Chronic diseases can often be managed by constantly delivering therapeutic amounts of drug for prolonged periods. A controlled release for extended duration would replace the need for multiple and frequent dosing. Local drug release would provide added benefit as a lower dose of drug at the target site will be needed as opposed to higher doses required by whole body administration. This would provide maximum efficacy with minimum side effects. Nonetheless, a problem with the known implantable drug delivery devices is that the delivery rate cannot be controlled, which leads to drug being released in an unpredictable pattern resulting in poor therapeutic management of patients. This dissertation is the result of development of an implantable drug delivery system that is capable of long-term zero order local release of drugs. The device can be optimized to deliver any pharmaceutical agent for any time period up to several years maintaining a controlled and desired rate. Initially significant efforts were dedicated to the characterization, biocompatibility, and loading capacity of nanoporous metal surfaces for controlled release of drugs. The physical characterization of the nanoporous wafers using Scanning electron microscropy (SEM) and atomic force microscopy techniques (AFM) yielded 3.55 x 10⁴ nm³ of pore volume / μm² of wafer surface. In vitro drug release study using 2 - octyl cyanoacrylate and methyl orange as the polymer-drug matrix was conducted and after 7 days, 88.1 ± 5.0 % drug was released. However, the initial goal to achieve zero order drug release rates for long periods of time was not achieved. The search for a better delivery system led to the design of a perforated microtube. The delivery system was designed and appropriate dimensions for the device size and hole size were estimated. Polyimide microtubes in different sizes (125-1000 μm) were used. Micro holes with dimensions ranging from 20-600 μm were fabricated on these tubes using photolithography, laser drilling, or manual drilling procedures. Small molecules such as crystal violet, prednisolone, and ethinyl estradiol were successfully loaded inside the tubes in powder or solution using manual filling or capillary filling methods. A drug loading of 0.05 – 5.40 mg was achieved depending on the tube size and the drug filling method used. The delivery system in different dimensions was characterized by performing in vitro release studies in phosphate buffered saline (pH 7.1-7.4) and in vitreous humor from the rabbit’s eye at 37.0 ± 1.0°C for up to four weeks. The number of holes was varied between 1 and 3. The tubes were loaded with crystal violet (CV) and ethinyl estradiol (EE). Linear release rates with R²>0.9900 were obtained for all groups with CV and EE. Release rates of 7.8±2.5, 16.2±5.5, and 22.5±6.0 ng/day for CV and 30.1±5.8 ng/day for EE were obtained for small tubes (30 μm hole diameter; 125 μm tube diameter). For large tubes (362-542 μm hole diameter; 1000 μm tube diameter), a release rate of 10.8±4.1, 15.8±4.8 and 22.1±6.7 μg/day was observed in vitro in PBS and a release rate of 5.8±1.8 μg/day was observed ex vivo in vitreous humor. The delivery system was also evaluated for its ability to produce a biologically significant amounts in cells stably transfected with an estrogen receptor/luciferase construct (T47D-KBluc cells). These cells are engineered to produce a constant luminescent signal in proportion to drug exposure. The average luminescence of 1144.8±153.8 and 1219.9±127.7 RLU/day, (RLU = Relative Luminescence Units), yet again indicating the capability of the device for long-term zero order release. The polyimide device was characterized for biocompatibility. An automated goniometer was used to determine the contact angle for the device, which was found to be 63.7±3.7degreees indicating that it is hydrophilic and favors cell attachment. In addition, after 72 h incubation with mammalian cells (RAW 267.4), a high cell distribution was observed on the device’s surface. The polyimide tubes were also investigated for any signs of inflammation using inflammatory markers, TNF-α and IL-1β. No significant levels of either TNF-α or IL-1β were detected in polyimide device. The results indicated that polyimide tubes were biocompatible and did not produce an inflammatory response. / text

