The tumor suppressor p53 has a close relation with reactive oxygen species (ROS). As an indispensable component of the cellular redox system, ROS not only have been established to be involved in p53-dependent apoptosis, but also regulate p53 activity. Recent studies revealed several novel actions of p53, such as transactivation of antioxidative proteins, mitochondria translocation and inhibition of glycolysis. The fate of cells where p53 signaling pathways are initiated is either survival or death. In this review, we examine the hypothesis that ROS regulate cell fate through p53, in a way that physiological ROS levels trigger the protective pathways, while p53 behaves more like a cell killer under cytotoxic oxidative stress.

Methylmercury (MeHg) is an environmental toxin to which we are exposed through the consumption of seafood. Reactive oxygen species (ROS) have been implicated in the mechanism of toxicity, and in vitro studies in our laboratory have implicated DNA oxidation, particularly the DNA repair enzyme oxoguanine glycosylase 1 (OGG1). My studies determined the effects of in utero exposure to MeHg on fetal brain DNA oxidation and postnatal neurodevelopmental deficits, and the role of ROS-mediated oxidative DNA damage using the free radical spin trap, α-phenyl-N-tert-butylnitrone (PBN), and DNA repair-deficient ogg1 knockout mice. While neither MeHg nor PBN altered DNA oxidation in fetal brain, MeHg caused cognitive deficits in passive avoidance and novel object recognition, the latter of which was blocked by PBN pretreatment, suggesting ROS involvement. Preliminary longevity studies following one litter from each treatment group to 16 months suggest that in utero MeHg treatment may shorten lifespan. Endogenous DNA oxidation was increased in the brains of ogg1 knockout fetuses compared to wild-type littermates, although this was not enhanced by MeHg. However, OGG1-deficient animals exhibited cognitive deficits in passive avoidance after MeHg treatment, suggesting a role for DNA damage. Furthermore, ogg1 knockout female mice exhibited a passive avoidance deficit compared to wild-type females regardless of treatment, corroborating a role for oxidative DNA damage in neurodevelopmental deficits. MeHg increased apoptosis in the hippocampal region of fetal brain, and may cause DNA double-strand breaks (DSBs), evidenced by enhanced phosphorylation of histone 2AX (γH2AX). Ogg1 knockout progeny exhibited increased cellular proliferation or migration in the developing hippocampal region, which was blocked by MeHg. My results provide the first evidence that: (1) MeHg may decrease lifespan; (2) PBN protects against some postnatal neurodevelopmental deficits caused by in utero exposure to MeHg; and (3) DNA repair-deficient progeny are more susceptible to postnatal cognitive deficits caused by in utero MeHg exposure, suggesting that ROS-mediated DNA oxidation plays a role in MeHg-initiated neurodevelopmental deficits.

Beauvoirian Therapy is a new interdisciplinary model of psychotherapeutic treatment for depressed patients who have suffered from oppression. By bridging together philosophy, theory, literature and psychology, Beauvoirian Therapy is presented in a condensed and accessible psychological treatment format which can be synergized with other current psychotherapeutic techniques. This unprecedented approach, in bringing literature to an applied therapeutic model, has been formulated by synthesizing central themes of Beauvoir’s thought, with particular emphasis on her philosophy drawn from The Ethics of Ambiguity (Beauvoir, 1947) and creating an applied model which can be adapted and modified. The themes are represented in quotations and are used as data. The treatment prompts and question segments have been inductively formulated to produce therapeutic explorative inferences to add relevant and pertinent factors to the explorative discussions. Beauvoirian Therapy is based on overarching Beauvoirian themes arranged and framed for a unique Beauvoirian approach to address modern-day oppression.

Digital Forensics (DF) is defined as the ensemble of methods, tools and techniques used to collect, preserve and analyse digital data originating from any type of digital media involved in an incident with the purpose of extracting valid evidence for a court of law. DF investigations are usually performed as a response to a digital crime and, as such, they are termed Reactive Digital Forensic (RDF). An RDF investigation takes the traditional (or post-mortem) approach of investigating digital crimes after incidents have occurred. This involves identifying, preserving, collecting, analyzing, and generating the final report. Although RDF investigations are effective, they are faced with many challenges, especially when dealing with anti-forensic incidents, volatile data and event reconstruction. To tackle these challenges, Proactive Digital Forensic (PDF) is required. By being proactive, DF is prepared for incidents. In fact, the PDF investigation has the ability to proactively collect data, preserve it, detect suspicious events, analyze evidence and report an incident as it occurs. This dissertation focuses on the detection and analysis phase of the proactive investigation system, as it is the most expensive phase of the system. In addition, theories behind such systems will be discussed. Finally, implementation of the whole proactive system will be tested on a botnet use case (Zeus). / Graduate / 0984 / 0537 / soltanalharbi@hotmail.com

