NILU Brage
Not a member yet
3619 research outputs found
Sort by
Decitabine potentiates efficacy of doxorubicin in a preclinical trastuzumab-resistant HER2-positive breast cancer models
Get PDFAcquired 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.publishedVersio
An In Vitro Dosimetry Tool for the Numerical Transport Modeling of Engineered Nanomaterials Powered by the Enalos RiskGONE Cloud Platform
Get PDFA freely available “in vitro dosimetry” web application is presented enabling users to predict the concentration of nanomaterials reaching the cell surface, and therefore available for attachment and internalization, from initial dispersion concentrations. The web application is based on the distorted grid (DG) model for the dispersion of engineered nanoparticles (NPs) in culture medium used for in vitro cellular experiments, in accordance with previously published protocols for cellular dosimetry determination. A series of in vitro experiments for six different NPs, with Ag and Au cores, are performed to demonstrate the convenience of the web application for calculation of exposure concentrations of NPs. Our results show that the exposure concentrations at the cell surface can be more than 30 times higher compared to the nominal or dispersed concentrations, depending on the NPs’ properties and their behavior in the cell culture medium. Therefore, the importance of calculating the exposure concentration at the bottom of the cell culture wells used for in vitro arrays, i.e., the particle concentration at the cell surface, is clearly presented, and the tool introduced here allows users easy access to such calculations. Widespread application of this web tool will increase the reliability of subsequent toxicity data, allowing improved correlation of the real exposure concentration with the observed toxicity, enabling the hazard potentials of different NPs to be compared on a more robust basis.publishedVersio
A surrogate-assisted measurement correction method for accurate and low-cost monitoring of particulate matter pollutants
Get PDFAir pollution involves multiple health and economic challenges. Its accurate and low-cost monitoring is important for developing services dedicated to reduce the exposure of living beings to the pollution. Particulate matter (PM) measurement sensors belong to the key components that support operation of these systems. In this work, a modular, mobile Internet of Things sensor for PM measurements has been proposed. Due to a limited accuracy of the PM detector, the measurement data are refined using a two-stage procedure that involves elimination of the non-physical signal spikes followed by a non-linear correction of the responses using a multiplicative surrogate model. The correction layer is derived from the sparse and non-uniform calibration data, i.e., a combination of the measurements from the PM monitoring station and the sensor obtained in the same location over a specified (relatively short) interval. The device and the method have been both demonstrated based on the data obtained during three measurement campaigns. The proposed correction scheme improves the fidelity of PM measurements by around two orders of magnitude w.r.t. the responses for which the post-processing has not been considered. Performance of the proposed surrogate-assisted technique has been favorably compared against the benchmark approaches from the literature.A surrogate-assisted measurement correction method for accurate and low-cost monitoring of particulate matter pollutantspublishedVersio
Economic Feasibility of Power/Heat Cogeneration by Biogas–Solid Oxide Fuel Cell (SOFC) Integrated Systems
Get PDFBased upon the thermodynamic simulation of a biogas-SOFC integrated process and the costing of its elements, the present work examines the economic feasibility of biogas-SOFCs for combined heat and power (CHP) generation, by the comparison of their economic performance against the conventional biogas-CHP with internal combustion engines (ICEs), under the same assumptions. As well as the issues of process scale and an SOFC’s cost, examined in the literature, the study brings up the determinative effects of: (i) the employed SOFC size, with respect to its operational point, as well as (ii) the feasibility criterion, on the feasibility assessment. Two plant capacities were examined (250 m3·h−1 and 750 m3·h−1 biogas