bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacokinetic modeling and simulation for assessing renal impairment effect on the pharmacokinetics of mirogabalin
Authors: Yin Ophelia Q. P. , Merante Domenico , Truitt Kenneth , Miller Raymond
Published: July 2015

A population pharmacokinetic model was developed to describe plasma concentrations of mirogabalin and lactam metabolite, obtained following a single oral dose of 5 mg mirogabalin to subjects with varying degrees of renal function.A 2‐compartment model was used for both mirogabalin and lactam metabolite. Body weight was a significant covariate on volume of distribution of mirogabalin and lactam metabolite, whereas creatinine clearance significantly affected both renal and nonrenal clearance of mirogabalin. The total clearance of mirogabalin was decreased by 25%, 54%, and 76% in subjects with mild, moderate, and severe renal impairment, respectively, relative to normal controls. Simulation results showed that in comparison with the normal renal function group receiving mirogabalin 15 mg once or twice daily, dose reduction by 50% or 75% in subjects with moderate or severe renal impairment would produce similar AUCss values, but 37%–43% or 28%–32% lower Cmax,ss of mirogabalin. Predicted mirogabalin AUCss was 26% higher, whereas Cmax,ss was similar in subjects with mild renal impairment compared with those having normal renal function taking the same dose. Results support a dose reduction by 50% or 75% in subjects with moderate or severe renal impairment. No dose adjustment seemed necessary for subjects with mild renal impairment.
Recognition of human telomeric G‐quadruplex DNA by berberine analogs: effect of substitution at the 9 and 13 positions of the isoquinoline moiety
Authors: Bhowmik Debipreeta , Fiorillo Gaetano , Lombardi Paolo , Suresh Kumar G.
Published: July 2015

G‐quadruplex forming sequences are widely distributed in human genome and serve as novel targets for regulating gene expression and chromosomal maintenance. They offer unique targets for anticancer drug development. Here, the interaction of berberine (BC) and two of its analogs bearing substitution at 9 and 13‐position with human telomeric G‐quadruplex DNA sequence has been investigated by biophysical techniques. Both the analogs exhibited several‐fold higher binding affinity than berberine. The Scatchard binding isotherms revealed non‐cooperative binding. 9‐ω‐amino hexyl ether analog (BC1) showed highest affinity (1.8 × 106 M−1) while the affinity of the 13‐phenylpropyl analog (BC2) was 1.09 × 106 M−1. Comparative fluorescence quenching and polarization anisotropy of the emission spectra gave evidence for a stronger stacking interaction of the analogs compared to berberine. The thiazole orange displacement assay has clearly established that the analogs were more effective in displacing the end stacked dye in comparison to berberine. However, the binding of the analogs did not induce any major structural perturbation in the G‐quadruplex structure, but led to higher thermal stability. Energetics of the binding indicated that the association of the analogs was exothermic and predominantly entropy driven phenomenon. Increasing the temperature resulted in weaker binding; the enthalpic contribution increased and the entropic contribution decreased. A small negative heat capacity change with significant enthalpy–entropy compensation established the involvement of multiple weak noncovalent interactions in the binding process. The 9‐ω‐amino hexyl ether analog stabilized the G‐quadruplex structure better than the 13‐phenyl alkyl analog. Copyright © 2015 John Wiley & Sons, Ltd.
When the dark ones become darker: How promotion focus moderates the effects of the dark triad on supervisor performance ratings
Authors: Smith Mickey B. , Craig Wallace J. , Jordan Patti
Published: July 2015

The current study adds to a growing body of research on dark personality traits by investigating the moderating role of promotion focus on the relationships among dark triad traits and facets of job performance. Specifically, we investigated the effects of the dark triad (i.e., Machiavellianism, narcissism, and psychopathy) on supervisor ratings of performance, and the moderating effect promotion focus has on those effects. Using field data, we surveyed 549 employees from a manufacturing company in the USA and obtained supervisor ratings of task performance and helping behavior for each employee. We found support for multiple hypotheses, which suggests that managers rated narcissistic and psychopathic employees as having poorer task performance and psychopathic employees as engaging in fewer helping behaviors than employees low in those traits. Furthermore, promotion focus strengthened these negative relationships. We did not find these effects for Machiavellianism. Implications of these findings for future dark personality research as well as the practical implications for managers and organizations are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Significant differences in late Quaternary bedrock erosion and transport: East versus West Greenland ∼70°N – evidence from the mineralogy of offshore glacial marine sediments
Authors: ANDREWS JOHN T. , BJORK ANDERS A. , EBERL DENNIS D. , JENNINGS ANNE E. , VERPLANCK EMILY P.
Published: July 2015

We use quantitative X‐ray diffraction to determine the mineralogy of late Quaternary marine sediments from the West and East Greenland shelves offshore from early Tertiary basalt outcrops. Despite the similar basalt outcrop area (60 000–70 000 km2), there are significant differences between East and West Greenland sediments in the fraction of minerals (e.g. pyroxene) sourced from the basalt outcrops. We demonstrate the differences in the mineralogy between East and West Greenland marine sediments on three scales: (1) modern day, (2) late Quaternary inputs and (3) detailed down‐core variations in 10 cores from the two margins. On the East Greenland Shelf (EGS), late Quaternary samples have an average quartz weight per cent of 6.2 ± 2.3 versus 12.8 ± 3.9 from the West Greenland Shelf (WGS), and 12.02 ± 4.8 versus 1.9 ± 2.3 wt% for pyroxene. K‐means clustering indicated only 9% of the samples did not fit a simple EGS vs. WGS dichotomy. Sediments from the EGS and WGS are also isotopically distinct, with the EGS having higher ϵNd(−18 to 4) than those from the WGS (ϵNd = −25 to −35). We attribute the striking dichotomy in sediment composition to fundamentally different long‐term Quaternary styles of glaciation on the two basalt outcrops.
Transcutaneous in vivo Raman spectroscopy of breast tumors and pretumors
Authors: Bhattacharjee T. , Maru G. , Ingle A. , Murali Krishna C.
Published: July 2015

