bluuebunny/crossref_metadata_2025 huggingface dataset:
Suitability of North American Regional Reanalysis (NARR) output for hydrologic modelling and analysis in mountainous terrain
Authors: Trubilowicz Joel W. , Shea J. M. , Jost G. , Moore R. D.
Published: January 2016

Meteorological observations at high elevations in mountainous regions are often lacking. One opportunity to fill this data gap is through the use of downscaled output from weather reanalysis models. In this study, we tested the accuracy of downscaled output from the North American Regional Reanalysis (NARR) against high‐elevation surface observations at four ridgetop locations in the southern Coast Mountains of British Columbia, Canada. NARR model output was downscaled to the surface observation locations through three‐dimensional interpolation for air temperature, vapour pressure and wind speed and two‐dimensional interpolation for radiation variables. Accuracy was tested at both the 3‐hourly and daily time scales. Air temperature displayed a high level of agreement, especially at the daily scale, with root mean square error (RMSE) values ranging from 0.98 to 1.21 °C across all sites. Vapour pressure downscaling accuracy was also quite high (RMSE of 0.06 to 0.11 hPa) but displayed some site specific bias. Although NARR overestimated wind speed, there were moderate to strong linear relations (r2 from 0.38 to 0.84 for daily means), suggesting that the NARR output could be used as an index and bias‐corrected. NARR output reproduced the seasonal cycle for incoming short‐wave radiation, with Nash–Sutcliffe model efficiencies ranging from 0.78 to 0.87, but accuracy suffered on days with cloud cover, resulting in a positive bias and RMSE ranged from 42 to 46 Wm− 2. Although fewer data were available, incoming long‐wave radiation from NARR had an RMSE of 19 Wm− 2 and outperformed common methods for estimating incoming long‐wave radiation. NARR air temperature showed potential to assist in hydrologic analysis and modelling during an atmospheric river storm event, which are characterized by warm and wet air masses with atypical vertical temperature gradients. The incorporation of a synthetic NARR air temperature station to better represent the higher freezing levels resulted in increased predicted peak flows, which better match the observed run‐off during the event. Copyright © 2016 John Wiley & Sons, Ltd.
Comparing Fathers' Physical and Toy Play and Links to Child Behaviour: An Exploratory Study
Authors: St George Jennifer , Fletcher Richard , Palazzi Kerrin
Published: January 2016

Increasing amounts of research show that fathers' involvement in children's lives contributes to the child's social, emotional and cognitive development; however, much of the evidence comes from fathers' caregiving and object play. This exploratory study compared the characteristics of 24 Australian fathers' play in two contexts – toy play and physical play – and examined the association of these play contexts with children's development. Correlational analyses revealed few conceptual similarities between toy play and physical play (rough‐and‐tumble). Rough‐and‐tumble quality was associated with children's emotional and behavioural functioning and self‐regulation, while intrusiveness in toy play related only to self‐regulation. The findings are discussed in terms of widening the conceptual and methodological reach of fathering measures in order to better capture the range of fathers' parenting behaviours and to be able to determine mechanisms of influence. Copyright © 2016 John Wiley & Sons, Ltd.
The multiple stressor ecological risk assessment for the mercury-contaminated South River and upper Shenandoah River using the Bayesian network-relative risk model
Authors: Landis Wayne G , Ayre Kimberley K , Johns Annie F , Summers Heather M , Stinson Jonah , Harris Meagan J , Herring Carlie E , Markiewicz April J
Published: January 2016

We have conducted a regional scale risk assessment using the Bayesian Network Relative Risk Model (BN-RRM) to calculate the ecological risks to the South River and upper Shenandoah River study area. Four biological endpoints (smallmouth bass, white sucker, Belted Kingfisher, and Carolina Wren) and 4 abiotic endpoints (Fishing River Use, Swimming River Use, Boating River Use, and Water Quality Standards) were included in this risk assessment, based on stakeholder input. Although mercury (Hg) contamination was the original impetus for the site being remediated, other chemical and physical stressors were evaluated. There were 3 primary conclusions from the BN-RRM results. First, risk varies according to location, type and quality of habitat, and exposure to stressors within the landscape. The patterns of risk can be evaluated with reasonable certitude. Second, overall risk to abiotic endpoints was greater than overall risk to biotic endpoints. By including both biotic and abiotic endpoints, we are able to compare risk to endpoints that represent a wide range of stakeholder values. Third, whereas Hg reduction is the regulatory priority for the South River, Hg is not the only stressor driving risk to the endpoints. Ecological and habitat stressors contribute risk to the endpoints and should be considered when managing this site. This research provides the foundation for evaluating the risks of multiple stressors of the South River to a variety of endpoints. From this foundation, tools for the evaluation of management options and an adaptive management tools have been forged. Integr Environ Assess Manag 2017;13:85–99. © 2016 SETAC

Key Points

Both chemical and ecological stressors influenced the spatial patterns of risk, which varied among regions according to location, type and quality of habitat, and exposure to stressors within the landscape. Overall risk to abiotic endpoints was greater than overall risk to biotic endpoints, and by including both categories, we were are able to compare risks that represent a wide range of stakeholder values. Though Hg reduction is the regulatory priority for the South River, ecological and habitat stressors also contribute risk to the endpoints and should be considered when managing this site. This assessment has provided a framework for evaluating management activities and long-term monitoring goals for the South River Study Area and similarly contaminated sites.
Long‐term cancer risk after hysterectomy on benign indications: Population‐based cohort study
Authors: Altman Daniel , Yin Li , Falconer Henrik
Published: January 2016

