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Showing papers by "University of Erlangen-Nuremberg published in 2020"


Journal ArticleDOI
TL;DR: In this article, the authors present guidelines for the management of patients with coronary artery disease (CAD), which is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries.
Abstract: Coronary artery disease (CAD) is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries, whether obstructive or non-obstructive. This process can be modified by lifestyle adjustments, pharmacological therapies, and invasive interventions designed to achieve disease stabilization or regression. The disease can have long, stable periods but can also become unstable at any time, typically due to an acute atherothrombotic event caused by plaque rupture or erosion. However, the disease is chronic, most often progressive, and hence serious, even in clinically apparently silent periods. The dynamic nature of the CAD process results in various clinical presentations, which can be conveniently categorized as either acute coronary syndromes (ACS) or chronic coronary syndromes (CCS). The Guidelines presented here refer to the management of patients with CCS. The natural history of CCS is illustrated in Figure 1.

3,448 citations


Journal ArticleDOI
TL;DR: This Consensus Statement is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications to reduce misunderstanding and misinterpretation of research data generated in various experimental models.
Abstract: Epithelial-mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by 'the EMT International Association' (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.

931 citations


Journal ArticleDOI
Jens Kattge1, Gerhard Bönisch2, Sandra Díaz3, Sandra Lavorel  +751 moreInstitutions (314)
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements.
Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

882 citations


Journal ArticleDOI
TL;DR: A consensus between researchers in the field is reported on procedures for testing perovskite solar cell stability, which are based on the International Summit on Organic Photovoltaic Stability (ISOS) protocols, and additional procedures to account for properties specific to PSCs are proposed.
Abstract: Improving the long-term stability of perovskite solar cells is critical to the deployment of this technology. Despite the great emphasis laid on stability-related investigations, publications lack consistency in experimental procedures and parameters reported. It is therefore challenging to reproduce and compare results and thereby develop a deep understanding of degradation mechanisms. Here, we report a consensus between researchers in the field on procedures for testing perovskite solar cell stability, which are based on the International Summit on Organic Photovoltaic Stability (ISOS) protocols. We propose additional procedures to account for properties specific to PSCs such as ion redistribution under electric fields, reversible degradation and to distinguish ambient-induced degradation from other stress factors. These protocols are not intended as a replacement of the existing qualification standards, but rather they aim to unify the stability assessment and to understand failure modes. Finally, we identify key procedural information which we suggest reporting in publications to improve reproducibility and enable large data set analysis. Reliability of stability data for perovskite solar cells is undermined by a lack of consistency in the test conditions and reporting. This Consensus Statement outlines practices for testing and reporting stability tailoring ISOS protocols for perovskite devices.

621 citations


Journal ArticleDOI
TL;DR: A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries.
Abstract: Aims: The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. Methods and results: In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index >= 30 kg/m(2)) and diabetes has increased two- to three-fold during the last 30years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5-23.1%] vs. 15.7% (IQR 14.5-21.1%)}, diabetes [7.7% (IQR 7.1-10.1%) vs. 5.6% (IQR 4.8-7.0%)], and among males smoking [43.8% (IQR 37.4-48.0%) vs. 26.0% (IQR 20.9-31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0-10.8) vs. 16.7% (IQR 13.9-19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655-8115)] compared with high-income [2235 (IQR 1896-3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. Conclusion: A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest.

