Identification of presumed pathogenic KRT3 and KRT12 gene mutations associated with Meesmann corneal dystrophy.

PurposeTo report potentially pathogenic mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes in two individuals with clinically diagnosed Meesmann corneal dystrophy (MECD).MethodsSlit-lamp examination was performed on the probands and available family members to identify characteristic features of MECD. After informed consent was obtained, saliva samples were obtained as a source of genomic DNA, and screening of KRT3 and KRT12 was performed. Potentially pathogenic variants were screened for in 200 control chromosomes. PolyPhen-2, SIFT, and PANTHER were used to predict the functional impact of identified variants. Short tandem repeat genotyping was performed to confirm paternity.ResultsSlit-lamp examination of the first proband demonstrated bilateral, diffusely distributed, clear epithelial microcysts, consistent with MECD. Screening of KRT3 revealed a heterozygous missense variant in exon 1, c.250C>T (p.(Arg84Trp)), which has a minor allele frequency of 0.0076 and was not identified in 200 control chromosomes. In silico analysis with PolyPhen-2 and PANTHER predicted the variant to be damaging to protein function; however, SIFT analysis predicted tolerance of the variant. The second proband demonstrated bilateral, diffusely distributed epithelial opacities that appeared gray-white on direct illumination and translucent on retroillumination. Neither parent demonstrated corneal opacities. Screening of KRT12 revealed a novel heterozygous insertion/deletion variant in exon 6, c.1288_1293delinsAGCCCT (p.(Arg430_Arg431delinsSerPro)). This variant was not present in either of the proband's parents or in 200 control chromosomes and was predicted to be damaging by PolyPhen-2, PANTHER, and SIFT. Haplotype analysis confirmed paternity of the second proband, indicating that the variant arose de novo.ConclusionsWe present a novel KRT12 mutation, representing the first de novo mutation and the first indel in KRT12 associated with MECD. In addition, we report a variant of uncertain significance in KRT3 in an individual with MECD. Although the potential pathogenicity of this variant is unknown, it is the first variant affecting the head domain of K3 to be reported in an individual with MECD and suggests that disease-causing variants associated with MECD may not be restricted to primary sequence alterations of either the helix-initiation or helix-termination motifs of K3 and K12

Tandem concentrator solar cells with 30 percent (AMO) power conversion efficiency

Very high efficiency concentrator solar panels are envisioned as economical and reliable electrical power subsystems for space based platforms of the future. GaAs concentrator cells with very high efficiencies and good sub-bandgap transmissions can be fabricated on standard wafers. GaSb booster cell development is progressing very well; performance characteristics are still improving dramatically. Consistent GaAs/GaSb stacked cell AMO efficiencies greater than 30 percent are expected

Application of Beamforming Methods to Full-Scale Military Jet Noise

Over the past decade, beamforming in aeroacoustics applications have undergone significant advances. Cross beamforming methods improve upon traditional beamforming in that they relax the assumption of multiple-source incoherence. This paper compares the abilities of three cross beamforming methods to reproduce source and field characteristics for an extended, partially correlated source that mimics supersonic jet noise radiation. Standard cross beamforming and two related methods that involve regularization—the hybrid method and improved generalized inverse beamforming—are applied to a numerically generated dataset along a near-field line. Estimated levels and coherence lengths are compared with benchmarks at the source as well as near and far-field locations. All three methods are successful in reproducing the field and source properties in high-amplitude regions. Although regularization generally helps to improve both source and field reconstructions, results are sensitive to regularization parameters, particularly for the generalized inverse method. The successful application of the three methods demonstrate the utility of cross-beamforming in formulating equivalent source models for accurate field prediction of complex sources, including jet noise

Affinities and Beyond! Developing Ways of Seeing in Online Spaces

This article presents an insider view of an online community of adults involved in sharing digital photography through a host website, Flickr. It describes how reciprocal teaching and learning partnerships in a dynamic multimodal environment are achieved through the creation of a ‘Third Space’ or ‘Affinity Space’, where ‘Funds of Knowledge’ are shared and processed in such a way that new meanings and discourses are generated. It is argued that this process is evidence of valuable learning and of the deepening of global understandings within the local space of Flickr. The new understandings are at least partly identifiable on the Flickr space, through the co-constructed ‘folksonomy’ or ‘online taxonomy’ of ways of looking at the world. Further, the article provides evidence for broadening existing definitions of literacy, at a time when the visual mode increasingly works interactively with verbal cues and explanations

Stick-Slip Motion and Phase Transition in a Block-Spring System

We study numerically stick slip motions in a model of blocks and springs being pulled slowly. The sliding friction is assumed to change dynamically with a state variable. The transition from steady sliding to stick-slip is subcritical in a single block and spring system. However, we find that the transition is continuous in a long chain of blocks and springs. The size distribution of stick-slip motions exhibits a power law at the critical point.Comment: 8 figure

When probabilistic seismic hazard climbs volcanoes: the Mt. Etna case, Italy – Part 2: Computational implementation and first results

