TY  - JOUR
A1  - Dornelas, Maria
A1  - Antão, Laura H.
A1  - Moyes, Faye
A1  - Bates, Amanda E.
A1  - Magurran, Anne E.
A1  - Adam, Dušan
A1  - Akhmetzhanova, Asem A.
A1  - Appeltans, Ward
A1  - Arcos, José Manuel
A1  - Arnold, Haley
A1  - Ayyappan, Narayanan
A1  - Badihi, Gal
A1  - Baird, Andrew H.
A1  - Barbosa, Miguel
A1  - Barreto, Tiago Egydio
A1  - Bässler, Claus
A1  - Bellgrove, Alecia
A1  - Belmaker, Jonathan
A1  - Benedetti-Cecchi, Lisandro
A1  - Bett, Brian J.
A1  - Bjorkman, Anne D.
A1  - Błażewicz, Magdalena
A1  - Blowes, Shane A.
A1  - Bloch, Christopher P. Bloch
A1  - Bonebrake, Timothy C.
A1  - Boyd, Susan
A1  - Bradford, Matt
A1  - Brooks, Andrew J.
A1  - Brown, James H.
A1  - Bruelheide, Helge
A1  - Budy, Phaedra
A1  - Carvalho, Fernando
A1  - Castañeda-Moya, Edward
A1  - Chen, Chaolun Allen
A1  - Chamblee, John F.
A1  - Chase, Tory J.
A1  - Siegwart Collier, Laura
A1  - Collinge, Sharon K.
A1  - Condit, Richard
A1  - Cooper, Elisabeth J.
A1  - Cornelissen, J. Hans C.
A1  - Cotano, Unai
A1  - Crow, Shannan Kyle
A1  - Damasceno, Gabriella
A1  - Davies, Claire H.
A1  - Davis, Robert A.
A1  - Day, Frank P.
A1  - Degraer, Steven
A1  - Doherty, Tim S.
A1  - Dunn, Timothy E.
A1  - Durigan, Giselda
A1  - Duffy, J. Emmett
A1  - Edelist, Dor
A1  - Edgar, Graham J.
A1  - Elahi, Robin
A1  - Elmendorf, Sarah C.
A1  - Enemar, Anders
A1  - Ernest, S. K. Morgan
A1  - Escribano, Rubén
A1  - Estiarte, Marc
A1  - Evans, Brian S.
A1  - Fan, Tung-Yung
A1  - Turini Farah, Fabiano
A1  - Loureiro Fernandes, Luiz
A1  - Farneda, Fábio Z.
A1  - Fidelis, Alessandra
A1  - Fitt, Robert
A1  - Fosaa, Anna Maria
A1  - Franco, Geraldo Antonio Daher Correa
A1  - Frank, Grace E.
A1  - Fraser, William R.
A1  - García, Hernando
A1  - Cazzolla Gatti, Roberto
A1  - Givan, Or
A1  - Gorgone-Barbosa, Elizabeth
A1  - Gould, William A.
A1  - Gries, Corinna
A1  - Grossman, Gary D.
A1  - Gutierréz, Julio R.
A1  - Hale, Stephen
A1  - Harmon, Mark E.
A1  - Harte, John
A1  - Haskins, Gary
A1  - Henshaw, Donald L.
A1  - Hermanutz, Luise
A1  - Hidalgo, Pamela
A1  - Higuchi, Pedro
A1  - Hoey, Andrew
A1  - Van Hoey, Gert
A1  - Hofgaard, Annika
A1  - Holeck, Kristen
A1  - Hollister, Robert D.
A1  - Holmes, Richard
A1  - Hoogenboom, Mia
A1  - Hsieh, Chih-hao
A1  - Hubbell, Stephen P.
A1  - Huettmann, Falk
A1  - Huffard, Christine L.
A1  - Hurlbert, Allen H.
A1  - Ivanauskas, Natália Macedo
A1  - Janík, David
A1  - Jandt, Ute
A1  - Jażdżewska, Anna
A1  - Johannessen, Tore
A1  - Johnstone, Jill
A1  - Jones, Julia
A1  - Jones, Faith A. M.
A1  - Kang, Jungwon
A1  - Kartawijaya, Tasrif
A1  - Keeley, Erin C.
