a hydrophobic shield. The experimental data were confirmed by conformational studies, which showed three‐dimensional shapes with different packings and extensions. Such features determine the physicochemical properties of the bacterial envelope, and might contribute to the ability to adapt the membrane surface to the host.
Penta‐2,4‐dien‐1‐ones by Formal [3+2] Cycloaddition–Rearrangement of Electron‐Deficient Diethyl 2‐(Dicyanomethylene)malonate with Alk­ynes
Authors: Donckele Etienne J. , Reekie Tristan A. , Trapp Nils , Diederich François
Published: January 2016

The reactions of diethyl 2‐(dicyanomethylene)malonate, an electron‐deficient alkene, with donor‐activated and unactivated alkynes have been investigated. Moderately electron‐rich and unactivated alkynes undergo efficient formal [3+2] cycloaddition–rearrangement cascades to provide the corresponding penta‐2,4‐dien‐1‐one adducts in yields of up to 84 %. The structures of the solid dienone products were confirmed by X‐ray diffraction analysis. The buta‐1,3‐diene moieties in the dienones do not adopt planar s‐trans conformations but rather nonplanar geometries in which the two olefinic bonds are nearly orthogonal to each other. This transformation proceeds with excellent regioselectivity and with a wide range of alkynes without the need for a catalyst. Under the optimized reaction conditions, no competition with the [2+2] cycloaddition–retroelectrocyclization reaction (CA–RE) was observed.
Policy influence on clean coal uptake in China, India, Australia, and USA
Authors: Dzonzi‐Undi Junice , Li Shixiang
Published: January 2016

This comparative study assesses clean coal related policies in China, India, Australia, and USA; and the impact of those, on uptake of clean coal technologies (CCTs) by industry. The study identifies types and examples of CCTs that can be incorporated and applied in reducing coal power related emissions; defines nature and categories of clean coal policies for purposes of exploring policies a particular country is using; and then analyzes the influence of a particular policy to the country's situation. Results indicate that progress on commercial development and deployment of these technologies is very possible in both developing and developed countries and fiscal policies are likely to increase uptake and prospects for uptake by private industry. However, integration of non‐fiscal policies with participation of private coal energy industry may also help to achieve remarkable development and uptake. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 906–913, 2016
Power efficient CoMP‐joint transmission with two stage QoSs
Authors: Kim Seung‐Yeon , Cho Choong‐Ho
Published: January 2016

Power efficiency has become an important design goal for wireless communications, and a coordinated multi‐point (CoMP) with joint transmission (JT) scheme can be implemented to improve the cell edge throughput by increasing the signal‐to‐interference ratio, which in turn leads to power savings through cooperative transmission. To this end, we propose a power control scheme in which the cooperating base station can reduce its own transmission power while remaining within two stage quality of service (QoS) constraints, including the call‐blocking probability and outage probability. For the two QoS constraints, we introduce call admission control and signal‐to‐interference ratio models for CoMP‐JT that consider a two‐dimensional Markov chain and the sum of multiple exponential random components. The results of the call blocking and outage probabilities are used to obtain the power consumption model and analyse the performance for the CoMP‐JT with the proposed power control technique. Both the analytical and numerical results show that the proposed power control strategy can reduce the power consumption for the cellular network with the two stage QoSs. Copyright © 2016 John Wiley & Sons, Ltd.
Systems toxicology of chemically induced liver and kidney injuries: histopathology‐associated gene co‐expression modules
Authors: Te Jerez A. , AbdulHameed Mohamed Diwan M. , Wallqvist Anders
Published: January 2016

Organ injuries caused by environmental chemical exposures or use of pharmaceutical drugs pose a serious health risk that may be difficult to assess because of a lack of non‐invasive diagnostic tests. Mapping chemical injuries to organ‐specific histopathology outcomes via biomarkers will provide a foundation for designing precise and robust diagnostic tests. We identified co‐expressed genes (modules) specific to injury endpoints using the Open Toxicogenomics Project‐Genomics Assisted Toxicity Evaluation System (TG‐GATEs) – a toxicogenomics database containing organ‐specific gene expression data matched to dose‐ and time‐dependent chemical exposures and adverse histopathology assessments in Sprague–Dawley rats. We proposed a protocol for selecting gene modules associated with chemical‐induced injuries that classify 11 liver and eight kidney histopathology endpoints based on dose‐dependent activation of the identified modules. We showed that the activation of the modules for a particular chemical exposure condition, i.e., chemical‐time‐dose combination, correlated with the severity of histopathological damage in a dose‐dependent manner. Furthermore, the modules could distinguish different types of injuries caused by chemical exposures as well as determine whether the injury module activation was specific to the tissue of origin (liver and kidney). The generated modules provide a link between toxic chemical exposures, different molecular initiating events among underlying molecular pathways and resultant organ damage. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.
The Relationship Between Nonsuicidal Self‐Injury and Suicidal Ideation
Authors: Wester Kelly L. , Ivers Nathaniel , Villalba José A. , Trepal Heather C. , Henson Robert
Published: January 2016

