| 1. |
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| 2. |
- Alonso-Mori, Roberto, et al.
(author)
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Energy-dispersive X-ray emission spectroscopy using an X-ray free-electron laser in a shot-by-shot mode
- 2012
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:47, s. 19103-19107
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Journal article (peer-reviewed)abstract
- The ultrabright femtosecond X-ray pulses provided by X-ray free-electron lasers open capabilities for studying the structure and dynamics of a wide variety of systems beyond what is possible with synchrotron sources. Recently, this probe-before-destroy approach has been demonstrated for atomic structure determination by serial X-ray diffraction of microcrystals. There has been the question whether a similar approach can be extended to probe the local electronic structure by X-ray spectroscopy. To address this, we have carried out femtosecond X-ray emission spectroscopy (XES) at the Linac Coherent Light Source using redox-active Mn complexes. XES probes the charge and spin states as well as the ligand environment, critical for understanding the functional role of redox-active metal sites. K beta(1,3) XES spectra of Mn-II and Mn-2(III,IV) complexes at room temperature were collected using a wavelength dispersive spectrometer and femtosecond X-ray pulses with an individual dose of up to > 100 MGy. The spectra were found in agreement with undamaged spectra collected at low dose using synchrotron radiation. Our results demonstrate that the intact electronic structure of redox active transition metal compounds in different oxidation states can be characterized with this shot-by-shot method. This opens the door for studying the chemical dynamics of metal catalytic sites by following reactions under functional conditions. The technique can be combined with X-ray diffraction to simultaneously obtain the geometric structure of the overall protein and the local chemistry of active metal sites and is expected to prove valuable for understanding the mechanism of important metalloproteins, such as photosystem II.
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| 3. |
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| 4. |
- Hattne, Johan, et al.
(author)
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Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers
- 2014
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In: Nature Methods. - 1548-7091 .- 1548-7105. ; 11:5, s. 545-548
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Journal article (peer-reviewed)abstract
- X-ray free-electron laser (XFEL) sources enable the use of crystallography to solve three-dimensional macromolecular structures under native conditions and without radiation damage. Results to date, however, have been limited by the challenge of deriving accurate Bragg intensities from a heterogeneous population of microcrystals, while at the same time modeling the X-ray spectrum and detector geometry. Here we present a computational approach designed to extract meaningful high-resolution signals from fewer diffraction measurements.
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| 5. |
- Hattne, Johan, et al.
(author)
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Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers
- 2014
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In: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:5, s. 545-548
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Journal article (peer-reviewed)abstract
- X-ray free-electron laser (XFEL) sources enable the use of crystallography to solve three-dimensional macromolecular structures under native conditions and without radiation damage. Results to date, however, have been limited by the challenge of deriving accurate Bragg intensities from a heterogeneous population of microcrystals, while at the same time modeling the X-ray spectrum and detector geometry. Here we present a computational approach designed to extract meaningful high-resolution signals from fewer diffraction measurements.
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| 6. |
- Kern, Jan, et al.
(author)
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Room temperature femtosecond X-ray diffraction of photosystem II microcrystals
- 2012
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:25, s. 9721-9726
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Journal article (peer-reviewed)abstract
- Most of the dioxygen on earth is generated by the oxidation of water by photosystem II (PS II) using light from the sun. This lightdriven, four-photon reaction is catalyzed by the Mn4CaO5 cluster located at the lumenal side of PS II. Various X-ray studies have been carried out at cryogenic temperatures to understand the intermediate steps involved in the water oxidation mechanism. However, the necessity for collecting data at room temperature, especially for studying the transient steps during the O-O bond formation, requires the development of new methodologies. In this paper we report room temperature X-ray diffraction data of PS II microcrystals obtained using ultrashort (<50 fs) 9 keV X-ray pulses from a hard X-ray free electron laser, namely the Linac Coherent Light Source. The results presented here demonstrate that the probe before destroy approach using an X-ray free electron laser works even for the highly-sensitive Mn4CaO5 cluster in PS II at room temperature. We show that these data are comparable to those obtained in synchrotron radiation studies as seen by the similarities in the overall structure of the helices, the protein subunits and the location of the various cofactors. This work is, therefore, an important step toward future studies for resolving the structure of the Mn4CaO5 cluster without any damage at room temperature, and of the reaction intermediates of PS II during O-O bond formation.
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| 7. |
- Kern, Jan, et al.
