Isotopic proxies for microbial and environmental change : insights hydrogen isotopes and the Ediacaran Khufai Formation

Microbes have profoundly influenced the Earth’s environments through time. Records of these interactions come primarily from the development and implementation of proxies that relate known modern processes to chemical signatures in the sedimentary record. This thesis is presented in two parts, focusing first on novel proxy development in the modern and second on interpretation of past environments using well-established methods. Part 1, presented in two chapters, builds on previous observations that different microbial metabolisms produce vastly different lipid hydrogen isotopic compositions. Chapter 1 evaluates the potential environmental expression of metabolism-based fractionation differences by exploiting the natural microbial community gradients in hydrothermal springs. We find a very large range in isotopic composition that can be demonstrably linked to the microbial source(s) of the fatty acids at each sample site. In Chapter 2, anaerobic culturing techniques are used to evaluate the hydrogen isotopic fractionations produced by anaerobic microbial metabolisms. Although the observed fractionation patterns are similar to those reported for aerobic cultures for some organisms, others show large differences. Part 2 changes focus from the modern to the ancient and uses classical stratigraphic methods combined with isotope stratigraphy to interpret microbial and environmental changes during the latest Precambrian Era. Chapter 3 presents a detailed characterization of the facies, parasequence development, and stratigraphic architecture of the Ediacaran Khufai Formation. Chapter 4 presents measurements of carbon, oxygen, and sulfur isotopic ratios in stratigraphic context. Large oscillations in the isotopic composition of sulfate constrain the size of the marine sulfate reservoir and suggest incorporation of an enriched isotopic source. Because this data was measured in stratigraphic context, we can assert with confidence that these isotopic shifts are not related to stratigraphic surfaces or facies type but instead reflect the evolution of the ocean through time. This data integrates into the chemostratigraphic global record and contributes to the emerging picture of changing marine chemistry during the latest Precambrian Era.

Steady capillary-gravity waves on deep water

The properties of capillary-gravity waves of permanent form on deep water are studied. Two different formulations to the problem are given. The theory of simple bifurcation is reviewed. For small amplitude waves a formal perturbation series is used. The Wilton ripple phenomenon is reexamined and shown to be associated with a bifurcation in which a wave of permanent form can double its period. It is shown further that Wilton's ripples are a special case of a more general phenomenon in which bifurcation into subharmonics and factorial higher harmonics can occur. Numerical procedures for the calculation of waves of finite amplitude are developed. Bifurcation and limit lines are calculated. Pure and combination waves are continued to maximum amplitude. It is found that the height is limited in all cases by the surface enclosing one or more bubbles. Results for the shape of gravity waves are obtained by solving an integra-differential equation. It is found that the family of solutions giving the waveheight or equivalent parameter has bifurcation points. Two bifurcation points and the branches emanating from them are found specifically, corresponding to a doubling and tripling of the wavelength. Solutions on the new branches are calculated.

Liquid silicate equation of state : using shock waves to understand the properties of the deep Earth

The equations of state (EOS) of several geologically important silicate liquids have been constrained via preheated shock wave techniques. Results on molten Fe₂SiO₄ (fayalite), Mg₂SiO₄ (forsterite), CaFeSi₂O₆ (hedenbergite), an equimolar mixture of CaAl₂Si₂O₈-CaFeSi₂O₆ (anorthite-hedenbergite), and an equimolar mixture of CaAl₂Si₂O₈-CaFeSi₂O₆-CaMgSi₂O₆(anorthite-hedenbergite-diopside) are presented. This work represents the first ever direct EOS measurements of an iron-bearing liquid or of a forsterite liquid at pressures relevant to the deep Earth (> 135 GPa). Additionally, revised EOS for molten CaMgSi₂O₆ (diopside), CaAl₂Si₂O₈ (anorthite), and MgSiO₃ (enstatite), which were previously determined by shock wave methods, are also presented.

