Fibrillar collagen plays an important role in maintaining soft tissue integrity and providing chemical and physical cues for cell fate... Show moreFibrillar collagen plays an important role in maintaining soft tissue integrity and providing chemical and physical cues for cell fate decisions. Collagen remodeling, which alternates the amount, distribution, and biomechanics of collagen, primarily type I (COLI) and type III (COLIII), can change tissue properties. This process is essential not only in biological developments but also in pathological processes. Thus, it is meaningful to understand the correlation between collagen remodeling and tissue dysfunction and investigate the cells' response to fibrous protein matrices. However, current studies in biochemical analysis of collagen and biomechanical study of tissues were carried out at different scales. So it is hard to correlate the data to draw solid conclusions. In this thesis research, we used two collagen disorder associated pathological conditions, pelvic organ prolapse (POP) and micropapillary serous carcinoma (MPSC) of the fallopian tube, as models to unravel the correlation between tissue dysfunctions and the impaired microenvironment relevant to the composition, nanostructure, and biomechanics of a collagen fibril. In the case of POP, we found the collagen fibers in tissues of POP patients were less abundant but stiffer than those of non-POP individuals, implying a loose and fragile matrix that is weakly integrated with other components of the connective tissue to provide adequate support of the pelvic organs. On the other hand, the collagen D-period, the characteristic banding feature which signals the proper assembly of collagen molecules, decreased in POP tissues. We surmised that the molecular level changes of collagen in POP were accountable for the weak matrix mechanics, verified by a systematic in vitro study.
We also examined the collagen matrix alternation in MPSC of the fallopian tube, which is thought to cause ovarian cancer via metastasis. Since cancer metastasis is often related to collagen remodeling, we examined the collagen matrix alternation in this disease. We observed the heterogeneous distribution of COLI and COLIII in the papillae of the tumor tissue. Noticeably, COLI was accumulated at the papillae tip, whereas COLIII was dominant at the papillae base. We also observed the absence of collagen matrix between the micropapillary tip and the fibrosis base. Such an uneven collagen distribution implies that the matrix exerted distinctive forces on the tumor cells to regulate their behaviors, including cell migration, directional growth, and shedding from the primary tumor to initiate metastasis. These conclusions have been supported by the results of our in vitro experiments.
In investigating the effect of the microenvironment on cell behavior, we established and validated an AFM-based method to collect and quantitatively analyze the mRNA samples from targeted live cells at the single-cell level. This method overcomes issues, such as severe cell damage or even cell death, the capability of time-dependent and in situ analyses, in current methods. The application of the method in studying heterogeneous gene expression in single cells and the interaction between cancer cells and cancer-associated fibroblasts was demonstrated. We also demonstrated that this method can be potentially used to quantitatively analyze the gene expression level changes in a targeted cell in response to the microenvironment. Show less
Artificial Intelligence (AI) holds a great promise in the healthcare. It provides a variety of advantages with its application in clinical... Show moreArtificial Intelligence (AI) holds a great promise in the healthcare. It provides a variety of advantages with its application in clinical diagnosis, disease prediction, and treatment, with such interests intensifying in the medical image field. AI can automate various cumbersome data processing techniques in medical imaging such as segmentation of left ventricular chambers and image-based classification of diseases. However, full clinical implementation and adaptation of emerging AI-based tools face challenges due to the inherently opaque nature of such AI algorithms based on Deep Neural Networks (DNN), for which computer-trained bias is not only difficult to detect by physician users but is also difficult to safely design in software development. In this work, we examine AI application in Cardiac Magnetic Resonance (CMR) using an automated image classification task, and thereby propose an AI quality control framework design that differentially evaluates the black-box DNN via carefully prepared input data with shape and fidelity variations to probe system responses to these variations. Two variants of the Visual Geometric Graphics with 19 neural layers (VGG19) was used for classification, with a total of 60,000 CMR images. Findings from this work provides insights on the importance of quality training data preparation and demonstrates the importance of data shape variability. It also provides gateway for computation performance optimization in training and validation time. Show less
This study aimed to verify that whether a low-coverage genome can work as an effective approach to isolate Lepidopteran microsatellites. As... Show moreThis study aimed to verify that whether a low-coverage genome can work as an effective approach to isolate Lepidopteran microsatellites. As microsatellites are useful tool to study population genetics, and there are many Lepidopteran agriculture pests which can cause huge economic damages every year, additionally, Lepidoptera have abundant similar flanking sequences making it difficult to develop reliable microsatellites. However, there are not enough published genomes of Lepidoptera species. If low-coverage Lepidopteran genomes can be used to isolate reliable microsatellites, the low-coverage genomes would be an effective and economical approach for microsatellites isolation, because low-coverage genome sequencing is much cheaper and less time-consuming than the published genome sequencing. Show less
Photograph of the Aaron Galleries Booth at the Art 20 exhibition, at Park Place Armory in 2006, including Mary Henry's painting The Chelsea... Show morePhotograph of the Aaron Galleries Booth at the Art 20 exhibition, at Park Place Armory in 2006, including Mary Henry's painting The Chelsea Way visible at center. Inscription on verso: "Art 20 - Park Ave. Armory 2006 Mary Henry 'The Chelsea Way' on the aisle Aaron Galleries Booth." Show less
Photograph of the Aaron Galleries Booth at the Art 20 exhibition, at Park Place Armory in 2006, including Mary Henry's painting The Chelsea... Show morePhotograph of the Aaron Galleries Booth at the Art 20 exhibition, at Park Place Armory in 2006, including Mary Henry's painting The Chelsea Way visible at center right. Inscription on verso: "Art 20 - Park Ave. Armory 2006 Mary Henry 'The Chelsea Way' on the aisle Aaron Galleries Booth." Show less
Photograph of the Aaron Galleries Booth at the Art 20 exhibition, at Park Place Armory in 2006, including Mary Henry's painting The Chelsea... Show morePhotograph of the Aaron Galleries Booth at the Art 20 exhibition, at Park Place Armory in 2006, including Mary Henry's painting The Chelsea Way visible at right. Inscription on verso: "Art 20 - Park Ave. Armory 2006 Mary Henry 'The Chelsea Way' on the aisle Aaron Galleries Booth." Show less