Hyaluronic Acid Enhances Gene Delivery into the Cochlea

Abstract Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98453/1/hum%2E2011%2E086.pd

Polarisation of the omega meson in the pd-->3He+omega reaction at 1360 and 1450 MeV

The tensor polarisation of omega mesons produced in the pd-->3He+omega reaction has been studied at two energies near threshold. The 3He nuclei were detected in coincidence with the pi0pi+pi- or pi0gamma decay products of the omega. In contrast to the case of phi meson production, the omega mesons are found to be unpolarised. This brings into question the applicability of the Okubo-Zweig-Iizuka rule when comparing the production of vector mesons in low energy hadronic reactions.Comment: 11 pages, 4 figure

Black Holes in Higher-Dimensional Gravity

These lectures review some of the recent progress in uncovering the phase structure of black hole solutions in higher-dimensional vacuum Einstein gravity. The two classes on which we focus are Kaluza-Klein black holes, i.e. static solutions with an event horizon in asymptotically flat spaces with compact directions, and stationary solutions with an event horizon in asymptotically flat space. Highlights include the recently constructed multi-black hole configurations on the cylinder and thin rotating black rings in dimensions higher than five. The phase diagram that is emerging for each of the two classes will be discussed, including an intriguing connection that relates the phase structure of Kaluza-Klein black holes with that of asymptotically flat rotating black holes.Comment: latex, 49 pages, 5 figures. Lectures to appear in the proceedings of the Fourth Aegean Summer School, Mytiline, Lesvos, Greece, September 17-22, 200

Constant curvature f(R) gravity minimally coupled with Yang-Mills field

We consider the particular class of f(R) gravities minimally coupled with Yang - Mills (YM) field in which the Ricci scalar =R_{0}= constant in all dimensions d\geq4. Even in this restricted class the spacetime has unlimited scopes determined by an equation of state of the form P_{eff}={\omega}{\rho}. Depending on the distance from the origin (or horizon of a black hole) the state function {\omega}(r) takes different values. It is observed that {\omega}\rightarrow(1/3) (the ultra relativistic case in 4 - dimensions) and {\omega}\rightarrow-1 (the cosmological constant) are the limiting values of our state function {\omega}(r) in a spacetime centered by a black hole. This suggests that having a constant {\omega} throughout spacetime around a charged black hole in f(R) gravity with constant scalar curvature is a myth.Comment: 12 pages 2 figures, Some references and 2 figures are added with minor changes. Final version for publication in European Physical Journal

Virtual Compton Scattering and Neutral Pion Electroproduction in the Resonance Region up to the Deep Inelastic Region at Backward Angles

We have made the first measurements of the virtual Compton scattering (VCS) process via the H$(e,e'p)\gamma$ exclusive reaction in the nucleon resonance region, at backward angles. Results are presented for the $W$-dependence at fixed $Q^2=1$ GeV$^2$, and for the $Q^2$-dependence at fixed $W$ near 1.5 GeV. The VCS data show resonant structures in the first and second resonance regions. The observed $Q^2$-dependence is smooth. The measured ratio of H$(e,e'p)\gamma$ to H$(e,e'p)\pi^0$ cross sections emphasizes the different sensitivity of these two reactions to the various nucleon resonances. Finally, when compared to Real Compton Scattering (RCS) at high energy and large angles, our VCS data at the highest $W$ (1.8-1.9 GeV) show a striking $Q^2$- independence, which may suggest a transition to a perturbative scattering mechanism at the quark level.Comment: 20 pages, 8 figures. To appear in Phys.Rev.

Classical Yang-Mills Black hole hair in anti-de Sitter space

The properties of hairy black holes in Einstein–Yang–Mills (EYM) theory are reviewed, focusing on spherically symmetric solutions. In particular, in asymptotically anti-de Sitter space (adS) stable black hole hair is known to exist for frak su(2) EYM. We review recent work in which it is shown that stable hair also exists in frak su(N) EYM for arbitrary N, so that there is no upper limit on how much stable hair a black hole in adS can possess

Measurement of the Atmospheric Muon Spectrum from 20 to 3000 GeV

The absolute muon flux between 20 GeV and 3000 GeV is measured with the L3 magnetic muon spectrometer for zenith angles ranging from 0 degree to 58 degree. Due to the large exposure of about 150 m2 sr d, and the excellent momentum resolution of the L3 muon chambers, a precision of 2.3 % at 150 GeV in the vertical direction is achieved. The ratio of positive to negative muons is studied between 20 GeV and 500 GeV, and the average vertical muon charge ratio is found to be 1.285 +- 0.003 (stat.) +- 0.019 (syst.).Comment: Total 32 pages, 9Figure

Probing the DeltaNN component of 3He

The 3He(gamma,pi^+/- p) reactions were measured simultaneously over a tagged photon energy range of 800<E_gamma<1120 MeV, well above the Delta resonance region. An analysis was performed to kinematically isolate Delta knockout events from conventional Delta photoproduction events, and a statistically significant excess of pi+p events was identified, consistent with Delta++ knockout. Two methods were used to estimate the DeltaNN probability in the 3He ground state, corresponding to the observed knockout cross section. The first gave a lower probability limit of 1.5+/-0.6+/-0.5%; the second yielded an upper limit of about 2.6%.Comment: 14 page

Dynamics of the 16^{16}O(e,e'p) cross section at high missing energies

We measured the cross section and response functions (R_L, R_T, and R_LT) for the 16O(e,e'p) reaction in quasielastic kinematics for missing energies 25 60 MeV and P_miss > 200 MeV/c, the cross section is relatively constant. Calculations which include contributions from pion exchange currents, isobar currents and short-range correlations account for the shape and the transversity but only for half of the magnitude of the measured cross section

Extended Theories of Gravity and their Cosmological and Astrophysical Applications

We review Extended Theories of Gravity in metric and Palatini formalism pointing out their cosmological and astrophysical application. The aim is to propose an alternative approach to solve the puzzles connected to dark components.Comment: 44 pages, 11 figure