Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2008. / Vita. Includes bibliographical references.

The activity of PEA3, a member of the Ets proto-oncogene family of transcription factors, is associated with various normal and aberrant developmental processes. PEA3 is believed to function in vivo as a transcription factor which regulates the gene expression of its cellular targets. In particular, PEA3 motifs are found in the regulatory regions of several genes implicated in tumor progression and metastasis. Aberrant PEA3 activity has been linked to the development and progression of several types of cancer, particularly, breast cancer and Ewing's sarcoma. To assist in the understanding of the role that PEA3 plays in these processes, constitutively-activated alleles of PEA3 were created by fusing a segment of the EWS gene to murine PEA3; to essentially mimic the EWS-Ets fusion proteins isolated from the human cancer syndrome, Ewing's sarcoma. Five EWS-PEA3 chimeric genes were constructed and one (EWSΔN268PEA3), is an exact murine version of an EWS-human PEA3 fusion gene isolated from Ewing's sarcoma. Transcriptional analysis of the EWS-PEA3 chimeras revealed that with the exception of one mutant, all the chimeras possessed increased transcriptional activity in comparison to normal PEA3 . Furthermore, it was suggested that the transcriptional activity of the chimeras may be regulated by Ras, although this observation requires additional validation. The chimeras were not found to possess any transforming activity, however, this finding does not suggest that the chimeras are not oncogenic in nature. In conclusion, these findings suggest that the EWS-PEA3 chimeras may indeed function as activated versions of the PEA3 transcription factor. / Thesis / Master of Science (MS)

No description available.

The first step in the assembly of an overset grid system is to cut holes or to mark points that are inside a solid body and outside the domain of interest. Most existing approaches have been developed for use only with structured grids. A fast and robust approach that can be applied to structured, unstructured, or generalized grid topologies, with a minimum of user inputs, is desired. A new hole cutting process is presented that utilizes a Cartesian Binary tree representation of the geometry to provide a fast and efficient algorithm applicable to generalized grids. An algorithm has also been developed to mark the fringe points and find its donors. The effectiveness of the algorithm is demonstrated by testing it on generalized and structured grids.

No description available.

Global Navigation Satellite Systems (GNSS) for vehicle navigation and timing are widely relied upon by many users in a variety of different sectors such as transit, financial, military, and many others. There are a number of ways for an agent to purposefully degrade a GNSS user's navigation performance. One such attack is a spoofing attack where the agent transmits signals with the same signal structure as GNSS signals, but they are modified to produce an incorrect navigation solution. Resiliency to these attacks is important for GNSS navigation. Two methods for GNSS resiliency are explored in this dissertation. The first method uses a Controlled Reception Pattern Antenna and receiver in order to obtain direction of arrival estimates of all visible signals and their computed pseudoranges. Two contributions were produced for this method. The first contribution is an optimization of a DoA cost metric that use DoA estimates along with known GNSS ephemerides to distinguish authentic signals from spoofed signals. The second contribution of this work is a combined DoA/pseudorange cost metric to improve the classification of authentic signals from spoofed signals as well as improve its robustness to multi-transmitter spoofing attacks. The second method uses a method known as Chimera, which involves authenticating the civilian L1C GPS signal using a digital signature in the navigation message and punctures in the spreading code. This method can be used to distinguish authentic and spoofed signals, however, a delay between the time the signal is tracked by the receiver and the time when it can be determined authentic is inherent in Chimera and degrades navigation performance. This delay can range from 2 seconds to 3 minutes. Four additional contributions have been made in support of Chimera. The first Chimera contribution is the design and evaluation of a navigation system for Chimera using a tightly coupled GPS/INS extended SRIF that accounts for the Chimera authentication delays. The second Chimera contribution is an investigation into staggering of the authentication times of the GPS satellites in order to improve navigation results. The third Chimera contribution is the development of a RMS or maximum steady-state position error metric to compare the accuracy achieved by different authentication group designs when used in conjunction with the previously discussed filter from the first Chimera contribution. The fourth Chimera contribution investigates different authentication group designs to find groups that will produce low value metrics. These investigations included local authentication group optimization, synthesizing a global design using local designs, and the effects of time and IMU grade. Each of these contributions has a significant impact on improving either the resilience of a GPS receiver to spoofing or the navigation accuracy of a GPS receiver that is inherently resilient to spoofing. / Doctor of Philosophy / Global Positioning System (GPS) navigation and timing plays a pivotal role in a variety of different sectors such as transit, financial, military, and many others. There have been instances where a signal is purposefully generated to look similar to a GPS signal in order to mislead a GPS user of their true position, velocity, and timing. This type of attack is known as a spoofing attack. This dissertation discusses two methods to identify these spoofed signals so that they are not used to disrupt nominal navigation and timing. The first method uses multiple GPS antennas to determine the direction of all visible signals. This dissertation provides an algorithm to distinguish the authentic GPS signals from the spoofed signals using the determined signal directions. The second method is for the GPS satellites to watermark the GPS signal they transmit, using modern encryption techniques, to be able to authenticate incoming signals. This method, however, produces a delay between when the signal is received by a GPS user and when it can be deemed authentic. This delay is a problem for navigation. This dissertation develops techniques for dealing with this delay by incorporating an Inertial Measurement Unit (IMU). This dissertation also proposes the idea to stagger the time that the digital signature, which is needed for signal verification, is sent from different GPS satellites. Lastly, this dissertation investigates how different staggered groupings of GPS satellites improve navigation performance and provides a metric for quantifying the navigation performance of different groupings. Overall, the dissertation's contributions to the first method improve the resilience of a receiver to spoofing attacks while the contributions to the second method improve navigation performance of an inherently resilient method.

