Activation of A3 adenosine receptors has been shown to protect the myocardium from ischaemia reperfusion injury in a number of animal models. The PI3K - AKT and MEK1/2 - ERK1/2 cell survival pathways have been shown to play a critical role in regulating myocardial ischaemia reperfusion injury. In this study we investigated whether the A3 adenosine receptor agonist 2-CL-IB-MECA protects the myocardium from ischaemia reperfusion injury, when administered at reperfusion or post reperfusion and whether the protection involved the PI3K – AKT or MEK 1/2 – ERK1/2 cell survival pathways. In the Langendorff model of ischaemia reperfusion injury isolated perfused rat hearts underwent 35 minutes of ischaemia and 120 minutes of reperfusion. Administration of 2-CL-IB-MECA (1nM) at reperfusion significantly decreased infarct size to risk ratio compared to non-treated ischeamic reperfused control hearts. This protection was abolished in the presence of the PI3K inhibitor Wortmannin or MEK1/2 inhibitor UO126. Western blot analysis determined that administration of 2-CL-IB-MECA (1 nM) upregulated ERK1/2 phosphorylation. In the adult rat cardiac myocyte model of hypoxia/reoxygenation cells underwent 6 hours of hypoxia and 18 hours of reoxygenation. Administration of 2-CL-IB-MECA (1 nM) at the onset of reoxygenation significantly decreased cellular apoptosis and necrosis. Administration of 2-CL-IB-MECA (1nM) in the presence of the Wortmannin or UO126 significantly reversed this anti-apoptotic effect and anti-necrotic effect. Our data further showed that 2-CL-IB-MECA protects myocytes subjected to hypoxia/reoxygenation injury via decreasing cleaved-caspase 3 activity that was abolished in presence of the PI3K inhibitor but not in the presence of the MEK1/2 inhibitor UO126. Administration of 2-CL-IB-MECA (100nM) at the onset of reperfusion also significantly decreased infarct size to risk ratio in the ischaemic reperfused rat heart compared to controls that was reversed in the presence of Wortmannin or Rapamycin. This protection was associated with an increase in PI3K-AKT / p70S6K / BAD phosphorylation. 2-CL-IB-MECA (100nM) administered at reoxygenation also significantly protected adult rat cardiac myocytes from hypoxia/reoxygenation injury 28 in an anti-apoptotic and anti-necrotic manner. This anti-apoptotic/necrotic effect of 2-CL-IB-MECA was abolished in the presence Wortmannin. Furthermore, that this protection afforded by 2-CL-IB-MECA (100nM) when administered at reoxygenation was associated with a decrease in cleaved caspase 3 activity that was abolished in the presence of the Wortmannin Interestingly, postponing the administration of 2-CL-IB-MECA to 15 or 30 minutes after the onset of reperfusion significantly protected the isolated perfused rat heart from ischaemia reperfusion injury in a Wortmannin and UO126 sensitive manner. This protection was associated with an increase in AKT and ERK1/2 phosphorylation. Administration of the A3 agonist 2-CL-IB-MECA 15 or 30 minutes after the onset of reoxygenation significantly protected isolated adult rat cardiac myocytes subjected to 6 hours of hypoxia and 18 hours of reoxygenation from injury in an anti-apoptotic/necrotic manner. This anti-apoptotic was abolished upon PI3K inhibition with Wortmannin or MEK1/2 inhibition with UO126. The anti-necrotic effect of 2-CL-IB-MECA when administered 15 or 30 minutes post-reperfusion was not abolished in the presence of the inhibitors. Delaying the administration of 2-CL-IB-MECA to 15 or 30 minutes after reoxygenation was associated with a decrease in cleaved-caspase 3 activity that was abolished in the presence of Wortmannin but not in the presence of the MEK 1/2inhibitor UO126. Collectively, we have demonstrated for the first time that administration of 2-CL-IB-MECA at the onset of reperfusion protects the ischaemic reperfused rat myocardium from lethal ischaemia reperfusion injury in a PI3K and MEK1/2 sensitive manner. Delaying the administration of 2-CL-IB-MECA to 15 or 30 minutes after the onset of reperfusion of reoxygenation also significantly protects the isolated perfused rat heart from ischaemia reperfusion injury and the adult rat cardiac myocyte from hypoxia/reoxygenation injury in an anti apoptotic / necrotic manner. Furthermore, that this protection is associated with recruitment of the PI3K-AKT and MEK1/2 – ERK1/2 cell survival pathways.

