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Superconducting Electromechanical and Nanophotonic Devices for Quantum Measurement and Conversion
Get PDFMicroscale and nanoscale mechanical resonators have been used in advanced technological applications, from high precision time keeping and mass sensing, to processing high frequency signals in mobile communications. In the last few decades, they have been an important part of progress in the field of quantum information and metrology and have been proposed as quantum memories or transducers for measuring or connecting different types of quantum systems.
The field of cavity optomechanics and electromechanics is concerned with coupling the electromagnetic field of a resonant optical cavity or electrical circuit to mechanical motion. These systems provide potential means to control and engineer the state of a mechanical object at the quantum level. This thesis contains the description of mechanical systems in megahertz to a few hundred megahertz frequency range formed by nano-fabricating photonic, phononic, and electrical circuits on a chip. These structures are designed to provide a large radiation pressure coupling between mechanical motion and electromagnetic fields to address and manipulate motional degrees of freedom. Qualitatively novel quantum effects are expected when one takes a step beyond linear coupling and exploits higher order interactions. To that end, we integrate electrical, mechanical and photonic structures in a multimode photonic crystal structure to observe "x2-coupling", where the optical cavity frequency is coupled to the square of the mechanical displacement. Moreover, we have developed two integrated on-chip platforms based on Si3N4 and Si nanomembranes capable of interfacing superconducting qubits and optical photons and realizing reversible microwave-to-optical conversion. We employ radiation pressure to cool these mechanical resonators to their quantum ground state. Finally, we demonstrate a form of electromechanical crystal for coupling microwave photons and hypersonic phonons of frequency ωm/2π = 0.425 GHz by capacitively coupling a phononic crystal acoustic cavity to a superconducting microwave resonator. Moving to higher frequency acoustic cavities not only facilitates the integration of electromechanical circuits and nanophotonic systems capable of operation in the resolved sideband limit of optomechanics for noise-free quantum signal conversion, but it opens up the possibility of using phonons as information carriers via phononic circuits. Utilizing a two-photon resonance condition for efficient microwave pumping and phononic bandgap shield to eliminate acoustic radiation, we achieve large cooperative electromechanical coupling (C ≈ 30) and intrinsic decay time of 2.3 ms. Moreover, electrical read-out of the phonon occupancy shows that the acoustic mode thermalizes close to its quantum ground-state of motion (phonon occupancy nm=1.5) at a fridge temperature of Tf = 10 mK. We conclude by considering several designs and fabrication improvements to the hypersonic electromechanical crystals that would enable them to perform quantum conversion between the electrical and acoustic
domain.</p
Investigations of DNA-Mediated Redox Signaling Between E.coli DNA Repair Pathways
Get PDFThe 4Fe4S cluster has been identified in various DNA-processing proteins spanning a variety of biological functions and all domains of life. Recently, a novel functional role for the cluster has been identified for proteins in DNA repair and replication as a redox switch for DNA binding. Human DNA primase utilizes this redox switch to coordinate primer handoff in replication. The enzymatic activity of DNA polymerase δ is tuned by the redox-switch, allowing for a fast and reversible regulation of replication in response to oxidative stress. In all cases, the redox of the 4Fe4S cluster is achieved through DNA-mediated charge transport (CT), the ability for DNA to carry charge through its π-stack. Due to the reliance of this phenomena on the π-stacking of the nitrogenous bases, DNA CT is sensitive to DNA lesions and mismatches and can proceed over long molecular distances if the DNA is well-stacked. Given this powerful biological phenomena, new inter-protein signaling interactions have been identified with important downstream consequences for genome fidelity. Here, we investigate the ways DNA-mediated charge transport between DNA processing enzymes results in efficient DNA repair or prevention of DNA-damage.
First, we investigated Dps, a bacterial ferritin that protects DNA from oxidative stress and implicated in bacterial survival and virulence. Dps iron sites can scavenge diffusing oxidants directly but additionally electrons and electron holes can be rapidly transported through the base-pair π-stack though DNA CT, thus providing an additional mechanism of genome protection by Dps. Using X-band EPR, we monitored formation of mononuclear high-spin Fe(III) sites of low symmetry as a gauge of effective Dps protection via oxidation of its iron sites. Using poly(dGdC)2 or poly(dAdT)2 DNA, we uncovered the dependence of DNA protection by Dps to the formation of guanine radical intermediates. Oxidation of Dps iron sites depended on the presence of the W52 residue. Point mutations of W52 revealed its involvement in an electron transfer (ET) pathway for the oxidation of the Dps iron sites. Finally, we investigated the in vivo consequences of the Dps W52 residue by complementing knockout Dps E.coli with plasmids expressing WT, W52A, or W52Y Dps and applying oxidative stress to the cells through hydrogen peroxide treatment. These assays further demonstrated the ability of Dps to protect the E.coli genome from harmful oxidants DNA-mediated electron transfer processes.
