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Antarctica's Lambert Glacier drains about one-sixth of the ice from the East Antarctic Ice Sheet and is considered stable due to the strong buttressing provided by the Amery Ice Shelf. While previous projections of the sea-level contribution from this sector of the ice sheet have predicted significant mass loss only with near-complete removal of the ice shelf, the ocean warming necessary for this was deemed unlikely. Recent climate projections through 2300 indicate that sufficient ocean warming is a distinct possibility after 2100. This work explores the impact of parametric uncertainty on projections of the response of the Lambert–Amery system (hereafter “the Amery sector”) to abrupt ocean warming through Bayesian calibration of a perturbed-parameter ice-sheet model ensemble. We address the computational cost of uncertainty quantification for ice-sheet model projections via statistical emulation, which employs surrogate models for fast and inexpensive parameter space exploration while retaining critical features of the high-fidelity simulations. To this end, we build Gaussian process (GP) emulators from simulations of the Amery sector at a medium resolution (4–20 km mesh) using the Model for Prediction Across Scales (MPAS)-Albany Land Ice (MALI) model. We consider six input parameters that control basal friction, ice stiffness, calving, and ice-shelf basal melting. From these, we generate 200 perturbed input parameter initializations using space filling Sobol sampling. For our end-to-end probabilistic modeling workflow, we first train emulators on the simulation ensemble and then calibrate the input parameters using observations of the mass balance, grounding line movement, and calving front movement with priors assigned via expert knowledge. Next, we use MALI to project a subset of simulations to 2300 using ocean and atmosphere forcings from a climate model for both low- and high-greenhouse-gas-emission scenarios. From these simulation outputs, we build multivariate emulators by combining GP regression with principal component dimension reduction to emulate multivariate sea-level contribution time series data from the MALI simulations. We then use these emulators to propagate uncertainty from model input parameters to predictions of glacier mass loss through 2300, demonstrating that the calibrated posterior distributions have both greater mass loss and reduced variance compared to the uncalibrated prior distributions. Parametric uncertainty is large enough through about 2130 that the two projections under different emission scenarios are indistinguishable from one another. However, after rapid ocean warming in the first half of the 22nd century, the projections become statistically distinct within decades. Overall, this study demonstrates an efficient Bayesian calibration and uncertainty propagation workflow for ice-sheet model projections and identifies the potential for large sea-level rise contributions from the Amery sector of the Antarctic Ice Sheet after 2100 under high-greenhouse-gas-emission scenarios.

We examine results from two transient modeling experiments that simulate the Last Interglacial period (LIG) using the state-of-the-art Community Earth System Model (CESM2), with a focus on climate and ocean changes relevant to the possible collapse of the Antarctic ice sheet. The experiments simulate the early millennia of the LIG warm period using orbital forcing, greenhouse gas concentrations, and vegetation appropriate for 127 ka. In the first case (127ka), no other changes are made; in the second case (127kaFW), we include a 0.2 Sv freshwater forcing in the North Atlantic. Both are compared with a pre-industrial control simulation (piControl). In the 127ka simulation, the global average temperature is only marginally warmer (0.004 °C) than in the piControl. When freshwater forcing is added (127kaFW), there is surface cooling in the Northern Hemisphere (NH) and warming in the Southern Hemisphere (SH), consistent with the bipolar seesaw effect. Near the Antarctic ice sheet, the 127ka simulation generates notable ocean warming (up to 0.4 °C) at depths below 200 m compared to the piControl. In contrast, the addition of freshwater in the North Atlantic in the 127kaFW run results in a multi-century subsurface ocean cooling that rebounds slowly over multiple millennia near the Antarctic ice sheet. These results have implications for the thermal forcing (and thereby mass balance) of the Antarctic ice sheet. We explore the physical processes that lead to this result and discuss implications for climate forcing of Antarctic ice sheet mass loss during the LIG.

The paper deals with the concept of nation, or Czechness, in the views of the poet, theoretician and artist Karel Hlaváček (1874–1898). In the mid-nineties of the 19th century, Hlaváček belonged to the inner circle around the magazine Moderní revue. In this environment, issues related to national identity, especially in the field of art and culture, but also in the political and social context, were often discussed. At that time, however, Hlaváček was also active in the Sokol association, whose national, i.e. Czech, dimension was not negligible. The texts he published in the Sokol press often differed significantly from those in the pages of Moderní revue, even in terms of the concept of the nation. The difference between the well-known text Nacionalism a internationalism (Moderní revue, December 1896) and his extensive study of Sokol as a social movement, which he published a few months later in the magazine Sokol (October 1897), is absolutely crucial. Hlaváček’s views will be placed in the broader intellectual context of European decadent art.

