Bacteriophage MooMoo is a temperate phage that was isolated and propagated on Mycobacterium smegmatis (M. smeg). It typically produces turbid plaques, however spontaneous clear plaque mutants can be readily isolated. Both turbid (MooMoo-T) and clear plaque (MooMoo-C) formers can establish stable lysogens, but the parental turbid plaque forming phage has a higher lysogenic frequency. The phage repressor protein typically plays the central role in regulating the lysis/lysogeny decision. Therefore, we expected that the mutation responsible for the clear plaque phenotype would be located in the repressor gene. Remarkably, whole genome sequencing detected a single base pair mutation in the minor tail protein gene (gp19). The regulatory role of the repressor protein could not be excluded considering it was unclear how the mutation in gp19 was leading to the altered plaque phenotype. To locate the phage repressor, we used bioinformatics to identify several candidate genes with helix-turn-helix and DNA binding motifs (gp42, gp43 and gp44). We also cloned the parental and mutant gp19 genes. Each candidate gene was cloned into a shuttle vector. The clones of gp43, gp44 and both derivatives of gp19 did not prevent MooMoo growth, whereas the clones of gp42 inhibited phage growth. Based on these results, we concluded that gp42 is the phage repressor for MooMoo. To determine if the presence of gp19 alters lysogenic frequency, lysogeny assays of wild-type (WT) and mutant gp19 clones were evaluated. Compared to the MooMoo-C lysate, the cloned copy of the mutant gp19 showed a slight increase in lysogeny efficiency. The lysogeny frequencies on strains that carry cloned copies of gp19 (WT or mutant) were similar to those obtained on strains that lacked the plasmids. From these results, we concluded, the presence of either parental or mutant gp19 clones does not affect the lysogeny frequency. To determine if host cell physiology was affected by lysogeny, carbon, nitrogen, phosphorus and sulfur utilization resources were screened using high-throughput phenotypic microarrays. From these results, we concluded the presence of the WT or mutant prophage had no significant effect on the utilization of the resources tested.

A city consists of many elements such as humans, buildings, and roads. The complexity of cities is difficult to measure using Euclidean geometry. In this study, we use fractal geometry (scaling analysis) to measure the complexity of urban areas. We observe urban development from different perspectives using the bottom-up approach. In a bottom-up approach, we observe an urban region from a basic to higher level from our daily life perspective to an overall view. Furthermore, an urban environment is not constant, but it is complex; cities with greater complexity are more prosperous. There are many disciplines that analyze changes in the Earth’s surface, such as urban planning, detection of melting ice, and deforestation management. Moreover, these disciplines can take advantage of remote sensing for research. This study not only uses satellite imaging to analyze urban areas but also uses check-in and points of interest (POI) data. It uses straightforward means to observe an urban environment using the bottom-up approach and measure its complexity using fractal geometry.   Web 2.0, which has many volunteers who share their information on different platforms, was one of the most important tools in this study. We can easily obtain rough data from various platforms such as the Stanford Large Network Dataset Collection (SLNDC), the Earth Observation Group (EOG), and CloudMade. The check-in data in this thesis were downloaded from SLNDC, the POI data were obtained from CloudMade, and the nighttime lights imaging data were collected from EOG. In this study, we used these three types of data to derive natural cities representing city regions using a bottom-up approach. Natural cities were derived from open geographic data without human manipulation. After refining data, we used rough data to derive natural cities. This study used a triangulated irregular network to derive natural cities from check-in and POI data.   In this study, we focus on the four largest US natural cities regions: Chicago, New York, San Francisco, and Los Angeles. The result is that the New York City region is the most complex area in the United States. Box-counting fractal dimension, lacunarity, and ht-index (head/tail breaks index) can be used to explain this. Box-counting fractal dimension is used to represent the New York City region as the most prosperous of the four city regions. Lacunarity indicates the New York City region as the most compact area in the United States. Ht-index shows the New York City region having the highest hierarchy of the four city regions. This conforms to central place theory: higher-level cities have better service than lower-level cities. In addition, ht-index cannot represent hierarchy clearly when data distribution does not fit a long-tail distribution exactly. However, the ht-index is the only method that can analyze the complexity of natural cities without using images.

