Hideo Mabuchi, Ph.D - US grants

Recent theoretical work in quantum optics has revealed deep connections between measurement and decoherence, which may be understood as dynamical counterparts of the connection between information and entropy. This progress has largely been enabled by quantum trajectory theory, which we seek to verify experimentally. To do so we will first implement and test quantitatively two advanced methods for real-time quantum measurement (adaptive homodyne detection and quantum Kalman filtering), which have
been derived on the basis of quantum trajectory theory. We will then utilize these techniques in experiments on hypersensitivity to perturbations, quantifying the amount of information that must continuously be gathered about environmental perturbations to keep the entropy of a system below a fixed value. Quantum trajectory theory provides a basis for predicting how this quantity should vary with the complexity of the observed system's dynamics.

EIA-0113443
Winfree, Erik
California Institute of Technology

Title: Biomolecular Computing by DNA/Enzyme Systems

Dr. Erik Winfree and Dr. Hideo Mabuchi are working together to develop techniques and instruments for high-precision quantitative analysis of the DNA molecular devices. These are being designed, characterized and optimized to investigate issues such as robustness and error-tolerance of these DNA molecular devices. The technical objectives being achieved in this project are: development of spFRET instrument capable of counting individual photons from single molecules; characterization of conformal states, kinetics, and thermodynamics of DNA switches; characterization of the activities of two enzymes, RNAP and RNase, on the DNA switches; development of stochastic models of in vitro transcriptional circuits; and investigation of robust algorithms and error-control for transcriptional circuits.

Through this project, the PIs are establishing a set of experimental systems and techniques for exploring computation by biological molecules. This will provide fundamental knowledge and principles for nanoscale computation, such as models of computation, molecular algorithms, physical limits, sources of error and error correction strategies. Thus the aim is to leverage the advanced control over biochemical systems to begin establishing a broader foundation for reliable molecular computing.

This is an interdisciplinary project of theoretical research on design of quantum and biomolecular information processing systems. Specifically, the rate at which increases in the size/complexity of an information processing system can lead to improvements in robustness against environmental perturbations and systematic implementation errors are being investigated, starting with utilization of model reduction methods from control theory to develop general methods for scrutinizing the robustness of large but finite quantum and biomolecular systems and proceeding to detailed analyses of the efficiency of various known error-correction schemes. The overall goal is to be able to elucidate fundamental limits on the degree of redundancy required to achieve a given level of robustness. An integral part of this research is development of a new course on multi-scale design of information processing systems.

This award supports further development of an instrument based on use of a Fabry-Perot for cavity-enhanced spectroscopy of biological molecules. The instrument will use an extremely high-finesse optical cavity to enhance the sensitivity of laser absorption spectroscopy, in a configuration that allows the study of molecules in liquid solvents or in phospholipid membranes. This approach has the potential to be able to provide information about the dynamic behavior of individual biological molecules, an important theme in modern biology. The device will be tested using bacteriochlorophyll, one component of the bacterial photosynthetic reaction center. Although much is known about the dynamics of electron transfer and the atomic structure of such reaction centers, the information comes from studies of the bulk properties of large numbers of molecules. Information about dynamics of individual molecules has the potential to provide substantial improvement in understanding of the interrelationship of structure and function in the reaction center. The broader impacts of this research reflect both the participation of graduate and undergraduate students from a wide range of academic disciplines and, as a result of the biophysical research activities that the instrument will make possible, high visibility in the quantum optics and optical metrology communities. This visibility is likely to encourage greater technical cross-fertilization between these fields and the biological sciences. An acceleration of the development of highly sophisticated optical instrumentation for biological experiments could have substantial impact on the future progress of the technology used in biological research.

This research project focuses on experimental and theoretical research on continuous observation and feedback control of single-atom dynamics in cavity QED. The focus will be on a newly discovered class of supercritical Hopf bifurcations that are predicted both by semi-classical and quantum models for the atom-cavity dynamics. The plan is to investigate quantum-classical correspondence between these models via experiments with real-time filtering and feedback, and to use single-atom bifurcations as a setting to study the interaction of quantum fluctuations with semi-classical dynamical instabilities. An experimental apparatus to perform cavity QED with a Fabry-Perot optical resonator and atoms guided by a magnetic micro-structure will be constructed. The broader impact involves education of graduate students as well as efforts in diversity and outreach.

