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The Hydraulic Shift: Reclaiming Mumbai’s Riverscapes
No full textThe fragmentation of Mumbai’s rivers through the pressures of
continuous development and engineering control demands an
urgent paradigm shift, one that reclaims riverscapes as living
infrastructural systems that are more than mere conduits of
waste. Using the case of the Dahisar, the thesis positions the
river within a complex gradient of “socio-natures” that form an
interconnected ecological system. The thesis proposes that
in Dahisar’s contested aqueous terrain, multi-scalar systems
are necessary for holding, permeating, and circulating waste
and water. Beyond creating hydraulic synergies, it facilitates
the creation of new publics through decentralized governance,
polyfunctional typologies, and place-based planning. The
manifesto designs a series of scenarios centering Mumbai’s
rivers as infrastructural systems that catalyze spatial justice.
Using these as instruments of advocacy, the thesis argues
that designing for resilience in the era of climate flux requires
integrating ecological systems, public stewardship, and spatial
multiplicities to collectively shape urban futures.Department of Urban Planning and Desig
Behind the Hedges
No full textThe screenplay, Behind the Hedges, is a romantic thriller with a high-society criminal twist. It follows the story of 30-year-old Samantha Lowenstein, an ocean-rescue, first responder who is forced to confront a former love, while facing dangers from a well-connected, sex trafficking network operating in the shadows of her Hamptons community. Our culture often sanitizes the devastating psychological, physical, mental, and emotional effects of human trafficking. This feature screenplay is an exploration to raise awareness of the global epidemic of human sex trafficking. It juxtaposes a love story that reveals the power inherent in love to triumph over all things both good and bad with the smoke and mirror show of high society criminals who profit from the sex trafficking of children and young women. Samantha’s story deals with fundamental concerns of human nature like faith, family, friendship, freedom, greed, and love.Extension Studie
Spectral statistics of non-Hermitian and non-linear random matrix models
No full textThis thesis presents several results on the universality phenomena of large random matrices. The first part of this thesis concerns the ensemble of non-Hermitian random matrices with independent identically distributed (i.i.d.) entries. We study the behavior of the eigenvalues and eigenvectors of this ensemble in two symmetry classes: with real-valued and complex-valued entries.
Firstly, we consider an ensemble of real non-symmetric i.i.d. matrices with entries that have finite moments. We show that its -point correlation function in the bulk away from the real line converges to a universal limit. This work builds on the previous result of Maltsev and Osman \cite{MO}, showing the local bulk universality in the complex for the complex version of this ensemble.
Secondly, we consider a constant-size subset of left and right eigenvectors of an i.i.d. complex non-Hermitian matrix associated with the eigenvalues with pairwise distances at least . We show that arbitrary constant rank projections of these eigenvectors are asymptotically Gaussian and jointly independent.
Finally, motivated by applications in statistics, we consider certain large random matrices, called \emph{random inner-product kernel matrices}, which are essentially given by a non-linear function applied entrywise to a sample-covariance matrix, , where is random and normalized in such a way that typically has order-one arguments. We consider the \emph{polynomial regime}, where for some . Earlier work by various authors showed that, when the columns of are either uniform on the sphere or standard Gaussian vectors, and when is an integer (the linear regime is particularly well-studied), the bulk eigenvalues of such matrices behave in a simple way: They are asymptotically given by the free convolution of the semicircular and Mar\v{c}enko--Pastur distributions, with relative weights given by expanding in the Hermite basis. In the final part of this thesis, we show that this phenomenon is universal, holding as soon as has i.i.d. entries with all finite moments.Mathematic
“We are all part of one another.”: Cross-Racial Learning and Solidarity at the College of Ethnic Studies
No full textThis yearlong qualitative study blends counterstory methodology and portraiture to explore themes of cross-racial learning and solidarity at San Francisco State University’s College of Ethnic Studies. While most research on culturally sustaining pedagogy focuses on the academic and psychosocial benefits students of color observe when learning about their own heritage, little is known about whether these same indicators of growth apply cross-racially. Through participant observations of three courses and 40 semi-structured interviews, I examine how students benefit when learning about a minoritized ethnic-racial community that differs from their own. Furthermore, I build upon conventional measurements, moving beyond grades and test scores by considering civic engagement as a metric to illuminate the efficacy of Ethnic Studies as a field. Ultimately, students overwhelmingly describe how cross-racial learning through relational Ethnic Studies courses significantly improves their scholastic and personal well-being; beyond that, and more importantly to them, Ethnic Studies is “bigger than a syllabus,” and grades are “secondary.” They care more about engaging in cross-racial solidarity, which during this study they primarily demonstrated through on-campus protests for Palestinian liberation.Educatio
Specificity and other Biophysical Properties to Guide Developability of Agonistic Bispecific Antibodies
No full text"Antibody therapeutics have a wide range of applications across many disease areas, including both monoclonal and bispecific molecules. During the initial identification and development of these antibody therapeutics, biophysical properties such as poor stability, low solubility, non-specificity, aggregation, or hydrophobicity can lead to unfavorable development and toxicity profiles. Non-specificity can be an early indicator of poor developability, but has mostly been studied in monoclonal antibodies, not bispecific antibodies. A diverse set of fourteen agonistic bispecific antibodies, composed of six unique binders for BMPRII and five unique binders for ALK1, were selected to be expressed and characterized for their biophysical properties. The agonist bispecific antibodies did not show appreciable increases in non-specificity compared to the parental monoclonal antibodies, although there was an increase in freeze-thaw induced aggregation in bispecific antibodies. These results indicate that the antibody format and biochemical properties of the antibody have a larger influence on overall developability than the mechanism of action of the bispecific antibody."Extension Studie
Investigation of the C-terminal cyclic imide degron targeted by cereblon
No full textThe E3 ubiquitin ligase substrate adapter cereblon (CRBN) has garnered widespread
interest from the research lab to the clinic. Since its first association with neurological
development and subsequent discovery as the primary target of thalidomide, CRBN has emerged
as a promising E3 ligase for targeted protein degradation, an emerging drug modality that
promotes degradation of challenging therapeutic targets. However, while there is a strong
understanding of small molecule-induced substrates and activities of CRBN, the endogenous
substrates and physiological functions of CRBN have not been fully elucidated. Here, I present
the identification of the C-terminal cyclic imide modification as an endogenous mark on substrates,
termed a degron, that are recognized and removed by CRBN, followed by the systematic
characterization of two separate mechanisms of C-terminal cyclic imide formation in biological
systems.
