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The Encoding of Decision Variables in Orbitofrontal Cortex (OFC) Is Longitudinally Stable and Varies by Cortical Layer
No full textEconomic choices entail computing the values of different options and then making choice by comparing values. Work in primates and rodents has shown that these mental processes rely on the OFC. Neurophysiology studies identified in OFC distinct groups of neurons encoding the value of individual options, the binary choice outcome, and the chosen value. These variables capture both the input and the output of the decision process, suggesting a decision circuit existing in OFC. A primary challenge for the field is to assess the structure and mechanisms governing this circuit. A first fundamental question is whether the circuit is stable over long periods of time. The second question is whether the building block of this circuit, i.e., different groups of cells, are anatomically distinct – e.g., located in different cortical layers. To address these two issues, we used two-photon calcium imaging to record from the OFC of mice choosing between different juice rewards. Confirming neurophysiology results, different groups of cells encoded individual offer values, their spatial configuration, the choice outcome, and the chosen value. We recorded longitudinally from individual neurons for up to 20 weeks. And we manually classified neurons from L2/3 and L5. For each cell and each pair of sessions, we compared the activity profiles using cosine similarity, and we assessed whether the cell encoded the same variable in both sessions. These analyses demonstrated a high degree of stability in the activity profiles and consistency in the functional properties of individual neurons. Furthermore, the classification of neurons based on the cortical layer (L2/3 or L5) showed that (i) all groups of neurons populate multiple cortical layers, but (ii) good-based offer values and offer spatial configurations are more represented in L2/3, while (iii) spatial configuration-based offer value and chosen outcome are more represented in L5. These findings shed light on the circuit structure of OFC and lay the ground to dissect the neuronal mechanisms underlying economic choices
Single-step Aerosol Methods for Lignin Valorization: From Fundamentals to Scale-up
Get PDFGrowing consumption of fossil resources for energy and materials production has significantly increased greenhouse gas emissions, which will have an increasingly negative, and potentially catastrophic, environmental impact in the future. Lignocellulosic biomass is one of the few sustainable carbon resources that has the abundance and geographical distribution to displace fossil-based fuels and materials. However, the under-utilization of by-products such as lignin fraction remains a key challenge in expanding the utilization of lignocellulosic materials, necessitating the development of technologies for valorization of lignin into high-value products. Lignin is a promising precursor for the synthesis of a diverse range of high-value nanomaterials. However, the conventional solvothermal techniques to obtain lignin-based nanomaterials often involve multistep batch processes and large volumes of solvents/activating agents that are not cost-effective and environmentally benign, thereby limiting their scalability. Therefore, to advance scalable (i.e., environmentally benign and economically viable) valorization of lignin to lignin-based nanomaterials, it is essential to develop alternative techniques. This thesis demonstrates the development of gas-phase aerosol techniques for the valorization of lignin to lignin-based nanoparticles (NPs). Key features of the aerosol technique include ultrafast processing (seconds), continuous and single-step operation, minimal use of solvents, and precise control over material properties. This thesis is divided into three sections concerning the: (1) demonstration of a furnace aerosol reactor (FuAR) for the controlled synthesis of lignin-based NPs; (2) design and development of a novel aerosol reactor for the in-situ synthesis of lignin-based nanocomposites; and (3) scalability assessment of FuAR for the synthesis of carbon nanoparticles (CNPs) from lignin. The first section demonstrates the application of FuAR for the controlled synthesis of lignin-based NPs, specifically lignin nanoparticles (LNPs) and CNPs, from bulk lignin. The key operating parameters of FuAR, lignin concentration, temperature, and residence time, are systematically investigated for their roles in determining the nanoparticle size, morphology, surface area, and chemical structure. Furthermore, the impacts of various inter/intra particle processes (such as nucleation, reactions, collision, and sintering) on nanoparticle properties are illustrated to enable controlled synthesis of NPs. To determine the kinetics of simultaneous reaction and sintering, a generalized geometric model (GM) predicting the size and shape evolution of multiparticle aggregates is