| 1. |
- Demuth, Andreas, et al.
(author)
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Pathogenomics: An updated European Research Agenda
- 2008
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In: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-7257 .- 1567-1348. ; 8:3, s. 386-393
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Journal article (peer-reviewed)abstract
- The emerging genomic technologies and bioinformatics provide novel opportunities for studying life-threatening human pathogens and to develop new applications for the improvement of human and animal health and the prevention, treatment, and diagnosis of infections. Based on the ecology and population biology of pathogens and related organisms and their connection to epidemiology, more accurate typing technologies and approaches will lead to better means of disease control. The analysis of the genome plasticity and gene pools of pathogenic bacteria including antigenic diversity and antigenic variation results in more effective vaccines and vaccine implementation programs. The study of newly identified and uncultivated microorganisms enables the identification of new threats. The scrutiny of the metabolism of the pathogen in the host allows the identification of new targets for anti-infectives and therapeutic approaches. The development of modulators of host responses and mediators of host damage will be facilitated by the research on interactions of microbes and hosts, including mechanisms of host damage, acute and chronic relationships as well as commensalisms. The study of multiple pathogenic and non-pathogenic microbes interacting in the host will improve the management of multiple infections and will allow probiotic and prebiotic interventions. Needless to iterate, the application of the results of improved prevention and treatment of infections into clinical tests will have a positive impact on the management of human and animal disease. The Pathogenomics Research Agenda draws on discussions with experts of the Network of Excellence "EuroPathoGenomics" at the management board meeting of the project held during 18-21 April 2007, in the Villa Vigoni, Menaggio, Italy. Based on a proposed European Research Agenda in the field of pathogenomics by the ERA-NET PathoGenoMics the meeting's participants updated the established list of topics as the research agenda for the future.
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| 2. |
- Haenssle, H A, et al.
(author)
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Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists.
- 2018
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 29:8, s. 1836-1842
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Journal article (peer-reviewed)abstract
- Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking.Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge.In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P=0.19) and specificity to 75.7% (±11.7%, P<0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P<0.01) and level-II (75.7%, P<0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P<0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge.For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification.This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).
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| 3. |
- Blum, Jurgen, et al.
(author)
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Evidence for the formation of comet 67p/churyumov-gerasimenko through gravitational collapse of a bound clump of pebbles
- 2017
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 469, s. 755-773
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Journal article (peer-reviewed)abstract
- The processes that led to the formation of the planetary bodies in the Solar system are still not fully understood. Using the results obtained with the comprehensive suite of instruments onboard the European Space Agency's Rosetta mission, we present evidence that comet 67P/Churyumov-Gerasimenko likely formed through the gentle gravitational collapse of a bound clump of mm-sized dust aggregates ('pebbles'), intermixed with microscopic ice particles. This formation scenario leads to a cometary make-up that is simultaneously compatible with the global porosity, homogeneity, tensile strength, thermal inertia, vertical temperature profiles, sizes and porosities of emitted dust and the steep increase in water-vapour production rate with decreasing heliocentric distance, measured by the instruments onboard the Rosetta spacecraft and the Philae lander. Our findings suggest that the pebbles observed to be abundant in protoplanetary discs around young stars provide the building material for comets and other minor bodies.
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| 4. |
- Capelo, Holly L., et al.
(author)
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Observation of aerodynamic instability in the flow of a particle stream in a dilute gas
- 2019
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 622
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Journal article (peer-reviewed)abstract
- Forming macroscopic solid bodies in circumstellar discs requires local dust concentration levels significantly higher than the mean. Interactions of the dust particles with the gas must serve to augment local particle densities, and facilitate growth past barriers in the metre size range. Amongst a number of mechanisms that can amplify the local density of solids, aerodynamic streaming instability (SI) is one of the most promising. This work tests the physical assumptions of models that lead to SI in protoplanetary discs (PPDs). We conduct laboratory experiments in which we track the three-dimensional motion of spherical solid particles fluidised in a low-pressure, laminar, incompressible, gas stream. The particle sizes span the Stokes-Epstein drag regime transition and the overall dust-to-gas mass density ratio, is close to unity. A recently published study establishes the similarity of the laboratory flow to a simplified PPD model flow. We study velocity statistics and perform time-series analysis of the advected flow to obtain experimental results suggesting an instability due to particle-gas interaction: (i) there exist variations in particle concentration in the direction of the mean relative motion between the gas and the particles, that is the direction of the mean drag forces; (ii) the particles have a tendency to catch up to one another when they are in proximity; (iii) particle clumping occurs on very small scales, which implies local enhancements above the background by factors of several tens; (iv) the presence of these density enhancements occurs for a mean approaching or greater than 1; (v) we find evidence for collective particle drag reduction when the local particle number density becomes high and when the background gas pressure is high so that the drag is in the continuum regime. The experiments presented here are precedent-setting for observing SI under controlled conditions and may lead to a deeper understanding of how it operates in nature.
