No description available.

This thesis project serves to fill experimental gaps needed to advance the goal of performing pre-clinical trials using an orthotopic rat glioblastoma model to evaluate the efficacy of high-frequency electroporation (H-FIRE) and QUAD-CTX tumor receptor-targeted cytotoxic conjugate therapies, individually and in combination, in selectively and thoroughly treating glioblastoma multiforme. In order to achieve this, an appropriate model must be developed and characterized. I have transduced F98 rat glioma cells to express red-shifted firefly luciferase, which will facilitate longitudinal tumor monitoring in vivo through bioluminescent imaging. I have characterized their response to H-FIRE relative to DI TNC1 rat astrocytes. I have demonstrated the presence of the molecular targets of QUAD in F98 cells. The in vitro characterization of this model has enabled preclinical studies of this promising glioblastoma therapy in an immunocompetent rat model, an important step before advancing ultimately to clinical human trials. / Master of Science / Treating glioblastoma multiforme (GBM), a form of cancer found in the brain, has not been very successful; patients rarely live two years following diagnosis, and there have been no major breakthrough advances in treatment to improve this outlook for decades. We have been working on two treatments which we hope to combine. The first is high-frequency electroporation (H-FIRE), which uses electrical pulses to kill GBM cells while leaving healthy cells alive and blood vessels intact. The second is QUAD-CTX, which combines a toxin with two types of protein that attach to other proteins that are more common on the surface of GBM cells than healthy cells. We have shown these to be effective at disproportionately killing human GBM cells growing in a lab setting. Before H-FIRE and QUAD-CTX may be tested on humans, we need to show them to be effective in an animal model, specifically rats. I have chosen rat glioma cells that will behave similarly to human GBM and a rat species that will not have an immune response to them. I have made these cells bioluminescent so that we may monitor the tumors as they grow and respond to our treatments. I have also shown that QUAD-CTX kills these rat glioma cells, as does H-FIRE. Because of this work, we are ready to begin testing these two treatments in rats.

