Design and analysis of nucleic acid reaction pathways

Nucleic acids are a useful substrate for engineering at the molecular level. Designing the detailed energetics and kinetics of interactions between nucleic acid strands remains a challenge. Building on previous algorithms to characterize the ensemble of dilute solutions of nucleic acids, we present a design algorithm that allows optimization of structural features and binding energetics of a test tube of interacting nucleic acid strands. We extend this formulation to handle multiple thermodynamic states and combinatorial constraints to allow optimization of pathways of interacting nucleic acids. In both design strategies, low-cost estimates to thermodynamic properties are calculated using hierarchical ensemble decomposition and test tube ensemble focusing. These algorithms are tested on randomized test sets and on example pathways drawn from the molecular programming literature. To analyze the kinetic properties of designed sequences, we describe algorithms to identify dominant species and kinetic rates using coarse-graining at the scale of a small box containing several strands or a large box containing a dilute solution of strands.

Two-colour laser-induced electron dynamics in two-level quantum system

To attempt to control the quantum state of a physical system with a femtosecond two-colour laser field, a model for the two-level system is analysed as a first step. We investigate the coherent control of the two-colour laser pulses propagating in a two-level medium. Based on calculating the influence of the laser field with various laser parameters on the electron dynamics, it is found the electronic state can be changed up and down by choosing the appropriate laser pulses and the coherent control of the two-colour laser pulses can substantially modify the behaviour of the electronic dynamics: a quicker change of two states can be produced even for small pulse duration. Moreover, the oscillatory structures around the resonant frequency and the propagation features of the laser pulses depend sensitively on the relative phase of the two-colour laser pulses. Finally, the influence of a finite lifetime of the upper level is discussed in brief.

Mechanistic studies of reactions at the single-molecule level using microfluidics with applications in molecular diagnostics

Motivated by needs in molecular diagnostics and advances in microfabrication, researchers started to seek help from microfluidic technology, as it provides approaches to achieve high throughput, high sensitivity, and high resolution. One strategy applied in microfluidics to fulfill such requirements is to convert continuous analog signal into digitalized signal. One most commonly used example for this conversion is digital PCR, where by counting the number of reacted compartments (triggered by the presence of the target entity) out of the total number of compartments, one could use Poisson statistics to calculate the amount of input target.

However, there are still problems to be solved and assumptions to be validated before the technology is widely employed. In this dissertation, the digital quantification strategy has been examined from two angles: efficiency and robustness. The former is a critical factor for ensuring the accuracy of absolute quantification methods, and the latter is the premise for such technology to be practically implemented in diagnosis beyond the laboratory. The two angles are further framed into a “fate” and “rate” determination scheme, where the influence of different parameters is attributed to fate determination step or rate determination step. In this discussion, microfluidic platforms have been used to understand reaction mechanism at single molecule level. Although the discussion raises more challenges for digital assay development, it brings the problem to the attention of the scientific community for the first time.

This dissertation also contributes towards developing POC test in limited resource settings. On one hand, it adds ease of access to the tests by incorporating massively producible, low cost plastic material and by integrating new features that allow instant result acquisition and result feedback. On the other hand, it explores new isothermal chemistry and new strategies to address important global health concerns such as cyctatin C quantification, HIV/HCV detection and treatment monitoring as well as HCV genotyping.

Computational modeling and psychophysics in low- and mid-level vision

This thesis addresses a series of topics related to the question of how people find the foreground objects from complex scenes. With both computer vision modeling, as well as psychophysical analyses, we explore the computational principles for low- and mid-level vision.

We first explore the computational methods of generating saliency maps from images and image sequences. We propose an extremely fast algorithm called Image Signature that detects the locations in the image that attract human eye gazes. With a series of experimental validations based on human behavioral data collected from various psychophysical experiments, we conclude that the Image Signature and its spatial-temporal extension, the Phase Discrepancy, are among the most accurate algorithms for saliency detection under various conditions.

In the second part, we bridge the gap between fixation prediction and salient object segmentation with two efforts. First, we propose a new dataset that contains both fixation and object segmentation information. By simultaneously presenting the two types of human data in the same dataset, we are able to analyze their intrinsic connection, as well as understanding the drawbacks of today’s “standard” but inappropriately labeled salient object segmentation dataset. Second, we also propose an algorithm of salient object segmentation. Based on our novel discoveries on the connections of fixation data and salient object segmentation data, our model significantly outperforms all existing models on all 3 datasets with large margins.

In the third part of the thesis, we discuss topics around the human factors of boundary analysis. Closely related to salient object segmentation, boundary analysis focuses on delimiting the local contours of an object. We identify the potential pitfalls of algorithm evaluation for the problem of boundary detection. Our analysis indicates that today’s popular boundary detection datasets contain significant level of noise, which may severely influence the benchmarking results. To give further insights on the labeling process, we propose a model to characterize the principles of the human factors during the labeling process.

The analyses reported in this thesis offer new perspectives to a series of interrelating issues in low- and mid-level vision. It gives warning signs to some of today’s “standard” procedures, while proposing new directions to encourage future research.

Absolute phase control of spectra effects in a two-level medium driven by two-color ultrashort laser pulses

Using a omega-3 omega combination scenario, we investigate the absolute phase control of the spectra effects for ultrashort laser pulses propagating in a two-level medium. It is found that the higher spectral components can be controlled by the absolute phases. In particular, different absolute phase combinations can lead to the buildup or split of the even harmonics. (c) 2006 Elsevier B.V. All rights reserved.