Breast cancer is the most common cancer amongst women worldwide. Early detection of this cancer results in better prognosis. Owing to the disadvantages of currently available screening tools for early detection of this cancer, rapid and sensitive alternatives such as optical spectroscopic techniques are being extensively explored. Detection of premalignant lesions using these techniques has been reported. However, premalignant lesions are risk indicators and may not be true predictors of tumor development. Therefore, the current study aims at correlation between spectral changes and tumor appearance. In this context, transcutaneous in vivo spectra were acquired from same carcinogen‐induced rats immediately before carcinogen treatment, 3, 8–10, and 12–14 weeks after carcinogen treatment and from frank tumors. These were analyzed using multivariate statistical tools principal component analysis and principal component linear discriminant analysis. Further, a complex test data set consisting of spectra from rats of varying ages, tumor appearance times, and tumor induction protocols was used to test the feasibility of correctly identifying controls and pretumors using Raman spectroscopy. Results suggest feasibility of distinguishing pretumor spectra from controls. Taking into consideration the heterogeneity of afflicted breast, rat‐wise analysis was performed wherein a rat was declared ‘will develop tumor’, even if one spectrum was found abnormal. Using this criterion, in vivo Raman spectroscopy could predict tumor appearance with 82% sensitivity and 95% specificity. Prospectively, combined with emerging technologies like deep Raman spectroscopy and fiber‐probe‐based whole sample imaging, Raman spectroscopy may prove as an invaluable adjunct to currently available breast cancer screening tools. Copyright © 2015 John Wiley & Sons, Ltd.
Chemical profiling and antioxidant activity of Bolivian propolis
Authors: Nina Nélida , Quispe Cristina , Jiménez‐Aspee Felipe , Theoduloz Cristina , Giménez Alberto , Schmeda‐Hirschmann Guillermo
Published: July 2015

BACKGROUND

Propolis is a relevant research subject worldwide. However, there is no information so far on Bolivian propolis. Ten propolis samples were collected from regions with high biodiversity in the main honey production places in Bolivia and were analyzed for their total phenolics (TP), flavonoids (TF) and antioxidant activity. The chemical profiles of the samples were assessed by TLC, HPLC‐DAD, HPLC‐DAD‐MS/MSn and NMR analysis.

RESULTS

TP, TF, TLC and NMR analysis showed significant chemical differences between the samples. Isolation of the main constituents by chromatography and identification by HPLC‐DAD‐MS/MSn achieved more than 35 constituents. According to their profiles, the Bolivian propolis can be classified into phenolic‐rich and triterpene‐rich samples. Propolis from the valleys (Cochabamba, Chuquisaca and Tarija) contained mainly prenylated phenylpropanoids, while samples from La Paz and Santa Cruz contained cycloartane and pentacyclic triterpenes. Phenolic‐rich samples presented moderate to strong antioxidant activity while the triterpene‐rich propolis were weakly active.

CONCLUSION

High chemical diversity and differential antioxidant effects were found in Bolivian propolis. Our results provide additional evidence on the chemical composition and bioactivity of South American propolis. © 2015 Society of Chemical Industry
Simultaneous determination of three chloroacetic acids, three herbicides, and 12 anions in water by ion chromatography
Authors: Luo Ximing , Chen Liang , Zhao Yanqing
Published: July 2015

An ion chromatography method was developed for the simultaneous detection of three soluble herbicides (glyphosate, bentazone and picloram), three chlorine disinfection byproducts (monochloroacetic acid, dichloroacetic acid and trichloroacetic acid) and 12 anions in water (Cl–, Br–, SO42–, CO32–, ClO3–, ClO4–, BrO3–, PO43–, NO2–, NO3–, CH3COO– and COO–). High linearity (r2 > 0.996) was observed for all target analytes for each respective concentration range. The limit of detection and limit of quantitation were between 0.21–0.85 and 0.06–25.46 μg/L, respectively. However, the interference effect of Cl–, NO3–, SO42– and CO32– on some target analytes must be considered during the analysis. Sample pre‐treatment by a hydrogen column (H‐column) required to reduce the negative effect of CO32–. Additionally, sample pre‐treatment by a sliver–hydrogen column (Ag–H‐column) is required when Cl– > 100 mg/L and SO42– < 50 mg/L, and pre‐treatment by both a barium column (Ba‐column) and an H‐column is required when Cl– > 100 mg/L and SO42– > 50 mg/L. When Cl– > 100 mg/L, SO42– > 50 mg/L and CO32– > 20 mg/L, the sample pre‐treatment by either an Ag–H–Ba‐column or an Ag–H‐column and Ba‐column is required to minimize interference.
Electrical Stimulation of Human Mesenchymal Stem Cells on Conductive Nanofibers Enhances their Differentiation toward Osteogenic Outcomes
Authors: Hardy John G. , Villancio‐Wolter Maria K. , Sukhavasi Rushi C. , Mouser David J. , Aguilar David , Geissler Sydney A. , Kaplan David L. , Schmidt Christine E.
Published: July 2015

Tissue scaffolds allowing the behavior of the cells that reside within them to be controlled are of particular interest for tissue engineering. Herein, the preparation of conductive fiber–based bone tissue scaffolds (nonwoven mats of electrospun polycaprolactone with an interpenetrating network of polypyrrole and polystyrenesulfonate) is described that enable the electrical stimulation of human mesenchymal stem cells to enhance their differentiation toward osteogenic outcomes.