With the increase in globalization of Integrated Circuit (IC) design and production, hardware trojans have become a serious threat to manufacturers as well as consumers. These trojans could be intensionally or accidentally embedded in ICs to make a system vulnerable to hardware attacks. The implementation of critical applications using ICs makes the effect of trojans an even more serious problem. Moreover, the presence of untrusted foundries and designs cannot be eliminated since the need for ICs is growing exponentially and the use of third party software tools to design the circuits is now common. In addition if a trusted foundry for fabrication has to be developed, it involves a huge investment. Therefore, hardware trojan detection techniques are essential. Very Large Scale Integration (VLSI) system designers must now consider the security of a system against internal and external hardware attacks. Many hardware attacks rely on system vulnerabilities. Moreover, an attacker may rely on deprocessing and reverse engineering to study the internal structure of a system to reveal the system functionality in order to steal secret keys or copy the system. Thus hardware security is a major challenge for the hardware industry. Many hardware attack mitigation techniques have been proposed to help system designers build secure systems that can resist hardware attacks during the design stage, while others protect the system against attacks during operation. In this dissertation, the idea of quantifying hardware attacks, hardware trojans, and hardware trojan detection techniques is introduced. We analyze and classify hardware attacks into risk levels based on three dimensions Accessibility/Resources/Time (ART). We propose a methodology and algorithms to aid the attacker/defender to select/predict the hardware attacks that could use/threaten the system based on the attacker/defender capabilities. Because many of these attacks depends on hardware trojans embedded in the system, we propose a comprehensive hardware trojan classification based on hardware trojan attributes divided into eight categories. An adjacency matrix is generated based on the internal relationship between the attributes within a category and external relationship between attributes in different categories. We propose a methodology to generate a trojan life-cycle based on attributes determined by an attacker/defender to build/investigate a trojan. Trojan identification and severity are studied to provide a systematic way to compare trojans. Trojan detection identification and coverage is also studied to provide a systematic way to compare detection techniques and measure their e effectiveness related to trojan severity. We classify hardware attack mitigation techniques based on the hardware attack risk levels. Finally, we match these techniques to the attacks the could countermeasure to help defenders select appropriate techniques to protect their systems against potential hardware attacks. / Graduate / 0544 / 0984 / samerm@uvic.ca

ENGLISH ABSTRACT: Current understanding of the hydraulic stability of a stacked geotextile tube structure under wave attack is limited. Failure mechanisms that lead to instability are complicated and there is, as yet, no generic approved design method. 2D physical modelling in the large wave/current flume of the Stellenbosch University was done to test various set-up and hydraulic conditions to determine the hydraulic stability of a stacked geotextile tube structure against wave attack. Sixty-five test runs of approximately 1,000 waves each were run. Modelling was done on two different scales that had good similitude, despite the fact that the same geotextile and fill material were used in both. The results provided by the physical modelling gave wave conditions larger than anticipated for hydraulic stability. It was found that the term ―failure‖ was too loosely defined in most cases and that, depending on the definition of structure failure the severity of the wave conditions at failure increased substantially. Sliding was found to be the key failure mechanism for a structure constructed from stacked, 80% sand filled, geotextile tubes. The crest tube receives the most severe loading and is the critical tube in the structure. Structures with double tube crests were found to be negligibly more stable than structures with single tube crests, but reduce energy transmission to the leeside of the structure. Impact loading of the structure combined with wave transmission over the structure explained the wave force on the