Wilderness therapy, the practice of sending troubled young people into nature in order to re-socialize them, poses a paradox. Time spent in wilderness is imagined to produce civilizing effects on young people, rendering them better prepared to live responsible and productive lives in society. Study of wilderness therapy, therefore, provides insight into constructions of youth and nature in contemporary American society. This thesis emerges from ethnographic research conducted at Camp E-Wen-Akee, a therapeutic camping program for troubled youth, in Benson, Vermont, USA. In addition to living with the three groups of campers in their rustic camp sites and engaging in camp activities, I facilitated two camper-run research projects, and interviewed camp staff members, and the state social workers responsible for sending adjudicated youth to residential programs. I find that camp life is an achievement of many heterogeneous actors, some of whom are human and others nonhuman. The resulting work is an ethnography of a nature-culture, wherein I describe how the camp mobilizes various resources to create the conditions for therapeutic change. The differing nature narratives of campers and the adults indicated that expectations for nature are at least in part, outcomes of class processes. Close attention to camp life shows that therapy is a social strategy brought into being at a number of scales: the material body, built and temporal architectures, landscape, and 'public' wilderness outside of camp's borders. I find at each scale a tension between the ordering tactics deployed by camp staff members and resistance posed by campers and 'nature' alike. Campers' identities are meant to change as a result o f repeated performances of prosocial behavior, and the on-going circulation of success stories. Together these practices underscore that what one person does always has effects on others. The irony uncovered i n this research is that while troubled youth are sent to a nature imagined as separate from society, Camp E-Wen-Akee provides young people with an ecological model for social life. Wilderness therapy is the outcome not of a separation between nature and society, but of ongoing relations between the two. / Arts, Faculty of / Geography, Department of / Graduate

In this project, the performance aspects of a new early generation 1310 nm Sampled-Grating Distributed Bragg Reflector (SG-DBR) semiconductor laser are investigated. SG-DBR lasers are ideal for Source Swept Optical Coherence Tomography (SS-OCT), a Fourier-Domain based approach for OCT, necessitating a tunable wavelength source. Three internal sections control the frequency output for tuning, along with two amplifiers for amplitude control. These O-band SG-DBR devices are now being produced in research quantities. SG-DBR lasers have been produced at 1550 and 1600 nm for some times. Fundamental questions regarding the performance of the 1310 nm devices must be quantified. Standard metrics including the laser linewidth, amplitude modulation and frequency modulation responses are characterized. The intrinsic electrical parasitics of the laser diode segments and packaging are also investigated. In addition, testing fixture including a Thermal Electric Cooler (TEC) controller is for the characterization task. Measurements of these key metrics are essential to the enhancement of future devices, aiding in the optimization of more mature products.

No description available.

This paper describes efforts to optimize the parameters for a platoon identification and accommodation algorithm that minimizes vehicle emissions. The algorithm was developed and implemented in the AnyLogic framework, and was validated by comparing it to the results of prior research. A four-module flowchart was developed to analyze the traffic data and to identify platoons. The platoon end time was obtained from the simulation and used to calculate the offset of the downstream intersection. The simulation calculates vehicle emissions with the aid of the VT-Micro microscopic emission model. Optimization experiments were run to determine the relationship between platoon parameters and minimum- and maximum-emission scenarios. Optimal platoon identification parameters were found from these experiments, and the simulation was run with these parameters. The total time of all vehicles in the simulation was also found