The zebrafish has emerged as an important genetic model system for the study of vertebrate development. However, while genetics is a powerful tool for the study of early gene functions, the approach is more limited when it comes to understanding later functions of genes that have essential roles in early embryogenesis. There is thus a need to manipulate gene expression at different times, and ideally only in some regions of the developing embryo. Methods for conditional gene regulation have been established in Drosophila, C.elegans and the mouse, utilizing conditional gene activation systems such as the Gal4-UAS system (fly) and the cre/lox recombination system (mouse). While these tools are also being developed in zebrafish, the accessibility of the zebrafish embryo makes other approaches both possible and desirable. We have taken advantage of a heat-shock inducible system that uses the hsp70 promoter that is activated by cellular stress, such as heat. Having established that this global heat shock method allows temporal control of gene expression, we aimed to spatially control gene expression by applying controlled thermal heat to only a small region of the embryo. This would allow us to determine cell- and tissue-autonomous roles for developmentally important genes in an embryo with otherwise normal gene function. We have now developed a device that uses a laser to heat a defined region of the embryo, and thus activate the hsp70 promoter only in restricted regions of the embryo. The output of a 75 mW red laser pointer was focused into the 50 µm diameter core of an optical fiber, whose cleaved and coated end was used to heat, and thus induce, gene expression in a defined area. We have established conditions that allow controlled heating and trans-gene activation in small regions of the embryo without inducing cell death. This new tool will allow us to study the cell-autonomous roles of embryonic signaling molecules in cell differentiation, proliferation, and survival in a variety of tissues and at different times.

Radio frequency identification (RFID) technology is a useful technology that has myriad applications in technology, retail, manufacturing, and healthcare settings. Not dependent upon line-of-sight, RFID can scan devices in their proximity and report the information to connected (wired or other wireless) information systems. Once touted as the panacea for home healthcare, RFID devices can add benefit to patients in remote settings. RFID devices have been used to optimize systems in areas such as manufacturing and healthcare to expose inefficiencies in a system or process. Unlike manufacturing, however, RFID in healthcare settings presents security and privacy concerns to the people being tracked by the devices – particularly healthcare workers including nurses and doctors. This research presented a theoretical model that assessed the effect of five independent variables, namely, cognitive factors, of privacy concerns regarding surveillance and RFID devices and trust in the electronic medium, subjective norm, existence of security policy, and persistence of data on a dependent variable - intention to use RFID. The theoretical model presented in this research is based on the technology acceptance model and the extended theory of planned behavior. The research showed significant relationships between the cognitive factors of privacy concerns regarding surveillance and RFID devices, and trust and the electronic medium and perception of external control on intention to use. The theoretical model used in this research can be refined to better understand intention to use RFID in hospital environments.

A patient specific image planning system (IPS) was developed that can be used to assist in kV imaging technique selection during localization for radiotherapy. The IPS algorithm performs a divergent ray-trace through a three dimensional computed tomography (CT) data set. Energy-specific attenuation through each voxel of the CT data set is calculated and imaging detector response is integrated into the algorithm to determine the absolute values of pixel intensity and image contrast. Phantom testing demonstrated that image contrast resulting from under exposure, over exposure as well as a contrast plateau can be predicted by use of a prospective image planning algorithm. Phantom data suggest the potential for reducing imaging dose by selecting a high kVp without loss of image contrast. In the clinic, image acquisition parameters can be predicted using the IPS that reduce patient dose without loss of useful image contrast.

There is a chronic lack of donor hearts to meet the need for heart transplant both in the US and worldwide. Further, the use of available hearts is limited by the short period between collection and implantation during which the heart can be safely preserved ex vivo. Using mid-thermic Langendorff machine perfusion, we have been able to preserve the metabolic function of a healthy heart for up to 8 hours, twice the limit for current static cold storage. We have also been able to preserve the metabolic function of a damaged DCD Heart collected 30 minutes after cardiac arrest for a period of 8 hours. We further investigated whether it was possible to improve the preservation of DCD heart using treatment with 10 μM Triiodothyronine to stimulate the tissue metabolism and we did find a reduction in damage markers in the treated DCD hearts as compared to the untreated group.

