The reliability of modern gas turbine engines is largely due to careful damage tolerant design a method of structural design based on the assumption that flaws (cracks) exist in any structure and will continue to grow with usage. With proper monitoring, largely in the form of periodic inspections at conservative intervals reliability and safety is maintained. These methods while reliable can lead to the early retirement of some components and unforeseen failure if design assumptions fail to reflect reality. With improvements to sensor and computing technology there is a growing interest in a system that could continuously monitor the health of structural aircraft as well as forecast future damage accumulation in real-time. Through the use of two-dimensional and three-dimensional numerical modeling the initial goals and findings for this continued work include: (a) establishing measurable parameters directly linked to the health of the blade and (b) the feasibility of detecting accumulated damage to the structural material and thermal barrier coating as well as the onset of damage causing structural failure.

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Introduction: The effect of electrical stimulation on muscle degeneration and regeneration is largely unknown and it has not been studied in conjunction with telomeres. The consumption of non-steroidal anti-inflammatory drugs (NSAIDs) is widespread in athletes and the general population when faced with muscle soreness or injury. Furthermore, the effect of NSAIDs on muscle regeneration is controversial and its effect on telomere lengths is also unknown. Methods: Young adult males performed 200 electrically stimulated maximal isokinetic contractions with one leg (ES) and the other worked as a control (CON). They received either 1200mg ibuprofen (IBU) per day or placebo (PLA) from 21 days pre- to 30 days post-exercise. Muscle biopsies were obtained from the vastus lateralis of the CON leg at baseline (H0) and ES leg at 2.5h (H2.5) and both legs at 2, 7 and 30 days post-exercise. Blood samples were obtained at the same time points and at day 4 post-exercise. Afterwards the muscle and blood specimen were analysed for skeletal muscle and peripheral blood telomere lengths by Southern blot and signs of muscle degeneration and regeneration were quantified histologically. Results: Histological changes occurred in the ES leg, including; increased proportion of damaged myofibres (2.1±2.8%) and infiltrated myofibres (5.0±6.0%) at day 7, small myofibres (3.0±4.4%) and internally located myonuclei (2.9±3.1%) at day 30. The IBU group had significantly less internally located myonuclei at day 30 compared to PLA (1.7±2.4% vs. 4.1±3.8%). No significant differences were observed in skeletal muscle mean and minimum telomere lengths between ES and CON leg, between IBU and PLA group or between time points. Peripheral blood mean telomere lengths were not significantly different between IBU and PLA group, but between time points; H0 (9.6±1.2kb) and H2.5 (9.1±1.1kb) were significantly shorter than day 4 (10.3±1.6kb) and day 7 (10.1±1.5kb) (P<0.05). Conclusion: Electrically stimulated contractions caused significant muscle degeneration and regeneration in the 30 days post-exercise. Electrical stimulation also appeared to cause fluctuations in peripheral blood telomere lengths, but not skeletal muscle telomeres. The intake of ibuprofen appeared to interfere with muscle regeneration, but did not seem to affect the peripheral blood or skeletal muscle telomeres. However, due to marked individual variations and the small participant group it is difficult to conclude on the effects of electrical stimulation and ibuprofen on proliferative potential. Further studies are warranted to elucidate the effects of electrical stimulation and ibuprofen on blood and skeletal muscle telomeres.

