INTEGRAL Observations of GW170104 Savchenko, V.; Ferrigno, C.; Bozzo, E. ...
Astrophysical journal. Letters,
09/2017, Letnik:
846, Številka:
2
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We used data from the International Gamma-Ray Astrophysics Laboratory (INTEGRAL) to set upper limits on the γ-ray and hard X-ray prompt emission associated with the gravitational-wave event GW170104, ...discovered by the Laser Interferometer Gravitational-wave Observatory (LIGO)/Virgo collaboration. The unique omnidirectional viewing capability of the instruments on board INTEGRAL allowed us to examine the full 90% confidence level localization region of the LIGO trigger. Depending on the particular spectral model assumed and the specific position within this region, the upper limits inferred from the INTEGRAL observations range from Fγ = 1.9 × 10−7 erg cm−2 to Fγ = 10−6 erg cm−2 (75 keV-2 MeV energy range). This translates into a ratio between the prompt energy released in γ-rays along the direction to the observer and the gravitational-wave energy of Eγ/EGW < 2.6 × 10−5. Using the INTEGRAL results, we cannot confirm the γ-ray proposed counterpart to GW170104 by the Astro-Rivelatore Gamma a Immagini Leggero (AGILE) team with the mini-Calorimeter (MCAL) instrument. The reported flux of the AGILE/MCAL event, E2, is not compatible with the INTEGRAL upper limits within most of the 90% LIGO localization region. There is only a relatively limited portion of the sky where the sensitivity of the INTEGRAL instruments was not optimal and the lowest-allowed fluence estimated for E2 would still be compatible with the INTEGRAL results. This region was also observed independently by Fermi/Gamma-ray Burst Monitor and AstroSAT, from which, as far as we are aware, there are no reports of any significant detection of a prompt high-energy event.
We present a catalog of 9017 X-ray sources identified in Chandra observations of a 2°X 08 field around the Galactic center. This enlarges the number of known X-ray sources in the region by a factor ...of 2.5. The catalog incorporates all of the ACIS-I observations as of 2007 August, which total 2.25 Ms of exposure. At the distance to the Galactic center (8 kpc), we are sensitive to sources with luminosities of 4 X 1032 erg s-1 (0.5-8.0 keV; 90% confidence) over an area of 1 deg2, and up to an order of magnitude more sensitive in the deepest exposure (1.0 Ms) around Sgr A*. The positions of 60% of our sources are accurate to <1 '' (95% confidence), and 20% have positions accurate to <05. We search for variable sources, and find that 3% exhibit flux variations within an observation, and 10% exhibit variations from observation-to-observation. We also find one source, CXOUGC J174622.7 - 285218, with a periodic 1745 s signal (1.4% chance probability), which is probably a magnetically accreting cataclysmic variable. We compare the spatial distribution of X-ray sources to a model for the stellar distribution, and find 2.8s evidence for excesses in the numbers of X-ray sources in the region of recent star formation encompassed by the Arches, Quintuplet, and Galactic center star clusters. These excess sources are also seen in the luminosity distribution of the X-ray sources, which is flatter near the Arches and Quintuplet than elsewhere in the field. These excess point sources, along with a similar longitudinal asymmetry in the distribution of diffuse iron emission that has been reported by other authors, probably have their origin in the young stars that are prominent at l 01.
During the first observing run of LIGO, two gravitational wave events and one lower-significance trigger (LVT151012) were reported by the LIGO/Virgo collaboration. At the time of LVT151012, the ...INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) was pointing at a region of the sky coincident with the high localization probability area of the event and thus permitted us to search for its electromagnetic counterpart (both prompt and afterglow emission). The imaging instruments on board INTEGRAL (IBIS/ISGRI, IBIS/PICsIT, SPI, and the two JEM-X modules) have been exploited to attempt the detection of any electromagnetic emission associated with LVT151012 over three decades in energy (from 3 keV to 8 MeV). The omni-directional instruments on board the satellite, i.e., the SPI-ACS and the IBIS/Veto, complemented the capabilities of the IBIS/ISGRI and IBIS/PICsIT for detections outside their imaging field of view in order to provide an efficient monitoring of the entire LVT151012 localization region at energies above 75 keV. We did not find any significant transient source that was spatially and/or temporally coincident with LVT151012, obtaining tight upper limits on the associated hard X-ray and γ-ray radiation. For typical spectral models, the upper limits on the fluence of the emission from any 1 s counterpart of LVT151012 ranges from Fγ = 3.5 × 10-8 erg cm-2 (20–200 keV), within the field of view of the imaging instruments, to Fγ = 7.1 × 10-7 erg cm-2 (75–2000 keV), considering the least favorable location of the counterpart for a detection by the omni-directional instruments. These results can be interpreted as a tight constraint on the ratio of the isotropic equivalent energy released in the electromagnetic emission to the total energy of the gravitational waves: E75−2000 keV/EGW< 4.4 × 10-5. Finally, we provide an exhaustive summary of the capabilities of all instruments on board INTEGRAL to hunt for γ-ray counterparts of gravitational wave events, exploiting both serendipitousand pointed follow-up observations. This will serve as a reference for all future searches.
