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Search: WFRF:(Wiesner M)

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1.
  • Adrian-Martinez, S., et al. (author)
  • A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
  • 2013
  • In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
  • Journal article (peer-reviewed)abstract
    • We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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2.
  • Evans, P. A., et al. (author)
  • Swift Follow-up Observations of Candidate Gravitational-wave Transient Events
  • 2012
  • In: The Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 203:2
  • Journal article (peer-reviewed)abstract
    • We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were selected with low latency by the network of GW detectors (within less than 10 minutes) and their candidate sky locations were observed by the Swift observatory (within 12 hr). Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge." With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime, multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.
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3.
  • Aasi, J., et al. (author)
  • Parameter estimation for compact binary coalescence signals with the first generation gravitational-wave detector network
  • 2013
  • In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 88:6
  • Journal article (peer-reviewed)abstract
    • Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a "blind injection'' where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M(circle dot)-25M(circle dot) and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.
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4.
  • Aasi, J., et al. (author)
  • Search for gravitational waves from binary black hole inspiral, merger, and ringdown in LIGO-Virgo data from 2009-2010
  • 2013
  • In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:2
  • Journal article (peer-reviewed)abstract
    • We report a search for gravitational waves from the inspiral, merger and ringdown of binary black holes (BBH) with total mass between 25 and 100 solar masses, in data taken at the LIGO and Virgo observatories between July 7, 2009 and October 20, 2010. The maximum sensitive distance of the detectors over this period for a (20, 20)M-circle dot coalescence was 300 Mpc. No gravitational wave signals were found. We thus report upper limits on the astrophysical coalescence rates of BBH as a function of the component masses for nonspinning components, and also evaluate the dependence of the search sensitivity on component spins aligned with the orbital angular momentum. We find an upper limit at 90% confidence on the coalescence rate of BBH with nonspinning components of mass between 19 and 28M(circle dot) of 3:3 x 10(-7) mergers Mpc(-3) yr(-1).
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5.
  • Aasi, J., et al. (author)
  • The characterization of Virgo data and its impact on gravitational-wave searches
  • 2012
  • In: Classical and Quantum Gravity. - : IOP Publishing. - 1361-6382 .- 0264-9381. ; 29:15
  • Journal article (peer-reviewed)abstract
    • Between 2007 and 2010 Virgo collected data in coincidence with the LIGO and GEO gravitational-wave (GW) detectors. These data have been searched for GWs emitted by cataclysmic phenomena in the universe, by non-axisymmetric rotating neutron stars or from a stochastic background in the frequency band of the detectors. The sensitivity of GW searches is limited by noise produced by the detector or its environment. It is therefore crucial to characterize the various noise sources in a GW detector. This paper reviews the Virgo detector noise sources, noise propagation, and conversion mechanisms which were identified in the three first Virgo observing runs. In many cases, these investigations allowed us to mitigate noise sources in the detector, or to selectively flag noise events and discard them from the data. We present examples from the joint LIGO-GEO-Virgo GW searches to show how well noise transients and narrow spectral lines have been identified and excluded from the Virgo data. We also discuss how detector characterization can improve the astrophysical reach of GW searches.
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6.
  • Aasi, J., et al. (author)
  • Einstein@Home all-sky search for periodic gravitational waves in LIGO S5 data
  • 2013
  • In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:4
  • Journal article (peer-reviewed)abstract
    • This paper presents results of an all-sky search for periodic gravitational waves in the frequency range [50, 1190] Hz and with frequency derivative range of similar to[-20, 1.1] x 10(-10) Hz s(-1) for the fifth LIGO science run (S5). The search uses a noncoherent Hough-transform method to combine the information from coherent searches on time scales of about one day. Because these searches are very computationally intensive, they have been carried out with the Einstein@Home volunteer distributed computing project. Postprocessing identifies eight candidate signals; deeper follow-up studies rule them out. Hence, since no gravitational wave signals have been found, we report upper limits on the intrinsic gravitational wave strain amplitude h(0). For example, in the 0.5 Hz-wide band at 152.5 Hz, we can exclude the presence of signals with h(0) greater than 7.6 x 10(-25) at a 90% confidence level. This search is about a factor 3 more sensitive than the previous Einstein@Home search of early S5 LIGO data.
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7.
  • Hudson, Thomas J., et al. (author)
  • International network of cancer genome projects
  • 2010
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
  • Journal article (peer-reviewed)abstract
    • The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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8.
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9.
  • Eschbach, Judith, et al. (author)
  • PGC-1 is a male-specific disease modifier of human and experimental amyotrophic lateral sclerosis
  • 2013
  • In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:17, s. 3477-3484
  • Journal article (peer-reviewed)abstract
    • Amyotrophic lateral sclerosis (ALS) is a devastating, adult-onset neurodegenerative disorder of the upper and lower motor systems. It leads to paresis, muscle wasting and inevitably to death, typically within 35 years. However, disease onset and survival vary considerably ranging in extreme cases from a few months to several decades. The genetic and environmental factors underlying this variability are of great interest as potential therapeutic targets. In ALS, men are affected more often and have an earlier age of onset than women. This gender difference is recapitulated in transgenic rodent models, but no underlying mechanism has been elucidated. Here we report that SNPs in the brain-specific promoter region of the transcriptional co-activator PGC-1, a master regulator of metabolism, modulate age of onset and survival in two large and independent ALS populations and this occurs in a strictly male-specific manner. In complementary animal studies, we show that deficiency of full-length (FL) Pgc-1 leads to a significantly earlier age of onset and a borderline shortened survival in male, but not in female ALS-transgenic mice. In the animal model, FL Pgc-1-loss is associated with reduced mRNA levels of the trophic factor Vegf-A in males, but not in females. In summary, we indentify PGC-1 as a novel and clinically relevant disease modifier of human and experimental ALS and report a sex-dependent effect of PGC-1 in this neurodegenerative disorder.
