14 research outputs found
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
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Growth and Strain of Hybrid Perovskite Films: Impacts on Stability and Light Emission
Hybrid halide perovskites (HHPs) are being commercialized as solar cells and are being investigated for use in a wide variety of other optoelectronic devices. The most efficient solar cells rely on alloys of the cubic perovskite AMX3 structure, such as (CS.FA,MA)Pb(I,Br)3, where FA and MA stand for formamidinium and methylammonium. HHPs have incredibly versatile structure and consequently, emission color, making them attractive for light emitting diodes or lasers. In addition to the AMX3 structure, HHPs can be made as two-dimensional (2D) materials, whereby large bulky organic cations separate M-X (metal-halide) semiconducting sheets. Tuning the thickness of the M-X layer changes the color of the exciton emission, and thus much effort has been devoted to making optoelectronic devices from 2D perovskites. Generally, HHP-based devices rely on polycrystalline thin films, which poses challenges: polycrystalline thin films contain grain boundaries, exhibit film strain, and are prone to forming undesired crystalline phases.Here, the fundamental structural, ionic and optical properties of HHP thin films are investigated. The first section is dedicated to understanding how film strains, such as those imparted by commercial fabrication procedures, may change sub-grain structure and cause degradation of the HHP. The second section examines phase stability and halide interdiffusion in mixed-halide 3D alloys. The third and fourth sections report phase-pure 2D film fabrication, and examine how strain and residual solvent can turn off certain emission features intrinsic to the 2D phase in question. These results help extend the utility of HHPs for optoelectronic devices by providing design rules for how to grow films with targeted structural and optoelectronic properties
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Growth and Strain of Hybrid Perovskite Films: Impacts on Stability and Light Emission
Hybrid halide perovskites (HHPs) are being commercialized as solar cells and are being investigated for use in a wide variety of other optoelectronic devices. The most efficient solar cells rely on alloys of the cubic perovskite AMX3 structure, such as (CS.FA,MA)Pb(I,Br)3, where FA and MA stand for formamidinium and methylammonium. HHPs have incredibly versatile structure and consequently, emission color, making them attractive for light emitting diodes or lasers. In addition to the AMX3 structure, HHPs can be made as two-dimensional (2D) materials, whereby large bulky organic cations separate M-X (metal-halide) semiconducting sheets. Tuning the thickness of the M-X layer changes the color of the exciton emission, and thus much effort has been devoted to making optoelectronic devices from 2D perovskites. Generally, HHP-based devices rely on polycrystalline thin films, which poses challenges: polycrystalline thin films contain grain boundaries, exhibit film strain, and are prone to forming undesired crystalline phases.Here, the fundamental structural, ionic and optical properties of HHP thin films are investigated. The first section is dedicated to understanding how film strains, such as those imparted by commercial fabrication procedures, may change sub-grain structure and cause degradation of the HHP. The second section examines phase stability and halide interdiffusion in mixed-halide 3D alloys. The third and fourth sections report phase-pure 2D film fabrication, and examine how strain and residual solvent can turn off certain emission features intrinsic to the 2D phase in question. These results help extend the utility of HHPs for optoelectronic devices by providing design rules for how to grow films with targeted structural and optoelectronic properties
Dynamic motion of organic spacer cations in Ruddlesden-Popper lead halide perovskites by solid-state NMR spectroscopy
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Ferroelastic Hysteresis in Thin Films of Methylammonium Lead Iodide
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Ferroelastic Hysteresis in Thin Films of Methylammonium Lead Iodide
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Phase Stability and Diffusion in Lateral Heterostructures of Methyl Ammonium Lead Halide Perovskites
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Chemical and Structural Diversity of Hybrid Layered Double Perovskite Halides
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Chemical and Structural Diversity of Hybrid Layered Double Perovskite Halides
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Bright magnetic dipole radiation from two-dimensional lead-halide perovskites.
Light-matter interactions in semiconductors are uniformly treated within the electric dipole approximation; multipolar interactions are considered "forbidden." We experimentally demonstrate that this approximation inadequately describes light emission in two-dimensional (2D) hybrid organic-inorganic perovskites (HOIPs), solution processable semiconductors with promising optoelectronic properties. By exploiting the highly oriented crystal structure, we use energy-momentum spectroscopies to demonstrate that an exciton-like sideband in 2D HOIPs exhibits a multipolar radiation pattern with highly directed emission. Electromagnetic and quantum-mechanical analyses indicate that this emission originates from an out-of-plane magnetic dipole transition arising from the 2D character of electronic states. Symmetry arguments and temperature-dependent measurements suggest a dynamic symmetry-breaking mechanism that is active over a broad temperature range. These results challenge the paradigm of electric dipole-dominated light-matter interactions in optoelectronic materials, provide new perspectives on the origins of unexpected sideband emission in HOIPs, and tease the possibility of metamaterial-like scattering phenomena at the quantum-mechanical level