Search for diffuse neutrino flux from astrophysical sources with MACRO

Many galactic and extragalactic astrophysical sources are currently considered promising candidates as high energy neutrino emitters. Astrophysical neutrinos can be detected as upward-going muons produced in charged-current interactions with the medium surrounding the detector. The expected neutrino fluxes from various models start to dominate on the atmospheric neutrino background at neutrino energies above some tens of TeV. We present the results of a search for an excess of high energy upward-going muons among the sample of data collected by MACRO during ~5.8 years of effective running time. No significant evidence for this signal was found. As a consequence, an upper limit on the flux of upward-going muons from high-energy neutrinos was set at the level of 1.7 10^(-14) cm^(-2) s^(-1) sr^(-1). The corresponding upper limit for the diffuse neutrino flux was evaluated assuming a neutrino power law spectrum. Our result was compared with theoretical predictions and upper limits from other experiments.Comment: 19 pages, 8 figures, 2 table

Activation of DNA-PK by Ionizing Radiation Is Mediated by Protein Phosphatase 6

DNA-dependent protein kinase (DNA-PK) plays a critical role in DNA damage repair, especially in non-homologous end-joining repair of double-strand breaks such as those formed by ionizing radiation (IR) in the course of radiation therapy. Regulation of DNA-PK involves multisite phosphorylation but this is incompletely understood and little is known about protein phosphatases relative to DNA-PK. Mass spectrometry analysis revealed that DNA-PK interacts with the protein phosphatase-6 (PP6) SAPS subunit PP6R1. PP6 is a heterotrimeric enzyme that consists of a catalytic subunit, plus one of three PP6 SAPS regulatory subunits and one of three ankyrin repeat subunits. Endogenous PP6R1 co-immunoprecipitated DNA-PK, and IR enhanced the amount of complex and promoted its import into the nucleus. In addition, siRNA knockdown of either PP6R1 or PP6 significantly decreased IR activation of DNA-PK, suggesting that PP6 activates DNA-PK by association and dephosphorylation. Knockdown of other phosphatases PP5 or PP1γ1 and subunits PP6R3 or ARS-A did not reduce IR activation of DNA-PK, demonstrating specificity for PP6R1. Finally, siRNA knockdown of PP6R1 or PP6 but not other phosphatases increased the sensitivity of glioblastoma cells to radiation-induced cell death to a level similar to DNA-PK deficient cells. Our data demonstrate that PP6 associates with and activates DNA-PK in response to ionizing radiation. Therefore, the PP6/PP6R1 phosphatase is a potential molecular target for radiation sensitization by chemical inhibition

High-energy Neutrino Astronomy: The Cosmic Ray Connection

This is a review of neutrino astronomy anchored to the observational fact that Nature accelerates protons and photons to energies in excess of $10^{20}$ and $10^{13}$ eV, respectively. Although the discovery of cosmic rays dates back close to a century, we do not know how and where they are accelerated. Basic elementary-particle physics dictates a universal upper limit on their energy of $5\times10^{19}$ eV, the so-called Greisen-Kuzmin-Zatsepin cutoff; however, particles in excess of this energy have been observed by all experiments, adding one more puzzle to the cosmic ray mystery. Mystery is fertile ground for progress: we will review the facts as well as the speculations about the sources including gamma ray bursts, blazars and top-down scenarios. The important conclusion is that, independently of the specific blueprint of the source, it takes a kilometer-scale neutrino observatory to detect the neutrino beam associated with the highest energy cosmic rays and gamma rays. We also briefly review the ongoing efforts to commission such instrumentation.Comment: 83 pages, 18 figures, submitted to Reports on Progress in Physic

Astrophysical Origins of Ultrahigh Energy Cosmic Rays

In the first part of this review we discuss the basic observational features at the end of the cosmic ray energy spectrum. We also present there the main characteristics of each of the experiments involved in the detection of these particles. We then briefly discuss the status of the chemical composition and the distribution of arrival directions of cosmic rays. After that, we examine the energy losses during propagation, introducing the Greisen-Zaptsepin-Kuzmin (GZK) cutoff, and discuss the level of confidence with which each experiment have detected particles beyond the GZK energy limit. In the second part of the review, we discuss astrophysical environments able to accelerate particles up to such high energies, including active galactic nuclei, large scale galactic wind termination shocks, relativistic jets and hot-spots of Fanaroff-Riley radiogalaxies, pulsars, magnetars, quasar remnants, starbursts, colliding galaxies, and gamma ray burst fireballs. In the third part of the review we provide a brief summary of scenarios which try to explain the super-GZK events with the help of new physics beyond the standard model. In the last section, we give an overview on neutrino telescopes and existing limits on the energy spectrum and discuss some of the prospects for a new (multi-particle) astronomy. Finally, we outline how extraterrestrial neutrino fluxes can be used to probe new physics beyond the electroweak scale.Comment: Higher resolution version of Fig. 7 is available at http://www.angelfire.com/id/dtorres/down3.html. Solicited review article prepared for Reports on Progress in Physics, final versio

Far IR spectra of Ag 2CdI 4 at temperature range 10–420 K: complementary experimental and first-principle theoretical study

71.15.Mb Density functional theory, local density approximation, gradient and other corrections, 78.30.Hv Other nonmetallic inorganics,

International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU

OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients