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converged phenotypes of immune cells in aging
No full textThe aging of population is one of the most important social issues in the next several decades. It’s urgent to find methods to alleviate sufferings of age-related diseases and improve the life quality of the olds. Most aging research focuses on the hallmarks and biomarkers at the molecular level, organic level, and individual level, but the understanding of aging at the cellular level, especially the biophysical properties of cells is limited. Here, we studied the biophysical properties, including motility, morphology, and morpho-dynamics, of human B cells in a 2D environment in vitro, and analyzed the relationship between biophysical features and age. We found that motility and morphology features were modestly correlated with age. Morpho-dynamics features showed higher correlations with age, both collectively and individually. The combination of all motility, morphology, and morpho-dynamics features did not outperform morpho-dynamics features alone. Finally, we examined the relations between age and pairs of biophysics features using a generalized linear model, which showed that combination of skewness of the bounding box area and the kurtosis of the area resulted in the lowest prediction error (error = 11 years)
U.S. Foreign Policy Decision-Making: The Obama And Trump Administrations' Decisions Regarding Lethal Aid to Ukraine, 2014-2017
No full textThe Obama and Trump Administrations held completely different foreign policy decision making processes, and both President Barack Obama and President Donald J. Trump themselves were on opposite poles with their own leadership styles. Yet, their approaches to countering the 2014 Russian aggression against Ukraine did not vary greatly regarding U.S. policy and foreign assistance to Ukraine. Both imposed sanctions against Russia and both provided foreign assistance to Ukraine, increased U.S. troop presence in Europe, and worked with the North Atlantic Treaty Organization (NATO) to ensure security and stability in Europe. Although these two Presidents and their Administrations were at opposite extremes of each other on matters of domestic and foreign policy, the only major difference to their U.S. policy towards Ukraine was whether the U.S. should arm Ukraine with lethal aid, in particular the Javelins-anti-tank missiles. Obama left the White House without authorizing lethal aid to Ukraine and Trump approved defensive lethal aid during his first year in office. Based on existing literature and on more than 25 interviews with senior officials from both Administrations, this thesis forms a new insider perspective of the decision-making timeline of events that influenced each of these President’s indecision or decision to provide U.S. defensive lethal aid to Ukraine. This thesis examines the models of both the rational unitary actor and the organizational model of foreign policy decision-making. The framework of this thesis follows the foreign policy determinants that influenced both Obama and Trump and provides a study of how the U.S. Presidents arrived at their foreign policy decision. Ultimately, this thesis adds to the current literature on foreign policy decision-making by assessing Obama and Trump as rational actors and by looking into their administration, the bureaucracy, and the politics that influenced their decision-making on whether the U.S. should provide lethal defensive aid to Ukraine to counter Russia’s continuous overt aggression between 2014-2017
Endplate Senescent Osteoclasts Induce Sensory Innervation and Spine Pain
No full textSpine pain is the most common musculoskeletal problem globally, affecting individuals of all ages. Spine pain management remains challenging for researchers and clinicians, and new therapeutic approaches are needed to overcome the increasing number of individuals with spine pain. Here we report that in mice, increased senescent osteoclasts (SnCs) are observed in spinal hypersensitivity mice models like lumbar spine instability (LSI) or aging. Induced sensory nerve innervation and the H-type vessel growing in the porous endplate are also confirmed. We show that administering a senolytic drug, Navitoclax (ABT263), eliminates the senescent osteoclast cells; as a result, it significantly reduces spinal hypersensitivity, spinal degeneration, the porosity of endplate, sensory nerve innervation, and H-type vessel growth in the endplate. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of well-established sensory nerve mediators further indicates increased Netrin-1, NGF, and decreased Sema3A secretion mediated by SnCs. These findings suggest that eliminating SnCs by ABT263 could have massive therapeutic applications for spine pain by abrogating endplate porosity and sensory innervation
Deployment, Managed Charging, and Equity: How can U.S. distribution utilities support and enable equitable electrification of transportation?
Get PDFThis study examines the critically important ways in which electric distribution utilities can support and enable the U.S. transition to full electrification of the transportation sector in an equitable manner. It evaluates the state of the market, reviews characteristics of charging behavior for different use cases and applications, and identifies what roles electric distribution utilities can, and should, play. The study finds that utilities have key roles in two broad respects: deployment and energy management. Without utility involvement in deployment of charging infrastructure, the electrification of transportation likely be inadequate to meet policy targets, and without utility involvement in managing the load, the electrification of transportation will require costly grid upgrades that will undermine the value proposition of electrification. Additionally, a cross-cutting theme applicable to both of these roles has to do with equity – ensuring that all demographics have access to – and can benefit from – transportation electrification
MODELING FLOWS AS CONTINUOUS DETERMINISTIC SYSTEMS AND AS AGENT-BASED STOCHASTIC SYSTEMS.
