The discovery of carbon nanotubes by Iijima in 1991 has created a torrent of new research activities. Research on carbon nanotubes ranges from studying their fundamental properties, such as their electron band structure and plasma frequencies, to developing new applications, such as self-assembled nano-circuits and field emission displays. Robust models are now needed to enable a better understanding of the electronic response of carbon nanotubes. We use time-dependent density functional theory to derive a two-fluid two-dimensional (2D) hydrodynamic model describing the collective response of a multiwalled carbon nanotube with dielectric media embedded inside or surrounding the nanotube. We study plasmon hybridization of the nanotube system in the UV range, the stopping force for ion channelling, the dynamical image potential for fast ions, channelled diclusters and point dipoles, and the energy loss for ions with oblique trajectories. Comparisons are made of results obtained from the 2D hydrodynamic model with those obtained from an extension of the 3D Kitagawa model to cylindrical geometries.

Negative Poisson’s ratio, or auxetic, materials present the possibility of designing structures and components with tailored or enhanced mechanical properties. This thesis explores the phenomenon of auxetic behaviour in cubic crystals using classical and quantum modelling techniques and assesses the validity of these techniques when predicting auxetic behaviour in cubic elemental metals. These techniques are then used to explore the mechanism of this behaviour. The findings of the atomistic modelling are then used as a template to create networks of bending beams with tailored Poisson’s ratio behaviour.

Real-Time Strategy (RTS) is a sub-genre of strategy games which is running in real-time, typically in a war setting. The player use workers to gather resources, which in turn is used for creating new buildings, training combat units and build upgrades and research. The game is won when all buildings of the opponents have been destroyed. The numerous tasks that need to be handled in real-time can be very demanding for a player. Computer players (bots) for RTS games face the same challenges, and also have to navigate units in highly dynamic game worlds and deal with other low-level tasks such as attacking enemy units within fire range. This thesis is a compilation of nine papers. The first four papers deal with navigation in dynamic game worlds, which can be very complex and resource demanding. Typically it is solved by using pathfinding algorithms. We investigate an alternative approach based on Artificial Potential Fields and show how a PF based navigation system can be used without any need of pathfinding algorithms. In RTS games players usually have a limited visibility of the game world, known as Fog of War. Bots on the other hand often have complete visibility to aid the AI in making better decisions. In a paper we show that a Multi-Agent PF based bot with limited visibility can match and even surpass bots with complete visibility in some RTS scenarios. In the sixth paper we show how the bot can be extended and used in a full RTS scenario with base building and unit construction. This is followed by a paper where we propose a flexible and expandable RTS game architecture that can be modified at several levels of abstraction to test different techniques and ideas. The proposed architecture is implemented in the famous RTS game StarCraft, and we show how the high-level architecture goals of flexibility and expandability can be achieved. The last two papers present two studies related to gameplay experience in RTS games. In games players usually have to select a static difficulty level when playing against computer opponents. In the first study we use a bot that during runtime can adapt the difficulty level depending on the skills of the opponent, and study how it affects the perceived enjoyment and variation in playing against the bot. To create bots that are interesting and challenging for human players a goal is often to create bots that play more human-like. In the second study we asked participants to watch replays of recorded RTS games between bots and human players. The participants were asked to guess and motivate if a player was controlled by a human or a bot. This information was then used to identify human-like and bot-like characteristics for RTS game players.

