Matrix Metalloproteinase-13 (MMP-13) belongs to a large family of proteolytic enzymes which are characterized by their ability to degrade the extracellular matrix components. MMP-13 appears to have a critical role in tumor invasion and metastasis. In this study, several fluorogenic probes specific for MMP-13 were designed and characterized. These synthesized probes could be modified with chelators to be applied for imaging MMP-13 in breast cancer and/or multiple myeloma models. The activity and selectivity of MMP-13 and other MMPs against these probes were studied through two approaches. It was found that these probes were cleaved by all MMPs, but MMP-13 showed the highest activity and selectivity towards these peptides. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

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Estimating large covariance and precision (inverse covariance) matrices has become increasingly important in high dimensional statistics because of its wide applications. The estimation problem is challenging not only theoretically due to the constraint of its positive definiteness, but also computationally because of the curse of dimensionality. Many types of estimators have been proposed such as thresholding under the sparsity assumption of the target matrix, banding and tapering the sample covariance matrix. However, these estimators are not always guaranteed to be positive-definite, especially, for finite samples, and the sparsity assumption is rather restrictive. We propose a novel two-stage adaptive method based on the Cholesky decomposition of a general covariance matrix. By banding the precision matrix in the first stage and adapting the estimates to the second stage estimation, we develop a computationally efficient and statistically accurate method for estimating high dimensional precision matrices. We demonstrate the finite-sample performance of the proposed method by simulations from autoregressive, moving average, and long-range dependent processes. We illustrate its wide applicability by analyzing financial data such S&P 500 index and IBM stock returns, and electric power consumption of individual households. The theoretical properties of the proposed method are also investigated within a large class of covariance matrices.

This thesis presents a simple force-based model of moving and interacting cells that incorporates a realistic description of cell adhesion and applies it to a system of spherical cells. In addition, several results in matrix theory are proved with the end of showing that the equations produced by the model uniquely determine the motion of the system or cells.

A non-microtubule-based spindle matrix has been observed in Drosophila melanogaster meiotic and somatic cells. This matrix comprises the proteins: Skeletor, Megator and Chromator, which localize to the nuclear periphery and chromosomes at prophase and to the microtubule spindle during mitosis and meiosis. This matrix might play a role in nuclear organization and microtubule assembly and stabilization. It is important to determine the presence or absence of this matrix in other species in order to compare form and function to that in Drosophila. These matrix proteins were studied in both normally dividing cells and cells in which division was disrupted. Our evidence suggests that a spindle matrix exists in meiocytes and embryos of the cricket, Acheta domesticus, and in a mammalian cell line established from Chinese hamster ovary cells. We report the results of our studies on the spindle matrix in invertebrate and mammalian cells and discuss implications of these findings.

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No description available.

In today's technology, with digitally controlled optic sensing devices, there exists a need for a fast and accurate calibration procedure. Typical display devices and optic fiber bundles are plagued with inaccuracies. There are many sources of error such as delay, time constants, pixel distortion, pixel bleeding, and noise. The calibration procedure must measure these inaccuracies, and compute a set of correction factors. These correction factors are then used in real time to alter the command data, such that the intended pixels are correctly commanded. This paper discusses a calibration procedure, which employs a special matrix inverse algorithm. This algorithm, which is only applicable to sparse symmetric band diagonal matrices, successfully inverts a 10,000 by 10,000 matrix in less than four seconds on a VAX-11/780. It is estimated that, when using conventional Gauss-Jordan matrix inverse techniques, 4800 hours are required to compute the same matrix inverse. This paper also documents the BlendI routines, which will be used as a calibration procedure for BlendI System.