A1  - Kelt, Douglas A.
A1  - Kinnear, Rebecca
A1  - Klanderud, Kari
A1  - Knutsen, Halvor
A1  - Koenig, Christopher C.
A1  - Kortz, Alessandra R.
A1  - Král, Kamil
A1  - Kuhnz, Linda A.
A1  - Kuo, Chao-Yang
A1  - Kushner, David J.
A1  - Laguionie-Marchais, Claire
A1  - Lancaster, Lesley T.
A1  - Lee, Cheol Min
A1  - Lefcheck, Jonathan S.
A1  - Lévesque, Esther
A1  - Lightfoot, David
A1  - Lloret, Francisco
A1  - Lloyd, John D.
A1  - López-Baucells, Adrià
A1  - Louzao, Maite
A1  - Madin, Joshua S.
A1  - Magnússon, Borgþór
A1  - Malamud, Shahar
A1  - Matthews, Iain
A1  - McFarland, Kent P.
A1  - McGill, Brian
A1  - McKnight, Diane
A1  - McLarney, William O.
A1  - Meador, Jason
A1  - Meserve, Peter L.
A1  - Metcalfe, Daniel J.
A1  - Meyer, Christoph F. J.
A1  - Michelsen, Anders
A1  - Milchakova, Nataliya
A1  - Moens, Tom
A1  - Moland, Even
A1  - Moore, Jon
A1  - Moreira, Carolina Mathias
A1  - Müller, Jörg
A1  - Murphy, Grace
A1  - Myers-Smith, Isla H.
A1  - Myster, Randall W.
A1  - Naumov, Andrew
A1  - Neat, Francis
A1  - Nelson, James A.
A1  - Nelson, Michael Paul
A1  - Newton, Stephen F.
A1  - Norden, Natalia
A1  - Oliver, Jeffrey C.
A1  - Olsen, Esben M.
A1  - Onipchenko, Vladimir G.
A1  - Pabis, Krzysztof
A1  - Pabst, Robert J.
A1  - Paquette, Alain
A1  - Pardede, Sinta
A1  - Paterson, David M.
A1  - Pélissier, Raphaël
A1  - Peñuelas, Josep
A1  - Pérez-Matus, Alejandro
A1  - Pizarro, Oscar
A1  - Pomati, Francesco
A1  - Post, Eric
A1  - Prins, Herbert H. T.
A1  - Priscu, John C.
A1  - Provoost, Pieter
A1  - Prudic, Kathleen L.
A1  - Pulliainen, Erkki
A1  - Ramesh, B. R.
A1  - Ramos, Olivia Mendivil
A1  - Rassweiler, Andrew
A1  - Rebelo, Jose Eduardo
A1  - Reed, Daniel C.
A1  - Reich, Peter B.
A1  - Remillard, Suzanne M.
A1  - Richardson, Anthony J.
A1  - Richardson, J. Paul
A1  - van Rijn, Itai
A1  - Rocha, Ricardo
A1  - Rivera-Monroy, Victor H.
A1  - Rixen, Christian
A1  - Robinson, Kevin P.
A1  - Rodrigues, Ricardo Ribeiro
A1  - de Cerqueira Rossa-Feres, Denise
A1  - Rudstam, Lars
A1  - Ruhl, Henry
A1  - Ruz, Catalina S.
A1  - Sampaio, Erica M.
A1  - Rybicki, Nancy
A1  - Rypel, Andrew
A1  - Sal, Sofia
A1  - Salgado, Beatriz
A1  - Santos, Flavio A. M.
A1  - Savassi-Coutinho, Ana Paula
A1  - Scanga, Sara
A1  - Schmidt, Jochen
A1  - Schooley, Robert
A1  - Setiawan, Fakhrizal
A1  - Shao, Kwang-Tsao
A1  - Shaver, Gaius R.
A1  - Sherman, Sally
A1  - Sherry, Thomas W.
A1  - Siciński, Jacek
A1  - Sievers, Caya
A1  - da Silva, Ana Carolina
A1  - da Silva, Fernando Rodrigues
A1  - Silveira, Fabio L.
A1  - Slingsby, Jasper
A1  - Smart, Tracey
A1  - Snell, Sara J.
