352 research outputs found
Reliable low-cost fabrication of low-loss waveguides with 5.4-dB optical gain
A reliable and reproducible deposition process for the fabrication of waveguides with losses as low as 0.1 dB/cm has been developed. The thin films are grown at ~ 5 nm/min deposition rate and exhibit excellent thickness uniformity within 1% over 50times50 mm2 area and no detectable incorporation. For applications of the films in compact, integrated optical devices, a high-quality channel waveguide fabrication process is utilized. Planar and channel propagation losses as low as 0.1 and 0.2 dB/cm, respectively, are demonstrated. For the development of active integrated optical functions, the implementation of rare-earth-ion doping is investigated by cosputtering of erbium during the layer growth. Dopant levels between 0.2-5times are studied. At concentrations of interest for optical amplification, a lifetime of the 4I13/2 level as long as 7 ms is measured. Gain measurements over 6.4-cm propagation length in a 700-nm-thick channel waveguide result in net optical gain over a 41-nm-wide wavelength range between 1526-1567 nm with a maximum of 5.4 dB at 1533 n
The Parkinson's Disease genome-wide association study locus browser
Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus. Methods: We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data. Results: We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets. Conclusions: Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered
Rare-earth-ion-doped Al<sub>2</sub>O<sub>3</sub> waveguides for active integrated optical devices
Growth, micro-structuring, spectroscopy, and optical gain in as-deposited waveguides
Deposition and micro-structuring of layers with low background losses (0.11 dB/cm) and lifetimes up to 7 ms have been optimized for active devices. Net gain of 0.7 dB/cm at 1533 nm has been measured.\ud
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Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson's disease on chromosome 7p15.3
Genome wide association studies (GWAS) for Parkinson's disease (PD) have previously revealed a significant association with a locus on chromosome 7p15.3, initially designated as the glycoprotein non-metastatic melanoma protein B (GPNMB) locus. In this study, the functional consequences of this association on expression were explored in depth by integrating different expression quantitative trait locus (eQTL) datasets (Braineac, CAGEseq, GTEx, and Phenotype-Genotype Integrator (PheGenI)). Top risk SNP rs199347 eQTLs demonstrated increased expressions of GPNMB, KLHL7, and NUPL2 with the major allele (AA) in brain, with most significant eQTLs in cortical regions, followed by putamen. In addition, decreased expression of the antisense RNA KLHL7-AS1 was observed in GTEx. Furthermore, rs199347 is an eQTL with long non-coding RNA (AC005082.12) in human tissues other than brain. Interestingly, transcript-specific eQTLs in immune-related tissues (spleen and lymphoblastoid cells) for NUPL2 and KLHL7-AS1 were observed, which suggests a complex functional role of this eQTL in specific tissues, cell types at specific time points. Significantly increased expression of GPNMB linked to rs199347 was consistent across all datasets, and taken in combination with the risk SNP being located within the GPNMB gene, these results suggest that increased expression of GPNMB is the causative link explaining the association of this locus with PD. However, other transcript eQTLs and subsequent functional roles cannot be excluded. This highlights the importance of further investigations to understand the functional interactions between the coding genes, antisense, and non-coding RNA species considering the tissue and cell-type specificity to understand the underlying biological mechanisms in PD
Optimization of Al<sub>2</sub>O<sub>3</sub>:Er<sup>3+</sup> waveguide technology for active integrated optical devices
Investigation of optical gain in Al<sub>2</sub>O<sub>3</sub>:Er channel waveguide amplifiers
Reactively co-sputtered aluminum oxide layers with low background loss and varying Er concentrations have been deposited. Net optical gain of 0.76 dB/cm was obtained for an Er concentration of 0.9× in a channel waveguide
A population scale analysis of rare SNCA variation in the UK Biobank
Parkinson's disease (PD) is a complex neurodegenerative disease with a variety of genetic and environmental factors contributing to disease. The SNCA gene encodes for the alpha-synuclein protein which plays a central role in PD, where aggregates of this protein are one of the pathological hallmarks of disease. Rare point mutations and copy number gains of the SNCA gene have been shown to cause autosomal dominant PD, and common DNA variants identified using Genome-Wide Association Studies (GWAS) are a moderate risk factor for PD. The UK Biobank is a large-scale population prospective study including ~500,000 individuals that has revolutionized human genetics. Here we assessed the frequency of SNCA variation in this cohort and identified 30 subjects carrying variants of interest including duplications (n = 6), deletions (n = 6) and large complex likely mosaic events (n = 18). No known pathogenic missense variants were identified. None of these subjects were reported to be a PD case, although it is possible that these individuals may develop PD at a later age, and whilst three had known prodromal features, these did not meet defined clinical criteria for being considered ‘prodromal’ cases. Seven of the 18 large complex carriers showed a history of blood based cancer. Overall, we identified copy number variants in the SNCA region in a large population based cohort without reported PD phenotype and symptoms. Putative mosaicism of the SNCA gene was identified, however, it is unclear whether it is associated with PD. These individuals are potential candidates for further investigation by performing SNCA RNA and protein expression studies, as well as promising clinical trial candidates to understand how duplication carriers potentially escape PD
Penetrance of Parkinson's Disease in LRRK2 p.G2019S Carriers Is Modified by a Polygenic Risk Score
Pentti Tienari työryhmän jäsenenä.Background Although the leucine-rich repeat kinase 2 p.G2019S mutation has been demonstrated to be a strong risk factor for PD, factors that contribute to penetrance among carriers, other than aging, have not been well identified. Objectives To evaluate whether a cumulative genetic risk identified in the recent genome-wide study is associated with penetrance of PD among p.G2019S mutation carriers. Methods We included p.G2019S heterozygote carriers with European ancestry in three genetic cohorts in which the mutation carriers with and without PD were selectively recruited. We also included the carriers from two data sets: one from a case-control setting without selection of mutation carriers and the other from a population sampling. Associations between polygenic risk score constructed from 89 variants reported recently and PD were tested and meta-analyzed. We also explored the interaction of age and PRS. Results After excluding eight homozygotes, 833 p.G2019S heterozygote carriers (439 PD and 394 unaffected) were analyzed. Polygenic risk score was associated with a higher penetrance of PD (odds ratio: 1.34; 95% confidence interval: [1.09, 1.64] per +1 standard deviation; P = 0.005). In addition, associations with polygenic risk score and penetrance were stronger in the younger participants (main effect: odds ratio 1.28 [1.04, 1.58] per +1 standard deviation; P = 0.022; interaction effect: odds ratio 0.78 [0.64, 0.94] per +1 standard deviation and + 10 years of age; P = 0.008). Conclusions Our results suggest that there is a genetic contribution for penetrance of PD among p.G2019S carriers. These results have important etiological consequences and potential impact on the selection of subjects for clinical trials. (c) 2020 International Parkinson and Movement Disorder SocietyPeer reviewe
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