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Vaccine Companies Versus the Retail Investor
Get PDFThe price reactions of COVID-19 vaccine development candidate companies are examined in order to explain how prices behave in highly-publicized scenarios and how retail investors are impacted. Findings indicate that retail investors were susceptible to inappropriate timing of the market and sustained losses on average. Various methods of prior analysis and their limitations are introduced including observation of trading volume makeup, event-themed reactions, and financial statement extraction that may guide subsequent navigation of volatile trading landscapes. Portfolio methods of mitigating losses due to lack of information or misinformation are also explained
Copper Metabolism Directly Influences Kinase Functionality to Modulate Signal Transduction in Cancer
No full textCopper (Cu) is an essential micronutrient involved in a myriad of fundamental biological processes. The importance of Cu in growth and development can be seen in rare genetic disorders manifested by a disruption in Cu homeostasis. However, the known repertoire of cuproproteins do not fully explain the growth defects observed. A new class of cuproproteins has emerged that consists of protein kinases. While traditionally viewed as a static cofactor, Cu is now appreciated as a dynamic regulator of signaling processes. The first Cu-dependent kinases identified were MEK1/2, linking Cu directly to the control of cell proliferation, apoptosis, survival, differentiation, motility, and metabolism through the MAPK pathway. Here, we identify autophagy kinases ULK1/2 and Hippo signaling kinases LATS1/2 as additional Cu-dependent kinases. Specifically, further analysis revealed that Cu is required for ULK1/2 kinase activity and that the depletion of Cu can blunt autophagy. Moreover, in the context of autophagy-dependent lung adenocarcinomas driven by KRASG12D or BRAFV600E, we identified that Cu depletion or disruption of ULK1-Cu binding dampened autophagy and decreased tumor growth. ULK1/2 Cu regulation may present a new therapeutic opportunity to target autophagy in cancers. In efforts to identify other Cu-dependent kinases and specifically those that may render limitations to Cu chelation therapy, we found that core kinases within the Hippo pathway, tumor suppressors LATS1/2, also bind to and are influenced by the Cu availability. Unlike Cu regulation of MEK1/2 and ULK1/2 in an oncogenic capacity, the Cu-dependent LATS1/2 kinase activity suggests that Cu chelation may result in activation of oncogenic transcriptional coactivators YAP/TAZ in facilitating the expression of genes associated with growth and survival. Here, we identified that Cu chelation combined with YAP suppression or treatment with YAP inhibitor, verteporfin, further suppressed growth and enhanced apoptosis in BRAFV600E-driven melanoma cells. These findings identify a new combination strategy to enhance the durability of Cu chelation. Taken together, the identification of ULK1/2 and LATS1/2 as Cu-responsive signaling molecules further define the contribution of Cu to cell growth and this newfound understanding reveals new therapeutic opportunities for Cu chelation that can be leveraged for the treatment of cancers
MRI Assessment of Maternal Uteroplacental Circulation in Pregnancy
No full textHypertensive pregnancy disorders (HPD) such as preeclampsia are highly associated with maternal vascular malperfusion of the placenta, an organ that exchanges nutrients and oxygen between the maternal circulation and the growing fetus. Adverse pregnancy outcomes are difficult to predict because there is insufficient understanding of how poor maternal arterial remodeling leads to disease. There is also a lack of reliable tools to evaluate these changes in early gestation. The hypothesis of this dissertation was that magnetic resonance imaging (MRI) could noninvasively evaluate uteroplacental function in vivo through a combination of arterial spin labeling (ASL), 4D flow, and time-of-flight (TOF) techniques which were already effective in the evalution of other cardiovascular diseases. These flow and perfusion imaging studies were conducted on human pregnant volunteers in their second and third trimesters at 1.5T. Many of them were also examined by conventional Doppler ultrasound (US) and followed through delivery. Flow-sensitive Alternating Inversion Recovery (FAIR) ASL MRI with background suppression was found to be feasible in detecting placental perfusion signal despite the presence of motion artifacts. An important consideration when studying placental ASL was the slow movement of maternal arterial blood in a large cavity called the intervillous space. This was a unique feature of placental anatomy which distinguished it from other organs containing capillaries. It became apparent that traditional models to estimate perfusion from MRI were no longer applicable. In this work, a statistical approach was first developed to filter out motion artifacts, followed by a coordinate transformation to better represent the lobular distribution of blood flow in the intervillous space of the placenta. The uterine arteries (UtAs) are the main maternal blood supply of the placenta and have also long been suspected to be involved in HPD, though US-based measurements have not yet been found to be highly predictive for widespread clinical use. In this work, 4D