Cervical spine injury can range from minor to severe or fatal, where severe injuries can result in incomplete or complete quadriplegia. There are close to 45,000 Canadians currently affected by paralysis due to traumatic spinal cord injury (tSCI) with an estimated 1700 new cases each year. The majority of tSCI occur in automotive collisions, and current methods for injury prediction are limited to predicting the likelihood for occupant injury but lack the detail to predict the specific injury and location at the tissue level. This research focused on major injuries associated with high impact automotive collisions such as rollover type collisions. Although whiplash is an injury commonly associated with automotive collisions, it was not considered for this study based on the low risk of neurological impairment. The goal of this study was to develop a cervical spine segment finite element model capable of predicting severe injuries such as ligament tears, disc failure, and bone fracture. The segment models used in this study were developed from previous cervical spine segment models representative of a 50th percentile male. The segment models included the vertebrae, detailed representations of the disc annulus fibres and nucleus, and the associated ligaments. The original model was previously verified and validated under quasi-static loading conditions for physiological ranges of motion. To accomplish the objectives of this research, the original models were modified to include updated material properties with the ability to represent tissue damage corresponding to injuries. Additional verification of the model was required to verify that the new material properties provided a physically correct response. Progressive failure was introduced in the ligament elements to produce a more biofidelic failure response and a tied contact between the vertebral bony endplates and the disc was used to represent disc avulsion. To represent the onset of bone fracture, a critical plastic strain failure criterion was implemented, and elements exceeding this criterion were eroded. The changes made to the material models were based on experimental studies and were not calibrated to produce a specific result. After verifying the modifications were implemented successfully, the models were validated against experimental segment failure tests. Modes of loading investigated included tension, compression, flexion, extension and axial rotation. In each case, the simulated response of the segment was evaluated against the average failure load, displacement at failure, and the observed injuries reported in the experimental studies. Additionally, qualitative analysis of elevated stress locations in the model were compared to reported fracture sites. Overall, the simulations showed good agreement with the experimental failure values, and produced tissue failure that was representative of the observed tissue damage in the experimental tests. The results of this research have provided a solid basis for cervical spine segment level injury prediction. Some limitations include the current implementation of bone fracture under compressive loads, and failure within the annulus fibrosus fibres of the disc should be investigated for future models. In addition to material model modifications, further investigation into the kinetics and kinematics of the upper cervical spine segment are important to better understand the complex interactions between the bone geometry and ligaments. This would give insight into the initial positioning and expected response in subsequent models. Future research will include integrating the current segment-level failure criteria into a full cervical spine model for the purpose of predicting severe cervical spine injury in simulated crash scenarios, with future applications in sports injury prevention and protective equipment.

The application of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA)-salt, to unilaterally nephrectomised rats induces severe hypertension due to volume-overload, and mimics human primary aldosteronism. Importantly, DOCA-salt hypertension is characterized by severe cardiac and renal lesions triggered by nuclear factor kappa B (NF-kappaB), activating protein (AP-1), and transforming growth factor beta1 (TGF-beta1) leading to end-stage organ damage. Although DOCA-salt hypertension is a low renin model, local production of angiotensin-II and aldosterone in cardiac and renal tissues stimulate TGF-beta1, fibronectin and collagen-1 causing fibrosis and hypertrophy. Since TGF-beta1 gene promoter contains binding sites for NF-kappaB and AP-1, cross-talk between TGF-beta1, NF-kappaBnand AP-1 can be envisaged. Accordingly, the activation of TGF-beta1, fibronectin, collagen, NF-kappaB and AP-1 may constitute a potent destructive force in hypertension.