The sources of the majority of the high-energy astrophysical neutrinos observed with the IceCube neutrino telescope at the South Pole are unknown. So far, only a flaring gamma-ray blazar was ...compellingly associated with the emission of high-energy neutrinos. However, several studies suggest that the neutrino emission from the gamma-ray blazar population only accounts for a small fraction of the total astrophysical neutrino flux. In this work we probe the production of high-energy neutrinos in the cores of active galactic nuclei (AGN), induced by accelerated cosmic rays in the accretion disk region. We present a likelihood analysis based on eight years of IceCube data, searching for a cumulative neutrino signal from three AGN samples created for this work. The neutrino emission is assumed to be proportional to the accretion disk luminosity estimated from the soft x-ray flux. Next to the observed soft x-ray flux, the objects for the three samples have been selected based on their radio emission and infrared color properties. For the largest sample in this search, an excess of high-energy neutrino events with respect to an isotropic background of atmospheric and astrophysical neutrinos is found, corresponding to a post-trial significance of 2.60σ. If interpreted as a genuine signal with the assumptions of a proportionality of x-ray and neutrino fluxes and a model for the subthreshold flux distribution, then this observation implies that at 100 TeV, 27%–100% of the observed neutrinos arise from particle acceleration in the core of AGN at 1σ confidence interval.
Abstract The dentistry literature shows consensus to use the Garvie and Nicholson equation modified by Toraya to quantify the Y-TZP phase transformation. However, this method does not include the ...possibility of cubic phase transformation and crystallographic texture after artificial ageing, and in this case, it is possible to observe errors of quantification. Objectives The aim of this study was to evaluate a dental Y-TZP ageing kinetic of phase transformation under pressure and hydrothermal conditions (130° C, 2 bar) and to compare the methods of quantification by the equation of Garvie and Nicholson modified by Toraya and the Rietveld refinement method. Methods Discs of Y-TZP (12 mm Ø × 1.2 mm in height) were divided into groups ( n = 4) according to the ageing times (in the range of 6 and 138 h). The superficial characterisation was made using SEM and the XDR for crystallographic analysis. Results An aggressive superficial degradation process at the beginning of phase transformation in 6–10 h of ageing was observed by SEM. The phase transformation quantification showed differences between the methods. It was observed the increase and stabilisation of monoclinic phase until 80% at 40 h of ageing by the Garvie and Nicholson modified by Toraya equation, compared to 60% of monoclinic phase and approximately 30% of cubic phase observed by the Rietveld method. Conclusion The Toraya equation showed an overestimated result of monoclinic quantification compared to the Rietveld method. Clinical significance The overestimated result of monoclinic phase could lead to different interpretation about the dental Y-TZP ageing process.
Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding ...patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses.
In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes overall survival (OS) and progression-free survival (PFS) among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone.
Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS.
Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.
•Treatment of concomitant melanoma with ICI resulted in durable clinical responses despite concomitant CLL.•The ORR to first-line ICI was 41% and median duration of response was 18 months.•Prior treatment for CLL was associated with poor ICI-dependent outcomes, including ORRs, OS, and PFS.•Clinical benefit was achieved without exacerbation of CLL or clearly increased adverse event rates.
The formation of ordered protein and peptide assemblies is a phenomenon related to a wide range of human diseases. However, the mechanism of assembly at the molecular level remains largely unknown. ...Minimal models enable the exploration of the underlying interactions that are at the core of such self-assembly processes. In particular, the ability of phenylalanine, a single aromatic amino acid, to form an amyloid-like structure has challenged the previous dogma viewing a peptide backbone as a prerequisite for assembly. The driving forces controlling the nucleation and assembly in the absence of a peptide backbone remain to be identified. Here, aiming to unravel these forces, we explored the kinetics and thermodynamics of three phenylalanine-containing molecules during their assembly process: the amino acid phenylalanine, which accumulates in phenylketonuria patients, the diphenylalanine core-motif of the amyloid β peptide related to Alzheimer’s disease, and the extended triphenylalanine peptide which forms a range of distinct nanostructures in vitro. We found that the aggregation propensity, regarding the critical monomer concentration, strongly increases with size, with triphenylalanine being the most aggregation-prone species under our experimental conditions. In the context of classical nucleation theory, this increase in aggregation propensity can be attributed to the larger free energy decrease upon aggregation of larger peptides and is not due to the presence/absence of a peptide bond per se. Taken together, this work provides insights into the aggregation processes of chemically simple systems and suggests that both backbone-containing peptides and backbone-lacking amino acids assemble through a similar mechanism, thus supporting the classification of amino acids in the continuum of amyloid-forming building blocks.
