Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing

AbstractTendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion formation, and Prostaglandin E2 (PGE2) is associated with both adhesion formation and tendinopathy. In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation. S100a4-Cre; EP4flox/flox (EP4cKOS100a4) repairs healed with improved gliding function at day 14, followed by impaired gliding at day 28, relative to wild type. Interestingly, EP4cKOS100a4 resulted in only transient deletion of EP4, suggesting up-regulation of EP4 in an alternative cell population in these mice. Loss of EP4 in Scleraxis-lineage cells did not alter gliding function, suggesting that Scx-lineage cells are not the predominant EP4 expressing population. In contrast, a dramatic increase in α-SMA+, EP4+ double-positive cells were observed in EP4cKOS100a4 suggesting that EP4cKOS100a4 repairs heal with increased infiltration of EP4 expressing α-SMA myofibroblasts, identifying a potential mechanism of late up-regulation of EP4 and impaired gliding function in EP4cKOS100a4 tendon repairs.</jats:p

How do you know it is true? integrity in research and publications: AOA critical issue

High-quality medical care is the result of clinical decisions based upon scientific principles garnered from basic, translational, and clinical research. Information regarding the natural history of diseases and their responses to various treatments is introduced into the medical literature through the approximately one million PubMed journal articles published each year. Pharmaceutical and device companies, universities, departments, and researchers all stand to gain from research publication. Basic and translational research is highly competitive. Success in obtaining research funding and career advancement requires scientific publication in the medical literature. Clinical research findings can lead to changes in the pattern of orthopaedic practice and have implications for the utilization of pharmaceuticals and orthopaedic devices. Research findings can be biased by ownership of patents and materials, funding sources, and consulting arrangements. The current high-stakes research environment has been characterized by an increase in plagiarism, falsification or manipulation of data, selected presentation of results, research bias, and inappropriate statistical analyses. It is the responsibility of the orthopaedic community to work collaboratively with industry, universities, departments, and medical researchers and educators to ensure the integrity of the content of the orthopaedic literature and to enable the incorporation of best practices in the care of orthopaedic patients

The Cosmic Microwave Background in an Inhomogeneous Universe - why void models of dark energy are only weakly constrained by the CMB

The dimming of Type Ia supernovae could be the result of Hubble-scale inhomogeneity in the matter and spatial curvature, rather than signaling the presence of a dark energy component. A key challenge for such models is to fit the detailed spectrum of the cosmic microwave background (CMB). We present a detailed discussion of the small-scale CMB in an inhomogeneous universe, focusing on spherically symmetric `void' models. We allow for the dynamical effects of radiation while analyzing the problem, in contrast to other work which inadvertently fine tunes its spatial profile. This is a surprisingly important effect and we reach substantially different conclusions. Models which are open at CMB distances fit the CMB power spectrum without fine tuning; these models also fit the supernovae and local Hubble rate data which favours a high expansion rate. Asymptotically flat models may fit the CMB, but require some extra assumptions. We argue that a full treatment of the radiation in these models is necessary if we are to understand the correct constraints from the CMB, as well as other observations which rely on it, such as spectral distortions of the black body spectrum, the kinematic Sunyaev-Zeldovich effect or the Baryon Acoustic Oscillations.Comment: 23 pages with 14 figures. v2 has considerably extended discussion and analysis, but the basic results are unchanged. v3 is the final versio

Do primordial Lithium abundances imply there's no Dark Energy?

Explaining the well established observation that the expansion rate of the universe is apparently accelerating is one of the defining scientific problems of our age. Within the standard model of cosmology, the repulsive 'dark energy' supposedly responsible has no explanation at a fundamental level, despite many varied attempts. A further important dilemma in the standard model is the Lithium problem, which is the substantial mismatch between the theoretical prediction for 7-Li from Big Bang Nucleosynthesis and the value that we observe today. This observation is one of the very few we have from along our past worldline as opposed to our past lightcone. By releasing the untested assumption that the universe is homogeneous on very large scales, both apparent acceleration and the Lithium problem can be easily accounted for as different aspects of cosmic inhomogeneity, without causing problems for other cosmological phenomena such as the cosmic microwave background. We illustrate this in the context of a void model.Comment: 14 pages, 4 figures. v2: minor rearrangements in the text, comments and references expanded, results unchange

Study of damage control systems for space station

Damage control systems for detecting and locating overboard and onboard leak and damage modes on space station