This correlational study was conducted with 403 undergraduate college students from 2 universities. The authors used path analysis and bootstrap regression to analyze the relationships between variables. Locus of control and family connectedness related to current nonsuicidal self‐injury (NSSI) engagement. However, when entered into the same regression, the variables current NSSI engagement and current NSSI number of methods used mediated all other relationships with suicidal ideation. Implications to current theories and clinical practice are provided.
The Power of Language and Labels: “The Mentally Ill” Versus “People With Mental Illnesses”
Authors: Granello Darcy Haag , Gibbs Todd A.
Published: January 2016

Undergraduate students (N= 221), adults in a community sample (N= 211), and professional counselors and counselors‐in‐training (N= 269) were given a measure of tolerance. Within each sample, half of the participants were given a version that used the term “the mentally ill” and half were given a version that used the term “people with mental illnesses.” Individuals receiving the version with the term “the mentally ill” had lower levels of tolerance. Professional counselors had the largest differences in tolerance on the basis of language.
Attachment Orientations: Predicting Psychological Distress in German and Turkish Samples
Authors: Turan Numan , Kocalevent Rüya‐Daniela , Quintana Stephen M. , Erdur‐Baker Özgür , Diestelmann Jacob
Published: January 2016

This study examined the relationship between attachment orientations and psychological distress, as well as cultural moderation in this relationship, among 241 university students from Germany and Turkey. Attachment orientations predicted the elevation of psychological distress in both samples. Attachment anxiety in the German sample and attachment avoidance in the Turkish sample showed stronger association with the elevation in psychological distress. The results and potential implications for counseling research and practice are discussed.
Multicultural and Social Justice Counseling Competencies: Guidelines for the Counseling Profession
Authors: Ratts Manivong J. , Singh Anneliese A. , Nassar‐McMillan Sylvia , Butler S. Kent , McCullough Julian Rafferty
Published: January 2016

In 2014, the Association for Multicultural Counseling and Development (AMCD) appointed a committee to revise the Multicultural Counseling Competencies developed by Sue, Arredondo, and McDavis inand operationalized by Arredondo et al. in. This article reflects the updated competencies, titled the Multicultural and Social Justice Counseling Competencies (MSJCC; Ratts, Singh, Nassar‐McMillan, Butler, & McCullough,), which were endorsed by AMCD on June 29, 2015, and by the American Counseling Association on July 20, 2015. A conceptual framework of the MSJCC visually depicts the relationships among the competencies' key constructs: multicultural and social justice praxis, quadrants, domains, and competencies. Implications are discussed.

En 2014, la Asociación para la Consejería y el Desarrollo Multicultural (AMCD, en sus siglas en inglés) formó un comité para revisar las Competencias en Consejería Multicultural desarrolladas por Sue, Arredondo y McDavis en 1992 y operacionalizadas por Arredondo et al. en 1996. Este artículo refleja las competencias actualizadas, denominadas Competencias en Consejería Multicultural y de Justicia Social (MSJCC, en sus siglas en inglés; Ratts, Singh, Nassar‐McMillan, Butler, & McCullough, 2015a), que fueron avaladas por la AMCD el 29 de junio de 2015 y por la Asociación Americana de Consejería el 20 de julio de 2015. Un marco conceptual de las MSJCC muestra visualmente las relaciones entre los constructos principales de las competencias: la praxis multicultural y en justicia social, los cuadrantes, dominios y competencias. Se discuten las implicaciones.
Mouthparts in Leptotrombidium larvae (Acariformes: Trombiculidae)
Authors: Shatrov Andrey B. , Takahashi Mamoru , Misumi Hitoko , Takahashi Yumi
Published: January 2016

