12023 research outputs found
Sort by
Pressure and Stress Transients in Autoinjector Devices
Get PDFThe viscosity of drug solutions delivered parenterally has been increasing over the years. Injecting viscous drug solutions using spring-actuated autoinjector devices is challenging due to a number of technical and human factor constraints. Some of the related challenges are investigated in this thesis.
Actuation of autoinjector devices powered using stiff springs can create deleterious pressure and stress transients which are not needed to achieve the normal functions of the device. Experimental measurements have shown that peak pressures and stresses substantially larger than what is needed to achieve the normal device function can occur during the actuation phase, creating unnecessary potential for device failure.
The acceleration of the syringe during actuation can be very large, often creating transient cavitation in the cone region. The occurrence or absence of cavitation is determined by the relative timing of syringe pressurization and syringe acceleration, which is affected by several factors such as the presence, location, and size of an air gap inside the syringe, and the friction between the plunger-stopper and the syringe.
Experiments and numerical simulations have shown that sharp pressure waves traveling inside the syringe can be amplified within the cone terminating the syringe. Despite the potential for shock focusing, the impulsive pressurization and the rapid deceleration of pre-filled syringes create a potential for failure which is localized in the syringe shoulder and at the junction between the flange and the barrel, not inside the cone. The cavitation events, on the other hand, create a potential for failure which is limited to a region in close proximity of the bubble upon collapse. The collapse of cavitation bubbles located within the syringe cone can be enhanced due to geometrical effects, and the resulting stresses can be large enough to cause syringe failure.
This thesis demonstrates that static and quasi-static analyses do not provide accurate estimates of the peak pressures and stresses occurring within the device. The pressure and stresses created by the highly dynamic events occurring during actuation need to be accounted for during device design in order to improve device reliability, the user's experience, and patient's adherence to prescribed treatments. The findings discussed in this work provide insights and guidance as to how the transient events can be mitigated.</p
Electronic Structure and Spectroscopy of Tetranuclear Mn4O4 and CaMn3O4 Complexes as Models of the Oxygen Evolving Complex in Photosystem II
Get PDFThis thesis describes a series of studies devoted toward the synthesis of model complexes that mimic aspects of structure, redox state, and spectroscopy of the oxygen evolving complex (OEC) of Photosystem II. The OEC is a unique metallocofactor featuring a heteronuclear CaMn4 core that catalyzes water oxidation. While advances in spectroscopic and structural techniques offer an ever more detailed view of the structure of the S-state catalytic intermediates, the precise mechanism of O−O bond formation remains debated. Aspects such as (1) role of Ca2+, (2) the location of the substrate waters, and (3) the (electronic) structure of the S-state intermediates remain unclear. To obtain a better understanding of the OEC, systematic structure−function(property) studies on relevant model complexes may be necessary. Despite significant efforts to prepare tetra- and pentanuclear complexes as models of the OEC, relevant complexes in terms of structure, redox state, spectroscopy, and reactivity are rare, likely due to the synthetic challenges of accessing a series of isolable clusters that are suitable for comparisons.
Chapter 1 presents a survey of tetramanganese model compounds with an emphasis on redox state and electronic structure, as probed by magnetometry and EPR spectroscopy. Structurally characterized model complexes are grouped according to Mn oxidation states and the S-state that they are mirroring. In contrast to the vast number of spectroscopic studies on the OEC, studies that probe the effect of systematic changes in structure on the spectroscopy of model complexes are rare in the literature.
Chapter 2 presents ongoing synthetic efforts to prepare accurate structural models of the OEC. The synthesis of accurate structural models is hampered by the low structural symmetry of the cluster, the presence of two types of metals, and the propensity of oxo moieties to form extended oligomeric structures. Desymmetrization of the previously reported trinucleating ligand leads to the formation of tetranuclear Mn4II precursors. Oxidation in the presence of Ca2+ leads to a CaMn4O2 model of the OEC, underscoring the utility of low-symmetry multinucleating ligands in the synthesis of hitherto unobserved oxo-bridged multimetallic core geometries related to the OEC.
Chapter 3 presents a series of [MnIIIMn3IVO4] cuboidal complexes as spectroscopic models of the S2 state of the OEC. Such complexes resemble the oxidation state and EPR spectra of the S2 state, and the effect of systematic changes in the nature of the bridging ligands on spectroscopy was studied. Results show that the electronic structure of tetranuclear Mn complexes is highly sensitive to even small geometric changes and the nature of the bridging ligands. Model studies suggest that the spectroscopic properties of the OEC may also react very sensitively to small changes in structure; the effect of protonation state and other reorganization processes needs to be carefully assessed.