It is anticipated that massive amounts of energy will be transferred long distances via High-Voltage Direct Current (HVDC) links in the future and the prospect of having meshed HVDC grids is envisioned, for example the European super grid. Such a power system would benefit greatly if HVDC circuit breakers could reliably clear faults within the HVDC network. Different ways to break large direct currents have been proposed throughout the years and one distinguished concept is based on generating an artificial zero-crossing of the current and pass it through a mechanical interrupter as it opens. This concept is implemented in the Voltage-Source Converter Assisted Resonant Current (VARC) circuit breakers developed at Scibreak which require auxiliary power from an off-line supply unit to energize their electronic equipment. This thesis continuous and builds on research previously carried out at Scibreak on a special Auxiliary Power Supply (APS) concept for 525 kV HVDC applications. In essence, it is a unique modularized high-frequency transformer whose power transfer and voltage withstand capabilities are the cornerstones of its design. The APS must supply an adequate amount of power to drive the VARC circuit breakers with preferably high efficiency while also fulfilling the considerable insulation demands of HVDC grids. A feasibility study of this APS concept was carried out by building a parametric 3D model in the Finite Element Analysis (FEA) software Ansys Maxwell which includes all parts that affect both its magnetic and electrical properties. The initial model reproduced experimental results from a magnetic APS prototype and was then used to explore a plethora of different geometries and materials with regards to its magnetic and dielectric designs. Specific design candidates were selected for more in-depth analysis and experimental work. All obtained results together with knowledge of commercially available materials show that the APS holds great promise to meet the necessary design criteria for its HVDC applications. Its dielectric design is well suited to continuously handle an operating voltage of 525 kV DC, meet the required impulse voltage levels of the grid and properly shield the magnetic structure. It is expected to have a long life time where the design criterion was always 30 years in this work. Moreover, its magnetic design is anticipated to supply a few kW of active power with efficiencies between 80 to 95 percent and manage a continuous operating time of 5 min. Both design aspects are interchangeable to a decent extent in order to cope with one another and produce a compromised design. / Det förväntas att enorma mängder energi kommer överföras långa sträckor med Högspänd Likström (HVDC) i framtiden och blivande HVDC-nät håller på att föreställas, till exempel det europeiska superelnätet. Ett sådant kraftsystem skulle ha stor nytta av HVDC-brytare som tillförlitligt kan bryta felströmmar inom HVDC-nätet. Olika sätt att bryta stora likströmmar har föreslagits med åren och ett distinkt koncept bygger på att generera en artificiell nollgenomgång av strömmen och föra den genom en mekanisk brytarkammare när den öppnas. Detta koncept är implementerat i de så kallade VARC-strömbrytarna som utvecklas hos Scibreak, vilka kräver hjälpmatning av effekt från en extern försörjningsenhet för att driva deras elektroniska utrustning. Denna avhandling fortsätter och bygger vidare på forskning som tidigare utförts hos Scibreak på ett speciellt Hjälpmatningskoncept (APS) för 525 kV HVDC-tillämpningar. I huvudsak är det en unik modulariserad högfrekvenstransformator vars kraftöverföring och spänningståligheter är huvudfokusen i dess design. Hjälpmatningen måste kunna leverera en tillräcklig mängd effekt för att driva VARC-brytarna med företrädesvis hög verkningsgrad, samtidigt som den ska uppfylla de betydande isolationskraven för HVDC-nät. En genomförbarhetsstudie av detta APS-koncept gjordes genom att bygga en parametrisk 3D modell i Finita Elementmetodsprogramvaran (FEM) Ansys Maxwell som inkluderar alla delar som påverkar både dess magnetiska och elektriska egenskaper. Den initiala modellen reproducerade experimentella resultat från en magnetisk APS-prototyp och användes sedan för att utforska en uppsjö av olika geometrier och material med avseende på dess magnetiska och dielektriska konstruktioner. Specifika designkandidater valdes ut för mer djupgående analys och experimentiellt arbete. Alla erhållna resultat tillsammans med kunskap om kommersiellt tillgängliga material visar att APS:n har stora möjligheter att uppfylla alla nödvändiga kriterier för sina HVDC-tillämpningar. Dess dielektriska design är väl lämpad för att kontinuerligt hantera en driftspänning på 525 kV DC, möta de erforderliga stötspänningståligheterna i nätet och ordentligt skydda den magnetiska strukturen. Den förväntas ha en lång livstid där designkriteriet alltid var 30 år i detta arbete. Dessutom förväntas dess magnetiska design leverera några kW aktiv effekt med verkningsgrader mellan 80 till 95 procent och klara en kontinuerlig drifttid på 5 min. Båda designaspekterna kan justeras i en någorlunda utsträckning för möta de krav som ställs från varandra och producera en kompromissad design.

