Comprehensive genomic profiles of small cell lung cancer

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer

Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe

Search for Neutral Heavy Leptons Produced in Z Decays

Weak isosinglet Neutral Heavy Leptons ($\nu_m$) have been searched for using data collected by the DELPHI detector corresponding to $3.3\times 10^{6}$ hadronic~Z$^{0}$ decays at LEP1. Four separate searches have been performed, for short-lived $\nu_m$ production giving monojet or acollinear jet topologies, and for long-lived $\nu_m$ giving detectable secondary vertices or calorimeter clusters. No indication of the existence of these particles has been found, leading to an upper limit for the branching ratio $BR($Z$^0\rightarrow \nu_m \overline{\nu})$ of about $1.3\times10^{-6}$ at 95\% confidence level for $\nu_m$ masses between 3.5 and 50 GeV/$c^2$. Outside this range the limit weakens rapidly with the $\nu_m$ mass. %Special emphasis has been given to the search for monojet--like topologies. One event %has passed the selection, in agreement with the expectation from the reaction: %$e^+e^- \rightarrow\ell \bar\ell \nu\bar\nu$. The results are also interpreted in terms of limits for the single production of excited neutrinos