Visualizing the Simulation of 3-D Underwater Sensor Networks

The majority of sensor network research deals with land-based networks, which are essentially two-dimensional, and thus the majority of simulation and animation tools also only handle such networks. Underwater sensor networks on the other hand, are essentially 3D networks because the depth at which a sensor node is located needs to be considered as well. Due to that additional dimension, specialized tools need to be used when conducting simulations for experimentation. The School of Engineering’s Underwater Sensor Network (UWSN) lab is conducting research on underwater sensor networks and requires simulation tools for 3D networks. The lab has extended NS-2, a widely used network simulator, so that it can simulate three-dimensional networks. However, NAM, a widely used network animator, currently only supports two-dimensional networks and no extensions have been implemented to give it three-dimensional capabilities. In this project, we develop a network visualization tool that functions similarly to NAM but is able to render network environments in full 3-D. It is able to take as input a NS-2 trace file (the same file taken as input by NAM), create the environment, position the sensor nodes, and animate the events of the simulation. Further, the visualization tool is easy to use, especially friendly to NAM users, as it is designed to follow the interfaces and functions similar to NAM. So far, the development has fulfilled the basic functionality. Future work includes fully functional capabilities for visualization and much improved user interfaces.

The role of SRC family kinase activation in prostate cancer growth and lymph node metastasis

Aberrant expression and/or activation of Src Family of non-receptor protein tyrosine kinases (SFKs) occur frequently during progressive stages of multiple types of human malignancies, including prostate cancer. Two SFKs, Src and Lyn, are expressed and implicated in prostate cancer progression. Work in this dissertation investigated the specific roles of Src and Lyn in the prostate tumor progression, and the effects of SFK inhibition on prostate tumor growth and lymph node metastasis in pre-clinical mouse models. ^ Firstly, using a pharmacological inhibitor of SFKs in clinical trials, dasatinib, I demonstrated that SFK inhibition affects both cellular migration and proliferation in vitro. Systemic administration of dasatinib reduced primary tumor growth, as well as development of lymph node metastases, in both androgen-sensitive and -resistant orthotopic prostate cancer mouse models. Immunohistochemical analysis of the primary tumors revealed that dasatinib treatment decreased SFK phosphorylation but not expression, resulting in decreased cellular proliferation and increased apoptosis. For this analysis of immunohistochemical stained tissues, I developed a novel method of quantifying immunohistochemical stain intensity that greatly reduced the inherent bias in analyzing staining intensity. ^ To determine if Src and Lyn played overlapping or distinct roles in prostate cancer tumor growth and progression, Src expression alone was inhibited by small-interfering RNA. The resulting stable cell lines were decreased in migration, but not substantially affected in proliferation rates. In contrast, an analogous strategy targeting Lyn led to stable cell lines in which proliferation rates were significantly reduced. ^ Lastly, I tested the efficacy of a novel SFK inhibitor (KX2-391) targeting peptide substrate-binding domain, on prostate cancer growth and lymph node metastasis in vivo. I demonstrated that KX2-391 has similar effects as dasatinib, an ATP-competitive small molecular inhibitor, on both the primary tumor growth and development of lymph node metastasis in vivo, work that contributed to the first-in-man Phase I clinical trial of KX2-391. ^ In summary, studies in this dissertation provide the first demonstration that Src and Lyn activities affect different cellular functions required for prostate tumor growth and metastasis, and SFK inhibitors effectively reduce primary tumor growth and lymph node metastasis. Therefore, I conclude that SFKs are promising therapeutic targets for treatment of human prostate cancer. ^

Design, Calibration, and Evaluation of Depth-of-Interaction-Capable PET Detector Modules

High-resolution, small-bore PET systems suffer from a tradeoff between system sensitivity, and image quality degradation. In these systems long crystals allow mispositioning of the line of response due to parallax error and this mispositioning causes resolution blurring, but long crystals are necessary for high system sensitivity. One means to allow long crystals without introducing parallax errors is to determine the depth of interaction (DOI) of the gamma ray interaction within the detector module. While DOI has been investigated previously, newly available solid state photomultipliers (SSPMs) well-suited to PET applications and allow new modules for investigation. Depth of interaction in full modules is a relatively new field, and so even if high performance DOI capable modules were available, the appropriate means to characterize and calibrate the modules are not. This work presents an investigation of DOI capable arrays and techniques for characterizing and calibrating those modules. The methods introduced here accurately and reliably characterize and calibrate energy, timing, and event interaction positioning. Additionally presented is a characterization of the spatial resolution of DOI capable modules and a measurement of DOI effects for different angles between detector modules. These arrays have been built into a prototype PET system that delivers better than 2.0 mm resolution with a single-sided-stopping-power in excess of 95% for 511 keV g's. The noise properties of SSPMs scale with the active area of the detector face, and so the best signal-to-noise ratio is possible with parallel readout of each SSPM photodetector pixel rather than multiplexing signals together. This work additionally investigates several algorithms for improving timing performance using timing information from multiple SSPM pixels when light is distributed among several photodetectors.

Isolation and characterization of cDNAs encoding novel homeoproteins from chondrocytes

Bone morphogenesis is a complex biological process. The multistep process of chondrogenesis is the most important aspect of endochondral bone formation. To study the mechanisms which control this multistep pathway of chondrogenesis during embryonic development, I started by isolating cDNAs encoding novel transcriptional factors from chondrocytes. Several such cDNAs encoding putative homeoproteins were identified from a rat chondrosarcoma cDNA preparation. I have been concentrating on characterizing two of these cDNAs. The deduced amino acid sequence of the first homeoprotein, Cart-1, contains a prd-type homeodomain. Northern hybridization and RNase protection analysis revealed that Cart-1 RNAs were present at high levels in a well differentiated rat chondrosarcoma tumor and in a cell line derived from this tumor. Cart-1 transcripts were also detected in primary chondrocytes, but not in numerous other cell types except very low levels in testis. In situ hybridization of rat embryos at different stages of development revealed relatively high levels of Cart-1 RNAs in prechondrocytic mesenchymal cells and in early chondrocytes of cartilage primordia. It is speculated that Cart-1 might play an important role in chondrogenesis. The second putative homeoprotein, rDlx, contains a Distal-less-like homeodomain. rDlx RNAs were also present at high levels in the rat chondrosarcoma tumor and in the cell line derived from this tumor. In situ hybridization of rat embryos revealed high levels of rDlx transcripts in the developing cartilages and perichondria of mature cartilages. rDlx transcripts were also detected in a number of nonchondrogenic tissues such as forebrain, otic vesicles, olfactory epithelia, apical ectodermal ridge (AER) of limb buds, the presumptive Auerbach ganglia of gastrointestinal tract. The unique expression pattern of rDlx suggests that it might play important roles in chondrogenesis and other aspects of embryogenesis. ^