Gene expression signatures but not cell cycle checkpoint functions distinguish AT carriers from normal individuals

Ataxia telangiectasia (AT) is a rare autosomal recessive disease caused by mutations in the ataxia telangiectasia-mutated gene ( ATM). AT carriers with one mutant ATM allele are usually not severely affected although they carry an increased risk of developing cancer. There has not been an easy and reliable diagnostic method to identify AT carriers. Cell cycle checkpoint functions upon ionizing radiation (IR)-induced DNA damage and gene expression signatures were analyzed in the current study to test for differential responses in human lymphoblastoid cell lines with different ATM genotypes. While both dose- and time-dependent G1 and G2 checkpoint functions were highly attenuated in ATM−/− cell lines, these functions were preserved in ATM+/− cell lines equivalent to ATM+/+ cell lines. However, gene expression signatures at both baseline (consisting of 203 probes) and post-IR treatment (consisting of 126 probes) were able to distinguish ATM+/− cell lines from ATM+/+ and ATM−/− cell lines. Gene ontology (GO) and pathway analysis of the genes in the baseline signature indicate that ATM function-related categories, DNA metabolism, cell cycle, cell death control, and the p53 signaling pathway, were overrepresented. The same analyses of the genes in the IR-responsive signature revealed that biological categories including response to DNA damage stimulus, p53 signaling, and cell cycle pathways were overrepresented, which again confirmed involvement of ATM functions. The results indicate that AT carriers who have unaffected G1 and G2 checkpoint functions can be distinguished from normal individuals and AT patients by expression signatures of genes related to ATM functions.

Next Generation Cellular Network Planning

In this chapter, a multi-layer ATM architecture is proposed for the interconnection of current and future mobile communications nodes. Consisting of different ATM node types with respect to switching capability, the proposed architecture is adapted to current 2G and evolving 3G systems as well as future 4G wireless systems, as a common and shared backbone transmission network interconnecting core and access nodes between each other and Internet or PLMN/PSTN. Moreover, facing the huge expansion of transmission interconnection network that will support current and future generation mobile communications, a modification of the standard ATM cell structure is introduced in order to efficiently support user mobility functional procedures. The proposed ATM architecture is integrated over a suitable, with respect to region and capacity, physical interface, consisting of SDH or SONET for wide area topologies, wireless links for outdoor areas and LED-POF combination for indoor areas. Being an interesting alternative over copper or traditional fiber, POF characteristics and performance issues are analyzed.

Next Generation Cellular Network Planning

In this chapter, a multi-layer ATM architecture is proposed for the interconnection of current and future mobile communications nodes. Consisting of different ATM node types with respect to switching capability, the proposed architecture is adapted to current 2G and evolving 3G systems as well as future 4G wireless systems, as a common and shared backbone transmission network interconnecting core and access nodes between each other and Internet or PLMN/PSTN. Moreover, facing the huge expansion of transmission interconnection network that will support current and future generation mobile communications, a modification of the standard ATM cell structure is introduced in order to efficiently support user mobility functional procedures. The proposed ATM architecture is integrated over a suitable, with respect to region and capacity, physical interface, consisting of SDH or SONET for wide area topologies, wireless links for outdoor areas and LED-POF combination for indoor areas. Being an interesting alternative over copper or traditional fiber, POF characteristics and performance issues are analyzed.