We examine the 18 April 2002 sawtooth event. We find that the strong magnetic field dipolarizations observed in association with each tooth are not global in occurrence but are rather confined to the ...nightside. In addition, we find that the flux increases are not globally dispersionless. Instead, each tooth is associated with a nonglobal, but wider‐than‐usual, dispersionless injection region that is consistent with the high Kp versions of the standard injection boundary model (which places the entire nightside segment of geosynchronous orbit tailward of the injection boundary for values of Kp above about 5). We also find evidence that at least one of the teeth was likely triggered by a pressure pulse. The auroral distribution shows a repeatable evolution in which a wide double‐oval configuration gradually thins. Following this, a localized substorm‐like brightening in the dusk to midnight sector occurs on the lower branch of the double oval which subsequently expands rapidly poleward and azimuthally. A new expanded double oval configuration emerges from this expansion phase activity and the cycle repeats itself for the duration of the sawtooth event. The observations presented give considerable support to the contention that sawtooth events are actually sequences of quasi‐periodic substorms. We suggest that sawtooth events can be viewed as a magnetospheric mode similar to Steady Magnetospheric Convection intervals (SMCs) except that for sawtooth events, the flow of energy from the solar wind into the magnetosphere becomes too large to dissipate without the periodic occurrence of substorms. We further suggest that the quasi‐periodicity arises because the magnetosphere may only become susceptible to external or internal triggering after it has been driven beyond a stability threshold. This hypothesis can account for the existence of more potential external triggers (in the interplanetary magnetic field or solar wind) than teeth in that the magnetosphere may be selectively responsive to them.
To identify the biochemical and molecular genetic defect in a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder.
Measurement ...of the mitochondrial energy-generating system (MEGS) capacity in muscle and enzyme analysis in muscle and fibroblasts were performed. Relevant parts of the mitochondrial DNA were analysed by sequencing. Transmitochondrial cybrids were obtained by fusion of 143B206 TK(-) rho zero cells with patient-derived enucleated fibroblasts. Immunoblotting techniques were applied to study the complex V assembly.
A homoplasmic nonsense mutation m.8529G-->A (p.Trp55X) was found in the mitochondrial ATP8 gene in the patient's fibroblasts and muscle tissue. Reduced complex V activity was measured in the patient's fibroblasts and muscle tissue, and was confirmed in cybrid clones containing patient-derived mitochondrial DNA. Immunoblotting after blue native polyacrylamide gel electrophoresis showed a lack of holocomplex V and increased amounts of mitochondrial ATP synthase subcomplexes. An in-gel activity assay of ATP hydrolysis showed activity of free F(1)-ATPase in the patient's muscle tissue and in the cybrid clones.
We describe the first pathogenic mutation in the mitochondrial ATP8 gene, resulting in an improper assembly and reduced activity of the complex V holoenzyme.
Primary tumor location is an established prognostic factor in patients with (metastatic) colon cancer. Colon tumors can be divided into left‐sided and right‐sided tumors. The aim of this study was to ...determine the impact of primary tumor location on treatment and overall survival (OS) in patients with peritoneal metastases (PM) from colon cancer. This study is a retrospective, population‐based cohort study. Records of patients diagnosed with colon cancer and synchronous PM, from 1995 through 2016, were retrieved from the Netherlands Cancer Registry (NCR). Data on diagnosis, staging, and treatment were extracted from the medical records by specifically trained NCR personnel. Information on survival status was updated annually using a computerized link with the national civil registry. In total, 7930 patients were included in this study; 4555 (57.4%) had a right‐sided and 3375 (42.6%) had a left‐sided primary tumor. In multivariable analysis right‐sided primary tumor was associated with worse OS (HR: 1.11, 95% CI 1.03‐1.19, P = .007). Of all patients diagnosed with PM, 564 (7.1%) underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC). Patients with left‐sided primary tumors were more often candidates for CRS‐HIPEC (6.5% vs. 8.0%, P = .008). OS of patients with right‐ and left‐sided tumors who underwent CRS‐HIPEC did not significantly differ. In conclusion, primary right‐sided colon cancer was an independent prognostic factor for decreased OS in patients diagnosed with synchronous PM. In patients treated with CRS‐HIPEC location of the primary tumor did not influence survival.