Mouthparts of Leptotrombidium larvae (Acariformes: Trombiculidae), potential vectors of tsutsugamushi disease agents, were studied in detail using light microscopy, scanning electron microscopy, and transmission electron microscopy. The mouthparts incorporated within the pseudotagma gnathosoma are composed of the infracapitulum ventrally and the chelicerae dorsally. The ventral wall of the infracapitulum is formed by a wide mentum posteriorly and a narrowed malapophysis anteriorly. The malapophysis firmly envelops the distal cheliceral portions by its lateral walls. The lateral lips of the malapophysis are flexible structures hiding the cheliceral blades in inactive condition and turning back forming a type of temporary sucker closely applied to the host skin during feeding. The roof of the infracapitulum is formed by a weakly sclerotized labrum anteriorly and a cervix with the capitular apodemes extending posteriorly. The labral muscles are lacking. The capitular apodemes serve as origin for pharyngeal dilators running to the dorsal wall of the pharynx fused with the bottom of the infracapitulum. The basal cheliceral segments are separated from each other besides the very posterior portions where they are movably joined by the inner walls. The sigmoid pieces serve for insertion of the cheliceral elevators originating at the posterior portions of the basal segments. The movable digits reveal the solid basal sclerite and the cheliceral blade curved upward with a tricuspid cap on its tip. Dendrites of nerve cells run along the digits to their tips. The ganglia are placed within the basal segments just behind the movable digits. The chelicerae also reveal well developed flexible fixed digits overhanging the basal portions of the blades. The gnathosoma possesses several sets of extrinsic muscles originating at the scutum and at the soft cuticle behind it. Laterally, the gnathosoma bears five‐segmented palps with a trifurcate palpal claw. J. Morphol. 277:424–444, 2016. © 2016 Wiley Periodicals, Inc.
Evaluation of Raman spectroscopy for prediction of antitumor response to silibinin and its nanoparticulates in DMBA‐induced oral carcinogenesis
Authors: Gohulkumar M. , Kumar Piyush , Murali Krishna C. , Krishnakumar N.
Published: January 2016

Raman spectroscopy is a vibrational spectroscopic technique that can be used to monitor the therapeutic efficacy of anticancer drugs during carcinogenesis in a non‐invasive and label‐free manner. The present study aims to investigate the biochemical changes exerted upon free silibinin (SIL) and its nanoparticulate (SILNPs) treatment against 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced oral carcinogenesis in the fingerprint region of 1800–500 cm−1 using HE‐785 Raman spectrometer. Raman spectra differed significantly between the control and tumor tissues, with tumor tissues characterized by increased intensities of vibrational bands such as nucleic acids, phenylalanine and tryptophan and a lower percentage of lipids when compared to the control tissues. Further, oral administration of free SIL and SILNPs significantly increased lipids and decreased the levels of tryptophan, phenylalanine and nucleic acid contents. Overall, the treatment of nanoparticulate SIL was found to be a more potent antitumor effect than free SIL in preventing the formation of tumor and also brought back the several Raman bands to a normal range in the buccal mucosa of hamsters during DMBA‐induced oral carcinogenesis. In addition, the detailed secondary structure of proteins in the control and experimental groups is also presented. Furthermore, the diagnostic algorithms based on principal component linear discriminant analysis (PC‐LDA) achieved an overall sensitivity of 94–100% and specificity of 76–100%. These results further demonstrate that Raman spectroscopy associated with PC‐LDA diagnostic algorithms could be a valuable tool for rapid and sensitive detection of specific biomolecular changes at the molecular level in response to anticancer drug. Copyright © 2015 John Wiley & Sons, Ltd.
Toxic effects of lab‐grade butyl rubber stoppers on aerobic methane oxidation
Authors: Niemann Helge , Steinle Lea , Blees Jan , Bussmann Ingeborg , Treude Tina , Krause Stefan , Elvert Marcus , Lehmann Moritz F.
Published: January 2016

Methods for measuring aerobic methane oxidation (MOx) rates in aquatic environments are often based on the incubation of water samples, during which the consumption of methane (CH4) is monitored. Typically, incubation vessels are sealed with butyl rubber because these elastomers are essentially impermeable for gases. We report on the potential toxicity of five different commercially available, lab‐grade butyl stoppers on MOx activity in samples from marine and lacustrine environments. MOx rates in incubations sealed with non‐halogenated butyl were > 50% lower compared to parallel incubations with halogenated butyl rubber stoppers, suggesting toxic effects associated with the use of the non‐halogenated butyl type. Aqueous extracts of non‐halogenated butyl rubber were contaminated with high amounts of various organic compounds including potential bactericides such as benzyltoluenes and phenylalkanes. Comparably small amounts of organic contaminants were liberated from the halogenated butyl rubber stoppers but only two halogenated stopper types were found that did not seem to leach any organics into the incubation medium. Furthermore, the non‐halogenated and two types of the halogenated butyl elastomers additionally leached comparably high amounts of zinc. While the source of the apparent toxicity with the use of the non‐halogenated rubber stoppers remains elusive, our results indicate that leaching of contaminants from some butyl rubber stoppers can severely interfere with the activity of MOx communities, highlighting the importance of testing rubber stoppers for their respective contamination potential. The impact of leachates from butyl rubber on the assessment of biogeochemical reaction rates other than MOx seems likely but needs to be verified.
Tuning the Mechanical Properties of Poly(Ethylene Glycol) Microgel‐Based Scaffolds to Increase 3D Schwann Cell Proliferation
Authors: Zhou Wenda , Stukel Jessica M. , Cebull Hannah L. , Willits Rebecca Kuntz
Published: January 2016

