We report on a terrestrial gamma ray flash (TGF) that occurred on 15 August 2014 coincident with an altitude‐triggered lightning at the International Center for Lightning Research and Testing (ICLRT) ...in North Central Florida. The TGF was observed by a ground‐level network of gamma ray, close electric field, distant magnetic field, Lightning Mapping Array (LMA), optical, and radar measurements. Simultaneous gamma ray and LMA data indicate that the upward positive leader of the triggered lightning flash induced relativistic runaway electron avalanches when the leader tip was at about 3.5 km altitude, resulting in the observed TGF. Channel luminosity and electric field data show that there was an initial continuous current (ICC) pulse in the lightning channel to ground during the time of the TGF. Modeling of the observed ICC pulse electric fields measured at close range (100–200 m) indicates that the ICC pulse current had both a slow and fast component (full widths at half maximum of 235 μs and 59 μs) and that the fast component was more or less coincident with the TGF, suggesting a physical association between the relativistic runaway electron avalanches and the ICC pulse observed at ground. Our ICC pulse model reproduces moderately well the measured close electric fields at the ICLRT as well as three independent magnetic field measurements made about 250 km away. Radar and LMA data suggest that there was negative charge near the region in which the TGF was initiated.
Key Points
Best documented TGF observed at ground
Second TGF induced by triggered lightning
An ICC pulse occurred simultaneously (within 20 μs) of the TGF
The Gamma‐ray Burst Monitor (GBM) on the Fermi Gamma‐ray Space Telescope detected 12 intense terrestrial gamma ray flashes (TGFs) during its first year of observation. Typical maximum energies for ...most of the TGFs are ∼30 MeV, with one TGF having a 38 MeV photon; two of the TGFs are softer and longer than the others. After correcting for instrumental effects, a representative bright TGF is found to have a fluence of ∼0.7 photons cm−2. Pulses are either symmetrical or have faster risetimes than fall times; they are well fit with Gaussian or lognormal functions. The fastest risetime observed was 7 μs, constraining the source radius to be less than about 2 km from the velocity of light. TGFs with multiple pulses separated in time have been known since their discovery; the GBM sample also includes clear cases of partially overlapping pulses. Four TGFs are associated with lightning locations from the World Wide Lightning Location Network. With the several μs absolute time accuracy of GBM, the time order can be confidently identified: one TGF occurred before the lightning, two were simultaneous, and one TGF occurred after the lightning.
We present the first Fermi Space Telescope Gamma Ray Burst Monitor (GBM) catalog of 4,144 terrestrial gamma ray flashes (TGFs), detected since launch in 11 July 2008 through 31 July 2016. We discuss ...the updates and improvements to the triggered data and off‐line search algorithms, comparing this improved detection rate of ∼800 TGFs per year with event rates from previously published TGF catalogs from other missions. A Bayesian block algorithm calculated the temporal and spectral properties of the TGFs, revealing a delay between the hard (>300 keV) and soft (≤300 keV) photons of around 27 μs. Detector count rates of “low‐fluence” events were found to have average rates exceeding 150 kHz. Searching the World‐Wide Lightning Location Network data for radio sferics within ±5 min of each TGF revealed a clean sample of 1,314 World‐Wide Lightning Location Network locations, which were used to to accurately locate TGF‐producing storms. It also revealed lightning and storm activity for specific regions, as well as seasonal and daily variations of global lightning patterns. Correcting for the orbit of Fermi, we quantitatively find a marginal excess of TGFs being produced from storms over land near oceans (i.e., narrow isthmuses and small islands). No difference was observed between the duration of TGFs over the ocean and land. The distribution of TGFs at a given local solar time for predefined American, Asian, and African regions were confirmed to correlate well with known regional lightning rates.
Key Points
This catalog contains the largest released samples of TGFs and associated radio data
This study shows quantitatively that TGFs preferentially occur over land near coastlines
A Bayesian block algorithm was used to extract the spectral and temporal properties of each TGF
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.
