Signalling pathways and gene expression profiles in prostate cancer

In general, cancer, encompassing prostate cancer (PCa), is a disease that utilises signalling pathways to progress through the uncontrolled proliferation of cancerous cells. Although the mechanisms of how the cells evade intrinsic or extrinsic signals of death and keep on dividing is not completely understood, there is a plethora of evidence that point to certain signalling molecules that are crucial conveyors of the fine tuning that slightly differs in cancer in comparison to control states. The present chapter provides a detailed description of the key regulators of PCa cell life and unveils their closely communicating proteins that aid in the fine tuning of the cancerous state

Working with OpenCL to Speed Up a Genetic Programming Financial Forecasting Algorithm: Initial Results

The genetic programming tool EDDIE has been shown to be a successful financial forecasting tool, however it has suffered from an increase in execution time as new features have been added. Speed is an important aspect in financial problems, especially in the field of algorithmic trading, where a delay in taking a decision could cost millions. To offset this performance loss, EDDIE has been modified to take advantage of multi-core CPUs and dedicated GPUs. This has been achieved by modifying the candidate solution evaluation to use an OpenCL kernel, allowing the parallel evaluation of solutions. Our computational results have shown improvements in the running time of EDDIE when the evaluation was delegated to the OpenCL kernel running on a multi-core CPU, with speed ups up to 21 times faster than the original EDDIE algorithm. While most previous works in the literature reported significantly improvements in performance when running an OpenCL kernel on a GPU device, we did not observe this in our results. Further investigation revealed that memory copying overheads and branching code in the kernel are potentially causes of the (under-)performance of the OpenCL kernel when running on the GPU device

Expert systems for real-time monitoring and fault diagnosis

Methods for building real-time onboard expert systems were investigated, and the use of expert systems technology was demonstrated in improving the performance of current real-time onboard monitoring and fault diagnosis applications. The potential applications of the proposed research include an expert system environment allowing the integration of expert systems into conventional time-critical application solutions, a grammar for describing the discrete event behavior of monitoring and fault diagnosis systems, and their applications to new real-time hardware fault diagnosis and monitoring systems for aircraft

Airfoil shape and thickness effects on transonic airloads and flutter

A transient pulse technique is used to obtain harmonic forces from a time-marching solution of the complete unsteady transonic small perturbation potential equation. The unsteady pressures and forces acting on a model of the NACA 64A010 conventional airfoil and the MBB A-3 supercritical airfoil over a range of Mach numbers are examined in detail. Flutter calculations at constant angle of attack show a similar flutter behavior for both airfoils, except for a boundary shift in Mach number associated with corresponding Mach number shift in the unsteady aerodynamic forces. Differences in the static aeroelastic twist behavior for the two airfoils are significant

Near-Term Options for a Nuclear Thermal Propulsion Flight Demonstrator

The Appropriations Bill passed by the US Congress in February 2019 instructed NASA to direct not less than $100,000,000 for the development of nuclear thermal propulsion, of which not less than$70,000,000 shall be for the design of a flight demonstration by 2024 for which a multi-year plan is required by both the House and the Senate within 180 days of enactment of this agreement." As part of NASAs response to this direction, the Advanced Concepts Office (ACO) at the Marshall Space Flight Center (MSFC) was tasked with leading a study to develop a nuclear thermal propulsion (NTP) flight demonstration (FD) concept and evaluate its feasibility with respect to the near-term schedule goal. During formulation for the NTP FD study, two perspectives emerged with regards to FD concept design. The first seeks to strictly observe the immediate near-term schedule goal, embracing a completely off-the-shelf, high-TRL approach to subsystem design and component selection. The downside to this approach is that the propulsion performance to be expected from such a design is significantly lower than what NTP promises for operational systems, and the value of the flight demo is potentially reduced due to a lack of traceability. The second approach advocates for an FD concept that shows increased traceability to the projected designs of operational systems, providing risk reduction for future NTP-enabled missions. This option comes at the cost of schedule and development risks, as it requires some new investments in nuclear reactor fuels and design. In order to understand the implications and differences between these two approaches, the ACO team elected to perform a concept design of each type, labeling the immediate near-term concept Flight Demo 1 (FD1), and the higher traceability concept Flight Demo 2 (FD2). This paper will present a summary of the mission profiles and system designs for both FD1 and FD2, identifying key drivers and challenges for each design