2D in vitro studies have demonstrated that Schwann cells prefer scaffolds with mechanical modulus approximately 10× higher than the modulus preferred by nerves, limiting the ability of many scaffolds to promote both neuron extension and Schwann cell proliferation. Therefore, the goals of this work are to develop and characterize microgel‐based scaffolds that are tuned over the stiffness range relevant to neural tissue engineering and investigate Schwann cell morphology, viability, and proliferation within 3D scaffolds. Using thiol‐ene reaction, microgels with surface thiols are produced and crosslinked into hydrogels using a multiarm vinylsulfone (VS). By varying the concentration of VS, scaffold stiffness ranges from 0.13 to 0.76 kPa. Cell morphology in all groups demonstrates that cells are able to spread and interact with the scaffold through day 5. Although the viability in all groups is high, proliferation of Schwann cells within the scaffold ofG* = 0.53 kPa is significantly higher than other groups. This result is ≈5× lower than previously reported optimal stiffnesses on 2D surfaces, demonstrating the need for correlation of 3D cell response to mechanical modulus. As proliferation is the first step in Schwann cell integration into peripheral nerve conduits, these scaffolds demonstrate that the stiffness is a critical parameter to optimizing the regenerative process.

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Stability of an interconnected Schrödinger–heat system in a torus region
Authors: Guo Yaping , Wang Jun‐Min , Zhao Dong‐Xia
Published: January 2016

In this paper, we study the exponential stability of a two‐dimensional Schrödinger–heat interconnected system in a torus region, where the interface between the Schrödinger equation and the heat equation is of natural transmission conditions. By using a polar coordinate transformation, the two‐dimensional interconnected system can be reformulated as an equivalent one‐dimensional coupled system. It is found that the dissipative damping of the whole system is only produced from the heat part, and hence, the heat equation can be considered as an actuator to stabilize the whole system. By a detailed spectral analysis, we present the asymptotic expressions for both eigenvalues and eigenfunctions of the closed‐loop system, in which the eigenvalues of the system consist of two branches that are asymptotically symmetric to the line Reλ =− Imλ. Finally, we show that the system is exponentially stable and the semigroup, generated by the system operator, is of Gevrey class δ > 2. Copyright © 2016 John Wiley & Sons, Ltd.
Molecular classification of fatty liver by high‐throughput profiling of protein post‐translational modifications
Authors: Urasaki Yasuyo , Fiscus Ronald R , Le Thuc T
Published: January 2016

We describe an alternative approach to classifying fatty liver by profiling protein post‐translational modifications (PTMs) with high‐throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high‐fat diet. Nutrient‐sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O‐N‐acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high‐throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Deficiencies in the Management of Iron Deficiency Anemia During Childhood
Authors: Powers Jacquelyn M. , Daniel Catherine L. , McCavit Timothy L. , Buchanan George R.
Published: January 2016

Limited high‐quality evidence supports the management of iron deficiency anemia (IDA). To assess our institutional performance in this area, we retrospectively reviewed IDA treatment practices in 195 consecutive children referred to our center from 2006 to mid‐2010. The majority of children were ≤4 years old (64%) and had nutritional IDA (74%). In 11‐ to 18‐year‐old patients (31%), the primary etiology was menorrhagia (42%). Many were referred directly to the emergency department and/or prescribed iron doses outside the recommended range. Poor medication adherence and being lost‐to‐follow‐up were common. Substantial improvements are required in the management of IDA.
An ambient detection system for visualization of charged particles generated with ionization methods at atmospheric pressure
Authors: Hommersom Bob , Syed Sarfaraz U. A. H. , Eijkel Gert B. , Kilgour David P. A. , Goodlett David R. , Heeren Ron M. A.
Published: January 2016

Rationale

With the current state‐of‐the‐art detection of ions only taking place under vacuum conditions, active pixel detectors that operate under ambient conditions are of particular interest. These detectors are ideally suited to study and characterize the charge distributions generated by ambient ionization sources.

