Current diagnostic and therapeutic nanocarriers, including liposomes, micelles, and polymeric- and protein-based nanoparticles, are designed to have key functional properties such as: (i) longevity in the bloodstream, leading to accumulation of therapeutic cargos in neoplastic areas with leaky vasculatures; (ii) targeting of specific pathological sites through surface modification with targeting ligands; (iii) stimuli-responsive characteristics for controlled drug release under specific conditions. While some of these drug delivery systems have advanced into clinical stages, other nanocarriers remain under development to overcome issues with effective delivery such as lack of target-ability and fast clearance from circulation. Self-assembling peptides have recently shown great potential as nanocarrier materials for drug and gene delivery, owing to their safety, efficiency, and targeting capabilities. An amino acid pairing strategy enables us to design self/co-assembling peptides with multiple functionalities to fulfill drug delivery requirements. This thesis focuses on functionalization and characterization of self/co-assembling peptides as nanocarriers for hydrophobic anticancer drug delivery. Diethylene glycol (DEG) conjugation and protein binding are the two modification strategies used in this thesis to impart longevity and target-ability upon the peptide-based delivery system. The studies include: (i) characterization of self-assembling properties of the diethylene glycol (DEG)-conjugated amino acid pairing peptide AAP8, (ii) investigation of the self/co-assembling features of a model ionic-complementary peptide (EAR8-II) in complex with the hydrophobic drug pirarubicin, and the anticancer activity of the complex, (iii) the interactions between peptide-drug complexes and serum proteins from the thermodynamic viewpoint, (iv) quantification of the effect of protein binding to the peptide-based delivery system on immune responses and biocompatibility, and (v) exploration of the targeting capability of albumin-bound peptide-drug complexes towards lung cancer cells. Uncontrollable aggregation of AAP8 was the first issue to address in order to develop a promising platform for the peptide-based delivery system. Diethylene glycol (DEG), a short segment of polyethylene glycol (PEG), was conjugated to AAP8 either at one or both terminals, and then self-assembling and drug encapsulation properties of both functionalized AAP8s were characterized to evaluate the effect of DEG-modification. The results illustrated a significant reduction in uncontrollable aggregation, and the formation of uniform fibular nanostructures. In addition, DEG conjugation provided the peptide with safer features towards immune cells by reducing cellular toxicity to macrophages. Moreover, DEG-functionalization improved hydrophobic drug stabilization, as demonstrated by sustained cytotoxic efficacy against lung carcinoma cells over a relatively long time compared to the non-functionalized AAP8. Protein binding strategy was the second approach to utilize the peptide-based delivery system with more biocompatibility and target-ability features. EAR8-II was studied as a model ionic-complementary peptide with high capability of pirarubicin encapsulation and anticancer activities against different cancer cells. Albumin as a most abundant protein in serum was selected to assess its binding affinity to the delivery system, and evaluate its binding effect on immune responses and anticancer activities. The results showed a central role of albumin in the in vitro delivery of peptide-drug complexes to target lung cancer cells based on the following characteristics: (a) Non-covalent binding of albumin to the complex through hydrogen bonding and Van der Waals interactions. The interaction was confirmed by physicochemical methods such as fluorescence quenching and isothermal titration calorimeter (ITC). (b) Shielding properties of albumin for the complex against macrophages and blood components (erythrocytes and complement protein C5b-9). In the presence of albumin, phagocytosis and cytokine expression level of macrophages and hemolytic activity of the peptide-drug complex reduced significantly due to the smaller particle size of the albumin-bound complexes compared to unprotected ones. (c) Targeting the lung cancer cells, possibly because of the inhibition of the albumin-binding protein SPARC (secreted protein, acidic and rich in cysteine). SPARC is a glycoprotein over expressed in lung cancer cells with high affinity to albumin. The results from in vitro SPARC expression in A549 cells, a type of human non-small cell lung carcinoma (NSCLC), showed a significant drop by the albumin-bound complex at the mRNA level evaluated by qRT-PCR. This effect can be explained by transporting the albumin-bound complex into the cell surface, binding to the SPARC proteins, and so inhibiting the SPARC expressions. This work lays out a foundation for modification and characterization of the self/co-assembly peptide-based nanocarriers for hydrophobic anticancer drug delivery, especially to improve longevity and target-ability properties.

