Strength of tantalum at high pressures through Richtmyer-Meshkov laser compression experiments and simulations

Strength at extreme pressures (>1 Mbar or 100 GPa) and high strain rates (106-108 s-1) of materials is not well characterized. The goal of the research outlined in this thesis is to study the strength of tantalum (Ta) at these conditions. The Omega Laser in the Laboratory for Laser Energetics in Rochester, New York is used to create such extreme conditions. Targets are designed with ripples or waves on the surface, and these samples are subjected to high pressures using Omega’s high energy laser beams. In these experiments, the observational parameter is the Richtmyer-Meshkov (RM) instability in the form of ripple growth on single-mode ripples. The experimental platform used for these experiments is the “ride-along” laser compression recovery experiments, which provide a way to recover the specimens having been subjected to high pressures. Six different experiments are performed on the Omega laser using single-mode tantalum targets at different laser energies. The energy indicates the amount of laser energy that impinges the target. For each target, values for growth factor are obtained by comparing the profile of ripples before and after the experiment. With increasing energy, the growth factor increased.

Engineering simulations are used to interpret and correlate the measurements of growth factor to a measure of strength. In order to validate the engineering constitutive model for tantalum, a series of simulations are performed using the code Eureka, based on the Optimal Transportation Meshfree (OTM) method. Two different configurations are studied in the simulations: RM instabilities in single and multimode ripples. Six different simulations are performed for the single ripple configuration of the RM instability experiment, with drives corresponding to laser energies used in the experiments. Each successive simulation is performed at higher drive energy, and it is observed that with increasing energy, the growth factor increases. Overall, there is favorable agreement between the data from the simulations and the experiments. The peak growth factors from the simulations and the experiments are within 10% agreement. For the multimode simulations, the goal is to assist in the design of the laser driven experiments using the Omega laser. A series of three-mode and four-mode patterns are simulated at various energies and the resulting growth of the RM instability is computed. Based on the results of the simulations, a configuration is selected for the multimode experiments. These simulations also serve as validation for the constitutive model and the material parameters for tantalum that are used in the simulations.

By designing samples with initial perturbations in the form of single-mode and multimode ripples and subjecting these samples to high pressures, the Richtmyer-Meshkov instability is investigated in both laser compression experiments and simulations. By correlating the growth of these ripples to measures of strength, a better understanding of the strength of tantalum at high pressures is achieved.

On the Role of Delays in Biological Systems : Analysis and Design

This work quantifies the nature of delays in genetic regulatory networks and their effect on system dynamics. It is known that a time lag can emerge from a sequence of biochemical reactions. Applying this modeling framework to the protein production processes, delay distributions are derived in a stochastic (probability density function) and deterministic setting (impulse function), whilst being shown to be equivalent under different assumptions. The dependence of the distribution properties on rate constants, gene length, and time-varying temperatures is investigated. Overall, the distribution of the delay in the context of protein production processes is shown to be highly dependent on the size of the genes and mRNA strands as well as the reaction rates. Results suggest longer genes have delay distributions with a smaller relative variance, and hence, less uncertainty in the completion times, however, they lead to larger delays. On the other hand large uncertainties may actually play a positive role, as broader distributions can lead to larger stability regions when this formalization of the protein production delays is incorporated into a feedback system.

Furthermore, evidence suggests that delays may play a role as an explicit design into existing controlling mechanisms. Accordingly, the reccurring dual-feedback motif is also investigated with delays incorporated into the feedback channels. The dual-delayed feedback is shown to have stabilizing effects through a control theoretic approach. Lastly, a distributed delay based controller design method is proposed as a potential design tool. In a preliminary study, the dual-delayed feedback system re-emerges as an effective controller design.

First principles based multiparadigm modeling of electronic structures and dynamics

Electronic structures and dynamics are the key to linking the material composition and structure to functionality and performance.