During the flight of missiles, depending on the flight conditions, rotation of missiles around its centerline can cause instabilities. To override this issue, missile generally is designed in 2 sections. In the missile, the rear tail section and the front section are to rotate freely by means of bearings. Tail section on which bearings are mounted is designed according to thermal loads due to flow of hot gasses through the nozzle and mechanical loads due to inertial load, interference fit and thread preload which appear during flight of missile. The purpose of this thesis is to determine the most suitable structural parameters according to the flight conditions of missile. The geometrical and load parameters which have effect on the results were determined. Finite element model is formed by using FEA software. After that, transient nonlinear thermo-mechanical analyses are performed and the most effective parameter on VM (Von-Mises) stress and force is determined. DOE (Design of Experiments) method was used to determine the most suitable values for the structural parameters. Totally 27 different configurations are studied to achieve to the most suitable values for variable set. It is observed that VM stress and force results for all configurations are within the &plusmn / %5 ranges. So this means parameters don&rsquo / t affect the systems response very much. By taking manufacturing processes into consideration, configuration with the highest bearing inner/outer ring interference is taken. From the comparison of the results, the most suitable configuration is obtained after checking forces and VM stress on the bearings.

CYP2D6 metabolizes codeine to morphine, the active analgesic metabolite. Variation in brain CYP2D6 activity may affect brain morphine levels after codeine administration and thereby influence analgesia. We investigate the effect of inhibiting brain CYP2D on codeine-induced analgesia. METHODS: Rats received intracerebroventricular (i.c.v.) injections of CYP2D inhibitors or vehicle controls. Rats were then given subcutaneous codeine injections and analgesia was measured with the tail-flick test. Morphine and codeine concentrations in brain and plasma were measured. CYP2D activity in brain and liver were assessed in vitro. RESULTS: Compared to vehicle treatment, i.c.v. inhibitor treatments resulted in lower codeine-induced analgesia, lower morphine levels in brain but not in plasma after codeine injections, and lower CYP2D activity in brain membranes but not in liver microsomes. CONCLUSIONS: Inhibiting brain CYP2D reduces codeine’s metabolism to morphine, resulting in less analgesia. Variation in brain CYP2D6 activity may influence response to codeine and other CYP2D6 substrates.

CYP2D6 metabolizes codeine to morphine, the active analgesic metabolite. Variation in brain CYP2D6 activity may affect brain morphine levels after codeine administration and thereby influence analgesia. We investigate the effect of inhibiting brain CYP2D on codeine-induced analgesia. METHODS: Rats received intracerebroventricular (i.c.v.) injections of CYP2D inhibitors or vehicle controls. Rats were then given subcutaneous codeine injections and analgesia was measured with the tail-flick test. Morphine and codeine concentrations in brain and plasma were measured. CYP2D activity in brain and liver were assessed in vitro. RESULTS: Compared to vehicle treatment, i.c.v. inhibitor treatments resulted in lower codeine-induced analgesia, lower morphine levels in brain but not in plasma after codeine injections, and lower CYP2D activity in brain membranes but not in liver microsomes. CONCLUSIONS: Inhibiting brain CYP2D reduces codeine’s metabolism to morphine, resulting in less analgesia. Variation in brain CYP2D6 activity may influence response to codeine and other CYP2D6 substrates.