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11.
  • Lindström, Björn, et al. (author)
  • Fast failures in the LHC and the future high luminosity LHC
  • 2020
  • In: Physical Review Accelerators and Beams. - : AMER PHYSICAL SOC. - 2469-9888. ; 23:8
  • Journal article (peer-reviewed)abstract
    • An energy of 362 MJ is stored in each of the two LHC proton beams for nominal beam parameters. This will be further increased to about 700 MJ in the future high luminosity LHC (HL-LHC) and uncontrolled beam losses represent a significant hazard for the integrity and safe operation of the machine. In this paper, a number of failure mechanisms that can lead to a fast increase of beam losses are analyzed. Most critical are failures in the magnet protection system, namely the quench heaters and a novel protection system called coupling-loss induced quench (CLIQ). An important outcome is that magnet protection has to be evaluated for its impact on the beam and designed accordingly. In particular, CLIQ, which is to protect the new HL-LHC triplet magnets, constitutes the fastest known failure in the LHC if triggered spuriously. A schematic change of CLIQ to mitigate the hazard is presented. A loss of the beam-beam kick due to the extraction of one beam is another source of beam losses with a fast onset. A significantly stronger impact is expected in the upcoming LHC Run III and HL-LHC as compared to the current LHC, mainly due to the increased bunch intensity. Its criticality and mitigation methods are discussed. It is shown that symmetric quenches in the superconducting magnets for the final focusing triplet can have a significant impact on the beam on short timescales. The impact on the beam due to failures of the beam-beam compensating wires as well as coherent excitations by the transverse beam damper are also discussed.
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12.
  • Abolfathi, Bela, et al. (author)
  • The LSST DESC DC2 Simulated Sky Survey
  • 2021
  • In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 253:31
  • Journal article (peer-reviewed)abstract
    • We describe the simulated sky survey underlying the second data challenge (DC2) carried out in preparation for analysis of the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) by the LSST Dark Energy Science Collaboration (LSST DESC). Significant connections across multiple science domains will be a hallmark of LSST; the DC2 program represents a unique modeling effort that stresses this interconnectivity in a way that has not been attempted before. This effort encompasses a full end-to-end approach: starting from a large N-body simulation, through setting up LSST-like observations including realistic cadences, through image simulations, and finally processing with Rubin's LSST Science Pipelines. This last step ensures that we generate data products resembling those to be delivered by the Rubin Observatory as closely as is currently possible. The simulated DC2 sky survey covers six optical bands in a wide-fast-deep area of approximately 300 deg2, as well as a deep drilling field of approximately 1 deg2. We simulate 5 yr of the planned 10 yr survey. The DC2 sky survey has multiple purposes. First, the LSST DESC working groups can use the data set to develop a range of DESC analysis pipelines to prepare for the advent of actual data. Second, it serves as a realistic test bed for the image processing software under development for LSST by the Rubin Observatory. In particular, simulated data provide a controlled way to investigate certain image-level systematic effects. Finally, the DC2 sky survey enables the exploration of new scientific ideas in both static and time domain cosmology.
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13.
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14.
  • De Brito, A. N., et al. (author)
  • Evidence against atomiclike resonant auger decay in N2 doubly excited core states by high-resolution experiments
  • 2001
  • In: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947. ; 64:5, s. 547021-547024
  • Journal article (peer-reviewed)abstract
    • The resonant Auger decay spectra associated with doubly excited core-hole states near the N 1s threshold in the nitrogen molecule was measured. Electron-yield spectrum was obtained by setting a kinetic-energy window at 384 eV and scanning across the threshold region. At ground 410, 414, and 416 eV, photon energy, three dominant structures were observed. The increased signal-to-background ratio, intensity and resolution at third generation facilities were found to cast a different light on the dynamics of core photoionization in molecules.
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15.
  • Feifel, R., et al. (author)
  • "Hidden" vibrations in CO : Reinvestigation of resonant Auger decay for the C 1s → π* excitation
  • 2002
  • In: Physical Review A - Atomic, Molecular, and Optical Physics. - 1050-2947. ; 65:5 A, s. 527011-527018
  • Journal article (peer-reviewed)abstract
    • The higher vibrational levels of the C 1s→π* excitation in carbon monooxide (CO) were investigated by using resonant Auger electron spectroscopy. The absorption profile of the CO was recorded in the partial electron yield mode. The results showed that the vibrational states were not seen in a total yield absorption spectrum whereas they were shown to be discernable in a partial electron yield spectrum.
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17.
