Anti-Semaphorin 4D Rescues Motor,Cognitive, and Respiratory Phenotypes in a Rett Syndrome Mouse Model

Rett syndrome is a neurodevelopmental disorder caused by mutations of the methyl-CpG binding protein 2 gene. Abnormal physiological functions of glial cells contribute to pathogenesis of Rett syndrome. Semaphorin 4D (SEMA4D) regulates processes central to neuroinflammation and neurodegeneration including cytoskeletal structures required for process extension, communication, and migration of glial cells. Blocking SEMA4D-induced gliosis may preserve normal glial and neuronal function and rescue neurological dysfunction in Rett syndrome. We evaluated the pre-clinical therapeutic efficacy of an anti-SEMA4D monoclonal antibody in the Rett syndrome Mecp2T158A transgenic mouse model and investigated the contribution of glial cells as a proposed mechanism of action in treated mice and in primary glial cultures isolated from Mecp2T158A/y mutant mice. SEMA4D is upregulated in neurons while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1-positive cells are upregulated in Mecp2T158A/y mice. Anti-SEMA4D treatment ameliorates Rett syndrome-specific symptoms and improves behavioural functions in both pre-symptomatic and symptomatic cohorts of hemizygous Mecp2T158A/y male mice. Anti-SEMA4D also reduces astrocyte and microglia activation in vivo. In vitro experiments demonstrate an abnormal cytoskeletal structure in mutant astrocytes in the presence of SEMA4D, while anti-SEMA4D antibody treatment blocks SEMA4D–Plexin B1 signaling and mitigates these abnormalities. These results suggest that anti-SEMA4D immunotherapy may be an effective treatment option to alleviate symptoms and improve cognitive and motor function in Rett syndrome.     

Escaping the Trough: Towards Real-World Impact of Tabletop Research

In the past decade, there has been increasing interest in studying tabletop technologies in HCI. Using the Gartners Hype Cycle as an analytical framework, this article presents developments in tabletop research within the last decade. The objective is to determine the level of maturity of tabletop technologies with respect to the research foci and the extent to which tabletops have shown their worth in real world settings. We identify less studied topics in the current body of literature with the primary aim of evoking further discussions of the current and future research challenges. We analyzed 542 research publications and categorized these according to eight types of research foci. Findings show that only 3% of all studies are conducted in natural settings, i.e. there is a clear tendency to emphasize laboratory evaluations of tabletop technology. Also, very few studies demonstrate relative benefits of tabletops over other technologies in collaborative settings (1%). We argue for a need to increase emphasis on understanding real-world use and impact rather than developing new tabletop technologies.     

Analog VLSI neural networks: implementation issues and examples inoptimization and supervised learning

Time-critical neural network applications that require fully parallel hardware implementations for maximal throughput are considered. The rich array of technologies that are being pursued is surveyed, and the analog CMOS VLSI medium approach is focused on. This medium is messy in that limited dynamic range, offset voltages, and noise sources all reduce precision. The authors examine how neural networks can be directly implemented in analog VLSI, giving examples of approaches that have been pursued to date. Two important application areas are highlighted: optimization, because neural hardware may offer a speed advantage of orders of magnitude over other methods; and supervised learning, because of the widespread use and generality of gradient-descent learning algorithms as applied to feedforward networks     

Noise in Photomultiplier Tubes

Direct measurements of the statistical gain fluctuations occurring in the electron multiplication process in a sampling of multiplier phototubes are reported. The results are expressed in terms of the effective reduction of the photocathode quantum efficiency, i.e. the noise factor, as determined by a comparison of the experimentally observed output signal-to-noise ratio with the expected ratio based on independent direct current measurements of photocathode quantum efficiency. The spread in the measured magnitudes of the resultant noise factor, in nominally identical tube types, is sufficient to demonstrate that both photocathode quantum efficiency and electron multiplier noise factor should be specified if optimum detector performance is to be assured.     

Hole diffusion length in high purity n-GaAs

Measurements on high purity epitaxial n-GaAs surface barrier diodes with the scanning electron microscope have shown that the hole diffusion length is 200 ωm. This is in agreement with the value of hole lifetime calculated from Hall's theory of recombination processes. The lower values obtained in earlier work are attributed to the lower purity of the material used.     

Photoemission spectroscopy of heterojunctions of amorphoushydrogenated silicon with silicon oxide and nitride

A study of the growth and electronic structure of a-Si:H/a-SiN_x:H and a-Si:H/a-SiO_x:H heterojunctions by photoemission spectroscopy is discussed. The interfaces in a-Si:H/a-SiO_x are atomically abrupt, except for the SiO_x on the Si interface which is graded over ~3 Å due to plasma oxidation. The offset energies between the a-Si:H valence band and those of a-SiN_x:H and a-SiO_x:H are 1.2 and 4.0 eV, respectively. Extra H(~2×10¹⁵) is incorporated in the Si on the SiN_x interface region. The hole wave functions in a-Si:H are localized on a scale of 1-2 interatomic distances     

Flux‐Limited Diffusion for Multiple Scattering in Participating Media

For the rendering of multiple scattering effects in participating media, methods based on the diffusion approximation are an extremely efficient alternative to Monte Carlo path tracing. However, in sufficiently transparent regions, classical diffusion approximation suffers from non‐physical radiative fluxes which leads to a poor match to correct light transport. In particular, this prevents the application of classical diffusion approximation to heterogeneous media, where opaque material is embedded within transparent regions. To address this limitation, we introduce flux‐limited diffusion, a technique from the astrophysics domain. This method provides a better approximation to light transport than classical diffusion approximation, particularly when applied to heterogeneous media, and hence broadens the applicability of diffusion‐based techniques. We provide an algorithm for flux‐limited diffusion, which is validated using the transport theory for a point light source in an infinite homogeneous medium. We further demonstrate that our implementation of flux‐limited diffusion produces more accurate renderings of multiple scattering in various heterogeneous datasets than classical diffusion approximation, by comparing both methods to ground truth renderings obtained via volumetric path tracing.     

Direct raytracing of a closed-form fluid meniscus

We present a direct raytracing method for implicitly described fluid surfaces that takes into account the effects of capillary solid coupling at the boundaries. The method is independent of the underlying fluid simulation method and solely based on distance fields. We make use of the closed-form solution of the meniscus shape at the fluid interface to achieve the effect of surface tension exerted by the solid object. The shape of the liquid at these boundaries is influenced by various physical properties such as the force of gravity and the affinity between the liquid and the solid material. We generate contact angles at the boundaries without the need for computationally intensive small-scale simulation. At render time, we combine the closed-form solution for a small-scale effect with the numerical solution of a large-scale simulation. Our method is applicable for any implicit representation of the fluid surface and does not require an explicit extraction of the surface geometry. Therefore, it is especially useful for particle-based simulations. Furthermore, the solution is guaranteed to yield the correct contact angle and, for certain scenarios, it delivers the entirely correct solution throughout the interface; even in general scenarios, it yields plausible results. As for an example, we implemented and tested the proposed method in the setting of a smoothed particle hydrodynamics (SPH) fluid simulation.