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Construction and Self‐Assembly of Single‐Chain Polymer Nanoparticles via Coordination Association and Electrostatic Repulsion in Water
Authors: Zhu Zhengguang , Xu Na , Yu Qiuping , Guo Lei , Cao Hui , Lu Xinhua , Cai Yuanli
Published: July 2015

Simultaneous coordination‐association and electrostatic‐repulsion interactions play critical roles in the construction and stabilization of enzymatic function metal centers in water media. These interactions are promising for construction and self‐assembly of artificial aqueous polymer single‐chain nanoparticles (SCNPs). Herein, the construction and self‐assembly of dative‐bonded aqueous SCNPs are reported via simultaneous coordination‐association and electrostatic‐repulsion interactions within single chains of histamine‐based hydrophilic block copolymer. The electrostatic‐repulsion interactions are tunable through adjusting the imidazolium/imidazole ratio in response to pH, and in situ Cu(II)‐coordination leads to the intramolecular association and single‐chain collapse in acidic water. SCNPs are stabilized by the electrostatic repulsion of dative‐bonded block and steric shielding of nonionic water‐soluble block, and have a huge specific surface area of function metal centers accessible to substrates in acidic water. Moreover, SCNPs can assemble into micelles, networks, and large particles programmably in response to the solution pH. These unique media‐sensitive phase‐transformation behaviors provide a general, facile, and versatile platform for the fabrication of enzyme‐inspired smart aqueous catalysts.

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Surface Grafting via Photo‐Induced Copper‐Mediated Radical Polymerization at Extremely Low Catalyst Concentrations
Authors: Laun Joachim , Vorobii Mariia , de los Santos Pereira Andres , Pop‐Georgievski Ognen , Trouillet Vanessa , Welle Alexander , Barner‐Kowollik Christopher , Rodriguez‐Emmenegger Cesar , Junkers Tanja
Published: July 2015

Surface‐initiated photo‐induced copper‐mediated radical polymerization is employed to graft a wide range of polyacrylate brushes from silicon substrates at extremely low catalyst concentrations. This is the first time that the controlled nature of the reported process is demonstrated via block copolymer formation and re‐initiation experiments. In addition to unmatched copper catalyst concentrations in the range of few ppb, film thicknesses up to almost 1 μm are achieved within only 1 h.

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Genome‐wide identification of differential methylation between primary and recurrent hepatocellular carcinomas
Authors: Cui Chenghua , Lu Zheming , Yang Liu , Gao Yanhong , Liu Wei , Gu Liankun , Yang Chen , Wilson James , Zhang Zhiqian , Xing Baocai , Deng Dajun , Sun Zhong Sheng
Published: July 2015

A biomarker capable of clinically predicting hepatocellular carcinoma (HCC) recurrence has not previously been established. Here genome‐wide differential methylation between primary and recurrent HCC cell lines (Hep‐11 and Hep‐12) from the same patient was characterized. The HCC samples from two independent cohorts, complete with follow‐up data, were used to validate the feasibility of the selected methylation biomarkers in predicting HCC prognosis. A methylation array assay identified 30 candidate genes or intergenic‐fragments with an absolute methylation fold‐change >2.0 between these cell lines; 22 candidates were hypomethylated in Hep‐12 cells relative to Hep‐11 cells. Bisulfite sequencing confirmed these results. Most importantly, classification of tumors by LINE‐2 methylation level was significantly associated with HCC recurrence in both cohorts (P < 0.02). Similarly, MAD1L1 and LINC00682 methylation levels also correlated with HCC recurrence. Survival analysis showed that a combined baseline LINE‐2, MAD1L1, and LINC00682 methylation signature was significantly associated with short recurrence‐free survival in patients from both cohorts. A synergic effect was observed between these markers on both recurrence‐free survival (P < 0.010) and overall survival (P < 0.040). In conclusion, low levels of LINE‐2, MAD1L1, and LINC00682 methylation were associated with recurrence and decreased overall survival in HCC patients. © 2015 Wiley Periodicals, Inc.
Synthesen in Kavitäten
Authors: Nachtsheim Boris J.
Published: July 2015

Durch Selbstassemblierung gebildete Hohlräume — Kavitäten — helfen dabei, Reaktionen, die kationische Schritte durchlaufen, mit teils ungewöhnlichen Selektivitäten zu katalysieren.
Efficient numerical methods for boundary data and right‐hand side reconstructions in elliptic partial differential equations
Authors: Rashedi Kamal , Adibi Hojatollah , Dehghan Mehdi
Published: July 2015

