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    Finding Beauty in Pain: working through pigment and blood in the works of Hervé Guibert, Léon-Gontran Damas, and Caio Fernando Abreu

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    This study focuses on issues of race and AIDS. I bring these issues together to think about how they have both been understood through similar processes of stigmatization and shaming, and to analyze the narrative responses created by writers in order to handle the grief associated with the weight of such stereotyping, and to create beauty out of ugliness. The literature of AIDS and the long history of racial stigma emerge in response to such grief,and the act of writing becomes an act of mourning for the writers I study (Léon-Gontran Damas [France], Caio Fernando Abreu [Brazil)] and Hervé Guibert [France]). All three write from an acute state of bereavement which propels them to push against marginalization. They embrace their minoritized selves, and reconstruct their diseased and racialized or outcasted bodies along terms that help them honor their differences rather than reject them. My two objectives with this dissertation are: first, to show how Damas, Abreu, and Guibert reject the external gaze and push against monolithic ideas of what it means to exist in a corporeal and spiritual sense; and second, to focus on questions of reception and appreciation, and on the impact the writing has on their readers.Romance Languages and Literature

    Internal state modulation of striatal dopamine signaling

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    Dopamine (DA) concentration in the striatum fluctuates on two timescales: fast, sub-second “phasic” changes, and slow, minutes to hours long, shifts in the “tonic” baseline. Phasic striatal DA fluctuations may represent a prediction error signal, or the difference between what an agent expects to happen and what actually happens. Animals are thought to implement this prediction error in a temporal difference learning framework to update policies mapping states to actions to learn how to attain rewards and avoid threats in the environment. Although much progress has been made to understand the heterogeneity of this phasic signal across striatal subregions and how different stimuli evoke different phasic dopaminergic signals, much less is known on the role that internal state of the agent plays in shaping phasic and tonic DA signaling. To investigate how internal state modulates phasic and tonic DA signaling, I employed fluorescence lifetime photometry at high temporal resolution (FLiP-R) coupled with novel DA sensors to measure absolute levels of DA in the striatum. I conducted recordings and manipulations of DA signaling in two striatal subregions - the nucleus accumbens core (NAC) in which phasic DA signaling is thought to represent a reward-prediction error, and the tail of striatum (TS) in which phasic DA signaling is thought to represent a threat-prediction error. In the TS, hunger increases tonic DA while suppressing the phasic TS DA response to modulate exploration of novel, potentially threatening stimuli. The hunger signal that modulates the phasic TS DA signaling pathway derives from the activity of hypothalamic agouti-related peptide (AgRP) neurons. In the NAC, hunger increases the tonic DA level, which in turn modulates an animal’s motivation to work for a fixed reward. I thus delineate how phasic and tonic DA signaling integrates internal state across different striatal subregions to modulate different aspects of behavior.Neuroscienc

    Structural Characterization of Outer Membrane Protein Folding Intermediates

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    Transmembrane proteins with a β-barrel topology are found in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria. These proteins are folded by a conserved protein complex termed the β-barrel assembly machine (BAM). Structural evidence has demonstrated that the central component of the complex, BamA – itself a β-barrel, interacts with substrates via β-augmentation. However, the mechanism by which BAM allows a substrate to fold is unclear, and what features of the machine allow it to effectively fold many different substrate barrels of varying size and shape is unknown. First, we develop a disulfide crosslinking assay that we use to identify folding intermediates of substrate barrels as they are assembled on BAM. We use this assay to show that two β-barrel substrates, BamA and LptD, pass through multiple shared intermediates during their folding on the BAM complex. Next, we structurally characterize three of these sequential folding intermediates of a BamA barrel substrate folding on BAM using cryo-electron microscopy. This “movie” of snapshots shows that β-strands are added to the nascent substrate barrel from a disordered state within the machine BamA lumen. The snapshots also show how the machine BamA barrel variably distorts according to the stage of folding of a single barrel, and suggest that a substrate’s efficient release from the machine requires a properly ordered global substrate architecture. iv Finally, we structurally characterize two large substrate barrels, LptD and FimD, in the process of folding on the BAM complex. These structures suggest that BamA barrel distortion and β-templating of substrate strands from the BamA lumen are general folding features. They also present twists on this general folding mechanism, and allow us to propose models for how BAM folds large barrels which contain soluble plug domains. Together, these results provide a detailed structural picture of outer membrane protein folding, show how substrates grow via sequential addition of β-strands, and suggest that BAM’s ability to fold many different barrels is rooted in its ability to variably distort, allowing a substrate to find its thermodynamic minimum structure no matter the substrate barrel’s ultimate shape.Chemistry and Chemical Biolog