Methods

The direct imaging capabilities of the active pixel detector are used to investigate the spatial distributions of charged droplets generated by three ionization sources, named electrospray ionization (ESI), paper spray ionization (PSI) and surface acoustic wave nebulization (SAWN). The ionization spray (ESI/PSI) and ionization plume (SAWN) originating from each source are directly imaged. The effect of source parameters such as spray voltage for ESI and PSI, and the angle of the paper spray tip on the charge distributions, is investigated. Two types of SAWN liquid interface, progressive wave (PW) and standing wave (SW), are studied.

Results

Direct charge detection under ambient conditions is demonstrated using an active pixel detector. Direct charge distributions are obtained of weak, homogeneous/focused and dispersed spray plumes by applying low, intermediate and high spray potentials, respectively, for ESI. Spray plume footprints obtained for various angles of PSI shows the possibility to focus the ion beam as a function of the paper angle. Differences between two designs of the SAWN interface are determined. Droplet charge flux changes are illustrated in a way similar to a total ion chromatogram.

Conclusions

The use of this active pixel detector allows the rapid characterization and optimization of different ambient ionization sources without the actual use of a mass spectrometer. Valuable illustrations are obtained of changes in spatial distribution and number of charges detected for ESI, PSI and SAWN ion plumes. Copyright © 2015 John Wiley & Sons, Ltd.
Ion transfer from an atmospheric pressure ion funnel into a mass spectrometer with different interface options: Simulation‐based optimization of ion transmission efficiency
Authors: Mayer Thomas , Borsdorf Helko
Published: January 2016

Rationale

We optimized an atmospheric pressure ion funnel (APIF) including different interface options (pinhole, capillary, and nozzle) regarding a maximal ion transmission. Previous computer simulations consider the ion funnel itself and do not include the geometry of the following components which can considerably influence the ion transmission into the vacuum stage.

Methods

Initially, a three‐dimensional computer‐aided design (CAD) model of our setup was created using Autodesk Inventor. This model was imported to the Autodesk Simulation CFD program where the computational fluid dynamics (CFD) were calculated. The flow field was transferred to SIMION 8.1. Investigations of ion trajectories were carried out using the SDS (statistical diffusion simulation) tool of SIMION, which allowed us to evaluate the flow regime, pressure, and temperature values that we obtained.

Results

The simulation‐based optimization of different interfaces between an atmospheric pressure ion funnel and the first vacuum stage of a mass spectrometer require the consideration of fluid dynamics. The use of a Venturi nozzle ensures the highest level of transmission efficiency in comparison to capillaries or pinholes. However, the application of radiofrequency (RF) voltage and an appropriate direct current (DC) field leads to process optimization and maximum ion transfer. The nozzle does not hinder the transfer of small ions.

Conclusions

Our high‐resolution SIMION model (0.01 mm grid unit–1) under consideration of fluid dynamics is generally suitable for predicting the ion transmission through an atmospheric‐vacuum system for mass spectrometry and enables the optimization of operational parameters. A Venturi nozzle inserted between the ion funnel and the mass spectrometer permits maximal ion transmission. Copyright © 2015 John Wiley & Sons, Ltd.
Ein hochlagenorientiertes und duktilitätsgesteuertes Stahlgütewahlkonzept
Authors: Eichler Björn , Feldmann Markus
Published: January 2016

Die europäischen Stahlbaunormen enthalten ein vereinfacht aufbereitetes Modell der Stahlsortenwahl zur Vermeidung von Sprödbruch (DIN EN 1993‐1‐10), das auf einem bruchmechanischen Zähigkeitsnachweis in der Tieflage basiert. Für die eindeutige Charakterisierung des Materialverhaltens von ferritischen Baustählen ist jedoch die Entwicklung der Zähigkeitseigenschaften über den vollständigen Temperaturbereich und damit auch das Hochlagenverhalten entscheidend. Letzteres beeinflusst das Duktilitätsvermögen des Werkstoffs und damit seine Fähigkeit zur plastischen Umverteilung, was insbesondere bei festigkeitskontrollierten Versagensarten bei der Bemessung im Grenzzustand der Tragfähigkeit implizit als gegeben vorausgesetzt wird. Die in DIN EN 1993‐1‐1 in dieser Hinsicht existierenden Duktilitätskriterien werden als unzureichend angesehen, da sie weder mechanisch eindeutig zu begründen sind, noch aus dem Hochlagenverhalten abgeleitet werden können. Ähnliches gilt für den in Deutschland für dickere Bleche einiger Stahlsorten noch zu erbringenden Aufschweißbiegeversuch nach SEP 1390. Als Grundlage der Stahlgütewahl für die verformungsgesteuerte Bemessung wurde in diesem Sinne ein zähigkeitsorientiertes Modell zur Werkstoffwahl entwickelt, mit dem sich Hochlagenanforderungen in Form von Hochlagenkerbschlagwerten KVUS zur Einstellung eines notwendigen Duktilitätsniveaus quantifizieren und ferner Hochlage und Übergangsbereich mit der Tieflage verknüpfen lassen.

