Chemotherapeutics are potent molecules capable of systematically treating cancer. As healthy tissues contain features also inherent to cancer cells, treatment often results in unwanted sideeffect. As chemotherapeutic side-effect produces significant harm and often limits optimal drug dosing, new strategies must be developed to improve treatment selectivity. A prodrug strategy provides one option to improve the selectivity of an established chemotherapeutic. By modifying a pharmaceutically active drug, interaction with biology may be functionally masked. Subsequent ‘un-masking’ the prodrug exclusively at the intended treatment site may direct treatment only to where the anticancer effect is required. This thesis progresses the novel approach of bioorthogonal organometallic (BOOM) prodrug activation. A metal catalyst and masked chemotherapeutic constitute reaction partners to provide a new strategy for intratumoural prodrug activation. Whereby the prodrug and metal catalyst are independently non-cytotoxic, in combination the prodrug undergoes catalytic activation to deliver an anticancer affect. By positioning the metal catalyst within a tumour (i.e. by microsurgery), an administered masked prodrug sensitive to catalyst-mediated activation could allow for ‘targeted’ chemotherapy localised to the tumour site. The design, synthesis and study of new BOOM prodrug candidates are reported herein. Novel protecting groups are developed to enhance drug masking to biology and subsequent catalyst-mediated activation. Prodrug screening studies are carried out in cancer cell culture models, with zebrafish and in ex vivo rodent model tumour explants. The catalyst, a palladium (Pd0) functionalised bead system, is optimised for enhanced activation, drug release and in vivo implantation. The potentially infinite generation of active chemotherapeutics exclusively in tumour would increase the efficacy of treatment whilst reducing harmful effect on healthy tissue.

Chemotherapy is widely used to treat various forms of cancer. However, some chemotherapeutic drugs, due to their antineoplastic properties, also act upon healthy cells which normally replicate rapidly causing a plethora of undesirable side effects. One rising and promising therapeutic strategy is the development of prodrugs. Prodrugs are derivatives of the pharmaceutically active drugs but require an enzymatic or biochemical transformation within a certain biological space in order for it to become activated and capable of exerting the desired pharmacological effect. As a novel prodrug approach, this thesis describes the pioneering use of a bioorthogonal organometallic (BOOM) activation strategy to develop spatially-controlled anticancer treatments. Bioorthogonal reactions are selective chemical processes between two abiotic reagents in a biological system that do not interfere with the system’s biotic components. In BOOM reactions, one of the reagents is a metal catalyst, which if immobilized, could in principle allow for the local transformation of a continuous flow of a bioorthogonal chemo-substrate indefinitely. To exploit the benefits of this paradigm in anticancer therapy, this thesis reports the design, synthesis and screening of a set of prodrugs masked with bioorthogonal protecting groups sensitive to activation by a catalysts-based “activating device”. Specifically, it describes the synthesis of palladium (Pd0) functionalized resins (the activating device) capable of activating cytotoxic pyrimidine analogue prodrugs masked with Pd0-labile protecting groups. Both the Pd0 functionalized resins and the BOOM-activated prodrugs are independently non-cytotoxic. However, once in combination together, the Pd0 is capable of mediating the removal of the masking groups in situ and rendering the drugs in their cytotoxic state with comparable antiproliferative properties to the unmodified parental drugs in vitro. The Pd0 resins also display biocompatibility and local catalytic activity inside zebrafish embryos. This approach is intended to generate a more targeted therapeutic treatment regime while minimizing harm to normal healthy tissues through the local generation of prodrugs which are not dependent on intrinsic biological activators but by an external activating device, thus reducing the systemic presence of the drug.

