The heat-shock response is one of the many complex physiological systems that organisms have developed in order to protect their cells against stress. This response is initiated by the binding of heat shock factor 1 (HSF1) to the promoters of genes containing heat-shock elements (HSEs,) which results in the expression of several proteins, among them the proteo-protective inducible heat-shock protein (hsp70i). Due to HSF1s critical role in this process, an active area of research is trying to understand of how HSF1 executes its function. Considering the rapidity with which the field of cell biology is expanding, in particular the sub-field of nuclear compartmentalization, this study seeks to understand how nuclear structure affects the function of HSF1. Specifically, this study investigates the potential role for the interaction between HSF1 and the translocated promoter region protein (Tpr,) a structural component of the nuclear pore, an interaction initially identified by yeast two-hybrid analysis, in the transcription of hsp70i. Due to Tprs location and its putative function in nucleo-cytoplasmic trafficking, this works seeks to answer to the question, Does Tpr play a role in the export of HSF1-driven mRNAs? In a similar vein, heat-shock transcription factor 2 (HSF2,) a less well-understood member of the heat-shock transcription factor family, also interacts with Tpr in the yeast two-hybrid assay. HSF2 has recently been shown to have an active role during mitosis, when the hsp70i gene is being bookmarked for potential expression that might be needed in early G1, when most genes are unable to be expressed. This body of work also seeks to answer the question of, Does the Tpr/HSF2 interaction have a role in positioning the gene in relation to the nuclear pore after mitosis? This study was performed using both novel and standard in vivo and in vitro molecular biology techniques. It ultimately aims to clarify the less understood, although much broader, subject of how does transcription occur in the three-dimensional space of the nucleus.

Par-4 is a leucine zipper domain protein that induces apoptosis on its own in certain cancer cells and in Ras-transformed cells, but not in normal or immortalized cells. Par-4 induces apoptosis by activation of the Fas death receptor pathway and co-parallel inhibition of NF-B transcription activity. Cells that are resistant to apoptosis by Par-4 alone, however, are greatly sensitized by Par-4 to the action of other pro-apoptotic insults such as growth factor withdrawal, TNF, ionizing radiation, intracellular calcium elevation, or those involved in neuronal degeneration such as Alzheimer's, Parkinson's, Huntington's and Stroke. Previous studies have suggested that the apoptosis-sensitization potential of Par-4 is dependent upon inhibition of PKC or WT1 cell survival function by direct interaction between the leucine zipper domain at the carboxy-terminus of Par-4 and the zinc finger domains of PKC or WT1. In this study, I performed structure-function analysis using GFP-fusion proteins and deletion mutants to identify the functional localization and domains of Par-4 that are essential for apoptosis induction. My findings suggest that apoptosis by Par-4 is dependent on its translocation to the nucleus for induction of apoptosis. A bipartite nuclear localization signal sequence corresponding to amino acids 137-155 was necessary for nuclear translocation of Par-4. Importantly, the core residues 137-204 in the center part of Par-4 were necessary and sufficient to induce Fas pathway activation, inhibition of nuclear NF-B transcription activity and apoptosis. These findings imply that binding of Par-4 via its leucine zipper domain to other proteins is dispensable for apoptosis by Par-4.

Speech communication is gaining in popularity in many different contexts as technology evolves. With the introduction of mobile electronic devices such as cell phones and laptops, and fixed electronic devices such as video and teleconferencing systems, more people are communicating which leads to an increasing demand for new services and better speech quality. Methods to enhance speech recorded by microphones often operate blindly without prior knowledge of the signals. With the addition of multiple microphones to allow for spatial filtering, many blind speech enhancement methods have to operate blindly also in the spatial domain. When attempting to improve the quality of spoken communication it is often necessary to be able to reliably determine the location of the speakers. A dedicated source localization method on top of the speech enhancement methods can assist the speech enhancement method by providing the spatial information about the sources. This thesis addresses the problem of speech-source localization, with a focus on the problem of localization in the presence of multiple concurrent speech sources. The primary work consists of methods to estimate the direction of arrival of multiple concurrent speech sources from an array of sensors and a method to correct the ambiguities when estimating the spatial locations of multiple speech sources from multiple arrays of sensors. The thesis also improves the well-known SRP-based methods with higher-order statistics, and presents an analysis of how the SRP-PHAT performs when the sensor array geometry is not fully calibrated. The thesis is concluded by two envelope-domain-based methods for tonal pattern detection and tonal disturbance detection and cancelation which can be useful to further increase the usability of the proposed localization methods. The main contribution of the thesis is a complete methodology to spatially locate multiple speech sources in enclosed environments. New methods and improvements to the combined solution are presented for the direction-of-arrival estimation, the location estimation and the location ambiguity correction, as well as a sensor array calibration sensitivity analysis.