In this article, we discuss the application of two important numerical methods, Ritz–Galerkin and Method of Fundamental Solutions (MFS), for solving some inverse problems, arising in the context of two‐dimensional elliptic equations. The main incentive for studying the considered problems is their wide applications in engineering fields. In the previous literature, the use of these methods, particularly MFS for right hand side reconstruction has been limited, partly due to stability concerns. We demonstrate that these diculties may be surmounted if the aforementioned methods are combined with techniques such as dual reciprocity method(DRM). Moreover, we incorporate some iterative regularization techniques. This fact is especially veried by taking into account the noisy data with boundary conditions. In addition, parts of this article are dedicated to the problem of boundary data approximation and the issue of numerical stability, ending with a general discussion on the advantages and disadvantages of various methods. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 1995–2026, 2015
A new approach for admissibility analysis of the direct discontinuous Galerkin method through Hilbert matrices
Authors: Vidden Chad N
Published: July 2015

This article continues the study of the so‐called direct discontinuous Galerkin (DDG) method for diffusion problems as developed in [Liu and Yan, SIAM J Numer Anal 47 (2009), 475–698;, Liu and Yan, Commun Comput Phys 8 (2010), 541–564; C. Vidden and J. Yan, J Comput Math 31 (2013), 638–662; H. Liu, Math Comp (in press)]. A key feature of the DDG method lies with the numerical flux design which includes two (or more) free parameters. This article identifies the class of all admissible numerical flux choices (Theorem 2.2) for degree n polynomial approximations for the symmetric DDG method [C. Vidden and J. Yan, J Comput Math 31 (2013), 638–662], guaranteeing stability of the resulting method. Our main contribution is the new technique of analysis for the DDG admissibility condition. The strategy is to directly evaluate the admissibility condition (Lemma 2.4) by choosing a simple polynomial basis. The admissibility condition is then transformed into an eigenvalue problem resulting in showing needed properties of inverse Hilbert matrices (Lemma 2.3, Appendix). Numerical tests are provided to confirm theoretical results. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 32: 350–367, 2016
Survey Instruments for Knowledge, Skills, Attitudes and Behaviour Related to Evidence‐based Practice in Occupational Therapy: A Systematic Review
Authors: Buchanan Helen , Siegfried Nandi , Jelsma Jennifer
Published: July 2015

The purpose of this study was to evaluate, through a systematic review, assessment instruments for evidence‐based practice (EBP). The specific objectives were to (1) identify survey instruments testing EBP knowledge, skills, attitudes and behaviour; (2) determine the attributes measured by each instrument; (3) evaluate the psychometric properties of the instruments; and (4) evaluate the methodological quality of the instruments. Using the Cochrane approach, searches were conducted in Pubmed, EBSCOHost and Scopus from inception to February 2014. Papers were screened by two independent assessors, and data were extracted by one researcher. Forty papers reporting 34 instruments met the inclusion criteria and were included in the qualitative synthesis. Most instruments measured EBP behaviour (n = 33) and attitudes (n = 21).

This review provides a single source of information to enable researchers to select the most robust descriptive instruments to measure EBP learner attributes. Instruments used only with occupational therapists may have resulted in some instruments being missed. For further research, it is recommended that attention is given to developing objective instruments with a focus on knowledge and skills. Copyright © 2015 John Wiley & Sons, Ltd.
Changing trends in carrier screening for genetic disease in the United States
Authors: Nazareth Shivani B. , Lazarin Gabriel A. , Goldberg James D.
Published: July 2015

Genetic disease is the leading cause of infant death in the United States, accounting for approximately 20% of annual infant mortality. Advances in genomic medicine and technological platforms have made possible low cost, pan‐ethnic expanded genetic screening that enables obstetric care providers to offer screening for over 100 recessive genetic diseases. However, the rapid integration of genomic medicine into routine obstetric practice has raised some concerns about the practical implementation of such testing. These changing trends in carrier screening, along with concerns and potential solutions, will be addressed. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.
8.2% pure selenide kesterite thin‐film solar cells from large‐area electrodeposited precursors
Authors: Vauche Laura , Risch Lisa , Sánchez Yudania , Dimitrievska Mirjana , Pasquinelli Marcel , Goislard de Monsabert Thomas , Grand Pierre‐Philippe , Jaime‐Ferrer Salvador , Saucedo Edgardo
Published: July 2015

Cu2ZnSnSe4 solar cell absorbers are synthesized by large‐area electrodeposition of metal stack precursors followed by selenization. A champion solar cell exhibits 8.2% power conversion efficiency, a new record for Cu2ZnSnSe4 solar cells prepared from electrodeposited metallic precursors. Significant improvements of device performance are achieved by the application of two etching procedures and buffer layer optimization. These results validate electrodeposition as a credible alternative to vacuum processes (sputtering, co‐evaporation) for earth‐abundant thin‐film solar cell fabrication at low cost. Copyright © 2015 John Wiley & Sons, Ltd.
Fabrication and Properties of Insensitive CNT/HMX Energetic Nanocomposites as Ignition Ingredients
Authors: Li Hanjian , Ren Hui , Jiao Qingjie , Du Shujing , Yu Lan
Published: July 2015

