| 1. |
- Aartsen, M. G., et al.
(author)
-
Very high-energy gamma-ray follow-up program using neutrino triggers from IceCube
- 2016
-
In: Journal of Instrumentation. - 1748-0221. ; 11
-
Journal article (peer-reviewed)abstract
- We describe and report the status of a neutrino-triggered program in IceCube that generates real-time alerts for gamma-ray follow-up observations by atmospheric-Cherenkov telescopes (MAGIC and VERITAS). While IceCube is capable of monitoring the whole sky continuously, high-energy gamma-ray telescopes have restricted fields of view and in general are unlikely to be observing a potential neutrino-flaring source at the time such neutrinos are recorded. The use of neutrino-triggered alerts thus aims at increasing the availability of simultaneous multi-messenger data during potential neutrino flaring activity, which can increase the discovery potential and constrain the phenomenological interpretation of the high-energy emission of selected source classes (e. g. blazars). The requirements of a fast and stable online analysis of potential neutrino signals and its operation are presented, along with first results of the program operating between 14 March 2012 and 31 December 2015.
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| 2. |
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| 3. |
- Mayer, Manuel, et al.
(author)
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Constraints on particle acceleration in SS433/W50 from MAGIC and HESS observations
- 2018
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Journal article (peer-reviewed)abstract
- Context. The large jet kinetic power and non-thermal processes occurring in the microquasar SS 433 make this source a good candidate for a very high-energy (VHE) gamma-ray emitter. Gamma-ray fluxes above the sensitivity limits of current Cherenkov telescopes have been predicted for both the central X-ray binary system and the interaction regions of SS 433 jets with the surrounding W50 nebula. Non-thermal emission at lower energies has been previously reported, indicating that efficient particle acceleration is taking place in the system. Aims. We explore the capability of SS 433 to emit VHE gamma rays during periods in which the expected flux attenuation due to periodic eclipses (P-orb similar to 13.1 days) and precession of the circumstellar disk (P-pre similar to 162 days) periodically covering the central binary system is expected to be at its minimum. The eastern and western SS 433/W50 interaction regions are also examined using the whole data set available. We aim to constrain some theoretical models previously developed for this system with our observations. Methods. We made use of dedicated observations from the Major Atmospheric Gamma Imaging Cherenkov telescopes (MAGIC) and High Energy Spectroscopic System (H.E.S.S.) of SS 433 taken from 2006 to 2011. These observation were combined for the first time and accounted for a total effective observation time of 16.5 h, which were scheduled considering the expected phases of minimum absorption of the putative VHE emission. Gamma-ray attenuation does not affect the jet/medium interaction regions. In this case, the analysis of a larger data set amounting to similar to 40-80 h, depending on the region, was employed. Results. No evidence of VHE gamma-ray emission either from the central binary system or from the eastern/western interaction regions was found. Upper limits were computed for the combined data set. Differential fluxes from the central system are found to be less than or similar to 10(-12)-10(-13) TeV-1 cm(-2) s(-1) in an energy interval ranging from similar to few x 100 GeV to similar to few TeV. Integral flux limits down to similar to 10(-12)-10(-13) ph cm(-2) s(-1) and similar to 10(-13)-10(-14) ph cm(-2) s(-1) are obtained at 300 and 800 GeV, respectively. Our results are used to place constraints on the particle acceleration fraction at the inner jet regions and on the physics of the jet/medium interactions. Conclusions. Our findings suggest that the fraction of the jet kinetic power that is transferred to relativistic protons must be relatively small in SS 433, q(p) <= 2.5 x 10(-5), to explain the lack of TeV and neutrino emission from the central system. At the SS 433/W50 interface, the presence of magnetic fields greater than or similar to 10 mu G is derived assuming a synchrotron origin for the observed X-ray emission. This also implies the presence of high-energy electrons with E-e up to 50 TeV, preventing an efficient production of gamma-ray fluxes in these interaction regions.
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| 4. |
- Arndt, D. S., et al.
(author)
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STATE OF THE CLIMATE IN 2017
- 2018
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In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
-
Research review (peer-reviewed)
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| 5. |
- Arndt, D. S., et al.
(author)
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State of the Climate in 2016
- 2017
-
In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
-
Journal article (peer-reviewed)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 6. |
- Ahnen, M. L., et al.
(author)
-
Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies
- 2016
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
-
Journal article (peer-reviewed)abstract
- We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.
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| 7. |
- Aleksic, J., et al.
(author)
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MAGIC reveals a complex morphology within the unidentified gamma-ray source HESS J1857+026
- 2014
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 571
-
Journal article (peer-reviewed)abstract
- Aims. HESS J1857+026 is an extended TeV gamma-ray source that was discovered by H. E. S. S. as part of its Galactic plane survey. Given its broadband spectral energy distribution and its spatial coincidence with the young energetic pulsar PSR J1856+0245, the source has been put forward as a pulsar wind nebula (PWN) candidate. MAGIC has performed follow-up observations aimed at mapping the source down to energies approaching 100 GeV in order to better understand its complex morphology. Methods. HESS J1857+026 was observed by MAGIC in 2010, yielding 29 h of good quality stereoscopic data that allowed us to map the source region in two separate ranges of energy. Results. We detected very-high-energy gamma-ray emission from HESS J1857+026 with a significance of 12 sigma above 150 GeV. The differential energy spectrum between 100 GeV and 13 TeV is described well by a power law function dN/dE = N-0(E/1TeV)(-Gamma) with N-0 = (5.37 +/- 0.44(stat) +/- 1.5(sys)) X 10(-12) (TeV-1 cm(-2) s(-1)) and Gamma = 2.16 +/- 0.07(stat) +/- 0.15(sys), which bridges the gap between the GeV emission measured by Fermi-LAT and the multi-TeV emission measured by H.E.S.S.. In addition, we present a detailed analysis of the energy-dependent morphology of this region. We couple these results with archival multiwavelength data and outline evidence in favor of a two-source scenario, whereby one source is associated with a PWN, while the other could be linked with a molecular cloud complex containing an HII region and a possible gas cavity.
