Constraints on Ultrahigh-Energy Cosmic-Ray Sources from a Search for Neutrinos above 10 PeV with IceCube.

We report constraints on the sources of ultrahigh-energy cosmic rays (UHECRs) above 10^{9} GeV, based on an analysis of seven years of IceCube data. This analysis efficiently selects very high- energy neutrino-induced events which have deposited energies from 5×10^{5} GeV to above 10^{11} GeV. Two neutrino-induced events with an estimated deposited energy of (2.6±0.3)×10^{6} GeV, the highest neutrino energy observed so far, and (7.7±2.0)×10^{5} GeV were detected. The atmospheric background-only hypothesis of detecting these events is rejected at 3.6σ. The hypothesis that the observed events are of cosmogenic origin is also rejected at >99% CL because of the limited deposited energy and the nonobservation of events at higher energy, while their observation is consistent with an astrophysical origin. Our limits on cosmogenic neutrino fluxes disfavor the UHECR sources having a cosmological evolution stronger than the star formation rate, e.g., active galactic nuclei and γ-ray bursts, assuming proton-dominated UHECRs. Constraints on UHECR sources including mixed and heavy UHECR compositions are obtained for models of neutrino production within UHECR sources. Our limit disfavors a significant part of parameter space for active galactic nuclei and new-born pulsar models. These limits on the ultrahigh-energy neutrino flux models are the most stringent to date.

Searches for Sterile Neutrinos with the IceCube Detector.

The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous ν_{µ} or ν[over ¯]_{µ} disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3+1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin^{2}2θ_{24}≤0.02 at Δm^{2}∼0.3 eV^{2} at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of |U_{e4}|^{2}.

Flavor Ratio of Astrophysical Neutrinos above 35 TeV in IceCube.

A diffuse flux of astrophysical neutrinos above 100 TeV has been observed at the IceCube Neutrino Observatory. Here we extend this analysis to probe the astrophysical flux down to 35 TeV and analyze its flavor composition by classifying events as showers or tracks. Taking advantage of lower atmospheric backgrounds for showerlike events, we obtain a shower-biased sample containing 129 showers and 8 tracks collected in three years from 2010 to 2013. We demonstrate consistency with the (fe:fµ:fτ)⊕≈(1:1:1)⊕ flavor ratio at Earth commonly expected from the averaged oscillations of neutrinos produced by pion decay in distant astrophysical sources. Limits are placed on nonstandard flavor compositions that cannot be produced by averaged neutrino oscillations but could arise in exotic physics scenarios. A maximally tracklike composition of (0:1:0)⊕ is excluded at 3.3σ, and a purely showerlike composition of (1:0:0)⊕ is excluded at 2.3σ.

Evidence for Astrophysical Muon Neutrinos from the Northern Sky with IceCube.

Results from the IceCube Neutrino Observatory have recently provided compelling evidence for the existence of a high energy astrophysical neutrino flux utilizing a dominantly Southern Hemisphere data set consisting primarily of ν(e) and ν(τ) charged-current and neutral-current (cascade) neutrino interactions. In the analysis presented here, a data sample of approximately 35,000 muon neutrinos from the Northern sky is extracted from data taken during 659.5 days of live time recorded between May 2010 and May 2012. While this sample is composed primarily of neutrinos produced by cosmic ray interactions in Earth's atmosphere, the highest energy events are inconsistent with a hypothesis of solely terrestrial origin at 3.7σ significance. These neutrinos can, however, be explained by an astrophysical flux per neutrino flavor at a level of Φ(E(ν))=9.9(-3.4)(+3.9)×10(-19) GeV(-1) cm(-2) sr(-1) s(-1)(E(ν)/100 TeV(-2), consistent with IceCube's Southern-Hemisphere-dominated result. Additionally, a fit for an astrophysical flux with an arbitrary spectral index is performed. We find a spectral index of 2.2(-0.2)(+0.2), which is also in good agreement with the Southern Hemisphere result.

Observation of high-energy astrophysical neutrinos in three years of IceCube data.

A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm-2 s-1 sr-1 per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7σ. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.

Measurement of atmospheric neutrino oscillations with IceCube.

