Search for Relativistic Magnetic Monopoles with Eight Years of IceCube Data.

We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.995c, without any explicit restriction on the monopole mass. We constrain the flux of relativistic cosmic magnetic monopoles to a level below 2.0×10^{-19} cm^{-2} s^{-1} sr^{-1} over the majority of the targeted speed range. This result constitutes the most strict upper limit to date for magnetic monopoles with ß≳0.8 and up to ß∼0.995 and fills the gap between existing limits on the cosmic flux of nonrelativistic and ultrarelativistic magnetic monopoles.

Search for Unstable Sterile Neutrinos with the IceCube Neutrino Observatory.

We present a search for an unstable sterile neutrino by looking for a resonant signal in eight years of atmospheric ν_{µ} data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (stable) three-neutrino and the 3+1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with p values of 2.8% and 0.81%, respectively, we do not observe evidence for 3+1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are Δm_{41}^{2}=6.7_{-2.5}^{+3.9} eV^{2}, sin^{2}2θ_{24}=0.33_{-0.17}^{+0.20}, and g^{2}=2.5π±1.5π, where g is the decay-mediating coupling. The preferred regions of the 3+1+decay model from short-baseline oscillation searches are excluded at 90% C.L.

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale ν_{µ} Disappearance at IceCube.

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{µτ}. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of -0.0041≤ε_{µτ}≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date.

eV-Scale Sterile Neutrino Search Using Eight Years of Atmospheric Muon Neutrino Data from the IceCube Neutrino Observatory.

The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305 735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01 and 100 eV^{2}. The best-fit point is found to be at sin^{2}(2θ_{24})=0.10 and Δm_{41}^{2}=4.5 eV^{2}, which is consistent with the no sterile neutrino hypothesis with a p value of 8.0%.

Characteristics of the Diffuse Astrophysical Electron and Tau Neutrino Flux with Six Years of IceCube High Energy Cascade Data.

We report on the first measurement of the astrophysical neutrino flux using particle showers (cascades) in IceCube data from 2010-2015. Assuming standard oscillations, the astrophysical neutrinos in this dedicated cascade sample are dominated (∼90%) by electron and tau flavors. The flux, observed in the sensitive energy range from 16 TeV to 2.6 PeV, is consistent with a single power-law model as expected from Fermi-type acceleration of high energy particles at astrophysical sources. We find the flux spectral index to be γ=2.53±0.07 and a flux normalization for each neutrino flavor of ϕ_{astro}=1.66_{-0.27}^{+0.25} at E_{0}=100 TeV, in agreement with IceCube's complementary muon neutrino results and with all-neutrino flavor fit results. In the measured energy range we reject spectral indices γ≤2.28 at ≥3σ significance level. Because of high neutrino energy resolution and low atmospheric neutrino backgrounds, this analysis provides the most detailed characterization of the neutrino flux at energies below ∼100 TeV compared to previous IceCube results. Results from fits assuming more complex neutrino flux models suggest a flux softening at high energies and a flux hardening at low energies (p value ≥0.06). The sizable and smooth flux measured below ∼100 TeV remains a puzzle. In order to not violate the isotropic diffuse gamma-ray background as measured by the Fermi Large Area Telescope, it suggests the existence of astrophysical neutrino sources characterized by dense environments which are opaque to gamma rays.

Time-Integrated Neutrino Source Searches with 10 Years of IceCube Data.

This Letter presents the results from pointlike neutrino source searches using ten years of IceCube data collected between April 6, 2008 and July 10, 2018. We evaluate the significance of an astrophysical signal from a pointlike source looking for an excess of clustered neutrino events with energies typically above ∼1 TeV among the background of atmospheric muons and neutrinos. We perform a full-sky scan, a search within a selected source catalog, a catalog population study, and three stacked Galactic catalog searches. The most significant point in the northern hemisphere from scanning the sky is coincident with the Seyfert II galaxy NGC 1068, which was included in the source catalog search. The excess at the coordinates of NGC 1068 is inconsistent with background expectations at the level of 2.9σ after accounting for statistical trials from the entire catalog. The combination of this result along with excesses observed at the coordinates of three other sources, including TXS 0506+056, suggests that, collectively, correlations with sources in the northern catalog are inconsistent with background at 3.3σ significance. The southern catalog is consistent with background. These results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector.

Natural conception rates in subfertile couples following fertility awareness training.

