Treasures @ UT Dallas
Not a member yet
7697 research outputs found
Sort by
Tracking Dissemination of Plasmids in the Murine Gut Using Hi-C Sequencing and Bayesian Landmark-based Shape Analysis of Tumor Pathology Images
No full textStarting from the experimental design and simple group result comparison using studentst test to the analysis need of explosively growing digital information in the big data era,
extensive statistical approaches have been developed and incorporated into biology studies
in order to understand the mechanism of life processes and disease. The term ”omics” refers
to the various disciplines in biology performing a comprehensive, or global, assessment of
a set of biological features in a high-throughput way, such as genomics, transcriptomics,
proteomics and metagenomics. When analyzing such a huge amount of data, a proper
framework needs to be developed with a thorough knowledge of the associated biology as well
as statistical models. In this work, I focus on two critical health-related problems, antibiotic
resistance spread in microbial communities by conjugative plasmids, and the association
between tumor shape and prognosis in pathology images. In my first work, metagenomics
and Hi-C sequencing were employed to analyze plasmid dissemination from Enterococcus
faecalis donor strains in the murine intestine. I clustered assembled contigs into metagenomeassembled genomes (MAGs) and showed that the quality of obtained MAGs was improved by
combining those two types of sequencing techniques. Then, I demonstrated that Hi-C is able
to detect the in situ hosts of native resistance genes in the murine gut microbiota. We also
confirmed the association between introduced E. faecalis plasmids and the donor strains and
found potential new gram-positive host for the pAM830 resistance plasmid. In my second
work, we developed a framework with a novel automatic landmark detection model for
tumor shape boundary in pathology image called Bayesian LAndmark-based Shape Analysis
(BayesLASA). Two types of landmark-based boundary roughness features were proposed,
and we demonstrated the predictive value of them in a large cohort of lung cancer patients
Electrical Reliability of Twinned Metallic Nanowires
No full textIn today’s technology, the transistors have reached such a small size that it is increasingly costly
to shrink them more. Therefore, the industry is leaning towards increased functionality of the
devices rather than miniaturizing. Thus, new technologies are emerging e.g., stretchable, and
wearable electronics. In addition to the high current density (~107 A/cm2) requirement due to
smaller size, these technologies require excellent mechanical and optical properties.
Metallic nanowires are excellent candidates for these devices meeting all the requirements.
However, as surface to volume ratio increases, in nanoscale, the energy carriers- phonons (heat)
and electrons (electricity), are scattered increasingly. Additionally, diffusion through the grain
boundaries also increases. Moreover, a significant portion of these devices use random networks
of nanowires, where conduction is not uniform, leading to more current density in some of its
members, and hence localized failure of individual nanowires. Thus, assessing the electrical
reliability of individual nanowires is needed. The reliability can be assessed by characterizing- 1)
Joule heating and 2) electromigration.
Studies show that the presence of a twin boundary across the path of an atomic vacancy slows
down its diffusion. Since electromigration is a vacancy diffusion process, we are interested in
studying the failure of twinned nanowires. However, silver nanowires are more prone to
degradation over time and electromigration tests can go on for weeks. Hence, silver nanowires
were selected for Joule heating study, which does not require longevity, and gold nanowires were
selected for electromigration study. Thus, the goals of this dissertation are as follows:
1. To quantify the failure current densities of silver nanowires in relation to diameter with
theoretical validation.
2. To quantify the median time to failures by electromigration of twinned gold nanowires at
different temperatures.
3. To compare the electromigration data between twinned gold nanowires and other
interconnects with grain boundaries, to observe the effect of twins on electromigration.
In the Joule heating study of silver nanowires, we established the behavior of their failure current
density against diameter for 93 samples. Heat transfer modelling was employed to explain the
results, and Weibull statistics were used to quantify failure probabilities. The scatter observed in
the measurements was attributed to surface roughness variations. The results quantify the Joule
heating electrical reliability of silver nanowires and highlight the importance of heat transfer in
increasing it.
