bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing the 3Rs in regulatory ecotoxicology: A pragmatic cross-sector approach
Authors: Burden Natalie , Benstead Rachel , Clook Mark , Doyle Ian , Edwards Peter , Maynard Samuel K , Ryder Kathryn , Sheahan Dave , Whale Graham , van Egmond Roger , Wheeler James R , Hutchinson Thomas H 
Published: October 2015

Abstract
The ecotoxicity testing of chemicals for prospective environmental safety assessment is an area in which a high number of vertebrates are used across a variety of industry sectors. Refining, reducing, and replacing the use of animals such as fish, birds, and amphibians for this purpose addresses the ethical concerns and the increasing legislative requirements to consider alternative test methods. Members of the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group, consisting of representatives from academia, government organizations, and industry, have worked together over the past 6 y to provide evidence bases to support and advance the application of the 3Rs in regulatory ecotoxicity testing. The group recently held a workshop to identify the areas of testing, demands, and drivers that will have an impact on the future of animal use in regulatory ecotoxicology. As a result of these discussions, we have developed a pragmatic approach to prioritize and realistically address key opportunity areas, to enable progress toward the vision of a reduced reliance on the use of animals in this area of testing. This paper summarizes the findings of this exercise and proposes a pragmatic strategy toward our key long-term goals—the incorporation of reliable alternatives to whole-organism testing into regulations and guidance, and a culture shift toward reduced reliance on vertebrate toxicity testing in routine environmental safety assessment. Integr Environ Assess Manag 2016;12:417–421. © 2015 SETAC
Key Points
There is much scope to advance the application of the 3Rs (replacement, refinement, and reduction in the use of animals) in regulatory ecotoxicity testing. A working group of experts in this field across academia, government organizations, and industry have identified the key drivers in which there are high demands on vertebrate testing, and have explored opportunities to address them. The group proposes a pragmatic strategy whereby key short-, medium-, and long-term goals could be achieved to enable realistic progress in advancing the application of the 3Rs in this area. This evaluation will help to inform the development of high-impact projects that facilitate the uptake of novel 3Rs approaches relevant to regulatory ecotoxicology.
Biodistribution and toxicity of spherical aluminum oxide nanoparticles
Authors: Park Eun‐Jung , Lee Gwang‐Hee , Yoon Cheolho , Jeong Uiseok , Kim Younghun , Cho Myung‐Haing , Kim Dong‐Wan 
Published: October 2015

AbstractWith the rapid development of the nano‐industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ‐aluminum oxide hydroxide nanoparticles (γ‐AlOHNPs), γ‐ and α‐AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ‐AlONPs, followed by the α‐AlONPs and γ‐AlOHNPs. In mice, γ‐AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)‐8 were observed in the blood of mice dosed with γ‐AlOHNPs (10 mg kg−1). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS‐2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK‐293 (kidney). The results showed γ‐AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ‐AlOHNPs, but not γ‐AlONPs or α‐AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ‐AlOHNPs compared with γ‐AlONPs and α‐AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs. Copyright © 2015 John Wiley & Sons, Ltd.
Prediction of Drug Clearance in Premature and Mature Neonates, Infants, and Children ≤2 Years of Age: A Comparison of the Predictive Performance of 4 Allometric Models
Authors: Mahmood Iftekhar 
Published: October 2015

AbstractThe objective of this study was to evaluate the predictive performance of 4 allometric models to predict clearance in pediatric ages ranging from premature neonates to children ≤2 years of age. Four allometric models were used to predict clearances of 28 drugs in children from preterm neonates to 2 years of age (n = 564). The 4 models are (1) basal metabolic rate–dependent model; (2) age‐dependent exponent model; (3) an allometric model based on kidney and liver weights as well as kidney and liver blood flow; and (4) an allometric model based on a fixed exponent of 0.75. The predictive performance of these models was evaluated by comparing the predicted clearance of the studied drugs with the observed clearance in an individual child. The results of the study indicated that the 3 new proposed models predicted the mean clearance of the drugs with reasonable accuracy (≤50% prediction error). On the other hand, the exponent of 0.75 produced substantial prediction error. Predicted individual clearance values were ≥50% in approximately 30% of the children by the proposed 3 methods and 73% by exponent 0.75. The 3 new proposed allometric models can predict mean clearances of drugs in children from premature neonates to ≤2 years of age with reasonable accuracy and are of practical value during pediatric drug development.
Perceived social impact, social worth, and job performance: Mediation by motivation
Authors: Castanheira Filipa 
Published: October 2015

