IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis

Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17ra(ΔK13)). Following oral Candida infection, Il17ra(ΔK13) mice exhibited fungal loads and weight loss indistinguishable from Il17ra(−/−) mice. Susceptibility in Il17ra(ΔK13) mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3(−/−) mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3expression

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Leopard syndrome

LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4–5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS), chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should address growth and motor development and congenital anomalies, in particular cardiac defects that should be monitored annually. Hypertrophic cardiomyopathy needs careful risk assessment and prophylaxis against sudden death in patients at risk. Hearing should be evaluated annually until adulthood. With the only exception of ventricular hypertrophy, adults with LS do not require special medical care and long-term prognosis is favourable

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

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