591 citations


Journal ArticleDOI
TL;DR: In this article, the authors investigated the joint design of the beamformers and AN covariance matrix at the AP and the phase shifters at the RISs for maximization of the system sum-rate while limiting the maximum information leakage to the potential eavesdroppers.
Abstract: In this paper, intelligent reflecting surfaces (IRSs) are employed to enhance the physical layer security in a challenging radio environment. In particular, a multi-antenna access point (AP) has to serve multiple single-antenna legitimate users, which do not have line-of-sight communication links, in the presence of multiple multi-antenna potential eavesdroppers whose channel state information (CSI) is not perfectly known. Artificial noise (AN) is transmitted from the AP to deliberately impair the eavesdropping channels for security provisioning. We investigate the joint design of the beamformers and AN covariance matrix at the AP and the phase shifters at the IRSs for maximization of the system sum-rate while limiting the maximum information leakage to the potential eavesdroppers. To this end, we formulate a robust non-convex optimization problem taking into account the impact of the imperfect CSI of the eavesdropping channels. To address the non-convexity of the optimization problem, an efficient algorithm is developed by capitalizing on alternating optimization, a penalty-based approach, successive convex approximation, and semidefinite relaxation. Simulation results show that IRSs can significantly improve the system secrecy performance compared to conventional architectures without IRS. Furthermore, our results unveil that, for physical layer security, uniformly distributing the reflecting elements among multiple IRSs is preferable over deploying them at a single IRS.

552 citations


Journal ArticleDOI
TL;DR: The updated recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.
Abstract: Objective To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA). Methods According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined. Results The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed. Conclusion These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.

492 citations


Journal ArticleDOI
TL;DR: Perovskite QD resurfacing is reported to achieve a bipolar shell consisting of an inner anion shell, and an outer shell comprised of cations and polar solvent molecules, to fabricate blue and green light-emitting diodes with improved mobility.
Abstract: Colloidal quantum dot (QD) solids are emerging semiconductors that have been actively explored in fundamental studies of charge transport1 and for applications in optoelectronics2. Forming high-quality QD solids—necessary for device fabrication—requires substitution of the long organic ligands used for synthesis with short ligands that provide increased QD coupling and improved charge transport3. However, in perovskite QDs, the polar solvents used to carry out the ligand exchange decompose the highly ionic perovskites4. Here we report perovskite QD resurfacing to achieve a bipolar shell consisting of an inner anion shell, and an outer shell comprised of cations and polar solvent molecules. The outer shell is electrostatically adsorbed to the negatively charged inner shell. This approach produces strongly confined perovskite QD solids that feature improved carrier mobility (≥0.01 cm2 V−1 s−1) and reduced trap density relative to previously reported low-dimensional perovskites. Blue-emitting QD films exhibit photoluminescence quantum yields exceeding 90%. By exploiting the improved mobility, we have been able to fabricate CsPbBr3 QD-based efficient blue and green light-emitting diodes. Blue devices with reduced trap density have an external quantum efficiency of 12.3%; the green devices achieve an external quantum efficiency of 22%. A solution-based ligand-exchange strategy enables the realization of close-packed quantum dot solid films with near-unity photoluminescence quantum yield and high charge carrier mobility.

451 citations


Posted Content
TL;DR: Face2Face addresses the under-constrained problem of facial identity recovery from monocular video by non-rigid model-based bundling and convincingly re-render the synthesized target face on top of the corresponding video stream such that it seamlessly blends with the real-world illumination.
Abstract: We present Face2Face, a novel approach for real-time facial reenactment of a monocular target video sequence (e.g., Youtube video). The source sequence is also a monocular video stream, captured live with a commodity webcam. Our goal is to animate the facial expressions of the target video by a source actor and re-render the manipulated output video in a photo-realistic fashion. To this end, we first address the under-constrained problem of facial identity recovery from monocular video by non-rigid model-based bundling. At run time, we track facial expressions of both source and target video using a dense photometric consistency measure. Reenactment is then achieved by fast and efficient deformation transfer between source and target. The mouth interior that best matches the re-targeted expression is retrieved from the target sequence and warped to produce an accurate fit. Finally, we convincingly re-render the synthesized target face on top of the corresponding video stream such that it seamlessly blends with the real-world illumination. We demonstrate our method in a live setup, where Youtube videos are reenacted in real time.

448 citations


Journal ArticleDOI
TL;DR: In this paper, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrants alone in postmenopaugmentation.
Abstract: Background In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopau...