Primary tumor location is an established prognostic factor for patients with colon cancer. Little is known about the impact of tumor location on the outcomes of patients with peritoneal metastases. In a population‐based study in the Netherlands, primary right‐sided colon cancer was an independent prognostic factor for decreased survival in patients with synchronous peritoneal metastases. In patients with synchronous peritoneal metastases treated with CRS‐HIPEC, location of the primary tumor did not influence survival.
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes for selected patients with colorectal peritoneal metastases (PM), but recurrence rates ...are high. The aim of this study was to develop a tool to predict recurrence in patients with colorectal PM that undergo CRS-HIPEC.
For this retrospective cohort study, data of patients that underwent CRS-HIPEC for colorectal PM from four Dutch HIPEC centers were used. Exclusion criteria were perioperative systemic therapy and peritoneal cancer index (PCI) ≥20. Nine previously identified factors were considered as predictors: gender, age, primary tumor characteristics (location, nodal stage, differentiation, and mutation status), synchronous liver metastases, preoperative Carcino-Embryonal Antigen (CEA), and peritoneal cancer index (PCI). The prediction model was developed using multivariable Cox regression and validated internally using bootstrapping. The performance of the model was evaluated by discrimination and calibration.
In total, 408 patients were included. During the follow-up, recurrence of disease occurred in 318 patients (78%). Significant predictors of recurrence were PCI (HR 1.075, 95% CI 1.044–1.108) and primary tumor location (left sided HR 0.719, 95% CI 0.550–0.939). The prediction model for recurrence showed fair discrimination with a C-index of 0.64 (95% CI 0.62, 0.66) after internal validation. The model was well-calibrated with good agreement between the predicted and observed probabilities.
We developed a prediction tool that could aid in the prediction of recurrence in patients with colorectal PM who undergo CRS-HIPEC.
As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA ...repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg-/- mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4-5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg-/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mitochondrial dysfunction during acute metabolic crises is considered an important pathomechanism in inherited disorders of propionate metabolism, i.e. propionic and methylmalonic acidurias. ...Biochemically, these disorders are characterized by accumulation of propionyl-CoA and metabolites of alternative propionate oxidation. In the present study, we demonstrate uncompetitive inhibition of PDHc (pyruvate dehydrogenase complex) by propionyl-CoA in purified porcine enzyme and in submitochondrial particles from bovine heart being in the same range as the inhibition induced by acetyl-CoA, the physiological product and known inhibitor of PDHc. Evaluation of similar monocarboxylic CoA esters showed a chain-length specificity for PDHc inhibition. In contrast with CoA esters, non-esterified fatty acids did not inhibit PDHc activity. In addition to PDHc inhibition, analysis of respiratory chain and tricarboxylic acid cycle enzymes also revealed an inhibition by propionyl-CoA on respiratory chain complex III and alpha-ketoglutarate dehydrogenase complex. To test whether impairment of mitochondrial energy metabolism is involved in the pathogenesis of propionic aciduria, we performed a thorough bioenergetic analysis in muscle biopsy specimens of two patients. In line with the in vitro results, oxidative phosphorylation was severely compromised in both patients. Furthermore, expression of respiratory chain complexes I-IV and the amount of mitochondrial DNA were strongly decreased, and ultrastructural mitochondrial abnormalities were found, highlighting severe mitochondrial dysfunction. In conclusion, our results favour the hypothesis that toxic metabolites, in particular propionyl-CoA, are involved in the pathogenesis of inherited disorders of propionate metabolism, sharing mechanistic similarities with propionate toxicity in micro-organisms.
Sensory hair cells in the cochlea, like most neuronal populations that are postmitotic, terminally differentiated, and non-regenerating, depend on robust mechanisms of self-renewal for lifelong ...survival. We report that hair cell homeostasis requires a specific sub-branch of the DNA damage nucleotide excision repair pathway, termed transcription-coupled repair (TCR). Cockayne syndrome (CS), caused by defects in TCR, is a rare DNA repair disorder with a broad clinical spectrum that includes sensorineural hearing loss. We tested hearing and analyzed the cellular integrity of the organ of Corti in two mouse models of this disease with mutations in the Csb gene (CSB(m/m) mice) and Csa gene (Csa(-/-) mice), respectively. Csb(m/m) and Csa(-/-) mice manifested progressive hearing loss, as measured by an increase in auditory brainstem response thresholds. In contrast to wild-type mice, mutant mice showed reduced or absent otoacoustic emissions, suggesting cochlear outer hair cell impairment. Hearing loss in Csb(m/m) and Csa(-/-) mice correlated with progressive hair cell loss in the base of the organ of Corti, starting between 6 and 13 weeks of age, which increased by 16 weeks of age in a basal-to-apical gradient, with outer hair cells more severely affected than inner hair cells. Our data indicate that the hearing loss observed in CS patients is reproduced in mouse models of this disease. We hypothesize that accumulating DNA damage, secondary to the loss of TCR, contributes to susceptibility to hearing loss.
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