We present the first statistically significant detection of neutrino oscillations in the high-energy regime (>20 GeV) from an analysis of IceCube Neutrino Observatory data collected in 2010 and 2011. This measurement is made possible by the low-energy threshold of the DeepCore detector (~20 GeV) and benefits from the use of the IceCube detector as a veto against cosmic-ray-induced muon background. The oscillation signal was detected within a low-energy muon neutrino sample (20-100 GeV) extracted from data collected by DeepCore. A high-energy muon neutrino sample (100 GeV-10 TeV) was extracted from IceCube data to constrain systematic uncertainties. The disappearance of low-energy upward-going muon neutrinos was observed, and the nonoscillation hypothesis is rejected with more than 5σ significance. In a two-neutrino flavor formalism, our data are best described by the atmospheric neutrino oscillation parameters |Δm(32)(2)|=(2.3(-0.5)(+0.6))×10(-3) eV(2) and sin(2)(2θ(23))>0.93, and maximum mixing is favored.

First observation of PeV-energy neutrinos with IceCube.

We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04±0.16 and 1.14±0.17 PeV, respectively, the highest neutrino energies observed so far. These events are consistent with fully contained particle showers induced by neutral-current ν(e,µ,τ) (ν(e,µ,τ)) or charged-current ν(e) (ν(e)) interactions within the IceCube detector. The events were discovered in a search for ultrahigh energy neutrinos using data corresponding to 615.9 days effective live time. The expected number of atmospheric background is 0.082±0.004(stat)(-0.057)(+0.041)(syst). The probability of observing two or more candidate events under the atmospheric background-only hypothesis is 2.9×10(-3) (2.8σ) taking into account the uncertainty on the expected number of background events. These two events could be a first indication of an astrophysical neutrino flux; the moderate significance, however, does not permit a definitive conclusion at this time.

Measurement of the ν µ energy spectrum with IceCube-79: IceCube Collaboration.

IceCube is a neutrino observatory deployed in the glacial ice at the geographic South Pole. The ν µ energy unfolding described in this paper is based on data taken with IceCube in its 79-string configuration. A sample of muon neutrino charged-current interactions with a purity of 99.5% was selected by means of a multivariate classification process based on machine learning. The subsequent unfolding was performed using the software Truee. The resulting spectrum covers an E ν -range of more than four orders of magnitude from 125 GeV to 3.2 PeV. Compared to the Honda atmospheric neutrino flux model, the energy spectrum shows an excess of more than 1.9 σ in four adjacent bins for neutrino energies E ν ≥ 177.8 TeV . The obtained spectrum is fully compatible with previous measurements of the atmospheric neutrino flux and recent IceCube measurements of a flux of high-energy astrophysical neutrinos.

Increased circulating monocyte activation in patients with unstable coronary syndromes.

OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.

Development of a general analysis and unfolding scheme and its application to measure the energy spectrum of atmospheric neutrinos with IceCube: IceCube Collaboration.

We present the development and application of a generic analysis scheme for the measurement of neutrino spectra with the IceCube detector. This scheme is based on regularized unfolding, preceded by an event selection which uses a Minimum Redundancy Maximum Relevance algorithm to select the relevant variables and a random forest for the classification of events. The analysis has been developed using IceCube data from the 59-string configuration of the detector. 27,771 neutrino candidates were detected in 346 days of livetime. A rejection of 99.9999 % of the atmospheric muon background is achieved. The energy spectrum of the atmospheric neutrino flux is obtained using the TRUEE unfolding program. The unfolded spectrum of atmospheric muon neutrinos covers an energy range from 100 GeV to 1 PeV. Compared to the previous measurement using the detector in the 40-string configuration, the analysis presented here, extends the upper end of the atmospheric neutrino spectrum by more than a factor of two, reaching an energy region that has not been previously accessed by spectral measurements.

Optical detection of triggered atherosclerotic plaque disruption by fluorescence emission analysis.