In Chapter 1, I introduce the ubiquitin-proteasome system and outline the families and
substrate recognition mechanisms of E3 ubiquitin ligases. I then detail the chemically induced
activity of CRBN, focusing on the history of CRBN-engaging agents and their more recent
application in targeted protein degradation. Finally, I review the ubiquitin-dependent and -
independent interactors of CRBN and outline the association of CRBN with multiple biological
pathways and diseases.
In Chapter 2, I describe the efforts to identify C-terminal cyclic imides that occur by
cyclization of asparagine and glutamine (denoted as cN and cQ, respectively) as a degron of
CRBN. I recount the chemical biology and proteomic approaches used to uncover and validate
the functional engagement of cN and cQ moieties by CRBN and the prevalence of these
modifications in the proteome. I then briefly discuss the use of the C-terminal cyclic imide degron
as versatile and selective ligands for targeted protein degradation.
In Chapter 3, I investigate the C-terminal cyclic imides that stem from spontaneous
intramolecular cleavage that constitutes a previously overlooked form of protein damage. The
intrinsic and extrinsic factors that promote asparagine cleavage events to afford C-terminal cyclic
imides in comparison to deamidation, a related form of protein damage, are discussed. Using
glutathione synthetase (GSS) as a representative substrate, I demonstrate the regulation of
protein damage that progresses through the C-terminal cyclic imide in the presence of CRBN and
the association of unmitigated cleavage events with protein aggregation in the absence of CRBN.
In Chapter 4, I report the discovery of an enzymatic mechanism of C-terminal cyclic imide
formation. I delineate the efforts to characterize the enzyme-mediated formation of the
aspartimide on multiple peptides and proteins ending with C-terminal asparagine and the
recognition of these substrates by CRBN. Finally, I present glutamine synthetase (GLUL) as a
substrate of CRBN that is recognized via the enzymatically generated aspartimide degron. I
conclude with a discussion of the implications of this emerging pathway and future perspectives
on the biology of CRBN and C-terminal cyclic imide modifications. Collectively, the degron
formation mechanisms and endogenous substrates shed light on the role of CRBN in protein
quality control, signaling, and metabolism.Chemistry and Chemical Biolog
Impact of an SPM Enriched Omega-3 Fatty Acid Dietary Supplement on Periodontal Regeneration
No full textSpecialized pro-resolving lipid mediators (SPMs) biosynthesized from essential
polyunsaturated fatty acids (PUFA) promote resolution of inflammation and enhance stem cell
proliferation and differentiation leading to tissue regeneration. SPMs are derived from
lipoxygenase-driven conversion of long-chain PUFA, such as arachidonic acid,
eicosapentaenoic acid and docosahexaenoic acid. Periodontitis is an inflammatory disease of
the supporting structures of the teeth that involves an interplay between microbial biofilm and
the host immune response leading to inflammatory-immune destruction of connective tissue
attachment and bone. Regeneration of hard and soft tissues lost to periodontal disease is
limited and not predictable. Flap surgery, enamel matrix proteins, bone and soft tissue grafting
have been employed to regenerate periodontal tissues lost to disease, generally with poor
outcomes.
