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Situating Emotion Within a Predictive Mind: Neural Dynamics Underlying a Naturalistic Emotional Experience
No full textEmotions signal elements of the environment that we should address, and critically, experiences that we should learn from. Despite considerable efforts and a proliferation of methods for analyzing and interpreting fine-grained patterns of functional brain activity (i.e., neural signatures), the specific neural bases of emotion remain unclear, which renders a vague understanding how subjective emotional experience emerges and influences processing and learning from ongoing experience. Whereas common approaches to this question search for neural signatures of emotion in brief ‘snapshots’ of brain activity (i.e., brain states) following emotional stimuli, we draw from the theory of predictive processing and test whether the magnitude of naturalistic emotion is instead represented in spatiotemporal trajectories between brain states – that is, the way brain activity unfolds over time. The present study uses neural event segmentation to identify meaningful states of neural activity during a naturalistic, unstructured, and highly impactful emotional experience: receiving grades on real-world University exams. 40 participants completed functional brain scans while anticipating and viewing their grades on major Chemistry exams (4 exams per participant; 160 exams total). The proposed analyses will 1) identify the neural regions that encode the onset of emotional events and characterize their temporal dynamics during ongoing emotional experience, 2) investigate whether the brain encodes features of emotional stimuli via neural signatures or spatiotemporal trajectories, and 3) whether neural states underlying highly individualized emotional experiences reoccur over time, potentially reflecting recurrent or generalized emotional contents of one’s experience. These analyses promise to clarify the neural architecture that subserves emotion and shed light on the reciprocal influences between emotion and expectations during learning.</p
Engagement with a Cognitive Behavioral Stress Management Website: Assessment of a Waitlist-Controlled Trial among Women with Breast Cancer
No full textAmong existing telehealth interventions, cognitive behavioral stress management (CBSM) offers particular benefit for reducing psychosocial suffering and promoting disease adaptation, particularly among patients with cancer. Among patients with breast cancer, CBSM has been adapted and tested in person, and while efficacious, many barriers stand in the way of in-person treatments for cancer survivorship. CBSM has been tested via telehealth for patients with breast and prostate cancer, which may offer an alternative and accessible method for intervention delivery.This trial delivered synchronous, 10-week videoconferenced CBSM plus access to an asynchronous website to women with nonmetastatic breast cancer. In the current dissertation, three studies were conducted to examine predictors and outcomes of engagement.The first study tested patient-level characteristics, including sociodemographic, medical, geographic, and psychosocial characteristics on program engagement with CBSM. No patient-level predictors impacted program-level engagement. The second study determined the effects of therapist adherence and competence in videoconferenced sessions on weekly participant engagement. Few patient-level covariates, including receipt of adjuvant treatment, predicted engagement over and above other predictors. Lastly, no effects of therapist behaviors, patient engagement, or the combination of these effects on patient post-intervention outcomes (i.e., negative and positive affect, fatigue, pain, depressive and intrusive symptoms, and sleep disturbance) emerged. Patient-level factors, including days since surgery and pre-CBSM outcome values predicted post-CBSM outcomes over therapist behaviors and engagement.Overall, findings point to the potential for treatment-related factors to impact engagement and uptake of asynchronous digital interventions. Future directions include expansion of engagement measurement modeling and modifications of asynchronous interventions to encourage engagement through human centered design.</p
A Passive Acoustic Approach to Studying Rice’s Whales (Balaenoptera ricei) in the Gulf of Mexico: Detection, Sound Propagation, and Call Density Estimation
No full textCritically endangered Rice’s whales (Balaenoptera ricei) in the northeastern Gulf of Mexico rank among the most vulnerable marine mammals, with their population estimated at fewer than 100 individuals. Effective conservation and management of this species require accurate, year-round monitoring of their distribution, density, and habitat use. This work presents a comprehensive suite of methodologies addressing these challenges. First, I developed the first automated deep learning detectors for Rice’s whale vocalizations, significantly improving detection precision and efficiency over traditional spectrogram cross-correlation methods. Using an extensive dataset collected over multiple years, these detectors enable faster processing of large passive acoustic datasets critical for long-term monitoring. Building on this foundation, I modeled site-specific acoustic propagation conditions across an 18-element sparse hydrophone array deployed within the species' core distribution area to quantify spatiotemporal variation in call detectability and normalize call detections. This approach provided improved understanding of intra-annual shifts in Rice’s whale distribution and habitat use while accounting for environmental variability affecting call detectability. Finally, I applied spatial capture-recapture techniques to passive acoustic data to generate the first relative estimates of Rice’s whale call density across time, laying groundwork to potentially use passive acoustic recordings for future abundance estimation. Together, these advancements provide a robust scientific basis for informing mitigation strategies, regulatory protections, and recovery planning for Rice’s whales.</p
Tail Wags Dog: Influence of "Solubilizing Tails" on the Binding Affinities of Photoswitchable Kinase Inhibitors
No full textMore than 70% of all human proteins are phosphorylated by protein kinases revealed in the human kinome, highlighting their relevance as they modulate the activity, localization, and binding partners of target substrates. In particular, phosphorylation of the epidermal growth factor receptor (EGFR) relates it to cellular survival, proliferation, and development. Such a diverse role implicates their involvement in tumorigenesis and cancer progression which calls for the development of proficient EGFR inhibitors. Recent studies hint toward activity external to its ATP binding site that somehow increases the binding affinity of those particular kinase inhibitors – a region not thoroughly explored.In response, we have developed photoswitchable derivatives containing similar motifs with the addition of solubilizing moieties. Unique to these potential EGFR inhibitors, is their ability to reversibly isomerize between trans and cis conformations upon ultra-violet and visible light exposure, enabling the assessment of external interactions that aid in binding to the receptor’s ATP pocket. In this work, the design, synthesis, and photophysical properties of a new generation of EGFR probes are reported, along with the optimal conditions of isomerization amidst competing mechanisms and the kinetics of both the forward and reverse processes. These findings will help in the development of more potent and selective small-molecule kinase inhibitors.</p
Greenwashing by Meat and Dairy Companies
No full textAnimal agriculture has disproportionate environmental impacts relative to other food production, and animal agriculture alone accounts for at least 16.5% of all global greenhouse gas (GHG) emissions. Many of the largest meat and dairy companies are aware of environmental concerns and make explicit environmental statements and commitments. Here, we evaluated the most recent sustainability reports and websites (2021–2024) of 33 of the world’s largest meat and dairy companies. We identified 1,240 environmental claims, 70% of which (862) were climate related. Companies provided peer-reviewed scientific evidence to support only three of the 1,240 environmental claims, two of which were climate related. Instead, 98% (1,219 claims) had content suggestive of greenwashing. “Empty claims,” defined as claims that either exaggerate achievements or have limited prospects for achieving articulated goals, were the most prevalent. While all 33 companies engage in some form of greenwashing, Danone made the greatest number of claims demonstrating greenwashing, 105 claims (9%) of 1,219 in total. Fifty claims (4%) directly related to possible financial benefits to the company that encourage the industry to maintain business-as-usual or expand them. Companies making the most greenwashing claims were not necessarily the highest emitters. Unchecked greenwashing misleads consumers and investors and further delays the fundamental changes in high-emitting industries necessary to limit global warming.</p
Expanding Regulatory Cells in GVHD Target Tissues: In Vivo Administration of TL1A-Ig Fusion Protein and IL-2
