Effect of low-Raman window position on correlated photon-pair generation in a chalcogenide Ge11.5As24Se64.5 nanowire

We investigated correlated photon-pair generation via spontaneous four-wave mixing in an integrated chalcogenideGe11.5As24Se64.5photonicnanowire. The coincidence to accidental ratio, a key measurement for the quality of correlated photon-pair sources, was measured to be only 0.4 when the photon pairs were generated at 1.9 THz detuning from the pump frequency due to high spontaneous Raman noise in this regime. However, the existence of a characteristic low-Raman window at around 5.1 THz in this material's Raman spectrum and dispersion engineering of the nanowire allowed us to generate photon pairs with a coincidence to accidental ratio of 4.5, more than 10 times higher than the 1.9 THz case. Through comparing the results with those achieved in chalcogenide As2S3waveguides which also exhibit a low Raman-window but at a larger detuning of 7.4 THz, we find that the position of the characteristic low-Raman window plays an important role on reducing spontaneous Raman noise because the phonon population is higher at smaller detuning. Therefore the ultimate solution for Raman noise reduction in Ge11.5As24Se64.5 is to generate photon pairs outside the Raman gain band at more than 10 THz detuning

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

Structural and functional conservation of key domains in InsP3 and ryanodine receptors.

Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6 Å) and without (3.0 Å) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-β and IBC-α, identifies two discrete interfaces (α and β) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the β-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-β or B domain), to gate the pore

High index contrast polysiloxane waveguides fabricated by dry etching

The authors demonstrate the production of low loss enhanced index contrast waveguides by reactive ion etching of IPG™ polysiloxane thin films. The use of a silica mask and CHF₃∕O₂etch gas led to large etch selectivity between the silica and IPG™ of >20 and etch rates of >100nm∕min. This work indicates that compact optical circuits could be successfully fabricated for telecommunication applications using polysiloxane films.The support of the Australian Research Council through its Linkage grant and Federation Fellow programs is gratefully acknowledged as well as the financial support of RPO Inc

A New Hardware Correlator in Korea: Performance Evaluation using KVN observations

We report results of the performance evaluation of a new hardware correlator in Korea, the Daejeon correlator, developed by the Korea Astronomy and Space Science Institute (KASI) and the National Astronomical Observatory of Japan (NAOJ). We conducted Very Long Baseline Interferometry (VLBI) observations at 22~GHz with the Korean VLBI Network (KVN) in Korea and the VLBI Exploration of Radio Astrometry (VERA) in Japan, and correlated the aquired data with the Daejeon correlator. For evaluating the performance of the new hardware correlator, we compared the correlation outputs from the Daejeon correlator for KVN observations with those from a software correlator, the Distributed FX (DiFX). We investigated the correlated flux densities and brightness distributions of extragalactic compact radio sources. The comparison of the two correlator outputs show that they are consistent with each other within $<8\%$, which is comparable with the amplitude calibration uncertainties of KVN observations at 22~GHz. We also found that the 8\% difference in flux density is caused mainly by (a) the difference in the way of fringe phase tracking between the DiFX software correlator and the Daejeon hardware correlator, and (b) an unusual pattern (a double-layer pattern) of the amplitude correlation output from the Daejeon correlator. The visibility amplitude loss by the double-layer pattern is as small as 3\%. We conclude that the new hardware correlator produces reasonable correlation outputs for continuum observations, which are consistent with the outputs from the DiFX software correlator.Comment: 13 pagee, 9 figures, 3 tables, to appear in JKAS (received February 9, 2015; accepted March 16, 2015

Neprilysin Deficiency Protects Against Fat-Induced Insulin Secretory Dysfunction by Maintaining Calcium Influx

Neprilysin contributes to free fatty acid (FFA)-induced cellular dysfunction in nonislet tissues in type 2 diabetes. Here, we show for the first time that with prolonged FFA exposure, islet neprilysin is upregulated and this is associated with reduced insulin pre-mRNA and ATP levels, oxidative/nitrative stress, impaired potassium and calcium channel activities, and decreased glucose-stimulated insulin secretion (GSIS). Genetic ablation of neprilysin specifically protects against FFA-induced impairment of calcium influx and GSIS in vitro and in vivo but does not ameliorate other FFA-induced defects. Importantly, adenoviral overexpression of neprilysin in islets cultured without FFA reproduces the defects in both calcium influx and GSIS, suggesting that upregulation of neprilysin per se mediates insulin secretory dysfunction and that the mechanism for protection conferred by neprilysin deletion involves prevention of reduced calcium influx. Our findings highlight the critical nature of calcium signaling for normal insulin secretion and suggest that interventions to inhibit neprilysin may improve β-cell function in obese humans with type 2 diabetes

Glycotope structures and intramolecular affinity factors of plant lectins for Tn/T antigens

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All optical wavelength conversion via cross phase modulation in chalcogenide glass rib waveguides

We demonstrate all-optical wavelength conversion in a 5 cm As2S3 chalcogenide glass rib waveguide with 5.4 ps pulses over a wavelength range of 10 nm near 1550 nm. We present frequency resolved optical gating (FROG) measurements that show good converted pulse integrity in terms of amplitude and phase in the frequency and time domains. The short interaction length ensures that dispersion induced walkoff does not hinder the conversion range of the device