Hysterectomy on benign indications is associated with an increased risk for adverse health effects. However, little is known about the association between hysterectomy and subsequent cancer occurrence later in life. The purpose of this study was to assess the effect of hysterectomy on the incidence of cancer. In this population‐based cohort study, we used data on 111,595 hysterectomized and 537,9843 nonhysterectomized women from nationwide Swedish Health Care registers including the Inpatient Register, the Cancer Register and the Cause of Death Register between 1973 and 2009. Hysterectomy with or without concomitant bilateral salpingo‐ophorectomy (BSO) performed on benign indications was considered as exposure and incidence of primary cancers was used as outcome measure. Rare primary cancers (<100 cases for the two groups combined) were excluded from analysis. A marginal risk reduction for any cancer was observed for women with previous hysterectomy and for those with hysterectomy and concurrent BSO (HR 0.93, 95% CI 0.91–0.95 and HR 0.92, 95% CI 0.87–0.96, respectively). Compared to nonhysterectomized women, significant risks were observed for thyroid cancer (HR 1.76, 95% CI 1.45–2.14). For both hysterectomy and hysterectomy with BSO, an association with brain cancer was observed (HR 1.48, 95% CI 1.32–1.65 and HR 1.45, 95% CI 1.15–1.83, respectively). Hysterectomy, with or without BSO, was not associated with breast, lung or gastrointestinal cancer. We conclude that hysterectomy on benign indications is associated with an increased risk for thyroid and brain cancer later in life. Further research efforts are needed to identify patient groups at risk of malignancy following hysterectomy.
Risk assessment to guide cervical screening strategies in a large Chinese population
Authors: Zhao Fang‐Hui , Hu Shang‐Ying , Zhang Qian , Zhang Xun , Pan Qin‐Jing , Zhang Wen‐Hua , Gage Julia C. , Wentzensen Nicolas , Castle Philip E. , Qiao You‐Lin , Katki Hormuzd A. , Schiffman Mark
Published: January 2016

Three different cervical screening methods [cytology, human papillomavirus(HPV) testing and visual inspection with acetic acid(VIA)] are being considered in China for the national cervical screening program. Comparing risks of CIN3 and cervical cancer (CIN3+) for different results can inform test choice and management guidelines. We evaluated the immediate risk of CIN3+ for different screening results generated from individual and combined tests. We compared tests using a novel statistic designed for this purpose called Mean Risk Stratification (MRS), in a pooled analysis of 17 cross sectional population‐based studies of 30,371Chinese women screened with all 3 methods and diagnosed by colposcopically‐directed biopsies. The 3 tests combined powerfully distinguished CIN3+ risk; triple‐negative screening conferred a risk of 0.01%, while HPV‐positive HSIL+ that was VIA‐positive yielded a risk of 57.8%. Among the three screening tests, HPV status most strongly stratified CIN3+ risk. Among HPV‐positive women, cytology was the more useful second test. In HPV‐negative women, the immediate risks of CIN3+ ranged from 0.01% (negative cytology), 0.00% (ASC‐US), 1.1% (LSIL), to 6.6 (HSIL+). In HPV‐positive women, the CIN3+ risks were 0.9% (negative cytology), 3.6% (ASC‐US), 6.3% (LSIL) and 38.5% (HSIL+). VIA results did not meaningful stratify CIN3+ risk among HPV‐negative women with negative or ASC‐US cytology; however, positive VIA substantially elevated CIN3+ risk for all other, more positive combinations of HPV and cytology compared with a negative VIA. Because all 3 screening tests had independent value in defining risk of CIN3+, different combinations can be optimized as pragmatic strategies in different resource settings.
New i‐Perfect Cycle Decompositions via Vertex Colorings of Graphs
Authors: Buratti Marco , Costa Simone , Wang Xiaomiao
Published: January 2016

Generalizing a result by Buratti et al.[M. Buratti, F. Rania, and F. Zuanni, Some constructions for cyclic perfect cycle systems, Discrete Math 299 (2005), 33–48], we present a construction for i‐perfect k‐cycle decompositions of the complete m‐partite graph with parts of size k. These decompositions are sharply vertex‐transitive under the additive group of with R a suitable ring of order m. The construction works whenever a suitable i‐perfect map exists. We show that for determining the set of all triples for which such a map exists, it is crucial to calculate the chromatic numbers of some auxiliary graphs. We completely determine this set except for one special case where is the product of two distinct primes, is even, and . This result allows us to obtain a plethora of new i‐perfect k‐cycle decompositions of the complete graph of order (mod 2k) with k odd. In particular, if k is a prime, such a decomposition exists for any possible i provided that .
Metal distribution in the process of lignocellulosic ethanol production from heavy metal contaminated sorghum biomass
Authors: Vintila Teodor , Negrea Adina , Barbu Horia , Sumalan Radu , Kovacs Kornel
Published: January 2016

BACKGROUND

The objective of this work was to process the sorghum biomass obtained from crops cultivated on heavy metals polluted soil, for the production of lignocellulosic ethanol and to determine the amount of toxic metals in the intermediary, byproducts, and final products.