for minimum and maximum emissions scenarios. Time-space diagrams obtained from the simulations demonstrate that optimized parameters allow all cars to travel through the downstream intersection without waiting, and therefore cause a decrease in emissions by as much as 15.5%. This paper also discusses the outcome of efforts to leverage high resolution data obtained from WV-705 corridor in Morgantown, WV. The proposed model was developed for that purpose and implemented in the AnyLogic framework to simulate this particular road network with four coordinated signal-controlled intersections. The simulation was also used to calculate vehicle CO, HC, NOx emissions with the aid of the VT-Micro microscopic emission model. Offset variation was run to determine the optimal offsets for this particular road network with traffic volume, signal phase diagram and vehicle characteristics. A classifier was developed by discriminant analysis based on significant attributes of HRD. Equation of this classifier was developed to distinguish between set of timing plans that produce maximum emission from set of timing plans that produce maximum emission. Also, current work investigates the potential use of the GPS-based and similar priority systems by giving preemption through signalized intersections. Two flowcharts are developed to consider presence of emergency vehicle (EV) in the system so called EV life cycle and EV preemption (EVP). Three scenarios are implemented, namely base case scenario when no EV is involved, EV scenario when EV gets EVP only, and EV scenario when EV gets preemption by signals and right-of-way by other vehicles. Research makes an attempt to compare emission results of these scenarios to find out whether EV effects vehicle emission in the road network and what is the level of this influence if any. / Master of Science

According to NCHRP Report 493, there are five major left turn signal indications for permitted operations in the United States. They are: Circular Green (CG), Flashing Circular Red (FCR), Flashing Red Arrow (FRA), Flashing Circular Yellow (FCY) and Flashing Yellow Arrow (FYA). The main goal of this thesis is to study the driver behavior and analyze safety of drivers for different left turn indications using a real-time driving simulator. Different signal indications alter driver behavior which influences velocity and acceleration profiles. These profiles influence vehicular emissions and hence need to be studied as well. For this purpose, different scenarios are implemented in the driving simulator. Data is analyzed using Microsoft Excel, JMP Statistical tool and MATLAB. Safety of drivers is analyzed with respect to the parameter "Time to Collision (TTC)" which is directly obtained from simulator data. Vehicular emissions and fuel consumption are calculated using VT-Micro microscopic emissions model. Graphs are plotted for TTC and total emissions. Results indicate that for a day-time scenario, FCY and FYA are the most suitable left-turning indications whereas FCR and FRA are most suitable for a night-time scenario. / Master of Science / There are five major left-turn indications for permitted operation in the United States. They are: Circular Green (CG), Flashing Circular Red (FCR), Flashing Red Arrow (FRA), Flashing Circular Yellow (FCY) and Flashing Yellow Arrow (FYA). Different states use different left-turn indications throughout the country. The level of driver comprehension for a particular signal indication will have an effect on the driving behavior and this in turn will affect fuel consumption and total emissions. The main goal of this thesis is to study driver behavior for different left-turning operations and to provide guidelines for the selection of signal indications. For this purpose, a real time driving simulator is used and different scenarios are implemented for left-turning operations. Data has been collected from the simulator to analyze driver safety in each scenario. Velocity and acceleration data from the simulator is used to calculate vehicular emissions to analyze environmental impact. The signal indication that best suits a given situation should provide maximum driver safety and minimum environmental impact. Graphs are plotted and results indicate that, during day time FCY and FYA are the most suitable indications whereas FCR and FRA are best suited for a night time scenario.

