Spatial genomic heterogeneity within localized, multifocal prostate cancer

Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

Radiochemical determination of 129I and 36Cl in MEGAPIE, a proton irradiated lead-bismuth eutectic spallation target

The concentrations of the long-lived nuclear reaction products 129I and 36Cl have been measured in samples from the MEGAPIE liquid metal spallation target. Samples from the bulk target material (lead-bismuth eutectic, LBE), from the interface of the metal free surface with the cover gas, from LBE/steel interfaces and from noble metal absorber foils installed in the cover gas system were analysed using Accelerator Mass Spectrometry at the Laboratory of Ion beam Physics at ETH Zürich. The major part of 129I and 36Cl was found accumulated on the interfaces, particularly at the interface of LBE and the steel walls of the target container, while bulk LBE samples contain only a minor fraction of these nuclides. Both nuclides were also detected on the absorber foils to a certain extent (≪ 1% of the total amount). The latter number is negligible concerning the radio-hazard of the irradiated target material; however it indicates a certain affinity of the absorber foils for halogens, thus proving the principle of using noble metal foils for catching these volatile radionuclides. The total amounts of 129I and 36Cl in the target were estimated from the analytical data by averaging within the different groups of samples and summing up these averages over the total target. This estimation could account for about half of the amount of 129I and 36Cl predicted to be produced using nuclear physics modelling codes for both nuclides. The significance of the results and the associated uncertainties are discussed.

Mikraʾe ḳodesh oder Fest-Reden und Fest-Vorbereitungsreden für Israeliten, auf alle Feste des Jahres

gehalten und hrsg. von Salomon Plessner

Fest-Predigten

von Leopold Löwenstein. Hrsg. aus Anlass seines 25jäehrigen Bezirksjubiläums durch die dankbaren Gemeinden seines Rabbinats-Bezirks Mosbach, Merchingen, Wertheim

Predigten

von Benjamin Rippner

Miḳraʾe ḳodesh oder Fest-Reden für Israeliten auf alle Feste des Jahres

von Salomon Plessner. Hrsg. von Elias Plessner

Reden gehalten am Neujahrsfeste und Versöhnungstage des Jahres 1893 in Frankfurt am Main

von Adolf Brüll

Kurz und lang : Ansprachen und Reden für die Festtage

von Simon Friedmann

Fest-Predigten für die hohen Feiertage des Jahres

gehalten von H. Joël ...

Fest-Predigten

von M. Steckelmacher, Stadt- und Conferenzrabbiner in Mannheim

23 Fest-Predigten und synagogale Vorträge : für alle h. Feiertage und Volksfeste

von L. Schlessinger