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What Jobs Offer (and Don’t Offer) Benefits to Low-Wage Workers? Evidence from a Nationally Representative Survey
Full text linkEmployer-based benefits are an important for the financial security and well-being of U.S. workers. These benefits are a key path to healthcare access, retirement security, and other beneficial outcomes. But employers may also offer services that support employees’ financial wellness, and relatively little is known about the extent to which supplemental financial-wellness benefits are offered to low-wage workers or about variation in offerings by industries. Drawing on data from the Workforce Economic Inclusion and Mobility (WEIM) survey of a nationally representative sample of 2,511 low-wage U.S. workers, this Research Brief presents findings on the types of benefits provided by employers to low-wage workers. It reports on the extent to which employers offer common benefits, such as health insurance, and financial wellness benefits such as financial counseling and wage advances. It also considers how the provision of these benefits vary across occupational categories
Circuit-specific vulnerability in a mouse model of Alzheimer\u27s Disease
Full text linkThe relationship between brainwide functional decline and accumulation of pathological protein aggregates in Alzheimer’s disease (AD) is complex and not well understood. A set of highly interconnected cortical regions known as the Default Mode Network (DMN) exhibits selective vulnerability to both functional decline and amyloid beta (Aβ) plaques in early AD. One possibility is that early Aβ accumulation in the DMN drives vulnerability. However, it is unknown whether there is something intrinsic to neuronal projections within the DMN that biases these circuits towards dysfunction. In this dissertation, I describe the development of a multisite in vivo electrophysiology pipeline for chronic single unit recording in freely behaving mice and subsequent experiments using this pipeline in a mouse model of Alzheimer’s Disease with global cortical Aβ burden (APP/PS1) in order to directly test this hypothesis. Specifically, I track the interactions of a population of neurons within a DMN region and two additional populations that comprise monosynaptic targets, one within and the other outside the DMN. In addition, I show recordings from single neurons in CA1 and examine hippocampal sharp-wave ripple triggered interactions between in-DMN and out-DMN cortical circuits. I examine the statistics of local activity as well as inter-regional communication in a region, genotype, and brain-state dependent manner. Our data reveal dysfunction restricted to within-DMN projecting circuits. In contrast, communication along neuronal projections that originate in the DMN but target non-DMN populations are equivalent in APP/PS1 and control mice. Circuit dysfunction is found to be most evident in non-rapid eye movement (NREM) sleep, on the timescale of hours as well as within sharp-wave ripples, a stereotyped hippocampal event that contributes to memory consolidation in the cortex. Our results indicate that neighboring cells in the DMN exhibit differential intrinsic vulnerability to amyloid injury dependent on their projection targets
The Impact of Blood-Based Biomarkers and Disease-Modifying Medications on Anticipated Reactions of Learning Alzheimer Disease Risk Information
Full text linkIn recent years, the Alzheimer disease (AD) field has seen significant advancements, including the development of blood-based biomarker (BBBM) tests for risk assessment and the approval of new disease-modifying therapies. These innovations are rapidly reshaping the landscape of clinical care. However, public understanding and attitudes toward these developments remain unclear. To address this gap, the present study used a vignette-based, cross-sectional survey grounded in the Health Belief Model (HBM) to examine older adults’ awareness, knowledge, and anticipated reactions to BBBM testing and novel AD treatments. A nationally representative sample of 450 adults (aged 55+) in terms of race, ethnicity, and gender identity completed the survey. Participants were randomly assigned to one of four experimental conditions (High Risk, Intermediate Risk, Low Risk, Control), each presented with varying levels of hypothetical AD risk and with information on new therapies. Results suggested that although general awareness of these clinical advancements was low, participants reported high levels of interest in them. Moreover, exposure to higher hypothetical risk levels elicited heightened psychological distress and stronger intention to make behavioral changes. However, information about available treatments appeared to reduce the perceived threat of AD. Finally, consistent with the HBM, perceptions of susceptibility, benefits, barriers, and self-efficacy significantly predicted willingness to pursue BBBM testing and treatment, as well as anticipated behavioral and emotional responses to risk information. These findings offer important insights into how emerging AD innovations might be effectively integrated into clinical practice and communicated to the public
Senescent Cancer-Associated Fibroblasts Mediate Immunosuppression and Promote Breast Cancer Progression
