Novel Materials Based on Poly(2-Oxazoline): Synthesis, Molecular Characterization, and Application in Drug Delivery(2023-06-01) [Dissertation]
Advisor: Hadjichristidis, Nikos
Committee members: Nunes, Suzana Pereira; Khashab, Niveen M.; Avgeropoulos, ApostolosPoly(2-oxazolines) (POxs) are a class of polymers that have gained significant interest in biomedical applications. POxs are mainly synthesized using living cationic ring-opening polymerization (CROP) under microwave irradiation. POxs are considered pseudo-polypeptides because they are similar to polypeptides. Nevertheless, they are more chemically stable than polypeptides due to the presence of tertiary amides. POxs The major goal of this research is to synthesize and characterize a novel well-defined amphiphilic block copolymer based on POxs. These amphiphilic block copolymers can comprise core cross-linked star polymers (CCS) or linear block copolymers. This research demonstrates and describes the synthesis of poly(2-methyl-2-oxazoline-b-poly(2,2'-(1,4-phenylene)bis-2-oxazoline)-co-(2-n-2-butyl-2-oxazoline)(PMeOx-b-P(PhenBisOx-co-ButOx) amphiphilic core cross-linked star polymers (CCS) based on POxs. The CCS polymers are synthesized via sequential CROP in two steps by synthesizing Poly(2-methyl-2-oxazoline) (PMeOx) as the living arms followed by cross-linking of the core 2, 2’-(1,4-phenylene)bis-2-oxazoline (PhenBisOx) as the cross-linker and 2-n-butyl-2-oxazoline (ButOx) as a hydrophobic monomer to form the core of the CCS polymers. In addition, this research will clarify the other kinds of amphiphilic copolymers based on aggregation-induced emission (AIE) fluorophores, tetraphenylethylene (TPE) as an initiator that have been synthesized by a combination of cationic and anionic ROP. First, the difunctional initiator TPE-(OH)2 was synthesized via McMurry coupling reaction. Then, two kinds of triblock copolymers, TPE-poly(2-methyl-2-oxazoline)-b-poly(ε-caprolactone) (TPE-(PMeOx-b-PCL)2) and TPE-poly(ε-caprolactone)-b-poly(2-methyl-2-oxazoline) (TPE-(PCL-b-PMeOx)2), were synthesized by altering the sequence of polymerization. The resulting polymers, CCS polymers and the triblock copolymers were loaded with the anticancer drug doxorubicin (DOX) and their in vitro properties, cytotoxicity, and drug release at different pH were studied. Furthermore, the resulting polymers were characterized by size exclusion chromatography (SEC), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). All results in this research showed that the amphiphilic block copolymers, the CCS polymers and the triblock copolymers could be suitable carriers for drug delivery systems.
Comprehensive Kinetic Study of Oxidative Coupling of Methane (OCM) over La2O3-based catalysts(2022-12) [Dissertation]
Advisor: Sarathy, Mani
Committee members: Gascon, Jorge; Farooq, Aamir; Chin, Ya-Huei (Cathy)Oxidative coupling of methane (OCM) represents a potentially viable method to convert methane directly into more desirable products such as ethane, and ethylene. In this dissertation, a comprehensive kinetic study of oxidative coupling of methane was performed over La2O3-based catalysts. An accurate and reliable gas-phase model is critical for the entire mechanism. The gas-phase kinetics was first studied using a jet-stirred reactor without catalyst. Both experiments and simulations were conducted under various operating conditions using different gas-phase models. Quantities of interest and rate of production analyses on hydrocarbon products were also performed to evaluate the models. NUIGMech1.1 was selected as the most comprehensive model to describe the OCM gas-phase kinetics and used for the next study. Next, microkinetic analysis on La2O3-based catalysts with different dopants was performed. The Ce addition has the greatest boost over the performance. The kinetics at low conversion regimes were analyzed and correlated to the catalysts’ properties. The activation energy for methane hydrogen abstraction was estimated, with the formation rate of primary products, which suggested that the initiation reaction steps were similar for La2O3-based catalyst. A homogeneous-heterogeneous kinetic model for La2O3/CeO2 catalyst was then constructed. By applying in situ XRD, the doping of CeO2 not only enhanced catalytic performance but also improved catalyst stability from CO2 and H2O. A wide range of operating conditions was investigated experimentally and numerically, where a packed bed reactor model was constructed based on the dimensions of experimental setup and catalyst characterization. The rate of production (ROP) was also performed to identify the important reactions and prove the necessity of surface reactions for the OCM process. Laser-induced fluorescence was implemented to directly observe the presence of formaldehyde. The last section includes the implementation of in situ laser diagnosis techniques at the near-surface region to solve the existing challenges. Raman scattering was implemented to quantitate the concentration profiles of major stable species near the surface and measure the in situ local temperatures at different heights above the catalyst surface, to study the kinetics transiting from the surface edge to the near-surface gas phase and provide a new perspective in OCM kinetic studies.
Investigation of Multiphase Spray Characteristics at High-temperature and High-pressure Conditions using Engine Combustion Network (ECN) standard injectors.(2022-12) [Dissertation]
Advisor: Im, Hong G.