An upper shelf oriented and ductility‐controlled steel selection concept. The European steel work codes contain a simplified steel selection method for the avoidance of brittle fracture (DIN EN 1993‐1‐10) that is based on a fracture mechanical consideration of toughness properties in the lower shelf of the toughness transition curve. For the unambiguous characterisation of the material behaviour of ferrite structural steels the development of the toughness properties for the full temperature range and therewith the upper shelf behaviour is crucial. The latter affects the material’s ductile capacity and thereby its ability for plastic redistribution that is presumed as an integral element for the strength functions in case of the ultimate limit state design. In this respect only inadequate ductility criteria exist to date in DIN EN 1993‐1‐1 which cannot clearly be justified by mechanical means nor derived from upper shelf aspects. Something similar applies to the so‐called Aufschweißbiegeversuch acc. to SEP 1390 that in Germany still in some cases is obligatory for thicker elements of several steel grades. In this light a toughness‐oriented model for the choice of steel material for the plastic design taking inelastic redistributions into account was developed which allows to quantify upper shelf demands for adjusting a required ductility level by combining the upper shelf and the transition region with the lower shelf.
Stahl in der Bildhauerei – Tragwerksentwurf der Skulptur “le chemin de l’eau” in Paris
Authors: Avgerinou Stella , Vayas Ioannis , Adamakos Kostas
Published: January 2016

Angelika Korovessi, eine prominente griechische Bildhauerin, entwarf eine Stahlskulptur, die in Paris vor einem öffentlichen Gebäude permanent ausgestellt ist. Die Skulptur ist eine abstrakte geometrische Komposition aus nichtrostendem Stahl und steht auf einem Sockel, der in einem Wasserbecken unter der Wasseroberfläche liegt. Die einzelnen Teile der Skulptur bestehen aus geschweißten, dünnwandigen, rechteckigen Hohlquerschnitten variabler Höhen, die miteinander durch kurze Rohrstücke verbunden sind. Das Werk wurde in Athen hergestellt, für den Transport in zwei Teile geteilt und vor Ort in Paris zusammengebaut. Dieser Beitrag berichtet über die Modellierung, die rechnerischen Nachweise und der Konstruktion des Kunstwerkes.

Steel in sculpture – Structural design of the sculpture “le chemin de l’eau” in Paris. Aggelika Korovessi, a prominent Greek sculptress, designed a sculpture to be permanently exhibited outside a public building in Paris. The sculpture is an abstract geometric composition from stainless steel and rests on a basis which is submerged in water. The individual parts are composed from welded thin‐walled rectangular hollow sections with variable heights that are connected by short tubes. The sculture was fabricated in Athens, divided in two pieces because of transportation reasons and assembled on site in Paris. This paper reports on the design and construction of the artwork.
Adenosinergic Immunosuppression by Human Mesenchymal Stromal Cells Requires Co-Operation with T cells
Authors: Kerkelä Erja , Laitinen Anita , Räbinä Jarkko , Valkonen Sami , Takatalo Maarit , Larjo Antti , Veijola Johanna , Lampinen Milla , Siljander Pia , Lehenkari Petri , Alfthan Kaija , Laitinen Saara
Published: January 2016

