MSC-Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis

SummaryMesenchymal stem/stromal cells (MSCs) are progenitor cells shown to participate in breast tumor stroma formation and to promote metastasis. Despite expanding knowledge of their contributions to breast malignancy, the underlying molecular responses of breast cancer cells (BCCs) to MSC influences remain incompletely understood. Here, we show that MSCs cause aberrant expression of microRNAs, which, led by microRNA-199a, provide BCCs with enhanced cancer stem cell (CSC) properties. We demonstrate that such MSC-deregulated microRNAs constitute a network that converges on and represses the expression of FOXP2, a forkhead transcription factor tightly associated with speech and language development. FOXP2 knockdown in BCCs was sufficient in promoting CSC propagation, tumor initiation, and metastasis. Importantly, elevated microRNA-199a and depressed FOXP2 expression levels are prominent features of malignant clinical breast cancer and are associated significantly with poor survival. Our results identify molecular determinants of cancer progression of potential utility in the prognosis and therapy of breast cancer

Searching for High-energy Neutrino Emission from Galaxy Clusters with IceCube

Galaxy clusters have the potential to accelerate cosmic rays (CRs) to ultrahigh energies via accretion shocks or embedded CR acceleration sites. The CRs with energies below the Hillas condition will be confined within the cluster and eventually interact with the intracluster medium gas to produce secondary neutrinos and gamma rays. Using 9.5 yr of muon neutrino track events from the IceCube Neutrino Observatory, we report the results of a stacking analysis of 1094 galaxy clusters with masses ≳10$^{14}$ M⊙ and redshifts between 0.01 and ∼1 detected by the Planck mission via the Sunyaev–Zel’dovich effect. We find no evidence for significant neutrino emission and report upper limits on the cumulative unresolved neutrino flux from massive galaxy clusters after accounting for the completeness of the catalog up to a redshift of 2, assuming three different weighting scenarios for the stacking and three different power-law spectra. Weighting the sources according to mass and distance, we set upper limits at a 90% confidence level that constrain the flux of neutrinos from massive galaxy clusters (≳10$^{14}$ M⊙) to be no more than 4.6% of the diffuse IceCube observations at 100 TeV, assuming an unbroken E−$^{2.5}$ power-law spectrum

Searches for Neutrinos from Gamma-Ray Bursts using the IceCube Neutrino Observatory

Gamma-ray bursts (GRBs) are considered as promising sources of ultra-high-energy cosmic rays (UHECRs) due to their large power output. Observing a neutrino flux from GRBs would offer evidence that GRBs are hadronic accelerators of UHECRs. Previous IceCube analyses, which primarily focused on neutrinos arriving in temporal coincidence with the prompt gamma rays, found no significant neutrino excess. The four analyses presented in this paper extend the region of interest to 14 days before and after the prompt phase, including generic extended time windows and targeted precursor searches. GRBs were selected between May 2011 and October 2018 to align with the data set of candidate muon-neutrino events observed by IceCube. No evidence of correlation between neutrino events and GRBs was found in these analyses. Limits are set to constrain the contribution of the cosmic GRB population to the diffuse astrophysical neutrino flux observed by IceCube. Prompt neutrino emission from GRBs is limited to $\lesssim$1% of the observed diffuse neutrino flux, and emission on timescales up to $10^4$ s is constrained to 24% of the total diffuse flux

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale νμ_{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 εμτ. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of −0.0041≤εμτ≤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

Multimessenger Gamma-Ray and Neutrino Coincidence Alerts using HAWC and IceCube sub-threshold Data

The High Altitude Water Cherenkov (HAWC) and IceCube observatories, through the Astrophysical Multimessenger Observatory Network (AMON) framework, have developed a multimessenger joint search for extragalactic astrophysical sources. This analysis looks for sources that emit both cosmic neutrinos and gamma rays that are produced in photo-hadronic or hadronic interactions. The AMON system is running continuously, receiving sub-threshold data (i.e. data that is not suited on its own to do astrophysical searches) from HAWC and IceCube, and combining them in real-time. We present here the analysis algorithm, as well as results from archival data collected between June 2015 and August 2018, with a total live-time of 3.0 years. During this period we found two coincident events that have a false alarm rate (FAR) of $<1$ coincidence per year, consistent with the background expectations. The real-time implementation of the analysis in the AMON system began on November 20th, 2019, and issues alerts to the community through the Gamma-ray Coordinates Network with a FAR threshold of $<4$ coincidences per year.Comment: 14 pages, 5 figures, 3 table

Search for Quantum Gravity Using Astrophysical Neutrino Flavour with IceCube

Along their long propagation from production to detection, neutrino states undergo quantum interference which converts their types, or flavours. High-energy astrophysical neutrinos, first observed by the IceCube Neutrino Observatory, are known to propagate unperturbed over a billion light years in vacuum. These neutrinos act as the largest quantum interferometer and are sensitive to the smallest effects in vacuum due to new physics. Quantum gravity (QG) aims to describe gravity in a quantum mechanical framework, unifying matter, forces and space-time. QG effects are expected to appear at the ultra-high-energy scale known as the Planck energy, $E_{P}\equiv 1.22\times 10^{19}$~giga-electronvolts (GeV). Such a high-energy universe would have existed only right after the Big Bang and it is inaccessible by human technologies. On the other hand, it is speculated that the effects of QG may exist in our low-energy vacuum, but are suppressed by the Planck energy as $E_{P}^{-1}$ ($\sim 10^{-19}$~GeV$^{-1}$), $E_{P}^{-2}$ ($\sim 10^{-38}$~GeV$^{-2}$), or its higher powers. The coupling of particles to these effects is too small to measure in kinematic observables, but the phase shift of neutrino waves could cause observable flavour conversions. Here, we report the first result of neutrino interferometry~\cite{Aartsen:2017ibm} using astrophysical neutrino flavours to search for new space-time structure. We did not find any evidence of anomalous flavour conversion in IceCube astrophysical neutrino flavour data. We place the most stringent limits of any known technologies, down to $10^{-42}$~GeV$^{-2}$, on the dimension-six operators that parameterize the space-time defects for preferred astrophysical production scenarios. For the first time, we unambiguously reach the signal region of quantum-gravity-motivated physics.Comment: The main text is 7 pages with 3 figures and 1 table. The Appendix includes 5 pages with 3 figure

All-flavor constraints on nonstandard neutrino interactions and generalized matter potential with three years of IceCube DeepCore data

We report constraints on nonstandard neutrino interactions (NSI) from the observation of atmospheric neutrinos with IceCube, limiting all individual coupling strengths from a single dataset. Furthermore, IceCube is the first experiment to constrain flavor-violating and nonuniversal couplings simultaneously. Hypothetical NSI are generically expected to arise due to the exchange of a new heavy mediator particle. Neutrinos propagating in matter scatter off fermions in the forward direction with negligible momentum transfer. Hence the study of the matter effect on neutrinos propagating in the Earth is sensitive to NSI independently of the energy scale of new physics. We present constraints on NSI obtained with an all-flavor event sample of atmospheric neutrinos based on three years of IceCube DeepCore data. The analysis uses neutrinos arriving from all directions, with reconstructed energies between 5.6 GeV and 100 GeV. We report constraints on the individual NSI coupling strengths considered singly, allowing for complex phases in the case of flavor-violating couplings. This demonstrates that IceCube is sensitive to the full NSI flavor structure at a level competitive with limits from the global analysis of all other experiments. In addition, we investigate a generalized matter potential, whose overall scale and flavor structure are also constrained