production), and their feasibilities were assessed by the Internal Rate of Return (IRR), the Net Present Value (NPV) and the Pay Back Time (PBT) criteria. For SOFC costs at 1100 and 2000 EUR·kWel−1, foreseen in 2035 and 2030, respectively, SOFCs were found to increase investment (by 2.5–4.5 times, depending upon a plant’s capacity and the SOFC’s size) and power generation (by 13–57%, depending upon the SOFC’s size), the latter increasing revenues. SOFC-CHP exhibits considerably lower IRRs (5.3–13.4% for the small and 16.8–25.3% for the larger plant), compared to ICE-CHP (34.4%). Nonetheless, according to NPV that does not evaluate profitability as a return on investment, small scale biogas-SOFCs (NPVmax: EUR 3.07 M) can compete with biogas-ICE (NPV: EUR 3.42 M), for SOFCs sized to operate at 70% of the maximum power density (MPD) and with a SOFC cost of 1100 EUR·kWel−1, whereas for larger plants, SOFC-CHP can lead to considerably higher NPVs (EUR 12.5–21.0 M) compared to biogas-ICE (EUR 9.3 M). Nonetheless, PBTs are higher for SOFC-CHP (7.7–11.1 yr and 4.2–5.7 yr for the small and the large plant, respectively, compared to 2.3 yr and 3.1 yr for biogas-ICE) because the criterion suppresses the effect of SOFC-CHP-increased revenues to a time period shorter than the plant’s lifetime. Finally, the economics of SOFC-CHP are optimized for SOFCs sized to operate at 70–82.5% of their MPD, depending upon the SOFC cost and the feasibility criterion. Overall, the choice of the feasibility criterion and the size of the employed SOFC can drastically affect the economic evaluation of SOFC-CHP, whereas the feasibility criterion also determines the economically optimum size of the employed SOFC.publishedVersio
Is Glacial Meltwater a Secondary Source of Legacy Contaminants to Arctic Coastal Food Webs?
Get PDFClimate change-driven increases in air and sea temperatures are rapidly thawing the Arctic cryosphere with potential for remobilization and accumulation of legacy persistent organic pollutants (POPs) in adjacent coastal food webs. Here, we present concentrations of selected POPs in zooplankton (spatially and seasonally), as well as zoobenthos and sculpin (spatially) from Isfjorden, Svalbard. Herbivorous zooplankton contaminant concentrations were highest in May [e.g., ∑polychlorinated biphenyls (8PCB); 4.43, 95% CI: 2.72–6.3 ng/g lipid weight], coinciding with the final stages of the spring phytoplankton bloom, and lowest in August (∑8PCB; 1.6, 95% CI: 1.29–1.92 ng/g lipid weight) when zooplankton lipid content was highest, and the fjord was heavily impacted by sediment-laden terrestrial inputs. Slightly increasing concentrations of α-hexachlorocyclohexane (α-HCH) in zooplankton from June (1.18, 95% CI: 1.06–1.29 ng/g lipid weight) to August (1.57, 95% CI: 1.44–1.71 ng/g lipid weight), alongside a higher percentage of α-HCH enantiomeric fractions closer to racemic ranges, indicate that glacial meltwater is a secondary source of α-HCH to fjord zooplankton in late summer. Except for α-HCH, terrestrial inputs were generally associated with reduced POP concentrations in zooplankton, suggesting that increased glacial melt is not likely to significantly increase exposure of legacy POPs in coastal fauna.publishedVersio
First documentation of plastic ingestion in the arctic glaucous gull (Larus hyperboreus)
Get PDFArctic wildlife is facing multiple stressors, including increasing plastic pollution. Seabirds are intrinsic to marine ecosystems, but most seabird populations are declining. We lack knowledge on plastic ingestion in many arctic seabird species, and there is an urgent need for more information to enable risk assessment and monitoring. Our study aimed to investigate the occurrence of plastics in glaucous gulls (Larus hyperboreus) breeding on Svalbard. The glaucous gull is a sentinel species for the health of the arctic marine ecosystem, but there have been no studies investigating plastic occurrence in this species since 1994. As a surface feeder and generalist living in an area with high human activity on Svalbard, we expected to find plastic in its stomach. We investigated for plastic >1 mm and documented plastic ingestion for the first time in glaucous gulls, with a frequency of occurrence of 14.3% (n = 21). The plastics were all identified as user plastics and consisted of polypropylene (PP) and polystyrene (PS). Our study provides new quantitative and qualitative data on plastic burden and polymer type reported in a standardized manner establishing a reference point for future research and monitoring of arctic gulls on national and international levels.First documentation of plastic ingestion in the arctic glaucous gull (Larus hyperboreus)publishedVersio
