The Boosted Fast Flux Loop (BFFL) will expand the Advanced Test Reactor (ATR) at Idaho National Laboratory. Part of the BFFL is a new corrosion test cap section for testing in the ATR. The corrosion test cap section was designed with parallel channels to reduce the pressure drop and allow coolant contact with specimens. The fluid experiment conducted by Idaho State University found the pressure drop not characteristic of parallel channel flow but greater than without parallel channels. A Computation Fluid Dynamics simulation using STAR-CCM+ was conducted with the objectives of showing sufficient flow through the test cap section for a corrosion test, verifying the fluid experiment's validity, and explaining the abnormal pressure drop. The simulation used a polyhedral volume mesh and the k-e turbulent model with segregated equations. Convergence depended on a low continuity residual and an unchanging pressure drop result. The simulation showed the same pattern as the fluid experiment. The simulation provided evidence of flow through the test cap section needed for a corrosion test. The specimen holding assembly was found to be a small contributor to the pressure drop. The counterintuitive pressure drop was found to be the sum of many factors produced from the geometry of the test cap section. The inlet of the test cap section behaved as a diverging nozzle before a sudden expansion into the test cap section chamber with both creating a pressure drop. The chaotic flow inside the chamber gave rise to pressure loss from mixing. The fluid exited the chamber through a sudden contraction to a converging nozzle behaving exit, again, producing a pressure drop. By varying the flow rate in the simulation, a disturbance in the flow where the gap fluid separated into the parallel channels was found at high flow rates. At low flow rates the pressure drop anomaly was not found. The corrosion test cap section could be used in the ATR but with a higher pressure drop than desirable. The design of the corrosion test cap section created the abnormal pressure drop.

Microbiological monitoring of water is of primary importance for preservation of human health, particularly in an arid zone like the U.S. southwest. In this work, infrared spectroscopic methods were developed to identify and quantify microorganisms present in water and water-related environmental samples. Focus of the work was primarily on evaluating the impact of various sterilization methods on microorganism physiology as gauged by the non-invasive approach of infrared spectroscopy. This work demonstrates that FTIR techniques can be used to identify changes in the physiology of microorganisms and that for heat treatment, a correlation between spectral changes and the viability of microorganisms can be made.

This dissertation deals with techniques that enhance the detection of ground targets by airborne radar. The methods employed deal with the problem of air to ground detection by breaking the problem into two broad categories. The first category deals with improving detection of moving targets by using space-time adaptive processing (STAP) in a multistatic configuration. Mult-static STAP provides increased detection performance by observing targets from multiple perspectives. Multiple viewing perspectives afford more opportunities to the combined system for observing radial velocity of the target more directly, thus increasing Doppler that helps distinguish the target from background clutter. Detection performance also improves through an increased number of independent observations of a target, which reduces the likelihood of the target fading for the combined system. Increasing detection performance by increasing the number of independent observations is referred to in communications theory as channel diversity. The second part of this dissertation deals with the problem of distinguishing stationary targets from background clutter within a Synthetic Aperture Radar image. Stationary target discrimination is accomplished by exploiting the statistical nature of multifaceted metallic objects within a scene. The performance improvement for both moving and non-moving improvement methods is characterized and compared to other systems that attempt to accomplish the same end using different means.

Simultaneous localisation and mapping (SLAM) is an often used positioning approach in GPS denied indoor environments. This thesis presents a novel method of combining SLAM with autonomous/aided target detection and recognition (ATD/R), which is beneficial for both methods. The method uses physical objects that are recognisable by ATR as unambiguous features in SLAM, while SLAM provides the ATR with better position estimates. The intended application is to improve the positioning of a first responder moving through an indoor environment, where the map offers localisation and simultaneously helps locate people, furniture and potentially dangerous objects like gas cannisters. The developed algorithm, dubbed ATR-SLAM, uses existing methods from different fields such as EKF-SLAM and ATR based on rectangle estimation. Landmarks in the form of 3D point features based on NARF are used in conjunction with identified objects and 3D object models are used to replace landmarks when the same information is used. This leads to a more compact map representation with fewer landmarks, which partly compensates for the introduced cost of the ATR. Experiments performed using point clouds generated from a time-of-flight laser scanner show that ATR-SLAM produces more consistent maps and more robust loop closures than EKF-SLAM using only NARF landmarks.