In the electromigration study of gold nanowires, we studied 30 samples at 3 temperatures. The
median time to failure at each temperature has a lognormal distribution that can be described
with maximum likelihood estimation. Electromigration activation energy was determined using
Black’s equation. This is an important indicator of the modes of diffusion and the results
highlight the importance of passivating the surface of nanowires to reduce electromigration. The
study is divided into 5 chapters. Chapter 1 provides a background. Chapter 2 describes the
experimental procedures. The results from Joule heating test are shown in Chapter 3. Chapter 4
shows the results from electromigration test. Chapter 5 shows the direction of future work
Human-machine Collaborative Vulnerability Discovery for C/C++
No full textSoftware security auditing, which includes code vulnerability detection, severity and impact
analysis, proof-of-concept exploitation, patching, and patch efficacy assessment, is a critical
step during the software development and maintenance process. If not properly assessed,
large applications can turn into a Pandora’s box that can bring destruction to the cyber
world if exploited. Unfortunately, due to lack of expertise, increasing size of code bases,
frequency of releases, and cost constraints, software producers are finding it increasingly
difficult to complete comprehensive end-to-end security assessments prior to software release
and deployment. More reliable, robust, extensible, and automated tools are needed to fulfil
this demand at this scale.
This dissertation proposes Cross Domain Code Property Graphs (CDCPG), a new relational
graph representation of software artifacts (source and assembly code) that can be mined to
find violations of code safety and security properties. The approach encapsulates lower level
constraint checking to present auditors a high level correspondence, facilitating discovery and
analysis of vulnerabilities that are concealed or invisible at the source level without binary
analysis.
In contrast with state-of-the-art static analysis tools, the approach presents generated alarms
sorted by vulnerability score calculated based on the feature set. The proposed point-of-
interest (POI) triaging method can detect 80% of reported vulnerable functions on average
by exploring 34% of high risk functions, and achieve nearly 100% by exploring 60%.
A CDCPG prototype implemented for the DARPA CHESS (Computers and Humans Exploring Software Security) program is evaluated, with results demonstrating high accuracy
and effectiveness on large code bases compared to prior works. Collaborations with other auditing approaches (e.g., fuzzing-based approaches) is facilitated by broadcasting the detected
POIs, which contain both source- and binary-level locations. The information improves the
effectiveness of trace analyses, such as inter-procedural control-flow graph construction and
analysis.
The research also resulted in a new repository of real-world vulnerable function data, which
is the largest of its kind published in the open literature. Based on this raw data, this
dissertation further develops a framework to extract features from software artifacts to create
tabular data sets. The framework exhibits high utility for feature-based learning models to
predict vulnerabilities, solving an open problem that has prevented existing vulnerability
classification tools from being effectively evaluated on real-world open source data that is
heavily imbalanced. The approach innovates a novel semi-supervised learning methodology
that leverages triplet mixup data augmentation to address the imbalanced data problem in
tabular security data sets
Modeling Fill Factor Losses in Organic Solar Cells
No full textDetermining how certain electronic devices can outperform other devices is of immense interest
in the modern world. Many advance experimental characterization techniques have been applied
such as X-ray diffraction, scanning electron microscopy, and transmission electron microscopy to
aid in the understanding of device performance. However, simulations often offer a more effective
complementary to experiments in discovering the physics governing new materials. First
principles or ab initio simulations offer a big advantage since they require no experimental
information at all. Empirical methods, on the other hand, need previously determined experimental
values to match the experiment. In this thesis, I explain how I further simplify the present
understanding of emerging materials from a theoretical perspective. I first discussed why
experiments observed fill factor losses in dilute-donor organic solar cells by performing kinetic
Monte Carlo simulations. From my kinetic Monte Carlo simulations, I discovered a linear relation
between the fill factor and the fraction of donors touching the anode and concluded that fill factor
losses are due to donors not touching the anode. In addition to studying the fill factor losses, I
studied solvent effects on the highest occupied molecular orbital energy of solute molecules by
implementing a first solvation shell method. A first solvation shell is a mix between implicit
solvent methods and explicit solvent methods. I found that present implicit solvent methods are
not sensitive to solvent choice because those methods cannot discern how solvents and ambient
temperature perturb the solute geometries. Finally, I also studied how the bandgap of Tellurium
becomes more suitable as a channel material when scaled to extremely small sizes (~1-3 nm)
Engineering and Biological Applications of Turn-on Fluorescent Protein-based Sensors for Chloride
No full textChloride is the most abundant anion in our body and is essential for all forms of life. The transport
of chloride is linked to cellular functions including cell volume, pH regulation, cell division,
muscle contraction, and neuroexcitation. However, dysregulation of cellular chloride transport has
been implicated in human diseases such as cystic fibrosis, pancreatitis, and epilepsy suggesting
that chloride could be a signal of cellular status. Moreover, we lack a clear molecular-level picture
of what chloride is doing. In this thesis, I will discuss the various approaches researchers have used
to study chloride in biological systems. Chapter 1 will review the different types of fluorescent
proteins that have been used to develop sensors for chloride. To expand on the current state of the
art, we have revealed the first examples of standalone turn-on fluorescent protein-based sensors
for chloride using the naturally occurring yellow fluorescent protein from the jellyfish Phialidium
sp., which is ratiometric and undergoes an excited state proton transfer in the presence of chloride
(Chapter 2), and the engineered mNeonGreen protein from the cephalochordate Branchiostoma
lanceloatum (Chapter 3). Given that the mNeonGreen sensor operates best at pH 4.5, Chapter 4
will describe how we designed and carried out double site-saturation mutagenesis of noncoordinating residues in the mNeonGreen chloride binding pocket. This protein engineering effort
not only improved the chloride sensing properties of mNeonGreen at physiological pH but also
generated sensors with the largest turn-on fluorescence responses to chloride thus far (ChlorON).