An adaptive wing, a zero mass ux ow control device for low speed airfoil separation control, is investigated both experimentally and computationally at low speeds. The adaptive mechanism in the wings provides variable camber that can be actuated across a range of frequencies and amplitudes. Piezoelectric actuators are housed in a NACA 4415 airfoil with a chord length of :203 m. The entire adaptive wing assembly is then wrapped under a layer of latex membrane to provide a exible and smooth upper surface pro le. Experimental diagnostics include ow visualization, particle image velocimetry, as well as lift and drag measurements. The numerical simulation uses a 2D incompressible CFD code based on a nite-volume structured formulation with a chimera overset grid for the purpose of parallel computing. In the current study, the dimensionless speed range examined is 2:5 104 Re 1:5 105, where particular focus is given to Re 7:5 104, where Re = U` . All experiments and simulations are conducted in the range of attack angles from 0 24 and between reduced frequency values from 0 f+ 1:09, where f+ = f` U1 . Both experimental and computational results show that the region of separation is reduced when the actuation is turned on, thus enhancing aerodynamic e ciency. The maximum coe cient of lift increases by 26% when the reduced frequency, f+, is approximately :2, where the ow control mechanism appears to be most e ective. Phase-locked PIV and CFD vorticity plots reveal that the downward motion of the surface actuation decelerates the boundary ow and increases surface pressure, resulting in the formation of a series of cross-stream vortices that provides uid entrainment towards the suction surface, hence reducing separation.

Gene transcription in individual living cells is inevitably a stochastic and dynamic process. Little is known about how cells and organisms learn to balance the fidelity of transcriptional control and the stochasticity of transcription dynamics. In an effort to elucidate the contribution of environmental signals to this intricate balance, a Three State Model was recently proposed, and the transcription system was assumed to transit among three different functional states randomly. In this work, we employ this model to demonstrate how the stochastic dynamics of gene transcription can be characterized by the three transition parameters. We compute the probability distribution of a zero transcript event and its conjugate, the distribution of the time durations in gene on or gene off periods, the transition frequency between system states, and the transcriptional bursting frequency. We also exemplify the mathematical results by the experimental data on prokaryotic and eukaryotic transcription. The analysis reveals that no promoters will be definitely turned on to transcribe within a finite time period, no matter how strong the induction signals are applied, and how abundant the activators are available. Although stronger extrinsic signals could enhance promoter activation rate, the promoter creates an intrinsic ceiling that no signals could cross over in a finite time. Consequently, among a large population of isogenic cells, only a portion of the cells, but not the whole population, could be induced by environmental signals to express a particular gene within a finite time period. We prove that the gene on duration follows an exponential distribution, and the gene off intervals show a local maximum that is best described by assuming two sequential exponential process. The transition frequencies are determined by a system of stochastic differential equations, or equivalently, an iterative scheme of integral operators. We prove that for each positive integer n , there associates a unique time, called the peak instant, at which the nth transcript synthesis cycle since time zero proceeds most likely. These moments constitute a time series preserving the nature order of n.

<p>Livestock keeping has been the essential source of livelihood in Babati District for many hundreds of years. The traditional ecological knowledge about this semi-arid environment has influenced the general view on livestock management. This essay discusses the measures that are, or could be taken in Babati District to prevent overstocking and overgrazing in the woodlands. With the continuing population density increase also the livestock population grows. More houses and roads are built and the grazing lands diminish. To avoid overgrazing forest management programmes restrict grazing in forests. This additionally decreases availability of grazing land. My conclusion is that minimizing number of livestock is necessary to not exceed carrying capacity of pasture during drought. Hence this is not free from problems since it is traditionally rooted to have a large number of livestock as a buffer of energy and wealth. One solution for both how to prevent overstocking and how to survive with small number of livestock is to practise zero-grazing. Zero-grazing is to keep a small number of healthy big cattle e.g. exotic cows or crossbreeds in stables or tied up. However, when tying cattle on the spot the fact that cattle have four legs is disregarded.</p>

The Poincare-Miranda Theorem is a topological result about the existence of a zero of a function under particular boundary conditions. In this thesis, we explore proofs of the Poincare-Miranda Theorem that are discrete in nature - that is, they prove a continuous result using an intermediate lemma about discrete objects. We explain a proof by Tkacz and Turzanski that proves the Poincare-Miranda theorem via the Steinhaus Chessboard Theorem, involving colorings of partitions of n-dimensional cubes. Then, we develop a new proof of the Poincare-Miranda Theorem that relies on a polytopal generalization of Sperner's Lemma of Deloera - Peterson - Su. Finally, we extend these discrete ideas to attempt to prove the existence of a zero with the boundary condition of Morales.

