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We report the detection by the Astrorivelatore Gamma a Immagini Leggero (AGILE) satellite of terrestrial gamma ray flashes (TGFs) obtained with the minicalorimeter (MCAL) detector operating in the energy range 0.3–100 MeV. We select events typically lasting a few milliseconds with spectral and directional selections consistent with the TGF characteristics previously reported by other space missions. During the period 1 June 2008 to 31 March 2009 we detect 34 high‐confidence events showing millisecond durations and a geographical distribution peaked over continental Africa and Southeast Asia. For the first time, AGILE‐MCAL detects photons associated with TGF events up to 40 MeV. We determine the cumulative spectral properties of the spectrum in the range 0.5–40 MeV, which can be effectively described by a Bremsstrahlung spectrum. We find that both the TGF cumulative spectral properties and their geographical distribution are in good agreement with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) results.

Fast radio bursts (FRBs) are millisecond radio pulses originating from powerful enigmatic sources at extragalactic distances. Neutron stars with large magnetic fields (magnetars) have been considered as the sources powering the FRBs, but the connection requires further substantiation. Here we report the detection by the AGILE satellite on 28 April 2020 of an X-ray burst in temporal coincidence with a bright FRB-like radio burst from the Galactic magnetar SGR 1935+2154. The burst observed in the hard X-ray band (18–60 keV) lasted about 0.5 s, it is spectrally cut off above 80 keV and implies an isotropically emitted energy of about 10 40  erg. This event demonstrates that a magnetar can produce X-ray bursts in coincidence with FRB-like radio bursts. It also suggests that FRBs associated with magnetars can emit X-ray bursts. We discuss SGR 1935+2154 in the context of FRBs with low–intermediate radio energies in the range 10 38 –10 40  erg. Magnetars with magnetic fields B  ≈ 10 15  G may power these FRBs, and new data on the search for X-ray emission from FRBs are presented. We constrain the bursting X-ray energy of the nearby FRB 180916 to be less than 10 46  erg, smaller than that observed in giant flares from Galactic magnetars. In April 2020, the AGILE satellite registered an X-ray burst temporally coincident with a radio burst from the Galactic magnetar SGR 1935+2154. As seen in hard X-rays, the burst was cut off above 80 keV and had an isotropically emitted energy of about 10 40  erg.

The well-known Crab Nebula is at the center of the SN1054 supernova remnant. It consists of a rotationally powered pulsar interacting with a surrounding nebula through a relativistic particle wind. The emissions originating from the pulsar and nebula have been considered to be essentially stable. Here, we report the detection of strong gamma-ray (100 mega-electron volts to 10 giga-electron volts) flares observed by the AGILE satellite in September 2010 and October 2007. In both cases, the total gamma-ray flux increased by a factor of three compared with the non-flaring flux. The flare luminosity and short time scale favor an origin near the pulsar, and we discuss Chandra Observatory x-ray and Hubble Space Telescope optical follow-up observations of the nebula. Our observations challenge standard models of nebular emission and require power-law acceleration by shock-driven plasma wave turbulence within an approximately 1-day time scale.

Cygnus X-3: a microquasar shows flare Galactic microquasars are binaries with a neutron star or stellar-mass black hole accreting gas from a companion star. They can accelerate particles to relativistic energies and emit radio flares, but the mechanism of jet energization is not known. A survey of the Cygnus region between mid-2007 and mid-2009 has detected four major γ-ray flaring episodes with energies over 100 MeV, each lasting 1 or 2 days, emanating from the microquasar Cygnus X-3. There is a clear pattern of temporal correlation between the γ-ray flares and transitional spectral states of radio and X-ray emission. Particle acceleration occurred a few days before radio jet ejections for two of the flares, suggesting that jet formation involves the production of highly energetic particles. Super-massive black holes in active galaxies can accelerate particles to relativistic energies, producing jets with associated γ-ray emission. Galactic 'microquasars' also produce relativistic jets; however, apart from an isolated event detected in Cygnus X-1, there has hitherto been no systematic evidence for the acceleration of particles to gigaelectronvolt or higher energies in a microquasar. Here, a report of four γ-ray flares with energies above 100 MeV from the microquasar Cygnus X-3 illuminates this important problem. Super-massive black holes in active galaxies can accelerate particles to relativistic energies 1 , producing jets with associated γ-ray emission. Galactic ‘microquasars’, which are binary systems consisting of a neutron star or stellar-mass black hole accreting gas from a companion star, also produce relativistic jets, generally together with radio flares 2 . Apart from an isolated event detected 3 in Cygnus X-1, there has hitherto been no systematic evidence for the acceleration of particles to gigaelectronvolt or higher energies in a microquasar, with the consequence that we are as yet unsure about the mechanism of jet energization. Here we report four γ-ray flares with energies above 100 MeV from the microquasar Cygnus X-3 (an exceptional X-ray binary 4 , 5 , 6 that sporadically produces radio jets 7 , 8 , 9 ). There is a clear pattern of temporal correlations between the γ-ray flares and transitional spectral states of the radio-frequency and X-ray emission. Particle acceleration occurred a few days before radio-jet ejections for two of the four flares, meaning that the process of jet formation implies the production of very energetic particles. In Cygnus X-3, particle energies during the flares can be thousands of times higher than during quiescent states.