Committee members: Farooq, Aamir; Sun, Shuyu; Kaario, Ossi TapaniTransportation sector is the backbone of today’s society and its being revolutionized by the development of electric cars. The subject of electrification of the fleet involves many challenges starting from building the require infrastructure all the way to securing raw material for batteries. Charging times and energy density are also two major challenges especially in heavy transportation. With current technologies it is impractical to use electric trucks as the advantages of direct injection engines are unmatched. A typical diesel car or truck has a very long range reaching around 1000 km using single fuel tank. The high energy density of fossil fuels is a corner stone of the heavy transportation sector. It is hard to imagine electric trucks without a breakthrough in battery technology that has very high energy density. High pressure combustion has great potential in extracting more power from liquid fuel. This is mainly attributed to the instant vaporization because of the vanishing surface tension once the fuel goes through a supercritical process, thus energy to vaporize the fuel is saved. Another advantage is in the better mixing that the highly dense and the highly diffused fluid possesses in that region. On the other hand, many of the modelling aspects requires to be investigated. For example, which equation of state predicts the correct density and what are the effect of the pressure and temperature dependant fluid properties on the spray development. To isolate the effect of the high pressure combustion from other possible modelling effects and to facilitate the investigation, simulations using both OpenFOAM and CONVERGE were conducted. First the morphologies of Spray C was numerically characterized under high-temperature and high-pressure conditions. The Volume of fluid method captured the cavitation properly upon using 7.8 μm mesh. The mass flow rate and the transient of the injection process were accurately captured. Implementation of appropriate high pressure models using OpenFOAM to account for real fluid effects showed that three-parameter Redlich-Kwong Peng-Robinson equation of state were superior than two-parameters realfluid equation of state. The correctness of fuel density and viscosity is dependant of the equation of state with ideal gas equation of state being inferior to the realfluid equation of state. The combustion characteristics of Spray A were investigated using coupled Eulerian-Lagrangian approach. This approach demonstrated the ability of the modeling framework in predicting wide variety of parametric effects.
Investigation and Functional Characterization of Arabidopsis WLIM2A (LIN11, ISL1, MEC3) and Universal Stress Protein (USP1) in Plant Immunity(2022-11-27) [Dissertation]
Advisors: Hirt, Heribert; Rayapuram, Naganand
Committee members: Arold, Stefan T.; Blilou, Ikram; Colcombet, JeanMitogen-activated protein kinases (MAPKs) are a family of highly conserved serine/threonine protein kinases which link upstream receptors to their downstream targets. These targets can be localized in the cytoplasm or the nucleus. Pathogens produce pathogen-associated molecular patterns (PAMPs) that are known to trigger the activation of MAPK cascades. In plants, MAPK signaling cascades regulate development and cellular processes such as stress responses, immunity, and apoptosis by means of the phosphorylation of specific targets. Phosphoproteomics analysis of PAMP-induced Arabidopsis plants led to the identification of several putative MAPK targets. USP1 (Universal Stress Protein A) (At1g11360) and WLIM2A (At2g39900) are two potential phosphorylation targets of MAPKs, and are the focus of this thesis. So far, little is known about their role in plant immunity. CRISPR-Cas9 generated knockout usp1 mutant lines enhanced resistance to infection by Pst DC3000, usp1 mutant showed a reduced level of apoplast reactive oxygen species accumulation and upregulation of defense marker genes such as WRKY29 and FRK1. Transcriptome analyses revealed that immune hormone signaling genes such as salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) are differentially regulated. These hormones are responsible for primary defense responses against biotrophic and necrotrophic pathogens. Although the physiological role of USP1 has been established, the biochemical and molecular functions are unknown. We discovered a new role for USP1, demonstrating that it functions as a molecular chaperone and is involved in thermal priming. Overall, these data show that phosphoprotein USP1 plays an important role in orchestrating plant immunity. CRISPR-Cas9 generated knockout wlim2a mutant showed susceptibility to infection by Pst DC3000. wlim2a mutants showed a reduced level of apoplast reactive oxygen species accumulation and upregulation of defense marker genes such as WRKY29 and FRK1. Transcriptome analyses revealed that immune hormone signaling genes such as salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) are differentially regulated in wlim2a mutants. These hormones are responsible for primary defense responses against biotrophic and necrotrophic pathogens. wlim2a mutants show enhanced fungal infection by Botrytis cinerea. Overall, the data shows that WLIM2A phosphorylation is important during plant immunity.
A 5D Magnetic Tracking System for Placement Verification of Umbilical Catheters and Endotracheal Tubes in Neonates(2022-11-25) [Dissertation]
Advisor: Kosel, Jürgen
Committee members: Salama, Khaled N.; Inal, Sahika; Carrara, SandroThe use of subcutaneous medical devices has advanced the field of clinical medicine and surgery. However, localizing devices internally requires imaging techniques such as x-ray or ultrasound. A novel 5D magnetic tracking system for subcutaneous medical catheters is presented, providing the capability for precise device localization in an extremely compact and portable pocket-size format. It is entirely benign, avoids x-rays, and can be used to immediately confirm the proper instrument placement. The magnetic tracking system has been implemented on umbilical catheters and endotracheal tubes and is characterized by bench-test, cadaveric and in-vivo studies. The systems consist of a magnetic tip fixed to the distal end of the subcutaneous device, as well as a Magnetic Sensing Device that utilizes magnetic field sensors to localize the magnetic tip. Various Magnetic Sensing Devices have been developed, each with a specific use case in mind within the clinical environment. The magnetic tip is made from a soft, flexible, and lightweight magnetic composite material that is capable of sustaining a high magnetic remanence field whilst also being non-cytotoxic. The bench tests show high localization accuracy for a distance up to 4 cm. The accuracy is slightly reduced during cadaveric and in-vivo tests, due to external factors impacting the application, such as the dermal surface topography and the method of establishing the reference frame before radiographic imaging. A bias circuit has been developed and implemented to increase the operational depth of the magnetic tracking system and prevents sensor saturation at close distances. The magnetic tracking system has shown to be robust in performance and functionality in real-world clinical applications, and with its intuitive approach and portability, it has the potential to make real-time subcutaneous device tracking widely accessible.
