pinecone/core-2020-05-10-deduplication huggingface dataset:
On the formulation of snow thermal conductivity in large-scale sea ice models

An assessment of the performance of a state-of-the-art large-scale coupled sea ice - ocean model, including a new snow multilayer thermodynamic scheme, is performed. Four 29-years-long simulations are compared against each other and against sea ice thickness and extent observations. Each simulation uses a separate parameterization for snow thermo-physical properties. The first simulation uses a constant thermal conductivity and prescribed density profiles. The second and third parameterizations use typical power-law relationships linking thermal conductivity directly to density (prescribed as in the first simulation). The fourth parameterization is newly developed and consists of a set of two linear equations relating the snow thermal conductivity and density to the mean seasonal wind speed. Results show that simulation 1 leads to a significant overestimation of the sea ice thickness due to overestimated thermal conductivity, particularly in the Northern Hemisphere. Parameterizations 2 and 4 lead to a realistic simulation of the Arctic sea ice mean state. Simulation 3 results in the underestimation of the sea ice basal growth in both hemispheres, but is partly compensated by lateral growth and snow ice formation in the Southern Hemisphere. Finally, parameterization 4 improves the simulated snow depth distributions by including snow packing by wind, and shows potential for being used in future works. The intercomparison of all simulations suggests that the sea ice model is more sensitive to the snow representation in the Arctic than it is in the Southern Ocean, where the sea ice thickness is not driven by temperature profiles in the snow
The climate time scale in the approach to radiative-convective equilibrium

In this paper, we discuss the importance of the surface boundary condition (fixed versus interactive surface temperature) for the long time scale of approach to Radiative-Convective Equilibrium (RCE). Using a simple linearized two-variable model for surface-atmosphere interaction, we derive an analytic expression for τ[subscript C], a long climate relaxation time scale that remains well defined and much longer than either mixing time scale of Tompkins and Craig (1998b), even in the limit that the heat capacity of the surface vanishes. We show that the size of τ[subscript C] is an intrinsic property of the coupling between the atmosphere and surface, and not a result of the thermal inertia of the surface alone. When the surface heat capacity is low, τ[subscript C] can be several times longer than expected, due to the effects of moisture on the effective heat capacity of the atmosphere. We also show that the theoretical expression for τ[subscript C] is a good predictor of best fit exponential relaxation time scales in a single-column model with full physics, across a range of surface temperatures and surface heat capacities.National Science Foundation (U.S.) (Grant 1136480
Funding Data from Publication Acknowledgements: Coverage, Uses and
  Limitations

This article contributes to the development of methods for analysing research
funding systems by exploring the robustness and comparability of emerging
approaches to generate funding landscapes useful for policy making. We use a
novel dataset of manually extracted and coded data on the funding
acknowledgements of 7,510 publications representing UK cancer research in the
year 2011 and compare these 'reference data' with funding data provided by Web
of Science (WoS) and MEDLINE/PubMed. Findings show high recall (about 93%) of
WoS funding data. By contrast, MEDLINE/PubMed data retrieved less than half of
the UK cancer publications acknowledging at least one funder. Conversely, both
databases have high precision (+90%): i.e. few cases of publications with no
acknowledgement to funders are identified as having funding data. Nonetheless,
funders acknowledged in UK cancer publications were not correctly listed by
MEDLINE/PubMed and WoS in about 75% and 32% of the cases, respectively.
'Reference data' on the UK cancer research funding system are then used as a
case-study to demonstrate the utility of funding data for strategic
intelligence applications (e.g. mapping of funding landscape, comparison of
funders' research portfolios).Comment: in press, Journal of the Association for Information Science and
  Technology 201
Long-term exposure to bis(2-ethylhexyl)phthalate (DEHP) inhibits growth of guppy fish (Poecilia reticulata)

Bis(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer that is a commonly found contaminant of aquatic environments. However, little is known about the long-term effects of DEHP on fish development, as previous studies yielded conflicting results and mostly investigated the effects of concentrations higher than those found in natural habitats. We thus aimed to investigate the effects of DHEP (i) at concentrations present in the environment, and (ii) under conditions that might accentuate any deleterious consequences (larvae rather than adult fish, use of higher temperature). Different concentrations of DEHP (0.1-10 microg l(-1)rpar; applied continuously for 91 days were tested on guppy fish that were less than one week old at the beginning of the treatment. As early as 14 days after the start of exposure, guppies treated with 10 microg l(-1) DEHP showed significantly reduced body length as compared with control fish. The inhibitory effect of DEHP was concentration-dependent and increased with time, leading to a maximal reduction in body length of 15 and 40% at 1 and 10 microg l(-1) DEHP, respectively. The effect was even more pronounced for body weight, which was diminished by up to 40 and 70% at 1 and 10 microg l(-1) DEHP, respectively. The reduction in growth was still significant at 91 days of DEHP treatment, whereas the Fulton's condition factor was unaffected. While DEHP significantly blocked growth in both male and female guppies, no shift in the sexual development was observed. These data show that DEHP, at concentrations present in aquatic environments, can profoundly affect development in fish. Copyright (c) 2009 John Wiley & Sons, Ltd
Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

