Acute noradrenergic activation induces insulin resistance in human skeletal muscle

We assessed in normal subjects the effects of an acute increase in forearm norepinephrine (NE) release, evoked by -20 mmHg lower body negative pressure (LBNP), on insulin-mediated muscle glucose uptake. Seven normal subjects underwent the following two insulin euglycemic clamps in random sequence: one during application of LBNP and the other without LBNP (control study). In the control study, hyperinsulinemia (approximately 60 microU/ml) produced a significant increment in forearm NE release, measured by using the forearm perfusion technique combined with infusion of tritiated NE (from 4.91 +/- 1 to 7.94 +/- 1.33 ng.l-1.min-1; P < 0.05). Forearm glucose uptake rose from 0.97 +/- 0.13 to 5.2 +/- 0.2 mg.l-1.min-1 in response to insulin infusion. When the insulin clamp was performed during LBNP, forearm NE release rose to significantly higher values than those of the control study (from 4.33 +/- 0.52 to 12.7 +/- 1.46 ng.l-1.min-1; P < 0.01 vs. control). Under these conditions, the stimulatory effect of insulin on forearm glucose uptake was markedly reduced (from 0.78 +/- 0.10 to 3.2 +/- 0.7 mg.l-1.min-1; P < 0.02 vs. control). Forearm blood flow and plasma epinephrine and free fatty acid concentrations were comparable in the two study sessions. These data demonstrate that an acute activation of endogenous NE release antagonizes insulin-mediated glucose uptake in forearm skeletal muscle, probably accounted for by a direct metabolic effect of NE.We assessed in normal subjects the effects of an acute increase in forearm norepinephrine (NE) release, evoked by -20 mmHg lower body negative pressure (LBNP), on insulin-mediated muscle glucose uptake. Seven normal subjects underwent the following two insulin euglycemic clamps in random sequence: one during application of LBNP and the other without LBNP (control study). In the control study, hyperinsulinemia (≃60 μU/ml) produced a significant increment in forearm NE release, measured by using the forearm perfusion technique combined with infusion of tritiated NE (from 4.91 ± 1 to 7.94 ± 1.33 ng · l -1 · min -1 ; P < 0.05). Forearm glucose uptake rose from 0.97 ± 0.13 to 5.2 ± 0.2 mg · l -1 · min -1 in response to insulin infusion. When the insulin clamp was performed during LBNP, forearm NE release rose to significantly higher values than those of the control study (from 4.33 ± 0.52 to 12.7 ± 1.46 ng · l -1 · min -1 ; P < 0.01 vs. control). Under these conditions, the stimulatory effect of insulin on forearm glucose uptake was markedly reduced (from 0.78 ± 0.10 to 3.2 ± 0.7 mg · l -1 · min -1 ; P < 0.02 vs. control). Forearm blood flow and plasma epinephrine and free fatty acid concentrations were comparable in the two study sessions. These data demonstrate that an acute activation of endogenous NE release antagonizes insulin-mediated glucose uptake in forearm skeletal muscle, probably accounted for by a direct metabolic effect of NE

Investigation of the quasifission process by theoretical analysis of experimental data of fissionlike reaction products

The fusion excitation function is the important quantity in planning experiments for the synthesis of superheavy elements. Its values seem to be determined by the experimental study of the hindrance to complete fusion by the observation of mass, angular and energy distributions of the fissionlike fragments. There is ambiguity in establishment of the reaction mechanism leading to the observed binary fissionlike fragments. The fissionlike fragments can be produced in the quasifission, fast fission, and fusion-fission processes which have overlapping in the mass (angular, kinetic energy) distributions of fragments. The branching ratio between quasifission and complete fusion strongly depends on the characteristics of the entrance channel. In this paper we consider a wide set of reactions (with different mass asymmetry and mass symmetry parameters) with the aim to explain the role played by many quantities on the reaction mechanisms. We also present the results of study of the $^{48}$Ca+$^{249}$Bk reaction used to synthesize superheavy nuclei with Z = 117 by the determination of the evaporation residue cross sections and the effective fission barriers $$ of excited nuclei formed along the de-excitation cascade of the compound nucleus.Comment: 21 pages, 15 figures, 2 table

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer. © 2011 Macmillan Publishers Limited All rights reserved

Simulation studies for the Mini-EUSO detector

Mini-EUSO is a mission of the JEM-EUSO program flying onboard the International Space Station since August 2019. Since the first data acquisition in October 2019, more than 35 sessions have been performed for a total of 52 hours of observations. The detector has been observing Earth at night-time in the UV range and detected a wide variety of transient sources all of which have been modeled through Monte Carlo simulations. Mini-EUSO is also capable of detecting meteors and potentially space debris and we performed simulations for such events to estimate their impact on future missions for cosmic ray science from space. We show here examples of the simulation work done in this framework to analyze the Mini-EUSO data. The expected response of Mini-EUSO with respect to ultra high energy cosmic ray showers has been studied. The efficiency curve of Mini-EUSO as a function of primary energy has been estimated and the energy threshold for Cosmic Rays has been placed to be above 10$^{21}$ eV. We compared the morphology of several transient events detected during the mission with cosmic ray simulations and excluded that they can be due to cosmic ray showers. To validate the energy threshold of the detector, a system of ground based flashers is being used for end-to-end calibration purposes. We therefore implemented a parameterization of such flashers into the JEM-EUSO simulation framework and studied the response of the detector with respect to such sources