Cyclotetramethylene tetranitramine (HMX)‐coated carbon nanotube (CNT) nanocomposites with uniform structures were prepared using the recrystallization method. Characterization (SEM, TEM, XRD, BET, etc.) was performed to determine the micromorphology, crystal structure, and specific surface area. The energetic particles were homogeneously distributed on the surfaces of the CNTs, and the maximum thickness of the coating layer was approximately 120 nm, whereas the average crystal size was less than 50 nm. The test results of the thermal behavior showed that the thermal decomposition temperature decreased as the CNT content increased, and the maximum thermal conductivity was approximately 27.3 times higher than that of pure HMX. The sensitivities of the CNT/HMX nanocomposites to impact, friction, and shock were maximally reduced by 73 %, 29 %, and 74 % compared with those of pure HMX, respectively, which demonstrated a significant safety improvement. In the CNT/HMX nanocomposites, aluminum and ferric oxide were used to fabricate a new type of ignition composition. Based on comparative studies, the results showed that the ignition composition was porous and that its particles were more evenly distributed compared with the conventional counterparts. The thermal conductivity was improved by 21 %. The impact and friction sensitivities were also maximally reduced by 21 % and 27 %, respectively. The combustion heat was also increased by 9 % compared with that of a mixture of the same components.
Microsecond simulations of mdm2 and its complex with p53 yield insight into force field accuracy and conformational dynamics
Authors: Pantelopulos George A. , Mukherjee Sudipto , Voelz Vincent A.
Published: July 2015

The p53‐MDM2 complex is both a major target for cancer drug development and a valuable model system for computational predictions of protein‐ligand binding. To investigate the accuracy of molecular simulations of MDM2 and its complex with p53, we performed a number of long (200 ns to 1 µs) explicit‐solvent simulations using a range of force fields. We systematically compared nine popular force fields (AMBER ff03, ff12sb, ff14sb, ff99sb, ff99sb‐ildn, ff99sb‐ildn‐nmr, ff99sb‐ildn‐phi, CHARMM22*, and CHARMM36) against experimental chemical shift data, and found similarly accurate results, with microsecond simulations achieving better agreement compared to 200‐ns trajectories. Although the experimentally determined apo structure has a closed binding cleft, simulations in all force fields suggest the apo state of MDM2 is highly flexible, and able to sample holo‐like conformations, consistent with a conformational selection model. Initial structuring of the MDM2 lid region, known to competitively bind the binding cleft, is also observed in long simulations. Taken together, these results show molecular simulations can accurately sample conformations relevant for ligand binding. We expect this study to inform future computational work on folding and binding of MDM2 ligands. Proteins 2015; 83:1665–1676. © 2015 Wiley Periodicals, Inc.
Isotopic composition of sheep wool records seasonality of climate and diet
Authors: Zazzo A. , Cerling T. E. , Ehleringer J. R. , Moloney A. P. , Monahan F. J. , Schmidt O.
Published: July 2015

Rationale

Hair keratin is a very important material in ecological and archaeological studies because it grows continuously, can be obtained non‐invasively, does not require extensive processing prior to analysis and can be found in archaeological sites. Only a few studies have examined seasonal variations in hair isotope values, and there is no published dataset examining the isotope variability recorded in the keratinous tissues of stationary (i.e., non‐migrating) domestic mammals.

Methods

Thirty‐six Irish sheep were sampled in eight farms every three months between September 2006 and June 2007. A shearing strategy was adopted to sample only the most recently grown wool in order to represent an average of the summer, autumn, winter and spring conditions. The stable isotope ratios of the ground samples were measured using two different stable isotope mass spectrometers operated in dual‐inlet (C, N) and continuous‐flow (O, H) mode.

Results

Wool O isotope ratios are a good proxy for seasonal variability in climate and can be used to anchor a chronology independently of other isotope records (C, N) that are influenced by diet or physiology. By contrast, interpretation of seasonal variations in hair H isotope composition in terms of climate is more complex probably due to the influence of dietary H. The C and N isotope values of grass‐fed animals varied seasonally, probably reflecting the annual cycle of seasonal variation in grass isotope values. The highest δ13C values were measured in summer‐grown wool, while the highest δ15N values were measured in winter‐grown wool. Supplementation of the sheep diet with concentrates was detected easily and was marked by an increase in δ13C values and a decrease in δ15N values in winter‐grown wool.

Conclusions

The present study demonstrates that time‐resolved sampling and stable isotope ratio analysis of sheep wool can be used to identify short‐term changes in diet and climate and therefore offer a tool to examine a wide variety of present and past husbandry practices. Copyright © 2015 John Wiley & Sons, Ltd.
Liquid chromatography/tandem mass spectrometry study of forced degradation of azilsartan medoxomil potassium
Authors: Swain Debasish , Patel Prinesh N. , Palaniappan Ilayaraja , Sahu Gayatri , Samanthula Gananadhamu
Published: July 2015

Rationale

Azilsartan medoxomil potassium (AZM) is a new antihypertensive drug introduced in the year 2011. The presence of degradation products not only affects the quality, but also the safety aspects of the drug. Thus, it is essential to develop an efficient analytical method which could be useful to selectively separate and identify the degradation products of azilsartan medoxomil potassium.

Methods

AZM was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions. Separation of the drug and degradation products was achieved by a liquid chromatography (LC) method using an Acquity UPLC® C18 CSH column with mobile phase consisting of 0.02% trifluoroacetic acid and acetonitrile using a gradient method. Identification and characterization of the degradation products was carried out using LC/electrospray ionization quadrupole time‐of‐flight mass spectrometry (ESI‐QTOFMS).

Results

A total of five degradation products (DP 1 to DP 5) were formed under various stress conditions and their structures were proposed with the help of tandem mass spectrometry (MS/MS) experiments and accurate mass data. A common degradation product (DP 4) was observed under all the degradation conditions. DP 1, DP 2 and DP 5 were observed under acid hydrolytic conditions whereas DP 3 was observed under alkaline conditions.

