Introduction 52Mn (t½ =5.59 d, β+ = 29.6%, Eβmax = 0.58 MeV) has great potential as a long lived PET isotope for use in cell tracking studies, observation of immunologic response to disease states, or as an alternative to manganese-based MRI contrast agents. Its favorable max positron energy leads to superb imaging resolution, comparable to that of 18F.[1] Manganese is naturally taken up by cells via a multitude of pathways including the divalent metal transporter (DMT1), ZIP8, transferrin receptors (TfR), store-operated Ca2+ channels (SOC-Ca2+), and ionotropic glutamate receptor Ca2+ channels (GluR).[2] These natural transport mechanisms make 52Mn an attractive isotope for applications necessitating non-perturbative cell uptake. In particular, cell tracking is critical to the development and translation of stem cell therapies in regenerative medicine. Alternative-ly, 52Mn could be used in immunotherapy techniques such as adoptive cellular therapy (ACT) to evaluate the ability of external immune cells to reach their intended target. Material and Methods 52Mn was produced by natCr(p,x)52Mn using 16 MeV protons. The average thick target production yield was 0.23 mCi/µA-h with less than 0.25% co-production of 54Mn. Small amounts of 51Cr were observed in the target, but were absent from the radiochemically separated product. Target construction consisted of a water jet cooled chromium disc (3/4” diameter, 0.4” thick). Targets were purchased from Kamis Inc, and are 99.95% pure. Targets withstood beam currents of 30 µA with no visible aberration. Chromium targets were etched by concentrated HCl following bombardment. Mn2+ ions were extracted from 9M HCl to 0.8M trioctylamine in cyclohexane leaving the bulk chromium in the aqueous phase. After isolating the organic phase, 0.001M NH4OH was used to back-extract the Mn2+ ions to aqueous phase. This purification cycle was conducted a total of three times for each 52Mn production. Results and Conclusion For a starting bulk chromium mass of 456 ± 1 mg, a post-separation chromium mass of 5.35 ± 0.04 ng was measured by microwave plasma atomic emission spectrometry (MP-AES). This mass reduction corresponds to an average separation factor of 440 for a single purification cycle. Each purification cycle had a 52Mn recovery efficiency of 73 ± 7 % (n = 6), resulting in an overall separation efficiency of approximately 35 %. These efficiencies and separation factors agree reasonably well with the work conducted by Lahiri et. al.[3] Prior to use, the product was passed through a C-18 Sep-Pak to remove any residual organic phase. After four target irradiations and etchings, some pitting became noticeable on the target face. These have not yet compromised the o-ring seal with the target deplater, but it is possible that target replacement after every 6–9 52Mn productions will be necessary moving forward. Following the successful separation of 52Mn from chromium, in vitro experiments were conducted to demonstrate the uptake of 52Mn by human stem cells and mouse tumor cells. A linear uptake response was observed as a function of the amount of activity exposed to the cells for both cell models. These experiments have shown great promise for 52Mn as a long-lived PET isotope in cell tracking studies. Details will be presented.

Le présent travail de thèse s’inscrit dans le contexte fondamental de la propulsion marine instationnaire. Il analyse les performances propulsives des profils de différents rapports d’aspects (envergure par rapport à la corde), en oscillation harmonique de tangage. On modélise la principale partie active d’un système propulsif naturel, tel une nageoire caudale de poisson, par des profils simples, minces et rigides quasiment identiques, à l’exception du rapport d’aspect très important du premier profil (4.8), dit bidimensionnel, et très faible du second (1/6), dit tridimensionnel. Le mouvement de tangage est imposé au tiers de corde, en partant du bord d’attaque des profils immergés dans un écoulement. L’objectif étant de faire varier le nombre de Strouhal, basé sur l’amplitude d’excursion totale du bord de fuite du profil, dans une gamme relativement faible et étroite, où évoluent plusieurs espèces aquatiques. Cette gamme est donc intéressante pour l’étude des systèmes propulsifs artificiels. L’aptitude à la propulsion a été déduite en analysant la structure de l’écoulement induit dans le sillage, et en déterminant l’effort réel exercé par le profil sur l’écoulement. En raison des effets importants de la traînée induite associée aux tourbillons marginaux et de ceux de la traînée visqueuse, inversement proportionnelle au rapport d’aspect, il apparait que les performances propulsives du profil tridimensionnel sont bien moindres que celles du profil bidimensionnel. L’influence des configurations du battement sur les performances propulsives a également été étudiée. / This thesis work is part of the fundamental context of unsteady marine propulsion. The propulsive performances of different aspect ratios (span to corde) profiles, in harmonic pitching motion are analyzed. The main active part of a natural propulsion system, such as a fish caudal fin, is modelled by simple, thin and rigid profiles that are almost identical, with the exception of the very high aspect ratio of the first profile (4.8), called two-dimensional, and very low aspect ratio of the second (1/6), called three-dimensional. The pitching motion is imposed on the third corde, starting from the leading edge of the profiles immersed in a flow. The objective is to vary the Strouhal number, based on the total excursion amplitude of the trailing edge of the profile, over a relatively small and narrow range, where several aquatic species evolve. This range is therefore interesting for the study of artificial propulsion systems. The propulsion capability was inferred by analyzing the structure of the induced flow in the wake, and by determining the actual force exerted by the profile on the flow. Due to the significant effects of the induced drag associated with marginal vortices and those of the viscous drag, inversely proportional to the aspect ratio, it appears that the propulsive performance of the three-dimensional profile is much lower than that of the two-dimensional profile. The influence of flapping parameters on propulsive performance has also been studied.