393 citations


Journal ArticleDOI
TL;DR: The delocalization of exciton and electron wavefunction due to strong π-π packing of Y6 is the key for the high performance of this state-of-the-art OSC system.
Abstract: A major challenge for organic solar cell (OSC) research is how to minimize the tradeoff between voltage loss and charge generation. In early 2019, we reported a non-fullerene acceptor (named Y6) that can simultaneously achieve high external quantum efficiency and low voltage loss for OSC. Here, we use a combination of experimental and theoretical modeling to reveal the structure-property-performance relationships of this state-of-the-art OSC system. We find that the distinctive π–π molecular packing of Y6 not only exists in molecular single crystals but also in thin films. Importantly, such molecular packing leads to (i) the formation of delocalized and emissive excitons that enable small non-radiative voltage loss, and (ii) delocalization of electron wavefunctions at donor/acceptor interfaces that significantly reduces the Coulomb attraction between interfacial electron-hole pairs. These properties are critical in enabling highly efficient charge generation in OSC systems with negligible donor-acceptor energy offset. Y6, as a non-fullerene acceptor for organic solar cells, has attracted intensive attention because of the low voltage loss and high charge generation efficiency. Here, Zhang et al. find that the delocalization of exciton and electron wavefunction due to strong π-π packing of Y6 is the key for the high performance.

DOI
Claudia Backes1, Claudia Backes2, Amr M. Abdelkader3, Concepción Alonso4, Amandine Andrieux-Ledier5, Raul Arenal6, Raul Arenal7, Jon Azpeitia6, Nilanthy Balakrishnan8, Luca Banszerus9, Julien Barjon5, Ruben Bartali10, Sebastiano Bellani11, Claire Berger12, Claire Berger13, Reinhard Berger14, M.M. Bernal Ortega15, Carlo Bernard16, Peter H. Beton8, André Beyer17, Alberto Bianco18, Peter Bøggild19, Francesco Bonaccorso11, Gabriela Borin Barin20, Cristina Botas, Rebeca A. Bueno6, Daniel Carriazo21, Andres Castellanos-Gomez6, Meganne Christian, Artur Ciesielski18, Tymoteusz Ciuk, Matthew T. Cole, Jonathan N. Coleman1, Camilla Coletti11, Luigi Crema10, Huanyao Cun16, Daniela Dasler22, Domenico De Fazio3, Noel Díez, Simon Drieschner23, Georg S. Duesberg24, Roman Fasel20, Roman Fasel25, Xinliang Feng14, Alberto Fina15, Stiven Forti11, Costas Galiotis26, Costas Galiotis27, Giovanni Garberoglio28, Jorge M. Garcia6, Jose A. Garrido, Marco Gibertini29, Armin Gölzhäuser17, Julio Gómez, Thomas Greber16, Frank Hauke22, Adrian Hemmi16, Irene Hernández-Rodríguez6, Andreas Hirsch22, Stephen A. Hodge3, Yves Huttel6, Peter Uhd Jepsen19, I. Jimenez6, Ute Kaiser30, Tommi Kaplas31, HoKwon Kim29, Andras Kis29, Konstantinos Papagelis26, Konstantinos Papagelis32, Kostas Kostarelos33, Aleksandra Krajewska34, Kangho Lee24, Changfeng Li35, Harri Lipsanen35, Andrea Liscio, Martin R. Lohe14, Annick Loiseau5, Lucia Lombardi3, María Francisca López6, Oliver Martin22, Cristina Martín36, Lidia Martínez6, José A. Martín-Gago6, José I. Martínez6, Nicola Marzari29, Alvaro