An essential issue in developing semiconductor devices for photovoltaics is to design materials with optimal band gaps and relative positioning of band levels. Approximate DFT methods have been justified to predict band gaps from KS/GKS eigenvalues, but the accuracy is decisively dependent on the choice of XC functionals. We show here for CuInSe₂ and CuGaSe₂, the parent compounds of the promising CIGS solar cells, conventional LDA and GGA obtain gaps of 0.0-0.01 and 0.02-0.24 eV (versus experimental values of 1.04 and 1.67 eV), while the historically first global hybrid functional, B3PW91, is surprisingly the best, with band gaps of 1.07 and 1.58 eV. Furthermore, we show that for 27 related binary and ternary semiconductors, B3PW91 predicts gaps with a MAD of only 0.09 eV, which is substantially better than all modern hybrid functionals, including B3LYP (MAD of 0.19 eV) and screened hybrid functional HSE06 (MAD of 0.18 eV).

The laboratory performance of CIGS solar cells (> 20% efficiency) makes them promising candidate photovoltaic devices. However, there remains little understanding of how defects at the CIGS/CdS interface affect the band offsets and interfacial energies, and hence the performance of manufactured devices. To determine these relationships, we use the B3PW91 hybrid functional of DFT with the AEP method that we validate to provide very accurate descriptions of both band gaps and band offsets. This confirms the weak dependence of band offsets on surface orientation observed experimentally. We predict that the CBO of perfect CuInSe₂/CdS interface is large, 0.79 eV, which would dramatically degrade performance. Moreover we show that band gap widening induced by Ga adjusts only the VBO, and we find that Cd impurities do not significantly affect the CBO. Thus we show that Cu vacancies at the interface play the key role in enabling the tunability of CBO. We predict that Na further improves the CBO through electrostatically elevating the valence levels to decrease the CBO, explaining the observed essential role of Na for high performance. Moreover we find that K leads to a dramatic decrease in the CBO to 0.05 eV, much better than Na. We suggest that the efficiency of CIGS devices might be improved substantially by tuning the ratio of Na to K, with the improved phase stability of Na balancing phase instability from K. All these defects reduce interfacial stability slightly, but not significantly.

A number of exotic structures have been formed through high pressure chemistry, but applications have been hindered by difficulties in recovering the high pressure phase to ambient conditions (i.e., one atmosphere and room temperature). Here we use dispersion-corrected DFT (PBE-ulg flavor) to predict that above 60 GPa the most stable form of N₂O (the laughing gas in its molecular form) is a 1D polymer with an all-nitrogen backbone analogous to cis-polyacetylene in which alternate N are bonded (ionic covalent) to O. The analogous trans-polymer is only 0.03-0.10 eV/molecular unit less stable. Upon relaxation to ambient conditions both polymers relax below 14 GPa to the same stable non-planar trans-polymer, accompanied by possible electronic structure transitions. The predicted phonon spectrum and dissociation kinetics validate the stability of this trans-poly-NNO at ambient conditions, which has potential applications as a new type of conducting polymer with all-nitrogen chains and as a high-energy oxidizer for rocket propulsion. This work illustrates in silico materials discovery particularly in the realm of extreme conditions.

Modeling non-adiabatic electron dynamics has been a long-standing challenge for computational chemistry and materials science, and the eFF method presents a cost-efficient alternative. However, due to the deficiency of FSG representation, eFF is limited to low-Z elements with electrons of predominant s-character. To overcome this, we introduce a formal set of ECP extensions that enable accurate description of p-block elements. The extensions consist of a model representing the core electrons with the nucleus as a single pseudo particle represented by FSG, interacting with valence electrons through ECPs. We demonstrate and validate the ECP extensions for complex bonding structures, geometries, and energetics of systems with p-block character (C, O, Al, Si) and apply them to study materials under extreme mechanical loading conditions.

Despite its success, the eFF framework has some limitations, originated from both the design of Pauli potentials and the FSG representation. To overcome these, we develop a new framework of two-level hierarchy that is a more rigorous and accurate successor to the eFF method. The fundamental level, GHA-QM, is based on a new set of Pauli potentials that renders exact QM level of accuracy for any FSG represented electron systems. To achieve this, we start with using exactly derived energy expressions for the same spin electron pair, and fitting a simple functional form, inspired by DFT, against open singlet electron pair curves (H₂ systems). Symmetric and asymmetric scaling factors are then introduced at this level to recover the QM total energies of multiple electron pair systems from the sum of local interactions. To complement the imperfect FSG representation, the AMPERE extension is implemented, and aims at embedding the interactions associated with both the cusp condition and explicit nodal structures. The whole GHA-QM+AMPERE framework is tested on H element, and the preliminary results are promising.