Der Aufbau und die erste Nutzung eines kompakten Flugzeitsystems zur energiedispersiven Untersuchung der Wechselwirkung von schnellen Neutronen mit Materialien sind Inhalt eines Vernetzungsprojektes des Forschungszentrums Rossendorf, an dem auch die Technische Universität Dresden im Rahmen eines gemeinsamen DFG-Projektes mitarbeitet. Die geplanten Flugzeit-Experimente mit gepulsten Neutronen werden an der Strahlungsquelle ELBE durchgeführt werden. Erste Ergebnisse zur Entwicklung eines Neutronen-Produktionstargets werden vorgestellt. Mit Hilfe von Strahlungstransport- und Finite-Elemente-Programmen wurden die Verteilungen der Energiefreisetzung des von der Strahlungsquelle ELBE genutzten Elektronenstrahls und der Temperatur im Neutronen-Radiator sowie die zu erwartenden Teilchenspektren und -flüsse am Messplatz berechnet. Überlegungen zur Entwicklung des Strahlfängers werden diskutiert.

Der Aufbau und die erste Nutzung eines kompakten Flugzeitsystems zur energiedispersiven Untersuchung der Wechselwirkung von schnellen Neutronen mit Materialien sind Inhalt eines Vernetzungsprojektes des Forschungszentrums Rossendorf, an dem auch die Technische Universität Dresden im Rahmen eines gemeinsamen DFG-Projektes mitarbeitet. Die geplanten Flugzeit-Experimente mit gepulsten Neutronen werden an der Strahlungsquelle ELBE durchgeführt werden. Erste Ergebnisse zur Entwicklung eines Neutronen-Produktionstargets werden vorgestellt. Mit Hilfe von Strahlungstransport- und Finite-Elemente-Programmen wurden die Verteilungen der Energiefreisetzung des von der Strahlungsquelle ELBE genutzten Elektronenstrahls und der Temperatur im Neutronen-Radiator sowie die zu erwartenden Teilchenspektren und -flüsse am Messplatz berechnet. Überlegungen zur Entwicklung des Strahlfängers werden diskutiert.

Introduction 52Mn (t½ =5.59 d, β+ = 29.6%, Eβmax = 0.58 MeV) has great potential as a long lived PET isotope for use in cell tracking studies, observation of immunologic response to disease states, or as an alternative to manganese-based MRI contrast agents. Its favorable max positron energy leads to superb imaging resolution, comparable to that of 18F.[1] Manganese is naturally taken up by cells via a multitude of pathways including the divalent metal transporter (DMT1), ZIP8, transferrin receptors (TfR), store-operated Ca2+ channels (SOC-Ca2+), and ionotropic glutamate receptor Ca2+ channels (GluR).[2] These natural transport mechanisms make 52Mn an attractive isotope for applications necessitating non-perturbative cell uptake. In particular, cell tracking is critical to the development and translation of stem cell therapies in regenerative medicine. Alternative-ly, 52Mn could be used in immunotherapy techniques such as adoptive cellular therapy (ACT) to evaluate the ability of external immune cells to reach their intended target. Material and Methods 52Mn was produced by natCr(p,x)52Mn using 16 MeV protons. The average thick target production yield was 0.23 mCi/µA-h with less than 0.25% co-production of 54Mn. Small amounts of 51Cr were observed in the target, but were absent from the radiochemically separated product. Target construction consisted of a water jet cooled chromium disc (3/4” diameter, 0.4” thick). Targets were purchased from Kamis Inc, and are 99.95% pure. Targets withstood beam currents of 30 µA with no visible aberration. Chromium targets were etched by concentrated HCl following bombardment. Mn2+ ions were extracted from 9M HCl to 0.8M trioctylamine in cyclohexane leaving the bulk chromium in the aqueous phase. After isolating the organic phase, 0.001M NH4OH was used to back-extract the Mn2+ ions to aqueous phase. This purification cycle was conducted a total of three times for each 52Mn production. Results and Conclusion For a starting bulk chromium mass of 456 ± 1 mg, a post-separation chromium mass of 5.35 ± 0.04 ng was measured by microwave plasma atomic emission spectrometry (MP-AES). This mass reduction corresponds to an average separation factor of 440 for a single purification cycle. Each purification cycle had a 52Mn recovery efficiency of 73 ± 7 % (n = 6), resulting in an overall separation efficiency of approximately 35 %. These efficiencies and separation factors agree reasonably well with the work conducted by Lahiri et. al.[3] Prior to use, the product was passed through a C-18 Sep-Pak to remove any residual organic phase. After four target irradiations and etchings, some pitting became noticeable on the target face. These have not yet compromised the o-ring seal with the target deplater, but it is possible that target replacement after every 6–9 52Mn productions will be necessary moving forward. Following the successful separation of 52Mn from chromium, in vitro experiments were conducted to demonstrate the uptake of 52Mn by human stem cells and mouse tumor cells. A linear uptake response was observed as a function of the amount of activity exposed to the cells for both cell models. These experiments have shown great promise for 52Mn as a long-lived PET isotope in cell tracking studies. Details will be presented.

