Showing papers by "Peter Möller published in 2019"

A modular transcriptome map of mature B cell lymphomas

Abstract: Germinal center-derived B cell lymphomas are tumors of the lymphoid tissues representing one of the most heterogeneous malignancies. Here we characterize the variety of transcriptomic phenotypes of this disease based on 873 biopsy specimens collected in the German Cancer Aid MMML (Molecular Mechanisms in Malignant Lymphoma) consortium. They include diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt’s lymphoma, mixed FL/DLBCL lymphomas, primary mediastinal large B cell lymphoma, multiple myeloma, IRF4-rearranged large cell lymphoma, MYC-negative Burkitt-like lymphoma with chr. 11q aberration and mantle cell lymphoma. We apply self-organizing map (SOM) machine learning to microarray-derived expression data to generate a holistic view on the transcriptome landscape of lymphomas, to describe the multidimensional nature of gene regulation and to pursue a modular view on co-expression. Expression data were complemented by pathological, genetic and clinical characteristics. We present a transcriptome map of B cell lymphomas that allows visual comparison between the SOM portraits of different lymphoma strata and individual cases. It decomposes into one dozen modules of co-expressed genes related to different functional categories, to genetic defects and to the pathogenesis of lymphomas. On a molecular level, this disease rather forms a continuum of expression states than clearly separated phenotypes. We introduced the concept of combinatorial pattern types (PATs) that stratifies the lymphomas into nine PAT groups and, on a coarser level, into five prominent cancer hallmark types with proliferation, inflammation and stroma signatures. Inflammation signatures in combination with healthy B cell and tonsil characteristics associate with better overall survival rates, while proliferation in combination with inflammation and plasma cell characteristics worsens it. A phenotypic similarity tree is presented that reveals possible progression paths along the transcriptional dimensions. Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt’s lymphoma and particularly on ‘double-hit’ MYC and BCL2 transformed lymphomas. The transcriptome map provides a tool that aggregates, refines and visualizes the data collected in the MMML study and interprets them in the light of previous knowledge to provide orientation and support in current and future studies on lymphomas and on other cancer entities.

Molecular characteristics of diffuse large B-cell lymphoma in the Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin lymphomas (PETAL) trial: correlation with interim PET and outcome

Abstract: Molecular characteristics of diffuse large B-cell lymphoma in the Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin lymphomas (PETAL) trial: correlation with interim PET and outcome Julia Richter , Andreas Hüttmann , Jan Rekowski , Christine Schmitz, Selina Gärtner, Andreas Rosenwald, Martin-Leo Hansmann, Sylvia Hartmann , Peter Möller, Hans-Heinrich Wacker, Alfred Feller, Christoph Thorns, Stefan Müller, Ulrich Dührsen and Wolfram Klapper 1

Calculated fission-fragment mass yields and average total kinetic energies of heavy and superheavy nuclei

Abstract: Fission-fragment mass and total-kinetic-energy (TKE) distributions following fission of even-even nuclides in the region $74 \leq Z \leq 126$ and $92 \leq N \leq 230$, comprising 896 nuclides have been calculated using the Brownian shape-motion method. The emphasis is the region of superheavy nuclei. To show compatibility with earlier results the calculations are extended to include earlier studied regions. An island of asymmetric fission is obtained in the superheavy region, $106\leq Z\leq114$ and $162\leq N\leq 176$, where the heavy fragment is found to be close to $^{208}$Pb and the light fragment adjusts accordingly. Most experimentally observed $\alpha$-decay chains of superheavy nuclei with $Z > 113 $ terminate by spontaneous fission in our predicted region of asymmetric fission. In these cases, the pronounced large asymmetry is accompanied by a low TKE value compatible with measurements.

