PMI: A Delta Psi(m) Independent Pharmacological Regulator of Mitophagy

Mitophagy is central to mitochondrial and cellular homeostasis and operates via the PINK1/Parkin pathway targeting mitochondria devoid of membrane potential (ΔΨm) to autophagosomes. Although mitophagy is recognized as a fundamental cellular process, selective pharmacologic modulators of mitophagy are almost nonexistent. We developed a compound that increases the expression and signaling of the autophagic adaptor molecule P62/SQSTM1 and forces mitochondria into autophagy. The compound, P62-mediated mitophagy inducer (PMI), activates mitophagy without recruiting Parkin or collapsing ΔΨm and retains activity in cells devoid of a fully functional PINK1/Parkin pathway. PMI drives mitochondria to a process of quality control without compromising the bio-energetic competence of the whole network while exposing just those organelles to be recycled. Thus, PMI circumvents the toxicity and some of the nonspecific effects associated with the abrupt dissipation of ΔΨm by ionophores routinely used to induce mitophagy and represents a prototype pharmacological tool to investigate the molecular mechanisms of mitophagy

Fourier, Gauss, Fraunhofer, Porod and the Shape from Moments Problem

We show how the Fourier transform of a shape in any number of dimensions can be simplified using Gauss's law and evaluated explicitly for polygons in two dimensions, polyhedra three dimensions, etc. We also show how this combination of Fourier and Gauss can be related to numerous classical problems in physics and mathematics. Examples include Fraunhofer diffraction patterns, Porods law, Hopfs Umlaufsatz, the isoperimetric inequality and Didos problem. We also use this approach to provide an alternative derivation of Davis's extension of the Motzkin-Schoenberg formula to polygons in the complex plane.Comment: 21 pages, no figure

Low energy supersymmetry with a neutralino LSP and the CDF ee\gamma\gamma + missing E_T event

We present a refined and expanded analysis of the CDF ee\gamma\gamma + \Et event as superpartner production, assuming the lightest neutralino is the lightest supersymmetric particle. A general low-energy Lagrangian is constrained by a minimum cross section times branching ratio into two electrons and two photons, kinematics consistent with the event, and LEP1-LEP130 data. We examine how the supersymmetric parameters depend on the kinematics, branching ratios and experimental predictions with a selectron interpretation of the event, and discuss to what extent these are modified by other interpretations. Predictions for imminent CERN LEP upgrades and the present and future Fermilab Tevatron are presented. Finally, we briefly discuss the possible connection to other phenomena including a light stop, the neutralino relic density, the shift in $R_b$ and the associated shift in $\alpha_s$, and implications for the form of the theory.Comment: 57 pages, LaTeX, uses epsf.sty, 19 figures. Version accepted for publication in Phys. Rev. D, with minor changes and a few clarification

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

Summary: Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. : Maffioletti et al. generate human 3D artificial skeletal muscles from healthy donors and patient-specific pluripotent stem cells. These human artificial muscles accurately model severe genetic muscle diseases. They can be engineered to include other cell types present in skeletal muscle, such as vascular cells and motor neurons. Keywords: skeletal muscle, pluripotent stem cells, iPS cells, myogenic differentiation, tissue engineering, disease modeling, muscular dystrophy, organoid

Breakdown of Lindstedt Expansion for Chaotic Maps

In a previous paper of one of us [Europhys. Lett. 59 (2002), 330--336] the validity of Greene's method for determining the critical constant of the standard map (SM) was questioned on the basis of some numerical findings. Here we come back to that analysis and we provide an interpretation of the numerical results by showing that no contradiction is found with respect to Greene's method. We show that the previous results based on the expansion in Lindstedt series do correspond to the transition value but for a different map: the semi-standard map (SSM). Moreover, we study the expansion obtained from the SM and SSM by suppressing the small divisors. The first case turns out to be related to Kepler's equation after a proper transformation of variables. In both cases we give an analytical solution for the radius of convergence, that represents the singularity in the complex plane closest to the origin. Also here, the radius of convergence of the SM's analogue turns out to be lower than the one of the SSM. However, despite the absence of small denominators these two radii are lower than the ones of the true maps for golden mean winding numbers. Finally, the analyticity domain and, in particular, the critical constant for the two maps without small divisors are studied analytically and numerically. The analyticity domain appears to be an perfect circle for the SSM analogue, while it is stretched along the real axis for the SM analogue yielding a critical constant that is larger than its radius of convergence.Comment: 12 pages, 3 figure

Development of a high-altitude airborne dial system: The Lidar Atmospheric Sensing Experiment (LASE)

The ability of a Differential Absorption Lidar (DIAL) system to measure vertical profiles of H2O in the lower atmosphere was demonstrated both in ground-based and airborne experiments. In these experiments, tunable lasers were used that required real-time experimenter control to locate and lock onto the atmospheric H2O absorption line for the DIAL measurements. The Lidar Atmospheric Sensing Experiment (LASE) is the first step in a long-range effort to develop and demonstrate an autonomous DIAL system for airborne and spaceborne flight experiments. The LASE instrument is being developed to measure H2O, aerosol, and cloud profiles from a high-altitude ER-2 (extended range U-2) aircraft. The science of the LASE program, the LASE system design, and the expected measurement capability of the system are discussed

Detecting a light Higgs boson at the Fermilab Tevatron through enhanced decays to photon pairs

We analyze the prospects of the Tevatron for finding a Higgs boson in the two photon decay mode. We conclude that the Standard Model (SM) Higgs boson will likely not be discovered in this mode. However, we motivate several theories beyond the SM, including the MSSM, that predict a Higgs boson with enhanced branching fractions into photons, and calculate the luminosity needed to discover a general Higgs boson at the Tevatron by a two-photon invariant mass peak at large transverse momentum. We find that a high luminosity Tevatron will play a significant role in discovering or constraining these theories.Comment: 20 pages, latex, 5 figure

Transport properties and magnetic field induced localization in the misfit cobaltite [Bi2_2Ba1.3_{1.3}K0.6_{0.6}Co0.1_{0.1}]RS^{RS}[CoO2_2]1.97_{1.97} single crystal

Resistivity under magnetic field, thermopower and Hall coefficient are systematically studied for [Bi$_2$Ba$_{1.3}$K$_{0.6}$Co$_{0.1}$]$^{RS}$[CoO$_2$]$_{1.97}$ single crystal. In-plane resistivity ($\rho_{ab}$(T)) shows metallic behavior down to 2 K with a $T^2$ dependence below 30 K; while out-of-plane resistivity ($\rho_{c}(T)$) shows metallic behavior at high temperature and a thermal activation semiconducting behavior below about 12 K. Striking feature is that magnetic field induces a ln(1/$T$) diverging behavior in both $\rho_{ab}$ and $\rho_{c}(T)$ at low temperature. The positive magnetoresistance (MR) could be well fitted by the formula based on multi-band electronic structure. The ln(1/$T$) diverging behavior in $\rho_{ab}$ and $\rho_{c}(T)$ could arise from the magnetic-field-induced 2D weak localization or spin density wave.Comment: 7 pages, 8 figure