Given their unique structural properties, quantum rings (QRs) structures have recently been of particular interest for investigating quantum interference which is called the neutral charged exciton optical Aharonov-Bohm (AB) effect. A delocalized wavefunction around the rim is a prerequisite for the AB effect, but asymmetry and anisotropy seem to have been overlooked in the spectroscopy of QRs. In this thesis, the presence of a localized state in a single GaAs QR is presented.

Wave transport in strongly scattering, disordered media is investigated experimentally using ultrasonic techniques. Several cases of anomalous wave transport (deviations from conventional diffusion) are studied through experiments on aluminum mesoglass samples, which were designed and created for this purpose. The anomalous wave behaviour is contrasted with conventional diffusion, observed at some frequencies via both transmission and backscattering measurements on wide, thick, slab-shaped samples. The coherent backscattering (CBS) effect is measured experimentally for strongly scattered acoustic waves in three dimensions (3D), and is compared for the first time with theory for diffusive elastic waves in 3D to give an estimate of the diffusion coefficient. At other frequencies, an Anderson localization regime is observed, and is studied in detail. The first experimental study of CBS for localized elastic waves in 3D is presented. By comparing both backscattering and transmission measurements with predictions from a ‘local’ self-consistent theory of localization, the first experimental observation of a complete Anderson mobility gap for elastic waves in 3D is reported. In this mobility gap, large contributions to backscattered intensity from recurrent scattering were observed, enabling the first experimental study of recurrent scattering on its own. The time-dependence of the recurrent scattering, R(t), is shown to agree with theoretical predictions in the diffuse and localized regimes. At the mobility edge, R(t) shows a surprisingly slow decay, prompting further theoretical work. Localization and criticality are also investigated via statistical measurements of ultrasound from cubic mesoglasses of different sizes. Finite-size scaling of multifractal quantities is observed in these cubic samples, and a preliminary fit with theory to determine critical parameters of the Anderson transition is demonstrated. Finally, a sample is which is a candidate to exhibit superdiffusion of ultrasound is studied via a range of experimental techniques, showing subtle deviations from diffusion and opening doors for the next steps in this study. / May 2016

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Neuroanatomical work has shown that the auditory system is different in different mammals, with primates and bats representing two extremes in this regard. It has been suggested that these differences are related to auditory localization. The present work examined auditory localization in several representative mammalian speciesa squirrel monkey, bat {Phyllostomus hastatus), albino rat and cat. A semi-naturalistic localization situation was used. The animal was placed in a wire cage located in a sound-deadened room. Two loudspeakers were located one on either side of the cage. Two response lavers were located in the front wall of the cage, flanking a liquid food dispenser. When tone bursts were presented from one of the loudspeakers, a response on the "correct" lever resulted in the delivery of a small amount of food to the animal. The left-hand lever was correct when the tone bursts were from the left-hand loudspeaker, the right-hand lever was correct when the tone bursts were from the right-hand loudspeaker. The percentage of correct responses on both levers was the measure of performance on the discrimination under a given set of conditions. [TRUNCATED] / 2031-01-01

Wireless capsule endoscopy (WCE) offers a patient-friendly, non-invasive and painless investigation of the entire small intestine, where other conventional wired endoscopic instruments can barely reach. As a critical component of the capsule endoscopic examination, physicians need to know the precise position of the endoscopic capsule in order to identify the position of intestinal disease after it is detected by the video source. To define the position of the endoscopic capsule, we need to have a map of inside the human body. However, since the shape of the small intestine is extremely complex and the RF signal propagates differently in the non-homogeneous body tissues, accurate mapping and localization inside small intestine is very challenging. In this dissertation, we present an in-body simultaneous localization and mapping technique (Body-SLAM) to enhance the positioning accuracy of the WCE inside the small intestine and reconstruct the trajectory the capsule has traveled. In this way, the positions of the intestinal diseases can be accurately located on the map of inside human body, therefore, facilitates the following up therapeutic operations. The proposed approach takes advantage of data fusion from two sources that come with the WCE: image sequences captured by the WCE's embedded camera and the RF signal emitted by the capsule. This approach estimates the speed and orientation of the endoscopic capsule by analyzing displacements of feature points between consecutive images. Then, it integrates this motion information with the RF measurements by employing a Kalman filter to smooth the localization results and generate the route that the WCE has traveled. The performance of the proposed motion tracking algorithm is validated using empirical data from the patients and this motion model is later imported into a virtual testbed to test the performance of the alternative Body-SLAM algorithms. Experimental results show that the proposed Body-SLAM technique is able to provide accurate tracking of the WCE with average error of less than 2.3cm.

