The light emitted by stars and accreting compact objects through the history of the universe is encoded in the intensity of the extragalactic background light (EBL). Knowledge of the EBL is important ...to understand the nature of star formation and galaxy evolution, but direct measurements of the EBL are limited by galactic and other foreground emissions. Here, we report an absorption feature seen in the combined spectra of a sample of gamma-ray blazars out to a redshift of z ~1.6. This feature is caused by attenuation of gamma rays by the EBL at optical to ultraviolet frequencies and allowed us to measure the EBL flux density in this frequency band.
We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. ...There were 9 dose-escalation cohorts ranging from 20 mg to 600 mg once daily with twice-daily regimens of 240 mg and 300 mg. Twenty-four of 25 evaluable chronic lymphocytic leukemia (CLL) patients (96%) responded to ONO/GS-4059, with a median treatment duration of 80 weeks; 21 CLL patients remain on treatment. Lymph node responses were rapid and associated with a concurrent lymphocytosis. Eleven of 12 evaluable patients with mantle cell lymphoma (92%) responded (median treatment duration, 40 weeks). Eleven of 31 non–germinal center B-cell diffuse large B-cell lymphoma patients (35%) responded but median treatment duration was 12 weeks due to development of progressive disease. ONO/GS-4059 was very well tolerated with 75% of adverse events (AEs) being Common Toxicity Criteria for Adverse Events version 4.0 grade 1 or grade 2. Grade 3/4 AEs were mainly hematologic and recovered spontaneously during therapy. One CLL patient experienced a grade 3 treatment-related bleeding event (spontaneous muscle hematoma) but no clinically significant diarrhea, cardiac dysrhythmias, or arthralgia were observed. No maximal tolerated dose (MTD) was reached in the CLL cohort. In the non-Hodgkin lymphoma cohort, 4 patients developed a dose-limiting toxicity, yielding an MTD of 480 mg once daily. ONO/GS-4059 has significant activity in relapsed/refractory B-cell malignancies without major drug-related toxicity. The selectivity of ONO/GS-4059 should confer advantages in combination therapies. This trial was registered at www.clinicaltrials.gov as #NCT01659255.
•We report a first-in-human dose-escalation study in relapsed/refractory B-cell malignancies with the potent BTK inhibitor ONO/GS-4059.•ONO/GS-4059 induced clinically durable responses in relapsed/refractory B-cell malignancies without significant toxicities.
We present a catalog of sources detected above 10 GeV by the Fermi Large Area Telescope (LAT) in the first 7 years of data using the Pass 8 event-level analysis. This is the Third Catalog of Hard ...Fermi-LAT Sources (3FHL), containing 1556 objects characterized in the 10 GeV-2 TeV energy range. The sensitivity and angular resolution are improved by factors of 3 and 2 relative to the previous LAT catalog at the same energies (1FHL). The vast majority of detected sources (79%) are associated with extragalactic counterparts at other wavelengths, including 16 sources located at very high redshift (z > 2). Of the sources, 8% have Galactic counterparts and 13% are unassociated (or associated with a source of unknown nature). The high-latitude sky and the Galactic plane are observed with a flux sensitivity of 4.4 to 9.5 × 10−11 ph cm−2 s−1, respectively (this is approximately 0.5% and 1% of the Crab Nebula flux above 10 GeV). The catalog includes 214 new γ-ray sources. The substantial increase in the number of photons (more than 4 times relative to 1FHL and 10 times to 2FHL) also allows us to measure significant spectral curvature for 32 sources and find flux variability for 163 of them. Furthermore, we estimate that for the same flux limit of 10−12 erg cm−2 s−1, the energy range above 10 GeV has twice as many sources as the range above 50 GeV, highlighting the importance, for future Cherenkov telescopes, of lowering the energy threshold as much as possible.
The region around the Galactic Center (GC) is now well established to be brighter at energies of a few GeV than what is expected from conventional models of diffuse gamma-ray emission and catalogs of ...known gamma-ray sources. We study the GeV excess using 6.5 yr of data from the Fermi Large Area Telescope. We characterize the uncertainty of the GC excess spectrum and morphology due to uncertainties in cosmic-ray source distributions and propagation, uncertainties in the distribution of interstellar gas in the Milky Way, and uncertainties due to a potential contribution from the Fermi bubbles. We also evaluate uncertainties in the excess properties due to resolved point sources of gamma rays. The GC is of particular interest, as it would be expected to have the brightest signal from annihilation of weakly interacting massive dark matter (DM) particles. However, control regions along the Galactic plane, where a DM signal is not expected, show excesses of similar amplitude relative to the local background. Based on the magnitude of the systematic uncertainties, we conservatively report upper limits for the annihilation cross-section as a function of particle mass and annihilation channel.
The origin of Galactic cosmic rays is a century-long puzzle. Indirect evidence points to their acceleration by supernova Shockwaves, but we know little of their escape from the shock and their ...evolution through the turbulent medium surrounding massive stars. Gamma rays can probe their spreading through the ambient gas and radiation fields. The Fermi Large Area Telescope (LAT) has observed the star-forming region of Cygnus X. The 1-to 100-gigaelectronvolt images reveal a 50-parsec-wide cocoon of freshly accelerated cosmic rays that flood the cavities carved by the stellar winds and ionization fronts from young stellar clusters. It provides an example to study the youth of cosmic rays in a superbubble environment before they merge into the older Galactic population.