Artificial breathing is vital when it comes to treatment of critically ill patients where the natural breathing mechanism is insufficient. With the help of mechanical ventilators, the natural breathing mechanism of the patient can be assisted or even exchanged with the artificial breathing from the machine. Small errors and unexpected events in these systems may lead to serious damages on the patients, causing even more harm than good. Therefore, these systems require a lot of testing and monitoring to ensure functionality. With the use of accurate simulation models, testing time can be reduced by running test in the simulation environment instead of on the actual machine. The simulation models can also be used for monitoring functions in real time, making sure the ventilation of the patient is working as expected. When it comes to simulating a ventilator system controlled with high frequency ventilation techniques, the existing simulation models fail to reproduce the high frequency dynamics that appear during high frequency ventilation. This paper proposes a modelling approach for mechanical ventilator systems exposed to high frequency dynamics. Focus is placed on modeling the patient circuit including the inspiratory and expiratory tubes, the humidifier with the dry line tube, the Y-piece, the tracheal tube and the patient lungs. The model is based on mathematical models representing the thermodynamic and pneumatic behaviour of the system. It is built using Simulink with regular and customized building blocks from Simscape. Compared to pre-existing simulation models, this model includes the inertia effects of the gas which is crucial when it comes to accurately modeling the system while being exposed to fast changes in flow and pressure. To evaluate the model performance, the simulated pressure and flow at the patient port are compared to measured data from an experimental setup. From the results of this thesis it was seen that the model is very sensitive to the patient model used in the simulation environment, which means that the patient model has to be remodeled in order to archive a better model performance. Compared to the pre-existing model used for comparison in this thesis, it is seen that an increased parameter model produces more accurate results. / Konstgjord andning är livsavgörande när det kommer till behandling av kritiskt sjuka patienter där den naturliga andningsmekanismen inte fungerar som den ska. Med hjälp av mekanisk ventilation kan den naturliga andningsmekanismen hos patienten assisteras eller helt ersättas av denna konstgjorda andning. Små fel eller oväntade händelser i dessa system kan vara livsfarliga för patienten och kan orsaka mer skada än nytta. Detta gör att dessa system kräver mycket testning och övervakning för att säkerställa att allt fungerar som tänkt. Med hjälp av noggranna simuleringsmodeller kan testtiden minskas samtidigt som dessa simuleringsmodeller kan användas för övervakning av systemet i realtid, detta för att säkerställa systemets funktion. När det kommer till simulering av ventilatorsystem som ventileras med högfrekventa ventilationstekniker, misslyckas de befintliga simuleringsmodellerna att återskapa den högfrekventa dynamik som uppstår under högfrekvent ventilation. Denna uppsatts föreslår en modelleringsmetod för att kunna modellera mekaniska ventilatorsystem som utsätts för högfrekvent dynamik. Fokus för projektet har varit att modellera patientkretsen inklusive inandnings- och utandningsslangarna, luftfuktaren med torrlinjeslangen, Y-kopplingen, trakealtuben och patientens lungor. Modellen är baserad på matematiska modeller som representerar systemets termodynamiska och pneumatiska beteende. Den är byggd i Simulink med existerande och anpassade block från Simscape. Jämfört med redan existerande simuleringsmodeller inkluderar denna modell gasens tröghetseffekter, vilket är avgörande när det gäller att noggrant modellera systemet samtidigt som det utsätts för snabba förändringar i flöde och tryck. För att utvärdera modellens prestanda jämförs det simulerade trycket och flödet vid patientporten med uppmätta data från en experimentell uppställning i labbmiljö. Resultaten från detta projekt visar att modellen är väldigt känslig för patientmodellen som används i simuleringsmiljön, vilket innebär att patientmodellen måste rekonstrueras för att uppnå en bättre prestanda för modellen. Jämfört med den redan existerande modellen som används för jämförelse i denna avhandling, syns det att en ökad parametermodell ger ett resultat närmare de uppmätta signalerna från det verkliga systemet.

In recent years, advancements in additive manufacturing (AM) technologies have paved the way for 3D-printed flexible hybrid electronics (FHE) and created opportunities for extending these gains to RF applications. However, printed metal interconnects and devices are typically characterized by high porosity and chemical impurities that significantly limit their electrical conductivity and RF performance compared to bulk equivalents. Using direct ink writing (DIW), two silver inks, a nanoflake suspension and a nanoparticle-reactive ink, were investigated to understand the relationship between free interfacial energy, sintering behavior, DC conductivity, and RF loss. The printed silver samples were characterized using scanning electron microscopy, x-ray diffraction, and x-ray photoelectron spectroscopy to monitor microstructural evolution, grain size and orientation, and chemical purity as a function of heat treatment temperature. Three heat treatments were applied to each ink: the manufacturer's recommendation, 225°C for 30 minutes, and 350°C for 30 minutes. Four-wire structures and coplanar waveguides were printed to compare the DC and RF performance up to 18 GHz, respectively. The results show that ink formulations that facilitate larger grains, high density, and good chemical purity have superior RF performance. A low resistivity of 1.4 times bulk Ag, average of 0.8% greater RF loss factor than evaporated Ag, and a maximum current density of 4.6 x 105 A/cm2 were achieved with printed structures. This work highlights the importance of engineering a high density and high purity microstructure in printed silver components necessary for high-performance printed electronics.

No description available.

No description available.

No description available.

No description available.

No description available.