SummaryThis study was designed to test the relationship between perceived social impact, social worth, supervisor‐rated job performance (1 month later), and mediating effects by commitment to customers and work engagement. The hypotheses were tested with structural equation modeling analysis in a field study with 370 customer‐service employees from bank, retail, and sales positions. Results confirm that perceived social impact is associated with better job performance and that this relationship is mediated by work engagement. Furthermore, results support a second mediating mechanism in which perceived social impact and social worth are associated with engagement through affective commitment to customers. Finally, it was found that engaged employees are rated as better performers by supervisors 1 month later. This study supports the motivational approach to performance and highlights the role that interactions with customers may play in motivating service employees. Practical implications are discussed by highlighting the need to consider the social dynamics in service contexts. Copyright © 2015 John Wiley & Sons, Ltd.
In vitro screening of natural feed additives from crustaceans, diatoms, seaweeds and plant extracts to manipulate rumen fermentation
Authors: Belanche Alejandro , Ramos‐Morales Eva , Newbold C Jamie 
Published: October 2015

AbstractBACKGROUNDEight natural products from animal, unicellular algae, brown seaweed and plant origins were chosen according to their theoretical antimicrobial activity: Diatomaceous earths (DE), insoluble chitosan (ICHI), soluble chitosan (CHI), seaweed meal (SWM), Ascophyllum nodosum (ASC), Laminaria digitata (LAM), neem oil (NOIL) and an ivy fruit extract rich in saponins (IVY). Dose–response incubations were conducted to determine their effect on rumen fermentation pattern and gas production, while their anti‐protozoal activity was tested using 14C‐labelled bacteria.RESULTSDE, SWM, NOIL and ICHI had very small effects on rumen function when used at inclusion rate up to 2 g L−1. ASC had anti‐protozoal effects (up to −23%) promoting a decrease in gas production and methanogenesis (−15%). LAM increased VFA production (+7%) and shifted from butyrate to acetate. CHI also shifted fermentation towards propionate production and lower methane (−23%) and protozoal activity (−56%). IVY decreased protozoal activity (−39%) and ammonia concentration (−56%), as well as increased feed fermentation (+11% VFA concentration) and shifted from acetate to propionate production.CONCLUSIONSASC, LAM, CHI and IVY showed promising potential in vitro as feed additives to improve rumen function, thus more research is needed to investigate their mode of action in the rumen microbial ecosystem. © 2015 Society of Chemical Industry
Long‐term intake of white tea prevents oxidative damage caused by adriamycin in kidney of rats
Authors: Espinosa Cristóbal , López‐Jiménez José A , Pérez‐Llamas Francisca , Guardiola Francisco A , Esteban Maria A , Arnao Marino B , Zamora Salvador 
Published: October 2015