The Large Area Telescope (LAT) aboard the Fermi spacecraft routinely observes high-energy emission from gamma-ray bursts (GRBs). Here we present the second catalog of LAT-detected GRBs, covering the ...first 10 yr of operations, from 2008 to 2018 August 4. A total of 186 GRBs are found; of these, 91 show emission in the range 30-100 MeV (17 of which are seen only in this band) and 169 are detected above 100 MeV. Most of these sources were discovered by other instruments (Fermi/GBM, Swift/BAT, AGILE, INTEGRAL) or reported by the Interplanetary Network (IPN); the LAT has independently triggered on four GRBs. This catalog presents the results for all 186 GRBs. We study onset, duration, and temporal properties of each GRB, as well as spectral characteristics in the 100 MeV-100 GeV energy range. Particular attention is given to the photons with the highest energy. Compared with the first LAT GRB catalog, our rate of detection is significantly improved. The results generally confirm the main findings of the first catalog: the LAT primarily detects the brightest GBM bursts, and the high-energy emission shows delayed onset as well as longer duration. However, in this work we find delays exceeding 1 ks and several GRBs with durations over 10 ks. Furthermore, the larger number of LAT detections shows that these GRBs not only cover the high-fluence range of GBM-detected GRBs but also sample lower fluences. In addition, the greater number of detected GRBs with redshift estimates allows us to study their properties in both the observer and rest frames. Comparison of the observational results with theoretical predictions reveals that no model is currently able to explain all results, highlighting the role of LAT observations in driving theoretical models.
Abstract Gamma-ray bursts (GRBs) are particle acceleration sites that can emit photons in the very high-energy (VHE) domain through nonthermal processes. From 2004 until 2018, the current generation ...of Imaging Atmospheric Cherenkov Telescopes (IACTs) did not detect any GRB in the VHE domain. However, from 2018 to 2020, five detections were reported. In this work, we try to solve the case of the missing VHE GBRs prior to 2018. We aim to identify GRBs that might have eluded VHE detection in past years by the H.E.S.S., MAGIC, and VERITAS IACTs. To do so, we study GRBs with known redshift detected by Swift from 2004 until June 2022. We first identify all GRBs that could have been observed by these IACTs since 2004, considering observation conditions and visibility constraints. We assume a relation between the X-rays and the VHE gamma rays based on the VHE GRBs detected to date and combine this with the redshift measurements, instrument response information, and observation conditions to predict the observed VHE gamma-ray flux from the Swift X-Ray Telescope measurements. We report findings on 12 bright low-redshift GRBs that we identify as most likely to have been detected in the VHE domain by current IACTs. The rate of IACT-detectable GRBs with ideal observation conditions is <1 VHE GRB per year with the current configuration. With its lower energy threshold and higher sensitivity, this rate increases to ∼4 VHE GRBs per year with the Cherenkov Telescope Array.
The spatial extension of a γ-ray source is an essential ingredient to determine its spectral properties, as well as its potential multiwavelength counterpart. The capability to spatially resolve ...γ-ray sources is greatly improved by the newly delivered Fermi-Large Area Telescope (LAT) Pass 8 event-level analysis, which provides a greater acceptance and an improved point-spread function, two crucial factors for the detection of extended sources. Here, we present a complete search for extended sources located within 7° from the Galactic plane, using 6 yr of Fermi-LAT data above 10 GeV. We find 46 extended sources and provide their morphological and spectral characteristics. This constitutes the first catalog of hard Fermi-LAT extended sources, named the Fermi Galactic Extended Source Catalog, which allows a thorough study of the properties of the Galactic plane in the sub-TeV domain.
We present the second catalog of flaring gamma-ray sources (2FAV) detected with the Fermi All-sky Variability Analysis (FAVA), a tool that blindly searches for transients over the entire sky observed ...by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. With respect to the first FAVA catalog, this catalog benefits from a larger data set, the latest LAT data release (Pass 8), as well as from an improved analysis that includes likelihood techniques for a more precise localization of the transients. Applying this analysis to the first 7.4 years of Fermi observations, and in two separate energy bands 0.1-0.8 GeV and 0.8-300 GeV, a total of 4547 flares were detected with significance greater than (before trials), on the timescale of one week. Through spatial clustering of these flares, 518 variable gamma-ray sources were identified. Based on positional coincidence, likely counterparts have been found for 441 sources, mostly among the blazar class of active galactic nuclei. For 77 2FAV sources, no likely gamma-ray counterpart has been found. For each source in the catalog, we provide the time, location, and spectrum of each flaring episode. Studying the spectra of the flares, we observe a harder-when-brighter behavior for flares associated with blazars, with the exception of BL Lac flares detected in the low-energy band. The photon indexes of the flares are never significantly smaller than 1.5. For a leptonic model, and under the assumption of isotropy, this limit suggests that the spectrum of freshly accelerated electrons is never harder than .
We present the fourth Fermi Large Area Telescope catalog (4FGL) of γ-ray sources. Based on the first eight years of science data from the Fermi Gamma-ray Space Telescope mission in the energy range ...from 50 MeV to 1 TeV, it is the deepest yet in this energy range. Relative to the 3FGL catalog, the 4FGL catalog has twice as much exposure as well as a number of analysis improvements, including an updated model for the Galactic diffuse γ-ray emission, and two sets of light curves (one-year and two-month intervals). The 4FGL catalog includes 5064 sources above 4 significance, for which we provide localization and spectral properties. Seventy-five sources are modeled explicitly as spatially extended, and overall, 358 sources are considered as identified based on angular extent, periodicity, or correlated variability observed at other wavelengths. For 1336 sources, we have not found plausible counterparts at other wavelengths. More than 3130 of the identified or associated sources are active galaxies of the blazar class, and 239 are pulsars.
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