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Resonant Nanocantilever Chemical Vapor Sensors
Get PDFChemical vapor sensors are used in a wide variety of fields such as security, environmental monitoring, the food and beverage industry, and healthcare to detect disease biomarkers on exhaled breath. An electronic nose is composed of an array of cross-responsive chemical vapor sensors, in which every sensor responds to a varying degree to each chemical vapor, creating a "fingerprint" for that vapor. Incorporating an electronic nose into a highly-miniaturized vapor detection system, capable of bringing near laboratory-quality analysis into the field, requires the use of extremely small, fast, and sensitive sensors. One option is resonant nanocantilevers, which respond to changes in mass and stiffness by shifts in resonant frequency, and are capable of detecting mass-loading at the attogram (10-18 g) level in ambient conditions.
To determine whether nanocantilevers can be used in an electronic nose, an array of five nanocantilevers, wherein each sensor was coated with a different dropcast polymer film (2-10 nm thick), were exposed to seven chemical vapors with a range of functional groups. The array successfully discriminated between all vapors, indicating that sensor responses were dominated by vapor absorption into polymer films, and not by non-specific physisorption. The thinness of the polymer film, combined with the small vapor capture area of the nanocantilevers, resulted in lower sensitivity than desired, limiting their effectiveness. To overcome this challenge, surface initiated atom transfer radical polymerization (SI-ATRP) was used to grow a 100 nm thick, uniform films of poly(methylmethacrylate) (PMMA), poly(methyl acrylate) (PMA), and poly(n-butyl methacrylate) (PBMA) on nanocantilevers. The thick polymer films absorbed more vapor, significantly increasing nanocantilever sensitivity. To determine the relative roles of mass loading and stiffness change on nanocantilever sensor response, SI-ATRP was combined with chromium masking, enabling polymer film growth to be localized to either the clamped end (sensitive to stiffness) or the free end (sensitive to mass-loading) of the nanocantilevers. These experiments revealed that changes in stiffness, induced by vapor absorption into the polymer films, dominated the sensor responses, and not mass-loading as was initially assumed. This work demonstrated that an array resonant nanocantilevers can be successfully used a sensitive, nanoscale electronic nose.</p
Chemical and Neural Regulation of Embryonic Branching Morphogenesis
Get PDFLung development is a complex process orchestrated by as many as 40 different types of cells and many signaling and regulatory factors. The spatial sequence of branching of bronchial epithelial tubes is stereotyped. However, it remains unknown how the timing of branch formation is encoded and whether this branching clock function is unique for different tissue types or is conserved across species and lineages that undergo iterative branching. Investigations of the function of the sarcoplasmic-endoplasmic reticulum calcium ATP-ase (SERCA) reveal that protein kinase C (PKC)-modulated SERCA activity controls branch formation across tissues and species.
SERCA controls the rate of intersomitic blood vessel sprouting and branching in zebrafish embryos in a dose-dependent manner. Vessel sprouting recovers upon removal of inhibition and restoration of pump activity. Regulation of cell motility is responsible for these effects.
Similarly, during Drosophila embryonic development, SERCA activity is required for the proper formation of both the central nervous system axon tracts and the network of tracheal tubules that deliver oxygen to tissues. SERCA blockade results in breaks in the tracheal structure and displaced axons. Removal of inhibitor partially rescues these defects, while simultaneous treatment with both SERCA inhibitor and PKC activator remarkably rescues tracheal and neural development. Dynamic imaging of Drosophila embryonic tracheal morphogenesis demonstrates that SERCA's principal function is to govern cell migration. Together, these finding reveal that SERCA regulates cell migration, and this serves as a conserved mechanism that governs branch formation in various cell types and species during development.
