Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA;SEONLA-BSA),or with dextran (SEONDEX). Both micronuclei testing and the detection of H2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system

Inert Coats of Magnetic Nanoparticles Prevent Formation of Occlusive Intravascular Co-aggregates With Neutrophil Extracellular Traps

If foreign particles enter the human body, the immune system offers several mechanisms of response. Neutrophils forming the first line of the immune defense either remove pathogens by phagocytosis, inactivate them by degranulation or release of reactive oxygen species or immobilize them by the release of chromatin decorated with the granular proteins from cytoplasm as neutrophil extracellular traps (NETs). Besides viable microbes like fungi, bacteria or viruses, also several sterile inorganic particles including nanoparticles reportedly activate NET formation. The physicochemical nanoparticle characteristics fostering NET formation are still elusive. Here we show that agglomerations of non-stabilized superparamagnetic iron oxide nanoparticles (SPIONs) induce NET formation by isolated human neutrophils, in whole blood experiments under static and dynamic conditions as well as in vivo. Stabilization of nanoparticles with biocompatible layers of either human serum albumin or dextran reduced agglomeration and NET formation by neutrophils. Importantly, this passivation of the SPIONs prevented vascular occlusions in vivo even when magnetically accumulated. We conclude that higher order structures formed during nanoparticle agglomeration primarily trigger NET formation and the formation of SPION-aggregated NET-co-aggregates, whereas colloid-disperse nanoparticles behave inert and are alternatively cleared by phagocytosis

The SPARC Water Vapor Assessment II: assessment of satellite measurements of upper tropospheric humidity

Nineteen limb-viewing data sets (occultation, passive thermal, and UV scattering) and two nadir upper tropospheric humidity (UTH) data sets are intercompared and also compared to frost-point hygrometer balloon sondes. The upper troposphere considered here covers the pressure range from 300-100 hPa. UTH is a challenging measurement, because concentrations vary between 2-1000 ppmv (parts per million by volume), with sharp changes in vertical gradients near the tropopause. Cloudiness in this region also makes the measurement challenging. The atmospheric temperature is also highly variable ranging from 180-250 K. The assessment of satellite-measured UTH is based on coincident comparisons with balloon frost-point hygrometer sondes, multi-month mapped comparisons, zonal mean time series comparisons, and coincident satellite-to-satellite comparisons. While the satellite fields show similar features in maps and time series, quantitatively they can differ by a factor of 2 in concentration, with strong dependencies on the amount of UTH. Additionally, time-lag response-corrected Vaisala RS92 radiosondes are compared to satellites and the frost-point hygrometer measurements. In summary, most satellite data sets reviewed here show on average similar to 30 % agreement amongst themselves and frost-point data but with an additional similar to 30 % variability about the mean bias. The Vaisala RS92 sonde, even with a time-lag correction, shows poor behavior for pressures less than 200 hPa

The SPARC Water Vapor Assessment II: assessment of satellite measurements of upper tropospheric humidity

Nineteen limb-viewing data sets (occultation, passive thermal, and UV scattering) and two nadir upper tropospheric humidity (UTH) data sets are intercompared and also compared to frost-point hygrometer balloon sondes. The upper troposphere considered here covers the pressure range from 300–100 hPa. UTH is a challenging measurement, because concentrations vary between 2–1000 ppmv (parts per million by volume), with sharp changes in vertical gradients near the tropopause. Cloudiness in this region also makes the measurement challenging. The atmospheric temperature is also highly variable ranging from 180–250 K. The assessment of satellite-measured UTH is based on coincident comparisons with balloon frost-point hygrometer sondes, multi-month mapped comparisons, zonal mean time series comparisons, and coincident satellite-to-satellite comparisons. While the satellite fields show similar features in maps and time series, quantitatively they can differ by a factor of 2 in concentration, with strong dependencies on the amount of UTH. Additionally, time-lag response-corrected Vaisala RS92 radiosondes are compared to satellites and the frost-point hygrometer measurements. In summary, most satellite data sets reviewed here show on average ∼30 % agreement amongst themselves and frost-point data but with an additional ∼30 % variability about the mean bias. The Vaisala RS92 sonde, even with a time-lag correction, shows poor behavior for pressures less than 200 hPa

The SPARC water vapour assessment II: comparison of annual, semi-annual and quasi-biennial variations in stratospheric and lower mesospheric water vapour observed from satellites

In the framework of the second SPARC (Stratosphere-troposphere Processes And their Role in Climate) water vapour assessment (WAVAS-II), the amplitudes and phases of the annual, semi-annual and quasi-biennial variation in stratospheric and lower mesospheric water were compared using 30 data sets from 13 different satellite instruments. These comparisons aimed to provide a comprehensive overview of the typical uncertainties in the observational database which can be considered in subsequent observational and modelling studies. For the amplitudes, a good agreement of their latitude and altitude distribution was found. Quantitatively there were differences in particular at high latitudes, close to the tropopause and in the lower mesosphere. In these regions, the standard deviation over all data sets typically exceeded 0.2 ppmv for the annual variation and 0.1 ppmv for the semi-annual and quasi-biennial variation. For the phase, larger differences between the data sets were found in the lower mesosphere. Generally the smallest phase uncertainties can be observed in regions where the amplitude of the variability is large. The standard deviations of the phases for all data sets were typically smaller than a month for the annual and semi-annual variation and smaller than 5 months for the quasi-biennial variation. The amplitude and phase differences among the data sets are caused by a combination of factors. In general, differences in the temporal variation of systematic errors and in the observational sampling play a dominant role. In addition, differences in the vertical resolution of the data, the considered time periods and influences of clouds, aerosols as well as non-local thermodynamic equilibrium (NLTE) effects cause differences between the individual data sets