This thesis presents a spatial sound rendering system for the use in immersive virtual environments. Spatial sound rendering aims at artificially reproducing the acoustics of a space. It has many applications such as music production, movies, electronic gaming and teleconferencing. Conventionally, spatial sound rendering is implemented by digital signal processing algorithms derived from perceptual models or simplified physical models. While being flexible and/or efficient, these models are not able to capture the acoustical impression of a space faithfully. On the other side, convolving the sound sources with properly measured impulse responses produces the highest possible fidelity, but it is not practically useful for many applications because one impulse response corresponds to one source/listener configuration so that the sources or the listeners can not be relocated. In this thesis, techniques for measuring multichannel room impulse responses (MMRIR) are reviewed. Then, methods for analyzing measured MMRIR and rendering virtual acoustical environment based on such analysis are presented and evaluated. The analysis can be performed off-line. During this stage, a set of filters that represent the characteristics of the air and walls inside the acoustic space are obtained. Based on the assumption that the MMRIR acquired at one "good" position in the target space can be used to simulate the late reverb at other positions in the same space, appropriate segments that can be used as reverb tails are extracted from the measured MMRIR. The rendering system first constructs an early reflection model based on the positions of the listener-source pair and the filters derived, then combines with the late reverb segments to form a complete listener-source-room acoustical model that can be used to synthesize high quality multi-channel audio for arbitrary listener-source positions. Another merit of the proposed framework is that it is scalable. At the expense of slightly degraded rendering quality, the computational complexity can be greatly reduced. This makes this framework suitable for a wide range of applications that have different quality and complexity requirements. The proposed framework has been evaluated by formal listening tests. These tests have proven the effectiveness in preserving the spatial quality while positioning the listener-source pair accurately, as well as justified the key assumptions made by the proposed system.

In this thesis, multidimensional signal processing techniques to mitigate disturbances in synthetic aperture systems such as radio telescopes are investigated. Here, two computationally efficient three-dimensional (3D) spatio-temporal (ST) finite impulse response (FIR) cone filter bank structures are proposed. Furthermore, a strategy is proposed to design 3D ST FIR frustum filter banks, having double-frustum-shaped passbands oriented along the temporal axis, derived from appropriate 3D ST FIR cone filter banks. Both types of cone and frustum filter banks are almost alias free and provide near-perfect reconstruction. In the proposed cone and frustum filter banks, both temporal and spatial filtering operations can be carried out at a significantly lower rate compared to previously reported 3D ST FIR cone filter banks implying lower power consumption. Furthermore, the proposed cone and frustum filter banks require a significantly lower computational complexity than previously reported 3D ST FIR cone and frustum filter banks. Importantly, this is achieved without deteriorating the improvement in signal-to-interference-plus-noise ratio. A theoretical analysis of brightness distribution (BD) errors caused by parameter perturbations and mismatches among the transfer functions of receivers employed in synthetic aperture systems is presented. First, the BD errors caused by perturbations in the transfer functions of low noise amplifiers (LNAs) and anti-aliasing filters (AAFs) are considered, and the characteristics of the additive BD error and its effects on synthesized BDs are thoroughly analyzed. Second, the conditions that should be satisfied by the transfer functions of digital beamformers to eliminate the BD errors caused by their phase responses are examined. The sufficient condition to eliminate the BD errors is that the transfer functions are matched, and, interestingly, the phase responses are not necessary to be linear. Furthermore, the BD errors caused by typical tolerances of passive L and C elements used to implement the AAFs and those caused by the random variations of gain from LNA to LNA are quantified through numerical simulations. The simulations indicate that substantial BD errors are observed at frequencies that are close to the passband edge of the AAFs. / Graduate

Deafness in early development can alter how the brain responds to sound, compromising the restoration of hearing with cochlear implants. We asked how the naïve brain responds to initial cochlear implant stimulation in children who are deaf. Results indicated large variability in initial responses. Deafness associated with GJB-2 mutations led to more uniformity in cortical responses than other etiologies. Responses associated with GJB-2 mutations were characterized by a response peak with large contributions from temporal and frontal regions of the brain. This response may reflect an early stage of auditory development. By contrast, another response type, typical of normal hearing children, received less contribution from frontal regions. Through consistent cochlear implant use, frontal regions of the brain may not be as strongly recruited. Effects of deafness in early development are heterogeneous, which may reflect differences in etiology of deafness and different stages of auditory development.

