Breast tumor copy number aberration phenotypes and genomic instability

BACKGROUND: Genomic DNA copy number aberrations are frequent in solid tumors, although the underlying causes of chromosomal instability in tumors remain obscure. Genes likely to have genomic instability phenotypes when mutated (e.g. those involved in mitosis, replication, repair, and telomeres) are rarely mutated in chromosomally unstable sporadic tumors, even though such mutations are associated with some heritable cancer prone syndromes. METHODS: We applied array comparative genomic hybridization (CGH) to the analysis of breast tumors. The variation in the levels of genomic instability amongst tumors prompted us to investigate whether alterations in processes/genes involved in maintenance and/or manipulation of the genome were associated with particular types of genomic instability. RESULTS: We discriminated three breast tumor subtypes based on genomic DNA copy number alterations. The subtypes varied with respect to level of genomic instability. We find that shorter telomeres and altered telomere related gene expression are associated with amplification, implicating telomere attrition as a promoter of this type of aberration in breast cancer. On the other hand, the numbers of chromosomal alterations, particularly low level changes, are associated with altered expression of genes in other functional classes (mitosis, cell cycle, DNA replication and repair). Further, although loss of function instability phenotypes have been demonstrated for many of the genes in model systems, we observed enhanced expression of most genes in tumors, indicating that over expression, rather than deficiency underlies instability. CONCLUSION: Many of the genes associated with higher frequency of copy number aberrations are direct targets of E2F, supporting the hypothesis that deregulation of the Rb pathway is a major contributor to chromosomal instability in breast tumors. These observations are consistent with failure to find mutations in sporadic tumors in genes that have roles in maintenance or manipulation of the genome

Slow Fourier Transforms on Fast Microprocessors

This paper describes our attempts to both reach this speed in our own hand-built code, and to explain why the speed is so low

Progress in Recognizing Typeset Mathematics

Printed mathematics has a number of features which distinguish it from conventional text. These include structure in two dimensions (fractions, exponents, limits), frequent font changes, symbols with variable shape (quotient bars), and substantially differing notational conventions from source to source. When compounded with more generic problems such as noise and merged or broken characters, printed mathematics offers a challenging arena for recognition. Our project was initially driven by the goal of scanning and parsing some 5,000 pages of elaborate mathematics (tables of definite integrals). While our prototype system demonstrates success on translating noise-free typeset equations into Lisp expressions appropriate for further processing, a more semantic top-down approach appears necessary for higher levels of performance. Such an approach may benefit the incorporation of these programs into a more general document processing viewpoint. We intend to release to the public our somewh..

Le Peuple : organe quotidien du syndicalisme

16 décembre 19331933/12/16 (A13,N4717)-1933/12/16