presented. Using the experimental results on nanoparticle properties and knowledge of reaction and sintering kinetics of lignin obtained from the GM, a detailed mechanism for the evolution of bulk lignin to LNPs and CNPs in FuAR is proposed. The as-synthesized LNPs and CNPs are evaluated for their performance in UV protection and supercapacitor applications, respectively. CNPs exhibited a specific capacitance of 247 F/g at 0.5 A/g with excellent capacity retainment of over 98% after 10,000 cycles, which is a clear demonstration of their superior performance compared with supercapacitors synthesized earlier from lignin. Moreover, the FuAR approach requires significantly less time for CNPs synthesis: on the order of seconds in comparison to hours for conventional solvothermal methods, highlighting significant promise for rapid valorization of lignin. The second section focuses on the design and development of a novel aerosol-based reactor to advance the application of the FuAR system for in-situ synthesis of lignin-based carbon nanocomposites, specifically Carbon-Silicon (C-Si) and Carbon-Sulfur (C-S). The fundamentals involved in the aerosol reactor design and the impact of processing parameters on composite properties are systematically investigated. Based on the analysis results, detailed mechanisms for the formation of C-S and C-Si composites in the respective FuAR-based systems are proposed. The impact of the distribution and loading of Si in C-Si and S in C-S on their performance as electrodes in Li-ion batteries is investigated to establish property function relationships. The third section assesses the scalability of the FuAR system for the synthesis of CNPs using a comprehensive life cycle assessment (LCA). Initially, the assessment is focused on lab-scale FuAR to investigate the significance of various processing parameters on the environmental impact of CNPs synthesis. Based on the LCA of lab-scale FuAR, an optimized scaled-up FuAR design, that incorporates recirculation of exhaust gas, heat recovery, and H2O recovery, is proposed. The scaled-up FuAR exhibited a global warming potential of 28.31 kg CO2 eq./kg of carbon material and 0.117 kg CO2 eq./F of capacitance based on mass and energy storage performance in supercapacitors, respectively. The superior sustainability along with the simple (single-step, continuous, and rapid) operation indicates the significant promise of using FuAR for the synthesis of CNPs from lignin. Finally, this dissertation also includes the demonstration of electrospray for lignin valorization. In summary, this dissertation comprehensively covers all aspects, from fundamentals to scale-up, for advancing scalable valorization of lignin to high-value nanomaterials using single-step aerosol techniques
Biophysical Adaptations of Collective Cell Migration through Multiscale Obstructions and Collagen Fibers in Extracellular Matrices
No full textCollective cell migration is a multiscale process, regulated by mechanosensitive proteins, adhesions between cells and with the extracellular matrix (ECM), and force propagation across length scales. The collective cell migration occurs as the cells receive the mechanical stimuli from the extracellular matrix and respond by generating forces to migrate. This behavior is widely observed in biological processes such as wound repair, angiogenesis, and pathogenic events like cancer metastasis and adipose tissue dysfunction. In these processes, cells often encounter heterogeneous topologies that disrupt and alter collective migration, yet it remains unclear how changes in matrix topology affect migration speed and cell-cell coordination. In the context of cancer metastasis, the presence of heterogeneous subpopulations within collectively migrating cells introduces additional complexity in understanding invasion and metastasis. The distinct roles of various cell types in generating protrusions to invade and in remodeling collagen, warrant further investigation. This dissertation aims to address these ambiguities and provide a comprehensive understanding of the factors that influence collective cell migration. Chapter 2 studies how the matrix obstructions affect the leader and follower cells in collective migrating epithelial monolayers. Using microfabricated Polydimethylsiloxane (PDMS) that has obstructions on the migrating surface in different orientation, density, and geometry, the cellular response and disorder are measured in meso- and micro- length scale. The study highlights that healthy cell populations with the optimal balance between cell-cell cohesiveness and cellular protrusions are more sensitive to obstructions compared to the aggressive and dysfunctional cells composed of either hyperactive leader or unruffled follower cells. Chapter 3 explores the tumor microenvironment, where heterogeneous cell subpopulations contribute to the complexity of understanding collective cell migration. Spheroids consisting of either tumor cells (4T1s), cancer-associated fibroblasts (CAFs), or a co-culture of 4T1s and CAFs are embedded within a three-dimensional collagen matrix. This study highlights the critical need to distinguish between cellular subtypes and their specific functions, as these cells, individually or co-dependently, affect both net invasion and collagen deformation. In order to effectively target the tumor invasion, the deeper functional understanding of cellular protrusions or the contractility in specific collagen densities is necessary