Prior studies have shown that Resolvin E1 enhances resolution of inflammation, restores
horizontal and vertical bone defects and produces significant bone regeneration. Prior work in
the pig demonstrated that Benzo-Lipoxin A4 (BLXA4), a stable analog mimetic of lipoxin A4,
encapsulated in nanoparticle liposomes, significantly improved surgical outcomes and improved
regeneration of bone. The aim of this study was to determine whether a dietary supplement that
contains the omega-3 fatty acids EPA and DHA, and is enriched with the precursors for SPMs,
enhances periodontal regeneration. Interproximal periodontal defects 6 mm in depth were
created using burs in 3 female adult Göttingen Miniature Pigs, the defects were created in all 4
quadrants around second and fourth premolars and were maintained by placement of sterile
orthodontic wires. The sites were left untreated for 40 days to stabilize periodontal disease and
ligatures were thereafter removed, and established, stable periodontal disease was surgically
treated 40 days later. Each Pig was assigned to a treatment group 40 days after ligature
removal; surgical debridement only (negative control), surgical debridement with delivery of 0.5
µg of BLXA4 in a lipid nanoparticle solution to each of eight treatment sites (two per quadrant)
using a P20 micro-pipette (positive control), and surgical debridement and daily dietary
supplementation with an enriched omega-3 supplement (Lipinova®, Solutex) (3ml, added to a
small portion of regular food or Gatorade) until the end of the study. Animals were euthanized
90 days later and jaws harvested. MicroCT scans were performed before jaws samples were
decalcified for histological analyses. Blood samples were obtained from each pig for
metabolipidomic analysis by LC-MS/MS. Three-dimensional bone analysis with Micro CT
revealed significant reduction in defect depth in the Diet and BLX4 groups compared to control
(ANOVA, p 0.005). Metabololipidomics analysis revealed a significant shift in SPM profiles in
the BLXA4 and diet groups compared to control. This study in a large animal model
demonstrates that dietary supplementation with omega-3 PUFA enhances bone regeneration to
a similar level to a very low dose of the active molecule, BLXA4. SPMs are known to activate
wound healing with tissue regeneration and directly improve bone healing and regeneration.
Dietary supplementation with a specific omega-3 PUFA preparation that is enriched with SPM
precursors exhibited statistically significant improvement in tissue healing and regeneration.Oral Biolog
From Chalkboard to Chatbots: The Integration of Artificial Influence on Pedagogical Practices
No full textThis study examines the impact of artificial intelligence (AI) on higher education. Through highlighting the manifold intricacies of AI use, a distinct perspective on the digital transformation confronting pedagogy will be provided, considering the implications for curriculum development and faculty labor dynamics. Quantitative and qualitative research methods capture the rich mosaic of the faculty insights and experiences, leveraging anonymized surveys and in-depth interviews. As such, two scopes will be examined. Firstly, the vanguard touch of AI on educational methodologies, and the subsequence socio-cultural dynamics of post-secondary institutions in light of the introduction of AI technologies into pedagogical systems. Amidst the constructs of anthropology, Cultural Relativism, Practice Theory, Actor-Network Theory, and Technological Pedagogical Content Knowledge will be considered in an attempt to abate the gap of awareness in human-tech synergies, all while seeking to contribute to the subfield of digital anthropology. As its overarching purpose, this thesis emphasizes that AI does not merely augment academic experiences and outcomes but can cultivate a milieu where technology and human values coexist in symbiotic harmony.Extension Studie
How and What Does GPT Capture about Non-Compositionality?
No full textThe impressive performance and prevalence of transformers such as GPT in language modeling necessitates examination of the inner workings of the "black box" deep learning models. Language models have historically faced difficulties encoding non-compositional phrases---expressions with a meaning that is different from the combination of meanings of the individual words---such as "hot dog." Thus, we analyze whether and how transformer GPT-2 captures non-compositionality. We examine the internal representations of the model when processing non-compositional phrases through contextualized word embeddings and attention weights, the key components of the transformer architecture. We discover differences in both word representations and attention patterns between compositional and non-compositional phrases, especially in the upper layers. To determine the extent to which GPT-2 encodes non-compositionality, we implement two probing tasks. The first task shows that GPT-2 can encode the correct paraphrase of an idiom with high accuracy. The second probing task additionally reveals that GPT-2 can distinguish between literal and idiomatic expressions with high accuracy. Attention head ablation experiments on the second probing task show that a high performance is maintained even when over 40\% of heads are directly ablated. Our work provides a better understanding of how phrases are processed, which is critical to developing more interpretable architectures and linguistic representations.Computer Scienc
The Control Point at Coskata: Barrier Beaches and Disturbance Conservation
No full textNantucket’s barrier beaches are a culturally and ecologically significant landscape, threatened to disappear in the face of rising sea levels. Acknowledging how current conservation practices are not protecting from this threat, this thesis is an exploration of an alternative practice, discovered through local knowledge, that perpetuates the cultural activities and sacred ecology that supports them. This system of barrier beaches is supported by a disturbance regime, dependent on erosion and sediment deposition. This regime can be harnessed through the community’s cultural connection and land stewardship practices, proposing an opportunity for disturbance conservation. A new practice designed around the geomorphologic movements that support dune and ecosystem development at a rate which matches present rising sea levels. The three actions of Breach, Drop, and Plant, informed by their context and applied to a future regime, together design a new landform for the barrier beaches of Nantucket, while celebrating its historical use.Department of Landscape Architectur