Rewriting Schemes for Flash Memory

Flash memory is a leading storage media with excellent features such as random access and high storage density. However, it also faces significant reliability and endurance challenges. In flash memory, the charge level in the cells can be easily increased, but removing charge requires an expensive erasure operation. In this thesis we study rewriting schemes that enable the data stored in a set of cells to be rewritten by only increasing the charge level in the cells. We consider two types of modulation scheme; a convectional modulation based on the absolute levels of the cells, and a recently-proposed scheme based on the relative cell levels, called rank modulation. The contributions of this thesis to the study of rewriting schemes for rank modulation include the following: we

•propose a new method of rewriting in rank modulation, beyond the previously proposed method of “push-to-the-top”;

•study the limits of rewriting with the newly proposed method, and derive a tight upper bound of 1 bit per cell;

•extend the rank-modulation scheme to support rankings with repetitions, in order to improve the storage density;

•derive a tight upper bound of 2 bits per cell for rewriting in rank modulation with repetitions;

•construct an efficient rewriting scheme that asymptotically approaches the upper bound of 2 bit per cell.

The next part of this thesis studies rewriting schemes for a conventional absolute-levels modulation. The considered model is called “write-once memory” (WOM). We focus on WOM schemes that achieve the capacity of the model. In recent years several capacity-achieving WOM schemes were proposed, based on polar codes and randomness extractors. The contributions of this thesis to the study of WOM scheme include the following: we

•propose a new capacity-achievingWOM scheme based on sparse-graph codes, and show its attractive properties for practical implementation;

•improve the design of polarWOMschemes to remove the reliance on shared randomness and include an error-correction capability.

The last part of the thesis studies the local rank-modulation (LRM) scheme, in which a sliding window going over a sequence of real-valued variables induces a sequence of permutations. The LRM scheme is used to simulate a single conventional multi-level flash cell. The simulated cell is realized by a Gray code traversing all the relative-value states where, physically, the transition between two adjacent states in the Gray code is achieved by using a single “push-to-the-top” operation. The main results of the last part of the thesis are two constructions of Gray codes with asymptotically-optimal rate.

Imperfection Insensitive Thin Shells

The buckling of axially compressed cylindrical shells and externally pressurized spherical shells is extremely sensitive to even very small geometric imperfections. In practice this issue is addressed by either using overly conservative knockdown factors, while keeping perfect axial or spherical symmetry, or adding closely and equally spaced stiffeners on shell surface. The influence of imperfection-sensitivity is mitigated, but the shells designed from these approaches are either too heavy or very expensive and are still sensitive to imperfections. Despite their drawbacks, these approaches have been used for more than half a century.

This thesis proposes a novel method to design imperfection-insensitive cylindrical shells subject to axial compression. Instead of following the classical paths, focused on axially symmetric or high-order rotationally symmetric cross-sections, the method in this thesis adopts optimal symmetry-breaking wavy cross-sections (wavy shells). The avoidance of imperfection sensitivity is achieved by searching with an evolutionary algorithm for smooth cross-sectional shapes that maximize the minimum among the buckling loads of geometrically perfect and imperfect wavy shells. It is found that the shells designed through this approach can achieve higher critical stresses and knockdown factors than any previously known monocoque cylindrical shells. It is also found that these shells have superior mass efficiency to almost all previously reported stiffened shells.

Experimental studies on a design of composite wavy shell obtained through the proposed method are presented in this thesis. A method of making composite wavy shells and a photogrametry technique of measuring full-field geometric imperfections have been developed. Numerical predictions based on the measured geometric imperfections match remarkably well with the experiments. Experimental results confirm that the wavy shells are not sensitive to imperfections and can carry axial compression with superior mass efficiency.