PURPOSE: To analyze cumulative pregnancy rates of subfertile couples after fertility awareness training. METHODS: A prospective observational cohort study followed 187 subfertile women, who had received training in self-observation of the fertile phase of the menstrual cycle with the Sensiplan method, for 8 months. The women, aged 21-47 years, had attempted to become pregnant for 3.5 years on average (range 1-8 years) before study entry. Amenorrhea, known tubal occlusion and severe male factor had been excluded. An additional seven women, who had initially been recruited, became pregnant during the cycle immediately prior to Sensiplan training: this is taken to be the spontaneous pregnancy rate per cycle in the cohort in the absence of fertility awareness training. RESULTS: The cumulative pregnancy rate of subfertile couples after fertility awareness training was 38% (95% CI 27-49%; 58 pregnancies) after eight observation months, which is significantly higher than the estimated basic pregnancy rate of 21.6% in untrained couples in the same cohort. For couples who had been seeking to become pregnant for 1-2 years, the pregnancy rate increased to 56% after 8 months. A female age above 35 (cumulative pregnancy rate 25%, p = 0.06), couples who had attempted to become pregnant for more than 2 years (cumulative pregnancy rate 17%, p < 0.01), all significantly reduce the chances of conceiving naturally at some point. CONCLUSIONS: Training women to identify their fertile window in the menstrual cycle seems to be a reasonable first-line therapy in the management of subfertility.

Observation of high-energy neutrinos from the Galactic plane.

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, is unknown. Because of deflection by interstellar magnetic fields, cosmic rays produced within the Milky Way arrive at Earth from random directions. However, cosmic rays interact with matter near their sources and during propagation, which produces high-energy neutrinos. We searched for neutrino emission using machine learning techniques applied to 10 years of data from the IceCube Neutrino Observatory. By comparing diffuse emission models to a background-only hypothesis, we identified neutrino emission from the Galactic plane at the 4.5σ level of significance. The signal is consistent with diffuse emission of neutrinos from the Milky Way but could also arise from a population of unresolved point sources.

[Use of medical archives for research and patient care]. / Nutzung von medizinischen Datenarchiven für Forschungs- und Patientenversorgungszwecke.

In recent years, technology in healthcare has experienced a dynamic increase, with the collection of data being a central component. In particular, artificial intelligence (AI), such as machine learning and deep learning, makes it possible to perform comprehensive analyses of large amounts of data and to draw conclusions based on correlations and pattern recognition. This paper describes the benefits and challenges of big data in patient care.

Evidence for neutrino emission from the nearby active galaxy NGC 1068.

A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy's active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of [Formula: see text] neutrinos at tera-electron volt energies, with a global significance of 4.2σ, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera-electron volt gamma rays from this source.

Remote entanglement between a single atom and a Bose-Einstein condensate.

Entanglement between stationary systems at remote locations is a key resource for quantum networks. We report on the experimental generation of remote entanglement between a single atom inside an optical cavity and a Bose-Einstein condensate (BEC). To produce this, a single photon is created in the atom-cavity system, thereby generating atom-photon entanglement. The photon is transported to the BEC and converted into a collective excitation in the BEC, thus establishing matter-matter entanglement. After a variable delay, this entanglement is converted into photon-photon entanglement. The matter-matter entanglement lifetime of 100 µs exceeds the photon duration by 2 orders of magnitude. The total fidelity of all concatenated operations is 95%. This hybrid system opens up promising perspectives in the field of quantum information.

[Fractures and luxations in small mammals]. / Frakturen und Luxationen beim Kleinsäuger.

Most traumata in small mammals occur at home. Diagnosis and therapy can be compared with that in the dog and cat, but species-specific differences have to be considered. For fracture treatment a butterfly-cast can be sufficient for stabilization in special cases. In most cases satisfying results can be obtained with a "tie-in-fixator" treatment. Dislocations of the elbow joint are treated by reduction or stabilization through suture techniques or temporary arthrodesis.

Cell surface immunoglobulin. II. Isolation and characterization of immunoglobulin from mouse splenic lymphocytes.

The proteins on surfaces of living splenic lymphocytes from normal BALB/c mice were iodinated enzymatically. Such cells were fractionated into two sub-populations: one composed almost exclusively of small lymphocytes and the other mainly of large lymphocytes and plasma cells. Specific immunoprecipitation of radiolabeled surface Ig obtained from lysates of these cell populations indicated that approximately 2-3% of the acid-precipitable radioactivity from the cell surface is Ig. Moreover, 95% of the H chain radioactivity from the Ig of the small lymphocyte fraction and 90% from the large lymphocyte-plasma cell fraction was characterized as micro by precipitation with anti-micro sera as well as by molecular weight determination on polyacrylamide gels in sodium dodecyl sulfate. The Ig was recovered from the cell surface in the form of an IgM monomer. Control experiments suggested that the monomer did not result from depolymerization of 19S IgM by the methods used to radiolabel and isolate the molecule. (3)H-tyrosine labeling of IgM produced by meyloma cells and radio-iodination of IgM in solution gave the same ratios of microL radioactivity as radiolabeling of IgM on cells, indicating that the tyrosine residues of L and micro-chains of cell surface IgM are available to the lactoperoxidase during the iodination. This is consistent with the hypothesis that cell surface IgM is entirely on the outside of the plasma membrane presumably attached to it by its Fc fragment. These results, together with previous reports by others, suggest that IgM, in its monomeric form, is the main antigen-specific receptor on lymphocytes of normal mice.