Abstract Pharmacodynamic (PD) models are mathematical models of cellular reaction networks that include drug mechanisms of action. These models are useful for studying predictive therapeutic outcomes of novel drug therapies in silico. However, PD models are known to possess significant uncertainty with respect to constituent parameter data, leading to uncertainty in the model predictions. Furthermore, experimental data to calibrate these models is often limited or unavailable for novel pathways. In this study, we present a Bayesian optimal experimental design approach for improving PD model prediction accuracy. We then apply our method using simulated experimental data to account for uncertainty in hypothetical laboratory measurements. This leads to a probabilistic prediction of drug performance and a quantitative measure of which prospective laboratory experiment will optimally reduce prediction uncertainty in the PD model. The methods proposed here provide a way forward for uncertainty quantification and guided experimental design for models of novel biological pathways.

Cryogenic magic angle spinning (MAS) is a standard technique utilized for dynamic nuclear polarization (DNP) in solid-state nuclear magnetic resonance (NMR). Here we describe the optimization and implementation of a stator for cryogenic MAS with 9.5 mm diameter spherical rotors, allowing for DNP experiments on large sample volumes. Designs of the stator and rotor for cryogenic MAS build on recent advancements of MAS spheres and take a step further to incorporate sample insert and eject and a temperature-independent spinning stability of ±1 Hz. At a field of 7 T and spinning at 2.0 kHz with a sample temperature of 105–107 K, DNP enhancements of 256 and 200 were observed for 124 and 223 µL sample volumes, respectively, each consisting of 4 M 13C, 15N-labeled urea and 20 mM AMUPol in a glycerol–water glassy matrix.

Purpose: Population-scale, exome-sequenced cohorts with linked electronic health records (EHR) permit genome-first exploration of phenotype. Phenotype and cancer risk are well characterized in children with a pathogenic DICER1 (HGNC ID:17098) variant. Here, the prevalence, penetrance, and phenotype of pathogenic germline DICER1 variants in adults were investigated in 2 population-scale cohorts. Methods: Variant pathogenicity was classified using published DICER1 ClinGen criteria in the UK Biobank (469,787 exomes; unrelated: 437,663) and Geisinger (170,503 exomes; unrelated: 109,789) cohorts. In the UK Biobank cohort, cancer diagnoses in the EHR, cancer, and death registry were queried. For the Geisinger cohort, the Geisinger Cancer Registry and EHR were queried. Results: In the UK Biobank, there were 46 unique pathogenic DICER1 variants in 57 individuals (1:8242; 95% CI: 1:6362-1:10,677). In Geisinger, there were 16 unique pathogenic DICER1 variants (including 1 microdeletion) in 21 individuals (1:8119; 95% CI: 1:5310-1:12,412). Cohorts were well powered to find larger effect sizes for common cancers. Cancers were not significantly enriched in DICER1 heterozygotes; however, there was a ∼4-fold increased risk for thyroid disease in both cohorts. There were multiple ICD10 codes enriched >2-fold in both cohorts. Conclusion: Estimates of pathogenic germline DICER1 prevalence, thyroid disease penetrance, and cancer phenotype from genomically ascertained adults are determined in 2 large cohorts.