Full text linkBreast cancer is the most frequently diagnosed cancer among women worldwide, and aging is the largest risk factor for breast cancer development. The process of aging is typically accompanied by a progressive accumulation of senescent cells, which are characterized by a series of markers such as p16INKA4 (p16) positivity and a distinctive profile of secretory factors including mitogens, cytokines, and extracellular matrix (ECM) proteins that are collectively recognized as senescence-associated secretory phenotype (SASP). Numerous data so far have shown that senescent stromal cells play critical roles in modulating tumor microenvironment and progression. For example, senescent fibroblasts induced in vitro could promote angiogenesis when co-implanted with human MDA-MB-231 breast tumor cells into immunocompromised mice, ultimately leading to accelerated tumor growth. Similarly, senescent skin fibroblasts established via ectopic p27 expression could suppress tumor immunosurveillance when co-inoculated with mouse skin tumor cells, which resulted in more robust tumor development. While these data provide compelling evidence of the pro-tumorigenic nature of senescent stroma, it remains understudied whether and how spontaneously arising senescent stroma contributes to breast cancer tumorigenesis. Clinically, high p16 positivity in stroma strongly correlates with ductal carcinoma in situ (DCIS) recurrence, raising the possibility that p16+ senescent stromal cells do contribute to breast cancer progression. To explore this hypothesis, we carried out single-cell RNA sequencing (scRNA-seq) analyses of human breast cancer samples and murine spontaneous mammary tumors. We found that senescence was restricted to a specific myofibroblastic cancer-associated fibroblasts (myCAFs) subpopulation that expresses numerous immune and extracellular matrix SASP factors that could impact tumor immunosurveillance. We refer to these cells as senescent CAFs (senCAFs). To investigate how senCAFs impact tumorigenesis, we crossed MMTV-PyMT (PyMT) mice that spontaneously develop mammary tumors to INK-ATTAC (INK) mice, which allows selective elimination of p16+ senescent cells. Depletion of senCAFs in PyMT/INK mice led to significantly delayed tumor onset and changes in various tumor-infiltrating immune cells including natural killer (NK) cells, both of which could be recapitulated by treating PyMT mice with a senolytic drug. Monoclonal antibody-mediated NK cell depletion in the PyMT model indicated that NK cells are required for senCAF’s tumor-promoting effect. Finally, we found that ECM deposited by senCAFs but not control fibroblasts that resembled non-senescent myCAFs directly inhibited NK cell killing of tumor cells. Together our data highlights that senCAFs contribute to mammary gland tumorigenesis by modulating tumor immunity and suggests that senolytic treatment may limit breast cancer progression
Essays in International Macroeconomics and Sovereign Default
Full text linkMy dissertation consists of two essays studying sovereign default determinants in low-income countries. In chapter one, “Institutional Investment and Multilateral Debt Relief”, I study the effectiveness of well-designed debt relief programs into improving institutional quality. I focus my analysis in the Heavily Indebted Poor Countries (HIPC) Initiative, created in 1996 by the IMF and the World Bank, with the intention to assure sustainable debt levels in exchange of a multilateral debt relief. To obtain the relief, HIPC had to show a track record of institutional investments to improve institutional quality. I propose two proxies for institutional quality perceived by private investors: the amount of funds lent and the sovereign default on those loans. Using data from 30 HIPC in the Sub-Saharan African region, I find that receiving the relief is positively correlated with lending from private investors, and negatively correlated with sovereign default in private sector funds. Since default expectations are key determinants of lending decisions and countries could self-select into the HIPC Initiative, I build a structural sequential dynamic discrete choice model with multiple sequential choices that includes observed and unobserved heterogeneity. Agents raise funds from multilateral and private sources and decide on institutional investment, default or repayment, the type of default, and the optimal debt allocations. The model captures a reduction in sovereign default on private bonds as an explanation of the equilibrium increase in the bonds\u27 level. In chapter two, “Partial Default and Exogenous Exchange Rate Shocks”, I study the effect of nominal exchange rate shocks in currency unions on the sovereign default intensive margin. The essay builds on a partial default structural model with endogenous intensive margin decisions. I consider a fixed exchange rate regime environment where all nominal depreciations happen exogenously, and countries can decide how much to optimally default on their sovereign debt (partial default). I calibrate the model to the African Financial Community (CFA) franc zones, where the domestic currencies have been pegged to a foreign currency since 1945 (first the French Franc and then the Euro) with only one domestic nominal devaluation. The model demonstrates that nominal depreciations increase the debt burden on the economy, resulting in a higher percentage of partial defaults, which aligns with empirical evidence. In addition, a robust analysis shows that the existence of a sovereign default intensive margin reduces negative welfare effects of nominal depreciations by about 25%
