Molecular Markers of Oral Lichen Planus

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease and is detected in between 0.5% - 2.2% of the population. WHO has defined OLP as a potentially precancerous disorder, representing a generalized state associated with a significantly increased risk of cancer. However, only 0.5 – 2.9% of OLP lesions will progress to cancer. Currently, there are no prognostic markers to identify the lesions at increased risk for malignant transformation. The main aim of these studies was to identify cellular and molecular markers in order to understand the pathogenesis of atrophic OLP and its progression towards malignancy. Selected markers for cell proliferation, adhesion, apoptosis, and lymphocytic infiltration were assessed by immunohistochemistry in addition to static cytometry analyses for DNA content. DNA quantification of epithelial cells in 82 biopsy samples derived from atrophic lichen planus showed altered DNA content in 41% of the samples. DNA content was associated with proliferation activity, topoisomerase IIalpha, desmocollin-1 and infection with human papillomavirus. CD27+ and CD38+ lymphocytes were detected in inflammatory cell infiltrate, indicating an abnormal homing of B cells from blood circulation to tissue. Physiologic cell death, apoptosis, is frequently seen in OLP, but its pathways are unknown. Here it was shown that caspases 2 and 12 were up-regulated in OLP, indicating that intracellular apoptosis, rather than an external causal factor, is triggering apoptosis. However, this thesis could not identify any singular prognostic marker of malignancy in OLP. Thus, every OLP patient should receive regular follow-up care to identify cancer risk patients at an early stage.

The strategic use of military contractors : American commercial military service providers in Bosnia and Liberia, 1995-2009

Drawing from strategic theory, this study investigates the strategic roles of commercial companies providing military services, frequently referred to as private military companies. Theoretically, the thesis analyzes how states organize its military capabilities in order to be able to wield power within the international system while empirically, it examines the character and role of commercial companies that provide military training services to the United States Government and partner nations. The reason for this rather instrumental and functional, rather than critical, approach is that this work is written within the discipline known as War Studies. Strategic theory is used first to logically organize the empirical findings in two case studies and then to develop an analytical framework with which the strategic roles of companies providing military services can be investigated. The analysis has been conducted using both new and hitherto unknown sources in the shape of interviews as well as previously classified telegrams, but also draws on previous research and other secondary sources. The main findings are that commercial companies have five typical strategic roles: first, they cloak the state by substituting traditional uniformed troops; second, they act as trailblazers by securing US influence in new regions and by breaking new ground by contributing to the build-up of new partners; third, they act as scene setters by preparing the ground for military exit out of a theater of operations or by facilitating inter-operability between foreign militaries and the US military; fourth, they can be used to infiltrate the security structures of foreign countries; fifth and finally, they can be used to provide offensive capabilities by providing either kinetic or cyber warfare effects. Another finding is that military service contracting is an important part of the US strategic culture.

Herpes simplex virus type 1 (HSV-1) pathogenesis and HSV gene therapy of experimental autoimmune encephalomyelitis

The aim of this thesis was to develop new herpes simplex virus (HSV) vectors for gene therapy of experimental autoimmune encephalomyelitis (EAE), the principal model of multiple sclerosis (MS), and to study the pathogenesis of wild-type HSV-1 and HSV-1 vectors in vivo. By introducing potential immunomodulatory factors into mice with EAE we strived to develop therapies and possibly find molecules improving recovery from EAE. We aimed at altering the immune response by inducing favorable Th2-type cytokines, thus shifting the immune response from a Th1- or a Th17-response. Our HSV vector expressing interleukin (IL)-5 modulated the cytokine responses, decreased inflammation and alleviated EAE. The use of a novel method, bacterial artificial chromosome (BAC), for engineering recombinant HSV facilitated the construction of a new vector expressing leukemia inhibitory factor (LIF). LIF is a neurotropic cytokine with broad functions in the central nervous system (CNS). LIF promotes oligodendrocyte maturation and decreases demyelination and oligodendrocyte loss. The BAC-derived HSV-LIF vector alleviated the clinical symptoms, induced a higher number of oligodendrocytes and modulated T cell responses. By administering HSV via different infection routes, e.g. peripherally via the nose or eye, or intracranially to the brain, the effect of the immune response on HSV spread at different points of the natural infection route was studied. The intranasal infection was an effective delivery route of HSV to the trigeminal ganglion and CNS, whereas corneal infection displayed limited spread. The corneal and intranasal infections induced different peripheral immune responses, which might explain the observed differences in viral spread.

Analysis of Automotive Cybersecurity - Attack surfaces and users’ privacy concerns

Modern automobiles are no longer just mechanical tools. The electronics and computing services they are shipping with are making them not less than a computer. They are massive kinetic devices with sophisticated computing power. Most of the modern vehicles are made with the added connectivity in mind which may be vulnerable to outside attack. Researchers have shown that it is possible to infiltrate into a vehicle’s internal system remotely and control the physical entities such as steering and brakes. It is quite possible to experience such attacks on a moving vehicle and unable to use the controls. These massive connected computers can be life threatening as they are related to everyday lifestyle. First part of this research studied the attack surfaces in the automotive cybersecurity domain. It also illustrated the attack methods and capabilities of the damages. Online survey has been deployed as data collection tool to learn about the consumers’ usage of such vulnerable automotive services. The second part of the research portrayed the consumers’ privacy in automotive world. It has been found that almost hundred percent of modern vehicles has the capabilities to send vehicle diagnostic data as well as user generated data to their manufacturers, and almost thirty five percent automotive companies are collecting them already. Internet privacy has been studies before in many related domain but no privacy scale were matched for automotive consumers. It created the research gap and motivation for this thesis. A study has been performed to use well established consumers privacy scale – IUIPC to match with the automotive consumers’ privacy situation. Hypotheses were developed based on the IUIPC model for internet consumers’ privacy and they were studied by the finding from the data collection methods. Based on the key findings of the research, all the hypotheses were accepted and hence it is found that automotive consumers’ privacy did follow the IUIPC model under certain conditions. It is also found that a majority of automotive consumers use the services and devices that are vulnerable and prone to cyber-attacks. It is also established that there is a market for automotive cybersecurity services and consumers are willing to pay certain fees to avail that.