The role of bone sialoprotein in the tendon-bone insertion

© 2016 International Society of Matrix Biology. Tendons/ligaments insert into bone via a transitional structure, the enthesis, which is susceptible to injury and difficult to repair. Fibrocartilaginous entheses contain fibrocartilage in their transitional zone, part of which is mineralized. Mineral-associated proteins within this zone have not been adequately characterized. Members of the Small Integrin Binding Ligand N-linked Glycoprotein (SIBLING) family are acidic phosphoproteins expressed in mineralized tissues. Here we show that two SIBLING proteins, bone sialoprotein (BSP) and osteopontin (OPN), are present in the mouse enthesis. Histological analyses indicate that the calcified zone of the quadriceps tendon enthesis is longer in Bsp-/- mice, however no difference is apparent in the supraspinatus tendon enthesis. In an analysis of mineral content within the calcified zone, micro-CT and Raman spectroscopy reveal that the mineral content in the calcified fibrocartilage of the quadriceps tendon enthesis are similar between wild type and Bsp-/- mice. Mechanical testing of the patellar tendon shows that while the tendons fail under similar loads, the Bsp-/- patellar tendon is 7.5% larger in cross sectional area than wild type tendons, resulting in a 16.5% reduction in failure stress. However, Picrosirius Red staining shows no difference in collagen organization. Data collected here indicate that BSP is present in the calcified fibrocartilage of murine entheses and suggest that BSP plays a regulatory role in this structure, influencing the growth of the calcified fibrocartilage in addition to the weakening of the tendon mechanical properties. Based on the phenotype of the Bsp-/- mouse enthesis, and the known in vitro functional properties of the protein, BSP may be a useful therapeutic molecule in the reattachment of tendons and ligaments to bone

Search for astrophysical sources of neutrinos using cascade events in IceCube

The IceCube neutrino observatory has established the existence of a flux of high-energy astrophysical neutrinos inconsistent with the expectation from atmospheric backgrounds at a significance greater than $5\sigma$. This flux has been observed in analyses of both track events from muon neutrino interactions and cascade events from interactions of all neutrino flavors. Searches for astrophysical neutrino sources have focused on track events due to the significantly better angular resolution of track reconstructions. To date, no such sources have been confirmed. Here we present the first search for astrophysical neutrino sources using cascades interacting in IceCube with deposited energies as small as 1 TeV. No significant clustering was observed in a selection of 263 cascades collected from May 2010 to May 2012. We show that compared to the classic approach using tracks, this statistically-independent search offers improved sensitivity to sources in the southern sky, especially if the emission is spatially extended or follows a soft energy spectrum. This enhancement is due to the low background from atmospheric neutrinos forming cascade events and the additional veto of atmospheric neutrinos at declinations $\lesssim-30^\circ$.Comment: 14 pages, 9 figures, 1 tabl

Measurement of the multi-TeV neutrino cross section with IceCube using Earth absorption

Neutrinos interact only very weakly, so they are extremely penetrating. However, the theoretical neutrino-nucleon interaction cross section rises with energy such that, at energies above 40 TeV, neutrinos are expected to be absorbed as they pass through the Earth. Experimentally, the cross section has been measured only at the relatively low energies (below 400 GeV) available at neutrino beams from accelerators \cite{Agashe:2014kda, Formaggio:2013kya}. Here we report the first measurement of neutrino absorption in the Earth, using a sample of 10,784 energetic upward-going neutrino-induced muons observed with the IceCube Neutrino Observatory. The flux of high-energy neutrinos transiting long paths through the Earth is attenuated compared to a reference sample that follows shorter trajectories through the Earth. Using a fit to the two-dimensional distribution of muon energy and zenith angle, we determine the cross section for neutrino energies between 6.3 TeV and 980 TeV, more than an order of magnitude higher in energy than previous measurements. The measured cross section is $1.30^{+0.21}_{-0.19}$ (stat.) $^{+0.39}_{-0.43}$ (syst.) times the prediction of the Standard Model \cite{CooperSarkar:2011pa}, consistent with the expectation for charged and neutral current interactions. We do not observe a dramatic increase in the cross section, expected in some speculative models, including those invoking new compact dimensions \cite{AlvarezMuniz:2002ga} or the production of leptoquarks \cite{Romero:2009vu}.Comment: Preprint version of Nature paper 10.1038/nature2445

Search for Relativistic Magnetic Monopoles with IceCube

We present the first results in the search for relativistic magnetic monopoles with the IceCube detector, a subsurface neutrino telescope located in the South Polar ice cap containing a volume of 1 km$^{3}$. This analysis searches data taken on the partially completed detector during 2007 when roughly 0.2 km$^{3}$ of ice was instrumented. The lack of candidate events leads to an upper limit on the flux of relativistic magnetic monopoles of \Phi_{\mathrm{90%C.L.}}\sim 3\e{-18}\fluxunits for $\beta\geq0.8$. This is a factor of 4 improvement over the previous best experimental flux limits up to a Lorentz boost $\gamma$ below $10^{7}$. This result is then interpreted for a wide range of mass and kinetic energy values.Comment: 11 pages, 11 figures. v2 is minor text edits, no changes to resul

Lateral Distribution of Muons in IceCube Cosmic Ray Events

In cosmic ray air showers, the muon lateral separation from the center of the shower is a measure of the transverse momentum that the muon parent acquired in the cosmic ray interaction. IceCube has observed cosmic ray interactions that produce muons laterally separated by up to 400 m from the shower core, a factor of 6 larger distance than previous measurements. These muons originate in high pT (> 2 GeV/c) interactions from the incident cosmic ray, or high-energy secondary interactions. The separation distribution shows a transition to a power law at large values, indicating the presence of a hard pT component that can be described by perturbative quantum chromodynamics. However, the rates and the zenith angle distributions of these events are not well reproduced with the cosmic ray models tested here, even those that include charm interactions. This discrepancy may be explained by a larger fraction of kaons and charmed particles than is currently incorporated in the simulations

Book Reviews

With the observation of high-energy astrophysical neutrinos by the IceCube Neutrino Observatory, interest has risen in models of PeV-mass decaying dark matter particles to explain the observed flux. We present two dedicated experimental analyses to test this hypothesis. One analysis uses 6 years of IceCube data focusing on muon neutrino ‘track’ events from the Northern Hemisphere, while the second analysis uses 2 years of ‘cascade’ events from the full sky. Known background components and the hypothetical flux from unstable dark matter are fitted to the experimental data. Since no significant excess is observed in either analysis, lower limits on the lifetime of dark matter particles are derived: we obtain the strongest constraint to date, excluding lifetimes shorter than $10^{28}$ s at 90% CL for dark matter masses above 10 TeV