  • Hjelte, I., et al. (author)
  • Evidence for ultra-fast dissociation of molecular water from resonant Auger spectroscopy
  • 2001
  • In: Chemical Physics Letters. - 0009-2614. ; 334:1-3, s. 151-158
  • Journal article (peer-reviewed)abstract
    • We present direct evidence for ultra-fast dissociation of molecular water in connection photo-excitation of the O1s→4a1 resonance. The core-excited H2O molecules are shown to dissociate into core-excited O*H and neutral H on a time scale comparable to the core hole lifetime, i.e. a few femtoseconds. This conclusion is based on a resonant Auger study, qualitative arguments and ab initio calculations. 'Hot bands' connected to Auger transitions from vibrationally excited OH fragments are identified, and these exhibit a dynamical behavior which qualitatively follows the change in excess energy.
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19.
  • Micic, V., et al. (author)
  • Impact of Sodium Humate Coating on Collector Surfaces on Deposition of Polymer-Coated Nanoiron Particles
  • 2017
  • In: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:16, s. 9202-9209
  • Journal article (peer-reviewed)abstract
    • The affinity between nanoscale zerovalent iron (nano-ZVI) and mineral surfaces hinders its mobility, and hence its delivery into contaminated aquifers. We have tested the hypothesis that the attachment of poly(acrylic acid)-coated nano-ZVI (PAA-nano-ZVI) to mineral surfaces could be limited by coating such surfaces with sodium (Na) humate prior to PAA-nano-ZVI injection. Na humate was expected to form a coating over favorable sites for PAA-nano-ZVI attachment and hence reduce the affinity of PAA-nano-ZVI for the collector surfaces through electrosteric repulsion between the two interpenetrating charged polymers. Column experiments demonstrated that a low concentration (10 mg/L) Na humate solution in synthetic water significantly improved the mobility of PAA-nano-ZVI within a standard sand medium. This effect was, however, reduced in more heterogeneous natural collector media from contaminated sites, as not an adequate of the collector sites favorable for PAA-nano-ZVI attachment within these media appear to have been screened by the Na humate. Na humate did not interact with the surfaces of acid-washed glass beads or standard Ottawa sand, which presented less surface heterogeneity. Important factors influencing the effectiveness of Na humate application in improving PAA-nano-ZVI mobility include the solution chemistry, the Na humate concentration, and the collector properties.
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20.
  • Rosenqvist, L., et al. (author)
  • Femtosecond dissociation of ozone studied by the Auger Doppler effect
  • 2001
  • In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 115:8, s. 3614-3620
  • Journal article (peer-reviewed)abstract
    • The peaks arising from the decay of the excited oxygen atom were studied. Fast dissociation of core-excited ozone was confirmed by the presence of Auger emission from atomic oxygen in the decay spectrum from the ozone OT 1s-σ*(7a1) state. No such emission was observed after excitation of the corresponding state on the central oxygen atom. An angle-dependent energy shift of the atomic lines was observed. Analysis of the energy shift revealed that the kinetic energy released in the dissociation process is approximately 3.3 ± 0.3eV. An energy release of 8.45 was found by application of a Born-Haber cycle.
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21.
  • Wang, H., et al. (author)
  • Filtering core excitation spectra : Vibrationally resolved constant ionic state studies of N 1s → 2π core-excited NO
  • 2001
  • In: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 34:22, s. 4417-4426
  • Journal article (peer-reviewed)abstract
    • High-resolution electron spectroscopy studies of the NO molecule in the regions of the N 1s → 2π core excitations have been performed. By selecting electrons within certain binding energy ranges, either the Auger electron yield - a good approximation for the x-ray absorption spectrum - or the electrons emitted after decay to a particular ionic final state (constant ionic state (CIS)) were detected. By selecting the X 1Σ+ (2π0) final state, the superposition of several intermediate state can be disentangled by exploiting a selection rule which permits only two of the three dipole-allowed intermediate states to decay to this specific final state. This makes it possible to obtain more detailed information on the potential energy curves of the intermediate states than is available from regular absorption measurements. We have also obtained CIS spectra for individual vibrational sublevels within this state. The role of lifetime vibrational interference on the appearance of these spectra is discussed.
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22.
  • Wiesner, M., et al. (author)
  • The electron-phonon interaction at deep Bi 2 Te3-semiconductor interfaces from Brillouin light scattering
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 7:1
  • Journal article (peer-reviewed)abstract
    • It is shown that the electron-phonon interaction at a conducting interface between a topological insulator thin film and a semiconductor substrate can be directly probed by means of high-resolution Brillouin light scattering (BLS). The observation of Kohn anomalies in the surface phonon dispersion curves of a 50 nm thick Bi2Te3 film on GaAs, besides demonstrating important electron-phonon coupling effects in the GHz frequency domain, shows that information on deep interface electrons can be obtained by tuning the penetration depth of optically-generated surface phonons so as to selectively probe the interface region, as in a sort of quantum sonar.
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23.