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| 5. |
- Hedin, Jonas, et al.
(author)
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The MAGIC meteoric smoke particle sampler
- 2014
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In: Journal of Atmospheric and Solar-Terrestrial Physics. - : Elsevier BV. - 1364-6826 .- 1879-1824. ; 118, s. 127-144
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Journal article (peer-reviewed)abstract
- Between a few tons to several hundred tons of meteoric material enters the Earth's atmosphere each day, and most of this material is ablated and vaporized in the 70-120 km altitude region. The subsequent chemical conversion, re-condensation and coagulation of this evaporated material are thought to form nanometre sized meteoric smoke particles (MSPs). These smoke particles are then subject to further coagulation, sedimentation and global transport by the mesospheric circulation. MSPs have been proposed as a key player in the formation and evolution of ice particle layers around the mesopause region, i.e. noctilucent clouds (NLC) and polar mesosphere summer echoes (PMSE). MSPs have also been implicated in mesospheric heterogeneous chemistry to influence the mesospheric odd oxygen/odd hydrogen (O-x/HOx) chemistry, to play an important role in the mesospheric charge balance, and to be a significant component of stratospheric aerosol and enhance the depletion of O-3. Despite their apparent importance, little is known about the properties of MSPs and none of the hypotheses can be verified without direct evidence of the existence, altitude and size distribution, shape and elemental composition. The aim of the MAGIC project (Mesospheric Aerosol - Genesis, Interaction and Composition) was to develop an instrument and analysis techniques to sample for the first time MSPs in the mesosphere and return them to the ground for detailed analysis in the laboratory. MAGIC meteoric smoke particle samplers have been flown on several sounding rocket payloads between 2005 and 2011. Several of these flights concerned non-summer mesosphere conditions when pure MSP populations can be expected. Other flights concerned high latitude summer conditions when MSPs are expected to be contained in ice particles in the upper mesosphere. In this paper we present the MAGIC project and describe the MAGIC MSP sampler, the measurement procedure and laboratory analysis. We also present the attempts to retrieve MSPs from these flights, the challenges inherent to the sampling of nanometre sized particles and the subsequent analysis of the sampled material, and thoughts for the future. Despite substantial experimental efforts, the MAGIC project has so far failed to provide conclusive results. While particles with elemental composition similar to what is to be expected from MSPs have been found, the analysis has been compromised by challenges with different types of contamination and uncertainties in the sticking efficiency of the particles on the sampling surfaces.
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| 6. |
- Jansson, Karl Wahlberg, et al.
(author)
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The role of pebble fragmentation in planetesimal formation II. Numerical simulations
- 2017
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 835:1
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Journal article (peer-reviewed)abstract
- Some scenarios for planetesimal formation go through a phase of collapse of gravitationally bound clouds of millimeter- to centimeter-size pebbles. Such clouds can form, for example, through the streaming instability in protoplanetary disks. We model the collapse process with a statistical model to obtain the internal structure of planetesimals with solid radii between 10 and 1000 km. During the collapse, pebbles collide, and depending on their relative speeds, collisions have different outcomes. A mixture of particle sizes inside a planetesimal leads to better packing capabilities and higher densities. In this paper we apply results from new laboratory experiments of dust aggregate collisions (presented in a companion paper) to model collision outcomes. We find that the internal structure of a planetesimal is strongly dependent on both its mass and the applied fragmentation model. Low-mass planetesimals have no/few fragmenting pebble collisions in the collapse phase and end up as porous pebble piles. The number of fragmenting collisions increases with increasing cloud mass, resulting in wider particle size distributions and higher density. The collapse is nevertheless "cold" in the sense that collision speeds are damped by the high collision frequency. This ensures that a significant fraction of large pebbles survive the collapse in all but the most massive clouds. Our results are in broad agreement with the observed increase in density of Kuiper Belt objects with increasing size, as exemplified by the recent characterization of the highly porous comet 67P/Churyumov-Gerasimenko.
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| 7. |
- Krivov, Alexander V., et al.