Second, we assessed the redox properties of EndoIII and MutY, two base excision repair glycosylases containing 4Fe4S clusters, in the presence and absence of DNA. Previous work has shown these proteins to have a midpoint redox potential around 80mV vs. NHE when bound to DNA with a positive shift in potential in the absence of DNA. However, electrochemical details that define this midpoint potential have not been uncovered. Using a pyrolytic graphite edge electrode, we measured the midopoint potential of point mutations of EndoIII where point charges are flipped near the cluster (K208E, Y205H, and E200K) in the absence of DNA. Our measurements suggest that a change in a single point charge is not enough to shift the 4Fe4S cluster midpoint potential dramatically. Addition of a poly-L-glutamate polyanion introduced a slight negative shift (~20mV), but with the introduction of DNA a large negative shift was observed (70mV). Overall, binding to the DNA polyanion is the dominant effect in tuning the redox potential of the 4Fe4S cluster, helping to explain why all DNA binding proteins with 4Fe4S clusters studied to date have similar DNA-bound potentials.
With these similar DNA-bound potentials, inter-protein redox signaling should occur. Previous works have demonstrated DNA-mediated redox signaling such as EndoIII signaling to DinG helicase, involved in R-loop maturation, increasing cellular survival by resolving deleterious R-loops. Additionally, different cluster- containing repair proteins of different functions and domains of life have been shown using atomic force microscopy (AFM) to localize to DNA mismatches through a redox switch for DNA-binding affinity. Given a DNA-mediated redox signaling system to scan the genome for lesions, the expression levels of these proteins may play a role in defining the scanning efficiency. We identified that the EndoIII E.coli knockout strain was sensitive to UV irradiation. This implies that EndoIII assists the nucleotide excision repair (NER) pathway via DNA-mediated redox signaling. However, knockout of MutY, another 4Fe4S glycosylase, does not impart the same UV sensitivity, and thus suggests key differences between MutY and EndoIII that define effective DNA-mediated redox signaling. Thus, the effect of protein expression level on the efficiency of DNA-mediated redox signaling was investigated using inducible protein expression of EndoIII to rescue UV-sensitivity. Using both plasmid-based and genome integrated constructs, we uncovered that low amounts of EndoIII expression were enough to rescue the growth defect, and overexpression of WT EndoIII leads to a greater defect caused by excess non-specific enzyme activity. These findings further informed investigation of this unique protein signaling interaction between EndoIII and NER protein UvrC.
With proper EndoIII rescue plasmids, we further characterized the DNA- mediated redox signaling interaction between EndoIII and UvrC. Using UV-irradiation of genetic knockout strains and growth curve analysis, we demonstrate that EndoIII expression is essential for efficient repair of UV-induced DNA lesions, as measured through quantitative changes in growth lag-time when wild-type or mutant EndoIII is present in the cell. Electrochemical analysis of EndoIII point mutants quantify the DNA-CT inefficiencies that lead to the observed phenotypes. EndoIII, a BER repair protein, assists the NER pathway in the repair of UV-induced DNA lesions via DNA-mediated redox signaling. These results give evidence of a new signaling crosstalk between two distinct DNA repair pathways.</p
Microstructure and Small-Scale Deformation of Al₀.₇CoCrFeNi High-Entropy Alloy
Get PDFNovel engineering materials are continuously being designed for structural applications, particularly for improved mechanical properties such as high strength, enhanced ductility, and great thermal stability. High entropy alloys (HEAs) as an emerging material can be distinguished from other metal systems as a five-or-more-component alloy in which the constituents are in equiatomic or near equiatomic proportions, thereby maximizing the configurational entropy.
This thesis is focused on understanding the microstructure of an aluminum-containing HEA in relation to its small-scale mechanical properties. Physical phenomena such as size-effect, slip sizes, temperature effect, crystallographic orientation effect, influence of interface, and small perturbations in atom motions are studied.
Uniaxial compression experiments were conducted on nanopillars fabricated from the individual phases (i.e. Face Centered Cubic (FCC) and Body Cubic Centered (BCC) present in the Al0.7CoCrFeNi HEA. We observed the presence of a size-effect in both phases, with smaller pillars having substantially greater strengths compared with bulk and with larger sized samples. The size-effect power law exponent m in τy α D-m for the BCC phase was − 0.28, which is lower than that of most pure BCC metals, and the FCC phase had m = − 0.66, which is equivalent to most pure FCC metals. These results are discussed in the framework of nano-scale plasticity and the intrinsic lattice resistance through the interplay of the internal (microstructural) and external (dimensional) size effects.