    Stereotypes that Dumbfound: Comprehensive Investigations Across Content, Methods, and Demography

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    Stereotypes help humans navigate a complex social world by offering heuristics about the characteristics of social groups. Nevertheless, stereotypes can hinder decision-making along two paths. First, even when stereotypes are accurate at the group-level, meaning they reflect statistically significant differences between groups (e.g., height differences between men and women), stereotypes can prevent accurate inferences at the individual-level. Second, when stereotypes are inaccurate at the group-level, all inferences that follow – at the group-level and individual-level – are necessarily inaccurate. Across five chapters, I examine stereotypes with group-level accuracy and group-level inaccuracy to obtain general insights about their magnitude (how robust is the stereotype?), pervasiveness (which groups or places exhibit the stereotype most strongly or weakly?), mechanisms (what features drive the effect?), and malleability (can even entrenched stereotypes change?). In doing so, I show how both types of stereotypes can dumbfound because they (a) impede accurate inferences, (b) conflict with ground-truth data and/or (c) contradict participants’ own stated beliefs and values. Chapter I (Morehouse et al., 2022; CRESP) presents 7 experiments (N > 7,000) probing the nature of a stereotype with group-level accuracy: surgeon=male. In particular, I examine the magnitude, prevalence, mechanisms, and malleability of this gender-occupation stereotype, and whether it is sufficiently strong to prevent logical inferences. A Supplemental Chapter (Morehouse, Pan, Contreras, & Banaji, 2024; ICML) extends this work by exploring whether a Large Language Model – GPT-4 – similarly exhibits gender-occupation stereotypes across a set of 1,016 diverse occupations. Additionally, I tested whether systematic changes to the input prompt influence the degree of observed bias. Chapter II (Morehouse et al., 2025; Scientific Reports) leverages an archival dataset with over 600,000 respondents to interrogate the “American=White” stereotype. Although the US has been historically majority-White, this stereotype lacks group-level accuracy because all Americans, regardless of ethnic ancestry, are American. Beyond benchmarking stereotype strength at the societal-level, I uncover individual-level and regional-level predictors of this American=White effect and use time-series models to examine whether it has changed over the past 17 years (2007-2023). Chapter III (Morehouse, Maddox & Banaji, PNAS) reports 13 experiments (N > 60,000) to test a stereotype that dumbfounds by defying biological fact and participants’ explicitly held beliefs: “Human=White.” In addition to probing its existence, I examine whether this stereotype is pervasive across U.S. demographic groups (e.g., gender and political ideology) and conduct exploratory analyses to assess its emergence in non-US countries. Finally, Chapter IV (Morehouse, Ueda, Saiki, & Banaji, in prep) investigates whether these findings are unique to dominant groups in Western contexts or represent a more universal “Human=Own (Dominant) Group” effect. Specifically, four samples of Japanese participants (tested in two Japanese writing systems, Katakana and Kanji) were recruited to test the magnitude and prevalence of a “Human=Japanese” effect in Japan. Together, these five chapters harness data from ~700,000 respondents across 37 experiments to demonstrate that (1) even stereotypes with group-level accuracy prevent simple inferences; (2) implicit stereotypes with group-level inaccuracy are surprisingly robust and pervasive across groups and geography; (3) certain demographic characteristics consistently predict stereotype strength; and (4) even widely held stereotypes are malleable; they are sensitive to targeted interventions and the passage of time. In doing so, this body of work illuminates the features that create, maintain, and change stereotypes that dumbfound.Psycholog