Cancer cells exhibit genomic instability and are commonly defective in DNA damage signalling and/or DNA repair. There are many types of DNA damage inducing agents such as mechanical stress on chromosomes during recombination, chemotherapeutics, ionising and ultraviolet radiation and endogenously produced free radicals. These genetic lesions pose a serious threat to the cell and evoke a rapid and intricate DNA damage response signalling pathway involving many transducer and effector pathways including cell cycle arrest, DNA repair, chromatin remodelling, and apoptotic pathways. Genetic mutations within genes in this pathway often lead to genomic instability and cancer. The main effectors of the DNA damage response are the protein kinases ATM and ATR which are rapidly activated in response to DNA damage induction and phosphorylate a large and diverse number of targets including the checkpoint kinases Chk1, and Chk2, the tumour suppressors p53 and BRCA1 and chromatin associated proteins such as H2AX. BRCA1 is a key transducer molecule within the DNA damage response. This is evident from its loss, which leads to defects in many damage response processes such as cell cycle arrest and DNA repair. BRCA1s binding partner BARD1 has also been implicated in the DNA damage response and recent reports indicate that these proteins co-operate in this pathway. This study utilises a multifaceted approach to further characterise the function of the BRCA1/BARD1 complex within the DNA damage response. Firstly we have used shRNA to deplete the BRCA1/BARD1 complex and have shown that the BRCA1/BARD1 complex is required for ATM/ATR dependent phosphorylation of p53Ser-15 in response to IR and UV induced DNA damage. In contrast, we have shown that the phosphorylation of a number of other ATM/ATR dependent targets including H2AX, Chk2, and c-jun do not require the BRCA1/BARD1 complex. The study has also revealed that the prior phosphorylation of BRCA1 at Ser-1423 and Ser-1524 is required for the phosphorylation of p53 at Ser-15. Furthermore, we have shown that these phosphorylation events are required for IR induced G1/S cell cycle arrest via transcriptional induction of the cyclin dependent kinase inhibitor p21. The second part of this study involved the characterisation of a putative BRCA1 interacting protein – The KRAB associated protein 1 (Kap1). During this study we have been unable to confirm Kap1 as a bona fide BRCA1 interactor, however we have identified a clear role for Kap1 in the DNA damage response pathway. Using Mass spectrometric phospho amino acid mapping we have identified a novel Chk2 dependent phosphorylation site, Ser-473, within Kap1. Furthermore, we have shown that this phosphorylation event may regulate Histone H3-Lys-9 acetylation after DNA damage possibly regulating chromatin relaxation. This study has also identified a number of novel Kap1 interacting proteins, which appear to be regulated by Kap1 phosphorylation at Ser-473. These interactors may play an important role in the regulation of chromatin modification and/or structure after DNA damage. By studying the role of BRCA1 in the DNA damage response pathway we have not only uncovered a novel scaffolding function for BRCA1 in the G1/S checkpoint but have also identified a novel protein, Kap1, acting within the DNA damage response pathway. This study has identified a role for Kap-1 in the regulation of chromatin structure in response to DNA damage via the ATM – Chk2 pathway.

Cancer cells exhibit genomic instability and are commonly defective in DNA damage signalling and/or DNA repair. There are many types of DNA damage inducing agents such as mechanical stress on chromosomes during recombination, chemotherapeutics, ionising and ultraviolet radiation and endogenously produced free radicals. These genetic lesions pose a serious threat to the cell and evoke a rapid and intricate DNA damage response signalling pathway involving many transducer and effector pathways including cell cycle arrest, DNA repair, chromatin remodelling, and apoptotic pathways. Genetic mutations within genes in this pathway often lead to genomic instability and cancer. The main effectors of the DNA damage response are the protein kinases ATM and ATR which are rapidly activated in response to DNA damage induction and phosphorylate a large and diverse number of targets including the checkpoint kinases Chk1, and Chk2, the tumour suppressors p53 and BRCA1 and chromatin associated proteins such as H2AX. BRCA1 is a key transducer molecule within the DNA damage response. This is evident from its loss, which leads to defects in many damage response processes such as cell cycle arrest and DNA repair. BRCA1s binding partner BARD1 has also been implicated in the DNA damage response and recent reports indicate that these proteins co-operate in this pathway. This study utilises a multifaceted approach to further characterise the function of the BRCA1/BARD1 complex within the DNA damage response. Firstly we have used shRNA to deplete the BRCA1/BARD1 complex and have shown that the BRCA1/BARD1 complex is required for ATM/ATR dependent phosphorylation of p53Ser-15 in response to IR and UV induced DNA damage. In contrast, we have shown that the phosphorylation of a number of other ATM/ATR dependent targets including H2AX, Chk2, and c-jun do not require the BRCA1/BARD1 complex. The study has also revealed that the prior phosphorylation of BRCA1 at Ser-1423 and Ser-1524 is required for the phosphorylation of p53 at Ser-15. Furthermore, we have shown that these phosphorylation events are required for IR induced G1/S cell cycle arrest via transcriptional induction of the cyclin dependent kinase inhibitor p21. The second part of this study involved the characterisation of a putative BRCA1 interacting protein – The KRAB associated protein 1 (Kap1). During this study we have been unable to confirm Kap1 as a bona fide BRCA1 interactor, however we have identified a clear role for Kap1 in the DNA damage response pathway. Using Mass spectrometric phospho amino acid mapping we have identified a novel Chk2 dependent phosphorylation site, Ser-473, within Kap1. Furthermore, we have shown that this phosphorylation event may regulate Histone H3-Lys-9 acetylation after DNA damage possibly regulating chromatin relaxation. This study has also identified a number of novel Kap1 interacting proteins, which appear to be regulated by Kap1 phosphorylation at Ser-473. These interactors may play an important role in the regulation of chromatin modification and/or structure after DNA damage. By studying the role of BRCA1 in the DNA damage response pathway we have not only uncovered a novel scaffolding function for BRCA1 in the G1/S checkpoint but have also identified a novel protein, Kap1, acting within the DNA damage response pathway. This study has identified a role for Kap-1 in the regulation of chromatin structure in response to DNA damage via the ATM – Chk2 pathway.