RESULTS

In the process of cellulolytic enzymes production by fungi using sorghum bagasse as substrate, a small amount of heavy metals passed into the liquid phase. During pretreatment by steam and alkali, the concentration of metals increased in the solid phase, while in the liquid phase the metals were not detected. After hydrolysis and fermentation of the pretreated biomass, the metals concentration in the solid fraction of the liquid increased, due to dissolution of the main fraction of the organic solids, although a fraction of the metals was found in the liquid fraction of the fermentation medium. During the distillation, some Pb and Cu were extracted into the distillate. Zn and Cd accumulated in the distillation residue.

CONCLUSION

The highest amounts of heavy metals accumulate in the solid residue, a small part is retained in the distillation residue, with traces of Pb and Cu potentially occurring in the distilled ethanol. © 2016 Society of Chemical Industry
Synthesis and Biological Evaluation of Some Novel Isoxazole Derivatives
Authors: Hamama W. S. , Ibrahim M. E. , Zoorob H. H.
Published: January 2016

The reaction of 5‐amino‐3‐methylisoxazole (1) with formalin and secondary amines gave the corresponding Mannich bases 3, 4, 5, 6. Alkylation of isoxazole derivative 1 with Mannich bases hydrochloride gave unsubstituted isoxazolo[5,4‐b]pyridine derivatives 8a, 8b via alkylation at position 4. Moreover, coupling reaction of 1 with different diazonium salts gave the corresponding mono and bisazo dyes of isoxazole derivative. The newly synthesized compounds were screened for their antitumor activity compared with 5‐fluorouracil as a well‐known cytotoxic agent using Ehrlich ascites carcinoma cells. Interestingly, the obtained results showed clearly that compounds 3, 15, 8b, 4, 8a, and 5 exhibited high antitumor activity than 5‐fluorouracil.
Repeatability and sensitivity of measurements in patients with head and neck squamous cell carcinoma at 3T
Authors: Panek Rafal , Welsh Liam , Dunlop Alex , Wong Kee H. , Riddell Angela M. , Koh Dow‐Mu , Schmidt Maria A. , Doran Simon , Mcquaid Dualta , Hopkinson Georgina , Richardson Cheryl , Nutting Christopher M. , Bhide Shreerang A. , Harrington Kevin J. , Robinson Simon P. , Newbold Kate L. , Leach Martin O.
Published: January 2016

Purpose

To determine whether quantitation of
is sufficiently repeatable and sensitive to detect clinically relevant oxygenation levels in head and neck squamous cell carcinoma (HNSCC) at 3T.

Materials and Methods

Ten patients with newly diagnosed locally advanced HNSCC underwent two magnetic resonance imaging (MRI) scans between 24 and 168 hours apart prior to chemoradiotherapy treatment. A multiple gradient echo sequence was used to calculate
maps. A quadratic function was used to model the blood transverse relaxation rate as a function of blood oxygenation. A set of published coefficients measured at 3T were incorporated to account for tissue hematocrit levels and used to plot the dependence of fractional blood oxygenation (Y) on
values, together with the corresponding repeatability range. Repeatability of
using Bland–Altman analysis, and calculation of limits of agreement (LoA), was used to assess the sensitivity, defined as the minimum difference in fractional blood oxygenation that can be confidently detected.

Results

LoA for 22 outlined tumor volumes were 13%. The
dependence of fractional blood oxygenation increases monotonically, resulting in increasing sensitivity of the method with increasing blood oxygenation. For fractional blood oxygenation values above 0.11, changes in
were sufficient to detect differences in blood oxygenation greater than 10% (Δ
 > LoA for ΔY > 0.1).

Conclusion

Quantitation of
at 3T can detect clinically relevant changes in tumor oxygenation within a wide range of blood volumes and oxygen tensions, including levels reported in HNSCC. J. Magn. Reson. Imaging 2016;44:72–80.
A person‐centered approach to commitment research: Theory, research, and methodology
Authors: Meyer John P. , Morin Alexandre J.S.
Published: January 2016

There has been a recent increase in the application of person‐centered research strategies in the investigation of workplace commitments. To date, research has focused primarily on the identification, within a population, of subgroups presenting different cross‐sectional or longitudinal configurations of commitment mindsets (affective, normative, and continuance) and/or targets (e.g., organization, occupation, and supervisor), but other applications are possible. In an effort to promote a substantive methodological synergy, we begin by explaining why some aspects of commitment theory are best tested using a person‐centered approach. We then summarize the results of existing research and suggest applications to other research questions. Next, we turn our attention to methodological issues, including strategies for identifying the best profile structure, testing for consistency across samples, time, culture, and so on, and incorporating other variables in the models to test theory regarding profile development, consequences, and change trajectories. We conclude with a discussion of the practical implications of taking a person‐centered approach to the study of commitment as a complement to the more traditional variable‐centered approach. Copyright © 2016 John Wiley & Sons, Ltd.
Bayesian geoadditive modelling of climate extremes with nonparametric spatially varying temporal effects
Authors: Yang Chi , Xu Jing , Li Yang
Published: January 2016