DNA is best known as the genetic storage medium for life. However, its unique structural properties make it attractive for engineering nanoscale structures and devices. Remarkably, synthetic DNA systems can be programmed to self-assemble into complex objects implementing dynamic mechanical tasks by appropriately designing the sequence of bases (A,C,G and T) comprising the constituent DNA strands. When mixed, the strands "hybridize" in prescribed ways by forming "base-pairs" between complementary bases (A with T, C with G). DNA nanotechnology explores and develops these capabilities for applications in nanorobotics, nanofabrication, biomolecular computation, biosensing, nanoelectronics and nanomedicine.
In principle, equilibrium and kinetic properties of a DNA strand can be characterized by the features of its "free energy landscape". Likely equilibrium structures correspond to deep valleys in the landscape, and the rate of conversion between two structures depends on the nature of the valleys and ridges separating them. The dynamics of a folding DNA strand define a path somewhat analogous to a ball rolling over the landscape. To analyze functional DNA systems with moving parts, it is important to identify large-scale landscape features that dominate experiments. Unfortunately, in practical problems, existing physical models define landscapes with fine-grained detail that obscures the large-scale features. For example, DNA systems commonly have theoretical landscapes containing more states than there are atoms in the universe, though experiments suggest that a small number of features dominate the landscape.
The project will develop algorithms for efficiently exploring large landscapes that cannot be enumerated explicitly, including coarse-graining approaches to simulate the temporal evolution of physically meaningful "macrostates" without having to simulate full "microstate" landscapes. These macrostate predictions will guide and interpret experimental studies of DNA systems of fundamental interest to current nanorobotics and biosensing efforts. Custom-built fluorescence instruments will probe free energy landscapes at the level of single molecules. While our expertise in DNA nanotechnology motivates our experiments on synthetic DNA, the new coarse-graining theory, computational algorithms, and experimental methods will be equally applicable to analysis of natural RNA molecules (such as the mutant of human telomerase RNA that is thought to cause dyskeratosis congenita by altering the free energy landscape of a conformational switch).
Our research objectives are integral with an education program dedicated to training undergraduates, graduate students, and postdocs in distinctly interdisciplinary research groups that currently involve Applied & Computational Mathematics, Applied Physics, Biochemistry, Bioengineering, Biology, Chemistry, Chemical Engineering, Computer Science, Computation & Neural Systems, and Physics. This is coupled with an outreach program that brings local high school science students to Caltech to discover DNA nanotechnology, meet with lab members in small informal groups, and generate enthusiasm for pursuing careers in science and engineering. We will also continue our policy of freely distributing the source code for our analysis and design software.

This award provides continued support for the Institute for Quantum Information (IQI), which was founded at Caltech in September 2000. The IQI is devoted to building the theoretical foundations of quantum information science across a broad front encompassing quantum algorithms, quantum cryptography, quantum information theory, fault-tolerant quantum information processing, and physical implementations of quantum computing. Basic advances in all of these areas are needed to bring revolutionary quantum technologies closer to realization.

The strength of the IQI rests on three distinctive qualities: a focus on interdisciplinary research, an emphasis on fostering the career development of world-class postdoctoral talent, and devotion to an active visitor program. The IQI promotes synergistic interactions among scientists with a variety of backgrounds. Physicists and computer scientists collaborate on investigations of quantum algorithms and quantum cryptographic protocols. Control theorists and physicists team up to illuminate the structure of entanglement. Theorists and experimenters join forces to conceive feasible realizations of quantum hardware. The IQI has attracted and trained top postdoctoral scholars, seven of whom have moved on to faculty positions (or the equivalent) elsewhere, thus significantly strengthening the world effort in QIS. The visitor program fuels intellectual excitement, facilitates collaborations and exchanges of scientific ideas, and performs a highly valued service for the international QIS community.

With the end of scalability of conventional silicon-based information technology on the horizon, it is vitally important to explore aggressively new paradigms for information technology. IQI contributions are dedicated to broadening the nation's technical base and ensuring US leadership in the future development of quantum science and technology.

Funding for this award is provided through the Physics at the Information Frontier program in the Physics Division and the Office of Multidisciplinary Activities in the Mathematical and Physical Sciences Directorate and the Emerging Models and Technologies for Computation Cluster in the Computing and Communications Foundations Division in the Computer and Information Science and Engineering Directorate.

