A broad range of element size, element shape, and interelement spacing/element size ratio combinations at high and low ambient illuminance levels was used to determine optimal combinations for a 5 X 7 dot matrix visual display. Three tasks - a reading test, a random search task, and a structured (menu) search task - were used to enhance the utility of the research. All tasks were displayed on a CRT display 1.02 m from the subject. There were different overall results for the reading and the search tasks, as shown by an analysis of variance. The smaller elements (0.76 and 1.14 mm) and the 0.5 space/size ratio produced the shortest reading times, while the shortest search times came from the larger elements (1.14 and 1.52 rum). The square shape and low illuminance level (5.4 lux) had the shortest times for all three tasks. For a general purpose display, the combination of a square 1.14 rum dot, with 0.57 mm edge-to-edge spacing is recommended, to be used with the lowest practical ambient illuminance. / Master of Science

The purpose of this study was to determine the effects of three medical treatments, topical oxytetracycline, topical prednisolone acetate, and systemic flunixin meglumine, on the activity of two proteinases, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), in equine tear film. The study design consisted of twelve ophthalmically normal horses separated into three groups of four in a cross-over study design. Each group was treated for 5 days with flunixin meglumine (500mg IM bid), topical 1% prednisolone acetate (0.2ml tid), or topical oxytetracycline (0.2ml tid), followed by a 9-day washout period. All topical medications were applied to the left eye and the right eye was treated with a placebo. Tears were collected before the first treatment on day one and the morning following the last treatment on day 5. Tear film proteinase activity was measured using gelatin zymography and measurements of optical density. Statistical analysis of the difference between the treated and untreated eyes and the eyes before and after treatment was performed using mixed effects model for ANOVA. When eyes were compared after treatment, there was no significant difference between treated and placebo eyes for MMP-2 or MMP-9 for any of the treatments. When post-treated eyes were compared to pre-treated eyes, there was a significant decrease in MMP-2 activity in the left eye of horses treated with flunixin meglumine (P=0.0259). There were no differences in MMP-2 and MMP-9 activity for the other treatments. In conclusion, topical 1% prednisolone acetate and topical oxytetracycline did not significantly change MMP-2 or MMP-9 activity in normal equine tear film. Systemic flunixin meglumine had an inhibitory, but questionable, effect on MMP-2 activity in normal equine tear film. This project was funded by Patricia Bonsall Stuart Award for Equine Research. / Master of Science

Diabetic retinopathy (DR) is an incurable, chronic disease that is the leading cause of blindness in working-age adults. A prominent characteristic of DR is the extensive dysfunction within the retina microvasculature. Specialized vascular cells known as pericytes (PCs) are lost or become dysfunctional during disease progression; a thickening of the extracellular matrix (ECM) composing the vascular basement membrane (vBM) and endothelial cell (EC) tight junction disruption are also key features of this disease and contribute to its pathogenesis. PC loss is believed to be a central cue for disease initiation. However, studies inducing PC loss and observing acute changes in the vasculature did not report severe vessel damage or vBM thickening, suggesting that the effects of PC loss occur over a longer period of time. Because the chronic effects of PC loss are more difficult to ascertain, especially in a complex condition such as DR, the mechanisms underlying microvascular defects in DR remain poorly understood. The work presented in this dissertation focuses on pericyte-endothelial cell interactions and their interplay with the ECM/vBM during a variety of physiological and pathological conditions. First, we isolated and functionally validated a primary mouse embryonic PC cell line that we then applied to a co-culture model with ECs to better understand the dynamic interactions between these two critical components of the capillary wall. In the co-culture model, we found that primary PCs promoted EC organization into vessel-like structures and enhanced EC-EC junctions. To complement these in vitro studies, we analyzed animal models and human tissue for the PC-EC interactions and ECM/vBM remodeling under different conditions (physiological and pathological). Moreover, we analyzed microglia and astrocytes to enhance our understanding of the tissue-vessel interface, bolstering our experimental results and facilitating the generation of more hypotheses for future research. Overall, our work suggests that PC-EC interactions in diabetic scenarios play a crucial role in ECM/vBM remodeling; engagement with the ECM/vBM in turn impacted PC behaviors including migration away from the endothelium and induced EC loss of tight junctions, key changes in the onset and progression of DR. / Doctor of Philosophy / Diabetic retinopathy is a group of eye diseases occurring in patients suffering from diabetes and is the leading cause of adult blindness among the working-aged. About one in three people with diabetes over the age of 40 have overt signs of DR. The primary cause for this disease is long-term, high blood sugar levels that damages blood vessels systemically as well as in the eye. Current treatments for DR can prevent the condition from getting worse, but no treatment exists that results in a complete cure. This work described in this dissertation focuses on the interactions between vascular pericytes and endothelial cells, two of the main cell types that compose capillaries (i.e. the smallest blood vessels important for oxygen delivery). The studies presented herein also focus on the response of these cells to the extracellular matrix, a scaffold of proteins that surround pericytes and endothelial cells to stabilize blood vessels. We found that extracellular matrix components dramatically increase as a result of the interactions between pericytes and endothelial cells exposed to diabetic conditions. These changes in the extracellular matrix also had important effects on pericytes and endothelial cells and their engagement with their environment and other cells. Taken together, our work suggests that pericyte-endothelial cell interactions and their crosstalk with the ECM play an important role in blood vessel formation and in the accumulation of microvascular defects that fuel diabetic retinopathy progression.

