12023 research outputs found
Sort by
Resonant Production of Sterile Neutrinos in the Early Universe
No full textWe examine the cosmological impacts of a light resonantly produced sterile neutrino in the early universe. Such a neutrino could be produced through lepton number-driven Mikheyev-Smirnov-Wolfenstein conversion of active neutrinos, resulting in a non-thermal spectrum of both sterile
and active neutrinos. If this process occurs during weak decoupling and big bang nucleosynthesis, it would affect the electron neutrino flux and therefore the n/p ratio. This allows us to use observations of primordial helium (Yp), primordial deuterium (D/H), and Neff to place limits on
this process
Dynamic Stall on Vertical Axis Wind Turbines
Get PDFIn this study the dynamics of flow over the blades of vertical axis wind turbines was investigated using a simplified periodic motion to uncover the fundamental flow physics and provide insight into the design of more efficient turbines. Time-resolved, two-dimensional velocity measurements were made with particle image velocimetry on a wing undergoing pitching and surging motion to mimic the flow on a turbine blade in a non-rotating frame. Dynamic stall prior to maximum angle of attack and a leading edge vortex development were identified in the phase-averaged flow field and captured by a simple model with five modes, including the first two harmonics of the pitch/surge frequency identified using the dynamic mode decomposition. Analysis of these modes identified vortical structures corresponding to both frequencies that led the separation and reattachment processes, while their phase relationship determined the evolution of the flow.
Detailed analysis of the leading edge vortex found multiple regimes of vortex development coupled to the time-varying flow field on the airfoil. The vortex was shown to grow on the airfoil for four convection times, before shedding and causing dynamic stall in agreement with 'optimal' vortex formation theory. Vortex shedding from the trailing edge was identified from instantaneous velocity fields prior to separation. This shedding was found to be in agreement with classical Strouhal frequency scaling and was removed by phase averaging, which indicates that it is not exactly coupled to the phase of the airfoil motion.
The flow field over an airfoil undergoing solely pitch motion was shown to develop similarly to the pitch/surge motion; however, flow separation took place earlier, corresponding to the earlier formation of the leading edge vortex. A similar reduced-order model to the pitch/surge case was developed, with similar vortical structures leading separation and reattachment; however, the relative phase lead of the separation mode, corresponding to earlier separation, necessitated that a third frequency to be incorporated into the reattachment mode to provide a relative lag in reattachment.
Finally, the results are returned to the rotating frame and the effects of each flow phenomena on the turbine are estimated, suggesting kinematic criteria for the design of improved turbines.</p
A Fully-Nonlocal Energy-based Formulation and High-performance Realization of the Quasicontinuum Method
Get PDFThe quasicontinuum (QC) method was introduced to coarse-grain crystalline atomic ensembles in order to bridge the scales from individual atoms to the micro- and mesoscales. Though many QC formulations have been proposed with varying characteristics and capabilities, a crucial cornerstone of all QC techniques is the concept of summation rules, which attempt to efficiently approximate the total Hamiltonian of a crystalline atomic ensemble by a weighted sum over a small subset of atoms. In this work we propose a novel, fully-nonlocal, energy-based formulation of the QC method with support for legacy and new summation rules through a general energy-sampling scheme. Our formulation does not conceptually differentiate between atomistic and coarse-grained regions and thus allows for seamless bridging without domain-coupling interfaces. Within this structure, we introduce a new class of summation rules which leverage the affine kinematics of this QC formulation to most accurately integrate thermodynamic quantities of interest. By comparing this new class of summation rules to commonly-employed rules through analysis of energy and spurious force errors, we find that the new rules produce no residual or spurious force artifacts in the large-element limit under arbitrary affine deformation, while allowing us to seamlessly bridge to full atomistics. We verify that the new summation rules exhibit significantly smaller force artifacts and energy approximation errors than all comparable previous summation rules through a comprehensive suite of examples with spatially non-uniform QC discretizations in two and three dimensions. Due to the unique structure of these summation rules, we also use the new formulation to study scenarios with large regions of free surface, a class of problems previously out of reach of the QC method. Lastly, we present the key components of a high-performance, distributed-memory realization of the new method, including a novel algorithm for supporting unparalleled levels of deformation. Overall, this new formulation and implementation allows us to efficiently perform simulations containing an unprecedented number of degrees of freedom with low approximation error
Field and Laboratory Studies of Atmospheric Organic Aerosol
Get PDFThis thesis is the culmination of field and laboratory studies aimed at assessing processes that affect the composition and distribution of atmospheric organic aerosol. An emphasis is placed on measurements conducted using compact and high-resolution Aerodyne Aerosol Mass Spectrometers (AMS). The first three chapters summarize results from aircraft campaigns designed to evaluate anthropogenic and biogenic impacts on marine aerosol and clouds off the coast of California. Subsequent chapters describe laboratory studies intended to evaluate gas and particle-phase mechanisms of organic aerosol oxidation.