This essay advances a libertarian theory of moral rights, which responds effectively to some serious objections that have been raised against libertarianism. I show how libertarianism can explain children’s rights to certain physical integrity and aid. I defend strong moral rights of human, pre-natal organisms, infants and children against all agents to certain non-interference with their physical integrity. I also argue that parents’ moral obligation to aid their offspring follows from a moral principle that prohibits agents to actively harm rights-bearers. Since this is the core principle of all versions of libertarianism, we gain simplicity and coherence. In chapter two, I explain my theory’s similarities and differences to a libertarian theory of moral rights advanced by Robert Nozick in his 1974 book Anarchy, State, and Utopia. I explain the structure and coherence of negative moral rights as advanced by Nozick. Then, I discuss what these negative rights are rights to, and the criteria for being a rights-bearer. In chapter three, I formulate a clear distinction between active and passive behaviour, and discuss the moral importance of foreseeing consequences of one’s active interventions. In chapter four, I claim that some pre-natal human organisms, human infants, and children, are rights-bearers. I formulate a morally relevant characterization of potentiality, and argue that possession of such potentiality is sufficient to have negative rights against all agents. In chapter five, I discuss whether potential moral subjects, in addition, have positive moral rights against all agents to means sufficient to develop into actual moral subjects. I argue that this suggestion brings some difficulties when applied to rights-conflicts. In chapter six, I argue that potential moral subjects’ rights to means necessary to develop into actual moral subjects can be defended in terms of merely negative rights. By adopting the view advanced in this chapter, we get a simple, coherent theory. It avoids the difficulties in the view advanced in chapter five, while keeping its intuitively plausible features. In chapter seven, I discuss whether the entitlement theory is contradictory and morally repugnant. I argue that my version of the entitlement theory is not.

Afin de caractériser les moûts de Melon B. et de Sauvignon Blanc en composition et de modéliser leur profil d'oxydation, diverses méthodologies analytiques quantitatives ont été développées et validées. La quantification par dilution isotopique des précurseurs de thiols a nécessité la synthèse de molécules marquées qui ont également servies de traceurs lors d'études de filiation dans des milieux complexes. Ainsi, au cours de la fermentation alcoolique, nous avons pu démontrer que le S-3-(hexan-1-ol)-glutathion (G3MH) et la S-4-(4-méthylpentan-2-one)-glutathion (G4MMP) sont métabolisés par la levure et libèrent le 3-mercaptohexan-1-ol (3MH) et la 4-méthyl-4-mercaptopentan-2-one (4MMP) avec des rendements de conversion molaires proches de 4,4 % et 0,3 % respectivement. La modélisation des phénomènes d'oxydation à l'échelle laboratoire a permis par ailleurs de vérifier, comme le laissaient supposer leurs structures chimiques, que les précurseurs de thiols ne sont pas dégradés par les mécanismes oxydatifs affectant les moûts. Au contraire, une formation de G3MH concomitante avec le pic de production du Grape Reaction Product (GRP) est observée. La validation de ces observations à l'échelle industrielle a été conduite par comparaison des pressurages traditionnel et inerté. L' élaboration d'un moût de Melon B. sous gaz inerte n'est pas favorable à la production de G3MH d'origine pré-fermentaire, et a pour conséquence une diminution des teneurs en 3MH dans les vins correspondants, sans pour autant, déprécier les qualités organoleptiques des vins jeunes. Pour le Sauvignon Blanc, le potentiel aromatique de type thiol n'est pas affecté par le type de pressurage, mais une diminution très significative en 3MH dans les vins issus des cuvées obtenues sous gaz inerte est observée. La voie du (E)-2-hexènal qui est certainement impliquée, pourrait expliquer cette perte aromatique. Ainsi, de manière globale, dans nos conditions expérimentales, une oxydation ménagée et raisonnée des moûts de Melon B., et dans une moindre mesure de Sauvignon Blanc, est favorable à la qualité aromatique des vins du Val de Loire. / In order to characterize Melon B. and Sauvignon Blanc musts in composition and to study their oxidation profiles, several analytical methodologies have been developed and validated. The quantification of thiols precursors by Stable Isotope Dilution Assay required the synthesis of labeled molecules, which have been used either as analytical standards or as tracers for relationship studies in complex matrices. Thus, we established that, during the alcoholic fermentation, the S-3-(hexan-1-ol)-glutathione (G3MH) and the S-4-(4-méthylpentan-2-one)-glutathione (G4MMP) are metabolized by the yeast to release the 3-mercaptohexan-1-ol (3MH) and the 4-méthyl-4-mercaptopentan-2-one (4MMP) with molar conversion yields close to 4.4 % and 0.3 % respectively. Oxidation mechanisms study at laboratory scale demonstrated that aromatic potential was not affected by oxidative reactions, as expected in regard to their chemical structures. On the contrary, the G3M H was produced in the same time as the Grape Reaction Product peak (GRP). The validation of these observations at industrial scale was conducted by comparing traditional and inerted pressing systems. The elaboration of a Melon B. must under inert gas was not in favor of a G3MH pre-fermentary production, which induced a decrease of 3MH concentration in wine without affecting the organoleptic qualities of young wines. For Sauvignon Blanc must, the aromatic potential was not affected by the kind of pressing systems but a significant decrease in 3MH was observed in the wines obtained with juices from the beginning of pressing. The E-(2)-hexenal pathway could certainly explain such aromatic losses. Thus, under our experimental conditions, a mild and controlled oxidation of Melon B. must and, in a certain extend of Sauvignon Blanc must, is in favor of the aromatic quality of wines from Loire Valley.