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| 8. |
- Aleksic, J., et al.
(author)
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Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes
- 2015
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In: Journal of High Energy Astrophysics. - : Elsevier BV. - 2214-4048 .- 2214-4056. ; 5-6, s. 30-38
-
Journal article (peer-reviewed)abstract
- The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between October 2009 and April 2011. Analysis of this data sample using the latest improvements in the MAGIC stereoscopic software provided an unprecedented precision of spectral and night-by-night light curve determination at gamma rays. We derived a differential spectrum with a single instrument from 50 GeV up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC results, combined with Fermi-LAT data, show a flat and broad Inverse Compton peak. The overall fit to the data between 1 GeV and 30 TeV is not well described by a log-parabola function. We find that a modified log-parabola function with an exponent of 2.5 instead of 2 provides a good description of the data (chi(2)(red) = 35/26). Using systematic uncertainties of the MAGIC and Fermi-LAT measurements we determine the position of the Inverse Compton peak to be at (53 +/- 3(stat)+ 31(syst)-13(syst)) GeV, which is the most precise estimation up to date and is dominated by the systematic effects. There is no hint of the integral flux variability on daily scales at energies above 300 GeV when systematic uncertainties are included in the flux measurement. We consider three state-of-the-art theoretical models to describe the overall spectral energy distribution of the Crab Nebula. The constant B-field model cannot satisfactorily reproduce the VHE spectral measurements presented in this work, having particular difficulty reproducing the broadness of the observed IC peak. Most probably this implies that the assumption of the homogeneity of the magnetic field inside the nebula is incorrect. On the other hand, the time-dependent 1D spectral model provides a good fit of the new VHE results when considering a 80 mu G magnetic field. However, it fails to match the data when including the morphology of the nebula at lower wavelengths.
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| 9. |
- Brownstein, Catherine A., et al.
(author)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Journal article (peer-reviewed)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 10. |
- Ades, M., et al.
(author)
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Global Climate : in State of the climate in 2019
- 2020
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In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Journal article (peer-reviewed)
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| 11. |
- Ades, M., et al.
(author)
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GLOBAL CLIMATE
- 2020
-
In: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
-
Journal article (peer-reviewed)
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| 12. |
- Coll, M., et al.
(author)
-
Towards Oxide Electronics: a Roadmap
- 2019
-
In: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 482, s. 1-93
-
Journal article (peer-reviewed)abstract
- At the end of a rush lasting over half a century, in which CMOS technology has been experiencing a constant and breathtaking increase of device speed and density, Moore’s law is approaching the insurmountable barrier given by the ultimate atomic nature of matter. A major challenge for 21st century scientists is finding novel strategies, concepts and materials for replacing silicon-based CMOS semiconductor technologies and guaranteeing a continued and steady technological progress in next decades. Among the materials classes candidate to contribute to this momentous challenge, oxide films and heterostructures are a particularly appealing hunting ground. The vastity, intended in pure chemical terms, of this class of compounds, the complexity of their correlated behaviour, and the wealth of functional properties they display, has already made these systems the subject of choice, worldwide, of a strongly networked, dynamic and interdisciplinary research community. Oxide science and technology has been the target of a wide four-year project, named Towards Oxide-Based Electronics (TO-BE), that has been recently running in Europe and has involved as participants several hundred scientists from 29 EU countries. In this review and perspective paper, published as a final deliverable of the TO-BE Action, the opportunities of oxides as future electronic materials for Information and Communication Technologies ICT and Energy are discussed. The paper is organized as a set of contributions, all selected and ordered as individual building blocks of a wider general scheme. After a brief preface by the editors and an introductory contribution, two sections follow. The first is mainly devoted to providing a perspective on the latest theoretical and experimental methods that are employed to investigate oxides and to produce oxide-based films, heterostructures and devices. In the second, all contributions are dedicated to different specific fields of applications of oxide thin films and heterostructures, in sectors as data storage and computing, optics and plasmonics, magnonics, energy conversion and harvesting, and power electronics.
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| 13. |
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| 14. |
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| 15. |
- Chumakov, A., et al.
(author)
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Sprayed Nanometer-Thick Hard-Magnetic Coatings with Strong Perpendicular Anisotropy for Data Storage Applications
- 2022
-
In: ACS Applied Nano Materials. - : American Chemical Society (ACS). - 2574-0970. ; 5:7, s. 8741-8754
-
Journal article (peer-reviewed)abstract
- The rapid growth of digital information in the world necessitates a big leap in improving the existing technologies for magnetic recording. For the best modern perpendicular recording, the highest coercivity materials with minimal volume are required. We present a study of a facile technology for establishing mono- and multilayer surfaces from various single-domain flat magnetic nanoparticles that exhibit a strong perpendicular-oriented magnetic moment on solid and flexible substrates. Surfactant-free, hard ferromagnetic, and single-domain anisotropic strontium hexaferrite SrFe12O19nanoparticles with a perpendicular magnetic moment orientation and two different aspect ratios are self-ordered into magnetic thin nanofilms, exploiting the templating effect of cellulose nanofibrils and magnetic fields. Uniform magnetic coatings obtained by the scalable layer-by-layer spray deposition from a monolayer coverage up to thicknesses of a few tens of nanometers show a preferred in-plane orientation of the hard-magnetic nanoparticles. High coercivities of the films of up to 5 kOe and a high perpendicular anisotropy of Mr⊥/Ms> 80% are found. The application of the magnetic field during film deposition ensures additional improvement in perpendicular magnetic anisotropy and the appearance of residual magnetization in the film of up to 0.6Ms. For low-aspect-ratio nanoparticles stacked in periodic planar structures, the signs of the photonic band gap are revealed. The ability to create scalable, thin magnetic structures based on nanosized particles/building blocks opens great opportunities for their application in a wide variety of optoelectronic and magnetic storage devices.