The 2013 Nucleation in California Experiment (NiCE) was a campaign designed to study environments impacted by nucleated and/or freshly formed aerosol particles. Terrestrial biogenic aerosol with > 85% organic mass was observed to reside in the free troposphere above marine stratocumulus. This biogenic organic aerosol (BOA) originated from the Northwestern United States and was transported to the marine atmosphere during periodic cloud-clearing events. Spectra recorded by a cloud condensation nuclei counter demonstrated that BOA is CCN active. BOA enhancements at latitudes north of San Francisco, CA coincided with enhanced cloud water concentrations of organic species such as acetate and formate.
Airborne measurements conducted during the 2011 Eastern Pacific Emitted Aerosol Cloud Experiment (E-PEACE) were aimed at evaluating the contribution of ship emissions to the properties of marine aerosol and clouds off the coast of central California. In one study, analysis of organic aerosol mass spectra during periods of enhanced shipping activity yielded unique tracers indicative of cloud-processed ship emissions (m/z 42 and 99). The variation of their organic fraction (f42 and f99) was found to coincide with periods of heavy (f42 > 0.15; f99 > 0.04), moderate (0.05 < f42 < 0.15; 0.01 < f99 < 0.04), and negligible (f42 < 0.05; f99 < 0.01) ship influence. Application of these conditions to all measurements conducted during E-PEACE demonstrated that a large fraction of cloud droplet (72%) and dry aerosol mass (12%) sampled in the California coastal study region was heavily or moderately influenced by ship emissions. Another study investigated the chemical and physical evolution of a controlled organic plume emitted from the R/V Point Sur. Under sunny conditions, nucleated particles composed of oxidized organic compounds contributed nearly an order of magnitude more cloud condensation nuclei (CCN) than less oxidized particles formed under cloudy conditions. The processing time necessary for particles to become CCN active was short ( < 1 hr) compared to the time needed for particles to become hygroscopic at sub-saturated humidity ( > 4 hr).
Laboratory chamber experiments were also conducted to evaluate particle-phase processes influencing aerosol phase and composition. In one study, ammonium sulfate seed was coated with a layer of secondary organic aerosol (SOA) from toluene oxidation followed by a layer of SOA from α-pinene oxidation. The system exhibited different evaporative properties than ammonium sulfate seed initially coated with α-pinene SOA followed by a layer of toluene SOA. This behavior is consistent with a shell-and-core model and suggests limited mixing among different SOA types. Another study investigated the reactive uptake of isoprene epoxy diols (IEPOX) onto non-acidified aerosol. It was demonstrated that particle acidity has limited influence on organic aerosol formation onto ammonium sulfate seed, and that the chemical system is limited by the availability of nucleophiles such as sulfate.
