Ledroit Park, A Portrait In Black And White: A Study Of Historic Districts, Social Change, And The Process Of Neighborhood Placemaking

This research examines the process of placemaking in LeDroit Park, a residential Washington, DC, neighborhood with a historic district at its core. Unpacking the entwined physical and social evolution of the small community within the context of the Nation’s Capital, this analysis provides insight into the role of urban design and development as well as historic designation on shaping collective identity. Initially planned and designed in 1873 as a gated suburb just beyond the formal L’Enfant-designed city boundary, LeDroit Park was intended as a retreat for middle and upper-class European Americans from the growing density and social diversity of the city. With a mixture of large romantic revival mansions and smaller frame cottages set on grassy plots evocative of an idealized rural village, the physical design was intentionally inwardly-focused. This feeling of refuge was underscored with a physical fence that surrounded the development, intended to prevent African Americans from nearby Howard University and the surrounding neighborhood, from using the community’s private streets to access the City of Washington. Within two decades of its founding, LeDroit Park was incorporated into the District of Columbia, the surrounding fence was demolished, and the neighborhood was racially integrated. Due to increasingly stringent segregation laws and customs in the city, this period of integration lasted less than twenty years, and LeDroit Park developed into an elite African American enclave, using the urban design as a bulwark against the indignities of a segregated city. Throughout the 20th century housing infill and construction increased density, yet the neighborhood never lost the feeling of security derived from the neighborhood plan. Highlighting the architecture and street design, neighbors successfully received historic district designation in 1974 in order to halt campus expansion. After a stalemate that lasted two decades, the neighborhood began another period of transformation, both racial and socio-economic, catalyzed by a multi-pronged investment program led by Howard University. Through interviews with long-term and new community members, this investigation asserts that the 140-year development history, including recent physical interventions, is integral to placemaking, shaping the material character as well as the social identity of residents.

HIV Reverse Transcriptase Fidelity And Inhibition Are Modulated By Divalent Cations In A Concentration-Dependent Manner In Vitro

Human immunodeficiency virus (HIV) rapidly evolves through generation and selection of mutants that can escape drug therapy. This process is fueled, in part, by the presumably highly error prone polymerase reverse transcriptase (RT). Fidelity of polymerases can be influenced by cation co-factors. Physiologically, magnesium (Mg2+) is used as a co-factor by RT to perform catalysis, however, alternative cations including manganese (Mn2+), cobalt (Co2+), and zinc (Zn2+) can also be used. I demonstrate here that fidelity and inhibition of HIV RT can be influenced differently, in vitro, by divalent cations depending on their concentration. The reported mutation frequency for purified HIV RT in vitro is typically in the 10-4 range (per nucleotide addition), making the enzyme several-fold less accurate than most polymerases. Paradoxically, results examining HIV replication in cells indicate an error frequency that is ~10 times lower than the error rate obtained in the test tube. Here, I reconcile, at least in part, these discrepancies by showing that HIV RT fidelity in vitro is in the same range as cellular results, in physiological concentrations of free Mg2+ (~0.25 mM). At low Mg2+, mutation rates were 5-10 times lower compared to high Mg2+ conditions (5-10 mM). Alternative divalent cations also have a concentration-dependent effect on RT fidelity. Presumed promutagenic cations Mn2+ and Co2+ decreases the fidelity of RT only at elevated concentrations, and Zn2+, when present in low concentration, increases the fidelity of HIV-1 RT by ~2.5 fold compared to Mg2+. HIV-1 and HIV-2 RT inhibition by nucleoside (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) in vitro is also affected by the Mg2+ concentration. NRTIs lacking 3'-OH group inhibited both enzymes less efficiently in low Mg2+ than in high Mg2+; whereas inhibition by the “translocation defective RT inhibitor”, which retains the 3ʹ-OH, was unaffected by Mg2+ concentration, suggesting that NRTIs with a 3ʹ-OH group may be more potent than other NRTIs. In contrast, NNRTIs were more effective in low vs. high Mg2+ conditions. Overall, the studies presented reveal strategies for designing novel RT inhibitors and strongly emphasize the need for studying HIV RT and RT inhibitors in physiologically relevant low Mg2+ conditions.