Cell surface immunoglobulin. 3. Isolation and characterization of immunoglobulin from nonsecretory human lymphoid cells.

Cells from an established line of Burkitt lymphoma (Daudi) were enzymatically radioiodinated, and labeled Ig from the cell surface was isolated and studied. Subcellular fractionation of labeled cells confirmed that intracellular proteins from the cytoplasm are not iodinated by this method. Radioactive Ig was identified as monomeric (8S) IgM, and an average of 10(5) Ig molecules was found per cell. Ig molecules could be released from the plasma membrane by detergent lysis under nonreducing conditions indicating that attachment of Ig to the plasma membrane occurs via noncovalent interactions. The ratio of micro/L radioactivity in surface Ig was the same as that of total cellular Ig radioiodinated in solution suggesting that a large portion of the Fc fragment is not buried within the membrane. In contrast to the results obtained with cell surface Ig, most intracellular Ig was found as "free" micro- and L chains regardless of whether lysates were labeled with (125)I or cells were labeled with leucine-(3)H. The results indicate that only a small percentage of the total Ig of Daudi cells is associated with the cell surface and suggest that covalent assembly of Ig occurs at or near the time that the molecule becomes part of the plasma membrane. Similarities between cell surface Ig on normal splenic lymphocytes and Daudi cells suggest that the latter is a neoplasm of bone marrow-derived lymphocytes.

Propofol increased the interleukin-6 to interleukin-10 ratio more than isoflurane after surgery in long-term alcoholic patients.

This study investigated the effect of an anaesthetic regimen on the immune response in 40 long-term alcoholic patients undergoing surgery. Patients were randomly allocated to receive either propofol or isoflurane during surgery. Plasma cytokines interleukin (IL)-6 and IL-10 were measured at defined times and rates of post-operative infections were documented. The IL-6/IL-10 ratio significantly increased with propofol compared with isoflurane on day 1 after surgery and the IL-10 level significantly increased with isoflurane on day 1 after surgery. The overall post-operative infection rate was significantly higher in isoflurane-treated patients. Our findings indicate that propofol anaesthesia might be the more favourable regimen, with the IL-6/IL-10 ratio indicating an attenuation of the immune imbalance after surgery in long-term alcoholic patients. These results support the undertaking of a properly powered clinical trial to determine if propofol anaesthesia can reduce the postoperative infection rate in this special patient population.

Cyclic nucleotides of canine antral smooth muscle. Effects of acetylcholine, catecholamines and gastrin.

1. The effects of acetylcholine, catecholamines and gastrin on the intracellular content of cyclic AMP and cyclic GMP in antral circular muscle have been determined. 2. Acetylcholine results in a significant but transient increase in intracellular cyclic GMP. 3. Isoproterenol and norepinephrine increase intracellular cyclic AMP. Based on half-maximal effective doses, isoproterenol is 2.7-times more effective than norepinephrine. The increase in intracellular cyclic AMP by both agents is inhibited by propranolol but not phentolamine, indicating that both agents act on the muscle cell by a beta-receptor-coupled mechanism. 4. Gastrin has no demonstrable effect on either cyclic AMP or cyclic GMP. This suggests that while gastrin and acetylcholine can produce a like myoelectric response in the muscle cell, the action of gastrin is mediated by a separate receptor, presumably on the muscle cell, and not by a release of acetylcholine.

Effect of hormonal and neuronal agents on adenylate cyclase from smooth muscle of the gastric antrum.

Smooth muscle adenylate cyclase of a membrane preparation of canine gastric antrum has been characterized, and the effect of hormonal and neuronal agents examined. The enzyme is active in the presence of Mg2+ or Mn2+, but is inhibited by Ca2+. The Km is 0.5 mM ATP, similar to the Km of skeletal muscle adenylate cyclase. The enzyme is activated by isoproterenol but not norepinephrine, consistent with a beta 2-catecholamine receptor-adenylate cyclase interaction. Secretin activates the enzyme in concentrations as low as 1 . 10(-11) M, while glucagon was effective only at 1 . 10(-6) M. Prostaglandin E1 and E2 have a biphasic effect with activation of adenylate cyclase at 1 . 10(-5) M and a small but significant inhibition of enzyme activity at 1 . 10(-11) M.