In addition to higher stresses observed at cryogenic temperature in both phases, the microstructural analysis of the deformed pillar via Transmission Electron Microscopy (TEM) showed that FCC pillars undergo deformation by planar-slip dislocation activities even at temperatures of 40 K. Bulk FCC HEAs have been studied to deform via twinning mechanism at low temperatures. The BCC phase, however, confirms dislocation–driven plasticity and twinning at 40 K. These results are explained from the intrinsic nature of the dislocation structure of both phases at low temperatures.
The effect of an 'interphase' in micron-sized HEA pillars was studied from different orientation configurations of the BCC | FCC phases. Slip transmission across the phases was observed in high symmetry orientation combination of both phases. Configurations having a mixture of both low and high symmetry orientations vary in deformation mechanisms. We explain these findings in relation to crystal orientation effect of the combining half pillars, competing plastic mechanisms, dislocation – boundary interactions and how these findings correlate with their mechanical response.
Also, we conducted dynamic mechanical analysis on the FCC and BCC HEA nanopillars to reveal their damping properties. Higher storage modulus and damping factor values were observed in FCC and BCC the nanopillars. Storage Moduli in the nano-sized HEAs are a factor of 2 greater than both bulk BCC and FCC HEA counterparts. The difference is due to greater surface contribution of the external atoms in the small-sized HEAs.</p
Decomposing Formal Specifications Into Assume-Guarantee Contracts for Hierarchical System Design
Get PDFSpecifications for complex engineering systems are typically decomposed into specifications for individual subsystems in a way that ensures they are implementable and simpler to develop further. We describe a method to algorithmically construct specifications for components that should implement a given specification when assembled. By eliminating variables that are irrelevant to realizability of each component, we simplify the specifications and reduce the amount of information necessary for operation.
To identify these variables, we parametrize the information flow between components.
The specifications are written in the Temporal Logic of Actions, TLA+, with liveness properties restricted to an implication of conjoined recurrence properties, known as GR(1). We study whether GR(1) contracts exist in the presence of full information, and prove that memoryless GR(1) contracts that preserve safety do not always exist, whereas contracts in GR(1) with history-determined variables added do exist. We observe that timed stutter-invariant specifications of open-systems in general require GR(2) liveness properties for expressing them.
We formalize a definition of realizability in TLA+, and define an operator for forming open-systems from closed-systems, based on a variant of the while-plus operator. The resulting open-system properties are realizable when expected to be. We compare stepwise implication operators from the literature, and establish relations between them, and examine the arity required for expressing these operators. We examine which symmetric combinations of stepwise implication and implementation kind avoid circular dependence, and show that only Moore components specified by strictly causal stepwise implication avoid circular dependence.
The proposed approach relies on symbolic algorithms for computing specifications. To convert the generated specifications from binary decision diagrams to readable formulas over integer variables, we symbolically solve a minimal covering problem. We implemented an algorithm for minimal covering over lattices originally proposed for two-level logic minimization. We formalized the computation of essential elements and cyclic core that is part of this algorithm, and machine-checked the proofs of safety properties using a proof assistant. Proofs supporting the thesis are organized as TLA+ modules in appendices.</p
A Line-Free Method of Monopoles for 3D Dislocation Dynamics
Get PDFDespite the emergence of architected materials for various applications, metals still play a key role in engineering in general and aeronautics in particular. Turbine blades in jets engines for instance are made from single-crystal Nickel superalloys. As a result, studying the failure mechanism of these crystalline materials would help understand the limits of their applications. At the core of this mechanism are line defects called dislocations. Indeed, the plastic deformation of metals is governed by the motion of dislocation ensembles inside the crystal. In this thesis, we propose a novel approach to dislocation dynamics through the method of monopoles. In this approach, we discretize the dislocation line as a collection of points (or monopoles), each of which carries a Burgers "charge" and an element of line. The fundamental difference between our method and current methods for dislocation dynamics lies in the fact that the latter discretize the dislocation as a collection of line segments from which spans a need to keep track of the connectivity of the nodes. In our approach, we propose a "line-free" discretization where a linear connectivity or sequence between monopoles need not be defined. This attribute of the formulation offers significant computational advantages in terms of simplicity and efficiency. Through verification examples, we show that our method is consistent with existing results for simple configurations. We then build on this success to investigate increasingly complex examples, this with the ultimate goal of simulating the plastic deformation of a BCC grain in an elastic matrix.</p
Bioresorbable Vascular Scaffolds Gain Ductility, Resistance to Hydrolysis, and Radial Strength via a Unique Poly L-lactide Microstructure
Get PDFAdvances in tissue engineering over the past few decades are poised to revolutionize drug delivery and biomedical implants. Bioresorbable vascular scaffolds (BVS), which are made from the semicrystalline polymer poly (L-lactide), are an example of polymers saving and improving the quality of human life. BVSs are emerging as a promising alternative to metal stents for the treatment of coronary heart disease (CHD), one of the leading causes of death in the world. In contrast to permanent stents, BVSs are designed to have a limited lifespan in the body; they restore blood flow through the occluded artery by lending it support for 3-6 months, but are completely resorbed in 2-3 years, leaving behind a healthy artery. This transient character of BVS restores vasomotion in the treated artery and can eliminate the risk of thrombosis, a dreaded complication regarded as the bane of stenting.