Novel Linear and Star Poly(vinylidene fluoride)-Based Polymers: Synthesis, Characterization and Applications(2022-11-24) [Dissertation]
Advisor: Hadjichristidis, Nikos
Committee members: Nunes, Suzana Pereira; Cavallo, Luigi; Ameduri, BrunoPoly(vinylidene fluoride) PVDF is a semi-crystalline fluoropolymer that attracted researchers' attention more than a decade ago due to its remarkable properties, such as mechanical strength, thermal stability, chemical resistance, good processability, and excellent aging resistance. Due to these excellent properties, PVDF is applied in many applications such as membranes and filtration, biomedical applications, drug delivery, batteries, energy generation, energy storage, sensors, actuators, and energy harvesting applications. The dissertation was inspired by PVDF’s outstanding properties and applications. First of all, the effect of chain topology of on the crystallization and polymorphism between linear and star PVDF homopolymers were studied. Well-defined linear and stars PVDF homopolymers architectures were synthesized by reversible addition−fragmentation chain transfer (RAFT) polymerization. The non-isothermal crystallization study showed an increase in the amount of ferroelectric β-phase with respect to the paraelectric α-phase as the number of arms in the PVDF stars increases. This finding is explained by the increased topological complexity in the stars of several arms, which leads to the preferential formation of the less thermodynamically stable ferroelectric β-phase. Moreover, the isothermal crystallization kinetics of the PVDF stars was faster than the linear PVDF as a result of their speedier nucleation. Secondly, we report the synthesis of poly(n-isopropylacrylamide)-b-poly(vinylidene fluoride) (PNIPAM-b-PVDF), amphiphilic block copolymers with linear and star architectures by RAFT sequential living polymerization. Due to the presence of a lower critical solution temperature (LCST) for PNIPAM (coil-globule transition around 32 °C), the synthesized PNIPAM-b-PVDF block copolymers have thermo-responsive behavior, therefore, potential application in the fabrication of thermo-responsive membranes. All fabricated membranes by nonsolvent-induced phase separation (NIPS) method exhibited thermo-responsive behavior with water permeability and PEG rejection experiments. Moreover, the several heating-cooling cycles showed that the thermal-responsive behavior of these membranes are reversible and stable. Finally, a suggested potential future work is given to synthesize other PVDF-based block copolymers via sequential living polymerizations.
Wide Bandgap Semiconductor Device Design via Machine Learning(2022-11-02) [Dissertation]
Advisor: Li, Xiaohang
Committee members: Elatab, Nazek; Gan, Qiaoqiang; Ryou, Jae-HyunThe research of III-nitride wide-bandgap semiconductor devices, such as laser diodes (LDs), ultra-violet (UV) light-emitting diodes (LEDs), and high electron mobility transistors (HEMTs), has recently increased. Numerous opportunities exist for performance improvement in the wide bandgap semiconductor device structure, including material selection, compound compositions, polarization effects, and layer thicknesses. On the other hand, they can make optimization more challenging. It still takes a lot of resources to analyze and test complicated structures in a systematic manner. This dissertation creates a new path for device design by using TCAD and machine learning to deliver quick forecasts of III-nitride semiconductor device performance. The dissertation includes three major components. In Chapter 2, the TCAD-assisted HEMT device design is discussed. We demonstrate the performance improvement of using the new material BAlN as an interlayer in GaN/AlGaN HEMT devices and compare the various interlayer design alternatives for HEMTs. In chapter 3, we propose asymmetrical p-AlGaN/i-InGaN/n-AlGaN tunnel junctions (TJs) by combining machine learning (ML) with TCAD calculations. The resistances for 22254 various TJ structures were predicted by the model, which creates a tool for real-time TJ resistance prediction. Based on our TJ predictions, we proposed asymmetric TJ with higher Al content in the p-layer and lower TJ resistance. In Chapter 4, using the stacked XGBoost/LightGBM algorithm, we thoroughly examined the superlattice (SL) electron blocking layer (EBL) for AlGaN deep ultra-violet (DUV) LEDs. Based on the ML model, we suggest a low Al-content SL-EBL (1 nm/5 nm Al0.7Ga0.3N/Al0.58Ga0.42N) that is simpler, experimentally realizable and can greatly improve carrier transport. Additionally, we examine the prediction data and show how the composition and thickness affect the improvement of the IQE. The work contributes to the advancement of using SL-EBLs for high-efficiency DUV LEDs by providing methodical research on SL-EBLs. This dissertation presents novel approaches to the design of electrical and optical wide bandgap semiconductor devices, which opens up a new avenue for future research. It is possible that it might be used in a broad variety of fields, including illumination, sensing, disinfection, and power devices.