Das Themenfeld der Holografie eignet sich hervorragend für einen Aufbau metakonzeptioneller Fähigkeiten seitens der Schülerinnen und Schüler bei der Verwendung verschiedener Lichtmodelle. Zusätzlich gilt es als eines der wenigen Experimente in der gymnasialen Oberstufe als hochgradig motivierend. Diese Dissertation beschäftigt sich daher mit der Übertragung des Maker-Buchs „Hologramme zum Selbermachen“ in einen modernen Physik-Unterricht. Hierbei gliedert sich die Arbeit in drei Kernbereiche: 1) Entwicklung einer schülergerechten und an den Unterricht anknüpfbaren Experimentier-Plattform, 2) Analyse der Eignung des Maker-Buchs für den Unterricht und 3) Entwicklung von Unterrichtsmaterialien, die die Inhalte des Buchs in einen forschenden und schüleraktiven Physik-Unterricht integrieren. Es wird außerdem gezeigt, dass sich das Schema zur Erstellung der Materialien eignet, andere Bände der Buchreihe „1.000 Laser-Hacks für MAKER“ mit geringem Aufwand in die Schule zu übertragen.

Transcription factors (TFs) are ubiquitous gene expression regulators and play essential roles in almost all biological processes. This Ph.D. project is primarily focused on the functional characterisation of MYB112 - a member of the R2R3-MYB TF family from the model plant Arabidopsis thaliana. This gene was selected due to its increased expression during senescence based on previous qRT-PCR expression profiling experiments of 1880 TFs in Arabidopsis leaves at three developmental stages (15 mm leaf, 30 mm leaf and 20% yellowing leaf). MYB112 promoter GUS fusion lines were generated to further investigate the expression pattern of MYB112. Employing transgenic approaches in combination with metabolomics and transcriptomics we demonstrate that MYB112 exerts a major role in regulation of plant flavonoid metabolism. We report enhanced and impaired anthocyanin accumulation in MYB112 overexpressors and MYB112-deficient mutants, respectively. Expression profiling reveals that MYB112 acts as a positive regulator of the transcription factor PAP1 leading to increased anthocyanin biosynthesis, and as a negative regulator of MYB12 and MYB111, which both control flavonol biosynthesis. We also identify MYB112 early responsive genes using a combination of several approaches. These include gene expression profiling (Affymetrix ATH1 micro-arrays and qRT-PCR) and transactivation assays in leaf mesophyll cell protoplasts. We show that MYB112 binds to an 8-bp DNA fragment containing the core sequence (A/T/G)(A/C)CC(A/T)(A/G/T)(A/C)(T/C). By electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation coupled to qPCR (ChIP-qPCR) we demonstrate that MYB112 binds in vitro and in vivo to MYB7 and MYB32 promoters revealing them as direct downstream target genes. MYB TFs were previously reported to play an important role in controlling flavonoid biosynthesis in plants. Many factors acting upstream of the anthocyanin biosynthesis pathway show enhanced expression levels during nitrogen limitation, or elevated sucrose content. In addition to the mentioned conditions, other environmental parameters including salinity or high light stress may trigger anthocyanin accumulation. In contrast to several other MYB TFs affecting anthocyanin biosynthesis pathway genes, MYB112 expression is not controlled by nitrogen limitation, or carbon excess, but rather is stimulated by salinity and high light stress. Thus, MYB112 constitutes a previously uncharacterised regulatory factor that modifies anthocyanin accumulation under conditions of abiotic stress. / Transkriptionsfaktoren (TFs) sind ubiquitäre Regulatoren der Genexpression und spielen eine essentielle Rolle in nahezu allen biologischen Prozessen. Diese Doktorarbeit hat vor allem die funktionelle Charakterisierung von MYB112 zum Thema, einem Mitglied der R2R3-MYB-TF-Familie aus der Modellpflanze