Conclusions

AZM was found to degrade under hydrolytic, oxidative and photolytic stress conditions. The structures of all the degradation products were proposed. The degradation pathway for the formation of degradation products was also hypothesized. A selective method was developed to quantify the drug in the presence of degradation products which is useful to monitor the quality of AZM. Copyright © 2015 John Wiley & Sons, Ltd.
Numeric score‐based conditional and overall change‐in‐status indices for ordered categorical data
Authors: Lyles Robert H. , Kupper Lawrence L. , Barnhart Huiman X. , Martin Sandra L.
Published: July 2015

Planned interventions and/or natural conditions often effect change on an ordinal categorical outcome (e.g., symptom severity). In such scenarios, it is sometimes desirable to assign a priori scores to observed changes in status, typically giving higher weight to changes of greater magnitude. We define change indices for such data based upon a multinomial model for each row of a c × c table, where the rows represent the baseline status categories. We distinguish an index designed to assess conditional changes within each baseline category from two others designed to capture overall change. One of these overall indices measures expected change across a target population. The other is scaled to capture the proportion of total possible change in the direction indicated by the data, so that it ranges from −1 (when all subjects finish in the least favorable category) to +1 (when all finish in the most favorable category). The conditional assessment of change can be informative regardless of how subjects are sampled into the baseline categories. In contrast, the overall indices become relevant when subjects are randomly sampled at baseline from the target population of interest, or when the investigator is able to make certain assumptions about the baseline status distribution in that population. We use a Dirichlet‐multinomial model to obtain Bayesian credible intervals for the conditional change index that exhibit favorable small‐sample frequentist properties. Simulation studies illustrate the methods, and we apply them to examples involving changes in ordinal responses for studies of sleep deprivation and activities of daily living. Copyright © 2015 John Wiley & Sons, Ltd.
Barriers for Deriving Transgene-Free Pig iPS Cells with Episomal Vectors
Authors: Du Xuguang , Feng Tao , Yu Dawei , Wu Yuanyuan , Zou Huiying , Ma Shuangyu , Feng Chong , Huang Yongye , Ouyang Hongsheng , Hu Xiaoxiang , Pan Dengke , Li Ning , Wu Sen
Published: July 2015

To date no authentic embryonic stem cell (ESC) line or germline-competent-induced pluripotent stem cell (iPSC) line has been established for large animals. Despite this fact, there is an impression in the field that large animal ESCs or iPSCs are as good as mouse counterparts. Clarification of this issue is important for a healthy advancement of the stem cell field. Elucidation of the causes of this failure in obtaining high quality iPSCs/ESCs may offer essential clues for eventual establishment of authentic ESCs for large animals including humans. To this end, we first generated porcine iPSCs using nonintegrating replicating episomal plasmids. Although these porcine iPSCs met most pluripotency criteria, they could neither generate cloned piglets through nuclear transfer, nor contribute to later stage chimeras through morula injections or aggregations. We found that the reprogramming genes in iPSCs could not be removed even under negative selection, indicating they are required to maintain self-renewal. The persistent expression of these genes in porcine iPSCs in turn caused differentiation defects in vivo. Therefore, incomplete reprogramming manifested by a reliance on sustained expression of exogenous-reprogramming factors appears to be the main reason for the inability of porcine iPSCs to form iPSC-derived piglets. Stem Cells  2015;33:3228–3238
Chorioamniotic membrane separation after fetoscopy in monochorionic twin pregnancy: incidence and impact on perinatal outcome
Authors: Ortiz J. U. , Eixarch E. , Peguero A. , Lobmaier S. M. , Bennasar M. , Martinez J. M. , Gratacós E.
Published: July 2015

Objective

To evaluate the incidence of chorioamniotic membrane separation (CMS) after fetoscopy in monochorionic diamniotic (MCDA) twins and its impact on pregnancy outcome.

Methods

The study group comprised a consecutive series of 338 women with an MCDA pregnancy complicated by twin–twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR) treated with selective laser photocoagulation of communicating vessels (SLPCV) or cord occlusion (CO). Data obtained included cervical length, gestational age at procedure, type and duration of surgery and placental location. The incidence of CMS, the rates of miscarriage and preterm prelabor rupture of membranes (PPROM), gestational age at delivery and neonatal survival were recorded.

Results

Of the study population of MCDA pregnancies, 270 (79.9%) had TTTS and 68 (20.1%) had sIUGR. SLPCV was performed in 252 (74.6%) cases and CO in 86 (25.4%). Postoperative CMS was observed in 70 (20.7%) cases. Patients with CMS had higher rates of miscarriage (14.3% vs 7.1%; P = 0.049), PPROM before 32 weeks (43.3% vs 13.7%; P < 0.001) and preterm delivery before 32 weeks (53.3% vs 26.1%; P < 0.001) and a lower rate of neonatal survival of at least one twin (81.7% vs 93.6%; P = 0.003). Multivariate analysis showed that gestational age at surgery was the only independent predictor, with the highest proportion of CMS occurring in cases that underwent surgery before 18 weeks' gestation (odds ratio, 2.941 (95% CI, 1.640–5.275); P < 0.001). There was no influence of cervical length, placental location, duration of surgery or type of surgery on the risk of CMS.