The boom microphone has been used to record dialogue on a film set for decades. As a boom operator it can be difficult in certain situations to acquire an ideal placement for the boom microphone. It depends on the frame and the lighting on the set. There are situations where the boom operator is forced to place the microphone underneath the actors instead of the standard overhead position. To investigate the difference between these techniques, and what audio quality attributes that affect the viewers’ choice of preference, a listening test has been constructed. The subjects were instructed to choose preferences in four trials of stimuli that had been recorded with both microphone techniques. To collect further data the subjects were also instructed to describe the differences they perceived between the stimuli. A statistically significant result was not found, except for one of the trials, the trained listeners preferred the underneath microphone technique for the second female stimuli. A difference between the techniques was difficult to determine from the answers given by the subjects. The conclusion was made that there is not a clear preference between the microphone techniques. Even though one of the trials was significant a clear difference could not be found in the analysis of the qualitative data.

Thin cylindrical shell structures may provide an interesting breakthrough for deployable structures for small satellites. Its bi-stable behaviour allows two different stable configurations: coiled and deployed. Several projects worldwide are using tape springs for satellites and for the SEAM project, at KTH, 1 meter long tape springs will be used for booms. This thesis investigates the energy stored inside the tape spring according to its layup configuration and the different fiber orientations. With a thickness around 0.3 mm and a length of one meter, the booms will deploy sensors with a quite low deployment speed in order to minimize the shick load during the deployment phase. A Matlab code is written to compare the stored strain energy. Another aim is to find an adequate layout all along the tape spring, it means change the fiber orientation to decrease the energy released, but also generating main manufacturing issue.

Sverige kommer inom en snar tid att stå inför stora förändringar på arbetsmarknaden gällande generationer. Baby boom generationen kommer att gå i pension och arbetsmarknaden tas över av generation X och Y. Genom att baby boomers lämnar arbetslivet och tar med sig sina kunskaper, blir det ett stort tomrum som kan vara svårt att fylla av de nästkommande generationerna. Emellertid har generation X och Y andra kunskaper som baby boomers saknar. Karakteristiska värderingar återfinns hos de olika generationerna, exempelvis värdesätter baby boomers hårt arbete och lojalitet. Generation Y tycker däremot att tillfredställelse i arbetet samt fritid är av betydelse. Vårt syfte är att undersöka huruvida det finns skillnader mellan generationerna inom arbetslivet kring värderingar och attityder. Värderingar kan liknas vid begreppet organisationskultur eftersom det hjälper medarbetare att få en känsla av identitet och samhörighet inom arbetslivet. Detta leder till gemensamma mål och visioner, vilket på sikt ökar produktiviteten. Både en kvalitativ samt kvantitativ metod tillämpades, vilket genomfördes med hjälp av tre intervjuer samt 68 enkäter på både kundsupport och bankkontor. Undersökningen visar att det inte finns stora skillnader mellan generationernas värderingar och attityder inom den undersökta banken. Organisationskulturen är stark vilket leder till att värderingarna inte syns. Fortsättningsvis visar resultatet att kulturen är starkare än egenskaperna som är karakteristiska för varje enskild generation. Resultatet visar slutligen att ett flertal av de teoretiska värderingarna inte stämmer överens med medarbetarnas svar. Det finns en märkbar skillnad mellan de båda avdelningarna, vilket kan förklaras genom arbetsgruppens storlek samt den egna organisationskulturen. / Within a short time, Sweden will be undergoing major changes on the labor market regarding generations. The Baby boom generation will retire soon and the labor market will mostly consist of Generation X and Y. By leaving the labor market, the Baby boomers are taking their knowledge with them; consequently there will be a huge void, which can be difficult to fill by the next generations. However, Generation X and Y have other knowledge, which the Baby boomers lack. Characteristic values are found among the generations. The Baby boomers value hard work and loyalty while Generation Y value a balance between the private and working life. Our purpose is to examine whether generational differences in the workplace on values and attitudes exist. Values can be similar to the organizational culture because it helps the employees to gain a sense of identity and belonging in the workplace. This leads to common goals and visions, which eventually increases productivity. Qualitative and quantitative methods were used, which was implemented through three interviews and 68 surveys on both the customer service and bank office. The study shows that there are not major differences between the values and attitudes of the generations within the examined bank. The organizational culture is strong, leading to values being hidden. Furthermore, the result shows that the culture is stronger than the traits, which are characteristic of each generation. Lastly, the results indicate a number of the theoretical values do not agree with what the employees responded. A notable difference between the two departments can be explained by the size of the working group and their own organizational culture.

