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Theoretical Convergence of Numerical Schemes for Couped 3D-1D Partial Differential Equations
No full textThis work addresses the theoretical convergence and numerical solution of coupled partial differential equations (PDEs) with mixed dimensionality, specifically diffusion-advection equations posed in a three-dimensional domain coupled with a one-dimensional line. These systems arise in various scientific and engineering applications, where different physical phenomena are modeled in different spatial dimensions. The coupling between the three-dimensional and the one-dimensional PDEs relies on lateral averaging across an interface, facilitating the interaction between the 3D and 1D components. The primary focus is on the development and analysis of numerical schemes for solving such coupled systems, specifically using the finite element method (FEM) and the discontinuous Galerkin method. We consider two sets of boundary conditions.
In the first problem, we impose the Neumann and Dirichlet boundary conditions at the boundary points of the one-dimensional PDE. Under suitable conditions on the magnitude of the advection field, we establish the existence and uniqueness of the weak solution, providing a theoretical foundation for the problem. We also formulate and analyze a finite element-based scheme, giving rigorous proofs of existence, uniqueness, and optimal priori error bound for the scheme. The results show that the scheme is theoretically sound and can be applied in practice.
In the second problem, we consider another set of boundary conditions and assume that the coupled problem is well-posed. We develop a scheme that combines finite element method for the three-dimensional problem and the interior penalty discontinuous Galerkin method for the one-dimensional problem. We establish the existence and uniqueness of the discrete solution and also show the convergence of the method by deriving a priori error estimates
S.O.S. for cost-effective and computationally efficient targeted microbial pathogen detection in clinical and public health settings
No full textThe COVID-19 pandemic forever underscored the importance of rapid, accurate, and cost-effective pathogen diagnostics for public health and clinical settings. Thanks to recent advancements in DNA sequencing, microbial pathogens are now studied at unprecedented scale and depth. However, in environmental (e.g. wastewater) and clinical (e.g. blood) samples, microbial pathogens often represent a tiny fraction of the total nucleic acids, rendering untargeted sequencing impractical with respect to cost. Additionally, untargeted approaches require 24 to 72 hours for sequencing and thus cannot fully replace fluorescence probe-based assays due to their rapid turnaround times, simple experimental workflows, lower sample quality requirements, and accessible instrumentation. Targeted amplification techniques, such as polymerase chain reaction (PCR) or hybrid capture, address these limitations by selectively enriching nucleic acid sequences of interest by millions- or billions-fold, significantly reducing sequencing costs and enabling compatibility with fluorescence probe-based detection technologies.
In the first part of this thesis I present SADDLE, a stochastic algorithm for the design of multiplex PCR primer sets that minimizes primer dimer formation. One major challenge in the design of highly multiplexed PCR primer sets is the large number of potential primer dimer species that grows quadratically with the number of primers to be designed. Simultaneously, there are exponentially many choices for multiplex primer sequence selection, resulting in systematic evaluation approaches being computationally intractable. SADDLE tackles these problems by implementing a novel algorithm that estimates the dimer likelihood of the whole primer set in linear time. Combined with simulated annealing, SADDLE efficiently explores the potential primer sets and reduces dimer formation by more than 10-fold in real experimental settings.
Second, I present Olivar, a first step towards a fully automated, variant-aware design of tiled amplicons for pathogen genomes. Existing methods take a one-shot approach for tiled amplicon design, resulting in semi-optimized primer sets that need further manual optimization. Olivar converts each nucleotide of the target genome into a numeric risk score, capturing undesired sequence features that should be avoided, including variations and repetitive sequences. It then evaluates thousands of possible primer combinations with a highly efficient loss function. In a direct comparison with the most widely used primer set for SARS-CoV-2 sequencing in ARTIC, Olivar has up to 3-fold higher mapping rates on real wastewater samples while retaining similar coverage.
Lastly, I present Seqwin, an annotation-free method for relaxed search of clade-specific marker sequences based on minimizer graphs. These markers are critical for pathogen identification, disease surveillance and taxonomy classification. Earlier methods search for maximal unique matches with suffix trees, but they are susceptible to sequence variations and are limited by the rapidly expanding genomic databases. More recent solutions improve scalability through clustering protein-coding genes, but they require genome annotation and restrict marker discovery to coding regions. Seqwin takes a novel approach of clustering minimizers into graph nodes, eliminating the expensive annotation step while achieving linear scalability, allowing it to run on computing systems with limited resources.