The purpose of this study was to determine whether the job satisfaction and motivating potential of nursing jobs would be higher for nurses using Patient Focused Care (PFC) compared with nurses not using PFC. Nurses from a large metropolitan hospital served as subjects. Data were collected using three instruments designed to measure job satisfaction and motivating potential. Those instruments were the Job Diagnostic Survey, the Job Descriptive Inventory, and the McCloskey/Mueller Satisfaction Scale. It was hypothesized that nurses working on PFC nursing units would demonstrate greater job satisfaction and motivating potential than nurses working on non-PFC nursing units. The hypotheses were not supported. Results were explained by, among other things, accounting for the nature of the instruments used. The two instruments which gave data counter to the hypothesized direction were not nursing-oriented.

This thesis consists of four papers that concern error estimates for the Born-Oppenheimer molecular dynamics, and adaptive algorithms for the Car-Parrinello and Ehrenfest molecular dynamics. In Paper I, we study error estimates for the Born-Oppenheimer molecular dynamics with nearly crossing potential surfaces. The paper first proves an error estimate showing that the difference of the values of observables for the time-independent Schrödinger equation, with matrix valued potentials, and the values of observables for the ab initio Born-Oppenheimer molecular dynamics of the ground state depends on the probability to be in the excited states and the nuclei/electron mass ratio. Then we present a numerical method to determine the probability to be in the excited states, based on the Ehrenfest molecular dynamics, and stability analysis of a perturbed eigenvalue problem. In Paper II, we present an approach, motivated by the so called Landau-Zener probability estimation, to systematically choose the artificial electron mass parameters appearing in the Car-Parrinello and Ehrenfest molecular dynamics methods to approximate the Born-Oppenheimer molecular dynamics solutions. In Paper III, we extend the work presented in Paper II for a set of more general problems with more than two electron states. A main conclusion of Paper III is that it is necessary to resolve the near avoided conical intersections between all electron eigenvalue gaps, including gaps between the occupied states. In Paper IV, we numerically compare, using simple model problems, the Ehrenfest molecular dynamics using the adaptive mass algorithm proposed in Paper II and III and the Born-Oppenheimer molecular dynamics based on the so called purification of the density matrix method concluding that the Born-Oppenheimer molecular dynamics based on purification of density matrix method performed better in terms of computational efficiency. / <p>QC 20161102</p>

Mesoscopic devices, such as nano-wires, are of interest for the next step in creating spintronic devices. With the ability to manipulate electrons and their spin, spintronic devices may be realised. To that end the different effects found in low-dimensional devices must be studied and understood. In this thesis  the influence that lateral spin-orbit coupling (LSOC) has on a nanowire, with asymmetrical confinement potential, is studied. The nanowire is studied through a numerical approach, using the Hartree-Fock method with Dirac interactions to solve the eigenvalue problem of an idealised infinite nanowire. The nanowire has a split-gate that generates the electrostatic asymmetrical confinement potential. It is found that the lateral spin-orbit coupling has little to no effect without any longitudinal effects in the wire, such as source-drain bias. The electrons will spontaneously create spin-rows in the device due to spin polarization. The spin polarization is triggered by using LSOC, numerical noise or from a weak magnetic field. / Mesoskopiska anordningar, som nano-trådar, tros vara ett viktigt steg för att skapa spinnelektronik. För att kunna skapa spinnelektronik behövs kunskap om hur elektroner kan manipuleras. Generellt måste därför existerande fenomen i nanoelektronik studeras. I denna avhandling studeras hur ''lateral spin-orbit koppling'' (LSOC) influerar en nanotråd som har en asymmetrisk potentialbarriär. Hartree-Fock metoden, med Dirac potential för elektron-elektron interaktioner, användes för att beräkna energinivåerna för en idealisk, oändligt lång nanotråd. Nanotråden har en split-gate som alstrar den elektrostatiska, asymmetriska potentialbarriären. "Lateral spin-orbit koppling" visar sig ha minimal effekt då longitudinella effekter, exempelvis spänning, saknas. Elektronerna placerar sig spontant i spinn-rader i tråden vid spontan spinn polarisation. Spinn polarisationen sätts igång av LSOC, numeriska störningar eller från svagt pålagt magnetfält.