Search for GUT Monopoles at Super-Kamiokande

GUT monopoles captured by the Sun's gravitation are expected to catalyze proton decays via the Callan-Rubakov process. In this scenario, protons, which initially decay into pions, will ultimately produce \nu_{e}, \nu_{\mu} and \bar{\nu}_{\mu}. After undergoing neutrino oscillation, all neutrino species appear when they arrive at the Earth, and can be detected by a 50,000 metric ton water Cherenkov detector, Super-Kamiokande (SK). A search for low energy neutrinos in the electron total energy range from 19 to 55 MeV was carried out with SK and gives a monopole flux limit of F_M(\sigma_0/1 mb) < 6.3 \times 10^{-24} (\beta_M/10^{-3})^2 cm^{-2} s^{-1} sr^{-1} at 90% C.L., where \beta_M is the monopole velocity in units of the speed of light and \sigma_0 is the catalysis cross section at \beta_M=1. The obtained limit is more than eight orders of magnitude more stringent than the current best cosmic-ray supermassive monopole flux limit, F_M < 1 \times 10^{-15} cm^{-2} s^{-1} sr^{-1} for \beta_M < 10^{-3} and also two orders of magnitude lower than the result of the Kamiokande experiment, which used a similar detection method.Comment: 15 pages, 6 figure

An Indirect Search for WIMPs in the Sun using 3109.6 days of upward-going muons in Super-Kamiokande

We present the result of an indirect search for high energy neutrinos from WIMP annihilation in the Sun using upward-going muon (upmu) events at Super-Kamiokande. Datasets from SKI-SKIII (3109.6 days) were used for the analysis. We looked for an excess of neutrino signal from the Sun as compared with the expected atmospheric neutrino background in three upmu categories: stopping, non-showering, and showering. No significant excess was observed. The 90% C.L. upper limits of upward-going muon flux induced by WIMPs of 100 GeV/c$^2$ were 6.4$\times10^{-15}$ cm$^{-2}$ sec$^{-1}$ and 4.0$\times10^{-15}$ cm$^{-2}$ sec$^{-1}$ for the soft and hard annihilation channels, respectively. These limits correspond to upper limits of 4.5$\times10^{-39}$ cm$^{-2}$ and 2.7$\times10^{-40}$ cm$^{-2}$ for spin-dependent WIMP-nucleon scattering cross sections in the soft and hard annihilation channels, respectively.Comment: Add journal reference. Also fixed typo and cosmetic things in the old draf

Search for Matter-Dependent Atmospheric Neutrino Oscillations in Super-Kamiokande

We consider muon neutrino to tau neutrino oscillations in the context of the Mass Varying Neutrino (MaVaN) model, where the neutrino mass can vary depending on the electron density along the flight path of the neutrino. Our analysis assumes a mechanism with dependence only upon the electron density, hence ordinary matter density, of the medium through which the neutrino travels. Fully-contained, partially-contained and upward-going muon atmospheric neutrino data from the Super--Kamiokande detector, taken from the entire SK--I period of 1489 live days, are compared to MaVaN model predictions. We find that, for the case of 2-flavor oscillations, and for the specific models tested, oscillation independent of electron density is favored over density dependence. Assuming maximal mixing, the best-fit case and the density-independent case do not differ significantly.Comment: 6 pages, 1 figur

CMB observations in LTB universes: Part I: Matching peak positions in the CMB spectrum

Acoustic peaks in the spectrum of the cosmic microwave background in spherically symmetric inhomogeneous cosmological models are studied. At the photon-baryon decoupling epoch, the universe may be assumed to be dominated by non-relativistic matter, and thus we may treat radiation as a test field in the universe filled with dust which is described by the Lema\^itre-Tolman-Bondi (LTB) solution. First, we give an LTB model whose distance-redshift relation agrees with that of the concordance $\Lambda$CDM model in the whole redshift domain and which is well approximated by the Einstein-de Sitter universe at and before decoupling. We determine the decoupling epoch in this LTB universe by Gamow's criterion and then calculate the positions of acoustic peaks. Thus obtained results are not consistent with the WMAP data. However, we find that one can fit the peak positions by appropriately modifying the LTB model, namely, by allowing the deviation of the distance-redshift relation from that of the concordance $\Lambda$CDM model at $z>2$ where no observational data are available at present. Thus there is still a possibility of explaining the apparent accelerated expansion of the universe by inhomogeneity without resorting to dark energy if we abandon the Copernican principle. Even if we do not take this extreme attitude, it also suggests that local, isotropic inhomogeneities around us may seriously affect the determination of the density contents of the universe unless the possible existence of such inhomogeneities is properly taken into account.Comment: 20 pages, 5 figure