AbstractBACKGROUNDWhite tea infusion (Camelia sinensis) has antioxidants properties. The infusion contains polyphenols that have been proposed to induce antioxidant response element (ARE) response via nuclear factor E2‐related factor 2 (NRF2). Adriamycin (ADR) has antitumour properties and oxidative effects. Oxidative stress is related to a variety of kidney diseases. Prevention of the oxidative stress through long‐term intake of white tea and the study of the molecular mechanisms involved in protection could be of great interest. Rats were given distilled water, 0.015 or 0.045 g of solid white tea extract kg−1 body weight for 12 months. Animals received an injection of ADR. In kidney, oxidative stress parameters were measured, the expressions of nuclear factor E2‐related factor 2 gene (Nrf2), and detoxifying and antioxidants genes were analysed, and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) were measured.RESULTSADR administration increased oxidative parameters and decreased the antioxidant activity; significantly increased the expression of analysed genes and the activity of CAT and SOD and decreased GR activity. The highest white tea dose protected redox status and inhibited ARE response.CONCLUSIONLong‐term intake of white tea protected kidney against the oxidative stress. ADR activated the ARE response but in animals treated with the highest dose of white tea, this response was inhibited, probably for antioxidant protection. © 2015 Society of Chemical Industry
Mapping the potential beverage quality of coffee produced in the Zona da Mata, Minas Gerais, Brazil
Authors: Silva Samuel de Assis , de Queiroz Daniel Marçal , Ferreira Williams Pinto Marques , Corrêa Paulo Cesar , Rufino José Luis dos Santos 
Published: October 2015

AbstractBACKGROUNDDetailed knowledge of coffee production systems enables optimization of crop management, harvesting and post‐harvest techniques. In this study, coffee quality is mapped as a function of coffee variety, altitude and terrain aspect attributes. The work was performed in the Zona da Mata, Minas Gerais, Brazil.RESULTSA large range of coffee quality grades was observed for the Red Catuai variety. For the Yellow Catuai variety, no quality grades lower than 70 were observed. Regarding the terrain aspect, samples from the southeast‐facing slope (SEFS) and the northwest‐facing slope (NWFS) exhibited distinct behaviors. The SEFS samples had a greater range of quality grades than did the NWFS samples. The highest grade was obtained from an NWFS point. The lowest quality values and the largest range of grades were observed at lower altitudes. The extracts from the highest‐altitude samples did not produce any low‐quality coffee.CONCLUSIONSThe production site's position and altitude are the primary variables that influenced the coffee quality. The study area has micro‐regions with grades ranging from 80 to 94. These areas have the potential for producing specialty coffees. © 2015 Society of Chemical Industry
Nondestructive Quantification of Local Plasticizer Concentration in PVC by 1H NMR Relaxometry
Authors: Adams Alina , Kwamen Rance , Woldt Benjamin , Graß Michael 
Published: October 2015

The properties of plasticized poly(vinyl chloride) (PVC) , one of the most important polymers today, are strongly dictated by the concentration of plasticizer. Yet, it has been impossible to quantify this concentration at different positions inside a PVC product without its destruction because of a lack of suitable analytical methods. Thus, this paper introduces a simple, fast, and efficient way to determine truly nondestructively the concentration of plasticizer in PVC by single‐sided nuclear magnetic resonance (NMR). With the help of correlation curves between the concentration of plasticizer inside nonaged PVC samples and the corresponding volume‐averaged NMR parameters, single‐sided NMR allows the quantification of the local concentration of plasticizer in aged PVC plates at different depths by spatially resolved relaxation measurements. The presented approach represents a fundamental step toward in situ characterization of plasticized PVC.
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Poly(ADP‐ribosyl)ation is involved in pro‐survival autophagy in porcine blastocysts
Authors: Lee Hye Ran , Gupta Mukesh Kumar , Kim Duk Hyeon , Hwang Jeong Ho , Kwon Bumsup , Lee Hoon Taek 
Published: October 2015

