Fant 778 publikasjoner. Viser side 16 av 33:
Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro—In Vivo Correlation
Data suitable for assembling a physiologically-based pharmacokinetic (PBPK) model for nanoparticles (NPs) remain relatively scarce. Therefore, there is a trend in extrapolating the results of in vitro and in silico studies to in vivo nanoparticle hazard and risk assessment. To evaluate the reliability of such approach, a pharmacokinetic study was performed using the same polyethylene glycol-coated gold nanoparticles (PEG-AuNPs) in vitro and in vivo. As in vitro models, human cell lines TH1, A549, Hep G2, and 16HBE were employed. The in vivo PEG-AuNP biodistribution was assessed in rats. The internalization and exclusion of PEG-AuNPs in vitro were modeled as first-order rate processes with the partition coefficient describing the equilibrium distribution. The pharmacokinetic parameters were obtained by fitting the model to the in vitro data and subsequently used for PBPK simulation in vivo. Notable differences were observed in the internalized amount of Au in individual cell lines compared to the corresponding tissues in vivo, with the highest found for renal TH1 cells and kidneys. The main reason for these discrepancies is the absence of natural barriers in the in vitro conditions. Therefore, caution should be exercised when extrapolating in vitro data to predict the in vivo NP burden and response to exposure.
MDPI
2022
Acquired drug resistance and metastasis in breast cancer (BC) are coupled with epigenetic deregulation of gene expression. Epigenetic drugs, aiming to reverse these aberrant transcriptional patterns and sensitize cancer cells to other therapies, provide a new treatment strategy for drug-resistant tumors. Here we investigated the ability of DNA methyltransferase (DNMT) inhibitor decitabine (DAC) to increase the sensitivity of BC cells to anthracycline antibiotic doxorubicin (DOX). Three cell lines representing different molecular BC subtypes, JIMT-1, MDA-MB-231 and T-47D, were used to evaluate the synergy of sequential DAC + DOX treatment in vitro. The cytotoxicity, genotoxicity, apoptosis, and migration capacity were tested in 2D and 3D cultures. Moreover, genome-wide DNA methylation and transcriptomic analyses were employed to understand the differences underlying DAC responsiveness. The ability of DAC to sensitize trastuzumab-resistant HER2-positive JIMT-1 cells to DOX was examined in vivo in an orthotopic xenograft mouse model. DAC and DOX synergistic effect was identified in all tested cell lines, with JIMT-1 cells being most sensitive to DAC. Based on the whole-genome data, we assume that the aggressive behavior of JIMT-1 cells can be related to the enrichment of epithelial-to-mesenchymal transition and stemness-associated pathways in this cell line. The four-week DAC + DOX sequential administration significantly reduced the tumor growth, DNMT1 expression, and global DNA methylation in xenograft tissues. The efficacy of combination therapy was comparable to effect of pegylated liposomal DOX, used exclusively for the treatment of metastatic BC. This work demonstrates the potential of epigenetic drugs to modulate cancer cells' sensitivity to other forms of anticancer therapy.
Elsevier
2022
The modified Target Diagram (MTD) was developed to evaluate the performance of low-cost sensors (LCS) for air quality monitoring in comparison with reference methods by reporting relative expanded uncertainty and its contributors. An MTD provides several pieces of information, including compliance with regulation, sources of error and how to diminish them, completeness and validity of LCS calibration etc. It allows the user to examine the effect of selecting different regression types and residual fitting on the LCS measurement uncertainty. The ordinary least squared regression with fitted residuals and dynamic between reference analyser uncertainty rather than constant ones yielded more realistic LCS measurement uncertainty compared to other options. The MTD is a fast visual tool to extract several pieces of information on evaluation of any candidate method against reference method.
Elsevier
2022
Royal Society of Chemistry (RSC)
2022
Machine learning-based stocks and flows modeling of road infrastructure
This paper introduces a new method to account for the stocks and flows of road infrastructure at the national level based on material flow accounting (MFA). The proposed method closes some of the current shortcomings in road infrastructures that were identified through MFA: (1) the insufficient implementation of prospective analysis, (2) heavy use of archetypes as a way to represent road infrastructure, (3) inadequate attention to the inclusion of dissipative flows, and (4) limited coverage of the uncertainties. The proposed dynamic bottom-up MFA method was tested on the Norwegian road network to estimate and predict the material stocks and flows between 1980 and 2050. Here, a supervised machine learning model was introduced to estimate the road infrastructure instead of archetypical mapping of different roads. The dissipation of materials from the road infrastructure based on tire–pavement interaction was incorporated. Moreover, this study utilizes iterative classified and regression trees, lifetime distributions, randomized material intensities, and sensitivity analyses to quantify the uncertainties.
