Dual Quorum Quenching Capsules: Disrupting two bacterial communication pathways that lead to virulence

Healthcare Associated Infections (HAIs) in the United States, are estimated to cost nearly $10 billion annually. And, while device-related infections have decreased, the 60% attributed to pneumonia, gastrointestinal pathogens and surgical site infections (SSIs) remain prevalent. Furthermore, these are often complicated by antibacterial resistance that ultimately cause 2 million illnesses and 23,000 deaths in the US annually. Antibacterial resistance is an issue increasing in severity as existing antibiotics are losing effectiveness, and fewer new antibiotics are being developed. As a result, new methods of combating bacterial virulence are required. Modulating communications of bacteria can alter phenotype, such as biofilm formation and toxin production. Disrupting these communications provides a means of controlling virulence without directly interacting with the bacteria of interest, a strategy contrary to traditional antibiotics. Inter- and intra-species bacterial communication is commonly called quorum sensing because the communication molecules have been linked to phenotypic changes based on bacterial population dynamics. By disrupting the communication, a method called ‘quorum quenching’, bacterial phenotype can be altered. Virulence of bacteria is both population and species dependent; each species will secrete different toxic molecules, and total population will affect bacterial phenotype9. Here, the kinase LsrK and lactonase SsoPox were combined to simultaneously disrupt two different communication pathways with direct ties to virulence leading to SSIs, gastrointestinal infection and pneumonia. To deliver these enzymes for site-specific virulence prevention, two naturally occurring polymers were used, chitosan and alginate. Chitosan, from crustacean shells, and alginate, from seaweed, are frequently studied due to their biocompatibility, availability, self-assembly and biodegrading properties and have already been verified in vivo for wound-dressing. In this work, a novel functionalized capsule of quorum quenching enzymes and biocompatible polymers was constructed and demonstrated to have dual-quenching capability. This combination of immobilized enzymes has the potential for preventing biofilm formation and reducing bacterial toxicity in a wide variety of medical and non-medical applications.

Quantitative and Qualitative Trade-Off Analysis of Drowsy Driver Detection Methods: Single Electrode Wearable EEG Device, Multi-Electrode Wearable EEG Device, and Head-Mounted Gyroscope

Drowsy driving impairs motorists’ ability to operate vehicles safely, endangering both the drivers and other people on the road. The purpose of the project is to find the most effective wearable device to detect drowsiness. Existing research has demonstrated several options for drowsiness detection, such as electroencephalogram (EEG) brain wave measurement, eye tracking, head motions, and lane deviations. However, there are no detailed trade-off analyses for the cost, accuracy, detection time, and ergonomics of these methods. We chose to use two different EEG headsets: NeuroSky Mindwave Mobile (single-electrode) and Emotiv EPOC (14- electrode). We also tested a camera and gyroscope-accelerometer device. We can successfully determine drowsiness after five minutes of training using both single and multi-electrode EEGs. Devices were evaluated using the following criteria: time needed to achieve accurate reading, accuracy of prediction, rate of false positives vs. false negatives, and ergonomics and portability. This research will help improve detection devices, and reduce the number of future accidents due to drowsy driving.

Move, for string quartet, piano, percussion and electronics

MOVE is a composition for string quartet, piano, percussion and electronics of approximately 15-16 minutes duration in three movements. The work incorporates electronic samples either synthesized electronically by the composer or recorded from acoustic instruments. The work aims to use electronic sounds as an expansion of the tonal palette of the chamber group (rather like an extended percussion setup) as opposed to a dominating sonic feature of the music. This is done by limiting the use of electronics to specific sections of the work, and by prioritizing blend and sonic coherence in the synthesized samples. The work uses fixed electronics in such a way that allows for tempo variations in the music. Generally, a difficulty arises in that fixed “tape” parts don’t allow tempo variations; while truly “live” software algorithms sacrifice rhythmic accuracy. Sample pads, such as the Roland SPD-SX, provide an elegant solution. The latency of such a device is close enough to zero that individual samples can be triggered in real time at a range of tempi. The percussion setup in this work (vibraphone and sample pad) allows one player to cover both parts, eliminating the need for an external musician to trigger the electronics. Compositionally, momentum is used as a constructing principle. The first movement makes prominent use of ostinato and shifting meter. The second is a set of variations on a repeated harmonic pattern, with a polymetric middle section. The third is a type of passacaglia, wherein the bassline is not introduced right away, but becomes more significant later in the movement. Given the importance of visual presentation in the Internet age, the final goal of the project was to shoot HD video of a studio performance of the work for publication online. The composer recorded audio and video in two separate sessions and edited the production using Logic X and Adobe Premiere Pro. The final video presentation can be seen at geoffsheil.com/move.