IPF is a progressive disease, characterized by dysregulated fibrosis of the extracellular matrix (ECM). The pathobiology of the disease is still unknown, and the median survival post-diagnosis is about 3-5 years. The two current US FDA approved drugs for IPF (nintedanib and pirfenidone) slow, but fail to reverse, disease progression. There is cumulating research that suggests the ECM is an active player in fibrosis. In this thesis, we summarized the current knowledge of ECM-cell interactions in the context of pulmonary fibrosis. To gain more mechanistic insight into the ECM characteristics that dictate cell behavior, we established a 3D ECM ex vivo system to assess the nonfibrotic and fibrotic ECM’s effect on fibroblasts. The ECM appears to promote both pathological and physiological cellular changes, depending on its structural and compositional properties. We also used this 3D ex vivo system as a preclinical tool to test the effect of directly inhibiting mechanotransduction in the fibrotic ECM – fibroblast profibrotic relationship. Lastly, since the fibrotic ECM seems to play a key role in progressive fibrosis, we evaluate if researchers are appropriately using the bleomycin model by starting interventions after ECM fibrosis is established. Over the past decade in the field, there has been an overall improvement in the appropriate therapeutic timing. In the preventative studies, however, there is still an inadequate characterization of inflammation. There is also poor transparency of preclinical-bleomycin data for clinically tested interventions for IPF. Addressing these shortcomings may improve the utility of the model at predicting an intervention’s success in clinical trials. These findings illustrate the ECM’s role in driving pulmonary fibrosis. Therefore, the ECM should be further investigated to understand disease progression, and reproduced in preclinical models to test interventions. This will improve the transition of pathobiological findings into efficient drug development for this devastating disease. / Thesis / Candidate in Philosophy / Idiopathic pulmonary fibrosis (IPF) (idiopathic - unknown cause; pulmonary - lungs; fibrosis - scarring) is characterized by progressive scarring of the lung extracellular matrix (ECM). The ECM is an organ’s backbone that provides structural and biochemical support to surrounding cells. Continued ECM scarring can lead to difficulty breathing, cough, and ultimately death. The cause of IPF is unknown, however, studies suggest that the scarred ECM can promote further scarring, and cause disease progression. In this thesis, we summarized the current knowledge of how the ECM interacts with cells. Using a 3D model we see that depending on the ECM’s structure and composition, it can promote both disease and healthy cellular changes. Lastly, we evaluate if researchers are appropriately using the bleomycin model (most common preclinical model for pulmonary fibrosis) by testing interventions after ECM fibrosis is established. We propose changes to improve its usefulness as a preclinical tool for IPF.

Cardiovascular disease is a leading cause of death worldwide. Changes in the cardiac extracellular matrix (ECM) are associated with cardiac pathologies such as cardiomyopathy and cardiac hypertrophy. The ECM is a dynamic scaffold of proteoglycans, fibrous proteins, and glycoproteins that sheathes and protects many organs and tissues, including the heart, by attenuating mechanical stress. Misregulation of ECM proteins triggers changes in matrix stiffness, which can lead to age-associated and congenital heart defects. ECM rigidity is also important to the migration of cells, such as hemocytes, the invertebrate blood cells. In the embryo, hemocytes also perform fibroblast functions, through the deposition of the ECM proteins Collagen and Laminin. Hemocytes are hypothesized to be critical for ECM assembly, and by extension, for heart development. The consequences of impaired hemocyte function in the embryo and during larval growth are unknown and are the focus of this research. Using Drosophila melanogaster as a model, I used genetic tools to manipulate hemocyte survival and motility to assess their role in ECM organization and structure around the heart. Concerted gene knockdown and confocal microscopy techniques were employed to evaluate the effects of altered hemocyte abundance and motility on hemocyte behaviour and resulting changes to the ECM. Here I provide evidence to support a role for hemocytes in the turnover of a vital ECM protein, the Type IV Collagen Viking. I also developed a novel protocol to photobleach and observe fluorescence recovery in intact, living larvae using confocal microscopy. Recovery of fluorescence of GFP tagged ECM is a measure of the rate of ECM protein turnover during development or growth. This novel technique has allowed for assessment of recovery of Viking-GFP after photobleaching in vivo, as a measue of Viking protein turnover at the cardiac ECM. This new technique can be employed to determine the turnover of other major ECM proteins. Combining hemocyte impairment with photobleaching provides the opportunity to observe innate protein turnover at the ECM in real time, both in normal and hemocyte-deprived matrices. Recovery of Viking-GFP fluorescence was also observed in hemocyte-deprived conditions. My findings reveal gradual recovery of Viking-GFP at the cardiac ECM in controls, and potentially slower recovery in hemocyte-impaired conditions. These observations suggest a role of hemocytes in ECM protein turnover. This work will help reveal the role of hemocytes in organizing the cardiac ECM and provides a novel technique for the in vivo assessment of ECM protein turnover. Ultimately, this research sheds light on how hemocyte function affects overall structure of the cardiac ECM and contributes to an enhanced understanding of how changes in this ECM influence predisposition to and progress of cardiac disease. / Thesis / Master of Science (MSc)