Effects of Surprisal and Prediction Uncertainty on Detailed and Gist Aspects of Memory
Full text linkSchemas guide comprehension and memory of everyday activities, yet theories differ on how schema‐unexpected or schema‐expected events affect memory. In this study, we compared predictions from the Schema‐Linked Interactions between Medial Prefrontal Cortex and Medial Temporal Lobe (SLIMM) model, which proposes a U‐shaped function for gist memory (both highly expected and highly unexpected events are well remembered) and a linear function for detailed memory, with those of the Schema Copy Plus Tag (SC+T) theory, which proposes a linear function for both gist and detailed memory. Participants read everyday activity narratives with events varying in surprisal, prediction uncertainty, and relevance to goals. Memory was tested after 30-minute and 24-hour delays. We found that gist memory discrimination increased linearly with surprisal, favoring SC+T. Unexpected events yielded fewer false alarms, suggesting that their memory discrimination stems partly from reduced confusion at retrieval. Moreover, memory for both expected and unexpected events decayed at similar rates over 24 hours, aligning with SC+T’s prediction rather than SLIMM’s proposal that memory for expected events decays at a slower rate than memory for unexpected events does. In addition to surprisal, we examined the role of prediction uncertainty—moments when observers could not confidently forecast upcoming actions—on memory. Gist memory was higher for events that followed high‐uncertainty segments, consistent with the hypothesis that people allocate extra attention when they cannot predict what happens next. Finally, we found that subjective surprise depends strongly on whether an event is inappropriate relative to the schema and is amplified when such violations occur in goal‐relevant actions. These findings suggest humans develop more precise predictions for goal-central aspects of activities, and that humans allocate enhanced attention to moments of high uncertainty or high surprisal, optimizing the encoding of everyday experiences
Mutant-Specific Analysis of Tumor Cell Heterogeneity in Glioblastoma
Full text linkGlioblastoma (GBM) is an aggressive brain tumor driven by the interplay between tumor cell-intrinsic and -extrinsic heterogeneity, enabling rapid evolution. To investigate how canonical GBM mutations promote functional plasticity, we developed an isogenic human neural stem cell (NSC) model of GBM by sequential addition of TERT promoter, TP53, and PDGFRA point mutations. TP53 loss-of-function increased TERT expression during serial mutagenesis, but only triple mutant NSCs reliably formed lethal brain tumors in vivo that recapitulate GBM. Tumor cell evolution triggered stress-related metabolic changes and transitioned toward a neuronal progenitor network driven by transcription factor INSM1. INSM1 is highly expressed in human GBM tumors and, during cortical development, in intermediate progenitor cells (IPC), which give rise to neurons. Remarkably, INSM1 knockdown in triple mutant NSCs and primary GBM cells disrupted oncogenic gene expression and function and inhibited the in vivo tumorigenicity of triple mutant NSCs, highlighting the functional importance of an IPC-like cell state in GBM pathogenesis
Microfluidic platforms for multiplexed studies of bacteria: design, fabrication, and applications in bacterial research
No full textMicrobes carry out a wide range of functions essential to environmental systems, industrial processes, and biomedical applications. However, many microbial behaviors are governed by physical and chemical cues that are difficult to control or isolate in conventional laboratory systems. Processes such as extracellular electron uptake and secondary metabolite production remain incompletely understood due to the limitations of current experimental tools. This dissertation presents the development of multiplexed, miniaturized platforms designed to enable high-resolution, parallel investigation of microbial activity across a range of growth environments. The first is a scalable microfluidic bioelectrochemical cell platform that supports multiplexed electrochemical and optical measurements to study extracellular electron uptake in bacteria. The second is a modular microfluidic cassette system developed to investigate Streptomyces bacteria growth and secondary metabolism at the solid–liquid interface
Enhancing Ion Transport and Electron Transfer in Redox Flow Batteries Through Component Design