Nesting Ecology and Conservation of Sea Turtles in the Saudi Arabian Red Sea(2022-11) [Dissertation]
Advisor: Berumen, Michael L.
Committee members: Jones, Burton; Alafifi, Abdulkader Musa; Brainard, Russell E.In the Saudi Arabian Red Sea, two of the seven species of sea turtles are known to nest and forage along the coast, the hawksbill turtle (Eretmochelys imbricata) and the green turtle (Chelonia mydas). As a result of some life history characteristics, sea turtles are particularly vulnerable to anthropogenic impacts. Under Saudi Arabia’s Vision 2030 and the recent opening of its borders to recreational tourists, the country aims to develop several large-scale projects along the Red Sea coast, locally known as “giga-projects”. Thus, imminent pressures from coastal development highlight the urgency needed for multi-country cooperation in protecting sea turtles in the region. This dissertation aims to establish some baseline data and protocols for future work to meet the data needs of the relevant conservation authorities in Saudi Arabia. In particular, this thesis contributes new and important information to some of the identified knowledge gaps for the Red Sea region, including sea turtle habitat use, threat assessment (plastic and heavy metal pollution), and evaluating hatching success. I used satellite telemetry to understand foraging home ranges of hawksbill and green turtles, post-nesting migrations, and inter-nesting habitat use of green turtles. Additionally, I used photo identification to understand the abundance and behavior of turtles at a Rabigh fringing reef, in the central Red Sea. I assessed two anthropogenic contaminants as a threat to Red Sea turtles: heavy metal contamination and plastic ingestion. Heavy metal concentrations in the sand were evaluated at the largest green turtle rookery in Saudi Arabia, Ras Baridi, which is located next to a cement factory. I also assessed the concentration of heavy metals in the tissues of dead hatchlings found at Ras Baridi. Additionally, I studied plastic ingestion in ten deceased turtles found along the Saudi Arabian Red Sea. In my last data chapter, I assessed the hatching success of green turtle nests, and investigated clutch relocation as a possible method of increasing success. The final chapter summarizes the results from this research in the context of the 2004 PERSGA Marine Turtle Conservation Plan, and provides possible conservation strategy recommendations to protect Red Sea turtles
Visualization of the combustion process using a narrow throat pre-chamber geometry for a heavy-duty engine(2022-11) [Dissertation]
Advisor: Turner, James W. G.
Committee members: Magnotti, Gaetano; Finkbeiner, Thomas; Armas, OctavioLean combustion is one of the most applied methods to increase engine efficiency and maintain a good trade-off with engine emissions. The pre-chamber combustion (PCC) is one of the most promising combustion concepts to extend the lean operating limits of the engine. The Narrow throat pre-chamber has shown long lean limit extension than other ignition sources. The pre-chamber combustion and main-chamber combustion were studied in a Heavy-Duty optical engine using methane fuel to determine the generalities of the combustion process in the two volumes: pre- and main chamber. The combustion process was recorded using three collection systems: (a) Natural Flame Luminosity (NFL), (b) OH* Chemiluminescence, and (c) CH* Chemiluminescence. Additionally, the effect of three pre-chamber geometrical parameters, volume, nozzle area and throat diameter, on the pre-chamber combustion was also addressed in this research. The generalities of the pre-chamber combustion inside the pre-chamber exhibited a flame propagation nature for the combustion process, with high propagation velocities inside the throat. The main chamber process for the reference narrow throat pre-chamber exhibited defined jets from six of the twelve jets corresponding to the bottom row of nozzles for the reference pre-chamber. Regarding the geometrical parameters, the throat area to nozzle area ratio determines the propagation mode for the main chamber, evolving from only six jets and ultra-low throat intensity for ultra-low ratios to, twelves jethe ts with same penetration and high throat intensity for ratios above one.
Microstructural Analysis and Engineering of III-Nitride-Based Heterostructures for Optoelectronic Devices(2022-11) [Dissertation]
Advisor: Ohkawa, Kazuhiro
Committee members: Ooi, Boon S.; Roqan, Iman S.; Sakai, AkiraAfter the invention of the high-efficiency blue light-emitting diode (LED) at the end of the twentieth century, a new generation of light-emitting devices based on III-nitrides emerged, showcasing the capabilities of this semiconductor family. Despite the current limitations in the fabrication of III-nitrides, their optical and electronic properties still place them as some of the most promising semiconductors to continue the development of optoelectronic devices. To take full advantage of the versatility offered by these materials, the fabrication of novel III-nitride-based devices demands rigorous control of all of its stages. From the initial deposition of the materials, which involves controlling the composition and size of often complex heterostructures, up to the microfabrication processing used to create a final device, any deficiency occurring will negatively impact the performance of the device. Most of the time, these deficiencies reflect in microscopic defects, hindering their detection and identification of their origin. Without such knowledge, the deficiencies cannot be fixed, stalling the improvement of the device fabrication process and, consequently, its performance. This dissertation presents a variety of methodological approaches to characterize, from a microstructural point of view, different properties of novel III-nitride-based heterostructures and devices. The characterizations include studying the structure, interface, composition, and crystalline defects of different heterostructures and evaluating the microfabrication quality of microscopic LEDs. The results of the different characterizations contributed to developing novel LED and photocatalytic devices, for example, a single-quantum-well InGaN-based red LED with a high color purity, a monolithic phosphor-free white LED, microscopic green LEDs with a size smaller than 5×5 μm$^2$, and metal oxide/GaN-based photocatalysts with improved resilience to photocorrosion. The analyses and results presented in this dissertation strongly relied on the analytical capabilities offered by transmission electron microscopy, which proved to be a convenient and versatile tool for the characterization of many aspects related to the fabrication of III-nitride-based optoelectronic devices.