<p>Altered metabolism is a hallmark of almost all cancers. A tumor’s metabolic phenotype can drastically change its ability to proliferate and to survive stressors such as hypoxia or therapy. Metabolism can be used as a diagnostic marker, by differentiating neoplastic and normal tissue, and as a prognostic marker, by providing information about tumor metastatic potential. Metabolism can further be used to guide treatment selection and monitoring, as cancer treatments can influence metabolism directly by targeting a specific metabolic dysfunction or indirectly by altering upstream signaling pathways. Repeated measurement of metabolic changes during the course of treatment can therefore indicate a tumor’s response or resistance. Recently, well-supported theories indicate that the ability to modulate metabolic phenotype underpins some cancer cells’ ability to remain dormant for decades and recur with an aggressive phenotype. It follows that accurate identification and repeated monitoring of a tumor’s metabolic phenotype can bolster understanding and prediction of a tumor’s behavior from diagnosis, through treatment, and (sadly) sometimes back again.</p><p>The two primary axes of metabolism are glycolysis and mitochondrial metabolism (OXPHOS), and alteration of either can promote unwanted outcomes in cancer. In particular, increased glucose uptake independent of oxygenation is a well-known mark of aggressive cancers that are more likely to metastasize and evade certain therapies. Lately, mitochondria are also gaining recognition as key contributors in tumor metabolism, and mitochondrial metabolism has been shown to promote metastasis in a variety of cell types. Most tumor types rely on a combination of both aerobic glycolysis and mitochondrial metabolism, but the two axes’ relative contributions to ATP production can vary wildly. Knowledge of both glycolytic and mitochondrial endpoints is required for actionable, systems-level understanding of tumor metabolic preference. </p><p>Several technologies exist that can measure endpoints informing on glycolytic and/or mitochondrial metabolism. However, these technologies suffer from a combination of prohibitive cost, low resolution, and lack of repeatability due to destructive sample treatments.</p><p>There is a critical need to bridge the gap in pre-clinical studies between single-endpoint whole body imaging and destructive ex vivo assays that provide multiple metabolic properties, neither of which can provide adequate spatiotemporal information for repeated tumor monitoring. Optical technologies are well-suited to non-destructive, high resolution imaging of tumor metabolism. A carefully chosen set of endpoints can be measured across a variety of length scales and resolutions to obtain a complete picture of a tumor’s metabolic state. First, the fluorescent glucose analog 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) can be used to report on glucose uptake. The fluorophore tetramethylrhodamine, ethyl ester (TMRE) reports on mitochondrial membrane potential, which provides information regarding capacity for oxidative phosphorylation. Vascular oxygenation (SO2) and morphological features, which are critical for interpretation of 2-NBDG and TMRE uptake, can be obtained using only endogenous contrast from hemoglobin. </p><p>Three specific aims were proposed toward the ultimate goal of developing an optical imaging toolbox that utilizes exogenous fluorescence and endogenous absorption contrast to characterize cancer metabolic phenotype in vivo. </p><p>In Aim 1, we optimized the fluorescent glucose analog 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) to report on glycolytic demand in vivo. Our primary goal was to demonstrate that correcting 2-NBDG uptake (NBDG60) by the rate of delivery (RD) showed improved contrast between distinct tumor phenotypes. We showed that the ratio 2-NBDG60/RD served as a delivery-corrected measure of glucose uptake in the dorsal skin flap window chamber models containing normal tissues and tumors. Delivery correction was able to minimize the effects of a large change in the injected 2-NBDG dose. Further, the endpoint showed a significant inverse correlation