Non‐stationary modelling of climate extremes has attracted significant attention in recent years. Generalized extreme value (GEV) distribution is the standard approach for modelling block extremes. The non‐stationary form of GEV distribution with location and scale parameters linearly regressing to time has been widely used for single‐site time series of climate extremes. In the present paper, such a model is extended to be geoadditive for regional climate extremes with nonparametric spatially varying temporal effects. The model is implemented through the Bayesian hierarchical approach and is applied to the annual minimum surface air temperature in Mainland China as a demonstration. The five bivariate functions representing the regional regression parameters in the model are approximated by low‐rank thin plate regression splines. All the necessary software tools for producing a thin plate regression spline basis and Markov Chain Monte Carlo sampling can be seamlessly integrated and called through the R software environment. Results show that the model can capture the spatial inhomogeneity and temporal non‐stationarity features of regional climate extremes. Expressions for return levels with different return periods and their trends are also derived accordingly. Trends in different return levels, especially those in the ‘extreme state’ (e.g., 50‐year return level) that cannot be inferred by usual observational trend analysis, can also be derived through samples drawn from posterior predictive distributions. The regional trend in a 50‐year return level is quite different to that in a 2‐year return level. More attention should be paid to trends in the extreme state of climate under climate change.
Grazing intensity effects on the partitioning of evapotranspiration in the semiarid typical steppe ecosystems in Inner Mongolia
Authors: Wang Lei , Liu Huizhi , Bernhofer Christian
Published: January 2016

Grazing intensity effects on the evapotranspiration (ET) partitioning into evaporation (E) and transpiration (T) were investigated using eddy covariance measurement data during the growing season (May to September) from 2005 to 2008 over typical steppes in Inner Mongolia, China. Four grazing intensities were examined (UG79, ungrazed since 1979; WG, winter grazed; CG, continuously grazed; HG, heavily grazed). Soil water content (SWC) significantly influenced daily T/ET by affecting T and E in different ways. On a monthly scale, T/ET at UG79 (0.46–0.77) increased with vegetation growth regardless of the uneven distribution of precipitation. The mean T/ET at UG79 for the growing season ranged from 0.50 to 0.74 for 2005 to 2008. In the normal precipitation year (2006), WG and HG reduced T/ET because they significantly reduced T through the removal of leaf area. In the dry year (2005), this negative effect on T was depressed by summer droughts, while WG and HG decreased E primarily due to the decreased interception of rainfall by the canopy. The grazing effect on T/ET was opposite to that in 2006. These results indicate that grazing effects on ET partitioning could vary with soil water conditions in the semiarid typical steppe ecosystems.
Isostatic compensation of Quaternary vertical crustal motions: coupling between uplift of Britain and subsidence beneath the North Sea
Authors: Westaway Rob
Published: January 2016

New data from offshore and onshore regions confirm the view that the Quaternary uplift of Britain and subsidence beneath the North Sea are coupled, mediated by lower‐crustal flow induced by the lateral pressure gradient caused by climate‐driven surface processes. Most measured onshore uplift rates, in both upland and lowland localities, are only applicable since the Mid‐Pleistocene Revolution; beforehand, generally lower rates prevailed. Earlier (?Oligocene–Pliocene) phases of uplift and subsidence had typically even lower rates; furthermore, the western margin of the North Sea depocentre was ∼200 km farther from the modern coastline of north‐east England. In the earliest Cenozoic, complex isostatic adjustments occurred in response to the magmatism associated with the Iceland mantle plume; the contemporaneous land surface (relative to the present‐day rock column) in northern England was typically ∼1500 m OD. However, this activity died out during the Palaeogene; the main effect of these events on the modern isostatic configuration was via the emplacement of thick mafic underplating, which now constricts the mobile lower‐crustal layer, explaining the Late Cenozoic ultra‐stability of Ireland. The evidence enables interpretations of the present‐day topography of Britain as static, caused by the Iceland mantle plume, or actively developing in response to plate motions or plate boundary forces, to be excluded.
Prognostic relevance of preoperative diabetes mellitus and the degree of hyperglycemia on the outcomes of resected pancreatic ductal adenocarcinoma
Authors: Lee Woohyung , Yoon Yoo‐Seok , Han Ho‐Seong , Cho Jai Young , Choi YoungRok , Jang Jae Yool , Choi Hanlim
Published: January 2016

Introduction

The prognostic relevance of preoperative diabetes mellitus (DM) on the outcomes of resected pancreatic ductal adenocarcinoma (PDAC) is controversial. Most previous studies evaluated the prognostic role of DM based on a single blood test.

Methods

The participants included 147 patients with PDAC who underwent pancreatectomy between September 2003 and June 2012. They were divided into following groups according to the preoperative DM and degree of hyperglycemia defined by glycosylated hemoglobin (HbA1c): non‐DM (n = 70), DM with HbA1c < 9.0% (n = 52), and DM with HbA1c ≥ 9.0% (n = 25).