Mayoral37, Alvaro Mayoral7, John B. McManus1, Manuela Melucci, Javier Méndez6, Cesar Merino, Pablo Merino6, Andreas Meyer22, Elisa Miniussi16, Vaidotas Miseikis11, Neeraj Mishra11, Vittorio Morandi, Carmen Munuera6, Roberto Muñoz6, Hugo Nolan1, Luca Ortolani, A. K. Ott38, A. K. Ott3, Irene Palacio6, Vincenzo Palermo39, John Parthenios26, Iwona Pasternak40, Amalia Patanè8, Maurizio Prato21, Maurizio Prato41, Henri Prevost5, Vladimir Prudkovskiy12, Nicola M. Pugno42, Nicola M. Pugno43, Nicola M. Pugno44, Teófilo Rojo45, Antonio Rossi11, Pascal Ruffieux20, Paolo Samorì18, Léonard Schué5, Eki J. Setijadi10, Thomas Seyller46, Giorgio Speranza10, Christoph Stampfer9, I. Stenger5, Wlodek Strupinski40, Yuri Svirko31, Simone Taioli28, Simone Taioli47, Kenneth B. K. Teo, Matteo Testi10, Flavia Tomarchio3, Mauro Tortello15, Emanuele Treossi, Andrey Turchanin48, Ester Vázquez36, Elvira Villaro, Patrick Rebsdorf Whelan19, Zhenyuan Xia39, Rositza Yakimova, Sheng Yang14, G. Reza Yazdi, Chanyoung Yim24, Duhee Yoon3, Xianghui Zhang17, Xiaodong Zhuang14, Luigi Colombo49, Andrea C. Ferrari3, Mar García-Hernández6 
Trinity College, Dublin1, Heidelberg University2, University of Cambridge3, Autonomous University of Madrid4, Université Paris-Saclay5, Spanish National Research Council6, University of Zaragoza7, University of Nottingham8, RWTH Aachen University9, Kessler Foundation10, Istituto Italiano di Tecnologia11, University of Grenoble12, Georgia Institute of Technology13, Dresden University of Technology14, Polytechnic University of Turin15, University of Zurich16, Bielefeld University17, University of Strasbourg18, Technical University of Denmark19, Swiss Federal Laboratories for Materials Science and Technology20, Ikerbasque21, University of Erlangen-Nuremberg22, Technische Universität München23, Bundeswehr University Munich24, University of Bern25, Foundation for Research & Technology – Hellas26, University of Patras27, Center for Theoretical Studies, University of Miami28, École Polytechnique Fédérale de Lausanne29, University of Ulm30, University of Eastern Finland31, Aristotle University of Thessaloniki32, University of Manchester33, Polish Academy of Sciences34, Aalto University35, University of Castilla–La Mancha36, ShanghaiTech University37, University of Exeter38, Chalmers University of Technology39, Warsaw University of Technology40, University of Trieste41, Instituto Politécnico Nacional42, Queen Mary University of London43, University of Trento44, University of the Basque Country45, Chemnitz University of Technology46, Charles University in Prague47, University of Jena48, University of Texas at Dallas49
29 Jan 2020
TL;DR: In this article, the authors present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures, adopting a 'hands-on' approach, providing practical details and procedures as derived from literature and from the authors' experience, in order to enable the reader to reproduce the results.
Abstract: © 2020 The Author(s). We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resourceconsuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown.