  • Wiesner, S., et al. (author)
  • Effects of environmental dynamicity on requirements engineering for complex systems
  • 2017
  • In: IFIP WG 5.7 International Conference on Advances in Production Management Systems, APMS 2017. - Cham : Springer. - 9783319669229 ; , s. 255-262
  • Conference paper (peer-reviewed)abstract
    • With customers demanding more and more holistic answers to their problems, solution providers respond with complex systems, integrating product, service and ICT elements into their offer. These solutions need to be aligned to a high number of requirements, coming not only from the individual customer but also from an environment of network partners, technology providers and other stakeholders. Especially for Product-Service Systems, where the solution provider takes responsibility in the operational phase, this environment is dynamic over the system life cycle. Stakeholders may enter or leave, as well as changing needs and technological capabilities. This makes the requirements towards the solution volatile, demanding a suitable Requirements Engineering approach. In this paper, it is discussed how environmental dynamicity can be monitored for its effect on requirements, with a special focus on organizational issues. Through a literature review and industrial case studies it is analysed, how it can be ensured that environmental changes can be taken into account in Requirements Engineering, leading to an optimal system configuration to address the customer problem.
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24.
  • Abdelwahab, Mahmoud Tareq, et al. (author)
  • Clofazimine pharmacokinetics in patients with TB : dosing implications
  • 2020
  • In: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 75:11, s. 3269-3277
  • Journal article (peer-reviewed)abstract
    • Background: Clofazimine is in widespread use as a key component of drug-resistant TB regimens, but the recommended dose is not evidence based. Pharmacokinetic data from relevant patient populations are needed to inform dose optimization. Objectives: To determine clofazimine exposure, evaluate covariate effects on variability, and simulate exposures for different dosing strategies in South African TB patients. Patients and methods: Clinical and pharmacokinetic data were obtained from participants with pulmonary TB enrolled in two studies with intensive and sparse sampling for up to 6 months. Plasma concentrations were measured by LC-MS/MS and interpreted with non-Linear mixed-effects modelling. Body size descriptors and other potential covariates were tested on pharmacokinetic parameters. We simulated different dosing regimens to safely shorten time to average daily concentration above a putative target concentration of 0.25 mg/L. Results: We analysed 1570 clofazimine concentrations from 139 participants; 79 (57%) had drug-resistant TB and 54 (39%) were HIV infected. Clofazimine pharmacokinetics were well characterized by a three-compartment model. Clearance was 11.5 L/h and peripheral volume 10500 L for a typical participant. Lower plasma exposures were observed in women during the first few months of treatment, explained by higher body fat fraction. Model-based simulations estimated that a Loading dose of 200 mg daily for 2 weeks would achieve average daily concentrations above a target efficacy concentration 37 days earlier in a typical TB participant. Conclusions: Clofazimine was widely distributed with a Long elimination half-Life. Disposition was strongly influenced by body fat content, with potential dosing implications for women with TB.
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25.
  • Basu, Swaraj, et al. (author)
  • Accurate mapping of mitochondrial DNA deletions and duplications using deep sequencing
  • 2020
  • In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:12
  • Journal article (peer-reviewed)abstract
    • Deletions and duplications in mitochondrial DNA (mtDNA) cause mitochondrial disease and accumulate in conditions such as cancer and age-related disorders, but validated high-throughput methodology that can readily detect and discriminate between these two types of events is lacking. Here we establish a computational method, MitoSAlt, for accurate identification, quantification and visualization of mtDNA deletions and duplications from genomic sequencing data. Our method was tested on simulated sequencing reads and human patient samples with single deletions and duplications to verify its accuracy. Application to mouse models of mtDNA maintenance disease demonstrated the ability to detect deletions and duplications even at low levels of heteroplasmy. Author summary Deletions in the mitochondrial genome cause a wide variety of rare disorders, but are also linked to more common conditions such as neurodegeneration, diabetes type 2, and the normal ageing process. There is also a growing awareness that mtDNA duplications, which are also relevant for human disease, may be more common than previously thought. Despite their clinical importance, our current knowledge about the abundance, characteristics and diversity of mtDNA deletions and duplications is fragmented, and based to large extent on a limited view provided by traditional low-throughput analyses. Here, we describe a bioinformatics method, MitoSAlt, that can accurately map and classify mtDNA deletions and duplications using high-throughput sequencing. Application of this methodology to mouse models of mitochondrial deficiencies revealed a large number of duplications, suggesting that these may previously have been underestimated.
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26.
  • Bugiardini, Enrico, et al. (author)
  • MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy
  • 2019
  • In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 28:16, s. 2711-2719
  • Journal article (peer-reviewed)abstract
    • Mitochondrial disorders are clinically and genetically heterogeneous and are associated with a variety of disease mechanisms. Defects of mitochondrial protein synthesis account for the largest subgroup of disorders manifesting with impaired respiratory chain capacity; yet, only a few have been linked to dysfunction in the protein components of the mitochondrial ribosomes. Here, we report a subject presenting with dyskinetic cerebral palsy and partial agenesis of the corpus callosum, while histochemical and biochemical analyses of skeletal muscle revealed signs of mitochondrial myopathy. Using exome sequencing, we identified a homozygous variant c.215C>T in MRPS25, which encodes for a structural component of the 28S small subunit of the mitochondrial ribosome (mS25). The variant segregated with the disease and substitutes a highly conserved proline residue with leucine (p.P72L) that, based on the high-resolution structure of the 28S ribosome, is predicted to compromise inter-protein contacts and destabilize the small subunit. Concordant with the in silico analysis, patient's fibroblasts showed decreased levels of MRPS25 and other components of the 28S subunit. Moreover, assembled 28S subunits were scarce in the fibroblasts with mutant mS25 leading to impaired mitochondrial translation and decreased levels of multiple respiratory chain subunits. Crucially, these abnormalities were rescued by transgenic expression of wild-type MRPS25 in the mutant fibroblasts. Collectively, our data demonstrate the pathogenicity of the p.P72L variant and identify MRPS25 mutations as a new cause of mitochondrial translation defect.