flow MRI enabled visualization of the tortuous UtAs while measuring volumetric flow rate. Its performance in predicting incidence of preeclampsia and small-for-gestational age births was comparable to Doppler US. When considering the innovative potential of 4D flow MRI to capture complex flow dynamics, this validation demonstrated the value of continuing technical development for improving HPD risk assessment. Furthermore, centerline extraction of the maternal pelvic arteries in TOF MRI, from the descending aorta to the UtAs and external iliac arteries, provided quantitative metrics to characterize the geometry including path length and curvature. Pulse wave velocity (PWV) was estimated using path length by TOF MRI and velocimetry by 2D phase contrast and 4D flow MRI with results showing sensitivity to differences between UtAs and external iliac arteries. These approaches provided physiological metrics to explore and characterize the remodeling process of the uteroplacental arteries. This dissertation demonstrates the feasibility of measuring structure and hemodynamics of the maternal vascular blood supply using non-contrast MRI that can lead to the more reliable biomarkers of adverse pregnancy outcomes needed to diagnose and treat HPD
Accelerated Risk Assessment and Domain Adaptation for Autonomous Vehicles
No full textAutonomous vehicles (AVs) are already driving on public roads around the US; however, their rate of deployment far outpaces quality assurance and regulatory efforts. Consequently, even the most elementary tasks, such as automated lane keeping, have not been certified for safety, and operations are constrained to narrow domains. First, due to the limitations of worst-case analysis techniques, we hypothesize that new methods must be developed to quantify and bound the risk of AVs. Counterintuitively, the better the performance of the AV under consideration, the harder it is to accurately estimate its risk as failures become rare and difficult to sample. This thesis presents a new estimation procedure and framework that can efficiently evaluate and AV\u27s risk even in the rare event regime. We demonstrate the approach\u27s performance on a variety of AV software stacks. Second, given a framework for AV evaluation, we turn to a related question: how can AV software be efficiently adapted for new or expanded operating conditions? We hypothesize that stochastic search techniques can improve the naive trial-and-error approach commonly used today. One of the most challenging aspects of this task is that proficient driving requires making tradeoffs between performance and safety. Moreover, for novel scenarios or operational domains there may be little data that can be used to understand the behavior of other drivers. To study these challenges we create a low-cost scale platform, simulator, benchmarks, and baseline solutions. Using this testbed, we develop a new population-based self-play method for creating dynamic actors and detail both offline and online procedures for adapting AV components to these conditions. Taken as a whole, this work represents a rigorous approach to the evaluation and improvement of AV software
Mitochondrial DNA Regulation of the Nuclear Epigenome
No full textLife without energy flow is impossible. Thermodynamically, an organism is a system maintained in a non-equilibrium steady state by energy expenditure, permitting it to reduce its own entropy at the expense of the environment (Morowitz, 1968; Wallace, 2010). Mitochondria are the major source of energy in the eukaryotic cell. They convert the chemical energy of ingested hydrocarbons into the high-energy bond of adenosine triphosphate (ATP). This is accomplished by the combination of electron flow through the electron transport system (ETC), the generation of an electrochemical gradient across the mitochondrial inner membrane, and the use of the resulting potential energy to generate ATP. The mitochondrial inner membrane electrochemical gradient can also be used to generate electromagnetic energy (Maxwell, 2013) and heat energy to sustain the body temperature. In order to maintain order at the expense of energy, organisms require systems to store and access information. Deoxyribonucleic acid (DNA) polymers allow information storage in the form of genes (HERSHEY and CHASE, 1952; WATSON and CRICK, 1953) which are present in the mitochondria (Attardi, 1985; M. M. NASS and S. NASS, 1963; S. NASS and M. M. NASS, 1963) and the nucleus. In the nucleus, DNA is wound around proteins called histones which in turn can be altered in structure and function by post-translational modifications (methylation, acetylation, phosphorylation, etc). In this thesis, mitochondrial energy production and genetic information storage and retrieval are discussed. The effect of mitochondrial DNA on nuclear information system is revealed and a model of how mutations in mtDNA can cause human disease is proposed
Topics in Mirror Symmetry for Fano Varieties and Meromorphic Ddp Correspondence