We are submitting this proposal to request NSF support for a Quantum Control Summer
School, to be held 8-14 August 2005 at the California Institute of Technology. This
school is being organized in response to burgeoning interest among physicists, engineers
and applied mathematicians in exploring the principles and applications of control in
systems whose behavior is manifestly quantum mechanical. The lectures will be addressed
mainly to graduate students and senior researchers who are just getting started in the
field, but will include some advanced presentations to provide some perspective on
research frontiers. We have already secured seed funding for the summer school from
Caltech's initiative in Information Science and Technology, but we are seeking additional
support from government agencies including the NSF and AFOSR.
Intellectual merit: Control theory is a central discipline in modern engineering, but so
far there has been only preliminary research on extending its constitutive methodologies
to incorporate quantum dynamics and measurement. Applications areas for quantum control
theory range from protein structure determination to precision measurement and metrology,
and deep connections have been identified with the field of quantum computation. We
anticipate that this summer school can play a critical role in stimulating the development
of quantum control, as it has the enthusiastic support of important constituencies in
control theory, mathematical physics, atomic physics, quantum optics and condensed matter
physics.
Broader impact: This summer school will provide a unique educational experience for both
students and senior researchers who attend. Its topic is inherently interdisciplinary and
has sufficiently strong intellectual appeal to draw the attention of leading researchers
in both engineering and pure physics. It seems reasonable to hope that events of this
kind will spur a synthesis of quantum physics, dynamical systems theory and probability
theory in the same way that early workshops on quantum computation facilitated the
development of a common language for physicists and computer scientists.

Intellectual merit: We propose a broad-based program of experimental research to advance our understanding of the degree to which van der Waals interactions may ultimately limit the performance of photonic-atom chips. At the same time, we will improve our ability to fabricate devices with a high degree of integration between the photonic and atom-trapping "layers." Photonic-atom chips are a leading candidate for a technology platform to enable scalable and robust quantum communication networks, and efforts to develop them have drawn together cutting-edge methodology from the fields of nanofabrication, atomic physics and photonic engineering. In the long run, the line of research we are initiating should lead to an improved understanding of how perturbative and strongly-coupled quantum electrodynamics come together in research involving gas-phase atoms and dielectric microresonators. This type of research will be crucial for realizing the great promise of nanotechnology approaches to quantum information processing.


Broader impact: The fabrication techniques we will develop and the results of our surface-effects studies will have relevance for research beyond the field of quantum information science. For example, they will be highly valuable for applied work on the development of chip-scale sensors (atomic clocks and atom-interferometric inertial sensors) and basic research on developing atom-chip systems to study quantum degenerate gases confined to one or two dimensions. The proposed research will contribute significantly to the interdisciplinary training of graduate students, who will engage both in highly focused technical work on improved fabrication methods and in more conceptual research on atom cooling and trapping and quantum electrodynamics.

The research objective of this award is to utilize advanced methods of control engineering to enable a new performance regime for feedback tracking microscopy. Feedback tracking microscopy is a powerful new technique for studying the dynamics of individual macromolecules, which has already begun to make significant new contributions to our understanding of biological macromolecules such as DNA. Prior experiments in this area have been limited to the study of relatively large molecules and have required the use of many fluorescent dyes to label the molecule under study. The technical advances we will pursue under this NSF award will make it possible to apply feedback tracking microscopy to a wide range of molecules of moderate size using only a few fluorescent dyes for labeling. We will make these advances by applying modern methods of control theory to design improved feedback tracking algorithms, and through the development of advanced signal-processing electronics and motion-control hardware. Deliverables will include publications on the improved algorithms and apparatus, as well as more detailed technical documentation to be made freely available in electronic format.

If successful, the results of this research will enable new experiments in single-molecule biophysics and biochemistry, making it possible to apply feedback tracking microscopy for example to individual enzymes and ribozymes. Feedback tracking can be used greatly to enhance the sensitivity of traditional optical measurement techniques such as fluorescence correlation spectroscopy (FCS) and fluorescence resonance energy transfer (FRET). It is reasonable to hope that tracking-FCS and tracking-FRET measurements on single enzymes/ribozymes will deepen our understanding of stochastic kinetics and persistent heterogeneity in these important classes of biomolecules. The PI will incorporate the results of such work in his introductory-graduate level course on applied control theory, and the graduate student funded by this NSF award will benefit from a highly interdisciplinary training at the interface of modern engineering and biophysics/biochemistry.

This project will pursue a program of theoretical research to further develop a novel approach to autonomous quantum error correction. It will build on recent results which analyzed circuit designs that exploit coherent feedback, to implement quantum memories based on simple quantum codes without any need for external timing or control logic. This approach has the potential to contribute new strategies for robust quantum information processing that make optimal use of physical resources. Previous work will be extended to design coherent feedback circuits that implement quantum memories based on more sophisticated quantum codes that can correct for arbitrary single-qubit errors, and to explore advanced concepts such as circuit compression to exploit the quantum-mechanical nature of coherent feedback signals. The work will substantially strengthen connections among the abstract theory of quantum error correction, circuit theory as it exists in electrical engineering, and quantum optics/nanophotonics.

