Strength of patient cohorts and biobanks for cardiomyopathy research

In 2011 the Netherlands Heart Foundation allocated funding (CVON, Cardiovasculair Onderzoek Nederland) to stimulate collaboration between clinical and preclinical researchers on specific areas of research. One of those areas involves genetic heart diseases, which are frequently caused by pathogenic variants in genes that encode sarcomere proteins. In 2014, the DOSIS (Determinants of susceptibility in inherited cardiomyopathy: towards novel therapeutic approaches) consortium was initiated, focusing their research on secondary disease hits involved in the onset and progression of cardiomyopathies. Here we highlight several recent observations from our consortium and collaborators which may ultimately be relevant for clinical practice

An Ultrahigh-energy γ\gamma-ray Bubble Powered by a Super PeVatron

International audienceWe report the detection of a $\gamma$-ray bubble spanning at least 100$\rm deg^2$ in ultra high energy (UHE) up to a few PeV in the direction of the star-forming region Cygnus X, implying the presence Super PeVatron(s) accelerating protons to at least 10 PeV. A log-parabola form with the photon index $\Gamma (E) = (2.71 \pm 0.02) + (0.11 \pm 0.02) \times \log_{10} (E/10 \ {\rm TeV})$ is found fitting the gamma-ray energy spectrum of the bubble well. UHE sources, `hot spots' correlated with very massive molecular clouds, and a quasi-spherical amorphous $\gamma$-ray emitter with a sharp central brightening are observed in the bubble. In the core of $\sim 0.5^{\circ}$, spatially associating with a region containing massive OB association (Cygnus OB2) and a microquasar (Cygnus X-3), as well as previously reported multi-TeV sources, an enhanced concentration of UHE $\gamma$-rays are observed with 2 photons at energies above 1 PeV. The general feature of the bubble, the morphology and the energy spectrum, are reasonably reproduced by the assumption of a particle accelerator in the core, continuously injecting protons into the ambient medium

LHAASO-KM2A detector simulation using Geant4

International audienceKM2A is one of the main sub-arrays of LHAASO, working on gamma ray astronomy and cosmic ray physics at energies above 10 TeV. Detector simulation is the important foundation for estimating detector performance and data analysis. It is a big challenge to simulate the KM2A detector in the framework of Geant4 due to the need to track numerous photons from a large number of detector units (>6000) with large altitude difference (30 m) and huge coverage (1.3 km^2). In this paper, the design of the KM2A simulation code G4KM2A based on Geant4 is introduced. The process of G4KM2A is optimized mainly in memory consumption to avoid memory overffow. Some simpliffcations are used to signiffcantly speed up the execution of G4KM2A. The running time is reduced by at least 30 times compared to full detector simulation. The particle distributions and the core/angle resolution comparison between simulation and experimental data of the full KM2A array are also presented, which show good agreement

Pointing calibration of LHAASO-WFCTA telescopes using bright stars

International audienceOne of the main scientific objectives of the Large High Altitude Air Shower Observatory (LHAASO) is to perform accurate measurements of the energy spectra for different cosmic ray masses, from a few TeV to 100 PeV. As one of the main sub-arrays of LHAASO, the Wide Field-of-View Cherenkov Telescope Array (WFCTA), which consists of 18 telescopes, can help in achieving this goal. The pointing accuracy of each telescope is crucial for reconstructing energy and determining mass-sensitive parameters. In this study, a method for absolute pointing calibration using ultraviolet bright stars was established. The proposed method can achieve a pointing accuracy of approximately 0.02° by using more than five stars. When more stars are used in the telescope’s field of view, the accuracy of the pointing calibration can be improved, e.g, a pointing accuracy of 0.01° can be achieved when using more than 15 stars. A high-precision inclinometer with a monitor resolution of 0.003° was installed on the camera to monitor the zenith direction of the telescope at every second. After calibration using bright stars, the absolute pointing accuracy of the inclinometer was 0.02°. •Method for absolute pointing calibration using ultraviolet bright stars established.•A pointing accuracy of ∼0.02°can be achieved using more than five stars.•A pointing accuracy of 0.01°can be achieved when using more than 15 stars•Accuracy of the pointing calibration increases with number of bright stars

An Ultrahigh-energy γ\gamma-ray Bubble Powered by a Super PeVatron

International audienceWe report the detection of a $\gamma$-ray bubble spanning at least 100$\rm deg^2$ in ultra high energy (UHE) up to a few PeV in the direction of the star-forming region Cygnus X, implying the presence Super PeVatron(s) accelerating protons to at least 10 PeV. A log-parabola form with the photon index $\Gamma (E) = (2.71 \pm 0.02) + (0.11 \pm 0.02) \times \log_{10} (E/10 \ {\rm TeV})$ is found fitting the gamma-ray energy spectrum of the bubble well. UHE sources, `hot spots' correlated with very massive molecular clouds, and a quasi-spherical amorphous $\gamma$-ray emitter with a sharp central brightening are observed in the bubble. In the core of $\sim 0.5^{\circ}$, spatially associating with a region containing massive OB association (Cygnus OB2) and a microquasar (Cygnus X-3), as well as previously reported multi-TeV sources, an enhanced concentration of UHE $\gamma$-rays are observed with 2 photons at energies above 1 PeV. The general feature of the bubble, the morphology and the energy spectrum, are reasonably reproduced by the assumption of a particle accelerator in the core, continuously injecting protons into the ambient medium

Does or did the supernova remnant Cassiopeia A operate as a PeVatron?