Full text linkRedox flow batteries (RFBs) are large-scale and long-duration electricity storage systems with decoupled energy and power units, granting them design flexibility. Despite their expanding applications, RFBs are still more expensive than competitive electricity storage systems due to the high cost of materials and relatively low power density. Hence, either the cost of materials must decrease through the development of cheaper materials with enhanced properties, or the power density must improve through efficient component design. This dissertation focuses on optimizing two main components of RFBs: ion-exchange membranes (IEMs) and flow field plates (FF plates). Anion-exchange membranes (AEMs) innately prevent cation cross-transfer. Therefore, AEMs are ideal to use as IEMs in RFB applications due to the cationic nature of the active species. However, AEMs lack chemical stability in the acidic environment of most RFBs. To increase the AEM durability, two durable polymers were blended with the lab-developed AEM, quaternized cardo poly (ether ketone) (QPEK-C): poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-co-HFP) and polybenzimidazole (PBI). The blend of QPEK-C and PVDF-co-HFP resulted in an immiscible polymer-blended AEM, requiring morphology control via tuning the blend composition and casting temperature. The PVDF-co-HFP blending improved the durability of QPEK-C-based AEMs (21% conductivity loss vs. 63% over a week in 0.9M cerium (III/IV) in 2M methanesulfonic acid). However, the PVDF-co-HFP blending sacrificed ionic conductivity (11 vs. 13 mS.cm-1). In contrast, blending PBI with QPEK-C resulted in a miscible polymer-blended AEM. The PBI blending improved the durability of QPEK-C-based AEMs (100% ionic conductivity retention) while enhancing the ionic conductivity due to the synergic relationship between PBI and QPEK-C (\u3e17 vs. 13 mS.cm-1). PBI/QPEK-C blended AEM outperformed commercial AEMs, showing that polymer blending is a useful strategy to improve the durability of membranes for RFBs and similar electrochemical systems. After improving the durability and performance of RFBs through AEM design, this dissertation focuses on investigating conductive polymer composites (CPCs) as a common set of materials for FF plates. A facile CPC fabrication method was introduced, and the effect of the shape and size of major and minor fillers were investigated in CPCs. As major fillers, Carbon nanofibers (CNFs) produced the most conductive and strongest CPCs. Elongated nanofillers of ~100 nm diameter were identified as the most effective minor fillers. As a result, thin CPCs (~0.9 mm) were developed with excellent chemical stability (Retaining conductivity over a week in 0.9M cerium (III/IV) in 2M methanesulfonic acid) and a lower area-specific resistance (ASR, 17.6-22.1 vs. 26.2 m.cm2) than common graphitic bipolar plates (BP, 3.175 mm). The lower ASR of CPCs promotes their use in FF plates of RFBs. Finally, this dissertation studies the effect of FF geometry and electrode properties on the performance of RFBs. Using dimensional analysis, nine dimensionless parameters were identified to comprehensively describe RFB systems. A semi-analytical model was developed, encompassing fluid dynamics, mass transport, kinetics, and thermodynamics. The model was validated with the literature data. The model provided a map of dimensionless mass transport and kinetics parameters and identified stagnant zones, especially at the end of the inlet and outlet channels of interdigitated FFs. Appropriate geometry modifications were proposed to inhibit the stagnant zones depending on the electrode thicknesses and channel sizes
Tools for Studying Respiratory Syncytial Virus Infection with Fluorescence Microscopy
Full text linkRespiratory Syncytial Virus (RSV) poses a significant burden in the United States, particularly among young children, older adults, and those with underlying health conditions. Despite recent progress in vaccine availability, there are still aspects of RSV infection that we do not understand, including mechanisms of viral entry and assembly. To address this challenge, we develop tools that are compatible with existing, widely available fluorescence-based imaging systems. Specifically, we develop a fluorescent RSV system harboring a fluorescent reporter and tags on the surface proteins using site-specific labeling. This engineered viral strain maintains strong replication kinetics, labels with high efficiency, and allows us to visualize infected cells and the virions they produce. This enables real-time tracking of viral interactions during the infection process, which we harness to identify a role for virus morphology in complement activation. We further expand this work by utilizing genetic code expansion to develop a recoded strain of RSV, in which the multifunctional nucleoprotein is site-specifically modified with a noncanonical amino acid. We leverage this tool to visualize RSV assembly, capturing the transfer of nucleoprotein complexes from cytoplasmic condensates directly to budding viral filaments at the cell surface and to cytoplasmic compartments containing viral surface proteins. In order to leverage these tools in the context of differentiated human airway cells HAECs, we develop devices to culture, differentiate, and perform live, high-resolution imaging on air-liquid interface cultures compatible with confocal fluorescence microscopy. These devices differentiate HAECs with equal capacity to existing platforms. We image RSV attachment in live ciliated cells with 300 nm of resolution at up to 100fps. Lastly, we investigate the role of cilia in RSV binding and infection in differentiated HAECs. Notably, we find that RSV preferentially binds to ciliated cells and that genetic mutations resulting in ciliary dysmotility influence RSV binding and cell-type selectivity. Collectively, these tools establish a new methodology that could be extended to study other respiratory disease