<p> Emerging evidence indicates that upregulation of the heme oxygenase (HO) system is cytoprotective with antioxidant, antihypertensive and antihypertrophic effects. Interestingly, the promoter region of HO-1 gene harbors consensus-binding sites for NF-kappaB and AP-1; therefore, the HO system may regulate these transcription factors to counteract tissue insults. However, the multifaceted interactions between the HO system, NF-kappaB, AP-1, TGF-beta1, fibronectin and collagen in mineralocorticoid-induced end-stage-organ damage have not been fully characterized. Similarly, the effect of the HO system on tissue angiotensin-II and aldosterone levels in mineralocorticoid-induced hypertension remains unclear. Therefore, the present study was designed to investigate the antihypertrophic effect of the HO system in cardiac and renal tissue of DOCA-salt hypertensive rats. In this study, the HO inducer, hemin, lowered blood pressure and attenuated cardiac/renal hypertrophy, whereas the HO inhibitor, chromium mesoporphyrin (CrMP), nullified the effects of hemin and exacerbated cardiac/renal injury the DOCA-salt hypertensive rats. The protective effect of hemin was associated with increased HO-1, HO activity, cyclic guanosine monophosphate (cGMP), superoxide dismutase activity, ferritin and the total antioxidant capacity in the cardiac and renal tissue. In contrast, angiotensin-II, aldosterone, 8-isoprostane, NF-kappaB and AP-1 were significantly downregulated. Furthermore, hemin therapy attenuated TGF-beta1 and extracellular matrix (ECM) proteins such as fibronectin and collagen, with corresponding reduction of cardiac histopathological lesions, including longitudinal/cross-sectional muscle fiber thickness, scarring, muscular hypertrophy, coronary arteriolar thickening and collagen deposition. Similarly, hemin attenuated structural lesions in the kidney such as glomerular hypertrophy, glomerular sclerosis, mononuclear cell infiltration, tubular cast formation, tubular dilation and renal arteriolar thickening with concomitant improvement of kidney function as evidenced by reduction of plasma creatinine, proteinuria, but enhanced creatinine clearance.<p> Collectively, these results suggest that the HO system suppressed hypertension, cardiac and renal fibrosis, and hypertrophy in the DOCA-salt hypertensive rat by downregulating transcription factors such as NF-kappaB and AP-1, reducing ECM proteins such as fibronectin and collagen, decreasing local tissue production of angiotensin-II and aldosterone, and improved renal functional capacity.

DNA is susceptible to both exogenous and endogenous damaging agents. Damage is constantly reversed by a wide range of DNA repair pathways. Lesions which escape such repair may cause nucleotide mis-pairing and stalled replication, resulting in mutagenesis and cell death, respectively if left unresolved. Stalled replication is particularly dangerous because replication fork collapse can lead to double-strand breaks (DSBs) and chromosome rearrangement, a hallmark of cancer. DNA damage tolerance (DDT) is defined as a mechanism that allows DNA synthesis to occur in the presence of replication-blocking lesions.<p> DDT, also known as post-replication repair (PRR) in yeast, has been well characterized in the lower eukaryotic model Saccharomyces cerevisiae to consist of error-free and error-prone (mutagenic) pathways. Mono-ubiquitination of proliferating cell nuclear antigen (PCNA) by the Rad6-Rad18 complex promotes mutagenesis by recruiting low fidelity translesion synthesis (TLS) polymerases, while continual Lys63-linked poly-ubiquitination of PCNA by the Mms2-Ubc13-Rad5 complex promotes error-free lesion bypass. Since most of the genes involved in DNA metabolism are conserved within eukaryotes, from yeast to human, I tested the hypothesis that mammalian cells also possess two-pathway DDT in response to DNA damage. Namely, the error-free pathway is dependent on the Ubc13-Mms2 complex, while the error-prone pathway utilizes the TLS polymerases, such as Rev3.<p> By utilizing cultured mammalain cells and producing antibodies against human Ubc13, Mms2 and Rev3, I was able to show that all three proteins associate with PCNA in S-phase cells, and that this association is enhanced following DNA damage. Ubc13-Mms2 association with PCNA was enhanced in response to DSBs. Furthermore, suppression of Ubc13 or Mms2 using interfering RNA technology resulted in increased spontaneous DSBs. In response to UV exposure, Rev3 co-localized with PCNA and two other TLS polymerases, Rev1 and Pol-Ø, at the damage site. UV-induced Rev3 nuclear focus formation was dependent on Rev1 but independent of Pol-£b. Surprisingly, over-expression of Pol-£b was sufficient to induce spontaneous Rev3 nuclear foci. It was further demonstrated that Rev1 and Pol-Ø were independently recruited to the damage site and did not require Rev3. These observations support and extend the polymerase switch model which regulates the activity of the replicative and TLS polymerases. Finally, simultaneous suppression of Rev3 along with Ubc13 or Mms2 resulted in a synergistic sensitivity to UV, whereas simultaneous suppression of Ubc13 and Pol-Ø resulted in an additive effect. These results are consistent with those in yeast cells, implying a comparable mammalian two-pathway DDT model.<p> Additional interesting observations were made. Firstly, Ubc13 interacts with Uev1A, a close homolog of Mms2, which is involved in the NF-£eB signaling pathway independent of DNA damage. Secondly, Rev3 appears to be excluded from the nucleus in a fraction of low passage normal non-S-phase cells, whereas in tumor derived cell lines, Rev3 is consistently enriched in the nucleus independent of cell cycle stage. Finally, Rev3 is elevated during mitosis and associates with condensed chromosomes, suggesting a possible novel role in mitosis. Consistent with this notion, chronic ablation of Rev3 resulted in cell death with inappropriate chromosome segregations. The above preliminary observations require further investigation.