An efficient computational method for the buckling analysis of corrugated and stiffened cylindrical shells subject to axial compression has been developed in this thesis. This method modifies the traditional Bloch wave method based on the stiffness matrix method of rotationally periodic structures. A highly efficient algorithm has been developed to implement the modified Bloch wave method. This method is applied in buckling analyses of a series of corrugated composite cylindrical shells and a large-scale orthogonally stiffened aluminum cylindrical shell. Numerical examples show that the modified Bloch wave method can achieve very high accuracy and require much less computational time than linear and nonlinear analyses of detailed full finite element models.

This thesis presents parametric studies on a series of externally pressurized pseudo-spherical shells, i.e., polyhedral shells, including icosahedron, geodesic shells, and triambic icosahedra. Several optimization methods have been developed to further improve the performance of pseudo-spherical shells under external pressure. It has been shown that the buckling pressures of the shell designs obtained from the optimizations are much higher than the spherical shells and not sensitive to imperfections.

Optimal Data Distributions in Machine Learning

In the first part of the thesis we explore three fundamental questions that arise naturally when we conceive a machine learning scenario where the training and test distributions can differ. Contrary to conventional wisdom, we show that in fact mismatched training and test distribution can yield better out-of-sample performance. This optimal performance can be obtained by training with the dual distribution. This optimal training distribution depends on the test distribution set by the problem, but not on the target function that we want to learn. We show how to obtain this distribution in both discrete and continuous input spaces, as well as how to approximate it in a practical scenario. Benefits of using this distribution are exemplified in both synthetic and real data sets.

In order to apply the dual distribution in the supervised learning scenario where the training data set is fixed, it is necessary to use weights to make the sample appear as if it came from the dual distribution. We explore the negative effect that weighting a sample can have. The theoretical decomposition of the use of weights regarding its effect on the out-of-sample error is easy to understand but not actionable in practice, as the quantities involved cannot be computed. Hence, we propose the Targeted Weighting algorithm that determines if, for a given set of weights, the out-of-sample performance will improve or not in a practical setting. This is necessary as the setting assumes there are no labeled points distributed according to the test distribution, only unlabeled samples.

Finally, we propose a new class of matching algorithms that can be used to match the training set to a desired distribution, such as the dual distribution (or the test distribution). These algorithms can be applied to very large datasets, and we show how they lead to improved performance in a large real dataset such as the Netflix dataset. Their computational complexity is the main reason for their advantage over previous algorithms proposed in the covariate shift literature.

In the second part of the thesis we apply Machine Learning to the problem of behavior recognition. We develop a specific behavior classifier to study fly aggression, and we develop a system that allows analyzing behavior in videos of animals, with minimal supervision. The system, which we call CUBA (Caltech Unsupervised Behavior Analysis), allows detecting movemes, actions, and stories from time series describing the position of animals in videos. The method summarizes the data, as well as it provides biologists with a mathematical tool to test new hypotheses. Other benefits of CUBA include finding classifiers for specific behaviors without the need for annotation, as well as providing means to discriminate groups of animals, for example, according to their genetic line.

Design of antenna-coupled lumped-element titanium nitride KIDs for long-wavelength multi-band continuum imaging

Many applications in cosmology and astrophysics at millimeter wavelengths including CMB polarization, studies of galaxy clusters using the Sunyaev-Zeldovich effect (SZE), and studies of star formation at high redshift and in our local universe and our galaxy, require large-format arrays of millimeter-wave detectors. Feedhorn and phased-array antenna architectures for receiving mm-wave light present numerous advantages for control of systematics, for simultaneous coverage of both polarizations and/or multiple spectral bands, and for preserving the coherent nature of the incoming light. This enables the application of many traditional "RF" structures such as hybrids, switches, and lumped-element or microstrip band-defining filters.

Simultaneously, kinetic inductance detectors (KIDs) using high-resistivity materials like titanium nitride are an attractive sensor option for large-format arrays because they are highly multiplexable and because they can have sensitivities reaching the condition of background-limited detection. A KID is a LC resonator. Its inductance includes the geometric inductance and kinetic inductance of the inductor in the superconducting phase. A photon absorbed by the superconductor breaks a Cooper pair into normal-state electrons and perturbs its kinetic inductance, rendering it a detector of light. The responsivity of KID is given by the fractional frequency shift of the LC resonator per unit optical power.