The liquid EOS are incorporated into a model, which employs linear mixing of volumes to determine the density of compositionally intermediate liquids in the CaO-MgO-Al₂O₃-SiO₂-FeO major element space. Liquid volumes are calculated for temperature and pressure conditions that are currently present at the core-mantle boundary or that may have occurred during differentiation of a fully molten mantle magma ocean.

The most significant implications of our results include: (1) a magma ocean of either chondrite or peridotite composition is less dense than its first crystallizing solid, which is not conducive to the formation of a basal mantle magma ocean, (2) the ambient mantle cannot produce a partial melt and an equilibrium residue sufficiently dense to form an ultralow velocity zone mush, and (3) due to the compositional dependence of Fe2+ coordination, there is a threshold of Fe concentration (molar X_Fe ≤ 0.06) permitted in a liquid for which its density can still be approximated by linear mixing of end-member volumes.

Deep tissue fluorescence imaging with time-reversed light

Advances in optical techniques have enabled many breakthroughs in biology and medicine. However, light scattering by biological tissues remains a great obstacle, restricting the use of optical methods to thin ex vivo sections or superficial layers in vivo. In this thesis, we present two related methods that overcome the optical depth limit—digital time reversal of ultrasound encoded light (digital TRUE) and time reversal of variance-encoded light (TROVE). These two techniques share the same principle of using acousto-optic beacons for time reversal optical focusing within highly scattering media, like biological tissues. Ultrasound, unlike light, is not significantly scattered in soft biological tissues, allowing for ultrasound focusing. In addition, a fraction of the scattered optical wavefront that passes through the ultrasound focus gets frequency-shifted via the acousto-optic effect, essentially creating a virtual source of frequency-shifted light within the tissue. The scattered ultrasound-tagged wavefront can be selectively measured outside the tissue and time-reversed to converge at the location of the ultrasound focus, enabling optical focusing within deep tissues. In digital TRUE, we time reverse ultrasound-tagged light with an optoelectronic time reversal device (the digital optical phase conjugate mirror, DOPC). The use of the DOPC enables high optical gain, allowing for high intensity optical focusing and focal fluorescence imaging in thick tissues at a lateral resolution of 36 µm by 52 µm. The resolution of the TRUE approach is fundamentally limited to that of the wavelength of ultrasound. The ultrasound focus (~ tens of microns wide) usually contains hundreds to thousands of optical modes, such that the scattered wavefront measured is a linear combination of the contributions of all these optical modes. In TROVE, we make use of our ability to digitally record, analyze and manipulate the scattered wavefront to demix the contributions of these spatial modes using variance encoding. In essence, we encode each spatial mode inside the scattering sample with a unique variance, allowing us to computationally derive the time reversal wavefront that corresponds to a single optical mode. In doing so, we uncouple the system resolution from the size of the ultrasound focus, demonstrating optical focusing and imaging between highly diffusing samples at an unprecedented, speckle-scale lateral resolution of ~ 5 µm. Our methods open up the possibility of fully exploiting the prowess and versatility of biomedical optics in deep tissues.

Insights into the mechanism of human erythrocyte hexose transport : a transferred NOE study of glucose binding to GLUT1

