On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40 − 8 + 8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 M ⊙ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 Mpc ) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.

Tolerance to self-antigens prevents the elimination of cancer by the immune system1,2. We used synthetic chimeric antigen receptors (CARs) to overcome immunological tolerance and mediate tumor rejection in patients with chronic lymphocytic leukemia (CLL). Remission was induced in a subset of subjects, but most did not respond. Comprehensive assessment of patient-derived CAR T cells to identify mechanisms of therapeutic success and failure has not been explored. We performed genomic, phenotypic and functional evaluations to identify determinants of response. Transcriptomic profiling revealed that CAR T cells from complete-responding patients with CLL were enriched in memory-related genes, including IL-6/STAT3 signatures, whereas T cells from nonresponders upregulated programs involved in effector differentiation, glycolysis, exhaustion and apoptosis. Sustained remission was associated with an elevated frequency of CD27+CD45RO- CD8+ T cells before CAR T cell generation, and these lymphocytes possessed memory-like characteristics. Highly functional CAR T cells from patients produced STAT3-related cytokines, and serum IL-6 correlated with CAR T cell expansion. IL-6/STAT3 blockade diminished CAR T cell proliferation. Furthermore, a mechanistically relevant population of CD27+PD-1CD8+ CAR T cells expressing high levels of the IL-6 receptor predicts therapeutic response and is responsible for tumor control. These findings uncover new features of CAR T cell biology and underscore the potential of using pretreatment biomarkers of response to advance immunotherapies.

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 4σ 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.

Previous detections of individual astrophysical sources of neutrinos are limited to the Sun and the supernova 1987A, whereas the origins of the diffuse flux of high-energy cosmic neutrinos remain unidentified. On 22 September 2017, we detected a high-energy neutrino, IceCube-170922A, with an energy of ~290 tera-electron volts. Its arrival direction was consistent with the location of a known γ-ray blazar, TXS 0506+056, observed to be in a flaring state. An extensive multiwavelength campaign followed, ranging from radio frequencies to γ-rays. These observations characterize the variability and energetics of the blazar and include the detection of TXS 0506+056 in very-high-energy γ-rays. This observation of a neutrino in spatial coincidence with a γ-ray-emitting blazar during an active phase suggests that blazars may be a source of high-energy neutrinos.

We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19- leukemia that aberrantly expressed the anti-CD19 CAR. The CAR gene was unintentionally introduced into a single leukemic B cell during T cell manufacturing, and its product bound in cis to the CD19 epitope on the surface of leukemic cells, masking it from recognition by and conferring resistance to CTL019.

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In this paper, we have selected a sample of 64 teraelectronvolt blazars, with redshift, from those classified in the fourth Fermi Large Area Telescope source catalog a) . We have obtained the values of the relevant physical parameters by performing a log-parabolic fitting of the average-state multiwavelength spectral energy distributions. We estimate the range of the radiation zone parameters, such as the Doppler factor (D), the magnetic field strength (B), the radiative zone radius (R) and the peak Lorentz factor (γ p ) of nonthermal electrons. Here, we show that (1) there is a strong linear positive correlation between the intrinsic synchrotron peak frequency and the intrinsic inverse Compton scattering (ICs) peak frequency among different types of blazars; (2) if radio bands are excluded, the spectral index of each band is negatively correlated with the intrinsic peak frequency; (3) there is a strong linear negative correlation between the curvature at the peak and the intrinsic peak frequency of the synchrotron bump, and a weak positive correlation between the curvature at the peak and the intrinsic peak frequency of the ICs bump; (4) there is a strong linear positive correlation between the intrinsic ICs peak luminosity and intrinsic γ-ray luminosity and between the intrinsic ICs peak frequency and peak Lorentz factor;(5) there is a strong negative linear correlation between log B and log γ p ; and (6) there is no correlation between log R and log γ p .

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.