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Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection
No full textDue to copyright restrictions full text access from Treasures at UT Dallas is restricted to current UTD affiliates (use the provided Link to Article).Includes supplementary informationUrinary tract infections (UTIs) are the most commonly reported infections in adult women and have high rates of recurrence, especially in postmenopausal women. Recurrent UTI (RUTI) greatly reduces quality of life, places a significant burden on the healthcare system, and contributes to antimicrobial resistance. Because treatment of RUTI by long-term antibiotic therapy is often ineffective or poorly tolerated in elderly women, new therapies must be developed. The molecular basis of RUTI, especially in postmenopausal women, has remained unclear because modeling RUTI in mice is difficult, and human data are limited. Invasion of the urothelium and induction of host inflammation are hypothesized to be key mechanisms by which bacterial pathogens cause RUTI. To further our understanding of RUTI in humans, we performed a systematic analysis of urine and bladder biopsy samples from postmenopausal women undergoing cystoscopy with fulguration of trigonitis in the advanced management of antibiotic-refractory RUTI. We provide direct evidence that bacteria reside in the bladder wall of postmenopausal RUTI patients and that diverse bacterial species can be isolated from the bladder tissue. Histopathological scoring revealed significant edema and alterations of urothelial architecture in RUTI patient biopsies. Lymphocytes, including plasma B-cells, were detected within the mesenchyme, urothelium, and follicular aggregates in the majority of patients, indicating that the local adaptive immune response is active during human RUTI. These data provide conclusive evidence that bacteria invade the human urothelium and suggest that diverse bacterial species and the adaptive immune response play important roles in RUTI in humans. © 2019 Elsevier LtdNational Institutes of Health (NIH; grants R01-AI056404 and R01 GM115188) and the Welch Foundation (grant I-1561).School of Natural Sciences and Mathematic
Blockchain Land Registry Best Practices: the Political and Technical Feasibility of Harnessing Blockchain Technology to Improve Land Administration
No full textProperty rights and, by extension, trusted land administration, are essential elements to the
progress of any nation that is attempting to rise from poverty to wealth. Hernando DeSoto
estimates that there exists in the world $20 trillion dollars' worth of real estate owned by the
world’s poor that is illiquid, underproducing, and ineligible to be used as collateral for loans
because it is either improperly titled or not titled at all. Furthermore, the World Bank estimates
that 70% of the world’s population lacks legal title to their land. Blockchain, also known as
distributed ledger technology, has the potential to radically change record keeping and the
process of transferring title within the real estate industry. Blockchain land registries promise to
increase land tenure security and transparency thereby leading to increased access to credit using
land as collateral. This study catalogs political and technical obstacles to be overcome for the
successful implementation of a blockchain land registry pilot in a given jurisdiction and seeks to
understand the conditions in which a blockchain registry would succeed. There is a dearth of
studies examining the political and governance issues surrounding blockchain based land
registries which is problematics as the political obstacles are far more daunting than the
technical
Maximizing Fitness: Characterizing and Targeting Stress Signaling Pathways Important for Antibiotic Resistance and Cancer Therapy
No full textOver the course of my graduate career, I have had a unique opportunity to gain skills and expertise in two major research areas, cancer biology and microbiology. The most recent work focused on stress signaling in bacterial cells that promotes antibiotic resistance. Acinetobacter baumannii has emerged as a significant threat in healthcare settings due to its increasing multidrug resistance (MDR). With over 60% of clinical isolates exhibiting MDR, both the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have identified carbapenem-resistant A. baumannii as a critical target for antibiotic development. The recent emergence of colistin resistance through mutations in the lipid A biosynthesis pathway in A. baumannii further complicates treatment options because new antimicrobial strategies targeting this pathway may not be efficacious.
