Predictions for the Cosmogenic Neutrino Flux in Light of New Data from the Pierre Auger Observatory

The Pierre Auger Observatory (PAO) has measured the spectrum and composition of the ultrahigh energy cosmic rays with unprecedented precision. We use these measurements to constrain their spectrum and composition as injected from their sources and, in turn, use these results to estimate the spectrum of cosmogenic neutrinos generated in their propagation through intergalactic space. We find that the PAO measurements can be well fit if the injected cosmic rays consist entirely of nuclei with masses in the intermediate (C, N, O) to heavy (Fe, Si) range. A mixture of protons and heavier species is also acceptable but (on the basis of existing hadronic interaction models) injection of pure light nuclei (p, He) results in unacceptable fits to the new elongation rate data. The expected spectrum of cosmogenic neutrinos can vary considerably, depending on the precise spectrum and chemical composition injected from the cosmic ray sources. In the models where heavy nuclei dominate the cosmic ray spectrum and few dissociated protons exceed GZK energies, the cosmogenic neutrino flux can be suppressed by up to two orders of magnitude relative to the all-proton prediction, making its detection beyond the reach of current and planned neutrino telescopes. Other models consistent with the data, however, are proton-dominated with only a small (1-10%) admixture of heavy nuclei and predict an associated cosmogenic flux within the reach of upcoming experiments. Thus a detection or non-detection of cosmogenic neutrinos can assist in discriminating between these possibilities.Comment: 10 pages, 7 figure

The Particle Physics Reach of High-Energy Neutrino Astronomy

We discuss the prospects for high-energy neutrino astronomy to study particle physics in the energy regime comparable to and beyond that obtainable at the current and planned colliders. We describe the various signatures of high-energy cosmic neutrinos expected in both neutrino telescopes and air shower experiments and discuss these measurements within the context of theoretical models with a quantum gravity or string scale near a TeV, supersymmetry and scenarios with interactions induced by electroweak instantons. We attempt to access the particle physics reach of these experiments.Comment: Mini-review article for New Journal of Physics, "Focus on Neutrinos" issue. 27 pages, 11 figure

Indirect Search for Neutralino Dark Matter with High Energy Neutrinos

We investigate the prospects of indirect searches for supersymmetric neutralino dark matter. Relic neutralinos gravitationally accumulate in the Sun and their annihilations produce high energy neutrinos. Muon neutrinos of this origin can be seen in large detectors like AMANDA, IceCube and ANTARES. We evaluate the relic density and the detection rate in several models---the minimal supersymmetric model, minimal supergravity, and supergravity with non-universal Higgs boson masses at the grand unification scale. We make realistic estimates for the indirect detection rates including effects of the muon detection threshold, quark hadronization, and solar absorption. We find good prospects for detection of neutralinos with mass above 200 GeV.Comment: 36 pages in REVTEX, 18 figure

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers\u27 tissue of origin

Evidence for oxygenic photosynthesis half a billion years before the Great Oxidation Event

The early Earth was characterized by the absence of oxygen in the ocean–atmosphere system, in contrast to the well-oxygenated conditions that prevail today. Atmospheric concentrations first rose to appreciable levels during the Great Oxidation Event, roughly 2.5–2.3 Gyr ago. The evolution of oxygenic photosynthesis is generally accepted to have been the ultimate cause of this rise, but it has proved difficult to constrain the timing of this evolutionary innovation. The oxidation of manganese in the water column requires substantial free oxygen concentrations, and thus any indication that Mn oxides were present in ancient environments would imply that oxygenic photosynthesis was ongoing. Mn oxides are not commonly preserved in ancient rocks, but there is a large fractionation of molybdenum isotopes associated with the sorption of Mo onto the Mn oxides that would be retained. Here we report Mo isotopes from rocks of the Sinqeni Formation, Pongola Supergroup, South Africa. These rocks formed no less than 2.95 Gyr ago in a nearshore setting. The Mo isotopic signature is consistent with interaction with Mn oxides. We therefore infer that oxygen produced through oxygenic photosynthesis began to accumulate in shallow marine settings at least half a billion years before the accumulation of significant levels of atmospheric oxygen

Asymmetric Excitatory Synaptic Dynamics Underlie Interaural Time Difference Processing in the Auditory System

In order to localize sounds in the environment, the auditory system detects and encodes differences in signals between each ear. The exquisite sensitivity of auditory brain stem neurons to the differences in rise time of the excitation signals from the two ears allows for neuronal encoding of microsecond interaural time differences

A structured telephone-delivered intervention to reduce problem alcohol use (Ready2Change): study protocol for a parallel group randomised controlled trial