Nutrition and organism flows through tropical marine ecosystems(2022-11) [Dissertation]
Advisor: Jones, Burton
Committee members: Berumen, Michael L.; McCabe, Matthew; Ellis, JoanneIn tropical seascapes, coral reefs often exist in proximity to marine vegetated habitats such as seagrass, mangroves, and macroalgae. This habitat mosaic offers the possibility for connection and exchange of both organisms and nutrition between habitats, mediated by biological and physical processes. This dissertation examines flows of organisms and nutrition between coral reefs and tropical vegetated habitats in the central Red Sea through 3 different mechanisms: 1) Use of multiple habitat types by tropical marine fishes, 2) Transport of algal material to coral reefs via the foraging behavior and movements of herbivorous fishes, and 3) Physical flow of water between coastal habitats. The results of this thesis suggest that coastal tropical habitats maintain a variety of ecological links at different spatial and temporal scales. A large fraction (36%) of fish species found on coral reefs are also found in at least one marine vegetated habitat in the central Red Sea, with many species mainly living in vegetated habitats as juveniles. This demonstrates the value of mangrove, seagrass, and macroalgae habitats to coral reef fishes, and suggests that many species make ontogenetic migrations between reef and non-reef habitats through their lives. Two species of herbivorous reef fishes (Naso elegans and N. unicornis) were found on coral reefs with algae in their guts which likely originated from nearby Sargassum-dominated macroalgae canopies, representing a fish-mediated, cross-habitat flux of nutrition from macroalgae habitats to coral reefs. Finally, we used a combination of remote sensing, a dye tracer study, and in-water measurements to observe water movement from shallow seagrass and mangrove habitats to nearby lagoon and coral reef habitats. Water exiting seagrass and mangrove habitats had altered concentrations of various nutrients (such as increased particulate organic carbon or decreased dissolved nutrients), suggesting that Red Sea mangroves and seagrasses change nutrient concentrations in water and the movement of water from these habitats to coral reefs could supply reefs with an allochthonous source of nutrition. These various linkages, controlled by a range of physical and biological processes, highlight the interconnected nature of tropical coastal ecosystems, and thereby the need to conserve whole habitat mosaics in the pursuit to protect coral reefs and maintain healthy and functioning coastal ecosystems.
Hybrid Arborescent Polypept(o)ides for Biomedical Applications(2022-11) [Dissertation]
Advisor: Hadjichristidis, Nikos
Committee members: Khashab, Niveen M.; Nunes, Suzana Pereira; Gauthier, MarioThis work reports a novel biocompatible and biodegradable arborescent amphiphilic polypept(o)ides-based polymer poly(γ-benzyl L-glutamate)-co-poly(γ-tert-butyl L-glutamate)-g-polysarcosine (P(BG-co-Glu(OtBu))-g-PSar) as a smart dual-responsive targeting drug vehicle. The synthesis pathway in this work highlighted the grafting reaction improvement of the polypeptides core and using polysarcosine (PSar) corona as a coating agent. The responsiveness of the polymer is caused by the pH sensitivity of the polypeptides and the reducible linker introduced between the core and corona. While adding the tripeptides arginine, glycine, and aspartate (RGD) as a ligand on the unimolecular micelles’ surface increases the targeting ability of the polymer. During the building of the arborescent, the coupling sites were controlled by using γ-tert-butyl L-glutamate (Glu(OtBu)-NCA) as a second monomer besides γ-benzyl L-glutamate (BG-NCA) since the deprotection conditions are different for Bz and tBu groups. Knowing the coupling sites provides accuracy in calculating the molecular weight (MW) of graft polymers since it facilitates the determination of the grafting yield (Gy). The arborescent unimolecular micelles were formulated by coating the hydrophobic core with PSar hydrophilic corona. The distribution of the coupling sites on the substrates in the last generation yielded end-grafted and randomly-grafted unimolecular micelles. A comparison between those micelles by DLS, TEM, and AFM revealed that the end-grafted micelles showed more uniformity in terms of morphology and size distribution. Also, the surface modification achieved via RGD addition increased the shape uniformity and contributed to avoiding the particles’ aggregation. The sizes and shapes of end-grafted unimolecular micelles match the drug delivery systems (DDSs) requirements. Doxorubicin (DOX) was encapsulated physically into the unimolecular micelles to study the drug loading capacity (DLC) and drug loading efficiency (DLE). The maximum DLC and DLE were 14% and 28% w/w, respectively. The drug release profiles were investigated in healthy- and cancer-mimicking media. The results showed that in cancer-mimicking microenvironment (low pH and high glutathione (GSH) content), the drug diffused out the micelles faster. In addition, a slower drug release was noticed for RGD decorated unimolecular micelles. Finally, the biocompatibility, cytotoxicity, and cellular uptake of the unimolecular micelles were studied. The obtained results were promising as the arborescent unimolecular micelles showed excellent biocompatibility; meanwhile, the DOX-loaded unimolecular micelles have good cytotoxicity compared to free DOX. RGD targeting ligand contributes to increasing the cellular uptake and supports the sustained release.
