Indiana University-Purdue University Indianapolis (IUPUI) / Adaptive-optics optical coherence tomography (AOOCT) is a technology that has been rapidly advancing in recent years and offers amazing capabilities in scanning the human eye in vivo. In order to bring the ultra-high resolution capabilities to clinical use, however, newer technology needs to be used in the image reconstruction process. General purpose computation on graphics processing units is one such way that this computationally intensive reconstruction can be performed in a desktop computer in real-time. This work shows the process of AOOCT image reconstruction, the basics of how to use NVIDIA's CUDA to write parallel code, and a new AOOCT image reconstruction technology implemented using NVIDIA's CUDA. The results of this work demonstrate that image reconstruction can be done in real-time with high accuracy using a GPU.

Indiana University-Purdue University Indianapolis (IUPUI) / Aromatase inhibitors (AIs) are the current standard of care for the treatment of hormone receptor positive breast cancer in postmenopausal women. Nearly one-half of patients receiving AI therapy develop musculoskeletal toxicity that is characterized by joint and/or muscle pain and approximately one-fourth of patients discontinue their therapy as a result of musculoskeletal pain. Since there are no effective strategies for prevention or treatment, insight into the mechanisms of AI-induced pain is critical to improve treatment. However, there are few studies of AI effects in animal models of nociception. To determine whether AIs produce hypersensitivity in animal models of pain, I examined the effects of AI administration on mechanical, thermal, and chemical sensitivity in rats. The results demonstrate that (1) repeated injection of 5 mg/kg letrozole in male rats produces mechanical, but not thermal, hypersensitivity that extinguishes when drug dosing is stopped; (2) administering a single dose of 1 or 5 mg/kg letrozole in ovariectomized (OVX) rats also induces mechanical hypersensitivity, without altering thermal sensitivity and (3) a single dose of 5 mg/kg letrozole or daily dosing of letrozole or exemestane in male rats augments flinching behavior induced by intraplantar ATP injection. To determine whether the effects of AIs on nociceptive behaviors are mediated by activation or sensitization of peptidergic sensory neurons, I determined whether letrozole exposure alters release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons and from sensory nerve endings in rat spinal cord slices. No changes in basal, capsaicin-evoked or high extracellular potassium-evoked CGRP release were observed in sensory neuronal cultures acutely or chronically exposed to letrozole. Furthermore, letrozole exposure did not alter the ability of ATP to augment CGRP release from sensory neurons in culture. Finally, chronic letrozole treatment did not augment neuropeptide release from spinal cord slices. Taken together, these results do not support altered release of this neuropeptide into the spinal cord as mediator of letrozole-induced mechanical hypersensitivity and suggest the involvement of other mechanisms. Results from this dissertation provide a new experimental model for AI-induced hypersensitivity that could be beneficial in delineating mechanisms mediating pain during AI therapy.

Indiana University-Purdue University Indianapolis (IUPUI) / The islet beta cell is unique in its ability to synthesize and secrete insulin for use in the body. A number of factors including proinflammatory cytokines, free fatty acids, and islet amyloid are known to cause beta cell stress. These factors lead to lipotoxic, inflammatory, and ER stress in the beta cell, contributing to beta cell dysfunction and death, and diabetes. While transcriptional responses to beta cell stress are well appreciated, relatively little is known regarding translational responses in the stressed beta cell. To study translation, I established conditions in vitro with MIN6 cells and mouse islets that mimicked UPR conditions seen in diabetes. Cell extracts were then subjected to polyribosome profiling to monitor changes to mRNA occupancy by ribosomes. Chronic exposure of beta cells to proinflammatory cytokines (IL-1 beta, TNF-alpha, IFN-gamma), or to the saturated free fatty acid palmitate, led to changes in global beta cell translation consistent with attenuation of translation initiation, which is a hallmark of ER stress. In addition to changes in global translation, I observed transcript specific regulation of ribosomal occupancy in beta cells. Similar to other privileged mRNAs (Atf4, Chop), Pdx1 mRNA remained partitioned in actively translating polyribosomes during the UPR, whereas the mRNA encoding a proinsulin processing enzyme (Cpe) partitioned into inactively translating monoribosomes. Bicistronic luciferase reporter analyses revealed that the distal portion of the 5’ untranslated region of mouse Pdx1 (between bp –105 to –280) contained elements that promoted translation under both normal and UPR conditions. In contrast to regulation of translation initiation, deoxyhypusine synthase (DHS) and eukaryotic translation initiation factor 5A (eIF5A) are required for efficient translation elongation of specific stress relevant messages in the beta cell including Nos2. Further, p38 signaling appears to promote translational elongation via DHS in the islet beta cell. Together, these data represent new insights into stress induced translational regulation in the beta cell. Mechanisms of differential mRNA translation in response to beta cell stress may play a key role in maintenance of islet beta cell function in the setting of diabetes.