Gene amplifications associated with the development of hormone- resistant prostate cancer

Purpose: Hormone resistance remains a significant clinical problem in prostate cancer with few therapeutic options. Research into mechanisms of hormone resistance is essential. Experimental Design: We analyzed 38 paired (prehormone/posthormone resistance) prostate cancer samples using the Vysis GenoSensor. Archival microdissected tumor DNA was extracted, amplified, labeled, and hybridized to Amplione I DNA microarrays containing 57 oncogenes. Results: Genetic instability increased during progression from hormone-sensitive to hormone-resistant cancer (P = 0.008). Amplification frequencies of 15 genes (TERC, MYBL3, HRAS, PI3KCA, JUNB, LAMC2, RAF1, MYC, GARP, SAS, FGFR1, PGY1, MYCL1, MYB, FGR) increased by greater than 10% during hormone escape. Receptor tyrosine kinases were amplified in 73% of cases; this was unrelated to development of hormone resistance. However, downstream receptor tyrosine kinase signaling pathways showed increased amplification rates in resistant tumors for the mitogen-activated protein kinase (FGR/Src-2, HRAS, and RAF1; P = 0.005) and phosphatidylinositol 3'-kinase pathways (FGR/ Src-2, PI3K, and Akt; P = 0.046). Transcription factors regulated by these pathways were also more frequently amplified after escape (MYC family: 21% before versus 63% after, P = 0.027; MYB family: 26 % before versus 53 % after, P = 0.18). Conclusions: Development of clinical hormone escape is linked to phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways. These pathways may function independently of the androgen receptor or via androgen receptor activation by phosphorylation, providing novel therapeutic targets

Mechanism for the failure of the Edwards hypothesis in the SK spin glass

The dynamics of the SK model at T=0 starting from random spin configurations is considered. The metastable states reached by such dynamics are atypical of such states as a whole, in that the probability density of site energies, $p(\lambda)$, is small at $\lambda=0$. Since virtually all metastable states have a much larger $p(0)$, this behavior demonstrates a qualitative failure of the Edwards hypothesis. We look for its origins by modelling the changes in the site energies during the dynamics as a Markov process. We show how the small $p(0)$ arises from features of the Markov process that have a clear physical basis in the spin-glass, and hence explain the failure of the Edwards hypothesis.Comment: 5 pages, new title, modified text, additional reference

Spacecraft-spacecraft very long baseline interferometry. Part 1: Error modeling and observable accuracy

In Part 1 of this two-part article, an error budget is presented for Earth-based delta differential one-way range (delta DOR) measurements between two spacecraft. Such observations, made between a planetary orbiter (or lander) and another spacecraft approaching that planet, would provide a powerful target-relative angular tracking data type for approach navigation. Accuracies of better than 5 nrad should be possible for a pair of spacecraft with 8.4-GHz downlinks, incorporating 40-MHz DOR tone spacings, while accuracies approaching 1 nrad will be possible if the spacecraft incorporate 32-GHz downlinks with DOR tone spacing on the order of 250 MHz; these accuracies will be available for the last few weeks or months of planetary approach for typical Earth-Mars trajectories. Operational advantages of this data type are discussed, and ground system requirements needed to enable spacecraft-spacecraft delta DOR observations are outlined. This tracking technique could be demonstrated during the final approach phase of the Mars '94 mission, using Mars Observer as the in-orbit reference spacecraft, if the Russian spacecraft includes an 8.4-GHz downlink incorporating DOR tones. Part 2 of this article will present an analysis of predicted targeting accuracy for this scenario