Co 69 , 71 β -decay strength distributions from total absorption spectroscopy

Abstract: Background: The rapid neutron capture process is one of the main nucleosynthesis processes of elements heavier than Fe. Uncertainties in nuclear properties, such as masses, half-lives, and $\ensuremath{\beta}$-delayed neutron probabilities can cause orders of magnitude of variation within astrophysical $r$-process simulations. Presently, theoretical models are used to make global predictions of various nuclear properties for the thousands of nuclei required for these simulations, and measurements are required to benchmark these models, especially far from stability.Purpose: $\ensuremath{\beta}$-decay strength distributions can be used to not only inform astrophysical $r$-process simulations, but also to provide a stringent test for theoretical calculations. The aim of this work is to provide accurate strength distributions for $^{69,71}\mathrm{Co}\phantom{\rule{4pt}{0ex}}\ensuremath{\beta}$ decay.Method: The technique of total absorption spectroscopy was used to measure the $\ensuremath{\beta}$ decay of $^{69,71}\mathrm{Co}$ for the first time at the National Superconducting Cyclotron Laboratory. The ions were implanted in a double-sided silicon strip detector at the center of the Summing NaI(Tl) detector and identified using standard particle identification methods. The response of the detection system to the $\ensuremath{\beta}$-decay electron and subsequent $\ensuremath{\gamma}$-ray radiation was fit to the observed experimental data using a ${\ensuremath{\chi}}^{2}$-minimization technique.Results: $\ensuremath{\beta}$-feeding intensities and Gamow-Teller strength distributions were extracted from the fits of the experimental data. The $\ensuremath{\beta}$-decay intensities show that there is a large percentage of feeding to levels above 2 MeV, which have not been observed in previous studies. The resultant $\ensuremath{\beta}$-feeding intensities and Gamow-Teller strength distributions were compared to shell model and quasiparticle random phase approximation (QRPA) calculations.Conclusions: Comparing experimentally determined $\ensuremath{\beta}$-decay strength distributions provides a test of models, which are commonly used for global $\ensuremath{\beta}$-decay properties for astrophysical calculations. This work highlights the importance of performing detailed comparisons of models to experimental data, particularly far from stability and as close to the $r$-process path as possible.

Global microscopic calculations of odd-odd nuclei

Abstract: The macroscopic-microscopic finite-range droplet model is combined with a particle-rotor coupling model in order to systematically describe low-energy spectra of odd-odd nuclei. The odd proton and neutron are allowed to interact through effective nuclear forces representing the residual neutron-proton interaction. In particular, ground-state spins and parities are calculated and compared to data, where all 268 axially symmetric nuclei which have reliable spin and parity assignments in the Nubase 2016 database are considered. Using a residual neutron-proton interaction composed of both central and tensor terms the agreement with experimental ground-state spins and parities reaches 41% for spherical nuclei and 31% for deformed nuclei. The model is applied to study possible α-decay chains in superdeformed odd-odd nuclei, and Qα values are calculated considering favored decay-paths as compared to ground-state paths.

Aggressive B‑Zell-Lymphome

Abstract: Das Update der WHO-Klassifikation fur hamatopoetische Neoplasien bringt fur diagnostisch tatige Pathologen vor allem Anderungen im Bereich der aggressiven reifzelligen B‑Zell-Lymphome. Es stellt sich die Frage, welche Analysen bei der Diagnose der haufigsten Lymphomentitat, dem diffusen groszelligen B‑Zell-Lymphom, durchgefuhrt werden sollten. Von Bedeutung ist die Bestimmung der Ursprungszelle („cell of origin“), die Analyse von MYC-Translokationen und damit verbunden die Abgrenzung der neuen WHO-Entitaten der High-grade-B-Zell-Lymphome gegenuber dem diffusen groszelligen B‑Zell-Lymphom.

Fission modes in fermium isotopes with Brownian shape-motion model

Abstract: Fission-fragment mass and total-kinetic-energy distributions following fission of the fermium isotopes $^{256,258,260}\text{Fm}$ at low excitation energy have been calculated using the Brownian shape-motion model. A transition from asymmetric fission in $^{256}\text{Fm}$ to symmetric fission in $^{258}\text{Fm}$ is obtained. The total-kinetic-energy distributions for the three isotopes show radically different behaviour due to varying contributions from different fission modes, with a double-humped distribution for $^{258}\text{Fm}$.

[Revised version of the 4th edition of the WHO classification of malignant lymphomas : What is new?]

Abstract: After 8 years, the WHO has now published the updated version of the 4th edition of the classification of hematopoietic and lymphoid tumors. This update provides a conceptual rewrite of existing entities as well as some new provisional entities and categories, particularly among the aggressive B‑cell lymphomas. Important new diagnostic categories include the high-grade B‑cell lymphomas, the large B‑cell lymphoma with IRF4 rearrangement, and the Burkitt-like lymphoma with 11q aberrations. Of particular importance, new concepts concerning the taxonomy and classification of early lymphoid lesions or precursor lesions are included, such as the in situ follicular neoplasia or the in situ mantle cell neoplasia. In addition, the concept of indolent lymphoproliferations, such as breast-implant-associated anaplastic large cell lymphoma and the indolent T‑cell lymphoproliferative disorder of the gastrointestinal tract, has been strengthened. Finally, diagnostic criteria for existing lymphoma entities have been refined.

