Late Quaternary environmental history of Rauer Group, East Antarctica

In East Antarctica, small ice-free coastal areas are unique environments, located between the East Antarctic Ice Sheet (EAIS) and its outlet glacier systems on the one hand and the Southern Ocean on the other. Rauer Group is an ice-free archipelago in eastern Prydz Bay, which has been visited in March 2007. Geomorphological studies have been conducted there in order to shed light on the glacial history of the area. The recovery of long sediment cores from three marine inlets and one lake provided the possibility to reconstruct the late Pleistocene and Holocene environmental and climate history of the area for the first time. Since knowledge on climate and glacial history around East Antarctica is relatively sparse, this study contributes significantly to a broader understanding of the late Quaternary evolution of the region. The reconstructions presented in this thesis are based on a multi-proxy approach, comprising sedimentological, biogeochemical and paleontological studies on sedimentary records from lakes and marine inlets. Chronologies of the records have been obtained by radiocarbon dating. Radiocarbon ages from three different records indicate ice-free conditions on the islands in the late Pleistocene between 40-30 14C ka BP (44.7-34 cal ka BP). The presence of lacustrine as well as marine environments on/at Filla Island suggest that the EAIS reached only insignificantly beyond its present margin during that period. At the same time, relative sea-level reconstructions point to increased ice load in vicinity of the coast and a steeper than present ice sheet profile. A subsequent glacial overriding due to EAIS expansion during the Last Glacial Maximum can be inferred from a till layer and a hiatus in sediment cores from two marine basins, respectively. Glacial overriding within the last glacial is also suggested by the geomorphology of the islands. The inlets became ice-free prior to 11,200 cal yr BP, when biogenic sedimentation started. Deglaciation processes in the catchments, however, influenced the inlets until c. 9200 cal yr BP as evidenced by the input of minerogenic material. Holocene ice retreat was virtually complete prior to the Mid-Holocene, since a sediment record from a marine inlet 1.8 km in front of the present ice sheet, contains a complete marine record of the past 4500 years. Significant ice sheet expansion beyond present ice margins did not occur in Rauer Group since the Mid-Holocene. Concerning climatic conditions throughout the Holocene, an early Holocene climate optimum in Rauer Group is reflected by elevated marine productivity under relatively open-water conditions until 8200 cal yr BP. In the following cooler period sea ice on the marine inlets increased. In the Mid-Holocene the basins experienced an input of freshwater between c. 5700-3500 cal yr BP. Probably warmer climate conditions caused ice-sheet melting and increased precipitation on the islands. Neoglacial cooling in the late Holocene is reflected by an increase in sea ice in both inlets

Biokompatibilität von superparamagnetischen Eisenoxidnanopartikeln mit humanen Endothelzellen

Herz-Kreislauf-Krankheiten (HKK) sind die häufigste Todesursache weltweit. Atherosklerose stellt dabei eine der zentralen Ursachen für HKK dar. Der Einsatz von superparamagnetischen Eisenoxidnanopartikeln (superparamagnetic iron oxide nanoparticles = SPIONs) könnte, sowohl für die bildgebende Diagnostik als auch für die Therapie von Atherosklerose, einen entscheidenden Fortschritt ermöglichen. Kontrastmittel auf SPION-Basis bieten vielversprechende Möglichkeiten für eine exzellente Bildgebung in der MRT. In der Therapie könnten SPIONs als Drug-Targeting-Systeme fungieren, wodurch eingesetzte Medikamente eine lokale Wirkung mit geringen Nebenwirkungen erzielen. Bevor Kontrastmittel oder Medikamente auf SPION-Basis für die intravaskuläre Anwendung Verwendung finden können, müssen diese jedoch zuvor auf Toxizität geprüft werden. Im ersten Schritt ist es sinnvoll SPIONs auf ihre Biokompatibilität mit Endothelzellen zu testen, da dies bei intravaskulärer Applikation wichtige Gefäßzellen sind, mit denen die SPIONs in Kontakt treten. Diese Arbeit dient dazu fünf verschiedene SPION-Systeme auf Biokompatibilität mit humanen Endothelzellen zu untersuchen

Snow petrel stomach oil deposits ("Antarctic mumiyo") as archives for the environmental history of terrestrial East Antarctica