Abstract Turkey has emerged as a major actor in the Middle East over the last decade, since the ruling party AKP came to power in 2002. Turkey is now playing a mediation role in regional conflicts and has been speaking out loudly on sensitive issues such as the Iranian nuclear program and the Palestinian- Israeli conflict. Furthermore, Turkey has established close ties with the Arab world which has suffered the relationship with its long-time ally Israel. This new presence in Middle East has been criticized by Turkey's allies in west. Critics argue that the country is about to abandon its former western relationship and strengthen their ties with the Arab world instead. This thesis has two main purposes. First, an empirical purpose which is to describe and explain changes in Turkish foreign policy towards Middle East. Second, this thesis has a theoretical purpose, aiming to make a contribution to the study field also on a theoretical level. The ambition is therefore to provide with ideas and/or modify the model of Gustavsson in order to make it more applicable of other cases of foreign policy change. The theoretical framework applied on this thesis is Jakob Gustavsson's model for explaining foreign policy change. Turkey's foreign policy change will be analyzed through a qualitative case study that focuses on the country's relations with the Middle East. Based on Gustavsson's model, possible explanations to Turkey's foreign policy change towards Middle East are structural changes in the international and national system. The end of the bipolarity system during the cold war resulted in a major structural change, thus Turkey had to adapt to the new system by hammering out a new foreign policy doctrine. In addition to this, the growing opposition to a Turkish membership within the EU is considered to be another explanation to Turkey's improved relations with the Middle East. The results shows furthermore possible explanations on a national level such as growing economy, a strong Turkish public opinion, new actors and also AKP:s ideological affinity with Muslim aspirations. The Iraq crisis, which arose in 2003 when Turkey rejected a resolution authorizing the deployment of American forces in Turkey in a war against Iraq, functions as a catalysts for the changes in Turkish foreign policy. One of the main components in the model emphasizes that the individual key actor needs to go through a change within its belief system, however the author have not found such evidence in this case and thus suggests that this part of the model becomes slightly modified or even removed. Keywords: Turkey, AKP, Ahmet Davutoglu, Middle East, foreign policy change, zero problems towards neighbors

Fully understanding soot formation in flames is critical to the development of practical combustion devices, which typically operate at high pressures, and fire suppression systems in space. Flames display significant changes under microgravity and high-pressure conditions as compared to normal-gravity flames at atmospheric pressure, but the exact causes of these changes are not well-characterized. As such, the effects of gravity and pressure on the stability characteristics and sooting behavior of laminar coflow diffusion flames were investigated. To study these effects, a new highly-scalable combustion modelling tool was developed specifically for use on large multi-processor computer architectures. The tool is capable of capturing complex processes such as detailed chemistry, molecular transport, radiation, and soot formation/destruction in laminar diffusion flames. The proposed algorithm represents the current state of the art in combustion modelling, making use of a second-order accurate finite-volume scheme and a parallel adaptive mesh refinement algorithm on body-fitted, multi-block meshes. An acetylene-based, semi-empirical model was used to predict the nucleation, growth, and oxidation of soot particles. Reasonable agreement with experimental measurements for different fuels and pressures was obtained for predictions of flame height, temperature and soot volume fraction. Overall, the algorithm displayed excellent strong scaling performance by achieving a parallel efficiency of 70% on 384 processors. The effects of pressure and gravity were studied for flames of two different fuels: ethylene-air flames between pressures of 0.5–5 atm and methane-air flames between 1–60 atm. Based on the numerical predictions, zero-gravity flames had lower temperatures, broader soot-containing zones, and higher soot concentrations than normal-gravity flames at the same pressure. Buoyant forces caused the normal-gravity flames to narrow with increasing pressure while the increased soot concentrations and radiation at high pressures lengthened the zero-gravity flames. Low-pressure flames at both gravity levels exhibited a similar power-law dependence of the maximum carbon conversion on pressure which weakened as pressure was increased. This dependence decayed at a faster rate in zero gravity when pressure was increased beyond 1–10 atm.

