Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Software Architecture-based Adaptation for Pervasive Systems

An important requirement for pervasive computing systems is the ability to adapt at runtime to handle varying resources, user mobility, changing user needs, and system faults. In this paper we describe an approach in which dynamic adaptation is supported by the use of software architectural models to monitor an application and guide dynamic changes to it. The use of externalized models permits one to make reconfiguration decisions based on a global perspective of the running system, apply analytic models to determine correct repair strategies, and gauge the effectiveness of repair through continuous system monitoring. We illustrate the application of this idea to pervasive computing systems, focusing on the need to adapt based on performance-related criteria and models

Using Architectural Style as a Basis for System Self-repair

Abstract: An increasingly important requirement for software systems is the capability to adapt at run time in order to accommodate varying resources, system errors, and changing requirements. For such self-repairing systems, one of the hard problems is determining when a change is needed, and knowing what kind of adaptation is required. Recently several researchers have explored the possibility of using architectural models as a basis for run time monitoring, error detection, and repair. Each of these efforts, however, has demonstrated the feasibility of using architectural models in the context of a specific style. In this paper we show how to generalize these solutions by making architectural style a parameter in the monitoring/repair framework and its supporting infrastructure. The value of this generalization is that it allows one to tailor monitoring/repair mechanisms to match both the properties of interest (such as performance or security), and the available operators for run time adaptation. Key words: Dynamic adaptation, software architectures, performance analysis. 1

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases