TY - JOUR A1 - Mayer, Alexander E. A1 - Löffler, Mona C. A1 - Loza Valdés, Angel E. A1 - Schmitz, Werner A1 - El-Merahbi, Rabih A1 - Trujillo-Viera, Jonathan A1 - Erk, Manuela A1 - Zhang, Thianzhou A1 - Braun, Ursula A1 - Heikenwalder, Mathias A1 - Leitges, Michael A1 - Schulze, Almut A1 - Sumara, Grzegorz T1 - The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling JF - Science Signaling N2 - Hepatic activation of protein kinase C (PKC) isoforms by diacylglycerol (DAG) promotes insulin resistance and contributes to the development of type 2 diabetes (T2D). The closely related protein kinase D (PKD) isoforms act as effectors for DAG and PKC. Here, we showed that PKD3 was the predominant PKD isoform expressed in hepatocytes and was activated by lipid overload. PKD3 suppressed the activity of downstream insulin effectors including the kinase AKT and mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2). Hepatic deletion of PKD3 in mice improved insulin-induced glucose tolerance. However, increased insulin signaling in the absence of PKD3 promoted lipogenesis mediated by SREBP (sterol regulatory element-binding protein) and consequently increased triglyceride and cholesterol content in the livers of PKD3-deficient mice fed a high-fat diet. Conversely, hepatic-specific overexpression of a constitutively active PKD3 mutant suppressed insulin-induced signaling and caused insulin resistance. Our results indicate that PKD3 provides feedback on hepatic lipid production and suppresses insulin signaling. Therefore, manipulation of PKD3 activity could be used to decrease hepatic lipid content or improve hepatic insulin sensitivity. KW - Protein kinase D3 (PKD3) KW - cholesterol KW - diacylglycerol (DAG) KW - liver KW - metabolism Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250025 ET - accepted manuscript ER - TY - JOUR A1 - Schlottmann, Elisabeth A1 - Schicke, David A1 - Krüger, Felix A1 - Lingnau, Benjamin A1 - Schneider, Christian A1 - Höfling, Sven A1 - Lüdge, Kathy A1 - Porte, Xavier A1 - Reitzenstein, Stephan T1 - Stochastic polarization switching induced by optical injection in bimodal quantum-dot micropillar lasers JF - Optics Express N2 - Mutual coupling and injection locking of semiconductor lasers is of great interest in non-linear dynamics and its applications for instance in secure data communication and photonic reservoir computing. Despite its importance, it has hardly been studied in microlasers operating at mu W light levels. In this context, vertically emitting quantum dot micropillar lasers are of high interest. Usually, their light emission is bimodal, and the gain competition of the associated linearly polarized fundamental emission modes results in complex switching dynamics. We report on selective optical injection into either one of the two fundamental mode components of a bimodal micropillar laser. Both modes can lock to the master laser and influence the non-injected mode by reducing the available gain. We demonstrate that the switching dynamics can be tailored externally via optical injection in very good agreement with our theory based on semi-classical rate equations. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement KW - Nonlinear Dynamics KW - Bistability KW - Generation KW - Subject KW - Regimes KW - Physics KW - Vcsels Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228603 VL - 27 IS - 20 ER - TY - JOUR A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Hackenberg, Stephan T1 - Current Understanding of Nasal Epithelial Cell Mis-Differentiation JF - Journal of Inflammation Research N2 - The functional role of the respiratory epithelium is to generate a physical barrier. In addition, the epithelium supports the innate and acquired immune system through various cytokines and chemokines. However, epithelial cells are also involved in the pathogenesis of various respiratory diseases, some of which are mediated by increased permeability of the mucosal membrane or disturbed mucociliary transport. In addition, it has been shown that epithelial cells are involved in the development of inflammatory respiratory diseases. The following review article focuses on the aspects of epithelial mis-differentiation, in particular with respect to nasal mucosal barrier function, epithelial immunogenicity, nasal epithelial-mesenchymal transition and nasal microbiome. KW - nasal mucosal barrier function KW - tight junction KW - epithelial-mesenchymal transition KW - microbiome Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228562 VL - 12 ER - TY - JOUR A1 - Rasche, Leo A1 - Kumar, Manoj A1 - Gershner, Grant A1 - Samant, Rohan A1 - Van Hemert, Rudy A1 - Heidemeier, Anke A1 - Lapa, Constantin A1 - Bley, Thorsten A1 - Buck, Andreas A1 - McDonald, James A1 - Hillengass, Jens A1 - Epstein, Joshua A1 - Thanendrarajan, Sharmilan A1 - Schinke, Carolina A1 - van Rhee, Frits A1 - Zangari, Maurizio A1 - Barlogie, Bart A1 - Davies, Faith E. A1 - Morgan, Gareth J. A1 - Weinhold, Niels T1 - Lack of Spleen Signal on Diffusion Weighted MRI is associated with High Tumor Burden and Poor Prognosis in Multiple Myeloma: A Link to Extramedullary Hematopoiesis? JF - Theranostics N2 - Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM. KW - multiple myeloma KW - diffusion weighted mri KW - spleen KW - tumor burden KW - high risk KW - extramedullary hematopoiesis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224982 VL - 9 IS - 16 ER - TY - JOUR A1 - Roy, Denis Claude A1 - Lachance, Sylvie A1 - Cohen, Sandra A1 - Delisle, Jean-Sébastien A1 - Kiss, Thomas A1 - Sauvageau, Guy A1 - Busque, Lambert A1 - Ahmad, Imran A1 - Bernard, Lea A1 - Bambace, Nadia A1 - Boumédine, Radia S. A1 - Guertin, Marie-Claude A1 - Rezvani, Katayoun A1 - Mielke, Stephan A1 - Perreault, Claude A1 - Roy, Jean T1 - Allodepleted T-cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft-versus-host disease (GVHD) in the absence of GVHD prophylaxis JF - British Journal of Haematology N2 - Graft-versus-host disease (GVHD) is a major cause of transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and presents a challenge in haploidentical HSCT. GVHD may be prevented by ex vivo graft T-cell depletion or in vivo depletion of proliferating lymphocytes. However, both approaches pose significant risks, particularly infections and relapse, compromising survival. A photodepletion strategy to eliminate alloreactive T cells from mismatched donor lymphocyte infusions (enabling administration without immunosuppression), was used to develop ATIR101, an adjunctive therapy for use after haploidentical HSCT. In this phase I dose-finding study, 19 adults (median age: 54 years) with high-risk haematological malignancies were treated with T-cell-depleted human leucocyte antigen-haploidentical myeloablative HSCT followed by ATIR101 at doses of 1 x 10(4)-5 x 10(6) CD3(+) cells/kg (median 31 days post-transplant). No patient received post-transplant immunosuppression or developed grade III/IV acute GVHD, demonstrating the feasibility of ATIR101 infusion for evaluation in two subsequent phase 2 studies. Additionally, we report long-term follow -up of patients treated with ATIR101 in this study. At 1 year, all 9 patients receiving doses of 0 center dot 3-2 x 10(6) CD3(+) cells/kg ATIR101 remained free of serious infections and after more than 8 years, TRM was 0%, relapse-related mortality was 33% and overall survival was 67% in these patients. KW - haematopoietic stem cell KW - stem cell transplantation KW - graft-versus-host-disease KW - cell therapy and immunotherapy Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227075 VL - 186 IS - 5 ER - TY - JOUR A1 - Groll, J A1 - Burdick, J A A1 - Cho, D-W A1 - Derby, B A1 - Gelinsky, M A1 - Heilshorn, S C A1 - Jüngst, T A1 - Malda, J A1 - Mironov, V A A1 - Nakayama, K A1 - Ovsianikov, A A1 - Sun, W A1 - Takeuchi, S A1 - Yoo, J J A1 - Woodfield, T B F T1 - A definition of bioinks and their distinction from biomaterial inks JF - Biofabrication N2 - Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384–402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks. KW - bioink KW - biomaterial ink KW - definition Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-253993 VL - 11 IS - 1 ER - TY - JOUR A1 - Sierra, Miguel A. A1 - Sánchez, David A1 - Gutierrez, Rafael A1 - Cuniberti, Gianaurelio A1 - Domínguez-Adame, Francisco A1 - Díaz, Elena T1 - Spin-polarized electron transmission in DNA-like systems JF - Biomolecules N2 - The helical distribution of the electronic density in chiral molecules, such as DNA and bacteriorhodopsin, has been suggested to induce a spin–orbit coupling interaction that may lead to the so-called chirality-induced spin selectivity (CISS) effect. Key ingredients for the theoretical modelling are, in this context, the helically shaped potential of the molecule and, concomitantly, a Rashba-like spin–orbit coupling due to the appearance of a magnetic field in the electron reference frame. Symmetries of these models clearly