Essays in Economic Theory
No full textThis dissertation consists of three theoretical analyses. In the first chapter Who Takes Responsibility and Preventive Action? Centralized vs. Decentralized Risk Management in an Organization with Heterogeneous Agents, we investigate the optimal allocation of risk management responsibilities in organizations with multiple agents possessing heterogeneous preventive action costs. Extending the principal-agent framework to a multi-agent context, we analyze how a manager and agents choose preventive efforts to mitigate risks. Two scenarios are considered: (1) centralized risk management, where the manager bears all expected damages, and (2) decentralized risk management, where agents bear their own damages. Our findings show that centralized risk management often results in higher social welfare and is preferred by the manager when high-ability agents are present. Conversely, decentralized management becomes favorable when agents lack the ability to prevent risks effectively. This study contributes to organizational design by highlighting how agent heterogeneity influences risk responsibility allocation. In the second chapter Dynamics of Internal Promotion and External Recruitment (joint with Tomoya Tajika), we present a model describing an internal promotion race among individuals in different sectors where power shifts over time. The model includes a ratchet effect in which an employee attempts to manipulate their post-promotion reputation as a manager before they are promoted. The magnitude of this effect and the internal promotion rule are determined by beliefs about the job\u27s difficulty, which is updated over time, and potential subordinates\u27 cooperation. We use a dynamic model to compare internal promotion policies with external recruitment. We demonstrate that committing to internal promotion can provide more long-term profits than a mixture of internal and external recruitment. In the last chapter Government Comparison: Utilitarian vs. Growth Maximizer in a simple Endogenous Growth Model with Limited Prediction Ability, we analyze the relationship between government policies, economic growth, and household welfare using a simple endogenous growth model. We examine how different types of governments - utilitarian and growth maximizer - can affect household welfare while also considering the government\u27s prediction ability. Specifically, we investigate whether a growth maximizer government can better serve households by increasing economic growth. Our results suggest that for a certain range of prediction ability, a growth maximizer government may be better for households than a utilitarian government. This is because a utilitarian government may hesitate to invest in productivity, but when the government tries to maximize the growth rate, the amount of investment becomes large enough to have a positive impact on household welfare. By exploring these relationships, this paper contributes to our understanding of the role of government policies in promoting economic growth and improving household welfare
Unraveling Ancient Andean Camelid Herding Strategies Using Multi-Isotope Analyses
No full textPastoral communities around the globe form herding strategies based on traditional ecological knowledge to make sense of mutualistic human, animal, and environmental interactions. Pastoralists develop culturally specific traditional knowledge systems surrounding animals and environments that shape decision-making in herding practices and resource management strategies during times of crisis and change. To mitigate socio-political and climatic changes, such as conflict or competition over pastures, or flooding and drought, pastoralists convert local ecological knowledge into strategies including animal mobility across varying altitudes, pasture maintenance through irrigation and pasture rotation, and extended kin support for herding and caravanning. Previous archaeological studies have revealed that pastoralism has a long history of resilience and continuity across time and space in the Andes. However, the nuances of camelid management strategies and pastoral practices in response to sociopolitical processes and environmental changes have yet to be fully examined. This dissertation addresses two overarching research questions: 1) What ecological zones did herders choose for camelid and what does the animal diets reveal about herding strategies, such as local herding, long-distance mobility, or provisioning and foddering? 