The Spanish Infrared Camera onboard the EUSO-BALLOON (CNES) flight on August 24, 2014

The EUSO-Balloon (CNES) campaign was held during Summer 2014 with a launch on August 24. In the gondola, next to the Photo Detector Module (PDM), a completely isolated Infrared camera was allocated. Also, a helicopter which shooted flashers flew below the balloon. We have retrieved the Cloud Top Height (CTH) with the IR camera, and also the optical depth of the nonclear atmosphere have been inferred with two approaches: The first one is with the comparison of the brightness temperature of the cloud and the real temperature obtained after the pertinent corrections. The second one is by measuring the detected signal from the helicopter flashers by the IR Camera, considering the energy of the flashers and the location of the helicopter

The atmospheric science of JEM-EUSO

An Atmospheric Monitoring System (AMS) is critical suite of instruments for JEM-EUSO whose aim is to detect Ultra-High Energy Cosmic Rays (UHECR) and (EHECR) from Space. The AMS comprises an advanced space qualified infrared camera and a LIDAR with cross checks provided by a ground-based and airborne Global Light System Stations. Moreover the Slow Data Mode of JEM-EUSO has been proven crucial for the UV background analysis by comparing the UV and IR images. It will also contribute to the investigation of atmospheric effects seen in the data from the GLS or even to our understanding of Space Weather

Blocking Connexin-43 mediated hemichannel activity protects against early tubular injury in experimental chronic kidney disease

Background: Tubulointerstitial fibrosis represents the key underlying pathology of Chronic Kidney Disease (CKD), yet treatment options remain limited. In this study, we investigated the role of connexin43 (Cx43) hemichannel-mediated adenosine triphosphate (ATP) release in purinergic-mediated disassembly of adherens and tight junction complexes in early tubular injury. Methods: Human primary proximal tubule epithelial cells (hPTECs) and clonal tubular epithelial cells (HK2) were treated with Transforming Growth Factor Beta1 (TGFβ1) ± apyrase, or ATPγS for 48h. For inhibitor studies, cells were co-incubated with Cx43 mimetic Peptide 5, or purinergic receptor antagonists Suramin, A438079 or A804598. Immunoblotting, single-cell force spectroscopy and trans-epithelial electrical resistance assessed protein expression, cell-cell adhesion and paracellular permeability. Carboxyfluorescein uptake and biosensing measured hemichannel activity and real-time ATP release, whilst a heterozygous Cx43+/- mouse model with unilateral ureteral obstruction (UUO) assessed the role of Cx43 in vivo. Results: Immunohistochemistry of biopsy material from patients with diabetic nephropathy confirmed increased expression of purinergic receptor P2X7. TGFβ1 increased Cx43 mediated hemichannel activity and ATP release in hPTECs and HK2 cells. The cytokine reduced maximum unbinding forces and reduced cell-cell adhesion, which translated to increased paracellular permeability. Changes were reversed when cells were co-incubated with either Peptide 5 or P2-purinoceptor inhibitors. Cx43+/- mice did not exhibit protein changes associated with early tubular injury in a UUO model of fibrosis. Conclusion: Data suggest that Cx43 mediated ATP release represents an initial trigger in early tubular injury via its actions on the adherens and tight junction complex. Since Cx43 is highly expressed in nephropathy, it represents a novel target for intervention of tubulointerstitial fibrosis in CKD

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study

2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naı¨ve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P¼0.004). There was no interaction between AR and docetaxel status (P¼0.83 for OS, P¼0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; PA (p.L702H) and 520 3

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

Background There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC.Methods We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial).Results In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts.Conclusion Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required.Clinical trial number NCT02288936 (PREMIERE trial)