To better assess biomonitoring data in workers exposed to captan and folpet, the kinetics of ring metabolites [tetrahydrophthalimide (THPI), phthalimide (PI) and phthalic acid] were determined in urine and plasma of dermally exposed volunteers. A 10  mg kg(-1) dose of each fungicide was applied on 80  cm(2) of the forearm and left without occlusion or washing for 24  h. Blood samples were withdrawn at fixed time periods over the 72  h following application and complete urine voids were collected over 96  h post-dosing, for metabolite analysis. In the hours following treatment, a progressive increase in plasma levels of THPI and PI was observed, with peak levels being reached at 24  h for THPI and 10  h for PI. The ensuing elimination phase appeared monophasic with a mean elimination half-life (t(½) ) of 24.7 and 29.7 h for THPI and PI, respectively. In urine, time courses PI and phthalic acid excretion rate rapidly evolved in parallel, and a mean elimination t(½) of 28.8 and 29.6  h, respectively, was calculated from these curves. THPI was eliminated slightly faster, with a mean t(½) of 18.7  h. Over the 96  h period post-application, metabolites were almost completely excreted, and on average 0.02% of captan dose was recovered in urine as THPI while 1.8% of the folpet dose was excreted as phthalic acid and 0.002% as PI, suggesting a low dermal absorption fraction for both fungicides. This study showed the potential use of THPI, PI and phthalic acid as key biomarkers of exposure to captan and folpet
Toxicokinetic modeling of folpet fungicide and its ring-biomarkers of exposure in humans.

A human in vivo toxicokinetic model was built to allow a better understanding of the toxicokinetics of folpet fungicide and its key ring biomarkers of exposure: phthalimide (PI), phthalamic acid (PAA) and phthalic acid (PA). Both PI and the sum of ring metabolites, expressed as PA equivalents (PAeq), may be used as biomarkers of exposure. The conceptual representation of the model was based on the analysis of the time course of these biomarkers in volunteers orally and dermally exposed to folpet. In the model, compartments were also used to represent the body burden of folpet and experimentally relevant PI, PAA and PA ring metabolites in blood and in key tissues as well as in excreta, hence urinary and feces. The time evolution of these biomarkers in each compartment of the model was then mathematically described by a system of coupled differential equations. The mathematical parameters of the model were then determined from best fits to the time courses of PI and PAeq in blood and urine of five volunteers administered orally 1 mg kg(-1) and dermally 10 mg kg(-1) of folpet. In the case of oral administration, the mean elimination half-life of PI from blood (through feces, urine or metabolism) was found to be 39.9 h as compared with 28.0 h for PAeq. In the case of a dermal application, mean elimination half-life of PI and PAeq was estimated to be 34.3 and 29.3 h, respectively. The average final fractions of administered dose recovered in urine as PI over the 0-96 h period were 0.030 and 0.002%, for oral and dermal exposure, respectively. Corresponding values for PAeq were 24.5 and 1.83%, respectively. Finally, the average clearance rate of PI from blood calculated from the oral and dermal data was 0.09 ± 0.03 and 0.13 ± 0.05 ml h(-1) while the volume of distribution was 4.30 ± 1.12 and 6.05 ± 2.22 l, respectively. It was not possible to obtain the corresponding values from PAeq data owing to the lack of blood time course data
Proteomic profiling of halloysite clay nanotube exposure in intestinal cell co-culture

Halloysite is aluminosilicate clay with a hollow tubular structure with nanoscale internal and external diameters. Assessment of halloysite biocompatibility has gained importance in view of its potential application in oral drug delivery. To investigate the effect of halloysite nanotubes on an in vitro model of the large intestine, Caco-2/HT29-MTX cells in monolayer co-culture were exposed to nanotubes for toxicity tests and proteomic analysis. Results indicate that halloysite exhibits a high degree of biocompatibility characterized by an absence of cytotoxicity, in spite of elevated pro-inflammatory cytokine release. Exposure-specific changes in expression were observed among 4081 proteins analyzed. Bioinformatic analysis of differentially expressed protein profiles suggest that halloysite stimulates processes related to cell growth and proliferation, subtle responses to cell infection, irritation and injury, enhanced antioxidant capability, and an overall adaptive response to exposure. These potentially relevant functional effects warrant further investigation in in vivo models and suggest that chronic or bolus occupational exposure to halloysite nanotubes may have unintended outcomes
Effects of Asian sand dust particles on the respiratory and immune system.