Conclusions

CMS complicated one‐fifth of all MCDA pregnancies that underwent fetoscopy. It appeared to be more common in those who underwent surgery before 18 weeks' gestation and was associated with poorer outcomes. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Prospects of X‐ray photoemission electron microscopy at the first beamline of the Polish synchrotron facility ‘Solaris’
Authors: Ślęzak M. , Giela T. , Wilgocka‐Ślęzak D. , Spiridis N. , Ślęzak T. , Zając M. , Kozioł‐Rachwał A. , Socha R. P. , Stankiewicz M. , Warnicke P. , Pilet N. , Raabe J. , Quitmann C. , Korecki J.
Published: July 2015

The synchrotron radiation facility ‘Solaris’ is currently being built in Krakow, Poland. The first experimental beamline at Solaris will use bending magnet radiation and two exchangeable end stations: a spectroscopic X‐ray photoemission electron microscope and a soft X‐ray absorption spectroscopy chamber. We present the beamline specifications and exemplary results obtained with our end station microscope, which (in statu nascendi of Solaris) has been operated at the NanoXAS beamline in the Swiss Light Source. The end stations should be available for a broad user community at Solaris in 2016. Copyright © 2015 John Wiley & Sons, Ltd.
Staging Laparoscopy for Patients with cM0, Type 4, and Large Type 3 Gastric Cancer
Authors: Miki Yuichiro , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori
Published: July 2015

Background

Staging laparoscopy (SL) is considered useful for detecting peritoneal metastasis, a task that is difficult using conventional imaging modalities. However, indications for the procedure remain unclear, with differences evident across reports. The present study aimed to clarify the effectiveness and limitations of SL for patients with type 4 and large type 3 gastric cancer.

Methods

We included 88 patients with cM0, type 4 or large type 3 gastric cancer who underwent SL at the Shizuoka Cancer Center from August 2008 to June 2014, to determine the detection rate of peritoneal metastasis by SL. In addition, we calculated the false‐negative rate of SL by recruiting patients who were diagnosed as P0 at SL and underwent laparotomy within 28 days after the SL.

Results

P0CY0, P0CY1, P1CY0, and P1CY1 were diagnosed in 41 (46.6 %), 15 (17.0 %), 15 (17.0 %), and 17 (19.3 %) patients, respectively. Accordingly, clinically non‐evident peritoneal metastasis was found in 36.3 % of patients, and 53.4 % of patients were diagnosed with stage IV. In addition, 29 patients diagnosed as P0 at SL underwent laparotomy within 28 days after the SL. Among them, peritoneal metastasis was found in five patients. Thus, the false‐negative rate was 17.2 % (5/29, 95 % CI 7.6–34.6 %).

Conclusions

SL is useful for detecting previously unsuspected peritoneal metastasis and for avoiding unnecessary laparotomy, although the high false‐negative rate cannot be ignored. Patients with cM0, type 4, and large type 3 gastric cancer are considered suitable candidates for SL.
CO2‐Switchable Oil/Water Emulsion for Pipeline Transport of Heavy Oil
Authors: Lu Hongsheng , Guan Xueqian , Wang Baogang , Huang Zhiyu
Published: July 2015

By mixing an aqueous solution of tertiary amine, N,N‐dimethylethanolamine (DMEA), with naphthenic acid (RCOOH) derived from heavy oil, a CO2 switchable zwitterionic surfactant (RCOO−DMEAH+) aqueous system was constructed. The CO2 switchability of this zwitterionic surfactant was confirmed by visual inspection, pH measurements, and conductivity tests, i.e., the RCOO−DMEAH+ decomposed into RCOOH, DMEAH+ and HCO3− after bubbling CO2 through but switched back to its original state by subsequent bubbling N2 through at 80 °C to remove the CO2. The interfacial tension tests of heavy oil in DMEA aqueous solutions indicated that the solution containing 0.5 wt% of DMEA and 0.2 wt% of NaCl resulted in the lowest interfacial tension. The O/W emulsion formed when aqueous solutions of DMEA were used to emulsify heavy oil exhibited the best performance when the oil/water volume ratio, DMEA concentration, and NaCl concentration were 65:35, 0.5 and 0.2 wt%, respectively. The feasibility of pipeline transport of the O/W heavy oil emulsion was evaluated. The results illustrated that the demulsification of the O/W emulsion after transport could be easily realized by bubbling CO2 through. Although demulsification efficiency still needs to be improved, the recycling of the aqueous phase after demulsification by removal of CO2 looks promising.
Characterization of a Partially Purified Extract from Flax (Linumusitatissimum L.) Seed
Authors: Waszkowiak Katarzyna , Barthet Véronique J.
Published: July 2015

A water‐soluble partially purified extract from defatted flax seed was obtained and characterized; it contained proteins (828.8 g/Kg), as well as water‐soluble carbohydrates (101.4 g/Kg) and phenolic compounds (22.2 g/Kg), essentially secoisolariciresinol diglucoside (SDG, 18.40 g/Kg) and ferulic acid (1.45 g/Kg) and p–coumaric acid (2.07 mg/kg) mainly in their glycoside forms. Proteins of 23–24 kDa were the main protein fractions found in the extract. In an emulsion model system, the flax extract was able to inhibit the production of oxidation products (conjugated diene, peroxides and aldehydes) as well as the degradation of flax oil carotenoids. The antioxidant effects of the flax extract were concentration dependent. Oxidation kinetics of the emulsion supplemented with 0.10 % flax extract were similar to the oxidation kinetics of the control blank, whereas, oxidation parameters of the emulsion supplemented with 0.48 % (and higher) flax extract were equal to or better than the oxidation parameters obtained with the test control emulsion containing 0.01 % BHT. These results suggested that flax seed phenolic compounds (SDG) and low molecular weight proteins, both found in the studied extract, might have very strong antioxidant properties. This is paper number 1089 of the Canadian Grain Commission.
The impact of E-dictionary strategy training on EFL class
Authors: Koyama Toshiko
Published: July 2015