Multivariate Functional Data Analysis and Visualization(2022-11) [Dissertation]
Advisor: Genton, Marc G.
Committee members: Ombao, Hernando; Alouini, Mohamed-Slim; Shang, HanlinAs a branch of statistics, functional data analysis (FDA) studies observations regarded as curves, surfaces, or other objects evolving over a continuum. Although one has seen a flourishing of methods and theories on FDA, two issues are observed. Firstly, the functional data are sampled from common time grids; secondly, methods developed only for univariate functional data are challenging to be applied to multivariate functional data. After exploring model-based fitting for regularly observed multivariate functional data, we explore new visualization tools, clustering, and multivariate functional depths for irregularly observed (sparse) multivariate functional data. The four main chapters that comprise the dissertation are organized as follows. First, median polish for functional multivariate analysis of variance (FMANOVA) is proposed with the implementation of multivariate functional depths in Chapter 2. Numerical studies and environmental datasets are considered to illustrate the robustness of median polish. Second, the sparse functional boxplot and the intensity sparse functional boxplot, as practical exploratory tools that make visualization possible for both complete and sparse functional data, are introduced in Chapter 3. These visualization tools depict sparseness characteristics in the proportion of sparseness and relative intensity of fitted sparse points inside the central region, respectively. Third, a robust distance-based robust two-layer partition (RTLP) clustering of sparse multivariate functional data is introduced in Chapter 4. The RTLP clustering is based on our proposed elastic time distance (ETD) specifically for sparse multivariate functional data. Lastly, the multivariate functional integrated depth and the multivariate functional extremal depth based on multivariate depths are proposed in Chapter 5. Global and local formulas for each depth are explored, with theoretical properties being proved and the finite sample depth estimation for irregularly observed multivariate functional data being investigated. In addition, the simplified sparse functional boxplot and simplified intensity sparse functional boxplot for visualization without data reconstruction are introduced. Together, these four extensions to multivariate functional data make them more general and of applicational interest in exploratory multivariate functional data analysis.
Flexible Extremal Dependence Models for Multivariate and Spatial Extremes(2022-11) [Dissertation]
Advisor: Huser, Raphaël
Committee members: Bolin, David; Jasra, Ajay; Tawn, Jonathan AClassical models for multivariate or spatial extremes are mainly based upon the asymptotically justified max-stable or generalized Pareto processes. These models are suitable when asymptotic dependence is present. However, recent environmental data applications suggest that asymptotic independence is equally important. Therefore, development of flexible subasymptotic models is in pressing need. This dissertation consists of four major contributions to subasymptotic modeling of multivariate and spatial extremes. Firstly, the dissertation proposes a new spatial copula model for extremes based on the multivariate generalized hyperbolic distribution. The extremal dependence of this distribution is revisited and a corrected theoretical description is provided. Secondly, the dissertation thoroughly investigates the extremal dependence of stochastic processes driven by exponential-tailed Lévy noise. It shows that the discrete approximation models, which are linear transformations of a random vector with independent components, bridge asymptotic independence and asymptotic dependence in a novel way, whilst the exact stochastic processes exhibit only asymptotic independence. Thirdly, the dissertation explores two different notions of optimal prediction for extremes, and compares the classical linear kriging predictor and the conditional mean predictor for certain non-Gaussian models. Finally, the dissertation proposes a multivariate skew-elliptical link model for correlated highly-imbalanced (extreme) binary responses, and shows that the regression coefficients have a closed-form unified skew-elliptical posterior with an elliptical prior.
Machine learning in hardware via trained metasurface encoders: theory, design and applications(2022-11) [Dissertation]
Advisor: Fratalocchi, Andrea
Committee members: Moshkov, Mikhail; Ooi, Boon S.; Kivshar, YuriThe development of modern Machine Learning (ML) frameworks trained on large datasets established a rapid increase in the performance of cognitive computing algorithms for a wide range of applications. However, due to the processing capacity restrictions of electronics, scaling up the existing state-of-the-art is currently meeting a bottleneck. Recently, flat-optics arose as a promising alternative to conventional electronics due to intrinsic parallelism, tuneability, and high-speed of optical computations. Finding scalable, highly effective designs that can tolerate fabrication defects brought on by nanoscale manufacturing processes and the demanding design specifications of the end task is one of the main hurdles of flat optics. In this study, we address this problem by introducing an end-to-end optimization methodology that is robust to fabrication intolerance and performance losses due to material absorption and can simultaneously optimize in tens of millions of degrees of freedom. The core of this technology is universal approximators, a single surface of optical nanoresonators mathematically equivalent to a single layer of an artificial neural network (ANN). For these structures, we provide theoretical guarantees for universal approximation, an ability to approximate arbitrary defined material's transfer function. We validate this framework's capability by creating several optical components achieving near unity efficiencies for vectorial light processing with broadband spectral responses and pre-defined wavefront characteristics. In addition, leveraging the high-dimensional capabilities of that system, we present a novel concept of spectral-informed imaging, which does not require the use of spectral analyzers or complex mechanical filters but uses an artificial-intelligence engineered, "hardware" flat-optics surface that processes spectral encoding at the speed of light inside silicon (Si) metasurface.