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No description available.

In our efforts to engineer a DNA binding and cleaving protein with greater sequence discrimination, we have designed dimeric proteins derived from engrailed homeodomain and calmodulin. Previous research by our group has shown that a hydrolytically active lanthanide binding site can be incorporated into a DNA binding motif. To understand protein-DNA interaction and improve the sequence selectivity of the chimeric complex, two lanthanide-binding homodimers were designed and expressed. One of the dimers, F2, is coupled together by a flexible polypeptide linker and the other, R7C, is a disulfide cross-linked cysteine mutant at the N-terminus. Studies of fluorescence of tryptophan residues document that the overall affinity for lanthanide and calcium is similar to traditional EF-hand peptides (1-10 μM). Metal titrations monitored by circular dichroism (CD) revealed that the secondary structures of the dimers contained a lower degree of -helicity than the designed monomeric protein due to additional modifications, but because of their flexibility and their two active-site domain, hydrolytic activity was several folds faster than our previously designed proteins and peptides. Unlike earlier reports on our chimeras, F2 also demonstrated the capability to hydrolyze DNA in the presence of some biological relevant metal ions suggesting different cleavage mechanisms were carried out. Extensive DNA sequencing studies on cleavage patterns with oligonucleotide duplexes confirmed the unique sequence selectivity and kinetic properties of F2. Two engrailed homeodomain target sites, TAATTA, were favored for hydrolytic activity corresponding to one domain acting as a DNA anchor on the first target site while the other was an "opportunist" at recognizing the second site. Nonetheless, the hydrolytic behavior at the phosphodiester bond on a specific dsDNA sequence is in good agreement with the behavior of restriction endonucleases. Unlike restriction enzymes, metallated F2 has not only demonstrated the ability to cleave DNA plasmid, but it also excises the entire nucleotide on a selected sequence. This homodimer is the first example of an active and selective hydrolytic artificial nuclease based on the modular turn substitution design approach that can be a potential template for genomic modification.

Results from numerical simulation were performed to study flow and heat transfer in two types of rotating multi-pass cooling channels. Second moment closure model was used to solve flow in domain generated from Chimera method. The first type was a four-pass channel with two different inlet settings. The main flowing channel was rectangular channel (AR=2:1) with hydraulic diameter (Dh ) equals to 2/3 inch (16.9 mm). The first and fourth channel were set as different aspect ratio (AR=2:1; AR=1:1). Reynolds number (Re) used in this part was 10,000. The rotating angle was set as 90 degrees. The density ratio was set as 0.115. The rotation number varied from 0.0 to 0.22. It was showed that inlet effect only caused influence to flow and heat transfer in first two passages. The second type was a four-pass channel with/without addition of vane in smooth turn portion. The main flowing channel was rectangular channel (AR=2:1) with hydraulic diameter (Dh) equals to 2/3 inch. The first and fourth passages were set to be square duct (AR=1:1). The Reynolds number (Re) used in this part was 20,000. Three rotation numbers were set here (Ro=0.0; Ro=0.2; Ro=0.4). The density ratio and rotating angle varied from 0.12 to 0.32 and from 45 degrees to 90 degrees respectively. According to numerical results, it was revealed that the addition of vane in smooth turn portion did not cause influence to part before it. However, it caused significant influence to flow and heat transfer in smooth turn portion and part after it.