(author)
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Simultaneous Femtosecond X-ray Spectroscopy and Diffraction of Photosystem II at Room Temperature
- 2013
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 340:6131, s. 491-495
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Journal article (peer-reviewed)abstract
- Intense femtosecond x-ray pulses produced at the Linac Coherent Light Source (LCLS) were used for simultaneous x-ray diffraction (XRD) and x-ray emission spectroscopy (XES) of microcrystals of photosystem II (PS II) at room temperature. This method probes the overall protein structure and the electronic structure of the Mn4CaO5 cluster in the oxygen-evolving complex of PS II. XRD data are presented from both the dark state (S-1) and the first illuminated state (S-2) of PS II. Our simultaneous XRD-XES study shows that the PS II crystals are intact during our measurements at the LCLS, not only with respect to the structure of PS II, but also with regard to the electronic structure of the highly radiation-sensitive Mn4CaO5 cluster, opening new directions for future dynamics studies.
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| 8. |
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| 9. |
- Kern, Jan, et al.
(author)
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Taking snapshots of photosynthetic water oxidation using femtosecond X-ray diffraction and spectroscopy
- 2014
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4371-
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Journal article (peer-reviewed)abstract
- The dioxygen we breathe is formed by light-induced oxidation of water in photosystem II. O-2 formation takes place at a catalytic manganese cluster within milliseconds after the photosystem II reaction centre is excited by three single-turnover flashes. Here we present combined X-ray emission spectra and diffraction data of 2-flash (2F) and 3-flash (3F) photosystem II samples, and of a transient 3F' state (250 mu s after the third flash), collected under functional conditions using an X-ray free electron laser. The spectra show that the initial O-O bond formation, coupled to Mn reduction, does not yet occur within 250 mu s after the third flash. Diffraction data of all states studied exhibit an anomalous scattering signal from Mn but show no significant structural changes at the present resolution of 4.5 angstrom. This study represents the initial frames in a molecular movie of the structural changes during the catalytic reaction in photosystem II.
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| 10. |
- Sierra, Raymond G., et al.
(author)
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Nanoflow electrospinning serial femtosecond crystallography
- 2012
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In: Acta Crystallographica Section D. - : Wiley-Blackwell. - 0907-4449 .- 1399-0047. ; 68, s. 1584-1587
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Journal article (peer-reviewed)abstract
- An electrospun liquid microjet has been developed that delivers protein microcrystal suspensions at flow rates of 0.14-3.1 mu l min(-1) to perform serial femtosecond crystallography (SFX) studies with X-ray lasers. Thermolysin microcrystals flowed at 0.17 mu l min(-1) and diffracted to beyond 4 angstrom resolution, producing 14 000 indexable diffraction patterns, or four per second, from 140 mu g of protein. Nanoflow electrospinning extends SFX to biological samples that necessitate minimal sample consumption.
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| 11. |
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| 12. |
- Fokkens, Wytske J., et al.
(author)
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EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists
- 2012
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In: Rhinology. - 0300-0729. ; 50:1, s. 1-12
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Journal article (peer-reviewed)abstract
- The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also propose definitions for 'difficult to treat' rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between the upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists.
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| 13. |
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| 14. |
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| 15. |
- Mitzner, Rolf, et al.
(author)
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L-Edge X-ray Absorption Spectroscopy of Dilute Systems Relevant to Metalloproteins Using an X-ray Free-Electron Laser
- 2013
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In: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 4:21, s. 3641-3647
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Journal article (peer-reviewed)abstract
- L-edge spectroscopy of 3d transition metals provides important electronic structure information and has been used in many fields. However, the use of this method for studying dilute aqueous systems, such as metalloenzymes, has not been prevalent because of severe radiation damage and the lack of suitable detection systems. Here we present spectra from a dilute Mn aqueous solution using a high-transmission zone-plate spectrometer at the Linac Coherent Light Source (LCLS). The spectrometer has been optimized for discriminating the Mn L-edge signal from the overwhelming 0 K-edge background that arises from water and protein itself, and the ultrashort LCLS X-ray pulses can outrun X-ray induced damage. We show that the deviations of the partial-fluorescence yield-detected spectra from the true absorption can be well modeled using the state-dependence of the fluorescence yield, and discuss implications for the application of our concept to biological samples.
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| 16. |
- Sansoni, P, et al.
(author)
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New advances in CMV and immunosenescence
- 2014
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In: Experimental gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 55, s. 54-62
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Journal article (other academic/artistic)
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| 17. |
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| 18. |
- Bachert, C, et al.
(author)
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ICON: chronic rhinosinusitis
- 2014
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In: The World Allergy Organization journal. - : Elsevier BV. - 1939-4551. ; 7:1, s. 25-
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Journal article (peer-reviewed)
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| 19. |
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| 20. |
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| 21. |
- Claussnitzer, Melina, et al.