Fluorescence imaging experiments in mammalian cells expressing a ChlorON sensor demonstrate
how the advantage of using turn-on fluorescent sensors to provide spatial and temporal resolution
for mapping chloride dynamics. Lastly, Chapter 5 will highlight an alternative de novo strategy to
convert the membrane-bound, proton-pumping rhodopsin from the cyanobacterium Gloeobacter
violaceus (GR) into a non-pumping, red-shifted, and turn-on fluorescent sensor for chloride that
can be used to image chloride in bacteria. In this study, we identified how a single point mutation
of a key residue in the proton transport pathway can create a new chloride binding site in GR while
also altering the protein function and spectroscopic properties to sense chloride. Taken together,
this body of work lays the foundation of building protein-based hosts for chloride recognition and
illustrates how we can use and adapt naturally occurring proteins to expand the turn-on fluorescent
imaging toolkit for chloride that can enable the discovery of new roles for chloride in biology
Biochemical and Biophysical Characterization of Bacterial Transition Metal Transporters by Functional Reconstitution in Artificial Lipid Bilayers
No full textTransition metals play a vital role in all living organisms due to their key structural and functional
properties central to diverse metabolic processes. However, because of their high reactivity
organisms have evolved sophisticated biomolecular protein networks to control intercellular metal
ion homeostasis, without reaching toxic intracellular levels. Transmembrane transporter proteins
play a gate-keeper role in maintaining the dynamic flux of these transition metal ions across
biological membranes, thereby finely tuning metal delivery and availability in cells and subcellular
organelles. P-type ATPases are a superfamily of transmembrane primary active transporters
involved in translocating substrates against an electrochemical gradient which play a key role in
maintaining homeostasis of cellular concentrations of essential ions. They are classified into 5
classes (P1, P2, P3, P4 and P5) based on their substrate selectivity.
This dissertation is focused on studying the substrate selectivity and mechanism of translocation
in the P1B class of P-type ATPases which are involved in transition metal transport for both
essential and toxic transition metals. P1B-type ATPases are classified into 7 sub families (P1B-1 -
P1B-7 types) based on conserved amino acid motifs in their transmembrane helices that appear to
control each sub-family’s substrate selectivity, resulting in the existence of pumps that can
selectively translocate 1st, 2nd and 3rd row transition metals across the lipid bilayer. Considering
their central role in controlling cellular metal levels and extrusion in cells they are also acting as
virulence factors in pathogenic bacteria. Studies towards their characterization could therefore help
in establishing them as new potential therapeutic targets to develop novel antibiotics to overcome
the bacterial resistance observed with traditional antibiotics.
However, the substrate transport across lipid bilayers, the overall mechanism for cargo
translocation, and kinetics of these transporters remain elusive to a significant extent, due to lack
of molecular tools to study putative metal substrate transport across membranes in real-time in a
native-like environment.
In light of this, metal-stimulated ATPase activity assays were coupled with an experimental
platform based on multiple fluorescence sensor probes, to study substrate selectivity, transport
mechanism, including counterion transport and electrogenicity, and translocation kinetics in realtime with recombinantly expressed proteins belonging to P1B-1 (CopA from E. coli) and P1B-5 (Nia
from S. meliloti) classes reconstituted in artificial lipid bilayer vesicles known as proteoliposomes.
