Process development for a flexible vaccine vector platform based on recombinant life virus

Vaccines are one of the most important, safe and efficient interventions to protect people from illness, disability and death. In recent years several new viral outbreaks where no vaccines are currently available were reported worldwide. Therefore, the development of flexible processes for the production of vaccines is urgently needed. This project aims at developing a platform process for the production of different viral vaccines. The core technology is based on the fact that large recombinant genes coding for selected, foreign antigens can be inserted into the genome of a well-established virus vaccination vector. The vaccine delivers the selected antigens directly to macrophages and dendritic cells, the most potent and effective antigen-presenting cells, thereby triggering a specific immune response to the selected antigens. As a replicating vector, the vaccine continuously expresses antigens even after immunization. This setup results in a powerful, antigen-focused immune response, which is expected to confer long-term immunity. The challenges in production process design for such a vaccine are the establishment of a robust cell expansion and infection strategy as well the development of efficient downstream processing methods including several chromatography principals, ultra-diafiltration and employment of bio recognition principles. The implementation of a meaningful monitoring/characterization concept furthermore serves as a basis for reliable in-process control strategies

Does obesity affect acetabular cup position, spinopelvic function and sagittal spinal alignment? A prospective investigation with standing and sitting assessment of primary hip arthroplasty patients

Background: Total hip arthroplasty (THA) instability is influenced by acetabular component positioning, spinopelvic function and sagittal spinal alignment. Obesity is considered as a risk factor of THA instability, but the causal relationship remains unknown. This study aimed to investigate the influence of BMI on (1) spinopelvic function (lumbar flexibility, pelvic mobility and hip motion), (2) sagittal spinal alignment pre- and postoperatively and (3) acetabular cup position postoperatively in primary THA patients in a prospective setting. Methods: One hundred ninety patients receiving primary total hip arthroplasty were enrolled in a prospective cohort study and retrospectively analysed. All patients received stereoradiography (EOS) in standing and relaxed sitting position pre-and postoperatively. C7-sagittal vertical axis (C7-SVA), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), anterior plane pelvic tilt (APPT), and pelvic femoral angle (PFA) were assessed. Key parameters of the spinopelvic function were defined as lumbar flexibility ( increment LL = LLstanding - LLsitting), pelvic mobility ( increment PT = PTstanding - PTsitting) and hip motion ( increment PFA = PFA(standing) - PFA(sitting)). Pelvic mobility was further defined based on increment PT as stiff, normal and hypermobile ( increment PT 30 degrees). The patients were stratified to BMI according to WHO definition: normal BMI >= 18.5-24.9 kg/m(2) (n = 68), overweight >= 25.0-29.9 kg/m(2) (n = 81) and obese >= 30-39.9 kg/m(2) (n = 41). Post-hoc analysis according to Hochberg's GT2 was applied to determine differences between BMI groups. Results: Standing cup inclination was significant higher in the obese group compared to the normal BMI group (45.3 degrees vs. 40.1 degrees; p = 0.015) whereas standing cup anteversion was significantly decreased (22.0 degrees vs. 25.3 degrees; p = 0.011). There were no significant differences for spinopelvic function key parameter lumbar flexibility ( increment LL), pelvic mobility ( increment PT) and hip motion ( increment PFA) in relation to BMI stratified groups. The obese group demonstrated significant enhanced pelvic retroversion compared to the normal BMI group (APPT - 1.8 degrees vs. 2.4 degrees; p = 0.028). The preoperative proportion of stiff pelvic mobility was decreased in the obese group (12.2%) compared to normal (25.0%) and overweight (27.2%) groups. Spinal sagittal alignment in C7-SVA and PI-LL mismatch demonstrated significantly greater imbalance in the obese group compared to the normal BMI group (68.6 mm vs. 42.6 mm, p = 0.002 and 7.7 degrees vs. 1.2 degrees, p = 0.032, respectively) The proportion of patients with imbalanced C7-SVA was higher in the obese (58.5%) than in the normal BMI group (44.1%). Conclusions: The significantly increased spinal sagittal imbalance with altered pelvic mechanics is a potential cause for the reported increased risk of THA dislocations in obese patients. Consequently, the increased spinal sagittal imbalance in combination with normal pelvic mobility need to be taken into account when performing THA in obese patients