Deafness in early development can alter how the brain responds to sound, compromising the restoration of hearing with cochlear implants. We asked how the naïve brain responds to initial cochlear implant stimulation in children who are deaf. Results indicated large variability in initial responses. Deafness associated with GJB-2 mutations led to more uniformity in cortical responses than other etiologies. Responses associated with GJB-2 mutations were characterized by a response peak with large contributions from temporal and frontal regions of the brain. This response may reflect an early stage of auditory development. By contrast, another response type, typical of normal hearing children, received less contribution from frontal regions. Through consistent cochlear implant use, frontal regions of the brain may not be as strongly recruited. Effects of deafness in early development are heterogeneous, which may reflect differences in etiology of deafness and different stages of auditory development.

Resilience and post trauma responses often coexist, however, for the past decades, the trauma paradigm has served as the dominant explanatory framework for human suffering in post-conflict environments, while the resilience of individuals and communities affected by mass violence has not been given equal prominence. Consequently, mental health interventions in post-conflict zones often fail to respond to local realities and are ill equipped to foster local strengths. Drawing primarily from trauma, feminist and structural violence theories, this study strengthens understanding of adult resilience to traumatic exposure by examining the resilience of Quechua women in the aftermath of the political violence in Peru (1980-2000), and their endurance of racially and gender-targeted violence. The study uses a cross sectional survey to examine the resilience and posttraumatic responses of 151 Quechua women. Participants were recruited from an urban setting and three rural villages in Ayacucho, Peru. The study examines the associations between resilience, past exposure to violence, current life stress and post-trauma related symptoms as well as the individual and community factors associated with the resilience of Quechua women. In doing so, this study makes a unique contribution by simultaneously examining posttraumatic responses and resilience in a post-conflict society, an area with a dearth of research. Results indicate that resilience was not associated with overall posttraumatic stress related symptoms, but instead higher resilience was associated with lower level of avoidance symptoms and therefore with lesser likelihood of chronic symptoms. Findings also demonstrate that enhanced resilience was associated with women’s participation in civic associations, as well as being a returnee of mass displacement. Lower resilience was instead associated with lower levels of education, absence of income generated from a formal employment and the experience of sexual violence during the conflict. These results were triangulated with qualitative findings, which show that work, family, religion, and social participation are enhancing factors of resilience. The study highlights the courage and resilience of Quechua women despite persistent experiences of everyday violence. The importance to situate trauma and resilience within historical processes of oppression and social transformation as well as other implications for social work practice and research are discussed.

My thesis research investigated monoterpene responses in jack pine (Pinus banksiana Lamb.) to different agents to better understand how these responses may influence the spread of the mountain pine beetle (Dendroctonus ponderosae Hopkins; MPB) in the boreal forest. The results support that monoterpenes are inducible responses in jack pine. In the first study, methyl jasmonate application elicited the greatest response in juvenile and mature trees suggesting that jasmonic acid plays a role in jack pine defence responses. In the cross-induction study, I found evidence of an increase in resistance to Grosmannia clavigera with prior jack pine budworm defoliation (Choristoneura pinus pinus Freeman; JPBW). In contrast, needle monoterpenes greatly increased after G. clavigera inoculation and continued to increase during JPBW defoliation; however, JPBW increased its feeding rate to compensate for a change in host quality. Overall, monoterpene induction in jack pine depended on the agent(s) involved and their order. The systemic responses that were observed may have implications for MPB spread in the boreal forest. / Forest Biology and Managment

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