VictorJuiz/thesis huggingface dataset:
Deep understanding and generation of medical text and beyond

Human language text plays a pivotal role in medicine. We use text to represent and store our biomedical knowledge, to communicate clinical findings, and to document various forms of medical data as well as healthcare outcomes. While deep language understanding techniques based on neural representation learning have fundamentally advanced our ability to process human language, can we leverage this advancement to transform our ability to understand, generate and utilize medical text? If so, how can we achieve this goal? This dissertation aims to provide answers to these questions from three distinct perspectives. We first focus on a common form of medical text, biomedical scientific text, and study the long-standing challenge of extracting structured relational knowledge from this text. To handle the long textual context where biomedical relations are commonly found, we introduce a novel linguistically-motivated neural architecture that learns to represent a relation by exploiting the syntactic structure of a sentence. We show that this model not only demonstrates robust performance for biomedical relation extraction, but also achieves a new state of the art on relation extraction over general-domain text. In the second part of this work, we focus on a different form of medical text, clinical report text, and more specifically, the radiology report text commonly used to describe medical imaging studies. We study the challenging problem of compressing long, detailed radiology reports into more succinct summary text. We demonstrate how a neural sequence-to-sequence model that is tailored to the structure of radiology reports can learn to generate fluent summaries with substantial clinical validity. We further present a reinforcement learning-based method that optimizes this system for correctness, a crucial metric in medicine. Our system has the potential of saving doctors from repetitive labor and improving clinical communications. Finally, we connect text and image modalities in medicine, by addressing the challenge of transferring the knowledge that we learn from text understanding to understanding medical images. We present a novel method for improving medical image understanding by jointly modeling text and images in an unsupervised, contrastive manner. By leveraging the knowledge encoded in text, our method reduces the amount of labeled data needed for medical image understanding by an order of magnitude. Altogether, our studies demonstrate the great potential that deep language understanding and generation has in transforming medicine

Keywords: Biomedical Informatics.
Advisor: Manning Christopher D.
Altman Russ 
Potts Christopher
Defining the role of extracellular cGAMP signaling in health and disease

While cancer immunotherapy targeting the adaptive immune system has led to prolonged disease-free survival in otherwise terminal patients, there are few effective cancer therapies targeting the innate immune system. However, there is mounting evidence that the cGAMP-STING innate immune pathway is a promising anticancer target. While cGAMP is synthesized and functions inside the cytoplasm, recent evidence has shown that cGAMP is exported by cancer cells and imported by cGAMP-sensing responder cells in the host, thereby acting as a paracrine immunotransmitter. This thesis focuses on three key open questions in the field of extracellular cGAMP signaling: First, which cells within tumors directly respond to endogenous extracellular cGAMP? Second, how does cGAMP enter these cells? And third, can we specifically enhance extracellular cGAMP in vivo by inhibiting its degradation? We found that M1-polarized macrophages, monocytes, NK cells, and CD4+ T cells comprise the initial cGAMP-sensing populations within tumors. Additionally, we identified the first known cGAMP importer, SLC19A1, as well as the dominant cGAMP importer in primary human monocytes, SLC46A2. Finally, we discovered and characterized ENPP1-H362A, a point mutation that selectively inhibits cGAMP degradation while permitting normal ATP hydrolysis. While Enpp1-H362A mice do not exhibit the systemic calcification seen in Enpp1-null mice, they are significantly more resistant to HSV-1 infection and are more sensitive to radiation-induced inflammation, suggesting that extracellular cGAMP plays a critical role in broad disease contexts. Although we are still in the early stages of understanding this pathway, the extracellular cGAMP signaling pathway is a new frontier in immunotherapy that has the potential to revolutionize the treatment of a wide range of human diseases

Advisor: Li Lingyin
Dixon Scott James
Engleman Edgar G.
Long Jonathan Z.
Deglycosylation-mediated protein sequence edited NFE2L1 regulates ferroptosis

