VictorJuiz/thesis huggingface dataset:
Design and characterization of novel optical sensors for monitoring membrane tension in vivo
Keywords:  Department of Biology
Biology
molecular biology
membrane tension
mechanosensitive channel
osmotic shock
fluorescence
FRET
biosensor
Saccharomyces cerevisiae
Arabidopsis thaliana
Thesis

Cells must monitor and respond to chemical and physical changes in their environments. For example, swelling or shrinking in response to osmotic changes presents both chemical and physical stimuli. Mechanisms of sensing and responding to these stimuli fall into two broad categories: signal transducers and safety valves. Bacteria utilize the safety valve mechanism, as exemplified by the protein MscS (mechanosensitive channel of small conductance). A family of MscS-like (MSL) proteins has been identified in plants, including Arabidopsis thaliana. Several MSLs have been previously characterized, for example, MSL9 and MSL10 have been shown to respond to membrane stretching. By constructing fluorescent biosensors based on these MSLs, we aimed to design a sensor which reports on changes in membrane tension. Several such chimeric proteins have been constructed based on MSL9 and MSL10, and their response to hyperosmotic osmotic stress has been characterized in Saccharomyces cerevisiae. Surprisingly, we discovered that sensor expression in yeast leads to aggregation, and closer inspection of the aggregates reveals that the majority of the signal is derived from these aggregates. These sensor aggregates could be used to detect osmotic changes in yeast and other systems, however, these aggregates do not report on membrane tension at the cell surface. Future work with these sensors includes reducing aggregation in yeast systems as well as improving surface targeting. Applications include using these novel sensors for in vivo visualizations of membrane stress in physiological conditions, such as plant roots encountering a barrier, or the effect of membrane stress on growth and development.
Design and Characterization of Stretchable Antenna Systems
Keywords: Fan, Jonathan
stretchable electronics
antennas
medical implants
Thesis

Stretchable electronics are an exciting technology that enable new forms of biomedical monitoring and stimulation. However, there are limitations in existing design and fabrication techniques that interfere with their development. In this thesis, we address some of these limitations. Specifically, we automate the conversion from rigid to stretchable electronic designs; we discuss strategies for the simulation of stretchable electronics; we optimize the fabrication and transfer processes for stretchable electronics; and we characterize the impact of the conversion on the electrical characteristics of an antenna. Finally, we demonstrate the benefits of these refined techniques by developing a complicated device designed to wirelessly power a medical implant. These improvements enable the rapid design and prototyping of stretchable electronic devices, which will facilitate their further development and integration into new exciting applications in biomedical devices and elsewhere.
Design, demonstration, and space qualification of an ultraviolet LED based charge management system [electronic resource]
Keywords: Aeronautics and Astronautics.

When a spacecraft is in orbit, it is subject to numerous disturbance forces due to atmospheric drag, solar pressure, and other sources. Over the past several years, a number of missions ranging from tests of General Relativity to Earth observation have been proposed which require correcting for these disturbance forces so that the satellite can follow an orbit entirely dictated by the gravitational force, called the geodesic. One architecture that allows for this behavior is called "drag-free, " where the spacecraft contains a shielded free floating test mass. This test mass follows the geodesic and the spacecraft in turn follows the test mass. Thus, the spacecraft also follows the geodesic. While the test mass housing shields it from most disturbances, high energy particles in the space environment can penetrate the housing leading to charging of the test mass or the surrounding housing, leading to a voltage difference and a resulting electrostatic disturbance force. Controlling this charge is critical to meet the performance requirements for drag free sensors. Charge management using photoelectrons generated by the 254 nm UV line of Hg was first demonstrated on Gravity Probe B and is presently part of the LISA Pathfinder technology demonstration. My dissertation presents a new method of charge control using UV-LEDs operating at high frequency outside the science band of the proposed missions. I first present the results of ground tests and space qualification studies of the UV-LED devices showing less than 5% change in key performance parameters of the devices. Next, I present the design and results of a lab based demonstration of the AC charge management system which can successfully raise and lower the test mass potential. Next, I present the design of a satellite mission designed to test the UV-LEDs and AC charge management system in-situ, followed by the results of the mission. I show that key properties of the UV-LED devices change by less than 8% in flight and the AC charge management system is capable of bringing the test mass to within 200 mV of the spacecraft housing. Finally, I present results of materials coating studies, showing that various carbides including SiC and Mo2C are suitable for use as test mass coatings.
Design of a rugged, ultra-stable, space-flight-ready optical cavity system [electronic resource]
Keywords: Mechanical Engineering.