However, coupling these types of optical reception elements to KIDs is a challenge because of the impedance mismatch between the microstrip transmission line exiting these architectures and the high resistivity of titanium nitride. Mitigating direct absorption of light through free space coupling to the inductor of KID is another challenge. We present a detailed titanium nitride KID design that addresses these challenges. The KID inductor is capacitively coupled to the microstrip in such a way as to form a lossy termination without creating an impedance mismatch. A parallel plate capacitor design mitigates direct absorption, uses hydrogenated amorphous silicon, and yields acceptable noise. We show that the optimized design can yield expected sensitivities very close to the fundamental limit for a long wavelength imager (LWCam) that covers six spectral bands from 90 to 400 GHz for SZE studies.

Excess phase (frequency) noise has been observed in KID and is very likely caused by two-level systems (TLS) in dielectric materials. The TLS hypothesis is supported by the measured dependence of the noise on resonator internal power and temperature. However, there is still a lack of a unified microscopic theory which can quantitatively model the properties of the TLS noise. In this thesis we derive the noise power spectral density due to the coupling of TLS with phonon bath based on an existing model and compare the theoretical predictions about power and temperature dependences with experimental data. We discuss the limitation of such a model and propose the direction for future study.

Lock Acquisition and Sensitivity Analysis of Advanced LIGO Interferometers

Laser interferometer gravitational wave observatory (LIGO) consists of two complex large-scale laser interferometers designed for direct detection of gravitational waves from distant astrophysical sources in the frequency range 10Hz - 5kHz. Direct detection of space-time ripples will support Einstein's general theory of relativity and provide invaluable information and new insight into physics of the Universe.

Initial phase of LIGO started in 2002, and since then data was collected during six science runs. Instrument sensitivity was improving from run to run due to the effort of commissioning team. Initial LIGO has reached designed sensitivity during the last science run, which ended in October 2010.

In parallel with commissioning and data analysis with the initial detector, LIGO group worked on research and development of the next generation detectors. Major instrument upgrade from initial to advanced LIGO started in 2010 and lasted till 2014.

This thesis describes results of commissioning work done at LIGO Livingston site from 2013 until 2015 in parallel with and after the installation of the instrument. This thesis also discusses new techniques and tools developed at the 40m prototype including adaptive filtering, estimation of quantization noise in digital filters and design of isolation kits for ground seismometers.

The first part of this thesis is devoted to the description of methods for bringing interferometer to the linear regime when collection of data becomes possible. States of longitudinal and angular controls of interferometer degrees of freedom during lock acquisition process and in low noise configuration are discussed in details.

Once interferometer is locked and transitioned to low noise regime, instrument produces astrophysics data that should be calibrated to units of meters or strain. The second part of this thesis describes online calibration technique set up in both observatories to monitor the quality of the collected data in real time. Sensitivity analysis was done to understand and eliminate noise sources of the instrument.

Coupling of noise sources to gravitational wave channel can be reduced if robust feedforward and optimal feedback control loops are implemented. The last part of this thesis describes static and adaptive feedforward noise cancellation techniques applied to Advanced LIGO interferometers and tested at the 40m prototype. Applications of optimal time domain feedback control techniques and estimators to aLIGO control loops are also discussed.

Commissioning work is still ongoing at the sites. First science run of advanced LIGO is planned for September 2015 and will last for 3-4 months. This run will be followed by a set of small instrument upgrades that will be installed on a time scale of few months. Second science run will start in spring 2016 and last for about 6 months. Since current sensitivity of advanced LIGO is already more than factor of 3 higher compared to initial detectors and keeps improving on a monthly basis, upcoming science runs have a good chance for the first direct detection of gravitational waves.

Multilayer Active Shell Mirrors

This thesis presents a novel active mirror technology based on carbon fiber composites and replication manufacturing processes. Multiple additional layers are implemented into the structure in order to provide the reflective layer, actuation capabilities and electrode routing. The mirror is thin, lightweight, and has large actuation capabilities. These features, along with the associated manufacturing processes, represent a significant change in design compared to traditional optics. Structural redundancy in the form of added material or support structures is replaced by thin, unsupported lightweight substrates with large actuation capabilities.

