This research focuses on developing a comprehensive framework for designing and modeling experiments in the presence of multiple sources of competing prior knowledge. In particular, methodology is proposed for process optimization in high-cost, low-resource experimental settings where the underlying response function can be highly non-linear. In the first part of this research, an initial experimental design criteria is proposed for optimization problems by combining multiple, potentially competing, sources of prior information--engineering models, expert opinion, and data from past experimentation on similar, non-identical systems. New methodology is provided for incorporating and combining conjectured models and data into both the initial modeling and design stages. The second part of this research focuses on the development of a batch sequential design procedure for optimizing high-cost, low-resource experiments with complicated response surfaces. The success in the proposed approach lies in melding a flexible, sequential design algorithm with a powerful local modeling approach. Batch experiments are designed sequentially to adapt to balance space-filling properties and the search for the optimal operating condition. Local model calibration and averaging techniques are introduced to easily allow incorporation of statistical models and engineering knowledge, even if such knowledge pertains to only subregions of the complete design space. The overall process iterates between adapting designs, adapting models, and updating engineering knowledge over time. Applications to nanomanufacturing are provided throughout.

SammanfattningLångvarig smärta orsakar stort lidande för individen och belastar samhället ekonomiskt. Syftet med denna uppsats var att undersöka om en exponering in vivo-behandling inspirerad av Dialektisk beteendeterapi (DBT) för människor med långvarig ländryggssmärta var görbar samt om behandlingen gav effekt på smärtrelaterad problematik. Designen var en single case experimental design vilket är en beprövad design för att testa nya terapimetoder. Studien bestod av sex deltagare, alla med hög grad av smärtrelaterade katastroftankar, något som litteraturen visat predicera sämre behandlingsutfall. Behandlingen var DBT-inspirerad och indelad i tre faser; en första valideringsfas, en andra färdighetsfas och en tredje exponeringsfas. Fem av sex deltagare fick förbättringar på alla de primära utfallsmått, tre av sex deltagare fick förbättringar på samtliga primära- och sekundära utfallsmått. Framtida replikationer är motiverade. / AbstractChronic pain causes great suffering for the individual and burden society economically. The aim of this study was to examine whether an exposure in vivo treatment inspired by Dialectical Behavior Therapy (DBT) for people with chronic low back pain was feasible and whether the treatment had effect on pain-related problems. The design was a single case experimental design, which is a widely used design to test new therapy methods. The study consisted of six participants, all with high levels of pain catastrophizing, something that in the literature been linked to poor treatment outcomes. The treatment was inspired by DBT and divided into three phases: an initial validation phase, a second phase for skills training and a third exposure phase. The results were promising: five out of six participants had improved in all primary outcome measures. Three out of six participants had improvements in all primary and secondary outcome measures. Future replications are warranted.

Depression och insomni är två vanliga former av psykisk ohälsa. I den här studien undersöktes om en bevisat effektiv behandling för insomni, (KBT-I), påverkade grad av depressiva symtom hos personer med konstaterade symtom på såväl depression som insomni. I studien kontrollerades för en minskning av nedstämdhet kunde tillskrivas en ökad fysisk aktivitetsnivå. En single case experimental design användes för ändamålet, med dagliga skattningar av sömn, nedstämdhet och fysisk aktivitetsnivå. Symtom på såväl insomi som nedstämdhet minskade signifikant hos tre av sex deltagare. Minskad nedstämdhet kunde inte förklaras av ökad fysisk aktivitetsnivå. Samvariation observerades mellan depression och insomni. Resultaten visar att insomni och depression kan påverkas av samma behandling, vilket antyder förekomst av gemensamma vidmakthållande mekanismer. / Insomnia and depression are two common mental health problems. This study investigated whether a proven effective treatment for insomnia CBT-I, would change the severity of depressive symptoms, for participants with comorbid insomnia and depression. It was controlled for, whether a reduction in depressive symptoms could be the result of increased physical activity. A single case experimental design, including daily measurements of sleep, depression and physical activity, was used as a means to answer the research questions. Symptoms of both depression and insomnia were significantly reduced for three out of six participants. Increased physical activity was not able to explain the decrease in depression scores. A correlation was observed, between depression and insomnia. The results shows that insomnia and depression can be affected by the same treatment, which implies existence of common perpetual mechanisms.