Recent evidence suggests that inhibition of bromodomain and extra-terminal (BET) epigenetic readers may have clinical utility against acute myeloid leukemia (AML). Here we validate this hypothesis, ...demonstrating the efficacy of the BET inhibitor I-BET151 across a variety of AML subtypes driven by disparate mutations. We demonstrate that a common 'core' transcriptional program, which is HOX gene independent, is downregulated in AML and underlies sensitivity to I-BET treatment. This program is enriched for genes that contain 'super-enhancers', recently described regulatory elements postulated to control key oncogenic driver genes. Moreover, our program can independently classify AML patients into distinct cytogenetic and molecular subgroups, suggesting that it contains biomarkers of sensitivity and response. We focus AML with mutations of the Nucleophosmin gene (NPM1) and show evidence to suggest that wild-type NPM1 has an inhibitory influence on BRD4 that is relieved upon NPM1c mutation and cytosplasmic dislocation. This leads to the upregulation of the core transcriptional program facilitating leukemia development. This program is abrogated by I-BET therapy and by nuclear restoration of NPM1. Finally, we demonstrate the efficacy of I-BET151 in a unique murine model and in primary patient samples of NPM1c AML. Taken together, our data support the use of BET inhibitors in clinical trials in AML.
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.
Cosmic rays are particles (mostly protons) accelerated to relativistic speeds. Despite wide agreement that supernova remnants (SNRs) are the sources of galactic cosmic rays, unequivocal evidence for ...the acceleration of protons in these objects is still lacking. When accelerated protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma rays. This offers a compelling way to detect the acceleration sites of protons. The identification of pion-decay gamma rays has been difficult because high-energy electrons also produce gamma rays via bremsstrahlung and inverse Compton scattering. We detected the characteristic pion-decay feature in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope. This detection provides direct evidence that cosmic-ray protons are accelerated in SNRs.
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.
We report the detection of pulsed gamma-ray emission from the fast millisecond pulsars (MSPs) B1937+21 (also known as J1939+2134) and B1957+20 (J1959+2048) using 18 months of survey data recorded by ...the Fermi Large Area Telescope and timing solutions based on radio observations conducted at the Westerbork and Nancay radio telescopes. In addition, we analyzed archival Rossi X-ray Timing Explorer and XMM-Newton X-ray data for the two MSPs, confirming the X-ray emission properties of PSR B1937+21 and finding evidence (~4 Delta *s) for pulsed emission from PSR B1957+20 for the first time. In both cases the gamma-ray emission profile is characterized by two peaks separated by half a rotation and are in close alignment with components observed in radio and X-rays. These two pulsars join PSRs J0034--0534 and J2214+3000 to form an emerging class of gamma-ray MSPs with phase-aligned peaks in different energy bands. The modeling of the radio and gamma-ray emission profiles suggests co-located emission regions in the outer magnetosphere.
The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell ...numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells.
Adipose stromal cells (ASCs) were isolated from human subcutaneous adipose tissue and characterized by flow cytometry. ASCs secreted 1203+/-254 pg of vascular endothelial growth factor (VEGF) per 10(6) cells, 12 280+/-2944 pg of hepatocyte growth factor per 10(6) cells, and 1247+/-346 pg of transforming growth factor-beta per 10(6) cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980+/-1066 pg/10(6) cells (P=0.0016). The secretion of VEGF could also be augmented 200-fold by transfection of ASCs with a plasmid encoding VEGF (P<0.05). Conditioned media obtained from hypoxic ASCs significantly increased endothelial cell growth (P<0.001) and reduced endothelial cell apoptosis (P<0.05). Nude mice with ischemic hindlimbs demonstrated marked perfusion improvement when treated with human ASCs (P<0.05).
Our experiments delineate the angiogenic and antiapoptotic potential of easily accessible subcutaneous adipose stromal cells by demonstrating the secretion of multiple potentially synergistic proangiogenic growth factors. These findings suggest that autologous delivery of either native or transduced subcutaneous ASCs, which are regulated by hypoxia, may be a novel therapeutic option to enhance angiogenesis or achieve cardiovascular protection.
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