Multi-meter sea level rise (SLR) is thought to be possible within the next few centuries, with most of the uncertainty originating from the Antarctic land ice contribution. One source of uncertainty relates to the ice sheet model initialization. Since ice sheets have a long response time (compared to other Earth system components such as the atmosphere), ice sheet model initialization methods can have significant impacts on how the ice sheet responds to future forcings. To assess this, we generated 25 different ice sheet spin-ups, using the Community Ice Sheet Model (CISM) at a 4 km resolution. During each spin-up, we varied two key parameters known to impact the sensitivity of the ice sheet to future forcing: one related to the sensitivity of the ice shelf melt rate to ocean thermal forcing (TF) and the other related to the basal friction. The spin-ups all nudge toward observed thickness and enforce a no-advance calving criterion, such that all final spin-up states resemble observations but differ in their melt and friction parameter settings. Each spin-up was then forced with future ocean thermal forcings from 13 different CMIP6 models under the Shared Socioeconomic Pathway (SSP)5-8.5 emissions scenario and modern climatological surface mass balance data. Our results show that the effects of the ice sheet and ocean parameter settings used during the spin-up are capable of impacting multi-century future SLR predictions by as much as 2 m. By the end of this century, the effects of these choices are more modest, but still significant, with differences of up to 0.2 m of SLR. We have identified a combined ocean and ice parameter space that leads to widespread mass loss within 500 years (low friction and high melt rate sensitivity). To explore temperature thresholds, we also ran a synthetically forced CISM ensemble that is focused on the Amundsen region only. Given certain ocean and ice parameter choices, Amundsen mass loss can be triggered with thermal forcing anomalies between 1.5 and 2 ∘C relative to the spin-up. Our results emphasize the critical importance of considering ice sheet and ocean parameter choices during spin-up for SLR predictions and suggest the importance of including glacial isostatic adjustment in ice sheet simulations.

OBJECTIVES/GOALS: Theater has always served as a means of reflecting and understanding the human condition. Participatory theater further offers the option for viewers to participate in and thus additionally benefit from the performance itself. We use Playback Theater for outreach and research, eliciting information to guide research, education, and engagement. METHODS/STUDY POPULATION: Playback Theater is a type of improvisation that involves audience members recounting personal experiences which are then enacted by a theater troupe. Playback has evolved to include storytelling as a means of expressing and understanding difficult life experiences such as violence, bullying, incarceration, disaster, illness, etc. While not intended as therapy, it has been found to provoke insight and catharsis when used by trained practitioners. We are conducting Playback theater with LGBTQ+ and African American women to elucidate health disparities related to HIV/AIDS. Black/African Americans accounted for 42.1% of cases in 2019, and African American females are 15 times more likely to develop AIDS than white females. We hope to elucidate barriers to screening and treatment to inform early intervention. RESULTS/ANTICIPATED RESULTS: In community engagement, we employ a variety of strategies involving storytelling, since this simple act fosters multiple positive outcomes. For example, by talking about their experiences participants might find clarity about a difficult experience, facilitating coping or healing, or even letting go. By sharing their stories, others (clinicians, researchers, other patients, or the public) can learn what it is like to go through a particular illness or event. This knowledge can be used to allay patient fears or help researchers or clinicians to develop programming that better responds to needs. This novel approach to knowledge sharing also allows communication that may not otherwise be possible. Discussions about sensitive topics are enabled, often leading to shared understanding and potential solutions. DISCUSSION/SIGNIFICANCE: Through Playback Theater, we hope to identify and thus be able to address barriers to early screening and treatment for African American women and the LGBTQ+ population. We are also planning an event with children with cancer and their families to better understand their experiences and needs in both the clinical and familial settings.

Highly potent animal stem cells either self renew or launch complex differentiation programs, using mechanisms that are only partly understood. Drosophila female germline stem cells (GSCs) perpetuate without change over evolutionary time and generate cystoblast daughters that develop into nurse cells and oocytes. Cystoblasts initiate differentiation by generating a transient syncytial state, the germline cyst, and by increasing pericentromeric H3K9me3 modification, actions likely to suppress transposable element activity. Relatively open GSC chromatin is further restricted by Polycomb repression of testis or somatic cell-expressed genes briefly active in early female germ cells. Subsequently, Neijre/CBP and Myc help upregulate growth and reprogram GSC metabolism by altering mitochondrial transmembrane transport, gluconeogenesis, and other processes. In all these respects GSC differentiation resembles development of the totipotent zygote. We propose that the totipotent stem cell state was shaped by the need to resist transposon activity over evolutionary timescales.

The potential of psychedelics to persistently treat substance use disorders is known since the 1960s. However, the biological mechanisms responsible for their therapeutic effects have not yet been fully elucidated. While it is known that serotonergic hallucinogens induce changes in gene expression and neuroplasticity, particularly in prefrontal regions, theories on how specifically this counteracts the alterations that occur in neuronal circuitry throughout the course of addiction are largely unknown. This narrative mini-review endeavors to synthesize well-established knowledge from addiction research with findings and theories regarding the neurobiological effects of psychedelics to give an overview of the potential mechanisms that underlie the treatment of substance use disorders with classical hallucinogenic compounds and point out gaps in the current understanding.