We present the final results of the search for stellar gravitational collapses obtained by the MACRO experiment. The detector was active for a stellar collapse search for more than 11 years and it was sensitive to collapses occurring all over in our galaxy for 8.6 years. A real time system for a prompt recognition of neutrino bursts was developed and was operating on-line for almost the whole life of the experiment. No signal compatible with a neutrino burst from a galactic supernova was observed.

The AGILE satellite detects Terrestrial Gamma‐ray Flashes (TGFs) in the 0.35–100 MeV energy range using its Mini‐Calorimeter (MCAL) instrument with an average detection rate of 10 TGFs/month. Thanks to its Low Earth Orbit with only 2.5 degree of inclination, AGILE guarantees an unprecedented exposure above the equator, where both lightning activity and TGF detection peak. Here we report the comparison between the AGILE TGFs detected between March 2009 and February 2010 and full climatology lightning worldwide distribution based on satellite optical observations from LIS (Lightning Imaging Sensor) and OTD (Optical Transient Detector) instruments. This approach is complementary to the one‐to‐one TGF/lightning correlations by ground‐based sferics measurements. Based on mono and bi‐dimensional Kolmogorov‐Smirnov tests, we show that the AGILE TGFs and time‐averaged global lightning in the equatorial area are not drawn from the same distribution. However, we find significant regional differences in the degree of correlation as well as in the TGF/lightning ratio. In the case of south east Asia we find a 87% probability for the TGF and lightning being samples of the same distribution. This result supports the idea that the physical conditions at play in TGF generation can have strong geographical and climatological modulation. Based on the assumption that the observed range of TGF/flash ratio holds at all latitudes we can estimate a global rate of ≃ 220 ÷ 570 TGFs per day. The observed TGF/flash geographical modulation as well as the TGF global rate estimate are in agreement with previous observations. Key Points TGFs are spatially consistent with the global lightning distribution The TGF/flash ratio is 8 × 10−5 leading to a global rate of 300 TGFs/day

Pulsars are known to power winds of relativistic particles that can produce bright nebulae by interacting with the surrounding medium. These pulsar wind nebulae are observed by their radio, optical, and x-ray emissions, and in some cases also at TeV (teraelectron volt) energies, but the lack of information in the gamma-ray band precludes drawing a comprehensive multiwavelength picture of their phenomenology and emission mechanisms. Using data from the AGILE satellite, we detected the Vela pulsar wind nebula in the energy range from 100 MeV to 3 GeV. This result constrains the particle population responsible for the GeV emission and establishes a class of gamma-ray emitters that could account for a fraction of the unidentified galactic gamma-ray sources.

The final analysis of atmospheric neutrino events collected with the MACRO detector is presented. Three different classes of events, generated by neutrinos in different energy ranges, are studied looking at rates, angular distributions and estimated energies. The results are consistent for all the subsamples and indicate a flux deficit that depends on energy and path-length of neutrinos. The no-oscillation hypothesis is excluded at \\(\\sim 5\\sigma\\), while the hypothesis of \\(\\nu_\\mu \\to \\nu_\\tau\\) oscillation gives a satisfactory description of all data. The parameters with highest probability in a two flavor scenario are \\(\\sin^2 2\\theta_m = 1\\) and \\(\\Delta m^2 = 0.0023 \\textrm{eV}^2\\). This result is independent of the absolute normalization of the atmospheric neutrino fluxes. The data can also be used to put experimental constrain on this normalization.

We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range \\(4\\times 10^{-5}< \\beta < 1\\). Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of \\(1.4\\times 10^{-16}\\) cm-2 s-1 sr-1. This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole \\(\\beta\\) range in which GUT magnetic monopoles are expected.

Adenovirus-mediated p53 gene therapy for cancer is currently undergoing phase I/II clinical trials. The drug used in our clinical trials (p53 Ad; ACN53; SCH58500) consists of a replication-deficient, type 5 adenovirus vector expressing human wildtype p53 tumor suppressor under the control of the cytomegalovirus promoter. In preclinical models, p53 Ad has therapeutic efficacy against a wide range of human tumor types containing nonfunctional p53, both in vitro and in vivo. Results from early clinical trials using p53 gene therapy by itself support optimism for the future of this therapeutic approach. However, it is likely that many phase II/III trials will incorporate an arm comparing traditional chemotherapy against chemotherapy combined with p53 gene therapy. Therefore, it is important to study possible interactions between p53 Ad and chemotherapeutic drugs in preclinical models before starting the clinical trials. Proliferation of tumor cells was quantitated after incubation with various combinations of p53 Ad and chemotherapeutic drugs. Human tumor xenografts in scid mice were dosed with intraperitoneal or intratumoral p53 Ad with or without chemotherapeutic drugs and the tumor burden after therapy monitored. p53 Ad combined with cisplatin, doxorubicin, 5-fluorouracil, methotrexate, or etoposide inhibited cell proliferation more effectively than chemotherapy alone in SCC-9 head and neck, SCC-15 head and neck, SCC-25 head and neck, SK-OV-3 ovarian, DU-145 prostate, MDA-MB-468 breast, and MDA-MB-231 breast tumor cells. No obvious dependence on dosing schedule was observed. Greater anticancer efficacy was also demonstrated in four human tumor xenograft models in vivo. Of particular significance, there was enhanced efficacy using the three drug combination of p53 Ad, cisplatin, and paclitaxel in an ovarian cancer model. These results support the combination of p53 gene therapy with chemotherapy in clinical trials.