Epidemiologic studies have reported that Asian sand dust (ASD) particles can affect respiratory health; however, the mechanisms remain unclear. We investigated the effects of ASD on airway epithelial cells and immune cells, and their contributing factors to the effects. Human airway epithelial cells were exposed to ASD collected on 1-3 May (ASD1) and on 12-14 May (ASD2) 2011 in Japan and heat-treated ASD1 for excluding heat-sensitive substances (H-ASD) at a concentration of 0, 3, 30 or 90 µg ml(-1) for 4 or 24 h. Furthermore, bone marrow-derived dendritic cells (BMDC) from atopic prone mice were differentiated by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) then these BMDC were exposed to the ASD for 24 h. Also splenocytes as mixture of immune cells were exposed to the ASD for 72 h. All ASD dose dependently reduced viability of airway epithelial cells. Non-heated ASD showed a dose-dependent increase in the protein release of interleukin (IL)-6 and IL-8. The raises induced by ASD1 were higher than those by ASD2. ASD1 and ASD2 also elevated ICAM-1 at the levels of mRNA, cell surface protein and soluble protein in culture medium. In contrast, H-ASD did not change most of these biomarkers. Non-heated ASD showed enhancement in the protein expression of DEC205 on BMDC and in the proliferation of splenocytes, whereas H-ASD did not. These results suggest that ASD affect airway epithelial cells and immune cells such as BMDC and splenocytes. Moreover, the difference in ASD events and components adhered to ASD can contribute to the health effects
Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines

In the present study, we investigated the possible combined anticancer ability of bee venom (BV) and cisplatin towards two pairs of tumour cell lines: parental cervical carcinoma HeLa cells and their cisplatin-resistant HeLa CK subline, as well as laryngeal carcinoma HEp-2 cells and their cisplatin-resistant CK2 subline. Additionally, we identified several peptides of BV in the BV sample used in the course of the study and determined the exact concentration of MEL. BV applied alone in concentrations of 30 to 60 μg ml-1 displayed dose-dependent cytotoxicity against all cell lines tested. Cisplatin-resistant cervical carcinoma cells were more sensitive to BV than their parental cell lines (IC50 values were 52.50 μg ml-1 for HeLa vs. 47.64 μg ml-1 for HeLa CK cells), whereas opposite results were obtained for cisplatin-resistant laryngeal carcinoma cells (IC50 values were 51.98 μg ml-1 for HEp-2 vs. &gt; 60.00 μg ml-1 for CK2 cells). Treatment with BV alone induced a necrotic type of cell death, as shown by characteristic morphological features, fast staining with ethidium-bromide and a lack of cleavage of apoptotic marker poly (ADP-ribose) polymerase (PARP) on Western blot. Combined treatment of BV and cisplatin induced an additive and/or weak synergistic effect towards tested cell lines, suggesting that BV could enhance the killing effect of selected cells when combined with cisplatin. Therefore, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. Our results suggest that combined treatment with BV could be useful from the point of minimizing the cisplatin concentration during chemotherapy, consequently reducing and/or postponing the development of cisplatin resistance
Further studies toward a mouse model for biochemical assessment of neuropathic potential of organophosphorus compounds

Inhibition and aging of neuropathy target esterase (NTE) by neuropathic organophosphorus (OP) compounds triggers OP compound‐induced delayed neuropathy (OPIDN), whereas inhibition of acetylcholinesterase (AChE) produces cholinergic toxicity. The neuropathic potential of an OP compound is defined by its relative inhibitory potency toward NTE vs. AChE assessed by enzyme assays following dosing  in vivo  or after incubations of direct‐acting compounds or active metabolites with enzymes  in vitro . The standard animal model of OPIDN is the adult hen, but its large size and high husbandry costs make this species a burdensome model for assessing neuropathic potential. Although the mouse does not readily exhibit clinical signs of OPIDN, it displays axonal lesions and expresses brain AChE and NTE. Therefore, the present research was performed as a further test of the hypothesis that inhibition of mouse brain AChE and NTE could be used to assess neuropathic potential using mouse brain preparations  in vitro  or employing mouse brain assays following dosing of OP compounds  in vivo . Excellent correlations were obtained for inhibition kinetics  in vitro  of mouse brain enzymes vs. hen brain and human recombinant enzymes. Furthermore, inhibition of mouse brain AChE and NTE after dosing with OP compounds afforded ED 50  ratios that agreed with relative inhibitory potencies assessed  in vitro . Taken together, results with mouse brain enzymes demonstrated consistent correspondence between  in vitro  and  in vivo  predictors of neuropathic potential, thus adding to previous studies supporting the validity of a mouse model for biochemical assessment of the ability of OP compounds to produce OPIDN. Copyright © 2014 John Wiley & Sons, Ltd.    Although the mouse does not readily exhibit clinical signs of organophosphorus compound‐induced delayed neurotoxicity (OPIDN), it displays axonal lesions and expresses brain acetylcholinesterase (AChE) and neuropathy target esterase (NTE). The present research was performed as a further test of the hypothesis that inhibition of mouse brain AChE and NTE could be used to assess OPIDN potential using mouse brain preparations  in vitro  or employing mouse brain assays following dosing of OP compounds  in vivo . Our results support this hypothesis
Impact of acute arsenic and cadmium exposure on the expression of two haeme oxygenase genes and other antioxidant markers in common carp (Cyprinus carpio)