Synergistisk utnyttelse av metanproduktet fra Sentinel-SP for anvendelser i Arktis (STEPS)
Get PDFThe main goal of this feasibility study was to evaluate the potential of adding value to the Sentinel 5P TROPOMI methane product over Norway and the Arctic through the synergistic use of relevant observations from other Sentinel satellites and machine learning. We assessed the data availability of ESA operational and research-based WFMD XCH4 products over the Northern hemisphere, the Nordic countries and the Arctic/Northern latitudes. ESA’s XCH4 data have poor coverage over Norway. Seeing the two datasets as complementary, seems to be the most reasonable approach for utilization them. Furthermore, we investigated potential synergies between satellite products from different platforms. A random forest (RF) machine learning algorithm was implemented. It shows the importance of daytime land surface temperature (LST) as predictor variable for CH4. Our results indicate that the RF-model has a very good capability of filling small gaps in the data.Hovedmålet med denne mulighetsstudien var å evaluere potensialet for å tilføre verdi til Sentinel 5P TROPOMI-metanproduktet over Norge og Arktis gjennom synergistisk bruk av relevante observasjoner fra andre Sentinel-satellitter og maskinlæring. Vi vurderte datatilgjengeligheten til ESAs operasjonelle og forskningsbaserte WFMD XCH4-produkter over den nordlige halvkule, de nordiske landene og de arktiske/nordlige breddegrader. ESAs XCH4-data har dårlig dekning over Norge. Å se de to datasettene som komplementære, ser ut til å være den mest fornuftige tilnærmingen for å bruke dem. Videre undersøkte vi potensielle synergier mellom satellittprodukter fra ulike plattformer. En maskinlæringsalgoritme (Random forest, RF) ble implementert. Den viser viktigheten av jordoverflatetemperatur (LST) på dagtid som variabel for CH4. Våre resultater indikerer at RF-modellen har en meget god evne til å fylle små hull i dataene.publishedVersio
Population pharmacokinetic modeling of CSF to blood clearance: prospective tracer study of 161 patients under work-up for CSF disorders
Get PDFBackground
Quantitative measurements of cerebrospinal fluid to blood clearance has previously not been established for neurological diseases. Possibly, variability in cerebrospinal fluid clearance may affect the underlying disease process and may possibly be a source of under- or over-dosage of intrathecally administered drugs. The aim of this study was to characterize the cerebrospinal fluid to blood clearance of the intrathecally administered magnetic resonance imaging contrast agent gadobutrol (Gadovist, Bayer Pharma AG, GE). For this, we established a population pharmacokinetic model, hypothesizing that cerebrospinal fluid to blood clearance differs between cerebrospinal fluid diseases.
Methods
Gadobutrol served as a surrogate tracer for extra-vascular pathways taken by several brain metabolites and drugs in cerebrospinal fluid. We estimated cerebrospinal fluid to blood clearance in patients with different cerebrospinal fluid disorders, i.e. symptomatic pineal and arachnoid cysts, as well as tentative spontaneous intracranial hypotension due to cerebrospinal fluid leakage, idiopathic intracranial hypertension, or different types of hydrocephalus (idiopathic normal pressure hydrocephalus, communicating- and non-communicating hydrocephalus). Individuals with no verified cerebrospinal fluid disturbance at clinical work-up were denoted references.
Results
Population pharmacokinetic modelling based on 1,140 blood samples from 161 individuals revealed marked inter-individual variability in pharmacokinetic profiles, including differences in absorption half-life (time to 50% of tracer absorbed from cerebrospinal fluid to blood), time to maximum concentration in blood and the maximum concentration in blood as well as the area under the plasma concentration time curve from zero to infinity. In addition, the different disease categories of cerebrospinal fluid diseases demonstrated different profiles.