We conducted a systematic review to assess the potential pulmonary carcinogenicity of inhaled talc in humans. Our systematic review methods adhere to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and incorporated aspects from the US Institute of Medicine (IOM) and several United States (US) Environmental Protection Agency (EPA) frameworks for systematic reviews. A comprehensive literature search was conducted. Detailed data abstraction and study quality evaluation, adapting the US Toxic Substances Control Act (TSCA) framework, were central to our analysis. The literature search and selection process identified 23 primary studies that assessed exposure to talc and pulmonary cancer risks in humans (n = 19) and animals (n = 3). Integrating all streams of evidence according to the IOM framework yielded classifications of suggestive evidence of no association between inhaled talc and lung cancer and pleural mesothelioma at human-relevant exposure levels.

Abstract Background The lower Dipteran fungus fly, Sciara coprophila, has many unique biological features that challenge the rule of genome DNA constancy. For example, Sciara undergoes paternal chromosome elimination and maternal X chromosome nondisjunction during spermatogenesis, paternal X elimination during embryogenesis, intrachromosomal DNA amplification of DNA puff loci during larval development, and germline-limited chromosome elimination from all somatic cells. Paternal chromosome elimination in Sciara was the first observation of imprinting, though the mechanism remains a mystery. Here, we present the first draft genome sequence for Sciara coprophila to take a large step forward in addressing these features. Results We assembled the Sciara genome using PacBio, Nanopore, and Illumina sequencing. To find an optimal assembly using these datasets, we generated 44 short-read and 50 long-read assemblies. We ranked assemblies using 27 metrics assessing contiguity, gene content, and dataset concordance. The highest-ranking assemblies were scaffolded using BioNano optical maps. RNA-seq datasets from multiple life stages and both sexes facilitated genome annotation. A set of 66 metrics was used to select the first draft assembly for Sciara. Nearly half of the Sciara genome sequence was anchored into chromosomes, and all scaffolds were classified as X-linked or autosomal by coverage. Conclusions We determined that X-linked genes in Sciara males undergo dosage compensation. An entire bacterial genome from the Rickettsia genus, a group known to be endosymbionts in insects, was co-assembled with the Sciara genome, opening the possibility that Rickettsia may function in sex determination in Sciara. Finally, the signal level of the PacBio and Nanopore data support the presence of cytosine and adenine modifications in the Sciara genome, consistent with a possible role in imprinting.

Antarctic ice shelves are vulnerable to warming ocean temperatures, and some have already begun thinning in response to increased basal melt rates. Sea level is therefore expected to rise due to Antarctic contributions, but uncertainties in its amount and timing remain largely unquantified. In particular, there is substantial uncertainty in future basal melt rates arising from multi-model differences in thermal forcing and how melt rates depend on that thermal forcing. To facilitate uncertainty quantification in sea level rise projections, we build, validate, and demonstrate projections from a computationally efficient statistical emulator of a high-resolution (4 km) Antarctic ice sheet model, the Community Ice Sheet Model version 2.1. The emulator is trained to a large (500-member) ensemble of 200-year-long 4 km resolution transient ice sheet simulations, whereby regional basal melt rates are perturbed by idealized (yet physically informed) trajectories. The main advantage of our emulation approach is that by sampling a wide range of possible basal melt trajectories, the emulator can be used to (1) produce probabilistic sea level rise projections over much larger Monte Carlo ensembles than are possible by direct numerical simulation alone, thereby providing better statistical characterization of uncertainties, and (2) predict the simulated ice sheet response under differing assumptions about basal melt characteristics as new oceanographic studies are published, without having to run additional numerical ice sheet simulations. As a proof of concept, we propagate uncertainties about future basal melt rate trajectories, derived from regional ocean models, to generate probabilistic sea level rise estimates for 100 and 200 years into the future.

Abstract The hybrid design of the Pierre Auger Observatory allows for the measurement of the properties of extensive air showers initiated by ultra-high energy cosmic rays with unprecedented precision. By using an array of prototype underground muon detectors, we have performed the first direct measurement, by the Auger Collaboration, of the muon content of air showers between $$2\times 10^{17}$$ 2×1017 and $$2\times 10^{18}$$ 2×1018 eV. We have studied the energy evolution of the attenuation-corrected muon density, and compared it to predictions from air shower simulations. The observed densities are found to be larger than those predicted by models. We quantify this discrepancy by combining the measurements from the muon detector with those from the Auger fluorescence detector at $$10^{{17.5}}\, {\mathrm{eV}} $$ 1017.5eV and $$10^{{18}}\, {\mathrm{eV}} $$ 1018eV . We find that, for the models to explain the data, an increase in the muon density of $$38\%$$ 38% $$\pm 4\% (12\%)$$ ±4%(12%) $$\pm {}^{21\%}_{18\%}$$ ±18%21% for EPOS-LHC, and of $$50\% (53\%)$$ 50%(53%) $$\pm 4\% (13\%)$$ ±4%(13%) $$\pm {}^{23\%}_{20\%}$$ ±20%23% for QGSJetII-04, is respectively needed.