In summary, the primary contributions of this thesis are open-source computational approaches for designing targeted assays for pathogen detection, minimizing manual labor, automating optimization, and simplifying the end-to-end design to deployment process. All of these contributions are open source and freely available to public health and clinical labs across the globe, providing an S.O.S for rapid and accurate targeted detection of microbial pathogens
Estimating Past Events in Cancer Through Statistical Modeling of DNA Sequencing Data
Get PDFUnderstanding the evolutionary features of cancer remains a difficult task. Each
tumor is characterized by a mutational landscape that often represents a set of dis-
tinct tumor cells that compete for resources in their microenvironment, and whose
heterogeneity can prevent the success of targeted therapies.
Our first project proposes an intuitive model that builds on results in Coalescent
Theory to better understand this heterogeneity, by estimating the mutation rates,
growth rates, and arrival times of each distinct cluster (i.e. subclone) of tumor cells.
We demonstrate its robustness to high degrees of error that are introduced when
performing single cell DNA sequencing (scDNAseq) and propose further methods to
accommodate the truncation of the neutral fractions of mutations that commonly
occur in scDNAseq data. We further expand our model to work with pseudo-bulk
sequencing data produced by a whole genome, low sequencing-depth process. We then
examine trends in arrival times among cancer types, and discuss how this information
could be used to provide clinical insights.
Our second project expands on the previous work to accommodate true bulk
sequencing data, where we modify an existing deconvolution method to estimate mu-
tational burdens in subclones. Simulation results show robustness to variations in
underlying evolutionary parameters, feasible clonal hierarchies, and mutation bur-
dens. We further show superior performance to existing methods in estimating the
arrival times of subclones. We demonstrate the use of our model in detecting patterns
of arrival times amongst a pan-cancer cohort of bulk sequencing samples.
Our third project proposes a clustering method (SFS-FIT) for scDNAseq data
when tumors follow a form of branching evolution. Our simulation results show
superior performance over current state-of-the-art scDNAseq clustering methods, and
we also note a dramatic deterioration in the performance of previous methods in
the presence of genetic drift. We then apply SFS-FIT to scDNAseq datasets and
compare our findings to previous approaches. Together, these projects provide a
general framework for inference of the evolutionary parameters of subclones and the
timing of these crucial past events in cancer
2.1 Condemning & Making Obsolete Biological Weapons
Get PDFDeveloped from discussions hosted by the Pathogens and Bioweapons Theme group at the Spirit of Asilomar.This entreaty was created as part of The Spirit of Asilomar and the Future of Biotechnology summit (February 23-26, 2025) in Pacific Grove, CA.This entreaty from the 2025 Asilomar conference condemns the development, stockpiling, and use of biological weapons. It is a call to the global community to recognize risks, capabilities, and our responsibilities, as modern biology and emerging technologies underpin both the security and betterment of our shared future. The Biological Weapons Convention enshrines the norm against malicious uses of biology, while robust detection, attribution, and response are the capabilities to erode the operational effectiveness of bioweapons and render them ultimately obsolete. Achieving this goal depends on these capabilities being resourced, deployed, and broadly accessible alongside support for rapid design and manufacturing of countermeasures and for the scientific advances that can positively shape the world. This entreaty also represents the view of Asilomar participants that a world free of biological weapons is an international pursuit
Beyond Flash Joule Heating: Advanced Non-equilibrium Synthesis and Electron Microscopy Characterization
No full textFlash Joule heating (FJH) has emerged as a highly efficient method for synthesizing a diverse array of advanced materials. This ultrafast, non-equilibrium technique has demonstrated significant potential in transforming various carbon sources into turbostratic flash graphene, synthesizing refractory materials such as metal carbides, converting 2H-phase MoS2 into 1T-phase MoS2, and extracting valuable hydrogen gas from plastic waste. Despite these impressive achievements, FJH still faces critical limitations, including its requirement for material conductivity, restricted generality, and an inability to facilitate non-solid-state reactions.