Several studies motivated by the desire to improve as-manufactured figure quality are performed. Firstly, imperfections in thin CFRP laminates and their effect on post-cure shape errors are studied. Numerical models are developed and compared to experimental measurements on flat laminates. Techniques to mitigate figure errors for thicker laminates are also identified. A method of properly integrating the reflective facesheet onto the front surface of the CFRP substrate is also presented. Finally, the effect of bonding multiple initially flat active plates to the backside of a curved CFRP substrate is studied. Figure deformations along with local surface defects are predicted and characterized experimentally. By understanding the mechanics behind these processes, significant improvements to the overall figure quality have been made.

Studies related to the actuation response of the mirror are also performed. The active properties of two materials are characterized and compared. Optimal active layer thicknesses for thin surface-parallel schemes are determined. Finite element simulations are used to make predictions on shape correction capabilities, demonstrating high correctabiliity and stroke over low-order modes. The effect of actuator saturation is studied and shown to significantly degrade shape correction performance.

The initial figure as well as actuation capabilities of a fully-integrated active mirror prototype are characterized experimentally using a Projected Hartmann test. A description of the test apparatus is presented along with two verification measurements. The apparatus is shown to accurately capture both high-amplitude low spatial-frequency figure errors as well as those at lower amplitudes but higher spatial frequencies. A closed-loop figure correction is performed, reducing figure errors by 94%.

Measurement of the Polarization of the Cosmic Microwave Background with the BICEP2 and Keck Array Telescopes

Precision polarimetry of the cosmic microwave background (CMB) has become a mainstay of observational cosmology. The ΛCDM model predicts a polarization of the CMB at the level of a few μK, with a characteristic E-mode pattern. On small angular scales, a B-mode pattern arises from the gravitational lensing of E-mode power by the large scale structure of the universe. Inflationary gravitational waves (IGW) may be a source of B-mode power on large angular scales, and their relative contribution to primordial fluctuations is parameterized by a tensor-to-scalar ratio r. BICEP2 and Keck Array are a pair of CMB polarimeters at the South Pole designed and built for optimal sensitivity to the primordial B-mode peak around multipole l ~ 100. The BICEP2/Keck Array program intends to achieve a sensitivity to r ≥ 0.02. Auxiliary science goals include the study of gravitational lensing of E-mode into B-mode signal at medium angular scales and a high precision survey of Galactic polarization. These goals require low noise and tight control of systematics. We describe the design and calibration of the instrument. We also describe the analysis of the first three years of science data. BICEP2 observes a significant B-mode signal at 150 GHz in excess of the level predicted by the lensed-ΛCDM model, and Keck Array confirms the excess signal at > 5σ. We combine the maps from the two experiments to produce 150 GHz Q and U maps which have a depth of 57 nK deg (3.4 μK arcmin) over an effective area of 400 deg² for an equivalent survey weight of 248000 μK². We also show preliminary Keck Array 95 GHz maps. A joint analysis with the Planck collaboration reveals that much of BICEP2/Keck Array's observed 150 GHz signal at low l is more likely a Galactic dust foreground than a measurement of r. Marginalizing over dust and r, lensing B-modes are detected at 7.0σ significance.

Biological Activity of Rhodium Metalloinsertors and the Design of Bifunctional Conjugates

The Barton laboratory has established that octahedral rhodium complexes bearing the sterically expansive 5,6-chrysene diimine ligand can target thermodynamically destabilized sites, such as base pair mismatches, in DNA with high affinity and selectivity. These complexes approach DNA from the minor groove, ejecting the mismatched base pairs from the duplex in a binding mode termed metalloinsertion. In recent years, we have shown that these metalloinsertor complexes also exhibit cytotoxicity preferentially in cancer cells that are deficient in the mismatch repair (MMR) machinery.