Comparison of 125-I-insulin binding and degradation to isolated rat hepatocytes and liver membranes.

UNLABELLED: We have compared the ability of rat liver plasma membranes and isolated hepatocytes to bind and degrade insulin. Isolated cells were prepared in two different ways: by mechanical separation of cells and by collagenase digestion of extracellular matric. In all studies the binding and degradative characteristics of both types of hepatocyte preparations were identical. Furthermore, with one exception, the binding characteristics of membranes and cells were also quite similar. The only exception concerned the amount of insulin bound by hepatocytes as compared to liver membranes. Thus, at concentrations of cells (1.2 times 10(6) cells per milliliter) and membranes (150 mug. protein per milliliter) that gave equal binding at insulin concentrations less than 100 ng./ml., the amount of insulin specifically bound at insulin concentrations greater than 100 ng./ml. was greater with use of hepatocytes. Additional studies indicated that, in contrast to membranes, at the higher insulin concentration only 75 per cent of the previously bound insulin could be recovered from hepatocytes. Thus, a nondissociable component exists; which probably represents intracellular radioactivity and appears to account for the higher specific insulin binding by cells at higher insulin concentrations. When insulin degradation was studied at the above hepatocyte and plasma membrane concentrations, cells degraded 30 per cent more insulin than did membranes. Kinetic analysis of these data revealed that the Km for insulin degradation (5 times 10(-7) M at 37 degrees) was the same for both systems wereas the Vmax was greater with use of hepatocytes. IN CONCLUSION: (1) Preparation of hepatocytes by collagenase digestion does not appear to alter insulin binding or degradation; (2) studies of liver membranes and isolated hepatocytes obtained from normal rats should yield similar information about insulin-receptor interaction as long as insulin concentrations less than 100 ng./ml. are used; (3) at very high insulin concentrations, some of the radioactivity appears to enter the cells; (4) the kinetics of insulin degradation by hepatocytes and liver membranes are similar; and (5) insulin degradation appears to be primarily a membrane phenomenon.

Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990-1992): structure and results of a population-based registry.

The severe skin reactions erythema exsudativum multiforme majus (EEM with mucosal involvement, EEMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) are difficult to study as they are very rare diseases with an incidence of about two cases per 1 million inhabitants per year. We report on the structure of a registry with the aim of ascertaining all hospitalized cases of EEMM, SJS, and TEN in western Germany and Berlin. The registry is structured as an intensive reporting system, regularly contacting more than 1500 departments including 100% of the burn units (n = 34), departments of pediatrics (n = 241), departments of dermatology (n = 106), and 100% of all internal medicine departments in hospitals with intensive care facilities or with more than 200 beds (n = 1161). With a coverage rate up to 95% based on the number of responding departments between April 1, 1990 and December 31, 1992, from a total of 767 reported cases 353 patients with EEMM, SJS, and TEN were finally included in the registry. Most of these patients were directly reported to the registry; only 2.54% (9 of 353) were primarily registered by the German spontaneous reporting systems. Assuming an average population of 64.5 million for western Germany and Berlin an incidence up to 1.89 per 1 million inhabitants per year could be calculated for SJS and TEN.

Androgen binding sites in peripheral human mononuclear leukocytes of healthy males and females.

Androgen binding sites have been identified in circulating human mononuclear leukocytes of healthy donors of both sexes. Cells were separated from blood samples on a Ficoll gradient and incubated with different concentrations of [3H]testosterone in the presence or absence of a 400-fold excess of unlabelled testosterone. Binding data were derived from Scatchard analysis. The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the classic androgen receptors from genital skin fibroblast: in fertile adult males (n = 20) the binding sites showed (1) a high affinity for testosterone (1.32 +/- 0.49 nM; mean +/- SD), (2) a saturable capacity (184 +/- 52 binding sites per cell; mean +/- SD), and (3) a characteristic competitive binding profile for other steroid hormones (relative binding affinities: testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone, whereas aldosterone, 17-hydroxy-progesterone and cortisol did not compete appreciably). Furthermore the number of binding sites determined using [3H]dihydrotestosterone, [3H]RU-1881, or [3H]testosterone were comparable. This raises the possibility that androgen receptors in peripheral mononuclear leukocytes differ from those in genital skin fibroblasts. There was no apparent correlation between serum testosterone concentrations and androgen binding sites. In fertile women remarkable changes in androgen binding sites were seen in the course of the menstrual cycle, with a significant increase in the immediate preovulatory period. The presence of androgen receptors in peripheral mononuclear leukocytes provides for the first time the experimental basis for an hypothesis of direct, receptor-mediated effects of androgens on mature immunocompetent cells. The immunological implications of these results are discussed.