Chemical Probes and Strategies to Study Mycobacterial Cell Envelope Assembly

The cell envelope of Mycobacterium tuberculosis (Mtb) is central to its pathogenicity, immune evasion, and intrinsic drug resistance. While the importance of its glycan components is well recognized, their structural intricacies have hindered efforts to directly perturb and investigate their function. In this work, we discuss chemical approaches to study and manipulate mycobacterial cell envelope biosynthesis. Specifically, we present biosynthetic glycan labeling strategies that leverage the activity of native glycosyltransferases to probe arabinogalactan and mannose-containing glycolipids. Building upon prior work using lipid-linked probes to label mycobacterial arabinan, Chapter 2 details the development of azido-functionalized farnesyl phosphoryl mannose (AzFPM) probes that mimic native polyprenyl-phosphoryl donors and selectively label mannose-containing glycolipids in live mycobacteria. Chapter 3 showcases how these probes enable glycan substructure-specific labeling and biochemical enrichment of glycolipids across Corynebacterium glutamicum, Mycobacterium smegmatis, and Mtb. This strategy provides a platform to study glycolipid dynamics in wild-type cells, a task previously hindered by the lack of selective labeling tools. In Chapter 4, we further interrogate endogenous glycan biosynthesis by applying biosynthetic labeling probes in C. glutamicum. Perturbation of arabinan structure by probe incorporation led to impaired cell wall integrity and growth defects. In glycosyltransferase deletion strains, altered probe incorporation patterns revealed enzyme-specific roles in glycan assembly and architecture. Beyond novel labeling strategies, Chapter 5 describes the development of targeted inhibitors of galactan biosynthesis, an essential yet underexplored component of the mycobacterial cell wall. We employed a prodrug strategy to inhibit UDP-galactopyranose mutase (UGM), which catalyzes the committed step in Galf production. To overcome delivery challenges, we designed amide prodrugs activated intracellularly by amidases. One prodrug exhibited improved efficacy in Mtb, providing a promising lead for antibiotic development. Collectively, these studies establish biosynthetic labeling and targeted galactan inhibition as powerful tools for dissecting the structure and function of the mycobacterial cell envelope, offering new avenues for developing chemical probes and therapeutics against tuberculosis.Ph.D

Beyond Safety and Surveillance: New Possibilities for Public Light After Dark

As cities refocus planning and design goals in response to evolving global standards for urban well-being, sustainability, and spatial equity, research on best practices and innovative considerations for the public realm has expanded. As a result, a new movement in research and guidance on public light has emerged. Rather than continuing to view lighting as a punitive means of enforcing surveillance and public safety, this movement in research and practice advances radically inclusive, responsive design methods that use light to redress inequality in the built environment. This thesis builds on a growing body of research that establishes the powerful influence of light on human experience and perception, initiating a dialogue between different models for place-based approaches to lighting design in shared public spaces. Drawing on in-depth studies of these models, interviews with stakeholders, scholarship, policy, and design and planning practice, this thesis recommends that city planners serve as the bridge between ideation and implementation in a new era of urban illumination.M.C.P

Report to the President for year ended June 30, 2025, Department of Civil and Environmental Engineering

This report contains the following sections: Goals, Objectives, Priorities; Development and Fundraising, Research Activities and Accomplishments

The Community Retrofit Trust: Incentivizing Deep Energy Retrofits in Massachusetts' Triple Deckers

To meet its 2050 net-zero carbon emissions goals, Massachusetts must rapidly retrofit its aging stock of three-story multi-family homes, also known as “Triple Deckers.” However, high upfront capital costs, disparities between subsidized gas and electric energy rates, complex eligibility criteria, and misaligned incentives for landlords and renters constrain the widespread adoption of deep energy retrofits (DERs) in small multi-family homes. Drawing on energy democracy and reparative planning theory, this thesis reframes Triple Decker retrofits as a pathway to social and spatial transformation that empowers residents through cooperative participatory processes. This project proposes a practical framework for a “Community Retrofit Trust” which uses systems of distributed energy savings, community ownership of DER assets, and cooperative governance to ensure tenants, building owners, and neighbors in environmental justice communities share benefits from DERs while maintaining rental affordability. A proposed values-based decision-making process also helps community cooperatives adapt the Retrofit Trust’s framework to their unique social contexts. Descriptive case studies of two community solar initiatives illustrate how cooperative approaches that build trust, bundle projects and local expertise, and expand opportunities for participation can efficiently distribute energy benefits across a community while increasing investment and lowering costs. A feasibility analysis of a Community Retrofit Trust in Boston examines the strengths, challenges, and contradictions of incentivizing Triple Decker DERs through a cooperative approach.M.C.P