    Clinician-Client Alignment and Collaboration in Youth Psychotherapy

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    Despite considerable progress in youth mental health research, experts have continued to call for efforts to enhance the effectiveness and acceptability of youth psychotherapy. These efforts may be enhanced by examinations of methods, such as shared decision-making (SDM), that are designed to increase clinician-client alignment and collaboration in youth psychotherapy. Transdiagnostic youth psychotherapies, such as the Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH), may be particularly strong candidates for these methods, as they involve complex decision-making processes that can influence treatment plans and outcomes. To this end, this dissertation includes a collection of studies that are positioned to advance our understanding of the role of clinician-client alignment and collaboration in youth psychotherapy, with a focus on MATCH. In the first study, I explored SDM as a tool for navigating caregiver-youth-clinician discrepancies in the selection of youth psychotherapy targets, which can serve as a barrier to clinical decision-making, as well as building inclusive transdiagnostic treatment plans that integrate the unique perspectives of clinicians, caregivers, and youths. In the second study, I extended this focus on clinician-client alignment in the selection of youth psychotherapy targets to clinician-client alignment in the selection of an initial MATCH treatment protocol. Specifically, I examined measure-based clinician-client alignment—that is, the extent to which a clinician selected a treatment option that aligned with the “best-fit” for a given youth client, based on the information shared by the youth and their caregiver in surveys—as a predictor of caregiver-reported and youth-reported severity ratings of youth symptoms and psychotherapy top problems across treatment. Overall, improvements in these outcomes were found to be greater when the clinician-selected MATCH protocol aligned with the best-fit protocol of at least one of the clients (i.e., caregiver client and/or youth client), compared to when the clinician-selected MATCH protocol did not align with the best-fit protocol of either client. Finally, in the third study, I complemented this work on measure-based clinician-client alignment with that focusing on a second form of clinician-client alignment in youth psychotherapy: interaction-based. Specifically, I examined interaction-based clinician-client alignment and collaboration—that is, the extent to which a clinician includes clients in decision-making processes during sessions—within the context of MATCH. First, I conducted a comprehensive scoping review of measures designed to capture SDM elements in healthcare and used this information to develop, apply, evaluate, and extract preliminary data from an observational coding system of interaction-based clinician-client collaboration in 222 audio-recorded MATCH sessions. Trained coders were found to achieve high levels of interrater reliability, and we identified challenges in assessing the construct validity of this measure. Overall, clinicians were observed to use at least one SDM element in most sessions with both youth and caregiver clients but to a minimal level. Additionally, clinicians were found to apply SDM elements to a greater extent with caregiver, compared to youth, clients, despite more frequently using SDM elements with youth, relative to caregiver, clients. Taken together, this work is positioned to advance our understanding of how clinicians approach decision-making in youth psychotherapy, as well as how clinicians can leverage multiple forms of clinician-client alignment and collaboration to cultivate more inclusive and responsive approaches to care. This collection of studies has the potential to inform future research, such as that examining the extent to which clinician use of SDM may impact youth psychotherapy outcomes and the potential therapeutic benefits of SDM-focused training for clinicians.Psycholog