On the other hand, morphogens and cell-cell interactions are critical to form a complex, specialized organ such as the mammalian lung. Nerves are known to be present from the early stages of lung branching. Yet a role for nerves in modulating epithelial branching remains to be discerned. Denervation of embryonic mouse lung explants reveals that lung branching requires nerves. Targeted neural ablation, but not inhibition of acetylcholine receptors, halts lung branching and causes a reduction in endothelial cells and epithelial and mesenchymal proliferation. Likewise, ablation of nerves in Drosophila embryos derails tracheal morphogenesis. Therefore, nerves play a conserved role in directing epithelial airway branching.</p
Source Imaging with Dense Sensor Networks: Inversions Based on Adjoint Methods
Get PDFInversions of earthquake source slip from the recorded ground motions typically impose a number of restrictions on the source parameterization, which are needed to stabilize the inverse problem with sparse data. Such restrictions may include smoothing, causality considerations, predetermined shapes of the local source-time function, and constant rupture speed. The best regional networks have sensor spacing in the tens of kilometers range, much larger than the wavelengths relevant to key aspects of earthquake physics. Novel approaches to providing orders-of-magnitude denser sensing include low-cost sensors (Community Seismic Network) and space-based optical imaging (Geostationary Optical Seismometer). This thesis aims to understand whether the inversion results could be substantially improved, with fewer constraints, by the availability of much denser sensor networks than currently available.
Inversions that involve large number of sensors and 3D crustal velocity models are intractable with the current source inversion codes. Hence we have developed a new approach that can handle thousands of sensors in heterogeneous media. It employs iterative conjugate gradient optimization based on an adjoint method and involves iterative time-reversed 3D wave propagation simulations using the spectral element method (SPECFEM3D). We have also developed a variant of this adjoint-based method for layered media that utilizes pre-computed Green’s functions instead of the time-reversed wave propagation. The developed methods have been applied to two problems: impact of crustal structure uncertainties on source inversion and resolution of rise time as a function of network spacing and rupture velocity. In the first part, we show that typical uncertainties in crustal velocity models represented by a von Karman distribution of 5 km correlation length and 5% standard deviation (with Hurst exponent of zero), severely degrade the quality of source inversion. However, if the velocity uncertainties have a correlation of 500 m or a standard deviation of 1%, then source inversion has an adequate quality. In the second part we find that supershear ruptures show almost identical source recovery in terms of width of the slip pulse for network spacings ranging from few km to tens of km, even for rise times as short as 1 sec, while subshear ruptures require a network spacing finer than a penetration length that depends on rupture velocity and rise time, as their peak ground velocity decay rapidly with distance from the fault.
In summary, we have developed scalable source inversion tools that will enable exploiting the next generation of very dense earthquake observation systems, improvements in regional scale 3D tomography models and accelerated advancements in computing capabilities. These developments will be critical in resolving the fine spatio-temporal features of earthquake sources that are pertinent to fracture mechanics and earthquake physics. With the 3D iterative time-reversal imaging, one could aspire for extracting more information from the high frequency wavefield by considering joint improvement of source and structure.</p
Chemistry of Secondary Organic Aerosol Formation
Get PDFThe photooxidation of volatile organic compounds (VOCs) in the atmosphere can lead to the formation of secondary organic aerosol (SOA), a major component of fine particulate matter. Improvements to air quality require insight into the many reactive intermediates that lead to SOA formation, of which only a small fraction have been measured at the molecular level. This thesis describes the chemistry of secondary organic aerosol (SOA) formation from several atmospherically relevant hydrocarbon precursors. Photooxidation experiments of methoxyphenol and phenolic compounds and C12 alkanes were conducted in the Caltech Environmental Chamber. These experiments include the first photooxidation studies of these precursors run under sufficiently low NOx levels, such that RO2 + HO2 chemistry dominates, an important chemical regime in the atmosphere. Using online Chemical Ionization Mass Spectrometery (CIMS), key gas-phase intermediates that lead to SOA formation in these systems were identified. With complementary particle-phase analyses, chemical mechanisms elucidating the SOA formation from these compounds are proposed.