Chapter 4 presents a series of [YMn3O4] complexes as models of the [CaMn3O4] subsite of the OEC. The effect of systematic changes in the basicity and chelating properties of the bridging ligands on redox potential was studied. Results show that in the absence of ligand-induced geometric distortions that enforce a contraction of metal-oxo distances, increasing the basicity of the ligands results in a decrease of cluster reduction potential. A small contraction of metal-oxo/metal-metal distances by ~0.1 Å enforced by a chelating ligand results in an increase of cluster reduction potential even in the presence of strong basic donors. Such small, protein-induced changes in Ca-oxo/Ca-Mn distances may have a similar effect in tuning the redox potential of the OEC through entatic states, and may explain the cation size dependence on the progression of the S-state cycle.
Chapter 5 presents a series of [CaMn3O4] and [YMn3O4] complexes as models of the [CaMn3O4] subsite of the OEC. The effect of systematic changes in cluster geometry, heterometal identity, and bridging oxo protonation on cluster spin state structure was studied. Results show that the electronic structure of the Mn3IV core is highly sensitive to small geometric changes, the nature of the bridging ligands, and the protonation state of the bridging oxos: the spin ground states of essentially isostructural compounds can be S = 3/2, 5/2, or 9/2. Interpretation of EPR signals and subsequent structural assignments based on an S = 9/2 spin state of the CaMn3O4 subsite of the OEC must be done very cautiously.
While unfinished, appendices 1 and 2 present other important aspect in OEC model chemistry. Appendix 1 presents the synthesis of 17O-labeled [MnIIIMn3IVO4] and [CaMn3IVO4] complexes as models of the OEC. Ongoing characterization of μ3-oxos in such complexes provide valuable benchmarking parameters for future mechanistic studies. Appendix 2 presents the synthesis and characterization of [Mn4IVO4] cuboidal complexes as spectroscopic models of the S3 state of the OEC, the last observable intermediate prior to O−O bond formation at the OEC.</p
Quantum Nanophotonics with Ytterbium in Yttrium Orthovanadate
Get PDFQuantum light-matter interfaces that can reversibly map quantum information between photons and atoms are essential for building future quantum networks. Crystals doped with rare-earth ions (REIs) are an attractive solid-state platform for such light-matter interfaces due to their exceptional optical and spin coherence properties at cryogenic temperatures. Building scalable REI-based technology has proven to be challenging due to the inherently weak coupling of REIs with light. This thesis explores the integration of REIs with nanophotonic resonators to overcome this weak light-matter interaction and enable efficient, scalable quantum light-matter interfaces. Specifically, this work focuses on the development of quantum nanophotonics with ytterbium in yttrium orthovanadate.
This thesis begins with an introduction to a nanophotonic platform based on photonic crystal cavities fabricated directly in rare-earth host materials and highlights the initial successes of this platform with neodymium-doped materials. This motivates an examination of the optical and spin coherence properties of 171Yb:YVO4, a REI material that was previously unexplored for quantum technology applications. This material is found to have strong optical transitions compared to other REI-doped materials, a simple energy level structure, and long optical and spin coherence lifetimes.
The focus then turns to the detection and coherent manipulation of single ytterbium ions coupled to nanophotonic cavities. The Purcell-enhancement in these cavities enables efficient optical detection and spin initialization of individual ytterbium ions. We identify ions corresponding to different isotopes of ytterbium and show that the coupling of electron and nuclear spin in ytterbium-171 at zero-field gives rise to strong electron-spin-like transitions that are first-order insensitive to magnetic field fluctuations. This allows for coherent microwave control and the observation of long spin coherence lifetimes at temperatures up to 1 K. We then make use of the optical selection rules and energy structure of 171Yb:YVO4 to demonstrate high-fidelity single-shot optical readout of the spin state. These results establish nanophotonic devices in 171Yb:YVO4 as a promising platform for solid-state quantum light-matter interfaces.</p
Decoding the Past
Get PDFThe human genome is continuously evolving, hence the sequenced genome is a snapshot in time of this evolving entity. Over time, the genome accumulates mutations that can be associated with different phenotypes - like physical traits, diseases, etc. Underlying mutation accumulation is an evolution channel (the term channel is motivated by the notion of communication channel introduced by Shannon [1] in 1948 and started the area of Information Theory), which is controlled by hereditary, environmental, and stochastic factors. The premise of this thesis is to understand the human genome using information theory framework. In particular, it focuses on: (i) the analysis and characterization of the evolution channel using measures of capacity, expressiveness, evolution distance, and uniqueness of ancestry and uses these insights for (ii) the design of error correcting codes for DNA storage, (iii) inversion symmetry in the genome and (iv) cancer classification.