crest tube of the structure. A modified Goda (1974) method incorporating a wave reduction factor for wave transmission and an angle descriptive of the crest tube position were used. The descriptive angle was derived from results obtained from the physical modelling. The use of this method provides results that correlate well with those found in the physical modelling and with results obtained in previous research. The method has the additional advantage that it is less constrained by limitations for application than those of previous studies / AFRIKAANSE OPSOMMING: Die begrip van die hidroliese stabiliteit van ‘n struktuur gebou uit gepakte geotekstielsandbuise teen golf aanval, is tans beperk. Faal meganismes wat lei tot die onstabiliteit van ‘n struktuur is ingewikkeld en daar is geen generiese aanvaarde ontwerp metode tans in gebruik nie. 2D fisiesemodellering is in die groot golfkanaal van die Universiteit Stellenbosch uitgevoer. ‘n Verskeidenheid van struktuur-uitlegte en hidroliese toestande is getoets om die hidroliese stabiliteit van die struktuur teen golf aanval te bepaal. ‘n Totaal van 65 toetse van ongeveer 1,000 golwe elk is voltooi. Modellering is op twee verskillende skale gedoen, wat goed vergelyk het ten spyte van die feit dat dieselfde geotekstiel en vul materiaal in albei gebruik is. Resultate verkry vanaf die fisiese modellering het groter as verwagte golftoestande vir hidroliese stabiliteit gegee. Dit is gevind dat die definisie van faal (mislukking) in die meeste gevalle swak beskryf is en dat, afhangende van wat as faal van die struktuur beskou word, die golftoestande aansienlik beïnvloed word. Die skuif van die buise is die hoof faal meganisme vir ‘n gepakte geotekstielbuis-struktuur met ‘n vulpersentasie van 80%. Die buis op die kruin van die struktuur word die swaarste belas en is die kritiese buis in die struktuur. Strukture met dubbel buis kruine is onbeduidend meer stabiel as dié met slegs ‘n enkele buis as kruin. Die energie wat na die lysy van die struktuur oorgedra word, is egter beduidend minder. Impak belasting van die struktuur gekombineer met golf-transmissie oor die struktuur, verduidelik die stabiliteit van die buis op die kruin van die struktuur. ‘n Gemodifiseerde Goda (1974) metode met ‘n golfverminderigs faktor word gebruik om golf-transmissie oor die struktuur te akkommodeer, saam met ‘n hoek wat beskrywend is van die posisie van die kruin buis. Die beskrywende hoek is afgelei uit resultate verkry uit die fisiesemodellering. Hierdie metode gee resultate wat goed korreleer met dié verskaf deur die fisiese modellering en die resultate van vorige navorsing oor geotekstielbuis stabiliteit. Die metode het ‗n bykomende voordeel deurdat dit minder begrens is deur beperkings m.b.t. toepassing as die van vorige studies.

Detta arbete behandlar en specifik typ av överbelastningsattack som blir allt mer populär. Dessa attacker utförs genom öppna reläer med syftet att få ut en avsevärt mycket högre effekt än den som annars är uppnåbar. Granskning av attacker utförda genom tjänsterna DNS och NTP har utförts med syftet att ge en klar bild av hur allvarligt hotet är och även klargöra hur en systemadministratör kan säkra tjänsterna för att skydda både sina egna och andras resurser. Resultaten av undersökningar visar att en attack utförd genom en DNS-tjänst ger under optimala förhållanden en amplifikationsfaktor av "102.4" och en attack genom en NTP-tjänst ger under optimala förhållanden en amplifikationsfaktor av "229.16". Resultaten visar även att problemet kan lösas helt eller delvis genom att begränsa tillåtna nätverk eller stänga av rekursion i DNS och kommandon i NTP. / This work concerns a specific type of Denial of Service attack which is becoming increasingly popular. These attacks are carried out through open relays with the purpose of getting a significantly higher effect than otherwise achievable. Examination of attacks carried out through the services DNS and NTP have been conducted with the purpose of providing a clear picture of how serious the threat is and also clarify how a system administrator can secure the services to protect both their own and others resources. The results of our studies show that an attack performed through a DNS service gives under optimal conditions a amplification factor of "102.4" and an attack through a NTP service gives under optimal conditions a amplification factor of "229.16". The results also show that the problem can be solved in whole or in part by limiting the allowed network or disable recursion in DNS and commands in NTP.

