Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus.

Usher 1 patients are born profoundly deaf and then develop retinal degeneration. Thus they are readily identified before the onset of retinal degeneration, making gene therapy a viable strategy to prevent their blindness. Here, we have investigated the use of adeno-associated viruses (AAVs) for the delivery of the Usher 1B gene, MYO7A, to retinal cells in cell culture and in Myo7a-null mice. MYO7A cDNA, under control of a smCBA promoter, was packaged in single AAV2 and AAV5 vectors and as two overlapping halves in dual AAV2 vectors. The 7.9-kb smCBA-MYO7A exceeds the capacity of an AAV vector; packaging of such oversized constructs into single AAV vectors may involve fragmentation of the gene. Nevertheless, the AAV2 and AAV5 single vector preparations successfully transduced photoreceptor and retinal pigment epithelium cells, resulting in functional, full-length MYO7A protein and correction of mutant phenotypes, suggesting successful homologous recombination of gene fragments. With discrete, conventional-sized dual AAV2 vectors, full-length MYO7A was detected, but the level of protein expression was variable, and only a minority of cells showed phenotype correction. Our results show that MYO7A therapy with AAV2 or AAV5 single vectors is efficacious; however, the dual AAV2 approach proved to be less effective

Assessing the usability of tile-based interfaces to visually navigate 3-D parameter domains

Navigating 3-D parameter domains, such as color and orientation of an object, is a common task performed in most computer graphics applications. Although 1-D sliders are the most common interface for browsing such domains, they provide a tedious and difficult user experience that hampers finding desirable visual solutions. We present the Rhomb-i slider, a novel and visually enriching tile-based interface to navigate arbitrary 3-D parameter domains. Contrary to 1-D sliders, the Rhomb-i slider supports a sketch-based interface that gives simultaneous access to up to two parameters. We conducted a usability study to ascertain whether the proposed Rhomb-i slider is a more natural interface compared to 1-D sliders and other commonly used widgets for different 3-D parameter domains: HSV color space, super-shape curves, and rotation of a 3-D object. On the one hand, qualitative feedback and performance measures reveal that Rhomb-i sliders have similar results when compared to conventional HSV color interfaces, and are the preferred interface to efficiently explore the super-shapes parameter domain. On the other hand, Rhomb-i revealed to be a less efficient and effective interface to rotate a 3D object, thus paving the way to new design explorations regarding this tile-based interface

Stroke-based splatting: an efficient multi-resolution point cloud visualization technique

Current state-of-the-art point cloud visualization techniques have shortcomings when dealing with sparse and less accurate data or close-up interactions. In this paper, we present a visualization technique called stroke-based splatting, which applies concepts of stroke-based rendering to surface-aligned splatting, allowing for better shape perception at lower resolutions and close-ups. We create a painterly depiction of the data with an impressionistic aesthetic, which is a metaphor the user is culturally trained to recognize, thus attributing higher quality to the visualization. This is achieved by shaping each object-aligned splat as a brush stroke, and orienting it according to globally coherent tangent vectors from the Householder formula, creating a painterly depiction of the scanned cloud. Each splat is sized according to a color-based clustering analysis of the data, ensuring the consistency of brush strokes within neighborhood areas. By controlling brush shape generation parameters and blending factors between neighboring splats, the user is able to simulate different painting styles in real time. We have tested our method with data sets captured by commodity laser scanners as well as publicly available high-resolution point clouds, both having highly interactive frame rates in all cases. In addition, a user study was conducted comparing our approach to state-of-the-art point cloud visualization techniques. Users considered stroke-based splatting a valuable technique as it provides a higher or similar visual quality to current approaches

Nernst branes from special geometry

We construct new black brane solutions in $U(1)$ gauged ${\cal N}=2$ supergravity with a general cubic prepotential, which have entropy density $s\sim T^{1/3}$ as $T \rightarrow 0$ and thus satisfy the Nernst Law. By using the real formulation of special geometry, we are able to obtain analytical solutions in closed form as functions of two parameters, the temperature $T$ and the chemical potential $\mu$. Our solutions interpolate between hyperscaling violating Lifshitz geometries with $(z,\theta)=(0,2)$ at the horizon and $(z,\theta)=(1,-1)$ at infinity. In the zero temperature limit, where the entropy density goes to zero, we recover the extremal Nernst branes of Barisch et al, and the parameters of the near horizon geometry change to $(z,\theta)=(3,1)$.Comment: 37 pages. v2: numerical pre-factors of scalar fields q_A corrected in Section 3. No changes to conclusions. References adde

BPS dyons and Hesse flow

We revisit BPS solutions to classical N=2 low energy effective gauge theories. It is shown that the BPS equations can be solved in full generality by the introduction of a Hesse potential, a symplectic analog of the holomorphic prepotential. We explain how for non-spherically symmetric, non-mutually local solutions, the notion of attractor flow generalizes to gradient flow with respect to the Hesse potential. Furthermore we show that in general there is a non-trivial magnetic complement to this flow equation that is sourced by the momentum current in the solution.Comment: 25 pages, references adde

Linear Sigma Models with Torsion

Gauged linear sigma models with (0,2) supersymmetry allow a larger choice of couplings than models with (2,2) supersymmetry. We use this freedom to find a fully linear construction of torsional heterotic compactifications, including models with branes. As a non-compact example, we describe a family of metrics which correspond to deformations of the heterotic conifold by turning on H-flux. We then describe compact models which are gauge-invariant only at the quantum level. Our construction gives a generalization of symplectic reduction. The resulting spaces are non-Kahler analogues of familiar toric spaces like complex projective space. Perturbatively conformal models can be constructed by considering intersections.Comment: 40 pages, LaTeX, 1 figure; references added; a new section on supersymmetry added; quantization condition revisite

A canonical correlation analysis of the association between carcass and ham traits in pigs used to produce dry-cured ham

The association between carcass and ham traits in a pig population used to produce dry-cured ham was studied using canonical correlation analysis. The carcass traits examined were hot carcass weight (HCW), backfat thickness (BT) and loin depth (LD), and the ham traits studied were gross ham weight (GHW), trimmed ham weight (THW), ham inner layer fat thickness (HIFT), ham outer layer fat thickness (HOFT), pH (pH) and the Göfo value. Carcass and ham traits are not independent. The canonical correlations (r) between the carcass and ham traits at 130 kg were 0.77, 0.24 and 0.20 for the first, second and third canonical pair, respectively, and were all significant (p < 0.01) by the Wilks test. The corresponding canonical correlations between the three canonical variate pairs for the carcass and ham traits at 160 kg were 0.88, 0.42 and 0.14, respectively (p < 0.05 for all, except the third). The correlations between the traits and their canonical variate showed an association among HCW, GHW and THW, and between BT and HOFT. These results indicate that carcass traits should be used to cull pigs that are not suitable for dry-cured ham production