Breast cancer is one of the most commonly diagnosed forms of cancer amongst American women. Mammographic density has been strongly associated with breast cancer risk. Previous quantitative assessments of percent density have shown that women with higher percentage of fibroglandular tissue have a higher risk of being diagnosed with breast cancer. It has also been established that mammographic density is associated with higher water and lower fat content in the breast. This implies that women with breasts containing higher volumetric percentage of water and lower percentage of lipid are at a higher risk of developing breast cancer. The ability to quantify water and lipid in the breasts with mammographic images has the potential to stratify women based on breast cancer risk. Thus the purpose of this project was to employ dual-energy material decomposition technique to demonstrate the feasibility of quantifying water and lipid in breast tissue. Calibration study was performed to determine the fitting coefficients in the dual-energy non-linear inverse function to determine material thickness.

Postmortem breasts were imaged using a spectral mammography system and dual-energy material decomposition was implemented to quantify water and lipid in the breasts. The results from mammographic images were compared to results from chemical analysis, the reference standard. The thickness of water and lipid could be measured with RMS errors less than 1mm and density with RMS error less than 1% demonstrating a linear relationship. A high correlation between the two datasets was observed concluding that dual-energy mammography demonstrates the potential for breast cancer risk assessment based on water and lipid content.

Suspicious lesions detected during early screening requires the patient to undergo needle biopsy or further imaging examinations to determine the nature of the lesion. However, due to mammography’s low specificity for malignant lesions, several healthy women are often recalled for diagnostic procedures. Prior studies have suggested that breast lesion tissue containing higher than normal percentage of water and lower lipid have higher tendency of being malignant. The purpose of this project was also to further extend the application of dual-energy mammography to breast lesion characterization. Dual-energy images of postmortem breasts with lesion phantoms were studied. The measured thicknesses and densities of the lesions were compared to known values and a linear relationship was observed. RMS errors of less than 1mm and less than 10% were calculated for thickness and density respectively. The small errors were indicative of a good match between the measured datasets and the applied fitting function and further emphasized the accuracy of dual-energy mammography in lesion characterization.

Barth Syndrome (BTHS) is a rare genetic disorder caused by mutations in the gene that encodes tafazzin, a protein whose sole function is to remodel the mitochondrial phospholipid cardiolipin (CL). Despite comprising a small proportion of the body’s total phospholipid pool, the critical role CL plays in the structure and function of the mitochondrial inner membrane means that defects in CL composition lead to profound mitochondrial impairment. These mitochondrial defects, in turn, lead to the failure of high energy-demand systems, resulting in neutropenia, skeletal muscle weakness, and cardiomyopathy. While some researchers have suggested gene therapy or protein replacement as potential future treatments, it is conceivable that, if CL could be delivered to the defective mitochondria, the need for a functional tafazzin could be bypassed entirely. In the current study, we use the amphipathic plasma protein apolipoprotein A-I to solubilize CL into discoidal nanoparticles resembling HDL. These CL nanodisks (CLND) were incubated with a cell culture model of the neutropenia seen in BTHS. CL-ND treatment increased cellular CL levels and ameliorated the BTHS phenotype. To extend these findings to whole animals, a 10 week study was carried out using a mouse model of BTHS. However, at the end of the study, while the BTHS mice developed significant differences in CL composition characteristic of the disease, CL-ND treatment had no effect on CL content or composition. Thus, while CL-ND may eventually prove to be a useful therapy for BTHS, the current study highlights the difficulty of translating cell culture results to intact animals.

Carbohydrates are the most abundant biomolecule in nature and are involved mainly in the central metabolic processes of life and in providing structural integrity across the different domains of life. Carbohydrates also make up a major portion of our diets, with the low-molecular-weight and highly digestible carbohydrates serving as our main source of energy, while the high-molecular-weight and indigestible structures are carried to the distal gut where the gut microbes can utilize them. These gut microbes can in turn affect our physiology and health. Numerous studies have shown that dietary carbohydrates are implicated in some disease states, and that this can be mediated by the food-microbe-host interactions. It is therefore necessary that the analytical tools for carbohydrate characterization be able to speciate between the myriad structures of carbohydrates in food.