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| 16. |
- Fellinger, Joris, et al.
(author)
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Tungsten based divertor development for Wendelstein 7-X
- 2023
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In: Nuclear Materials and Energy. - 2352-1791. ; 37
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Journal article (peer-reviewed)abstract
- Wendelstein 7-X, the world’s largest superconducting stellarator in Greifswald (Germany), started plasma experiments with a water-cooled plasma-facing wall in 2022, allowing for long pulse operation. In parallel, a project was launched in 2021 to develop a W based divertor, replacing the current CFC divertor, to demonstrate plasma performance of a stellarator with a reactor relevant plasma facing materials with low tritium retention. The project consists of two tasks: Based on experience from the previous experimental campaigns and improved physics modelling, the geometry of the plasma-facing surface of the divertor and baffles is optimized to prevent overloads and to improve exhaust. In parallel, the manufacturing technology for a W based target module is qualified. This paper gives a status update of project. It focusses on the conceptual design of a W based target module, the manufacturing technology and its qualification, which is conducted in the framework of the EUROfusion funded WPDIV program. A flat tile design in which a target module is made of a single target element is pursued. The technology must allow for moderate curvatures of the plasma-facing surface to follow the magnetic field lines. The target element is designed for steady state heat loads of 10 MW/m2 (as for the CFC divertor). Target modules of a similar size and weight as for the CFC divertor are assumed (approx. < 0.25 m2 and < 60 kg) using the existing water cooling infrastructure providing 5 l/s and roughly maximum 15 bar pressure drop per module. The main technology under qualification is based on a CuCrZr heat sink made either by additive manufacturing using laser powder bed fusion (LPBF) or by uniaxial diffusion welding of pre-machined forged CuCrZr plates. After heat treatment, the plasma-facing side of the heat sink is covered by W or if feasible by the more ductile WNiFe, preferably by coating or alternatively by hot isostatic pressing W based tiles with a soft OFE-Cu interlayer. Last step is a final machining of the plasma-exposed surface and the interfaces to the water supply lines and supports to correct manufacturing deformations.
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| 17. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 18. |
- Böddecker, M., et al.
(author)
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Effect of uncertainty of material parameters on stress triaxiality and Lode angle in finite elasto-plasticity—A variance-based global sensitivity analysis
- 2023
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In: Advances in Industrial and Manufacturing Engineering. - 2666-9129. ; 7
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Journal article (peer-reviewed)abstract
- This work establishes a computational framework for the quantification of the effect of uncertainty of material model parameters on extremal stress triaxiality and Lode angle values in plastically deformed devices, whereby stress triaxiality and Lode angle are accepted as key indicators for damage initiation in metal forming processes. Attention is paid to components, the material response of which can be represented as elasto-plastic with proportional hardening as a prototype model, whereby the finite element method is used as a simulation approach generally suitable for complex geometries and loading conditions. Uncertainty about material parameters is characterized resorting to probability theory. The effects of material parameter uncertainty on stress triaxiality and Lode angle are quantified by means of a variance-based global sensitivity analysis. Such sensitivity analysis is most useful for apportioning the variance of the stress triaxiality and Lode angle to the uncertainty on material properties. The practical implementation of this sensitivity analysis is carried out resorting to a Gaussian process regression, Bayesian probabilistic integration and active learning in order to decrease the associated numerical costs. An example illustrates the proposed framework, revealing that parameters governing plasticity affect stress triaxiality and Lode angle the most.
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| 19. |
- Sverrild, A., et al.
(author)
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Tezepelumab decreases airway epithelial IL-33 and T2-inflammation in response to viral stimulation in patients with asthma
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In: Allergy: European Journal of Allergy and Clinical Immunology. - 0105-4538.
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Journal article (peer-reviewed)abstract
- Background: Respiratory virus infections are main triggers of asthma exacerbations. Tezepelumab, an anti-TSLP mAb, reduces exacerbations in patients with asthma, but the effect of blocking TSLP on host epithelial resistance and tolerance to virus infection is not known. Aim: To examine effects of blocking TSLP in patients with asthma on host resistance (IFNβ, IFNλ, and viral load) and on the airway epithelial inflammatory response to viral challenge. Methods: Bronchoalveolar lavage fluid (BALF, n = 39) and bronchial epithelial cells (BECs) were obtained from patients with uncontrolled asthma before and after 12 weeks of tezepelumab treatment (n = 13) or placebo (n = 13). BECs were cultured in vitro and exposed to the viral infection mimic poly(I:C) or infected by rhinovirus (RV). Alarmins, T2- and pro-inflammatory cytokines, IFNβ IFNλ, and viral load were analyzed by RT-qPCR and multiplex ELISA before and after stimulation. Results: IL-33 expression in unstimulated BECs and IL-33 protein levels in BALF were reduced after 12 weeks of tezepelumab. Further, IL-33 gene and protein levels decreased in BECs challenged with poly(I:C) after tezepelumab whereas TSLP gene expression remained unaffected. Poly(I:C)-induced IL-4, IL-13, and IL-17A release from BECs was also reduced with tezepelumab whereas IFNβ and IFNλ expression and viral load were unchanged. Conclusion: Blocking TSLP with tezepelumab in vivo in asthma reduced the airway epithelial inflammatory response including IL-33 and T2 cytokines to viral challenge without affecting anti-viral host resistance. Our results suggest that blocking TSLP stabilizes the bronchial epithelial immune response to respiratory viruses.
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| 20. |
- Alastrue, V, et al.
