Showing papers by "University of Jena published in 2019"
TL;DR: It is argued that contextual cues should be used as part of deep learning to gain further process understanding of Earth system science problems, improving the predictive ability of seasonal forecasting and modelling of long-range spatial connections across multiple timescales.
Abstract: Machine learning approaches are increasingly used to extract patterns and insights from the ever-increasing stream of geospatial data, but current approaches may not be optimal when system behaviour is dominated by spatial or temporal context. Here, rather than amending classical machine learning, we argue that these contextual cues should be used as part of deep learning (an approach that is able to extract spatio-temporal features automatically) to gain further process understanding of Earth system science problems, improving the predictive ability of seasonal forecasting and modelling of long-range spatial connections across multiple timescales, for example. The next step will be a hybrid modelling approach, coupling physical process models with the versatility of data-driven machine learning.
2,014 citations
08 Aug 2019
TL;DR: A comprehensive overview and analysis of the most recent research in machine learning principles, algorithms, descriptors, and databases in materials science, and proposes solutions and future research paths for various challenges in computational materials science.
Abstract: One of the most exciting tools that have entered the material science toolbox in recent years is machine learning. This collection of statistical methods has already proved to be capable of considerably speeding up both fundamental and applied research. At present, we are witnessing an explosion of works that develop and apply machine learning to solid-state systems. We provide a comprehensive overview and analysis of the most recent research in this topic. As a starting point, we introduce machine learning principles, algorithms, descriptors, and databases in materials science. We continue with the description of different machine learning approaches for the discovery of stable materials and the prediction of their crystal structure. Then we discuss research in numerous quantitative structure–property relationships and various approaches for the replacement of first-principle methods by machine learning. We review how active learning and surrogate-based optimization can be applied to improve the rational design process and related examples of applications. Two major questions are always the interpretability of and the physical understanding gained from machine learning models. We consider therefore the different facets of interpretability and their importance in materials science. Finally, we propose solutions and future research paths for various challenges in computational materials science.
1,301 citations
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
698 citations
TL;DR: SIRIUS 4 is a fast and highly accurate tool for molecular structure interpretation from mass-spectrometry-based metabolomics data and integrates CSI:FingerID for searching in molecular structure databases.
Abstract: Mass spectrometry is a predominant experimental technique in metabolomics and related fields, but metabolite structural elucidation remains highly challenging. We report SIRIUS 4 (https://bio.informatik.uni-jena.de/sirius/), which provides a fast computational approach for molecular structure identification. SIRIUS 4 integrates CSI:FingerID for searching in molecular structure databases. Using SIRIUS 4, we achieved identification rates of more than 70% on challenging metabolomics datasets. SIRIUS 4 is a fast and highly accurate tool for molecular structure interpretation from mass-spectrometry-based metabolomics data.
620 citations
Lawrence Livermore National Laboratory1, University of Rochester2, Rutherford Appleton Laboratory3, École Polytechnique4, Ohio State University5, University of Michigan6, University of Jena7, Russian Academy of Sciences8, Osaka University9, Academy of Sciences of the Czech Republic10, Chinese Academy of Sciences11, Shanghai Jiao Tong University12, Gwangju Institute of Science and Technology13, Colorado State University14, University of Szeged15
TL;DR: In this paper, the authors provide a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed, and what technologies are to be deployed to get to these new regimes, and some critical issues facing their development.
Abstract: In the 2015 review paper 'Petawatt Class Lasers Worldwide' a comprehensive overview of the current status of highpower facilities of >200 TW was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multidisciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
559 citations
TL;DR: Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide and can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Abstract: Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
472 citations
TL;DR: In this paper, the mass, spin, and redshift distributions of binary black hole (BBH) mergers with LIGO and Advanced Virgo observations were analyzed using phenomenological population models.