In this research work, a novel bottom-up LC-MS/MS-based glycomics method to characterize and quantify polysaccharides is presented. A non-enzymatic chemical reaction based on Fenton’s chemistry was used to depolymerize polysaccharides into smaller oligosaccharide structures. In Chapter 1, an overview of carbohydrate structures and a survey of various techniques for carbohydrates analysis is provided. In Chapter 2, the polysaccharide analysis workflow was optimized and used to identify polysaccharides in various types of food, while Chapter 3 demonstrated how the workflow was improved to provide accurate and reproducible quantitation of multiple polysaccharides. In Chapter 4, an integrated multi-glycomics protocol was outlined in the most detailed way. This protocol contained three different LC-MS/MS-based glycomics analyses, namely monosaccharide-, linkage-, and polysaccharide analyses. Several examples of applying these methods were also presented. Lastly, Chapter 5 provides the summary and the future implications of these analytical workflows in the field of carbohydrates research.

Advancement of additional methods for freshwater generation is imperative to effectively address the global water shortage crisis. In this regard, extraction of the ubiquitous atmospheric moisture is a powerful strategy allowing for decentralized access to potable water. The energy requirements as well as temporal and spatial restrictions of this approach can be substantially reduced if an appropriate sorbent is integrated in the atmospheric water generator. Recently, metal–organic frameworks (MOFs) have been successfully employed as sorbents to harvest water from air, making atmospheric water generation viable even in desert environments.

In Chapter 1, the concept of sorbent-assisted moisture extraction from air is introduced. Then, the use of MOFs as materials for atmospheric water harvesting is motivated and the progress in this field of research is summarized. At last, the design of water-harvesting units deploying MOFs as sorbents is reviewed.

In Chapter 2, the molecule-by-molecule water filling mechanism in the state-of-the-art water-harvesting metal–organic framework MOF-303 was deciphered by performing an extensive series of single-crystal X-ray diffraction measurements and DFT calculations at different water loadings. The first water molecules strongly bind to the pyrazole-based organic linkers, being followed by additional water molecules forming isolated clusters, then chains of clusters, and finally a water network.

In Chapter 3, equipped with the knowledge about the water-filling mechanism in MOF-303, its pores were modified by the multivariate mixed-linker approach, in which multiple functionalities line the pores across the crystal, to achieve accurate design of the geometry and strength of water interactions. A series of nine multivariate MOFs were synthesized, thereby precisely modulating the binding strength of the first water molecules and deliberately shaping the water uptake behavior. This resulted in higher water productivity, and tunability of regeneration temperature and enthalpy, without compromises to the capacity and hydrothermal stability of the frameworks.

In Chapter 4, new multivariate, MOF-303-based, water-harvesting frameworks based on readily available reactants are developed. The resulting MOF series exhibited an even larger degree of tunability in operational humidity range, regeneration temperature, and desorption enthalpy. Additionally, a novel, highly scalable synthetic route for MOF-303 and its multivariate derivatives was established. With this method, the space-time yields could be improved by two orders of magnitude in comparison to the conventional synthesis method. At last, this procedure allowed for the production of ~3.5 kg MOF per batch without major compromises to framework crystallinity, porosity, and water-harvesting performance.  In Chapter 5, the concept of a rapidly cycling water-harvesting device is explored. It is shown that MOF 303 can perform an adsorption–desorption cycle within minutes under a mild temperature-swing operation, which opened the way for high-productivity water harvesting through rapid, continuous cycling. These findings were implemented in a new atmospheric water harvester, which was successfully employed in the Mojave Desert, and generated ~1 L water per kg of MOF and day, representing an improvement by one order of magnitude over previously reported devices. This chapter demonstrates that creating sorbents capable of rapid water sorption dynamics, rather than merely focusing on high water capacities, is crucial to reach water production on a scale matching the human consumption.

In Chapter 6, quasielastic neutron scattering was utilized to probe the water mobility in a series of multivariate, MOF-303-based frameworks of same pore volume and size but with varying levels of hydrophilicity. It could be identified that the self-diffusion coefficients increase and activation energies of diffusion decrease with higher levels of framework hydrophobicity. Additionally, less confinement at low water loadings in MOF-303 resulted in comparatively high self-diffusivities and low activation energies of diffusion. Finally, a correlation with single-crystal X-ray structures of MOF-303 at different water loadings was established, which indicated a more prevalent intra-cluster mobility than inter-cluster self-diffusion of water molecules in the MOF pores.

In Chapter 7, future directions for the emerging field of atmospheric water harvesting with MOFs, encompassing both material and device improvements, are outlined.