We report on measurements of the all-particle cosmic ray energy spectrum and composition in the PeV to EeV energy range using 3 years of data from the IceCube Neutrino Observatory. The IceTop ...detector measures cosmic ray induced air showers on the surface of the ice, from which the energy spectrum of cosmic rays is determined by making additional assumptions about the mass composition. A separate measurement is performed when IceTop data are analyzed in coincidence with the high-energy muon energy loss information from the deep in-ice IceCube detector. In this measurement, both the spectrum and the mass composition of the primary cosmic rays are simultaneously reconstructed using a neural network trained on observables from both detectors. The performance and relative advantages of these two distinct analyses are discussed, including the systematic uncertainties and the dependence on the hadronic interaction models, and both all-particle spectra as well as individual spectra for elemental groups are presented.
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.
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 ϕastro = 1.66+0.25 −0.27 at E0 = 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 ≥ 3 σ 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.
Patients who have had an ischemic stroke are at risk of having another. Warfarin is the treatment of choice for the prevention of recurrent cardioembolic stroke. In this study, warfarin and aspirin ...were compared in the prevention of recurrent ischemic stroke due to causes other than cardioembolism. There was no significant difference between the warfarin and aspirin groups in either the rate of recurrence of ischemic stroke or the rate of hemorrhagic complications.
In this study, there was no significant difference between the warfarin and aspirin groups in the rate of recurrence of ischemic stroke.
Long-standing doubts, expressed as late as the 1980s, about the efficacy of warfarin for the prevention of stroke
1
were mitigated by the results of more recent clinical trials. Recurrence rates were lower with warfarin than with placebo in patients who had stroke after myocardial infarction.
2
The rates of first stroke in patients with atrial fibrillation were lower with warfarin than with a range of other therapies,
3
placebo,
4
or aspirin.
5
Also, in open-label studies, the rates of recurrent stroke were lower with warfarin than with placebo or aspirin.
6
Rates of adverse events with warfarin were acceptably low at the ranges of . . .
Abstract
We present a measurement of the high-energy astrophysical muon–neutrino flux with the IceCube Neutrino Observatory. The measurement uses a high-purity selection of 650k neutrino-induced muon ...tracks from the northern celestial hemisphere, corresponding to 9.5 yr of experimental data. With respect to previous publications, the measurement is improved by the increased size of the event sample and the extended model testing beyond simple power-law hypotheses. An updated treatment of systematic uncertainties and atmospheric background fluxes has been implemented based on recent models. The best-fit single power-law parameterization for the astrophysical energy spectrum results in a normalization of
ϕ
@
100
TeV
ν
μ
+
ν
¯
μ
=
1.44
−
0.26
+
0.25
×
10
−
18
GeV
−
1
cm
−
2
s
−
1
sr
−
1
and a spectral index
γ
SPL
=
2.37
−
0.09
+
0.09
, constrained in the energy range from 15 TeV to 5 PeV. The model tests include a single power law with a spectral cutoff at high energies, a log-parabola model, several source-class-specific flux predictions from the literature, and a model-independent spectral unfolding. The data are consistent with a single power-law hypothesis, however, spectra with softening above one PeV are statistically more favorable at a two-sigma level.
Observation of high-energy neutrinos from the Galactic plane Ackermann, M; Ahlers, M; Andeen, K ...
Science (American Association for the Advancement of Science),
2023-Jun-30, 2023-06-30, 20230630, Letnik:
380, Številka:
6652
Journal Article
Recenzirano
Odprti dostop
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.
Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development. Targeting the functional repertoire of macrophages may hold novel ...approaches for future atherosclerosis management. Here, we describe a previously unrecognized role of the epigenomic enzyme Histone deacetylase 3 (Hdac3) in regulating the atherosclerotic phenotype of macrophages. Using conditional knockout mice, we found that myeloid Hdac3 deficiency promotes collagen deposition in atherosclerotic lesions and thus induces a stable plaque phenotype. Also, macrophages presented a switch to anti‐inflammatory wound healing characteristics and showed improved lipid handling. The pro‐fibrotic phenotype was directly linked to epigenetic regulation of the Tgfb1 locus upon Hdac3 deletion, driving smooth muscle cells to increased collagen production. Moreover, in humans, HDAC3 was the sole Hdac upregulated in ruptured atherosclerotic lesions, Hdac3 associated with inflammatory macrophages, and HDAC3 expression inversely correlated with pro‐fibrotic TGFB1 expression. Collectively, we show that targeting the macrophage epigenome can improve atherosclerosis outcome and we identify Hdac3 as a potential novel therapeutic target in cardiovascular disease.
Synopsis
Hdac3 is shown to be an important modulator of the fibrotic phenotype of macrophages in atherosclerosis and, in humans, the expression of Hdac3 is linked to plaque vulnerability to rupture.
Myeloid Hdac3 deficiency promotes collagen deposition in atherosclerosis
Macrophage Hdac3 deletion enhances TGF‐β secretion thereby increasing collagen production by vascular smooth muscle cells and results in improved lipid handling by de‐repression of PPARγ and LXR responses
In humans, Hdac3 is upregulated in ruptured atherosclerotic lesions and is associated with inflammatory macrophages
Fine‐tuning of the macrophage phenotype by altering the epigenetic landscape can be applied to affect atherosclerotic disease outcome
Hdac3 is shown to be an important modulator of the fibrotic phenotype of macrophages in atherosclerosis and, in humans, the expression of Hdac3 is linked to plaque vulnerability to rupture.
The Glashow resonance describes the resonant formation of a W
boson during the interaction of a high-energy electron antineutrino with an electron
, peaking at an antineutrino energy of ...6.3 petaelectronvolts (PeV) in the rest frame of the electron. Whereas this energy scale is out of reach for currently operating and future planned particle accelerators, natural astrophysical phenomena are expected to produce antineutrinos with energies beyond the PeV scale. Here we report the detection by the IceCube neutrino observatory of a cascade of high-energy particles (a particle shower) consistent with being created at the Glashow resonance. A shower with an energy of 6.05 ± 0.72 PeV (determined from Cherenkov radiation in the Antarctic Ice Sheet) was measured. Features consistent with the production of secondary muons in the particle shower indicate the hadronic decay of a resonant W
boson, confirm that the source is astrophysical and provide improved directional localization. The evidence of the Glashow resonance suggests the presence of electron antineutrinos in the astrophysical flux, while also providing further validation of the standard model of particle physics. Its unique signature indicates a method of distinguishing neutrinos from antineutrinos, thus providing a way to identify astronomical accelerators that produce neutrinos via hadronuclear or photohadronic interactions, with or without strong magnetic fields. As such, knowledge of both the flavour (that is, electron, muon or tau neutrinos) and charge (neutrino or antineutrino) will facilitate the advancement of neutrino astronomy.
The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype
Pseudomonas ...aeruginosa
infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (
n
= 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old interquartile range (IQR): 64–79 versus an average of 50 years old (IQR: 30–73) (
p
= 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16–22) versus 15 (IQR: 10–19) (
p
= 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (
p
= 0.048). The Kaplan–Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 IQR: 7.0–11.5 versus 18.5 IQR: 8–30 days in those who did not receive the antibody;
p
= 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11
P. aeruginosa
pneumonia.
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