Journal ArticleDOI
TL;DR: It is shown that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels, and Histopathology of the lungs and other organs from CO VID-19 patients showed congestions of numerous micro- Vessels by aggregated NETs associated with endothelial damage.


Journal ArticleDOI
TL;DR: The most recent developments of antibacterial biopolymeric nanofibrous wound dressings, particularly those made of biohybrids, are reviewed and their antibacterial efficiency is evaluated based on a comprehensive literature analysis.

Journal ArticleDOI
TL;DR: Whether such therapies may pose a risk — or even a benefit — in the context of the current COVID-19 pandemic is discussed.
Abstract: COVID-19, caused by the SARS-CoV-2 virus, has become pandemic. With sharply rising infection rates, patient groups characterized by an enhanced infection risk will be challenged by the virus. In this context, patients with chronic immune-mediated inflammatory diseases are of particular interest, as these diseases are characterized by an intrinsic immune dysfunction leading to inflammation that may enhance risk for severe infection. Immune-mediated inflammatory diseases are often treated with cytokine blocking therapy. This comment discusses whether such therapies may pose a risk — or even a benefit — in the context of the current COVID-19 pandemic.

30 Mar 2020
TL;DR: New features and enhanced algorithms made available in version 5.0 of the SCIP Optimization Suite, in particular for the LP solver SoPlex, the Steiner tree solver SCIP-Jack, the MISDP solverSCIP-SDP, and the parallelization framework UG are described.
Abstract: The SCIP Optimization Suite provides a collection of software packages for mathematical optimization centered around the constraint integer programming frame- work SCIP. This paper discusses enhancements and extensions contained in version 7.0 of the SCIP Optimization Suite. The new version features the parallel presolving library PaPILO as a new addition to the suite. PaPILO 1.0 simplifies mixed-integer linear op- timization problems and can be used stand-alone or integrated into SCIP via a presolver plugin. SCIP 7.0 provides additional support for decomposition algorithms. Besides im- provements in the Benders’ decomposition solver of SCIP, user-defined decomposition structures can be read, which are used by the automated Benders’ decomposition solver and two primal heuristics. Additionally, SCIP 7.0 comes with a tree size estimation that is used to predict the completion of the overall solving process and potentially trigger restarts. Moreover, substantial performance improvements of the MIP core were achieved by new developments in presolving, primal heuristics, branching rules, conflict analysis, and symmetry handling. Last, not least, the report presents updates to other components and extensions of the SCIP Optimization Suite, in particular, the LP solver SoPlex and the mixed-integer semidefinite programming solver SCIP-SDP.

Journal ArticleDOI
TL;DR: An adaptive access scheme is proposed, which adapts the access latency to guarantee reliable massive access for practical systems with unknown channel sparsity level and the state evolution of the proposed GMMV-AMP algorithm is derived to predict its performance.
Abstract: This paper considers massive access in massive multiple-input multiple-output (MIMO) systems and proposes an adaptive active user detection and channel estimation scheme based on compressive sensing. By exploiting the sporadic traffic of massive connected user equipments and the virtual angular domain sparsity of massive MIMO channels, the proposed scheme can support massive access with dramatically reduced access latency. Specifically, we design non-orthogonal pseudo-random pilots for uplink broadband massive access, and formulate the active user detection and channel estimation as a generalized multiple measurement vector compressive sensing problem. Furthermore, by leveraging the structured sparsity of the uplink channel matrix, we propose an efficient generalized multiple measurement vector approximate message passing (GMMV-AMP) algorithm to realize joint active user detection and channel estimation based on a spatial domain or an angular domain channel model. To jointly exploit the channel sparsity present in both the spatial and the angular domains for enhanced performance, a Turbo-GMMV-AMP algorithm is developed for detecting the active users and estimating their channels in an alternating manner. Finally, an adaptive access scheme is proposed, which adapts the access latency to guarantee reliable massive access for practical systems with unknown channel sparsity level. Additionally, the state evolution of the proposed GMMV-AMP algorithm is derived to predict its performance. Simulation results demonstrate the superiority of the proposed active user detection and channel estimation schemes compared to several baseline schemes.

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TL;DR: This letter studies the sum-rate and shows analytically how RS unifies, outperforms, and specializes to SDMA, OMA, NOMA, and multicasting as a function of the disparity of the channel strengths and the angle between the user channel directions.
Abstract: Considering a two-user multi-antenna Broadcast Channel, this letter shows that linearly precoded Rate-Splitting (RS) with Successive Interference Cancellation (SIC) receivers is a flexible framework for non-orthogonal transmission that generalizes, and subsumes as special cases, four seemingly different strategies, namely Space Division Multiple Access (SDMA) based on linear precoding, Orthogonal Multiple Access (OMA), Non-Orthogonal Multiple Access (NOMA) based on linearly precoded superposition coding with SIC, and physical-layer multicasting. This letter studies the sum-rate and shows analytically how RS unifies, outperforms, and specializes to SDMA, OMA, NOMA, and multicasting as a function of the disparity of the channel strengths and the angle between the user channel directions.