This study examines binding of α- and β-D-glucose in their equilibrium mixture to the glucose transporter (GLUT1) in human erythrocyte membrane preparations by an ^1H NMR method, the transferred NOE (TRNOE). This method is shown theoretically and experimentally to be a sensitive probe of weak ligand-macromolecule interactions. The TRNOEs observed are shown to arise solely from glucose binding to GLUT1. Sites at both membrane faces contribute to the TRNOEs. Binding curves obtained are consistent with a homogeneous class of sugar sites, with an apparent K_D which varies (from ~30 mM to ~70 mM for both anomers) depending on the membrane preparation examined. Preparations with a higher proportion of the cytoplasmic membrane face exposed to bulk solution yield higher apparent KK_Ds. The glucose transport inhibitor cytochalasin B essentially eliminates the TRNOE. Nonlinearity was found in the dependence on sugar concentration of the apparent inhibition constant for cytochalasin B reversal of the TRNOE observed in the α anomer (and probably the β anomer); such nonlinearity implies the existence of ternary complexes of sugar, inhibitor and transporter. The inhibition results furthermore imply the presence of a class of relatively high-affinity (K_D < 2mM) sugar sites specific for the α anomer which do not contribute to NMR-observable binding. The presence of two classes of sugar-sensitive cytochalasin B sites is also indicated. These results are compared with predictions of the alternating conformer model of glucose transport. Variation of apparent K_D in the NMR-observable sites, the formation of ternary complexes and the presence of an anomer-specific site are shown to be inconsistent with this model. An alternate model is developed which reconciles these results with the known transport behavior of GLUT1. In this model, the transporter possesses (at minimum) three classes of sugar sites: (i) transport sites, which are alternately exposed to the cytoplasmic or the extracellular compartment, but never to both simultaneously, (ii) a class of sites (probably relatively low-affinity) which are confined to one compartment, and (iii) the high-affinity α anomer-specific sites, which are confined to the cytoplasmic compartment.

A study of protein targeting reveals insights into mitigating protein aggregation

A unique chloroplast Signal Recognition Particle (SRP) in green plants is primarily dedicated to the post-translational targeting of light harvesting chlorophyll-a/b binding (LHC) proteins. Our study of the thermodynamics and kinetics of the GTPases of the system demonstrates that GTPase complex assembly and activation are highly coupled in the chloroplast GTPases, suggesting they may forego the GTPase activation step as a key regulatory point. This reflects adaptations of the chloroplast SRP to the delivery of their unique substrate protein. Devotion to one highly hydrophobic family of proteins also may have allowed the chloroplast SRP system to evolve an efficient chaperone in the cpSRP43 subunit. To understand the mechanism of disaggregation, we showed that LHC proteins form micellar, disc-shaped aggregates that present a recognition motif (L18) on the aggregate surface. Further molecular genetic and structure-activity analyses reveal that the action of cpSRP43 can be dissected into two steps: (i) initial recognition of L18 on the aggregate surface; and (ii) aggregate remodeling, during which highly adaptable binding interactions of cpSRP43 with hydrophobic transmembrane domains of the substrate protein compete with the packing interactions within the aggregate. We also tested the adaptability of cpSRP43 for alternative substrates, specifically in attempts to improve membrane protein expression and inhibition of amyloid beta fibrillization. These preliminary results attest to cpSRP43’s potential as a molecular chaperone and provides the impetus for further engineering endeavors to address problems that stem from protein aggregation.

Palladium-catalyzed asymmetric allylic alkylation: insights, application toward cyclopentanoid and cycloheptanoid molecules, and the total synthesis of several daucane sesquiterpenes

The asymmetric construction of quaternary stereocenters is a topic of great interest in the organic chemistry community given their prevalence in natural products and biologically active molecules. Over the last decade, the Stoltz group has pursued the synthesis of this challenging motif via a palladium-catalyzed allylic alkylation using chiral phosphinooxazoline (PHOX) ligands. Recent results indicate that the alkylation of lactams and imides consistently proceeds with enantioselectivities substantially higher than any other substrate class previously examined in this system. This observation prompted exploration of the characteristics that distinguish these molecules as superior alkylation substrates, resulting in newfound insights and marked improvements in the allylic alkylation of carbocyclic compounds.

General routes to cyclopentanoid and cycloheptanoid core structures have been developed that incorporate the palladium-catalyzed allylic alkylation as a key transformation. The unique reactivity of α-quaternary vinylogous esters upon addition of hydride or organometallic reagents enables divergent access to γ-quaternary acylcyclopentenes or cycloheptenones through respective ring contraction or carbonyl transposition pathways. Derivatization of the resulting molecules provides a series of mono-, bi-, and tricyclic systems that can serve as valuable intermediates for the total synthesis of complex natural products.