Revidierte Fassung der 4. Ausgabe der WHO-Klassifikation maligner Lymphome

Abstract: Nach 8 Jahren liegt nun eine Neufassung der 4. Ausgabe der WHO-Klassifikation lymphatischer Neoplasien vor. Sie beinhaltet sowohl eine konzeptionelle Neufassung bestehender Entitaten wie auch – wenige – provisorische neue Entitaten bzw. Kategorien, vor allem unter den aggressiven B‑Zell-Lymphomen. Hier sind vor allem das High-grade-B-Zell-Lymphom, das groszellige B‑Zell-Lymphom mit IRF4-Translokation und das Burkitt-ahnliche Lymphom mit Aberrationen in 11q zu nennen. Von besonderer Bedeutung sind auch neuere Konzepte zur Taxonomie und Klassifikation fruher lymphatischer Lasionen bzw. moglicher Vorstufen, wie die in-situ follikulare Neoplasie und die in-situ Mantelzellneoplasie, die Beschreibung indolenter Lymphoproliferationen wie das Brustimplantat-assoziierte anaplastische groszellige Lymphom und die indolente T‑Zell-Lymphoproliferation des Gastrointestinaltrakts sowie generell die Scharfung diagnostischer Kriterien bestehender Entitaten.

Revidierte Fassung der 4. Ausgabe der WHO-Klassifikation maligner Lymphome: Was ist neu?

Abstract: ZusammenfassungNach 8 Jahren liegt nun eine Neufassung der 4. Ausgabe der WHO-Klassifikation lymphatischer Neoplasien vor. Sie beinhaltet sowohl eine konzeptionelle Neufassung bestehender Entitäten wie auch – wenige – provisorische neue Entitäten bzw. Kategorien, vor allem unter den aggressiven B‑Zell-Lymphomen. Hier sind vor allem das High-grade-B-Zell-Lymphom, das großzellige B‑Zell-Lymphom mit IRF4-Translokation und das Burkitt-ähnliche Lymphom mit Aberrationen in 11q zu nennen. Von besonderer Bedeutung sind auch neuere Konzepte zur Taxonomie und Klassifikation früher lymphatischer Läsionen bzw. möglicher Vorstufen, wie die in-situ follikuläre Neoplasie und die in-situ Mantelzellneoplasie, die Beschreibung indolenter Lymphoproliferationen wie das Brustimplantat-assoziierte anaplastische großzellige Lymphom und die indolente T‑Zell-Lymphoproliferation des Gastrointestinaltrakts sowie generell die Schärfung diagnostischer Kriterien bestehender Entitäten.AbstractAfter 8 years, the WHO has now published the updated version of the 4th edition of the classification of hematopoietic and lymphoid tumors. This update provides a conceptual rewrite of existing entities as well as some new provisional entities and categories, particularly among the aggressive B‑cell lymphomas. Important new diagnostic categories include the high-grade B‑cell lymphomas, the large B‑cell lymphoma with IRF4 rearrangement, and the Burkitt-like lymphoma with 11q aberrations. Of particular importance, new concepts concerning the taxonomy and classification of early lymphoid lesions or precursor lesions are included, such as the in situ follicular neoplasia or the in situ mantle cell neoplasia. In addition, the concept of indolent lymphoproliferations, such as breast-implant-associated anaplastic large cell lymphoma and the indolent T‑cell lymphoproliferative disorder of the gastrointestinal tract, has been strengthened. Finally, diagnostic criteria for existing lymphoma entities have been refined.

[Aggressive B‑cell lymphomas : Recommendations from the German Panel of Reference Pathologists in the Competence Network on Malignant Lymphomas on diagnostic procedures according to the current WHO classification, update 2017].

Abstract: The update of the 4th edition of the WHO classification for hematopoietic neoplasms introduces changes in the field of mature aggressive B‑cell lymphomas that are relevant to diagnostic pathologists. In daily practice, the question arises of which analysis should be performed when diagnosing the most common lymphoma entity, diffuse large B‑cell lymphoma. We discuss the importance of the cell of origin, the analysis of MYC translocations, and the delineation of the new WHO entities of high-grade B‑cell lymphomas.

Fission Properties Relevant for GW170817

Abstract: The recent observation of gravitational waves and electromagnetic counterpart to GW170817 [1] has provided fresh impetus to understand the formation of the heaviest elements on the periodic table. The merging of two neutron stars offers a potentially robust site for the neutron-rich nucleosynthesis of these elements in the rapid neutron capture process (r process). However, many challenging problems remain in both the astrophysical modeling of merger events and the nuclear physics inputs. Among the nuclear physics needs for the r process, fission properties may be particularly important. The dynamical ejecta of mergers is expected to be so neutron-rich that the resulting r process produces nuclei above the predicted \(N=184\) shell closure and terminates via fission. We focus our discourse on recent nuclear model developments in the description of fission, apart of the Fission In R-process Elements (FIRE) collaboration. We discuss new calculations of neutron-induced and \(\beta \)-delayed fission properties using FRDM2012. We present new microscopic fission yields predicted from FRLDM. We report on the relevance of these calculations to nucleosynthetic yields, the impact on reheating of the ejecta in addition to the influence on kilonova observables.