This dissertation is inspired by the requirements of the mini Space Time Asymmetry Research (mSTAR) experiment, which proposes to detect variations in the speed of light as small as two parts in 10^17. The mSTAR experimental apparatus is based on an optical cavity orbiting the earth in a satellite. This optical cavity must have an ultra-stable length and be precisely aligned with an external optical system. Potential disturbances of the cavity length include contact forces, inertial forces, and thermal expansion. Additionally, the precise alignment of the optical cavity and the external optical system must survive launch and ascent to orbit. I discuss a series of strategies for the design of a rugged, ultra-stable, space-flight- ready optical cavity system. This series begins with the creation of a general purpose genetic algorithm topology optimization program. In an attempt to minimize cavity length changes due to contact forces, I apply this program to the design of a strain- attenuating optical cavity spacer. The results of this optimization highlight some of the complications inherent in optical cavity optimization, and they prompt a study of the limitations of finite element precision. In response to these limitations I then develop a general purpose parallelized design space search program and apply it to the design of an inertially insensitive optical cavity spacer. I then seek to minimize thermal expansion and identify twenty-six athermal pairs of materials. Next, I optimize the optical cavity mode-matching optics for simplicity and compactness. Finally, the results of these design strategies are synthesized in two detailed designs for an optical cavity system that, compared with the state-of-the-art, are potentially more rugged, less expensive, less thermally sensitive, contain lower levels of residual stress, and have a more robust mode-matching optics alignment system.
Design of low power image sensor for computational photography [electronic resource]
Keywords: Electrical Engineering.

This research investigates the design of the peripheral circuits of a CMOS image sensor in order to determine the minimum energy required to read an image. A novel interleaved readout architecture with partial settling is proposed and implemented. Unlike prior designs, this image sensor removes the need for a high-bandwidth gain stage that consumes a large amount of static power. We use a successive approximation register analog-to-digital converter (SAR ADC), pulse the current used to settle the imager bitlines, and minimize this current by only partially settling the SAR input capacitance to the bitline voltage. The residual systematic error is removed in the digital domain. Gain adjustment can be accomplished by varying the floating diffusion capacitance CFD inside pixels. In addition, instead of reading out all the columns simultaneously through the conventional ADC-per-column architecture, which has a very poor routing efficiency with pixel scaling, we share multiple columns to a single ADC and read them sequentially within a row time. Thus, the proposed image sensor accomplishes both high power efficiency and fast readout speed. A 320Hx240V prototype sensor with two column-shared 10-bit synchronous SAR-ADCs is implemented with 180nm technology, which consumes 1.46mW operating at 130fps. The figure of merit (FOM) computed in terms of energy consumed at each pixel per frame is 146pJ/pixel/frame. This number is about 5 times smaller than prior designs. The performance of the prototype is limited by the ADC quantization noise and finite partial settling attenuation. In addition, the synchronous SAR ADC dissipates a large amount of power at the conversion clock tree distribution. A few additional optimizations can address these issues and achieve an image sensor with a FOM of 102pJ/pixel/frame.
Design research on the core needs of children and families during stem cell transplantation [electronic resource]
Keywords: Cancer Biology.

While undergoing medical treatment for life-threatening illnesses, patients - and their family members - often experience emotional and psychological distress. This is particularly true during pediatric stem cell transplantation, where hospital isolation restrictions further impact normal childhood and family functioning. Many experience the extremes of anxiety, depression, or post-traumatic stress symptoms. In this dissertation, we take a human-centered design needfinding approach to identify the internal "core needs" of children and their family members that are heightened during pediatric stem cell transplantation. Importantly, we learn how these needs are affected by their isolation environment, including the social milieu and hospital organization. The emotional and psychological vulnerability of the population demanded a finely crafted sensitive interview style, to help the interviewees comfortably reflect on their difficult past experiences. This resulted in the design of new activity-based tools and techniques that elicit deeply emotional stories and offer opportunities for positively transforming them. Interviews were also conducted with the interdisciplinary care team. Overall, five common core needs were identified: emotional and mental strength, social relatedness, autonomy, connectedness, and normalcy. By honing in on these core needs, new supportive care programs, interventions, hospital policies, clinical operations and care practices may be designed with the patient's and family's well-being in mind.
Designing and fabricating a capacitive micromachined ultrasonic transducer for use in a novel photoacoustic microscope [electronic resource]
Keywords: Electrical Engineering.