The allylic alkylation and ring contraction methodology has been employed to prepare variably functionalized bicyclo[5.3.0]decane molecules and enables the enantioselective total syntheses of daucene, daucenal, epoxydaucenal B, and 14-p-anisoyloxydauc-4,8-diene. This route overcomes the challenge of accessing β-substituted acylcyclopentenes by employing a siloxyenone to effect the Grignard addition and ring opening in a single step. Subsequent ring-closing metathesis and aldol reactions form the hydroazulene core of these targets. Derivatization of a key enone intermediate allows access to either the daucane sesquiterpene or sphenobolane diterpene carbon skeletons, as well as other oxygenated scaffolds.

Exploiting seismic waveforms of ambient noise and earthquakes

In this thesis, I apply detailed waveform modeling to study noise correlations in different environments, and earthquake waveforms for source parameters and velocity structure.

Green's functions from ambient noise correlations have primarily been used for travel-time measurement. In Part I of this thesis, by detailed waveform modeling of noise correlation functions, I retrieve both surface waves and crustal body waves from noise, and use them in improving earthquake centroid locations and regional crustal structures. I also present examples in which the noise correlations do not yield Green's functions, yet the results are still interesting and useful after case-by-case analyses, including non-uniform distribution of noise sources, spurious velocity changes, and noise correlations on the Amery Ice Shelf.

In Part II of this thesis, I study teleseismic body waves of earthquakes for source parameters or near-source structure. With the dense modern global network and improved methodologies, I obtain high-resolution earthquake locations, focal mechanisms and rupture processes, which provide critical insights to earthquake faulting processes in shallow and deep parts of subduction zones. Waveform modeling of relatively simple subduction zone events also displays new constraints on the structure of subducted slabs.

In summary, behind my approaches to the relatively independent problems, the philosophy is to bring observational insights from seismic waveforms in critical and simple ways.

The deep ocean density structure at the Last Glacial Maximum : What was it and why?

The search for reliable proxies of past deep ocean temperature and salinity has proved difficult, thereby limiting our ability to understand the coupling of ocean circulation and climate over glacial-interglacial timescales. Previous inferences of deep ocean temperature and salinity from sediment pore fluid oxygen isotopes and chlorinity indicate that the deep ocean density structure at the Last Glacial Maximum (LGM, approximately 20,000 years BP) was set by salinity, and that the density contrast between northern and southern sourced deep waters was markedly greater than in the modern ocean. High density stratification could help explain the marked contrast in carbon isotope distribution recorded in the LGM ocean relative to that we observe today, but what made the ocean's density structure so different at the LGM? How did it evolve from one state to another? Further, given the sparsity of the LGM temperature and salinity data set, what else can we learn by increasing the spatial density of proxy records?

We investigate the cause and feasibility of a highly and salinity stratified deep ocean at the LGM and we work to increase the amount of information we can glean about the past ocean from pore fluid profiles of oxygen isotopes and chloride. Using a coupled ocean--sea ice--ice shelf cavity model we test whether the deep ocean density structure at the LGM can be explained by ice--ocean interactions over the Antarctic continental shelves, and show that a large contribution of the LGM salinity stratification can be explained through lower ocean temperature. In order to extract the maximum information from pore fluid profiles of oxygen isotopes and chloride we evaluate several inverse methods for ill-posed problems and their ability to recover bottom water histories from sediment pore fluid profiles. We demonstrate that Bayesian Markov Chain Monte Carlo parameter estimation techniques enable us to robustly recover the full solution space of bottom water histories, not only at the LGM, but through the most recent deglaciation and the Holocene up to the present. Finally, we evaluate a non-destructive pore fluid sampling technique, Rhizon samplers, in comparison to traditional squeezing methods and show that despite their promise, Rhizons are unlikely to be a good sampling tool for pore fluid measurements of oxygen isotopes and chloride.