Snow petrels (Pagodroma nivea) are endemic to Antarctica. Their feeding grounds are located within the pack ice or open waters of the Southern Ocean. They feed on fish, krill and squid with changing proportions depending on sea ice conditions. The birds breed in un-glaciated areas along the coast but also on inland nunataks and mountain ranges up to 440 km from the coast. Their nests are sheltered in rock cavities, which are defended by the petrels against potential intruders (e.g., competitors and Skuas) by ejecting proventricular stomach oil. The stomach oil accumulates and fossilizes around the breeding sites, thus forming centimetre to decimetre thick deposits of so-called Antarctic mumiyo. The distribution, age, and composition of the mumiyo deposits provide information concerning the environmental history at the breeding sites and potentially also on the sea-ice conditions of the adjacent ocean. The paleoenvironmental information concerns the position of marine and lacustrine shorelines, and the extent of glaciers or the ice sheet, since the nests only occur on dry and un-glaciated grounds. Information on the sea-ice history may be provided by biogeochemical proxies to be measured on the mumiyo, however, these proxies still need to be tested. First radiocarbon-dating of mumiyo deposits from mountain ranges in Dronning Maud Land was carried out by Hiller et al. (1995). The results indicated snow petrel occupation during the last glacial, however, with some question marks arising from poor temporal resolution due to the employment of conventional 14C dating only. Here, we present first combined 14C AMS, biomarker and inorganic geochemical data that were obtained on mumiyo deposits from Petermann Range, Dronning Maud Land. The mumyio shows a finely laminated internal structure. 14C ages indicate a consistent age-depth relation spanning from 17 ka to > 58 ka. These data confirm the existence of un-glaciated areas during the Last Glacial Maximum (LGM), as assumed by Hiller et al. (1995), and extend the archive far into Marine Isotope Stage (MIS) 3, which is poorly understood in coastal Antarctica. The biomarker and inorganic composition characterizes the material and has some potential to establish proxies for the environmental conditions at the surface of the adjacent Southern Ocean. Keywords: Mumiyo deposits, Dronning Maud Land, environmental history References Hiller, A., Hermichen, W.D., Wand, U. 1995. Radiocarbon-dated subfossil stomach oil deposits from petrel nesting sites: Novel paleoenvironmental records from continental Antarctica. Radiocarbon 37, 171-18

Determination of Hydrophilic and Amphiphilic Organic Pollutants in the Aquatic Environment

Environmental chemists performing monitoring or process-oriented fate and behavior studies on organic micropollutants face the challenge of having to determine low concentrations of problem compounds in complex mixtures and difficult matrices, such as sewage sludge, surface and groundwater. Selective extraction and enrichment help to overcome sensitivity limitations and also to reduce the number of different species in the sample. A subsequent chromatographic separation step, together with analyte-specific detection, finally allows to identify and quantify single analytes in the presence of other organic material. This article describes a selection of analytical development work carried out at EAWAG for the determination of hydrophilic and amphiphilic organic pollutants in the aquatic environment

Facilitating positive L1 transfer through explicit spelling instruction for EFL learners with dyslexia: An intervention study

There is growing evidence that dyslexia may involve difficulty with implicit learning, which may hinder learners with dyslexia to acquire spelling skills in a foreign language through implicit instruction. Paradoxically, this is exactly how Dutch students with dyslexia learn English spelling at school. This research aims to determine if implementing explicit spelling instruction, based on a direct comparison between L1 Dutch and L2 English spelling, facilitates the development of spelling skills of dyslexic learners in English as a Foreign Language. The participants were 40 Dutch-speaking secondary-school students independently diagnosed with dyslexia (age 12–14). Twenty participants attended their regular English lessons (comparison group), whereas 20 other participants received explicit contrastive spelling instruction once a week for eight weeks (intervention group). The results reveal that during the eight weeks of the intervention spelling skills of the intervention group developed faster than those of the control group, and they remained at the same level five weeks after the intervention. These findings suggest that even a relatively short intervention based on explicit instruction of spelling rules and cross-linguistic comparisons has a facilitative effect on the development of spelling skills of students with dyslexia in a foreign language

Hyvinvointia itsemyötätunnolla ja työtä kehittämällä

Persoonaan kohdistuvat tiedolliset ja taidolliset vaatimukset sekä kilpailullinen (työ)elämä ohjaavat yksilöä neuroottiseen itsen kehittämiseen.Lääkärit osaavat suhtautua potilaisiin ja kollegoihin myötätuntoisesti. Itsemyötätunto sen sijaan on monelle vierasta.Johtamiskoulutukseen osallistuneiden lääkärien kurssivastauksista paljastui huolestuttavaa kuormittuneisuutta.Esiin nousi sekä sisäistettyä vaativuutta että rakenteellisia ongelmia, jotka heikentävät kokonaisvaltaista hyvinvointia.Itsemyötätunto ja työn kehittäminen voivat edistää sekä lääkärien että yhteiskunnan hyvinvointia.</p

First-Line everolimus and cisplatin in patients with advanced extrapulmonary neuroendocrine carcinoma:a nationwide phase 2 single-arm clinical trial