No full textThis thesis consists of two parts, each of which can be read independently. The first part is about mirror symmetry of Fano varieties and related topics. We introduce the notion of a hybrid Landau-Ginzburg (LG) model, which is a mirror partner of a Fano variety with a chosen anti-canonical divisor. We formulate Kontsevich\u27s homological mirror symmetry conjecture of such mirror pairs and show that it implies the mirror P=W conjecture, a refined Hodge number relation between associated mirror log Calabi-Yau varieties. Next, we discuss the deformation theory of hybrid LG models and related Hodge numbers. The second part is based on a joint work with Jia-choon Lee. We study the relation between Hitchin system and Calabi-Yau integrable system in the meromorphic setting of type A, motivated by the work of Diaconescu-Donagi-Pantev. We consider a symplectization of the meromorphic Hitchin integrable system, which is a semi-polarized integrable system in the sense of Kontsevich and Soibelman. On the Hitchin side, we show that the moduli space of unordered diagonally framed Higgs bundles forms an integrable system in this sense and recovers the meromorphic Hitchin system as the fiberwise compact quotient. Then we construct a new family of quasi-projective Calabi-Yau threefolds and show that its relative intermediate Jacobian fibration, as a semi-polarized integrable system, is isomorphic to the moduli space of unordered diagonally framed Higgs bundles
Enrollment and Finance: An Exploration of the Community College Baccalaureate
No full textUnstable financial investment in higher education from public sources, coupled with current and projected enrollment declines, is putting financial strain on colleges and universities across American higher education. As an enrollment-dependent sector that relies most heavily on public support, this stress is particularly acute for community colleges. One potential mechanism through which community colleges may address these enrollment- and finance-related issues is by extending their academic offerings to include bachelor’s degrees – commonly known as the community college baccalaureate or CCB. Supporters of these initiatives believe CCBs may benefit students and local economies by providing academic, geographic, and financial access to economically relevant four-year credentials, while proving beneficial for institutions by potentially attracting new students and funding. Meanwhile, opponents of these programs remain concerned that community colleges will be unable to offer quality credentials and may never have the resources necessary to maintain a dual two-year and four-year mission, while potentially abandoning their historic missions of broad access. Despite the very public debate that has ensued surrounding CCB adoption, research is only beginning to document their potential effects; extant empirical literature regarding the institutional effects of CCBs is particularly slim. This study attempts to address this gap in knowledge by using longitudinal panel data and quasi-experimental methods to estimate the effect of community college baccalaureate adoption on institutional enrollment and finance at participating institutions. Results from this study shed light on the extent to which CCBs meet their goal of increasing access, measured by institutional enrollment, while also contributing to the discussion of resources stress at the institution level by documenting potential shifts in revenue generation and spending post-CCB adoption. Findings from this study may prove particularly useful for policy makers and institutional practitioners as they determine the potential institutional benefits of offering baccalaureate-level education while operating within an increasingly resource-constrained context
Distributed, Scalable and Resilient Information Acquisition for Multi-Robot Teams
No full textAdvances in robotic mobility and sensing technology have the potential to provide new capabilities in a wide variety of information acquisition problems including environmental monitoring, structure inspection, localization and mapping of unknown environments, and search and rescue, amongst many others. In particular, teams composed of multiple robots have shown great potential in solving these problems, though it is challenging to design efficient algorithms that are distributed and scale well, and even more complex in hazardous or challenging environments. The purpose of this dissertation is to provide novel algorithms to the capabilities of multi-robot teams to gather information which are distributed, scalable, and resilient. The first part of the dissertation introduces the single-robot information acquisition problem, and focuses on algorithms that may be used for individual robots to plan their own trajectories. The methods presented here are search-based, meaning that an individual robot has a finite set of actions and is seeking to efficiently build a search tree over a known planning horizon. The first method presented details how to use the concept of algebraic redundancy and closeness to achieve a smooth trade-off of completeness in the exploration process, as an anytime planning algorithm. Next we show how a single robot can compute an admissible and consistent heuristic which guides the search towards the most informative regions of the state space, using the classic A* planning algorithm, drastically improving the search efficiency. The next chapter of the dissertation focuses on how to build on the single robot planning algorithms to create efficient algorithms for multi-robot teams, which operate in a distributed manner and scalable manner. The first method presented is coordinate descent,5otherwise known in the literature as sequential greedy assignment. This algorithm is implemented in a multi-robot target tracking hardware