The thesis develops the acoustic theory of the propagation of the shook waves produced by an aircraft in supersonic flight through an atmosphere in which the speed of sound decreases linearly with altitude. The problem is first studied in terms of the geometry of the rays along which the shock wave travels away from its point of origin and into the surrounding atmosphere. The equation of the rays is derived and certain important properties of the rays are discussed. It is shown how these results lead to a systematic graphical procedure for determining the location of the shock wave of a maneuvering aircraft. The theory is then considered in terms of the geometry of the "wave fronts" which represent the instantaneous positions of the individual disturbances created along the flight path. The shape of a wave front and its growth with time are determined. From this the equations for the envelope of a one-parameter family of wave fronts are obtained. The envelope equations are solved in parametric form and several examples are worked out which show some effects of flight maneuvers upon shock wave propagation. / M.S.

Conventional stereo vision systems rely on two spatially fixed cameras to gather depth information about a scene. The cameras typically have a fixed distance between them, known as the baseline. As the baseline increases, the estimated 3D information becomes more accurate, which makes it advantageous to have as large a baseline as possible. However, large baselines have problems whenever objects approach the cameras. The objects begin to leave the field of view of the cameras, making it impossible to determine where they are located in 3D space. This becomes especially important if an object of interest must be actuated upon and is approached by a vehicle. In an attempt to overcome this limitation, this thesis introduces a variable baseline stereo system that can adjust its baseline automatically based on the location of an object of interest. This allows accurate depth information to be gathered when an object is both near and far. The system was designed to operate under, and automatically move to a large range of different baselines. This thesis presents the mechanical design of the stereo boom. This is followed by a derivation of a control scheme that adjusts the baseline based on an estimate object location, which is gathered from stereo vision. This algorithm ensures that a certain incident angle on an object of interest is never surpassed. This maximum angle is determined by where a stereo correspondence algorithm, Semi-Global Block Matching, fails to create full reconstructions. / Master of Science