No full textThe heart of research in engineering and science entails developing predictive dynamical equations from observations. For instance, traditional modeling approaches involve developing constitutive equations from experiments in solid mechanics or developing subgrid-scale models for coarse-grained equations in fluid dynamics, as these systems require detailed simulations that can be computationally expensive. Modern data-driven and ML techniques can also be used to discover these equations and deduce reduced order models for nominally infinite dimensional dynamical systems (PDEs) or stochastic (SDEs), which capture the physics well. We can even bypass these equations and instead, predict the desired dynamics in a fully data-driven manner.
In this thesis, I will focus first on a multiphase fluid system with PDE dynamics, namely thin films flowing down an inclined plane and exhibiting spatiotemporal wave patterns. And second, on SDEs arising in agent-based models of a population of interacting agents in a stock market, with behaviors similar to disease transmission in the field of epidemiology. In the first topic, I will show how to develop reduced order models and learn PDEs to predict the amplitude of the wave directly from data, as well as a new approach to recover the full velocity field from partial observations of the amplitude of the wave. For the second problem, I will show how we can use these techniques to learn the effective Langevin-type SDE that governs the behavior of the distribution of agents close to a tipping point where the distributions become unstable. The developed models are more accurate and have a wider range of applicability than traditional analytically derived models
“IS MY TAP WATER SAFE TO DRINK?”: ANALYZING PUBLIC DRINKING WATER REPORTS AND PROVIDING EVIDENCE-BASED RECOMMENDATIONS FOR THEIR IMPROVEMENT
No full textApproximately ninety (90) percent of Americans are served by public water systems. A subset of public water systems, known as community water systems (CWSs), are required to provide their customers with an annual water quality report, known as a Consumer Confidence Report (CCR). These reports are meant to be the “centerpiece of public right-to-know” under the Safe Drinking Water Act. However, previous research indicates that CCRs are overly technical, difficult to read, and of questionable use to the public. Public trust in tap water has declined in the years since the Flint, Michigan water crisis; such distrust is exacerbated among minority populations, and can have a myriad of deleterious environmental and financial impacts as people turn to bottled beverages instead of drinking tap water. The Environmental Protection Agency (EPA) has oversight of CWSs, and is re-writing the legislation governing CCRs. This thesis argues that improving CCRs could improve transparency and trust among customers of CWSs, and examines a current sample of sixty (60) for their communication quality and adherence to SDWA criteria. These outcomes are then compared against information about each water system, including the number of individuals served by, and the demographic constituency of, the utility. Lastly, this thesis examines a selection of international water quality reports from other English-speaking countries to determine how public water information is conveyed to customers in countries outside the United States. The final chapter concludes with evidence-based recommendations for EPA’s consideration as they re-write the CCR Rule
ROLE OF BONE-DERIVED PDGF-BB IN AGE-ASSOCIATED BRAIN CALCIFICATION
No full textThe calcification of small blood vessels in the brain is a common pathology that often accompanies neurodegenerative and neuroinflammatory diseases in elderly individuals. Although the pathogenesis of calcification in larger blood vessels in peripheral tissues has been extensively studied, little is known about the mechanisms underlying the calcification of small brain blood vessels. Our previous findings demonstrate that elevated levels of platelet-derived growth factor- BB (PDGF-BB) produced by preosteoclasts in bone contribute to the calcification of brain microvessels. Aged mice have a higher incidence of developing brain calcified nodules in the thalamus region compared to young mice and is also associated with increased levels of serum PDGF-BB. We found that preosteoclast-specific transgenic mice with high serum PDGF-BB levels developed thalamic calcification similar to that seen in aged mice, while preosteoclast- specific knockout mice had diminished thalamic calcification. Additionally, PDGF-BB was found to promote calcification in small brain blood vessels in an ex vivo culture system. In this study, we report that the osteogenic gene array and single-cell RNA sequencing analyses showed an upregulation of many osteogenic differentiation genes and phosphate transporters Slc20a1 in cerebral microvessels when treated with recombinant PDGF-BB. Furthermore, PDGF-BB was found to activate the ERK signaling pathway and its downstream target RUNX2, which binds to the promoter region of Slc20a1 to promote gene transcription. In summary, our findings suggest that PDGF-BB produced by preosteoclasts in bone induces the calcification of brain microvessels by promoting osteoblastic differentiation and activating ERK-RUNX2-Slc20a1 signaling in cerebrovascular cells
CORRELATIONS BETWEEN URBAN TREE AND BEE POPULATIONS: PRELIMINARY, NEIGHBORHOOD-SCALE STUDY
No full textGreen resource disparity between high and low socioeconomic neighborhoods in urban areas impact community environmental and ecological health, popularly measured by tree equity. Denver, CO is no exception. Urban parks play a critical role in ecosystem health and environmental functioning, and provide critical greenspaces needed to address green resource disparities. Connectivity within and between these parks depends on surrounding resources and, therefore, how the socioeconomic status of a park’s surrounding neighborhood relates to overall ecosystem health within the neighborhood’s park(s) is an important relationship to observe. This study attempts to understand how varying tree populations within neighborhoods of starkly different socioeconomic statuses relate to ecosystem health. Bee biodiversity and abundance is a bioindicator of ecosystem health. This study obtained bee population data from parks within Denver’s lowest and highest income neighborhoods. Both parks showed similar biodiversity of the neighborhood tree populations and the biodiversity of the bee populations.