In the field of consumer goods the ecommerce industry has been growing rapidly. This rapid growth has created significant pressure on traditional retailers forcing them to institute change or risk being removed from the market. The primary objective of this study was to examine the shopping behavior of Umeå inhabitants in the Retail vs. Online Channels of the clothing sector. The goal was to identify key decision factors that cause consumers to choose a specific purchasing channel and use this information to create and test a conceptual model. The model focused on five decision factors including: (1) Loyalty (online, retail), (2) Physical Product, (3) Price, (4) Promotion, and (5) Convenience. We were also were interested in whether IT affinity (level of Internet browsing experience) had a direct relationship to the decision factors. To satisfy our research objective a deductive quantitative method was chosen. Information was tested in the form of a self-completion survey using a sample taken from 113 Umeå, Sweden residents between the ages of 18-29. This age group was specifically chosen, as almost 90% made purchases within a 4-month period (HUI, 2012 p.6). In the final analysis we concluded that all five decision factors in the Online Channel correlated whether positively or negatively, i.e., in some manner affected the final purchasing decision. The decision factors Loyalty Online, Promotion, and Physical Product were the strongest factors influencing the decision to purchase online. Price and IT Affinity correlated with Convenience, which in turn, correlated with Promotion, a decision factor contributing to online purchasing. Physical Product negatively correlated. Regarding the Retail Channel, the Physical Product was the strongest and only significant decision factor correlating positively to retail purchasing. With this understanding we conclude to a certain extent that consumers with a strong desire to try a physical product need other motivational factors to change channels toward online purchasing. Research on a larger scale would provide additional insight in this rapidly growing and interesting market.

High performance twin-tail aircraft, like the F-15 and F/A-18, encounter a condition known as tail buffet. At high angles of attack, vortices are generated at the wing fuselage interface (shoulder) or other leading edge extensions. These vortices are directed toward the twin vertical tails. When the flow interacts with the vertical tail it creates pressure variations that can oscillate the vertical tail assembly. This results in fatigue cracks in the vertical tail assembly that can decrease the fatigue life and increase maintenance costs. For many years, research has been conducted to understand this phenomenon of buffet and to reduce its adverse effects on the fatigue life of aerospace structures. Many proposed solutions to this tail buffet problem have had limited success. These include strengthening the tail, modifying the vortex flow, using an active rudder control, and leading edge extensions. Some of the proposed active controls include piezoelectric actuators. Recently, an offset piezoceramic stack actuator was used on an F-15 wind tunnel model to control buffet induced vibrations at high angles of attack. The controller was based on acceleration feedback control methods. In this thesis a procedure for designing the offset piezoceramic stack actuators is developed. This design procedure includes determining the quantity and type of piezoceramic stacks used in these actuators. The changes of stresses, in the vertical tail caused by these actuators during an active control, are investigated. In many cases, linear controllers are very effective in reducing vibrations. However, during flight, the natural frequencies of the vertical tail structural system changes as the airspeed increases. This in turn, reduces the effectiveness of a linear controller. Other causes such as the unmodeled dynamics and nonlinear effects due to debonds also reduce the effectiveness of linear controllers. In this thesis, an adaptive neural network is used to augment the linear controller to correct these effects.

Many performance measurement algorithms can only evaluate measure active managers' performance after a period of operating time. However, most investors are interested in monitoring the active managers' performances at any time, especially, when the performance is going down. So that the investors can adjust the targets and contents of their portfolios to reduce their risks. Yashchin,Thomas and David (1997) proposed to use a statistical quality control (SQC) procedure to monitor active managers' performances. In particular, they established the IR (Information Ratio) control charts under normality assumption to monitor the dynamic performances of active managers. However, the distributions of IR statistic usually possess fat tail property. Since the underlying distribution of IR is an important hypothesis in building up the control chart, we consider the heavy tail distributions, such as mixture normal and generalized error distribution to fit the IR data. Based on the fitted distribution, the IR control charts are rebuilt. By simulations and empirical studies, the remedial control charts are found to detect the shifts of active managers' performances more sensitively.

