TY - JOUR A1 - Akshat, Puri A1 - Aaboud, M. A1 - Aad, G. A1 - Abbott, B. A1 - Abdinov, O. A1 - Abeloos, B. A1 - Abhayasinghe, D. K. A1 - Abidi, S. H. A1 - Abou Zeid, O. S. A1 - Abraham, N. L. A1 - Abramowicz, H. A1 - Abreu, H. A1 - Abulaiti, Y. A1 - Acharya, B. S. A1 - Adachi, S. A1 - Adam, L. A1 - Adamczyk, L. A1 - Adelman, J. A1 - Adersberger, M. A1 - Adiguzel, A. A1 - Adye, T. A1 - Affolder, A. A. A1 - Afik, Y. A1 - Agheorghiesei, C. A1 - Aguilar-Saavedra, J. A. A1 - Ahmadov, F. A1 - Aiellil, G. A1 - Akatsuka, S. A1 - Akesson, T. P. A. A1 - Akilli, E. A1 - Akimov, A. V. A1 - Alberghi, G. L. A1 - Albert, J. A1 - Albicocco, P. A1 - Alconada Verzini, M. J. A1 - Alderweireld, S. A1 - Aleksa, M. A1 - Aleksandrov, I. N. A1 - Alexa, C. A1 - Alexopoulos, T. A1 - Alhroob, M. A1 - Ali, B. A1 - Alimonti, G. A1 - Alison, J. A1 - Andre, S. P. A1 - Allaire, C. A1 - Allbrooke, B. M. M. A1 - Allen, B. W. A1 - Allport, P. P. A1 - Aloisio, A. A1 - Alonso, A. A1 - Alonso, F. A1 - Alpigiani, C. A1 - Alshehri, A. A. A1 - Alstaty, M. I. A1 - Alvarez, Gonzalez B. A1 - Alvarez Piqueras, D. A1 - Alviggi, M. G. A1 - Amadio, B. T. A1 - Amaral, Coutinho, Y. A1 - Ambler, A. A1 - Ambroz, L. A1 - Amelung, C. A1 - Amidei, D. A1 - Amor Dos Santos, S. P. A1 - Amoroso, S. A1 - Amrouche, C. S. A1 - Anastopoulos, C. A1 - Ancu, L. S. A1 - Andari, N. A1 - Andeen, T. A1 - Anders, C. F. A1 - Anders, J. K. A1 - Anderson, K. J. A1 - Andreazza, A. A1 - Andrei, V. A1 - et al, T1 - Measurement of angular and momentum distributions of charged particles within and around jets in Pb plus Pb and pp collisions at root s(NN)=5.02 TeV with ATLAS at the LHC : XXVIIth International Conference on Ultrarelativistic Nucleus-Nucleus Collisions (Quark Matter 2018) JF - Nuclear Physics A N2 - Studies of the fragmentation of jets into charged particles in heavy-ion collisions can help in understanding the mechanism of jet quenching by the hot and dense QCD matter created in such collisions, the quark-gluon plasma. These proceedings present a measurement of the angular distribution of charged particles around the jet axis in root s(NN) = 5.02 TeV Pb+Pb and pp collisions, done using the ATLAS detector at the LHC. The measurement is performed inside jets reconstructed with the anti-k(t) algorithm with radius parameter R = 0.4, and is extended to regions outside the jet cone. Results are presented as a function of Pb+Pb collision centrality, and both jet and charged-particle transverse momenta. KW - jets KW - fragmentation functions KW - jet shapes Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224703 VL - 982 IS - 2 ER - TY - JOUR A1 - Rademaker, Manuel E. A1 - Schuberth, Florian A1 - Dijkstra, Theo K. T1 - Measurement error correlation within blocks of indicators in consistent partial least squares : Issues and remedies JF - Internet Research N2 - Purpose The purpose of this paper is to enhance consistent partial least squares (PLSc) to yield consistent parameter estimates for population models whose indicator blocks contain a subset of correlated measurement errors. Design/methodology/approach Correction for attenuation as originally applied by PLSc is modified to include a priori assumptions on the structure of the measurement error correlations within blocks of indicators. To assess the efficacy of the modification, a Monte Carlo simulation is conducted. Findings In the presence of population measurement error correlation, estimated parameter bias is generally small for original and modified PLSc, with the latter outperforming the former for large sample sizes. In terms of the root mean squared error, the results are virtually identical for both original and modified PLSc. Only for relatively large sample sizes, high population measurement error correlation, and low population composite reliability are the increased standard errors associated with the modification outweighed by a smaller bias. These findings are regarded as initial evidence that original PLSc is comparatively robust with respect to misspecification of the structure of measurement error correlations within blocks of indicators. Originality/value Introducing and investigating a new approach to address measurement error correlation within blocks of indicators in PLSc, this paper contributes to the ongoing development and assessment of recent advancements in partial least squares path modeling. KW - Monte Carlo simulation KW - Structural equation modelling KW - Consistent partial least squares KW - Measurement error correlation KW - Model specification Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224901 VL - 29 IS - 3 ER - TY - JOUR A1 - Ruiz, E. Josue A1 - Diefenbacher, Markus E. A1 - Nelson, Jessica K. A1 - Sancho, Rocio A1 - Pucci, Fabio A1 - Chakraborty, Atanu A1 - Moreno, Paula A1 - Annibaldi, Alessandro A1 - Liccardi, Gianmaria A1 - Encheva, Vesela A1 - Mitter, Richard A1 - Rosenfeldt, Mathias A1 - Snijders, Ambrosius P. A1 - Meier, Pascal A1 - Calzado, Marco A. A1 - Behrens, Axel T1 - LUBAC determines chemotherapy resistance in squamous cell lung cancer JF - Journal