play a crucial role in explaining the observed effect, but a thorough analysis has been largely ignored in the literature. In this work, we present a study of these symmetries and how they can be exploited to enhance chiral-induced spin selectivity in helical molecular systems. KW - chirality-induced spin selectivity KW - helical molecules KW - spin transport KW - spin polarization KW - DNA electronic transport Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193813 SN - 2218-273X VL - 10 IS - 1 ER - TY - JOUR A1 - Schleicher, Bernd A1 - Arbet-Engels, Axel A1 - Baack, Dominik A1 - Balbo, Matteo A1 - Biland, Adrian A1 - Blank, Michael A1 - Bretz, Thomas A1 - Bruegge, Kai A1 - Bulinski, Michael A1 - Buss, Jens A1 - Doerr, Manuel A1 - Dorner, Daniela A1 - Elsaesser, Dominik A1 - Grischagin, Sergej A1 - Hildebrand, Dorothee A1 - Linhoff, Lena A1 - Mannheim, Karl A1 - Mueller, Sebastian Achim A1 - Neise, Dominik A1 - Neronov, Andrii A1 - Noethe, Maximilian A1 - Paravac, Aleksander A1 - Rhode, Wolfgang A1 - Schulz, Florian A1 - Sedlaczek, Kevin A1 - Shukla, Amit A1 - Sliusar, Vitalii A1 - Willert, Elan A1 - Walter, Roland T1 - Fractional Variability—A Tool to Study Blazar Variability JF - Galaxies N2 - Active Galactic Nuclei emit radiation over the whole electromagnetic spectrum up to TeV energies. Blazars are one subtype with their jets pointing towards the observer. One of their typical features is extreme variability on timescales, from minutes to years. The fractional variability is an often used parameter for investigating the degree of variability of a light curve. Different detection methods and sensitivities of the instruments result in differently binned data and light curves with gaps. As they can influence the physics interpretation of the broadband variability, the effects of these differences on the fractional variability need to be studied. In this paper, we study the systematic effects of completeness in time coverage and the sampling rate. Using public data from instruments monitoring blazars in various energy ranges, we study the variability of the bright TeV blazars Mrk 421 and Mrk 501 over the electromagnetic spectrum, taking into account the systematic effects, and compare our findings with previous results. Especially in the TeV range, the fractional variability is higher than in previous studies, which can be explained by the much longer (seven years compared to few weeks) and more complete data sample. KW - blazars KW - variability KW - fractional variability KW - active galactic nuclei Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197348 SN - 2075-4434 VL - 7 IS - 2 ER - TY - JOUR A1 - Rödel, Michaela A1 - Teßmar, Jörg A1 - Groll, Jürgen A1 - Gbureck, Uwe T1 - Tough and Elastic alpha-Tricalcium Phosphate Cement Composites with Degradable PEG-Based Cross-Linker JF - Materials N2 - Dual setting cements composed of an in situ forming hydrogel and a reactive mineral phase combine high compressive strength of the cement with sufficient ductility and bending strength of the polymeric network. Previous studies were focused on the modification with non-degradable hydrogels based on 2-hydroxyethyl methacrylate (HEMA). Here, we describe the synthesis of suitable triblock degradable poly(ethylene glycol)-poly(lactide) (PEG-PLLA) cross-linker to improve the resorption capacity of such composites. A study with four different formulations was established. As reference, pure hydroxyapatite (HA) cements and composites with 40 wt% HEMA in the liquid cement phase were produced. Furthermore, HEMA was modified with 10 wt% of PEG-PLLA cross-linker or a test series containing only 25% cross-linker was chosen for composites with a fully degradable polymeric phase. Hence, we developed suitable systems with increased elasticity and 5-6 times higher toughn ess values in comparison to pure inorganic cement matrix. Furthermore, conversion rate from alpha-tricalcium phosphate (alpha-TCP) to HA was still about 90% for all composite formulations, whereas crystal size decreased. Based on this material development and advancement for a dual setting system, we managed to overcome the drawback of brittleness for pure calcium phosphate cements. KW - dual setting system KW - bending strength KW - calcium phosphate cement KW - composite material KW - HEMA KW - hydroxyapatite KW - free radical polymerization Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226437 VL - 12 IS - 53 ER - 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 -