Ischemic stroke is characterized by a disruption of blood supply to a part of the brain tissue, which leads to a focal ischemic infarct. The expression and activity of MMP-9 is increased in ischemic stroke and is considered to be one of the main factors responsible for damages to the cerebral vasculature, resulting in compromised blood-brain barrier (BBB) integrity. However, the regulatory mechanisms of MMP-9 expression and activity are not well established in ischemic stroke. Since hypoxia/ischemia and reperfusion generates reactive oxygen species (ROS), I hypothesize that ROS is one of factors involved in up-regulation of MMP-9 expression in brain cells and ROS-mediated effect may occur via MAPK signaling pathway. My study has provided the evidence that ROS is responsible for an increase in MMP-9 expression in astrocytes mediated via MAPK-AP1 signaling pathway. Preliminary studies with an in vitro model of the BBB suggest that inhibition of MMP-9 is a critical component of reducing ROS-induced BBB permeability.

Infection with challenge virus standard-11 (CVS) strain, a laboratory fixed rabies virus strain, induces neuronal process degeneration in both in vivo and in vitro models. CVS-induced axonal swellings of primary rodent dorsal root ganglion neurons are associated with 4-hydroxy-2-nonenal staining indicating a critical role of oxidative stress. Mitochondrial dysfunction is one of the most important causes of oxidative stress. We hypothesized that CVS infection induces mitochondrial dysfunction leading to oxidative stress. We investigated the effects of CVS infection on several mitochondrial parameters in different cell types. CVS infection increased electron transport chain capacity, Complex I and IV activities, but did not affect Complex II-III, citrate synthase, and malate dehydrogenase activities. CVS maintained normal oxidative phosphorylation capacity and proton leak, indicating a tight mitochondrial coupling. Possibly as a result of enhanced Complex activity and efficient coupling, a high mitochondrial membrane potential was generated. CVS infection reduced the intracellular ATP level and altered the cellular redox state as indicated by high NADH/NAD+ ratio. CVS infection was associated with a higher rate of hydrogen peroxide production. We conclude that CVS infection induces mitochondrial dysfunction leading to ROS overgeneration, oxidative stress and neuronal process degeneration.

No description available.

Digital Forensics (DF) is defined as the ensemble of methods, tools and techniques used to collect, preserve and analyse digital data originating from any type of digital media involved in an incident with the purpose of extracting valid evidence for a court of law. DF investigations are usually performed as a response to a digital crime and, as such, they are termed Reactive Digital Forensic (RDF). An RDF investigation takes the traditional (or post-mortem) approach of investigating digital crimes after incidents have occurred. This involves identifying, preserving, collecting, analyzing, and generating the final report. Although RDF investigations are effective, they are faced with many challenges, especially when dealing with anti-forensic incidents, volatile data and event reconstruction. To tackle these challenges, Proactive Digital Forensic (PDF) is required. By being proactive, DF is prepared for incidents. In fact, the PDF investigation has the ability to proactively collect data, preserve it, detect suspicious events, analyze evidence and report an incident as it occurs. This dissertation focuses on the detection and analysis phase of the proactive investigation system, as it is the most expensive phase of the system. In addition, theories behind such systems will be discussed. Finally, implementation of the whole proactive system will be tested on a botnet use case (Zeus). / Graduate / 0984 / 0537 / soltanalharbi@hotmail.com

This Master of Applied Science thesis presents a single phase grid connected DC/AC inverter with reactive power (VAR) control for residential photovoltaic (PV) applications. The inverter, utilizing the voltage sourced inverter (VSI) configuration, allows the local residential PV generation to actively supply reactive power to the utility grid. A low complexity grid synchronization method was introduced to generate the parallel and orthogonal components of the grid voltage in a highly computationally efficient manner in order to create a synchronized current reference to the current control loop. In addition, the inverter is able to use a small long life film type capacitor on the DC-link by utilizing a notch filter on the voltage control loop. Simulations were performed on PSCAD/EMTDC platform and a prototype was also developed in the lab to prove the effectiveness of the controllers and the grid synchronization method.

This Master of Applied Science thesis presents a single phase grid connected DC/AC inverter with reactive power (VAR) control for residential photovoltaic (PV) applications. The inverter, utilizing the voltage sourced inverter (VSI) configuration, allows the local residential PV generation to actively supply reactive power to the utility grid. A low complexity grid synchronization method was introduced to generate the parallel and orthogonal components of the grid voltage in a highly computationally efficient manner in order to create a synchronized current reference to the current control loop. In addition, the inverter is able to use a small long life film type capacitor on the DC-link by utilizing a notch filter on the voltage control loop. Simulations were performed on PSCAD/EMTDC platform and a prototype was also developed in the lab to prove the effectiveness of the controllers and the grid synchronization method.