Abstract: We present results on the mass, spin, and redshift distributions with phenomenological population models using the 10 binary black hole (BBH) mergers detected in the first and second observing runs completed by Advanced LIGO and Advanced Virgo. We constrain properties of the BBH mass spectrum using models with a range of parameterizations of the BBH mass and spin distributions. We find that the mass distribution of the more massive BH in such binaries is well approximated by models with no more than 1% of BHs more massive than 45 M and a power-law index of (90% credibility). We also show that BBHs are unlikely to be composed of BHs with large spins aligned to the orbital angular momentum. Modeling the evolution of the BBH merger rate with redshift, we show that it is flat or increasing with redshift with 93% probability. Marginalizing over uncertainties in the BBH population, we find robust estimates of the BBH merger rate density of R= (90% credibility). As the BBH catalog grows in future observing runs, we expect that uncertainties in the population model parameters will shrink, potentially providing insights into the formation of BHs via supernovae, binary interactions of massive stars, stellar cluster dynamics, and the formation history of BHs across cosmic time.
464 citations
TL;DR: This review summarizes significant advances from both experimental and theoretical calculations with a focus on comparing the intercalation of three alkali metal ions (Li+, Na+, K+) into graphite and aims to clarify the intimate host-guest relationships and the underlying mechanisms.
Abstract: Reversibly intercalating ions into host materials for electrochemical energy storage is the essence of the working principle of rocking-chair type batteries. The most relevant example is the graphite anode for rechargeable Li-ion batteries which has been commercialized in 1991 and still represents the benchmark anode in Li-ion batteries 30 years later. Learning from past lessons on alkali metal intercalation in graphite, recent breakthroughs in sodium and potassium intercalation in graphite have been demonstrated for Na-ion batteries and K-ion batteries. Interestingly, some significant differences proved to exist for the intercalation of Na+ and K+ into graphite compared with the Li+ case. Such different host-guest interactions are unique depending on the host materials and electrolytes, which greatly contribute to a deeper understanding of intercalation-type electrode materials for next generation alkali metal ion batteries. This review summarizes significant advances from both experimental and theoretical calculations with a focus on comparing the intercalation of three alkali metal ions (Li+, Na+, K+) into graphite and aims to clarify the intimate host-guest relationships and the underlying mechanisms. New approaches developed to achieve favorable intercalation coupled with the challenges in this field are also discussed. We also extrapolate alkali metal ion intercalation in graphite to mono-/multi-valent ions in layered electrode materials, which will deepen the understanding of intercalation chemistry and provide guidance to explore new guests and hosts.
447 citations
TL;DR: This paper discusses suited systems, surveys the relevant literature, and defines future research needs for these warehousing systems especially suited for e-commerce retailers.
346 citations
TL;DR: Beetles diversity appears to have resulted from multiple factors, including low extinction rates over a long evolutionary history, codiversification with angiosperms, and adaptive radiations of specialized herbivorous beetles following convergent horizontal transfers of microbial genes encoding PCWDEs.
Abstract: The order Coleoptera (beetles) is arguably the most speciose group of animals, but the evolutionary history of beetles, including the impacts of plant feeding (herbivory) on beetle diversification, remain poorly understood. We inferred the phylogeny of beetles using 4,818 genes for 146 species, estimated timing and rates of beetle diversification using 89 genes for 521 species representing all major lineages and traced the evolution of beetle genes enabling symbiont-independent digestion of lignocellulose using 154 genomes or transcriptomes. Phylogenomic analyses of these uniquely comprehensive datasets resolved previously controversial beetle relationships, dated the origin of Coleoptera to the Carboniferous, and supported the codiversification of beetles and angiosperms. Moreover, plant cell wall-degrading enzymes (PCWDEs) obtained from bacteria and fungi via horizontal gene transfers may have been key to the Mesozoic diversification of herbivorous beetles—remarkably, both major independent origins of specialized herbivory in beetles coincide with the first appearances of an arsenal of PCWDEs encoded in their genomes. Furthermore, corresponding (Jurassic) diversification rate increases suggest that these novel genes triggered adaptive radiations that resulted in nearly half of all living beetle species. We propose that PCWDEs enabled efficient digestion of plant tissues, including lignocellulose in cell walls, facilitating the evolution of uniquely specialized plant-feeding habits, such as leaf mining and stem and wood boring. Beetle diversity thus appears to have resulted from multiple factors, including low extinction rates over a long evolutionary history, codiversification with angiosperms, and adaptive radiations of specialized herbivorous beetles following convergent horizontal transfers of microbial genes encoding PCWDEs.