International audienceFor decades, supernova remnants (SNRs) have been considered the prime sources of Galactic Cosmic rays (CRs). But whether SNRs can accelerate CR protons to PeV energies and thus dominate CR flux up to the knee is currently under intensive theoretical and phenomenological debate. The direct test of the ability of SNRs to operate as CR PeVatrons can be provided by ultrahigh-energy (UHE; $E_\gamma \geq 100$~TeV) $\gamma$-rays. In this context, the historical SNR Cassiopeia A (Cas A) is considered one of the most promising target for UHE observations. This paper presents the observation of Cas A and its vicinity by the LHAASO KM2A detector. The exceptional sensitivity of LHAASO KM2A in the UHE band, combined with the young age of Cas A, enabled us to derive stringent model-independent limits on the energy budget of UHE protons and nuclei accelerated by Cas A at any epoch after the explosion. The results challenge the prevailing paradigm that Cas A-type SNRs are major suppliers of PeV CRs in the Milky Way

Optimization of performance of the KM2A full array using the Crab Nebula

International audienceThe full array of the Large High Altitude Air Shower Observatory (LHAASO) has been in operation since July 2021. For its kilometer-square array (KM2A), we have optimized the selection criteria for very high and ultra-high energy $\gamma$-rays, using the data collected from August 2021 to August 2022, resulting in an improvement on significance of about 15$\%$ compared with previous cuts. With the implementation of these new selection criteria, the angular resolution is also significantly improved by approximately 10$\%$ at tens of TeV. Other aspects of the full KM2A array performance, such as the pointing error are also calibrated using the Crab Nebula. The resulting energy spectrum of the Crab Nebula in the energy range of 10-1000 TeV can be well fitted by a log-parabola model, which is consistent with the previous results from LHAASO and other experiments

Measurement of ultra-high-energy diffuse gamma-ray emission of the Galactic plane from 10 TeV to 1 PeV with LHAASO-KM2A

International audienceThe diffuse Galactic $\gamma$-ray emission, mainly produced via interactions between cosmic rays and the diffuse interstellar medium, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this work we report the measurements of diffuse $\gamma$-rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner ($15^{\circ}10$~TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of $-2.99\pm0.04$, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of $\sim3$ than the prediction. A similar spectrum with an index of $-2.99\pm0.07$ is found in the outer Galaxy region, and the absolute flux for $10\lesssim E\lesssim60$ TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show slight deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations

Does or did the supernova remnant Cassiopeia A operate as a PeVatron?

International audienceFor decades, supernova remnants (SNRs) have been considered the prime sources of Galactic Cosmic rays (CRs). But whether SNRs can accelerate CR protons to PeV energies and thus dominate CR flux up to the knee is currently under intensive theoretical and phenomenological debate. The direct test of the ability of SNRs to operate as CR PeVatrons can be provided by ultrahigh-energy (UHE; $E_\gamma \geq 100$~TeV) $\gamma$-rays. In this context, the historical SNR Cassiopeia A (Cas A) is considered one of the most promising target for UHE observations. This paper presents the observation of Cas A and its vicinity by the LHAASO KM2A detector. The exceptional sensitivity of LHAASO KM2A in the UHE band, combined with the young age of Cas A, enabled us to derive stringent model-independent limits on the energy budget of UHE protons and nuclei accelerated by Cas A at any epoch after the explosion. The results challenge the prevailing paradigm that Cas A-type SNRs are major suppliers of PeV CRs in the Milky Way

Measurement of ultra-high-energy diffuse gamma-ray emission of the Galactic plane from 10 TeV to 1 PeV with LHAASO-KM2A

International audienceThe diffuse Galactic $\gamma$-ray emission, mainly produced via interactions between cosmic rays and the diffuse interstellar medium, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this work we report the measurements of diffuse $\gamma$-rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner ($15^{\circ}10$~TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of $-2.99\pm0.04$, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of $\sim3$ than the prediction. A similar spectrum with an index of $-2.99\pm0.07$ is found in the outer Galaxy region, and the absolute flux for $10\lesssim E\lesssim60$ TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show slight deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations