Active Transport of Peptides Across the Intact Human Tympanic Membrane.

We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients

Azimuthal anisotropy: transition from hydrodynamic flow to jet suppression

Measured 2nd and 4th azimuthal anisotropy coefficients v_{2,4}(N_{part}), p_T) are scaled with the initial eccentricity \varepsilon_{2,4}(N_{part}) of the collision zone and studied as a function of the number of participants N_{part} and the transverse momenta p_T. Scaling violations are observed for p_T \alt 3 GeV/c, consistent with a $p_T^2$ dependence of viscous corrections and a linear increase of the relaxation time with $p_T$. These empirical viscous corrections to flow and the thermal distribution function at freeze-out constrain estimates of the specific viscosity and the freeze-out temperature for two different models for the initial collision geometry. The apparent viscous corrections exhibit a sharp maximum for p_T \agt 3 GeV/c, suggesting a breakdown of the hydrodynamic ansatz and the onset of a change from flow-driven to suppression-driven anisotropy.Comment: 5 pages, 4 figs; submitted for publicatio

Constraints on models for the initial collision geometry in ultra relativistic heavy ion collisions

Monte Carlo (MC) simulations are used to compute the centrality dependence of the collision zone eccentricities ($\epsilon_{2,4}$), for both spherical and deformed ground state nuclei, for different model scenarios. Sizable model dependent differences are observed. They indicate that measurements of the $2^{\text{nd}}$ and $4^{\text{th}}$ order Fourier flow coefficients $v_{2,4}$, expressed as the ratio $\frac{v_4}{(v_2)^2}$, can provide robust constraints for distinguishing between different theoretical models for the initial-state eccentricity. Such constraints could remove one of the largest impediments to a more precise determination of the specific viscosity from precision $v_{2,4}$ measurements at the Relativistic Heavy Ion Collider (RHIC).Comment: 4 pages, 3 figs - version accepted for publicatio

Using Pupillometry to Characterize Visual Perception in Autistic Mouse Models

Fragile X syndrome (FXS) is the leading genetic cause of autism. Individuals with Fragile X Syndrome (FXS) commonly display social, behavioral, and intellectual disabilities. Perceptual deficits and their underlying neural activity remain poorly characterized in FXS and other autism spectrum disorders (ASD’s). To explore visual perception in autism, we developed camera based pupil tracking software using OpenCV (an open-source computer vision library) capable of measuring visually evoked changes in pupil area and position in the FXS mouse model (Fmr1 KO). Changes in pupil area and position are believed to correlate with changes in arousal or visual processing and may serve as an indirect readout of brain state. To explore visually evoked changes in pupil area, head-restrained wild type or Fragile X mice were exposed to visual stimulation consisting of sinusoidal gratings. The average pupil area of Fragile X mice was increased compared to wild type controls. Our results suggest that online pupillometry has a high potential to serve as a diagnostic tool for autism spectrum disorders

Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as potential substrates for proteolytic maturation

The CA (capsid) domain of immature HIV-1 Gag and the adjacent spacer peptide 1 (SP1) play a key role in viral assembly by forming a lattice of CA hexamers, which adapts to viral envelope curvature by incorporating small lattice defects and a large gap at the site of budding. This lattice is stabilized by intrahexameric and interhexameric CA-CA interactions, which are important in regulating viral assembly and maturation. We applied subtomogram averaging and classification to determine the oligomerization state of CA at lattice edges and found that CA forms partial hexamers. These structures reveal the network of interactions formed by CA-SP1 at the lattice edge. We also performed atomistic molecular dynamics simulations of CA-CA interactions stabilizing the immature lattice and partial CA-SP1 helical bundles. Free energy calculations reveal increased propensity for helix-to-coil transitions in partial hexamers compared to complete six-helix bundles. Taken together, these results suggest that the CA dimer is the basic unit of lattice assembly, partial hexamers exist at lattice edges, these are in a helix-coil dynamic equilibrium, and partial helical bundles are more likely to unfold, representing potential sites for HIV-1 maturation initiation