Mesenchymal stem/stromal cells (MSCs) have the capacity to counteract excessive inflammatory responses. MSCs possess a range of immunomodulatory mechanisms, which can be deployed in response to signals in a particular environment and in concert with other immune cells. One immunosuppressive mechanism, not so well-known in MSCs, is mediated via adenosinergic pathway by ectonucleotidases CD73 and CD39. In this study, we demonstrate that adenosine is actively produced from adenosine 5′-monophosphate (AMP) by CD73 on MSCs and MSC-derived extracellular vesicles (EVs). Our results indicate that although MSCs express CD39 at low level and it colocalizes with CD73 in bulge areas of membranes, the most efficient adenosine production from adenosine 5′-triphosphate (ATP) requires co-operation of MSCs and activated T cells. Highly CD39 expressing activated T cells produce AMP from ATP and MSCs produce adenosine from AMP via CD73 activity. Furthermore, adenosinergic signaling plays a role in suppression of T cell proliferation in vitro. In conclusion, this study shows that adenosinergic signaling is an important immunoregulatory mechanism of MSCs, especially in situations where ATP is present in the extracellular environment, like in tissue injury. An efficient production of immunosuppressive adenosine is dependent on the concerted action of CD39-positive immune cells with CD73-positive cells such as MSCs or their EVs.
MicroRNA Regulates Hepatocytic Differentiation of Progenitor Cells by Targeting YAP1
Authors: Jung Kwang Hwa , McCarthy Ryan L. , Zhou Chong , Uprety Nadima , Barton Michelle Craig , Beretta Laura
Published: January 2016

MicroRNA expression profiling in human liver progenitor cells following hepatocytic differentiation identified miR-122 and miR-194 as the microRNAs most strongly upregulated during hepatocytic differentiation of progenitor cells. MiR-194 was also highly upregulated following hepatocytic differentiation of human embryonic stem cells (hESCs). Overexpression of miR-194 in progenitor cells accelerated their differentiation into hepatocytes, as measured by morphological features such as canaliculi and expression of hepatocytic markers. Overexpression of miR-194 in hESCs induced their spontaneous differentiation, a phenotype accompanied with accelerated loss of the pluripotent factors OCT4 and NANOG and decrease in mesoderm marker HAND1 expression. We then identified YAP1 as a direct target of miR-194. Inhibition of YAP1 strongly induced hepatocytic differentiation of progenitor cells and YAP1 overexpression reversed the miR-194-induced hepatocytic differentiation of progenitor cells. In conclusion, we identified miR-194 as a potent inducer of hepatocytic differentiation of progenitor cells and further identified YAP1 as a mediator of miR-194's effects on hepatocytic differentiation and liver progenitor cell fate.
Maternal serum PAPP‐A and free β‐hCG at 12, 22 and 32 weeks' gestation in screening for pre‐eclampsia
Authors: Wright A. , Guerra L. , Pellegrino M. , Wright D. , Nicolaides K. H.
Published: January 2016

Objective

To examine the distribution of maternal serum pregnancy‐associated plasma protein‐A (PAPP‐A) and free β‐human chorionic gonadotropin (β‐hCG) at 12, 22 and 32 weeks' gestation in singleton pregnancies which develop pre‐eclampsia (PE) and examine the performance of these biomarkers in screening for PE.

Methods

Serum PAPP‐A and free β‐hCG were measured in 94 989 cases at 11–13 weeks, 7597 at 19–24 weeks and 8088 at 30–34 weeks' gestation. Bayes' theorem was used to combine the a‐priori risk from maternal characteristics and medical history with PAPP‐A and free β‐hCG. The empirical and model‐based performance of screening for preterm PE requiring delivery < 37 weeks' gestation and term PE with delivery ≥ 37 weeks was estimated.

Results

Combined screening with maternal factors and serum PAPP‐A at 11–13 and 30–34 weeks and with maternal factors and serum free β‐hCG at 19–24 and 30–34 weeks improved the prediction provided by maternal factors alone for preterm PE. The detection rate, at a 10% false‐positive rate, for preterm PE by screening with maternal factors was about 45% which improved to 51% and 53% by combined screening with PAPP‐A at 11–13 weeks and 30–34 weeks, respectively, and 55% and 54% by combined screening with free β‐hCG at 19–24 weeks and 30–34 weeks, respectively. Measurement of serum PAPP‐A and free β‐hCG was not useful in the prediction of term PE.

Conclusions

Measurement of serum PAPP‐A and free β‐hCG could improve the prediction of preterm PE provided by maternal characteristics and medical history alone. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Power and Nursing Practice
Authors: Wilkinson Geoff , Miers Margaret
Published: January 2016

This reader samples a wide range of modern theological, religious and philosophical discussion on the problem of evil, understood both in terms of the practical or spiritual problem of coping with evil, and the theological problem of explaining its presence in God’s world.
Improved pinocembrin production in Escherichia coli by engineering fatty acid synthesis
Authors: Cao Weijia , Ma Weichao , Zhang Bowen , Wang Xin , Chen Kequan , Li Yan , Ouyang Pingkai
Published: January 2016