This literature review posits that the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an attractive candidate therapeutic target in the setting of acute myocardial infarction (AMI). This transcription factor binds to antioxidant response elements (ARE) in the promoter region of a battery of genes that collectively encode an array of antioxidant, phase II drug metabolism, metabolically stabilizing, and overall cytoprotective enzymes, facilitating their transcription at basal levels and increasing transcription in response to various cellular stressors. Following a brief background tutorial on normal cardiac myocyte cellular physiology, key events that occur early in ischemia and reperfusion are outlined and integrated. These include ionic and metabolic dysregulation, electron transport chain uncoupling, mitochondrial depolarization, and the generation of reactive oxygen species (ROS). Abrupt changes in response to ischemia prime opening of the mitochondrial permeability transition pore (MPTP) and cardiac myocytes to generate a burst of ROS upon reperfusion–two key events that contribute to the umbrella term ischemia-reperfusion injury (IRI). How ROS damage cells is then outlined, and through a ROS-centric viewpoint, a case will be made as to how exogenous upregulation of Nrf2 could protect and/or salvage at-risk tissue immediately subjected to infarction and neighboring tissue in the peri-infarct zone (PIZ). The history of how Nrf2 came to be known as the "master regulator of oxidative stress" is reviewed, as well as the discovery of the canonical mechanism of Nrf2 regulation via Kelch-like ECH-associated protein 1 (Keap1) and other alternative mechanisms of endogenous Nrf2 regulation. Finally, compiling interdisciplinary evidence from research publications around the world, the benefits of therapeutically targeting Nrf2 are considered given the timescale and context of acute MI. Drug delivery methods, potential challenges, and limitations are then considered. Cardiac tissue is a dynamic substrate that exhibits changes for up to 90 days after AMI and patient outcomes are directly related to the extent of tissue lost following infarction/reperfusion. Targeting Nrf2 addresses an unmet need, as current clinical therapies focus on precluding occlusions and prompt reperfusion of infarcted tissue, but do not explicitly target at-risk tissue following infarcts and/or present-day reperfusion methodologies.

Background Patients who experience a stroke or transient ischemic attack (TIA) are at high risk of recurrent stroke, but little is known about temporal trends in unselected populations. Reports of low adherence to recommended treatments indicate a need for enhanced secondary preventive follow-up to achieve the full potential of evidence-based treatments. In addition, socioeconomic factors have been associated with poor health outcomes in a variety of contexts. Therefore, it is important to assess the implementation and results of secondary prevention in different socioeconomic groups. Aims The aims of this thesis were to assess temporal trends in ischemic stroke recurrence and evaluate the implementation and results of a nurse-led, telephone-based follow-up program to improve blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels after stroke/TIA. Methods In study I, we collected baseline data for unique patients with an ischemic stroke event between 1998 and 2009 (n=196 765) from the Swedish Stroke Register (Riksstroke). Recurrent ischemic stroke events within 1 year were collected from the Swedish National Inpatient Register (IPR) and the cumulative incidence was compared between four time periods using the Kaplan-Meier survival analysis and the logrank test. Implementation (study II) and 1-year results (study III-IV) for the secondary preventive follow-up were studied in the NAILED (Nurse-based Age-independent Intervention to Limit Evolution of Disease) study. Between 1 Jan 2010 and 31 Dec 2013, the baseline characteristics of consecutive patients admitted to Östersund Hospital for acute stroke or TIA were collected prospectively (n=1776). Consenting patients in a condition permitting telephone-based follow-up were randomized to nurse-led, telephone-based follow-up or follow-up according to usual care. Follow-up was cunducted at 1 and 12 months after discharge and the intervention included BP and LDL-C measurements, titration of medication, and lifestyle counseling. In study II, we analyzed factors associated with non-participation in the randomized phase of the NAILED study, including association with education level. In addition, we compared the 1-year prognosis in terms of cumulative survival between participants and non-participants. In study III, we compared differences in BP and LDL-C levels between