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27.
  • Burmeister, F., et al. (author)
  • A study of the inner-valence ionization region in HCl and DCl
  • 2004
  • In: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 37:6, s. 1173-1183
  • Journal article (peer-reviewed)abstract
    • An in-depth photoionization study of the inner-valence electrons in HCl and DCl has been performed using synchrotron radiation. A series of photoelectron spectra of HCl were obtained at a resolution of 23 meV over the binding energy range 25-30.5 eV at various excitation energies and at two different electron collection angles relative to the plane of polarization of the undulator radiation. In addition, photoelectron spectra of DCl were recorded at two different excitation energies. These spectra were compared directly with the threshold photoelectron spectra of HCl and DCl that were recorded previously under similar resolution conditions (similar to30 meV). This comparative study reveals new information on the nature of the numerous band systems observed in this binding energy region. In addition, we present the experimental confirmation of the theoretical prediction given by Andersson et al (2001 Phys. Rev. A 65 012705) that a vibrational progression showing interference structure would appear in the main inner-valence ionization band in the photoelectron spectrum of DCl at a resolution of 10 meV.
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28.
  • Burmeister, F, et al. (author)
  • Nonadiabatic effects in photoelectron spectra of HCl and DCl. I. Experiment
  • 2002
  • In: Physical Review A (Atomic, Molecular and Optical Physics). - 1050-2947. ; 65:1
  • Journal article (peer-reviewed)abstract
    • The HCl inner-valence photoelectron band at 26 eV binding energy has been recorded at high resolution. Discrete peaks arising from at least two separate vibrational progressions are superimposed on the broad continuum. Fano profiles are visible in one of the progressions. This indicates interference between superimposed electronic states, where weak avoided crossing allows two adiabatic states to couple. In the isotopic DCl molecular spectrum, the discrete lines are less pronounced, due to slower dissociation and therefore less coupling between the continuum and the bound state.
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30.
  • Denti, Paolo, et al. (author)
  • Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis : A Prospective Population Pharmacokinetic Study
  • 2022
  • In: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 75:1, s. 141-151
  • Journal article (peer-reviewed)abstract
    • Background In 2010, the World Health Organization (WHO) revised dosing guidelines for treatment of childhood tuberculosis. Our aim was to investigate first-line antituberculosis drug exposures under these guidelines, explore dose optimization using the current dispersible fixed-dose combination (FDC) tablet of rifampicin/isoniazid/pyrazinamide; 75/50/150 mg, and suggest a new FDC with revised weight bands. Methods Children with drug-susceptible tuberculosis in Malawi and South Africa underwent pharmacokinetic sampling while receiving first-line tuberculosis drugs as single formulations according the 2010 WHO recommended doses. Nonlinear mixed-effects modeling and simulation was used to design the optimal FDC and weight-band dosing strategy for achieving the pharmacokinetic targets based on literature-derived adult AUC(0-24h) for rifampicin (38.7-72.9), isoniazid (11.6-26.3), and pyrazinamide (233-429 mg center dot h/L). Results In total, 180 children (42% female; 13.9% living with human immunodeficiency virus [HIV]; median [range] age 1.9 [0.22-12] years; weight 10.7 [3.20-28.8] kg) were administered 1, 2, 3, or 4 FDC tablets (rifampicin/isoniazid/pyrazinamide 75/50/150 mg) daily for 4-8, 8-12, 12-16, and 16-25 kg weight bands, respectively. Rifampicin exposure (for weight and age) was up to 50% lower than in adults. Increasing the tablet number resulted in adequate rifampicin but relatively high isoniazid and pyrazinamide exposures. Administering 1, 2, 3, or 4 optimized FDC tablets (rifampicin/isoniazid/pyrazinamide 120/35/130 mg) to children < 6, 6-13, 13-20. and 20-25 kg, and 0.5 tablet in < 3-month-olds with immature metabolism, improved exposures to all 3 drugs. Conclusions Current pediatric FDC doses resulted in low rifampicin exposures. Optimal dosing of all drugs cannot be achieved with the current FDCs. We propose a new FDC formulation and revised weight bands. Current pediatric dosing guidelines lead to infant rifampicin exposures much lower than in adults, whereas isoniazid and pyrazinamide exposures are similar. A new fixed-dose combination (FDC) with rifampicin/isoniazid/pyrazinamide 120/35/130 mg and weight bands of < 6, 6-13, 13-20, and 20-25 kg could improve treatment.
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33.
  • Fink, RF, et al. (author)
  • Spin-orbit selectivity observed for the HCl+ ((X)over-tilde (II)-I-2) state using resonant photoemission
  • 2002
  • In: Physical Review A (Atomic, Molecular and Optical Physics). - 1050-2947. ; 65:3
  • Journal article (peer-reviewed)abstract
    • We report the experimental observation of a strongly selective population of the spin-orbit components in the HCl+ (X) over tilde (2)Pi(Omega) states after excitation into the dissociative 2p(-1)6sigma* core excited state. A progression of highly excited vibrational states with either the Omega=3/2 or Omega=1/2 component of the final state is populated, respectively, when the excitation is tuned in the 2p(3/2)(-1)6sigma*or2p(1/2)(-1)6 sigma* part of the resonance. This effect is explained theoretically to be due to the orientational selectivity of the excitation process and the preference of the L-2,L-3 VV Auger process to produce valence holes with the same orientation as the core holes.