Functional genomic studies of the structure and regulation of eukaryotic transcriptomes

The main focus of this thesis is the use of high-throughput sequencing technologies in functional genomics (in particular in the form of ChIP-seq, chromatin immunoprecipitation coupled with sequencing, and RNA-seq) and the study of the structure and regulation of transcriptomes. Some parts of it are of a more methodological nature while others describe the application of these functional genomic tools to address various biological problems. A significant part of the research presented here was conducted as part of the ENCODE (ENCyclopedia Of DNA Elements) Project.

The first part of the thesis focuses on the structure and diversity of the human transcriptome. Chapter 1 contains an analysis of the diversity of the human polyadenylated transcriptome based on RNA-seq data generated for the ENCODE Project. Chapter 2 presents a simulation-based examination of the performance of some of the most popular computational tools used to assemble and quantify transcriptomes. Chapter 3 includes a study of variation in gene expression, alternative splicing and allelic expression bias on the single-cell level and on a genome-wide scale in human lymphoblastoid cells; it also brings forward a number of critical to the practice of single-cell RNA-seq measurements methodological considerations.

The second part presents several studies applying functional genomic tools to the study of the regulatory biology of organellar genomes, primarily in mammals but also in plants. Chapter 5 contains an analysis of the occupancy of the human mitochondrial genome by TFAM, an important structural and regulatory protein in mitochondria, using ChIP-seq. In Chapter 6, the mitochondrial DNA occupancy of the TFB2M transcriptional regulator, the MTERF termination factor, and the mitochondrial RNA and DNA polymerases is characterized. Chapter 7 consists of an investigation into the curious phenomenon of the physical association of nuclear transcription factors with mitochondrial DNA, based on the diverse collections of transcription factor ChIP-seq datasets generated by the ENCODE, mouseENCODE and modENCODE consortia. In Chapter 8 this line of research is further extended to existing publicly available ChIP-seq datasets in plants and their mitochondrial and plastid genomes.

The third part is dedicated to the analytical and experimental practice of ChIP-seq. As part of the ENCODE Project, a set of metrics for assessing the quality of ChIP-seq experiments was developed, and the results of this activity are presented in Chapter 9. These metrics were later used to carry out a global analysis of ChIP-seq quality in the published literature (Chapter 10). In Chapter 11, the development and initial application of an automated robotic ChIP-seq (in which these metrics also played a major role) is presented.

The fourth part presents the results of some additional projects the author has been involved in, including the study of the role of the Piwi protein in the transcriptional regulation of transposon expression in Drosophila (Chapter 12), and the use of single-cell RNA-seq to characterize the heterogeneity of gene expression during cellular reprogramming (Chapter 13).

The last part of the thesis provides a review of the results of the ENCODE Project and the interpretation of the complexity of the biochemical activity exhibited by mammalian genomes that they have revealed (Chapters 15 and 16), an overview of the expected in the near future technical developments and their impact on the field of functional genomics (Chapter 14), and a discussion of some so far insufficiently explored research areas, the future study of which will, in the opinion of the author, provide deep insights into many fundamental but not yet completely answered questions about the transcriptional biology of eukaryotes and its regulation.

Dissecting neural circuits for vision in nonhuman primates using fMRI-guided electrophysiology and optogenetics

The visual system is a remarkable platform that evolved to solve difficult computational problems such as detection, recognition, and classification of objects. Of great interest is the face-processing network, a sub-system buried deep in the temporal lobe, dedicated for analyzing specific type of objects (faces). In this thesis, I focus on the problem of face detection by the face-processing network. Insights obtained from years of developing computer-vision algorithms to solve this task have suggested that it may be efficiently and effectively solved by detection and integration of local contrast features. Does the brain use a similar strategy? To answer this question, I embark on a journey that takes me through the development and optimization of dedicated tools for targeting and perturbing deep brain structures. Data collected using MR-guided electrophysiology in early face-processing regions was found to have strong selectivity for contrast features, similar to ones used by artificial systems. While individual cells were tuned for only a small subset of features, the population as a whole encoded the full spectrum of features that are predictive to the presence of a face in an image. Together with additional evidence, my results suggest a possible computational mechanism for face detection in early face processing regions. To move from correlation to causation, I focus on adopting an emergent technology for perturbing brain activity using light: optogenetics. While this technique has the potential to overcome problems associated with the de-facto way of brain stimulation (electrical microstimulation), many open questions remain about its applicability and effectiveness for perturbing the non-human primate (NHP) brain. In a set of experiments, I use viral vectors to deliver genetically encoded optogenetic constructs to the frontal eye field and faceselective regions in NHP and examine their effects side-by-side with electrical microstimulation to assess their effectiveness in perturbing neural activity as well as behavior. Results suggest that cells are robustly and strongly modulated upon light delivery and that such perturbation can modulate and even initiate motor behavior, thus, paving the way for future explorations that may apply these tools to study connectivity and information flow in the face processing network.

New insights into the formation and modification of carbonate-bearing minerals and methane gas in geological systems using multiply substituted isotopologues

This thesis describes the use of multiply-substituted stable isotopologues of carbonate minerals and methane gas to better understand how these environmentally significant minerals and gases form and are modified throughout their geological histories. Stable isotopes have a long tradition in earth science as a tool for providing quantitative constraints on how molecules, in or on the earth, formed in both the present and past. Nearly all studies, until recently, have only measured the bulk concentrations of stable isotopes in a phase or species. However, the abundance of various isotopologues within a phase, for example the concentration of isotopologues with multiple rare isotopes (multiply substituted or 'clumped' isotopologues) also carries potentially useful information. Specifically, the abundances of clumped isotopologues in an equilibrated system are a function of temperature and thus knowledge of their abundances can be used to calculate a sample’s formation temperature. In this thesis, measurements of clumped isotopologues are made on both carbonate-bearing minerals and methane gas in order to better constrain the environmental and geological histories of various samples.

Clumped-isotope-based measurements of ancient carbonate-bearing minerals, including apatites, have opened up paleotemperature reconstructions to a variety of systems and time periods. However, a critical issue when using clumped-isotope based measurements to reconstruct ancient mineral formation temperatures is whether the samples being measured have faithfully recorded their original internal isotopic distributions. These original distributions can be altered, for example, by diffusion of atoms in the mineral lattice or through diagenetic reactions. Understanding these processes quantitatively is critical for the use of clumped isotopes to reconstruct past temperatures, quantify diagenesis, and calculate time-temperature burial histories of carbonate minerals. In order to help orient this part of the thesis, Chapter 2 provides a broad overview and history of clumped-isotope based measurements in carbonate minerals.

In Chapter 3, the effects of elevated temperatures on a sample’s clumped-isotope composition are probed in both natural and experimental apatites (which contain structural carbonate groups) and calcites. A quantitative model is created that is calibrated by the experiments and consistent with the natural samples. The model allows for calculations of the change in a sample’s clumped isotope abundances as a function of any time-temperature history.

In Chapter 4, the effects of diagenesis on the stable isotopic compositions of apatites are explored on samples from a variety of sedimentary phosphorite deposits. Clumped isotope temperatures and bulk isotopic measurements from carbonate and phosphate groups are compared for all samples. These results demonstrate that samples have experienced isotopic exchange of oxygen atoms in both the carbonate and phosphate groups. A kinetic model is developed that allows for the calculation of the amount of diagenesis each sample has experienced and yields insight into the physical and chemical processes of diagenesis.

The thesis then switches gear and turns its attention to clumped isotope measurements of methane. Methane is critical greenhouse gas, energy resource, and microbial metabolic product and substrate. Despite its importance both environmentally and economically, much about methane’s formational mechanisms and the relative sources of methane to various environments remains poorly constrained. In order to add new constraints to our understanding of the formation of methane in nature, I describe the development and application of methane clumped isotope measurements to environmental deposits of methane. To help orient the reader, a brief overview of the formation of methane in both high and low temperature settings is given in Chapter 5.