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M. G. Aartsen1, Markus Ackermann, Jenni Adams1, Juanan Aguilar2  +361 moreInstitutions (48)
TL;DR: The results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector.
Abstract: This Letter presents the results from pointlike neutrino source searches using ten years of IceCube data collected between April 6, 2008 and July 10, 2018. We evaluate the significance of an astrophysical signal from a pointlike source looking for an excess of clustered neutrino events with energies typically above ∼1 TeV among the background of atmospheric muons and neutrinos. We perform a full-sky scan, a search within a selected source catalog, a catalog population study, and three stacked Galactic catalog searches. The most significant point in the northern hemisphere from scanning the sky is coincident with the Seyfert II galaxy NGC 1068, which was included in the source catalog search. The excess at the coordinates of NGC 1068 is inconsistent with background expectations at the level of 2.9σ after accounting for statistical trials from the entire catalog. The combination of this result along with excesses observed at the coordinates of three other sources, including TXS 0506+056, suggests that, collectively, correlations with sources in the northern catalog are inconsistent with background at 3.3σ significance. The southern catalog is consistent with background. These results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector.

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16 Apr 2020-Gut
TL;DR: The current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation and the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.
Abstract: The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome coronavirus 2. Although COVID-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to COVID-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of COVID-19. Here, the current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.

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TL;DR: An evidence-based, joint global consensus guideline approach to the management of Desmoid tumor focussing on molecular genetics, indications for an active treatment, and available systemic therapeutic options is presented.

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Marco Ajello1, R. Angioni2, R. Angioni3, Magnus Axelsson4  +149 moreInstitutions (42)
TL;DR: The 4LAC catalog of active galactic nuclei (AGNs) detected by the Fermi Gamma-ray Space Telescope Large Area Telescope (4LAC) between 2008 August 4 and 2016 August 2 contains 2863 objects located at high Galactic latitudes (|b|>10°deg}).
Abstract: The fourth catalog of active galactic nuclei (AGNs) detected by the Fermi Gamma-ray Space Telescope Large Area Telescope (4LAC) between 2008 August 4 and 2016 August 2 contains 2863 objects located at high Galactic latitudes (|b|>10{\deg}). It includes 85% more sources than the previous 3LAC catalog based on 4 years of data. AGNs represent at least 79% of the high-latitude sources in the fourth Fermi-Large Area Telescope Source Catalog (4FGL), which covers the energy range from 50 MeV to 1 TeV. In addition, 344 gamma-ray AGNs are found at low Galactic latitudes. Most of the 4LAC AGNs are blazars (98%), while the remainder are other types of AGNs. The blazar population consists of 24% Flat Spectrum Radio Quasars (FSRQs), 38% BL Lac-type objects (BL Lacs), and 38% blazar candidates of unknown types (BCUs). On average, FSRQs display softer spectra and stronger variability in the gamma-ray band than BL Lacs do, confirming previous findings. All AGNs detected by ground-based atmospheric Cherenkov telescopes are also found in the 4LAC.

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TL;DR: It is shown that both mice and humans with autoimmune arthritis can have dysbiosis and barrier leakiness prior to major signs of inflammatory arthritis, and treatment of mice with a zonulin antagonist can limit collagen-induced arthritis.
Abstract: Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function. Intestinal dysbiosis is associated with an ever-growing list of autoimmune diseases. Here the authors show that both mice and humans with autoimmune arthritis can have dysbiosis and barrier leakiness prior to major signs of inflammatory arthritis, and treatment of mice with a zonulin antagonist can limit collagen-induced arthritis.

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TL;DR: This comprehensive review will stimulate the design of new experiments and guide the selection of appropriate constitutive models for specific applications, and propose appropriate mechanical modeling approaches that are as complex as necessary but as simple as possible.
Abstract: Brain tissue is not only one of the most important but also the most complex and compliant tissue in the human body. While long underestimated, increasing evidence confirms that mechanics plays a critical role in modulating brain function and dysfunction. Computational simulations–based on the field equations of nonlinear continuum mechanics–can provide important insights into the underlying mechanisms of brain injury and disease that go beyond the possibilities of traditional diagnostic tools. Realistic numerical predictions, however, require mechanical models that are capable of capturing the complex and unique characteristics of this ultrasoft, heterogeneous, and active tissue. In recent years, contradictory experimental results have caused confusion and hindered rapid progress. In this review, we carefully assess the challenges associated with brain tissue testing and modeling, and work out the most important characteristics of brain tissue behavior on different length and time scales. Depending on the application of interest, we propose appropriate mechanical modeling approaches that are as complex as necessary but as simple as possible. This comprehensive review will, on the one hand, stimulate the design of new experiments and, on the other hand, guide the selection of appropriate constitutive models for specific applications. Mechanical models that capture the complex behavior of nervous tissues and are accurately calibrated with reliable and comprehensive experimental data are key to performing reliable predictive simulations. Ultimately, mathematical modeling and computational simulations of the brain are useful for both biomedical and clinical communities, and cover a wide range of applications ranging from predicting disease progression and estimating injury risk to planning surgical procedures.


