Indiana University-Purdue University Indianapolis (IUPUI) / Sensing, integrating, and relaying signals from the environment through proteins, metabolites, and lipids to the lung are critical for proper development. Moonlighting proteins, such as AIMP1, are a unique subset that serves at least two independent physiological functions. Encoded by gene AIMP1, AIMP1 has two known functions: (1) C-terminus EMAP II domain of full-length AIMP1 can be secreted out of the cell to chemoattract myeloid cells; (2) intracellular full-length protein interacts with tRNA synthetases in protein translation. However, despite the linkage of protein expression levels of with several lung pathologies such as bronchopulmonary dysplasia (BPD), effectively targeting the protein encoded by AIMP1 has been a challenge due to poorly understood mechanisms. This thesis explores physiological, signaling, and immunological moonlighting mechanisms of first, the extracellular EMAP II then the intracellular AIMP1. Experiments utilize both in vitro and in vivo models, including a murine model of BPD and Cre-mediated exon-deletion knockout. Experimental results provide evidence that in the BPD model, EMAP II levels are elevated and sustained – first in bronchial epithelial cells then in macrophages. Mice exposed to sustained and elevated EMAP II protein levels resemble the BPD phenotype while neutralization partially rescued the phenotype, implying EMAP II as a potential therapeutic target against BPD. Results from studies exploring EMAP II’s signaling mechanism identify transient stimulation of JAK-STAT3 phosphorylation, commonly found in inflammation-resolving macrophages. In contrast, it induces unique transcriptional changes that are reversible both by JAK-STAT inhibitor and siRNA-mediated knockdown of Stat3. Studies using AIMP1 knockout mouse reveal a novel function for the intracellular AIMP1. AIMP1 knockout mice exhibited neonatal lethality with a respiratory distress phenotype, decreased type I alveolar cell expression, and disorganized bronchial epithelium, suggesting a role in lung maturation. In vitro experiments suggest that a portion of AIMP1 residing in the cell’s membrane interacts with various phosphatidylinositols and contributes toward F-actin deposition and assembly. Data from these experimental studies provide insight into how the various functions of the promiscuous AIMP1 gene affect lung development. These studies exemplify not only characterize novel moonlighting mechanisms of AIMP1, but also highlight the importance of characterizing moonlighting proteins to promote therapeutic preventions. / 2020-02-21

This research focuses on estimation and analysis of stream sinuosity using GIS. Fifty-five streams including 13 streams of order 0, 17 streams of order 1, 15 streams of order 2 and 10 streams of order 3 in Virginia were considered. Several GIS datasets from various sources, including the Virginia Base Mapping Program (VBMP) and United States Geological Survey (USGS), were used to generate stream networks using GIS. Sinuosity was computed using GIS based on a technique comparable to the approach used in an Environmental Monitoring and Assessment Program's (EMAP's) field survey report. Field sinuosity data from EMAP report were used as reference data for analyzing the accuracy of sinuosity values from different GIS data sources and resolutions. The GIS technique was implemented for computing sinuosity for 55 streams in Virginia using vector data including the VBMP Hydro44 and National Hydrography Data (NHD). Insufficient statistical evidence was found to support the hypothesis that the computed sinuosity values using Hydro44 and NHD data are different from EMAP field data for all 55 streams. Sinuosity values computed using Hydro44 and NHD were found to increase with the increase in EMAP sinuosity (positive correlation) for all 55 streams. EMAP data on sinuosity, however, did not predict sinuosity values computed using Hydro44 (R² = 27%) and NHD (R² = 10%) sources well. It was found that the GIS technique of computing sinuosity using digital data such as Hydro44 (VBMP source) and NHD (USGS source 1:24,000) is better suited for stream orders 2 and 3. Insufficient statistical evidence was found that computed sinuosity values for streams derived using various resolutions (i.e., DTM 3m, DTM 10m, DTM 30m, DEM 10m and DEM 30m) are different from EMAP field data. Positive correlation was observed between sinuosity values for streams derived in all resolutions with EMAP field data. DTM 10m resolution data yielded best correlation value (75%) with EMAP field data. / Master of Science

Submitted by Cleide Dantas (cleidedantas@ufpa.br) on 2014-11-14T13:30:11Z No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) Dissertacao_ModelagemFiltragemDistorcoes.pdf: 7630304 bytes, checksum: f4663ae7412a96d4ebf62dbb11a7a564 (MD5) / Approved for entry into archive by Ana Rosa Silva (arosa@ufpa.br) on 2014-11-17T12:55:55Z (GMT) No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) Dissertacao_ModelagemFiltragemDistorcoes.pdf: 7630304 bytes, checksum: f4663ae7412a96d4ebf62dbb11a7a564 (MD5) / Made available in DSpace on 2014-11-17T12:55:55Z (GMT). No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) Dissertacao_ModelagemFiltragemDistorcoes.pdf: 7630304 bytes, checksum: f4663ae7412a96d4ebf62dbb11a7a564 (MD5) Previous issue date: 1994 / PETROBRAS - Petróleo Brasileiro S.A. / As distorções estáticas são um grave problema que afeta o método magnetotelúrico e muitas tentativas têm sido feitas para eliminar ou minimizar os seus efeitos. Este trabalho trata de uma técnica nova que trata deste problema, o método EMAP, que é uma adaptação do método magnetotelúrico na qual as medidas de campo elétrico são feitas em uma linha contínua de dipolos conectados entre si, e os dados coletados desta maneira são tratados com um filtro espacial passa-baixa dependente da frequência. Este trabalho é composto de duas partes principais, a simulação numérica dos dados contaminados com as distorções estáticas e a filtragem destes dados com o filtro espacial passa-baixa. Na primeira parte, aplicamos o método dos elementos finitos para simular a resposta dos dipolos elétricos, os quais fazem as medidas do campo elétrico. Na segunda parte aplicamos a janela de Hanning como filtro passa-baixa apropriado para tratar os dados. / Static distortions are a serius problem to the magnetotelluric method and many atempts to eliminate or to minimize them in the MT data have been tried with more or less success. This work is an overview on a new technique that deals with this problem, the EMAP method, witch is a modification of the traditional MT method in witch the measures of the electric field are made in a continuous line of dipoles equally spaced, and the data so obtained are filtered with a spatial low-pass, frequency dependent digital filter. This work is composed of two main parts, the numerical simulation of electric field data distorted by the static shift and the aplication of the spatial low-pass filter to minimize the static shift. In the first part, we use the finite elements method to simulate the response of the electric dipole witch actually makes the electric field measurements; in the second part, we aply the Hanning window as the spatial filter to treat the data.

The DNA damage response is a cell-wide response that coordinates repair and cell-cycle progression. Crucial to fidelity of genetic propagation, survival, and apoptosis, dysfunctions in the response are at the root of genome instability syndromes and cancer predisposition in mammalian cells. Within the response lie hubs of coordination, called checkpoints, whose members and organization are ubiquitous amongst eukaryotes. The high conservation of these checkpoints enable the study of their dynamics by proxy via simpler model organisms. We use the budding yeast, Saccharomyces cerevisiae, to study the replication and DNA damage checkpoints --- both implicated in DNA damage repair. Using a yEGFP reporter driven by the RNR3 promoter and reporter-based synthetic genetic array analysis, we created a detector of potential checkpoint activation in response to two doses of MMS, 0.015% and 0.060% (v/v). The high-throughput screens and differential epistasis miniarray analyses (EMAPs) yield unanticipated involvement of oxidative stress response, ribosomal biogenesis, and chromatin remodelling genes.