This thesis is an experimental investigation on the binding of self-assembling peptides to oligodeoxynucleotides (ODNs) and the characterization of the resulting peptide-ODN complexes/aggregates, the first key step in the development of a peptide-based gene delivery system. Effects of pH, charge distribution along the peptide backbone, and oligonucleotide sequences on the peptide-ODN binding were investigated by a series of physicochemical methods. UV-Vis absorption and fluorescence anisotropy experiments demonstrate that aggregates are formed after mixing the peptide and ODN in aqueous solution. The aggregates in solution can be centrifuged out. Based on this property, the fraction of ODNs incorporated in the peptide-ODN aggregates can be obtained by comparing the UV-Vis absorption of the solution before and after centrifugation. Binding isotherms are generated by a binding density function analysis of the UV absorbance results. The binding parameters are extracted from the analysis of the binding isotherms based on the McGhee and von Hippel model. Equilibrium binding parameter studies show that the binding of two self-assembling peptides, EAK16-II and EAK 16-IV, to model single and double-stranded ODNs at pH 4 is stronger than at pH 7, and that no binding occurs at pH 11. These results demonstrate that electrostatic interactions play an important role in the EAK-ODN binding because EAKs are more positively charged at low pH. EAKs bind more strongly to dG16 than to the other ODN sequences dC16 and dGC16. This demonstrates that the hydrogen bond might be involved because they promote the binding of the lysine residues of the peptide to dG16 to a greater extent than to dC16. The charge distribution along the peptides is found to have an effect on the binding. EAK16-IV, whose positively charged residues are clustered at one end of the peptide, binds to the ODNs more strongly than EAK16-II, whose positively charged residues are distributed throughout the peptide chain, at the same pH. The binding process of EAKs to the ODNs was investigated by fluorescence anisotropy and static light scattering experiments. The results show that individual EAK and ODN molecules complex first, followed by the aggregation of these complexes into large aggregates. The nature of the resulting peptide-ODN complexes/aggregates is examined by UV-Vis absorption, fluorescence anisotropy, and PAGE experiments. The results demonstrate that free EAK, free ODNs, and small EAK-ODN complexes, which can not be centrifuged out, exist in the supernatant, and that large aggregates are collected in the pellets after centrifugation of the solution. The size of the resulting EAK-ODN complexes/aggregates measured by AFM and DLS is around a few hundreds of nanometers at low EAK concentrations. The accessibility of the ODNs to the quencher in the solution is reduced by 40 % and 60 % after binding to EAK16-II and EAK16-IV, respectively, as determined by fluorescence quenching experiments on EAK-ODN mixture solutions. An ODN protection from Exonuclease 1 degradation is provided by the EAK16-II or EAK16-IV matrix when they are mixed with the ODNs at pH 4. However, the ODNs are protected to a much lower degree when the EAK-ODN aggregates are prepared at pH 7. The EAK-ODN aggregates prepared at pH 7 are found to dissociate more easily than those prepared at pH 4 when they are incubated with exonuclease I solution at pH 9.5. These results suggest that the ODN protection afforded by the EAK-ODN aggregates is correlated with their structural stability after being incubated with the nuclease solution. The stability of the EAK-ODN aggregates after dilution is determined by UV-Vis absorption. No detectable dissociation of the aggregates is observed over 20 hrs after a 5- and 10-fold dilution of the solution in the same buffer used for their preparation. The EAK-ODN aggregates remain stable after the solutions are centrifuged, and re-dissolved in fresh buffer solutions. The ability of an EAK matix to protect ODNs from nuclease degradation together with its biocompatibility and low-toxicity suggests that EAK self-assembling peptides could be used as carriers for gene delivery.