"Precise and accurate localization and motion classification is an emerging fundamental areas for scientific research and engineering developments. Such science and technology began from the broad out door area applications, and gradually grew into smaller and more complicated in-door area and more recently it is proceeding into in-body area networking for medical applications. Localization and motion classification technologies have their own specific challenges depending on the application and environment, which are left for scientists and engineers to overcome. One major challenge is that location estimation and motion classification often use hand-held devices or wearable sensors. Such devices and sensors usually work in indoor, near body environments and the human object has certain effects on the measurements. In that situation, existing mathematical models for general environments are no longer accurate and new models and analytical approaches are required to deal with the human body effects. This has opened opportunities for researchers to tackle a number of demanding problems. This dissertation focuses on three novel problems in localization and motion classification using radio propagation (RF) modeling, in and around the human body. (1) We develop an empirical Time-of-Arrival (TOA) ranging error model for radio propagation from body-mounted sensors to external access points, for human body tracking in indoor environment. This model reflects the effects of human angular motion on TOA ranging estimation, which enables accurate analysis for conventional TOA-based human tracking systems. (2) We use empirical data collected from a RF connection between a pair of body-mounted sensors to classify seven frequently appeared human body motions. This RF based classification approach has enabled health monitoring applications for first responders, hospital patient, and elderly care centers and in most of the situations it can replace the costly video base monitoring systems. (3) We use radio propagation models from body-mounted sensor to medical implants and the moving pattern of micro-robots inside the body to analyze the accuracy of hybrid localization inside the human body. This analysis demonstrates the feasibility of millimeter level of accurate localization inside the human body, which opens up possibilities for 3D reconstruction of the interior of human GI tract."

Our increased reliance on localization devices such as GPS navigation has led to an increased demand for localization solutions in all environments, including indoors. Indoor localization has received considerable attention in the last several years for a number of application areas including first responder localization to targeted advertising and social networking. The difficult multipath encountered indoors degrades the performance of RF based localization solutions and so far no optimal solution has been published. This dissertation presents an algorithm called Coherent Array Reconciliation Tomography (CART), which is a Direct Positioning Algorithm (DPA) that incorporates signal fusion to perform a simultaneous leading edge and position estimate for a superior localization solution in a high multipath environment. The CART algorithm produces position estimates that are near optimal in the sense that they achieve nearly the best theoretical accuracy possible using an Impulse Radio (IR) Ultra-Wideband (UWB) waveform. Several existing algorithms are compared to CART including a traditional two step Leading Edge Detection (LED) algorithm, Singular value Array Reconciliation Tomography (SART), and Transactional Array Reconciliation Tomography (TART) by simulation and experimentation. As shown under heavy simulated multipath conditions, where traditional LED produces a limited solution and the SART and TART algorithms fail, the CART algorithm produces a near statistically optimal solution. Finally, the CART algorithm was also successfully demonstrated experimentally in a laboratory environment by application to the fire fighter homing device that has been a part of the ongoing research at Worcester Polytechnic Institute (WPI).

With the rise in aging population, about 6.8 million American residents are depen- dent on mobility devices for their day to day activity. More than 40% of these users have di?culty in moving the mobility device on their own. These numbers serve as a motivation on developing a system than can help in manipulation with simple muscle activity and localize the mobility device in the user's home in case of medical emergencies. This research is aimed at creating a user interface of Elec- tromyographic Sensor, attached to the forearm, incorporated with present smart wheelchairs and a simple localization technique using ducial markers. The main outcome of the research is a simulator of the smart wheelchair to analyze the results of my research.