The proteoliposomes were used as an in-vitro tool to determine metal selectivity and the kinetic
parameters for metal transport by encapsulating fluorescent detector probes featuring turn-on
florescence signal upon substrate ion binding and translocation.
However, the use of the proteoliposomes is challenging due to their intrinsic structural instability
and susceptibility to stressors like temperature, aging, and chemicals, which limits their shelf life.
Therefore, an experimental approach was developed to stabilize membrane proteins and
proteoliposomes by encapsulating them in a sheddable metal organic framework, which reduces
their susceptibility to external stressors. This platform sheds light on developing methods to utilize
proteoliposomes in biochemical and biophysical investigation of transmembrane proteins and in
drug delivery applications. In addition, this approach would help to overcome the challenges of
cold-chain therapeutic transport of liposomal vaccine formulations
¡Una Casa por Mes!: Architecture, Consumerism, and the Construction of Middle-class Identity in the Valley of Mexico, 1877-1968
No full textThis dissertation explores the modernization of the built environment in the Valley of Mexico
from 1877 to 1968 and its role in creating a modern middle-class Mexican identity. This
dissertation argues that government officials, architects, urban planners, and advertisers
manipulated the built environment to produce a modern, middle-class identity predicated on
order and economic progress during the Porfiriato (1877-1911) and consumer capitalism and
protectionist economic policies during the Mexican Miracle, (1946-1970). I demonstrate that
architects and planners designed spaces to encourage middle-class citizens to imagine
themselves as consumers through the construction of new colonias (neighborhoods) and home
interiors designed to accommodate new domestic technologies. Advertisers of new homes
appealed to the middle-class desires for status and preyed on their anxieties around social
changes in the city. Outdoor advertising contributed to the consumer imaginary where the built
environment became a canvas for dreams of capitalist consumption. Print advertising contributed
to the consumer imaginary by fusing traditional middle-class values to a capitalist consumer
economy. The introduction of new modes of retail, such as US-style supermarkets and shopping
centers aimed at the middle-class, fortified the notion of a modern consumer class.
The necessary conditions for modernization are rooted in the introduction of liberal reforms in
the nineteenth which restructured the built environment of Mexico City through the freeing of
Church lands and dissolution of large land-holdings, encouraging the expansion of the city to the
west. The modernization project began in earnest during the Porfiriato with the introduction of
technologies, such as streetcars and electricity. These new technologies introduced new ways for
citizens to interact with their environment, producing behavior that often clashed with Porfirian
notions of order. After 1920, the modernization project became enmeshed with postrevolutionary
goals of nation-building when government officials introduced urban planning, hoping to solve
the problems wrought by social change and inbound migration. These efforts met with varying
degrees of success as the built environment was envisioned by planning officials as a conduit for
commerce. One architect, Mario Pani, believed the solution for the growing problems of the city
was to abandon it altogether. His Ciudad Satélite concept, a self-contained “city outside the
city,” located in Naucalpan 30 miles northeast of Mexico City, promoted itself as the pinnacle of
modern life for middle-class Mexicans, who embraced it as the basis for a new identity built on
traditional tenets of life as gente decente.
The benefits of modernization were uneven and not everyone benefited from the introduction of
these technologies. From the Porfiriato to the end of the Mexican Miracle, changes in Mexico
City’s infrastructure exacerbated material inequalities and class divisions. Government officials’
insistence on regulating the built environment was met with opposition and resistance. Planning
schemes often privileged economic development and disregarded the needs of citizens across the
region. The benefits of the protectionist economic policies were also uneven, and while some
middle-class Mexicans (such as the residents of Ciudad Satélite) enjoyed the benefits of the
Mexican Miracle, the problems wrought by modernization spread throughout the Valley of
Mexico. This dissertation demonstrates the often contradictory nature of both modernization and
the middle-class Mexican identity that arose from it
Probing Dynamic Cellular Properties Using Genome Editing and Systems Biology
No full textGenome editing has revolutionized not only the future of biological research, but also holds the
promise of being a powerful therapeutic for genetic diseases. When considering the multitude of
genetic regulations that contribute to various biological processes and their individual
contributions that permit diseased cellular states, especially in instances where more than a single
genetic aberration is attributed to the diseased phenotype, it is crucial to consider the
interconnectivities of gene regulators and their individual contributions to cell health. Biological
network maps that reveal the relation of gene products to one another can provide insight into the
biological properties they govern. A biological network map consists of nodes (gene products)
connected by edges that are dictated by the nature of the interaction between the two nodes.
