Context-aware access control in ubiquitous computing (CRAAC)

Ubiquitous computing (UbiComp) envisions a new computing environment, where computing devices and related technology are widespread (i.e. everywhere) and services are provided at anytime. The technology is embedded discreetly in the environment to raise users' awareness. UbiComp environments support the proliferation of heterogeneous devices such as embedded computing devices, personal digital assistants (PDAs), wearable computers, mobile phones, laptops, office desktops (PCs), and hardware sensors. These devices may be interconnected by common networks (e.g. wired, wireless), and may have different levels of capabilities (i.e. computational power, storage, power consumption, etc). They are seamlessly integrated and interoperated to provide smart services (i.e. adaptive services). A UbiComp environment provides smart services to users based on the users' and/or system's current contexts. It provides the services to users unobtrusively and in turn the user's interactions with the environment should be as non-intrusive and as transparent as possible. Access to such smart services and devices must be controlled by an effective access control system that adapts its decisions based on the changes in the surrounding contextual information. This thesis aims at designing an adaptive fine-grained access control solution that seamlessly fits into UbiComp environments. The solution should be flexible in supporting the use of different contextual information and efficient, in terms of access delays, in controlling access to resources with divergent levels of sensitivity. The main contribution of this thesis is the proposal of the Context-Risk-Aware Access Control (CRAAC) model. CRAAC achieves fine-grained access control based upon the risk level in the underlying access environment and/or the sensitivity level of the requested resource object. CRAAC makes new contributions to the access control field, those include 1) introducing the concept of level of assurance based access control, 2) providing a method to convert the contextual attributes values into the corresponding level of assurance, 3) Proposing two methods to aggregate the set of level of assurance into one requester level of assurance, 4) supporting four modes of working each suits a different application context and/or access control requirements, 5) a comprehensive access control architecture that supports the CRAAC four modes of working, and 6) an evaluation of the CRAAC performance at runtime.EThOS - Electronic Theses Online Serviceral Centre and Educational BureauCairo UniversityGBUnited Kingdo

Personalized Cancer Vaccine Development for Brain and Colon Cancers Using Synthetic HDL Nanoparticles

Immunotherapy is an attractive treatment option for many cancers because it has the potential to reverse the immunosuppressive tumor microenvironment, target tumor antigens, and maintain a long-lasting anti-tumor response. Brain cancers are top candidates for such therapies because current standard-of-care is limited to surgery, radiation, and chemotherapy; surgery often fails to resect 100% of the tumor, and delivery of chemotherapeutic drugs to the brain is very inefficient due to the blood-brain barrier’s tightly regulated microenvironment. New immunotherapies for colon cancers are also being explored because of the difficulties of resection, surgery, and adverse effects associated with current targeted therapies and immune checkpoint blockade. Thus, drug delivery vehicles are being designed to carry antigens and other immunostimulatory molecules directly to tumors or tumor-draining lymph nodes for site-specific treatment that is minimally invasive and reduces off-target side effects. Within this dissertation, we explored (1) the ability of sHDL nanodiscs to deliver neoantigens for glioblastoma multiforme (GBM) to exert specific anti-tumor effects, (2) whether immunogenicity of colon adenocarcinoma neoantigen-loaded sHDL nanodiscs following formulation simplification is retained, and (3) the ability of sHDL nanodiscs to co-deliver chemo- and immuno-therapeutic entities to colon adenocarcinoma tumors. In the first project, we found that delivery of neoantigens by sHDL nanodisc was significantly more effective compared to delivery of soluble neoantigens in neoantigen-specific CD8+ T cell production, tumor growth reduction, and survival prolongation in murine GBM models. These anti-tumor effects were augmented by the addition of immune checkpoint blockade anti-PD-L1, and neoantigen-loaded sHDLs in combination with anti-PD-L1 reversed immunosuppression within the tumor microenvironment by significantly increasing CD8+ T cells and decreasing their PD-1 expression and Treg frequencies within the tumor. In the second project, we showed that we were able to simplify our formulation process for neoantigen-loaded sHDL through chemical modification of two neoantigen peptides using short-chain PEG and lipoprotein films. We verified that the simplified PEGylated formulations induced neoantigen-specific CD8+ T cell expansion similar to our traditional formulations. Although prophylactic vaccination did not slow MC38 colon adenocarcinoma tumor growth or extend overall survival equally between the two neoantigens Reps1 and Adpgk, we did see that PEGylated formulations and traditional formulations exhibited anti-tumor efficacy similar to each other. Together, these results indicated that nanovaccine synthesis could be streamlined for clinical translation. In the third project, we demonstrated the therapeutic advantage of co-delivering chemo- and immune-therapeutic entities on sHDL nanodiscs in a murine colon adenocarcinoma model. In vivo evaluation of docetaxel-loaded sHDL (DTX-sHDL) co-loaded with CpG revealed that CpG significantly improved the antitumor efficacy of DTX, suppressing tumor growth and prolonging survival in mice treated with DTX-sHDL/CpG as compared to mice treated with DTX-sHDL or DTX alone. Complete responses were achieved in two of the seven mice treated with DTX-sHDL/CpG without inducing any systemic toxicities, supporting the hypothesis that combination therapy with an immuno-stimulatory component would augment the antitumor efficacy of chemotherapy alone. In full, this dissertation (1) exposed a highly efficacious, tumor-specific, and personalized nanovaccine design for improving treatment of patients with Glioblastoma multiforme (GBM), (2) streamlined the neoantigen-sHDL nanovaccine formulation process for clinical translation, and (3) proposed an efficient method for co-delivery of chemo- and immuno-therapeutic entities for site-specific, non-toxic cancer treatment using sHDL nanodiscs. We believe that sHDL nanodiscs are versatile drug delivery vehicles and could set the stage for personalized and combinatorial cancer nanovaccine design.PHDPharmaceutical SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155064/1/scheetzl_1.pd

Treatment of Later Humoral Rejection with Anti-CD20 Monoclonal Antibody Rituximab: A Single Centre Experience

Humoral or vascular rejection is a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ that results in immune complex deposition on the vascular endothelium, activation of the complement cascade, production of endothelial dysfunction and regional ischaemic injury