Oxides in aqueous solution: stability and activity at the atomic scale

In dieser Dissertation wurden mithilfe oberflächenphysikalischer und elektrochemischer Methoden Metalloxide in wässriger Lösung untersucht. Die Stabilität und Aktivität von Modellsystemen wurde auf atomarer Ebene behandelt. Der Fokus lag insbesondere auf Rastersondenmikroskopie unter Umgebungsdruck und in Flüssigkeit. Einkristalline Oberflächen wurden im Ultrahochvakuum (UHV) präpariert und mit Rastertunnelmikroskopie (engl. Scanning Tunneling Microscopy, STM), Niederenergetischer Elektronenbeugung (engl. Low Energy Electron Diffraction, LEED), Röntgenphotoelektronenspektroskopie (engl. X-Ray Photoelectron Spectroscopy, XPS) und niederenergetischer Ionenstreuung charakterisiert. In flüssigen Elektrolyten wurden die elektrochemischen Eigenschaften der Einkristalloberflächen mit zyklischer Voltammetrie und elektrochemischer Impedanzspektroskopie und ihre atomare Struktur mit elektrochemischer Rastertunnelmikroskopie untersucht. Nach den elektrochemischen Messungen wurden die Oberflächen bei Umgebungsbedingungen mit Rasterkraftmikroskopie und im UHV mit STM, LEED und XPS charakterisiert.Dabei wurden Proben mit zunehmender Komplexität und technologischer Relevanz herangezogen. Eingangs wurde die potentialabhägige Adsorption von Iodionen auf der Edelmetalloberfläche Au(111), in saurer Lösung untersucht. Weitere Stabilitätsuntersuchungen in saurer Lösung erfolgten auf den Oberflächen von isolierendem, zweidimensionalem hexagonalen Bornitirid, gewachsen auf Rh(111) und einem Oxid mit breiter Bandlücke, Titandioxid TiO2 (110). Ferner zeigte sich, dass die (001) und (110) Oberflächen von Magnetit Fe3O4, einem metallischen Eisenoxid, in neutraler bis stark alkalischer Lösung stabil sind. Weiters ist die Stabilität dieser Oberflächen auch während Elektrolyse in alkalischer Lösung als Anodenmaterial gegeben. Die Aktivität der unterschiedlichen atomaren Strukturen wurde verglichen. Aufbauend auf diesen Erkenntnissen wurde nickeldotiertes Fe3O4 (001) als Modellsystem für die Sauerstoffevolution in alkalischer Lösung untersucht.Die Auflösung von Wolfram in wässriger Lösung und die darauffolgende Adsorption von hydratisiertem Wolframoxid wurde auf allen oben erwähnten Einkristalloberflächen festgestellt. Als STM-Spitzenmaterial, alternativ zu Wolfram, werden Platiniridiumlegierung und reines Iridium vorgeschlagen.This thesis is an electrochemical surface science study of oxides in aqueous solution. Stability and activity of model systems is studied at the atomic scale, with a focus on scanning probe microscopy in ambient atmosphere and liquid.Single crystal surfaces are prepared in ultra high vacuum and characterised with scanning tunneling microscopy (STM), low-energy electron diffraction (LEED), X- ray photoelectron spectroscopy (XPS) and low-energy ion spectroscopy (LEIS). Elec- trochemical methods include cyclic voltammetry (CV) and impedance spectroscopy. Stability in liquid electrolyte is studied with electrochemical STM (EC-STM). The surfaces are post characterised by atomic force microscopy (AFM) at ambient conditions and STM, LEED and XPS in UHV.Complexity and technological relevance of the studied model systems is continu- ously increased with time and learning curve. The potential dependent adsorption of iodine adsorbed on nobel metal Au(111) surfaces is studied in acidic solution. Further stability measurements in acidic solution include two-dimensional hexagonal boron nitride grown on Rh(111) and wide-band gap semiconductor oxide TiO2(110). Metallic iron oxide magnetite Fe3O4 single crystal surfaces (001) and (111) are shown to be stable from neutral to alkaline solutions. Based on this findings, Fe3O4(001) doped with Ni is used as a model system for the oxygen evolution reaction (OER) in alkaline media.Tungsten dissolution and subsequent hydrated tungsten oxide adsorption is stud- ied on all of the studied single crystal surfaces and alternatives for the use of tungsten tips are presented, including PtIr alloys and pure Ir as tip material.18

