| 1. |
- Mposhi, Archibold, et al.
(författare)
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The Mitochondrial Epigenome : An Unexplored Avenue to Explain Unexplained Myopathies?
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:4
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in either mitochondrial DNA (mtDNA) or nuclear genes that encode mitochondrial proteins may lead to dysfunctional mitochondria, giving rise to mitochondrial diseases. Some mitochondrial myopathies, however, present without a known underlying cause. Interestingly, methylation of mtDNA has been associated with various clinical pathologies. The present study set out to assess whether mtDNA methylation could explain impaired mitochondrial function in patients diagnosed with myopathy without known underlying genetic mutations. Enhanced mtDNA methylation was indicated by pyrosequencing for muscle biopsies of 14 myopathy patients compared to four healthy controls, at selected cytosines in the Cytochrome B (CYTB) gene, but not within the displacement loop (D-loop) region. The mtDNA methylation patterns of the four healthy muscle biopsies were highly consistent and showed intriguing tissue-specific differences at particular cytosines with control skin fibroblasts cultured in vitro. Within individual myopathy patients, the overall mtDNA methylation pattern correlated well between muscle and skin fibroblasts. Despite this correlation, a pilot analysis of four myopathy and five healthy fibroblast samples did not reveal a disease-associated difference in mtDNA methylation. We did, however, detect increased expression of solute carrier family 25A26 (SLC25A26), encoding the importer of S-adenosylmethionine, together with enhanced mtDNA copy numbers in myopathy fibroblasts compared to healthy controls. To confirm that pyrosequencing indeed reflected DNA methylation and not bisulfite accessibility, mass spectrometry was employed. Although no myopathy-related differences in total amount of methylated cytosines were detected at this stage, a significant contribution of contaminating nuclear DNA (nDNA) was revealed, and steps to improve enrichment for mtDNA are reported. In conclusion, in this explorative study we show that analyzing the mitochondrial genome beyond its sequence opens novel avenues to identify potential molecular biomarkers assisting in the diagnosis of unexplained myopathies.
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| 2. |
- Wiedner, M.C., et al.
(författare)
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Heterodyne Receiver for Origins
- 2021
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Ingår i: Journal of Astronomical Telescopes, Instruments, and Systems. - 2329-4221 .- 2329-4124. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The Heterodyne Receiver for Origins (HERO) is the first detailed study of a heterodyne focal plane array receiver for space applications. HERO gives the Origins Space Telescope the capability to observe at very high spectral resolution (R = 107) over an unprecedentedly large far-infrared (FIR) wavelengths range (111 to 617 μm) with high sensitivity, with simultaneous dual polarization and dual-frequency band operation. The design is based on prior successful heterodyne receivers, such as Heterodyne Instrument for the Far-Infrared/Herschel, but surpasses it by one to two orders of magnitude by exploiting the latest technological developments. Innovative components are used to keep the required satellite resources low and thus allowing for the first time a convincing design of a large format heterodyne array receiver for space. HERO on Origins is a unique tool to explore the FIR universe and extends the enormous potential of submillimeter astronomical spectroscopy into new areas of astronomical research.
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| 3. |
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| 4. |
- Huijben, Jilske A., et al.
(författare)
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Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury
- 2019
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Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.Methods: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.Results. The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).Conclusions: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.
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| 5. |
- Wiedner, M.C., et al.
(författare)
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The origins space telescope and the heterodyne receiver for origins (HERO)
- 2019
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Ingår i: ISSTT 2019 - 30th International Symposium on Space Terahertz Technology, Proceedings Book. ; , s. 204-207
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Konferensbidrag (refereegranskat)abstract
- The Origins Space Telescope is one of four large mission concept studies carried out by NASA for the 2020 Decadal survey. Origins is a far-infrared telescope designed to understand the evolution of galaxies and black holes, to follow the trail of water from protostars to habitable planets and to search for biosignatures in the atmospheres of exoplanets. The Heterodyne Receiver for Origins (HERO) is the high spectral resolution receiver. It is the first heterodyne array receiver designed to fly on a satellite and an example for possible future focal plane arrays for space. HERO has focal plane arrays with nine pixels in two polarization. HERO covers a large frequency range between 486 and 2700 GHz in only 4 frequency bands, requiring local oscillators with fractional bandwidth of 45%. HERO uses the best superconducting mixers with noise temperatures between 1 and 3 hf/k and an intermediate bandwidth of 6 to 8 GHz. HERO can carry out dual polarization and dual-frequency observations. The major challenges for the HERO design are the low cooling power and the low electrical power available on a spacecraft, which impact the choice of the cryogenic amplifiers and backends. SiGe cryogenic amplifiers with a consumption of less than 0.5 mW, as well as CMOS spectrometers with a power consumption below 2W are the baseline for HERO. The development plan includes broadband (45%) multiplier-amplifier chains, low noise mixers (1-3 hf/k), low-power consuming (< 05.mW) cryogenic amplifiers and low-power consuming spectrometer backends (< 2W).
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| 6. |
- Roelfsema, P. R., et al.