The microbiology-focused portion of this dissertation elucidates the role of the A. baumannii BaeSR two-component regulatory system (TCS) in stress response and antibiotic tolerance, focusing on its regulation of the paa operon, which is involved in phenylacetic acid (PAA) catabolism. Our research demonstrates that baeR deletion (baeR) downregulates expression of the paa operon genes, while baeR overexpression restores wild type expression levels in both ΔbaeR and ΔgacS mutants. Together our findings suggest BaeSR directly activates paa gene expression, which was previously not known. We provide evidence that BaeR directly binds to the paa operon promoter, where it likely activates transcription to regulate a response that promotes fitness in stress. Notably, both baeR and paa mutants exhibited compromised growth when exposed to sub-inhibitory concentrations of antibiotics such as kanamycin, indicating reduced tolerance to aminoglycoside-induced stress.
The data suggest that BaeR-mediated regulation of the paa operon is a mechanism to sense and response to environmental stress such as antibiotic treatment. Our study provides novel insights into the stress response pathways for a significant nosocomial pathogen, and identifies potential targets for inhibitor development, contributing to the ongoing efforts to combat multidrug-resistant A. baumannii infections.
In separate work completed during my graduate tenure, I characterized heme-sequestering proteins. Heme is a critical nutritional, metabolic, and signaling molecule that plays a vital role in mitochondrial respiration and ATP generation in lung tumor cells. While pathogenic microbes exploit host heme for metallonutrient acquisition, we developed small heme-sequestering proteins (HeSPs) derived from bacterial hemophores. These HeSPs demonstrate high affinity for heme, inducing apoptosis in non-small cell lung cancer (NSCLC) cells, suppressing tumor growth in xenograft models, and significantly reducing oxygen consumption and ATP levels.
Our research reveals a correlation between elevated heme synthesis and uptake and the progression of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Employing a genetically engineered KLLuc mouse model, we demonstrated that HeSP2 treatment, which inhibits heme uptake in tumor cells, effectively halted lung tumor progression in both ADC and SCC. HeSP2 not only suppressed tumor growth but also reduced angiogenesis alleviated tumor hypoxia, and diminished oxidative phosphorylation activity. These findings suggest that targeting heme metabolism represents a promising therapeutic strategy for lung cancer treatment, potentially offering a novel approach to combat this devastating disease.
Together, these studies illustrate the significance of targeting stress response pathways in both cancer and antibiotic-resistant infections. By elucidating the mechanisms underlying heme sequestration in lung tumors and the regulatory roles of the BaeSR system in A. baumannii, we provide a comprehensive understanding from the perspective of the host and bacterium into how these pathways can be harnessed for innovative therapeutic strategies. Addressing these stress responses could pave the way for more effective treatments against both aggressive tumors and persistent bacterial infections, enhancing our ability to manage these significant health challenges
Chronic Recording Performance of Intracortical Microelectrode Arrays: Study Design, Bioactive Coatings, and Effects on Neuronal Populations
No full textImplanted microelectrode arrays allow for recording and stimulation of neural tissue with high
spatial resolution. These devices are used to study the brain and form the basis of brain-computer
interfaces which are used as rehabilitative devices to restore function in individuals with
neurological disease or damage. However, the long-term use of these devices is limited by a
degradation in performance and reliability over time. A major contributor to this degradation is
thought to be the chronic tissue response resulting from the implanted device which is
characterized by neuroinflammation and oxidative stress. By using bioactive coatings to mitigate
oxidative stress and neuroinflammation it may be possible to improve the long-term outcomes of
these devices. In this dissertation we evaluate the use of bioactive coatings on the chronic
recording performance of intracortical microelectrode arrays. In pursuit of this goal, we
demonstrate: (1) there is a wide, but converging range of time points used to evaluate chronic