Call number: LD2668 .T4 1985 E39 / Master of Science

This research compared the use of an electronic meeting system tool to a manual group process in large and small groups in a controlled laboratory experiment. Outcomes measured include the quality of decision, the time taken in various stages of the decision making process, and group member satisfaction. A research model of the variables influencing group decision making was developed. The six independent variables included in this model are group size, the rule by which the group makes a decision, the incentives driving the group, the distribution of useful information within the group, the task complexity, and the meeting support (electronic or manual). In this research group size and method of support were manipulated, while the other variables were controlled. A decision-making task was developed for this research to specify and manipulate the six independent variables. The task described a product mix problem in which information on each product was given to group members. The group shared information and jointly determined an outcome. The group used an unanimous decision rule to choose a solution. A numerical outcome was used to objectively measure decision quality. Each member of the group received a cash payoff determined by the group's solution as incentive in accomplishing the task. All groups found the optimal solution. The simplicity of the task may have minimized the differences found between groups. There was no significant difference in general member satisfaction or time to decision. Prior knowledge was found to influence general member satisfaction and the time needed for the group to share information. Members of large groups perceived more uneven distribution of participation than members of small groups. Voting differences were very large: large groups took significantly more votes than small groups, and electronic groups took significantly more votes than manual groups. "Conjunctive" and "disjunctive" task descriptions are used to discuss task/tool interaction.

Statistically based experimental designs were applied to optimise medium constituent for biogas production utilizing N-­‐acetylglucosamine as a carbon source for Clostridium beijerinckii and Clostridium paraputrificum. The important medium constituents influencing total biogas produced, identified by the Plackett and Burman method, were FeSO4.7H2O and initial pH for C. beijerinckii cultures whilst for C. paraputrificum cultures N-­‐acetylglucosamine, L-­‐ cysteine.HCl.H2O and MgCl2. A one factor L-­‐cysteine.HCl.H2O optimization design was applied to investigate the ideal concentration of L-­‐cysteine.HCl.H2O required to achieve an anaerobic environment for optimum C. beijerinckii total biogas production. The Method of Steepest Ascent was then employed to locate the optimal area of the significant medium variables. Using the Box-­‐behnken method, experimental results showed that there were significant linear effects of independent variables, N-­‐acetylglucosamine for C. beijerinckii cultures and for C. paraputrificum cultures N-­‐acetylglucosamine, L-­‐cysteine.HCl.H2O and MgCl2 on total biogas volume. Significant curvature or quadratic effects of N-­‐ acetylglucosamine and L-­‐cysteine.HCl.H2O were identified for C. paraputrificum cultures. There were no significant interaction effects between medium constituent variables on resulting biogas volume. The optimal conditions for the maximum volume of biogas produced for C. beijerinckii cultures were 21 g/l of N-­‐ acetylglucosamine, 0.1 g/l of FeSO4.7H2O and initial pH of 6.11 and for C. paraputrificum were 29 g/l of N-­‐acetylglucosamine, 0.27 g/l of L-­‐ cysteine.HCl.H2O and 0.4 g/l of MgCl2. Using this statistical optimization strategy, the total biogas volume from N-­‐acetylglucosamine utilization increased from 150 ml/l to 6533 ml /l in the C. beijerinckii cultures and 100 ml/l to 5350 ml/l in the C. paraputificum cultures. The maximum yield of bio-­‐hydrogen by C. paraputrificum from N-­‐acetylglucosamine was 2.55 mol of H2 / mol of N-­‐ acetylglucosamine and by C. beijerinckii was 2.43 mol of H2 / mol of N-­‐ acetylglucosamine.