(author)
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Leveraging cross-species transcription factor binding site patterns: from diabetes risk Loci to disease mechanisms.
- 2014
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In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 156:1-2, s. 343-358
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms.
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| 22. |
- Cooper, Lyndon F., et al.
(author)
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Immediate Provisionalization of Dental Implants Placed in Healed Alveolar Ridges and Extraction Sockets : A 5-year Prospective Evaluation
- 2014
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In: International Journal of Oral & Maxillofacial Implants. - : Quintessence. - 0882-2786 .- 1942-4434. ; 29:3, s. 709-717
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Journal article (peer-reviewed)abstract
- Purpose: This 5-year prospective multicenter study compared implant survival and success, peri-implant health and soft tissue responses, crestal bone level stability, and complication rates following immediate loading of single OsseoSpeed implants placed in anterior maxillary healed ridges or extraction sockets. Materials and Methods: Individuals requiring anterior tooth replacement with single implants were treated and immediately provisionalized. Definitive all-ceramic crowns were placed at 12 weeks. Implant survival, bone levels, soft tissue levels, and peri-implant health were monitored for 5 years. Results: One hundred thirteen patients received implants in fresh sockets (55) and healed ridges (58). After 5 years, 45 and 49 patients remained for evaluation, respectively. During the first year, three implants failed in the extraction socket group (94.6% survival) and one implant failed in the healed ridge group (98.3% survival); this difference was not significant. No further implant failures were recorded. After 5 years, the interproximal crestal bone levels were located a mean of 0.43 +/- 0.63 mm and 0.38 +/- 0.62 mm from the reference points of implants in sockets and healed ridges (not a significant difference). In both groups, papillae increased over time and peri-implant mucosal zenith positions were stable from the time of definitive crown placement in sockets and healed ridges. Compared to flap surgery for implants in healed ridges, flapless surgery resulted in increased peri-implant mucosal tissue dimension (average, 0.78 +/- 1.34 mm vs 0.19 +/- 0.79 mm). Conclusion: After 5 years, the bone and soft tissue parameters that characterize implant success and contribute to dental implant esthetics were similar following the immediate provisionalization of implants in sockets and healed ridges. The overall tissue responses and reported implant survival support the immediate provisionalization of dental implants in situations involving healed ridges and, under ideal circumstances, extraction sockets.
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| 23. |
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| 24. |
- Green, Richard E., et al.
(author)
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Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1335-
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Journal article (peer-reviewed)abstract
- To provide context for the diversification of archosaurs-the group that includes crocodilians, dinosaurs, and birds-we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
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| 25. |
- Junquera, Tomas, et al.
(author)
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Design of a New Horizontal Test Cryostat for Scrfcavities at the Uppsala University
- 2014
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In: SRF2013: Proceedings of the 16th International Conference on RF Superconductivity. - 9783954501434 ; , s. 325-327
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Conference paper (other academic/artistic)abstract
- At Uppsala University, the FREIA facility for researchand development of new accelerators and associatedinstrumentation, is presently in construction. Associatedto a new Helium Liquefier, a Horizontal Test Cryostat willbe used for high power RF tests of completely equippedSC cavities. This paper presents the main characteristicsof the cryostat. Two types of cavities have beenconsidered for test purpose: SC elliptical cavities forfuture free electron lasers and SC cavities for highintensity proton accelerators. A special valve boxincluding a subcooling stage and power coupler coolingwith supercritical Helium supply have been designed, fortemperature operation ranging from 2 K to 4.2 K. Thisfacility will play an essential role in the development andtest of cavities, couplers and cryomodules for the ESSproject. High power RF sources will be installed in orderto allow unique and complete tests of spoke cavities andcryomodules at high nominal peak power.
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| 26. |
- Rockstuhl, C., et al.
(author)
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Large scale simulations in the realm of nanooptics
- 2010
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9780819480002 ; 7604
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Conference paper (other academic/artistic)abstract
- The realm of nanooptics is usually characterized by the interaction of light with structures having relevant feature sizes much smaller than the wavelength. To model such problems, a large variety of methods exists. However, most of them either require a periodic arrangement of a unit cell or can handle only single entities. But there exists a great variety of functional devices which may have either a spatial extent much larger than the wavelength and which comprise structural details with sizes in the order of a fraction of the wavelength or they may consist of an amorphous arrangement of strongly scattering entities. Such structures require large scale simulations where the fine details are retained. In this contribution we outline our latest research on such devices and detail the computational peculiarities we have to overcome. Presenting several examples, we show how simulations support the physical understanding of these devices. Examples are randomly textured surfaces used for solar cells, where guided modes excited in the light absorbing layers strongly affect the solar cell efficiency, amorphous metamaterials and stochastically arranged nanoantennas. The usage of computational experiments will be motivated by the unprecedented insight into the functionality of such components. © 2010 Copyright SPIE - The International Society for Optical Engineering.