Indiana University-Purdue University Indianapolis (IUPUI) / Heat is one of the most important factors in our atmosphere for precipitation (thunderstorm) formation. Thermal energy from local urban land-cover is also a common source of heat in the lower atmosphere. This phenomenon is known as the urban heat island effect (UHI) and is identified as a substantial cause to a changing climate in surface weather modification. The proceeding study investigates this connection between the UHI and surface weather using remote sensing platforms A ten-year analysis of the Indianapolis UHI and thunderstorms were studied from the summer months of May, June, July, August and September (MJJAS) from 2002 until 2011. LANDSAT space borne satellite technology and land-surface based weather radar technology was used in this analysis for thunderstorm investigation. Precipitation areas identified from land-based NEXRAD WSR-88D technology were used to identify convection from non-synoptic forcing and non-normal surface diurnal heating scenarios. Only convection appearing from the UHI were studied and analyzed. Results showed twenty-one events over eighteen days with the year 2005 and 2011 having the largest frequency of events. The month of August had the largest concentration with seven events during the late afternoon hours. UHI results showed July had the largest heat island magnitude with April and September having the lowest magnitude in UHI temperatures. Three events of the twenty-one storm paths did not had a significant mean temperature difference in the heat island below the storm reflectivity. The nineteen storm paths that were significant had a warmer area underneath storm path development by an average 6.2°C than surrounding areas. UHI initiation points showed twelve of the twenty-one events having statistically significant differences between 2 km initiation areas and the rest of the study areas. Land-cover results showed low intensity developed areas had the most land-cover type (48%) in the 2km initiation buffer regions.

Indiana University-Purdue University Indianapolis (IUPUI) / In recent decades, Petri nets (PNs) have been used to model traffic networks for different purposes, such as signal phase control, routing, and traffic flow estimation, etc. Because of the complex nature of traffic networks where both discrete and continuous dynamics come into play, the Hybrid Petri net (HPN) model becomes an important tool for the modeling and analysis of traffic networks. In Chapter 1 a brief historical summery about traffic systems control and then related work is mentioned followed by the major contributions in this research. Chapter 2 provides a theoretical background on Petri nets. In Chapter 3, we develop a HPN model for a single signalized intersection first, then we extend this model to study a simple traffic network that consists of two successive intersections. Time delays between different points of network are also considered in order to make the model suitable for analysis and simulation. In addition to HPN models, we also consider discrete Petri nets where their modeling simplicity enables the characterization of the occurrences of all events in the system. This discrete PN is particularly useful to give a higher-level representation of the traffic network and study its event occurrences and correlations. In Chapter 4, we build a discrete PN model to represent a traffic network with two successive intersections. However, we find that the model leads to unbounded places which cannot accurately reflect the dynamics of the traffic in terms of event occurrences. Hence, we introduce the Modified Binary Petri nets (MBPN) to overcome the limitation and resolve the confliction problem when we design our controllers. This MBPN model is a powerful tool and can be useful for the modeling and analysis of many other applications in traffic networks. Chapter 5 gives a summary for each chapter, provides conclusion and discusses future work for both discrete and hybrid Petri nets.

Indiana University-Purdue University Indianapolis (IUPUI) / Although interprofessional education (IPE) opportunities can help prepare students for future practice and patient-centered care, many health professions students in the country are not educated in an environment with opportunities to learn with, from, or about students from other health professions. With upcoming curricular changes at the Indiana University School of Medicine (IUSM) and the Indiana University School of Nursing (IUSN), IPE remains at the forefront of these changes in both schools. To date, few studies have explored student, faculty, and administrators’ conceptualizations of IPE prior to formal implementation. Additionally, previous studies have not compared IPE conceptualizations across these groups. This multiple-case study explores and compares how groups of stakeholders from the IUSM (Indianapolis) and the IUSN (Indianapolis) conceptualize IPE. Data collection included the examination of discipline-specific public documents and one-on-one interviews (N=25) with pre-licensure students, clinical faculty, and administrators from each school. Coding and extraction of themes transpired through within-case and cross-case analysis and data supported the following findings: the ‘business of medicine’ may prevent IPE from becoming a priority in education; stakeholders’ conceptualizations of IPE are shaped through powerful experiences in education and practice; students desire more IPE opportunities at the institution; stakeholders at the IUSN have a long-standing investment in IPE; and the institution requires a ‘culture shift’ in order to sustain IPE efforts. The findings suggest that IPE belongs in all education sectors and IPE efforts deserve reward and reimbursement. The findings also insinuate that leadership, roles, and team training education belong in IPE and IPE culture requires all individuals’ (e.g., student, faculty, administrators, patients) commitment. Importantly, the institution must continue IPE development, research, and dissemination. These findings can help shape curricula as time progresses, increase the likelihood of developing a successful new curriculum, and prompt ongoing reflection about IPE. This information can influence how institutions approach IPE and may lead to a more successful and informed IPE curriculum in the first years of implementation. And, hopefully what is learned through IPE will be translated into healthcare practice environments.