Multidrug resistance (MDR) is a major obstacle limiting chemotherapeutic efficacy. The purpose of these studies was to investigate the potential application of injectable paclitaxel (PX) and doxorubicin (Dox)-loaded nanoparticles (NPs) engineered from oil-in-water microemulsion precursors for overcoming P-glycoprotein (P-gp)- mediated drug resistance in solid tumors. An in-vitro study was performed to test whether the oil (stearyl alcohol and cetyl alcohol) used to make lipid nanoparticles could be metabolized. The results showed that the concentrations of the fatty alcohols within nanoparticles, which were quantitatively determined over time by gas chromatography, decreased to only 10-20% of the initial concentration after 15-24 h of incubation with horse liver dehydrogenase (HLADH) and NAD+ at 37ºC. Moreover, the surfactant Brij 78 (polyoxyethylene 20-sterayl ether) in the nanoparticles influenced the activity of the enzyme. Novel Cremophor EL-free paclitaxel-loaded nanoparticles were developed using experimental design combining Taguchi array and sequential simplex optimization. The resulting PX G78 and PX BTM NPs were stable at 4ºC over five months and in PBS at 37ºC over 102 h. Release of PX from PX NPs was slow and sustained without initial burst release. Interestingly, PX BTM NPs could be lyophilized without cryoprotectants and without changing any physiochemical properties and bioactivities. Cytotoxicity studies in breast cancer MDA-MB-231 cells showed that PX NPs have similar anti-cancer activities compared to Taxol. Optimized Dox-loaded NPs were prepared using an ion-pair agent, sodium tetradecyl sulfate (STS), to mask Dox charge and to enhance its entrapment in NPs. In-vitro cytotoxicity studies were carried out in both sensitive and resistant human cancer cells treated with PX and Dox-loaded NPs. All of drug-loaded NPs decreased IC50 values by 6-13-fold in resistant cells compared to free drugs. A series of in-vitro assays were used to understand the underlying mechanisms. The results, in part, showed that the NPs inhibited P-gp and transiently depleted ATP, leading to enhanced uptake and prolonged retention of the drugs in P-gp-overexpressing cancer cells. Finally, in-vivo anti-cancer efficacy studies were performed using pegylated PX BTM NPs after intravenous (i.v.) injection and showed marked anti-cancer efficacy in nude mice bearing resistant NCI/ADR-RES tumors versus all control groups. These results suggest that NPs may be used to both target drug and biological mechanisms to overcome MDR.

During the synthesis of well arrayed nano/micro structures through wet chemical methods, plenty of parameters are usually involved. Consequently, it is extremely time- and cost-consuming to find out the optimized synthesis conditions by using the conventional "changing one separate factor at a time" (COST) strategy. Instead, the "statistical experimental design" method has been proven in a few works to be an efficient method for experiments involving many parameters.  With this method, the responses could be optimized efficiently by using only a few experiments. Besides, several responses can be optimized simultaneously. Also, models could be built up and the changing tendency can be plotted to predict the required experimental settings for specific tasks. Two types of well arrayed structures including monolayer arrays of silica spheres and vertically aligned ZnO rod arrays were investigated in this work. Monolayer arrays of silica spheres were synthesized by using a dual-speed spin coating method. With assistance of statistical experimental design, the accelerating rate, the second rotation speed and time of the dual-speed spin coating system were found as non-significant parameters to the ordering degree of the obtained monolayer, and thus they can be fixed. This finding could remarkably increase the feasibility of optimizing the practical process. On the other hand, the relative humidity, the first rotation speed and the suspension concentration are identified as the significant parameters to the structures of the monolayer. Moreover, the optimal values for these three parameters were identified: 23% for the relative humidity, 1000 rpm for the first rotation speed and 30 wt.% for the suspension concentration. With these optimized parameters, the area of the obtained silica sphere monolayers reached over 1 cm2 and the defect-free domain size reached over 4000 μm2. These values are considerably higher compared to the previously reported values. Vertically aligned ZnO rod arrays were fabricated by chemical bath deposition. Parameters including precursor concentration, pH value, reaction temperature, reaction time and addition of capping agent were optimized by using statistical experimental design to improve and optimize the growth quality of ZnO rod arrays. Through several stages of optimization, the growth quality of the obtained structures was remarkably enhanced from sparse or clustered ZnO rods to upright and dense ZnO rods. The boundary conditions to achieve vertically aligned ZnO rods, such as a neutral solution and a precursor concentration over 0.02M, were determined. The changing tendency of the texture coefficient and aspect ratio with the factors was also plotted to predict the required experimental settings for specific requests. The points or regions to achieve the optimal properties were identified as well. For instance, the concentration should be as close as to 0.1 M, while the reaction temperature should be limited to 80-90 ◦C, to achieve the ideal preferential growth. With the optimized parameters, the texture coefficient reached almost the perfect value 1, and the aspect ratio was elevated to 21. Moreover, to obtain a dense ZnO thin film, tri-sodium citrate was added to the reaction system. The diameter was systematically controlled through varying the parameters. When both the diameter and the texture coefficient reached the optimal values, the rods were merged together to form a dense ZnO thin film. Furthermore, comments on the statistical experimental method are proposed, and both the advantages and disadvantages are presented according to the present thesis work. This might help the researchers to avoid the disadvantages and thus to employ this method more efficiently in the future. / <p>QC 20150903</p>