Technological challenges must be objectively and rigorously studied through simulation and modeling with the transition to more advanced air transportation systems. This dissertation addresses two relevant problems in air transportation: airport runway infrastructure evaluation and the prediction of worldwide demand for future supersonic aircraft. Both topics aim to improve air transportation mobility, which benefits society and contributes to economic growth. The Federal Aviation Administration (FAA) Advisory Circular (AC) 150/5325-4B contains the current method of estimating runway length requirements at small airports. With the introduction and significant growth of new-generation aircraft operations, the aircraft group approach and the oversimplification of several design variables described in the AC are problematic. This dissertation developed a series of modules to address these problems. These modules are integrated into the Small Aircraft Runway Length Analysis Tool (SARLAT), a stand-alone computer program used by airport designers. The latest version of SARLAT incorporates 67 individual aircraft performance characteristics based on a robust data processing, consolidation, and validation workflow. A conservative regression-based model has been developed to account for non-zero runway gradients and different runway surface conditions. A comparison between the FAA AC and SARLAT indicates that the current design methods are conservative for new-generation corporate jets but fall short for modern piston and turboprop aircraft. The models developed include aircraft stage length and payload-range analysis to assist airport designers and improve decision-making. The stage length analysis model uses Traffic Flow Management System (TFMS) data to estimate the cumulative distribution distances flown by individual aircraft. Using a time-step numerical simulation, the payload-range analysis developed a series of MATLAB functions to quantify the trade-offs between the aircraft's useful load and mission range. Another model developed in the dissertation and integrated into SARLAT determines the critical aircraft operating at the airport. All federally-funded projects require this process as part of the Airport Improvement Program (AIP). The models developed in the dissertation lead to more accurate and cost-effective estimates of runway length designs. The desire for supersonic transport was revived recently with advancements in aeronautical technologies and worldwide economic growth. Recent studies have developed various open-loop systems to assess worldwide demand and fleet size of future supersonic aircraft designs, assuming a fixed percentage of business passengers willing to switch to supersonic travel (i.e., switch rate). However, these studies overlooked the strong causality between supersonic transport airfare, the cost of the aircraft, and the market size for an assumed switch rate. To address this important causal gap, this dissertation develops a four-discipline coupled system, the Low Boom Systems Analysis Model Version 2 (LBSAM2). This system captures the dynamics between passenger preferences, fleet assignment, aircraft development cost, and aircraft operational economics to reach an equilibrium point. The passenger preference model quantifies the differences between supersonic and subsonic travel by introducing a "Value of Comfort" (VOC) concept to account for comfort loss due to seat pitch reductions. The fleet assignment model finds the minimum number of aircraft required to satisfy worldwide supersonic demand, which is subject to several constraints, including aircraft routes, airport curfews, aircraft utilization, and aircraft maintenance requirements. The aircraft development and life cycle cost models consider total aircraft production, technical specifications, and various operating and maintenance costs to derive a Cost per Passenger Nautical Mile (CPM) for each concept of supersonic aircraft. The integrated LBSAM2 shows that low-boom aircraft designs could attract 28% more business travelers worldwide than Mach cut-off designs (i.e., supersonic aircraft must slow down while flying overland to avoid excessive sonic booms over populated areas). Higher passenger demand for low-boom aircraft increases aircraft production leading to lower unit airframe cost, which achieves parity with the Mach cut-off design. This dissertation conducted a sensitivity analysis to investigate the effect of jet fuel prices on the market potential based on realistic and optimistic assumptions for airport emissions, noise, and landing fees. The estimated number of aircraft required and annual passengers are sensitive to fuel prices and operational factors. The potential market for a 50-passenger low-boom supersonic design ranges between 315 and 719 in 2040, depending on assumptions and jet fuel price. Based on a forecast of $5/gallon Sustainable Aviation Fuel (SAF) fuel price in 2040, LBSAM2 indicates that the low-boom design is not economically viable with only a worldwide projected demand of 1.24 million passengers. The models developed in this dissertation advance the state of knowledge in air transportation engineering. First, the dissertation develops an integrated method to predict runway length requirements at small airports. The models developed include detailed aircraft performance models for 67 individual aircraft with correction factors for runway grade and runway surfaces. Other models developed estimate aircraft payload-range diagrams, historical stage length analysis, and an automated critical aircraft determination to obtain a final recommended runway length. These functions have been integrated into the SARLAT tool - a stand-alone and user-friendly computer program. SARLAT provides information for airport designers and planners to streamline runway length design and improve the decision-making process in evaluating runway extension projects. This dissertation developed passenger preference and optimization network fleet analysis modules to predict supersonic aircraft