Furthermore, there seems to be a correlation between tree abundance and bee abundance. While more data and research are needed moving forward, this alludes to multiple intersecting relationships. Greenspaces in neighborhoods with low socioeconomic status and lower tree canopies have the capacity to host comparably biodiverse bee populations to high socioeconomic status neighborhoods when tree biodiversity between the two neighborhoods is similar, despite several present environmental injustices. These findings also indicate ways to improve ecosystem health across neighborhoods via growing tree canopies and diversifying tree populations. These results align with other research findings that show diversified and equitably distributed urban forests, supporting overall ecosystem health and functioning
SCALING OF HIGH-PLEX, SPATIAL TRANSCRIPTOMICS IN ENDOMETRIAL CARCINOMAS USING NOVEL AUTOMATED DETECTION
No full textEndometrial cancer (EC) is on the rise, especially the more aggressive Type 2 EC (EC2) with poor prognosis despite early detection and intervention. To better understand the immune suppressive behavior observed in EC2, detecting the spatial distribution of immune cells within endometrial carcinomas is crucial. We used formalin-fixed, paraffin-embedded tumor sections and ligation in situ hybridization and lock’n’roll nucleic amplification (LISH-LNR) to target a high-plex panel of immune RNA transcripts. The combination of LISH-LNR with Veranome Spatial Pipeline (VSPL) is a novel application, enabling automated "sample-to-insight" process to be scaled to high-plex RNA panels. 3 key questions were posed: Can LISH effectively access high-plex target RNA panels within FFPE EC2? Can LISH-LNR tissue be reliably imaged and decoded using VSPL on FFPE EC2? Does VSPL output reflect observed EC2 molecular behaviors? LISH (without spatial imaging) yielded a correlation R = 0.82 with pre-cancerous tissue and R = 0.95 for advanced stage EC2 to TCGA-derived RNA-seq references. From FFPE EC2 sections, VSPL obtain multiplex scans, spatially decoded all scans. Validation with EC2 FFPE sections yielded a correlation R = 0.94 with pre-cancerous tissue and R = 0.74 for advanced stage EC2 to TCGA-derived RNA-seq references. Technical challenges in multi-round imaging consistency throughout the 20-hour imaging process still persist. Spatial detection of cancer-derived immunoglobulin, heavy chain, gamma, as well as cytotoxic and regulatory T-cell biomarkers, were used to validate biological behavior in EC2 sections
PORTRAIT IN PINK: HOW ADVANCED REACTORS WILL SHAPE IMPLEMENTATION OF THE 45V CLEAN HYDROGEN TAX CREDIT
No full textAdvanced nuclear reactors and clean hydrogen have an opportunity to scale together and diversify the hydrogen production market away from fossil fuel-based production. The market for clean hydrogen is expected to grow significantly by 2030 and beyond, relying on the deployment of low greenhouse gas (GHG) emission energy sources. However, plugging an electrolyzer into the grid assumes the electricity generation's average and marginal emissions profile, which is often more than producing hydrogen using fossil fuels. Developing clean hydrogen production avenues is critical to making hydrogen available at the projected demand rate. Due to their high capacity factors, nuclear reactors can ensure clean hydrogen production continues when renewable sources are unavailable. The first advanced reactor to be approved is scheduled to go into commercial service in 2029, with other reactor designs following suit. If construction begins before the end of 2032, an advanced reactor could take advantage of the newly passed Section 45V clean hydrogen production tax credit included in the Inflation Reduction Act of 2022 (P.L. 117-169). Conventional nuclear facilities are also participating in hydrogen production through cost-share partnerships and demonstration projects.
Clean hydrogen will be critical to a low GHG emissions energy system. According to Department of Energy research, pink and green hydrogen have the lowest emissions profile and will see the steepest decline in production costs. Pink hydrogen, as nuclear-powered electrolysis is known, has the potential to maintain production reliability and resiliency through readily available electricity when compared to green hydrogen, as renewable-powered electrolysis is known, which would require significant energy storage technology developments to overcome intermittency. Pink hydrogen will provide reliability and resiliency for clean hydrogen production and will form a critical piece of the hydrogen economy. Moreover, whether or not advanced reactors are constructed in time to take advantage of the 45V PTC, prices for electrolyzers and other pink hydrogen production costs are expected to decline due to the tax credit, benefitting the entire hydrogen economy and meeting goals for reduced GHG emissions set out by policymakers. Advanced nuclear reactor development is well paired to expand with hydrogen production as demand for both rises