of Experimental Medicine N2 - Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10(+), but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-kappa B signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-kappa B activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment. KW - Solid tumors Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227146 VL - 216 IS - 2 ER - TY - JOUR A1 - Robin, Marie A1 - de Wreede, Liesbeth C. A1 - Wolschke, Christine A1 - Schetelig, Johannes A1 - Eikema, Diderik-Jan A1 - Van Lint, Maria Teresa A1 - Knelange, Nina Simone A1 - Beelen, Dietrich A1 - Brecht, Arne A1 - Niederwieser, Dietger A1 - Vitek, Antonin A1 - Bethge, Wolfgang A1 - Arnold, Renate A1 - Finke, Jürgen A1 - Volin, Liisa A1 - Yakoub-Agha, Ibrahim A1 - Nagler, Arnon A1 - Poiré, Xavier A1 - Einsele, Hermann A1 - Chevallier, Patrice A1 - Holler, Ernst A1 - Ljungman, Per A1 - Robinson, Stephen A1 - Radujkovic, Alekxandar A1 - McLornan, Donal A1 - Chalandon, Yves A1 - Kröger, Nicolaus T1 - Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis JF - Haematologica N2 - Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events Aoccur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64% (60-68%) and overall survival was 74% (71-78%) at ten years; results were better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients aged <45 years and 33% (13-53%) in patients aged >= 65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors. KW - Prognostic scoring system KW - Societe Francaise KW - Gruppo-italiano KW - European group KW - Late mortality KW - Midollo-Osseo KW - LATE DEATHS KW - Survival KW - Blood KW - Ruxolitinib Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226386 VL - 104 IS - 9 ER - TY - JOUR A1 - Radeloff, Katrin A1 - Radeloff, Andreas A1 - Tirado, Mario Ramos A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Kleinsasser, Norbert H. A1 - Hackenberg, Stephan T1 - Long-Term Impact of Zinc Oxide Nanoparticles on Differentiation and Cytokine Secretion of Human Adipose-Derived Stromal Cells JF - Materials N2 - Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 mu g/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs. KW - zinc oxide KW - nanoparticles KW - toxicity KW - differentiation potential KW - human adipose-derived stromal cells KW - stem cells Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224779 VL - 12 IS - 1823 ER - TY - JOUR A1 - Rudelius, Martina A1 - Rosenfeldt, Mathias Tillmann A1 - Leich, Ellen A1 - Rauert-Wunderlich, Hilka A1 - Solimando, Antonio Giovanni A1 - Ott, German A1 - Rosenwald, Andreas A1 - Beilhack, Andreas T1 - Inhibition of focal adhesion kinase overcomes resistance of mantle cell lymphoma to ibrutinib in the bone marrow microenvironment JF - Haematologica N2 - Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells co-cultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi-based focal adhesion kinase silencing was performed. We showed that focal adhesion kinase is highly expressed in bone marrow infiltrates of mantle cell lymphoma and in mantle cell lymphoma cell lines. Stroma-mediated activation of focal adhesion kinase led to activation of multiple kinases (AKT, p42/44 and NF-kappa B), that are important for prosurvival and proliferation signaling. Interestingly, RNAi-based focal adhesion kinase silencing or inhibition with small molecule inhibitors (FAKi) resulted in blockage of targeted cell invasion and induced apoptosis by inactivation of multiple signaling cascades, including the classic and alternative NF-kappa B pathway. In addition, the combined treatment of ibrutinib and FAKi was highly synergistic, and ibrutinib resistance of mantle cell lymphoma could be overcome. These data demonstrate that focal adhesion kinase is important for stroma-mediated survival and drug resistance in mantle cell lymphoma, providing indications for a targeted therapeutic strategy. KW - NF-Kappa-B KW - Stromal cells KW - Induced apoptosis KW - Fak regulation KW - Phase- KW - Multiple KW - Activation KW - Mechanisms KW - Migration KW - Pathogenesis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227117 VL - 103 IS - 1 ER - TY - JOUR A1 - Stuckensen, Kai A1 - Lamo-Espinosa, José M. A1 - Muiños-López, Emma A1 - Ripalda-Cemboráin, Purificación A1 - López-Martínez, Tania A1 - Iglesias, Elena A1 - Abizanda, Gloria A1 - Andreu, Ion A1 - Flandes-Iparraguirre, María A1 - Pons-Villanueva, Juan A1 - Elizalde, Reyes A1 - Nickel, Joachim A1 - Ewald, Andrea A1 - Gbureck, Uwe A1 - Prósper, Felipe A1 - Groll, Jürgen A1 - Granero-Moltó, Froilán T1 - Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP−2 and enhanced bone regeneration JF - Materials N2 - In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing. KW - rhBMP–2 KW - collagen sponge KW - cryostructured scaffolds KW - bone critical size defect Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195966 SN - 1996-1944 VL - 12 IS - 19 ER - TY - JOUR A1 - Näschen, Kristian A1 - Diekkrüger, Bernd A1 - Evers, Mariele A1 - Höllermann, Britta A1 - Steinbach, Stefanie A1 - Thonfeld, Frank T1 - The