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34.
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35.
  • Giertz, A., et al. (author)
  • Vibrationally resolved photoelectron spectra of the carbon 1s and nitrogen 1s shells in hydrogen cyanide
  • 2002
  • In: Chemical Physics. - 0301-0104. ; 277:1, s. 83-90
  • Journal article (peer-reviewed)abstract
    • Vibrational structures of the C1s and N1s photoelectron spectra of gas-phase HCN have been investigated using monochromated third-generation synchrotron radiation. Both spectra exhibit resolved fine structure associated with several vibrationally excited states. In the C1s spectrum a single vibrational progression is observed, while the N1s spectrum is more complex. High-level ab initio calculations were performed to simulate the spectra and the agreement with the experimental results is good. Based on the calculations, the C1s ionisation is found to induce vibrations solely in the C≡N stretching mode with an energy of 280 meV, while the N1s ionisation generates vibrations also in the C-H stretching mode with an energy of about 387 meV, as well as combinations of these two modes.
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36.
  • Hjelte, I, et al. (author)
  • Evidence for ultra-fast dissociation of molecular water from resonant Auger spectroscopy
  • 2001
  • In: CHEMICAL PHYSICS LETTERS. - : ELSEVIER SCIENCE BV. - 0009-2614. ; 334:1-3, s. 151-158
  • Journal article (peer-reviewed)abstract
    • We present direct evidence for ultra-fast dissociation of molecular water in connection photo-excitation of the Ols --> 4a(1) resonance. The core-excited H2O molecules are shown to dissociate into core-excited O*H and neutral H on a time scale comparable
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37.
  • Hjelte, I, et al. (author)
  • Evidence of ultra-fast dissociation in ammonia observed by resonant Auger electron spectroscopy
  • 2003
  • In: Chemical Physics Letters. - 0009-2614. ; 370:5-6, s. 781-788
  • Journal article (peer-reviewed)abstract
    • We present evidence for ultra-fast dissociation of molecular ammonia when photo-excited to the Nls --> 4a(1) core-hole state. This finding is based on resonant Auger spectroscopical results as well as qualitative arguments concerning the photon energy dependence of the Auger structures. Calculations of the excited state potential based on the Z + l approximation were performed. Both the calculations and the measurements indicate that the most likely fragmentation pathway for the core excited ammonia molecules leads to NH2* and H fragments. (C) 2003 Elsevier Science B.V. All rights reserved.
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38.
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39.
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40.
  • Myrseth Oltedal, Velaug, et al. (author)
  • Vibrational structure and vibronic coupling in the carbon 1s photoelectron spectra of benzene and deuterobenzene
  • 2002
  • In: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084. ; 4:24, s. 5937-5943
  • Journal article (peer-reviewed)abstract
    • Vibrationally resolved C1s photoelectron spectra of benzene and d(6)-benzene have been recorded using monochromated synchrotron radiation at photon energies of 330 eV. The spectrum of normal benzene displays considerable vibrational structure. Particularly noteworthy is the strong excitation of a combined CCH-bending and CC-stretching mode which splits the main peak into two well-defined maxima. In d(6)-benzene, the vibrational energy levels are less well separated and the vibrational structure is reduced to strong asymmetry of the main peak and a broad tail extending toward higher ionization energy. The recorded spectra are analyzed using first-principle and curve-fitting procedures. A theoretical model that allows for incomplete localization of the core hole, results in very good fits to the experimental spectra of both benzene and d(6)-benzene.
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41.
  • Ngwalero, Precious, et al. (author)
  • Relationship between Plasma and Intracellular Concentrations of Bedaquiline and Its M2 Metabolite in South African Patients with Rifampin-Resistant Tuberculosis
  • 2021
  • In: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:11
  • Journal article (peer-reviewed)abstract
    • Bedaquiline is recommended for the treatment of all patients with rifampin-resistant tuberculosis (RR-TB). Bedaquiline accumulates within cells, but its intracellular pharmacokinetics have not been characterized, which may have implications for dose optimization. We developed a novel assay using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure the intracellular concentrations of bedaquiline and its primary metabolite M2 in patients with RR-TB in South Africa. Twenty-one participants were enrolled and underwent sparse sampling of plasma and peripheral blood mononuclear cells (PBMCs) at months 1, 2, and 6 of treatment and at 3 and 6 months after bedaquiline treatment completion. Intensive sampling was performed at month 2. We used noncompartmental analysis to describe plasma and intracellular exposures and a population pharmacokinetic model to explore the relationship between plasma and intracellular pharmacokinetics and the effects of key covariates. Bedaquiline concentrations from month 1 to month 6 of treatment ranged from 94.7 to 2,540 ng/ml in plasma and 16.2 to 5,478 ng/ml in PBMCs, and concentrations of M2 over the 6-month treatment period ranged from 34.3 to 496 ng/ml in plasma and 109.2 to 16,764 ng/ml in PBMCs. Plasma concentrations of bedaquiline were higher than those of M2, but intracellular concentrations of M2 were considerably higher than those of bedaquiline. In the pharmacokinetic modeling, we estimated a linear increase in the intracellular-plasma accumulation ratio for bedaquiline and M2, reaching maximum effect after 2 months of treatment. The typical intracellular-plasma ratios 1 and 2 months after start of treatment were 0.61 (95% confidence interval [CI]: 0.42 to 0.92) and 1.10 (95% CI: 0.74 to 1.63) for bedaquiline and 12.4 (95% CI: 8.8 to 17.8) and 22.2 (95% CI: 15.6 to 32.3) for M2. The intracellular-plasma ratios for both bedaquiline and M2 were decreased by 54% (95% CI: 24 to 72%) in HIV-positive patients compared to HIV-negative patients. Bedaquiline and M2 were detectable in PBMCs 6 months after treatment discontinuation. M2 accumulated at higher concentrations intracellularly than bedaquiline, supporting in vitro evidence that M2 is the main inducer of phospholipidosis.
