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2.
  • Chen, Cong, et al. (author)
  • Tomographic reconstruction of circularly polarized high-harmonic fields : 3D attosecond metrology.
  • 2016
  • In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 2:2
  • Journal article (peer-reviewed)abstract
    • Bright, circularly polarized, extreme ultraviolet (EUV) and soft x-ray high-harmonic beams can now be produced using counter-rotating circularly polarized driving laser fields. Although the resulting circularly polarized harmonics consist of relatively simple pairs of peaks in the spectral domain, in the time domain, the field is predicted to emerge as a complex series of rotating linearly polarized bursts, varying rapidly in amplitude, frequency, and polarization. We extend attosecond metrology techniques to circularly polarized light by simultaneously irradiating a copper surface with circularly polarized high-harmonic and linearly polarized infrared laser fields. The resulting temporal modulation of the photoelectron spectra carries essential phase information about the EUV field. Utilizing the polarization selectivity of the solid surface and by rotating the circularly polarized EUV field in space, we fully retrieve the amplitude and phase of the circularly polarized harmonics, allowing us to reconstruct one of the most complex coherent light fields produced to date.
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  • Fan, Tingting, et al. (author)
  • Bright circularly polarized soft X-ray high harmonics for X-ray magnetic circular dichroism
  • 2015
  • 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. ; 112:46, s. 14206-14211
  • Journal article (peer-reviewed)abstract
    • We demonstrate, to our knowledge, the first bright circularly polarized high-harmonic beams in the soft X-ray region of the electromagnetic spectrum, and use them to implement X-ray magnetic circular dichroism measurements in a tabletop-scale setup. Using counterrotating circularly polarized laser fields at 1.3 and 0.79 mu m, we generate circularly polarized harmonics with photon energies exceeding 160 eV. The harmonic spectra emerge as a sequence of closely spaced pairs of left and right circularly polarized peaks, with energies determined by conservation of energy and spin angular momentum. We explain the single-atom and macroscopic physics by identifying the dominant electron quantum trajectories and optimal phase-matching conditions. The first advanced phase-matched propagation simulations for circularly polarized harmonics reveal the influence of the finite phase-matching temporal window on the spectrum, as well as the unique polarization-shaped attosecond pulse train. Finally, we use, to our knowledge, the first tabletop X-ray magnetic circular dichroism measurements at the N-4,N-5 absorption edges of Gd to validate the high degree of circularity, brightness, and stability of this light source. These results demonstrate the feasibility of manipulating the polarization, spectrum, and temporal shape of high harmonics in the soft X-ray region by manipulating the driving laser waveform.
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5.
  • Gakidou, E., et al. (author)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
  • 2017
  • In: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1345-1422
  • Journal article (peer-reviewed)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124.1 million DALYs [95% UI 111.2 million to 137.0 million]), high systolic blood pressure (122.2 million DALYs [110.3 million to 133.3 million], and low birthweight and short gestation (83.0 million DALYs [78.3 million to 87.7 million]), and for women, were high systolic blood pressure (89.9 million DALYs [80.9 million to 98.2 million]), high body-mass index (64.8 million DALYs [44.4 million to 87.6 million]), and high fasting plasma glucose (63.8 million DALYs [53.2 million to 76.3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9.3% (6.9-11.6) decline in deaths and a 10.8% (8.3-13.1) decrease in DALYs at the global level, while population ageing accounts for 14.9% (12.7-17.5) of deaths and 6.2% (3.9-8.7) of DALYs, and population growth for 12.4% (10.1-14.9) of deaths and 12.4% (10.1-14.9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27.3% (24.9-29.7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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6.
  • Galluzzi, L, et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
  • 2009
  • In: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
  • Research review (peer-reviewed)abstract
    • Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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  • Giorgio, Elisa, et al. (author)
  • Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele-Specific Expression
  • 2013
  • In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 34:8, s. 1160-1171
  • Journal article (peer-reviewed)abstract
    • Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication-based mechanisms such fork stalling and template switching or microhomology-mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients' fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele-specific LMNB1 expression levels.
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9.
  • Kfir, Ofer, et al. (author)
  • Generation of bright phase-matched circularly-polarized extreme ultraviolet high harmonics
  • 2015
  • In: Nature Photonics. - 1749-4885 .- 1749-4893. ; 9:2, s. 99-105
  • Journal article (peer-reviewed)abstract
    • Circularly-polarized extreme ultraviolet and X-ray radiation is useful for analysing the structural, electronic and magnetic properties of materials. To date, such radiation has only been available at large-scale X-ray facilities such as synchrotrons. Here, we demonstrate the first bright, phase-matched, extreme ultraviolet circularly-polarized high harmonics source. The harmonics are emitted when bi-chromatic counter-rotating circularly-polarized laser pulses field-ionize a gas in a hollow-core waveguide. We use this new light source for magnetic circular dichroism measurements at the M-shell absorption edges of Co. We show that phase-matching of circularly-polarized harmonics is unique and robust, producing a photon flux comparable to linearly polarized high harmonic sources. This work represents a critical advance towards the development of table-top systems for element-specific imaging and spectroscopy of multiple elements simultaneously in magnetic and other chiral media with very high spatial and temporal resolution.
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10.
  • Kfir, Ofer, et al. (author)
  • Helicity-selective phase-matching and quasi-phase matching of circularly polarized high-order harmonics : towards chiral attosecond pulses
  • 2016
  • In: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 49:12
  • Journal article (peer-reviewed)abstract
    • Phase matching of circularly polarized high-order harmonics driven by counter-rotating bi-chromatic lasers was recently predicted theoretically and demonstrated experimentally. In that work, phase matching was analyzed by assuming that the total energy, spin angular momentum and linear momentum of the photons participating in the process are conserved. Here we propose a new perspective on phase matching of circularly polarized high harmonics. We derive an extended phase matching condition by requiring a new propagation matching condition between the classical vectorial bi-chromatic laser pump and harmonics fields. This allows us to include the influence of the laser pulse envelopes on phase matching. We find that the helicity dependent phase matching facilitates generation of high harmonics beams with a high degree of chirality. Indeed, we present an experimentally measured chiral spectrum that can support a train of attosecond pulses with a high degree of circular polarization. Moreover, while the degree of circularity of the most intense pulse approaches unity, all other pulses exhibit reduced circularity. This feature suggests the possibility of using a train of attosecond pulses as an isolated attosecond probe for chiral-sensitive experiments.
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