| 41. |
- Abeysekara, A. U., et al.
(author)
-
A Luminous and Isolated Gamma-Ray Flare from the Blazar B2 1215+30
- 2017
-
In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 836:2
-
Journal article (peer-reviewed)abstract
- B2 1215+30 is a BL-Lac-type blazar that was first detected at TeV energies by the MAGIC atmospheric Cherenkov telescopes and subsequently confirmed by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) observatory with data collected between 2009 and 2012. In 2014 February 08, VERITAS detected a large-amplitude flare from B2. 1215+30 during routine monitoring observations of the blazar 1ES. 1218+304, located in the same field of view. The TeV flux reached 2.4 times the Crab Nebula flux with a variability timescale of <3.6 hr. Multiwavelength observations with Fermi-LAT, Swift, and the Tuorla Observatory revealed a correlated high GeV flux state and no significant optical counterpart to the flare, with a spectral energy distribution where the gamma-ray luminosity exceeds the synchrotron luminosity. When interpreted in the framework of a onezone leptonic model, the observed emission implies a high degree of beaming, with Doppler factor delta > 10, and an electron population with spectral index p < 2.3.
|
|
| 42. |
- Archambault, S., et al.
(author)
-
VERITAS Observations of the Microquasar Cygnus X-3
- 2013
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 779:2
-
Journal article (peer-reviewed)abstract
- We report results from TeV gamma-ray observations of the microquasar Cygnus X-3. The observations were made with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) over a time period from 2007 June 11 to 2011 November 28. VERITAS is most sensitive to gamma rays at energies between 85 GeV and 30 TeV. The effective exposure time amounts to a total of about 44 hr, with the observations covering six distinct radio/X-ray states of the object. No significant TeV gamma-ray emission was detected in any of the states, nor with all observations combined. The lack of a positive signal, especially in the states where GeV gamma rays were detected, places constraints on TeV gamma-ray production in Cygnus X-3. We discuss the implications of the results.
|
|
| 43. |
|
|
| 44. |
- Chelban, V., et al.
(author)
-
PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation
- 2019
-
In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:2, s. 225-240
-
Journal article (peer-reviewed)abstract
- Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
|
|
| 45. |
- Aliu, E., et al.
(author)
-
Investigating the TeV Morphology of MGRO J1908+06 with VERITAS
- 2014
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 787:2
-
Journal article (peer-reviewed)abstract
- We report on deep observations of the extended TeV gamma-ray source MGRO J1908+06 made with the VERITAS very high energy gamma-ray observatory. Previously, the TeV emission has been attributed to the pulsar wind nebula (PWN) of theFermi-LAT pulsar PSR J1907+0602. We detect MGRO J1908+06 at a significance level of 14 standard deviations (14σ) and measure a photon index of 2.20 ± 0.10stat ± 0.20sys. The TeV emission is extended, covering the region near PSR J1907+0602 and also extending toward SNR G40.5-0.5. When fitted with a two-dimensional Gaussian, the intrinsic extension has a standard deviation of σsrc = 044 ± 002. In contrast to other TeV PWNe of similar age in which the TeV spectrum softens with distance from the pulsar, the TeV spectrum measured near the pulsar location is consistent with that measured at a position near the rim of G40.5-0.5, 033 away.
|
|
| 46. |
- D’Ammando, F., et al.
(author)
-
The most powerful flaring activity from the NLSy1 PMN J0948+0022
- 2015
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 446:3, s. 2456-2467
-
Journal article (peer-reviewed)abstract
- We report on multifrequency observations performed during 2012 December–2013 August of the first narrow-line Seyfert 1 galaxy detected in γ-rays, PMN J0948+0022 (z = 0.5846). A γ-ray flare was observed by the Large Area Telescope on board Fermi during 2012 December–2013 January, reaching a daily peak flux in the 0.1–100 GeV energy range of (155 ± 31) × 10−8 ph cm−2 s−1 on 2013 January 1, corresponding to an apparent isotropic luminosity of ∼1.5 × 1048 erg s−1. The γ-ray flaring period triggered Swift and Very Energetic Radiation Imaging Telescope Array System (VERITAS) observations in addition to radio and optical monitoring by Owens Valley Radio Observatory, Monitoring Of Jets in Active galactic nuclei with VLBA Experiments, and Catalina Real-time Transient Survey. A strong flare was observed in optical, UV, and X-rays on 2012 December 30, quasi-simultaneously to the γ-ray flare, reaching a record flux for this source from optical to γ-rays. VERITAS observations at very high energy (E > 100 GeV) during 2013 January 6–17 resulted in an upper limit of F>0.2 TeV < 4.0 × 10−12 ph cm−2 s−1. We compared the spectral energy distribution (SED) of the flaring state in 2013 January with that of an intermediate state observed in 2011. The two SEDs, modelled as synchrotron emission and an external Compton scattering of seed photons from a dust torus, can be modelled by changing both the electron distribution parameters and the magnetic field.
|
|
| 47. |
|
|
| 48. |
- Aliu, E., et al.
(author)
-
Observations of the Unidentified Gamma-Ray Source TeV J2032+4130 by VERITAS
- 2014
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 783
-
Journal article (peer-reviewed)abstract
- TeV J2032+4130 was the first unidentified source discovered at very high energies (VHEs; E > 100 GeV), with no obvious counterpart in any other wavelength. It is also the first extended source to be observed in VHE gamma rays. Following its discovery, intensive observational campaigns have been carried out in all wavelengths in order to understand the nature of the object, which have met with limited success. We report here on a deep observation of TeV J2032+4130 based on 48.2 hr of data taken from 2009 to 2012 by the Very Energetic Radiation Imaging Telescope Array System experiment. The source is detected at 8.7 standard deviations (σ) and is found to be extended and asymmetric with a width of 9.'5 ± 1.'2 along the major axis and 4.'0 ± 0.'5 along the minor axis. The spectrum is well described by a differential power law with an index of 2.10 ± 0.14stat ± 0.21sys and a normalization of (9.5 ± 1.6stat ± 2.2sys) × 10–13 TeV–1 cm–2 s–1 at 1 TeV. We interpret these results in the context of multiwavelength scenarios which particularly favor the pulsar wind nebula interpretation.
|
|
| 49. |
- Pagnamenta, A. T., et al.
(author)
-
An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy
- 2021
-
In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144, s. 584-600
-
Journal article (peer-reviewed)abstract
- The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose 47000 years ago. A wide age-range of patients (6-83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 +/- 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses.
|
|
| 50. |
|
|