326 citations
TL;DR: A comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress can be found in this article, which is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
Abstract: The grand challenges of contemporary fundamental physics-dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem-all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'. © 2019 IOP Publishing Ltd.
TL;DR: The squeezing injection was fully automated and over the first 5 months of the third joint LIGO-Virgo observation run O3 squeezing was applied for more than 99% of the science time, and several gravitational-wave candidates have been recorded.
Abstract: Current interferometric gravitational-wave detectors are limited by quantum noise over a wide range of their measurement bandwidth. One method to overcome the quantum limit is the injection of squeezed vacuum states of light into the interferometer’s dark port. Here, we report on the successful application of this quantum technology to improve the shot noise limited sensitivity of the Advanced Virgo gravitational-wave detector. A sensitivity enhancement of up to 3.2±0.1 dB beyond the shot noise limit is achieved. This nonclassical improvement corresponds to a 5%–8% increase of the binary neutron star horizon. The squeezing injection was fully automated and over the first 5 months of the third joint LIGO-Virgo observation run O3 squeezing was applied for more than 99% of the science time. During this period several gravitational-wave candidates have been recorded.
TL;DR: In this paper, the role of knowledge management in green innovation and corporate sustainable development (CSD) activities is examined, and it is found that knowledge management has a significant positive impact on CSD.
TL;DR: Heterologous immunity to a single, ubiquitous member of the microbiota as a central mechanism for systemic induction of human anti-fungal Th17 responses and as a potential risk factor for pulmonary inflammatory diseases is identified.
University of Würzburg1, University of Bayreuth2, University of Marburg3, University of Göttingen4, University of Ulm5, University of Bern6, University of Copenhagen7, Karlsruhe Institute of Technology8, Tanzania Commission for Science and Technology9, Technische Universität München10, College of African Wildlife Management11, University of Oldenburg12, University of Jena13, University of KwaZulu-Natal14, University of Dar es Salaam15, Tanzania Wildlife Research Institute16, Goethe University Frankfurt17, Kazan Federal University18, Smithsonian Tropical Research Institute19
TL;DR: The study reveals that climate can modulate the effects of land use on biodiversity and ecosystem functioning, and points to a lowered resistance of ecosystems in climatically challenging environments to ongoing land-use changes in tropical mountainous regions.
Abstract: Agriculture and the exploitation of natural resources have transformed tropical mountain ecosystems across the world, and the consequences of these transformations for biodiversity and ecosystem functioning are largely unknown1-3. Conclusions that are derived from studies in non-mountainous areas are not suitable for predicting the effects of land-use changes on tropical mountains because the climatic environment rapidly changes with elevation, which may mitigate or amplify the effects of land use4,5. It is of key importance to understand how the interplay of climate and land use constrains biodiversity and ecosystem functions to determine the consequences of global change for mountain ecosystems. Here we show that the interacting effects of climate and land use reshape elevational trends in biodiversity and ecosystem functions on Africa's largest mountain, Mount Kilimanjaro (Tanzania). We find that increasing land-use intensity causes larger losses of plant and animal species richness in the arid lowlands than in humid submontane and montane zones. Increases in land-use intensity are associated with significant changes in the composition of plant, animal and microorganism communities; stronger modifications of plant and animal communities occur in arid and humid ecosystems, respectively. Temperature, precipitation and land use jointly modulate soil properties, nutrient turnover, greenhouse gas emissions, plant biomass and productivity, as well as animal interactions. Our data suggest that the response of ecosystem functions to land-use intensity depends strongly on climate; more-severe changes in ecosystem functioning occur in the arid lowlands and the cold montane zone. Interactions between climate and land use explained-on average-54% of the variation in species richness, species composition and ecosystem functions, whereas only 30% of variation was related to single drivers. Our study reveals that climate can modulate the effects of land use on biodiversity and ecosystem functioning, and points to a lowered resistance of ecosystems in climatically challenging environments to ongoing land-use changes in tropical mountainous regions.
TL;DR: It is reported that osteoclasts that colonize fetal ossification centres originate from embryonic erythro-myeloid progenitors and are maintained after birth by fusion with circulating monocytes, and parabiosis or transfusion of monocytic cells results in long-term gene transfer in osteoclast in the absence of haematopoietic-stem-cell chimerism.