To overcome these limitations, several innovative strategies have been developed. One notable approach involves introducing immiscible conductive additives, specifically copper (Cu), into highly resistive amorphous boron (B), effectively enabling flash Joule heating. Surprisingly, during this modified process—termed plasma flash Joule heating (PFJH)—we observed spontaneous plasma generation, surpassing conventional temperature limits (~3000 K) and facilitating rapid crystallization of amorphous boron into crystalline form. Subsequent analysis revealed an unexpected and significant discovery: even after thorough removal of excess copper, copper atoms remained homogeneously embedded within the crystalline boron matrix, resulting in the unprecedented synthesis of copper-doped crystalline boron (Cu-B).
Further investigation using 3D micro electron diffraction demonstrated that the rapid heating and cooling intrinsic to PFJH prevented phase segregation, effectively trapping immiscible copper atoms within the boron lattice. This Cu-B composite exhibited notably altered mechanical properties, including a reduced modulus (~267 GPa) and Vickers hardness (~20 GPa), alongside a remarkable optical transition from indirect to direct bandgap. This unexpected change in bandgap structure induced pronounced photoluminescence (PL), revealing a novel material functionality unattainable through conventional methods. These findings highlight PFJH's potential as an ultrafast, non-equilibrium approach for synthesizing novel materials exhibiting extraordinary and unforeseen physical properties.
To expand the versatility of Joule heating further, we introduced an indirect heating method called Flash-within-Flash (FWF) Joule heating. This innovative approach greatly broadens the applicability of FJH, enabling the synthesis of 22 different compounds with properties comparable or superior to commercially available materials. Emphasizing sustainability, FWF addresses critical issues such as energy efficiency, minimal water consumption, scalability, and diverse material synthesis. FWF rapidly produces 10 transition metal dichalcogenides (TMDs), 3 Group-XIV dichalcogenides, and 9 non-TMD materials, with each synthesis completed within five seconds under ambient conditions. Moreover, FWF uniquely allows phase-selective synthesis and generates single-crystalline bulk powders. The enhanced tribological performance of FWF-produced MoSe2 compared to commercial materials further demonstrates the technique's effectiveness. Additionally, the versatility of FWF in facilitating atom substitution and doping establishes it as a robust protocol for general inorganic material synthesis.
Acknowledging the limitations associated with non-solid-state reactions, we developed Flash Vapor Deposition (FVD), a novel reactor design combining chemical vapor deposition (CVD) with the rapid heating principles of FWF Joule heating. Traditional CVD methods suffer from slow temperature ramping, restricting their effectiveness for rapid monolayer synthesis and complex coatings. Our redesigned FVD apparatus incorporates an outer tube containing carbon felt within an inert atmosphere, enabling rapid, uniform radiative heating. The inner tube, isolated from direct contact with heating components, contains reagents and substrates, with precise mass transport achieved through controlled gas flow. This innovative design facilitates the rapid synthesis of high-quality monolayer TMDs directly on substrates such as Si/SiO2.
Collectively, these advancements significantly enhance the versatility and efficacy of flash Joule heating, transforming it into a comprehensive, ultrafast, non-equilibrium synthesis platform. By overcoming previous limitations, these developed techniques pave the way for broad and impactful applications across various domains in materials science, positioning flash Joule heating as a critical enabler of future material innovations. The logical sequence of the PhD work and findings are summarized in Figure 1 for visualization
R3: Rice Research Review Fall 2025
No full textThis issue of R3: Rice Research Review focuses on research aligned with the university’s strategic plan, Momentous. The magazine covers four key areas: innovations in health, thriving urban communities, sustainable futures and responsible artificial intelligence (AI)
The Design, Synthesis, and Implementation of Novel Heteroannulation Reagents for the Rapid Construction of Nitrogen Heterocycles
No full textThe design, synthesis, and implementation of novel heteroannulation reagents for the synthesis of diverse and highly substituted 5- and 6-membered nitrogen-containing heterocycles is described. These reagents enable straightforward access to many biologically active N-heterocycle motifs from cheap and readily available starting materials. The motivation for this work was to develop mild and efficient methods for the synthesis of privileged N-heterocyclic scaffolds.
Chapter 1 discusses the inspiration for the development of O-vinyl hydroxylamines as well as their rapid and scalable synthesis. Many diversely substituted derivatives were synthesized and multiple approaches for their synthesis are described.
In Chapter 2, the application of the newly developed O-vinyl hydroxylamines for the synthesis of 7-azaindoles and 7-azaindolines from pyridine N-oxides is described. A broad substrate scope was demonstrated including the late-stage functionalization of active pharmaceutical ingredients. This work established an efficient and scalable approach to 7-azaindoles and 7-azaindolines, which are privileged structural motifs in pharmaceuticals.