2) How were traditional pastoral strategies informed by socio-political (i.e., emergence and decline of ancient political states, settlement changes, heightened conflict) and environmental changes (i.e., long-term drought and flooding)? To answer these questions, this dissertation presents three case studies situated in the South American Andes from ca. 2000 BCE to 1540 CE to explore the various factors that influenced camelid herding strategies in the past. In Chapter 2, I conduct a multi-regionally and temporally comparative analysis of ancient Andean pastoralism to examine how people utilized diverse ecozones and resources during broad cultural and political changes in the past. This meta-analysis examines the influences of ecozones, population (dis)aggregation, and political (dis)integration on camelid herding practices as reflective of individual and communal decision-making. I compiled published and newly analyzed camelid carbon and nitrogen isotope values (n of samples = 504) obtained from bone collagen from 39 archaeological and modern sites spanning from the northern to the southern Andes and ranging in time between 2000 BCE and 1540 CE. My re-evaluation of these data shows that changes in camelid dietary patterns correlate with socio-political and environmental variables in the past, the likely outcome of herders responding to natural and anthropogenic pressures. Among other things, the data show that camelid ingestion of maize, which is not a natural camelid food, seems to correlate with supra-regional agricultural food-production regimes and exchange networks of early expansive states. In contrast, sites occupied during times of political fragmentation likely engaged in local subsistence strategies and localized herding practices. The distinct isotopic compositions of camelids from urban and rural sites reflect the different social roles of camelids, outlining the importance of contextual background for understanding animal management strategies. In Chapter 3, I examine herding strategies among communities participating in early Andean states where herders played an important role in provisioning and mobilizing resources. For the purpose of this study, I characterize camelid herding practices as: (1) short-term movements between distinct pastures located within the same altitudinal zone, (2) vertical or seasonal transhumance between highland and lowland pastures, (3) long-distance caravan journeys between highlands and lowlands, and (4) foddering or grazing on fallowed fields. I conducted multi-isotope analyses (δ13C, δ15N, δ18O and 87Sr/86Sr) of camelid bone (n = 10) and tooth remains (n = 52) from four archaeological sites associated with the Middle Horizon (500 – 1100 CE) Tiwanaku state: Wila Pucara (3800 masl), Pokotia (3800 masl), ACH-10 (3800 masl), and Omo M10 (1120 masl). Stable carbon and nitrogen analysis bone remains document long-term dietary patterns, while stable carbon isotope composition of sequential camelid tooth enamel sections reflects seasonal variations of camelid diets and movements in the first few years of life. New evidence for the consumption of maize or other C4 plants in a highland camelid indicates that some camelids were provisioned with crops. A subset of tooth enamel samples were also submitted for strontium analysis which confirms that Tiwanaku-affiliated herders pastured their camelids in highland environments. Intra-site variation in camelid herding practices provides evidence that these strategies were not standardized across different sites in the south-central Andes. These case studies indicate that Tiwanaku herding occurred predominately in the highlands, in which sites located further from the urban center had more variable access to different pastures or foddered their camelids. In Chapter 4, I examine the influence of political fragmentation, conflict, and long-term drought in the south-central Andean highlands and lowlands during the Late Intermediate Period (LIP; 1100-1450 CE) following the disintegration of the Tiwanaku state using four additional case studies: the fortified Colla site of Ayawiri (4,100 masl) and Konto Konto (~3800 masl) in the Lake Titicaca Basin, and the coastal Cabuza settlement of Los Batanes (500 masl), and the coastal Chiribaya Alta site of the eponymous culture (below 200 masl). These archaeological sites provide a multi-regional and localized perspective on pastoral practices. Multi-isotope analysis (δ13C, δ15N, δ18O and 87Sr/86Sr) conducted on camelid bone and teeth samples allowed for the reconstruction of camelid pastoral practices (vertical mobility, highland pasturing, and foddering) during the Late Intermediate Period. The results provide evidence of distinct mitigation strategies involving traditional knowledge-based approaches to camelid herding practices during a time of prolonged drought, decrease inter-regional exchange networks, and increased conflict. Highland herding population seems to have risked confrontation with neighboring communities in order to herd their camelids as far as the eastern Andes. These findings also provide the first evidence of maize consumption in the Ilo valley (below 200 masl), where camelids ingested C4 plants either from foddering or grazing on fallowed fields. By engaging in diverse herding practices, LIP communities were able to adapt to external stress resulting in the continuity of pastoralism over time. Ancient pastoral strategies not only involve environmental knowledge to maintain herds but also include socio-cultural and political knowledge systems that impacted decision-making and herding practices. This dissertation provides insights into the resilience of pastoral communities in extremely diverse landscapes. This study also highlights the significance of examining mutualistic human, animal, and environmental interactions as reflective of indigenous knowledge. These findings demonstrate how an in-depth investigation of diverse camelid herding strategies can aid in the interpretation of herding strategies in the ancient Andes and strengthen comparative studies of global pastoralism in the archaeological record
Studying the Dynamics of Neuromodulators in the Brain by Fluorescence Lifetime Imaging
No full textNeuromodulators in the brain are fundamental to neuronal functions and animal behaviors in health and diseases. The modulatory actions of neuromodulators highly rely on their spatiotemporal dynamics. Recent research has demonstrated the importance of both sustained and transient change in neuromodulators, likely due to tonic and phasic neuromodulator release. However, no traditional methods could simultaneously record both types of dynamics. Fluorescence lifetime of optical reporters could offer a solution because it both allows high temporal resolution and is impervious to sensor expression differences across chronic periods. Nevertheless, no fluorescence lifetime change across the entire classes of neuromodulator sensors was previously known. Here we find that several intensity-based neuromodulator sensors exhibit fluorescence lifetime responses. Demonstrating the advantage of fluorescence lifetime imaging, we show that lifetime measures in vivo neuromodulator dynamics both with high temporal resolution, and with consistency across animals and time. Additionally, we reason that the advantage of fluorescence lifetime imaging can be compromised by factors like autofluorescence in biological experiments. To explore the limits of fluorescence lifetime application in biological systems, we model the fluorescence lifetime signal from the sensors with non-sensor signals in biological applications and construct a flexible computational framework for realistic Fluorescence Lifetime Simulation for Biological Applications (FLiSimBA). Through simulations, we establish the quantitative limits of the insensitivity of fluorescence lifetime measurement to sensor expression in biological applications. Powered by FLiSimBA to push the technical boundary of fluorescence lifetime applications, we propose multiplexed dynamic imaging innovation that combines fluorescence intensity and lifetime measurement. This innovation can transform the number of signals that can be simultaneously monitored and enable a systems approach in studying signaling dynamics. Thus, we report a method that can simultaneously measure neuromodulator change over transient and chronic time scales, together with a computational framework that supports rigorous experimental design, accurate data interpretation and technological advancement. This method and computational framework promise to reveal the roles of multi-time scale neuromodulator dynamics in diseases, in response to therapies, and across development and aging
Cognitive Landscapes: Argument Evaluations, Misinformation Corrections, and Racial Attitudes in Modern Media
No full textThis dissertation explores three critical aspects of communication that significantly impact how individuals process information and form opinions in today\u27s polarized media landscape. While the experiments in each chapter do not directly interact, they collectively illuminate the complex interplay of cognitive biases, misperceptions, and counter-normative speech in shaping public discourse. The first chapter examines argument congruency bias, demonstrating how individuals evaluate arguments based on their alignment with pre-existing beliefs while still distinguishing between strong and weak reasoning. It also investigates the potential of objectivity priming to mitigate these biases, yielding insights into the challenges of overcoming ingrained cognitive patterns. The second chapter focuses on the effectiveness of culturally-relevant corrections in combating misinformation, particularly within minority communities. Through experiments with Latino and Black participants, it reveals that while corrections generally reduce misperceptions, the expected superiority of in-group corrections is not consistently observed. These findings suggest a nuanced dynamic where perceived expertise and credibility play crucial roles in correction effectiveness. The final chapter investigates how