Abstract: Osteoclasts are multinucleated giant cells that resorb bone, ensuring development and continuous remodelling of the skeleton and the bone marrow haematopoietic niche. Defective osteoclast activity leads to osteopetrosis and bone marrow failure1–9, whereas excess activity can contribute to bone loss and osteoporosis10. Osteopetrosis can be partially treated by bone marrow transplantation in humans and mice11–18, consistent with a haematopoietic origin of osteoclasts13,16,19 and studies that suggest that they develop by fusion of monocytic precursors derived from haematopoietic stem cells in the presence of CSF1 and RANK ligand1,20. However, the developmental origin and lifespan of osteoclasts, and the mechanisms that ensure maintenance of osteoclast function throughout life in vivo remain largely unexplored. Here we report that osteoclasts that colonize fetal ossification centres originate from embryonic erythro-myeloid progenitors21,22. These erythro-myeloid progenitor-derived osteoclasts are required for normal bone development and tooth eruption. Yet, timely transfusion of haematopoietic-stem-cell-derived monocytic cells in newborn mice is sufficient to rescue bone development in early-onset autosomal recessive osteopetrosis. We also found that the postnatal maintenance of osteoclasts, bone mass and the bone marrow cavity involve iterative fusion of circulating blood monocytic cells with long-lived osteoclast syncytia. As a consequence, parabiosis or transfusion of monocytic cells results in long-term gene transfer in osteoclasts in the absence of haematopoietic-stem-cell chimerism, and can rescue an adult-onset osteopetrotic phenotype caused by cathepsin K deficiency23,24. In sum, our results identify the developmental origin of osteoclasts and a mechanism that controls their maintenance in bones after birth. These data suggest strategies to rescue osteoclast deficiency in osteopetrosis and to modulate osteoclast activity in vivo. Multinucleated osteoclasts required for normal bone development and tooth eruption in the mouse originate from embryonic erythro-myeloid progenitors and are maintained after birth by fusion with circulating monocytes.
TL;DR: CABG may differ from PCI by providing "surgical collateralization," prolonging life by preventing myocardial infarction by providing flow distal to vessel occlusions.
Leipzig University1, Martin Luther University of Halle-Wittenberg2, Universidade Positivo3, University of Vigo4, Empresa Brasileira de Pesquisa Agropecuária5, ETH Zurich6, Moscow State University7, University of Freiburg8, University of Jena9, University of Catania10, Wageningen University and Research Centre11, Free University of Berlin12, Senckenberg Museum13, Colorado State University14, National Agriculture and Food Research Organization15, University of Nairobi16, Commonwealth Scientific and Industrial Research Organisation17, National Scientific and Technical Research Council18, Brandenburg University of Technology19, Cornell University20, University College Dublin21, United States Forest Service22, University of Toronto23, Aberystwyth University24, State University of New York at Cortland25, National University of Luján26, University of Trier27, University of the Philippines Mindanao28, Razi University29, Josip Juraj Strossmayer University of Osijek30, Kyushu University31, Minnesota Pollution Control Agency32, Aarhus University33, Northern Kentucky University34, Lincoln University (Missouri)35, University of Agricultural Sciences, Dharwad36, Fukushima University37, Matej Bel University38, Lancaster University39, Université d'Abobo-Adjamé40, Tarbiat Modares University41, Pachhunga University College42, University of São Paulo43, University of Hawaii at Hilo44, College of Tropical Agriculture and Human Resources45, Oklahoma State University–Stillwater46, Forest Research Institute47, University of Extremadura48, Katholieke Universiteit Leuven49, Research Institute for Nature and Forest50, Natural Resources Institute Finland51, University of Alcalá52, King Abdulaziz University53, COMSATS Institute of Information Technology54, University of Minnesota55, Federal University of Maranhão56, Jagiellonian University57, Technical University of Berlin58, University of Wisconsin-Madison59, Leibniz Association60, Braunschweig University of Technology61, University of Innsbruck62, Russian Academy of Sciences63, Keldysh Institute of Applied Mathematics64, Khalsa College, Amritsar65, University of La Laguna66, Kōchi University67, Universidad Pública de Navarra68, McGill University69, The Nature Conservancy70, University of Giessen71, Henan University72, University of Saint Mary73
TL;DR: It was found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms, which suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
Abstract: Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
National Heart Foundation of Australia1, Erasmus University Medical Center2, University of Paris3, University of Jena4, University College Dublin5, Utrecht University6, University of Bologna7, Karolinska University Hospital8, University of Bern9, Ege University10, Vita-Salute San Raffaele University11, Boston Children's Hospital12, Papworth Hospital13, Medical University of Vienna14
TL;DR: The evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device.