SUMMARYPoly(ADP‐ribosyl)ation (PARylation) prevents apoptosis through its involvement in pro‐survival autophagy in cultured cells; whether or not the same is true for pre‐implantation embryos has not yet been documented. In this study, we investigated the participation of PARylation and autophagy in in vitro porcine pre‐implantation embryo development. The transcript levels of autophagy‐related genes and poly(ADP‐ribose) polymerase 1 (PARP1), an enzyme required for PARylation, were transiently up‐regulated by fertilization, decreased at the late 1‐cell stage, and maintained until the blastocyst stage. LC3, a marker of autophagosomes, and poly(ADP‐ribose) (PAR) polymer were present in all stages of pre‐implantation development. Exposure of embryos to 3‐methyladenine, an autophagy inhibitor, or 3‐aminobenzamide, a PARP inhibitor, suppressed the development of blastocysts. Pharmacological inhibition of PARylation further suppressed pro‐survival autophagy by decreasing the expression of autophagy‐related genes (ATG5, BECLIN1, and LC3) and decreasing LC3 protein abundance while increasing the rate of apoptosis in blastocysts. Deficiency in autophagy also induced abnormal accumulation of SQSTM1/p62 aggregates in porcine blastocysts. Collectively, these data suggest that PARylation is involved in selective autophagic degradation of ubiquitinated proteins, functioning in a pro‐survival role, in porcine in vitro‐produced embryos. These pro‐survival regulatory mechanisms may be important for the control of embryo quality. Mol. Reprod. Dev. 83: 37–49, 2016. © 2015 Wiley Periodicals, Inc.
Endoneurial edema in sural nerve may indicate recent onset inflammatory neuropathy
Authors: Üçeyler Nurcan , Necula Gina , Wagemann Esther , Toyka Klaus V. , Sommer Claudia 
Published: October 2015

ABSTRACTIntroduction: Sural nerve biopsy is an important means of establishing the diagnosis of inflammatory neuropathies. We investigated the diagnostic value of endoneurial edema. Methods: Diagnostic sural nerve biopsies from 42 patients with inflammatory and 28 patients with noninflammatory neuropathies were re‐evaluated for the presence of endoneurial edema. Edema was assessed on hematoxylin‐eosin stained paraffin and frozen sections and on azure II‐methylene blue stained semithin sections. We determined the area of endoneurial edema on digitized images in relation to the entire endoneurial area of each fascicle. Results: Edema was more extensive in neuropathies with short disease duration (≤12 months) as compared to long duration (>12 months; P < 0.01). Edema in inflammatory neuropathies of ≤12 months duration covered a larger area than in noninflammatory neuropathies (P < 0.01), and the extent of edema correlated negatively with disease duration (P < 0.05). Conclusions: Endoneurial edema may be a useful additional disease marker in inflammatory neuropathies of recent onset. Muscle Nerve 53: 705–710, 2016
Fish tissue lipid‐C:N relationships for correcting δ13C values and estimating lipid content in aquatic food‐web studies
Authors: Hoffman Joel C. , Sierszen Michael E. , Cotter Anne M. 
Published: October 2015

RationaleNormalizing δ13C values of animal tissue for lipid content is necessary to accurately interpret food‐web relationships from stable isotope analysis. To reduce the effort and expense associated with chemical extraction of lipids, various studies have tested arithmetic mass balance to mathematically normalize δ13C values for lipid content; however, the approach assumes that lipid content is related to the tissue C:N ratio.MethodsWe evaluated two commonly used models for estimating tissue lipid content based on C:N ratio (a mass balance model and a stoichiometric model) by comparing model predictions to measure the lipid content of white muscle tissue. We then determined the effect of lipid model choice on δ13C values normalized using arithmetic mass balance. To do so, we used a collection of fish from Lake Superior spanning a wide range in lipid content (5% to 73% lipid).ResultsWe found that the lipid content was positively related to the bulk muscle tissue C:N ratio. The two different lipid models produced similar estimates of lipid content based on tissue C:N, within 6% for tissue C:N values <7. Normalizing δ13C values using an arithmetic mass‐balance equation based on either model yielded similar results, with a small bias (<1‰) compared with results based on chemical extraction.ConclusionsAmong‐species consistency in the relationship between fish muscle tissue C:N ratio and lipid content supports the application of arithmetic mass balance to normalize δ13C values for lipid content. The uncertainty associated with both lipid extraction quality and choice of model parameters constrains the achievable precision of normalized δ13C values to about ±1.0‰. Published in 2015. This article is a U.S. Government work and is in the public domain in the U.S.A.
Prediction of coronary artery disease risk based on multiple longitudinal biomarkers
Authors: Yang Lili , Yu Menggang , Gao Sujuan 
Published: October 2015