with blood glucose levels. Since glucose has been shown to competitively inhibit 2-NBDG transport into cells, this finding indicating that we were indeed reporting on glucose uptake. Importantly, the ratio was able to distinguish specific uptake of 2-NBDG from accumulation of a fluorescent control, 2-NBDLG, which is identical to 2-NBDG in molecular weight and fluorescent spectrum, but is unable to undergo active transport into the cell. </p><p>The ratio 2-NBDG60/RD was then leveraged to compare different tumor phenotypes and to characterize the dependence of glucose uptake on vascular oxygenation within these tumors. Our results showed that 2-NBDG60/RD was an effective endpoint for comparing in vivo glucose uptake of metastatic 4T1 and nonmetastatic 4T07 murine mammary adenocarcinomas. Further, the addition of vascular information revealed metabolic heterogeneity within the tumors. The primary conclusion of Aim 1 was that delivery-corrected 2-NBDG uptake (2-NBDG60/RD) is an appropriate indicator of glucose demand in both normal and tumor tissues.</p><p>In Aim 2, we optimized fluorescent tetramethyl rhodamine, ethyl ester (TMRE) for measurement of mitochondrial membrane potential (MMP). We then leveraged the relationships between MMP, glucose uptake, and vascular endpoints to characterize the in vivo metabolic landscapes of three distinct and extensively studied murine breast cancer lines: metastatic 4T1 and non-metastatic 67NR and 4T07. </p><p>Using two-photon microscopy, we confirmed that TMRE localizes to mitochondrial-sized features in the window chamber when delivered via tail vein. The kinetics of TMRE uptake were robust across both normal and tumor tissues, with a stable temporal window for measurement from 40-75 minutes after injection. We saw that TMRE uptake decreased as expected in response to hypoxia in non-tumor tissue, and in response to chemical inhibition with a mitochondrial uncoupler in both non-tumor and 4T1 tissue. MMP was increased in all tumor types relative to non-tumor (p<0.05), giving further confirmation that TMRE was reporting on mitochondrial activity.</p><p>We leveraged the relationships between the now-optimized endpoints of MMP (Aim 2), glucose uptake (Aim 1) and vascular endpoints (Aims 1 and 2) to characterize the in vivo metabolic landscapes of three distinct and extensively studied murine breast cancer lines: metastatic 4T1 and non-metastatic 67NR and 4T07. Imaging the combination of endpoints revealed a classic “Warburg effect” coupled with hyperpolarized mitochondria in 4T1; 4T1 maintained vastly increased glucose uptake and comparable MMP relative to 4T07 or 67NR across all SO2. We also showed that imaging trends were concordant with independent metabolomics analysis, though the lack of spatial and vascular data from metabolomics obscured a more detailed comparison of the technologies.</p><p>We observed that vascular features in tumor peritumoral areas (PA) were equally or more aberrant than vessels in the tumor regions that they neighbored. This prompted consideration of the metabolic phenotype of the PA. Regional metabolic cooperation between the tumor region and the PA was seen only in 4T1, where MMP was greater in 4T1 tumors and glucose uptake was greater in 4T1 PAs. </p><p>Because of their regional metabolic coupling as well as their demonstrated capacity for glycolysis and mitochondrial activity, we hypothesized that the 4T1 tumors would have an increased ability to maintain robust MMP during hypoxia. 67NR and 4T07 tumors showed expected shifts toward decreased MMP and increased glucose uptake during hypoxia, similar to the trends we observed in normal tissue. Surprisingly, 4T1 tumors appeared to increase mitochondrial metabolism during hypoxia, since MMP increased and SO2 dramatically decreased. Overall, this aim demonstrated two key findings: 1. TMRE is a suitable marker of mitochondrial membrane potential in vivo in normal tissue and tumors, and 2. imaging of multiple metabolic and vascular endpoints is crucial for the appropriate interpretation of a metabolic behavior. </p><p>Finally, in Aim 3 we evaluated the feasibility of combined 2-NBDG and TMRE imaging. The primary objective