Afin de réaliser correctement leur fonction, certains blocs analogiques ou numériques comme les miroirs de courant ou les SRAM, nécessitent des paires de transistors MOS électriquement identiques. Cependant, les dispositifs sur silicium, même appariés, subissent des variations locales aléatoires ce qui fait varier leurs performances électriques. Ce phénomène est connu sous le nom désappariement. L'objectif de cette thèse est de comprendre les causes physiques de ce désappariement, de le quantifier et de proposer des solutions pour le réduire. Dans ce contexte, quatre thèmes principaux sont développés. Le premier thème se focalise sur l'optimisation des méthodologies de mesures des phénomènes de désappariement. Une nouvelle méthode de mesure du désappariement de Vt et de β ainsi qu'un nouveau modèle de désappariement de ID sont proposés, analysés et appliqués à des données mesurées sur des technologies 28nm Bulk et FD SOI. Le second thème se concentre sur la caractérisation des différentes configurations de transistor MOS afin de proposer l'architecture optimale en fonction des applications visées. Ainsi, la possibilité de remplacer le LDEMOS par une configuration cascode est analysée en détail. Le troisième thème se focalise sur l'analyse et la modélisation des phénomènes de désappariement des transistors MOS avancés. Trois aspects sont analysés : 1) l'introduction du Ge dans le canal P des technologies 28nm BULK, 2) la suppression de la contribution de la grille sur le désappariement de Vt en utilisant la technologie 20 nm métal-Gate-Last 3) un descriptif des principaux contributeurs au désappariement de Vt, β et ID dans les technologies 28 et 14nm FD SOI. Le dernier thème traite du comportement du désappariement des transistors MOS après vieillissement. Un vieillissement NBTI a été appliqué sur des PMOS de la technologie 28nm FD SOI. Des modèles de comportement de Vt et de β en fonction du nombre de charges fixes ou d'états d'interfaces induits à l'interface Si/SiO2 ou dans l'oxyde sont proposés et analysés. / For correct operation, certain analog and digital circuits, such as current mirrors or SRAM, require pairs of MOS transistors that are electrically identical. Real devices, however, suffer from random local variations in the electrical parameters, a problem referred to as mismatch. The aim of this thesis is to understand the physical causes of mismatch, to quantify this phenomenon, and to propose solutions that enable to reduce its effects. In this context, four major areas are treated. The first one focuses on the optimization of mismatch measurement methodologies. A new technique for the measurement of Vt and β mismatch and an ID mismatch model are proposed, analyzed and applied to experimental data for 28 nm Bulk and FD SOI technologies. The second area focuses on the characterization of different configurations of MOS transistors in order to propose design architectures that are optimized for certain applications. Specifically, the possibility of replacing LDEMOS with transistors in cascode configuration is analyzed. The third area focuses on the analysis and modeling of mismatch phenomena in advanced Bulk and SOI transistors. Three aspects are analyzed: 1) the impact of the introduction of germanium in P channel of 28nm BULK transistors; 2) the elimination of the metal gate contribution to Vt mismatch by using 20nm Gate-last Bulk technology; 3) a descriptive study of the principal contributions to Vt, β and ID mismatch in 28 and 14 nm FD SOI technologies. The last area treats the mismatch trends with transistor aging. NBTI stress tests were applied to PMOS 28nm FD SOI transistors. Models of the Vt and β mismatch trends as a function of the induced interface traps and fixed charges at the Si/SiO2 interface and in the oxide were developed and discussed.

Die bakterielle Meningitis ist trotz der Anwendung modernster Antibiotika mit einer hohen Letalität und neurologischen Spätkomplikationen verbunden. Ein entscheidendes Ereignis ist dabei der Zusammenbruch der Blut-Hirn-Schranke (BHS). Die genauen Mechanismen, die zu ihrer Schädigung führen, sind bis heute unklar. In dieser Arbeit wurde untersucht, ob lebende Pneumokokken in einem Zellkulturmodell der BHS zu einer apoptotischen Zellschädigung von zerebralen Endothelzellen, als wichtigstem zellulären Bestandteil der BHS, führen und damit zu ihrer strukturellen Schädigung beitragen. Mittels verschiedener Detektionsmethoden (TUNEL, Fluoreszenzmikroskopie, Elektronenmikroskopie) konnte nachgewiesen werden, daß Streptococcus pneumoniae zu einem apoptotischen endothelialen Zelltod führt. Eine Beteiligung von Caspasen konnte weder mit direkter Aktivitätsmessung