In classical analyses of γ-ray data from imaging atmospheric Cherenkov telescopes (IACTs), such as the High Energy Stereoscopic System (H.E.S.S.), aperture photometry, or photon counting, is applied ...in a (typically circular) region of interest (RoI) encompassing the source. A key element in the analysis is to estimate the amount of background in the RoI due to residual cosmic ray-induced air showers in the data. Various standard background estimation techniques have been developed in the last decades, most of them rely on a measurement of the background from source-free regions within the observed field of view. However, in particular in the Galactic plane, source analysis and background estimation are hampered by the large number of, sometimes overlapping, γ-ray sources and large-scale diffuse γ-ray emission. For complicated fields of view, a three-dimensional (3D) likelihood analysis shows the potential to be superior to classical analysis. In this analysis technique, a spectromorphological model, consisting of one or multiple source components and a background component, is fitted to the data, resulting in a complete spectral and spatial description of the field of view. For the application to IACT data, the major challenge of such an approach is the construction of a robust background model. In this work, we apply the 3D likelihood analysis to various test data recently made public by the H.E.S.S. collaboration, using the open analysis frameworks ctools and Gammapy. First, we show that, when using these tools in a classical analysis approach and comparing to the proprietary H.E.S.S. analysis framework, virtually identical high-level analysis results, such as field-of-view maps and spectra, are obtained. We then describe the construction of a generic background model from data of H.E.S.S. observations, and demonstrate that a 3D likelihood analysis using this background model yields high-level analysis results that are highly compatible with those obtained from the classical analyses. This validation of the 3D likelihood analysis approach on experimental data is an important step towards using this method for IACT data analysis, and in particular for the analysis of data from the upcoming Cherenkov Telescope Array (CTA).
The Cherenkov Telescope Array and the KM3NeT neutrino telescopes are major upcoming facilities in the fields of
γ
-ray and neutrino astronomy, respectively. Possible simultaneous production of
γ
rays ...and neutrinos in astrophysical accelerators of cosmic-ray nuclei motivates a combination of their data. We assess the potential of a combined analysis of CTA and KM3NeT data to determine the contribution of hadronic emission processes in known Galactic
γ
-ray emitters, comparing this result to the cases of two separate analyses. In doing so, we demonstrate the capability of
Gammapy
, an open-source software package for the analysis of
γ
-ray data, to also process data from neutrino telescopes. For a selection of prototypical
γ
-ray sources within our Galaxy, we obtain models for primary proton and electron spectra in the hadronic and leptonic emission scenario, respectively, by fitting published
γ
-ray spectra. Using these models and instrument response functions for both detectors, we employ the
Gammapy
package to generate pseudo data sets, where we assume 200 h of CTA observations and 10 years of KM3NeT detector operation. We then apply a three-dimensional binned likelihood analysis to these data sets, separately for each instrument and jointly for both. We find that the largest benefit of the combined analysis lies in the possibility of a consistent modelling of the
γ
-ray and neutrino emission. Assuming a purely leptonic scenario as input, we obtain, for the most favourable source, an average expected 68% credible interval that constrains the contribution of hadronic processes to the observed
γ
-ray emission to below 15%.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe
. The emission from GRBs comprises a short (typically tens of ...seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed
. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments
. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive
. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.
By regulating the structure of chromatin, ATP-dependent chromatin remodeling complexes (remodelers) perform critical functions in the maintenance, transmission and expression of the eukaryotic ...genome. Although all known chromatin-remodeling complexes contain an ATPase as a central motor subunit, a number of distinct classes have been recognized. Recent studies have emphasized a more extensive functional diversification among closely related chromatin remodeling complexes than previously anticipated. Here, we discuss recent insights in the functional differences between two evolutionary conserved subclasses of SWI/SNF-related chromatin remodeling factors. One subfamily comprises yeast SWI/SNF, fly BAP and mammalian BAF, whereas the other subfamily includes yeast RSC, fly PBAP and mammalian PBAF. We review the subunit composition, conserved protein modules and biological functions of each of these subclasses of SWI/SNF remodelers. In particular, we will focus on the roles of specific subunits in developmental gene control and human diseases. Recent findings suggest that functional diversification among SWI/SNF complexes allows the eukaryotic cell to fine-tune and integrate the execution of diverse biological programs involving the expression, maintenance and duplication of its genome.
We present a case of peripheral T-cell lymphoma co-expressing CD3 and CD20, as well as demonstrating T-cell receptor gene rearrangement, in a patient who had been diagnosed with nodular sclerosis ...Hodgkin's disease 5 years previously. Although 15 cases of CD20-positive T-cell neoplasms have been previously reported in the literature, this is the first report of CD20-positive T-cell lymphoma occurring subsequent to treatment of Hodgkin's disease. The current case affords an opportunity to review the rarely reported expression of CD20 in T-cell neoplasms as well as the relationship between Hodgkin's disease and subsequently occurring non-Hodgkin's lymphomas. In addition, the identification of this case supports the suggestion that the use of CD20 antibodies alone in paraffin sections may lead to an incorrect determination of cell lineage in some cases.
Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we ...present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers.
Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies.
Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation.
Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.
•14.3% of patients with rare cancers and/or younger age of onset carried a PGV.•PGVs were highly enriched in certain rare cancer entities, i.e. wild-type GISTs and leiomyosarcomas.•High PGV yields in ATM, BRCA2, or PALB2 in rare cancer entities indicated potentially novel genotype–phenotype associations.•75% of patients with PGVs in cancer predisposition genes were newly diagnosed due to study participation (118/157).•45% of all PGVs supported molecularly informed therapeutic recommendations with a therapeutic benefit in 40% of patients.
Abstract The Cherenkov Telescope Array and the KM3NeT neutrino telescopes are major upcoming facilities in the fields of $$\gamma $$ γ -ray and neutrino astronomy, respectively. Possible simultaneous ...production of $$\gamma $$ γ rays and neutrinos in astrophysical accelerators of cosmic-ray nuclei motivates a combination of their data. We assess the potential of a combined analysis of CTA and KM3NeT data to determine the contribution of hadronic emission processes in known Galactic $$\gamma $$ γ -ray emitters, comparing this result to the cases of two separate analyses. In doing so, we demonstrate the capability of Gammapy, an open-source software package for the analysis of $$\gamma $$ γ -ray data, to also process data from neutrino telescopes. For a selection of prototypical $$\gamma $$ γ -ray sources within our Galaxy, we obtain models for primary proton and electron spectra in the hadronic and leptonic emission scenario, respectively, by fitting published $$\gamma $$ γ -ray spectra. Using these models and instrument response functions for both detectors, we employ the Gammapy package to generate pseudo data sets, where we assume 200 h of CTA observations and 10 years of KM3NeT detector operation. We then apply a three-dimensional binned likelihood analysis to these data sets, separately for each instrument and jointly for both. We find that the largest benefit of the combined analysis lies in the possibility of a consistent modelling of the $$\gamma $$ γ -ray and neutrino emission. Assuming a purely leptonic scenario as input, we obtain, for the most favourable source, an average expected 68% credible interval that constrains the contribution of hadronic processes to the observed $$\gamma $$ γ -ray emission to below 15%.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently ...recurs after resection. So far, the underlying pathogenesis is largely elusive.
Objectives
To identify genetic alterations by next‐generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH.
Methods
DNA and RNA from an EH lesion of an index patient were subjected to whole‐genome and RNA sequencing. Multiplex PCR‐based panel sequencing of genomic DNA isolated from archival formalin‐fixed paraffin‐embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations.
Results
We identified somatic mutations in genes of the mitogen‐activated protein kinase (MAPK) pathway (MAP2K1 and KRAS) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low‐frequency mutations affecting MAP2K1. In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells.
Conclusions
Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour.
What is already known about this topic?
Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour of unknown aetiology.
Cutaneous EH often shows a marked inflammatory infiltrate indicating a reactive origin.
What does this study add?
Half of the samples from cutaneous EH in this study showed activating mutations in the mitogen‐activated protein kinase pathway (MAP2K1 and KRAS).
Mutations were mutually exclusive.
What is the translational message?
Somatic mutations seem to contribute to the formation of a significant proportion of cutaneous EH.
The molecular alterations found might be sensitive for targeted therapies.
Linked Comment: W. Tan and J.S. Nelson. Br J Dermatol 2022; 186:393–394.
SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an ...energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.
ABSTRACT
We report on a search for persistent radio emission from the one-off fast radio burst (FRB) 20190714A, as well as from two repeating FRBs, 20190711A and 20171019A, using the MeerKAT radio ...telescope. For FRB 20171019A, we also conducted simultaneous observations with the High-Energy Stereoscopic System (H.E.S.S.) in very high-energy gamma rays and searched for signals in the ultraviolet, optical, and X-ray bands. For this FRB, we obtain a UV flux upper limit of $1.39 \times 10^{-16}~{\rm erg\, cm^{-2}\, s^{-1}}$Å−1, X-ray limit of $\sim 6.6 \times 10^{-14}~{\rm erg\, cm^{-2}\, s^{-1}}$ and a limit on the very high energy gamma-ray flux $\Phi (E\gt 120\, {\rm GeV}) \lt 1.7\times 10^{-12}\, \mathrm{erg\, cm^{-2}\, s^{-1}}$. We obtain a radio upper limit of ∼15 $\mu$Jy beam−1 for persistent emission at the locations of both FRBs 20190711A and 20171019A with MeerKAT. However, we detected an almost unresolved (ratio of integrated flux to peak flux is ∼1.7 beam) radio emission, where the synthesized beam size was ∼ 8 arcsec size with a peak brightness of $\sim 53\, \mu$Jy beam−1 at MeerKAT and $\sim 86\, \mu$Jy beam−1 at e-MERLIN, possibly associated with FRB 20190714A at z = 0.2365. This represents the first detection of persistent continuum radio emission potentially associated with a (as-yet) non-repeating FRB. If the association is confirmed, one of the strongest remaining distinction between repeaters and non-repeaters would no longer be applicable. A parallel search for repeat bursts from these FRBs revealed no new detections down to a fluence of 0.08 Jy ms for a 1 ms duration burst.
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