(author)
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Debris disc constraints on planetesimal formation
- 2018
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 474:2, s. 2564-2575
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Journal article (peer-reviewed)abstract
- Two basic routes for planetesimal formation have been proposed over the last decades. One is a classical 'slow-growth' scenario. Another one is particle concentration models, in which small pebbles are concentrated locally and then collapse gravitationally to form planetesimals. Both types of models make certain predictions for the size spectrum and internal structure of newly born planetesimals. We use these predictions as input to simulate collisional evolution of debris discs left after the gas dispersal. The debris disc emission as a function of a system's age computed in these simulations is compared with several Spitzer and Herschel debris disc surveys around A-type stars. We confirm that the observed brightness evolution for the majority of discs can be reproduced by classical models. Further, we find that it is equally consistent with the size distribution of planetesimals predicted by particle concentrationmodels - provided the objects are loosely bound 'pebble piles' as thesemodels also predict. Regardless of the assumed planetesimal formation mechanism, explaining the brightest debris discs in the samples uncovers a 'disc mass problem'. To reproduce such discs by collisional simulations, a total mass of planetesimals of up to ~1000 Earth masses is required, which exceeds the total mass of solids available in the protoplanetary progenitors of debris discs. This may indicate that stirring was delayed in some of the bright discs, that giant impacts occurred recently in some of them, that some systems may be younger than previously thought or that non-collisional processes contribute significantly to the dust production.
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| 8. |
- Syed, Mohtashim Bukhari, et al.
(author)
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The role of pebble fragmentation in planetesimal formation I. Experimental study
- 2017
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 834:2
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Journal article (peer-reviewed)abstract
- Previous work on protoplanetary dust growth shows a halt at centimeter sizes owing to the occurrence of bouncing at velocities of 0.1 m s-1 and fragmentation at velocities ≳;1 m s-1. To overcome these barriers, spatial concentration of centimeter-sized dust pebbles and subsequent gravitational collapse have been proposed. However, numerical investigations have shown that dust aggregates may undergo fragmentation during the gravitational collapse phase. This fragmentation in turn changes the size distribution of the solids and thus must be taken into account in order to understand the properties of the planetesimals that form. To explore the fate of dust pebbles undergoing fragmenting collisions, we conducted laboratory experiments on dust-aggregate collisions with a focus on establishing a collision model for this stage of planetesimal formation. In our experiments, we analyzed collisions of dust aggregates with masses between 0.7 and 91 g mass ratios between target and projectile from 1 to 126 at a fixed porosity of 65%, within the velocity range of 1.5-8.7 m s-1, at low atmospheric pressure of ∼10-3 mbar, and in free-fall conditions. We derived the mass of the largest fragment, the fragment size/mass distribution, and the efficiency of mass transfer as a function of collision velocity and projectile/target aggregate size. Moreover, we give recipes for an easy-to-use fragmentation and mass-transfer model for further use in modeling work. In a companion paper, we use the experimental findings and the derived dust-aggregate collision model to investigate the fate of dust pebbles during gravitational collapse.
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| 9. |
- Tschandl, Philipp, et al.
(author)
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Expert-Level Diagnosis of Nonpigmented Skin Cancer by Combined Convolutional Neural Networks.
- 2019
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In: JAMA dermatology. - : American Medical Association (AMA). - 2168-6084 .- 2168-6068. ; 55:1, s. 58-65
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Journal article (peer-reviewed)abstract
- Convolutional neural networks (CNNs) achieve expert-level accuracy in the diagnosis of pigmented melanocytic lesions. However, the most common types of skin cancer are nonpigmented and nonmelanocytic, and are more difficult to diagnose.To compare the accuracy of a CNN-based classifier with that of physicians with different levels of experience.A CNN-based classification model was trained on 7895 dermoscopic and 5829 close-up images of lesions excised at a primary skin cancer clinic between January 1, 2008, and July 13, 2017, for a combined evaluation of both imaging methods. The combined CNN (cCNN) was tested on a set of 2072 unknown cases and compared with results from 95 human raters who were medical personnel, including 62 board-certified dermatologists, with different experience in dermoscopy.The proportions of correct specific diagnoses and the accuracy to differentiate between benign and malignant lesions measured as an area under the receiver operating characteristic curve served as main outcome measures.Among 95 human raters (51.6% female; mean age, 43.4 years; 95% CI, 41.0-45.7 years), the participants were divided into 3 groups (according to years of experience with dermoscopy): beginner raters (<3 years), intermediate raters (3-10 years), or expert raters (>10 years). The area under the receiver operating characteristic curve of the trained cCNN was higher than human ratings (0.742; 95% CI, 0.729-0.755 vs 0.695; 95% CI, 0.676-0.713; P<.001). The specificity was fixed at the mean level of human raters (51.3%), and therefore the sensitivity of the cCNN (80.5%; 95% CI, 79.0%-82.1%) was higher than that of human raters (77.6%; 95% CI, 74.7%-80.5%). The cCNN achieved a higher percentage of correct specific diagnoses compared with human raters (37.6%; 95% CI, 36.6%-38.4% vs 33.5%; 95% CI, 31.5%-35.6%; P=.001) but not compared with experts (37.3%; 95% CI, 35.7%-38.8% vs 40.0%; 95% CI, 37.0%-43.0%; P=.18).Neural networks are able to classify dermoscopic and close-up images of nonpigmented lesions as accurately as human experts in an experimental setting.
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