Nodal ablation (i.e., knocking out a gene to render it non-functional) has been crucial in
understanding diseased states. However, this type of mutational analysis essentially disregards
the impact that individual edges have on the network as a whole. The goal of my dissertation
work was to utilize the genome editing tool Cas9 to disrupt the p53-miR-34a network in an edge-specific manner in order to demonstrate not only the complexity of these networks, but to also
underscore the importance that individual edges have on the tumor suppressor phenotype. To this
end, I, along with a team of researchers, developed a genetic screen using Cas9-bearing lentiviral
vectors to disrupt 93 miR-34a binding sites within the 3’ untranslated region (UTR) of 71 genes
impactful to cell survival under apoptotic conditions. I quantified the degree of apoptosis in two
colorectal cancer cell lines that differ in functional p53 status, and that each harbored miR-34a
binding site mutations within the pro-survival gene Bcl-2 3’UTR, demonstrating the importance
of the miR-34a-Bcl-2 edge on apoptotic progression. Concurrently, I investigated the
phenomenon of cell cycle desynchronization by tracking the DNA distribution of a population of
cells starting from a synchronized state until asynchrony with flow cytometry analysis. In doing
so, I utilized statistical tools to quantify the degree of desynchronization that does not rely on
individual cell cycle phase labeling. Additionally, with the help of my peers, tested and validated
a mathematical model the capitulates experimental observations. I explored the sensitivity of the
model to changes in its parameters to reveal that cell cycle variability within the population is a
main contributor to cell cycle desynchronization. Furthermore, I tested this model prediction by
treating cells with lipopolysaccharide to enhance cellular noise, resulting in a greater variability
of cell cycle duration, which was also shown to increase the rate of cell cycle desynchronization.
Taken together, my research provides insight into the importance individual edges have to
biological networks and their resulting phenotypes, as well as the underlying sources of cell
population heterogeneity and its contribution to cell cycle variability
Arrangements for Guitar Trio With Commentary
No full textThis dissertation is in two parts. Part I is a collection of my own guitar trio arrangements of
music not originally composed for guitar. Part II is this analytical essay which discusses my
work and the long tradition of transcriptions for guitar to which I am contributing. Guitar
transcription is quite common; however, there are differing methods and techniques as to how to
transcribe in and out of the plucked-string idiom. Chapter 1 contains surveys of the existing
tutors, texts, methods, theses, and dissertations on the subject. Building from the surveys in
Chapter 1, the remaining chapters outline my method for creating a new body of work for the
classical guitar. Chapter 2 explains how I approached and prepared the source materials for my
arrangements. In Chapter 3, I detail my process for transcribing and arranging selections for a
guitar ensemble. In Chapter 4, I cover the revision process and explain how I prepare printed
copies of the arrangement. Chapter 5 is a summary of my findings from a series of interviews
with other guitar arrangers. A Conclusion summarizes my changes to the source material and
offers additional paths to explore in this much-needed field of study
Theoretical Modelling of Transition Metal Oxide Compounds for Application in Electronic and Electrochemical Systems
No full textDensity functional theory (DFT) is the predominant methodology for predictive theoretical
calculation of material properties used today. It is extensively applied in solid-state physics,
chemistry, and materials science to model a wide range of systems on the atomic scale. The
popularity of DFT is due in large part to the high-degree of accuracy provided by the methodology,
coupled with a relatively low computational cost compared to alternatives like all-electron models.
While DFT has been very successful at predicting diverse sets of material properties, there are
crucial areas where DFT remains deficient. One of the most notable of these deficiencies is the
inability of DFT to accurately describe transition metal compounds. Transition metal compounds
are a huge material space with many technological applications. A comprehensive understanding
of the physics underlying commonly used computational methods is required in order to best to
correct these methods for a given class of compounds. This work begins with a survey of available
methodologies for modelling transition metal oxides. Subsequent sections detail the properties of
compounds investigated for specific technological application. Particular attention is given to
high-mobility p-type semiconductors, solid-electrolytes for Li-ion batteries, and properties of
amorphous phases