We aim at expanding the horizon of existing research on cyberattacks against the time-syncrhonized devices such as PMUs and PDCs, along with corresponding countermeasures. We develop a PMU-PDC cybersecurity testbed at Virginia Tech Power and Energy Center (PEC) lab. The testbed is able to simulate real-world GPS-spoofing attack (GSA) and false data injection attack (FDIA) scenarios. Moreover, the testbed can incorporates cyberattack detection algorithm in pseudo real-time. After that, we propose three stealthy attack scenarios that exploit the vulnerabilities of time-synchronization for both PMU and PDC. The next part of this dissertation is the enhancement of Hankel-matrix based bad data detection model. The existing general Hankel-matrix based bad data detection model provide satisfactory performance. However, it fails in differentiating GPS-spoofing attack from FDIA. We propose an enhanced phase angle Hankel-matrix model that can conclusively identify GPS-spoofing attack. Furthermore, we reduce the computational burden for Hankel-matrix based bad data and cyberattack detection models. Finally, we verify the effectiveness of our enhanced Hankel-matrix model for proposed stealthy attack scenarios. / Doctor of Philosophy / Modern power systems incorporate numerous smart metering devices and communication channels to provide better resiliency against hazardous situations. One such metering device is Phasor Measurement Device (PMU), what provides GPS time-synchronized measurements to the system operator. The time-synchronized measurements are critical in ensuring the cyber and physical security of grids. However, like other smart devices, PMUs are susceptible to conventional cyberattacks. In addition to conventional cyberattacks, PMUs are also vulnerable to attacks against its time-synchronization. In this work, we dig deep into the realm of cyberattacks against time-synchronization of PMUs. We propose novel stealthy attacks against PMU time synchronization. Furthermore, we enhance existing attack detection model to conclusively identify such stealthy attacks and implemented the model in cybersecurity testbed that we developed at Virginia Tech.

We propose sparse-matrix belief propagation, which executes loopy belief propagation in Markov random fields by replacing indexing over graph neighborhoods with sparse-matrix operations. This abstraction allows for seamless integration with optimized sparse linear algebra libraries, including those that perform matrix and tensor operations on modern hardware such as graphical processing units (GPUs). The sparse-matrix abstraction allows the implementation of belief propagation in a high-level language (e.g., Python) that is also able to leverage the power of GPU parallelization. We demonstrate sparse-matrix belief propagation by implementing it in a modern deep learning framework (PyTorch), measuring the resulting massive improvement in running time, and facilitating future integration into deep learning models. / Master of Science / We propose sparse-matrix belief propagation, a modified form of loopy belief propagation that encodes the structure of a graph with sparse matrices. Our modifications replace a potentially complicated design of indexing over graph neighborhoods with more optimized and easily interpretable sparse-matrix operations. These operations, available in sparse linear algebra libraries, can also be performed on modern hardware such as graphical processing units (GPUs). By abstracting away the original index-based design with sparse-matrices it is possible to implement belief propagation in a high-level language such as Python that can also use the power of GPU parallelization, rather than rely on abstruse low-level language implementations. We show that sparse-matrix belief propagation, when implemented in a modern deep learning framework (PyTorch), results in massive improvements irunning time when compared against the original index-based version. Additionally this implementation facilitates future integration into deep learning models for wider adoption and use by data scientists.

Yes / The dysregulation of Membrane - type 1 matrix metalloproteinase (MT1-MMP) has been extensively studied in numerous cancer types, and plays key roles in angiogenesis, cancer progression, and metastasis. MT1-MMP is a predictor of poor prognosis in osteosarcoma (OS), yet the molecular mechanisms of disease progression are unclear. This review provides a summary of the literature relating to the gene and protein expression of MT1-MMP (MMP-14) in OS clinical samples, evaluates the expression in cell lines and experimental models, and analyses its potential role in the progression and metastasis of OS. In addition, the therapeutic potential of MT1-MMP as a drug target has been assessed. Due to the biological complexity of MMPs, inhibition has proven to be challenging. However, exploiting the expression and proteolytic capacity of MT1-MMP could open new avenues in the search for novel, safer and selective drugs for use in OS. / This work was supported by the Bone Cancer Research Trust (No. BCRT 6218).

