CD8 Cells of Patients with Diffuse Cutaneous Leishmaniasis Display Functional Exhaustion: The Latter Is Reversed, In Vitro, by TLR2 Agonists

Leishmania mexicana (Lm) causes localized (LCL) and diffuse (DCL) cutaneous leishmaniasis. DCL patients have a poor cellular immune response leading to chronicity. It has been proposed that CD8 T lymphocytes (CD8) play a crucial role in infection clearance, although the role of CD8 cytotoxicity in disease control has not been elucidated. Lesions of DCL patients have been shown to harbor low numbers of CD8, as compared to patients with LCL, and leishmanicidal treatment restores CD8 numbers. The marked response of CD8 towards Leishmania parasites led us to analyze possible functional differences between CD8 from patients with LCL and DCL. We compared IFNγ production, antigen-specific proliferation, and cytotoxicity of CD8 purified from PBMC against autologous macrophages (MO) infected with Leishmania mexicana (MOi). Additionally, we analyzed tissue biopsies from both groups of patients for evidence of cytotoxicity associated with apoptotic cells in the lesions. We found that CD8 cell of DCL patients exhibited low cytotoxicity, low antigen-specific proliferation and low IFNγ production when stimulated with MOi, as compared to LCL patients. Additionally, DCL patients had significantly less TUNEL+ cells in their lesions. These characteristics are similar to cellular “exhaustion” described in chronic infections. We intended to restore the functional capacity of CD8 cells of DCL patients by preincubating them with TLR2 agonists: Lm lipophosphoglycan (LPG) or Pam3Cys. Cytotoxicity against MOi, antigen-specific proliferation and IFNγ production were restored with both stimuli, whereas PD-1 (a molecule associated with cellular exhaustion) expression, was reduced. Our work suggests that CD8 response is associated with control of Lm infection in LCL patients and that chronic infection in DCL patients leads to a state of CD8 functional exhaustion, which could facilitate disease spread. This is the first report that shows the presence of functionally exhausted CD8 T lymphocytes in DCL patients and, additionally, that pre-stimulation with TLR2 ligands can restore the effector mechanisms of CD8 T lymphocytes from DCL patients against Leishmania mexicana-infected macrophages

Yeasts associated with the production of distilled alcoholic beverages

Distilled alcoholic beverages are produced firstly by fermenting sugars emanating from cereal starches (in the case of whiskies), sucrose-rich plants (in the case of rums), fructooligosaccharide-rich plants (in the case of tequila) or from fruits (in the case of brandies). Traditionally, such fermentations were conducted in a spontaneous fashion, relying on indigenous microbiota, including wild yeasts. In modern practices, selected strains of Saccharomyces cerevisiae are employed to produce high levels of ethanol together with numerous secondary metabolites (eg. higher alcohols, esters, carbonyls etc.) which greatly influence the final flavour and aroma characteristics of spirits following distillation of the fermented wash. Therefore, distillers, like winemakers, must carefully choose their yeast strain which will be very important in providing the alcohol content and the sensory profiles of spirit beverages. This Chapter discusses yeast and fermentation aspects associated with the production of selected distilled spirits and highlights similarities and differences with the production of wine

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

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

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

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

The Mini-EUSO telescope on board the International Space Station: Launch and first results

Mini-EUSO is a telescope launched on board the International Space Station in 2019 and currently located in the Russian section of the station. Main scientific objectives of the mission are the search for nuclearites and Strange Quark Matter, the study of atmospheric phenomena such as Transient Luminous Events, meteors and meteoroids, the observation of sea bioluminescence and of artificial satellites and man-made space debris. It is also capable of observing Extensive Air Showers generated by Ultra-High Energy Cosmic Rays with an energy above 10$^{21}$ eV and detect artificial showers generated with lasers from the ground. Mini-EUSO can map the night-time Earth in the UV range (290 - 430 nm), with a spatial resolution of about 6.3 km and a temporal resolution of 2.5 μs, observing our planet through a nadir-facing UV-transparent window in the Russian Zvezda module. The instrument, launched on 2019/08/22 from the Baikonur cosmodrome is based on an optical system employing two Fresnel lenses and a focal surface composed of 36 Multi-Anode Photomultiplier tubes, 64 channels each, for a total of 2304 channels with single photon counting sensitivity and an overall field of view of 44°. Mini-EUSO also contains two ancillary cameras to complement measurements in the near infrared and visible ranges. In this paper we describe the detector and present the various phenomena observed in the first year of operation

Estimation of the exposure of the TUS space-based cosmic ray observatory

The TUS observatory was the first orbital detector aimed at the detection of ultra-high energy cosmic rays (UHECRs). It was launched on April 28, 2016, from the Vostochny cosmodrome in Russia and operated until December 2017. It collected ∼80,000 events with a time resolution of 0.8~μs. A fundamental parameter to be determined for cosmic ray studies is the exposure of an experiment. This parameter is important to estimate the average expected event rate as a function of energy and to calculate the absolute flux in case of event detection. Here we present results of a study aimed to calculate the exposure that TUS accumulated during its mission. The role of clouds, detector dead time, artificial sources, storms, lightning discharges, airglow and moon phases is studied in detail. An exposure estimate with its geographical distribution is presented. We report on the applied technique and on the perspectives of this study in view of the future missions of the JEM-EUSO program