Electromagnetically induced negative refractive index in a V-type four-level atomic system

We propose a scheme for realizing negative refractive index in a V-type four-level atomic system. It is shown that the negative refractive index can be achieved in a wide frequency band based on the effect of quantum coherence. It is also found that the frequency band of negative refractive index and the absorption property of left-handed material are manipulated by the pump and control fields. Furthermore, left-handed material with reduced absorption is possible by choosing appropriate parameters. (c) 2006 Elsevier B.V. All rights reserved.

Polarization evolution of a few-cycle ultrashort laser pulse propagating in a degenerate three-level medium

The propagation of an arbitrary polarized few-cycle ultrashort laser pulse in a degenerate three-level medium is investigated by using an iterative predictor-corrector finite-difference time-domain method. It is found that the polarization evolution of the ultrashort laser pulse is dependent not only on the initial atomic coherence of the medium but also on the polarization condition of the incident laser pulse. When the initial effective area is equal to 2 pi, complete linear-to-circular and circular-to-linear polarization conversion of few-cycle ultrashort laser pulses can be achieved due to the quantum interference effects between the two different transition paths.

Superluminal optical solitons in a four-level tripod atomic system

With one weak probe field and two strong pumping fields, superluminal optical solitons are formed in a lifetime-broadened four-level tripod atomic medium. With proper parameters, both dark and bright solitons can occur in the highly resonant medium. The corresponding group velocity of the solitons can be superluminal. Meanwhile, the conditions for superluminal solitons occurrence are given.

Self-healing Techniques for RF and mm-Wave Transmitters and Receivers

With continuing advances in CMOS technology, feature sizes of modern Silicon chip-sets have gone down drastically over the past decade. In addition to desktops and laptop processors, a vast majority of these chips are also being deployed in mobile communication devices like smart-phones and tablets, where multiple radio-frequency integrated circuits (RFICs) must be integrated into one device to cater to a wide variety of applications such as Wi-Fi, Bluetooth, NFC, wireless charging, etc. While a small feature size enables higher integration levels leading to billions of transistors co-existing on a single chip, it also makes these Silicon ICs more susceptible to variations. A part of these variations can be attributed to the manufacturing process itself, particularly due to the stringent dimensional tolerances associated with the lithographic steps in modern processes. Additionally, RF or millimeter-wave communication chip-sets are subject to another type of variation caused by dynamic changes in the operating environment. Another bottleneck in the development of high performance RF/mm-wave Silicon ICs is the lack of accurate analog/high-frequency models in nanometer CMOS processes. This can be primarily attributed to the fact that most cutting edge processes are geared towards digital system implementation and as such there is little model-to-hardware correlation at RF frequencies.

All these issues have significantly degraded yield of high performance mm-wave and RF CMOS systems which often require multiple trial-and-error based Silicon validations, thereby incurring additional production costs. This dissertation proposes a low overhead technique which attempts to counter the detrimental effects of these variations, thereby improving both performance and yield of chips post fabrication in a systematic way. The key idea behind this approach is to dynamically sense the performance of the system, identify when a problem has occurred, and then actuate it back to its desired performance level through an intelligent on-chip optimization algorithm. We term this technique as self-healing drawing inspiration from nature's own way of healing the body against adverse environmental effects. To effectively demonstrate the efficacy of self-healing in CMOS systems, several representative examples are designed, fabricated, and measured against a variety of operating conditions.

We demonstrate a high-power mm-wave segmented power mixer array based transmitter architecture that is capable of generating high-speed and non-constant envelope modulations at higher efficiencies compared to existing conventional designs. We then incorporate several sensors and actuators into the design and demonstrate closed-loop healing against a wide variety of non-ideal operating conditions. We also demonstrate fully-integrated self-healing in the context of another mm-wave power amplifier, where measurements were performed across several chips, showing significant improvements in performance as well as reduced variability in the presence of process variations and load impedance mismatch, as well as catastrophic transistor failure. Finally, on the receiver side, a closed-loop self-healing phase synthesis scheme is demonstrated in conjunction with a wide-band voltage controlled oscillator to generate phase shifter local oscillator (LO) signals for a phased array receiver. The system is shown to heal against non-idealities in the LO signal generation and distribution, significantly reducing phase errors across a wide range of frequencies.

Upper level and phase controlling group velocity in V-type system

With the external field coupling the two upper levels, we investigate the light pulse propagation properties with weak probe field in a V-type system. Due to the external upper level (UL) coupling field, the dispersion of the system has been influenced by the relative phase. It is shown that the UL field and the relative phase can be regarded as switches to manipulate light propagation between subluminal and superluminal. (c) 2007 Elsevier B.V. All rights reserved.

Optical solitons in a four-level inverted-Y system

With one weak probe field and two strong pumping fields, the possibility of producing superluminal optical solitons is discussed in a lifetime-broadened inverted-Y atomic medium with proper parameters. As the group velocity of the solitons is larger than c, its occurrence can be controlled by modulating the intensities and the detunings of lasers.

Controlling the group velocity in a five-level K-type atomic system

The properties of a five-level K-type system are investigated. With the controlling fields, the properties of the dispersion and absorption of the system are changed greatly. The system can produce anomalous dispersion regions with absorption and normal dispersion regions with absorption or transparency. Furthermore, the group velocity can be varied from subluminal to superluminal by varying the intensity of the controlling field and the probe detunings in principle. (C) 2008 Elsevier B.V. All rights reserved.