Hydrogen and Heat Storage in Metal Hydrides

Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in engl. SpracheDie Energiewende hin zu einer kohlenstofffreien Energieversorgung ist in vieler Hinsicht wünschenswert. Die Energieumwandlung von Sonnenenergie mit Photovoltaik und Windkraftwerken in elektrische Energie hat zwar das Potential, unseren Energiebedarf zu decken,doch macht die oft nicht bedarfsgerechte Produktion die Bereitstellung großer Energiespeicher erforderlich. Die elektrolytische Spaltung von Wasser und anschließende Speicherung chemischer Energie in Form von Wasserstoff bietet dieses Potential. Die große Herausforderung bei der Speicherung von Wasserstoff ist dessen geringe Dichte. Mit 0.0899 kg pro Kubikmeter bei 273 K und Atmosphärendruck ist er das Element mit der geringsten volumetrischen Dichte im Periodensystem. Um die starken intermolekularen Abstoßungskräfte zu überwinden, können die Wasserstoffatome in Metallhydridgittern eingelagert und so hohe volumetrische Dichten erzielt werden. Die Bildung von Metallhydriden ist exotherm. Die dabei freiwerdende Wärme bei Absorption muss dann bei Desorption wieder zugeführt werden. So können Metallhydride auch als Wärmespeicher Verwendung finden und durch Kopplung von Hydriden mit verschiedener Charakteristik Kombinationsspeicher als Wärmepumpen oder auch Kältemaschinen betrieben werden. In dieser Arbeit soll das Potential der gleichzeitigen Speicherung von Wasserstoff und Wärme in Metallhydriden für stationäre und mobile Anwendungen untersucht werden. Weiters werden Verbesserungspotentiale in der Wärmeübertragung und Kinetik von Metallhydridsystemen anhand eines Versuchsaufbaus von miteinander gekoppelten Metallhydridbetten untersucht. Der geplante Aufbau konnte großteils fertiggestellt werden. Weitere Arbeiten sind aber noch notwendig und werden in Folgearbeiten durchgeführt. Weiters wird der Betankungsvorgang für zwei ausgewählte Hydride simuliert. Verschiedene Speichertechnologien werden miteinander verglichen, um so das Potential der Metallhydridtechnologie aufzuzeigen. Abschließend wird ein Ausblick in die Entwicklung der elektrolytischen Wasserstoffproduktion gegeben.The energy transition towards a carbon free energy supply is in many ways desirable. The conversion of solar energy by photovoltaics and wind turbines into electric energy has the potential to meet our energy needs. Since production and demand differ in time and quantity the storage of great amounts of energy is necessary. The electrolytic conversion into chemical energy and the subsequent storage of hydrogen has this potential. The big challenge in the storage of hydrogen is its low density. With 0.0899 kg per cubic meter at 273 K and atmospheric pressure, it is the element with the lowest volumetric density in the periodic system. To overcome the strong intermolecular repulsion forces, hydrogen atoms can be absorbed in metal hydride lattices. Thus high volumetric densities can be obtained. The formation of metal hydrides is exothermic. The released heat during the absorption process must be fed back during the desorption process. Therefore metal hydrides can also be used as heat storage materials. By coupling different hydride beds through hydrogen as working media heat pumps and chillers can be built. In this thesis, the potential of the simultaneous storage of hydrogen and heat for stationary and mobile applications will be investigated. On the basis of an experimental assembly of two linked hydride beds improvement potential in the reaction kinetics and conduction of heat is examined. For the most part the proposed structure could be completed. However, further work is still necessary and is carried out in follow-up work. Furthermore the refuelling for two selected hydrides is simulated. Various storage technologies are compared to show the potential of metal hydrides. Finally an outlook on the development of electrolytic hydrogen production is given.11