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Haoyu Zhang1, Haoyu Zhang2, Thomas U. Ahearn1, Julie Lecarpentier3  +299 moreInstitutions (123)
TL;DR: A genome-wide association study including 133,384 breast cancer cases and 113,789 controls plus 18,908 BRCA1 mutation carriers of European ancestry provides an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

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TL;DR: The CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented and caution is suggested in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI.
Abstract: Author(s): Zhang, Lili; Awadalla, Magid; Mahmood, Syed S; Nohria, Anju; Hassan, Malek Z O; Thuny, Franck; Zlotoff, Daniel A; Murphy, Sean P; Stone, James R; Golden, Doll Lauren Alexandra; Alvi, Raza M; Rokicki, Adam; Jones-O'Connor, Maeve; Cohen, Justine V; Heinzerling, Lucie M; Mulligan, Connor; Armanious, Merna; Barac, Ana; Forrestal, Brian J; Sullivan, Ryan J; Kwong, Raymond Y; Yang, Eric H; Damrongwatanasuk, Rongras; Chen, Carol L; Gupta, Dipti; Kirchberger, Michael C; Moslehi, Javid J; Coelho-Filho, Otavio R; Ganatra, Sarju; Rizvi, Muhammad A; Sahni, Gagan; Tocchetti, Carlo G; Mercurio, Valentina; Mahmoudi, Michael; Lawrence, Donald P; Reynolds, Kerry L; Weinsaft, Jonathan W; Baksi, A John; Ederhy, Stephane; Groarke, John D; Lyon, Alexander R; Fradley, Michael G; Thavendiranathan, Paaladinesh; Neilan, Tomas G | Abstract: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

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TL;DR: This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record.

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TL;DR: The survey indicates that the impact of COVID-19 on STEMI presentations is likely to be substantial, with both lower presentations and a higher rate of delayed presentations occurring.
Abstract: Aims The COVID-19 pandemic required a significant redeployment of worldwide healthcare resources. Fear of infection, national lockdowns and altered healthcare priorities have the potential to impact utilisation of healthcare resources for non-communicable diseases. To survey health professionals' views of the impact of the COVID-19 pandemic on the rate and timing of admission of patients with ST-elevation myocardial infarction (STEMI), the European Society of Cardiology (ESC) administered an internet-based questionnaire to cardiologists and cardiovascular nurses across 6 continents. Methods and results 3101 responses were received from 141 countries across 6 continents. 88.3% responded that their country was in "total lockdown" and 7.1% in partial lockdown. 78.8% responded that the number of patients presenting with STEMI was reduced since the coronavirus outbreak and 65.2% indicated that the reduction in STEMI presentations was >40%. Approximately 60% of all respondents reported that STEMI patients presented later than usual and 58.5% that >40% of STEMI patients admitted to hospital presented beyond the optimal window for primary percutaneous intervention (PCI) or thrombolysis. Independent predictors of the reported higher rate of delayed STEMI presentation were a country in total lockdown, >100 COVID-19 cases admitted locally, and the complete restructuring of the local cardiology service. Conclusion The survey indicates that the impact of COVID-19 on STEMI presentations is likely to be substantial, with both lower presentations and a higher rate of delayed presentations occurring. This has potentially important ramifications for future healthcare and policy planning in the event of further waves of this pandemic.