(author)
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Anisotropic micro-sphere-based finite elasticity applied to blood vessel modelling
- 2009
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In: Journal of the Mechanics and Physics of Solids. - : Elsevier BV. - 1873-4782 .- 0022-5096. ; 57:1, s. 178-203
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Journal article (peer-reviewed)abstract
- A fully three-dimensional anisotropic elastic model for vascular tissue modelling is here presented. The underlying strain energy density function is assumed to additively decouple into volumetric and deviatoric contributions. A straightforward isotropic neo-Hooke-type law is used to model the deviatoric response of the ground substance, whereas a micro-structurally or rather micro-sphere-based approach will be employed to model the contribution and distribution of fibres within the biological tissue of interest. Anisotropy was introduced by means of the use of von Mises orientation distribution functions. Two different micro-mechanical approaches -- a, say phenomenological, exponential ansatz and a worm-like-chain-based formulation -- are applied to the micro-fibres and illustratively compared. The passage from micro-structural contributions to the macroscopic response is obtained by a computational homogenisation scheme, namely numerical integration over the surface of the individual micro-spheres. The algorithmic treatment of this integration is discussed in detail for the anisotropic problem at hand, so that several cubatures of the micro-sphere are tested in order to optimise the accuracy at reasonable computational cost. Moreover, the introduced material parameters are identified from simple tension tests on human coronary arterial tissue for the two micro-mechanical models investigated. Both approaches are able to recapture the experimental data. Based on the identified sets of parameters, we first discuss a homogeneous deformation in simple shear to evaluate the models' response at the micro-structural level. Later on, an artery-like two-layered tube subjected to internal pressure is simulated by making use of a non-linear finite element setting. This enables to obtain the micro- and macroscopic responses in an inhomogeneous deformation problem, namely a blood-vessel-representative boundary value problem. The effect of residual stresses is additionally included in the model by means of a multiplicative decomposition of the deformation gradient tensor which turns out to crucially affect the simulation results.
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| 21. |
- Alastrue, V., et al.
(author)
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On the use of non-linear transformations for the evaluation of anisotropic rotationally symmetric directional integrals. Application to the stress analysis in fibred soft tissues
- 2009
-
In: International Journal for Numerical Methods in Engineering. - : Wiley. - 1097-0207 .- 0029-5981. ; 79:4, s. 474-504
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Journal article (peer-reviewed)abstract
- Microsphere-based constitutive models are a helpful tool in the modelling of materials with a microstructure composed of contributing elements directionally arranged. This is the case, for instance, for fibred soft tissues. In these models, the macroscopic mechanical behaviour is obtained from the integration of the micro-structural contribution of each component (e.g. each fibre) over the surface of an underlying microsphere, which allows incorporating the mechanical features of the micro-constituents to the macroscopic response. The combination of this sort of models and the associated numerical techniques constitutes a powerful modelling tool for which an efficient integration scheme is required. In this regard, the unit sphere discretizations proposed by Bazant and Oh (ZAMM-J Appl Math Mech Z Angew Math Mech 1986; 66(1):37-49) have been used for the integration of the microscopic contributions in isotropic materials. Nevertheless, the inclusion of anisotropy has important implications with regard to the integration scheme, since very fine discretizations are needed to perform the integration accurately, causing the integration process to be very costly. In addition, the storage of internal variables at each integration direction of every integration point is required for constitutive models based on the use of internal variables at the micro-structural level, which renders this approach rather complex and memory demanding. In order to reduce the number of necessary integration directions, several non-linear transformations for the integration of rotationally symmetric functions over the Surface of the unit sphere are here presented. Their accuracy in the integration of the von Mises orientation distribution function is evaluated. Furthermore, a hyperelastic microsphere-based constitutive law for the modelling of soft biological tissues is used in order to check the accuracy and computational efficiency of the proposed transformations within a Finite Element context in inhomogeneous deformation problems. Simulation results show the suitability of the proposed methodology in order to accurately approximate the Value of the integrals within reasonable computational costs. Copyright (C) 2009 John Wiley & Sons, Ltd.
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| 22. |
- Baust, A., et al.
(author)
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Ultrastrong coupling in two-resonator circuit QED
- 2016
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In: Physical Review B. - 2469-9969 .- 2469-9950. ; 93:21, s. Art. no. 214501-
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Journal article (peer-reviewed)abstract
- We report on ultrastrong coupling between a superconducting flux qubit and a resonant mode of a system comprised of two superconducting coplanar stripline resonators coupled galvanically to the qubit. With a coupling strength as high as 17.5% of the mode frequency, exceeding that of previous circuit quantum electrodynamics experiments, we observe a pronounced Bloch-Siegert shift. The spectroscopic response of our multimode system reveals a clear breakdown of the Jaynes-Cummings approximation. In contrast to earlier experiments, the high coupling strength is achieved without making use of an additional inductance provided by a Josephson junction.
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| 23. |
- Erdogan, F, et al.
(author)
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Impact of low copy repeats on the generation of balanced and unbalanced chromosomal aberrations in mental retardation
- 2006
-
In: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-859X .- 1424-8581. ; 115:3-4, s. 247-253
-
Journal article (peer-reviewed)abstract
- Low copy repeats (LCRs) are stretches of duplicated DNA that are more than 1 kb in size and share a sequence similarity that exceeds 90%. Non-allelic homologous recombination (NAHR) between highly similar LCRs has been implicated in numerous genomic disorders. This study aimed at defining the impact of LCRs on the generation of balanced and unbalanced chromosomal rearrangements in mentally retarded patients. A cohort of 22 patients, preselected for the presence of submicroscopic imbalances, was analysed using submegabase resolution tiling path array CGH and the results were compared with a set of 41 patients with balanced translocations and breakpoints that were mapped to the BAC level by FISH. Our data indicate an accumulation of LCRs at breakpoints of both balanced and unbalanced rearrangements. LCRs with high sequence similarity in both breakpoint regions, suggesting NAHR as the most likely cause of rearrangement, were observed in 6/22 patients with chromosomal imbalances, but not in any of the balanced translocation cases studied. In case of chromosomal imbalances, the likelihood of NAHR seems to be inversely related to the size of the aberration. Our data also suggest the presence of additional mechanisms coinciding with or dependent on the presence of LCRs that may induce an increased instability at these chromosomal sites.
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| 24. |
- Frayling, Timothy M., et al.
(author)
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A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young: Evidence for Further Genetic Heterogeneity.
