The fourth catalog of active galactic nuclei (AGNs) detected by the Fermi Gamma-ray Space Telescope Large Area Telescope (4LAC) between 2008 August 4 and 2016 August 2 contains objects located at ...high Galactic latitudes ( ). It includes 85% more sources than the previous 3LAC catalog based on 4 yr of data. AGNs represent at least 79% of the high-latitude sources in the fourth Fermi-Large Area Telescope Source Catalog (4FGL), which covers the energy range from 50 MeV to 1 TeV. In addition, gamma-ray AGNs are found at low Galactic latitudes. Most of the 4LAC AGNs are blazars (98%), while the remainder are other types of AGNs. The blazar population consists of 24% Flat Spectrum Radio Quasars (FSRQs), 38% BL Lac-type objects, and 38% blazar candidates of unknown types (BCUs). On average, FSRQs display softer spectra and stronger variability in the gamma-ray band than BL Lacs do, confirming previous findings. All AGNs detected by ground-based atmospheric Cerenkov telescopes are also found in the 4LAC.
The majority of patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN) harbor mutations in JAK2 or MPL, which lead to constitutive activation of the JAK/STAT, PI3K and ERK signaling ...pathways. JAK inhibitors by themselves are inadequate in producing selective clonal suppression in MPN and are associated with hematopoietic toxicities. MK-2206 is a potent allosteric AKT inhibitor that was well tolerated, including no evidence of myelosuppression, in a phase I study of solid tumors. Herein, we show that inhibition of PI3K/AKT signaling by MK-2206 affected the growth of both JAK2V617F- or MPLW515L-expressing cells via reduced phosphorylation of AKT and inhibition of its downstream signaling molecules. Moreover, we demonstrate that MK-2206 synergizes with ruxolitinib in suppressing the growth of JAK2V617F-mutant SET2 cells. Importantly, MK-2206 suppressed colony formation from hematopoietic progenitor cells in patients with primary myelofibrosis and alleviated hepatosplenomegaly and reduced megakaryocyte burden in the bone marrows, livers and spleens of mice with MPLW515L-induced MPN. Together, these findings establish AKT as a rational therapeutic target in the MPNs.
The first statistically significant detection of the cosmic gamma -ray horizon (CGRH) that is independent of any extragalactic background light (EBL) model is presented. The CGRH is a fundamental ...quantity in cosmology. It gives an estimate of the opacity of the universe to very high energy (VHE) gamma -ray photons due to photon-photon pair production with the EBL. The only estimations of the CGRH to date are predictions from EBL models and lower limits from gamma -ray observations of cosmological blazars and gamma -ray bursts. Here, we present homogeneous synchrotron/synchrotron self-Compton (SSC) models of the spectral energy distributions of 15 blazars based on (almost) simultaneous observations from radio up to the highest energy gamma -rays taken with the Fermi satellite. These synchrotron/SSC models predict the unattenuated VHE fluxes, which are compared with the observations by imaging atmospheric Cherenkov telescopes. This comparison provides an estimate of the optical depth of the EBL, which allows us a derivation of the CGRH through a maximum likelihood analysis that is EBL-model independent. We find that the observed CGRH is compatible with the current knowledge of the EBL.
A literature review of modern transition-metal nanoclusters, with an emphasis on those nanoclusters which are catalytically active, is presented in two parts. Part One presents background information ...on transition-metal nanoclusters, including an overview of common synthetic routes, a description of how nanoclusters are stabilized, and a brief summary of the multiple characterization techniques used (and the type of information that they can provide). In Part Two, five specific nanocluster case studies are presented, case studies which compare and contrast the syntheses, characterization approaches, and catalytic applications of transition-metal nanoclusters.
Aims. In this paper, we characterize the first γ-ray flaring episode of the flat-spectrum radio quasar PKS 0346−27 (z = 0.991), as revealed by Fermi-LAT monitoring data, and the concurrent ...multi-wavelength variability observed from radio through X-rays. Methods. We studied the long- and short-term flux and spectral variability from PKS 0346−27 by producing γ-ray light curves with different time binning. We complement the Fermi-LAT data with multi-wavelength observations from the Atacama Large Millimeter Array (radio mm-band), the Rapid Eye Mount telescope (near-infrared) and Swift (optical-UV and X-rays). This quasi-simultaneous multi-wavelength coverage allowed us to construct time-resolved spectral energy distributions (SEDs) of PKS 0346−27 and compare the broadband spectral properties of the source between different activity states using a one-zone leptonic emission model. Results. PKS 0346−27 entered an elevated γ-ray activity state starting from the beginning of 2018. The high-state continued throughout the year, displaying the highest fluxes in May 2018. We find evidence of short-time scale variability down to approximately 1.5 h, which constrains the γ-ray emission region to be compact. The extended flaring period was characterized by a persistently harder spectrum with respect to the quiescent state, indicating changes in the broadband spectral properties of the source. This was confirmed by the multi-wavelength observations, which show a shift in the position of the two SED peaks by approximately two orders of magnitude in energy and peak flux value. As a result, the non-thermal jet emission completely outshines the thermal contribution from the dust torus and accretion disk during the high state. The broadband SED of PKS 0346−27 transitions from a typical Low-Synchrotron-Peaked (LSP) to the Intermediate-Synchrotron-Peaked (ISP) class, a behavior previously observed in other flaring γ-ray sources. Our one-zone leptonic emission model of the high-state SEDs constrains the γ-ray emission region to have a lower magnetic field, larger radius, and higher maximum electron Lorentz factors with respect to the quiescent SED. Finally, we note that the bright and hard γ-ray spectrum observed during the peak of flaring activity in May 2018 implies that PKS 0346−27 could be a promising target for future ground-based Cherenkov observatories such as the Cherenkov Telescope Array (CTA). The CTA could detect such a flare in the low-energy tail of its energy range during a high state such as the one observed in May 2018.
We present detailed observations of the bright short-hard gamma-ray burst GRB 090510 made with the Gammaray Burst Monitor (GBM) and Large Area Telescope (LAT) on board the Fermi observatory. GRB ...090510 is the first burst detected by the LAT that shows strong evidence for a deviation from a Band spectral fitting function during the prompt emission phase. The time-integrated spectrum is fit by the sum of a Band function with E-peak = 3.9 +/- 0.3 MeV, which is the highest yet measured, and a hard power-law component with photon index -1.62 +/- 0.03 that dominates the emission below approximate to 20 keV and above approximate to 100 MeV. The onset of the high-energy spectral component appears to be delayed by similar to 0.1 s with respect to the onset of a component well fit with a single Band function. A faint GBM pulse and a LAT photon are detected 0.5 s before the main pulse. During the prompt phase, the LAT detected a photon with energy 30.5(-2.6)(+5.8) GeV, the highest ever measured from a short GRB. Observation of this photon sets a minimum bulk outflow Lorentz factor, Gamma greater than or similar to 1200, using simple.. opacity arguments for this GRB at redshift z = 0.903 and a variability timescale on the order of tens of ms for the approximate to 100 keV-few MeV flux. Stricter high confidence estimates imply Gamma greater than or similar to 1000 and still require that the outflows powering short GRBs are at least as highly relativistic as those of long-duration GRBs. Implications of the temporal behavior and power-law shape of the additional component on synchrotron/synchrotron self-Compton, external-shock synchrotron, and hadronic models are considered.
The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In ...all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations.
Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation ...(allo-HSCT) is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited. We obtained data about 87 adult (≥18 years of age) patients retrospectively reported to the EBMT. The median survival time was 13.9 months. The three and five-year overall survival (OS) was 44% (95% CI 33-54%). Among 39 patients with a follow-up longer than 15 months, only three died. Relapse rate was 21% (95% CI 13-30%), while NRM reached 36% (95% CI 25-46%). Younger patients (<30 years of age) had better prognosis, with an OS of 59% (95% CI 45-73%) at three and five years vs 23% (95% CI 8-37%) for older ones. No difference in survival between reduced and myeloablative conditioning was found. To our knowledge, this is the largest report of adult HLH patients who underwent allo-HSCT. Patients who survive the first period after this procedure can expect a long disease-free survival. Both reduced intensity and myeloablative conditioning have therapeutic potential in adult HLH.
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