Bioengineering and Cell-derived Strategies for Salivary Gland Regeneration

Xerostomia (dry mouth symptoms) is a group of incurable debilitating conditions of salivary glands caused by aging, radiation/chemical exposure, or aberrant inflammation in the salivary glands. During this PhD thesis, we aimed to evaluate whether cell-derived strategies (e.g., extracellular vesicles, EVs) could be a potential new therapy to ameliorate salivary gland injury and restore function after radiotherapy or in autoimmune diseases. In addition, we aimed to develop new imaging techniques for both 2D and 3D analysis of larger samples which allows for quantification of disease and regenerative features. Firstly, we constructed an in vivo murine model of 25 Gy irradiation-induced salivary gland damage to evaluate the potential of human dental pulp stem cell (hDPSCs)-derived EVs. EVs were injected 3x weekly via tail vein, beginning immediately after irradiation. Salivary gland function was evaluated 18 days after irradiation using salivary gland flow rate (SFR), gene expression (by qRT-PCR) and histopathology. Next, we tested different methods to generate PCSS using a vibratome and evaluated the slices in terms of viability (by WST-1), gene expression (by qRT-PCR), secreted α-amylase activity (by α-amylase assay kit) and histological/light sheet fluorescence microscopy (LSFM) three-dimensional imaging. Following irradiation, SFR decreased while senescence-associated β-galactosidase-positive cells (via immunofluorescences) and senescence-related genes and secretory-phenotypes (e.g., p21 and MMP3 in qRT-PCR) increased. SFR was unchanged following EVs treatment, but senescence-associated genes and secretory-phenotypes decreased. We also demonstrated that in an animal model of Sjögren’s syndrome, which exhibit dry mouth symptoms, that hDPSCs-EVs could inhibit the acquisition of the senescent phenotype in salivary gland epithelial cells (SGECs) and alleviate the loss of glandular function. EVs were also found to perform these effects through an underlying immunomodulatory mechanism. For PCSS, we developed protocols to produce viable slices of controled thicknesses which retained the ability to secrete functional α-amylase for at least two days in ex vivo culture. Phenotypic salivary gland cell epithelial markers (e.g., Keratin 5 and Aquaporin 5) increased over time in PCSS (by qRT-PCR), indicating the retention of cells that are necessary for salivary glands’ function. We developed workflows to perform LSFM 3D visualization in whole salivary glands as well as the PCSS model. In conclusion, hDPSCs-EVs reduced senescence of salivary gland epithelial cells in both murine irradiation and Sjögren’s syndrome models and may become a promising future for xerostomia patients. For the murine PCSS, we successfully established an executable operating procedure at the methodological level to reliably generate viable and functional murine PCSS and developed new state-of-the-art analytical methods (such as LFSM 3D imaging and qRT-PCR) to increase the diversity of objective tools to evaluate PCSS. Therefore, this work laid the foundation for the future application of other therapies (such as irradiation therapy or EVs therapy) to the PCSS model. Those future applications could include drug screening or mechanism of injury study. At the same time, we developed a sustainable histology process to reduce xylene utilization in histological processing for salivary gland tissue processing. Therefore, this work has developed a set of in vitro and in vivo experiments with state-of-the-art methods to better understand disease mechanisms and to evaluate new therapies for salivary glands

Nanowire Photoelectrochemistry.

Recent applications of photoelectrochemistry at the semiconductor/liquid interface provide a renewable route of mimicking natural photosynthesis and yielding chemicals from sunlight, water, and air. Nanowires, defined as one-dimensional nanostructures, exhibit multiple unique features for photoelectrochemical applications and promise better performance as compared to their bulk counterparts. This article reviews the use of semiconductor nanowires in photoelectrochemistry. After introducing fundamental concepts essential to understanding nanowires and photoelectrochemistry, the review considers answers to the following questions: (1) How can we interface semiconductor nanowires with other building blocks for enhanced photoelectrochemical responses? (2) How are nanowires utilized for photoelectrochemical half reactions? (3) What are the techniques that allow us to obtain fundamental insights of photoelectrochemistry at single-nanowire level? (4) What are the design strategies for an integrated nanosystem that mimics a closed cycle in artificial photosynthesis? This framework should help readers evaluate the salient features of nanowires for photoelectrochemical applications, promoting the sustainable development of solar-powered chemical plants that will benefit our society in the long run

Pricing Strategy and Quick Response Adoption System with Strategic Customers

This study determined the competitive advantage of a quick response (QR) system when a firm faces forward-looking customers with heterogeneous and uncertain valuations for a product, uncertain demand, and two selling periods. We identify two classes of pricing strategies, namely, no-price commitment strategy and price commitment strategy. Interestingly, the unique equilibrium is proven to exist if and only if most customers have high tastes on a product’s value. We also prove that when customers possess beliefs about the markdown in the second period being smaller enough, a firm obtains a high profit with price commitment; otherwise he obtains a high profit without price commitment. Moreover, we distinguish the competitive advantage of a QR system from two strategies. When a firm uses no-price commitment strategy, the value of QR system in the first period decreases and in the second period increases with customer’s strategic behavior. When a firm provides price commitment, the value of QR system in the first period may increase, decrease, or decrease first and then increase with customer’s strategic behavior. And the value of QR in the second period under price commitment strategy decreases or rises first and then decreases with customer’s strategic behavior

Quantum Dimensions and Quantum Galois Theory

The quantum dimensions of modules for vertex operator algebras are defined and their properties are discussed. The possible values of the quantum dimensions are obtained for rational vertex operator algebras. A criterion for simple currents of a rational vertex operator algebra is given. A full Galois theory for rational vertex operator algebras is established using the quantum dimensions.Comment: 32 page