The mutational events characterizing this evolution channel can be divided into two categories, namely point mutations and duplications. While evolution through point mutations is unconstrained, giving rise to combinatorially many possibilities of what could have happened in the past, evolution through duplications adds constraints limiting the number of those possibilities. Further, more than 50% of the genome has been observed to consist of repeated sequences. We focus on the much constrained form of duplications known as tandem duplications in order to understand the limits of evolution by duplication. Our sequence evolution model consists of a starting sequence called seed and a set of tandem duplication rules. We find limits on the diversity of sequences that can be generated by tandem duplications using measures of capacity and expressiveness. Additionally, we calculate bounds on the duplication distance which is used to measure the timing of generation by these duplications. We also ask questions about the uniqueness of seed for a given sequence and completely characterize the duplication length sets where the seed is unique or non-unique. These insights also led us to design error correcting codes for any number of tandem duplication errors that are useful for DNA-storage based applications. For uniform duplication length and duplication length bounded by 2, our designed codes achieve channel capacity. We also define and measure uncertainty in decoding when the duplication channel is misinformed. Moreover, we add substitutions to our tandem duplication model and calculate sequence generation diversity for a given budget of substitutions.
We also use our duplication model to explain the inversion symmetry observed in the genome of many species. The inversion symmetry is popularly known as the 2nd Chargaff Rule, according to which in a single strand DNA, the frequency of a k-mer is almost the same as the frequency of its reverse complement. The insights gained by these problems led us to investigate the tandem repeat regions in the genome. Tandem repeat regions in the genome can be traced back in time algorithmically to make inference about the effect of the hereditary, environmental and stochastic factors on the mutation rate of the genome. By inferring the evolutionary history of the tandem repeat regions, we show how this knowledge can be used to make predictions about the risk of incurring a mutation based disease, specifically cancer. More precisely, we introduce the concept of mutation profiles that are computed without any comparative analysis, but instead by analyzing the short tandem repeat regions in a single healthy genome and capturing information about the individual's evolution channel. Using gradient boosting on data from more than 5,000 TCGA (The Cancer Genome Atlas) cancer patients, we demonstrate that these mutation profiles can accurately distinguish between patients with various types of cancer. For example, the pairwise validation accuracy of the classifier between PAAD (pancreas) patients and GBM (brain) patients is 93%. Our results show that healthy unaffected cells still contain a cancer-specific signal, which opens the possibility of cancer prediction from a healthy genome.</p
Topological Phases of Matter: Exactly Solvable Models and Classification
Get PDFIn this thesis, we study gapped topological phases of matter in systems with strong inter-particle interaction. They are challenging to analyze theoretically, because interaction not only gives rise to a plethora of phases that are otherwise absent, but also renders methods used to analyze non-interacting systems inadequate. By now, people have had a relatively systematic understanding of topological orders in two spatial dimensions. However, less is known about the higher dimensional cases. In Chapter 2, we will explore three dimensional long-range entangled topological orders in the framework of Walker-Wang models, which are a class of exactly solvable models for three-dimensional topological phases that are not known previously to be able to capture these phases. We find that they can represent a class of twisted discrete gauge theories, which were discovered using a different formalism. Meanwhile, a systematic theory of bosonic symmetry protected topological (SPT) phases in all spatial dimensions have been developed based on group cohomology. A generalization of the theory to group supercohomology has been proposed to classify and characterize fermionic SPT phases in all dimensions. However, it can only handle cases where the symmetry group of the system is a product of discrete unitary symmetries. Furthermore, the classification is known to be incomplete for certain symmetries. In Chapter 3, we will construct an exactly solvable model for the two-dimensional time-reversal-invariant topological superconductors, which could be valuable as a first attempt to a systematic understanding of strongly interacting fermionic SPT phases with anti-unitary symmetries in terms of exactly solvable models. In Chapter 4, we will propose an alternative classification of fermionic SPT phases using the spin cobordism theory, which hopefully can capture all the phases missing in the supercohomology classification. We test this proposal in the case of fermionic SPT phases with Z2 symmetry, where Z2 is either time-reversal or an internal symmetry. We find that cobordism classification correctly describes all known fermionic SPT phases in space dimensions less than or equal to 3.</p
Interfacial Behavior of 2D Materials in Devices for Solar Fuels and Sensing Applications