Abstract. This paper describes the model implementation and presents results of a probabilistic seismic hazard assessment (PSHA) for the Mt. Etna volcanic region in Sicily, Italy, considering local volcano-tectonic earthquakes. Working in a volcanic region presents new challenges not typically faced in standard PSHA, which are broadly due to the nature of the local volcano-tectonic earthquakes, the cone shape of the volcano and the attenuation properties of seismic waves in the volcanic region. These have been accounted for through the development of a seismic source model that integrates data from different disciplines (historical and instrumental earthquake datasets, tectonic data, etc.; presented in Part 1, by Azzaro et al., 2017) and through the development and software implementation of original tools for the computation, such as a new ground-motion prediction equation and magnitude–scaling relationship specifically derived for this volcanic area, and the capability to account for the surficial topography in the hazard calculation, which influences source-to-site distances. Hazard calculations have been carried out after updating the most recent releases of two widely used PSHA software packages (CRISIS, as in Ordaz et al., 2013; the OpenQuake engine, as in Pagani et al., 2014). Results are computed for short- to mid-term exposure times (10 % probability of exceedance in 5 and 30 years, Poisson and time dependent) and spectral amplitudes of engineering interest. A preliminary exploration of the impact of site-specific response is also presented for the densely inhabited Etna's eastern flank, and the change in expected ground motion is finally commented on. These results do not account for M  >  6 regional seismogenic sources which control the hazard at long return periods. However, by focusing on the impact of M  <  6 local volcano-tectonic earthquakes, which dominate the hazard at the short- to mid-term exposure times considered in this study, we present a different viewpoint that, in our opinion, is relevant for retrofitting the existing buildings and for driving impending interventions of risk reduction

Identification of plasma and urinary metabolites and catabolites derived from orange juice (poly)phenols: analysis by high-performance liquid chromatography–high-resolution mass spectrometry

Orange juice is a rich source of (poly)phenols, in particular, the flavanones hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside. Following the acute consumption of 500 mL of orange juice containing 398 μmol of (poly)phenols by 12 volunteers, 0–24 h plasma and urine samples were analyzed by targeted high-performance liquid chromatography–high-resolution mass spectrometry in order to identify flavanone metabolites and phenolic acid and aromatic catabolites. A total of 19 flavanone metabolites—comprising di-O-glucuronide, O-glucuronide, O-glucuronyl-sulfate, and sulfate derivatives of hesperetin, naringenin, and eriodictyol—and 65 microbial-derived phenolic catabolites, such as phenylpropanoid, phenylpropionic, phenylacetic, benzoic, and hydroxycarboxylic acids and benzenetriol and benzoylglycine derivatives, including free phenolics and phase II sulfate, glucuronide, and methyl metabolites, were identified or partially identified in plasma and/or urine samples. The data obtained provide a detailed evaluation of the fate of orange juice (poly)phenols as they pass through the gastrointestinal tract and are absorbed into the circulatory system prior to renal excretion. Potential pathways for these conversions are proposed

Stigmergy: A key driver of self-organization in bacterial biofilms

Bacterial biofilms are complex multicellular communities that are often associated with the emergence of large-scale patterns across the biofilm. How bacteria self-organize to form these structured communities is an area of active research. We have recently determined that the emergence of an intricate network of trails that forms during the twitching motility mediated expansion of Pseudomonas aeruginosa biofilms is attributed to an interconnected furrow system that is forged in the solidified nutrient media by aggregates of cells as they migrate across the media surface. This network acts as a means for self-organization of collective behavior during biofilm expansion as the cells following these vanguard aggregates were preferentially confined within the furrow network resulting in the formation of an intricate network of trails of cells. Here we further explore the process by which the intricate network of trails emerges. We have determined that the formation of the intricate network of furrows is associated with significant remodeling of the sub-stratum underlying the biofilm. The concept of stigmergy has been used to describe a variety of self-organization processes observed in higher organisms and abiotic systems that involve indirect communication via persistent cues in the environment left by individuals that influence the behavior of other individuals of the group at a later point in time. We propose that the concept of stigmergy can also be applied to describe self-organization of bacterial biofilms and can be included in the repertoire of systems used by bacteria to coordinate complex multicellular behaviors

Characterization of High-Power Rocket and Jet Noise Using Near-Field Acoustical Holography

Structural fatigue, hearing damage, and community disturbances are all consequences of rocket and jet noise, especially as they become more powerful. Noise-reduction schemes require accurate characterization of the noise sources within rocket plumes and jets. Nearfield acoustical holography (NAH) measurements were made to visualize the sound field in the jet exhaust region of an F-22 Raptor. This is one of the largest-scale applications of NAH since its development in the 1980s. A scan-based holographic measurement was made using a 90-microphone array with 15 cm regular grid spacing, for four engine power settings. The array was scanned through 93 measurement positions, along three different planes in a region near 7 m from the jet centerline and 23 m downstream. In addition, 50 fixed reference microphones were placed along the ground 11.6 m from the jet centerline, spanning 30.8 m. The reference microphones have been used to perform virtual coherence on the measurement planes. Statistically-optimized NAH (SONAH) has been used to backpropagate the sound field to the source region for low frequencies, and to identify jet noise characteristics. Ground reflection interference and other non-ideal measurement conditions must be dealt with. Details relating to jet coherence lengths and their relation to reference microphone requirements will be discussed. Preliminary results of this ongoing work will be presented. [Work supported by Air Force SBIR.