- 2003
-
In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 52:3, s. 872-881
-
Journal article (peer-reviewed)abstract
- Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non–insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15–20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of β-cell dysfunction. To facilitate the identification of novel MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage to chromosomes 6 (nonparametric linkage [NPL]score 2.12 at 71 cM) and 10 (NPL score 1.88 at 169–175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY.
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| 25. |
- Junker, Robert R., et al.
(author)
-
Covariation and phenotypic integration in chemical communication displays : Biosynthetic constraints and eco-evolutionary implications
- 2018
-
In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 220:3, s. 739-749
-
Journal article (peer-reviewed)abstract
- Chemical communication is ubiquitous. The identification of conserved structural elements in visual and acoustic communication is well established, but comparable information on chemical communication displays (CCDs) is lacking. We assessed the phenotypic integration of CCDs in a meta-analysis to characterize patterns of covariation in CCDs and identified functional or biosynthetically constrained modules. Poorly integrated plant CCDs (i.e. low covariation between scent compounds) support the notion that plants often utilize one or few key compounds to repel antagonists or to attract pollinators and enemies of herbivores. Animal CCDs (mostly insect pheromones) were usually more integrated than those of plants (i.e. stronger covariation), suggesting that animals communicate via fixed proportions among compounds. Both plant and animal CCDs were composed of modules, which are groups of strongly covarying compounds. Biosynthetic similarity of compounds revealed biosynthetic constraints in the covariation patterns of plant CCDs. We provide a novel perspective on chemical communication and a basis for future investigations on structural properties of CCDs. This will facilitate identifying modules and biosynthetic constraints that may affect the outcome of selection and thus provide a predictive framework for evolutionary trajectories of CCDs in plants and animals.
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| 26. |
- Martchenko, Ilya, et al.
(author)
-
Anisotropic magnetic particles in a magnetic field
- 2016
-
In: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 12:42, s. 8755-8767
-
Journal article (peer-reviewed)abstract
- We characterize the structural properties of magnetic ellipsoidal hematite colloids with an aspect ratio ρ ≈ 2.3 using a combination of small-angle X-ray scattering and computer simulations. The evolution of the phase diagram with packing fraction φ and the strength of an applied magnetic field B is described, and the coupling between orientational order of magnetic ellipsoids and the bulk magnetic behavior of their suspension addressed. We establish quantitative structural criteria for the different phase and arrest transitions and map distinct isotropic, polarized non-nematic, and nematic phases over an extended range in the φ-B coordinates. We show that upon a rotational arrest of the ellipsoids around φ = 0.59, the bulk magnetic behavior of their suspension switches from superparamagnetic to ordered weakly ferromagnetic. If densely packed and arrested, these magnetic particles thus provide persisting remanent magnetization of the suspension. By exploring structural and magnetic properties together, we extend the often used colloid-atom analogy to the case of magnetic spins.
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| 27. |
- Menzel, Annette, et al.
(author)
-
European phenological response to climate change matches the warming pattern
- 2006
-
In: Global Change Biology. - 1354-1013 .- 1365-2486. ; 12:10, s. 1969-1976
-
Journal article (peer-reviewed)abstract
- Global climate change impacts can already be tracked in many physical and biological systems; in particular, terrestrial ecosystems provide a consistent picture of observed changes. One of the preferred indicators is phenology, the science of natural recurring events, as their recorded dates provide a high-temporal resolution of ongoing changes. Thus, numerous analyses have demonstrated an earlier onset of spring events for mid and higher latitudes and a lengthening of the growing season. However, published single-site or single-species studies are particularly open to suspicion of being biased towards predominantly reporting climate change-induced impacts. No comprehensive study or meta-analysis has so far examined the possible lack of evidence for changes or shifts at sites where no temperature change is observed. We used an enormous systematic phenological network data set of more than 125000 observational series of 542 plant and 19 animal species in 21 European countries (1971-2000). Our results showed that 78% of all leafing, flowering and fruiting records advanced (30% significantly) and only 3% were significantly delayed, whereas the signal of leaf colouring/fall is ambiguous. We conclude that previously published results of phenological changes were not biased by reporting or publication predisposition: the average advance of spring/summer was 2.5 days decade -1 in Europe. Our analysis of 254 mean national time series undoubtedly demonstrates that species' phenology is responsive to temperature of the preceding months (mean advance of spring/summer by 2.5 days °C -1, delay of leaf colouring and fall by 1.0 day °C -1). The pattern of observed change in spring efficiently matches measured national warming across 19 European countries (correlation coefficient r = -0.69, P < 0.001).
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| 28. |
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| 29. |
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| 30. |
- Soranzo, Nicole, et al.
(author)
-
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
- 2009
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 38-1182
-
Journal article (peer-reviewed)abstract
- The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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| 31. |
- Staufer, M, et al.
(author)
-
Interpretation of x-ray emission spectra: NO adsorbed on Ru(001)
- 1999
-
In: JOURNAL OF CHEMICAL PHYSICS. - : AMER INST PHYSICS. - 0021-9606. ; 111:10, s. 4704-4713
-
Journal article (other academic/artistic)abstract
- A density functional investigation of the x-ray emission spectrum of NO adsorbed on Ru(001) has been carried out using model cluster calculations. The dipole matrix elements governing the emission probability were evaluated in the frozen ground-state appr
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| 32. |
- Trautmann, M., et al.