Flow tube experiments were conducted to examine the role of iron in the reactive uptake and chemical oxidation of glycolaldehyde. Aerosol particles doped with iron and hydrogen peroxide were mixed with gas-phase glycolaldehyde and photochemically aged in a custom-built flow reactor. Compared to particles free of iron, iron-doped aerosols significantly enhanced the oxygen to carbon (O/C) ratio of accumulated organic mass. The primary oxidation mechanism is suggested to be a combination of Fenton and photo-Fenton reactions which enhance particle-phase OH radical concentrations.</p
Phase Diagrams and Defect Thermodynamics to Devise Doping Strategies in Lead Chalcogenide Thermoelectric Materials and its Alloys
Get PDFThis thesis discusses the application of phase diagrams and the associated thermodynamics to semiconductor materials through theoretical computational calculations. The majority of work is focused on thermoelectric semiconducting materials that enable direct inter-conversion between electrical and thermal energy. First, one of the most efficient thermoelectric material, PbTe, is picked to demonstrate the assessment of unknown phase diagrams by combining two methods - DFT and CALPHAD. Since there had been no previous investigations of defect stability in this material using computations, DFT is used to deduce the stability of various intrinsic point defects, and in turn attribute origins of n- and p-type conductivity to the most stable defects. Then, the calculated defect formation energies are used in the Pb-Te thermodynamic model built using the CALPHAD method to compare the estimated solubility lines and non-stoichiometric range of the PbTe phase with experimental data. Next, another lead chalcogenide, PbSe, is picked to explore the phase stability of the PbSe phase upon the addition of dopants (Br, Cl, I, Na, Sb, Bi, In), which is a common strategy to make thermoelectric materials and devices more efficient. The range of efficiencies and thermoelectric properties as functions of composition and temperature that can be achieved depends on the amount of dopant that can be added without precipitating secondary phases. Also, depending on the system and its phase diagram, there can be more than one way of doping a material. To help detail which method(s) of doping into PbSe will result in maximum dopant solubility, a procedure similar to the above for PbTe is followed by using DFT in combination with Boltzmann statistics to map solvus boundaries of the PbSe phase, but now in the ternary phase space of composition and temperature. This method also helps predict electrical conductivity, n- or p-type, in each region of the phase diagrams that represent different doping methods.
Lastly, the role of surface energy contributions in changing phase stability at nano-dimensions is explored. The CALPHAD approach is employed to investigate these changes in three systems by calculating their phase diagrams at nano dimensions and comparing them with their bulk counterparts.</p
Novel Parylene Filters for Biomedical Applications
Get PDFMedical engineering plays a more and more important role in driving the fundamental biology research moving forward. The work presented in this thesis targets at engineer smart parylene filters for various biomedical applications. Three novel parylene membranes are discussed. The first device is parylene magnesium-embedded filter for circulating tumor cells isolation. Circulating tumor cells (CTCs) are cells that slough off the edges of a primary tumor and are swept away by the bloodstream or lymphatic system into the vasculature. They constitute seeds for subsequent growth of additional tumors in vital distant organs, triggering a mechanism that is responsible for the vast majority of cancer-related deaths. Thus CTCs in peripheral blood have been investigated as a valuable biomarker for patients with various types of cancers. However, CTCs are difficult targets to probe owing to their extremely low concentration in peripheral blood. Although rare, CTCs represent a potential approach for the detection, characterization and monitoring of non-haematologic cancers. Therefore, CTCs capture from whole blood has been identified to be an unmet need for cancer research and effective cell separation methods are required to facilitate the study of CTCs. In this study, we developed a novel design applying a buried sacrificial Magnesium (Mg) layer underneath the original microfilter. After filtration, the filter was immersed in DMEM. When the thin-film Mg was dissolved, the cells were released and thus were ready for further biology analysis.
The second device is parylene based microelectrode filter for single-islet electroisletogram. Other than direct insulin injection, one promising treatment for Type I diabetes is islet transplantation. However, one of the key lacking technologies of islet transplantation is high-throughput islet screening since each transplantation requires about one million islets. Islets, which are heterogeneous by nature, are currently screened as whole populations containing a range of functioning and dysfunctional characteristics. This work represents the first attempt to develop a MEMS technology for the screening of every single islet so as to guarantee no bad islet at all, which should improve results of islet transplant therapy. Here we report the first MEMS device designed for in vitro measuring of electroisletogram (EIG) of individual rat islets. Strong EIG signals in millivolt range are obtained. This work proves the feasibility of using MEMS and EIG for high-throughput screening, in contrast to patch-clamp measurements, of islets for transplantation to treat diabetes.