Chapter 3 describes another example of the utility of O-vinyl hydroxylamines; the heteroannulation of alkynes for the synthesis of diversely substituted pyrroles. This work demonstrated a highly atom-economical and mild approach to pyrroles and further established O-vinyl hydroxylamines as powerful reagents for the synthesis of multiple N-heterocyclic motifs.
Finally, Chapter 4 describes the synthesis of halogenated O-cyclopropyl hydroxylamines and progress towards their utilization for the synthesis of 6-membered N-heterocycles. A scalable route for their synthesis has been developed and results towards the synthesis of highly functionalized pyridines with these reagents is discussed
Housing Quality Registry: An Initial Look Across Neighborhoods in the Houston Area
No full textThe Kinder Institute for Urban Research’s Housing Quality Registry is an effort to better understand the conditions and quality of housing throughout the Houston area. At present, limited data exists to understand the quality of where people are living, and the registry is attempting to close that gap in knowledge and spur action to address the problem by conducting an ongoing survey of area residents. The registry is an open-access survey so anyone can participate, but in addition, targeted recruitments were conducted in two specific neighborhoods: Kashmere Gardens and Alief. This research brief is the second brief reporting preliminary findings from the Houston Quality Registry. Its results build on the initial brief by focusing on neighborhood differences, and in doing so provide important insights into the conditions of two specific areas in the city. Based on the findings from this study and the differences observed across neighborhoods, these preliminary results point to an additional need for further data collection to more fully understand and elevate the differences and disparities in housing quality around the area
Promoting Materials in a Digital World
No full textPresented at 2025 Federal Depository Library ConferenceHow do you promote government publications in a digital world? Hear from a panel of librarians as they share examples of displays, guides, and other tools to promote electronic materials. Learn about what works well and the resources available and tools to help you judge the effectiveness of your efforts
Fabrication and Design of miniature endoscopic objectives with 2-Photon Polymerization Additive Manufacturing
No full textMiniaturization of optical elements has made significant advancements over the years for endoscopy applications. However, the current fabrication and integration of these miniature optics into fiber-based endoscopes remain inefficient, leaving room for optical variability. Additionally, many of these endoscopes use GRIN lenses, which exhibit aberrations that degrade image quality at the edges of the field. In this thesis, two 3D-printed optical elements fabricated via Two-photon polymerization (2PP) additive manufacturing are presented to enable greater design flexibility and seamless integration directly onto fiber tips, eliminating the need for multi-step assembly.
The first is a reflective mini objective for Optical Coherence Tomography (OCT), providing a 1 mm Rayleigh range and a full width at half maximum (FWHM) spot size of ≤40 µm. A reflective gold coating is applied via sputter coating after 2PP fabrication, providing high reflectivity at 1310 nm. The 3D-printed lens includes a high-precision mount that is glued to the distal end of a single-mode fiber. This lens-fiber assembly is then encapsulated in a catheter housing and connected to a Mach–Zehnder interferometer. To evaluate the performance of the system, the imaging assembly was assessed for its point spread function size and used for endoscopic imaging of the middle ear of a pig ex vivo.
The second 3D-printed system is a proof-of-concept rod-like refractive objective designed for fluorescence imaging. The design leverages small refractive index differences between fully polymerized and non- or partially polymerized resin. Lens power is achieved through a sequence of low-power lenses. As a result, it is possible to obtain a rod-like format similar to that of GRIN lenses, but with greater design flexibility and improved performance correction. A compact, proof-of-concept 3D-printed rod-like objective designed for operation in free space is presented. This structure targets a resolution of 4.473 µm to enable high-resolution fluorescence imaging of a mouse colon. To mitigate stray light and increase contrast, methods such as painting the rod-like objective and using heat shrink tubing are explored. A USAF resolution target is used to validate the performance of the objective. Furthermore, two photoresists—IP-S and IP-Visio—are evaluated to assess their suitability for fluorescence imaging. IP-Visio, which exhibits significantly lower autofluorescence, allows fluorescence microscopy to be performed with reduced background interference, thereby improving the ability to visualize dyed cellular structures. Finally, a fluorescent image of a descending colon of a mice is captured