Fluorescence emission analysis (FEA) has proven to be very sensitive for the detection of elastin, collagen and lipids, which are recognized as the major sources of autofluorescence in vascular tissues. FEA has also been reported to detect venous thromboemboli. In this paper we have tested the hypothesis that FEA can reproducibly detect in vivo and in vitro triggered plaque disruption and thrombosis in a rabbit model. Fluorescence emission (FE) spectra, recorded in vivo, detected Russell's viper venom (RVV)-induced transformation of atherosclerotic plaque. FE intensity at 410-490 nm 4 weeks after angioplasty was significantly lower (P < 0.0033 by analysis of variance) in RVV-treated rabbits when compared to control animals with stable plaque. FE spectral profile analyses also demonstrated a significant change in curve shape as demonstrated by polynomial regression analysis (R2 from 0.980 to 0.997). We have also demonstrated an excellent correlation between changes in FE intensity and the structural characteristics detected at different stages of "unstable atherosclerotic plaque" development using multiple regression analysis (R2 = 0.989). Thus, FEA applied in vivo is a sensitive and highly informative diagnostic technique for detection of triggered atherosclerotic plaque disruption and related structural changes, associated with plaque transformation, in a rabbit model.

Laser-induced fluorescence (LIF) recognition of the structural composition of porcine heart valves.

Reconstruction and replacement of heart valves with grafts fro pig tissue is a common procedure. However, bioprosthetic valves wear out in a shorter time span than mechanical valves. Bioprosthetic valve structure may contribute to degenerative changes that lead to valve failure. There is, at present, no method to examine the structure of a tissue valve prior to implant. Laser-induced fluorescence (LIF) of natural fluorophores is an elegant method developed for the detection of tumors, dermal lesions and atherosclerosis. We have studied LIF as a potential diagnostic technique for analysis of valvular tissue. Using excimer laser excitation, we examined natural fluorescence recorded from porcine aortic, mitral and pulmonary valves. All three valve outflow surface tissue layers are less fluorescent at 390-450 nm than the inflow layers. Immunohistochemical analysis of collagen I and elastin content in inflow and outflow surface layers of all three valves correlated well with LIF intensities and dI/d lambda values at selected wavelengths. In conclusion, the differences observed in emitted LIF from valve surface layers are found to correlate well with diversity in the structural protein content. The LIF spectroscopic measurements may provide an appropriate tool for examination of tissue valve structure prior to use for implantation.

Evidence for high-energy extraterrestrial neutrinos at the IceCube detector.

We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4σ level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.

Effects of prostaglandins e(2) and f(2alpha) on the electrofusion of pea mesophyll protoplasts.

The effects of prostaglandins E(2) and F(2alpha) on the electrofusion of pea (Pisum sativum cv Ran 1) mesophyll protoplasts were examined. Prostaglandins E(2) and F(2alpha) influenced electrofusion by lowering the threshold voltage necessary for fusion of dielectrophoretically arranged pairs of protoplasts. The direct current voltage threshold decreased with increasing Ca(2+) concentration up to 0.1 millimolar CaCl(2) and the effects of prostaglandins E(2) and F(2alpha) were more pronounced when CaCl(2) was present in the medium. Treatment with calcium channel blocker methoxy verapamil did not change the prostaglandin effects, while the addition of ethyleneglycol-bis (beta-aminoethyl either)-N,N,N',N'-tetraacetic acid, which binds free Ca(2+), increased the threshold voltage. Influence of prostaglandins E(2) and F(2alpha) and Ca(2+) on the membrane fluidity was investigated by analysis of pyrene fluorescence spectra. The values of the ratio between the maximum fluorescence emission intensities of the excimer and the monomer forms (I(ex)/I(mon)) indicated that prostaglandins and Ca(2+) decrease the membrane fluidity. It is proposed that electrically evoked displacement of plasmalemma components takes part in the fusion process (U Zimmermann 1982 Biochim Biophys Acta 694: 227-277). We suggest that prostaglandins E(2) and F(2alpha) facilitate the electrofusion of pea mesophyll protoplasts by changing the fluidity of plasmalemma.

Electrically induced protoplast fusion using pulse electric fields for dielectrophoresis.