Results

There were no significant differences in cancer stage or postoperative complications among the three groups. The survival rate was significantly lower in the DM with HbA1c ≥ 9.0% group (22.3%) than in the non‐DM group (33.6%) and the DM with HbA1c < 9.0% group (33.8%) (P = 0.044). Multivariate analysis revealed that DM with HbA1c ≥ 9.0% (hazard ratio [HR] 2.495, 95% confidence interval [CI] 1.274–4.886, P = 0.008) and the presence of venous invasion (HR 1.836, 95%CI 1.072–3.146, P = 0.027) were independent prognostic factors for survival.

Conclusion

Uncontrolled severe hyperglycemia rather than preoperative DM negatively affects the survival outcomes following PDAC resection. J. Surg. Oncol. 2016;113:203–208. © 2016 Wiley Periodicals, Inc.
Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings
Authors: Adler Charles H. , Dugger Brittany N. , Hentz Joseph G. , Hinni Michael L. , Lott David G. , Driver‐Dunckley Erika , Mehta Shyamal , Serrano Geidy , Sue Lucia I. , Duffy Amy , Intorcia Anthony , Filon Jessica , Pullen Joel , Walker Douglas G. , Beach Thomas G.
Published: January 2016

Introduction

Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha‐synucleinopathy in early PD.

Methods

Twenty‐five early PD (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha‐synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive.

Results

Mean (standard deviation) age was 69.5 (8.3) for the PD group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six PD and 1 control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 (74%) PD and 2 of 9 (22%) control subjects. PD‐positive and ‐negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77% of cases), but were minor and transient.

Conclusions

Submandibular gland needle biopsies identified phosphorylated alpha‐synuclein staining in 74% of early PD subjects. False positives may be true false positives or may represent prodromal PD. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early PD may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation. © 2016 International Parkinson and Movement Disorder Society
Influence of macromolecule baseline on 1H MR spectroscopic imaging reproducibility
Authors: Birch Rebecca , Peet Andrew C. , Dehghani Hamid , Wilson Martin
Published: January 2016

Purpose

Poorly characterized macromolecular (MM) and baseline artefacts are known to reduce metabolite quantitation accuracy in 1H MR spectroscopic imaging (MRSI). Increasing echo time (TE) and improvements in MM analysis schemes have both been proposed as strategies to improve metabolite measurement reliability. In this study, the influence of TE and two MM analysis schemes on MRSI reproducibility are investigated.

Methods

An experimentally acquired baseline was collected using an inversion recovery sequence (TI = 750 ms) and incorporated into the analysis method. Intrasubject reproducibility of MRSI scans, acquired at 3 Tesla, was assessed using metabolite coefficients of variance (COVs) for both experimentally acquired and simulated MM analysis schemes. In addition, the reproducibility of TE = 35 ms, 80 ms, and 144 ms was evaluated.

Results

TE = 80 ms was the most reproducible for singlet metabolites with COVs < 6% for total N‐acetyl‐aspartate, total creatine, and total choline; however, moderate multiplet dephasing was observed. Analysis incorporating the experimental baseline achieved higher Glu and Glx reproducibility at TE = 35 ms, and showed improvements over the simulated baseline, with higher efficacy for poorer data.

Conclusion

Overall, TE = 80 ms yielded the most reproducible singlet metabolite estimates. However, combined use of a short TE sequence and the experimental baseline may be preferred as a compromise between accuracy, multiplet dephasing, and T2 bias on metabolite estimates. Magn Reson Med 77:34–43, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.
Yin Yang 1‐mediated epigenetic silencing of tumour‐suppressive microRNAs activates nuclear factor‐κB in hepatocellular carcinoma
Authors: Tsang Daisy PF , Wu William KK , Kang Wei , Lee Ying‐Ying , Wu Feng , Yu Zhuo , Xiong Lei , Chan Anthony W , Tong Joanna H , Yang Weiqin , Li May SM , Lau Suki S , Li Xiangchun , Lee Sau‐Dan , Yang Yihua , Lai Paul BS , Yu Dae‐Yeul , Xu Gang , Lo Kwok‐Wai , Chan Matthew TV , Wang Huating , Lee Tin L , Yu Jun , Wong Nathalie , Yip Kevin Y , To Ka‐Fai , Cheng Alfred SL
Published: January 2016