Unstable oil markets with rising environmental concerns have revived widespread interest in production of fuel ethanol from renewable materials. Cellulosic materials are abundant and prominent feedstocks for cheap ethanol production. However, due to recalcitrant structure of these materials, pretreatment is a prerequisite. Depending on the biomass, pretreatment and hydrolysis conditions, a number of degradation products and/or toxic components may be released that show strong inhibitory effects on the fermenting microorganisms. This thesis deals with application of encapsulation technology to ferment the highly toxic hydrolyzates without further pretreatment. Free cells could not tolerate presence of 5 g/l furfural in defined medium, and inhibitors in wood and peel hydrolyzates in batch mode of operation and fermentation failed. Continuous cultivation of wood hydrolyzate was only successful at 0.1 h−1 and the majority of cells lost their viability after 5 retention times. Encapsulated cell system could successfully ferment the synthetic medium containing 5 g/l furfural during sequential batch cultivations with ethanol yield of 0.41-0.42 g/g. Cultivation of undetoxified hydrolyzates was also carried out, where glucose and mannose were converted within 10 h without significant lag phase. However, a gradual decrease in cell activity was observed in sequential batches. Continuous cultivation was more successful, and wood hydrolyzate was fermented to ethanol by encapsulated S. cerevisiae at dilution rates up to 0.5 h−1. More than 75% of the encapsulated cells were viable in the worst conditions. Ethanol was produced with yield 0.44 g/g and specific productivity 0.14–0.17 g/g•h at all dilution rates. Contrary to wood hydrolyzate, where there is no preference for permeation of sugars or inhibitors through the capsules’ membrane, encapsulation technology was applied to eliminate inhibition of limonene in fermentation of orange wastes to ethanol. The capsules’ membrane, of hydrophilic nature, is practically impermeable to hydrophobic compounds such as limonene while allowing penetration of nutrients and products. While presence of 0.1% v/v limonene in the medium results in strong inhibition or even failure of cultivation with free cells, using this technique allowed fermentation of a medium containing 1.5% v/v limonene. The impact of encapsulation on the anaerobic growth pattern, morphological and physiological changes of S. cerevisiae over long-term application was investigated. The growth rate, total RNA and protein content of the encapsulated cells decreased gradually over repeated batch cultivations, while stored carbohydrates content increased. Within 20 batch cultivations, total RNA and protein content of encapsulated cells decreased by 39% and 24%, whereas glycogen and trehalose content increased by factors of 4.5 and 4, respectively. / <p>Akademisk avhandling som för avläggande av teknologie doktorsexamen vid Chalmers tekniska högskola försvaras vid offentlig disputation den 18 april 2008.</p>