noch mittels Inhibitionsexperimenten oder dem Nachweis von Caspase-spezifischen Substraten gezeigt werden. Insgesamt sind die Morphologie der Zellkerne und die spezifische Degradation der endothelialen DNS hinweisend für einen Apoptosis-Inducing-Factor-vermittelten Zelltod ohne Caspasenbeteiligung. Diese Form des Zelltodes ist bereits in anderen Zellmodellen, bisher jedoch nicht bei zerebralen Endothelzellen beschrieben worden. Auf Seiten des Bakteriums konnten Wasserstoffperoxid und Pneumolysin als Auslöser der Apoptose identifiziert werden. Die zytotoxische Potenz des Pneumolysins ist dabei an dessen Poren-formende Aktivität gebunden. Die Ergebnisse sind von potentieller klinischer Relevanz, da es bei einer Bakteriämie und während der Invasion der Pneumokokken in das ZNS zu einem direkten Kontakt zwischen Bakterien und zerebralen Endothelzellen kommt und sich daraus eine Möglichkeit zur Entwicklung adjuvanter Therapien ergeben könnte. / Despite sufficient antibiotic treatment, pneumococcal meningitis has remained a disease associated with high mortality and neurological sequelae. The disruption of the blood brain barrier (BBB) is regarded a key event in the initial phase of pneumococcal meningitis. However, the exact molecular mechanisms involved in this process are still unknown. The aim of this study was to determine if living pneumococci are able to induce apoptosis in cerebral endothelial cells - the main cellular component of BBB - and therefore might contribute to its damage. Using several different detection methods (TUNEL, fluorescence and electron microscopy), induction of apoptotic cell death of endothelial cells by pneumococci could be verified. An accompanying activation of caspases was not detectable, despite the use of specific detection techniques such as inhibition experiments, direct enzyme measurements and detection of caspase-specific protein cleavage. These results as well as the specific nuclear morphology and degradation of endothelial DNA suggest an involvement of the mitochondrial protein Apoptosis inducing factor (AIF). This is the first time this specific form of apoptotic, AIF-driven cell death has been described to be engaged in endothelial cells. On the part of the bacterium, pneumolysin and hydrogen peroxide were identified as the two main inducers of apoptosis. The cytotoxic potency of pneumolysin is related to its pore-forming activity. These results are of clinical relevance since pneumococci are known to reside in close proximity to cerebral endothelial cells during bacteriemia and their entry into the CNS. These findings could contribute to the development of adjuvant treatment of bacterial meningitis.

DieMenschheit ist vielfältigen chemischenWirkstoffen ausgesetzt – zum Beispiel durch Kosmetika und Pharmazeutika sowie durch viele andere chemische Quellen. Es wird angenommen, dass diese stetige Exposition mit Chemikalien gesundheitliche Beeinträchtigungen bei Menschen hervorruft. Zudem haben Regulierungsbehörden aus Europa und den USA festgestellt, dass es ein Risiko gibt, welches mit der kombinierten Exposition durch mehrere Chemikalien im Zusammenhang steht. Mögliche Kombinationen von Tausenden Wirkstoffen zu testen, ist sehr zeitaufwendig und nicht praktikabel. Das Hauptanliegen dieser Arbeit ist es, die Probleme von Off-target-Effekten chemischer Strukturen zu benennen – mit den Mitteln der Chemieinformatik, der strukturellen Bioinformatik sowie unter Berücksichtigung von computerbasierten, systembiologischen Ansätzen. Diese Dissertation ist in vier Hauptprojekte eingeteilt. ImProjekt I (Kapitel 3)wurde ein neuartiger Ensemble-Ansatz basierend auf der strukturellen Ähnlichkeit von chemischenWirkstoffen und Bestimmungen von toxischen Fragmenten implementiert,um die orale Toxizität bei Nagetieren vorherzusagen. Im Projekt II (Kapitel 4) wurden – auf der Grundlage von Daten des Tox21 Wettbewerbs – unterschiedliche Machine-Learning Modelle entwickelt und verglichen, um die Komponenten vorherzusagen, die in den toxikologischen Stoffwechselwegen mit Zielmolekülen interagieren von target-spezifischenWirkstoffen vorherzusagen. In Projekt III (Kapitel 5) wird ein neuartiger Ansatz beschrieben, welcher das dreigliedrige Konzept aus computerbasierter Systembiologie, Chemieinformatik und der strukturellen-Bioinformatik nutzt, um Medikamente zu bestimmen, welche das metabolische Syndrom hervorrufen. In Projekt IV (Kapitel 6) wurde in silico ein Screening Protokoll entwickelt, welches die strukturelle Ähnlichkeit, die pharmakophorischen Eigenschaften und die Überprüfung von computerbasierten Docking Studien berücksichtigt. / Exposure to various chemicals agents through cosmetics, medications, preserved