Background: Current population surveys suggest around 20% of Australians meet diagnostic criteria for an alcohol use disorder. However, only a minority seek professional help due to individual and structural barriers, such as low health literacy, stigma, geography, service operating hours and wait lists. Telephone-delivered interventions are readily accessible and ideally placed to overcome these barriers. We will conduct a randomised controlled trial (RCT) to examine the efficacy of a standalone, structured telephone-delivered intervention to reduce alcohol consumption, problem severity and related psychological distress among individuals with problem alcohol use. Methods/design: This is a single site, parallel group, two-arm superiority RCT. We will recruit 344 participants from across Australia with problem alcohol use. After completing a baseline assessment, participants will be randomly allocated to receive either the Ready2Change (R2C) intervention (n = 172, four to six sessions of structured telephone-delivered intervention, R2C self-help resource, guidelines for alcohol consumption and stress management pamphlets) or the control condition (n = 172, four phone check-ins < 5 min, guidelines for alcohol consumption and stress management pamphlets). Telephone follow-up assessments will occur at 4-6 weeks, 3 months, 6 months and 12 months post-baseline. The primary outcome is the Alcohol Use Disorders Identification Test (AUDIT) score administered at 3 months post-baseline. Secondary outcomes include change in AUDIT score (6 and 12 months post-baseline), change in number of past-month heavy drinking days, psychological distress, health and wellbeing, quality of life, client treatment evaluation and cost effectiveness. Discussion: This study will be one of the first RCTs conducted internationally to examine the impact of a standalone, structured telephone-delivered intervention to address problem alcohol use and associated psychological morbidity. The proposed intervention is expected to contribute to the health and wellbeing of individuals who are otherwise unlikely to seek treatment through mainstream service models, to reduce the burden on specialist services and primary care providers and to provide an accessible and proportionate response, with resulting cost savings for the health system and broader community. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000828224. Pre-registered on 16 May 2018

Impact of volatile phenols and their precursors on wine quality and control measures of Brettanomyces/Dekkera yeasts

Volatile phenols are aromatic compounds and one of the key molecules responsible for olfactory defects in wine. The yeast genus Brettanomyces is the only major microorganism that has the ability to covert hydroxycinnamic acids into important levels of these compounds, especially 4-ethylphenol and 4-ethylguaiacol, in red wine. When 4-ethylphenols reach concentrations greater than the sensory threshold, all wine’s organoleptic characteristics might be influenced or damaged. The aim of this literature review is to provide a better understanding of the physicochemical, biochemical, and metabolic factors that are related to the levels of p-coumaric acid and volatile phenols in wine. Then, this work summarizes the different methods used for controlling the presence of Brettanomyces in wine and the production of ethylphenols

A tale of two stories: astrocyte regulation of synaptic depression and facilitation

Short-term presynaptic plasticity designates variations of the amplitude of synaptic information transfer whereby the amount of neurotransmitter released upon presynaptic stimulation changes over seconds as a function of the neuronal firing activity. While a consensus has emerged that changes of the synapse strength are crucial to neuronal computations, their modes of expression in vivo remain unclear. Recent experimental studies have reported that glial cells, particularly astrocytes in the hippocampus, are able to modulate short-term plasticity but the underlying mechanism is poorly understood. Here, we investigate the characteristics of short-term plasticity modulation by astrocytes using a biophysically realistic computational model. Mean-field analysis of the model unravels that astrocytes may mediate counterintuitive effects. Depending on the expressed presynaptic signaling pathways, astrocytes may globally inhibit or potentiate the synapse: the amount of released neurotransmitter in the presence of the astrocyte is transiently smaller or larger than in its absence. But this global effect usually coexists with the opposite local effect on paired pulses: with release-decreasing astrocytes most paired pulses become facilitated, while paired-pulse depression becomes prominent under release-increasing astrocytes. Moreover, we show that the frequency of astrocytic intracellular Ca2+ oscillations controls the effects of the astrocyte on short-term synaptic plasticity. Our model explains several experimental observations yet unsolved, and uncovers astrocytic gliotransmission as a possible transient switch between short-term paired-pulse depression and facilitation. This possibility has deep implications on the processing of neuronal spikes and resulting information transfer at synapses.Comment: 93 pages, manuscript+supplementary text, 10 main figures, 11 supplementary figures, 1 tabl

Scalings for Submarine Melting at Tidewater Glaciers from Buoyant Plume Theory

Rapid dynamic changes at the margins of the Greenland Ice Sheet, synchronous with ocean warming, have raised concern that tidewater glaciers can respond sensitively to ocean forcing. Understanding of the processes encompassing ocean forcing nevertheless remains embryonic. The authors use buoyant plume theory to study the dynamics of proglacial discharge plumes arising from the emergence of subglacial discharge into a fjord at the grounding line of a tidewater glacier, deriving scalings for the induced submarine melting. Focusing on the parameter space relevant for high discharge tidewater glaciers, the authors suggest that in an unstratified fjord the often-quoted relationship between total submarine melt volume and subglacial discharge raised to the ⅓ power is appropriate regardless of plume geometry, provided discharge lies below a critical value. In these cases it is then possible to formulate a simple equation estimating total submarine melt volume as a function of discharge, fjord temperature, and calving front height. However, once linear stratification is introduced—as may be more relevant for fjords in Greenland—the total melt rate discharge exponent may be as large as ¾ (⅔) for a point (line) source plume and display more complexity. The scalings provide a guide for more advanced numerical models, inform understanding of the processes encompassing ocean forcing, and facilitate assessment of the variability in submarine melting both in recent decades and under projected atmospheric and oceanic warming