In Vivo Imaging of Human Cone Photoreceptor Inner Segments

PubMed Central

Scoles, Drew; Sulai, Yusufu N.; Langlo, Christopher S.; Fishman, Gerald A.; Curcio, Christine A.; Carroll, Joseph; Dubra, Alfredo

2014-01-01

Purpose. An often overlooked prerequisite to cone photoreceptor gene therapy development is residual photoreceptor structure that can be rescued. While advances in adaptive optics (AO) retinal imaging have recently enabled direct visualization of individual cone and rod photoreceptors in the living human retina, these techniques largely detect strongly directionally-backscattered (waveguided) light from normal intact photoreceptors. This represents a major limitation in using existing AO imaging to quantify structure of remnant cones in degenerating retina. Methods. Photoreceptor inner segment structure was assessed with a novel AO scanning light ophthalmoscopy (AOSLO) differential phase technique, that we termed nonconfocal split-detector, in two healthy subjects and four subjects with achromatopsia. Ex vivo preparations of five healthy donor eyes were analyzed for comparison of inner segment diameter to that measured in vivo with split-detector AOSLO. Results. Nonconfocal split-detector AOSLO reveals the photoreceptor inner segment with or without the presence of a waveguiding outer segment. The diameter of inner segments measured in vivo is in good agreement with histology. A substantial number of foveal and parafoveal cone photoreceptors with apparently intact inner segments were identified in patients with the inherited disease achromatopsia. Conclusions. The application of nonconfocal split-detector to emerging human gene therapy trials will improve the potential of therapeutic success, by identifying patients with sufficient retained photoreceptor structure to benefit the most from intervention. Additionally, split-detector imaging may be useful for studies of other retinal degenerations such as AMD, retinitis pigmentosa, and choroideremia where the outer segment is lost before the remainder of the photoreceptor cell. PMID:24906859

Localization of antibody binding sites in ultrathin sections of unembedded frog retinal tissue.

PubMed

Pease, D C; Nir, I; Clark, V; Hall, M

1983-01-01

Much ultrastructural detail is retained in tissue fixed only with aldehydes and subsequently air-dried after suspension in a polyvinyl acetate emulsion. The latter provides an external support only, but permits ultrathin sectioning; thus, an exposure of intracellular contents for potential immunocytochemical reactions is achieved. Sections of unembedded frog retina so prepared have been studied with success. The tissue was incubated first with a rabbit antiserum prepared against gradient purified bovine rod outer segments. Following incubation, reacted sites were labeled with ferritin-conjugated goat anti-rabbit IgG and stained with phosphotungstic acid. Intense labeling of the rod outer segments was clearly achieved, whereas the cone outer segments were without label. Other parts of the retina, including the ellipsoid region of both rods and cones, were also without significant label. These regions provided an intrinsic control for the specificity of the antiserum and established the validity of the general technique.

Acute Zonal Cone Photoreceptor Outer Segment Loss

PubMed Central

Sandhu, Harpal S.; Serrano, Leona W.; Traband, Anastasia; Lau, Marisa K.; Adamus, Grazyna; Avery, Robert A.

2017-01-01

Importance The diagnostic path presented narrows down the cause of acute vision loss to the cone photoreceptor outer segment and will refocus the search for the cause of similar currently idiopathic conditions. Objective To describe the structural and functional associations found in a patient with acute zonal occult photoreceptor loss. Design, Setting, and Participants A case report of an adolescent boy with acute visual field loss despite a normal fundus examination performed at a university teaching hospital. Main Outcomes and Measures Results of a complete ophthalmic examination, full-field flash electroretinography (ERG) and multifocal ERG, light-adapted achromatic and 2-color dark-adapted perimetry, and microperimetry. Imaging was performed with spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) and short-wavelength (SW) fundus autofluorescence (FAF), and NIR reflectance (REF). Results The patient was evaluated within a week of the onset of a scotoma in the nasal field of his left eye. Visual acuity was 20/20 OU, and color vision was normal in both eyes. Results of the fundus examination and of SW-FAF and NIR-FAF imaging were normal in both eyes, whereas NIR-REF imaging showed a region of hyporeflectance temporal to the fovea that corresponded with a dense relative scotoma noted on light-adapted static perimetry in the left eye. Loss in the photoreceptor outer segment detected by SD-OCT co-localized with an area of dense cone dysfunction detected on light-adapted perimetry and multifocal ERG but with near-normal rod-mediated vision according to results of 2-color dark-adapted perimetry. Full-field flash ERG findings were normal in both eyes. The outer nuclear layer and inner retinal thicknesses were normal. Conclusions and Relevance Localized, isolated cone dysfunction may represent the earliest photoreceptor abnormality or a distinct entity within the acute zonal occult outer retinopathy complex. Acute zonal occult outer retinopathy should be considered in patients with acute vision loss and abnormalities on NIR-REF imaging, especially if multimodal imaging supports an intact retinal pigment epithelium and inner retina but an abnormal photoreceptor outer segment. PMID:28384671

Histologic development of the human fovea from midgestation to maturity.