Simulation studies for the Mini-EUSO detector

Mini-EUSO is a mission of the JEM-EUSO program flying onboard the International Space Station since August 2019. Since the first data acquisition in October 2019, more than 35 sessions have been performed for a total of 52 hours of observations. The detector has been observing Earth at night-time in the UV range and detected a wide variety of transient sources all of which have been modelled through Monte Carlo simulations. Mini-EUSO is also capable of detecting meteors and potentially space debris and we performed simulations for such events to estimate their impact on future missions for cosmic ray science from space. We show here examples of the simulation work done in this framework to analyse the Mini-EUSO data. The expected response of Mini-EUSO with respect to ultra high energy cosmic ray showers has been studied. The efficiency curve of Mini-EUSO as a function of primary energy has been estimated and the energy threshold for Cosmic Rays has been placed to be above 10$^{21}$ eV. We compared the morphology of several transient events detected during the mission with cosmic ray simulations and excluded that they can be due to cosmic ray showers. To validate the energy threshold of the detector, a system of ground based flashers is being used for end-to-end calibration purposes. We therefore implemented a parameterisation of such flashers into the JEM-EUSO simulation framework and studied the response of the detector with respect to such sources

EUSO-SPB1 mission and science

The Extreme Universe Space Observatory on a Super Pressure Balloon 1 (EUSO-SPB1) was launched in 2017 April from Wanaka, New Zealand. The plan of this mission of opportunity on a NASA super pressure balloon test flight was to circle the southern hemisphere. The primary scientific goal was to make the first observations of ultra-high-energy cosmic-ray extensive air showers (EASs) by looking down on the atmosphere with an ultraviolet (UV) fluorescence telescope from suborbital altitude (33 km). After 12 days and 4 h aloft, the flight was terminated prematurely in the Pacific Ocean. Before the flight, the instrument was tested extensively in the West Desert of Utah, USA, with UV point sources and lasers. The test results indicated that the instrument had sensitivity to EASs of ⪆ 3 EeV. Simulations of the telescope system, telescope on time, and realized flight trajectory predicted an observation of about 1 event assuming clear sky conditions. The effects of high clouds were estimated to reduce this value by approximately a factor of 2. A manual search and a machine-learning-based search did not find any EAS signals in these data. Here we review the EUSO-SPB1 instrument and flight and the EAS search

Measurement of UV light emission of the nighttime Earth by Mini-EUSO for space-based UHECR observations

The JEM-EUSO (Joint Experiment Missions for Extreme Universe Space Observatory) program aims at the realization of the ultra-high energy cosmic ray (UHECR) observation using wide field of view fluorescence detectors in orbit. Ultra-violet (UV) light emission from the atmosphere such as airglow and anthropogenic light on the Earth\u27s surface are the main background for the space-based UHECR observations. The Mini-EUSO mission has been operated on the International Space Station (ISS) since 2019 which is the first space-based experiment for the program. The Mini-EUSO instrument consists of a 25 cm refractive optics and the photo-detector module with the 2304-pixel array of the multi-anode photomultiplier tubes. On the nadir-looking window of the ISS, the instrument is capable of continuously monitoring a ~300 km x 300 km area. In the present work, we report the preliminary result of the measurement of the UV light in the nighttime Earth using the Mini-EUSO data downlinked to the ground. We mapped UV light distribution both locally and globally below the ISS obit. Simulations were also made to characterize the instrument response to diffuse background light. We discuss the impact of such light on space-based UHECR observations and the Mini-EUSO science objectives

Neutrino Target-of-Opportunity Observations with Space-based and Suborbital Optical Cherenkov Detectors

Cosmic-ray accelerators capable of reaching ultra-high energies are expected to also produce very-high energy neutrinos via hadronic interactions within the source or its surrounding environment. Many of the candidate astrophysical source classes are either transient in nature or exhibit flaring activity. Using the Earth as a neutrino converter, suborbital and space-based optical Cherenkov detectors, such as EUSO-SPB2 and POEMMA, will be able to detect upward-moving extensive air showers induced by decay tau-leptons generated from cosmic tau neutrinos with energies ∼10 PeV and above. Both EUSO-SPB2 and POEMMA will be able to quickly repoint, enabling rapid response to astrophysical transient events. we calculate the transient sensitivity and sky coverage for both EUSO-SPB2 and POEMMA, accounting for constraints imposed by the Sun and the Moon on the observation time. We also calculate both detectors\u27 neutrino horizons for a variety of modeled astrophysical neutrino fluences. We find that both EUSO-SPB2 and POEMMA will achieve transient sensitivities at the level of modeled neutrino fluences for nearby sources. We conclude with a discussion of the prospects of each mission detecting at least one transient event for various modeled astrophysical neutrino sources

Neutrino Target-of-Opportunity Observations with Space-based and Suborbital Optical Cherenkov Detectors

Cosmic-ray accelerators capable of reaching ultra-high energies are expected to also produce very-high energy neutrinos via hadronic interactions within the source or its surrounding environment. Many of the candidate astrophysical source classes are either transient in nature or exhibit flaring activity. Using the Earth as a neutrino converter, suborbital and space-based optical Cherenkov detectors, such as POEMMA and EUSO-SPB2, will be able to detect upward-moving extensive air showers induced by decaying tau-leptons generated from cosmic tau neutrinos with energies ∼10 PeV and above. Both EUSO-SPB2 and POEMMA will be able to quickly repoint, enabling rapid response to astrophysical transient events. We calculate the transient sensitivity and sky coverage for both EUSO-SPB2 and POEMMA, accounting for constraints imposed by the Sun and the Moon on the observation time. We also calculate both detectors\u27 neutrino horizons for a variety of modeled astrophysical neutrino fluences. We find that both EUSO-SPB2 and POEMMA will achieve transient sensitivities at the level of modeled neutrino fluences for nearby sources. We conclude with a discussion of the prospects of each mission detecting at least one transient event for various modeled astrophysical neutrino sources