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42.
  • Rosenqvist, L, et al. (author)
  • Femtosecond dissociation of ozone studied by the Auger Doppler effect
  • 2001
  • In: JOURNAL OF CHEMICAL PHYSICS. - : AMER INST PHYSICS. - 0021-9606. ; 115:8, s. 3614-3620 Language: English
  • Journal article (peer-reviewed)abstract
    • A Doppler-type shift in the kinetic energy of atomic Auger electrons emitted after fast dissociation of O-3 molecules is observed. The resonant Auger spectrum from the decay of repulsive core-excited states reflects both the early molecular ozone decay an
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43.
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44.
  • Tanneau, Lénaïg, et al. (author)
  • Population Pharmacokinetics of Delamanid and its Main Metabolite DM-6705 in Drug-Resistant Tuberculosis Patients Receiving Delamanid Alone or Coadministered with Bedaquiline
  • 2022
  • In: Clinical Pharmacokinetics. - : Springer. - 0312-5963 .- 1179-1926.
  • Journal article (peer-reviewed)abstract
    • Background: Delamanid is a nitroimidazole, a novel class of drug for treating tuberculosis. Delamanid is primarily metabolized by albumin into the metabolite DM-6705. The aims of this analysis were to develop a population pharmacokinetic (PK) model to characterize the concentration-time course of delamanid and DM-6705 in adults with drug-resistant tuberculosis and to explore a potential drug-drug interaction with bedaquiline when co-administered. Methods: Delamanid and DM-6705 concentrations after oral administration, from 52 participants (of whom 26 took bedaquiline concurrently and 20 were HIV-1 positive) enrolled in the DELIBERATE trial were analyzed using nonlinear mixed-effects modeling.Results: Delamanid PK was described by a one-compartment disposition model with transit compartment absorption (mean absorption time of 1.45 h (95% confidence interval 0.501–2.20)) and linear elimination. The PK of DM-6705 metabolite, was described by a one-compartment disposition model with delamanid clearance as input and linear elimination. Predicted terminal half-life values for delamanid and DM-6705 were 15.1 hours and 7.8 days, respectively. The impact of plasma albumin concentrations on delamanid metabolism was not significant. Bedaquiline co-administration did not affect delamanid PK. Other than allometric scaling with body weight, no patients’ demographics were significant (including HIV). Conclusions: This is the first published joint PK model of delamanid and its DM-6705 metabolite. As such, it can be utilized in future exposure-response or exposure-safety analyses. Importantly, albumin concentrations, bedaquiline co-administration, and HIV co-infection (dolutegravir co-administration) did not have an effect on delamanid and DM-6705 PK.
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45.
  • Trzaskowska, A., et al. (author)
  • Dispersion of the surface phonons in semiconductor/topological insulator Si/Bi 2 Te 3 heterostructure studied by high resolution Brillouin spectroscopy
  • 2021
  • In: Ultrasonics. - : Elsevier BV. - 0041-624X. ; 117
  • Journal article (peer-reviewed)abstract
    • The dynamics and dispersion of surface phonons in heterostructure semiconductor/ topological insulator Si/Bi2Te3 was investigated using high resolution Brillouin light scattering method in the GHz frequency range. Both Rayleigh and Sezawa surface acoustic waves have been observed for wave vectors ranging from 0.006 to 0.023 nm−1. Anomaly in dispersion relations ω(q) for both surface waves were detected for the wave vector q = 0.016 nm−1. The finite element method (FEM) was used to simulate the observed shapes of ω(q) and to find the deformation profiles of surface acoustic waves. We attribute the observed changes to the coupling between low energy electrons and surface phonons. The coupling between helical Dirac states and surface phonons is discussed in the frame of accessible theoretical models.
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46.