experiment. Next, we formulate an energy-aware multi-robot information acquisition problem, which allows for heterogeneity and captures trade-offs between information and energy expenditure. However, this results in a non-monotone objective function. Therefore we propose a new algorithm based on distributed local search, which achieves performance guarantees through a diminishing returns property known as submodularity. The final chapter focuses on hazardous or failure prone environments that necessitate resilience to a fixed number of failures in the multi-robot team. We provide a definition of resilience, and formulate a resilient information acquisition problem. We then propose the first algorithm that solves this problem through an online application of robust trajectory planning, and provide theoretical guarantees on its performance. We then present three unique applications of the resilient multi-robot information acquisition framework, including target tracking, occupancy grid mapping, and persistent surveillance which demonstrate the efficacy of our approach
Essays on Local Governance in India
No full textThis dissertation studies local governments and the effects of their vertical and horizontal structures on public goods provision in India. The first chapter focuses on political representation and the vertical structure of decentralized governments. Political decentralization combined with minority representation has been purported to give power to the poor. Yet, it is unclear what form of minority representation can best achieve this. In this paper, I ask whether group (mis)alignment across local and intermediate level representations affect public goods distribution to the poor in the context of the Indian National Rural Employment Generation Scheme (NREGS), one of the world\u27s largest social welfare program. Exploiting changes in caste representation driven by India\u27s reservation system intended to increase minority caste representation, I show that minority representation at the local level alone does not increase the transfer of public goods to minority castes. Instead, I find more transfers when there is minority representation at both local and intermediate levels of government. Finally, I show policy-relevant heterogeneity effects coming from electoral motivations of intermediate level representatives and tastes for own caste under a decentralized government. The second chapter examines the horizontal aspect of local governance using India\u27s vastly different rural and urban local government structures. There have been increasing voices that rural local governments lack capacity to govern areas with burgeoning population. I test if this is true and whether local governance affects access to public services, such as treated tap water and closed drainage, in general. To do this, I compare public goods provision between rural and urban local governments after controlling for observables, level of urbanization, and fixed effects. Importantly, I create an objective measure of the extent of urbanization with daylight satellite data and population data. I find that despite the inclusion of these controls and fixed effects, there are positive and statistically significant effects of having an urban local government. I also provide results for placebo tests that show government structure does not directly impact access to private services. Finally, I explore financial decentralization of local governments as a channel
Material Point Methods for Simulating Material Fracture
No full textMaterial fracture surrounds us every day from tearing off a piece of fresh bread to dropping a glass on the floor. Modeling this complex physical process has a near limitless breadth of applications in everything from computer graphics and VFX to virtual surgery and geomechanical modeling. Despite the ubiquity of material failure, it stands as a notoriously difficult phenomenon to simulate and has inspired numerous efforts from computer graphics researchers and mechanical engineers alike, resulting in a diverse set of approaches to modeling the underlying physics as well as discretizing the branching crack topology. However, most existing approaches focus on meshed methods such as FEM or BEM that require computationally intensive crack tracking and re-meshing procedures. Conversely, the Material Point Method (MPM) is a hybrid meshless approach that is ideal for modeling fracture due to its automatic support for arbitrarily large topological deformations, natural collision handling, and numerous successfully simulated continuum materials. In this work, we present a toolkit of augmented Material Point Methods for robustly and efficiently simulating material fracture both through damage modeling and through plastic softening/hardening. Our approaches are robust to a multitude of materials including those of varying structures (isotropic, transversely isotropic, orthotropic), fracture types (ductile, brittle), plastic yield surfaces, and constitutive models. The methods herein are applicable not only to the needs of computer graphics (efficiency and visual fidelity), but also to the engineering community where physical accuracy is key. Most notably, each approach has a unique set of parametric knobs available to artists and engineers alike that make them directly deployable in applications ranging from animated movie production to large-scale glacial calving simulation