A1  - Soudzilovskaia, Nadejda A.
A1  - Souza, Gabriel B. G.
A1  - Souza, Flaviana Maluf
A1  - Souza, Vinícius Castro
A1  - Stallings, Christopher D.
A1  - Stanforth, Rowan
A1  - Stanley, Emily H.
A1  - Sterza, José Mauro
A1  - Stevens, Maarten
A1  - Stuart-Smith, Rick
A1  - Suarez, Yzel Rondon
A1  - Supp, Sarah
A1  - Tamashiro, Jorge Yoshio
A1  - Tarigan, Sukmaraharja
A1  - Thiede, Gary P.
A1  - Thorn, Simon
A1  - Tolvanen, Anne
A1  - Toniato, Maria Teresa Zugliani
A1  - Totland, Ørjan
A1  - Twilley, Robert R.
A1  - Vaitkus, Gediminas
A1  - Valdivia, Nelson
A1  - Vallejo, Martha Isabel
A1  - Valone, Thomas J.
A1  - Van Colen, Carl
A1  - Vanaverbeke, Jan
A1  - Venturoli, Fabio
A1  - Verheye, Hans M.
A1  - Vianna, Marcelo
A1  - Vieira, Rui P.
A1  - Vrška, Tomáš
A1  - Vu, Con Quang
A1  - Vu, Lien Van
A1  - Waide, Robert B.
A1  - Waldock, Conor
A1  - Watts, Dave
A1  - Webb, Sara
A1  - Wesołowski, Tomasz
A1  - White, Ethan P.
A1  - Widdicombe, Claire E.
A1  - Wilgers, Dustin
A1  - Williams, Richard
A1  - Williams, Stefan B.
A1  - Williamson, Mark
A1  - Willig, Michael R.
A1  - Willis, Trevor J.
A1  - Wipf, Sonja
A1  - Woods, Kerry D.
A1  - Woehler, Eric J.
A1  - Zawada, Kyle
A1  - Zettler, Michael L.
T1  - BioTIME: A database of biodiversity time series for the Anthropocene
JF  - Global Ecology and Biogeography
N2  - Motivation
The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.

Main types of variables included
The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.

Spatial location and grain
BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).

Time period and grain
BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.

Major taxa and level of measurement
BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.

Software format
.csv and .SQL.
KW  - biodiversity
KW  - global
KW  - spatial
KW  - species richness
KW  - temporal
KW  - turnover
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222846
VL  - 27
ER  - 
TY  - JOUR
A1  - Schilbach, Karin
A1  - Alkhaled, Mohammed
A1  - Welker, Christian
A1  - Eckert, Franziska
A1  - Blank, Gregor
A1  - Ziegler, Hendrik
A1  - Sterk, Marco
A1  - Müller, Friederike
A1  - Sonntag, Katja
A1  - Wieder, Thomas
A1  - Braumüller, Heidi
A1  - Schmitt, Julia
A1  - Eyrich, Matthias
A1  - Schleicher, Sabine
A1  - Seitz, Christian
A1  - Erbacher, Annika
A1  - Pichler, Bernd J.
A1  - Müller, Hartmut
A1  - Tighe, Robert
A1  - Lim, Annick
A1  - Gillies, Stephen D.
A1  - Strittmatter, Wolfgang
A1  - Röcken, Martin
A1  - Handgretinger, Rupert
T1  - Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation
JF  - OncoImmunology
N2  - Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-γ-dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS-IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16\(^{INK4a}\) and nuclear translocation of p-HP1γ, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo.