Syfte: Syftet med studien är att bidra med en ökad förståelse för hur kvalitetsförbättringsarbete används för att eliminera brister och fel inom byggbranschen. Metod:  Studien utfördes genom kvalitativ metod med hermeneutiskt synsätt samt tolkning. Fallstudien omfattar fyra intervjurespondenter varav en pilotstudie samt 42 enkäter till samtliga tjänstemän och medarbetare med ledaransvar på olika nivåer inom kvalitetsförbättringsarbetet. Insamlad data bearbetades med hjälp av tematisk analys för att sedan analyseras och tolkas. Slutligen drogs slutsatser från resultat och analysmaterialet. Resultat &amp; Slutsats: Med hjälp av litteraturgenomgången och resultatet av det undersökta fallföretaget har studien kommit fram till att det är utmanande och svårt men inte omöjligt att implementera kvalitetsförbättringsmetoder och tekniker i byggbranschen utifrån de unika förutsättningar som råder i byggbranschen. Det råder samsyn bland de tillfrågade gällande vad de upplever är de vanligast förekommande kvalitetsbrister och fel vid slutbesiktning. Några av de enkla och kortsiktiga steg som framkommit i studien som kan ha positiva och långsiktiga effekter är främst att se fel och brister som ett resultat av alla delar i processen, fokusera på kvalitet lika mycket under hela processen, att involvera utförandenivån även i planering och målsättning, att i större utsträckning driva kvalitetsförbättringsarbetet i team på arbetsplatserna, att träna och utbilda samtliga ledare för kvalitetsförbättringsarbete och kanske även medarbetarna för ökad delaktighet och kunskap, att utveckla systematik för faktabaserad kunskapsåterföring och att ge tillräckligt uppmärksamhet och erkännande till medarbetare för prestationer kanske genom att låta dem själva få redovisa och utvärdera sitt eget och varandras arbete.

There is a significant problem for the paper recycling industry known as “stickies”. “Stickies” are tacky species, present in recycled paper and coated broke, derived from coating formulations, adhesives, etc. They impact negatively on paper quality and cause web runnability problems by deposit build-up. To sustain recycling, stickies are controlled by adsorbing them onto minerals added to the recycled stock. So the aim of the project was to characterise non-porous and porous minerals suitable for paper-making, and then use the knowledge gained to improve the adsorption of stickies. The pore level properties of the minerals used to control stickies are highly relevant in regulating adsorption of the stickies. Levels of pore architecture were investigated by characterising filter media with porosimetry, porometry, electron microscopy and modelling the combined results. Seven samples were studied, with pore size distributions ranging from simple unimodal to complicated bimodal. Porometry, porosimetry and SEM, individually can only determine primary pore architecture. A combination of experimental and modelling techniques allows a full characterisation of pore architecture from primary to quaternary levels. Calcium carbonates can be modified to change the pore architecture, which affects properties such as wetting. Their pore architecture was investigated to understand why some modified calcium carbonates do not show two distinct wetting rates. The investigation implied a significant surface area could be attributed to nano rugosity. The nano rugosity was responsible for the enhanced wetting of a sample. A zero length column was used to study diffusion and desorption of benzene with calcium carbonate. Desorption and diffusion coefficients for calcium carbonate systems were calculated from the corrected concentration versus time measurements. They showed how the pore architecture affects diffusion and desorption. By comparing the experimental results with a pore network simulation, it was possible to deduce the relative effect of surface diffusion. The adsorption of stickies onto different mineral grades was investigated using a novel proxy method to determine equilibrium constants and adsorption isotherms. The results were then used to understand the influence of particle size on the adsorption behaviour, with three mechanisms proposed. The equilibrium constant and adsorption isotherm data also allowed comparisons between hydrophilic and hydrophobic adsorption onto grades of talc. Recommendations are made for the optimum use of minerals for the removal of stickies, and for in-situ methods for monitoring and optimising removal.

This paper develops a Bayesian Global VAR (GVAR) model to track the international transmission dynamics of two stylized shocks, namely a supply and demand shock to US-based safe assets. Our main findings can be summarized as follows. First, we find that (positive) supply-sided shocks lead to pronounced increases in economic activity which spills over to foreign countries. The impact of supply-sided shocks can also be seen for other quantities of interest, most notably equity prices and exchange rates in Europe. Second, a demand-sided shock leads to an appreciation of the US dollar and generally lower yields on US securities, forcing investors to shift their portfolios towards foreign fixed income securities. This yields sizable positive effects on US output, equity prices and a general decrease in financial market volatility. / Series: Department of Economics Working Paper Series