impact of land use/land cover change (LULCC) on water resources in a tropical catchment in Tanzania under different climate change scenarios JF - Sustainability N2 - Many parts of sub-Saharan Africa (SSA) are prone to land use and land cover change (LULCC). In many cases, natural systems are converted into agricultural land to feed the growing population. However, despite climate change being a major focus nowadays, the impacts of these conversions on water resources, which are essential for agricultural production, is still often neglected, jeopardizing the sustainability of the socio-ecological system. This study investigates historic land use/land cover (LULC) patterns as well as potential future LULCC and its effect on water quantities in a complex tropical catchment in Tanzania. It then compares the results using two climate change scenarios. The Land Change Modeler (LCM) is used to analyze and to project LULC patterns until 2030 and the Soil and Water Assessment Tool (SWAT) is utilized to simulate the water balance under various LULC conditions. Results show decreasing low flows by 6–8% for the LULC scenarios, whereas high flows increase by up to 84% for the combined LULC and climate change scenarios. The effect of climate change is stronger compared to the effect of LULCC, but also contains higher uncertainties. The effects of LULCC are more distinct, although crop specific effects show diverging effects on water balance components. This study develops a methodology for quantifying the impact of land use and climate change and therefore contributes to the sustainable management of the investigated catchment, as it shows the impact of environmental change on hydrological extremes (low flow and floods) and determines hot spots, which are critical for environmental development. KW - SWAT model KW - Land Change Modeler KW - Scenario analysis KW - Extreme flows KW - Tanzania KW - Kilombero Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193825 SN - 2071-1050 VL - 11 IS - 24 ER - TY - JOUR A1 - Villalobos, Alvaro S. A1 - Wiese, Jutta A1 - Imhoff, Johannes F. A1 - Dorador, Cristina A1 - Keller, Alexander A1 - Hentschel, Ute T1 - Systematic affiliation and genome analysis of Subtercola vilae DB165T with particular emphasis on cold adaptation of an isolate from a high-altitude cold volcano lake JF - Microorganisms N2 - Among the Microbacteriaceae the species of Subtercola and Agreia form closely associated clusters. Phylogenetic analysis demonstrated three major phylogenetic branches of these species. One of these branches contains the two psychrophilic species Subtercola frigoramans and Subtercola vilae, together with a larger number of isolates from various cold environments. Genomic evidence supports the separation of Agreia and Subtercola species. In order to gain insight into the ability of S. vilae to adapt to life in this extreme environment, we analyzed the genome with a particular focus on properties related to possible adaptation to a cold environment. General properties of the genome are presented, including carbon and energy metabolism, as well as secondary metabolite production. The repertoire of genes in the genome of S. vilae DB165\(^T\) linked to adaptations to the harsh conditions found in Llullaillaco Volcano Lake includes several mechanisms to transcribe proteins under low temperatures, such as a high number of tRNAs and cold shock proteins. In addition, S. vilae DB165\(^T\) is capable of producing a number of proteins to cope with oxidative stress, which is of particular relevance at low temperature environments, in which reactive oxygen species are more abundant. Most important, it obtains capacities to produce cryo-protectants, and to combat against ice crystal formation, it produces ice-binding proteins. Two new ice-binding proteins were identified which are unique to S. vilae DB165\(^T\). These results indicate that S. vilae has the capacity to employ different mechanisms to live under the extreme and cold conditions prevalent in Llullaillaco Volcano Lake. KW - cold adaptation KW - Subtercola vilae KW - genome analysis KW - systematic affiliation KW - Llullaillaco Volcano Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197394 SN - 2076-2607 VL - 7 IS - 4 ER - TY - JOUR A1 - González, María Magdalena A1 - Dorner, Daniela A1 - Bretz, Thomas A1 - García-González, José Andrés T1 - Unbiased long-term monitoring at TeV energies JF - Galaxies N2 - For the understanding of the variable, transient and non-thermal universe, unbiased long-term monitoring is crucial. To constrain the emission mechanisms at the highest energies, it is important to characterize the very high energy emission and its correlation with observations at other wavelengths. At very high energies, only a limited number of instruments is available. This article reviews the current status of monitoring of the extra-galactic sky at TeV energies. KW - monitoring KW - very high energies (VHE) KW - TeV energies Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197389 SN - 2075-4434 VL - 7 IS - 2 ER -