High-order harmonic generation from Rydberg states at fixed Keldysh parameter

Because the commonly adopted viewpoint that the Keldysh parameter $\gamma$ determines the dynamical regime in strong field physics has long been demonstrated to be misleading, one can ask what happens as relevant physical parameters, such as laser intensity and frequency, are varied while $\gamma$ is kept fixed. We present results from our one- and fully three-dimensional quantum simulations of high-order harmonic generation (HHG) from various bound states of hydrogen with $n$ up to 40, where the laser intensities and the frequencies are scaled from those for $n=1$ in order to maintain a fixed Keldysh parameter $\gamma$$< 1$ for all $n$. We find that as we increase $n$ while keeping $\gamma$ fixed, the position of the cut-off scales in well defined manner. Moreover, a secondary plateau forms with a new cut-off, splitting the HHG plateau into two regions. First of these sub-plateaus is composed of lower harmonics, and has a higher yield than the second one. The latter extends up to the semiclassical $I_p+3.17U_p$ cut-off. We find that this structure is universal, and the HHG spectra look the same for all $n\gtrsim 10$ when plotted as a function of the scaled harmonic order. We investigate the $n$-, $l$- and momentum distributions to elucidate the physical mechanism leading to this universal structure

Phase-dependent interference fringes in the wavelength scaling of harmonic efficiency

We describe phase-dependent wavelength scaling of high-order harmonic generation efficiency driven by ultra-short laser fields in the mid-infrared. We employ both numerical solution of the time-dependent Schr\"{o}dinger equation and the Strong Field Approximation to analyze the fine-scale oscillations in the harmonic yield in the context of channel-closing effects. We show, by varying the carrier-envelope phase, that the amplitude of these oscillations depend strongly on the number of returning electron trajectories. Furthermore, the peak positions of the oscillations vary significantly as a function of the carrier-envelope phase. Owing to its practical applications, we also study the wavelength dependence of harmonic yield in the "single-cycle" limit, and observe a smooth variation in the wavelength scaling originating from the vanishing fine-scale oscillations.Comment: 5 pages, 4 figure

In Vivo Confirmation of the Role of Statins in Reducing Nitric Oxide and C-Reactive Protein Levels in Peripheral Arterial Disease

AbstractObjectivesInflammatory and other processes mediating impairment of endothelial function, where there are increased levels of C-reactive protein (CRP) and plasma nitrites, have a part to play in the early stages of peripheral arterial disease (PAD). Our objective was to analyse the effect of statins on the plasma nitrite and CRP levels in PAD.Material and methodsA prospective study of 30 patients with PAD Fontaine stage II, with no prior treatment with statins, determined high sensitivity (hs)-CRP and lipid profile in the patients. Plasma nitrite levels were determined by colourimetric assay based on the Griess reaction, at baseline and after 1 month of treatment with atorvastatin 40mgday−1.ResultsA significant reduction in plasma nitrite levels was detected after the treatment with statins (11.88±7.8μM vs. 5.7±1.8μM, p=0.0001). There was also a significant reduction in hs-CRP levels (13.58±24.00 vs. 3.93±3.19, p=0.02).When the patients were stratified according to claudication stage, a significant reduction in nitrite levels was obtained, both in patients with PAD Fontaine stage IIA (9.5±3.3μM vs. 5.3±1.7μM, p=0.0001) and in stage IIB (16.6±11.6μM vs. 6.7±1.8μM, p=0.032).ConclusionsTreatment with statins lowers plasma nitrite and CRP levels in patients with PAD. Our data support the effects of statins in vivo that have been demonstrated on the endothelium ex vivo, suggesting a beneficial effect by acting on the initial processes that trigger the disease, reducing oxidative stress (increase in the bioavailability of nitric oxide as peroxynitrite levels decrease) and curtailing the inflammatory processes which perpetuate the disease

Elaboración de aplicaciones interactivas para la docencia en el grado Grado de Telecomunicación

En este trabajo se muestran los avances realizados en el desarrollo de aplicaciones basadas en laboratorios virtuales para el estudio de la Acústica en el Grado de Telecomunicación. En particular se muestra la extensión de la aplicación VSLM accesible vía on-line y de carácter libre. Esta aplicación está implementada en lenguaje MATLAB y se basa en una interfaz gráfica sencilla que permite simular el funcionamiento de un sonómetro offline. El módulo incorporado a la aplicación permite calcular el tiempo de reverberación y una serie de parámetros relacionados con el mismo para poder caracterizar acústicamente salas y recintos. De forma paralela se muestran los avances realizados en la mejora de la aplicación implementada con anterioridad por los autores dedicada al estudio de las ondas mecánicas en barras con diferentes condiciones de contorno. La aplicación estaba implementada inicialmente en MATLAB para la parte gráfica y el interfaz, mientras que la parte de cálculo se realizó en C++. En este trabajo se muestran los resultados iniciales y la toma de contacto para la unificación de la interfaz y el código que implementa el método numérico en C++ mediante la librería Qt.En este trabajo se muestran los avances realizados en el desarrollo de aplicaciones basadas en laboratorios virtuales para el estudio de la Acústica en el Grado de Telecomunicación. En particular se muestra la extensión de la aplicación VSLM accesible vía on-line y de carácter libre. Esta aplicación está implementada en lenguaje MATLAB y se basa en una interfaz gráfica sencilla que permite simular el funcionamiento de un sonómetro offline. El módulo incorporado a la aplicación permite calcular el tiempo de reverberación y una serie de parámetros relacionados con el mismo para poder caracterizar acústicamente salas y recintos. De forma paralela se muestran los avances realizados en la mejora de la aplicación implementada con anterioridad por los autores dedicada al estudio de las ondas mecánicas en barras con diferentes condiciones de contorno. La aplicación estaba implementada inicialmente en MATLAB para la parte gráfica y el interfaz, mientras que la parte de cálculo se realizó en C++. En este trabajo se muestran los resultados iniciales y la toma de contacto para la unificación de la interfaz y el código que implementa el método numérico en C++ mediante la librería Qt.Peer ReviewedPostprint (published version

Author Correction: Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans

An amendment to this paper has been published and can be accessed via a link at the top of the paper

DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration

Purpose: Determining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD). Methods: Genome and exome sequencing were performed for five unrelated cases of IRD with no identified variant. In vitro assays were developed to validate the variants identified (fibroblast assay, induced pluripotent stem cell [iPSC] derived retinal organoids, and a dynein motility assay). Results: Four novel DYNC2H1 variants (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) and one previously reported variant (V5, g.103339363T>G) were identified. In proband 1 (V1/V2), V1 was predicted to introduce a premature termination codon (PTC), whereas V2 disrupted the exon 41 splice donor site causing incomplete skipping of exon 41. V1 and V2 impaired dynein-2 motility in vitro and perturbed IFT88 distribution within cilia. V3, homozygous in probands 2–4, is predicted to cause a PTC in a retina-predominant transcript. Analysis of retinal organoids showed that this new transcript expression increased with organoid differentiation. V4, a novel missense variant, was in trans with V5, previously associated with Jeune asphyxiating thoracic dystrophy (JATD). Conclusion: The DYNC2H1 variants discussed herein were either hypomorphic or affecting a retina-predominant transcript and caused nonsyndromic IRD. Dynein variants, specifically DYNC2H1 variants are reported as a cause of non syndromic IRD

The ADAMTS13-VWF axis is dysregulated in chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is an important consequence of pulmonary embolism that is associated with abnormalities in haemostasis. We investigated the ADAMTS13-von Willebrand factor (VWF) axis in CTEPH, including its relationship with disease severity, inflammation, ABO groups and ADAMTS13 genetic variants.ADAMTS13 and VWF plasma antigen levels were measured in patients with CTEPH (n=208), chronic thromboembolic disease without pulmonary hypertension (CTED) (n=35), resolved pulmonary embolism (n=28), idiopathic pulmonary arterial hypertension (n=30) and healthy controls (n=68). CTEPH genetic ABO associations and protein quantitative trait loci were investigated. ADAMTS13-VWF axis abnormalities were assessed in CTEPH and healthy control subsets by measuring ADAMTS13 activity, D-dimers and VWF multimeric size.Patients with CTEPH had decreased ADAMTS13 (adjusted β -23.4%, 95% CI -30.9- -15.1%, p<0.001) and increased VWF levels (β +75.5%, 95% CI 44.8-113%, p<0.001) compared to healthy controls. ADAMTS13 levels remained low after reversal of pulmonary hypertension by pulmonary endarterectomy surgery and were equally reduced in CTED. We identified a genetic variant near the ADAMTS13 gene associated with ADAMTS13 protein that accounted for ∼8% of the variation in levels.The ADAMTS13-VWF axis is dysregulated in CTEPH. This is unrelated to pulmonary hypertension, disease severity or markers of systemic inflammation and implicates the ADAMTS13-VWF axis in CTEPH pathobiology

Assessing the digenic model in rare disorders using population sequencing data

An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in different scenarios. We suggest that this approach will be relevant with the advent of new sequencing efforts including hundreds of thousands of samples

Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish

Purpose: Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo. Methods: Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish. Results: We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients. Inhibition of p53 rescued several defects of kars1−/− knockouts. Conclusion: Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets