AAV-mediated transcription factor EB (TFEB) gene delivery ameliorates muscle pathology and function in the murine model of Pompe Disease

Pompe disease (PD) is a metabolic myopathy due to acid alpha-glucosidase deficiency and characterized by extensive glycogen storage and impaired autophagy. We previously showed that modulation of autophagy and lysosomal exocytosis by overexpression of the transcription factor EB (TFEB) gene was effective in improving muscle pathology in PD mice injected intramuscularly with an AAV-TFEB vector. Here we have evaluated the effects of TFEB systemic delivery on muscle pathology and on functional performance, a primary measure of efficacy in a disorder like PD. We treated 1-month-old PD mice with an AAV2.9-MCK-TFEB vector. An animal cohort was analyzed at 3 months for muscle and heart pathology. A second cohort was followed at different timepoints for functional analysis. In muscles from TFEB-treated mice we observed reduced PAS staining and improved ultrastructure, with reduced number and increased translucency of lysosomes, while total glycogen content remained unchanged. We also observed statistically significant improvements in rotarod performance in treated animals compared to AAV2.9-MCK-eGFP-treated mice at 5 and 8 months. Cardiac echography showed significant reduction in left-ventricular diameters. These results show that TFEB overexpression and modulation of autophagy result in improvements of muscle pathology and of functional performance in the PD murine model, with delayed disease progression

Mechanisms of Supersymmetry Breaking in the MSSM

Preliminary Remarks. Gauge mediated supersymmetry breaking. Gravity mediated supersymmetry breaking. Anomaly mediated supersymmetry breaking. Gaugino mediated supersymmetry breaking. Braneworld supersymmetry breaking. Conclusions.Comment: New references added, minor misprints corrected, text otherwise unchange

Light Mediated Superconducting Transistor

Bose-condensation of mass-less quasiparticles (photons) can be easily achieved at the room temperature in lasers. On the other hand, condensation of bosons having a non-zero mass requires usually ultra-low temperatures. Recently, it has been shown that polaritons, which are half-light-half-matter quasi-particles, may form condensed states at high temperatures (up to 300K). Polaritons composed by electron-hole pairs coupled to confined light modes in optical cavities may form a Bardeen-Cooper-Schriefer (BCS) superfluid. We propose a new transistor based on stimulated scattering of electron-hole pairs into the BCS polariton mode. A pn-junction embedded inside an optical cavity resonantly emits light into the cavity mode. If the cavity mode energy slightly exceeds the band-gap energy, it couples with electron-hole pairs with zero centre of mass wave-vector but non-zero wave-vector of relative motion. This creates a super-current in the plane of the structure. In an isotropic case, its direction is chosen by the system spontaneously. Otherwise, it is pinned to the external in-plane bias. We calculate the phase diagram for the electron-hole-polariton system.Comment: 11 pages, 3 figure

String mediated phase transitions

It is demonstrated from first principles how the existence of string-like structures can cause a system to undergo a phase transition. In particular, the role of topologically stable cosmic string in the restoration of spontaneously broken symmetries is emphasized. How the thermodynamic properties of strings alter when stiffness and nearest neighbor string-string interactions are included is discussed

DNA-Mediated Electrochemistry

The base pair stack of DNA has been demonstrated as a medium for long-range charge transport chemistry both in solution and at DNA-modified surfaces. This chemistry is exquisitely sensitive to structural perturbations in the base pair stack as occur with lesions, single base mismatches, and protein binding. We have exploited this sensitivity for the development of reliable electrochemical assays based on DNA charge transport at self-assembled DNA monolayers. Here, we discuss the characteristic features, applications, and advantages of DNA-mediated electrochemistry

Relativistic Photon Mediated Shocks

A system of equations governing the structure of a steady, relativistic radiation dominated shock is derived, starting from the general form of the transfer equation obeyed by the photon distribution function. Closure is obtained by truncating the system of moment equations at some order. The anisotropy of the photon distribution function inside the shock is shown to increase with increasing shock velocity, approaching nearly perfect beaming at upstream Lorentz factors $\Gamma_{-}>>1$. Solutions of the shock equations are presented for some range of upstream conditions. These solutions are shown to converge as the truncation order is increased.Comment: 5 pages, a shorter version will appear in PR

Strain-gradient mediated local conduction in strained bismuth ferrite films

It has been recently shown that the strain gradient is able to separate the light-excited electron-hole pairs in semiconductors, but how it affects the photoelectric properties of the photo-active materials remains an open question. Here, we demonstrate the critical role of the strain gradient in mediating local photoelectric properties in the strained BiFeO3 thin films by systematically characterizing the local conduction with nanometre lateral resolution in both dark and illuminated conditions. Due to the giant strain gradient manifested at the morphotropic phase boundaries, the associated flexo-photovoltaic effect induces on one side an enhanced photoconduction in the R-phase, and on the other side a negative photoconductivity in the morphotropic [Formula: see text]-phase. This work offers insight and implication of the strain gradient on the electronic properties in both optoelectronic and photovoltaic devices

Radion Mediated Supersymmetry Breaking

We point out that in supersymmetric theories with extra dimensions, radius stabilization can give rise to a VEV for the $F$ component of the radius modulus. This gives an important contribution to supersymmetry breaking of fields that propagate in the bulk. A particularly attractive class of models is obtained if the standard-model gauge fields propagate in the bulk, while the quark and lepton fields are localized on a brane. This leads to gaugino mediated supersymmetry breaking without the need for singlets in the hidden sector. We analyze a simple explicit model in which this idea is realized

Search for SUSY in Gauge Mediated and Anomaly Mediated Supersymmetry Breaking Models

In this note, recent results on the search for Gauge Mediated Supersymmetry Breaking (GMSB) and Anomaly Mediated Supersymmetry Breaking (AMSB) at the LEP and Tevatron colliders are summarized. We report on DZERO's search for GMSB in di-photon events with large missing transverse energy and discuss the sensitivity of similar searches based on future Tevatron integrated luminosities.Comment: 3 pages, 4 pages, talk presented at the International Europhysics Conference on High Energy Physics EPS, July 17th-23rd 2003, Aachen, German