140 research outputs found
A novel succinate dehydrogenase subunit B germline variant associated with head and neck paraganglioma in a Dutch kindred: A family-based study
- Publication venue
- 'Wiley'
- Publication date
- 25/01/2018
- Field of study
Genome Instability and Cance
Paraganglioma and pheochromocytoma upon maternal transmission of SDHD mutations
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2014
- Field of study
The SDHD gene encodes a subunit of the mitochondrial tricarboxylic acid cycle enzyme and tumor suppressor
Germline DLST variants promote epigenetic modifications in pheochromocytoma-paraganglioma
- Author
- Publication venue
- 'The Endocrine Society'
- Publication date
- 01/02/2021
- Field of study
Context: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors in which altered central metabolism appears to be a major driver of tumorigenesis, and many PPGL genes encode proteins involved in the tricarboxylic acid (TCA) cycle.Objective/design: While about 40% of PPGL cases carry a variant in a known gene, many cases remain unexplained. In patients with unexplained PPGL showing clear evidence of a familial burden or multiple tumors, we aimed to identify causative factors using genetic analysis of patient DNA and functional analyses of identified DNA variants in patient tumor material and engineered cell lines.Patients and Setting: Patients with a likely familial cancer burden of pheochromocytomas and/or paragangliomas and under investigation in a clinical genetic and clinical research setting in university hospitals.Results: While investigating unexplained PPGL cases, we identified a novel variant, c.1151C>T, p.(Pro384Leu), in exon 14 of the gene encoding dihydrolipoamide S-succinyltransferase (DLST), a component of the multi-enzyme complex 2-oxoglutarate dehydrogenase. Targeted sequence analysis of further unexplained cases identified a patient carrying a tumor with compound heterozygous variants in DLST, consisting of a germline variant, c.1121G>A, p.(Gly374Glu), together with a somatic missense variant identified in tumor DNA, c.1147A>G, p.(Thr383Ala), both located in exon 14. Using a range of in silico and functional assays we show that these variants are predicted to be pathogenic, profoundly impact enzyme activity, and result in DNA hypermethylation.Conclusions: The identification and functional analysis of these DLST variants further validates DLST as an additional PPGL gene involved in the TCA cycle.MTG
Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 30/04/2017
- Field of study
Genome Instability and Cance
A systems perspective on the death of a car company
- Author
- Publication venue
- 'Emerald'
- Publication date
- 01/01/2008
- Field of study
Purpose
â The aim of this paper is to understand how large and apparently successful organizations enter spirals of decline that are very difficult to reverse. The paper examines the case of Rover, once one of the largest car producers in the world, which collapsed in 2005. An analysis of strategic and operational choices made over a period of 40 years investigates the reasons for, and consequences of, a growing mismatch between the context faced by the company (industry dynamics, market conditions) and its operational capabilities, a mismatch that ultimately brought about the company's demise.
Design/methodology/approach
â The paper is based on interviews with 32 people, including senior managers (including four chief executives), government ministers and union officials who were key decision makers within, or close to, the company during the period 1968 and 2005. Secondary sources and documentary evidence (e.g. production and sales data) are used to build up a historical picture of the company and to depict its deteriorating financial and market position from 1968 onwards.
Findings
â The company was formed from a multitude of previously independent firms as part of a governmentâsponsored agenda to build a UK National Champion in the car industry. The merged company failed due to several factors including poor product development processes, poor manufacturing performance, difficult labour relations, a very wide product portfolio and a lack of financial control. Although strenuous efforts were made to address those issues, including periods of whole or part ownership by British Aerospace, Honda and BMW, the company's position deteriorated until eventually production volumes were too low for viable operation.
Practical implications
â The case of Rover highlights the importance of what has been termed âthe management unitâ in complex systems. The management unit comprises processes and routines to deal with challenges such as managing product portfolios, connecting strategic and operational choices, and scanning and responding to the environment. In the case of Rover, a number of factors taken together generated excessive load on a management unit frequently operating under conditions of resource scarcity. We conclude that viewing corporate failure from a systems perspective, rather than in terms of shortcomings in specific subsystems, such as manufacturing or product development, yields insights often absent in the operations management literature.
Originality/value
â The paper is of value by showing corporate failure from a systems perspective, rather than in terms of shortcomings in specific subsystems, such as manufacturing or product development; and yields insights often absent in the operations management literature. The Rover case featured in the paper demonstrates the usefulness of systems ideas to understanding at least some types of failure, not as an alterative to capabilityâbased approaches, but in addition to them
Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b
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- Yamamoto Kazuhiro
- Yamamoto Kohei
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- Ying M.
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- Yokoyama J.
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- Yu Hang
- Yu Haocun
- Yuzurihara H.
- Zadrzny A.
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- Zimmerman A.B.
- Zucker M.E.
- Zweizig J.
- Publication venue
- London : Institute of Physics Publ.
- Publication date
- 01/01/2022
- Field of study
We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society
Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run
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- Publication venue
- London : Institute of Physics Publ.
- Publication date
- 01/01/2022
- Field of study
Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society
Search for gravitational-wave transients associated with magnetar bursts in advanced LIGO and advanced Virgo data from the third observing run
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- Yeh S.-W
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- Ying M
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- Zhu Z.-H
- Zucker M.E
- Zweizig J
- Publication venue
- American Astronomical Society
- Publication date
- 01/01/2024
- Field of study
Gravitational waves are expected to be produced from neutron star oscillations associated with magnetar giant f lares and short bursts. We present the results of a search for short-duration (milliseconds to seconds) and longduration (âŒ100 s) transient gravitational waves from 13 magnetar short bursts observed during Advanced LIGO, Advanced Virgo, and KAGRAâs third observation run. These 13 bursts come from two magnetars, SGR1935 +2154 and SwiftJ1818.0â1607. We also include three other electromagnetic burst events detected by FermiGBM which were identified as likely coming from one or more magnetars, but they have no association with a known magnetar. No magnetar giant flares were detected during the analysis period. We find no evidence of gravitational waves associated with any of these 16 bursts. We place upper limits on the rms of the integrated incident gravitational-wave strain that reach 3.6 Ă 10âÂČÂł Hz at 100 Hz for the short-duration search and 1.1 Ă10âÂČÂČ Hz at 450 Hz for the long-duration search. For a ringdown signal at 1590 Hz targeted by the short-duration search the limit is set to 2.3 Ă 10âÂČÂČ Hz. Using the estimated distance to each magnetar, we derive upper limits upper limits on the emitted gravitational-wave energy of 1.5 Ă 1044 erg (1.0 Ă 1044 erg) for SGR 1935+2154 and 9.4 Ă 10^43 erg (1.3 Ă 1044 erg) for Swift J1818.0â1607, for the short-duration (long-duration) search. Assuming isotropic emission of electromagnetic radiation of the burst ïŹuences, we constrain the ratio of gravitational-wave energy to electromagnetic energy for bursts from SGR 1935+2154 with the available ïŹuence information. The lowest of these ratios is 4.5 Ă 103
Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO
- Author
- Abbott R.
- Abe H.
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- Publication venue
- American Astronomical Society
- Publication date
- 01/01/2023
- Field of study
The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages
A joint Fermi-GBM and Swift-BAT analysis of gravitational-wave candidates from the third gravitational-wave observing run
- Author
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- Abe H.
- Acernese F.
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- Publication venue
- American Astronomical Society
- Publication date
- 01/04/2024
- Field of study
We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers
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