In Chapter 6, a method for the measurement of methane clumped isotopologues via mass spectrometry is described. This chapter demonstrates that the measurement is precise and accurate. Additionally, the measurement is calibrated experimentally such that measurements of methane clumped isotope abundances can be converted into equivalent formational temperatures. This study represents the first time that methane clumped isotope abundances have been measured at useful precisions.

In Chapter 7, the methane clumped isotope method is applied to natural samples from a variety of settings. These settings include thermogenic gases formed and reservoired in shales, migrated thermogenic gases, biogenic gases, mixed biogenic and thermogenic gas deposits, and experimentally generated gases. In all cases, calculated clumped isotope temperatures make geological sense as formation temperatures or mixtures of high and low temperature gases. Based on these observations, we propose that the clumped isotope temperature of an unmixed gas represents its formation temperature — this was neither an obvious nor expected result and has important implications for how methane forms in nature. Additionally, these results demonstrate that methane-clumped isotope compositions provided valuable additional constraints to studying natural methane deposits.

Chelation-enforced metal-arene interactions : insights into substrate binding and catalysis by late transition metal complexes

Understanding and catalyzing chemical reactions requiring multiple electron transfers is an endeavor relevant to many outstanding challenges in the field of chemistry. To study multi-electron reactions, a terphenyl diphosphine framework was designed to support one or more metals in multiple redox states via stabilizing interactions with the central arene of the terphenyl backbone. A variety of unusual compounds and reactions and their relevance toward prominent research efforts in chemistry are the subject of this dissertation.

Chapter 2 introduces the para-terphenyl diphosphine framework and its coordination chemistry with group 10 transition metal centers. Both mononuclear and dinuclear compounds are characterized. In many cases, the metal center(s) are stabilized by the terphenyl central arene. These metal–arene interactions are characterized both statically, in the solid state, and fluxionally, in solution. As a proof-of-principle, a dinickel framework is shown to span multiple redox states, showing that multielectron chemistry can be supported by the coordinatively flexible terphenyl diphosphine.

Chapter 3 presents reactivity of the terphenyl diphosphine when bound to a metal center. Because of the dearomatizing effect of the metal center, the central arene of the ligand is susceptible to reactions that do not normally affect arenes. In particular, Ni-to-arene H-transfer and arene dihydrogenation reactions are presented. Additionally, evidence for reversibility of the Ni-to-arene H-transfer is discussed.

Chapter 4 expands beyond the chelated metal-arene interactions of the previous chapters. A dipalladium(I) terphenyl diphosphine framework is used to bind a variety of exogenous organic ligands including arenes, dienes, heteroarenes, thioethers, and anionic ligands. The compounds are structurally characterized, and many ligands exhibit unprecedented bindng modes across two metal centers. The relative binding affinities are evaluated spectroscopically, and equilibrium binding constants for the examined ligands are determined to span over 13 orders of magnitude. As an application of this framework, mild hydrogenation conditions of bound thiophene are presented.

Chapter 5 studies nickel-mediated C–O bond cleavage of aryl alkyl ethers, a transformation with emerging applications in fields such as lignin biofuels and organic methodology. Other group members have shown the mechanism of C–O bond cleavage of an aryl methyl ether incorporated into a meta-terphenyl diphosphine framework to proceed through β-H elimination of an alkoxide. First, the electronic selectivity of the model system is examined computationally and compared with catalytic systems. The lessons learned from the model system are then applied to isotopic labeling studies for catalytic aryl alkyl ether cleavage under dihydrogen. Results from selective deuteration experiments and mass spectrometry draw a clear analogy between the mechanisms of the model and catalytic systems that does not require dihydrogen for C–O bond cleavage, although dihydrogen is proposed to play a role in catalyst activation and catalytic turnover.

