Epidermal growth factor alters silica nanoparticle uptake and improves gold-nanoparticle-mediated gene silencing in A549 cells

Introduction: Delivery of therapeutic nanoparticles (NPs) to cancer cells represents a promising approach for biomedical applications. A key challenge for nanotechnology translation from the bench to the bedside is the low amount of administered NPs dose that effectively enters target cells. To improve NPs delivery, several studies proposed NPs conjugation with ligands, which specifically deliver NPs to target cells via receptor binding. One such example is epidermal growth factor (EGF), a peptide involved in cell signaling pathways that control cell division by binding to epidermal growth factor receptor (EGFR). However, very few studies assessed the influence of EGF present in the cell environment, on the cellular uptake of NPs.Methods: We tested if the stimulation of EGFR-expressing lung carcinomacells A549 with EGF affects the uptake of 59 nm and 422 nm silica (SiO2) NPs. Additionally, we investigated whether the uptake enhancement can be achieved with gold NPs, suitable to downregulate the expression of cancer oncogene c-MYC.Results: Our findings show that EGF binding to its receptor results in receptor autophosphorylation and initiate signaling pathways, leading to enhanced endocytosis of 59 nm SiO2 NPs, but not 422 nm SiO2 NPs. Additionally, we demonstrated an enhanced gold (Au) NPs endocytosis and subsequently a higher downregulation of c-MYC.Discussion: These findings contribute to a better understanding of NPs uptake in the presence of EGF and that is a promising approach for improved NPs delivery

MOSAiC goes O2A - Arctic Expedition Data Flow from Observations to Archives

During the largest polar expedition in history starting in September 2019, the German research icebreaker Polarstern spends a whole year drifting with the ice through the Arctic Ocean. The MOSAiC expedition takes the closest look ever at the Arctic even throughout the polar winter to gain fundamental insights and most unique on-site data for a better understanding of global climate change. Hundreds of researchers from 20 countries are involved. Scientists will use the in situ gathered data instantaneously in near-real time modus as well as long afterwards all around the globe taking climate research to a completely new level. Hence, proper data management, sampling strategies beforehand, and monitoring actual data flow as well as processing, analysis and sharing of data during and long after the MOSAiC expedition are the most essential tools for scientific gain and progress. To prepare for that challenge we adapted and integrated the research data management framework O2A “Data flow from Observations to Archives” to the needs of the MOSAiC expedition on board Polarstern as well as on land for data storage and access at the Alfred Wegener Institute Computing and Data Center in Bremerhaven, Germany. Our O2A-framework assembles a modular research infrastructure comprising a collection of tools and services. These components allow researchers to register all necessary sensor metadata beforehand linked to automatized data ingestion and to ensure and monitor data flow as well as to process, analyze, and publish data to turn the most valuable and uniquely gained arctic data into scientific outcomes. The framework further allows for the integration of data obtained with discrete sampling devices into the data flow. These requirements have led us to adapt the generic and cost-effective framework O2A to enable, control, and access the flow of sensor observations to archives in a cloud-like infrastructure on board Polarstern and later on to land based repositories for international availability. Major roadblocks of the MOSAiC-O2A data flow framework are (i) the increasing number and complexity of research platforms, devices, and sensors, (ii) the heterogeneous interdisciplinary driven requirements towards, e. g., satellite data, sensor monitoring, in situ sample collection, quality assessment and control, processing, analysis and visualization, and (iii) the demand for near real time analyses on board as well as on land with limited satellite bandwidth. The key modules of O2A's digital research infrastructure established by AWI are implementing the FAIR principles: SENSORWeb, to register sensor applications and sampling devices and capture controlled meta data before and alongside any measurements in the field Data ingest, allowing researchers to feed data into storage systems and processing pipelines in a prepared and documented way, at best in controlled near real-time data streams Dashboards allowing researchers to find and access data and share and collaborate among partners Workspace enabling researchers to access and use data with research software utilizing a cloud-based virtualized infrastructure that allows researchers to analyze massive amounts of data on the spot Archiving and publishing data via repositories and Digital Object Identifiers (DOI

Validation of methane and carbon monoxide from Sentinel-5 Precursor using TCCON and NDACC-IRWG stations

The Sentinel-5 Precursor (S5P) mission with the TROPOspheric Monitoring Instrument (TROPOMI) on board has been measuring solar radiation backscattered by the Earth\u27s atmosphere and surface since its launch on 13 October 2017. In this paper, we present for the first time the S5P operational methane (CH4) and carbon monoxide (CO) products\u27 validation results covering a period of about 3 years using global Total Carbon Column Observing Network (TCCON) and Infrared Working Group of the Network for the Detection of Atmospheric Composition Change (NDACC-IRWG) network data, accounting for a priori alignment and smoothing uncertainties in the validation, and testing the sensitivity of validation results towards the application of advanced co-location criteria. We found that the S5P standard and bias-corrected CH4 data over land surface for the recommended quality filtering fulfil the mission requirements. The systematic difference of the bias-corrected total column-averaged dry air mole fraction of methane (XCH4) data with respect to TCCON data is −0.26±0.56 % in comparison to −0.68±0.74 % for the standard XCH4 data, with a correlation of 0.6 for most stations. The bias shows a seasonal dependence. We found that the S5P CO data over all surfaces for the recommended quality filtering generally fulfil the missions requirements, with a few exceptions, which are mostly due to co-location mismatches and limited availability of data. The systematic difference between the S5P total column-averaged dry air mole fraction of carbon monoxide (XCO) and the TCCON data is on average 9.22±3.45 % (standard TCCON XCO) and 2.45±3.38 % (unscaled TCCON XCO). We found that the systematic difference between the S5P CO column and NDACC CO column (excluding two outlier stations) is on average 6.5±3.54 %. We found a correlation of above 0.9 for most TCCON and NDACC stations. The study shows the high quality of S5P CH4 and CO data by validating the products against reference global TCCON and NDACC stations covering a wide range of latitudinal bands, atmospheric conditions and surface conditions

