A novel approach to simulate gene-environment interactions in complex diseases

Background: Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.). Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results: We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS), a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions: By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte Carlo process allows random variability. A knowledge-based approach reduces the complexity of the mathematical model by using reasonable biological constraints and makes the simulation more understandable in biological terms. Simulated data sets can be used for the assessment of novel statistical methods or for the evaluation of the statistical power when designing a study

FLUXNET-CH₄ synthesis activity: objectives, observations, and future directions

We describe a new coordination activity and initial results for a global synthesis of eddy covariance CH4 flux measurements

The Fermi-LAT Light Curve Repository

The Fermi Large Area Telescope (LAT) light curve repository (LCR) is a publicly available, continually updated library of gamma-ray light curves of variable Fermi-LAT sources generated over multiple timescales. The Fermi-LAT LCR aims to provide publication-quality light curves binned on timescales of 3 days, 7 days, and 30 days for 1525 sources deemed variable in the source catalog of the first 10 years of Fermi-LAT observations. The repository consists of light curves generated through full likelihood analyses that model the sources and the surrounding region, providing fluxes and photon indices for each time bin. The LCR is intended as a resource for the time-domain and multi-messenger communities by allowing users to quickly search LAT data to identify correlated variability and flaring emission episodes from gamma-ray sources. We describe the sample selection and analysis employed by the LCR and provide an overview of the associated data access portal.Comment: Accepted for publication in ApJ Supplement Serie

Fermi-GBM Discovery of GRB 221009A: An Extraordinarily Bright GRB from Onset to Afterglow

We report the discovery of GRB 221009A, the highest flux gamma-ray burst ever observed by the Fermi Gamma-ray Burst Monitor (GBM). This GRB has continuous prompt emission lasting more than 600 seconds which smoothly transitions to afterglow visible in the GBM energy range (8 keV--40 MeV), and total energetics higher than any other burst in the GBM sample. By using a variety of new and existing analysis techniques we probe the spectral and temporal evolution of GRB 221009A. We find no emission prior to the GBM trigger time (t0; 2022 October 9 at 13:16:59.99 UTC), indicating that this is the time of prompt emission onset. The triggering pulse exhibits distinct spectral and temporal properties suggestive of the thermal, photospheric emission of shock-breakout, with significant emission up to ∼15 MeV. We characterize the onset of external shock at t0+600 s and find evidence of a plateau region in the early-afterglow phase which transitions to a slope consistent with Swift-XRT afterglow measurements. We place the total energetics of GRB 221009A in context with the rest of the GBM sample and find that this GRB has the highest total isotropic-equivalent energy (Eγ,iso=1.0×10^55 erg) and second highest isotropic-equivalent luminosity (Lγ,iso=9.9×10^53 erg/s) based on redshift of z = 0.151. These extreme energetics are what allowed us to observe the continuously emitting central engine of GBM from the beginning of the prompt emission phase through the onset of early afterglow

The Advanced Virgo+ status

The gravitational wave detector Advanced Virgo+ is currently in the commissioning phase in view of the fourth Observing Run (O4). The major upgrades with respect to the Advanced Virgo configuration are the implementation of an additional recycling cavity, the Signal Recycling cavity (SRC), at the output of the interferometer to broaden the sensitivity band and the Frequency Dependent Squeezing (FDS) to reduce quantum noise at all frequencies. The main difference of the Advanced Virgo + detector with respect to the LIGO detectors is the presence of marginally stable recycling cavities, with respect to the stable recycling cavities present in the LIGO detectors, which increases the difficulties in controlling the interferometer in presence of defects (both thermal and cold defects). This work will focus on the interferometer commissioning, highlighting the control challenges to maintain the detector in the working point which maximizes the sensitivity and the duty cycle for scientific data taking

Sensitivity of the Cherenkov Telescope Array to TeV photon emission from the Large Magellanic Cloud

A deep survey of the Large Magellanic Cloud at ∼0.1-100 TeV photon energies with the Cherenkov Telescope Array is planned. We assess the detection prospects based on a model for the emission of the galaxy, comprising the four known TeV emitters, mock populations of sources, and interstellar emission on galactic scales. We also assess the detectability of 30 Doradus and SN 1987A, and the constraints that can be derived on the nature of dark matter. The survey will allow for fine spectral studies of N 157B, N 132D, LMC P3, and 30 Doradus C, and half a dozen other sources should be revealed, mainly pulsar-powered objects. The remnant from SN 1987A could be detected if it produces cosmic-ray nuclei with a flat power-law spectrum at high energies, or with a steeper index 2.3-2.4 pending a flux increase by a factor of >3-4 over ∼2015-2035. Large-scale interstellar emission remains mostly out of reach of the survey if its >10 GeV spectrum has a soft photon index ∼2.7, but degree-scale 0.1-10 TeV pion-decay emission could be detected if the cosmic-ray spectrum hardens above >100 GeV. The 30 Doradus star-forming region is detectable if acceleration efficiency is on the order of 1−10 per cent of the mechanical luminosity and diffusion is suppressed by two orders of magnitude within <100 pc. Finally, the survey could probe the canonical velocity-averaged cross-section for self-annihilation of weakly interacting massive particles for cuspy Navarro-Frenk-White profiles

Sensitivity of the Cherenkov Telescope Array to spectral signatures of hadronic PeVatrons with application to Galactic Supernova Remnants

The local Cosmic Ray (CR) energy spectrum exhibits a spectral softening at energies around 3~PeV. Sources which are capable of accelerating hadrons to such energies are called hadronic PeVatrons. However, hadronic PeVatrons have not yet been firmly identified within the Galaxy. Several source classes, including Galactic Supernova Remnants (SNRs), have been proposed as PeVatron candidates. The potential to search for hadronic PeVatrons with the Cherenkov Telescope Array (CTA) is assessed. The focus is on the usage of very high energy $\gamma$-ray spectral signatures for the identification of PeVatrons. Assuming that SNRs can accelerate CRs up to knee energies, the number of Galactic SNRs which can be identified as PeVatrons with CTA is estimated within a model for the evolution of SNRs. Additionally, the potential of a follow-up observation strategy under moonlight conditions for PeVatron searches is investigated. Statistical methods for the identification of PeVatrons are introduced, and realistic Monte--Carlo simulations of the response of the CTA observatory to the emission spectra from hadronic PeVatrons are performed. Based on simulations of a simplified model for the evolution for SNRs, the detection of a $\gamma$-ray signal from in average 9 Galactic PeVatron SNRs is expected to result from the scan of the Galactic plane with CTA after 10 hours of exposure. CTA is also shown to have excellent potential to confirm these sources as PeVatrons in deep observations with $\mathcal{O}(100)$ hours of exposure per source.Comment: 34 pages, 16 figures, Accepted for publication in Astroparticle Physic

Open data from the third observing run of LIGO, Virgo, KAGRA and GEO

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 April of 2019 and lasting six months, O3b starting in November of 2019 and lasting five months, and O3GK starting in April of 2020 and lasting 2 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 dataset, 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.Comment: 27 pages, 3 figure