Conclusions
The present observations of considerable variation in cerebrospinal fluid to blood clearance between individuals in general and across neurological diseases, may suggest that defining cerebrospinal fluid to blood clearance can become a useful diagnostic adjunct for work-up of cerebrospinal fluid disorders. We also suggest that it may become useful for assessing clearance capacity of endogenous brain metabolites from cerebrospinal fluid, as well as measuring individual cerebrospinal fluid to blood clearance of intrathecal drugs.publishedVersio
Potential environmental impact of bromoform from Asparagopsis farming in Australia
Get PDFTo mitigate the rumen enteric methane (CH4) produced by ruminant livestock, Asparagopsis taxiformis is proposed as an additive to ruminant feed. During the cultivation of Asparagopsis taxiformis in the sea or in terrestrially based systems, this macroalgae, like most seaweeds and phytoplankton, produces a large amount of bromoform (CHBr3), which contributes to ozone depletion once released into the atmosphere. In this study, we focus on the impact of CHBr3 on the stratospheric ozone layer resulting from potential emissions from proposed Asparagopsis cultivation in Australia. The impact is assessed by weighting the emissions of CHBr3 with its ozone depletion potential (ODP), which is traditionally defined for long-lived halocarbons but has also been applied to very short-lived substances (VSLSs). An annual yield of ∼3.5 × 104 Mg dry weight is required to meet the needs of 50 % of the beef feedlot and dairy cattle in Australia. Our study shows that the intensity and impact of CHBr3 emissions vary, depending on location and cultivation scenarios. Of the proposed locations, tropical farms near the Darwin region are associated with the largest CHBr3 ODP values. However, farming of Asparagopsis using either ocean or terrestrial cultivation systems at any of the proposed locations does not have the potential to significantly impact the ozone layer. Even if all Asparagopsis farming were performed in Darwin, the CHBr3 emitted into the atmosphere would amount to less than 0.02 % of the global ODP-weighted emissions. The impact of remaining farming scenarios is also relatively small even if the intended annual yield in Darwin is scaled by a factor of 30 to meet the global requirements, which will increase the global ODP-weighted emissions up to ∼0.5 %.Potential environmental impact of bromoform from Asparagopsis farming in AustraliapublishedVersio
Overvåkning av atmosfærens sammensetning og avsetning i Norge
Get PDFThe Norwegian monitoring programme is set up to meet national and international obligations and needs for measurement data with a long-term commitment. The data are important for compliance monitoring as well as input for effect studies. The monitoring of atmospheric composition and deposition are organised under national programmes mainly funded by the Norwegian Environment Agency in addition to some direct support from the Ministry of Climate and Environment. NILU – Norwegian Institute for Air Research is responsible for the daily operation and reporting of the results from this monitoring. The monitoring aim to fulfil several inter-connected purposes and is divided in four main programmes: transboundary fluxes, contaminants, climate change and the ozone layer. In addition, regularly moss surveys are conducted to assess atmospheric deposition of pollutants such as heavy metals.Det norske overvåkingsprogrammet er satt opp for å møte nasjonale og internasjonale forpliktelser og behov for måledata med et langsiktig perspektiv. Dataene er viktige for å bevokte overholdelse av avtalte utslippsreduksjoner samt viktig grunnlagsdata for effektstudier. Overvåkningen er organisert under nasjonale programmer i hovedsak finansiert av Miljødirektoratet i tillegg til noe direkte støtte fra Klima- og miljødepartementet. NILU – Norsk institutt for luftforskning har ansvar for den daglige driften og rapporteringen av resultatene fra denne overvåkningen. Overvåkningen oppfyller flere sammenhengende fagområder og er delt inn i fire hovedprogrammer: grenseoverskridende luftforurensinger, miljøgifter klimaendringer og ozonlaget. I tillegg gjennomføres det jevnlig moseundersøkelser for å undersøke atmosfærisk avsetning av forurensninger som tungmetaller.publishedVersio