The American Cancer Society predicts there will be 110,070 new cases and 32,120 deaths due to gynecological malignancies in 2018. A major contributing factor to the high mortality associated with gynecological cancers is the recurrence of treatment-resistant tumors. Ovarian cancer (OC) remains the most lethal gynecological malignancy, yet the mechanisms responsible for regulating tumor resistance and vulnerability are largely unknown or undruggable. Therefore, the goal of this research is to identify mechanisms responsible for therapeutic resistance in gynecological cancers and discover innovative approaches to circumvent these molecular alterations. Our efforts began in OC where secondary analysis of gene expression data from OC studies revealed that Sab, an outer mitochondrial membrane (OMM) scaffold protein, was down-regulated in OC tumors compared to normal tissue controls. Our previous studies demonstrate that Sab-mediated OMM signaling induces cell death in cervical cancer. In the current study, we found that Sab concentrations corresponded to chemoresponsiveness in a panel of OC cells; wherein, OC cells with low Sab levels were chemo resistant. Dynamic BH3 profiling revealed that cells with high Sab expression were primed for apoptosis. Furthermore, over-expression of Sab in chemo resistant cells enhanced apoptotic priming and restored cellular vulnerability to cisplatin/paclitaxel treatment. Additionally, an examination of treatment-resistant metastatic uterine cancer (UC) cells were found to have low Sab concentrations compared to vulnerable primary site-derived UC cells. Ectopic expression of Sab in chemo resistant UC cells enhanced the susceptibility towards megestrol acetate and BH3-mimetic ABT-737. To exploit the relationship between Sab concentrations and chemo-responsiveness in gynecological cancer cells, we developed a high-throughput screening assay to detect Sab levels in chemo-resistant OC cells. In collaboration with the Torrey Pines Institute for molecular studies, we have identified compounds that can increase Sab levels in resistant OC cells. The identified compounds improved the effectiveness of cisplatin/paclitaxel therapy. We propose that Sab may be a prognostic marker to discern personalized treatments for gynecological cancer patients. Furthermore, pharmacologically enhancing Sab-mediated signaling may increase the efficacy of chemotherapeutic agents, which would mean lower doses that would limit toxic side-effects.

An increase in the cross-sectional area (CSA) of the pulmonary arteries has been implicated in the progression of emphysema in COPD patients. Standardization of vessel size requires matching segments of the airway with their corresponding blood vessels. Automated matching is still error-prone, and manual matching by sifting through 2D slices is tedious and time-consuming. We propose a virtual reality (VR) system for the visualization of the airway and the vascular tree as a means of streamlining the verification of appropriate airway/vascular segment pairs selected for quantitation of arterial CSAs. In this work, we outline the technical specifications and design considerations and challenges for such system; we also compare user's performance on the proposed system with the conventional 2D method.

Maximal oxygen uptake (VO2max) is regarded as the gold standard for assessing aerobic fitness. In 1923, Hill et al. proposed that VO2max represents the maximal ability of the body to take in and consume O2 during strenuous exercise. Recently, however, controversy has arisen over the issue of whether a leveling off, or "plateau" in VO2 is necessary to verify attainment of VO2max. Purpose: To compare two different VO2max protocols and determine if both protocols show direct evidence of an upper limit on VO2. Methods: Nine runners (18-35 years old) completed a continuous graded exercise test (CGXT), followed by a discontinuous graded exercise test (DGXT). The CGXT consisted of gradually increasing treadmill running speed to the point of volitional exhaustion; the highest speed attained was labeled the peak treadmill speed. Over the next several days, participants ran at 80%, 90%, 100%, 105%, and 110% of peak treadmill speed for 10 minutes, or until volitional exhaustion was reached. Results: All participants (n=9) achieved a "VO2 ceiling" (or upper limit) on the DGXT, while only 44% (n=4) achieved a "VO2 plateau" on the CGXT. There was no significant difference between the VO2max obtained from a CGXT (57.4 ± 2.6 mL*kg-1min-1) and DGXT (60.0 ± 3.1 mL*kg-1min-1). There was no difference between oxygen uptake measured at 90%, 100%, 105%, and 110% of PTV (p>0.05). However, the highest VO2 recorded at 80% PTV was significantly lower than that recorded at all other velocities (p<0.05). Conclusion: The VO2 ceiling effect on a DGXT is inherently different than the VO2 plateau effect on a CGXT. In this study, a ceiling was always seen on the DGXT, but a plateau was not always seen on the CGXT.

A consensus model combines statistical methods with signal processing to create a better picture of the family of related signals. In this thesis, we will consider 32 signals produced by a single electroencephalogram (EEG) recording session. The consensus model will be produced by using the S-Transform of the individual signals and then normalized to unit energy. A bootstrapping process is used to produce a consensus spectrum. This leads to the consensus model via the inverse S-Transform of the consensus spectrum. The method will be applied to both a control and experimental EEG to show how the results can be used in clinical settings to analyze experimental outcomes.

Use of positive distraction in the built healthcare environment to assist in alleviating stress in a patient was investigated. A backlit light image was mounted in the ceiling of an examination room to create a positive distraction for patients in the ETSU Pediatric Clinic in Johnson City, TN. Survey instruments were used to collect sample data from patients and physicians in a randomized, balanced controlled study designed to determine if patients experienced less stress in the room with the backlit image as compared to other rooms (treatments). Although a statistical difference was not determined between the room with the backlit image and positive and negative control rooms, patients in rooms containing nature art tended to exhibit less anxiety. Researched based knowledge for creating positive distractions in the built healthcare environment helps designers create environments that benefit the patients, their families and medical staff of healthcare facilities.

Despite the amount of research that has been conducted on self-injury there is a lack of empirically validated instruments with which to measure self-injurious behavior. The present study developed a measure to examine self-injury and the associated features. Undergraduate students (n = 184) were administered a set of surveys to assess demographics, self-injurious behavior, suicidal ideation, Axis I and Axis II disorders, and impulsivity. Results indicated that a reliable measure, able to assess the extent of self-injury as well as associated features, was developed. Such a measure will enable clinicians to better assess self-injury and enable researchers to more fully examine self-injury and its relationship to other disorders.