John Wiley & Sons
2022
The effect of the 2018 extreme meteorological conditions in Europe on methane (CH4) emissions is examined using estimates from four atmospheric inversions calculated for the period 2005–2018. For most of Europe, we find no anomaly in 2018 compared to the 2005–2018 mean. However, we find a positive anomaly for the Netherlands in April, which coincided with positive temperature and soil moisture anomalies suggesting an increase in biogenic sources. We also find a negative anomaly for the Netherlands for September–October, which coincided with a negative anomaly in soil moisture, suggesting a decrease in soil sources. In addition, we find a positive anomaly for Serbia in spring, summer and autumn, which coincided with increases in temperature and soil moisture, again suggestive of changes in biogenic sources, and the annual emission for 2018 was 33 ± 38% higher than the 2005–2017 mean. These results indicate that CH4 emissions from areas where the natural source is thought to be relatively small can still vary due to meteorological conditions. At the European scale though, the degree of variability over 2005–2018 was small, and there was negligible impact on the annual CH4 emissions in 2018 despite the extreme meteorological conditions.
This article is part of a discussion meeting issue ‘Rising methane: is warming feeding warming? (part 2)’.
2021
Safety assessment of titanium dioxide (E171) as a food additive
The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO2 nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO2 NPs < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO2 NPs (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico-chemical properties of TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut-off value for TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.
2021
Temporal trends of industrial organic contaminants can show how environmental burdens respond to changes in production, regulation, and other anthropogenic and environmental factors. Numerous studies have documented such trends from the Northern Hemisphere, while there is very limited data in the literature from sub-Saharan Africa. We hypothesized that the temporal trends of legacy and contemporary industrial contaminants in sub-Saharan Africa could greatly differ from the regions in which many of these chemicals were initially produced and more extensively used. For this purpose, a dated sediment core covering six decades from a floodplain system in urban Dar es Salaam, Tanzania, was analysed. The samples were analysed for selected legacy persistent organic pollutants (POPs) [polychlorinated biphenyls (PCBs) and polybrominated biphenyl ethers (PBDEs)] and chemicals of emerging concern (CECs) [alternative brominated flame retardants (aBFRs), chlorinated paraffins (CPs), and dechloranes]. All groups of chemicals showed a steep increase in concentrations towards the uppermost sediment layers reflecting the more recent years. Concentrations of the individual compound groups in surface sediment were found in the order CPs >> aBFRs ∼ ∑25PBDEs > dechloranes ∼ ∑32PCBs. Time trends for the individual compounds and compound groups differed, with ∑32PCBs showing presence in sediments since at least the early 1960s, while some CECs first occurred in sediments corresponding to the last decade. Investigations into potential drivers for the observed trends showed that socioeconomic factors related to growth in population, economy, and waste generation have contributed to increasing concentrations of PBDEs, aBFRs, CPs, and Dechlorane Plus. Further monitoring of temporal trends of industrial organic contaminants in urban areas in the Global South is recommended.
Frontiers Media S.A.
2022
The effective enrichment of perfluoroalkyl acids (PFAAs) in sea spray aerosols (SSA) demonstrated in previous laboratory studies suggests that SSA is a potential source of PFAAs to the atmosphere. In order to investigate the influence of SSA on atmospheric PFAAs in the field, 48 h aerosol samples were collected regularly between 2018 and 2020 at two Norwegian coastal locations, Andøya and Birkenes. Significant correlations (p < 0.05) between the SSA tracer ion, Na+, and PFAA concentrations were observed in the samples from both locations, with Pearson’s correlation coefficients (r) between 0.4–0.8. Such significant correlations indicate SSA to be an important source of atmospheric PFAAs to coastal areas. The correlations in the samples from Andøya were observed for more PFAA species and were generally stronger than in the samples from Birkenes, which is located further away from the coast and closer to urban areas than Andøya. Factors such as the origin of the SSA, the distance of the sampling site to open water, and the presence of other PFAA sources (e.g., volatile precursor compounds) can have influence on the contribution of SSA to PFAA in air at the sampling sites and therefore affect the observed correlations between PFAAs and Na+.
2021
Why is the city's responsibility for its air pollution often underestimated? A focus on PM2.5
While the burden caused by air pollution in urban areas is well documented, the origin of this pollution and therefore the responsibility of the urban areas in generating this pollution are still a subject of scientific discussion. Source apportionment represents a useful technique to quantify the city's responsibility, but the approaches and applications are not harmonized and therefore not comparable, resulting in confusing and sometimes contradicting interpretations. In this work, we analyse how different source apportionment approaches apply to the urban scale and how their building elements and parameters are defined and set. We discuss in particular the options available in terms of indicator, receptor, source, and methodology. We show that different choices for these options lead to very large differences in terms of outcome. For the 150 large EU cities selected in our study, different choices made for the indicator, the receptor, and the source each lead to an average difference of a factor of 2 in terms of city contribution. We also show that temporal- and spatial-averaging processes applied to the air quality indicator, especially when diverging source apportionments are aggregated into a single number, lead to the favouring of strategies that target background sources while occulting actions that would be efficient in the city centre. We stress that methodological choices and assumptions most often lead to a systematic and important underestimation of the city's responsibility, with important implications. Indeed, if cities are seen as a minor actor, plans will target the background as a priority at the expense of potentially effective local actions.
