Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics

AbstractEarly detection of axonal tissue loss in retinal nerve fiber layer (RNFL) is critical for effective treatment and management of diseases such as glaucoma. This study aims to evaluate the capability of ultrahigh-resolution optical coherence tomography with adaptive optics (UHR-AO-OCT) for imaging the RNFL axonal bundles (RNFBs) with 3×3×3μm3 resolution in the eye. We used a research-grade UHR-AO-OCT system to acquire 3°×3° volumes in four normal subjects and one subject with an arcuate retinal nerve fiber layer defect (n=5; 29–62years). Cross section (B-scans) and en face (C-scan) slices extracted from the volumes were used to assess visibility and size distribution of individual RNFBs. In one subject, we reimaged the same RNFBs twice over a 7month interval and compared bundle width and thickness between the two imaging sessions. Lastly we compared images of an arcuate RNFL defect acquired with UHR-AO-OCT and commercial OCT (Heidelberg Spectralis). Individual RNFBs were distinguishable in all subjects at 3° retinal eccentricity in both cross-sectional and en face views (width: 30–50μm, thickness: 10–15μm). At 6° retinal eccentricity, RNFBs were distinguishable in three of the five subjects in both views (width: 30–45μm, thickness: 20–40μm). Width and thickness RNFB measurements taken 7months apart were strongly correlated (p<0.0005). Mean difference and standard deviation of the differences between the two measurement sessions were −0.1±4.0μm (width) and 0.3±1.5μm (thickness). UHR-AO-OCT outperformed commercial OCT in terms of clarity of the microscopic retina. To our knowledge, these are the first measurements of RNFB cross section reported in the living human eye

Translation of Diverse Aramid- And 1,3-Dicarbonyl-peptides by Wild Type Ribosomes in Vitro

Here, we report that wild type Escherichia coli ribosomes accept and elongate precharged initiator tRNAs acylated with multiple benzoic acids, including aramid precursors, as well as malonyl (1,3-dicarbonyl) substrates to generate a diverse set of aramid-peptide and polyketide-peptide hybrid molecules. This work expands the scope of ribozyme- and ribosome-catalyzed chemical transformations, provides a starting point for in vivo translation engineering efforts, and offers an alternative strategy for the biosynthesis of polyketide-peptide natural products

Adaptive-optics Optical Coherence Tomography Processing Using a Graphics Processing Unit

Graphics processing units are increasingly being used for scientific computing for their powerful parallel processing abilities, and moderate price compared to super computers and computing grids. In this paper we have used a general purpose graphics processing unit to process adaptive-optics optical coherence tomography (AOOCT) images in real time. Increasing the processing speed of AOOCT is an essential step in moving the super high resolution technology closer to clinical viability

A First Close Look at the Balmer-edge Behavior of the Quasar Big Blue Bump

We have found for the first time a Balmer edge feature in the Big Blue Bump emission of a quasar. The feature is seen in the polarized flux spectrum of the quasar, where all the emissions from outside the nucleus are scraped off and removed. The existence of the Balmer-edge absorption feature directly indicates that the Big Blue Bump is indeed thermal and optically-thick.Comment: 2 pages, 2 figures. To be published in conference proceedings "Active Galactic Nuclei: from Central Engine to Host Galaxy

Local Radiation MHD Instabilities in Magnetically Stratified Media

We study local radiation magnetohydrodynamic instabilities in static, optically thick, vertically stratified media with constant flux mean opacity. We include the effects of vertical gradients in a horizontal background magnetic field. Assuming rapid radiative diffusion, we use the zero gas pressure limit as an entry point for investigating the coupling between the photon bubble instability and the Parker instability. Apart from factors that depend on wavenumber orientation, the Parker instability exists for wavelengths longer than a characteristic wavelength lambda_{tran}, while photon bubbles exist for wavelengths shorter than lambda_{tran}. The growth rate in the Parker regime is independent of the orientation of the horizontal component of the wavenumber when radiative diffusion is rapid, but the range of Parker-like wavenumbers is extended if there exists strong horizontal shear between field lines (i.e. horizontal wavenumber perpendicular to the magnetic field). Finite gas pressure introduces an additional short wavelength limit to the Parker-like behavior, and also limits the growth rate of the photon bubble instability to a constant value at short wavelengths. We also consider the effects of differential rotation with accretion disk applications in mind. Our results may explain why photon bubbles have not yet been observed in recent stratified shearing box accretion disk simulations. Photon bubbles may physically exist in simulations with high radiation to gas pressure ratios, but higher spatial resolution will be needed to resolve the asymptotically growing unstable wavelengths.Comment: The Astrophysical Journal, in pres