Arabidopsis thaliana. Ausgesucht wurde das Gen aufgrund seiner erhöhten Expression in seneszenten Blättern, basierend auf vorangegangenen qRT-PCR Expressions-Profiling Experimenten für 1880 TFs in Arabidopsis Blättern aus drei Entwicklungsstadien (15 mm Blatt, 30 mm Blatt und 20 % vergilbtes Blatt). MYB112-Promotor-GUS-Fusionslinien wurden generiert um das Expressionsmuster von MYB112 detailliert zu untersuchen. Unter Zuhilfenahme transgener Ansätze in Kombination mit Metabolomics und Transcriptomics können wir zeigen, dass MYB112 eine wichtige Rolle in der Regulation des pflanzlichen Flavonoid-Metabolismus spielt. In MYB112 Überexpressoren und MYB112-defizienten Mutanten kommt es zu erhöhter bzw. verminderter Anthocyanin-Akkumulation. Expressions-Profiling zeigt, dass MYB112 einerseits als ein positiver Regulator des Transkriptionsfaktors PAP1 fungiert, was zu einer erhöhten Anthocyanin-Biosynthese führt, andererseits als negativer Regulator von MYB12 und MYB111 auftritt, welche beide die Flavonol-Biosynthese kontrollieren. Wir haben früh auf MYB112 reagierende Gene durch eine Kombination verschiedener Ansätze identifiziert. Diese umfassen Genexpressions-Profiling (Affymetrix ATH1 Microarrays und qRT-PCR) und Transaktivierungs-Experimente in Mesophyll-Protoplasten aus Blättern. Wir zeigen, dass MYB112 an eine 8-bp DNA-Fragment, welches die Kernsequenz (A/T/G)(A/C)CC(A/T)(A/G/T)(A/C)(T/C) aufweist. Mit Hilfe von Electrophoretic Mobility Shift Assay (EMSA) und Chromatin-Immunopräzipitation gekoppelt mit qPCR (ChIP-qPCR) zeigen wir, dass MYB112 in vitro und in vivo an die Promotoren von MYB7 und MYB32 bindet was sie damit als direkte Zielgene von MYB112 identifiziert. Es wurde bereits gezeigt, dass MYB TFs eine wichtige Rolle bei der Kontrolle der Flavonoid-Biosynthese in Pflanzen haben. Viele Faktoren, die oberhalb des Anthocyanin-Biosyntheseweges agieren, werden bei Stickstofflimitierung oder erhöhter Saccharose-Konzentration auch verstärkt exprimiert. Außer den erwähnten Bedingungen können auch andere Umweltparameter, wie z. B. erhöhter Salzgehalt und Starklicht zu erhöhter Expression führen. Im Gegensatz jedoch zu einigen anderen MYB TFs, die einen Einfluss auf Gene des Anthocyanin-Biosyntheseweges ausüben, ist die Expression von MYB112 nicht durch Stickstoff-Limitierung oder Kohlenstoffüberfluss kontrolliert, sondern wird durch erhöhten Salzgehalt sowie Starklicht stimuliert. Somit ist MYB112 ein neuer Regulator, der eine Anthocyanin-Akkumulation unter abiotischen Stressbedingungen kontrolliert.

Physical experiments have a great potential in mathematics lessons. Students can actively discover how mathematical concepts are used. This paper shows results of research done how students got to know the different aspects of the concept of variable by doing simple physical experiments. Further it will be shown what other concepts could be touched by the same treatment.

Physical experiments have a great potential in mathematics lessons. Students can actively discover how mathematical concepts are used. This paper shows results of research done how students got to know the different aspects of the concept of variable by doing simple physical experiments. Further it will be shown what other concepts could be touched by the same treatment.

We live in a time of many challenges. The ‘Great Acceleration’ (Steffen et al., 2015) is a trend that can be observed in numerous fields in our world: be it the development of CO2 emissions, the land use or the enormous amount of produced plastics accompanied by massive environmental pollution. This ‘phenomenon’ is obviously directly linked to the way we live and how our society works. To meet these developments, we need to move away from the big, prone concepts that got us here in the first place, and instead build on a variety of dynamic and changing solutions.