Enhancer of zeste homolog 2 (EZH2) catalyses histone H3 lysine 27 trimethylation (H3K27me3) to silence tumour‐suppressor genes in hepatocellular carcinoma (HCC) but the process of locus‐specific recruitment remains elusive. Here we investigated the transcription factors involved and the molecular consequences in HCC development. The genome‐wide distribution of H3K27me3 was determined by chromatin immunoprecipitation coupled with high‐throughput sequencing or promoter array analyses in HCC cells from hepatitis B virus (HBV) X protein transgenic mouse and human cell models. Transcription factor binding site analysis was performed to identify EZH2‐interacting transcription factors followed by functional characterization. Our cross‐species integrative analysis revealed a crucial link between Yin Yang 1 (YY1) and EZH2‐mediated H3K27me3 in HCC. Gene expression analysis of human HBV‐associated HCC specimens demonstrated concordant overexpression of YY1 and EZH2, which correlated with poor survival of patients in advanced stages. The YY1 binding motif was significantly enriched in both in vivo and in vitro H3K27me3‐occupied genes, including genes for 15 tumour‐suppressive microRNAs. Knockdown of YY1 reduced not only global H3K27me3 levels, but also EZH2 and H3K27me3 promoter occupancy and DNA methylation, leading to the transcriptional up‐regulation of microRNA‐9 isoforms in HCC cells. Concurrent EZH2 knockdown and 5‐aza‐2'‐deoxycytidine treatment synergistically increased the levels of microRNA‐9, which reduced the expression and transcriptional activity of nuclear factor‐κB (NF‐κB). Functionally, YY1 promoted HCC tumourigenicity and inhibited apoptosis of HCC cells, at least partially through NF‐κB activation. In conclusion, YY1 overexpression contributes to EZH2 recruitment for H3K27me3‐mediated silencing of tumour‐suppressive microRNAs, thereby activating NF‐κB signalling in hepatocarcinogenesis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Recommendations for benefit–risk assessment methodologies and visual representations
Authors: Hughes Diana , Waddingham Ed , Mt‐Isa Shahrul , Goginsky Alesia , Chan Edmond , Downey Gerald F. , Hallgreen Christine E. , Hockley Kimberley S. , Juhaeri Juhaeri , Lieftucht Alfons , Metcalf Marilyn A. , Noel Rebecca A. , Phillips Lawrence D. , Ashby Deborah , Micaleff Alain ,   PROTECT Benefit–Risk Group
Published: January 2016

Purpose

The purpose of this study is to draw on the practical experience from the PROTECT BR case studies and make recommendations regarding the application of a number of methodologies and visual representations for benefit–risk assessment.

Methods

Eight case studies based on the benefit–risk balance of real medicines were used to test various methodologies that had been identified from the literature as having potential applications in benefit–risk assessment. Recommendations were drawn up based on the results of the case studies.

Results

A general pathway through the case studies was evident, with various classes of methodologies having roles to play at different stages. Descriptive and quantitative frameworks were widely used throughout to structure problems, with other methods such as metrics, estimation techniques and elicitation techniques providing ways to incorporate technical or numerical data from various sources. Similarly, tree diagrams and effects tables were universally adopted, with other visualisations available to suit specific methodologies or tasks as required. Every assessment was found to follow five broad stages: (i) Planning, (ii) Evidence gathering and data preparation, (iii) Analysis, (iv) Exploration and (v) Conclusion and dissemination.

Conclusions

Adopting formal, structured approaches to benefit–risk assessment was feasible in real‐world problems and facilitated clear, transparent decision‐making. Prior to this work, no extensive practical application and appraisal of methodologies had been conducted using real‐world case examples, leaving users with limited knowledge of their usefulness in the real world. The practical guidance provided here takes us one step closer to a harmonised approach to benefit–risk assessment from multiple perspectives. Copyright © 2016 John Wiley & Sons, Ltd.
Time‐Dependent and Immunosuppressive Drug–Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens
Authors: Felix Maria Julia Pereira , Felipe Claudia Rosso , Tedesco‐Silva Hélio , Osmar Medina‐Pestana José
Published: January 2016

Study Objective

To evaluate the safety and tolerability of immunosuppressive drugs used in a planned randomized conversion from a calcineurin inhibitor, tacrolimus, to a mammalian target of rapamycin inhibitor, sirolimus, in de novo kidney transplant recipients.

Design

Prospective safety analysis of data from a prospective, randomized, open‐label, controlled study.

Patients

A total of 119 adult kidney transplant recipients who received tacrolimus (TAC), mycophenolate sodium (MPS), and prednisone between February 2008 and May 2010; after 3 months of this regimen, 60 of these patients were randomized to conversion from TAC to sirolimus (SRL/MPS group), and 59 patients continued with the TAC regimen (TAC/MPS group).

Measurements and Main Results

Both groups were followed for 24 months after transplantation for immunosuppressive regimen–associated and time‐dependent occurrences of adverse events (AEs) and serious adverse events (SAEs). Before conversion from TAC to SRL, the cumulative incidence of AEs was 98%; 25% were SAEs. Gastrointestinal AEs (66%) and infections (58%) were the most frequent AEs. The incidences of TAC and MPS dose reductions due to AEs were 1.7% and 12%, respectively. After conversion, no significant differences were noted in the SRL/MPS group versus the TAC/MPS group in the cumulative incidences of AEs (100% vs 98%) and SAEs (27% vs 30%). The most common AEs were gastrointestinal (70% vs 54%, p=0.23) and infection (77% vs 73%, p=0.79) in the SRL/MPS versus TAC/MPS groups. The incidence of aphthous ulcer (28% vs 0%, p=< 0.01), sinusitis (10% vs 0%, p=0.01), dermatitis (15% vs 3%, p=0.03), and dyslipidemia (35% vs 14%, p=0.02) were higher in the SRL/MPS group compared with the TAC/MPS group. Cox proportion regression analysis showed a higher relative risk for gastrointestinal (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.2–3.01, p<0.05) and skin and subcutaneous tissue (HR 2.5, 95% CI 1.1–4.1, p<0.05) AEs in the SRL/MPS group compared with the TAC/MPS group. AE‐related dose reductions occurred in 18.3% of patients receiving SRL and 3.3% of patients receiving TAC. MPS dose reductions due to AEs occurred in 11.7% of patients receiving SRL and 13.6% of patients receiving TAC.

