Cathepsin C role in inflammatory gastroenterological, renal, rheumatic, and pulmonary disorders

Cathepsin C (CatC, syn. Dipeptidyl peptidase I) is a lysosomal cysteine proteinase expressed in several tissues including inflammatory cells. This enzyme is important for maintaining multiple cellular functions and for processing immune cell-derived proteases. While mutations in the CatC gene were reported in Papillon-Lefèvre syndrome, a rare autosomal recessive disorder featuring hyperkeratosis and periodontitis, evidence from clinical and preclinical studies points toward pro-inflammatory effects of CatC in various disease processes that are mainly mediated by the activation of neutrophil serine proteinases. Moreover, tumor-promoting effects were ascribed to CatC. The aim of this review is to highlight current knowledge of the CatC as a potential therapeutic target in inflammatory disorders

The next generation neutrino telescope: IceCube-Gen2

The IceCube Neutrino Observatory, a cubic-kilometer-scale neutrino detector at the geographic South Pole, has reached a number of milestones in the field of neutrino astrophysics: the discovery of a high-energy astrophysical neutrino flux, the temporal and directional correlation of neutrinos with a flaring blazar, and a steady emission of neutrinos from the direction of an active galaxy of a Seyfert II type and the Milky Way. The next generation neutrino telescope, IceCube-Gen2, currently under development, will consist of three essential components: an array of about 10,000 optical sensors, embedded within approximately 8 cubic kilometers of ice, for detecting neutrinos with energies of TeV and above, with a sensitivity five times greater than that of IceCube; a surface array with scintillation panels and radio antennas targeting air showers; and buried radio antennas distributed over an area of more than 400 square kilometers to significantly enhance the sensitivity of detecting neutrino sources beyond EeV. This contribution describes the design and status of IceCube-Gen2 and discusses the expected sensitivity from the simulations of the optical, surface, and radio components

Sensitivity of IceCube-Gen2 to measure flavor composition of Astrophysical neutrinos

The observation of an astrophysical neutrino flux in IceCube and its detection capability to separate between the different neutrino flavors has led IceCube to constraint the flavor content of this flux. IceCube-Gen2 is the planned extension of the current IceCube detector, which will be about 8 times larger than the current instrumented volume. In this work, we study the sensitivity of IceCube-Gen2 to the astrophysical neutrino flavor composition and investigate its tau neutrino identification capabilities. We apply the IceCube analysis on a simulated IceCube-Gen2 dataset that mimics the High Energy Starting Event (HESE) classification. Reconstructions are performed using sensors that have 3 times higher quantum efficiency and isotropic angular acceptance compared to the current IceCube optical modules. We present the projected sensitivity for 10 years of data on constraining the flavor ratio of the astrophysical neutrino flux at Earth by IceCube-Gen2

Mechanical design of the optical modules intended for IceCube-Gen2

IceCube-Gen2 is an expansion of the IceCube neutrino observatory at the South Pole that aims to increase the sensitivity to high-energy neutrinos by an order of magnitude. To this end, about 10,000 new optical modules will be installed, instrumenting a fiducial volume of about 8 km3. Two newly developed optical module types increase IceCube’s current sensitivity per module by a factor of three by integrating 16 and 18 newly developed four-inch PMTs in specially designed 12.5-inch diameter pressure vessels. Both designs use conical silicone gel pads to optically couple the PMTs to the pressure vessel to increase photon collection efficiency. The outside portion of gel pads are pre-cast onto each PMT prior to integration, while the interiors are filled and cast after the PMT assemblies are installed in the pressure vessel via a pushing mechanism. This paper presents both the mechanical design, as well as the performance of prototype modules at high pressure (70 MPa) and low temperature (−40∘C), characteristic of the environment inside the South Pole ice

The Surface Array of IceCube-Gen2

The science goals of IceCube-Gen2 include multi-messenger astronomy, astroparticle and particle physics. To this end, the observatory will include several detection methods, including a surface array and in-ice optical sensors. The array will have an approximately 8 km2 surface coverage, consisting of elevated scintillator panels and radio antennas to detect air showers in the energy range of several 100 TeV to a few EeV. The observatory’s design is unique in that the measurements using the surface array can be combined with the observations of ≥ 300 GeV muons, produced in the hadronic cascades, using the optical detectors in the ice. This allows for an enhanced ability to study cosmic-ray and hadronic physics as well as to boost the sensitivity for astrophysical neutrinos from the southern sky by reducing the primary background, atmospheric muons. We will present the baseline design of the surface array and highlight the expected scientific capabilitie

Estimating the coincidence rate between the optical and radio array of IceCube-Gen2