BACKGROUND: Extrapulmonary neuroendocrine carcinoma (EP-NEC) are an aggressive subgroup of neuroendocrine neoplasms (NEN). Advanced EP-NEC is generally treated with platinum-based cytotoxic regimens, but progressive disease occurs rapidly, resulting in a poor prognosis. Genetic alterations in the mammalian target for rapamycin (mTOR) pathway have been identified in NEN, providing a rationale for treatment with the mTOR-inhibitor everolimus. METHODS: A prospective phase 2 single-arm study included patients with advanced EP-NEC from three Dutch NEN expertise centres between March 2016 and January 2020. Treatment consisted of cisplatin 75 mg/m(2) every 3 weeks in combination with daily everolimus 7.5 mg for a maximum of six cycles, followed by maintenance everolimus until disease progression. Primary endpoint was disease control rate (DCR), defined as the sum of overall response rate (ORR) plus the rate of stable disease according to RECIST 1.1, assessed at 9-week intervals. Toxicity was evaluated according to CTCAE version 5.0. RESULTS: Thirty-nine patients, with a median age of 64 years (range: 28–74), of whom 20 (51%) were male, were enrolled. DCR was 82.1% (95% confidence interval (CI): 66.4–92.4), with an ORR of 58.9% (CI: 42.1–74.4). Median duration of response was 6.4 (CI: 5.8–7.0) months and median progression-free survival was 6.0 (CI: 4.3–7.8) months. Three patients (8%) had durable responses lasting  > 12 months. Median overall survival was 8.7 (CI: 7.8–9.6) months. Most common grade 3/4 toxicities were haematological (36%) and renal (21%). CONCLUSION: Everolimus in combination with cisplatin is an effective first-line treatment option for advanced EP-NEC, especially in highly selected patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02695459, https://clinicaltrials.gov/ct2/show/NCT02695459

Bayerisches Modellprojekt eHumanities – interdisziplinär zur Stärkung des Forschungsdatenmanagements in den digitalen Geistes- und Sozialwissenschaften

Das vom Bayerischen Staatsministerium für Wissenschaft und Kunst geförderte Projekt eHumanities – interdisziplinär entwickelt Tools und Best-Practice-Empfehlungen für das Forschungsdatenmanagement in den digitalen Geistes- und Sozialwissenschaften und darüber hinaus. Resultate sind u.a. ein Best-Practice-Guide für das Metadatenschema DataCite, eine aktualisierte und funktional erweiterte Version des DataCite-Metadatengenerators, DMP-Fragenkataloge für RDMO, Schulungs- und Lehrinhalte (z. B. Video-Tutorials, Lernmodule als Open Educational Resources) sowie eine Modellkooperation zwischen Informationsinfrastruktureinrichtungen. In diesem Kontext wurden eine technische Lösung zur Dateneinspeisung und -indexierung in einen Data Discovery Service sowie Best-Practice-Prozessabläufe zur Erschließung und Verfügbarhaltung der Daten geschaffen

Human plasma phospholipid transfer protein increases the antiatherogenic potential of high density lipoproteins in transgenic mice

Plasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoprotein particles and alters high density lipoprotein (HDL) subfraction patterns in vitro, but its physiological function is poorly understood. Transgenic mice that overexpress human PLTP were generated. Compared with wild-type mice, these mice show a 2.5- to 4.5-fold increase in PLTP activity in plasma. This results in a 30% to 40% decrease of plasma levels of HDL cholesterol. Incubation of plasma from transgenic animals at 37 degrees C reveals a 2- to 3-fold increase in the formation of pre-beta-HDL compared with plasma from wild-type mice. Although pre-beta-HDL is normally a minor subfraction of HDL, it is known to be a very efficient acceptor of peripheral cell cholesterol and a key mediator in reverse cholesterol transport. Further experiments show that plasma from transgenic animals is much more efficient in preventing the accumulation of intracellular cholesterol in macrophages than plasma from wild-type mice, despite lower total HDL concentrations. It is concluded that PLTP can act as an antiatherogenic factor preventing cellular cholesterol overload by generation of pre-beta-HDL

Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity

Metformin, the first-line drug to treat type 2 diabetes (T2D), inhibits mitochondrial glycerolphosphate dehydrogenase in the liver to suppress gluconeogenesis. However, the direct target and the underlying mechanisms by which metformin increases glucose uptake in peripheral tissues remain uncharacterized. Lipid phosphatase Src homology 2 domain-containing inositol-5-phosphatase 2 (SHIP2) is upregulated in diabetic rodent models and suppresses insulin signaling by reducing Akt activation, leading to insulin resistance and diminished glucose uptake. Here, we demonstrate that metformin directly binds to and reduces the catalytic activity of the recombinant SHIP2 phosphatase domain in vitro. Metformin inhibits SHIP2 in cultured cells and in skeletal muscle and kidney of db/db mice. In SHIP2-overexpressing myotubes, metformin ameliorates reduced glucose uptake by slowing down glucose transporter 4 endocytosis. SHIP2 overexpression reduces Akt activity and enhances podocyte apoptosis, and both are restored to normal levels by metformin. SHIP2 activity is elevated in glomeruli of patients with T2D receiving nonmetformin medication, but not in patients receiving metformin, compared with people without diabetes. Furthermore, podocyte loss in kidneys of metformin-treated T2D patients is reduced compared with patients receiving nonmetformin medication. Our data unravel a novel molecular mechanism by which metformin enhances glucose uptake and acts renoprotectively by reducing SHIP2 activity.Polianskyte-Prause, Z., Tolvanen, T. A., Lindfors, S., Dumont, V., Van, M., Wang, H., Dash, S. N., Berg, M., Naams, J.-B., Hautala, L. C., Nisen, H., Mirtti, T., Groop, P.-H., Wahala, K., Tienari, J., Lehtonen, S. Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity.Peer reviewe