In this thesis I present my work designing and fabricating a capacitive micromachined ultrasonic transducer (CMUT) for use in a novel photo-acoustic microscope. The CMUT device was designed to fit on the end of our collaborators' miniature fluorescent dual-axis confocal microscope to further increase the usefulness of the tool. Adding photo-acoustic imaging to the miniature fluorescent microscope eliminates the need for a fluorescent dye used specifically to identify vasculature. This allows dyes to be optimized to target tumor specific biomarkers to aid diagnosis and boundary definition. The device was designed so it could be packaged into a number of form factors for either handheld use or endoscopic screening. This is an important step for photo-acoustic microscopy because current laboratory systems are bulky and impractical for clinical use. Due to the advantages of the CMUT technology we were able to use a novel architecture to create a compact system.
Desynchronizing cell division waves in the xenopus laevis embryo with temperature gradients [electronic resource]
Keywords: Chemical and Systems Biology.

Developing animal embryos have fascinated scientists for centuries. Their morphology and dynamic behaviors are some of the most beautiful phenomena in all of biology, and their task of converting a single cell into a functional animal seems miraculous. This dissertation is an effort to understand the early embryonic cell division patterns that appear in diverse animal embryos using the frog Xenopus laevis as a model for embryogenesis. We characterized the timing and geometry of multiple waves that move throughout the embryo. By using a temperature gradient to perturb endogenous cell division timing, we found that these dazzling waves are caused by a simple and autonomous mechanism: the variance of intrinsic cell cycle period along the embryonic axes. Again using a temperature gradient, we found that relative cell division synchrony before the mid-blastula transition is required for normal mesodermal induction. Amazingly, desynchronized embryos with mesoderm induction defects go on to become healthy tadpoles. This suggests the existence of a previously unknown synchronizing mechanism during the developmental process of involution. The early X. laevis embryo is at once simple in its design, yet robust to perturbation. We hope others use this dissertation to aid in further understanding of the dynamic processes of early animal embryos.
Detailed thermodynamic investigation of carbon dioxide capture with amine functionalized mesoporous materials [electronic resource]
Keywords: Chemistry.

The work in this doctoral dissertation is divided into two parts. First, the synthesis and characterization of oxidized metal-salen complexes as models for galactose oxidase, a metalloenzyme that relies on ligand redox "non-innocence" for its activity, is explored. It is shown that simple changes to the salen ligand structure can dramatically affect the locus of oxidation with a variety of metal centers. A series of one- and two-electron oxidized copper(II)-salen complexes are characterized using a variety of spectroscopic, electrochemical, and theoretical methods. The second part of this dissertation explores the use of amine-functionalized mesoporous materials for carbon dioxide capture. We have investigated the thermodynamics and kinetics of carbon dioxide adsorption/desorption reactions for a series of diamine-functionalized SBA-15 materials. Enthalpic and entropic contributions to the free energy of carbon dioxide adsorption/desorption are correlated to the structure and surface distribution of sorbent molecules. Additionally, a novel and highly reproducible method for the bromomethylation of mesoporous carbon materials is reported. Bromomethylated materials can be derivatized further by a variety of methods to yield novel functional materials. Specifically, carbon materials functionalized further with diamines are capable of carbon dioxide capture by a process similar to that observed for diamine-functionalized SBA-15 materials.
Developing an electroacoustic portfolio [electronic resource]
Keywords: Music.

Taking my installation from 2012, The Workshop at the Back of the Barracks, this paper discusses how my reflections on this piece influenced the development of the five subsequent electroacoustic chamber compositions. During the installation the acoustic sound materials, that is, the movements and gestures of the visitors interacting with this installation, became embedded into an ongoing automated live electronic stream of sound. This embedding created what I call alternative audio images of the movements and gestures, something more than the creation of 1-plus-1electronic processing relationships. Similarly, the acoustic materials for each of the chamber pieces were created through a series of simple reinterpretations of standard notation made during the compositional process. These reinterpretations were analogous to the parameter value shifts that produced the live electronic streams. Following some introductory remarks and a description of the installation, the original performance instructions and scores for each of the subsequent chamber pieces are presented. In addition, the main elements of the source acoustic materials for each piece and their principle reinterpretations are described. Further, each chapter includes a description of the autonomous live electronic streams that the chamber musicians - performing the reinterpreted acoustic materials - became embedded into, and the alternative audio images, which were also produced by this embedding.
Development and application of next generation lanthanide-based time-resolved luminescence microscopy [electronic resource]
Keywords: Chemical and Systems Biology.