The aim was to study the effects of cadmium (Cd) and arsenic (As) on haeme oxygenases (HOs) and other oxidative stress biomarkers, and their roles in macromolecule damage in liver and kidney of common carp (Cyprinus carpio L.). HOs play a critical role in the defence system against oxidative damage, producing biliverdin and carbon monoxide with important free radical scavenging properties. However, increased HO activity in haeme degradation may also lead to a pro-oxidant effect through the liberation of Fe-modifying Cd and As toxicity. The response of an organism to exposure to toxic metals is in many cases brought about by changes at the level of gene expression. In this study, the genes ho-1 and ho-2 of the common carp were identified, and the changes in gene expressions were analysed from the aspect of Cd and As accumulation. Both ho-1 and ho-2 are transcriptionally induced by Cd and As, but their inductions differ in time course, dose response and tissue specificity. The expression of ho1 was mostly affected by As, primarily in the liver (45-fold), whereas it was enhanced with higher efficacy by Cd in the kidney (25-fold). The cellular redox status and the damage of lipid molecules were monitored via the ratio of reduced to oxidized glutathione, the levels of H2O2 and lipid peroxidation, and the activities of superoxide dismutase (SOD) and catalase (CAT). © 2014 John Wiley & Sons, Ltd
Are zebrafish larvae suitable for assessing the hepatotoxicity potential of drug candidates?

Drug-induced liver injury (DILI) is poorly predicted by single-cell-based assays, probably because of the lack of physiological interactions with other cells within the liver. An intact whole liver system such as one present in zebrafish larvae could provide added value in a screening strategy for DILI; however, the possible occurrence of other organ toxicities and the immature larval stage of the zebrafish might complicate accurate and fast analysis. We investigated whether expression analysis of liver-specific fatty acid binding protein 10a (lfabp10a) was an appropriate endpoint for assessing hepatotoxic effects in zebrafish larvae. It was found that expression analysis of lfabp10a was a valid marker, as after treatment with hepatotoxicants, dose-response curves could be obtained and statistically significant abnormal lfabp10 expression levels correlated with hepatocellular histopathological changes in the liver. However, toxicity in other vital organs such as the heart could impact liver outgrowth and thus had to be assessed concurrently. Whether zebrafish larvae were suitable for assessing human relevant drug-induced hepatotoxicity was assessed with hepatotoxicants and non-hepatotoxicants that have been marketed for human use and classified according to their mechanism of toxicity. The zebrafish larva showed promising predictivity towards a number of mechanisms and was capable of distinguishing between hepatotoxic and non-hepatotoxic chemical analogues, thus implying its applicability as a potential screening model for DILI. Copyright © 2015 John Wiley & Sons, Ltd.status: publishe
Toxicity of cobalt-chromium nanoparticles released from a resurfacing hip implant and cobalt ions on primary human lymphocytes in vitro

Adverse tissue responses to prostheses wear particles and released ions are important contributors to hip implant failure. In implant-related adverse reactions T-lymphocytes play a prominent role in sustaining the chronic inflammatory response. To further understand the involvement of lymphocytes in metal-on-metal (MoM) implant failure, primary human lymphocytes were isolated and treated with CoCr wear debris and Co ions, individually, and in combination, for 24, 48, and 120h. There was a significant increase in cell number where debris was present, as measured by the Neutral Red assay. Interleukin 6 (IL-6), interferon γ (IFNγ), and tumour necrosis factor α (TNFα) secretion levels significantly decreased in the presence of metal particles, as measured by ELISA. Interleukin 2 (IL-2) secretion levels were significantly decreased by both debris and Co ions. Flow cytometry analysis showed that the metal nanoparticles induced a significant increase in apoptosis after 48h exposure. This investigation showed that prolonged exposure (120h) to metal debris induces lymphocyte proliferation, suggesting that activation of resting lymphocytes may have occurred. Although cytokine production was affected mainly by metal debris, cobalt toxicity may also modulate IL-2 secretion, and even Co ion concentrations below the MHRA guideline levels (7ppb) may contribute to the impairment of immune regulation in vivo in patients with MoM implants
Adverse Outcome Pathways can drive non-animal approaches for safety assessment.

Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits