92 research outputs found
Recent progress in treatment of pulmonary arterial hypertension due to congenital heart disease
Atomic-scale confinement of optical fields
In the presence of matter there is no fundamental limit preventing
confinement of visible light even down to atomic scales. Achieving such
confinement and the corresponding intensity enhancement inevitably requires
simultaneous control over atomic-scale details of material structures and over
the optical modes that such structures support. By means of self-assembly we
have obtained side-by-side aligned gold nanorod dimers with robust
atomically-defined gaps reaching below 0.5 nm. The existence of
atomically-confined light fields in these gaps is demonstrated by observing
extreme Coulomb splitting of corresponding symmetric and anti-symmetric dimer
eigenmodes of more than 800 meV in white-light scattering experiments. Our
results open new perspectives for atomically-resolved spectroscopic imaging,
deeply nonlinear optics, ultra-sensing, cavity optomechanics as well as for the
realization of novel quantum-optical devices
Mode imaging and selection in strongly coupled nanoantennas
The number of eigenmodes in plasmonic nanostructures increases with
complexity due to mode hybridization, raising the need for efficient mode
characterization and selection. Here we experimentally demonstrate direct
imaging and selective excitation of the bonding and antibonding plasmon mode in
symmetric dipole nanoantennas using confocal two-photon photoluminescence
mapping. Excitation of a high-quality-factor antibonding resonance manifests
itself as a two-lobed pattern instead of the single spot observed for the broad
bonding resonance, in accordance with numerical simulations. The two-lobed
pattern is observed due to the fact that excitation of the antibonding mode is
forbidden for symmetric excitation at the feedgap, while concomitantly the mode
energy splitting is large enough to suppress excitation of the bonding mode.
The controlled excitation of modes in strongly coupled plasmonic nanostructures
is mandatory for efficient sensors, in coherent control as well as for
implementing well-defined functionalities in complex plasmonic devices.Comment: 11 pages, 5 figures, 1 supplementary informatio
Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation
Phenotypic Characterisation of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically with Pulmonary Arterial Hypertension
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis (PVOD/PCH). Here, we determined the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole genome sequencing was performed on DNA from patients with idiopathic and heritable PAH, as well as PVOD/PCH recruited to the NIHR BioResource - Rare Diseases Study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of < 1:10,000 in control data sets and predicted to be deleterious (by CADD, PolyPhen-2 and SIFT predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred and sixty-four patients with idiopathic or heritable PAH and 16 with PVOD/PCH were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of PVOD/PCH. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (KCO: 33 [IQR: 30 - 35] % predicted) and younger age at diagnosis (29 [23 - 38] years) as well as more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest, compared to PAH patients without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. PAH patients with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as idiopathic and heritable PAH. These patients cannot be identified reliably by CT, but a low KCO and a young age of diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation.The National Institute of Health Research (NIHR) BioResource for Rare Diseases provided funding for sequencing and analysis. The study was supported by a British Heart Foundation Special Project Grant and a Medical Research Council (UK) Experimental Challenge Award
Pulmonary venous occlusion and death in pulmonary arterial hypertension: survival analyses using radiographic surrogates
A polarizing situation: Taking an in-plane perspective for next-generation near-field studies
Experimentelle Studien ĂĽber den Nucleinstoffwechsel. 5. Mitteilung. Ăśber die Aufspaltung des Purinringes durch Bakterien der menschlichen Darmflora.
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