The promising success of the first and currently only clinically-approved BVS (FDA-approval in 2016) provides an impetus to continue its development. The struts of the BVS (~ 150μm) are nearly two times thicker than in metal stents (~ 80μm). A thicker device is challenging to implant and is unable to treat smaller and tortuous arteries. Furthermore, clinicians speculate that irregular blow flow over thicker struts may contribute towards thrombosis. An added complication of working with BVSs is that they are difficult to visualize with X-rays owing to the low atomic mass of polymers. The need for a BVS that is thinner, stronger, and radio-opaque is the motivation for this thesis, which aims to extend the benefits of transient implants to a broader patient population. Chapter I provides a brief chronological overview of the evolution of cardiovascular therapeutics to combat CHD. Chapters II and III elucidate micron-scale gradients in the PLLA microstructure of the clinically-approved BVS that overcome PLLA’s inherent brittleness and provide lasting radial support to the artery. Chapter IV discusses the fabrication of novel instrumentation to establish structure-property relationships for scaffolds, and Chapter V explores polylactide nanocomposites that not only increase radial strength in a thinner profile but also provide radio-opacity.</p
Probabilistic Protein Engineering
Get PDFMachine learning-guided protein engineering is a new paradigm that enables the optimization of complex protein functions. Machine-learning methods use data to predict protein function without requiring a detailed model of the underlying physics or biological pathways. They accelerate protein engineering by learning from information contained in all measured variants and using it to select variants that are likely to be improved. We begin with a review of the basics of machine learning with a focus on applications to protein engineering and protein sequence-function datasets (Chapter 1). We used the entire machine-learning guided engineering paradigm to engineer the algal-derived light-gated channel channelrhodopsin (ChR), which can be used to modulate neuronal activity with light. We build models that discover ChRs with strong plasma membrane localization in mammalian cells (Chapter 2) and unprecedented light sensitivity and photocurrents for optogenetic applications (Chapter 3). Machine learning-guided evolution requires a machine-learning model that learns the relationship between sequence and function. For machine-learning models to learn about protein sequences, protein sequences must be represented as vectors or matrices of numbers. How each protein sequence is represented determines what can be learned. We learn continuous vector encodings of sequences from patterns in unlabeled sequences (Chapter 4). Learned encodings are low-dimensional, do not require alignments, and may improve performance by transferring information in unlabeled sequences to specific prediction tasks. Alternately, we demonstrate an interpretable Gaussian process kernel tailored to biological sequences (Chapter 6). In addition to a model to predict function from sequence, engineering requires a method to use the model to choose sequences for the next round of evolution. Most machine-learning guided engineering strategies assume that selected sequences can be queried directly. However, in directed evolution it is common to design a library of sequences and then sample stochastic batches from that library. We propose a batched stochastic Bayesian optimization algorithm for iteratively designing and screening site-saturation mutagenesis libraries (Chapter 5).</p
General Strategies for Visible-Light Decaging Based on Quinone Photochemistry
Get PDFThe design, synthesis, and photochemistry of several quinone based photoremovable protecting groups is reported. A visible light (400-600 nm) intramolecular photoreduction of 1,4-benzoquinones and 1,4-naphthoquinones mediated by amine and sulfide substituents was employed to launch a fast thermal lactonization step. Both the trimethyl lock and o-coumarinic acid lactonizations were incorporated into these designs. Quantum yields in air equilibrated solvents are moderate (Φ = 0.01-0.10), and chemical yields are generally quantitative. Detailed mechanistic studies reveal a mechanism distinct from typical n,π* quinone photochemistry. Biological applications and longer wavelength derivatives were further explored.</p
Structure and Dynamics of HIV-1 Env Trimer
Get PDFThe human immunodeficiency virus-1 (HIV-1) infects CD4+ helper T cells by fusing its lipid membrane to the host cell plasma membrane. HIV-1 Envelope (Env) glycoprotein, a trimer of gp120-gp41 heterodimers, is the fusion machinery that mediates viral and host cell membrane fusion, which is initiated by interaction between the host cell receptor CD4 and viral glycoprotein gp120. Receptor binding induces conformational changes in the Env trimer such that coreceptor CCR5/CXCR4 can bind to gp120 and trigger subsequent membrane fusion steps. Previous cryo-electron tomography (cryoET) and spectroscopy studies have shown that CD4 binding induces changes in Env trimer from the closed, prefusion conformation to an open, CD4-bound conformation. However, the CD4-bound Env trimer is dynamic and flexible such that structural biology study of CD4-bound Env trimer is difficult.
