The NCATS BioPlanet – An Integrated Platform for Exploring the Universe of Cellular Signaling Pathways for Toxicology, Systems Biology, and Chemical Genomics

Chemical genomics aims to comprehensively define, and ultimately predict, the effects of small molecule compounds on biological systems. Chemical activity profiling approaches must consider chemical effects on all pathways operative in mammalian cells. To enable a strategic and maximally efficient chemical profiling of pathway space, we have created the NCATS BioPlanet, a comprehensive integrated pathway resource that incorporates the universe of 1,658 human pathways sourced from publicly available, manually curated sources, which have been subjected to thorough redundancy and consistency cross-evaluation. BioPlanet supports interactive browsing, retrieval, and analysis of pathways, exploration of pathway connections, and pathway search by gene targets, category, and availability of corresponding bioactivity assay, as well as visualization of pathways on a 3-dimensional globe, in which the distance between any two pathways is proportional to their degree of gene component overlap. Using this resource, we propose a strategy to identify a minimal set of 362 biological assays that can interrogate the universe of human pathways. The NCATS BioPlanet is a public resource, which will be continually expanded and updated, for systems biology, toxicology, and chemical genomics, available at http://tripod.nih.gov/bioplanet/

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 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

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

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)

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

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

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Fluorescence polarization measures energy funneling in single light-harvesting antennas-LH2 vs conjugated polymers.

Numerous approaches have been proposed to mimic natural photosynthesis using artificial antenna systems, such as conjugated polymers (CPs), dendrimers, and J-aggregates. As a result, there is a need to characterize and compare the excitation energy transfer (EET) properties of various natural and artificial antennas. Here we experimentally show that EET in single antennas can be characterized by 2D polarization imaging using the single funnel approximation. This methodology addresses the ability of an individual antenna to transfer its absorbed energy towards a single pool of emissive states, using a single parameter called energy funneling efficiency (ε). We studied individual peripheral antennas of purple bacteria (LH2) and single CP chains of 20 nm length. As expected from a perfect antenna, LH2s showed funneling efficiencies close to unity. In contrast, CPs showed lower average funneling efficiencies, greatly varying from molecule to molecule. Cyclodextrin insulation of the conjugated backbone improves EET, increasing the fraction of CPs possessing ε = 1. Comparison between LH2s and CPs shows the importance of the protection systems and the protein scaffold of LH2, which keep the chromophores in functional form and at such geometrical arrangement that ensures excellent EET