Here, we establish that a sensitive structure-activity relationship exists for rhodium metalloinsertors. We studied the relationship between the chemical structures of metalloinsertors and their effect on biological activity for ten complexes with similar DNA binding affinities, but wide variation in their lipophilicity. Drastic differences were observed in the selectivities of the complexes for MMR-deficient cells. Compounds with hydrophilic ligands were highly selective, exhibiting preferential cytotoxicity in MMR-deficient cells at low concentrations and short incubation periods, whereas complexes with lipophilic ligands displayed poor cell-selectivity. It was discovered that all of the complexes localized to the nucleus in concentrations sufficient for mismatch binding; however, highly lipophilic complexes also exhibited high mitochondrial uptake. Significantly, these results support the notion that mitochondrial DNA is not the desired target for our metalloinsertor complexes; instead, selectivity stems from targeting mismatches in genomic DNA.

We have also explored the potential for metalloinsertors to be developed into more complex structures with multiple functionalities that could either enhance their overall potency or impart mismatch selectivity onto other therapeutic cargo. We have constructed a family of bifunctional metalloinsertor conjugates incorporating cis-platinum, each unique in its chemical structure, DNA binding interactions, and biological activity. The study of these complexes in MMR-deficient cells has established that the cell-selective biological activity of rhodium metalloinsertors proceeds through a critical cellular pathway leading to necrosis.

We further explored the underlying mechanisms surrounding the biological response to mismatch recognition by metalloinsertors in the genome. Immunofluorescence assays of MMR-deficient and MMR-proficient cells revealed that a critical biomarker for DNA damage, phosphorylation of histone H2AX (γH2AX) rapidly accumulates in response to metalloinsertor treatment, signifying the induction of double strand breaks in the genome. Significantly, we have discovered that our metalloinsertor complexes selectively inhibit transcription in MMR-deficient cells, which may be a crucial checkpoint in the eventual breakdown of the cell via necrosis. Additionally, preliminary in vivo studies have revealed the capability of these compounds to traverse the complex environments of multicellular organisms and accumulate in MMR-deficient tumors. Our ever-increasing understanding of metalloinsertors, as well as the development of new generations of complexes both monofunctional and bifunctional, enables their continued progress into the clinic as promising new chemotherapeutic agents.

Scalable Methods for Deterministic Integration of Quantum Emitters in Photonic Crystal Cavities

We investigated four unique methods for achieving scalable, deterministic integration of quantum emitters into ultra-high Q{V photonic crystal cavities, including selective area heteroepitaxy, engineered photoemission from silicon nanostructures, wafer bonding and dimensional reduction of III-V quantum wells, and cavity-enhanced optical trapping. In these areas, we were able to demonstrate site-selective heteroepitaxy, size-tunable photoluminescence from silicon nanostructures, Purcell modification of QW emission spectra, and limits of cavity-enhanced optical trapping designs which exceed any reports in the literature and suggest the feasibility of capturing- and detecting nanostructures with dimensions below 10 nm. In addition to process scalability and the requirement for achieving accurate spectral- and spatial overlap between the emitter and cavity, these techniques paid specific attention to the ability to separate the cavity and emitter material systems in order to allow optimal selection of these independently, and eventually enable monolithic integration with other photonic and electronic circuitry.

We also developed an analytic photonic crystal design process yielding optimized cavity tapers with minimal computational effort, and reported on a general cavity modification which exhibits improved fabrication tolerance by relying exclusively on positional- rather than dimensional tapering. We compared several experimental coupling techniques for device characterization. Significant efforts were devoted to optimizing cavity fabrication, including the use of atomic layer deposition to improve surface quality, exploration into factors affecting the design fracturing, and automated analysis of SEM images. Using optimized fabrication procedures, we experimentally demonstrated 1D photonic crystal nanobeam cavities exhibiting the highest Q/V reported on substrate. Finally, we analyzed the bistable behavior of the devices to quantify the nonlinear optical response of our cavities.

MEMS for Diabetic Retinopathy

As the worldwide prevalence of diabetes mellitus continues to increase, diabetic retinopathy remains the leading cause of visual impairment and blindness in many developed countries. Between 32 to 40 percent of about 246 million people with diabetes develop diabetic retinopathy. Approximately 4.1 million American adults 40 years and older are affected by diabetic retinopathy. This glucose-induced microvascular disease progressively damages the tiny blood vessels that nourish the retina, the light-sensitive tissue at the back of the eye, leading to retinal ischemia (i.e., inadequate blood flow), retinal hypoxia (i.e., oxygen deprivation), and retinal nerve cell degeneration or death. It is a most serious sight-threatening complication of diabetes, resulting in significant irreversible vision loss, and even total blindness.