Connective tissue remodeling is an important area of study in biomedical engineering with respect to cancer and wound healing. Tissue remodeling components may be involved in the pathogenesis of open-angle glaucoma. Risk factors for open angle glaucoma include increased intraocular pressure (IOP), male gender, and advanced age. In a 1963 study, the hormone relaxin decreased IOP in the human eye through a mechanism that may involve the up-regulation of tissue remodeling matrix metalloproteinases (MMPs). The effects of age and gender on MMP and protein activity in porcine aqueous humor were determined in this study to identify correlations existing between MMP activity and glaucoma risk factors. Gelatin zymography identified MMPs at 66 kD and approximately 105 kD. The concentration of the 66 kD band compared to human MMP-2 standard was 0.22 ± 0.06 ng/ml for the adult female (AF) samples and 0.28 ± 0.04 ng/ml for the juvenile samples. This difference in concentration was statistically significant (p < 0.05). The concentration of the protease migrating to 66 kD was statistically independent of gender. Casein zymograms identified two non-MMP proteinases at 51 kD and 80 kD. The average total protein concentration for all aqueous humor samples was 2.54 ± 0.89 mg/ml. The mean IgG, transferrin, and albumin concentrations for all aqueous humor samples was 11.4 ± 4.2 mg/ml, 17.11 ± 6.8 mg/ml, and 78.0 ± 26.3 mg/ml respectively. Results from these experiments establish baseline levels of MMP and protein activity, allowing for identification of potential changes caused by relaxin in tissue culture studies. / Master of Science

No / Firewalls are crucial elements to enhance network security by examining the field value of every packet and decide whether to accept or discard the packet according to the firewall policy. However, the design of firewall policies, especially for enterprise networks, is complex and error-prone. This paper aims to propose an effective firewall design method to ensure the consistency, compactness and completeness of firewall rules. Specifically, we develop a new designing model, namely firewall design matrix, and the corresponding construction algorithm for mapping firewall rules to firewall design matrix. A firewall generation algorithm is proposed to generate the target firewall rules that are equivalent to the original ones while maintaining the completeness. Theoretical proof and extensive experiments on both real-world and synthetic firewalls are conducted to evaluate the performance of the proposed method. The results demonstrate that it can achieve a high compression ratio efficiently while maintaining the firewall rules conflict-free. Copyright (c) 2013 John Wiley & Sons, Ltd.

No / This paper presents a new approach to estimate the unknown frequencies of the constituent sinusoids in a noiseless signal. The signal comprising of unknown number of sinusoids of unknown amplitudes and unknown phases is measured in the time domain. The Hankel matrix of measured samples is used as a basis for further analysis in the Pisarenko harmonic decomposition. A new constraint, the Existence Factor (EF), has been introduced in the methodology based on the relationship between the frequencies of the unknown sinusoids and the eigenspace of Hankel matrix of signal's samples. The accuracy of the method has been tested through multiple simulations on different signals with an unknown number of sinusoidal components. Results showed that the proposed method has efficiently estimated all the unknown frequencies.

Hyaluronidase 2 (HYAL2) is a GPI-linked protein that is proposed to initiate the degradation of hyaluronan (HA), a major extracellular matrix component of many vertebrate tissues. Hyal2 knockout (KO) mice displayed craniofacial abnormalities and severe preweaning lethality. 54% of the surviving KOs developed a grossly dilated left or right atrium, requiring euthanasia, by 3 months of age. We hypothesize that the absence of HYAL2 leads to the accumulation of HA in organs/tissues where HA is normally abundant resulting in developmental defects and organs dysfunction. Molecular and histological analysis of HYAL2 KO hearts demonstrated extracellular accumulation of high molecular mass (HMM) HA in the heart valves, myocardium, serum and lungs which was associated with severe cardiopulmonary dysfunction. Further, structural and functional analyses of Hyal2 KO mouse hearts using high-frequency ultrasound revealed atrial dilation accompanied by diastolic dysfunction that was evident as early as 4 weeks of age, and progressed with age. Further, 50% of HYAL2 KO mice exhibited a triatrial heart (cor-triatriatum). Histological analyses revealed that the atrial dilation was the result of excess tissue, and did not correlate with the presence of cor triatrium. Hyal2 KO mice were found to have increased numbers of mesenchymal cells at early stages of development, presumably due to the presence of excess HA, that lead to cardiac dysfunction. Further examination of HYAL2 distribution in a broad range of mouse tissues, and accumulation of HA in its absence demonstrated that HYAL2 is mainly localized to endothelial cells and some specialized epithelial cells, and plays a major role in HMM-HA degradation. These studies demonstrated that HYAL2 is important for HA degradation and organ development. In the longer term, our findings will be valuable for understanding pathologies associated with the disruption of HA catabolism, and potentially in the identification of HYAL2-deficient patients. / May 2016