The formation of protoplast chains in suspensions of isolated pea (Pisum sativum cv Ran 1) mesophyll protoplasts induced by electric fields was studied. The chain formation induced by a sine-wave field (2 V, peak to peak; 500-0.1 kHz) was compared to that induced by an alternating pulse field (1 V, amplitude; 0.1-0.4 kHz). An increased number of dielectrophoretically paired protoplasts, formation of protoplast chains in the presence of CaCl(2) up to 5 mm, and protoplast fusion in the presence of 3 mm CaCl(2) were found when the pulse field was applied. The present results suggest the possibility of electrically induced protoplast fusion at cation concentrations that prevent fusion when sine-wave fields are applied.

Fluorescence spectroscopic analysis of circulating platelet activation during coronary angioplasty.

BACKGROUND AND OBJECTIVE: Platelet activation during percutaneous transluminal coronary angioplasty (PTCA) initiates thrombus formation and plaque regrowth at sites of arterial injury, limiting procedure efficacy. We have developed a simple assay for circulating platelet activation based on fluorescence analysis of membrane fluidity and intracellular calcium concentration and light scattering analysis of platelet aggregation. STUDY DESIGN/MATERIALS AND METHODS: Platelet activation state was measured in 45 patients undergoing angioplasty, before and after treatment with platelet inhibitors. RESULTS: PTCA alone produced a decrease in pyrene dimer formation (P0.0083) and an increase in light scattering at 650 nm (P0.0128). Treatment with ADP and GPIIb/IIIa receptor antagonists reduced PTCA induced changes in pyrene dimer formation. An unexpected decrease in pyrene dimer formation (P0.05) was detected when the GPIIb/IIIa receptor antagonist was given together with an ADP receptor antagonist. CONCLUSIONS: 1) Analysis of membrane fluidity provides a sensitive marker for platelet activation state. 2) Reduced membrane fluidity after combined platelet inhibitor treatments suggests reduced antiplatelet efficacy.

Effects of abscisic Acid treatment on the thermostability of the photosynthetic apparatus in barley chloroplasts.

Thermostability of the photosynthetic apparatus of abscisic acid (ABA)-treated seedlings of barley (Hordeum vulgare) was studied by light-scattering and by fluorescence measurements of isolated chloroplasts. ABA treatment markedly decreased heat damage of the chloroplast ultrastructure; an exogenous ABA concentration of 10(-5) molar was most effective. Heat-induced increase of the 77 kilodalton fluorescence ratio F(740)/F(685) was also smaller at this ABA concentration. The heat-induced increase of the initial chlorophyll fluorescence level (F(o)) was virtually eliminated in ABA-treated (10(-5) molar) chloroplasts up to 45 degrees C and slightly increased at 50 degrees C, relative to control chloroplasts where F(o) increased even at 35 degrees C and reached its maximal value at 45 degrees C. In control chloroplasts, F(o) increased with a 5-minute pretreatment temperature, an effect observed as low as 35 degrees C. F(o) was maximal at 45 degrees C. In contrast, chloroplasts treated with 10(-5) molar ABA did not exhibit a heat-induced increase in F(o) until 50 degrees C.

Detection of transplant vasculopathy in a rat aortic allograft model by fluorescence spectroscopic optical analysis.

BACKGROUND AND OBJECTIVE: Transplant vasculopathy is a leading cause of late cardiac graft loss. We have examined laser-induced fluorescence (LIF) spectroscopy as an optical diagnostic tool for detection of intimal plaque development and inflammatory cellular invasion in a rat model of aortic allograft transplant. STUDY DESIGN/MATERIALS AND METHODS: Infrarenal aortic segments were transplanted from Lewis to Sprague Dawley rats. A range of vasculopathy development was produced by treatment with a viral anti-inflammatory protein. LIF spectra were recorded from the intima of aortic implants at 28 days. Fluorescence intensity was analyzed for correlation with vasculopathy development. RESULTS: Significant differences in LIF intensity at 400-450 nm (P < or = 0.05 by ANOVA) were detected. LIF emission was correlated with plaque growth (R2 = 0.980), vessel narrowing (R2 = 0.964), and cellular invasion (R2 = 0.971) by regression analysis. CONCLUSION: LIF optical analysis provides a nontraumatic diagnostic approach for detection of atherosclerosis prior to cardiac transplant or during development of vasculopathy after transplant.