The third device is parylene-on-PDMS membrane for vaccine production. A parylene-on-PDMS design is proposed to supply oxygen to CV-1 cells for vaccine production. Because the cells are seeded and attached right onto the surface of the device, extra oxygen is provided through permeation from the PDMS and thin parylene layers. The permeation is studied and cell growth experiments are performed to demonstrate the feasibility of the device. Compared to commercialized bioreactors, this novel design could have large cell density because oxygen are supplied locally and shear force is not a limiting factor any more.
Besides the three devices, parylene properties are also studied and a novel origami design is proposed, which can potentially increase the surface areas of the membranes by fold the 2D flat film into 3D structures. Details are discussed in the following chapters.</p
Plasma Loop and Strapping Field Dynamics: Reproducing Solar Eruptions in the Laboratory
Get PDFCoronal mass ejections (CMEs) are dramatic eruptions of large, plasma structures from the Sun. These eruptions are important because they can harm astronauts, damage electrical infrastructure, and cause auroras. A mysterious feature of these eruptions is that plasma-filled solar flux tubes first evolve slowly, but then suddenly erupt. One model, torus instability, predicts an explosive-like transition from slow expansion to fast acceleration, if the spatial decay of the ambient magnetic field exceeds a threshold.
We create arched, plasma filled, magnetic flux ropes similar to CMEs. Small, independently-powered auxiliary coils placed inside the vacuum chamber produce magnetic fields above the decay threshold that are strong enough to act on the plasma. When the strapping field is not too strong and not too weak, expansion force build up while the flux rope is in the strapping field region. When the flux rope moves to a critical height, the plasma accelerates quickly, corresponding to the observed slow-rise to fast-acceleration of most solar eruptions. This behavior is in agreement with the predictions of torus instability.
Historically, eruptions have been separated into gradual CMEs and impulsive CMEs, depending on the acceleration profile. Recent numerical studies question this separation. One study varies the strapping field profile to produce gradual eruptions and impulsive eruptions, while another study varies the temporal profile of the voltage applied to the flux tube footpoints to produce the two eruption types. Our experiment reproduced these different eruptions by changing the strapping field magnitude, and the temporal profile of the current trace. This suggests that the same physics underlies both types of CME and that the separation between impulsive and gradual classes of eruption is artificial.</p
Technology for Single Cell Protein Analysis in Immunology and Cancer Prognostics
Get PDFThe first chapter of this thesis deals with automating data gathering for single cell microfluidic tests. The programs developed saved significant amounts of time with no loss in accuracy. The technology from this chapter was applied to experiments in both Chapters 4 and 5.
The second chapter describes the use of statistical learning to prognose if an anti-angiogenic drug (Bevacizumab) would successfully treat a glioblastoma multiforme tumor. This was conducted by first measuring protein levels from 92 blood samples using the DNA-encoded antibody library platform. This allowed the measure of 35 different proteins per sample, with comparable sensitivity to ELISA. Two statistical learning models were developed in order to predict whether the treatment would succeed. The first, logistic regression, predicted with 85% accuracy and an AUC of 0.901 using a five protein panel. These five proteins were statistically significant predictors and gave insight into the mechanism behind anti-angiogenic success/failure. The second model, an ensemble model of logistic regression, kNN, and random forest, predicted with a slightly higher accuracy of 87%.
The third chapter details the development of a photocleavable conjugate that multiplexed cell surface detection in microfluidic devices. The method successfully detected streptavidin on coated beads with 92% positive predictive rate. Furthermore, chambers with 0, 1, 2, and 3+ beads were statistically distinguishable. The method was then used to detect CD3 on Jurkat T cells, yielding a positive predictive rate of 49% and false positive rate of 0%.
The fourth chapter talks about the use of measuring T cell polyfunctionality in order to predict whether a patient will succeed an adoptive T cells transfer therapy. In 15 patients, we measured 10 proteins from individual T cells (~300 cells per patient). The polyfunctional strength index was calculated, which was then correlated with the patient's progress free survival (PFS) time. 52 other parameters measured in the single cell test were correlated with the PFS. No statistical correlator has been determined, however, and more data is necessary to reach a conclusion.