demand. The passenger preference model quantifies time-saving benefits and comfort loss between the subsonic and supersonic flights. A fleet assignment model has been developed to minimize the number of aircraft under aircraft routes, airport curfews, maximum daily aircraft utilization, and passenger demand constraints. Considering realistic operational constraints, LABSAM2 enables a quantitative comparison for system-level trade-off studies between aircraft weight, range, and ground noise from the sonic boom. Passenger mobility is a central focus of this dissertation. Enhancing passenger mobility not only meets the needs of air travelers but also stimulates economic growth by generating additional job opportunities. The development of SARLAT offers an accurate and cost-effective solution for determining runway length requirements at small airports, thereby improving their accessibility. Enhanced airport accessibility brings socio-economic benefits to surrounding communities. In addition, the dissertation developed a set of modules to predict worldwide supersonic passenger demand. Advancing passenger mobility through supersonic designs could foster socio-economic benefits by significantly reducing intercontinental travel time and expanding business opportunities for companies worldwide. / Doctor of Philosophy / The scope of this dissertation includes airport runway infrastructure evaluation and the worldwide demand for future supersonic aircraft. Both topics aim to improve air transportation mobility, which benefits society and contributes to economic growth. The existing method of determining runway length requirements categorizes aircraft into different groups and simplifies several design variables. However, the current group design approach and simplification are problematic for new-generation aircraft. This dissertation has developed a series of models to address these problems and then integrated these models into the Small Aircraft Runway Length Analysis Tool (SARLAT), a stand-alone computer program used by airport designers. The latest version of SARLAT incorporates 67 individual aircraft takeoff and landing distances with conservative correction factors for runway grade and different runway surfaces. Other models developed include aircraft payload-range diagrams and historical distances flown to assist airport designers in the decision-making process. The models developed in the dissertation lead to more accurate and cost-effective estimates of runway length designs. Recent studies have developed various methodologies to assess worldwide demand and fleet size of future supersonic aircraft designs, assuming a fixed percentage of business passengers willing to switch to supersonic travel (i.e., switch rate). However, these studies overlooked the strong causality between supersonic transport airfare, the cost of the aircraft, and the market size for an assumed switch rate. To address this important causal gap, the Low Boom Systems Analysis Model version 2 (LBSAM2) has been developed. The passenger preference model quantifies the differences between supersonic and subsonic travel by introducing a "Value of Comfort" (VOC) concept to account for comfort loss due to seat pitch reductions. The fleet assignment model finds the minimum number of aircraft required to satisfy worldwide supersonic demand, which is subject to several constraints, including aircraft routes, airport curfews, aircraft utilization, and aircraft maintenance requirements. The estimated number of aircraft required and annual passengers are sensitive to fuel prices and operational factors. The potential market for a 50-passenger low-boom supersonic design ranges between 315 and 719 in 2040. Based on a forecast of $5/gallon Sustainable Aviation Fuel (SAF) fuel price in 2040, LBSAM2 indicates that the low-boom design is not economically viable with only a worldwide projected demand of 1.24 million passengers. Considering realistic operational constraints, LABSAM2 enables a quantitative comparison for system-level trade-off studies between aircraft weight, range, and ground noise from the sonic boom. Passenger mobility is a central focus of this dissertation. Enhancing passenger mobility not only meets the needs of air travelers but also stimulates economic growth by generating additional job opportunities. The development of SARLAT offers an accurate and cost-effective solution for determining runway length requirements at small airports, thereby improving their accessibility. Enhanced airport accessibility brings socio-economic benefits to surrounding communities. In addition, the dissertation developed a set of modules to predict worldwide supersonic passenger demand. Advancing passenger mobility through supersonic designs could foster socio-economic benefits by significantly reducing intercontinental travel time and expanding business opportunities for companies worldwide.

Thesis (D. Min.)--New Orleans Baptist Theological Seminary, 1996. / Includes abstract and vita. Includes bibliographical references (leaves 184-189).

The aim of this Diploma Thesis is to bring attention to the resemblance between the work of one of the most important Hispanic American authors of 20th century, the Mexican Juan Rulfo, and his less well-known Chilean colleague, María Luisa Bombal. Even though the work of these writers has often been associated with the beginnings of the so-called Magical Realism, so far literary critics have not studied the parallelism in their poetics in detail. This work observes the deviation of these authors from the type of literature dominant in their time, and their effort to renovate it. Furthermore, it concerns the similarity in the approach to death in their work; it pays attention to the influence of the Nordic literature on their literary production. Another part of this work is dedicated to the parallels between the character of Susana San Juan from Rulfoˈs Pedro Páramo and Bombalˈs female characters. In addition to that, the work reflects the personal relationship between the authors in question.