Three methoxyphenol species (phenol, guaiacol, and syringol) were studied to model potential photooxidation schemes of biomass burning intermediates. SOA yields (ratio of mass of SOA formed to mass of primary organic reacted) exceeding 25% are observed. Aerosol growth is rapid and linear with the organic conversion, consistent with the formation of essentially non-volatile products. Gas and aerosol-phase oxidation products from the guaiacol system show that the chemical mechanism consists of highly oxidized aromatic species in the particle phase. Syringol SOA yields are lower than that of phenol and guaiacol, likely due to unique chemistry dependent on methoxy group position.
The photooxidation of several C12 alkanes of varying structure n-dodecane, 2-methylundecane, cyclododecane, and hexylcyclohexane) were run under extended OH exposure to investigate the effect of molecular structure on SOA yields and photochemical aging. Peroxyhemiacetal formation from the reactions of several multifunctional hydroperoxides and aldehyde intermediates was found to be central to organic growth in all systems, and SOA yields increased with cyclic character of the starting hydrocarbon. All of these studies provide direction for future experiments and modeling in order to lessen outstanding discrepancies between predicted and measured SOA.</p
Controlling Wave Propagation through Nonlinear Engineered Granular Systems
Get PDFWe study the fundamental dynamic behavior of a special class of ordered granular systems in order to design new, structured materials with unique physical properties. The dynamic properties of granular systems are dictated by the nonlinear, Hertzian, potential in compression and zero tensile strength resulting from the discrete material structure. Engineering the underlying particle arrangement of granular systems allows for unique dynamic properties, not observed in natural, disordered granular media. While extensive studies on 1D granular crystals have suggested their usefulness for a variety of engineering applications, considerably less attention has been given to higher-dimensional systems. The extension of these studies in higher dimensions could enable the discovery of richer physical phenomena not possible in 1D, such as spatial redirection and anisotropic energy trapping. We present experiments, numerical simulation (based on a discrete particle model), and in some cases theoretical predictions for several engineered granular systems, studying the effects of particle arrangement on the highly nonlinear transient wave propagation to develop means for controlling the wave propagation pathways. The first component of this thesis studies the stress wave propagation resulting from a localized impulsive loading for three different 2D particle lattice structures: square, centered square, and hexagonal granular crystals. By varying the lattice structure, we observe a wide range of properties for the propagating stress waves: quasi-1D solitary wave propagation, fully 2D wave propagation with tunable wave front shapes, and 2D pulsed wave propagation. Additionally the effects of weak disorder, inevitably present in real granular systems, are investigated. The second half of this thesis studies the solitary wave propagation through 2D and 3D ordered networks of granular chains, reducing the effective density compared to granular crystals by selectively placing wave guiding chains to control the acoustic wave transmission. The rapid wave front amplitude decay exhibited by these granular networks makes them highly attractive for impact mitigation applications. The agreement between experiments, numerical simulations, and applicable theoretical predictions validates the wave guiding capabilities of these engineered granular crystals and networks and opens a wide range of possibilities for the realization of increasingly complex granular material design
Ultralow-Loss Silica Resonators and Waveguides on a Silicon Chip
Get PDFCompared to fiber optic systems, on-chip optical devices provide reasonable optical performance and mechanical stability in a smaller footprint and at a lower cost. Such devices, including resonators and waveguides, have been applied in diverse areas of scientific research, including quantum information, nonlinear optics, cavity optomechanics, telecommunications, biodetection, rotation sensing, high stability microwave oscillators, and all-optical signal processing. As performance demands on these applications increase, resonators and waveguides with ultralow propagation loss become critical.
In this thesis, we first demonstrate a new resonator with a record Q factor of 875 million for on-chip devices. The fabrication of our device avoids the requirement for a specialized processing step, which in microtoroid resonators has made it difficult to control their size and achieve millimeter- and centimeter-scale diameters. Attaining these sizes is important in applications such as microcombs. The resonators not only set a new benchmark for the Q factor on a chip, but also provide, for the first time, full compatibility of this important device class with conventional semiconductor processing.