(author)
-
FUS-DDIT3 Fusion Protein-Driven IGF-IR Signaling is a Therapeutic Target in Myxoid Liposarcoma
- 2017
-
In: Clinical Cancer Research. - : American Association for Cancer Research (AACR). - 1078-0432 .- 1557-3265. ; 23:20, s. 6227-6238
-
Journal article (peer-reviewed)abstract
- Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS-DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS-DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis. Experimental Design: Immunohistochemical evaluation of key effectors of the IGF-IR/PI3K/Akt signaling axis was performed in a comprehensive cohort of myxoid liposarcoma specimens. FUS-DDIT3 dependency and biological function of the IGF-IR/PI3K/Akt signaling cascade were analyzed using a HT1080 fibrosarcoma-based myxoid liposarcoma tumor model and multiple tumor-derived myxoid liposarcoma cell lines. An established myxoid liposarcoma avian chorioallantoic membrane model was used for in vivo confirmation of the preclinical in vitro results. Results: A comprehensive subset of myxoid liposarcoma specimens showed elevated expression and phosphorylation levels of various IGF-IR/PI3K/Akt signaling effectors. In HT1080 fibrosarcoma cells, overexpression of FUS-DDIT3 induced aberrant IGF-IR/PI3K/Akt pathway activity, which was dependent on transcriptional induction of the IGF2 gene. Conversely, RNAi-mediated FUS-DDIT3 knockdown in myxoid liposarcoma cells led to an inactivation of IGF-IR/PI3K/Akt signaling associated with diminished IGF2 mRNA expression. Treatment of myxoid liposarcoma cell lines with several IGF-IR inhibitors resulted in significant growth inhibition in vitro and in vivo. Conclusions: Our preclinical study substantiates the fundamental role of the IGF-IR/PI3K/Akt signaling pathway in myxoid liposarcoma pathogenesis and provides a mechanism-based rationale for molecular-targeted approaches in myxoid liposarcoma cancer therapy. (C)2017 AACR.
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| 33. |
- Valero, C., et al.
(author)
-
Challenges in the Modeling of Wound Healing Mechanisms in Soft Biological Tissues
- 2015
-
In: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 1573-9686 .- 0090-6964. ; 43:7, s. 1654-1665
-
Journal article (peer-reviewed)abstract
- Numerical models have become one of the most powerful tools in biomechanics and mechanobiology allowing highly detailed simulations. One of the fields in which they have broadly evolved during the last years is in soft tissue modeling. Particularly, wound healing in the skin is one of the processes that has been approached by computational models due to the difficulty of performing experimental investigations. During the last decades wound healing simulations have evolved from numerical models which considered only a few number of variables and simple geometries to more complex approximations that take into account a higher number of factors and reproduce more realistic geometries. Moreover, thanks to improved experimental observations, a larger number of processes, such as cellular stress generation or vascular growth, that take place during wound healing have been identified and modeled. This work presents a review of the most relevant wound healing approximations, together with an identification of the most relevant criteria that can be used to classify them. In addition, and looking towards the actual state of the art in the field, some future directions, challenges and improvements are analyzed for future developments.
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| 34. |
- Valero, C., et al.
(author)
-
Modeling of anisotropic wound healing
- 2015
-
In: Journal of the Mechanics and Physics of Solids. - : Elsevier BV. - 1873-4782 .- 0022-5096. ; 79, s. 80-91
-
Journal article (peer-reviewed)abstract
- Biological soft tissues exhibit non-linear complex properties, the quantification of which presents a challenge. Nevertheless, these properties, such as skin anisotropy, highly influence different processes that occur in soft tissues, for instance wound healing, and thus its correct identification and quantification is crucial to understand them. Experimental and computational works are required in order to find the most precise model to replicate the tissues' properties. In this work, we present a wound healing model focused on the proliferative stage that includes angiogenesis and wound contraction in three dimensions and which relies on the accurate representation of the mechanical behavior of the skin. Thus, an anisotropic hyperelastic model has been considered to analyze the effect of collagen fibers on the healing evolution of an ellipsoidal wound. The implemented model accounts for the contribution of the ground matrix and two mechanically equivalent families of fibers. Simulation results show the evolution of the cellular and chemical species in the wound and the wound volume evolution. Moreover, the local strain directions depend on the relative wound orientation with respect to the fibers. (C) 2015 Elsevier Ltd. All rights reserved.
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| 35. |
- Bartel, T., et al.
(author)
-
A phenomenological model for the simulation of functional fatigue in shape memory alloy wires
- 2017
-
In: Meccanica. - : Springer Science and Business Media LLC. - 0025-6455 .- 1572-9648. ; 52:4-5, s. 973-988
-
Journal article (peer-reviewed)abstract
- In this contribution, a modelling framework for functional fatigue in shape memory alloy wires is introduced. The approach is in particular designed to reproduce the effective response determined by experiments as published in, e.g., Eggeler et al. (Mat Sci Eng A 378:24–33, 2004). In this context, the decrease of transformation stresses, the increase of irreversible strains, and the occurrence of “characteristic points” with respect to the stress-strain relation is explicitly covered in the model formulation. The modelling approach for the phase transformations itself offers a large potential for further micromechanically well-motivated model extensions.
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| 36. |
- Berntsson, Oskar, 1989, et al.
(author)
-
Sequential conformational transitions and alpha-helical supercoiling regulate a sensor histidine kinase
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Sensor histidine kinases are central to sensing in bacteria and in plants. They usually contain sensor, linker, and kinase modules and the structure of many of these components is known. However, it is unclear how the kinase module is structurally regulated. Here, we use nano- to millisecond time-resolved X-ray scattering to visualize the solution structural changes that occur when the light-sensitive model histidine kinase YF1 is activated by blue light. We find that the coiled coil linker and the attached histidine kinase domains undergo a left handed rotation within microseconds. In a much slower second step, the kinase domains rearrange internally. This structural mechanism presents a template for signal transduction in sensor histidine kinases.
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| 37. |
- Berntsson, Oskar, 1989, et al.