KW  - TH17 cells
KW  - cancer-targeted IL-12
KW  - differentiation
KW  - humanized mice
KW  - immunocytokine
KW  - immunotherapy
KW  - M1/M2 macrophages
KW  - rhabdomyosarcoma
KW  - TH1-induced senescence
KW  - tumor-infiltrating lymphocytes
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154579
VL  - 4
IS  - 7
ER  - 
TY  - JOUR
A1  - Welker, Armin
A1  - Kersten, Christian
A1  - Müller, Christin
A1  - Madhugiri, Ramakanth
A1  - Zimmer, Collin
A1  - Müller, Patrick
A1  - Zimmermann, Robert
A1  - Hammerschmidt, Stefan
A1  - Maus, Hannah
A1  - Ziebuhr, John
A1  - Sotriffer, Christoph
A1  - Schirmeister, Tanja
T1  - Structure‐Activity Relationships of Benzamides and Isoindolines Designed as SARS‐CoV Protease Inhibitors Effective against SARS‐CoV‐2
JF  - ChemMedChem
N2  - Inhibition of coronavirus (CoV)‐encoded papain‐like cysteine proteases (PL\(^{pro}\)) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure‐activity relationships (SAR) of the noncovalent active‐site directed inhibitor (R)‐5‐amino‐2‐methyl‐N‐(1‐(naphthalen‐1‐yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS‐CoV PL\(^{pro}\). Moreover, we report the discovery of isoindolines as a new class of potent PL\(^{pro}\) inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS‐CoV‐2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS‐CoV PL\(^{pro}\) are valuable starting points for the development of new pan‐coronaviral inhibitors.
KW  - antiviral agents
KW  - computational chemistry
KW  - drug design
KW  - protease inhibitors
KW  - structure-activity relationships
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225700
VL  - 16
IS  - 2
SP  - 340
EP  - 354
ER  - 
TY  - THES
A1  - Müller, Christian Robert
T1  - Nanoelektronische Feldeffekt-Transistoren und Quantenpunktspeicher auf der Basis von modulationsdotierten GaAs/AlGaAs Heterostrukturen
T1  - Nanoelectronic field-effect transistors and quantum-dot-flash memories based on modulation-doped GaAs/AlGaAs heterostructures
N2  - Diese Arbeit beschäftigt sich mit Elektronentransport in nanostrukturierten Bauelementen auf Halbleiterbasis, wobei im Speziellen deren Transistor- und Speichereigenschaften untersucht werden. Grundlage für die Bauelemente stellt eine modulationsdotierte GaAs/AlGaAs Heterostruktur dar, die mittels Elektronenstrahllithographie und nasschemischen Ätzverfahren strukturiert wird. Auf Grund der Bandverbiegung bildet sich in der Nähe des Heteroübergangs ein zweidimensionales Elektronengas (2DEG) aus, das als leitfähige Schicht in den Strukturen dient. Im Rahmen der Arbeit werden die Transporteigenschaften für unterschiedliche Bauelementdesigns untersucht, wobei die laterale Ausdehnung der Bauelemente wenige 10 nm beträgt. Die Charakterisierung des Elektronentransports erfolgt sowohl im linearen als auch nichtlinearen Transportregime für tiefe Temperaturen (T = 4.2 K) bis hin zu Raumtemperatur. Das erste experimentelle Kapitel beschäftigt sich mit dem Entwurf und der Charakterisierung von statischen Speicherzellen mit integriertem Floating Gate. Bei den hierfür hergestellten Bauelementen befindet sich eine Schicht selbstorganisierter Quantenpunkte (QDs) in direkter Nähe zum 2DEG. Der Abstand zwischen 2DEG und QDs ist kleiner als die Abschirmlänge im Halbleitermaterial, wodurch die QDs als Floating Gate dienen und Informationen elektrisch gespeichert werden können. Die Speicherzellen wurden in Form von Quantendraht-Transistoren (QWTs) und Y-Schaltern (YBSs) realisiert und bezüglich der Speicherfähigkeit der QDs sowohl bei tiefen Temperaturen als auch bei Raumtemperatur untersucht. Im zweiten experimentellen Kapitel dieser Arbeit wird ein neues, auf dem Feldeffekt beruhendes, Transistordesign vorgestellt. Die hierfür hergestellten Heterostrukturen besitzen ein 2DEG, das sich zwischen 33 nm und 80 nm unterhalb der Oberfläche der Heterostruktur befindet. Mittels in die Oberfläche der Heterostruktur geätzter Gräben wird eine Isolation zwischen den leitfähigen Regionen der Bauelemente geschaffen. Das einfache Design der sogenannten Three-Terminal Junctions (TTJs), in Verbindung mit dem oberflächennahen 2DEG, ermöglicht die monolithische Realisierung von integrierten logischen Gattern. Durch eine ausführliche Betrachtung des Transistorverhaltens der TTJs können sowohl Subthreshold Swings kleiner als das thermische Limit klassischer Feldeffekt-Transistoren als auch Hochfrequenzfunktionalität demonstriert werden.