Unfortunately, although current treatments of diabetic retinopathy (i.e., laser therapy, vitrectomy surgery and anti-VEGF therapy) can reduce vision loss, they only slow down but cannot stop the degradation of the retina. Patients require repeated treatment to protect their sight. The current treatments also have significant drawbacks. Laser therapy is focused on preserving the macula, the area of the retina that is responsible for sharp, clear, central vision, by sacrificing the peripheral retina since there is only limited oxygen supply. Therefore, laser therapy results in a constricted peripheral visual field, reduced color vision, delayed dark adaptation, and weakened night vision. Vitrectomy surgery increases the risk of neovascular glaucoma, another devastating ocular disease, characterized by the proliferation of fibrovascular tissue in the anterior chamber angle. Anti-VEGF agents have potential adverse effects, and currently there is insufficient evidence to recommend their routine use.

In this work, for the first time, a paradigm shift in the treatment of diabetic retinopathy is proposed: providing localized, supplemental oxygen to the ischemic tissue via an implantable MEMS device. The retinal architecture (e.g., thickness, cell densities, layered structure, etc.) of the rabbit eye exposed to ischemic hypoxic injuries was well preserved after targeted oxygen delivery to the hypoxic tissue, showing that the use of an external source of oxygen could improve the retinal oxygenation and prevent the progression of the ischemic cascade.

The proposed MEMS device transports oxygen from an oxygen-rich space to the oxygen-deficient vitreous, the gel-like fluid that fills the inside of the eye, and then to the ischemic retina. This oxygen transport process is purely passive and completely driven by the gradient of oxygen partial pressure (pO₂). Two types of devices were designed. For the first type, the oxygen-rich space is underneath the conjunctiva, a membrane covering the sclera (white part of the eye), beneath the eyelids and highly permeable to oxygen in the atmosphere when the eye is open. Therefore, sub-conjunctival pO₂ is very high during the daytime. For the second type, the oxygen-rich space is inside the device since pure oxygen is needle-injected into the device on a regular basis.

To prevent too fast or too slow permeation of oxygen through the device that is made of parylene and silicone (two widely used biocompatible polymers in medical devices), the material properties of the hybrid parylene/silicone were investigated, including mechanical behaviors, permeation rates, and adhesive forces. Then the thicknesses of parylene and silicone became important design parameters that were fine-tuned to reach the optimal oxygen permeation rate.

The passive MEMS oxygen transporter devices were designed, built, and tested in both bench-top artificial eye models and in-vitro porcine cadaver eyes. The 3D unsteady saccade-induced laminar flow of water inside the eye model was modeled by computational fluid dynamics to study the convective transport of oxygen inside the eye induced by saccade (rapid eye movement). The saccade-enhanced transport effect was also demonstrated experimentally. Acute in-vivo animal experiments were performed in rabbits and dogs to verify the surgical procedure and the device functionality. Various hypotheses were confirmed both experimentally and computationally, suggesting that both the two types of devices are very promising to cure diabetic retinopathy. The chronic implantation of devices in ischemic dog eyes is still underway.

The proposed MEMS oxygen transporter devices can be also applied to treat other ocular and systemic diseases accompanied by retinal ischemia, such as central retinal artery occlusion, carotid artery disease, and some form of glaucoma.

The design of multimesh, multidepth gillnet fleets for use in the Lake Victoria Fisheries Research Project

Multimesh, multidepth gillnet fleets are useful in assessing fish stock abundance, size distribution and depth distribution. Using data collected on net mesh selectivity for Nile perch, Lates niloticus (L.), in the Kenyan waters of Lake Victoria, suitable mesh sizes for gillnet fleets for use in the Lake Victoria Fisheries Research Project were determined. The modal selection length for Nile perch in the mesh sized used in the earlier experiment were determined, as was the size range vulnerable to capture. Initial trials suggest 60% of the Nile perch swim within 5 m of the bottom. Setting and hauling of the nets is simple and quick, allowing the nets to be used at the same time as other sampling programmes.