Meanwhile, we demonstrate a monolithic waveguide as long as 27 m (39 m optical path length), and featuring broadband loss rate values of (0.08 ± 0.01) dB/m measured over 7 m by optical backscattering. Resonator measurements show a further reduction of loss to 0.037 dB/m, close to that of optical fibers when first considered a viable technology. Scaling this waveguide to integrated spans exceeding 250 m and attenuation rates below 0.01 dB/m is discussed. This chip-based waveguide and resonator improve shock resistance, and afford the possibility of integration for system-on-a chip functionality.
We finally demonstrate a highly sensitive nanoparticle and virus detection method by using a thermal-stabilized reference interferometer in conjunction with an ultrahigh-Q microcavity. Sensitivity is sufficient to resolve shifts caused by binding of individual nanobeads in solution down to a record radius of 12.5 nm, a size approaching that of single protein molecules. A histogram of wavelength shift versus nanoparticle radius shows that particle size can be inferred from shift maxima.</p
Randomness and Noise in Information Systems
Get PDFThis dissertation is devoted to the study of randomness and noise in a number of information systems including computation systems, storage systems, and natural paradigms like molecular systems, where randomness plays important and distinct roles. Motivated by applications in engineering and science we address a number of theoretical research questions.
In a computation system, randomness enables to perform tasks faster, simpler, or more space efficient. Hence, randomness is a useful computational resource, and the research question we address is: How to efficiently extract randomness from natural sources?
In a molecular system such as a chemical reaction network or a gene regulatory network, randomness is inherent and serves as the key mechanism for producing the desired quantities of molecular species. A chemical reaction can be abstractly described as a probabilistic switch. Hence, given a set of probabilistic switches (with some fixed switching probabilities), the research question we address is: How to synthesize a stochastic network consisting of those switches that computes a pre-specified probability distribution?
In an information storage system, like flash memories where information is represented by a relatively small number of electrons, randomness is a threat to data reliability. Hence, the research question we address is: How to represent, write and read information in the presence of randomness (noise)?
This dissertation is focusing on the foregoing key questions and describes novel contributions related to randomness generation and extraction, stochastic system synthesis and coding for information storage
The Dynamics of White Dwarfs, Black Holes and Stellar Cusps
Get PDFThis thesis contains topics related mostly to the dynamics of white dwarfs (chapter 2), the dynamics of stars around binary super massive black holes (chapters 4, 5 and 6) and dynamics in the singular isothermal sphere (chapter 7).
In chapter 2 the kinematics of young (< 3x108yr) galactic white dwarfs are investigated. A relationship between the mass and kinematics of white dwarfs is demonstrated, whereby high- mass white dwarfs have low velocity dispersion. This is the result of less scattering during the shorter lifetime of their more massive precursors. The kinematics of the highest-mass white dwarfs (> 0.95 Msun) are also investigated, and it is shown that they are consistent with the majority being formed via single-star evolution from massive progenitor stars.
In chapter 3 it is shown that the coolest, oldest white dwarfs can be identified photometrically from their unique colors, and five new ultracool white dwarfs are spectroscopically confirmed.
In chapter 4 it is shown that close binary supermassive black holes (SMBHs) should produce a burst of tidal disruptions of up to 0.1 yr−1 as they form. The quiescent rate is ~10−5 yr−1 per galaxy, and it is therefore shown that binary SMBHs can potentially be identified via multiple tidal disruptions from the same system.
In chapter 5 we perform more extensive simulations of the dynamics of stars around binary SMBHs to better quantify and understand the stellar dynamics. By incorporating general relativistic corrections, we also investigate the processes undergone by compact remnants orbiting the binary SMBHs, analyzing both objects that plunge directly into the SMBHs, and those that undergo extreme mass ratio inspirals (EMRIs). The potential used to mimic general relativistic precession in these simulations is novel, and more accurate for the type of nearly parabolic orbits considered in this work: It is described in chapter 6.
In chapter 7 an analytic solution to the manner in which stars diffuse in the background of a singular isothermal sphere is developed. It is shown a self-similar solution should exist, and this solution is found.