Conclusion

SRL/MPS treatment was associated with a time‐dependent higher incidence of gastrointestinal and skin and subcutaneous tissue AEs, which occurred mainly during the first 6 months after conversion from TAC/MPS. Although the treatments with SRL or TAC after 3 months of transplantation showed different safety profiles, both regimens demonstrated adequate tolerability, with low rates of early discontinuation related to AEs.
Core − shell microgels with controlled structural properties
Authors: Battista Edmondo , Mazzarotta Alessia , Causa Filippo , Cusano Angela Maria , Netti Paolo Antonio
Published: January 2016

Microgels have gained great attention in the biomedical field for their wide application in diagnostic and drug delivery systems. The bulk properties as well as the surface features of these particular microparticles define their final performance. In particular, multifunctional microgels with complex architectures have been widely used in multiplex assays for their favourable capability to accommodate encoding systems and anchoring groups for probes to capture circulating targets by simply changing synthesis parameters. In this work a limited set of fluorescent encoded poly(ethyleneglycol) based microgels, of size ranging between 0.5 and 1.3 µm, with a core − shell architecture were obtained by combining precipitation and seeded polymerizations. Here we demonstrate the possibility of tailoring and controlling the bulk and surface properties according to the synthesis by fluorescence imaging and pH titrations. Concerning the structural characterization, we adopted a method to calculate polymer fraction volumes from AFM images and combined these with equilibrium swelling theory (Peppas–Merrill equation) to determine the mesh size of the microgels. Surface composition was probed by X‐ray photoelectron spectroscopy directly on freeze‐dried microgels. In such a way we were able to describe the organizations of the different adlayers also in response to pH, highlighting the possibility of some overlap of the adlayers representing physical barriers at the boundaries of each shell. © 2016 Society of Chemical Industry
Improving the photovoltaic performance of co‐evaporated Cu2ZnSnS4 thin‐film solar cells by incorporation of sodium from NaF layers
Authors: Mise Takahiro , Tajima Shin , Fukano Tatsuo , Higuchi Kazuo , Washio Tsukasa , Jimbo Kazuo , Katagiri Hironori
Published: January 2016

We have investigated the influence of sodium (Na) on the properties of co‐evaporated Cu2ZnSnS4 (CZTS) layer microstructures and solar cells. The photovoltaic performance and diode properties were improved by incorporating Na from NaF layers into the CZTS layers, while Na had a negligible effect on the microstructural properties of the layer. The best cell fabricated by using an optimal CZTS layer (Cu/(Zn + Sn) = 0.70, Zn/Sn = 1.8) yielded an active area efficiency of 5.23%. The analysis of device properties suggests that charge‐carrier recombination at CZTS/CdS interface is suppressed by intentional Na incorporation from NaF layers. Copyright © 2016 John Wiley & Sons, Ltd.
Establishment of polyethylene‐glycol‐mediated protoplast transformation for Lecanicillium lecanii and development of virulence‐enhanced strains against Aphis gossypii
Authors: Zhang Yan‐Jun , Xie Ming , Zhang Xiao‐Lin , Peng De‐Liang , Yu Wen‐Bin , Li Qiang , Li Qian , Zhao Jin‐Jin , Zhang Zhao‐Rong
Published: January 2016

BACKGROUND

Lecanicillium lecanii has been developed as a biopesticide and used in biological control of several agricultural insects. To improve fungal virulence, an optimised polyethylene glycol (PEG)‐mediated protoplast transformation system was established for L. lecanii. Pr1A‐like cuticle‐degrading protease gene (Cdep1) from Beauveria bassiana was transferred into L. lecanii, and its resulting activity against Aphis gossypii was assessed.

RESULTS

The optimised protoplast generation yielded 2.5 × 108 protoplasts g−1 wet mycelium of fungi, and gave nearly 98% viability and 80% regeneration on plates. Protease activities were increased about fivefold in transformants expressing CDEP1. The median lethal concentration (LC50) for transformants expressing CDEP1 was twofold lower than that for the wild type (WT). The median survival time (LT50) for transformants expressing CDEP1 was also 14.2% shorter than that for WT, though no significant difference. There were no significant differences in conidial germination as colony growth and conidial yield on plates between transformants expressing CDEP1 and WT. The transformants expressing CDEP1 grew significantly quicker than WT in insects. The transformants expressing CDEP1 were lower in conidial yields on insect cadavers, but insignificantly different from WT.

CONCLUSION

The PEG‐mediated protoplast transformation system was effective for L. lecanii, and the expression of CDEP1 significantly enhanced fungal virulence against cotton aphids. © 2016 Society of Chemical Industry
Al‐, Ga‐, and In‐doped ZnO thin films via aerosol assisted CVD for use as transparent conducting oxides
Authors: Potter Dominic B. , Bhachu Davinder S. , Powell Michael J. , Darr Jawwad A. , Parkin Ivan P. , Carmalt Claire J.
Published: January 2016