Regulated cell death is a fundamental biological phenomenon important for the maintenance of homeostasis and misregulated in disease. Cell death can be executed by several distinct and highly regulated pathways. One nonapoptotic mode of cell death is ferroptosis, an iron-dependent, oxidative form of cell death executed by lipid peroxidation. Here I describe a new method scalable time-lapse analysis of cell death kinetics (STACK) that allows for the continuous measurement of both live and dead cells over a given timeframe, and I develop mathematical models to parameterize cell death over time. Using the STACK approach, I uncovered new ways to understand and quantify cancer cell death and identify an off-target antioxidant effect of the FDA-approved drug bazedoxifene that can potently inhibit ferroptosis. Finally, I apply the STACK approach to uncover a role for the NGLY1/NFE2L1 pathway in the regulation of ferroptosis. Loss of NGLY1 or NFE2L1 promotes ferroptosis in cultured cells. NGLY1-mediated deglycosylation and subsequent protein sequence editing of NFE2L1 is necessary to protect cells against ferroptosis. Mechanistically, I find that sensitivity to ferroptosis upon NGLY1/NFE2L1 disruption is due to loss of the anti-ferroptotic protein GPX4. Genetic overexpression of GPX4 or the NFE2L1 related protein NFE2L2 can compensate for loss of NGLY1 or NFE2L1. Deglycosylation mutant mimic NFE2L18ND acts as a potent inhibitor of ferroptosis that can also compensate for loss of NFE2L2. In my work, I propose that ferroptosis inhibition may serve as a novel therapeutic intervention for the treatment of Ngly1 deficiency, a pathology associated with NGLY1/NFE2L1 dysfunction

Keywords: Biology.
Advisor: Bertozzi Carolyn R.
Dixon Scott James
Bogyo Matthew
Cyert Martha S.
Kopito Ron Rieger
Degree one contributions and open Gromov-Witten invariants

We show that it is possible to define the contribution of degree one covers of a disk to open Gromov-Witten invariants. We build explicit sections of obstruction bundles in order to extend the algebro-geometric techniques of Pandharipande to the case of domains with boundary

Keywords: Mathematics.
Advisor: Ionel Eleny
Eliashberg Y.
Venkatesh Saraswathi
Demanding deals : the politics of preferential trade agreements

Over the past 25 years, preferential trade agreements (PTAs) have been the primary forum for new international trade cooperation. Through these treaties, states have lowered their barriers to trade and investment flows as well as regulated a wide range of other policy areas. States expend considerable effort designing, negotiation, ratifying, and implementing these deals, with far-reaching economic and political consequences. This dissertation consists of three papers that add to our understanding of the politics of PTAs. The first paper argues that delayed implementation of the tariff concessions contained in PTAs has been crucial to their success. By allowing governments to pass part of the adjustment costs of liberalization onto future administrations, delays have made it possible for states to sign onto agreements removing substantially all remaining barriers. The second paper provides novel evidence on the role of exporters in shaping the content of PTAs, showing that the presence of motivated and concentrated exporters within a partner country is associated with increased market access commitments. Lastly the third paper applies the logic of reciprocal trade cooperation to the issue of investment. It asks why the lowering of investment barriers has taken place through PTAs, arguing that the preferential and broad nature of these agreements made them a particularly productive negotiating forum. Collectively, these papers add complexity to our conceptions of government preferences in their approach to the negotiation of trade agreements. Each paper also speaks to the role of both domestic and international political institutions in shaping the choices and strategies of governments. Lastly this dissertation offers insights into the conditions and decisions that enable successful cooperation, crucial at a time when international trade diplomacy is at a crossroads

Keywords: Political Science.
Advisor: Goldstein Judith 
Bagwell Kyle
Scheve Kenneth F.
Tomz Michael
Design and development of supported transition metal phosphide catalysts for syngas conversion to alcohols