Appendix A presents initial efforts toward heterodinuclear complexes as models for CO dehydrogenase and Fischer Tropsch chemistry. A catechol-incorporating terphenyl diphosphine is reported, and metal complexes thereof are discussed.

Appendix B highlights some structurally characterized terphenyl diphosphine complexes that either do not thematically belong in the research chapters or proved to be difficult to reproduce. These compounds show unusual coordination modes of the terphenyl diphosphine from which other researchers may glean insights.

Dynamic rupture simulation integrated with earthquake observations

Dynamic rupture simulations are unique in their contributions to the study of earthquake physics. The current rapid development of dynamic rupture simulations poses several new questions: Do the simulations reflect the real world? Do the simulations have predictive power? Which one should we believe when the simulations disagree? This thesis illustrates how integration with observations can help address these questions and reduce the effects of non-uniqueness of both dynamic rupture simulations and kinematic inversion problems. Dynamic rupture simulations with observational constraints can effectively identify non-physical features inferred from observations. Moreover, the integrative technique can also provide more physical insights into the mechanisms of earthquakes. This thesis demonstrates two examples of such kinds of integration: dynamic rupture simulations of the M_w 9.0 2011 Tohoku-Oki earthquake and of earthquake ruptures in damaged fault zones:

(1) We develop simulations of the Tohoku-Oki earthquake based on a variety of observations and minimum assumptions of model parameters. The simulations provide realistic estimations of stress drop and fracture energy of the region and explain the physical mechanisms of high-frequency radiation in the deep region. We also find that the overridding subduction wedge contributes significantly to the up-dip rupture propagation and large final slip in the shallow region. Such findings are also applicable to other megathrust earthquakes.

(2) Damaged fault zones are usually found around natural faults, but their effects on earthquake ruptures have been largely unknown. We simulate earthquake ruptures in damaged fault zones with material properties constrained by seismic and geological observations. We show that reflected waves in fault zones are effective at generating pulse-like ruptures and head waves tend to accelerate and decelerate rupture speeds. These mechanisms are robust in natural fault zones with large attenuation and off-fault plasticity. Moreover, earthquakes in damaged fault zones can propagate at super-Rayleigh speeds that are unstable in homogeneous media. Supershear transitions in fault zones do not require large fault stresses. In the end, we present observations in the Big Bear region, where variability of rupture speeds of small earthquakes correlates with the laterally variable materials in a damaged fault zone.

New Insights from Aperiodic Variability of Young Stars

Nearly all young stars are variable, with the variability traditionally divided into two classes: periodic variables and aperiodic or "irregular" variables. Periodic variables have been studied extensively, typically using periodograms, while aperiodic variables have received much less attention due to a lack of standard statistical tools. However, aperiodic variability can serve as a powerful probe of young star accretion physics and inner circumstellar disk structure. For my dissertation, I analyzed data from a large-scale, long-term survey of the nearby North America Nebula complex, using Palomar Transient Factory photometric time series collected on a nightly or every few night cadence over several years. This survey is the most thorough exploration of variability in a sample of thousands of young stars over time baselines of days to years, revealing a rich array of lightcurve shapes, amplitudes, and timescales.

I have constrained the timescale distribution of all young variables, periodic and aperiodic, on timescales from less than a day to ~100 days. I have shown that the distribution of timescales for aperiodic variables peaks at a few days, with relatively few (~15%) sources dominated by variability on tens of days or longer. My constraints on aperiodic timescale distributions are based on two new tools, magnitude- vs. time-difference (Δm-Δt) plots and peak-finding plots, for describing aperiodic lightcurves; this thesis provides simulations of their performance and presents recommendations on how to apply them to aperiodic signals in other time series data sets. In addition, I have measured the error introduced into colors or SEDs from combining photometry of variable sources taken at different epochs. These are the first quantitative results to be presented on the distributions in amplitude and time scale for young aperiodic variables, particularly those varying on timescales of weeks to months.