Al‐, Ga‐, and In‐doped ZnO thin films were deposited on glass substrates by aerosol assisted chemical vapour deposition (AACVD) at a deposition temperature of 450 °C. The air‐stable compound zinc acetylacetonate [Zn(acac)2] was used as a Zn source, whilst for the dopants of Al, Ga and In, the corresponding trichloride was used. Methanol solutions of the metal salts were used as precursor solutions and N2 carrier gas was used for the aerosol. Films were grown in approximately 30 min and were synthesised using dopant values of 5, 10, 15 and 20 mol.% (with respect to the Zn) in the precursor solution. XRD analysis showed that the films were wurtzite ZnO. XPS analysis confirmed the presence of the dopants in the films. Several of the films showed high transparency (>80%) in the visible range, and low resistivity (∼10−3 Ω cm).
Effects of Silymarin, Glycyrrhizin, and Oxymatrine on the Pharmacokinetics of Ribavirin and Its Major Metabolite in Rats
Authors: Liao Sha , Jin Xueyuan , Li Jinglai , Zhang Tianhong , Zhang Wenpeng , Shi Weiguo , Fan Shiyong , Wang Xiaoying , Wang Juan , Zhong Bohua , Zhang Zhenqing
Published: January 2016

The herb‐derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral (PO) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, PO), glycyrrhizin (15 mg/kg, intraperitoneal [IP]), or oxymatrine (60 mg/kg, PO). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration‐time curve (AUC0–t) and the peak plasma concentration (Cmax) of ribavirin and ribavirin base by 31.2–44.5% and 48.9–50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0–t of both ribavirin and its metabolite by 35.3–37.6% and 38.6–39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and Cmax. Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine. Copyright © 2016 John Wiley & Sons, Ltd.
Empirical study and prediction of liquids retention on structured polymer surfaces
Authors: Chiou Chung‐Han , Hsieh Sheng‐Jen
Published: January 2016

Liquids' contact angle hysteresis and critical retention volumes on five commonly used plastics with surface structures were studied. The chevron‐like groove structures, which are orthogonally arranged, make the liquid–solid contact line elongated while the droplet found staying in the Wenzel state. Various dimensions of surface structures were represented by contact length ratio σ. Advancing and receding contact angles of liquids on polymer surfaces with various conditions were reported. Reduced hysteresis H, which links between advancing and receding contact angles, was also studied and found to extend its availability on structured surfaces. The research found that surface structures have linear effects on liquids' advancing contact angles in the range of σ = 1.0 to 1.42. Linear regression analysis was hence proposed to predict advancing contact angles, and the results indicate that approximate 80% of data points have less than 6% error. An empirical model, which adopts liquid–solid surface tension as the source of liquids' retention force, was proposed to estimate liquids' critical retention volumes on inclined surfaces. The proposed model found good agreements with existing experiment data and demonstrated its superiority over previous ones. The present model provides an approach to predict liquids' storage/repellency on structured surfaces when the advancing contact angles are predictable. Copyright © 2016 John Wiley & Sons, Ltd.
The Orientations of Large Aspect‐Ratio Coiled‐Coil Proteins Attached to Gold Nanostructures
Authors: Chang Jae‐Byum , Kim Yong Ho , Thompson Evan , No Young Hyun , Kim Nam Hyeong , Arrieta Jose , Manfrinato Vitor R. , Keating Amy E. , Berggren Karl K.
Published: January 2016

Methods for patterning biomolecules on a substrate at the single molecule level have been studied as a route to sensors with single‐molecular sensitivity or as a way to probe biological phenomena at the single‐molecule level. However, the arrangement and orientation of single biomolecules on substrates has been less investigated. Here, the arrangement and orientation of two rod‐like coiled‐coil proteins, cortexillin and tropomyosin, around patterned gold nanostructures is examined. The high aspect ratio of the coiled coils makes it possible to study their orientations and to pursue a strategy of protein orientation via two‐point attachment. The proteins are anchored to the surfaces using thiol groups, and the number of cysteine residues in tropomyosin is varied to test how this variation affects the structure and arrangement of the surface‐attached proteins. Molecular dynamics studies are used to interpret the observed positional distributions. Based on initial studies of protein attachment to gold post structures, two 31‐nm‐long tropomyosin molecules are aligned between the two sidewalls of a trench with a width of 68 nm. Because the approach presented in this study uses one of twenty natural amino acids, this method provides a convenient way to pattern biomolecules on substrates using standard chemistry.
Hierarchical MoS2 Nanosheet@TiO2 Nanotube Array Composites with Enhanced Photocatalytic and Photocurrent Performances
Authors: Zheng Lingxia , Han Sancan , Liu Hui , Yu Pingping , Fang Xiaosheng
Published: January 2016

A novel type of hierarchical nanocomposites consisted of MoS2 nanosheet coating on the self‐ordered TiO2 nanotube arrays is successfully prepared by a facile combination of anodization and hydrothermal methods. The MoS2 nanosheets are uniformly decorated on the tube top surface and the intertubular voids with film appearance changing from brown to black color. Anatase TiO2 nanotube arrays (NTAs) with clean top surfaces and the appropriate amount of MoS2 precursors are key to the growth of perfect compositing TiO2@MoS2 hybrids with significantly enhanced photocatalytic activity and photocurrent response. These results reveal that the strategy provides a flexible and straightforward route for design and preparation nanocomposites based on functional semiconducting nanostructures with 1D self‐ordered TiO2 NTAs, promising for new opportunities in energy/environment applications, including photocatalysts and other photovoltaic devices.