Drop-impact Singular Jets, Acoustic Sound and Bouncing with Filaments(2022-10-30) [Dissertation]
Advisor: Thoroddsen, Sigurdur T
Committee members: Lacoste, Deanna; Mishra, Himanshu; Castrejon-Pita, Jose RafaelThis dissertation talks about the dynamics of the drop impact in two parts, the impact of the drop on the deep liquid pool with singular jet and sound emission, and the bouncing drop with filaments on the superhydrophoic solid surface. First, we use experiments and simulations to study drop impacts on a deep liquid pool, with a focus on fine vertical jetting and underwater sound emission from entrapped bubbles, during the rebounding of the hemispherical crater. The much larger parametric complexity introduced by the use of two immiscible liquids, compared to that for the same liquid, leads to an extended variety of compound-dimple shapes. The fastest jet occurs from the rebounding of a telescope dimple shape without bubble pinch-off, at around 45 m/s, which leaves a toroidal micro-bubbles from the air-cusp at the base of the dimple. The finest jets have diameter of only 12 µm. A new focusing mechanism for singular jetting from collapsing drop-impact craters is then proposed based on high-resolution numerical simulations. The fastest jet is confined in a converging conical channel with the entrained air sheet providing a free-slip outer boundary condition. Sound can be emitted from the oscillation of the entrapped dimple-bubble, while the tiny bubble from the initial impact is induced to oscillate with the entrapped bubble, triggering the double crest of the acoustic signal. We track the compression of the bubble volume from the high-speed imaging and relate it to the hydrophone signal. In the second part, we investigate the impact of a polymeric drop on a superhydrophobic solid substrate with micropillar structure. The drop spreads on the substrate, wets the tops of the pillars, and rebounds out of the superhydrophobic soild surface. Numerous liquid filaments are stretched from the liquid drop to the attached adjacent pillars, and minuscule threads would be left on the top of the pillars using the inclined superhydrophobic solid surface. The well-organized exposed polymer threads are left on the top of the pillars after solvent evaporation. The thickness of the deposition of filament bundles using the bouncing method are thinner than those formed by drop evaporation or drop rolling from SEM (scanning electron microscope) observation.
New tools for the description of intra/inter laminar coupling in laminates: experimental evidence and modeling approaches(2022-10-30) [Dissertation]
Advisor: Lubineau, Gilles
Committee members: Moran, Brian; Turon, Albert; Santamarina, CarlosCarbon fiber reinforced polymers (CFRP) are widely used in advanced industry, like aerospace, modern sports, and automobile. Compared to traditional metals, CFRP laminates have a higher strength to weight ratio and better corrosion resistance. Because of the heterogeneous and anisotropic behavior of CFRP laminates, their damage mechanisms include fiber/matrix debonding, diffuse matrix damage, matrix cracking, fiber breakage, and delamination. These damage mechanisms develop in different length scales and are deeply coupled with each other, especially the intra/interlaminar damage coupling. Therefore, a well understanding of intra/interlaminar damage coupling is vital for predicting integrity of laminated structures. The dissipation during delamination process includes the intrinsic (depends on local material) and extrinsic (depends on non-local structural effect) parts. The intrinsic part could be straightly calibrated through standard test, while the non-local extrinsic part is usually not fully elaborated. In this work, we will devote to fill the gap, both in experiments and simulation, which will encounter the effect of intra/inter laminar damage coupling on the extrinsic dissipation during delamination process. The non-local extrinsic dissipation is usually triggered by the intra/inter laminar damage coupling, depending the loading conditions and curing process. In this thesis, we first design a two step test (tensile-DCB) on a cross ply to quantitatively study the influence of intralaminar damage on interlaminar performance. The intralaminar damage effect has proven to be two-fold on the interlaminar performance as the preset transverse cracks could lead to fiber bridging and also local delamination. Secondly, we proposed a hybrid cohesive element to encounter the intra/interlaminar coupling in a pragmatic local way. The hybrid cohesive element not only calculate the out-of-plane separation but also the in-plane strain of the two surfaces of the interface elements, which could be used to estimate the intralaminar damage of adjacent layers. Meanwhile, the coupling damage in multidirectional delamination is also investigated through a modified double cantilever beam (DCB) test. A general hybrid cohesive element is developed, in which the influence of delamination direction on the local apparent toughness is also considered. Last but not least, we implement an experimental campaign to study the curing process effect on fiber bridging development in unidirectional mode I fracture. Through these studies, the intra/interlaminar damage coupling mechanism is better understood and the hybrid cohesive element prove its potential on simulation efficiency and robustness.