performance of MEAs in vivo, (2) the use of isoflurane anesthesia is appropriate when
evaluating common metrics of recording performance, (3) the use of bioactive Mn(III)tetrakis(4-
benzoic acid)porphyrin (MnTBAP) coatings, but not (3-aminopropyl)triethoxysilane (APTES)
coatings are capable of improving chronic recording performance, and (4) the efficacy of
MnTBAP coating is different for putative inhibitory and excitatory neurons
Unveiling Vrindavan: A Journey Through Art and Abstraction to the Vedic Spiritual Realm
No full textThis project, titled Unveiling Vrindavan, seeks to preserve and celebrate the cultural and spiritual
heritage of Vrindavan, a site of immense historical significance as the birthplace of Lord
Krishna. Faced with cultural erosion due to modernization, this work aims to unveil the hidden
glories of Vrindavan through art, inviting deeper appreciation and understanding. Inspired by the
Vedic narrative of Gopa Kumara’s journey from the Brhad-Bhagavatamrta, the project
illustrates a soul’s spiritual journey across five stages: disillusionment, enlightenment, resistance,
transcendence, and reunion. Employing three artistic mediums—watercolor for metaphorical
exploration, digital illustration for literal depiction, and abstraction for transcendental
experiences—this series offers a visual translation of Vrindavan’s spiritual essence. By
presenting a personal narrative of transformation, the project aspires to bridge cultural awareness
and spiritual reflection
Autonomous Navigation Using Active Visual-semantic SLAM
No full textThe use of robots has become increasingly prevalent in nearly every industry, with robots
found in not only manufacturing and transport, but also in healthcare and the home. This
trend has likewise been accompanied by a demand for greater robot autonomy and the capacity
to perform complex tasks unguided. In order to be able to do this, robots require the ability
to perceive entities within the environment not only geometrically, but also semantically, as
what an object is will dictate how it should be interacted with. Autonomous operation also
requires that a robot be able to perform simultaneous localization and mapping (SLAM)
within potentially unknown environments.
In this thesis, Robot Operating System is used to implement a system which allows a robot
to explore a previously unknown environment using a map generated by semantic SLAM. By
extracting information from the map, the robot can be directed towards different semantic
class instances found within the environment, with new instances found using frontier-based
exploration. A custom terrain costmap layer is also created to enable semantics-aware path
planning. The efficacy of these contributions are then demonstrated through experiments in
a simulated environment
Tailoring Graphene Architecture and Liquid-Wall Interactions for Sustainable Oil Recovery and Seawater Desalination
No full textThe growing global demand for sustainable solutions to environmental challenges, such as oil
contamination and freshwater scarcity, has necessitated the development of innovative materials
and systems. This dissertation investigates the design and optimization of graphene-based
architectures and their interactions with liquids at nanoscale to address these critical issues.
Through a combination of advanced fabrication techniques, molecular simulations, and
experimental validations, the research focuses on enhancing oil recovery and seawater desalination
processes by tailoring the three-dimensional architecture of graphene and tuning the interaction
between graphene and oil/water.
The study introduces graphene materials engineered with hierarchical structures, designed to
optimize oil transport and recovery rates in contaminated environments. By utilizing plasma-
enhanced chemical vapor deposition and freeze casting methods, the research demonstrates
significant improvements in spontaneous, continuous oil recovery efficiency. Furthermore, the
dissertation explores novel bi-functional devices capable of simultaneously desalinating seawater
and recovering oil, maximizing energy efficiency by utilizing solar power. In addition to
experimental advancements, molecular dynamics simulations provide insights into the fluid
behavior of oil and water in graphene nanochannels. The work reveals important mechanisms,
such as stick-slip flow and the influence of electric fields on water evaporation, offering new
pathways for optimizing fluid transport and water evaporation at the nanoscale.