No full textThe current approach to minimize transplant-associated complications, including graft-versus-host disease (GVHD), includes long-term pharmacological immune suppression, by which unwanted toxic side effects may accompany. Targeted allo-regulatory immunotherapies may serve to replace pan-immunosuppression. Investigations to manipulate regulatory cell populations to orchestrate transplant immune regulation are of value. Previous studies involving in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with the targeting of the IL-2 high-affinity receptor, CD25, with IL-2, resulted in transient but marked (~>30%) Treg expansion in donor mice spleen and lymph node that allowed for sufficient cell numbers for adoptive transfer to recipient mice, mediating suppressive activity with measurable effect. To further delineate the novel in vivo Treg expansion using TL1A-Ig in combination with low-dose IL-2 (IL-2LD) and its impact on the regulation of GVHD, these studies are analyzing alterations of recipient GVHD target organs at the cellular and microbiome level before and early post-transplant. TL1A-Ig+IL-2LD pretreatment induced a Treg expansion, persisting early post-aHSCT, leading to diminished GVHD and improved transplant outcomes. The expansion was accompanied by increased frequency of stable and functionally active Tregs, as evidenced by in vitro assays using cells from primary GVHD target tissues. In contrast to the infusion of donor Treg cells, the strategy developed here resulted in immunosuppressive target tissue environments in the recipient before receiving donor alloreactive T cells and successful preservation of GVL responses. Results of this study should allow for the harnessing of better adaptive cellular immunotherapy designed to manipulate regulatory cellular compartments of the recipient for GVHD, circumventing the need to produce large numbers of ex vivo manipulated Tregs and providing translational approaches to improve aHSCT outcomes. </p
Fluid Dynamics of Ciliated Marine Invertebrate Larvae Under Confinement
No full textCilia and ciliary-driven flows are ubiquitous in biological systems ranging from unicellular organisms like Paramecium to higher animals like humans. Here, we investigate the ciliary-driven flow fields generated by marine invertebrate larvae of sea star and sea urchin. Understanding the physics of ciliary-driven flows in these larvae are important for a variety of reasons. First, the flow regime belongs to low-to intermediate Reynolds numbers (0.1 to 1), where the fluid dynamics is not yet fully understood, hence this study would help to bridge the gap. Second, dysfunction in ciliary motility may lead to chronic diseases, so understanding ciliary-driven flows can help diagnosis and develop therapies.This thesis is focused on addressing an important aspect of ciliary-driven flows: the effects of confinement on the flows generated by microorganisms. We study sea star and sea urchin larvae with simple to complex geometries and quantify their flow fields by systematically varying the confinement height. We demonstrate that the number of vortices around these larvae change with the confinement strength. Moreover other flow parameters such as vortex size, velocity and rate of decay of velocity depends upon the confinement strength. In addition, the different types of larvae studied under confinement reveal that the flow field also depends upon the larval body plan and local morphology. Further, we showed that the results are in good agreement with a low Reynolds number based theoretical model based on superposition of Stokelets.Finally, we applied our techniques to quantify the flow fields generated by chemically treated sea urchin larvae, and Xenopus tadpoles with a specific ciliary motor protein knockdown. Our findings are broadly applicable to understanding and quantifying fluid flows generated by a wide range of ciliated organisms with complex body plans and morphologies from micrometer to millimeter scales
Racial, Ethnic, and Cultural Considerations in Hoarding Presentation, Assessment, and Vulnerability
No full textHoarding disorder is a severe and persistent mental illness that has detrimental effects at the individual, family, and community level. Despite these effects, there is a dearth of research examining how race, ethnicity, or culture may influence hoarding. We conducted two studies to examine hoarding phenomenology, assessment, and vulnerability across race and ethnicity. Study 1 combined data from crowdsourcing platforms (n = 1,185) and archival data from clinical research studies (n = 984) to test for measurement invariance of the Saving Inventory-Revised 9 across the primary ethnic (Hispanic/Latino and non-Hispanic/Latino) and racial (Asian, Black, and White) groups in the United States. Study 2 investigated potential nuances in hoarding symptoms and associated features across four groups from an online community sample: Asian (n = 73), Black (n = 68), Hispanic/Latino (n = 84), and White (n = 82). In the first study, we found evidence to support the cross-cultural validity of the three-factor model of hoarding, with some nuances related to item functioning across the racial groups. In our second study, we found that our participant groups differed in mean levels of clutter, acquiring, and saving beliefs, and the relationships between these variables also differed across groups. Materialism contributed to acquiring symptoms to a similar degree across groups. The findings from both studies indicate that sociocultural factors do impact hoarding in nuanced, yet important ways. Our research suggests a need to further investigate the role of sociocultural influences in hoarding to improve construct validity, assessment, and identification of vulnerability factors.</p
Comprehensive Immunogenomic Landscape of Uveal Melanoma
No full textUveal melanoma (UM) is the most common intraocular cancer in adults, with a high metastatic mortality rate due to early micrometastasis and an immunosuppressive microenvironment. Its genetic landscape includes two main mutation groups: activating mutations in the Gq signaling pathway, also found in benign nevi, which are insufficient alone for malignancy; and BSE mutations (BAP1, SF3B1, EIF1AX) that drive malignant progression and correlate with poor, intermediate, and favorable prognoses, respectively. UM can be classified into four prognostic groups based on Class status and PRAME, a cancer-testis antigen. To investigate early tumor evolution for these genomic subtypes, we utilized a targeted sequencing panel for more than 1000 cases, revealing biomarkers for the transition from low- to high-grade UM, aiding early diagnosis and treatment. The composition of the tumor immune microenvironment (TIM) influences prognosis, particularly a poor prognosis associated with increased infiltration of M2 macrophages linked to BAP1 inactivation. Loss of BAP1 derepresses PROS1 expression, subsequently activating MERTK to promote immunosuppressive macrophages, which supports metastasis and immune evasion. Using single-cell sequencing, we characterized how BAP1 inactivation and PRAME expression jointly develop an immunosuppressive TIM, aiding metastasis via pathways like cGAS-STING. Furthermore, we characterized T cell response during LAG3 inhibition therapy for metastatic disease. The research employs genetic analyses, scRNA-seq, and cell culture models to better understand the immunogenomic landscape of UM and develop targeted therapies. These findings offer new insights into early detection, prognosis, and potential treatments for UM.</p
Engineering Functional Materials: Microwire Platforms and Carbon Dots for Versatile Biomedical Applications
No full textThe treatment of spinal cord injuries, infections such as SARS-CoV-2, and the early detection of cancer present significant challenges in modern biomedicine. Neuroprosthetics are plagued by device failure and chronic inflammation, and severe side effects accompany systemic treatment. Chronic inflammation is also a major in SARS-CoV-2 infection. The pandemic caused by the outbreak of SARS-CoV-2 proved a need for advancement in both prevention and treatment of similar diseases. Equally pressing is the requirement for early cancer detection as a leading cause of death worldwide. Addressing these issues requires a multifaceted approach combining materials chemistry and traditional medicine. Hydrogel-based neural interfaces present a promising approach to combat the inflammation, oxidative stress, and tissue encapsulation that rapidly degrades neural interfaces post-implantation. This work investigates a novel platform that exploits covalent attachment of hydrogels to achieve mechanical compatibility while enabling sustained, localized delivery of anti-inflammatory agents at the implant interface. Concurrently, carbon dots (CDs) have emerged as versatile nanomaterials in therapeutics and diagnostics. Strategic design of heteroatom-doped CDs can mitigate viral infections and reduce oxidative stress. Thiol-functionalized CDs exhibit promising in vitro results in reducing SARS-CoV-2 uptake and free radicals involved in the inflammatory cascade. Exploiting tunable surface chemistry of CDs enables the development of a highly specific biosensing platform that relies on the intrinsic fluorescence of CDs to detect key biomarkers. Carbon nitride dots are presented as a biosensor for mushroom-derived tyrosinase enzyme —a model biomarker for human malignant melanoma—demonstrating selectivity over other analytes. Together, these investigations underscore the vital role of materials chemistry in tackling urgent biomedical challenges, laying a foundation for next-generation devices and therapies that can outperform existing methodologies.</p