Finally, the fifth chapter talks about the interactions between T cells and how that affects their protein secretion. It was observed that T cells in direct contact selectively enhance their protein secretion, in some cases by over 5 fold. This occurred for Granzyme B, Perforin, CCL4, TNFa, and IFNg. IL- 10 was shown to decrease slightly upon contact. This phenomenon held true for T cells from all patients tested (n=8). Using single cell data, the theoretical protein secretion frequency was calculated for two cells and then compared to the observed rate of secretion for both two cells not in contact, and two cells in contact. In over 90% of cases, the theoretical protein secretion rate matched that of two cells not in contact.</p
Robust Control of Evolutionary Dynamics
Get PDFThe application of principles from evolutionary biology has long been used to gain new insights into the progression and clinical control of both infectious diseases and neoplasms. This iterative evolutionary process consists of expansion, diversification and selection within an adaptive landscape - species are subject to random genetic or epigenetic alterations that result in variations; genetic information is inherited through asexual reproduction and strong selective pressures such as therapeutic intervention can lead to the adaptation and expansion of resistant variants. These principles lie at the center of modern evolutionary synthesis and constitute the primary reasons for the development of resistance and therapeutic failure, but also provide a framework that allows for more effective control.
A model system for studying the evolution of resistance and control of therapeutic failure is the treatment of chronic HIV-1 infection by broadly neutralizing antibody (bNAb) therapy. A relatively recent discovery is that a minority of HIV-infected individuals can produce broadly neutralizing antibodies, that is, antibodies that inhibit infection by many strains of HIV. Passive transfer of human antibodies for the prevention and treatment of HIV-1 infection is increasingly being considered as an alternative to a conventional vaccine. However, recent evolution studies have uncovered that antibody treatment can exert selective pressure on virus that results in the rapid evolution of resistance. In certain cases, complete resistance to an antibody is conferred with a single amino acid substitution on the viral envelope of HIV.
The challenges in uncovering resistance mechanisms and designing effective combination strategies to control evolutionary processes and prevent therapeutic failure apply more broadly. We are motivated by two questions: Can we predict the evolution to resistance by characterizing genetic alterations that contribute to modified phenotypic fitness? Given an evolutionary landscape and a set of candidate therapies, can we computationally synthesize treatment strategies that control evolution to resistance?
To address the first question, we propose a mathematical framework to reason about evolutionary dynamics of HIV from computationally derived Gibbs energy fitness landscapes -- expanding the theoretical concept of an evolutionary landscape originally conceived by Sewall Wright to a computable, quantifiable, multidimensional, structurally defined fitness surface upon which to study complex HIV evolutionary outcomes.
To design combination treatment strategies that control evolution to resistance, we propose a methodology that solves for optimal combinations and concentrations of candidate therapies, and allows for the ability to quantifiably explore tradeoffs in treatment design, such as limiting the number of candidate therapies in the combination, dosage constraints and robustness to error. Our algorithm is based on the application of recent results in optimal control to an HIV evolutionary dynamics model and is constructed from experimentally derived antibody resistant phenotypes and their single antibody pharmacodynamics. This method represents a first step towards integrating principled engineering techniques with an experimentally based mathematical model in the rational design of combination treatment strategies and offers predictive understanding of the effects of combination therapies of evolutionary dynamics and resistance of HIV. Preliminary in vitro studies suggest that the combination antibody therapies predicted by our algorithm can neutralize heterogeneous viral populations despite containing resistant mutations.</p
Computational Microscopy: Turning Megapixels into Gigapixels
Get PDFThe layout of a typical optical microscope has remained effectively unchanged over the past century. Besides the widespread adoption of digital focal plane arrays, relatively few innovations have helped improve standard imaging with bright-field microscopes. This thesis presents a new microscope imaging method, termed Fourier ptychography, which uses an LED to provide variable sample illumination and post-processing algorithms to recover useful sample information. Examples include increasing the resolution of megapixel-scale images to one gigapixel, measuring quantitative phase, achieving oil-immersion quality resolution without an immersion medium, and recovering complex
three dimensional sample structure