Two of the most common cancers are breast cancer and colorectal cancer. Up to 10% of cases of each are associated with a high risk of recurrence in an affected individual, or of occurrence in biological relatives. This results from the presence of an underlying mutation (or ‘pathogenic variant’) in a high-penetrance gene. Such cases are typically associated with an autosomal dominant pattern of inheritance, although this may not be obvious in the family history. Genetic testing can identify many (but not all) of these cases, and should be offered to those whose family history or clinical features suggest a high risk. Although testing for certain risk genes (e.g. BRCA1 or BRCA2) has been available for years, the advent of next-generation sequencing ‘gene panels’ now allows for simultaneous testing of many more genes at lower cost. This allows for more frequent detection of pathogenic variants in underlying genes than in the past, but also makes interpretation more complex. An index of suspicion for genetic cancers and appropriate referral to a genetics health professional are increasingly important.

Background: Microwave polymerization reduces the time of acrylic resin processing, but it is important to select a proper cycle to avoid overheating, porosity, and impairment to the materials' properties. Aims: To evaluate the microhardness of conventional (Vipi Cril-VC) and microwaved (Vipi Wave-VW) acrylic resins after microwave polymerization cycles and the cycles recommended by the manufacturer. It was also evaluated the effect of thermocycling on the microhardness of these materials. Methods and Materials: Specimens (n = 10) were made: 1. WB (water-bath recommended for VC polymerization); 2. M630/25 (10 min at 270 W; 5 min at 0 W; 10 min at 360 W: recommended for VW polymerization); 3. M550/3 (3 min at 550 W); and 4. M650/5 (5 min at 650 W). After 48 h in distilled water at 37°C, specimens were subjected to Knoop test under 25 g during 5 s. The same specimens were submitted to thermocycling (5,000 cycles; 5°C and 55°C; 60 s) and the microhardness was again measured. The results were analyzed by repeated measures one-way analysis of variance/Bonferroni for each material (α = 0.05). Results: For both materials, no difference was obtained for groups polymerized using the cycles recommended by the manufacturer (VC = 19.8 ± 0.9 KHN; VW = 21.0 ± 1.6 KHN) and M650/5 (VC = 19.9 ± 1.5 KHN; VW = 20.9 ± 0.8 KHN). After thermocycling, microhardness decreased in experimental cycles for VC (M550/3 = 17.0 ± 1.9 to 14.6 ± 1.2 KHN; M650/5 = 19.9 ± 1.5 to 17.8 ± 0.8 KHN) and in all microwave cycles for VW (M630/25 = 21.0 ± 1.6 to 18.3 ± 0.9 KHN; M550/3 = 17.5 ± 3.0 to 15.7 ± 2.0 KHN; M650/5 = 20.9 ± 0.8 to 18.2 ± 2.0 KHN) (P = 0.000). The lowest hardness was observed for both resins processed by M550/3 (P = 0.001). Conclusions: Both materials could be polymerized in microwave during 5 min showing hardness similar to the cycles recommended by the manufacturer. Thermocycling did not decrease the hardness of VC polymerized with both cycles recommended by the manufacturer and VW polymerized with the water-bath conventional cycle.

One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions. We report a collection of 1200 transgenic zebrafish strains made with the gene-break transposon (GBT) protein trap to simultaneously report and reversibly knockdown the tagged genes. Protein trap-associated mRFP expression shows previously undocumented expression of 35% and 90% of cloned genes at 2 and 4 days post-fertilization, respectively. Further, investigated alleles regularly show 99% gene-specific mRNA knockdown. Homozygous GBT animals in ryr1b, fras1, tnnt2a, edar and hmcn1 phenocopied established mutants. 204 cloned lines trapped diverse proteins, including 64 orthologs of human disease-associated genes with 40 as potential new disease models. Severely reduced skeletal muscle Ca2+ transients in GBT ryr1b homozygous animals validated the ability to explore molecular mechanisms of genetic diseases. This GBT system facilitates novel functional genome annotation towards understanding cellular and molecular underpinnings of vertebrate biology and human disease.