food, environments and many other sources have resulted in serious health issues in humans. Additionally, regulatory authorities from Europe and United States of America have recognized the risk associated with combined exposure to multiple chemicals. Testing all possible combinations of these thousands of compounds is impractical and time consuming. The main aim of the thesis is to address the problem of off-targets effects of chemical structures by applying and developing cheminformatics, structural bioinformatics and computational systems biology approaches. This dissertation is divided into four main projects representing four different computational methods to aid different level of toxicological investigations. In project I (chapter 3) a novel ensemble approach based on the structural similarity of the chemical compounds and identifications of toxic fragments was implemented to predict rodent oral toxicity. In project II (chapter 4) different machine learning models were developed and compared using Tox 21 challenge 2014 data, to predict the outcomes of the compounds that have the potential to interact with the targets active in toxicological pathways. In project III (chapter 5) a novel approach integrating the trio concept of ’computational system biology, cheminformatics and structural bioinformatics’ to predict drugs induced metabolic syndrome have been described. In project IV (chapter 6) a in silico screening protocol was established taking into the structurally similarity, pharmacophoric features and validation using computational docking studies. This approach led to the identification of novel binding site for acyclovir in the peptide binding groove of the human leukocyte antigen (HLA) specific allele.

The topic of this thesis is the design and synthesis of biaryl-based self adaptableligands for asymmetric metal catalysis. The results discussed in papers I-III are covered, together with some unpublished results concerning substrate-adaptable catalysts. A general survey of self-adaptable catalysts is presented first. The second chapter of this thesis starts with a survey of inversion barriers in biphenyl-based ligands and catalysts. Thereafter, the determination of barriers to conformational adaptation in dibenzoazepines and dibenzophosphepines is described. Palladium complexes with a diphosphine ligand or a diamine ligand, as well as the free diamine ligand, were studied. Entropies and enthalpies of activation were determined with variable temperature NMR spectroscopy. The mechanism of conformational change in the metal complexes was elucidated. The third chapter describes the synthesis of semiflexible and rigid phosphinite ligands, as well as their application in rhodium-catalysed asymmetric hydrogenation. Modest enantioselectivities (up to 63% ee) were obtained. The semiflexible ligand was found to behave like the most active rigid diastereomer. The fourth chapter describes the behaviour of amine and phosphoramidite ligands in model complexes relevant to the palladium-catalysed asymmetricallylic alkylation of benchmark substrates. Diphosphoramidite and aminephosphoramiditeligands were designed and synthesised. Pd(olefin) complexesof diamine and diphosphoramidite ligands were studied, and their symmetry determined. It was found that both types of ligands are able to adapt their conformation to the substrate. / QC20100630

There is a growing consensus that life-threatening cardiac arrhythmias like ventricular tachycardia (VT) or ventricular fibrillation (VF) arise because of the formation of spiral waves of electrical activation in cardiac tissue; unbroken spiral waves are associated with VT and broken ones with VF. Several experimental studies have shown that inhomogeneities in cardiac tissue can have dramatic effects on such spiral waves. In this thesis we try to understand these experimental results by carrying out detailed and systematic studies of the interaction of spiral waves with different types of inhomogeneities in mathematical models for cardiac tissue. In Chapter 1 we begin with a general introduction to cardiac arrhythmias, the cardiac conduction system, and the connection between electrical activation waves in cardiac tissue and cardiac arrhythmias. As we have noted above, VT and VF are believed to be associated with spiral waves of electrical activation on cardiac tissue; such spiral waves form because cardiac tissue is an excitable medium. Thus we give an overview of excitable media, in which sub-threshold perturbations decay but super-threshold perturbations lead to an action potential that consists of a rapid stage of depolarization of cardiac cells followed by a slow phase