exposure to various types of social media comments about race influences racial attitudes. Contrary to expectations, results indicate that brief exposures do not significantly alter deep-seated racial beliefs, highlighting the resilience of these attitudes and the limitations of social media in challenging entrenched norms. Together, these studies contribute to our understanding of how individuals navigate the complex information environment of the digital age. They underscore the persistence of cognitive biases, the challenges in correcting misinformation, and the need for more nuanced investigations into how social media interactions shape individual and collective attitudes toward race. These findings have important implications for designing effective interventions to promote critical thinking, combat misinformation, and foster more inclusive public discourse in an era of rapid information dissemination and polarization
Human-Environmental Dynamics in prehistoric Southwest China: Environmental Change and Chronology at Haimenkou, Yunnan
No full textThis dissertation investigates the environmental dynamics and chronological developments at Haimenkou, Southwest China, providing a nuanced understanding of human-environment interactions from the late Pleistocene through the Holocene. Utilizing geoarchaeological surveys, particle size analysis, loss-on-ignition, and diatom analysis, this research delineates shifts in landscape and settlement patterns in relation to climatic changes and human activities. The results indicate that adaptation to the wetland environment was gradual, with the extent of landscape modification intensifying over time. This modification involved forest clearance, leading to severe soil erosion on mountain slopes, which subsequently destroyed and buried neighboring settlements to Haimenkou. Through rigorous stratigraphic and radiocarbon analysis, the dissertation refines the chronological framework of settlement and abandonment at Haimenkou, correlating these with broader settlement patterns across mainland Southeast Asia. A novel statistical tool is applied to test for chronological gaps, confirming that the observed gap was due to an occupational hiatus rather than insufficient data or biased sampling. The study addresses a critical phase known as the “Missing Millennia”, a period before the occupation of Haimenkou marked by scant archaeological records and significant ecological and geomorphological transformations in the Mid-Holocene. The findings suggest that the Haimenkou site, positioned strategically along the river systems at the eastern edge of the Tibetan Plateau, served as a dynamic locus for early human settlement, agricultural development, and cultural transitions in mainland Southeast Asia. These results underscore the complex interplay between climatic forces and early human landscape management in shaping the archaeological preservation and environmental history of Southwest China, contributing valuable insights into the broader prehistoric dynamics of Southeast Asia
N-methyl-D-aspartate (NMDA) Receptors Control Calcium Signaling in Striatal Neurons to Guide Value-based Learning
No full textN-methyl-D-aspartate receptors (NMDARs) play an essential role in neuronal function. Activation of NMDARs leads to calcium influx into postsynaptic neurons, which regu?late many fundamental aspects of neuronal physiology including synaptic plasticity, gene expression, and excitability. In the striatum, the input region of the basal ganglia, NM?DAR activity has been shown to regulate physiological function of striatal neurons, such as synaptic plasticity and excitability, and they also modulate behavior, particularly op?erant learning. However, there are many fundamental questions about the signaling and effects of NMDARs in vivo that have yet to be resolved. Moreover, the link between the physiological and behavioral effects of NMDARs has not been investigated. In this Disser?tation, I first show that bulk calcium recordings through fiber photometry is an excellent tool to investigate dendritic calcium changes, since this technique primarily reflects non?somatic changes in calcium. Then, I demonstrate that most striatal calcium signaling is driven by NMDARs, as antagonism of these receptors almost entirely diminish calcium signaling, disrupting the relationship between calcium signaling and action potentials in vivo. Finally, using pharmacological manipulations coupled with home-cage operant learning, I show that NMDARs modulate value-based continuous learning on a trial?by-trial basis, and that antagonism of these receptors disrupts learning of a two-armed bandit task , particularly by diminishing learning from previously rewarded actions. All together, these results demonstrate an essential of NMDARs in both striatal physiology and value-based learning through calcium influx, particularly on a moment-to-moment timescale
MEMS 411: A diving surface breaker The JetCycle
Get PDFCreate a diving surface breaker for the WashU swimming and Diving team