In attempts to address the threats of climate change, countries are making efforts to mitigate their emissions of greenhouse gases like carbon dioxide (CO2). The transition from economies driven by energy and chemicals derived from fossil fuel feedstocks to cleaner alternative fuels and technologies are met with great challenges. In the field of fuel and chemical production specifically, the transformation of carbon monoxide (CO) and CO2, produced through alternative technologies, to value added chemical products require catalysts that are active, selective, and stable. Current research efforts have focused on heavy characterization of catalysts in attempts of establishing a structure-activity correlation to help design and engineer the catalyst of the future. This thesis will focus on the design and characterization of two supported transition metal phosphide (TMP) catalysts, molybdenum phosphide (MoP) and ruthenium phosphide (RuP), and a bimetallic nickel iron (NiFe) catalyst. The first TMP, MoP, was specifically designed and optimized for the higher alcohol synthesis (HAS) reaction from synthesis gas (syngas) (CO/H2). Higher alcohols are defined as an alcohol group containing two or more carbon atoms., like ethanol. Through a systematic design approach, the optimal amount of potassium (K) promoter, P and Mo was determined and synthesized on three different supports: amorphous silica (SiO2), ordered silica (SBA-15), and mesoporous carbon (C). The different combinations led to contrasting catalytic performance with respect the HAS activity. The second TMP, RuP, was designed and optimized for the methanol synthesis (MS) reaction. Ru catalysts are known as Fischer-Tropsch synthesis (FTS) catalysts as they selectively produce hydrocarbons. This study was able to change the intrinsic catalytic nature of Ru through addition of P. Catalytic results showed that the presence of P transformed the Ru FTS catalyst to a MS catalyst. The NiFe catalyst was tested for the ethane dehydrogenation reaction, in which the essential feedstock chemical ethylene is produced. This catalyst was tested for direct ethane dehydrogenation, in which only ethane is fed to the reactor along with H2 to mitigate coking, and oxidative ethane dehydrogenation, where CO2 is fed to promote the reacting and mitigate coking. The catalysts were also synthesized on two different supports, SiO2 and C, to quantify support effects. The overall goal of these studies was to determine the influence that addition of promoters, like K, phosphides, and secondary metals have on catalytic properties and how we might use that to design catalysts with improved activity, selectivity, and stability

Keywords: Chemical Engineering.
Advisor: Jaramillo Thomas Francisco
Abild-Pedersen Frank
Cargnello Matteo
Design and testing of an ankle-foot prosthesis and a hip exoskeleton to improve balance-related outcomes and prevent falls

Falling is a serious issue that affects millions of people, including people with lower limb amputation and older adults. Falls can lead to serious injury or death, and even the fear of falling results in restrictions on mobility and reductions in quality of life. Assistive devices could address this need by augmenting the three primary strategies humans use to maintain balance: applying ankle torque to modulate center of pressure and pushoff work, using hip torque to change center of mass position and velocity, and placing the foot to alter base of support. In my doctoral research, I have designed and tested devices intended to assist people with these three balance strategies. First, I designed a prosthetic foot with actuation in the frontal and sagittal planes, which is capable of modulating the center of pressure between the foot and the ground. I then used this foot to test the biomechanical effects of a prosthesis controller designed to mitigate the effects of uneven terrain. Finally, I designed a bilateral hip exoskeleton with actuation in the frontal and sagittal planes, which can be used to modulate hip torques and assist with foot placement. These projects have led to a better understanding of the relative efficacy of different balance enhancement techniques and have yielded new experimental tools for future studies of fall prevention

Keywords: Mechanical Engineering.
Advisor: Collins Steve (Steven Hartley)
Cutkosky Mark R. 
Okamura Allison
Design, fabrication and integration of large-scale stretchable strain sensor networks

An investigation was performed to develop a process to design, fabricate, and integrate a large-scale stretchable sensor network to measure strain distribution over a surface area. Capable of measuring actual strains of a structure is critical not only at the structural design phase to validate the design, but also useful to assure quality of the fabrication in the manufacturing phase. Furthermore, if the true measurements could be provided during service, the data could assist evaluating the integrity and safety of operation of the structures. However, the application of distributed strain gauges in an in-situ health monitoring system for critical structural components is oftentimes limited by complicated cabling and performance penalty. In this thesis, a novel method is proposed to revolutionize the traditional way of multipoint load monitoring by designing and deploying a vast quantity of microfabricated metal-foil strain gauges in the form of a stretchable sensor network to collect the measurements at each desired location under deformations and environmental conditions. Specifically, this thesis seeks to examine and tackle two essential challenging problems in embedding large-scale strain sensor networks into structures: (1) the wire effect -- because not only strain sensors but also the entire wires are attached to structures, a model was developed to establish the optimized wiring and eliminate the wire-induced error; (2) the thermal effect -- because strain measurement is strongly temperature dependent, a collocated sensor node design must be devised for accurate thermal compensation. In order to prove and validate the model and design, by taking advantage of advanced micro-electro-mechanical system fabrication and vacuum bag molding techniques, a streamlined process was developed to produce stretchable sensor networks from standard 4-inch silicon wafers and integrate them to structures of various configurations. The concept of distributed strain sensing was demonstrated through a composite panel featuring hotspot detection, load monitoring, and shape estimation functions. To conclude, potential applications of the developed approach for aerospace structures (e.g., space satellite) are proposed