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| 30. |
- Vogel, L., et al.
(author)
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Early in-flight detection of SO2 via Differential Optical Absorption Spectroscopy: a feasible aviation safety measure to prevent potential encounters with volcanic plumes
- 2011
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In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 4:9, s. 1785-1804
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Journal article (peer-reviewed)abstract
- Volcanic ash constitutes a risk to aviation, mainly due to its ability to cause jet engines to fail. Other risks include the possibility of abrasion of windshields and potentially serious damage to avionic systems. These hazards have been widely recognized since the early 1980s, when volcanic ash provoked several incidents of engine failure in commercial aircraft. In addition to volcanic ash, volcanic gases also pose a threat. Prolonged and/or cumulative exposure to sulphur dioxide (SO(2)) or sulphuric acid (H(2)SO(4)) aerosols potentially affects e. g. windows, air frame and may cause permanent damage to engines. SO(2) receives most attention among the gas species commonly found in volcanic plumes because its presence above the lower troposphere is a clear proxy for a volcanic cloud and indicates that fine ash could also be present. Up to now, remote sensing of SO(2) via Differential Optical Absorption Spectroscopy (DOAS) in the ultraviolet spectral region has been used to measure volcanic clouds from ground based, airborne and satellite platforms. Attention has been given to volcanic emission strength, chemistry inside volcanic clouds and measurement procedures were adapted accordingly. Here we present a set of experimental and model results, highlighting the feasibility of DOAS to be used as an airborne early detection system of SO(2) in two spatial dimensions. In order to prove our new concept, simultaneous airborne and ground-based measurements of the plume of Popocatepetl volcano, Mexico, were conducted in April 2010. The plume extended at an altitude around 5250 m above sea level and was approached and traversed at the same altitude with several forward looking DOAS systems aboard an airplane. These DOAS systems measured SO(2) in the flight direction and at +/- 40 mrad (2.3 degrees) angles relative to it in both, horizontal and vertical directions. The approaches started at up to 25 km distance to the plume and SO(2) was measured at all times well above the detection limit. In combination with radiative transfer studies, this study indicates that an extended volcanic cloud with a concentration of 10(12) molecules cm(-3) at typical flight levels of 10 km can be detected unambiguously at distances of up to 80 km away. This range provides enough time (approx. 5 min) for pilots to take action to avoid entering a volcanic cloud in the flight path, suggesting that this technique can be used as an effective aid to prevent dangerous aircraft encounters with potentially ash rich volcanic clouds.
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| 31. |
- Wagner, Henrik, et al.
(author)
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Cardiac arrest in the catheterisation laboratory: A 5-year experience of using mechanical chest compressions to facilitate PCI during prolonged resuscitation efforts.
- 2010
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In: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 81, s. 383-387
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Journal article (peer-reviewed)abstract
- PURPOSE: Lengthy resuscitations in the catheterisation laboratory carry extremely high rates of mortality because it is essentially impossible to perform effective chest compressions during percutaneous coronary intervention (PCI). The purpose of this study was to evaluate the use of a mechanical chest compression device, LUCAS, in the catheterisation laboratory, in patients who suffered circulatory arrest requiring prolonged resuscitation. MATERIALS AND METHODS: The study population was comprised of patients who arrived alive to the catheterisation laboratory and then required mechanical chest compression at some time during the angiogram, PCI or pericardiocentesis between 2004 and 2008 at the Lund University Hospital. This is a retrospective registry analysis. RESULTS: During the study period, a total of 3058 patients were treated with PCI for ST-elevation myocardial infarction (STEMI) of whom 118 were in cardiogenic shock and 81 required defibrillations. LUCAS was used in 43 patients (33 STEMI, 7 non-ST-elevation myocardial infarction (NSTEMI), 2 elective PCIs and 1 patient with tamponade). Five patients had tamponade due to myocardial rupture prior to PCI that was revealed at the start of the PCI, and all five died. Of the remaining 38 patients, 1 patient underwent a successful pericardiocentesis and 36 were treated with PCI. Eleven of these patients were discharged alive in good neurological condition. CONCLUSION: The use of mechanical chest compressions in the catheterisation laboratory allows for continued PCI or pericardiocentesis despite ongoing cardiac or circulatory arrest with artificially sustained circulation. It is unlikely that few, if any, of the patients would have survived without the use of mechanical chest compressions in the catheterisation laboratory.
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