Sensory association cortices receive diverse inputs with their role in representing and integrating multi-sensory content remaining unclear. Here we examined the neuronal correlates of an ...auditory-tactile stimulus sequence in the posterior parietal cortex (PPC) using 2-photon calcium imaging in awake mice. We find that neuronal subpopulations in layer 2/3 of PPC reliably represent texture-touch events, in addition to auditory cues that presage the incoming tactile stimulus. Notably, altering the flow of sensory events through omission of the cued texture touch elicited large responses in a subset of neurons hardly responsive to or even inhibited by the tactile stimuli. Hence, PPC neurons were able to discriminate not only tactile stimulus features (i.e., texture graininess) but also between the presence and omission of the texture stimulus. Whereas some of the neurons responsive to texture omission were driven by looming-like auditory sounds others became recruited only with tactile sensory experience. These findings indicate that layer 2/3 neuronal populations in PPC potentially encode correlates of expectancy in addition to auditory and tactile stimuli.
This technical note presents a solution to the problem of regulating a general nonlinear dynamical system to an economically optimal operating point. The system is characterized by a set of exogenous ...inputs as an abstraction of time-varying loads and disturbances. The economically optimal operating point is implicitly defined as a solution to a given constrained convex optimization problem, which is related to steady-state operation. The system outputs and the exogenous inputs represent respectively the decision variables and the parameters in the optimization problem. The proposed solution is based on a specific dynamic extension of the Karush-Kuhn-Tucker optimality conditions for the steady-state related optimization problem, which is conceptually related to the continuous-time Arrow-Hurwicz-Uzawa algorithm. Furthermore, it can be interpreted as a generalization of the standard output regulation problem with respect to a constant reference signal.
Abstract
In multi-messenger astronomy, rapid investigation of interesting transients is imperative. As an observatory with a 4
π
steradian field of view, and ∼99% uptime, the IceCube Neutrino ...Observatory is a unique facility to follow up transients, as well as to provide valuable insights for other observatories and inform their observational decisions. Since 2016, IceCube has been using low-latency data to rapidly respond to interesting astrophysical events reported by the multi-messenger observational community. Here, we describe the pipeline used to perform these followup analyses, and provide a summary of the 58 analyses performed as of July 2020. We find no significant signal in the first 58 analyses performed. The pipeline has helped inform various electromagnetic observation strategies, and has constrained neutrino emission from potential hadronic cosmic accelerators.
Using the IceCube Neutrino Observatory, we search for high-energy neutrino emission coincident with compact binary mergers observed by the LIGO and Virgo gravitational-wave (GW) detectors during ...their first and second observing runs. We present results from two searches targeting emission coincident with the sky localization of each GW event within a 1000 s time window centered around the reported merger time. One search uses a model-independent unbinned maximum-likelihood analysis, which uses neutrino data from IceCube to search for pointlike neutrino sources consistent with the sky localization of GW events. The other uses the Low-Latency Algorithm for Multi-messenger Astrophysics, which incorporates astrophysical priors through a Bayesian framework and includes LIGO-Virgo detector characteristics to determine the association between the GW source and the neutrinos. No significant neutrino coincidence is seen by either search during the first two observing runs of the LIGO-Virgo detectors. We set upper limits on the time-integrated neutrino emission within the 1000 s window for each of the 11 GW events. These limits range from 0.02 to 0.7 . We also set limits on the total isotropic equivalent energy, Eiso, emitted in high-energy neutrinos by each GW event. These limits range from 1.7 × 1051 to 1.8 × 1055 erg. We conclude with an outlook for LIGO-Virgo observing run O3, during which both analyses are running in real time.
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.
Zinc-manganese alloy coatings were electrodeposited using sulfate baths in the presence of a superimposed magnetic field up to 1 T parallel to the electrode surface. The effect of ratio Zn
2+
/Mn
2+
...on the elaborated coatings has been investigated using chronoamperometric measurements with potentiostatic technique. Crystallographic structure, morphology, roughness, and chemical composition of the coatings have been studied by X-ray diffraction (XRD), scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy analysis (EDXS), and profilometry. XRD diffraction method revealed that the coatings consisted of zinc (η phase) and/or epsilon phase (MnZn
3
). It has been found that the electrolytic bath with higher manganese ion concentration and lesser zinc ion concentration promotes the formation of MnZn
3
phase. Moreover, the magneto-hydrodynamic-convection (MHD) generated by the magnetic field superimposition favors the diffusion of zinc and manganese species on the working electrode surface, the electrochemical kinetics, and the content of manganese in the deposit.
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