The IceCube-Gen2 Neutrino Observatory is proposed to extend the all-flavour energy range of IceCube beyond PeV energies. It will comprise two key components: I) An enlarged 8km3 in-ice optical Cherenkov array to measure the continuation of the IceCube astrophysical neutrino flux and improve IceCube\u27s point source sensitivity above ∼100TeV; and II) A very large in-ice radio array with a surface area of about 500km2. Radio waves propagate through ice with a kilometer-long attenuation length, hence a sparse radio array allows us to instrument a huge volume of ice to achieve a sufficient sensitivity to detect neutrinos with energies above tens of PeV. The different signal topologies for neutrino-induced events measured by the optical and in-ice radio detector - the radio detector is mostly sensitive to the cascades produced in the neutrino interaction, while the optical detector can detect long-ranging muon and tau leptons with high accuracy - yield highly complementary information. When detected in coincidence, these signals will allow us to reconstruct the neutrino energy and arrival direction with high fidelity. Furthermore, if events are detected in coincidence with a sufficient rate, they resemble the unique opportunity to study systematic uncertainties and to cross-calibrate both detector components

Sensitivity of the IceCube-Gen2 Surface Array for Cosmic-Ray Anisotropy Studies

The energy of the transition from Galactic to extra-galactic origin of cosmic rays is one of the major unresolved issues of cosmic-ray physics. However, strong constraints can be obtained from studying the anisotropy in the arrival directions of cosmic rays. The sensitivity to cosmic-ray anisotropy is, in particular, a matter of statistics. Recently, the cosmic ray anisotropy measurements in the TeV to PeV energy range were updated from IceCube using 11 years of data. The IceCube-Gen2 surface array will cover an area about 8 times larger than the existing IceTop surface array with a corresponding increase in statistics and capability to investigate cosmic-ray anisotropy with higher sensitivity. In this contribution, we present details on the performed simulation studies and sensitivity to the cosmic-ray anisotropy signal for the IceCube-Gen2 surface array

Deep Learning Based Event Reconstruction for the IceCube-Gen2 Radio Detector

The planned in-ice radio array of IceCube-Gen2 at the South Pole will provide unprecedented sensitivity to ultra-high-energy (UHE) neutrinos in the EeV range. The ability of the detector to measure the neutrino’s energy and direction is of crucial importance. This contribution presents an end-to-end reconstruction of both of these quantities for both detector components of the hybrid radio array (\u27shallow\u27 and \u27deep\u27) using deep neural networks (DNNs). We are able to predict the neutrino\u27s direction and energy precisely for all event topologies, including the electron neutrino charged-current (νe-CC) interactions, which are more complex due to the LPM effect. This highlights the advantages of DNNs for modeling the complex correlations in radio detector data, thereby enabling a measurement of the neutrino energy and direction. We discuss how we can use normalizing flows to predict the PDF for each individual event which allows modeling the complex non-Gaussian uncertainty contours of the reconstructed neutrino direction. Finally, we discuss how this work can be used to further optimize the detector layout to improve its reconstruction performance

Performance Studies of the Acoustic Module for the IceCube Upgrade

The IceCube Upgrade will augment the existing IceCube Neutrino Observatory by deploying 700 additional optical sensor modules and calibration devices within its center at a depth of 1.5 to 2.5 km in the Antarctic ice. One goal of the Upgrade is to improve the positioning calibration of the optical sensors to increase the angular resolution for neutrino directional reconstruction. An acoustic calibration system will be deployed to explore the capability of achieving this using trilateration of propagation times of acoustic signals. Ten Acoustic Modules (AM) capable of sending and receiving acoustic signals with frequencies from 5 to 30 kHz will be installed within the detector volume. Additionally, compact acoustic sensors inside 15 optical sensor modules will complement the acoustic calibration system. With this system, we aim for an accuracy of a few tens of cm to localize the Acoustic Modules and sensors. Due to the longer attenuation length of sound compared to light within the ice, acoustic position calibration is especially interesting for the upcoming IceCube-Gen2 detector, which will have a string spacing of around 240 m. In this contribution we present an overview of the technical design of the Acoustic Module as well as results of performance tests with a first complete prototype

Direction reconstruction performance for IceCube-Gen2 Radio

The IceCube-Gen2 facility will extend the energy range of IceCube to ultra-high energies. The key component to detect neutrinos with energies above 10 PeV is a large array of in-ice radio detectors. In previous work, direction reconstruction algorithms using the forward-folding technique have been developed for both shallow (≲20 m) and deep in-ice detectors, and have also been successfully used to reconstruct cosmic rays with ARIANNA. Here, we focus on the reconstruction algorithm for the deep in-ice detector, which was recently introduced in the context of the Radio Neutrino Observatory in Greenland (RNO-G)