Vibration-based damage detection (VBDD) methods are structural health monitoring techniques that utilize changes to the dynamic characteristics of a structure (i.e. its natural frequencies, mode shapes, and damping properties) as indicators of damage. While conceptually simple, considerable research is still required before VBDD methods can be applied reliably to complex structures such as bridges. VBDD methods require reliable estimates of modal parameters (notably natural frequencies and mode shapes) in order to assess changes in the condition of a structure. This thesis presents the results of experimental and numerical studies investigating a number of issues related to the potential use of VBDD techniques in the structural health monitoring of bridges, the primary issue being the influence of the excitation source.<p> Two bridges were investigated as part of this study. One is located on Provincial Highway No. 9 over the Red Deer River south of Hudson Bay, Saskatchewan. The other is located near the Town of Broadview, Saskatchewan, off Trans-Canada Highway No. 1, 150 km east of the City of Regina. Field tests and numerical simulations were conducted using different types of excitation to evaluate the quality of the modal properties (natural frequencies and mode shapes) calculated using these excitation types, and thus to evaluate the performance of VBDD techniques implemented using the resulting modal data. Field tests were conducted using different sources of dynamic excitation: ambient, traffic excitation, and impact excitation. The purpose of field testing was to study the characteristics and repeatability of the modal parameters derived using the different types of dynamic excitation, and to acquire data that could be used to update a FE model for further numerical simulation.<p> A FE model of the Red Deer River bridge, calibrated to match the field measured dynamic properties, was subjected to different types of numerically simulated dynamic excitation with different noise (random variations) levels added to them. The types of dynamic excitation considered included harmonic forced excitation, random forced excitation and the subsequent free vibration decay, impact excitation, and different models of truck excitation. The bridge model was subjected to four different damage scenarios; in addition, six VBDD methods were implemented to evaluate their ability to identify and localize damage. The effects of uncertainty in the definition of controlled-force excitation sources and variation in measurement of the bridge response were also investigated.<p> Field tests on the Hudson Bay bridge showed that excitation induced by large trucks generally produced more reliable data than that of smaller vehicles due to higher signal-to-noise ratios in the measured response. It was also found that considering only the free vibration phase of the response after the vehicle left the bridge gave more reliable data. Impact excitation implemented the on Hudson Bay bridge using a spring-hammer yielded repeatable and high quality results, while using a heavy weight delectometer for impact excitation on the Broadview bridge produced results of lesser quality due to the occurrence of multiple strikes of the impact hammer. In general, wind induced vibration measurements taken from both bridges were less effective for defining modal properties than large vehicle loading or impact excitation. All of the VBDD methods examined in this study could detect damage if the comparison was made between modal parameters acquired by eigenvalue analyses of two FE models of the bridge, before and after damage. However, the performance of VBDD methods declined when the dynamic properties were calculated from response time histories and noise was introduced. In general, the damage index method performed better than other damage detection methods considered.<p> Numerical simulation results showed that harmonic excitation, impact excitation, and the free decay phase after random excitation yielded results that were consistent enough to be used for the identification of damage. The reliability of VBDD methods in detecting damage dropped once noise was introduced. Noise superimposed on the excitation force had little effect on the estimated modal properties and the performance of VBDD methods. On the other hand, noise superimposed on the measured dynamic response had a pronounced negative influence on the performance of the VBDD methods.