Acetyl-CoA Carboxylase Alpha the Rate-limiting Enzyme of Fatty Acid Synthesis Modulates Mitotic Progression and Chromosome Segregation(2022-10) [Dissertation]
Advisor: Fischle, Wolfgang
Committee members: Frøkjær-Jensen, Christian; Chodasiewicz, Monica; Verdin, EricWhile metabolic enzymes inside the cell nucleus were initially considered “contaminants”, recent evidence has shown that these fulfill essential functions in epigenetic regulation. Indeed a model is emerging in which local metabolite pools influence various nuclear processes. In this model, the subcellular distribution and organization of metabolic factors have a crucial role in the complex logic and regulation of nuclear functions. Cancer cells exploit nuclear metabolic enzymes to alter the synthesis and utilization of metabolites that sustain their transcriptional programs allowing their abnormal proliferation. Understanding the precise molecular mechanisms that modulate the distribution of nuclear metabolic enzymes and their related biological functions has the potential to uncover novel therapeutic vulnerabilities of malignant cells. Here, we describe an unexpected subcellular distribution of acetyl-CoA carboxylase alpha (ACC1), the rate-limiting enzyme of de novo fatty acid synthesis. We found that in cancer cells, ACC1 is not restricted to the cytoplasm. Instead, at mitosis and after the nuclear envelope breakdown, it transiently redistributes into filament-like structures that contact condensed chromosomes. Simultaneous profiling of protein-protein and -DNA interactions defined ACC1 association with different factors associated with the cellular machinery that modulates chromosome segregation, including the centromere, the kinetochore, and the fibrous corona. Inducible depletion of ACC1 resulted in altered mitotic progression and accumulation of chromosome segregation defects – effects that are abolished only with the reconstituted expression of catalytically active mutants of ACC1 but not its inactive counterparts. We further found that the abundance of malonyl-CoA – the main product of ACC1 enzymatic activity – gradually increases towards the onset of mitosis, being a significant determinant for histone malonylation. Overall we uncovered a previously unknown function of ACC1 in modulating mitotic progression and chromosome segregation. Our findings support a model where local niches of malonyl-CoA might act as signal molecules for faithful chromosome segregation.
Solvent-Resistant and Thermally Stable Polymeric Membranes for Liquid Separations(2022-10) [Dissertation]
Advisor: Nunes, Suzana Pereira
Committee members: Hadjichristidis, Nikos; Rosado, Alexandre S.; Lively, Ryan P.Membrane technology has great potential to complement traditional energy-intensive molecular separation processes such as distillation, with the advantage of low footprint generation. However, this would only be achieved with the development of better membranes able to operate in challenging conditions, including combinations of organic solvents, high temperatures, extreme pHs, and oxidative environments. This dissertation aims to use high-performance polymeric materials that can withstand temperatures of 120 °C in polar aprotic solvents like N,N-dimethylformamide as separation membranes, using different crosslinking strategies and alternative routes for commercially available material processing. The thesis will be divided into two main approaches. The first approach will start from soluble polyimides as precursors, with designed functionalities that allow post-membrane modifications, such as chemical crosslinking, thermal crosslinking, and thermal rearrangement to enhance the material's chemical resistance. The focus will be on the polyimide synthesis by an alternative one-step room-temperature polyhydroxyalkylation reaction. The chemical and thermal crosslinking take place without involving the imide bond, by incorporating a highly tunable functional group (isatin) in the synthesis of the materials. Propargyl as a pendant group will be used for the thermal crosslinking, and hydroxyl group for the thermal rearrangement. In all cases, the obtained membranes were stable in common organic solvents at 120 °C. The second approach will start from intrinsically solvent-resistant and commercially available poly(aryl ether ketone)s, turned into membranes by a closed-loop modification-regeneration strategy, to address long-term separations in organic solvents at high temperatures. We present for the first time porous poly(aryl ether ketone) flat-sheet and hollow fiber membranes prepared without the use of strong acids or high temperatures. Two methodologies are proposed. The developed strategies shall contribute toward avoiding the regular consumption of new materials and waste generation since the polymer used does not require crosslinking for its stability under organic solvents.
Synergistic Multi-Source Ambient Radio Frequency and Thermal Energy Harvesting for IoT Applications(2022-10) [Dissertation]
Advisor: Shamim, Atif
Committee members: Salama, Khaled N.; Lubineau, Gilles; Wu, KeThe Internet of Things (IoT) is an infrastructure of physical objects connected via the Internet that can exchange data to achieve efficient resource management. Billions of devices must be self-powered and low-cost considering the massive scale of the IoT. Thus, there is a need for low-cost ambient energy harvesters to power IoT devices. It is a challenging task since ambient energy might be unpredictable, intermittent and insufficient. For example, solar energy has limitations such as intermittence and unpredictability despite utilizing the highest power availability and relatively mature technology. Designing a multi-source energy harvester (MSEH) based on continuous and ubiquitous ambient energy sources might alleviate these issues by providing versatility and robustness of power supply. However, combining several energy harvesters into one module must be done synergistically to ensure miniaturization, compactness and more collected energy. Also, additive manufacturing techniques must be used to achieve low-cost harvesters and mass manufacturability. This dissertation presents two different kind of ambient energy harvesters, namely radio frequency energy harvester (RFEH) and thermal energy harvester (TEH). Each harvester is individually optimized and then synergistically combined into a MSEH. First, RFEH is designed for triple-band harvesting (GSM900, GSM1800, 3G2100) using the antenna-on-package concept and fabricated through 3D and screen printing. TEH collects energy from temperature fluctuations of ambient environment through a combination of thermoelectric generators and phase change materials. It is adapted specifically for the desert conditions of Saudi Arabia. Later, TEH and RFEH are combined to realize MSEH. Smart integration is achieved by designing a dual-function component, heatsink antenna, that serves as a receiving antenna of RFEH and a heatsink of TEH. The heatsink antenna has been optimized for both antenna radiation performance and heat transfer performance. Field tests showed that the MSEH can collect 3680μWh energy per day and the outputs of TEH and RFEH have increased 4 and 3 times compared to the independent TEH and RFEH respectively. To validate the utility of the MSEH, a temperature/humidity sensor has been successfully powered by the MSEH. Overall, sensor’s data can be wirelessly transmitted with time intervals of 3.5s, highlighting the effectiveness of the synergistic MSEH.