(author)
-
Time-Resolved X-Ray Solution Scattering Reveals the Structural Photoactivation of a Light-Oxygen-Voltage Photoreceptor
- 2017
-
In: Structure. - : Elsevier BV. - 0969-2126. ; 25:6
-
Journal article (peer-reviewed)abstract
- Light-oxygen-voltage (LOV) receptors are sensory proteins controlling a wide range of organismal adaptations in multiple kingdoms of life. Because of their modular nature, LOV domains are also attractive for use as optogenetic actuators. A flavin chromophore absorbs blue light, forms a bond with a proximal cysteine residue, and induces changes in the surroundings. There is a gap of knowledge on how this initial signal is relayed further through the sensor to the effector module. To characterize these conformational changes, we apply time-resolved X-ray scattering to the homodimeric LOV domain from Bacillus subtilis YtvA. We observe a global structural change in the LOV dimer synchronous with the formation of the chromophore photoproduct state. Using molecular modeling, this change is identified as splaying apart and relative rotation of the two monomers, which leads to an increased separation at the anchoring site of the effector modules.
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| 38. |
- Björling, Alexander, 1983, et al.
(author)
-
Structural photoactivation of a full-length bacterial phytochrome
- 2016
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 2:8
-
Journal article (peer-reviewed)abstract
- Phytochromes are light sensor proteins found in plants, bacteria, and fungi. They function by converting a photon absorption event into a conformational signal that propagates from the chromophore through the entire protein. However, the structure of the photoactivated state and the conformational changes that lead to it are not known. We report time-resolved x-ray scattering of the full-length phytochrome from Deinococcus radiodurans on micro-and millisecond time scales. We identify a twist of the histidine kinase output domains with respect to the chromophore-binding domains as the dominant change between the photoactivated and resting states. The time-resolved data further show that the structural changes up to the microsecond time scales are small and localized in the chromophore-binding domains. The global structural change occurs within a few milliseconds, coinciding with the formation of the spectroscopic meta-Rc state. Our findings establish key elements of the signaling mechanism of full-length bacterial phytochromes.
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| 39. |
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| 40. |
- Buckley, Patrick G, et al.
(author)
-
A full-coverage, high-resolution human chromosome 22 genomic microarrayfor clinical and research applications
- 2002
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 11:25, s. 3221-3229
-
Journal article (peer-reviewed)abstract
- We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
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| 41. |
- Buckley, Patrick G., et al.
(author)
-
Identification of genetic aberrations on chromosome 22 outside the NF2 locus in schwannomatosis and neurofibromatosis type 2
- 2005
-
In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 26:6, s. 540-9
-
Journal article (peer-reviewed)abstract
- Schwannomatosis is characterized by multiple peripheral and cranial nerve schwannomas that occur in the absence of bilateral 8th cranial nerve schwannomas. The latter is the main diagnostic criterion of neurofibromatosis type 2 (NF2), which is a related but distinct disorder. The genetic factors underlying the differences between schwannomatosis and NF2 are poorly understood, although available evidence implicates chromosome 22 as the primary location of the gene(s) of interest. To investigate this, we comprehensively profiled the DNA copy number in samples from sporadic and familial schwannomatosis, NF2, and a large cohort of normal controls. Using a tiling-path chromosome 22 genomic array, we identified two candidate regions of copy number variation, which were further characterized by a PCR-based array with higher resolution. The latter approach allows the detection of minute alterations in total genomic DNA, with as little as 1.5 kb per measurement point of nonredundant sequence on the array. In DNA derived from peripheral blood from a schwannomatosis patient and a sporadic schwannoma sample, we detected rearrangements of the immunoglobulin lambda (IGL) locus, which is unlikely to be due to a B-cell specific somatic recombination of IGL. Analysis of normal controls indicated that these IGL rearrangements were restricted to schwannomatosis/schwannoma samples. In the second candidate region spanning GSTT1 and CABIN1 genes, we observed a frequent copy number polymorphism at the GSTT1 locus. We further describe missense mutations in the CABIN1 gene that are specific to samples from schwannomatosis and NF2 and make this gene a plausible candidate for contributing to the pathogenesis of these disorders.
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| 42. |
- De Bustos, Cecilia, et al.
(author)
-
Tissue-specific variation in DNA methylation levels along human chromosome 1
- 2009
-
In: Epigenetics & Chromatin. - : Springer Science and Business Media LLC. - 1756-8935. ; 2, s. 7-
-
Journal article (peer-reviewed)abstract
- BACKGROUND: DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Most methods to scan the genome in different tissues for differentially methylated sites have focused on the methylation of CpGs in CpG islands, which are concentrations of CpGs often associated with gene promoters. RESULTS: Here, we use a methylation profiling strategy that is predominantly responsive to methylation differences outside of CpG islands. The method compares the yield from two samples of size-selected fragments generated by a methylation-sensitive restriction enzyme. We then profile nine different normal tissues from two human donors relative to spleen using a custom array of genomic clones covering the euchromatic portion of human chromosome 1 and representing 8% of the human genome. We observe gross regional differences in methylation states across chromosome 1 between tissues from the same individual, with the most striking differences detected in the comparison of cerebellum and spleen. Profiles of the same tissue from different donors are strikingly similar, as are the profiles of different lobes of the brain. Comparing our results with published gene expression levels, we find that clones exhibiting extreme ratios reflecting low relative methylation are statistically enriched for genes with high expression ratios, and vice versa, in most pairs of tissues examined. CONCLUSION: The varied patterns of methylation differences detected between tissues by our methylation profiling method reinforce the potential functional significance of regional differences in methylation levels outside of CpG islands.
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| 43. |
- de Ståhl, Teresita Díaz, et al.
(author)
-
Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array
- 2008
-
In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 29:3, s. 398-408
-
Journal article (peer-reviewed)abstract
- To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.
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| 44. |
- Endt, Sebastian, et al.