Acne is an extremely common condition, affecting almost 80% of adolescents and young adults. It is an inflammatory disease, characterised by comedones, papules, pustules and sometimes cysts. Factors causing acne include enhanced sebum excretion, hypercornification of the sebaceous duct, ductal coloniazation with Propionibacterium acnes and production of inflammation (Gollnick & Cunliffe, 2003:1). Because of the widespread use of topically applied antimicrobial agents in the treatment of inflammatory acne, resistance of disease-related micro-organisms developed. Therefore new strategies for the treatment of moderate inflammatory acne are necessary. Nicotinamide is a new approach to topical treatment of moderate inflammatory acne without the development of resistant micro-organisms (Otte et al., 2005:257). Using the skin as an alternative route for the administration of nicotinamide for the treatment of acne, may be beneficial. When nicotinamide permeates through the skin, it is directly delivered to the dermis, the place where action is needed and better results can thus be expected after the treatment has started. Another benefit is that smaller amounts of the drug are absorbed systemically with decreased adverse reactions. Unfortunately, using the skin as an alternative route for administering drugs (transdermal drug delivery), has numerous limitations. One of these limitations is the barrier function of the skin (Naik et al., 2000:319). Because of the skin's outstanding ability to protect the body against unwanted substances from its surroundings, it is necessary to use methods to enhance drug penetration through the skin. A new technology, named Pheroid™ technology, was used in this study to enhance penetration through the skin. This technology is based on the use of vesicular structures with no phospholipids or cholesterol to enhance penetration (Grobler et al., 2008:283). The aim of this study was to formulate four different semi-solid formulations with nicotinamide as the active ingredient, and to determine which of the formulations deliver nicotinamide best to the target site. Stability tests over a six months period were also performed on the different formulations. A 3% nicotinamide cream, with and without Pheroid™ vesicles, and a 3% nicotinamide gel, with and without Pheroid™ vesicles, were formulated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

AbstractBackground: ACL injuries is common and can result in long term disability or even have a career ending outcome for the athlete. Women are more exposed to ACL injuries than men are and several factors increase the risk of ACL injuries for women where one is the knee angle velocity. It seems that prevention programs involving plyometric- and strength training has been most effective on altering these risk factors for knee injuries. But many programs involve several exercises which makes it very time consuming. Since the gluteus muscles is our main hip abductor and hip stabilizer it is of great importance for controlling the knee. The ProPrioPlate (PPP) is a device that has been validated and shown to activate the gluteus medius 40% more in a squat compared to a regular bodyweight squat.Purpose: To investigate if a 6 week long training period, 3 sessions/ week, 5minutes/session with the PPP could decrease the mean abduction angular velocity (°/sec) of the knee joint in a Drop jump (DJ) in women with poor knee stabilityMethod: An experimental study design was used. Twelve female athletes with poor knee stability and signs of knee valgus in a drop jump conducted a 6 weeks training program to investigate any changes in abduction angular velocity in a DJ. 3D motion analyzes were performed before and after the training period. Wilcoxon signed ranked test was used to investigate if there were any changes in results between the different test occasions.Results: Median abduction angular velocity of the test performed before the intervention was -34. 34 (min -70. 65 max -11. 53) deg/sec and after the intervention median -34. 22 deg/sec (min -51. 97 max -3. 28). The P value was 0.24 which indicate that there were no statistical significant differences between the three testing occasions. Compliance to the intervention was low, 15%.Conclusion: A 6 weeks training period with the PPP did not decrease the abduction angular velocity. Due to low compliance rate amongst of subjects no conclusion regarding the effect of the device can be made. / Abstrakt:Bakgrund: Svenska ligament registret rapporterar ungefär 5000 främre korsbandsskador (ACL) årligen i Sverige. ACL skador kan resultera i långvarig frånvaro från sporten eller till och med att idrottaren inte längre kan fortsätta sin karriär. Kvinnor är mer utsatta för ACL skador än män och det är flera faktorer som ökar risken för ACL skador hos kvinnor. Forskningen pekar mot att träningsprogram som syftar till att minska risken för knäskador innefattar styrketräning och plyometrisk träning. Många träningsprogram för att minska risken för knäskador innefattar många övningar vilket gör det tidskrävande. ProPrioPlate (PPP) är ett träningsredskap som är validerat och har visats aktivera gluteus medius 40% mer i en knäböj på PPP jämfört med vanliga knäböj.Syftet med denna studie var att undersöka knätabduktionshastighet i ett dropp vertikalhopp innan och efter ett 6 veckors träningsprogram med PPP för kvinnor med bristande knästabilitet.Metod: En exprementell studiedesign har använts. Tjugo frivilliga kvinnliga idrottar med bristande knästabilitet och teckan på valgus vid dropjump genomförde ett 6 veckors träningsprogram för att undersöka om knäabduktionshastighet i ett dropp vertikalhopp förändrades efter träningsperioden. 3D analyser på testpersonerna genomfördes innan och efter träningsperioden. Wilcoxons signed ranked test användes för att undersöka skillnader mellan de olika test tillfällena.Resultat: Medianen av abduktionshastigheten före interventionen var -47,88 grader/sek (min -74,76 max -30.16), -34.34 (min -70.65 max -11.53) och efter interventionen -34.22 (min -51.97 max -3.28) grader/sek. P värdet var 0.24 vilket indikerar att det inte fanns någon signifikant skillnad mellan före- och eftertesterna. Följsamheten till träningen hos deltagarna var låg (15%).Slutsats: En 6 veckors träningsperiod med PPP minskade inte abduktionshastigheten i ett DJ. Låg åtföljnad av våra testpersoner till träningsperioden innebar att inga slutsatser gällande PPP kan utgöras.