Keywords: Mechanical Engineering.
Advisor: Chang Fu-Kuo
Cutkosky Mark R.
Howe Roger Thomas
Senesky Debbie
Design, modeling, and control of vine robots for exploration of unknown environments

Robots have great potential to be our eyes and hands in spaces too small or dangerous for humans to enter. Minimally invasive surgery, urban search and rescue, and water pipeline inspection are examples of applications where such robots could improve human health, safety, or productivity. However, most of today's robots are unsuitable for practical use in these applications, in large part because their physical bodies lack the necessary properties to navigate and manipulate the environment in these spaces. This dissertation focuses on a relatively unexplored robotic paradigm--robotic movement via plant-like tip-growth--and its application for exploration of unknown environments. In particular, we study soft growing "vine robots, " which lengthen from the tip by turning their body material inside out using internal fluid pressure, and are well suited for exploration of small spaces. First, we present research on design and human-in-the-loop control of vine robots, which allowed us to successfully use them in the field to explore small tunnels in an archeological site in Chavin, Peru. Then, we present work on design, modeling, and control to expand the capabilities of these robots in three areas: enabling controlled reversal of growth, transmitting pulling forces to the environment from the robot tip, and sensing both the environment around the robot and the robot's own shape

Keywords: Mechanical Engineering.
Advisor: Okamura Allison
Cutkosky Mark R.
Khatib Oussama
Design of active sensing smart skin for incipient slip detection in robotic applications

Tactile sensing is paramount for robots operating in human-centered environments to help in understanding interaction with objects. To enable robots to have sophisticated tactile sensing capability, researchers have developed different kinds of tactile sensors for robotic hands to realize the 'sense of touch'. In this study, we are focused on the incipient slip detection problem for robots which is known as one of the most challenging issues in robotic tactile sensing. Currently, most of the slip detection sensors are passive sensors which provide limited information about the sensing parameters. Therefore, this will usually require large amount of data and extra computation effort in accurately classifying slip conditions of robotic hands. Other sensing mechanisms such as optical approaches which can provide enriched sensing parameters for slip detection often suffer from complex sensor configurations and being inflexible in terms of customization. Active sensing, on the other hand, has the advantage of simple sensor configurations, and in the meantime can provide more sensing parameters which will improve the overall efficiency of the tactile sensing capabilities for incipient slip detection. In this thesis, by using the active sensing method, a novel active sensing smart skin technique is developed for incipient slip detection which leverages piezoelectric transducers as actuators/sensors. With this method, a robotic fingertip with the embedded actuator and sensor were created in which the actuator generates ultrasonic guided waves received by the sensor during a slip scenario. By analyzing the received signal using an attenuation-based method, we can monitor the entire contact area evolution during a slip scenario. Therefore, this method can serve as an excellent indicator for early slip detection with the advantage of accurately monitoring the contact condition. In addition, the frustrated total internal reflection method was used to validate the signal attenuation increases with the growing of the contact area. Built on these results, a unique robotic skin was then designed and fabricated which demonstrated robust and sensitive response for incipient slip detection. Finally, an LED slip alert system on a real gripper was developed to demonstrate the capability of our method to be applicable to real robotic finger situations

Keywords: Mechanical Engineering.
Advisor: Chang Fu-Kuo
Cutkosky Mark R. 
Senesky Debbie
Design principles for manipulation with astrictive contact

Anthropomorphic hands have existed in research circles for over thirty years, yet simple, parallel grippers continue to be the norm in manufacturing and real-world applications because they deliver strong grips in a light and compact package. Many-jointed hands have significant kinematic advantages over their less mobile counterparts but must also deliver robust strength without sacrificing that dexterity if they are to be adopted in more practical settings. Astrictive contact conditions, achieved through suction, gecko-inspired adhesives, and micro-spines, can improve grasp quality without decreasing mobility or increasing actuation effort but demand a novel set of design considerations. Rather than normal forces and point contacts, the principles of high contact area, shear load sharing, and even normal stress distribution determine the limits of manipulation capacity. These three conditions are explored theoretically and implemented practically on four robotic manipulators. Together, these prototypes form a framework for manipulation with astrictive contact through a combination of passive mechanical structures, practical controls, and novel actuation schemes

Keywords: Mechanical Engineering.
Advisor: Cutkosky Mark R.
Kennedy Monroe
Khatib Oussama