Tissue-engineering (TE) is one of the most innovative approaches for tackling many diseases and body parts that need to be replaced, by developing artificial tissues and organs. For this, tissue scaffolds play an important role in various TE applications. A tissue scaffold is a 3D (3D) structure with interconnected pore networks and used to facilitate cell growth and transport of nutrients and wastes while degrading gradually itself. Many fabrication techniques have been developed recently for incorporating living cells into the scaffold fabrication process and among them; dispensing-based rapid prototyping techniques have been drawn considerable attention due to its fast and efficient material processing. This research is aimed at conducting a preliminary study on the dispensing-based biofabrication of 3D cell-encapsulated alginate hydrogel scaffolds. Dispensing-based polymer deposition system was used to fabricate 3D porous hydrogel scaffolds. Sodium alginate was chosen and used as a scaffolding biomaterial. The influences of fabrication process parameters were studied. With knowledge and information gained from this study, 3D hydrogel scaffolds were successfully fabricated. Calcium chloride was employed as crosslinker in order to form hydrogels from alginate solution. The mechanical properties of formed hydrogels were characterized and examined by means of compressive tests. The influences of reagent concentrations, gelation time, and gelation type were studied. A post-fabrication treatment was used and characterized in terms of strengthening the hydrogels formed. In addition, the influence of calcium ions used as crosslinker on cell viability and proliferation during and after the dispensing fabrication process was examined and so was the influence of concentration of calcium solutions and exposing time in both media and alginate hydrogel. The study also showed that the density of encapsulated cells could affect the viscosity of alginate solution. In summary, this thesis presents a preliminary study on the dispensing-based biofabrication of 3D cell-encapsulated alginate hydrogel scaffolds. The results obtained regarding the influence of various factors on the cell viability and scaffold fabrication would form the basis and rational to continue research on fabricating 3D cell-encapsulated scaffolds for specific applications.

Untersucht wurde, wie hoch die Schädigungsrate abwandernder Lachssmolts bei der Passage einer Francisturbine in einer für Sachsen typischen Kleinwasserkraftanlage ist. Die Untersuchungen belegen, dass die Fische bereits am 20 mm-Rechen der Anlage und durch Scherkräfte der Leitschaufeln und am Turbinenrad erhebliche Schädigungen erleiden. Um diese zu vermeiden bzw. zu verringern, werden Maßnahmen und bauliche Veränderungen an der Wasserkraftanlage vorgeschlagen.

As a hydrophilic biopolymer, a DNA molecule is surrounded by water molecules in aqueous solution. The charge hopping mechanism indicates the competition between radical cation quenching by water molecules and migration along DNA partially determines the distance and efficiency of charge transport in DNA. Lipid can effectively bind DNA to induce hydrophobic environment around the DNA helix and reduce the water contact with bases in the DNA duplex. Therefore, the effect of water molecules on charge transport can be studied by comparison between nature DNA and DNA-lipid complexes. We synthesized several cationic lipids with various lengths of dialkyl chain (2, 8, 18) and spermine (Sp4+) binding core in this research, which posses strong DNA binding affinity due to their multi-charged spermine head-groups. Among those, C8GlySp4+ and C2GlySp4+ can form stable complex with DNA oligomer in aqueous solution, characterized by time dependent UV and CD spectrometry. C2GlySp4+ showed the similar inhibition on oxidative damage in GG steps as spermine while C8GlySp4+ demonstrated much more significant prohibitive effect at the same concentration. Since all the lipids bear the same binding core, they should afford the similar binding affinity towards DNA duplexes. we attributed the observation to the longer length of dialkyl group in C8GlySp4+, which can more effectively shield the DNA duplex from the water molecules than either spermine or C2GlySp4+. A kinetic model based on phonon-assist polaron hopping mechanism was proposed to rationalize the experimental results. The finding may give insight on the protection of DNA oxidative damage by reducing the access of the water molecule to DNA duplex and may have potential impact on the application of DNA as conducting biopolymer and protection of DNA in biological system.