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Molecular imaging is used in clinical and research settings. Since tools to study viral pathogenesis longitudinally and systemically are limited, molecular imaging is an attractive and largely unexplored tool. This review discusses molecular imaging probes and techniques for studying viruses, particularly those currently used in oncology that are applicable to virology. Expanding the repertoire of probes to better detect viral disease may make imaging even more valuable in (pre-)clinical settings.

Cape Cod, like most of the state and country, is facing a housing crisis, with limited rental vacancies and increasing housing costs for homes and year-round rentals. These issues are exacerbated by the Cape’s development constraints, as much of the land is already developed as single-family homes or cannot be developed because of limited septic tank capacity or environmental restrictions (Donahue Institute 2023a). Cape Cod’s housing market also consists of many second homes, with 40% of housing units being used as secondary, seasonal homes, which leaves them vacant during most of the year (U.S. Census Bureau 2022a). Additionally, the Cape has seen an increase in the number of seasonal homes and short-term rentals (STRs) since the COVID-19 Pandemic in 2020 when many looked to the Cape for a place to spend time and work remotely (Donahue Institute 2023a).STRs have provided local homeowners, including those who live in their homes year-round, with extra income, as well as allowed municipalities to fund infrastructure projects from increased tax revenue. However, allowing STRs to remain unregulated or under-regulated may lead to further reductions in available year-round rental housing and continued increases in property values, putting all housing - homeownership and rental - out of reach for low-and moderate-income households.In this thesis, I examine the impacts of increases in STRs on Cape Cod, as well as opportunities to mitigate impacts on the local housing market and the community through regulation and creation of financial incentive programs that encourage and promote year-round rental availability. Additionally, I do not just consider regulating STRs alone, because while they are a piece of the housing issues on Cape Cod, decreasing or eliminating their presence is not the only solution needed to uplift year-round housing availability. These alternative considerations include updating zoning to allow for ADUS, mixed-use development, and multi-family housing to offset the overabundance of single-family housing on the Cape.

In acute myeloid leukemia (AML), p53 tumor suppressor activity can be reduced due to enhanced expression of MDM2 which promotes the degradation of p53. In TP53 wild-type malignancies, therapy with small molecule antagonists of MDM2 results in antileukemic activity. Current treatment strategies, however, have been limited by poor tolerability and incomplete clinical activity. We have developed a proteolysis-targeting chimera (PROTAC) MS3227 that targets MDM2 by recruiting the E3 ligase Von Hippel-Lindau, resulting in proteasome-dependent degradation of MDM2. In WT TP53 leukemia cell lines, MS3227 led to activation of p53 targets p21, PUMA, and MDM2 and resulted in cell-cycle arrest, apoptosis, and decreased viability. The catalytic PROTAC MS3227 led to more potent activation when compared to a stoichiometric inhibitor, in part by dampening the negative feedback mechanism in the p53 – MDM2 circuit. The effectiveness of MS3227 was also observed in primary patient specimens with selectivity towards leukemic blasts. The addition of MS3227 enhanced the activity of other anti-leukemic agents including azacytidine, cytarabine, and venetoclax. In particular, MS3227 treatment was shown to downregulate MCL-1, a known mediator of resistance to venetoclax. A PROTAC-based approach may provide a means of improving MDM2 inhibition to gain greater therapeutic potential in AML.

Due to soil carbon (C) being greater than the atmosphere and vegetation combined, the fate of soil C could have lasting and drastic implications on atmospheric carbon dioxide concentrations. In recent years, the understanding of what constitutes “stable” soil organic C (C that is resistant to microbial decomposition) has shifted. Conventionally, stable soil organic C was considered to primarily comprise “recalcitrant” compounds difficult for microorganisms to break down. More recently, the importance of mineral interactions (especially that of non-crystalline short-range order minerals) with organic matter leading to mineral-associated C less accessible for microbial decomposition. Here, we utilized stable carbon and oxygen isotopes to investigate the potential stabilization and destabilization of native soil C in soils of different mineral assemblages in order to better understand how different minerals may protect soil C from microbial decomposition. In Chapter 1, I introduce the topics of soil carbon decomposition and what constitutes soil organic matter resistance to decomposition, the priming effect, and mineral and microbial drivers on soil carbon decomposition and priming. In Chapter 2, I present a comprehensive meta-analysis that demonstrates that priming is the typical response of fresh plant carbon input to soil yet may not lead to greater soil carbon loss. In Chapter 3, I show similar respiration and priming responses due to fresh inputs of either root exudate or plant litter carbon, and that soils abundant in short-range order minerals may lead to greater priming responses compared to soils less abundant in mineral-protected carbon. In Chapter 4, I show that the presence of short-range order minerals in soil leads to a reduction in taxon-specific bacterial growth for a large fraction of bacterial taxa, and that soil type maybe of equal or greater importance than taxonomy on bacterial growth rates. In Chapter 5, I demonstrate that short-term priming responses may be due to microbial growth more than disruption of mineral-protected carbon, and that fresh organic carbon input is quickly taken up in the mineral fraction of soil.