In the last decade, few topics in the area of cardiovascular disease (CVD) research have received as much attention as risk prediction. One of the well‐documented risk factors for CVD is high blood pressure (BP). Traditional CVD risk prediction models consider BP levels measured at a single time and such models form the basis for current clinical guidelines for CVD prevention. However, in clinical practice, BP levels are often observed and recorded in a longitudinal fashion. Information on BP trajectories can be powerful predictors for CVD events. We consider joint modeling of time to coronary artery disease and individual longitudinal measures of systolic and diastolic BPs in a primary care cohort with up to 20 years of follow‐up. We applied novel prediction metrics to assess the predictive performance of joint models. Predictive performances of proposed joint models and other models were assessed via simulations and illustrated using the primary care cohort. Copyright © 2015 John Wiley & Sons, Ltd.
Zur Beschreibung fahrbahnunebenheitsinduzierter Radkraftschwankungen von Straßenfahrzeugen auf der Basis stochastischer Differentialgleichungen
Authors: Friedl Roland 
Published: October 2015

AbstractFahrbahnunebenheiten stellen neben Brems‐ und Anfahrvorgängen die wichtigste Ursache für Schwingbewegungen von Straßenfahrzeugen dar. Ausgehend von einer Beschreibung der Fahrzeuge auf der Basis so genannter Starrkörpermodelle wird ein effizientes Verfahren zur Ermittlung fahrbahnunebenheitsinduzierter Fahrzeugschwingungen sowie der daraus resultierenden Streuungen vertikaler Radkräfte präsentiert. Die mathematische Beschreibung der Fahrbahnunebenheiten erfolgt dabei als normalverteilte vektorielle Zufallsprozesse, welche die wesentlichen Charakteristika realer Unebenheitsverläufe im stochastischen Sinne widerspiegeln. Wie experimentelle Untersuchungen belegen, kommt dabei der Berücksichtigung der Korrelation zwischen den versetzt am Fahrzeug wirkenden Unebenheitsamplituden in den einzelnen Reifenaufstandspunkten eine besondere Bedeutung zu. Durch eine Darstellung der stochastischen Eigenschaften realer Unebenheitsverläufe über so genannte Formfilter sowie eine Erweiterung der zugrundeliegenden Zustandsgleichung, wird eine Beschreibung des dadurch induzierten Schwingungsverhaltens von Straßenfahrzeugen auf der Basis stochastischer Differentialgleichungen möglich. Die darauf begründete Kovarianzanalyse linearer Schwingungssysteme, welche für normalverteilte Erregerprozesse die vollständige Information des Antwortverhaltens repräsentiert, stellt eine effiziente Methode zur Berechnung von Zufallsschwingungen infolge mehrfachkorrelierter stochastischer Erregung dar.Statistical analysis of vehicle vibrations due to random road roughness using stochastic differential equations. The pavement roughness as the main source of low frequent vehicle oscillations leads to a significant variation in the vertical wheel forces. Describing the pavement roughness as a normally distributed stochastic process, an efficient method to quantify these variations in the vertical wheel forces based on simplified vehicle models is shown. As can be seen from experiments, a proper consideration of the correlation between the roughness amplitudes acting at the several wheels is essential. Applying the spectral factorization theorem the transformation matrix of a shaping filter, a synthetic system describing the stochastic characteristics of the roughness amplitudes, can be obtained. By establishing a state space model of the shaping filter and combining it with that of the vehicle to an augmented state space model, stochastic differential equations can be used to describe the vibrations of vehicles due to random surface roughness. The covariance matrix, which for zero mean and normally distributed system input contains the total information about the system’s response, can be calculated very efficiently based on the Lyapunov matrix equation.