The development of efficient microbial processes for pinocembrin production has attracted considerable attention. However, pinocembrin biosynthetic efficiency is greatly limited by the low availability of the malonyl-CoA cofactor in Escherichia coli. Fatty acid biosynthesis is the only metabolic process in E. coli that consumes malonyl-CoA; therefore, we overexpressed the fatty acid biosynthetic pathway enzymes β-ketoacyl-ACP synthase III (FabH) and β-ketoacyl-ACP synthase II (FabF) alone and in combination, and investigated the effect on malonyl-CoA. Interestingly, overexpressing FabH, FabF or both enzymes in E. coli BL21 (DE3) decreased fatty acid synthesis and increased cellular malonyl-CoA levels 1.4-, 1.6-, and 1.2-fold, respectively. Furthermore, pinocembrin production was increased 10.6-, 31.8-, and 5.87-fold in recombinant strains overexpressing FabH, FabF and both enzymes, respectively. Overexpression of FabF, therefore, triggered the highest pinocembrin production and malonyl-CoA levels. The addition of cerulenin further increased pinocembrin production in the FabF-overexpressing strain, from 25.8 to 29.9 mg/L. These results demonstrated that overexpressing fatty acid synthases can increase malonyl-CoA availability and improve pinocembrin production in a recombinant E. coli host. This strategy may hold promise for the production of other important natural products in which cellular malonyl-CoA is rate limiting.
Out-of-hospital cardiac arrest: the prospect of E-CPR in the Maastricht region
Authors: Sharma A.S. , Pijls R.W.M. , Weerwind P.W. , Delnoij T.S.R. , de Jong W.C. , Gorgels A.P.M. , Maessen J.G.
Published: January 2016

Aim

The current outcome of out-of-hospital cardiac arrest (OHCA) patients in the Maastricht region was analysed with the prospect of implementing extracorporeal cardiopulmonary resuscitation (E-CPR).

Methods

A retrospective analysis of adult patients who were resuscitated for OHCA during a 24-month period was performed.

Results

195 patients (age 66 [57–75] years, 82 % male) were resuscitated for OHCA by the emergency medical services and survived to admission at the emergency department. Survival to hospital discharge was 46.2 %. Notable differences between non-survivors and survivors were observed and included: age (70 [58–79] years) vs. (63 [55–72] years, p = 0.01), chronic heart failure (18 vs. 7 %, p = 0.02), shockable rhythm (67 vs. 99 %, p < 0.01), and return of spontaneous circulation (ROSC) at departure from the site of the arrest (46 vs. 99 %, p < 0.01) and on arrival to the emergency department (43 vs. 98 %, p < 0.01), respectively. Acute coronary syndrome was diagnosed in 32 % of non-survivors vs. 59 % among survivors, p < 0.01. Therapeutic hypothermia was provided in non-survivors (20 %) vs. survivors (43 %), p < 0.01. Percutaneous coronary intervention (PCI) was performed in 14 % of non-survivors while 52 % of survivors received PCI (p < 0.01). No statistical significance was observed in terms of gender, witnessed arrest, bystander CPR, or automated external defibrillator deployed among the cohort. At hospital discharge, moderately severe neurological disability was present in six survivors.

Conclusion

These observations are compatible with the notion that a shockable rhythm, ROSC, and post-arrest care improve survival outcome. Potentially, initiating E-CPR in the resuscitation phase in patients with a shockable rhythm and no ROSC might serve as a bridge to definite treatment and improve survival outcome.
Observation of human embryonic behavior in vitro by high‐resolution time‐lapse cinematography
Authors: Iwata Kyoko , Mio Yasuyuki
Published: January 2016

Assisted reproductive technology (ART) has yielded vast amounts of information and knowledge on human embryonic development in vitro; however, still images provide limited data on dynamic changes in the developing embryos. Using our high‐resolution time‐lapse cinematography (hR‐TLC) system, we were able to describe normal human embryonic development continuously from the fertilization process to the hatched blastocyst stage in detail. Our hR‐TLC observation also showed the embryonic abnormality of a third polar body (PB)‐like substance likely containing a small pronucleus being extruded and resulting in single‐pronucleus (1PN) formation, while our molecular biological investigations suggested the possibility that some 1PN embryos could be diploid, carrying both maternal and paternal genomes. Furthermore, in some embryos the extruded third PB‐like substance was eventually re‐absorbed into the ooplasm resulting in the formation of an uneven‐sized, two‐PN zygote. In addition, other hR‐TLC observations showed that cytokinetic failure was correlated with equal‐sized, multi‐nucleated blastomeres that were also observed in the embryo showing early initiation of compaction. Assessment combining our hR‐TLC with molecular biological techniques enables a better understanding of embryonic development and potential improvements in ART outcomes.