Indiana University-Purdue University Indianapolis (IUPUI) / Intrinsically disordered proteins are proteins characterized by lack of stable tertiary structures under physiological conditions. Evidence shows that disordered proteins are not only highly involved in protein interactions, but also have the capability to associate with more than one partner. Short disordered protein fragments, called “molecular recognition features” (MoRFs), were hypothesized to facilitate the binding diversity of highly-connected proteins termed “hubs”. MoRFs often couple folding with binding while forming interaction complexes. Two protein disorder mechanisms were proposed to facilitate multiple partner binding and enable hub proteins to bind to multiple partners: 1. One region of disorder could bind to many different partners (one-to-many binding), so the hub protein itself uses disorder for multiple partner binding; and 2. Many different regions of disorder could bind to a single partner (many-to-one binding), so the hub protein is structured but binds to many disordered partners via interaction with disorder. Thousands of MoRF-partner protein complexes were collected from Protein Data Bank in this study, including 321 one-to-many binding examples and 514 many-to-one binding examples. The conformational flexibility of MoRFs was observed at atomic resolution to help the MoRFs to adapt themselves to various binding surfaces of partners or to enable different MoRFs with non-identical sequences to associate with one specific binding pocket. Strikingly, in one-to-many binding, post-translational modification, alternative splicing and partner topology were revealed to play key roles for partner selection of these fuzzy complexes. On the other hand, three distinct binding profiles were identified in the collected many-to-one dataset: similar, intersecting and independent. For the similar binding profile, the distinct MoRFs interact with almost identical binding sites on the same partner. The MoRFs can also interact with a partially the same but partially different binding site, giving the intersecting binding profile. Finally, the MoRFs can interact with completely different binding sites, thus giving the independent binding profile. In conclusion, we suggest that protein disorder with post-translational modifications and alternative splicing are all working together to rewire the protein interaction networks.

Indiana University-Purdue University Indianapolis (IUPUI) / This study examines the essential features of women’s experiences as members of a service association. It uses a qualitative method to understand how women make meaning from their membership in an all-female association and a mixed-gender association. The experiences were examined in comparative contexts. The study finds three common features in each association: joining, volunteering, and leading. In the mixed-gender association, women also experienced a process of assimilating into membership activities. The study provides scholars and association practitioners insights into the complex blend of members’ personal and professional interests with implications for membership recruitment and retention.

Indiana University-Purdue University Indianapolis (IUPUI) / Nurse-physician collaboration has received much attention over the past decade in the USA. The release of three reports from the Institute of Medicine implicated poor communication and collaboration among nurses and physicians as a major contributing factor to the incidence of sentinel events and medical errors. Despite the growing awareness of the imperative related to collaboration between nurses and physicians to ensure patient safety, the problem of poor nurse-physician collaboration remains endemic throughout the country. Indian nurses, along with many other internationally educated nurses, comprise 12-15.2% of the nursing workforce in the USA. Little is known about how Indian nurses culture potentially influences their ability to effectively collaborate with physicians to ensure patient safety. The purpose of this study is to understand Indian nurses’ attitudes and perceptions about nurse-physician collaboration. Hermeneutic interpretive phenomenology as influenced by the work of Martin Heidegger guided this study through the use of interviews via Skype. The overall experience of the Indian nurses was of one experiencing a dramatic positive change in nurse-physician collaboration in the USA as compared to India. Four themes emerged describing this phenomenon: Respect/feeling heard, Being Trusted, Assurance of Accountability, and Finding Freedom. Indian nurses practicing in the USA find a freedom that empowers them to collaborate with physicians for patient safety. They, as all nurses may, benefit from continuing educational opportunities that demonstrate ways to collaborate more fully.

Indiana University-Purdue University Indianapolis (IUPUI) / This study examined the roles of commitment and attributions in uninvolved partner responses to imagined sexual infidelity. Undergraduate students (N = 298) in dating relationships participated in a hypothetical sexual infidelity scenario in which they imagined their romantic partner engaged in sexual intercourse with someone else. Measured-variable path analysis was used to evaluate the predictive ability of commitment and attributions on negative emotional responses and predicted relationship continuation. The hypothesized conceptual model demonstrated poor fit to sample data. Through exploratory model building, an alternative model was generated that demonstrated good fit to sample data. A subset of commitment, investment, predicted negative affect. In addition, attributions predicted predictions of relationship continuation. Negative emotional responses were highly endorsed on a validated measure for emotional responses, the PANAS-X (Watson & Clark, 1994). Further, study findings highlight the importance of the use of a compliance check in assessing successful participant completion of imagined infidelity scenario. Unique study contributions include directions for further conceptual model development for this area of research as well as support for the use of compliance checks and careful selection of infidelity scenario.