Get PDFThe field of 2D materials has expanded widely in the past 15 years to include many materials beyond graphene. However, the applications of graphene and its derivatives are still limited by the lack of thorough knowledge on how to successfully integrate a 2D material into a device while maintaining its unique properties. The work in this thesis investigates the application of 2D materials, such as graphene, fluorinated graphene, and hexagonal boron nitride, in solar fuels and sensing devices to reveal patterns that can inform device design with these and other materials in the future. In the second chapter, lightly fluorinated graphene is investigated as a protective layer on silicon photoanodes. This material is shown to possess superior abilities as a protective layer against oxidizing conditions as well as other deleterious surface reactions. The introduction of fluorine atoms to the lattice at postulated to terminate defects found along grain boundaries, leading to enhanced stability over 24h. The third chapter addresses the energetics of silicon/2D material/liquid junctions to elucidate how the density of states in these materials affect the formation of efficient charge-separation junctions. Hexagonal boron nitride on p-type silicon is shown to form a superior junction to graphene, as measured by changes in the open-circuit potential against a range of one-electron redox couples. Finally, chapter four shows the integration of a monolayer of graphene into a polymer-based chemiresistive vapor sensor to substantially enhance the signal of the sensor over the graphene or polymer alone. The response is dependent on strain at the graphene interface as demonstrated by Raman spectroscopy.</p
Towards a Visipedia: Combining Computer Vision and Communities of Experts
Get PDFMotivated by the idea of a Visipedia, where users can search and explore by image, this thesis presents tools and techniques for empowering expert communities through computer vision. The collective aim of this work is to provide a scalable foundation upon which an application like Visipedia can be built. We conduct experiments using two highly motivated communities, the birding community and the naturalist community, and report results and lessons on how to build the necessary components of a Visipedia. First, we conduct experiments analyzing the behavior of state-of-the-art computer vision classifiers on long tailed datasets. We find poor feature sharing between classes, potentially limiting the applicability of these models and emphasizing the ability to intelligently direct data collection resources. Second, we devise online crowdsourcing algorithms to make dataset collection for binary labels, multiclass labels, keypoints, and mulit-instance bounding boxes faster, cheaper, and more accurate. These methods jointly estimate labels, worker skills, and train computer vision models for these tasks. Experiments show that we can achieve significant cost savings compared to traditional data collection techniques, and that we can produce a more accurate dataset compared to traditional data collection techniques. Third, we present two fine-grained datasets, detail how they were constructed, and analyze the test accuracy of state-of-the-art methods. These datasets are then used to create applications that help users identify species in their photographs: Merlin, an app assisting users in identifying birds species, and iNaturalist, an app that assists users in identifying a broad variety of species. Finally, we present work aimed at reducing the computational burden of large scale classification with the goal of creating an application that allows users to classify tens of thousands of species in real time on their mobile device. As a whole, the lessons learned and the techniques presented in this thesis bring us closer to the realization of a Visipedia.</p
Constraining the Mantle's Rheology Using Methods in Uncertainty Quantification
Get PDFAn accurate estimation of the large-scale forces in the mantle has been difficult to obtain as numerical models either do not use an accurate rheology nor reproduce surface observations. While much work has been done in developing high-fidelity forward models that capture the salient physics of shear-thinning and dynamic weakening, they fail to reproduce observations such as plate motions and topography. In this thesis, we develop an optimization methodology that minimizes the misfit in surface observations such as plate motions and average effective viscosity for certain regions of the mantle. We utilize adjoints to calculate the gradient, while using second-order adjoints to construct the Hessian so as to infer the rheological parameters of the mantle's rheology. Furthermore, we build on this optimization scheme by constructing the Gaussian approximation of the posterior distribution for the inferred rheological parameters using the Hessian and establish the trade-offs between each parameter through their conditional distributions. We further extend this Gaussian approximation to infer extrinsic quantities such as the stresses in the fault zones and the average effective viscosity in the hinge zones to not only quantify the uncertainty, but also to see partitioning of the coupling of each subduction zone
Adventures Through Time and Phase Space: Characterizing the Dynamic Radio Sky, From MHz to GHz, From Seconds to Years
Get PDFTime domain radio astronomy is on the cusp of a revolution. This is particularly true at low radio frequencies, where wide-field arrays are conducting deeper surveys than ever before, in pursuit of elusive transient phenomena. This thesis has opened an unprecedented window on the dynamic radio sky, spanning a wide range in frequency -- from MHz to GHz -- and a wide range of phenomena -- from searches for coherent radio bursts indicative of coronal mass ejections from nearby stars, to the detection of incoherent synchrotron emission from an outflow associated with the tidal disruption of a star by a supermassive black hole at the center of a galaxy.