Abstract: Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many-sometimes contradictory-observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device.
TL;DR: These findings identify carboxyl-terminal multisite phosphorylation as key step that drives acute μ-opioid receptor desensitization and long-term tolerance and predict that G-protein-biased µ-agonists are still likely to elicit severe adverse effects.
Abstract: Opioid analgesics are powerful pain relievers; however, over time, pain control diminishes as analgesic tolerance develops. The molecular mechanisms initiating tolerance have remained unresolved to date. We have previously shown that desensitization of the μ-opioid receptor and interaction with β-arrestins is controlled by carboxyl-terminal phosphorylation. Here we created knockin mice with a series of serine- and threonine-to-alanine mutations that render the receptor increasingly unable to recruit β-arrestins. Desensitization is inhibited in locus coeruleus neurons of mutant mice. Opioid-induced analgesia is strongly enhanced and analgesic tolerance is greatly diminished. Surprisingly, respiratory depression, constipation, and opioid withdrawal signs are unchanged or exacerbated, indicating that β-arrestin recruitment does not contribute to the severity of opioid side effects and, hence, predicting that G-protein-biased µ-agonists are still likely to elicit severe adverse effects. In conclusion, our findings identify carboxyl-terminal multisite phosphorylation as key step that drives acute μ-opioid receptor desensitization and long-term tolerance.
University of Adelaide1, Memorial Sloan Kettering Cancer Center2, University of Texas MD Anderson Cancer Center3, Kobe University4, University of Paris5, Dana Corporation6, Sapienza University of Rome7, Singapore General Hospital8, University of Michigan9, University of Jena10, Charité11, Cardiff University12, Veterans Health Administration13, Oregon Health & Science University14, University of Utah15, University of Amsterdam16, University of Bordeaux17, Novartis18, Goethe University Frankfurt19, Catholic University of Korea20
TL;DR: Asciminib was active in heavily pretreated patients with CML who had resistance to or unacceptable side effects from TKIs, including patients in whom ponatinib had failed and those with a T315I mutation.
Abstract: Background Asciminib is an allosteric inhibitor that binds a myristoyl site of the BCR-ABL1 protein, locking BCR-ABL1 into an inactive conformation through a mechanism distinct from those ...
TL;DR: This special issue is a first attempt to trace the ‘ecosystem’ discussion back to its roots—the ancient oikos, coined by the Greek philosopher Hesiod (700 BC), and aims to critically reflect on the usage of the term’, briefly summarize the extant literature and grasp the main features of entrepreneurial ecosystems, namely the economic, technological, and societal dimensions of entrepreneurial ecosystem.
Abstract: Despite the overwhelming use of the metaphor ‘ecosystem’ in academia, industry, policy, and management, exact definitions of what ‘ecosystems’ really comprise are scarce and often inconsistent. Existing vague descriptions in the literature do not consider the boundaries of respective agglomerations, hence, they impede the evaluation of performance and outcome measures of respective ecosystems. This special issue is a first attempt to trace the ‘ecosystem’ discussion back to its roots—the ancient oikos, coined by the Greek philosopher Hesiod (700 BC), and aims to critically reflect on the usage of the term ‘ecosystem’, briefly summarize the extant literature and grasp the main features of entrepreneurial ecosystems, namely the economic, technological, and societal dimensions of entrepreneurial ecosystems. We intend to focus on the key elements that characterize an ecosystem, and hence, untangle under what conditions entrepreneurial firms shape and influence economic, technological, and societal thinking within their ecosystem.