(författare)
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SPICA-A Large Cryogenic Infrared Space Telescope : Unveiling the Obscured Universe
- 2018
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Ingår i: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity. SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope. cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions. SPICA instruments offer spectral resolving power ranging from R similar to 50 through 11 000 in the 17-230 mu m domain and R similar to 28.000 spectroscopy between 12 and 18 mu m.SPICA will provide efficient 30-37 mu m broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 mu m. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of similar to 5 x 10(-20) W m (-2) (5 sigma/1 h)-over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
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| 7. |
- Wiedner, M.C., et al.
(författare)
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A Proposed Heterodyne Receiver for the Origins Space Telescope
- 2018
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Ingår i: IEEE Transactions on Terahertz Science and Technology. - 2156-342X .- 2156-3446. ; 8:6, s. 558-571
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Tidskriftsartikel (refereegranskat)abstract
- The HEterodyne Receiver for the Origins Space Telescope (HERO) is a proposed design for a heterodyne focal plane array for a large space mission. The Origins Space Telescope (OST) is one of the four missions selected to be studied by NASA for the 2020 Astronomy and Astrophysics Decadal survey. HERO is designed to observe the trail of water from the interstellar medium (ISM) to disks around protostars. In Concept 1, HERO provides continuous frequency coverage from 468 to 2700 GHz in five bands and a sixth band to cover 4700 GHz. Most bands include 2 × 64 pixels providing at least an order of magnitude higher mapping speeds than available with today's instruments. Receiver sensitivities are expected to be close to the quantum limit. HERO Concept 2, highly constrained by cost and denoted Little-HERO, includes four bands with continuous coverage from 486 to 2700 GHz and with focal plane arrays having only 2 × 9 pixels per band. Both of these THz receiver concepts will be described and the designs will be motivated by the science drivers, the space craft constraints and the latest technological developments. The HERO design builds on the highly successful Herschel/Heterodyne Instrument for the Far-Infrared, on Stratospheric Observatory for Far-Infrared Astronomy/upGREAT and many other heterodyne receivers, but surpasses these in terms of frequency coverage, array size and sensitivity, thanks to the latest technical advances. HERO can be considered an example of a new generation of heterodyne focal plane arrays for future space missions.
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| 8. |
- Wiedner, M.C., et al.
(författare)
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Heterodyn receiver for the Origins Space Telescope concept 2
- 2018
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10698
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Konferensbidrag (refereegranskat)abstract
- The Origins Space Telescope (OST) is a NASA study for a large satellite mission to be submitted to the 2020 Decadal Review. The proposed satellite has a fleet of instruments including the HEterodyne Receivers for OST (HERO). HERO is designed around the quest to follow the trail of water from the ISM to disks around protostars and planets. HERO will perform high-spectral resolution measurements with 2x9 pixel focal plane arrays at any frequency between 468GHz to 2,700GHz (617 to 111 μm). HERO builds on the successful Herschel/HIFI heritage, as well as recent technological innovations, allowing it to surpass any prior heterodyne instrument in terms of sensitivity and spectral coverage.
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| 9. |
- Roelfsema, P. R., et al.
(författare)
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In-orbit performance of Herschel-HIFI
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In this paper the calibration and in-orbit performance of the Heterodyne Instrument for the Far-Infrared (HIFI) is described.Methods: The calibration of HIFI is based on a combination of ground and in-flight tests. Dedicated ground tests to determine those instrument parameters that can only be measured accurately using controlled laboratory stimuli were carried out in the instrument level test (ILT) campaign. Special in-flight tests during the commissioning phase (CoP) and performance verification (PV) allowed the determination of the remaining instrument parameters. The various instrument observing modes, as specified in astronomical observation templates (AOTs), were validated in parallel during PV by observing selected celestial sources.Results: The initial calibration and in-orbit performance of HIFI has been established. A first estimate of the calibration budget is given. The overall in-flight instrument performance agrees with the original specification. Issues remain at only a few frequencies. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 10. |
- Benz, A. O., et al.
(författare)
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Hydrides in young stellar objects : Radiation tracers in a protostar-disk-outflow system
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L35-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Hydrides of the most abundant heavier elements are fundamental molecules in cosmic chemistry. Some of them trace gas irradiated by UV or X-rays. Aims: We explore the abundances of major hydrides in W3 IRS5, a prototypical region of high-mass star formation. Methods: W3 IRS5 was observed by HIFI on the Herschel Space Observatory with deep integration (≃2500 s) in 8 spectral regions. Results: The target lines including CH, NH, H3O+, and the new molecules SH+, H2O+, and OH+ are detected. The H2O+ and OH+ J = 1-0 lines are found mostly in absorption, but also appear to exhibit weak emission (P-Cyg-like). Emission requires high density, thus originates most likely near the protostar. This is corroborated by the absence of line shifts relative to the young stellar object (YSO). In addition, H2O+ and OH+ also contain strong absorption components at a velocity shifted relative to W3 IRS5, which are attributed to foreground clouds. Conclusions: The molecular column densities derived from observations correlate well with the predictions of a model that assumes the main emission region is in outflow walls, heated and irradiated by protostellar UV radiation. Herschel is an ESA space observatory with science instruments provided by a European-led Principal Investigator consortia and with important participation from NASA.Appendix (page 5) is only available in electronic form at http://www.aanda.org
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