The SPARC water vapour assessment II: biases and drifts of water vapour satellite data records with respect to frost point hygrometer records

Satellite data records of stratospheric water vapour have been compared to balloon-borne frost point hygrometer (FP) profiles that are coincident in space and time. The satellite data records of 15 different instruments cover water vapour data available from January 2000 through December 2016. The hygrometer data are from 27 stations all over the world in the same period. For the comparison, real or constructed averaging kernels have been applied to the hygrometer profiles to adjust them to the measurement characteristics of the satellite instruments. For bias evaluation, we have compared satellite profiles averaged over the available temporal coverage to the means of coincident FP profiles for individual stations. For drift determinations, we analysed time series of relative differences between spatiotemporally coincident satellite and hygrometer profiles at individual stations. In a synopsis we have also calculated the mean biases and drifts (and their respective uncertainties) for each satellite record over all applicable hygrometer stations in three altitude ranges (10–30 hPa, 30–100 hPa, and 100 hPa to tropopause). Most of the satellite data have biases <10 % and average drifts <1 % yr−1 in at least one of the respective altitude ranges. Virtually all biases are significant in the sense that their uncertainty range in terms of twice the standard error of the mean does not include zero. Statistically significant drifts (95 % confidence) are detected for 35 % of the ≈ 1200 time series of relative differences between satellites and hygrometers

Verwaltungsreform - Innovation - Implementation: Strategien erfolgreicher Verwaltungsmodernisierung im Vergleich

Im Sommersemester 2020 organisierten der Lehrstuhl für vergleichende Verwaltungs-wissenschaften und Policy Analyse und das WITI-Projekt der Deutschen Universität für Verwaltungswissenschaften Speyer das digitale Seminar „Verwaltungsreform – Innovation – Implementation: Strategien (erfolgreicher) Verwaltungsmodernisierung im Vergleich“. Im Rahmen der Qualifikationsziele des Seminars, welche unter anderem die methodische Vorbereitung der Studierenden auf die Erstellung der Masterarbeit umfassten, fertigten die Teilnehmenden Hausarbeiten zu ihren Vortragsthemen an. Aufgrund der durchweg erfreulichen Ergebnisse, der thematischen Nähe zum WITI-Projekt und ihrer Praxisrelevanz freuen wir uns, Ihnen die im Rahmen des Seminars entstandenen Hausarbeiten zu präsentieren. Inhaltlich beschäftigen sie sich neben der Entstehung von Innovationslaboren im öffentlichen Sektor und Nutzerorientierung als Bestandteil der Public Sector Innovation mit dem Scheitern der Verwaltungsstrukturreform in Brandenburg, Legitimierungsstrategien des Politiknetzwerks „Bürokratieabbau“ und der Einführung der einheitlichen Behördennummer 115 im Stadt- und Landkreis Karlsruhe. Die Hausarbeit zur Einführung eines einheitlichen E-Akte-Basisdienstes kann aus Datenschutzgründen leider nicht in Gänze abgedruckt werden, ein anonymisiertes Executive Summary möchten wir Ihnen aber nicht vorenthalten

Synthesis and Characterization of Tissue Plasminogen Activator—Functionalized Superparamagnetic Iron Oxide Nanoparticles for Targeted Fibrin Clot Dissolution

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted great attention in many biomedical fields and are used in preclinical/experimental drug delivery, hyperthermia and medical imaging. In this study, biocompatible magnetite drug carriers, stabilized by a dextran shell, were developed to carry tissue plasminogen activator (tPA) for targeted thrombolysis under an external magnetic field. Different concentrations of active tPA were immobilized on carboxylated nanoparticles through carbodiimide-mediated amide bond formation. Evidence for successful functionalization of SPIONs with carboxyl groups was shown by Fourier transform infrared spectroscopy. Surface properties after tPA immobilization were altered as demonstrated by dynamic light scattering and ζ potential measurements. The enzyme activity of SPION-bound tPA was determined by digestion of fibrin-containing agarose gels and corresponded to about 74% of free tPA activity. Particles were stored for three weeks before a slight decrease in activity was observed. tPA-loaded SPIONs were navigated into thrombus-mimicking gels by external magnets, proving effective drug targeting without losing the protein. Furthermore, all synthesized types of nanoparticles were well tolerated in cell culture experiments with human umbilical vein endothelial cells, indicating their potential utility for future therapeutic applications in thromboembolic diseases

Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEONLA-BSA), or with dextran (SEONDEX). Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system