Roy J. and Lucille A. Carver College of Medicine1, Columbia University2, Lund University3, Imperial College London4, Columbia University Medical Center5, Necker-Enfants Malades Hospital6, Hungarian Academy of Sciences7, Centre for Life8, University of Pennsylvania9, University of Milan10, Spanish National Research Council11, Mayo Clinic12, Radboud University Nijmegen13, Leibniz Association14, University of Jena15
TL;DR: The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples.
Abstract: The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy - dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) - have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients - namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.
Ludwig Maximilian University of Munich1, Leibniz Association2, University of Jena3, Guizhou University4, Huazhong University of Science and Technology5, University of Tennessee Health Science Center6, University of Virginia7, Information Technology University8, Maastricht University9, Technische Universität München10, Alnylam Pharmaceuticals11, Medical University of Vienna12, Schiller International University13
TL;DR: Treatment with small interfering RNA (siRNA) against C5, which is formed by all complement pathways, attenuated murine ChP inflammation, Aβ-associated microglia accumulation, and atherosclerosis reduces disease burden, and ApoE is a direct checkpoint inhibitor of unresolvable inflammation.
Abstract: Apolipoprotein-E (ApoE) has been implicated in Alzheimer’s disease, atherosclerosis, and other unresolvable inflammatory conditions but a common mechanism of action remains elusive. We found in ApoE-deficient mice that oxidized lipids activated the classical complement cascade (CCC), resulting in leukocyte infiltration of the choroid plexus (ChP). All human ApoE isoforms attenuated CCC activity via high-affinity binding to the activated CCC-initiating C1q protein (KD~140–580 pM) in vitro, and C1q–ApoE complexes emerged as markers for ongoing complement activity of diseased ChPs, Aβ plaques, and atherosclerosis in vivo. C1q–ApoE complexes in human ChPs, Aβ plaques, and arteries correlated with cognitive decline and atherosclerosis, respectively. Treatment with small interfering RNA (siRNA) against C5, which is formed by all complement pathways, attenuated murine ChP inflammation, Aβ-associated microglia accumulation, and atherosclerosis. Thus, ApoE is a direct checkpoint inhibitor of unresolvable inflammation, and reducing C5 attenuates disease burden. ApoE is a direct checkpoint inhibitor of unresolvable inflammation in neurodegenerative and cardiovascular diseases
TL;DR: This work used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus, and paves the way for haplotype-based analyses of viral quasispecies by showing the feasibility of intra-sample haplotype separation.
Abstract: Sequence analyses of RNA virus genomes remain challenging owing to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called "quasispecies." Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (1) RNA virus genomes and (2) subgenome-length (sg) RNAs composed of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus. By using DRS, we were able to map the longest (∼26-kb) contiguous read to the viral reference genome. By combining Illumina and Oxford Nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV)-229E genome (27.3 kb). Furthermore, by using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by showing the feasibility of intra-sample haplotype separation. Even though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that DRS may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.
TL;DR: In this paper, a statistical standard siren analysis of GW170817 is presented, which considers all galaxies brighter than 0.626{L}_{B}^{\star }$ as equally likely to host a binary neutron star merger.
Abstract: We perform a statistical standard siren analysis of GW170817. Our analysis does not utilize knowledge of NGC 4993 as the unique host galaxy of the optical counterpart to GW170817. Instead, we consider each galaxy within the GW170817 localization region as a potential host; combining the redshifts from all of the galaxies with the distance estimate from GW170817 provides an estimate of the Hubble constant, H 0. Considering all galaxies brighter than $0.626{L}_{B}^{\star }$ as equally likely to host a binary neutron star merger, we find ${H}_{0}={77}_{-18}^{+37}$ km s−1 Mpc−1 (maximum a posteriori and 68.3% highest density posterior interval; assuming a flat H 0 prior in the range $\left[10,220\right]$ km s−1 Mpc−1). We explore the dependence of our results on the thresholds by which galaxies are included in our sample, and we show that weighting the host galaxies by stellar mass or star formation rate provides entirely consistent results with potentially tighter constraints. By applying the method to simulated gravitational-wave events and a realistic galaxy catalog we show that, because of the small localization volume, this statistical standard siren analysis of GW170817 provides an unusually informative (top 10%) constraint. Under optimistic assumptions for galaxy completeness and redshift uncertainty, we find that dark binary neutron star measurements of H 0 will converge as $40 \% /\sqrt{(N)}$, where N is the number of sources. While these statistical estimates are inferior to the value from the counterpart standard siren measurement utilizing NGC 4993 as the unique host, ${H}_{0}={76}_{-13}^{+19}$ km s−1 Mpc−1 (determined from the same publicly available data), our analysis is a proof-of-principle demonstration of the statistical approach first proposed by Bernard Schutz over 30 yr ago.
