ZZ--Z′Z' mixing and oblique corrections in an SU(3)×U(1){\rm SU(3) \times U(1)} model

A global fit for experiments is included in this revised version.Comment: IFP-460-UNC, TRI-PP-93-11, 20 pages, 2 figures are appende

Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription- and replication-coupled repair pathways.

Illudin S is a natural sesquiterpene drug with strong anti-tumour activity. Inside cells, unstable active metabolites of illudin cause the formation of as yet poorly characterised DNA lesions. In order to identify factors involved in their repair, we have performed a detailed genetic survey of repair-defective mutants for responses to the drug. We show that 90% of illudin's lethal effects in human fibroblasts can be prevented by an active nucleotide excision repair (NER) system. Core NER enzymes XPA, XPF, XPG, and TFIIH are essential for recovery. However, the presence of global NER initiators XPC, HR23A/HR23B and XPE is not required, whereas survival, repair and recovery from transcription inhibition critically depend on CSA, CSB and UVS, the factors specific for transcription-coupled NER. Base excision repair and non-homologous end-joining of DNA breaks do not play a major role in the processing of illudin lesions. However, active RAD18 is required for optimal cell survival, indicating that the lesions also block replication forks, eliciting post-replication-repair-like responses. However, the translesion-polymerase DNA pol eta is not involved. We conclude that illudin-induced lesions are exceptional in that they appear to be ignored by all of the known global repair systems, and can only be repaired when trapped in stalled replication or transcription complexes. We show that the semisynthetic illudin derivative hydroxymethylacylfulvene (HMAF, Irofulven), currently under clinical trial for anti-tumour therapy, acts via the same mechanism

Euclidean Distances, soft and spectral Clustering on Weighted Graphs

We define a class of Euclidean distances on weighted graphs, enabling to perform thermodynamic soft graph clustering. The class can be constructed form the "raw coordinates" encountered in spectral clustering, and can be extended by means of higher-dimensional embeddings (Schoenberg transformations). Geographical flow data, properly conditioned, illustrate the procedure as well as visualization aspects.Comment: accepted for presentation (and further publication) at the ECML PKDD 2010 conferenc

Finite-temperature Fermi-edge singularity in tunneling studied using random telegraph signals

We show that random telegraph signals in metal-oxide-silicon transistors at millikelvin temperatures provide a powerful means of investigating tunneling between a two-dimensional electron gas and a single defect state. The tunneling rate shows a peak when the defect level lines up with the Fermi energy, in excellent agreement with theory of the Fermi-edge singularity at finite temperature. This theory also indicates that defect levels are the origin of the dissipative two-state systems observed previously in similar devices.Comment: 5 pages, REVTEX, 3 postscript figures included with epsfi

Field dependence of the vortex structure in chiral p-wave superconductors

To investigate the different vortex structure between two chiral pairing p_x +(-) i p_y, we calculate the pair potential, the internal field, the local density of states, and free energy in the vortex lattice state based on the quasiclassical Eilenberger theory, and analyze the magnetic field dependence. The induced opposite chiral component of the pair potential plays an important role in the vortex structure. It also produces H^{1/2}-behavior of the zero-energy density of states at higher field. These results are helpful when we understand the vortex states in Sr2RuO4.Comment: 11 pages, 10 figures, to be published in Phys. Rev.

Vortex structure in chiral p-wave superconductors

We investigate the vortex structure in chiral p-wave superconductors by the Bogoliubov-de Gennes theory on a tight-binding model. We calculate the spatial structure of the pair potential and electronic state around a vortex, including the anisotropy of the Fermi surface and superconducting gap structure. The differences of the vortex structure between $\sin p_x + {\rm i} \sin p_y$-wave and $\sin p_x - {\rm i} \sin p_y$-wave superconductors are clarified in the vortex lattice state. We also discuss the winding $\mp 3$ case of the $\sin{(p_x+p_y)} \pm {\rm i} \sin{(-p_x+p_y)}$-wave superconductivity.Comment: 10 pages, 8 figure

Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas

Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies.</p

Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas

Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies.</p