    The Role of Trade Imbalance and Asymmetry in Interstate Wars

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    While liberal international relations theory often emphasizes that trade interdependence fosters peace, recent patterns of violent interstate conflicts challenge this assumption. According to the Global Peace Index 2024, there are currently 56 active conflicts globally, most of which are ongoing since the end of WWII, and with fewer conflicts being resolved (The Institute for Economics & Peace, 2024). This thesis investigates the complex relationship between trade interdependence and interstate conflict, with particular attention to how imbalances and asymmetries in bilateral trade (dyads) can exacerbate rather than reduce conflict risks. Drawing on the Hague Centre for Strategic Studies’ (HCSS) dangerous dyads model and the Heidelberg Institute for International Conflict Research’s (HIIK) Conflict Barometer 2023, the study examines six high-risk dyads: Russia - Ukraine, Russia - Georgia, Afghanistan - Pakistan, China - India, Rwanda - Uganda, and Syria - Türkiye. The findings of this thesis challenge the liberal assumption that economic interdependence universally fosters peace and demonstrate that trade interdependence is not inherently pacifying. A hypothesis is proposed to explain the various political, economic, and social conditions under which trade interdependence transitions from peace to conflict. This thesis also contributes to the broader debate on trade and peace by suggesting that trade positions and outlooks are critical in understanding whether economic ties stabilize or destabilize interstate relations.Extension Studie

    Ending the Stalemate: Iran, the United States, and the Use of Applied History to Facilitate Changes in Diplomacy

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    This thesis explores the complex and adversarial relationship between the U.S. and Iran since 1979, including the impacts of sanctions, Iran's pursuit of nuclear weapons, regime change efforts, and alliances aimed at cooperation in the Middle East. Examining historical parallels highlights how applied history can inform diplomatic strategies. Sanctions, the primary U.S. approach toward Iran, have largely failed to influence Iranian policies and have caused significant negative effects. Historical examples, such as sanctions against Fascist Italy, reveal ineffectiveness in changing aggressive behavior. I suggest the Peace of Westphalia from 1648 as a model for creating a balanced Middle Eastern order involving major powers to reduce sectarian tensions and promote cooperation. Iran's nuclear program is crucial for its national security as a deterrent, and although Iran has not yet weaponized its capabilities, it is nearing threshold status. Therefore, I propose that Iran could use nuclear weapons to negotiate for sanctions relief, similar to South Africa's experience with its nuclear program. I also argue that political change in Iran should not rely on external military intervention, as past U.S. efforts in Iraq, Libya, and Afghanistan led to prolonged instability. The recommendation is that the U.S. avoid consideration of regime change as a strategy and focus on diplomatic engagement, learning from past mistakes. Analyzing historical cases reveals that a diplomatic approach with realistic negotiations offers the best path to regional stability, encouraging cooperation and mutual recognition to foster peace in the Middle East. Both nations should study history to avoid repeating errors, as understanding past conflicts helps clarify regional and ideological dynamics.Extension Studie

    Opportunity or Desperation: Investigating the COVID-19 Surge in Business Creation

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    -Applied Mathematic

    Monetizing Coffee Leaves and Fruit to Fund Regenerative Agriculture: A Case Study in Puerto Rico