N2  - In this thesis, electron transport in nano-structured, semiconductor devices is investigated with focus on transistor characteristics and memory effects. The investigated devices are based on a modulation-doped GaAs/AlGaAs heterostructure and are structured by electron-beam lithography and wet-chemical etching. Close to the heterointerface, a two-dimensional electron gas (2DEG) is formed and serves as conducting layer for the electron transport. Different devices with lateral dimensions of a few 10 nm are fabricated and are characterized in the linear and nonlinear transport regime at low temperatures, i.e. T = 4.2 K, as well as at room temperature. The first chapter is dedicated to the experimental results on the design and characterization of memory devices with a floating gate. The devices are based on a modulation-doped heterostructure with a layer of self-assembled quantum dots (QDs) in close vicinity to the conducting layer. The distance between QDs and 2DEG is less than the screening length and, therefore, the QDs serve as floating gate on the 2DEG. Hence, information can be stored electrically. For the memory devices, quantum-wire transistors (QWTs) and electron Y-branch switches (YBSs) are used and characterized, with respect to the floating-gate function of the QDs, at low temperatures and up to room temperature. In the second chapter of this thesis, a novel transistor design based on the field effect is presented. For this purpose, the 2DEG is situated between 33 and 80 nm below the surface of the heterostructure. The conducting parts of the devices are insulated from each other by etched insulation trenches. Due to the monolithic design of the three-terminal junctions (TTJs) with a shallow 2DEG, an integrated logic gate is realized. By analyzing the switching properties of the TTJs in detail, subthreshold swings below the thermal limit and high frequency functionality are demonstrated.
KW  - Galliumarsenid
KW  - Aluminiumarsenid
KW  - Heterostruktur-Bauelement
KW  - HEMT
KW  - SET-Transistor
KW  - Quantenpunkt
KW  - Nanodot-Speicher
KW  - Flash-Speicher
KW  - HEMT
KW  - field-effect transistor
KW  - quantum dot
KW  - flash memory
KW  - rectification
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-39948
ER  - 
TY  - JOUR
A1  - Müller, Konstantin
A1  - Leppich, Robert
A1  - Geiß, Christian
A1  - Borst, Vanessa
A1  - Pelizari, Patrick Aravena
A1  - Kounev, Samuel
A1  - Taubenböck, Hannes
T1  - Deep neural network regression for normalized digital surface model generation with Sentinel-2 imagery
JF  - IEEE Journal of Selected Topics in Applied Earth Observations and Remote Sensing
N2  - In recent history, normalized digital surface models (nDSMs) have been constantly gaining importance as a means to solve large-scale geographic problems. High-resolution surface models are precious, as they can provide detailed information for a specific area. However, measurements with a high resolution are time consuming and costly. Only a few approaches exist to create high-resolution nDSMs for extensive areas. This article explores approaches to extract high-resolution nDSMs from low-resolution Sentinel-2 data, allowing us to derive large-scale models. We thereby utilize the advantages of Sentinel 2 being open access, having global coverage, and providing steady updates through a high repetition rate. Several deep learning models are trained to overcome the gap in producing high-resolution surface maps from low-resolution input data. With U-Net as a base architecture, we extend the capabilities of our model by integrating tailored multiscale encoders with differently sized kernels in the convolution as well as conformed self-attention inside the skip connection gates. Using pixelwise regression, our U-Net base models can achieve a mean height error of approximately 2 m. Moreover, through our enhancements to the model architecture, we reduce the model error by more than 7%.
KW  - Deep learning
KW  - multiscale encoder
KW  - sentinel
KW  - surface model
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349424
SN  - 1939-1404
VL  - 16
ER  - 
TY  - JOUR
A1  - Rinaldetti, Sébastien
A1  - Pfirrmann, Markus
A1  - Manz, Kirsi
A1  - Guilhot, Joelle
A1  - Dietz, Christian
A1  - Panagiotidis, Panayiotidis
A1  - Spiess, Birgit
A1  - Seifarth, Wolfgang
A1  - Fabarius, Alice
A1  - Müller, Martin
A1  - Pagoni, Maria
A1  - Dimou, Maria
A1  - Dengler, Jolanta
A1  - Waller, Cornelius F.