was to enable simultaneous imaging of the two fluorophores by minimizing sources of “cross-talk”: chemical reaction, optical overlap, and confounding biological effects. A secondary objective was to transition our imaging method to a new platform, a reflectance-mode, high-resolution fluorescence imaging system built in our lab, which would expand the use of our technique beyond the dorsal window chamber model. We first used liquid chromatography- mass spectrometry to confirm that the chemical properties of the two fluorophores were compatible for simultaneous use, and indeed saw that the mixing of equimolar 2-NBDG and TMRE did not form any new chemical species. </p><p>We also performed a phantom study on the hyperspectral imaging system, used for all animal imaging in Aim 1 and Aim 2, to estimate the range of 2-NBDG and TMRE concentrations that are seen at the tissue level in normal and tumor window chambers. We created a new phantom set that spanned the range of estimated in vivo concentrations, and imaged them with the reflectance-mode fluorescence imaging system. The phantom experiments gave us two important findings. First, we saw that fluorescence intensity increased linearly with fluorophore concentration, allowing for accurate quantification of concentration changes between samples. Most importantly, we found that we could exploit the optical properties of the fluorophores and our system’s spectral detection capability to excite the two fluorophores independently. Specifically, we could excite 2-NBDG with a 488nm laser without detectable emission from TMRE, and could excite TMRE with a 555nm laser without detectable emission from 2-NBDG. With this characterization, the optical properties of the two fluorophores were considered compatible for simultaneous imaging. </p><p>Next, we sought to determine whether biological or delivery interactions would affect uptake of the two fluorophores. Surprisingly, both in vitro and in vivo imaging suggested that simultaneous dosing of the 2-NBDG and TMRE caused significant changes in uptake of both probes. Since we previously found that TMRE equilibrates rapidly at the tissue site, we hypothesized that staggering the injections to allow delivery of TMRE to tissue before injecting 2-NBDG would restore the full uptake of both fluorophores. Two sequential injection protocols were used: in the first group, TMRE was injected first followed by injection of 2-NBDG after only 1-5 minutes, and in the second group, TMRE was injected first followed by injection of 2-NBDG after 10-15 minutes. Both sequential injection strategies were sufficient to restore the final fluorescence of both fluorophores to that seen in the separate TMRE or 2-NBDG imaging cohorts; however, the shorter time delay caused changes to the initial delivery kinetics of 2-NBDG. We concluded that sequential imaging of TMRE followed by 2-NBDG with a 10-15 minute delay was therefore the optimal imaging strategy to enable simultaneous quantification of glucose uptake and mitochondrial membrane potential in vivo. </p><p>Applying the sequential imaging protocol to 4T1 tumors demonstrated a highly glycolytic phenotype compared to the normal animals, as we had seen in Aim 2. However, mitochondrial membrane potential was comparable for the normal and tumor groups. The next study will test an extended delay between the injections to allow more time for TMRE delivery to tumors prior to 2-NBDG injection. Overall, the key finding of Aim 3 was that a carefully chosen delivery strategy for 2-NBDG and TMRE enabled simultaneous imaging of the two endpoints, since chemical and optical cross-talk were negligible.</p><p>The work presented here indicates that an optical toolbox of 2-NBDG, TMRE, and vascular endpoints is well poised to reveal interesting and distinct metabolic phenomena in normal tissue and tumors. Future work will focus on the integration of optical spectroscopy with the microscopy toolbox presented here, to enable long-term studies of the unknown metabolic changes underlying a tumor’s response to therapy, its escape into dormancy, and ultimately, its recurrence.</p> / Dissertation

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