the intervention and control groups during the first year of follow-up and, in study IV, in relation to level of education (low, ≤10 years; high, >10 years). Results The cumulative 1-year incidence of recurrent ischemic stroke decreased from 15.0% to 12.0%. Among surviving stroke and TIA patients, 53.1% were included for randomization, 35.7% were excluded mainly due to physical or cognitive disability, and 11.2% declined participation in the randomized phase. A low level of education was independently associated with exclusion, as well as the patient’s decision to abstain from randomization. Excluded patients had a more than 12-times higher risk of death within 1 year than patients who were randomized. After 1 year of follow-up, the mean systolic BP, diastolic BP, and LDL-C levels were 3.3 mmHg (95% CI 0.3 to 6.3), 2.3 mmHg (95% CI 0.5 to 4.2), and 0.3 mmol/L (95% CI 0.1 to 0.4) lower in the intervention group than among controls. Among participants with values above the treatment goal at baseline, the differences in systolic BP and LDL-C levels were more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1; 0.6 mmol/L, 95% CI 0.4 to 0.9). In the intervention group, participants with a low level of education achieved similar or larger improvements in BP and LDL-C than participants with a high level of education. In the control group, BP remained unaltered and the LDL-C levels increased among participants with a low level of education. Conclusion The 1-year risk of ischemic stroke recurrence decreased in Sweden between 1998 and 2010. Nurse-led, telephone-based secondary preventive follow-up is feasible in just over half of the survivors of acute stroke and TIA and achieve better than usual care in terms of BP and LDL-C levels, and equality in BP improvements across groups defined by education level. However, a large proportion of stroke survivors are in a general condition precluding this form of follow-up, and their prognosis in terms of 1-year survival is poor. Patients with a low education level are over-represented within this group and among patients declining randomization for secondary preventive follow-up.

Within days of a major failed strike by attack helicopters during Operation Iraqi Freedom (OIF) analysts were questioning the value of such platforms on the modern battlefield. As OIF moved from combat to stability operations, helicopter losses from enemy action actually increased seemingly strengthening the argument of those who see the helicopter as unsuitable to some combat operations. Attack helicopter operations have diverged into two distinct categories, interdiction and close air support (CAS), since their inception. This thesis argues that attack helicopters are most suited to perform CAS while their employment in interdiction is problematic at best. Doctrine, tactics, and threat are studied as they applied in the Soviet-Afghan War, Desert Storm, and OIF in order to examine the issue across a range of time and types of warfare.

Vissa typer av cyberattacker har ökat kraftig mellan åren 2015 och 2016, detta uppmärksammas både i land och till sjöss. Med tanke på sjöfartens unika situation är det av intresse att undersöka hur rederier har valt att skydda sig mot cyberattacker. Fyra rederier har intervjuats angående IT-säkerheten på deras fartyg. Resultatet av intervjuerna har sedan ställts mot IMOs riktlinjer släppta år 2016 för att undersöka ifall det finns brister i IT-säkerheten på svenska fartyg. Resultatet visar att det finns brister på flera av rederierna som intervjuats framförallt i form av utbildning av personal. Resultatet visar också att det finns klara kontraster mellan mindre rederier och större rederier, där de mindre rederierna har färre åtgärder på plats medans de större rederierna har fler för att förhindra eller hantera en IT-attack. / Certain types of cyber attacks have increased between 2015 and 2016, this is acknowledged both on land in the shipping sector. Given the unique situation of shipping, it is of interest to investigate how shipping companies have chosen to protect themselves from cyberattacks. Four shipping companies have been interviewed regarding the cybersecurity of their vessels. The results of the interviews have since been compared against IMO's guidelines released in 2016 to investigate whether there are deficiencies in cybersecurity on swedish ships. The results show that there are shortcomings in several of the shipping companies interviewed, primarily in the form of training of personnel. The result also shows that there are clear contrasts between smaller shipping companies and larger shipping companies, where the smaller shipping companies have fewer measures in place while the larger shipping companies have more to prevent or handle a cyberattack.