Cette thèse est divisée en quatre parties. Dans la première, je vais présenter notre travail sur le run-up des vagues longues et sur les phénomènes d’amplification par résonance. Grâce à des simulations numériques basées sur les équations en eau peu profonde non-linéaires, nous montrons que dans le cas des vagues monochromatiques d’incidence normale sur une plage inclinée, une amplification résonante du run-up se produit lorsque la longueur de la vague d’entrée est 5.2 fois plus grande que la longueur de la plage. Nous montrons également que cette amplification résonante de run-up peut être observée à partir de plusieurs profils de vagues. Cependant, l’amplification résonante du run-up n’est pas limitée aux plages inclinées infinies. En faisant varier le profil bathymétrique, la résonance est également présente dans le cas de bathymétries linéaires par morceaux et pour des bathymétries réalistes. Dans la deuxième partie, je présente une nouvelle solution analytique pour étudier la propagation des tsunamis générés par une source non ponctuelle sur une profondeur constante en utilisant la théorie des vagues en eau peu profonde linéaires. La solution, qui repose sur la séparation des variables et sur une double transformée de Fourier dans l’espace, est exacte, facile à mettre en œuvre et permet l’étude d’ondes de formes réalistes comme les ondes en forme de N (N–waves). Dans la troisième partie, j'étudie l’effet de protubérances localisées sur la génération de vagues longues. Même lorsque le déplacement final est connu grâce à l’analyse sismique, le plancher océanique qui se déforme peut avoir du relief comme des montagnes et des failles. On étudie analytiquement l’effet de la bathymétrie sur la génération des vagues de surface, en résolvant les équations en eau peu profonde linéaires avec for. Nous constatons que quand la hauteur du rebord augmente, le piégeage partiel de la vague permet de réduire la hauteur des vagues dans le champ lointain, tout en l’amplifiant au-dessus du rebord. Je vais aussi présenter brièvement une solution de la même équation forcée au-dessus d’un cône. Enfin, dans la dernière partie, nous verrons si les petites îles peuvent protéger les côtes proches de tsunamis comme il est largement admis par les communautés locales. Des découvertes récentes sur le tsunami des îles Mentawai en 2010 montrent un run-up amplifié sur les zones côtières derrière de petites îles, par rapport au run-up sur les lieux adjacents, qui ne sont pas influencés par la présence des îles. Nous allons étudier les conditions de cette amplification du run-up en résolvant numériquement les équations en eau peu profonde non-linaires. Le dispositif expérimental est régi par cinq paramètres physiques. L’objectif est double: Trouver l’amplification maximale du run-up avec un nombre minimum de simulations. Nous présentons un plan d’expériences actif, récemment mis au point et basé sur les processus Gaussiens, qui réduit considérablement le coût de calcul. Après exécution de deux cents simulations, nous constatons que dans aucun des cas considérés l’île n’offre une protection à la zone côtière derrière elle. Au contraire, nous avons mesuré une amplification du run-up sur la plage derrière elle par rapport à une position latérale sur la plage non directement affectée par la présence de l’île. Cette amplification a atteint un facteur maximal de 1.7. Ainsi, les petites îles à proximité du territoire continental agissent comme des amplificateurs des vagues longues dans la région directement derrière elles et non comme des obstacles naturels comme il était communément admis jusqu’ici. / This thesis is divided in four parts. In the first one I will present our work on long wave run-up and some resonant amplification phenomena. With the use of numerical simulations for the nonlinear shallow water equations, we show that in the case of monochromatic waves normally incident on a plane beach, resonant run-up amplification occurs when the incoming wavelength is 5.2 times larger the beach length. We also show that this resonant run-up amplification can be observed for several wave profiles such as bichromatic, polychromatic and cnoidal. However, resonant run-up amplification is not restricted to infinitely sloping beaches. We varied the bathymetric profile, and we saw that resonance is present in the case of piecewise linear and real bathymetries. In the second part I will present a new analytical solution to study the propagation of tsunamis from a finite strip source over constant depth using linear shallow-water wave theory. The solution, which is based on separation of variables and a double Fourier transform in space, is exact, easy to implement and allows the study of realistic waveforms such as N-waves. In the third part I will explore the effect of localized bathymetric features on long wave generation. Even when the final displacement is known from seismic analysis, the deforming seafloor includes relief features such as mounts and trenches. We investigate analytically the effect of bathymetry on the surface wave generation, by solving the forced linear shallow water equation. Our model for bathymetry consists of a cylindrical sill on a flat bottom, to help understand the effect of seamounts on tsunami generation. We derive the same solution by applying both the Laplace and the Fourier transforms in time. We find that as the sill height increases, partial wave trapping reduces the wave height in the far field, while amplifying it above the sill. Finally, in the last part I will try to explore whether small islands can protect nearby coasts from tsunamis as it is widely believed by local communities. Recent findings for the 2010 Mentawai Islands tsunami show amplified run-up on coastal areas behind small islands, compared with the run-up on adjacent locations, not influenced by the presence of the islands. We will investigate the conditions for this run-up amplification by numerically solving the nonlinear shallow water equations. Our bathymetric setup consists of a conical island sitting on a flat bed in front of a plane beach and we send normally incident single waves. The experimental setup is governed by five physical parameters. The objective is twofold: Find the maximum run-up amplification with the least number of simulations. Given that our input space is five-dimensional and a normal grid approach would be prohibitively computationally expensive, we present a recently developed active experimental design strategy, based on Gaussian Processes, which significantly reduces the computational cost. After running two hundred simulations, we find that in none of the cases considered the island did offer protection to the coastal area behind it. On the contrary, we have measured run-up amplification on the beach behind it compared to a lateral location on the beach, not directly affected by the presence of the island, which reached a maximum factor of 1.7. Thus, small islands in the vicinity of the mainland will act as amplifiers of long wave severity at the region directly behind them and not as natural barriers as it was commonly believed so far.