Cancer cells exhibit genomic instability and are commonly defective in DNA damage signalling and/or DNA repair. There are many types of DNA damage inducing agents such as mechanical stress on chromosomes during recombination, chemotherapeutics, ionising and ultraviolet radiation and endogenously produced free radicals. These genetic lesions pose a serious threat to the cell and evoke a rapid and intricate DNA damage response signalling pathway involving many transducer and effector pathways including cell cycle arrest, DNA repair, chromatin remodelling, and apoptotic pathways. Genetic mutations within genes in this pathway often lead to genomic instability and cancer. The main effectors of the DNA damage response are the protein kinases ATM and ATR which are rapidly activated in response to DNA damage induction and phosphorylate a large and diverse number of targets including the checkpoint kinases Chk1, and Chk2, the tumour suppressors p53 and BRCA1 and chromatin associated proteins such as H2AX. BRCA1 is a key transducer molecule within the DNA damage response. This is evident from its loss, which leads to defects in many damage response processes such as cell cycle arrest and DNA repair. BRCA1s binding partner BARD1 has also been implicated in the DNA damage response and recent reports indicate that these proteins co-operate in this pathway. This study utilises a multifaceted approach to further characterise the function of the BRCA1/BARD1 complex within the DNA damage response. Firstly we have used shRNA to deplete the BRCA1/BARD1 complex and have shown that the BRCA1/BARD1 complex is required for ATM/ATR dependent phosphorylation of p53Ser-15 in response to IR and UV induced DNA damage. In contrast, we have shown that the phosphorylation of a number of other ATM/ATR dependent targets including H2AX, Chk2, and c-jun do not require the BRCA1/BARD1 complex. The study has also revealed that the prior phosphorylation of BRCA1 at Ser-1423 and Ser-1524 is required for the phosphorylation of p53 at Ser-15. Furthermore, we have shown that these phosphorylation events are required for IR induced G1/S cell cycle arrest via transcriptional induction of the cyclin dependent kinase inhibitor p21. The second part of this study involved the characterisation of a putative BRCA1 interacting protein – The KRAB associated protein 1 (Kap1). During this study we have been unable to confirm Kap1 as a bona fide BRCA1 interactor, however we have identified a clear role for Kap1 in the DNA damage response pathway. Using Mass spectrometric phospho amino acid mapping we have identified a novel Chk2 dependent phosphorylation site, Ser-473, within Kap1. Furthermore, we have shown that this phosphorylation event may regulate Histone H3-Lys-9 acetylation after DNA damage possibly regulating chromatin relaxation. This study has also identified a number of novel Kap1 interacting proteins, which appear to be regulated by Kap1 phosphorylation at Ser-473. These interactors may play an important role in the regulation of chromatin modification and/or structure after DNA damage. By studying the role of BRCA1 in the DNA damage response pathway we have not only uncovered a novel scaffolding function for BRCA1 in the G1/S checkpoint but have also identified a novel protein, Kap1, acting within the DNA damage response pathway. This study has identified a role for Kap-1 in the regulation of chromatin structure in response to DNA damage via the ATM – Chk2 pathway.

Universiẗat Diss., 2003--Essen.

While typical telemetry processing systems are fixed, ground-based assets, certain mission profiles or telemetry acquisition models may involve telemetry processing systems which reside on other platforms, such as ships, mobile vehicles, or airplanes. The design and implementation of telemetry processing systems for these platforms poses unique challenges, which may include requirements for unusual mechanical packaging, heightened electromagnetic sensitivity, or specialized electrical interfaces. This paper presents some of the key challenges involved in the design and implementation of an airborne telemetry processing system and discusses how lessons learned from solving these challenges may be applied to future telemetry processing system designs.

In response to DNA damage, mammalian cells activate various DNA repair pathways to remove DNA lesions and, meanwhile, halt cell cycle progressions to allow sufficient time for repair. The nucleotide excision repair (NER) and the ATR-dependent cell cycle checkpoint activation are two major cellular responses to DNA damage induced by UV irradiation. However, how these two processes are coordinated in the response is poorly understood. Here we showed that the essential NER factor XPA (xeroderma pigmentosum group A) underwent nuclear accumulation upon UV irradiation, and strikingly, such an event occurred in an ATR (Ataxia-Telangiectasia mutated and RAD3-related)-dependent manner. Either treatment of cells with ATR kinase inhibitors or transfection of cells with small interfering RNA targeting ATR compromised the UV-induced XPA nuclear translocation. Consistently, the ATR-deficient cells displayed no substantial XPA nuclear translocation while the translocation remained intact in ATM (Ataxia-Telangiectasia mutated)-deficient cells in response to UV irradiation. Moreover, we found that ATR is required for the UV-induced nuclear focus formation of XPA. Taken together, our results suggested that the ATR checkpoint pathway may modulate NER activity through the regulation of XPA redistribution in human cells upon UV irradiation.