<p>Over the past century, the automobile has become an integral part of modern industrializedsociety. Consumer demands, regulatory legislation, and the corporate need togenerate a profit, have been the most influential factors in driving forward the evolutionof the automobile. As the comfort, safety, and reliability of the automobile haveincreased, so has its complexity, and most definitely its mass.The work within this thesis addresses the twofold problem of economy and ecologywith respect to sustainable development of automobiles. Specifically, the conflictingproblems of reducing weight, and maintaining or improving noise, vibration, andharshness behaviour are addressed. Potential solutions to these problems must also beexecutable at the same, or preferably lower production costs. The hypothesis is that byreplacing acoustic treatments, aesthetic details, and complex systems of structural componentsboth on the interior and exterior of the vehicle with a single multi-functionalbody panel, functionality can be retained at a reduced mass (i.e. reduced consumptionof raw materials) and reduced fiscal cost.A case study is performed focusing on the roof structure of a production vehicle. Fullvehicle and component level acoustic testing is performed to acquire acoustic functionalrequirements. Vibro-mechanical testing at the component level is performedto acquire structural functional requirements complimentary to those in the vehiclesdesign specifications. Finite element modelling and analysis is employed to createa model representative of the as-tested component and evaluate its acoustic and mechanicalbehaviour numerically. Results of numerical simulations are compared withthe measured results for both acoustic and mechanical response in order to verify themodel and firmly establish a set of acoustic and mechanical constraints for future work.A new, multi-layered, multi-functional sandwich panel concept is proposed which replacesthe outer sheet metal, damping treatments, transverse beams, and interior trimof the existing structure. The new panel is weight optimized to a set of structural constraintsand its acoustic properties are evaluated. Results show a significant reductionin mass compared to the existing system with no degradation of the acoustic environment.A discussion of the results is presented, as is a suggestion for future research.</p>

Over the past century, the automobile has become an integral part of modern industrializedsociety. Consumer demands, regulatory legislation, and the corporate need togenerate a profit, have been the most influential factors in driving forward the evolutionof the automobile. As the comfort, safety, and reliability of the automobile haveincreased, so has its complexity, and most definitely its mass.The work within this thesis addresses the twofold problem of economy and ecologywith respect to sustainable development of automobiles. Specifically, the conflictingproblems of reducing weight, and maintaining or improving noise, vibration, andharshness behaviour are addressed. Potential solutions to these problems must also beexecutable at the same, or preferably lower production costs. The hypothesis is that byreplacing acoustic treatments, aesthetic details, and complex systems of structural componentsboth on the interior and exterior of the vehicle with a single multi-functionalbody panel, functionality can be retained at a reduced mass (i.e. reduced consumptionof raw materials) and reduced fiscal cost.A case study is performed focusing on the roof structure of a production vehicle. Fullvehicle and component level acoustic testing is performed to acquire acoustic functionalrequirements. Vibro-mechanical testing at the component level is performedto acquire structural functional requirements complimentary to those in the vehiclesdesign specifications. Finite element modelling and analysis is employed to createa model representative of the as-tested component and evaluate its acoustic and mechanicalbehaviour numerically. Results of numerical simulations are compared withthe measured results for both acoustic and mechanical response in order to verify themodel and firmly establish a set of acoustic and mechanical constraints for future work.A new, multi-layered, multi-functional sandwich panel concept is proposed which replacesthe outer sheet metal, damping treatments, transverse beams, and interior trimof the existing structure. The new panel is weight optimized to a set of structural constraintsand its acoustic properties are evaluated. Results show a significant reductionin mass compared to the existing system with no degradation of the acoustic environment.A discussion of the results is presented, as is a suggestion for future research.

Currently, opioids are extensively used in clinical practices in order to treat pain in patients. However, prolonged administration of opioids are not feasible due to the development of side effects especially tolerance, constipation, addiction and dependence. Our drug design is mainly aimed to reduce opioid induce side effects such as development of tolerance. The first strategy examined involves design and synthesis of peptide based single molecules that have a mu agonist and delta agonist pharmacophore in combination with a COX2 inhibitory pharmacophore. A new molecule, 3-17 having good delta agonist activity, partial COX2 inhibitory activity and weak mu agonist activity was produced. Moreover, Investigation of the bioactivities of the synthesized ligands including 3-17 in terms of their ligand receptor interactions were probed using NMR conformational analysis along with docking analysis to the respective homology modeled mu and delta opioid receptors as well as the COX2 enzyme. As a further continuation of this work, instead of peptide based mu agonist and delta agonist type pharmacophore, the highly mu selective fentanyl pharmacophore was used in combination with a pyrazole based and a pyrazolone based COX pharmacophore. Based on the SAR study and docking analysis of synthesized ligands to the homology modeled mu opioid receptor, an ideal tolerant position without significant loss of mu opioid agonist activity for fentanyl were found. The second strategy involves design and synthesis of a peptide based single molecule that has a mu agonist and a delta antagonist pharmacophore in combination with a NK1 antagonist pharmacophore. A novel molecule (4-2) containing delta antagonist activity, weak mu agonist activity and NK1 antagonist activity was identified. Its homology modeled mu opioid receptor bound conformation was compared with that of reference ligands. Docking analysis of modified 4-2 to the homology modeled mu opioid receptor revealed that it can be further modified to obtain better mu agonist activity. 4-2 showed antinociception for 45 min period of time after injection in tail flick assay. In addition to studies that were directed to avoid tolerance development due to opioid administration, peptide based potential analgesics such as biphalin was modified by introducing more peptidomimetic character in order to enhance its blood brain barrier permeability and proteolytic stability. The novel molecule (6-7) was produced in this study and its antinociception lasted for 30 min period of time after injection in the tail flick assay.