2021
American Geophysical Union (AGU)
2021
Aerosol particles are a complex component of the atmospheric system which influence climate directly by interacting with solar radiation, and indirectly by contributing to cloud formation. The variety of their sources, as well as the multiple transformations they may undergo during their transport (including wet and dry deposition), result in significant spatial and temporal variability of their properties. Documenting this variability is essential to provide a proper representation of aerosols and cloud condensation nuclei (CCN) in climate models. Using measurements conducted in 2016 or 2017 at 62 ground-based stations around the world, this study provides the most up-to-date picture of the spatial distribution of particle number concentration (Ntot) and number size distribution (PNSD, from 39 sites). A sensitivity study was first performed to assess the impact of data availability on Ntot's annual and seasonal statistics, as well as on the analysis of its diel cycle. Thresholds of 50 % and 60 % were set at the seasonal and annual scale, respectively, for the study of the corresponding statistics, and a slightly higher coverage (75 %) was required to document the diel cycle.
Although some observations are common to a majority of sites, the variety of environments characterizing these stations made it possible to highlight contrasting findings, which, among other factors, seem to be significantly related to the level of anthropogenic influence. The concentrations measured at polar sites are the lowest (∼ 102 cm−3) and show a clear seasonality, which is also visible in the shape of the PNSD, while diel cycles are in general less evident, due notably to the absence of a regular day–night cycle in some seasons. In contrast, the concentrations characteristic of urban environments are the highest (∼ 103–104 cm−3) and do not show pronounced seasonal variations, whereas diel cycles tend to be very regular over the year at these stations. The remaining sites, including mountain and non-urban continental and coastal stations, do not exhibit as obvious common behaviour as polar and urban sites and display, on average, intermediate Ntot (∼ 102–103 cm−3). Particle concentrations measured at mountain sites, however, are generally lower compared to nearby lowland sites, and tend to exhibit somewhat more pronounced seasonal variations as a likely result of the strong impact of the atmospheric boundary layer (ABL) influence in connection with the topography of the sites. ABL dynamics also likely contribute to the diel cycle of Ntot observed at these stations. Based on available PNSD measurements, CCN-sized particles (considered here as either >50 nm or >100 nm) can represent from a few percent to almost all of Ntot, corresponding to seasonal medians on the order of ∼ 10 to 1000 cm−3, with seasonal patterns and a hierarchy of the site types broadly similar to those observed for Ntot.
Overall, this work illustrates the importance of in situ measurements, in particular for the study of aerosol physical properties, and thus strongly supports the development of a broad global network of near surface observatories to increase and homogenize the spatial coverage of the measurements, and guarantee as well data availability and quality. The results of this study also provide a valuable, freely available and easy to use support for model comparison and validation, with the ultimate goal of contributing to improvement of the representation of aerosol–cloud interactions in models, and, therefore, of the evaluation of the impact of aerosol particles on climate.
2021
2021
As the leading climate mode of wintertime climate variability over Europe, the North Atlantic Oscillation (NAO) has been extensively studied over the last decades. Recently, studies highlighted the state of the Eurasian cryosphere as a possible predictor for the wintertime NAO. However, missing correlation between snow cover and wintertime NAO in climate model experiments and strong non-stationarity of this link in reanalysis data are questioning the causality of this relationship.
Here we use the large ensemble of Atmospheric Seasonal Forecasts of the 20th Century (ASF-20C) with the European Centre for Medium-Range Weather Forecasts model, focusing on the winter season. Besides the main 110-year ensemble of 51 members, we investigate a second, perturbed ensemble of 21 members where initial (November) land conditions over the Northern Hemisphere are swapped from neighboring years. The Eurasian snow–NAO linkage is examined in terms of a longitudinal snow depth dipole across Eurasia. Subsampling the perturbed forecast ensemble and contrasting members with high and low initial snow dipole conditions, we found that their composite difference indicates more negative NAO states in the following winter (DJF) after positive west-to-east snow depth gradients at the beginning of November. Surface and atmospheric forecast anomalies through the troposphere and stratosphere associated with the anomalous positive snow dipole consist of colder early winter surface temperatures over eastern Eurasia, an enhanced Ural ridge and increased vertical energy fluxes into the stratosphere, with a subsequent negative NAO-like signature in the troposphere. We thus confirm the existence of a causal connection between autumn snow patterns and subsequent winter circulation in the ASF-20C forecasting system.
2021
2022
Elevated stratopause events in the current and a future climate: A chemistry-climate model study
Elsevier
2021
Fate of Springtime Atmospheric Reactive Mercury: Concentrations and Deposition at Zeppelin, Svalbard
American Chemical Society (ACS)
2021
2021
2022
Calibration of CO, NO2, and O3 Using Airify: A Low-Cost Sensor Cluster for Air Quality Monitoring
MDPI
2021
2021
2021
2021
2021