This research project will provide interdisciplinary training for at least one graduate student, who will be required both to learn coherent-feedback quantum control theory and to understand fundamental aspects of quantum error correction theory beyond the usual basic concepts. The research makes essential use of technical methods developed quite recently by mathematical control theorists and applies them to important questions in quantum information theory, building important new bridges between these subject areas in the process. Such projects provide excellent source material for concrete examples in classroom teaching, such as the PI's existing graduate courses in "Estimation and Control Methods for Applied Physics" and "Quantum Device Physics of Atomic and Semiconductor Systems." They also provide important points of contact with colleagues in engineering and applied mathematics, who may be quite familiar with control theory and its connections to circuit design but have never thought of the relevance of their work for quantum physics.

Enter the text here that is the new abstract information for your application. The organization of the nucleus and the regulated folding of the genome plays essential roles in regulating gene expression, chromosome segregation and chromosome structure. Long range interactions in chromatin are required for activation of gene transcription and repression of genes during the differentiation of eukaryotic cells. Long-range contacts between different chromosomal loci also regulate processes such as antibody diversity and mitotic chromosome condensation. Despite the wide range of processes that involve chromatin loops we know very little about the mechanisms that drive chromatin folding and stabilize long range interactions in the genome. This proposal is focused on developing new methods to measure the formation of looped domains dependent upon the activity of the chromatin protein CTCF. CTCF is known to be required for the stabilization of looped regions in the genome but how it generates or stabilizes looped domains is unknown. We propose to first characterize the dynamics of CTCF dependent looping using defined chromatin substrates in vitro and on chromatinized plasmids in cell extracts. Using mutagenesis and depletion we will alter the binding affinity and dimerization properties of CTCF and its interaction with the loop stabilizing protein cohesin to determine how these activities regulate the frequency of loop generation. Using the insight we gain from these in vitro experiments we will compare the dynamics of loop formation to the statistics of long range interactions at the human globin locus. By depleting CTCF and cohesin we will relate the cellular statistics of loop formation to the in vitro mechanics of loop stabilization. Our studies should provide unique and novel insight into the processes that regulate the formation of long range chromatin interactions and how they relate to essential developmental and cell biological processes.

Working within a specific technical setting known as cavity quantum electrodynamics, this project pursues a program of experimental and theoretical research aimed at elucidating the essential physics of the 'mesoscopic' transition regime that lies between the deeply quantum-mechanical behavior of individual atoms and the classical behavior of large ensembles of atoms. Our findings are of basic interest both for fundamental physics and for future engineering applications in nanotechnology, which often seeks to exploit unique aspects of mesoscopic physics. Our approach is to conduct new experiments using several tens of atoms in a setting in which we have previously characterized the behavior of individual atoms and of ensembles of thousands of atoms. We will pursue rigorous quantitative comparisons between experimental data and computer simulations based on fundamental theoretical models.

The research crosses traditional boundaries between academic disciplines in science, engineering and mathematics. The graduate student working on the project receives unique interdisciplinary training and our research provides excellent source material for classroom teaching. The publications and research presentations based on this research can reach new audiences in engineering and applied mathematics who may commonly study some of the kinds of nonlinear dynamical behaviors that we are investigating, introducing them for the first time to novel quantum mechanical aspects that emerge in the mesoscopic, nanoscale regime.

This INSPIRE project is jointly funded by the Quantum Information Science (QIS) Program in the Physics Division in the Mathematical and Physical Sciences Directorate, the Atomic Molecular and Optical Physics Experiment (AMO-E) Program in the Physics Division in the Mathematical and Physical Sciences Directorate, the Algorithmic Foundations (AF) Program in the Computing and Communications Foundations Division in the Computer and Information Science and Engineering Directorate, the Electronics, Photonics and Magnetic Devices (EPMD) Program in the Electrical, Communications and Cyber Systems (ECCS) Division in the Engineering Directorate, and the NSF Office of Integrative Activities (OIA). A revolutionary approach to computing is under development using quantum information processing. However, there is still a gap between the testbeds for quantum information processing that exist today, and the more perfect hardware needed for an ideal quantum computer. This project seeks to fill this gap by finding ways to use variable amounts of quantum behavior to incrementally improve computing systems. The project will examine how to use quantum effects in order to provide benefits in terms of speed, energy, and hardware efficiency for applications in signal processing and machine learning. The project will produce open source software for modeling quantum networks and will train graduate students to develop quantum information processing systems.

