Investigation on the Benefits of Safety Margin Improvement in CANDU Nuclear Power Plant Using an FPGA-based Shutdown System

The relationship between response time and safety margin of CANadian Deuterium Uranium (CANDU) nuclear power plant (NPP) is investigated in this thesis. Implementation of safety shutdown system using Field Programmable Gate Array (FPGA) is explored. The fast data processing capability of FPGAs shortens the response time of CANDU shutdown systems (SDS) such that the impact of accident transient can be reduced. The safety margin, which is closely related to the reactor behavior in the event of an accident, is improved as a result of such a faster shutdown process. Theoretical analysis based on neutron dynamic theory is carried out to establish the fact that a faster shutdown process can mitigate accidental consequences. To provide more realistic test cases from a thermalhydraulic perspective, an industry grade simulation tool known as CATHENA is used to generate comparable accident-shutdown transients for different SDS response times. Results from both verification methods explicitly prove the feasibility of improving the safety margin via faster shutdown process. To demonstrate this concept, a prototype of the proposed faster SDS is constructed. The trip logic of CANDU shutdown system No.1 (SDS1) is converted into a digital hardware design and implemented within chosen FPGA platform. The functionality of the FPGA-based SDS1 is implemented, and the response times are tested and compared to those of the existing CANDU SDS1. The achieved 10.5 ms response time of the FPGA-based SDS1 is again applied to the CATHENA simulation process to quantitatively present the 26.98% improvement in the safety margin. To investigate potential improvement in safety margin by using FPGA technology, hardware-in-the-loop (HIL) simulation is performed by connecting the FPGA-based SDS1 to an NPP training simulator. The 6.26% improvement in safety margin has been verified, based on which a 10% potential power upgrade is discussed as another benefit of applying FPGA technology to CANDU NPPs

A Program Design Assistant

The DA will be a design assistant which can assist the programmer in low-level design. The input language of the DA is a cliché-based program description language that allows the specification and high-level design of commonly-written programs to be described concisely. The DA language is high-level in the sense that programmers need not bother with detailed design. The DA will provide automatic low-level design assistance to the programmer in selecting appropriate algorithms and data structures. It will also detect inconsistencies and incompleteness in program descriptions. A key related issue in this research is the representation of programming knowledge in a design assistant. The knowledge needed to automate low-level design and the knowledge in specific programming clichés have to be represented explicitly to facilitate reuse.MIT Artificial Intelligence Laborator

Proteomic Identification of the MYST Domain Histone Acetyltransferase TIP60 as a Coactivator of the Myeloid Transcription Factor C/EBPα

The transcription factor C/EBPα is a key player in granulopoiesis and leukemogenesis. In the present study, we sought to identify C/EBPα interacting proteins. A glutathione-S-transferase-C/EBPα fusion protein was used to pull down interacting proteins from U937 nuclear extracts. These proteins were analyzed by 2-D gel electrophoresis or 1-D nano LC and identified by mass spectrometry. The interaction between C/EBPand two novel interacting partners, the cell cycle regulator protein MCM5 and the MYST domain histone aceyltransferase TIP60, was confirmed by using pull-down and co-immunoprecipitation experiments. TIP60 was able to markedly enhance C/EBPα mediated transcriptional activation in reporter gene assays, suggesting that TIP60 is a co-activator of C/EBPα. This co-activator function of TIP60 was dependent on its intact histone aceyltransferase domain and on the C/EBPα DNA binding domain. TIP60 was found to be associated with the human C/EBPα promoter in vivo in a chromatin immunoprecipitation assay with a concomitant increase in histone H3 and H4 acetylation. Furthermore, we observed a lower expression of TIP60 mRNA in undifferentiated U937 CD11b- cells compared to retinoic acid induced differentiated U937 CD11b+ cells suggesting that higher TIP60 expression is associated with myeloid differentiation. Correlated expression between C/EBP and TIP60 was also observed in certain leukemia subtypes. These findings point to a functional synergism between C/EBP and TIP60 in myeloid differentiation and suggests that TIP60 might be an important player in leukemogenesis