of repolarization. During this repolarization phase the cells are refractory. We then give an overview of earlier studies of the effects of inhomogeneities in cardiac tissue; and we end with a brief description of the principal problems we study here. Chapter 2 describes the models we use in our work. We start with a general introduction to the cable equation and then discuss the Hodgkin-Huxley-formalism for the transport of ions across a cell membrane through voltage-gated ion channels. We then describe in detail the three models that we use for cardiac tissue, which are, in order of increasing complexity, the Panfilov model, the Luo Rudy Phase I (LRI) model, and the reduced Priebe Beuckelmann (RPB)model. We then give the numerical schemes we use for solving these model equations and the initial conditions that lead to the formation of spiral waves. For all these models we give representative results from our simulations and compare the states with spiral turbulence. In Chapter 3 we investigate the effects of conduction inhomogeneities (obstacles) in the three models introduced in Chapter 2. We outline first the experimental results that have provided the motivation for our study. We then discuss how we introduce obstacles in our simulations of the Panffilov, LRI, and RPB models for cardiac tissue. Next we present the results of our numerical studies of the effects, on spiral-wave dynamics, of the sizes, shapes, and positions of the obstacles. Our Principal result is that spiral-wave dynamics in these models depends sensitively on the position of the obstacle. We find, in particular, that, merely by changing the position of a conduction inhomogeneity, we may convert spiral turbulence (the analogue in our models of VF) to a single rotating spiral (the analogue of VT) anchored to the obstacle or vice versa; even more exciting is the possibility that, at the boundary between these two types of behaviour, we find a quiescent state Q with no spiral waves. Thus our study obtains all the possible qualitative behaviours found in experiments, namely, (1) VF might persist even in the presence of an obstacle, (2) it might be suppressed partially and become VT, or (3) it might be eliminated completely. In Chapter 4 we extend our work on conduction inhomogeneities (Chapter 3) to ionic inhomogeneities. Unlike conduction inhomogeneities, ionic inhomogeneities allow the conduction of activation waves. We find, nevertheless, that they too can lead to the anchoring of spiral waves or even the complete elimination of spiral-wave turbulence. Since spiral waves can enter the region in which there is an ionic inhomogeneity, their behaviours in the presence of such an inhomogeneity are richer than those with conduction inhomogeneities. We find, in particular, that a single spiral wave anchored at an ionic inhomogeneity can show temporal evolution that may be periodic, quasiperiodic, or even chaotic. In the last case the spiral wave shows a chaotic pattern inside the ionic inhomogeneity and a regular one outside it. Defibrillation is the control of arrhythmias such as VF. Most often defibrillation is effected electrically by administering a shock, either externally or via an internally implanted defibrillator. The development of low-amplitude defibrillation schemes, which minimise the deleterious effects of the applied shock, is a major challenge in the treatment of cardiac arrhythmias. Numerical studies of models for cardiac tissue provide us with convenient means of studying the elimination of spiral-wave turbulence by the application of external electrical stimuli; this is the numerical analogue of defibrillation. Over the years some low-amplitude defibrillation schemes have been suggested on the basis of such numerical studies. In Chapter 5 we discuss two such schemes that have been shown to suppress spiral-wave turbulence in two-dimensional models for cardiac tissue and also scroll-wave turbulence in three-dimensional models. One of these schemes uses local electrical pacing, typically in the centre of the simulation domain; the other applies the external electrical stimuli over a mesh. We study the efficacy of these schemes in the presence of conduction inhomogeneities. We find, in particular, that the local-pacing scheme, though effective in a homogeneous simulation domain, fails to control spiral turbulence in the presence of an obstacle and, indeed, might even facilitate spiral-wave break up. By contrast, the second scheme, which uses a mesh, succeeds in eliminating spiral-wave turbulence even in the presence of an obstacle. We end with some concluding remarks about the possible experimental implications of our study in Chapter 6.