The dust-eliminated shape of quasar spectra in the near-infrared: a hidden part of the big blue bump

The near-infrared shape of the big blue bump component in quasar spectra has been essentially unknown. It usually cannot be observed directly, due to the strong hot dust emission which dominates quasar spectra longward of ~1micron. However this is quite an important part of the spectrum theoretically. At least bare disk models provide quite a robust prediction for the overall continuum shape in the near-infrared. Self-gravity should become important in the outer, near-infrared emitting regions of the putative disk, possibly leaving a signature of disk truncation in the near-infrared. We propose here that this important part of the spectrum can be revealed for the first time by observing polarized flux from normal quasars. At least in some polarized quasars, the emission lines are all unpolarized and so the polarized flux should originate interior to the broad line region, and therefore also interior to the dust emitting region. This can then be used to eliminate the dust emission. We present the results of near-infrared polarimetry for such three quasars (Ton202, 4C37.43, B2 1208+32). The data for Ton202 have the highest S/N, and the near-infrared polarized flux in this case is measured to have quite a blue shape, nu^+0.42+-0.29 in F_nu, intriguingly consistent with the simple multi-temperature black body, bare disk prediction of nu^+1/3. All these data, although still with quite low S/N for the other two objects, demonstrate the unique potential of the technique with future better data. We also present similar data for other quasars and radio galaxies, and briefly discuss the nature of the polarization.Comment: MNRAS in pres

Epigenetic and Transcriptional Dysregulation in T cells of Patients with Atopic Dermatitis

Rationale: Atopic dermatitis (AD) is linked to genetic and environmental risk factors. The effect of these factors on molecular and transcriptional events is not well understood. Immunologically, AD involves skin barrier defects and CD4+ T cells that produce inflammatory cytokines and amplify epidermal dysfunction Our objective was to investigate epigenetic mechanisms that may account for genetic susceptibility in CD4+ T cells. Methods: We measured chromatin accessibility (ATAC-seq), NFKB1 binding (ChIP-seq), and gene expression (RNA-seq) in anti-CD3/CD28 stimulated CD4+ T cells from 6 subjects with active moderate-to-severe AD and 6 age-matched non-allergic controls. Results: AD genetic risk loci were enriched for open chromatin regions in stimulated CD4+ T cells. The majority of ATAC-seq peaks were shared between matched AD-control pairs, consistent with those sections of chromatin being equally available. In contrast, NFKB DNA binding motifs were enriched in AD-dependent open chromatin. NFKB1 ChIP-seq identified genomic regions that were more strongly bound in AD cases, more strongly bound in controls, or shared between cases and controls. Chromatin that was strongly accessible and bound by NFKB1 in AD was enriched for AD genetic risk variants. Using whole genome sequencing data, we identified genotype-dependent accessible chromatin at AD risk loci corresponding to 32 genes with genotype-dependent expression in stimulated CD4+ T cells. Conclusions: The response of CD4+ T cells to stimulation is AD-specific and results in differential chromatin accessibility and transcription factor binding. These differences in transcriptional regulation result in epigenetic and transcriptional dysregulation in CD4+ T cells of patients with AD

Frontiers in Non-invasive Cardiac Mapping: Rotors in Atrial Fibrillation-Body Surface Frequency-Phase Mapping