INTRODUCTION: Smoking is one of the single greatest causes of numerous preventable diseases. We were interested in developing an animal model of nicotine metabolism that can be used to examine the effects of potential CYP2A6 inhibitors on nicotine metabolism and nicotine-mediated behaviours. Pharmacogenetic studies have demonstrated that in humans, smoking behaviour is associated with rates of nicotine metabolism by the CYP2A6 enzyme. Mouse CYP2A5 shares structural and functional similarities to human CYP2A6 and has been implicated in nicotine self-administration behaviours in mice, therefore the mouse represents a potential animal model for studying nicotine metabolism. METHODS: We characterized nicotine and cotinine metabolism in two commonly used mouse strains (DBA/2 and C57Bl/6). We also examined the association between nicotine self-administration behaviours and nicotine metabolism, and the impact of direct manipulation (i.e. inhibition) of nicotine metabolism on nicotine pharmacodynamics (hot-plate and tail-flick tests) in mice. Finally, we studied the effect of selegiline (a known cytochrome P450 mechanism-based inhibitor) on nicotine metabolism in mice and in human CYP2A6. RESULTS: Nicotine metabolism in mice in vitro was mediated by CYP2A5, and this enzyme was responsible for over 70% and 90% of the metabolism of nicotine to cotinine and cotinine to 3-hydroxycotinine as shown by immuno-inhibition studies, respectively. A polymorphism in CYP2A5 between mouse strains, known to alter the probe substrate coumarin’s metabolism, did not affect nicotine metabolism but dramatically altered cotinine metabolism. Nicotine self-administration behaviour in mice was associated with level of hepatic CYP2A5 proteins and rates of nicotine metabolism in male mice. In inhibition studies, the CYP2A5/6 inhibitor methoxsalen inhibited both in vitro and in vivo nicotine metabolism in mice and substantially increased the anti-nociceptive effect of nicotine. Finally, selegiline was found to be an inhibitor of CYP2A5 decreasing nicotine metabolism in vitro and in vivo in mice. Moreover, we showed that selegiline is a mechanism-based inhibitor of CYP2A6 inhibiting nicotine metabolism irreversibly. CONCLUSION: The above data suggested that the mouse model may be suitable for examining the impact of inhibition (and genetic variation) on nicotine metabolism and nicotine-mediated behaviours and may potentially be used to screen for novel inhibitors of nicotine metabolism.

INTRODUCTION: Smoking is one of the single greatest causes of numerous preventable diseases. We were interested in developing an animal model of nicotine metabolism that can be used to examine the effects of potential CYP2A6 inhibitors on nicotine metabolism and nicotine-mediated behaviours. Pharmacogenetic studies have demonstrated that in humans, smoking behaviour is associated with rates of nicotine metabolism by the CYP2A6 enzyme. Mouse CYP2A5 shares structural and functional similarities to human CYP2A6 and has been implicated in nicotine self-administration behaviours in mice, therefore the mouse represents a potential animal model for studying nicotine metabolism. METHODS: We characterized nicotine and cotinine metabolism in two commonly used mouse strains (DBA/2 and C57Bl/6). We also examined the association between nicotine self-administration behaviours and nicotine metabolism, and the impact of direct manipulation (i.e. inhibition) of nicotine metabolism on nicotine pharmacodynamics (hot-plate and tail-flick tests) in mice. Finally, we studied the effect of selegiline (a known cytochrome P450 mechanism-based inhibitor) on nicotine metabolism in mice and in human CYP2A6. RESULTS: Nicotine metabolism in mice in vitro was mediated by CYP2A5, and this enzyme was responsible for over 70% and 90% of the metabolism of nicotine to cotinine and cotinine to 3-hydroxycotinine as shown by immuno-inhibition studies, respectively. A polymorphism in CYP2A5 between mouse strains, known to alter the probe substrate coumarin’s metabolism, did not affect nicotine metabolism but dramatically altered cotinine metabolism. Nicotine self-administration behaviour in mice was associated with level of hepatic CYP2A5 proteins and rates of nicotine metabolism in male mice. In inhibition studies, the CYP2A5/6 inhibitor methoxsalen inhibited both in vitro and in vivo nicotine metabolism in mice and substantially increased the anti-nociceptive effect of nicotine. Finally, selegiline was found to be an inhibitor of CYP2A5 decreasing nicotine metabolism in vitro and in vivo in mice. Moreover, we showed that selegiline is a mechanism-based inhibitor of CYP2A6 inhibiting nicotine metabolism irreversibly. CONCLUSION: The above data suggested that the mouse model may be suitable for examining the impact of inhibition (and genetic variation) on nicotine metabolism and nicotine-mediated behaviours and may potentially be used to screen for novel inhibitors of nicotine metabolism.