This effort builds on work designing circuits for autonomous continuous-time quantum error correction and ultra-low power information processing systems in photonic architectures. The theoretical component of the project will provide tools to study quantum feedback in various computer architectures operating with open quantum systems. This will be done using quantum stochastic differential equations (a form of quantum field theory that is adapted to resemble ordinary stochastic differential equations that are widely used in modern engineering) in order to improve the publicly-available open source software package (Mabuchilab/QNET on GitHub) and explore ways to extend these methods to nano-optomechanics and superconducting circuit QED. The experimental component of this project will complement the high-level study by testing lower-level architectural principles based on coherent-feedback quantum control, going beyond previous work by incorporating nonlinear controller dynamics and pulsed signal fields. Together, the theoretical and experimental parts of this project will advance the quantum information community's ability to rapidly construct rigorous quantum-optical models for complex coherent networks/circuits, facilitating the exploration of new high-level architectural principles.

The primary aims of this project are to develop new theory and new laboratory tools for analyzing the quantum-mechanical properties of ultrafast (very short) pulses of light. The project will push beyond familiar conditions, which is largely limited to long timescales and slowly-varying patterns of light (optical modes). The advances made will support future quantum engineering efforts to utilize ultrafast light pulses for computing, communication, and sensing. In the context of quantum technology, ultrafast quantum light may be expected to provide advantages over slowly-varying light by increasing the speed of computation, the rate at which information can be transmitted through a communication channel, or the bandwidth (response speed) of a sensor. The major themes of the project are the exploration of practical approaches to generating ultrafast light pulses with manifestly quantum properties (distinguished from conventional light pulses, for example, by exhibiting extremely low noise), the improvement of methods for analyzing quantum entanglement among ultrafast light pulses, and the development of a new class of laser-like optical devices called ultrafast optical parametric oscillators, which are of great interest to a broad spectrum of engineering research for potential use in future quantum technologies.

Technically speaking, the theoretical component of this project is structured around concrete studies of new device concepts for nanophotonic devices and circuits to generate and manipulate few-photon states of ultrafast optical pulses with non-Gaussian quantum states. The work will address fundamental issues in the modeling of quantum nonlinearities in nanophotonic devices with ultrafast pump and signal fields, motivated by applications such as the synthesis of cubic phase gates (for quantum computing) and realizing ultrafast optical parametric oscillators with pump thresholds in the few-photon regime. The latter devices are expected to require significant advances in efficiently modeling the quantum dynamics of optical systems with many (tens of thousands) of relevant optical modes. The experimental component of this project aims at the development and validation of measurement methods for characterizing time-domain entanglement among signal pulses in synchronously-pumped optical parametric oscillators, which is expected to develop strong connections with concepts from condensed matter physics (such as tensor network states). The experimental component will also include further work on a prototype synchronously-pumped optical parametric oscillator in which coherent feedback is utilized to establish programmable structures of entanglement across the output pulse train.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

This project is devoted to organizing a strategic visioning workshop on Ising Machines. The meeting will be held virtually over two days. Major themes include overarching issues for Ising Machines as special-purpose computers for non-convex optimization, strategies for maximizing the practical impact of future research on Ising Machines, and assessment of current status and next steps for hardware devices and architectures including both CMOS and non-CMOS (e.g. optical) platforms. Recasting the foundations of computational optimization to leverage emerging physics, mathematics, and management science will require an expansive technology co-design approach that facilitates simultaneous and coordinated rethinking of devices, architectures, algorithms and performance metrics, in order to develop a concrete vision for optimization co-design grounded in recent work on post-von Neumann Ising Machines (PVNIMs). The intention of the workshop is to spark the coalescence of vertically-integrated research communities around existing experimental hardware platforms and build consensus regarding overarching goals for improving both the basic understanding of non-convex optimization and the practical impact of frontier efforts. The workshop will also build a new community around the emerging technology of post-von Neumann Ising machines, and generally promote vertical integration of research on the theory and practice of non-convex optimization. Advances in this area have a high likelihood to impact broad areas of industry and policy. The summary document to be prepared by the Steering Committee after the workshop is intended likewise to influence research priorities across the CISE Directorate, leading to increased opportunities for interdisciplinary research and training in academic groups nationwide.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.