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    Coffee cultivation sustains more than 100 million livelihoods but illustrates agriculture’s environmental paradox: 70–80 % of smallholder households earn below living-income thresholds while contributing disproportionately to deforestation, biodiversity loss, and climate change. Regenerative agroforestry can restore ecosystems through enhanced biodiversity, carbon sequestration, and soil health, yet adoption remains limited by a “worse-before-better” gap of 10%–25 % yield penalties and establishment costs of 1,5001,500–3,000 per hectare. Existing instruments, including certifications, carbon credits, and subsidies, have not closed the estimated 4billionglobaltransitionfinancinggap.Thisthesisexaminedwhethermonetizingunderutilizedcoffeeplantbiomasscanbridgethatgap.A10acrecasestudyatCopperHillFarm(PuertoRico)modeledsixmanagementscenariosover10yearsusingstochasticNPVandMonteCarloanalysis.TheWholeTreeEconomicModel(WTEM)wasusedtoconvertcoffeeleavesandcascaraintomarketapprovedfunctionalingredients,creatingendogenousrevenuestreamsthatcomplementgreenbeansaleswhileusingexistingcooperativeinfrastructure.Primarydatasourcesincludedfarmlevelcostandproductionrecords,marketpricesforcoffeebeans,coffeeleaftea,andcascara,laborcosts,andcooperativeprocessingcoststructures.Keyvariablesmodeledacrossscenariosincludedannualnetpresentvalue,transitionperiodincomeadequacy,biomassharvestfrequency(14annualflushesforleaves),yielddynamicsunderregenerativetransition,andprocessingefficiencygainsthroughcooperativeinfrastructure.Scenariostestedconventionalmonoculture(S1),regenerativebaselinewithoutbiomassmonetization(S2),cascaraonlymonetization(S3),leafonlymonetization(S4),marketstressconditions(S5),andfullWTEMwithleavesandcascara(S6).ResultsdemonstratedWTEMseconomicimpactacross1,000MonteCarloiterations.Conventionalmonoculture(S1)exhibiteduniversalfailurewithmeanNPVof4 billion global transition-financing gap. This thesis examined whether monetizing under-utilized coffee-plant biomass can bridge that gap. A 10-acre case study at Copper Hill Farm (Puerto Rico) modeled six management scenarios over 10 years using stochastic NPV and Monte Carlo analysis. The Whole Tree Economic Model (WTEM) was used to convert coffee leaves and cascara into market- approved functional ingredients, creating endogenous revenue streams that complement green bean sales while using existing cooperative infrastructure. Primary data sources included farm-level cost and production records, market prices for coffee beans, coffee leaf tea, and cascara, labor costs, and cooperative processing cost structures. Key variables modeled across scenarios included annual net present value, transition-period income adequacy, biomass harvest frequency (1-4 annual flushes for leaves), yield dynamics under regenerative transition, and processing efficiency gains through cooperative infrastructure. Scenarios tested conventional monoculture (S₁), regenerative baseline without biomass monetization (S₂), cascara-only monetization (S₃), leaf-only monetization (S₄), market stress conditions (S₅), and full WTEM with leaves and cascara (S₆). Results demonstrated WTEM's economic impact across 1,000 Monte Carlo iterations. Conventional monoculture (S₁) exhibited universal failure with mean NPV of -119,128/ha, reflecting Puerto Rico's high labor costs and input premiums. Regenerative baseline (S₂) achieved positive viability in 100% of iterations with mean NPV of 52,353/ha,demonstratingthatregenerativepracticesprovideadvantagesviacostsavings.FullWTEM(S6)generatedmeanNPVof52,353/ha, demonstrating that regenerative practices provide advantages via cost savings. Full WTEM (S₆) generated mean NPV of 141,944/ha with 100% positive outcomes, representing 171% improvement over regenerative baseline and transforming negative conventional systems into highly profitable operations. Counterintuitively, leaf- only systems (S₄) achieved the highest performance at 195,307/hameanNPV,exceedingevenfullWTEMby195,307/ha mean NPV, exceeding even full WTEM by 53,363/ha due to superior per unit values and temporal complementarity advantages. The cascara-only scenarios (S₃) remained negative at a mean value of -$32,644/ha, confirming insufficient standalone viability. The study contributes three advances: (1) a dual-metric viability framework distinguishing economic versus financial barriers; (2) the theory of temporal complementarity, explaining how off-season leaf processing converts coordination problems into capacity-optimization opportunities; and (3) evidence that existing cooperative infrastructure can transform biomass waste into regenerative finance.Extension Studie