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Building a Gene Regulatory Network in Adult Mouse Skeletal Muscle Following Nerve Injury: Transcriptome Characterization and New Model for Functional cis-Regulatory Analysis In Vivo
Get PDFThe essential functional linkages of gene regulatory networks (GRNs) consist of the interactions between cis-regulatory DNA sequences and trans-acting regulatory factors. These genomically encoded regulatory interactions govern the differential gene expression programs which direct specific biological processes during development and adulthood. Detailed analysis of GRNs during development has yielded important insights regarding the structural and functional dynamics of cis-regulatory modules (CRMs) and cis-regulatory elements (CREs). Indeed, the comprehensive GRNs that have been characterized for various developmental processes provide a model for both the methodological approach and the intellectual understanding required to explore cis-regulatory architecture in other biological contexts. The present study focuses on the physiological context, investigating the GRNs that govern the molecular response to nerve injury in adult mouse skeletal muscle. Until now, high-quality GRN investigations in this context have been hampered by the absence of two fundamental components: a comprehensive catalog of genes differentially expressed after nerve injury, and an effective in vivo gene transfer technique to functionally test putative cis-regulatory modules. Using RNAseq, we have compiled a comprehensive list of all differentially expressed genes at 6.0, 12.0, 24.0, and 168.0 hours following nerve injury. This data has validated previously known differentially expressed genes, as well as identified novel candidates for cis-regulatory analysis. The in vivo gene transfer technique I have adapted and advanced targets an easily accessible muscle group for minimally invasive injection and electroporation of DNA; with it, I demonstrate highly efficient, reproducible, and stable gene transfer in mouse skeletal muscle. In addition, I have optimized the gene transfer technique not only for plasmid DNA reporter vectors, but also for BAC DNA reporter vectors, thus enabling cis-regulatory modules to be tested in a broad chromosomal environment. Finally, I have validated the capacity of this gene transfer method to functionally test CRMs, by identifying a nerve injury-associated CRM of the skeletal muscle-specific myogenin gene. The enhanced resolution provided by this technique allowed for qualitative and quantitative detection of increased reporter signal from a mutated version the nerve injury-associated CRM at ten days following denervation, when compared to the wild-type CRM, implicating it as the cis-acting regulatory sequence responsible for mediating the down-regulation of myogenin during late phase neurogenic skeletal muscle atrophy. This work lays the foundation from which a high-quality adult skeletal muscle GRN can be constructed for nerve injury and other muscle-associated disease states
The Structure of a Transmembrane Protein Sorting Complex
Get PDFThe biogenesis of membrane proteins is an essential process in biology. It requires the protection of hydrophobic transmembrane domains from aggregation in the cytosol as well as targeting to the proper membrane. Tail-anchored (TA) proteins have a single transmembrane helix near their carboxyl termini and require a post-translational mechanism for targeting and insertion. In yeast, the Guided Entry of Tail-anchored proteins (GET) pathway delivers TA proteins to the endoplasmic reticulum (ER). A sorting complex comprising Get4, Get5, and Sgt2 load ER destined TA proteins onto the targeting factor Get3. X-ray crystallography, solution NMR, and small angle X-ray scattering were used to characterize this assembly. Get4 and Get5 form an extended adapter complex. Get4 maintains Get3 in a state competent to receive TA proteins. The N-terminus of Get5 tightly binds Get4, while the C-terminus of Get5 is a homodimerization domain, resulting in a heterotetrameric assembly. A ubiquitin-like domain within Get5 binds the heat-shock protein (HSP) co-chaperone Sgt2, providing a physical link between ER destined TA protein targeting and protein folding pathways. Sgt2 is also an extended homodimeric complex, and can directly bind four major classes of HSPs. The Get4/Get5/Sgt2 sorting complex is multivalent, flexible and the binding of individual components is transient. These results build a model for post-translational protein targeting in eukaryotes that is distinct from other pathways