Standard comparison of local mental health care systems in eight European countries

Aims. There is a need of more quantitative standardised data to compare local Mental Health Systems (MHSs) across international jurisdictions. Problems related to terminological variability and commensurability in the evaluation of services hamper like-with-like comparisons and hinder the development of work in this area. This study was aimed to provide standard assessment and comparison of MHS in selected local areas in Europe, contributing to a better understanding of MHS and related allocation of resources at local level and to lessen the scarcity in standard service comparison in Europe. This study is part of the Seventh Framework programme REFINEMENT (Research on Financing Systems' Effect on the Quality of Mental Health Care in Europe) project. Methods. A total of eight study areas from European countries with different systems of care (Austria, England, Finland, France, Italy, Norway, Romania, Spain) were analysed using a standard open-access classification system (Description and Evaluation of Services for Long Term Care in Europe, DESDE-LTC). All publicly funded services universally accessible to adults (>= 18 years) with a psychiatric disorder were coded. Care availability, diversity and capacity were compared across these eight local MHS. Results. The comparison of MHS revealed more community-oriented delivery systems in the areas of England (Hampshire) and Southern European countries (Verona - Italy and Girona - Spain). Community-oriented systems with a higher proportion of hospital care were identified in Austria (Industrieviertel) and Scandinavian countries (Sor-Trondelag in Norway and Helsinki-Uusimaa in Finland), while Loiret (France) was considered as a predominantly hospital-based system. The MHS in Suceava (Romania) was still in transition to community care. Conclusions. There is a significant variation in care availability and capacity across MHS of local areas in Europe. This information is relevant for understanding the process of implementation of community-oriented mental health care in local areas. Standard comparison of care provision in local areas is important for context analysis and policy planning.Peer reviewe

Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults

Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0.012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10(-7) < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10(-8) < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH

DataSheet1_Epidermal growth factor alters silica nanoparticle uptake and improves gold-nanoparticle-mediated gene silencing in A549 cells.docx

Introduction: Delivery of therapeutic nanoparticles (NPs) to cancer cells represents a promising approach for biomedical applications. A key challenge for nanotechnology translation from the bench to the bedside is the low amount of administered NPs dose that effectively enters target cells. To improve NPs delivery, several studies proposed NPs conjugation with ligands, which specifically deliver NPs to target cells via receptor binding. One such example is epidermal growth factor (EGF), a peptide involved in cell signaling pathways that control cell division by binding to epidermal growth factor receptor (EGFR). However, very few studies assessed the influence of EGF present in the cell environment, on the cellular uptake of NPs.Methods: We tested if the stimulation of EGFR-expressing lung carcinomacells A549 with EGF affects the uptake of 59 nm and 422 nm silica (SiO2) NPs. Additionally, we investigated whether the uptake enhancement can be achieved with gold NPs, suitable to downregulate the expression of cancer oncogene c-MYC.Results: Our findings show that EGF binding to its receptor results in receptor autophosphorylation and initiate signaling pathways, leading to enhanced endocytosis of 59 nm SiO2 NPs, but not 422 nm SiO2 NPs. Additionally, we demonstrated an enhanced gold (Au) NPs endocytosis and subsequently a higher downregulation of c-MYC.Discussion: These findings contribute to a better understanding of NPs uptake in the presence of EGF and that is a promising approach for improved NPs delivery.</p

CELTIC CP5-026 WINNER+, D1.9 Final Innovation Report

This deliverable is the final innovation report from the innovation workpackage in WINNER+. The document describes the latest innovations and their assessment as well as summarizes the innovations developed in the work package during the project. We analyze the suitability of these innovations as technology enablers for improving current systems, in particular IMT Advanced and beyond

CELTIC CP5-026 WINNER+, D1.9 Final Innovation Report

This deliverable is the final innovation report from the innovation workpackage in WINNER+. The document describes the latest innovations and their assessment as well as summarizes the innovations developed in the work package during the project. We analyze the suitability of these innovations as technology enablers for improving current systems, in particular IMT Advanced and beyond

Data management in MOSAiC – Challenges of the Multidisciplinary drifting Observatory for the Study of Arctic Climate

During the MOSAiC expedition, the German research icebreaker Polarstern spends a full year drifting through the Arctic Ocean. Scientists from 20 countries participate in the largest polar expedition in history exploring the Arctic climate system. The experiment covers a large suite of in-situ and remote sensing observations of physical, ecological and biogeochemical parameters to describe the processes coupling the atmosphere, sea ice, and ocean. In addition to forefront instrumentation and observational techniques, proper data management is essential for large and complex projects and field programs. Key elements are agreements on consistent sampling strategies, the possibility to monitor the data flow, to facilitate near real-time processing, and analysis and sharing of data during and long after the expedition. Furthermore, data publication and documentation are crucial for such a collaborative effort and will build the legacy of the project and finally take climate science to the next level. We adapted our modular research data management framework O2A “Data flow from Observations to Archives” to meet the expedition requirements and ensure central data archival for generations to come. Researchers register all necessary sensor metadata beforehand. Essential metadata of scientific actions in the field are ingested immediately with the FloeNavi, a novel system enabling navigation on a drifting ice floe. O2A provides tools to automatize data ingestion, monitor the data flow and process, analyze and publish data. Integration of ship- and land-based components and a shared storage ensure seamless continuation of collaboration during and after the expedition laying the fundamentals for numerous data publications