[EN] Experimental and clinical data demonstrate that atrial fibrillation (AF) maintenance in animals and groups of patients depends on localized reentrant sources localized primarily to the pulmonary veins (PVs) and the left atrium(LA) posterior wall in paroxysmal AF but elsewhere, including the right atrium (RA), in persistent AF. Moreover, AF can be eliminated by directly ablating AFdriving sources or “rotors,” that exhibit high-frequency, periodic activity. The RADAR-AF randomized trial demonstrated that an ablation procedure based on a more target-specific strategy aimed at eliminating high frequency sites responsible for AF maintenance is as efficacious as and safer than empirically isolating all the PVs. In contrast to the standard ECG, global atrial noninvasive frequency analysis allows non-invasive identification of high-frequency sources before the arrival at the electrophysiology laboratory for ablation. Body surface potential map (BSPM) replicates the endocardial distribution of DFs with localization of the highest DF (HDF) and can identify small areas containing the high-frequency sources. Overall, BSPM had a sensitivity of 75% and specificity of 100% for capturing intracardiac EGMs as having LARA DF gradient. However, raw BSPM data analysis of AF patterns of activity showed incomplete and instable reentrant patterns of activation. Thus, we developed an analysis approach whereby a narrow band-pass filtering allowed selecting the electrical activity projected on the torso at the HDF, which stabilized the projection of rotors that potentially drive AF on the surface. Consequently, driving reentrant patterns (“rotors”) with spatiotemporal stability during >70% of the AF time could be observed noninvasibly after HDFfiltering. Moreover, computer simulations found that the combination of BSPM phase mapping with DF analysis enabled the discrimination of true rotational patterns even during the most complex AF. Altogether, these studies show that the combination of DF analysis with phase maps of HDF-filtered surface ECG recordings allows noninvasive localization of atrial reentries during AF and further a physiologically-based rationale for personalized diagnosis and treatment of patients with AF.Study supported in part by the Spanish Society of Cardiology (Becas Investigacio´ n Clı´nica 2009); the Universitat Polite` cnica de Vale`ncia through its research initiative program; the Generalitat Valenciana Grants (ACIF/2013/021); the Ministerio de Economia y Competividad, Red RIC; the Centro Nacional de Investigaciones Cardiovasculares (proyecto CNIC-13); the Coulter Foundation from the Biomedical Engineering Department (University of Michigan); the Gelman Award from the Cardiovascular Division (University of Michigan); the National Heart, Lung, and Blood Institute grants (P01-HL039707, P01-HL087226 and R01-HL118304), and the Leducq FoundationAtienza, F.; Climent, A.; Guillem Sánchez, MS.; Berenfeld, O. (2015). Frontiers in Non-invasive Cardiac Mapping: Rotors in Atrial Fibrillation-Body Surface Frequency-Phase Mapping. Cardiac Electrophysiology Clinics. 7(1):59-69. https://doi.org/10.1016/j.ccep.2014.11.002S59697

Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination - United States, 2001-2010

<p>Abstract</p> <p>Background</p> <p>Congenital rubella syndrome (CRS) is associated with several negative outcomes, including autism spectrum disorders (ASDs). The objective of this study was to estimate the numbers of CRS and ASD cases prevented by rubella vaccination in the United States from 2001 through 2010.</p> <p>Methods</p> <p>Prevention estimates were calculated through simple mathematical modeling, with values of model parameters determined from published literature. Model parameters included pre-vaccine era CRS incidence, vaccine era CRS incidence, the number of live births per year, and the percentage of CRS cases presenting with an ASD.</p> <p>Results</p> <p>Based on our estimates, 16,600 CRS cases (range: 8300-62,250) were prevented by rubella vaccination from 2001 through 2010 in the United States. An estimated 1228 ASD cases were prevented by rubella vaccination in the United States during this time period. Simulating a slight expansion in ASD diagnostic criteria in recent decades, we estimate that a minimum of 830 ASD cases and a maximum of 6225 ASD cases were prevented.</p> <p>Conclusions</p> <p>We estimate that rubella vaccination prevented substantial numbers of CRS and ASD cases in the United States from 2001 through 2010. These findings provide additional incentive to maintain high measles-mumps-rubella (MMR) vaccination coverage.</p