Overall, this dissertation contributes to the advancement of graphene-based technologies for
environmental remediation, providing a foundation for scalable, sustainable solutions to global oil
spill mitigation and freshwater production. The research opens new avenues for utilizing the
unique properties of graphene to address multifaceted environmental challenges through
innovative material design and application
Near-unity Biexciton Quantum Yield and Generation of Correlated Photon Pairs From CDS/CDSE/CDS Quantum Shells
No full textThis dissertation presents colloidal CdS-CdSe-CdS nanocrystals, referred to as quantum
shells (QSs), which exhibit enhanced biexciton quantum yield (BX QY) due to their unique
geometry. A quasi-2D confinement layer is wrapped into a spherical surface, increasing the
effective volume available for charge carriers and reducing electron-hole overlap. This structure
effectively suppresses Auger recombination while maintaining strong confinement, making
quantum shells promising candidates for optoelectronic applications that benefit from efficient
multiexciton generation. Single-particle spectroscopy techniques were employed to investigate
photoluminescence blinking, fluorescence lifetimes, and antibunching, demonstrating size-
dependent improvements in BX QY, with some QSs achieving near-unity yields. A non-
statistical scaling model is used to describe the evolution of radiative and non-radiative
processes, including estimations of BX lifetimes and Auger rates. Additionally, the high
BX QY enables the observation of stable and spectrally distinct photon pairs, a critical
property for generating single photons, correlated photon pairs, and entangled photon
states which are at the forefront of emerging quantum optics technologies. A rate equation
model incorporating non-ideal spectral filters is introduced to describe the behavior of the
observed photon correlations, and highlights the significance of unresolved emission lines and
background contributions. To facilitate further exploration into the potential of quantum
shells as sources of entangled photons, a theoretical description for the measurement of the
polarization state of the photon pair is provided
Unstrapping the Straitjacket: Confucianism, Modernity, and Singapore's “Oriental” Ascendancy
No full textThis dissertation critically examines the portrayal of Confucianism within Western scholarship,
particularly through the lens of John King Fairbank and Joseph Levenson, who characterized it
as an impediment to modernization. This study situates their interpretations within the
frameworks of Orientalism and Modernization Theory to reveal the influence of the Orientalism
of Max Weber, who first constructed a narrative that depicted Confucian values as static and
incompatible with Western ideals of progress. In contrast, this research notes the contributions of
Asian American scholars who reevaluate Confucianism as a dynamic and adaptable tradition
able to enrich modern governance. This dissertation then traces the Asian American scholar's
role in integrating Confucianism into the Singapore government. Ultimately, this work
showcases the need for diversity in understanding the complexities of cultural and intellectual
exchanges and argues that philosophies like Confucianism has a role in modernity
Allylic Functionalization Reactions Enabled by Photoinduced Radical Generation of Π-allylpalladium
No full textThis thesis describes two photocatalytic radical strategies for accessing π-allyl Pd(II) complexes
and the transformations thereof. In the first approach, a photoexcited Pd(0) catalyst engages alkyl
iodides in a single electron transfer event, producing alkyl radicals that undergo radical addition
to conjugated dienes to generate hybrid allyl Pd(I) radicals. These open-shell species can then
collapse into electrophilic π-allyl Pd(II) intermediates via radical–polar crossover. Subsequent
interception by external nucleophiles, such as amines, phenols, and malonates, through Tsuji–
Trost-type mechanism yields a range of carbofunctionalization products. This work represents one
of the early examples of alkene difunctionalization in palladium photocatalysis. The second
strategy involves generating hybrid allyl Pd(I) radicals by homolytically activating the allylic C–
H bonds of alkenes via hydrogen atom transfer to aryl radicals, which are similarly derived from
aryl bromides under photocatalytic conditions. Likewise, radical–polar crossover furnishes
classical π-allyl Pd(II) complexes, which upon nucleophilic attack by external nucleophiles afford
allylic C–H functionalization products. Notably, the aryl bromide serves as an oxidant in this
process, which is unconventional given their well-established role as cross-coupling partners in
transition metal catalysis. Furthermore, employing a chiral ligand renders the transformation
stereoselective, representing the first instance of asymmetric palladium photocatalysis. This
radical-based strategy provides new mechanisms for intermolecular C(sp3)–H functionalization
with the potential to complement current technologies or address their limitations