This thesis deals with Computational Fluid Dynamics (CFD)simulations of the flow around delta wings at high angles ofattack. These triangular wings, mainly used in militaryaircraft designs, experience the formation of two vortices ontheir lee-side at large angles of attack. The simulation ofthis vortical flow by solving the Navier-Stokes equations isthe subject of this thesis. The purpose of the work is toimprove the understanding of this flow and contribute to thedesign of such a wing by developing methods that enable moreaccurate and efficient CFD simulations. Simulations of the formation, burst and disappearance of thevortices while the angle of attack is changing are presented.The structured flow solver NSMB has been used to get thetime-dependent solutions of the flow. Both viscous and inviscidresults of a 70°-swept delta wing pitching in anoscillatory motion are reported. The creation of the dynamiclift and the hysteresis observed in the history of theaerodynamic forces are well reproduced. The second part of the thesis is focusing on automatic meshrefinement and its influence on simulations of the delta wingleading-edge vortices. All the simulations to assess the gridquality are inviscid computations performed with theunstructured flow solver EDGE. A first study reports on theeffects of refining thewake of the delta wing. A70°-swept delta wing at a Mach number of 0.2 and an angleof attack of 27° where vortex breakdown is present abovethe wing, is used as testcase. The results show a strongdependence on the refinement, particularly the vortex breakdownposition, which leads to the conclusion that the wake should berefined at least partly. Using this information, a grid for thewing in the wind tunnel is created in order to assess theinfluence of the tunnel walls. Three sensors for automatic meshrefinement of vortical flows are presented. Two are based onflow variables (production of entropy and ratio of totalpressures) while the third one requires an eigenvalue analysisof the tensor of the velocity gradients in order to capture theposition of the vortices in the flow. These three vortexsensors are successfully used for the simulation of the same70° delta wing at an angle of attack of 20°. Acomparison of the sensors reveals the more local property ofthe third one based on the eigenvalue analysis. This lattertechnique is applied to the simulation of the wake of a deltawing at an angle of attack of 20°. The simulations on ahighly refined mesh show that the vortex sheet shed from thetrailing-edge rolls up into a vortex that interacts with theleading-edge vortex. Finally the vortex-detection technique isused to refine the grid around a Saab Aerosystems UnmannedCombat Air Vehicle (UCAV) configuration and its flight dynamicscharacteristics are investigated. Key words:delta wing, high angle of attack, vortex,pitching, mesh refinement, UCAV, vortex sensor, tensor ofvelocity gradients.

The spatial stability of hypersonic conical boundary layers is investigated utilizing different numerical techniques. First, the development and verification of a Linearized Compressible Navier-Stokes solver (LinCS) is presented, followed by an investigation of different effects that affect the stability of the flow in free-flight/ground tests, such as: high-enthalpy effects, wall-temperature ratio, and three-dimensionality (i.e. angle-of-attack). A temporally/spatially high-order of accuracy parallelized Linearized Compressible Navier-Stokes solver in disturbance formulation was developed, verified and employed in stability investigations. Herein, the solver was applied and verified against LST, PSE and DNS, for different hypersonic boundary-layer flows over several geometries (e.g. flat plate - M=5.35 & 10; straight cone - M=5.32, 6 & 7.95; flared cone - M=6; straight cone at AoA = 6 deg - M=6). The stability of a high-enthalpy flow was investigated utilizing LST, LinCS and DNS of the experiments performed for a 5 deg sharp cone in the T5 tunnel at Caltech. The results from axisymmetric and 3D wave-packet investigations in the linear, weakly, and strongly nonlinear regimes using DNS are presented. High-order spectral analysis was employed in order to elucidate the presence of nonlinear couplings, and the fundamental breakdown of second mode waves was investigated using parametric studies. The three-dimensionality of the flow over the Purdue 7 deg sharp cone at M=6 and AoA =6 deg was also investigated. The development of the crossflow instability was investigated utilizing suction/blowing at the wall in the LinCS/DNS framework. Results show good agreement with previous computational investigations, and that the proper basic flow computation/formation of the vortices is very sensitive to grid resolution.