In this thesis the eigenstructure (eigenvalues and eigenvectors) assignment technique based algorithm has been developed for the design of controllers for power system applications. The application of the algorithm is demonstrated by designing power system stabilizers (PSSs) that are extensively used to address the small-signal rotor angle stability problems in power systems. In the eigenstructure assignment technique, the critical eigenvalues can be relocated as well as their associated eigenvectors can be modified. This method is superior and yield better dynamical performance compared to the widely used frequency domain design method, in which only the critical eigenvalues are relocated and no attempt is made to modify the eigenvectors. The reviewed published research has demonstrated successful application of the eigenstructure assignment technique in the design of controllers for small control systems. However, the application of this technique in the design of controllers for power systems has not been investigated rigorously. In contrast to a small system, a power system has a very large number state variables compared to the combined number of system inputs and outputs. Therefore, the eigenstructure assignment technique that has been successfully applied in the design of controllers for small systems could not be applied as is in the design of power system controllers. This thesis proposes a novel approach to the application of the eigenstructure assignment technique in the design of power system controllers. In this new approach, a multi-objective nonlinear optimization problem (MONLOP) is formulated by quantifying different design objectives as a function of free parametric vectors. Then the MONLOP is solved for the free parametric vectors using a nonlinear optimization technique. Finally, the solution of the controller parameters is obtained using the solved free parametric vectors. The superiority of the proposed method over the conventional frequency domain method is demonstrated by designing controllers for three different systems and validating the controllers through nonlinear transient simulations. One of the cases includes design of a PSS for the Manitoba Hydro system having about 29,000 states variables, which demonstrates the applicability of the proposed algorithm for a practical real-world system.

Passive dynamic walking is a manner of walking developed, partially or in whole, by the energy provided by gravity. Studying passive dynamic walking provides insight into human walking and is an invaluable tool for designing energy efficient biped robots. The objective of this research was to develop a new mathematical model of passive dynamic walking that modeled the ground reaction forces. A physical passive walker was built to validate the proposed mathematical model. The stability of the gait was analyzed using the proposed model. A novel method was created to determine the stability region of the model. Using the insights gained from the stability analysis, the relation between the angular momentum and the stability of the gait was examined. The proposed model matched the gait of the physical passive walker exceptionally well, both in trend and magnitude. The angular momentum of the passive walker was not found to correlate to the stability of the gait.

Acne is an extremely common condition, affecting almost 80% of adolescents and young adults. It is an inflammatory disease, characterised by comedones, papules, pustules and sometimes cysts. Factors causing acne include enhanced sebum excretion, hypercornification of the sebaceous duct, ductal coloniazation with Propionibacterium acnes and production of inflammation (Gollnick & Cunliffe, 2003:1). Because of the widespread use of topically applied antimicrobial agents in the treatment of inflammatory acne, resistance of disease-related micro-organisms developed. Therefore new strategies for the treatment of moderate inflammatory acne are necessary. Nicotinamide is a new approach to topical treatment of moderate inflammatory acne without the development of resistant micro-organisms (Otte et al., 2005:257). Using the skin as an alternative route for the administration of nicotinamide for the treatment of acne, may be beneficial. When nicotinamide permeates through the skin, it is directly delivered to the dermis, the place where action is needed and better results can thus be expected after the treatment has started. Another benefit is that smaller amounts of the drug are absorbed systemically with decreased adverse reactions. Unfortunately, using the skin as an alternative route for administering drugs (transdermal drug delivery), has numerous limitations. One of these limitations is the barrier function of the skin (Naik et al., 2000:319). Because of the skin's outstanding ability to protect the body against unwanted substances from its surroundings, it is necessary to use methods to enhance drug penetration through the skin. A new technology, named Pheroid™ technology, was used in this study to enhance penetration through the skin. This technology is based on the use of vesicular structures with no phospholipids or cholesterol to enhance penetration (Grobler et al., 2008:283). The aim of this study was to formulate four different semi-solid formulations with nicotinamide as the active ingredient, and to determine which of the formulations deliver nicotinamide best to the target site. Stability tests over a six months period were also performed on the different formulations. A 3% nicotinamide cream, with and without Pheroid™ vesicles, and a 3% nicotinamide gel, with and without Pheroid™ vesicles, were formulated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