The Private Sector in Public Transit: Evaluating Early US Experience in P3s

Problems in US public transit are well documented: transit providers struggle to develop new infrastructure, face high project costs and long implementation timelines, pursue designs that prioritize ease of delivery over value to the public, and struggle to sustain their operations. In response to these challenges, Public-Private Partnerships (“P3s” or “PPPs”) have been promoted as a way to deliver more infrastructure on faster timelines at lower cost and higher quality. As P3s have been increasingly considered for major transit projects, this thesis investigates their ability to deliver on promotional claims, and their ability to address key challenges in American public transportation. First, the thesis contextualizes contemporary P3s within a history of private sector involvement in US public transit. In addition to detailing how existing infrastructure came to be, this history intends to sharpen an understanding of contemporary P3s by considering how forms of private involvement have changed over time. It proceeds to develop detailed case studies for three major infrastructure projects that have proceeded under a P3 model: RTD’s Eagle P3 in Denver, Maryland MTA’s Purple Line in Southern Maryland, and Los Angeles Metro’s Sepulveda Transit Corridor Project. Combining historic research and contemporary case study analysis, the thesis seeks to understand the circumstances under which contemporary P3s have emerged, and to draw lessons from early experience. American transit providers have considered P3s for a variety of reasons, but have been primarily motivated by limited administrative and financial capacity, and by a perceived ability of private firms to deliver projects on faster timelines. Early P3s have facilitated provision, enabling projects that otherwise may not have been built, and have demonstrated their potential to ensure sustainable operations over long-term contract periods. But P3s have achieved mixed results in accelerating project timelines, and their ability to reduce lifecycle project costs remains unclear. While P3s seek to increase private involvement in transit provision, the model places a higher burden on upfront public planning compared to conventional delivery strategies. Public infrastructure owners can design P3s to leverage private sector resources and capacity, but the model comes with tradeoffs that should be carefully weighed against likely benefits. Ultimately, P3s can address a number of acute challenges in American public transit, but are unlikely to provide a workaround to fundamental political and financial challenges that limit transit development more broadly.M.C.P

Constraints on the photon polarisation in b → sγ transitions using B s 0 → ϕe+e− decays

An angular analysis of the B s 0 → ϕe+e− decay is performed using the proton-proton collision dataset collected between 2011 and 2018 by the LHCb experiment, corresponding to an integrated luminosity of 9 fb−1 at centre-of-mass energies of 7, 8 and 13 TeV. The analysis is performed in the very low dielectron invariant mass-squared region between 0.0009 and 0.2615 GeV2/c4. The longitudinal polarisation fraction of the ϕ meson is measured to be less than 11.5% at 90% confidence level. The A T R eCP observable, which is related to the lepton forward-backward asymmetry, is measured to be 0.116 ± 0.155 ± 0.006, where the first uncertainty is statistical and the second systematic. The transverse asymmetries, A T 2 and A T I mCP , which are sensitive to the virtual photon polarisation, are found to be −0.045 ± 0.235 ± 0.014 and 0.002 ± 0.247 ± 0.016, respectively. The results are consistent with Standard Model predictions

Report to the President for year ended June 30, 2025, Singapore-MIT Alliance for Research and Technology (SMART)

This report contains the following sections: Introduction, Research Highlights, Innovation and Entrepreneurship, and Outreach and Engagement

Properties of Low TC AlMn TES

Low T C AlMn transition-edge sensors (TESs) have been developed as sensitive thermometers for the Q-Array, which will use superconducting targets to measure the coherent elastic neutrino nucleus scattering spectrum in the RICOCHET experiment. The TESs are made of manganese-doped aluminum with a titanium and gold antioxidation layer. A prototype TES thermometer consists of two TESs in parallel, an input gold pad in metallic contact with the TESs and an output gold pad and gold thermal link meanders, which are each designed to control the flow of heat through the TESs. We have fabricated and measured low T C AlMn TES chips with or without thermal flow control structures. We present T C measurements of the TESs after the initial fabrication and further T C tuning by re-heating and summarize the thermal property studies of the prototype TES thermometer by measuring I-V curves and complex impedance

Against Character Constraints

This paper defends the following principle: For any visually perceptible set of objects and any visual phenomenal character, there could be a veridical perception of exactly those objects with that character. This principle is rejected by almost all contemporary theories of perception, yet rarely addressed directly. Many have taken the apparent inconceivability of a certain sort of ‘shape inversion'—as compared to the more plausible, frequently discussed ‘colour inversion’—as evidence that the spatial characters of our perceptions are uniquely suited to and/or revelatory of the structure of their objects, such that alleged perceptions of those objects that differed radically in spatial character could not be veridical. I argue that these conclusions are unjustified: I claim that the difficulty involved in constructing coherent ‘shape inversion’ scenarios is attributable to the complex relations among visual and tactile shape experiences, as opposed to relations between shape experiences and worldly shape properties

Mapping facade materials utilizing zero-shot segmentation for applications in urban microclimate research

To address the Urban Heat Island (UHI) effect-a significant urban climate challenge-detailed urban microclimate modeling is essential. Such modeling typically requires data on urban surface properties and morphologies from street canyons and buildings. Most urban surveying efforts have focused on morphological attributes such as sky view factor, vegetation or building surface ratio, while the mass-collection of facade materials has been hindered by the complexity of the segmentation task and the need for large and diverse labeled datasets. Recognizing the importance of mapping facade materials for urban thermal comfort, envelope heat emissions, and building energy studies, we employ computer vision-based state-of-the-art zero-shot learning paradigms for high-fidelity facade material extraction. Our approach circumvents the traditional need for extensive labeled training data, allowing for adaptation to a variety of urban contexts and material types. Tested in Dubai, Amsterdam, and Boston (three architecturally diverse cities), our algorithm successfully detects the predominant facade material in 68% of cases and identifies the top three present material classes in 85% of cases. Additionally, we show how material coverage identification is crucial for assessing outdoor thermal comfort, as evident in shifts in annual cold and heat stress hours across the climates of the three cities in a sample urban canyon