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

EUSO-SPB2 Telescope Optics and Testing

The Extreme Universe Space Observatory - Super Pressure Balloon (EUSO-SPB2) mission will fly two custom telescopes that feature Schmidt optics to measure Cherenkov- and fluorescence emission of extensive air showers from cosmic rays at the PeV and EeV-scale, and search for τ-neutrinos. Both telescopes have 1-meter diameter apertures and UV/UV-visible sensitivity. The Cherenkov telescope uses a bifocal mirror segment alignment, to distinguish between a direct cosmic ray that hits the camera versus the Cherenkov light from outside the telescope. Telescope integration and laboratory calibration will be performed in Colorado. To estimate the point spread function and efficiency of the integrated telescopes, a test beam system that delivers a 1-meter diameter parallel beam of light is being fabricated. End-to-end tests of the fully integrated instruments will be carried out in a field campaign at dark sites in the Utah desert using cosmic rays, stars, and artificial light sources. Laser tracks have long been used to characterize the performance of fluorescence detectors in the field. For EUSO-SPB2 an improvement in the method that includes a correction for aerosol attenuation is anticipated by using a bi-dynamic Lidar configuration in which both the laser and the telescope are steerable. We plan to conduct these field tests in Fall 2021 and Spring 2022 to accommodate the scheduled launch of EUSO-SPB2 in 2023 from Wanaka, New Zealand

Expected Performance of the EUSO-SPB2 Fluorescence Telescope

The Extreme Universe Space Observatory Super Pressure Balloon 2 (EUSO-SPB2) is under development, and will prototype instrumentation for future satellite-based missions, including the Probe of Extreme Multi-Messenger Astrophysics (POEMMA). EUSO-SPB2 will consist of two telescopes. The first is a Cherenkov telescope (CT) being developed to identify and estimate the background sources for future below-the-limb very high energy (E>10 PeV) astrophysical neutrino observations, as well as above-the-limb cosmic ray induced signals (E>1 PeV). The second is a fluorescence telescope (FT) being developed for detection of Ultra High Energy Cosmic Rays (UHECRs). In preparation for the expected launch in 2023, extensive simulations tuned by preliminary laboratory measurements have been performed to understand the FT capabilities. The energy threshold has been estimated at 10$^{18.2}$ eV, and results in a maximum detection rate at 10$^{18.6}$ eV when taking into account the shape of the UHECR spectrum. In addition, onboard software has been developed based on the simulations as well as experience with previous EUSO missions. This includes a level 1 trigger to be run on the computationally limited flight hardware, as well as a deep learning based prioritization algorithm in order to accommodate the balloon’s telemetry budget. These techniques could also be used later for future, space-based missions

Observation of ELVES with Mini-EUSO telescope on board the International Space Station

Mini-EUSO is a detector observing the Earth in the ultraviolet band from the International Space Station through a nadir-facing window, transparent to the UV radiation, in the Russian Zvezda module. Mini-EUSO main detector consists in an optical system with two Fresnel lenses and a focal surface composed of an array of 36 Hamamatsu Multi-Anode Photo-Multiplier tubes, for a total of 2304 pixels, with single photon counting sensitivity. The telescope also contains two ancillary cameras, in the near infrared and visible ranges, to complement measurements in these bandwidths. The instrument has a field of view of 44 degrees, a spatial resolution of about 6.3 km on the Earth surface and of about 4.7 km on the ionosphere. The telescope detects UV emissions of cosmic, atmospheric and terrestrial origin on different time scales, from a few s upwards. On the fastest timescale of 2.5 s, Mini EUSO is able to observe atmospheric phenomena as Transient Luminous Events and in particular the ELVES, which take place when an electromagnetic wave generated by intra-cloud lightning interacts with the ionosphere, ionizing it and producing apparently superluminal expanding rings of several 100 km and lasting about 100 s. These highly energetic fast events have been observed to be produced in conjunction also with Terrestrial Gamma-Ray Flashes and therefore a detailed study of their characteristics (speed, radius, energy ...) is of crucial importance for the understanding of these phenomena. In this paper we present the observational capabilities of ELVE detection by Mini-EUSO and specifically the reconstruction and study of ELVE characteristics

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