Scientific Preparations for Lunar Exploration with the European Lunar Lander

This paper discusses the scientific objectives for the ESA Lunar Lander Mission, which emphasise human exploration preparatory science and introduces the model scientific payload considered as part of the on-going mission studies, in advance of a formal instrument selection.Comment: Accepted for Publication in Planetary and Space Science 51 pages, 8 figures, 1 tabl

Proteolytic processing of the Alzheimer APP protein family during neuronal differentiation

Increased amyloid-β (Aβ) load in the brain, neurite degeneration, neuronal loss, and decreased levels of several neurotrophins are among the characteristics of Alzheimer’s disease (AD). Generation of Aβ occurs when the amyloid precursor protein (APP) is proteolytically processed by β- and γ-secretases in the amyloidogenic pathway. However, Aβ formation is prevented if APP is cleaved by α- and γ- secretases in the non-amyloidogenic pathway. The normal function of APP is still not fully known. It seems clear that the different fragments that are produced during proteolytic processing have different bioactive properties. APP and its metabolites have been implicated in neurite outgrowth, synaptogenesis, cell adhesion, neuroprotection and apoptosis. The aim of this thesis was to investigate how neurotrophic factors affect the synthesis and processing of APP and its two mammalian paralogues the APP-like protein-1 and-2 (APLP1 and APLP2). We also wanted to determine how the expression levels of α- and β- secretases were affected in response to these factors. In addition, we wanted to analyze if the levels and function of the most well characterized APP adaptor protein, Fe65, was regulated during neuronal differentiation. Our results show that retinoic acid (RA), insulin-like growth factor-1 (IGF-1), and brain derived neurotrophic factor (BDNF) all regulate expression levels and processing of the APP protein family. Interestingly, the increased processing of the APP family involves different signaling pathways. The PI3-K/Akt pathway is involved in IGF-1-induced APP and APLP1, but not APLP2, processing. In addition, RA-induced expression of the α-secretase, a disintegrin and metalloproteinase (ADAM) 10 is dependent on PI3-K, whereas PKC is involved in RA-induced expression of another α-secretase, ADAM17/TACE. Furthermore, we present evidence that maturation of the adaptor protein Fe65, as well as its docking to APP, increases concomitant with neuronal differentiation.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript

Proteolytic processing of the Alzheimer APP protein family during neuronal differentiation

Increased amyloid-β (Aβ) load in the brain, neurite degeneration, neuronal loss, and decreased levels of several neurotrophins are among the characteristics of Alzheimer’s disease (AD). Generation of Aβ occurs when the amyloid precursor protein (APP) is proteolytically processed by β- and γ-secretases in the amyloidogenic pathway. However, Aβ formation is prevented if APP is cleaved by α- and γ- secretases in the non-amyloidogenic pathway. The normal function of APP is still not fully known. It seems clear that the different fragments that are produced during proteolytic processing have different bioactive properties. APP and its metabolites have been implicated in neurite outgrowth, synaptogenesis, cell adhesion, neuroprotection and apoptosis. The aim of this thesis was to investigate how neurotrophic factors affect the synthesis and processing of APP and its two mammalian paralogues the APP-like protein-1 and-2 (APLP1 and APLP2). We also wanted to determine how the expression levels of α- and β- secretases were affected in response to these factors. In addition, we wanted to analyze if the levels and function of the most well characterized APP adaptor protein, Fe65, was regulated during neuronal differentiation. Our results show that retinoic acid (RA), insulin-like growth factor-1 (IGF-1), and brain derived neurotrophic factor (BDNF) all regulate expression levels and processing of the APP protein family. Interestingly, the increased processing of the APP family involves different signaling pathways. The PI3-K/Akt pathway is involved in IGF-1-induced APP and APLP1, but not APLP2, processing. In addition, RA-induced expression of the α-secretase, a disintegrin and metalloproteinase (ADAM) 10 is dependent on PI3-K, whereas PKC is involved in RA-induced expression of another α-secretase, ADAM17/TACE. Furthermore, we present evidence that maturation of the adaptor protein Fe65, as well as its docking to APP, increases concomitant with neuronal differentiation.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript

Svårtolkade spår efter en metallurgisk process: - et danskt exempel och dess paralleller i omvärlden

I samband med 1986 års utgrävningar av Nicolajgade 8 i Ribe, framkom ett antal fragment vitrifierad lera med invändiga avtryck. Dessa passade inte in bland de andra föremålen från bronsgjutarens arsenal utan stod utan förklaring. I samband med utgrävningarna på Birka 1990-1995 framkom ca 6000 fragment av likadan art. Dessa fragment och den metallurgiska process de representerar kommer att presenteras i denna artikel. Jämförelserna med Birkamaterialet kommer, utom då anges, att vara genomgående i texten

The cytotoxic effect of nanparticles delivered to the periphery of 3-dimensional tumor models

To deliver chemotherapeutic drugs to tumors, a drug delivery vehicle should overcome several challenges. The vehicle should stably retain the drug until it reaches tumor tissues and release the drug upon arrival at the target tissues. A nanoparticle (NP) that conditionally releases anticancer drug doxorubicin (DOX) was developed. This NP, referred to as PAMAM-SS-DOX or PAMAM-SS-NAC-DOX, consists of cationic polyamidoamine (PAMAM) dendrimer conjugated to DOX via a disulfide bond. The cationic charge allows NP interaction with negatively charged cells and the disulfide bond allows conditional, intracellular release of DOX via glutathione (GSH). In cases where chemotherapeutic drug delivery systems have been delivered to the tumor site in vivo, it is largely unknown or difficult to assess how NP intratumoral distribution affects NP cellular uptake and any subsequent cytotoxicity in tumors. Consequently, 3-dimensional (3D) tumor models were developed as tools for the evaluation of drug delivery system efficacy in vitro, in order to implement more effective NP chemotherapy in vivo. Consisting of human ovarian tumor cells (SKOV-3), “cells in collagen” and “cells in spheroid” 3D tumor models were developed to simulate common physiological barriers (the presence of extracellular matrix and high cell density, respectively) encountered by NP drug delivery systems after extravasation to the tumor site. The cytotoxicity of cisplatin (CDDP) and hyaluronic acid (HA) NPs carrying platinum (Pt-HA NPs) was investigated in both “cells in collagen” and “cells in spheroid” tumor models

The Underlying Pedagogy of Online Instruction

As part of a three-pronged exploratory study examined online faculty’s perception of the most valued pedagogical elements modality support effective online teaching and learning. Results from faculty focus groups revealed a number of key themes: Personalization, Faculty Efficiency, Instructor Presence, Making Connections, Immediacy and Content Development. Presentation will review the results of the focus groups and provide research-driven recommendations for maximizing instructor efficiency AND effectiveness while incorporating unique pedagogical elements