    Mechanisms driving the hypoxic rescue of ferredoxin and lipoate deficiency

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    The introduction of environmental oxygen on earth opened new avenues of biochemistry that enabled rapid evolution of greater complexity across the tree of life. However, oxygen levels must be maintained carefully to prevent toxic reactions that can result from toxic radical accumulation and oxidation reactions of critical cofactors. Oxygen is the most utilized substrate in the human body, and the largest consumer of oxygen is the electron transport chain in the mitochondria. Thus, mitochondrial function and oxygen tensions are inextricably linked together, and much of the work done in studying cellular adaptations to varying oxygen tensions has uncovered critical mitochondrial adaptations that alter functional capacity to maintain critical energetic functions under varying oxygen tensions. Recent work from the lab has suggested that various defects in mitochondrial function may benefit from exposure to low ambient oxygen. These defects not only included lesions in the electron transport chain, but also in other mitochondrial pathways such as the synthesis of iron sulfur clusters. Whether these diverse models of mitochondrial dysfunction are rescued by shared or distinct mechanisms under hypoxia remains unknown. I initially began my thesis studies examining the mitochondrial ferredoxin FDX2 and its role in iron sulfur cluster (ISC) synthesis. Ferredoxins are iron sulfur cluster proteins that serve as single electron donors. FDX2 is known to contribute electrons to the mitochondrial iron sulfur cluster assembly complex. A screen done in C. elegans in the lab had identified FDX2 mutations as suppressing phenotypes caused by the loss of FXN, an allosteric regulator of the ISC machinery. FXN had previously been found to be dispensable under low oxygen tensions in human cells and C. elegans. We investigated these FDX2 mutants in human cells and surprisingly found that overexpression of FDX2 resulted in a suppression of ISC synthesis in cells with normal FXN expression in normoxic, but not hypoxic oxygen tensions. Further work from collaborators confirmed that FDX2 and FXN required a fixed stoichiometry for optimum ISC machinery activity. Studies from other labs’ revealed the structure of the ISC machinery and showed that FDX2 and FXN competed for the same binding site on the structure. These pieces of evidence helped clarify our findings, suggesting that FDX2 overexpression inhibited FXN binding and subsequent activity. Our findings may provide clues into the potential mechanisms of FXN dispensability in low oxygen tensions. I was next intrigued by the fact that human mitochondria possessed a second ferredoxin – FDX1 – which was also localized to the mitochondrial matrix and had 50% identity with FDX2. Both ferredoxins were reported to receive electrons from the same reductase, FDXR. However, despite the similarities, the two ferredoxins were always reported to deliver electrons to distinct pathways, with FDX1 previously found to function in sterol synthesis and FDX2 in iron sulfur cluster synthesis. Additionally, FDX1 scored as dispensable in our labs’ previously published low/high oxygen CRISPR screen, while FDX2 did not. I was curious about investigating the discrepancies between these two proteins. Using a combination of CRISPR knockout studies in low and high oxygen tensions and proteomics, I confirmed that FDX1, but not FDX2, was dispensable for human cell proliferation under low oxygen tensions. Using TMT Proteomics, I found that FDX1 and FDX2 knockouts had different proteomic profiles. Finally, using protein modeling by Alpha Fold, I found that FDX1, but not FDX2 was required for the synthesis of the mitochondrial cofactor lipoate. Intriguingly, lipoate levels were not restored in these knockouts under low oxygen, and we confirmed that the lipoate synthesis enzyme LIAS was also dispensable under low O2, leading us to conclude that the cofactor might in fact be dispensable for human cell proliferation under low oxygen, identifying yet another model of mitochondrial dysfunction that could be dispensable under low oxygen tensions. Finally, I sought to understand the mechanism behind hypoxic rescue of lipoate deficiency, and how this mechanism was similar or different to that driving rescue of ETC and OXPHOS disruptions. I found that the inhibition of multiple ETC complexes, OXPHOS (CV) and loss of LIAS all lead to fitness defects at 21% O2 that are alleviated at 1% O2 in HepG2 cells. HIF activation was sufficient for rescue of LIAS and Complex II inhibition, and partially sufficient for rescue of other ETC or OXPHOS defects. Hypoxia broadly remodeled our HepG2 model cell line, and LIAS KO cells were rescued through a combination of increased glycolytic flux, reductive carboxylation through pyruvate carboxylase (PC), and activation of carbonic anhydrase 9 (CA9) under hypoxia. However, neither PC nor CA9 are needed for rescue of ETC or OXPHOS under hypoxia. Thus, we were able to identify a specific mechanism for hypoxic rescue of a defect in mitochondrial metabolism and conclude that the broad remodeling under hypoxia allowed for a myriad of distinct mechanisms to concurrently exist, allowing rescue of diverse mitochondrial insults.Biological and Biomedical Science

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