The present study attempts to clarify how effective strategy training has been with pocket electronic dictionaries for non-English major EFL learners in an English reading class. The study was designed on the basis of the results of my previous study (LET Kansai Chapter Collected Papers 15:109–119, 2015), which concluded that the reading task with dictionary strategy training for 10 weeks might positively affect the participants’ attitude to leaning, and also the dictionary strategies and reference skills have been well retained. The present study, therefore, provided the participants with: (1) metacognitive tasks as an outside-class activity; (2) setting a collaborative learning environment with peer review; (3) an explicit presentation of the strategies and reference skills with a projector. The results showed that the strategies and reference skills could have been retained by the nonEnglish majors doing these tasks. Additionally, their attitude to learning English seemed to be improved in the present study.
Coping Strategies and Postpartum Depressive Symptoms: a Structural Equation Modelling Approach
Authors: Gutiérrez-Zotes A. , Labad J. , Martín-Santos R. , García-Esteve L. , Gelabert E. , Jover M. , Guillamat R. , Mayoral F. , Gornemann I. , Canellas F. , Gratacós M. , Guitart M. , Roca M. , Costas J. , Luis Ivorra J. , Navinés R. , de Diego-Otero Y. , Vilella E. , Sanjuan J.
Published: July 2015

Background

Variables such as the mother's personality, social support, coping strategies and stressful events have been described as risk factors for postpartum depression. Structural Equation Modelling (SEM) analysis was used to examine whether neuroticism, perceived social support, perceived life events, and coping strategies are associated with postpartum depressive symptoms at the 8th and 32nd weeks.

Methods

A total of 1626 pregnant women participated in a longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Several measures were used: the Edinburgh Postnatal Depression Scale (EPDS), the Diagnostic Interview for Genetic Studies (DIGS), the Eysenck Personality Questionnaire (EPQ-RS), the St. Paul Ramsey life events scale and the Duke-UNC Functional Social Support Questionnaire. The brief COPE scale was used to measure coping strategies. SEM analysis was conducted for all women and in those women with a clinical diagnosis of postpartum depression.

Results

Passive coping strategies were associated with postpartum depressive symptoms at both visits (8th and 32nd weeks). Neuroticism was associated with more passive coping strategies and less active coping strategies. Neuroticism and life stress were positively correlated, and social support was negatively correlated with life stress and neuroticism.

Conclusions

Early identification of potential risk for symptomatology of depression postpartum should include assessment of neuroticism, life events, social support and coping strategies.
Nuclear versus cytosolic activity of the yeast Hog1 MAP kinase in response to osmotic and tunicamycin‐induced ER stress
Authors: García-Marqués Sara , Randez-Gil Francisca , Prieto Jose A.
Published: July 2015

We examined the physiological significance of the nuclear versus cytosolic localization of the MAPK Hog1p in the ability of yeast cells to cope with osmotic and ER (endoplasmic reticulum) stress. Our results indicate that nuclear import of Hog1p is not critical for osmoadaptation. Plasma membrane‐anchored Hog1p is still able to induce increased expression of GPD1 and glycerol accumulation. This is a key osmoregulatory event, although a small production of the osmolyte coupled with the nuclear import of Hog1p is sufficient to provide osmoresistance. On the contrary, the nuclear activity of Hog1p is dispensable for ER stress adaptation.
Multiple binding modes of a small molecule to human Keap1 revealed by X‐ray crystallography and molecular dynamics simulation
Authors: Satoh Mikiya , Saburi Hajime , Tanaka Tomoyuki , Matsuura Yoshinori , Naitow Hisashi , Shimozono Rieko , Yamamoto Naoyoshi , Inoue Hideki , Nakamura Noriko , Yoshizawa Yoshitaka , Aoki Takumi , Tanimura Ryuji , Kunishima Naoki
Published: July 2015

Keap1 protein acts as a cellular sensor for oxidative stresses and regulates the transcription level of antioxidant genes through the ubiquitination of a corresponding transcription factor, Nrf2. A small molecule capable of binding to the Nrf2 interaction site of Keap1 could be a useful medicine. Here, we report two crystal structures, referred to as the soaking and the cocrystallization forms, of the Kelch domain of Keap1 with a small molecule, Ligand1. In these two forms, the Ligand1 molecule occupied the binding site of Keap1 so as to mimic the ETGE motif of Nrf2, although the mode of binding differed in the two forms. Because the Ligand1 molecule mediated the crystal packing in both the forms, the influence of crystal packing on the ligand binding was examined using a molecular dynamics (MD) simulation in aqueous conditions. In the MD structures from the soaking form, the ligand remained bound to Keap1 for over 20 ns, whereas the ligand tended to dissociate in the cocrystallization form. The MD structures could be classified into a few clusters that were related to but distinct from the crystal structures, indicating that the binding modes observed in crystals might be atypical of those in solution. However, the dominant ligand recognition residues in the crystal structures were commonly used in the MD structures to anchor the ligand. Therefore, the present structural information together with the MD simulation will be a useful basis for pharmaceutical drug development.