Sonic Movie Memories: Sound, Childhood, and American Cinema

Though the trend rarely receives attention, since the 1970s many American filmmakers have been taking sound and music tropes from children’s films, television shows, and other forms of media and incorporating those sounds into films intended for adult audiences. Initially, these references might seem like regressive attempts at targeting some nostalgic desire to relive childhood. However, this dissertation asserts that these children’s sounds are instead designed to reconnect audience members with the multi-faceted fantasies and coping mechanisms that once, through children’s media, helped these audience members manage life’s anxieties. Because sound is the sense that Western audiences most associate with emotion and memory, it offers audiences immediate connection with these barely conscious longings. The first chapter turns to children’s media itself and analyzes Disney’s 1950s forays into television. The chapter argues that by selectively repurposing the gentlest sonic devices from the studio’s films, television shows like Disneyland created the studio’s signature sentimental “Disney sound.” As a result, a generation of baby boomers like Steven Spielberg comes of age and longs to recreate that comforting sound world. The second chapter thus focuses on Spielberg, who incorporates Disney music in films like Close Encounters of the Third Kind (1977). Rather than recreate Disney’s sound world, Spielberg uses this music as a springboard into a new realm I refer to as “sublime refuge” - an acoustic haven that combines overpowering sublimity and soothing comfort into one fantastical experience. The second half of the dissertation pivots into more experimental children’s cartoons like Gerald McBoing-Boing (1951) - cartoons that embrace audio-visual dissonance in ways that soothe even as they create tension through a phenomenon I call “comfortable discord.” In the final chapter, director Wes Anderson reveals that these sonic tensions have just as much appeal to adults. In films like The Royal Tenenbaums (2001), Anderson demonstrates that comfortable discord can simultaneously provide a balm for anxiety and create an open-ended space that makes empathetic connections between characters possible. The dissertation closes with a call to rethink nostalgia, not as a romanticization of the past, but rather as a reconnection with forgotten affective channels.

Radio Frequency Superconducting Quantum Interference Device Meta-atoms and Metamaterials: Experiment, Theory, and Analysis

Metamamterials are 1D, 2D or 3D arrays of articial atoms. The articial atoms, called "meta-atoms", can be any component with tailorable electromagnetic properties, such as resonators, LC circuits, nano particles, and so on. By designing the properties of individual meta-atoms and the interaction created by putting them in a lattice, one can create a metamaterial with intriguing properties not found in nature. My Ph. D. work examines the meta-atoms based on radio frequency superconducting quantum interference devices (rf-SQUIDs); their tunability with dc magnetic field, rf magnetic field, and temperature are studied. The rf-SQUIDs are superconducting split ring resonators in which the usual capacitance is supplemented with a Josephson junction, which introduces strong nonlinearity in the rf properties. At relatively low rf magnetic field, a magnetic field tunability of the resonant frequency of up to 80 THz/Gauss by dc magnetic field is observed, and a total frequency tunability of 100% is achieved. The macroscopic quantum superconducting metamaterial also shows manipulative self-induced broadband transparency due to a qualitatively novel nonlinear mechanism that is different from conventional electromagnetically induced transparency (EIT) or its classical analogs. A near complete disappearance of resonant absorption under a range of applied rf flux is observed experimentally and explained theoretically. The transparency comes from the intrinsic bi-stability and can be tuned on/ off easily by altering rf and dc magnetic fields, temperature and history. Hysteretic in situ 100% tunability of transparency paves the way for auto-cloaking metamaterials, intensity dependent filters, and fast-tunable power limiters. An rf-SQUID metamaterial is shown to have qualitatively the same behavior as a single rf-SQUID with regards to dc flux, rf flux and temperature tuning. The two-tone response of self-resonant rf-SQUID meta-atoms and metamaterials is then studied here via intermodulation (IM) measurement over a broad range of tone frequencies and tone powers. A sharp onset followed by a surprising strongly suppressed IM region near the resonance is observed. This behavior can be understood employing methods in nonlinear dynamics; the sharp onset, and the gap of IM, are due to sudden state jumps during a beat of the two-tone sum input signal. The theory predicts that the IM can be manipulated with tone power, center frequency, frequency difference between the two tones, and temperature. This quantitative understanding potentially allows for the design of rf-SQUID metamaterials with either very low or very high IM response.