This dissertation investigates the nature of submarine landslides along the deformation front of the northern Cascadia subduction zone. As the first slope stability analysis on the west coast of Vancouver Island, this study covers a variety of large-scale tectonic to small-scale, site-specific factors to investigate the nature of slope failure. Slope failure occurred mainly on the steep slopes of frontal ridges that were formed by compressive forces due to the subduction of the Juan de Fuca plate. Multi-beam swath bathymetry data are used to study the morphology of the whole margin and the geometry of two Holocene landslides that serve as representative examples. The overall margin stability is estimated using the critical taper theory, and a first-order limit equilibrium slope stability analysis provides threshold values for external forces to cause slope failure. The present-day pore pressure regime at different sites of the Cascadia margin is estimated from log-density data and expected ground accelerations are calculated via ground motion attenuation relationships. A comparison to threshold values derived from the limit equilibrium analysis suggests that, at present, slope stability is more sensitive to overpressure than to earthquake shaking. Differences in power spectral density derived from OBS-velocity data imply a slightly amplified ground response at the ridge crest compared to sites along the continental shelf and abyssal plain. Apart from estimating the trigger mechanisms of submarine landslides offshore Vancouver Island, a particular consideration is given to the potential link between slope failure and methane hydrate occurrence. The history of the gas hydrate stability zone (GHSZ) boundaries is investigated using information on regional sea-level history. Assuming colder ocean-bottom temperatures during the Holocene, a gradual shoaling of the BSR is inferred, which potentially could have caused hydrate melting. Pore pressure due to hydrate dissociation, as estimated by a previously developed method, varies over several orders of magnitude. Depending on sediment permeability, overpressure ratios can be comparable to threshold values. The two Holocene landslides are modeled numerically using a two-dimensional finite difference code in order to recreate the along-strike variability in ridge geometry and slide morphology observed along the northern Cascadia margin. Geometry and morphology correlate with the two prevalent slide mechanisms and model results suggest that sediment yield strength and average slide thickness are associated with the slide mechanism as well. / Graduate / 0373 / nscholz@uvic.ca

No description available.

The most common way to analyze slope stability is to employ limit equilibrium (LE) theory and obtain a factor of safety (FOS). Methods of LE analysis balance the forces, and/or moments that are driving and resisting slope movement. Generally, in geotechnical engineering practice, a slope that plays host to an important structure is designed with a minimum factor of safety (FOS) of 1.5 and slope movement is monitored throughout the structure’s serviceable life. No further analysis of slope stability is completed until failure occurs when a back analysis is undertaken for the design of remedial measures. This thesis builds on current methods to demonstrate a framework for analysis that can be followed to analyze the state of a slope throughout its serviceable life. The two bridges at North Battleford, Saskatchewan (Battlefords bridges) were used as case studies for this work. In 1967, the older of the two bridges experienced a slope failure at its south abutment immediately prior to its opening to the public. The failure was remediated reactively by means of subsurface drainage, a toe berm, and river training that included diversion/spur dikes to reduce scour at the landslide toe. Since remediation, there has been no other catastrophic failure at either bridge but slow movement continues in the south abutment slope. Laboratory data and field observations from the onsite inclinometers were provided by Clifton Associates Ltd. (CAL) and Saskatchewan Ministry of Highways and Infrastructure (SMHI). The following methodology was followed to develop a framework of analysis for low FOS slopes: 1. Synthesis of data collected during previous investigations at the Battlefords bridges; 2. Detailed site characterization using existing research and terrain analysis; 3. Back analysis of the critical section through original failure using traditional limit equilibrium methods to calibrate the soil strength properties; 4. Application of the calibrated soil strength properties to the original failure after remediation; 5. Estimation of unknown soil properties using instrumentation at the site. 6. Create a model of the new bridge south abutment with the calibrated strength properties from steps 4 & 5 using the finite element method (FEM). 7. Confirmation of the mechanism of failure and assessment of the shear strain and mobilized shear strength; and, 8. Comparison of the results of FEM and LEM models and relationship between factor of safety and mobilized shear strength. The framework presented in this thesis presents a method of modeling the instability of a slope. In the absence of triaxial testing data, it presents a range of mobilized shear strengths along the shear plane.

No description available.