TL;DR: The comparison of experimental and theoretical band gaps shows that the modified Becke–Johnson is at the moment the best available density functional, closely followed by the Heyd–Scuseria–Ernzerhof screened hybrid from 2006 and the high-local-exchange generalized-gradient approximation.
Abstract: We compile a large data set designed for the efficient benchmarking of exchange–correlation functionals for the calculation of electronic band gaps. The data set comprises information on the experimental structure and band gap of 472 nonmagnetic materials and includes a diverse group of covalent-, ionic-, and van der Waals-bonded solids. We used it to benchmark 12 functionals, ranging from standard local and semilocal functionals, passing through meta-generalized-gradient approximations, and several hybrids. We included both general purpose functionals, like the Perdew–Burke–Ernzerhof approximation, and functionals specifically crafted for the determination of band gaps. The comparison of experimental and theoretical band gaps shows that the modified Becke–Johnson is at the moment the best available density functional, closely followed by the Heyd–Scuseria–Ernzerhof screened hybrid from 2006 and the high-local-exchange generalized-gradient approximation.
TL;DR: In this review, novel engineered photothermal nanomaterials, such as noble metal-, carbon-, semiconductor-, and organic molecule-based PTT agents, as well as their targeted biomedical applications were summarized and discussed comprehensively.
01 Jun 2019
Albert Einstein Institution1, Leibniz University of Hanover2, University of Jena3, University of Wisconsin–Milwaukee4, Cornell University5, Institut des Hautes Études Scientifiques6, Sapienza University of Rome7, Cardiff University8, Istituto Nazionale di Fisica Nucleare9, University of Parma10, University of Zurich11, University of Cambridge12, University of Illinois at Urbana–Champaign13, University of Groningen14
TL;DR: In this article, a numerical relativity (NR) based approximation for the tidal part of the phasing was proposed for nonprecessing and precessing binary black hole systems, as implemented in the LSC Algorithm Library Suite.
Abstract: The combined observation of gravitational and electromagnetic waves from the coalescence of two neutron stars marks the beginning of multimessenger astronomy with gravitational waves (GWs). The development of accurate gravitational waveform models is a crucial prerequisite to extract information about the properties of the binary system that generated a detected GW signal. In binary neutron star systems (BNS), tidal effects also need to be incorporated in the modeling for an accurate waveform representation. Building on previous work [Phys. Rev. D 96, 121501 (2017)], we explore the performance of inspiral-merger waveform models that are obtained by adding a numerical relativity (NR) based approximant for the tidal part of the phasing ($\mathrm{NRTidal}$) to existing models for nonprecessing and precessing binary black hole systems, as implemented in the LSC Algorithm Library Suite. The resulting BNS waveforms are compared and contrasted to a set of target waveforms which we obtain by hybridizing NR waveforms (covering the last $\ensuremath{\sim}10$ orbits up to the merger and extending through the postmerger phase) with inspiral waveforms calculated from 30 Hz obtained with a state-of-the-art effective-one-body waveform model. While due to the construction procedure of the target waveforms, there is no error budget available over the full frequency range accessible by advanced GW detectors, the waveform set presents only an approximation of the real signal. We probe that the combination of the self-spin terms and of the $\mathrm{NRTidal}$ description is necessary to obtain minimal mismatches ($\ensuremath{\lesssim}0.01$) and phase differences ($\ensuremath{\lesssim}1\text{ }\text{ }\mathrm{rad}$) with respect to the target waveforms. We also discuss possible improvements and drawbacks of the $\mathrm{NRTidal}$ approximant in its current form.