A1  - Brümmendorf, Tim H.
A1  - Herbst, Regina
A1  - Burchert, Andreas
A1  - Janßen, Carsten
A1  - Goebeler, Maria Elisabeth
A1  - Jost, Philipp J.
A1  - Hanzel, Stefan
A1  - Schafhausen, Philippe
A1  - Prange-Krex, Gabriele
A1  - Illmer, Thomas
A1  - Janzen, Viktor
A1  - Klausmann, Martine
A1  - Eckert, Robert
A1  - Büschel, Gerd
A1  - Kiani, Alexander
A1  - Hofmann, Wolf-Karsten
A1  - Mahon, François-Xavier
A1  - Saussele, Susanne
T1  - Effect of ABCG2, OCT1, and ABCB1 (MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial
JF  - Clinical Lymphoma, Myeloma & Leukemia
N2  - Within the EURO-SKI trial, 132 chronic phase CML patients discontinued imatinib treatment. RNA was isolated from peripheral blood in order to analyze the expression of MDR1, ABCG2 and OCT1. ABCG2 was predictive for treatment-free remission in Cox regression analysis. High transcript levels of the ABCG2 efflux transporter (>4.5 parts per thousand) were associated with a twofold higher risk of relapse. Introduction: Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated. Materials and Methods: RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated. Results: The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (parts per thousand) was retained as the only significant variable (P=.02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P=.04). Patients with an ABCG2/GUSB transcript level >4.5 parts per thousand (n=93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (<= 4.5 parts per thousand; n=39) had a 12-month TFR rate of 72% (95% CI, 55%-82%). Conclusion: In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation. (C) 2018 The Authors. Published by Elsevier Inc.
KW  - ABCG2
KW  - Biomarker
KW  - CML
KW  - Imatinib
KW  - Prediction
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226281
VL  - 18
IS  - 4
ER  - 
TY  - JOUR
A1  - Müller, Laura S. M.
A1  - Cosentino, Raúl O.
A1  - Förstner, Konrad U.
A1  - Guizetti, Julien
A1  - Wedel, Carolin
A1  - Kaplan, Noam
A1  - Janzen, Christian J.
A1  - Arampatzi, Panagiota
A1  - Vogel, Jörg
A1  - Steinbiss, Sascha
A1  - Otto, Thomas D.
A1  - Saliba, Antoine-Emmanuel
A1  - Sebra, Robert P.
A1  - Siegel, T. Nicolai
T1  - Genome organization and DNA accessibility control antigenic variation in trypanosomes
JF  - Nature
N2  - Many evolutionarily distant pathogenic organisms have evolved similar survival strategies to evade the immune responses of their hosts. These include antigenic variation, through which an infecting organism prevents clearance by periodically altering the identity of proteins that are visible to the immune system of the host1. Antigenic variation requires large reservoirs of immunologically diverse antigen genes, which are often generated through homologous recombination, as well as mechanisms to ensure the expression of one or very few antigens at any given time. Both homologous recombination and gene expression are affected by three-dimensional genome architecture and local DNA accessibility2,3. Factors that link three-dimensional genome architecture, local chromatin conformation and antigenic variation have, to our knowledge, not yet been identified in any organism. One of the major obstacles to studying the role of genome architecture in antigenic variation has been the highly repetitive nature and heterozygosity of antigen-gene arrays, which has precluded complete genome assembly in many pathogens. Here we report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding4. Genome-wide chromosome conformation capture (Hi-C) reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. In addition, we performed a range of analyses—Hi-C, fluorescence in situ hybridization, assays for transposase-accessible chromatin using sequencing and single-cell RNA sequencing—that showed that deletion of the histone variants H3.V and H4.V increases antigen-gene clustering, DNA accessibility across sites of antigen expression and switching of the expressed antigen isoform, via homologous recombination. Our analyses identify histone variants as a molecular link between global genome architecture, local chromatin conformation and antigenic variation.
KW  - histone variants
KW  - genome architecture
KW  - single molecule real time (SMRT)
KW  - brucei genome
KW  - distance-dependent decay
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224265
VL  - 563
ER  -