3 resultados para Histone Code
em DigitalCommons@University of Nebraska - Lincoln
Resumo:
Many tools and techniques for addressing software maintenance problems rely on code coverage information. Often, this coverage information is gathered for a specific version of a software system, and then used to perform analyses on subsequent versions of that system without being recalculated. As a software system evolves, however, modifications to the software alter the software’s behavior on particular inputs, and code coverage information gathered on earlier versions of a program may not accurately reflect the coverage that would be obtained on later versions. This discrepancy may affect the success of analyses dependent on code coverage information. Despite the importance of coverage information in various analyses, in our search of the literature we find no studies specifically examining the impact of software evolution on code coverage information. Therefore, we conducted empirical studies to examine this impact. The results of our studies suggest that even relatively small modifications can greatly affect code coverage information, and that the degree of impact of change on coverage may be difficult to predict.
Resumo:
Not long ago, most software was written by professional programmers, who could be presumed to have an interest in software engineering methodologies and in tools and techniques for improving software dependability. Today, however, a great deal of software is written not by professionals but by end-users, who create applications such as multimedia simulations, dynamic web pages, and spreadsheets. Applications such as these are often used to guide important decisions or aid in important tasks, and it is important that they be sufficiently dependable, but evidence shows that they frequently are not. For example, studies have shown that a large percentage of the spreadsheets created by end-users contain faults. Despite such evidence, until recently, relatively little research had been done to help end-users create more dependable software. We have been working to address this problem by finding ways to provide at least some of the benefits of formal software engineering techniques to end-user programmers. In this talk, focusing on the spreadsheet application paradigm, I present several of our approaches, focusing on methodologies that utilize source-code-analysis techniques to help end-users build more dependable spreadsheets. Behind the scenes, our methodologies use static analyses such as dataflow analysis and slicing, together with dynamic analyses such as execution monitoring, to support user tasks such as validation and fault localization. I show how, to accommodate the user base of spreadsheet languages, an interface to these methodologies can be provided in a manner that does not require an understanding of the theory behind the analyses, yet supports the interactive, incremental process by which spreadsheets are created. Finally, I present empirical results gathered in the use of our methodologies that highlight several costs and benefits trade-offs, and many opportunities for future work.
Resumo:
Holocarboxylase synthetase (HCS) catalyzes the binding of biotin to lysine (K) residues in histones H3 and H4. Histone biotinylation marks play important roles in the repression of genes and retrotransposons. Preliminary studies suggested that K16 in histone H4 is a target for biotinylation by HCS. Here we demonstrated that H4K16bio is overrepresented in repeat regions {pericentromeric alpha satellite repeats; long terminal repeats (LTR)} compared with euchromatin promoters. H4K16bio was also enriched in the repressed interleukin-2 gene promoter. The enrichment at LTR22 and promoter 1 of the sodium-dependent multivitamin transporter (SMVT) depended on biotin supply; and was significantly lower in fibroblasts from an HCS-deficient patient compared with an HCS wild-type control. We conclude that H4K16bio is a real phenomenon and plays a role in the transcriptional repression of repeats and genes. HCS catalyzes the covalent binding of biotin to carboxylases, in addition to its role as a histone biotinyl ligase. HCS null individuals are not viable whereas HCS deficiency is linked to developmental delays and phenotypes such as short life span and low stress resistance. Here, we developed a 96-well plate assay for high-throughput analysis of HCS based on the detection of biotinylated p67 using IRDye-streptavidin and infrared spectroscopy. We demonstrated that the catalytic activity of rHCS depends on temperature and time, and proposed optimal substrate and enzyme concentrations to ensure ideal measurement of rHCS activity and its kinetics. Additionally, we demonstrated that this assay is sensitive enough to detect biotinylation of p67 by endogenous HCS from Jurkat lymphoid cells.