Statistical methods for multi-marker testing in genetic association studies

As the development of genotyping and next-generation sequencing technologies, multi-marker testing in genome-wide association study and rare variant association study became active research areas in statistical genetics. This dissertation contains three methodologies for association study by exploring different genetic data features and demonstrates how to use those methods to test genetic association hypothesis. The methods can be categorized into in three scenarios: 1) multi-marker testing for strong Linkage Disequilibrium regions, 2) multi-marker testing for family-based association studies, 3) multi-marker testing for rare variant association study. I also discussed the advantage of using these methods and demonstrated its power by simulation studies and applications to real genetic data.

Active surgical positioning device for a cochlear implant electrode array

Cochlear implants have been of great benefit in restoring auditory function to individuals with profound bilateral sensorineural deafness. The implants are used to directly stimulate auditory nerves and send a signal to the brain that is then interpreted as sound. This project focuses on the development of a surgical positioning tool to accurately and effectively place an array of stimulating electrodes deep within the cochlea. This will lead to improved efficiency and performance of the stimulating electrodes, reduced surgical trauma to the cochlea, and as a result, improved overall performance to the implant recipient. The positioning tool reported here consists of multiple fluidic chambers providing localized curvature control along the length of the attached silicon electrode array. The chambers consist of 200μm inner diameter PET (polyethylene therephthalate) tubes with 4μm wall thickness. The chambers are molded in a tapered helical configuration to correspond to the cochlear shape upon relaxation of the actuators. This ensures that the optimal electrode placement within the cochlea is retained after the positioning tool becomes dormant (for chronic implants). Actuation is achieved by injecting fluid into the PET chambers and regulating the fluidic pressure. The chambers are arranged in a stacked, overlapping design to provide fluid connectivity with the non-implantable pressure controller and allow for local curvature control of the device. The stacked tube configuration allows for localized curvature control of various areas along the length of the electrode and additional stiffening and actuating power towards the base. Curvature is affected along the entire length of a chamber and the result is cumulative in sections of multiple chambers. The actuating chambers are bonded to the back of a silicon electrode array.

A Surface Displacement Analysis for Volcan Pacaya from October 2001 through March 2013 by Means of 3-D Modeling of Precise Position GPS Data

Volcán Pacaya is one of three currently active volcanoes in Guatemala. Volcanic activity originates from the local tectonic subduction of the Cocos plate beneath the Caribbean plate along the Pacific Guatemalan coast. Pacaya is characterized by generally strombolian type activity with occasional larger vulcanian type eruptions approximately every ten years. One particularly large eruption occurred on May 27, 2010. Using GPS data collected for approximately 8 years before this eruption and data from an additional three years of collection afterwards, surface movement covering the period of the eruption can be measured and used as a tool to help understand activity at the volcano. Initial positions were obtained from raw data using the Automatic Precise Positioning Service provided by the NASA Jet Propulsion Laboratory. Forward modeling of observed 3-D displacements for three time periods (before, covering and after the May 2010 eruption) revealed that a plausible source for deformation is related to a vertical dike or planar surface trending NNW-SSE through the cone. For three distinct time periods the best fitting models describe deformation of the volcano: 0.45 right lateral movement and 0.55 m tensile opening along the dike mentioned above from October 2001 through January 2009 (pre-eruption); 0.55 m left lateral slip along the dike mentioned above for the period from January 2009 and January 2011 (covering the eruption); -0.025 m dip slip along the dike for the period from January 2011 through March 2013 (post-eruption). In all bestfit models the dike is oriented with a 75° westward dip. These data have respective RMS misfit values of 5.49 cm, 12.38 cm and 6.90 cm for each modeled period. During the time period that includes the eruption the volcano most likely experienced a combination of slip and inflation below the edifice which created a large scar at the surface down the northern flank of the volcano. All models that a dipping dike may be experiencing a combination of inflation and oblique slip below the edifice which augments the possibility of a westward collapse in the future.