Abstract Elves are a class of transient luminous events, with a radial extent typically greater than 250 km, that occur in the lower ionosphere above strong electrical storms. We report the observation of 1,598 elves, from 2014 to 2016, recorded with unprecedented time resolution (100 ns) using the fluorescence detector (FD) of the Pierre Auger Cosmic‐Ray Observatory. The Auger Observatory is located in the Mendoza province of Argentina with a viewing footprint for elve observations of 3·106 km 2, reaching areas above the Pacific and Atlantic Oceans, as well as the Córdoba region, which is known for severe convective thunderstorms. Primarily designed for ultrahigh energy cosmic‐ray observations, the Auger FD turns out to be very sensitive to the ultraviolet emission in elves. The detector features modified Schmidt optics with large apertures resulting in a field of view that spans the horizon, and year‐round operation on dark nights with low moonlight background, when the local weather is favorable. The measured light profiles of 18% of the elve events have more than one peak, compatible with intracloud activity. Within the 3‐year sample, 72% of the elves correlate with the far‐field radiation measurements of the World Wide Lightning Location Network. The Auger Observatory plans to continue operations until at least 2025, including elve observations and analysis. To the best of our knowledge, this observatory is the only facility on Earth that measures elves with year‐round operation and full horizon coverage.

The polarization observables T,E,P,H, and G in photoproduction of η mesons off protons are measured for photon energies from threshold to W=2400 MeV (T), 2280 MeV (E), 1620 MeV (P,H), or 1820 MeV (G), covering nearly the full solid angle. The data are compared to predictions from the SAID, MAID, JüBo, and BnGa partial-wave analyses. A refit within the BnGa approach including further data yields precise branching ratios for the Nη decay of nucleon resonances. A Nη-branching ratio of 0.33±0.04 for N(1650)1/2− is found, which reduces the large and controversially discussed Nη-branching ratio difference of the two lowest mass JP=1/2−-resonances significantly. Keywords: Baryon spectroscopy, Meson photoproduction, Polarization observables

Abstract H.A. Wilson, then R.H. Dicke, proposed to describe gravitation by a spatial change of the refractive index of the vacuum around a gravitational mass. Dicke extended this formalism in order to describe the apparent expansion of the universe by a cosmological time dependence of the global vacuum index. In this paper, we develop Dicke’s formalism. The metric expansion in standard cosmology (the time-dependent scale factor of the Friedmann–Lemaître curved spacetime metric) is replaced by a flat and static Euclidean metric with a change with time of the vacuum index. We show that a vacuum index increasing with time produces both the cosmological redshift and time dilation, and that the predicted evolution of the energy density of the cosmological microwave background is consistent with the standard cosmology. We then show that the type Ia supernovæ data, from the joint SDSS-II and SNLS SNe-Ia samples, are well modeled by a vacuum index varying exponentially as $$n(t)=exp(t/\tau _0)$$ n(t)=exp(t/τ0) , where $$\tau _0=8.0^{+0.2}_{-0.8}$$ τ0=8.0-0.8+0.2 Gyr. The main consequence of this formalism is that the cosmological redshift should affect any atom, with a relative decrease of the energy levels of about $$-2 \ 10^{-18} \ \mathrm {s}^{-1}$$ -210-18s-1 . Possibilities for an experimental investigation of this prediction are discussed.

An overview of the multi-messenger capabilities of the Pierre Auger Observatory is presented. The techniques and performance of searching for Ultra-High Energy neutrinos, photons and neutrons are described. Some of the most relevant results are reviewed, such as stringent upper bounds that were placed to a flux of diffuse cosmogenic neutrinos and photons, bounds placed on neutrinos emitted from compact binary mergers that were detected by LIGO and Virgo during their first and second observing runs, as well as searches for high energy photons and neutrons from the Galactic center that constrain the properties of the putative Galactic PeVatron, observed by the H.E.S.S. collaboration. The observation of directional correlations between ultra-high energy cosmic rays and either high energy astrophysical neutrinos or specific source populations, weighted by their electromagnetic radiation, are also discussed. They constitute additional multi-messenger approaches aimed at identifying the sources of high energy cosmic rays.