Einfluss des Timings von Informationen in Agency-Modellen

Diese Masterarbeit beschreibt anhand von diversen Agency-Modellen mit unterschiedlichen Zeitpunkten eines Informationsauftritts den Einfluss des Timings von Informationen in Agency-Modellen. Es werden stets einperiodige Agency-Modelle mit nur einem Agenten und einer auszuführenden Aktion betrachtet und dabei die Möglichkeit von Neuverhandlungen zwischen den Vertragspartnern vernachlässigt. Der Zeitpunkt des Empfangs eines Signals, welches Informationen liefert, ändert sich in den jeweiligen Modellen. Hier wird zwischen pre-contract information, ex ante information und ex post information unterschieden und dabei verschiedene Beobachtbarkeit des Signals unterstellt. Diese kann sowohl in Form von public information als auch in Form von private information im Verlauf des Agency-Konflikts verfügbar werden. Modellstrukturen bei private information werden unter Berücksichtigung von Kommunikation zwischen den Vertragspartnern untersucht, um möglichst alle Einflussnahmen der Information darstellen zu können. Im Rahmen der Modellanalysen können differenzierte Auswirkungen der Information beobachtet werden. Diese lassen sich eindeutig auf das Timing der Information zurückführen. Die Informationen beeinflussen in den betrachteten Modellen, abhängig vom Zeitpunkt ihres Auftretens, die Produktivität des Agenten, die Anreize des Agenten sowie die Leistungsbeurteilung. Auf Grund der verschiedenen möglichen Einflussnahmen der Informationen wird auch der Wert der Information durch das Timing der Information bestimmt. Daher ist das Timing von Informationen ein entscheidender Faktor in Agency-Modellen, welcher sowohl die Annahmen des Modells als auch das Ergebnis des Modells beeinflusst.This master thesis describes the impact of the timing of information in agency models. Therefore, several agency models with different timing of information receive are analysed. Those models share the same assumptions. They all have in common, that there is only one period, one agent and a single task. Furthermore, possibilities for renegotiation are excluded. The timing of a signal, which reveals information, is alternated in the observed models. It is distinguished between pre-contract information; ex ante information and ex post information and different observability of the signal is assumed. The signal can be either private information or public information. Models with private information are based upon communication between the principal and the agent. This is done in order to demonstrate a broad variety of different effects of information. In the process of the model analysis different effects of information are observed. Those effects are connected to the timing of information. Information can influence the productivity of an agent, the incentives of an agent and performance evaluation. Therefore, also the value of information is derived by the timing. Consequently, the timing of information is a critical factor in an agency model, which affects the assumptions and results of an agency model.Matthias MüllnerZusammenfassungen in Deutsch und EnglischAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinKarl-Franzens-Universität Graz, Masterarbeit, 2018(VLID)294590

Metal Underpotential Deposition to Quantify Defects in 2D Materials

We demonstrate how metal UPD may find use as a general tool to determine the collective defect area in hybrids between 2D materials (graphene, hexagonal boron nitride, etc.) and various substrate metals. By investigating copper UPD on a monolayer of hexagonal boron nitride (h-BN) on Rh(111), we explore how this process can be used to quantify the defects in the h-BN monolayer which form during its chemical vapor deposition. In addition, the UPD signature allows assessing the potential window of the h-BN/metal hybrid, which is important to explore its functionality under ambient and electrochemical conditions. Importantly, UPD itself does not alter the defect area on repeated cycling. Overpotential deposition, on the other hand, is shown to have significant consequences on the defect area. We show that this non-innocent Cu electrodeposition involves intercalation originating at initial defects, causing irreversible delamination of the h-BN layer; this effect therefore may be used for 2D material nanoengineering

Fluoride-free wet-chemical preparation of oxide single crystal surfaces:66th Annual Meeting of the Austrian Physical Society

The ultimate goal to perform surface science studies under technologically relevant conditions includes wet-chemical methods to prepare well-defined oxide surfaces [1]. The most widely practised approach is hydrofluoric acid etching, even though this chemical poses serious health risks and may inadvertently dope the surface with fluorine, an efficient electron donor [2]. Here, we present a rational yet versatile wet-chemical alternative to lengthy sputtering–annealing cycles in ultrahigh vacuum for preparing single crystal oxide samples for surface science investigations. The method does not require hydrofluoric acid, is environmentally benign and is demonstrated on rutile TiO2 (110), rutile TiO2 (011) and SrTiO3 (100), but may have much wider application potential, also for surfaces that are quickly destroyed by acids. The procedure consists of (i) ultrasonication in the presence of a dispersing agent to remove polishing debris; (ii) thermal annealing to produce equilibrium-shaped steps and terraces determined by the crystal miscut; and (iii) oxidative cleaning in an alkaline mixture to remove adsorbed organic contaminants from the surface. Each of the steps is optimised based on AFM and characterisation in ultrahigh vacuum, including by LEED and XPS. Following this wet-chemical preparation, we demonstrate atomically resolved electrochemical scanning tunnelling microscopy on TiO2 (110), on a sample that was never treated by sputtering–annealing