One of the fundamental experimental strategies of modern biology is "perturb and observe". Investigators perturb a complex biological system and, by observing the consequences of their experimental change, infer the function of the perturbed component(s). In order for researchers to be confident in their conclusions, perturbation and observation should have sufficient levels of specificity and sensitivity. Here, I describe two chemical technologies -- one observational and the other perturbational -- that enable better studies of biomolecules in whole-body organisms by making possible the selective visualization of lanthanide luminescence and the pharmacological control of protein stability. In chapter 1 and 2, I discuss a next-generation system for time-resolved lanthanide imaging. As luminescent lanthanide complexes have emission lifetimes that are > 100,000-fold longer than those of organic fluorophores, they can be selectively detected over fluorescent background by time-gating, enabling autofluorescence-free micrographs. However, the optical microscopy of lanthanide probes has not yet achieved detection limits and acquisition speed suitable for most biological applications. I describe three factors that have been impeding the efficient visualization of lanthanide luminescence, and present simple but powerful solutions to the respective problems. I also show novel imaging applications of lanthanide complexes that exploit unique chemical and photophysical properties of these organometallic probes. In chapter 3, I discuss the development of destabilizing domains (DDs) that allow rapid, reversible, and tunable control of protein levels in model organisms that thrive best at 20-25 °C. By genetically appending our DD to a protein of interest, the expression level of resulting fusion protein was successfully modulated by a small molecule ligand in C. elegans.
Development of a Classical Conditioning Protocol for Fear Based Memory in Siberian Hamsters
Keywords:  Department of Biology
Biology
Siberian Hamsters
Circadian Rhythms
Passive Avoidance
Thesis

Passive avoidance is a learned response to an aversive stimulus in which the animal has learned to avoid the stimulus by not approaching or engaging with it. Here, we develop a modified passive avoidance protocol for hamsters to assess long term passive avoidance performance over the course of 28 days. Shocked hamsters retained memory of an aversive foot shock over a long-term period of time. Since most memory is subject to circadian modulation, we investigated whether passive avoidance performance of hamsters varied between the morning (AM) and afternoon (PM). We demonstrate that there is no time of day effect to passive avoidance performance, and this suggests that there is no circadian modulation of passive avoidance in hamsters. We also demonstrate that there is no variation in passive avoidance performance between sexes. Thus, this modified passive avoidance test can be used in the future to assess the long-term memory performance of Siberian hamsters.
Development of diagnostic methods using cell-free nucleic acids [electronic resource]
Keywords: Bioengineering.

Thanks to the rapid development of next generation sequencing (NGS) technology, sequencing of circulating cell-free DNA has been widely used for noninvasive prenatal diagnosis and showed great potential for cancer detection. My thesis work is centered on the application of NGS to analyze cell-free nucleic acids for diagnostic purposes, from the cell-free RNA in the plasma of pregnant women to the cell-free DNA in the cerebrospinal fluid (CSF) of brain cancer patients. In the first part of my thesis, we characterized the composition and dynamic changes of circulating cell-free RNA during pregnancy. Plasma encompasses a broad spectrum of RNA molecules, derived from both human and microorganisms. While the composition of the microbiome in plasma remained relatively stable, the human genes involved in hormonal regulation and immune response were differentially expressed during pregnancy. We also demonstrated that pathogenic infections during pregnancy could be globally monitored through cell-free RNA sequencing (RNA-seq). In the second part of my thesis, we did a proof-of-principle study for the detection of brain tumor mutations in CSF. We measured the concentration and size distribution of cell-free DNA in CSF. We quantified the tumor allele fractions in the CSF and plasma of ten brain tumor patients. Tumor mutations could be detected in the CSF of nine out of the ten patients. Tumor allele fractions were generally higher in CSF compared to plasma, except for patients with systemic metastasis. We longitudinally monitored the treatment response and relapse of two brain cancer patients by sequencing the DNA in CSF.
The development of epigram in classical Greece [electronic resource]
Keywords: Classics.

The inscribed epigrams of early Greece give scholars an unparalleled opportunity to chronicle fully the early history of a literary genre. Short poems inscribed on stone and set up accompanying funerary monuments or dedications to the gods, epigrams possess specific temporal and spatial contexts. Unlike early Greece's much-studied oral poetry, which cannot be contextualized as precisely, inscribed epigrams allow us to study generic development across local contexts. This dissertation traces how inscribed epigram developed from a diverse set of regional traditions into a coherent genre across Greece, thereby providing the foundation for the later Western tradition of literary epigram.
The development of new methods for the intracellular delivery and release of messenger RNA and other biological polyanions using amphipathic molecular transporters [electronic resource]
Keywords: Chemistry.

The noncovalent, electrostatic complexation of an anionic cargo with a cationic molecular transporter represents a powerful strategy for the protection and delivery of otherwise cell-impermeable molecules. The work described herein has been directed at developing new, biodegradable transporters using the organocatalytic ring-opening polymerization of functionalized cyclic monomers. These transporters effectively self-assemble with polyanionic cargo such as nucleic acids like mRNA and siRNA, and inositol polyphosphates and deliver them to cells and living animals. We anticipate that the delivery and release strategies developed using responsive oligomeric biomaterials will contribute to further work aimed at both basic research and therapeutic applications of complex biological polyanions.