As the sole glycoprotein located on HIV-1 viral surface, Env trimer is the only target for neutralizing antibodies. Since HIV-1 mutates rapidly, most neutralizing antibodies are strain-specific. However, a small percent of HIV-1 infected patients can develop broadly neutralizing antibodies (bNAbs) that neutralize a wide spectrum of viruses. In 2011, our collaborator isolated a bNAb called 8ANC195. To understand how 8ANC195 recognizes Env trimer and prevents infection, we used a combination of structural biology and biochemistry tools. Interestingly, we found that 8ANC195 can recognize Env trimer in both its prefusion and CD4-bound conformations by targeting an epitope at gp120-gp41 interface. Furthermore, 8ANC195 stabilizes the Env-CD4 complex, allowing us to investigate the conformational changes induced by CD4 in atomic resolution. By solving and comparing single-particle cryo-EM structures of Env trimer in complex with CD4 and/or antibodies, we found that: 1) CD4 binding induces coreceptor binding site exposure through a β-sheet rearrangements in each gp120 monomer. Several key residues allosterically regulate this coreceptor binding site exposure. 2) CD4 binding induces Env trimer opening together with gp41 conformational changes, which represents an intermediate between prefusion gp41 and postfusion gp41. 3) Env trimer opening is necessary but not sufficient for coreceptor binding site exposure, while CD4 binding induces both, some antibodies can open Env trimer without exposing the coreceptor binding site. These conclusions further illuminate how Env trimer mediates membrane fusion and inform potential strategies blocking viral entry.</p
From Quantum Mechanics to Experimental Observables: Computational Investigations of Energy-Related Heterogeneous Catalysts
Get PDFOne of the most severe challenges in this decade is assuring more secure, more efficient, cleaner, and more sustainable energy to power our world. This work takes a catalytic approach to help overcome this challenge.
The Haber Bosch process is one of the towering achievements of industrial chemistry. It consumes a huge amount of energy due to the high temperature and high pressure reaction condition, and in turn, has enabled us to produce enough nitrogen fertilizer to feed the current world population. An essential goal of present research is therefore to dramatically reduce Haber Bosch energy cost by improving the catalytic performance of the presently used Fe-based heterogeneous catalysts. We use quantum mechanics (QM) and kinetic Monte Carlo (kMC) to predict reaction mechanisms and kinetics for NH3 synthesis on Fe(111) – the best Fe single crystal surface for NH3 synthesis. We find excellent agreement with a predicted turnover frequency (TOF) of 17.7 sec-1 per 2x2 site (5.3 x 10-9 moles/cm2/sec) compared to TOF=10 sec-1 per site from experiment, and we further predict that top-layer Co doping leads to an acceleration by a factor of 2.3 in reaction rates of ammonia synthesis.
Compared to the industrialized Haber Bosch reaction, renewable energy technologies are still in their infancy with a great deal of questions unanswered, as well as a lot of barriers to overcome. Here we report our atomistic understanding of how CO2 and H2O molecules adsorb on the catalyst surface and interact to initiate CO2 dissociation and subsequent product formation. Using synergistic experimental and theoretical analyses, we show that Cu and Ag operate entirely differently for the first step of activating CO2. We develop a method of predicting the ambient pressure XPS spectrum in an ab-initio multiscale fashion: from electronic structure, to atomic picture, to chemical reaction network (CRN), and eventually to the experimental observable. We bridge both the qualitative and quantitative gap from quantum mechanics to XPS, and demonstrate our approach by decoding the initial H2O adsorption and complex formation on Ag(111) surface, which we encourage to be the new standard protocol in this field.</p