A significant part of this work has involved the building of the Owens Valley Radio Observatory Long Wavelength Array (OVRO-LWA), a uniquely powerful radio telescope, with the ability to image the entire viewable sky at a 10 second cadence and across nearly 60 MHz of bandwidth. With the OVRO-LWA, I have developed the methods and techniques necessary for pushing further into unexplored regions of radio transient phase space, in the pursuit of sources of radio emission that provide unique insight into various astrophysical phenomena. This includes the follow-up of gravitational wave events in order to search for the signatures of prompt, coherent radio emission associated with compact object mergers, as well as targeted searches for stellar and exoplanetary radio emission as a means of better understanding planetary habitability.</p
Stochastic Multiscale Modeling of Dynamic Recrystallization
Get PDFMaterials by design is a core driver in enhancing sustainability and improving efficiency in a broad spectrum of industries. To this end, thermo-mechanical processes and many of the underlying phenomena were studied extensively in the context of specific cases. The goal of this thesis is threefold: First, we aim to establish a novel numerical model on the micro- and mesoscale that captures dynamic recrystallization in a generalized framework. Based on the inheritance of the idea of state switches, we term this scheme Field-Monte-Carlo Potts method. We employ a finite deformation framework in conjunction with a continuum-scale crystal plasticity formulation and extend the idea of state switches to cover both grain migration and nucleation. We introduce physically-motivated state-switch rules, based on which we achieve a natural marriage between the deterministic nature of crystal plasticity and the stochastic nature of dynamic recrystallization. Using a novel approach to undertake the states-switches in a transient manner, the new scheme benefits from enhanced stability and can, therefore, handle arbitrary levels of anisotropy. We demonstrate this functionality at the example of pure Mg at room temperature, which experiences strong anisotropy through the different hardening behavior on the 〈c+a〉-pyramidal and prismatic slip systems as opposed to the basal slip systems as well as through the presence of twinning as an alternative strain accommodating mechanisms. Building on this generalized approach, we demonstrate spatial convergence of the scheme along with the ability to capture the transformation from single- to multi-peak stress-strain behavior.
Second, motivated by the lack of transparency concerning the benefits of high-fidelity approaches in the modeling of dynamic recrystallization, we present two derivative models of the Field-Monte-Carlo Potts method, both of which afford reduced computational expense. One model preserves the spatial interpretation of grains, but imposes a Taylor assumption regarding the distribution of strain; the other reduces the spatial notion of a grain to a volume fraction in the idea of a Taylor model. In order to concentrate on the differences in accuracy between the various approaches, we fit all three schemes to experimental data for pure copper, which allows us to employ a well-understood crystal plasticity-based constitutive model and to simultaneously provide sufficient data for the analysis of the texture, stress and grain-size evolution. Owing to the large strains attained in these simulations, using the FFT-based scheme, we achieve capturing a precursor of continuous dynamic recrystallization. For low temperatures, the Taylor model fails to replicate the nucleation-dominated recrystallization process, whereas, at high temperatures, it shows compelling agreement with experiments and the two higher-fidelity models both in terms of the homogenized stress-evolution and the microstructural evolution.
Finally, we present a novel multiscale analysis of thermo-mechanical processes through coupling of the computationally efficient Taylor model for modeling dynamic recrystallization on the mesoscale to a max-ent based meshfree approach on the macroscale in the idea of vertical homogenization. We analyze the severe plastic deformation-based process of equal channel angular extrusion, which is intriguing from a numerical perspective due to the heavily localized zone of extensive shear deformation. By employing novel tools on the microscale regarding the stable update of internal variables as well as a careful interpretation of macroscale boundary conditions, we present the first multiscale analysis of a severe plastic deformation process informing simultaneously about the evolution of stress, texture and grain refinement. We attain convincing qualitative agreements for the evolution of the plunger force and texture. As an outlook on future investigations, we analyze multiple passes of the same billet in the form of route C with emphasis on the texture evolution after the second pass.</p