  • van Beek, Stijn W., et al. (author)
  • Model-Predicted Impact of ECG Monitoring Strategies During Bedaquiline Treatment
  • 2022
  • In: OPEN FORUM INFECTIOUS DISEASES. - : Oxford University Press. - 2328-8957. ; 9:8
  • Journal article (peer-reviewed)abstract
    • Background: The M2 metabolite of bedaquiline causes QT-interval prolongation, making electrocardiogram (ECG) monitoring of patients receiving bedaquiline for drug-resistant tuberculosis necessary. The objective of this study was to determine the relationship between M2 exposure and Fridericia-corrected QT (QTcF)-interval prolongation and to explore suitable ECG monitoring strategies for 6-month bedaquiline treatment.Methods: Data from the PROBeX study, a prospective observational cohort study, were used to characterize the relationship between M2 exposure and QTcF. Established nonlinear mixed-effects models were fitted to pharmacokinetic and ECG data. In a virtual patient population, QTcF values were simulated for scenarios with and without concomitant clofazimine. ECG monitoring strategies to identify patients who need to interrupt treatment (QTcF > 500 ms) were explored.Results: One hundred seventy patients were included, providing 1131 bedaquiline/M2 plasma concentrations and 1702 QTcF measurements; 2.1% of virtual patients receiving concomitant clofazimine had QTcF > 500 ms at any point during treatment (0.7% without concomitant clofazimine). With monthly monitoring, almost all patients with QTcF > 500 ms were identified by week 12; after week 12, patients were predominantly falsely identified as QTcF > 500 ms due to stochastic measurement error. Following a strategy with monitoring before treatment and at weeks 2, 4, 8, and 12 in simulations with concomitant clofazimine, 93.8% of all patients who should interrupt treatment were identified, and 26.4% of all interruptions were unnecessary (92.1% and 32.2%, respectively, without concomitant clofazimine).Conclusions: Our simulations enable an informed decision for a suitable ECG monitoring strategy by weighing the risk of missing patients with QTcF > 500 ms and that of interrupting bedaquiline treatment unnecessarily. We propose ECG monitoring before treatment and at weeks 2, 4, 8, and 12 after starting bedaquiline treatment.
  •  
47.
  • Wang, H, et al. (author)
  • Is there interference in the resonant Auger electron spectra of N 1s and O 1s -> 2 pi core excited NO?
  • 2003
  • In: Chemical Physics. - 0301-0104. ; 289:1, s. 31-44
  • Journal article (peer-reviewed)abstract
    • High-resolution, angle-resolved resonant Auger electron spectra of the NO molecule in the regions of both N and O 1s --> 2pi core electron excitations are presented. A large number of vibrational final states are resolved due to high energy resolution. Calculations based on lifetime vibrational interference (LVI) theory neglecting interference between different electronic intermediate states and between direct and resonant channels have been performed. A comparison between theoretical and experimental spectra shows that LVI theory describes the major spectroscopic features quite well. The same holds for the evolution of the angular averaged partial cross sections with the change of excitation energy. The angular distribution of particular vibrational final states are, however, not described successfully with LVI calculations at the present level of sophistication. A theoretical analysis supports that one reason for this deviation is electronic state interference. (C) 2002 Elsevier Science B.V. All rights reserved.
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48.
  • Wiesner, K., et al. (author)
  • Haematopoietic stem cells : Entropic landscapes of differentiation
  • 2018
  • In: Interface Focus. - : The Royal Society. - 2042-8898 .- 2042-8901. ; 8:6
  • Journal article (peer-reviewed)abstract
    • The metaphor of a potential epigenetic differentiation landscape broadly suggests that during differentiation a stem cell approaches a stable equilibrium state from a higher free energy towards a stable equilibrium state which represents the final cell type. It has been conjectured that there is an analogy to the concept of entropy in statistical mechanics. In this context, in the undifferentiated state, the entropy would be large since fewer constraints exist on the gene expression programmes of the cell. As differentiation progresses, gene expression programmes become more and more constrained and thus the entropy would be expected to decrease. In order to assess these predictions, we compute the Shannon entropy for time-resolved single-cell gene expression data in two different experimental set-ups of haematopoietic differentiation. We find that the behaviour of this entropy measure is in contrast to these predictions. In particular, we find that the Shannon entropy is not a decreasing function of developmental pseudo-time but instead it increases towards the time point of commitment before decreasing again. This behaviour is consistent with an increase in gene expression disorder observed in populations sampled at the time point of commitment. Single cells in these populations exhibit different combinations of regulator activity that suggest the presence of multiple configurations of a potential differentiation network as a result of multiple entry points into the committed state.
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49.
  • Wiesner, K, et al. (author)
  • Valence photoionization and resonant core excitation of ozone - experimental and theoretical study of the (C)over-tilde-state of O-3(+)
  • 2003
  • In: Chemical Physics Letters. - 0009-2614. ; 375:1-2, s. 76-83
  • Journal article (peer-reviewed)abstract
    • Resonant Auger electron spectra of core excited O-3 (O(F)1s(-1) 2b(1)(1)) are presented for the first time. The photoionization valence spectrum with sample purity and resolution superior to those published is presented. The first direct experimental evidence for the (C) over tilde (2) B-1 state of O-3(+) is found. Ab initio calculations of the resonant Auger electron (RAE) spectrum have been performed supporting the assignment of the (C) over tilde -state. (C) 2003 Elsevier Science B.V. All rights reserved.
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50.
  • Wiesner, M., et al. (author)
  • Detection of graphene microelectromechanical system resonance
  • 2014
  • In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 116:22, s. 224510-
  • Journal article (peer-reviewed)abstract
    • We present an experimental setup for fast detection of resonances of graphene microelectromechanical structures of different quality. The relatively simple technique used to read-out of the resonance frequency is the main advantage of the proposed system. The resolution is good enough to detect vibrations of the graphene resonator with the quality factor of ∼24 and resonance frequency of 104 MHz.
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