(author)
-
In Vivo Myelin Water Quantification Using Diffusion–Relaxation Correlation MRI : A Comparison of 1D and 2D Methods
- 2023
-
In: Applied Magnetic Resonance. - 0937-9347. ; 54:11-12, s. 1571-1588
-
Journal article (peer-reviewed)abstract
- Multidimensional Magnetic Resonance Imaging (MRI) is a versatile tool for microstructure mapping. We use a diffusion weighted inversion recovery spin echo (DW-IR-SE) sequence with spiral readouts at ultra-strong gradients to acquire a rich diffusion–relaxation data set with sensitivity to myelin water. We reconstruct 1D and 2D spectra with a two-step convex optimization approach and investigate a variety of multidimensional MRI methods, including 1D multi-component relaxometry, 1D multi-component diffusometry, 2D relaxation correlation imaging, and 2D diffusion-relaxation correlation spectroscopic imaging (DR-CSI), in terms of their potential to quantify tissue microstructure, including the myelin water fraction (MWF). We observe a distinct spectral peak that we attribute to myelin water in multi-component T1 relaxometry, T1-T2 correlation, T1-D correlation, and T2-D correlation imaging. Due to lower achievable echo times compared to diffusometry, MWF maps from relaxometry have higher quality. Whilst 1D multi-component T1 data allows much faster myelin mapping, 2D approaches could offer unique insights into tissue microstructure and especially myelin diffusion.
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| 45. |
- Fohlisch, A, et al.
(author)
-
Franck-Condon breakdown in core-level photoelectron spectroscopy of chemisorbed CO
- 1999
-
In: CHEMICAL PHYSICS LETTERS. - : ELSEVIER SCIENCE BV. - 0009-2614. ; 315:3-4, s. 194-200
-
Journal article (peer-reviewed)abstract
- The photon energy dependence of the vibrational fine structure in the Cls and Ols X-ray photoelectron main lines of chemisorbed CO on Ni(100) and Ru(0001) has been measured from 6 to 150 eV above the core-level thresholds. Significant deviations from the
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| 46. |
- Kaiser, T., et al.
(author)
-
Electrical and mechanical behaviour of metal thin films with deformation-induced cracks predicted by computational homogenisation
- 2021
-
In: International Journal of Fracture. - : Springer Science and Business Media LLC. - 0376-9429 .- 1573-2673. ; 231:2, s. 223-242
-
Journal article (peer-reviewed)abstract
- Motivated by advances in flexible electronic technologies and by the endeavour to develop non-destructive testing methods, this article analyses the capability of computational multiscale formulations to predict the influence of microscale cracks on effective macroscopic electrical and mechanical material properties. To this end, thin metal films under mechanical load are experimentally analysed by using in-situ confocal laser scanning microscopy (CLSM) and in-situ four point probe resistance measurements. Image processing techniques are then used to generate representative volume elements from the laser intensity images. These discrete representations of the crack pattern at the microscale serve as the basis for the calculation of effective macroscopic electrical conductivity and mechanical stiffness tensors by means of computational homogenisation approaches. A comparison of simulation results with experimental electrical resistance measurements and a detailed study of fundamental numerical properties demonstrates the applicability of the proposed approach. In particular, the (numerical) errors that are induced by the representative volume element size and by the finite element discretisation are studied, and the influence of the filter that is used in the generation process of the representative volume element is analysed.
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| 47. |
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| 48. |
- Kaliappan, Jayabal, et al.
(author)
-
Micromechanical modelling of switching phenomena in polycrystalline piezoceramics: application of a polygonal finite element approach
- 2011
-
In: Computational Mechanics. - : Springer Science and Business Media LLC. - 0178-7675 .- 1432-0924. ; 48:4, s. 421-435
-
Journal article (peer-reviewed)abstract
- A micromechanically motivated model is proposed to capture nonlinear effects and switching phenomena present in ferroelectric polycrystalline materials. The changing remnant state of the ferroelectric crystal is accounted for by means of so-called back fields-such as back stresses-to resist or assist further switching processes in the crystal depending on the local loading history. To model intergranular effects present in ferroelectric polycrystals, the computational model elaborated is embedded into a mixed polygonal finite element approach, whereby an individual ferroelectric grain is represented by one single irregular polygonal finite element. This computationally efficient coupled simulation framework is shown to reproduce the specific characteristics of the responses of ferroelectric polycrystals under complex electromechanical loading conditions in good agreement with experimental observations.
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| 49. |
- Lekki, J., et al.
(author)
-
On the follicular pathway of percutaneous uptake of nanoparticles: Ion microscopy and autoradiography studies
- 2007
-
In: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 260:1, s. 174-177
-
Journal article (peer-reviewed)abstract
- We report on the visualization of the penetration of sunscreen formulations containing TiO2 nanoparticles (about 20 nm primary particle size) into hair follicles of both human and porcine skin using the complementary methods of ion microscopy (PIXE, RBS, STIM) and autoradiography. Particles were found as deep as approx. 400 pin in the follicle, obviously introduced mechanically rather than by a diffusive process. No particles were observed in vital tissue nor in sebaceous glands. (c) 2007 Elsevier B.V. All rights reserved.
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| 50. |
- Liebi, Marianne, 1984, et al.
(author)
-
Small-angle X-ray scattering tensor tomography: Model of the three-dimensional reciprocal-space map, reconstruction algorithm and angular sampling requirements
- 2018
-
In: Acta Crystallographica Section A: Foundations and Advances. - 2053-2733. ; 74:1, s. 12-24
-
Journal article (peer-reviewed)abstract
- Small-angle X-ray scattering tensor tomography, which allows reconstruction of the local three-dimensional reciprocal-space map within a three-dimensional sample as introduced by Liebi et al. [Nature (2015), 527, 349-352], is described in more detail with regard to the mathematical framework and the optimization algorithm. For the case of trabecular bone samples from vertebrae it is shown that the model of the three-dimensional reciprocal-space map using spherical harmonics can adequately describe the measured data. The method enables the determination of nanostructure orientation and degree of orientation as demonstrated previously in a single momentum transfer q range. This article presents a reconstruction of the complete reciprocal-space map for the case of bone over extended ranges of q. In addition, it is shown that uniform angular sampling and advanced regularization strategies help to reduce the amount of data required.The mathematical framework and reconstruction algorithm for small-angle scattering tensor tomography are introduced in detail, as well as strategies which help to reduce the amount of data and therewith the measurement time required. Experimental validation is provided for the application to trabecular bone.
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