Resonance Energy Transfer-Based Molecular Switch Designed Using a Systematic Design Process Based on Monte Carlo Methods and Markov Chains

A RET network consists of a network of photo-active molecules called chromophores that can participate in inter-molecular energy transfer called resonance energy transfer (RET). RET networks are used in a variety of applications including cryptographic devices, storage systems, light harvesting complexes, biological sensors, and molecular rulers. In this dissertation, we focus on creating a RET device called closed-diffusive exciton valve (C-DEV) in which the input to output transfer function is controlled by an external energy source, similar to a semiconductor transistor like the MOSFET. Due to their biocompatibility, molecular devices like the C-DEVs can be used to introduce computing power in biological, organic, and aqueous environments such as living cells. Furthermore, the underlying physics in RET devices are stochastic in nature, making them suitable for stochastic computing in which true random distribution generation is critical.

In order to determine a valid configuration of chromophores for the C-DEV, we developed a systematic process based on user-guided design space pruning techniques and built-in simulation tools. We show that our C-DEV is 15x better than C-DEVs designed using ad hoc methods that rely on limited data from prior experiments. We also show ways in which the C-DEV can be improved further and how different varieties of C-DEVs can be combined to form more complex logic circuits. Moreover, the systematic design process can be used to search for valid chromophore network configurations for a variety of RET applications.

We also describe a feasibility study for a technique used to control the orientation of chromophores attached to DNA. Being able to control the orientation can expand the design space for RET networks because it provides another parameter to tune their collective behavior. While results showed limited control over orientation, the analysis required the development of a mathematical model that can be used to determine the distribution of dipoles in a given sample of chromophore constructs. The model can be used to evaluate the feasibility of other potential orientation control techniques.

Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine?

Precision medicine is an emerging approach to disease treatment and prevention that considers variability in patient genes, environment, and lifestyle. However, little has been written about how such research impacts emergency care. Recent advances in analytical techniques have made it possible to characterize patients in a more comprehensive and sophisticated fashion at the molecular level, promising highly individualized diagnosis and treatment. Among these techniques are various systematic molecular phenotyping analyses (e.g., genomics, transcriptomics, proteomics, and metabolomics). Although a number of emergency physicians use such techniques in their research, widespread discussion of these approaches has been lacking in the emergency care literature and many emergency physicians may be unfamiliar with them. In this article, we briefly review the underpinnings of such studies, note how they already impact acute care, discuss areas in which they might soon be applied, and identify challenges in translation to the emergency department (ED). While such techniques hold much promise, it is unclear whether the obstacles to translating their findings to the ED will be overcome in the near future. Such obstacles include validation, cost, turnaround time, user interface, decision support, standardization, and adoption by end-users.

Adaptive Brain-Computer Interface Systems For Communication in People with Severe Neuromuscular Disabilities

Brain-computer interfaces (BCI) have the potential to restore communication or control abilities in individuals with severe neuromuscular limitations, such as those with amyotrophic lateral sclerosis (ALS). The role of a BCI is to extract and decode relevant information that conveys a user's intent directly from brain electro-physiological signals and translate this information into executable commands to control external devices. However, the BCI decision-making process is error-prone due to noisy electro-physiological data, representing the classic problem of efficiently transmitting and receiving information via a noisy communication channel.

This research focuses on P300-based BCIs which rely predominantly on event-related potentials (ERP) that are elicited as a function of a user's uncertainty regarding stimulus events, in either an acoustic or a visual oddball recognition task. The P300-based BCI system enables users to communicate messages from a set of choices by selecting a target character or icon that conveys a desired intent or action. P300-based BCIs have been widely researched as a communication alternative, especially in individuals with ALS who represent a target BCI user population. For the P300-based BCI, repeated data measurements are required to enhance the low signal-to-noise ratio of the elicited ERPs embedded in electroencephalography (EEG) data, in order to improve the accuracy of the target character estimation process. As a result, BCIs have relatively slower speeds when compared to other commercial assistive communication devices, and this limits BCI adoption by their target user population. The goal of this research is to develop algorithms that take into account the physical limitations of the target BCI population to improve the efficiency of ERP-based spellers for real-world communication.

In this work, it is hypothesised that building adaptive capabilities into the BCI framework can potentially give the BCI system the flexibility to improve performance by adjusting system parameters in response to changing user inputs. The research in this work addresses three potential areas for improvement within the P300 speller framework: information optimisation, target character estimation and error correction. The visual interface and its operation control the method by which the ERPs are elicited through the presentation of stimulus events. The parameters of the stimulus presentation paradigm can be modified to modulate and enhance the elicited ERPs. A new stimulus presentation paradigm is developed in order to maximise the information content that is presented to the user by tuning stimulus paradigm parameters to positively affect performance. Internally, the BCI system determines the amount of data to collect and the method by which these data are processed to estimate the user's target character. Algorithms that exploit language information are developed to enhance the target character estimation process and to correct erroneous BCI selections. In addition, a new model-based method to predict BCI performance is developed, an approach which is independent of stimulus presentation paradigm and accounts for dynamic data collection. The studies presented in this work provide evidence that the proposed methods for incorporating adaptive strategies in the three areas have the potential to significantly improve BCI communication rates, and the proposed method for predicting BCI performance provides a reliable means to pre-assess BCI performance without extensive online testing.