Formal methods and digital systems validation for airborne systems

This report has been prepared to supplement a forthcoming chapter on formal methods in the FAA Digital Systems Validation Handbook. Its purpose is as follows: to outline the technical basis for formal methods in computer science; to explain the use of formal methods in the specification and verification of software and hardware requirements, designs, and implementations; to identify the benefits, weaknesses, and difficulties in applying these methods to digital systems used on board aircraft; and to suggest factors for consideration when formal methods are offered in support of certification. These latter factors assume the context for software development and assurance described in RTCA document DO-178B, 'Software Considerations in Airborne Systems and Equipment Certification,' Dec. 1992

A methodology for producing reliable software, volume 1

An investigation into the areas having an impact on producing reliable software including automated verification tools, software modeling, testing techniques, structured programming, and management techniques is presented. This final report contains the results of this investigation, analysis of each technique, and the definition of a methodology for producing reliable software

Faculty Senate Monthly Packet December 1997

The December 1997 Monthly packet includes the December agenda and appendices and the Faculty Senate minutes and attachments from the meeting held November 1997

Software maintenance by program transformation in a wide spectrum language

This thesis addresses the software maintenance problem of extracting high-level designs from code. The investigated solution is to use a mathematically-based formal program transformation system. The resulting tool, the Maintainer's Assistant, is based on Ward's [177] WSL (wide spectrum language) and method of proving program equivalence. The problems addressed include: how to reverse engineer from code alone (the only reliable source of information about a program [158]), how to express program transformations within the system, what kinds of transformations should be incorporated, how to make the tool simple to use, how to perform abstraction and how to create a tool suitable for use with large programs. Using the Maintainer's Assistant, the program code is automatically translated into WSL and the transformations, although tested for valid applicability by the system, are interactively applied by the user. Notable features include a mathematical simplifier, a large flexible transformation catalogue and, significantly, the use of an extension of WSL, A4etaWSL, for representing the transformations. MetaWSL expands WSL by incorporating a variety of extensions, including: program editing statements, pattern matching and template filling functions, symbolic mathematics and logic functions, statements for moving within the program’s syntax tree and statements for repeating an operation at each node of the tree. Using MetaWSL, 80% of the 601 transformations can be expressed in less than 20 program statements. The Maintainer's Assistant has been used on a wide variety of examples of up to several thousand lines, including commercial software written in IBM 370 assembler. It has been possible to transform initially unstructured programs into a hierarchy of procedures, facilitating subsequent design recovery. These results show that program transformation is a viable method of renovating old (370 assembler) code in a cost elective way, and that MetaWSL provides an effective basis for clearly and concisely expressing the required transformations

Human Haematopoietic Stem Cell Heterogeneity in Postnatal Haematopoiesis and Ontogeny

Haematopoietic stem cell (HSC) transplants are upheld as one of the most successful therapies in regenerative medicine. While improved purification and functionality assays have advanced understanding of steady-state haematopoiesis and the human bona fide HSC, evidence suggests significant heterogeneity exists within the HSC compartment in post-natal and pre-natal haematopoiesis. In post-natal haematopoiesis, both CD34+ and CD34- cells possess robust in vivo repopulating potential. CD34- repopulating cells, however, exhibit distinct repopulation kinetics, capacity to produce functional CD34+ repopulating cells, and accordingly have been speculated to reside at the apex of the human haematopoietic hierarchy. But a low repopulating cell frequency has hindered efforts to study these HSCs. We thus aim to improve purification of CD34- HSCs and further expand the knowledge of this immature stem pool. We successfully identified an additional positive selection marker, CD117 (c-Kit). Through limiting dilution analysis and serial transplantations of enriched CD34- repopulating cells in enhanced NSG mouse models, we observed repopulation and lineage commitment kinetics. To investigate the molecular mechanisms, we conducted single-cell RNAseq. With these new data we have asserted the importance of human CD34- HSCs their enormous therapeutic potential. In human foetal haematopoiesis, it is unknown whether CD34- repopulating cells emerge during ontogeny and play a role in foetal haematopoiesis. While reports for HSC-purifying markers have been produced, much of these studies have been restricted to foetal liver, a single gestational stage, and the CD34+ population. In humans, little is known about how the HSC cell surface marker phenotype adapts to the dynamic niches in the liver during expansion, homing to the bone marrow, and bone marrow colonisation. To address this, we optimised a multi-parameter flow cytometry panel and used it to investigate the expression of a number of reported HSC cell surface markers across first and second trimester liver and bone marrow. Through a combination of high-dimensional data analysis and mathematical modelling we have produced an antigen-based map of foetal haematopoietic stem cell and progenitor dynamics