PubMed

Hendrickson, Anita; Possin, Daniel; Vajzovic, Lejla; Toth, Cynthia A

2012-11-01

To describe the histologic development of the human central retina from fetal week (Fwk) 22 to 13 years. Retrospective observational case series. Retinal layers and neuronal substructures were delineated on foveal sections of fixed tissue stained in azure II-methylene blue and on frozen sections immunolabeled for cone, rod, or glial proteins. Postmortem tissue was from 11 eyes at Fwk 20-27; 8 eyes at Fwk 28-37; 6 eyes at postnatal 1 day to 6 weeks; 3 eyes at 9 to 15 months; and 5 eyes at 28 months to 13 years. At Fwk 20-22 the fovea could be identified by the presence of a single layer of cones in the outer nuclear layer. Immunolabeling detected synaptic proteins, cone and rod opsins, and Müller glial processes separating the photoreceptors. The foveal pit appeared at Fwk 25, involving progressive peripheral displacement of ganglion cell, inner plexiform, and inner nuclear layers. The pit became wider and shallower after birth, and appeared mature by 15 months. Between Fwk 25 and Fwk 38, all photoreceptors developed more distinct inner and outer segments, but these were longer on peripheral than foveal cones. After birth the foveal outer nuclear layer became much thicker as cone packing occurred. Cone packing and neuronal migration during pit formation combined to form long central photoreceptor axons, which changed the outer plexiform layer from a thin sheet of synaptic pedicles into the thickest layer in the central retina by 15 months. Foveal inner and outer segment length matched peripheral cones by 15 months and was 4 times longer by 13 years. These data are necessary to understand the marked changes in human retina from late gestation to early adulthood. They provide qualitative and quantitative morphologic information required to interpret the changes in hyper- and hyporeflexive bands in pediatric spectral-domain optical coherence tomography images at the same ages. Copyright © 2012 Elsevier Inc. All rights reserved.

The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch

PubMed Central

Daum, Janine M; Keles, Özkan; Holwerda, Sjoerd JB; Kohler, Hubertus; Rijli, Filippo M

2017-01-01

High-resolution daylight vision is mediated by cone photoreceptors. The molecular program responsible for the formation of their light sensor, the outer segment, is not well understood. We correlated daily changes in ultrastructure and gene expression in postmitotic mouse cones, between birth and eye opening, using serial block-face electron microscopy (EM) and RNA sequencing. Outer segments appeared rapidly at postnatal day six and their appearance coincided with a switch in gene expression. The switch affected over 14% of all expressed genes. Genes that switched off were rich in transcription factors and neurogenic genes. Those that switched on contained genes relevant for cone function. Chromatin rearrangements in enhancer regions occurred before the switch was completed, but not after. We provide a resource comprised of correlated EM, RNAseq, and ATACseq data, showing that the growth of a key compartment of a postmitotic cell involves an extensive switch in gene expression and chromatin accessibility. PMID:29106373

Cone structure in patients with usher syndrome type III and mutations in the Clarin 1 gene.

PubMed

Ratnam, Kavitha; Västinsalo, Hanna; Roorda, Austin; Sankila, Eeva-Marja K; Duncan, Jacque L

2013-01-01

To study macular structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment-outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where cones were lost. Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without cones in patients with CLRN1 mutations. High-resolution measures of retinal structure demonstrate patterns of cone loss associated with CLRN1 mutations. These findings provide insight into the effect of CLRN1 mutations on macular cone structure, which has implications for the development of treatments for USH3. clinicaltrials.gov Identifier: NCT00254605.

The Cellular Origins of the Outer Retinal Bands in Optical Coherence Tomography Images

PubMed Central

Jonnal, Ravi S.; Kocaoglu, Omer P.; Zawadzki, Robert J.; Lee, Sang-Hyuck; Werner, John S.; Miller, Donald T.

2014-01-01

Purpose. To test the recently proposed hypothesis that the second outer retinal band, observed in clinical OCT images, originates from the inner segment ellipsoid, by measuring: (1) the thickness of this band within single cone photoreceptors, and (2) its respective distance from the putative external limiting membrane (band 1) and cone outer segment tips (band 3). Methods. Adaptive optics-optical coherence tomography images were acquired from four subjects without known retinal disease. Images were obtained at foveal (2°) and perifoveal (5°) locations. Cone photoreceptors (n = 9593) were identified and segmented in three dimensions using custom software. Features corresponding to bands 1, 2, and 3 were automatically identified. The thickness of band 2 was assessed in each cell by fitting the longitudinal reflectance profile of the band with a Gaussian function. Distances between bands 1 and 2, and between 2 and 3, respectively, were also measured in each cell. Two independent calibration techniques were employed to determine the depth scale (physical length per pixel) of the imaging system. Results. When resolved within single cells, the thickness of band 2 is a factor of three to four times narrower than in corresponding clinical OCT images. The distribution of band 2 thickness across subjects and eccentricities had a modal value of 4.7 μm, with 48% of the cones falling between 4.1 and 5.2 μm. No significant differences were found between cells in the fovea and perifovea. The distance separating bands 1 and 2 was found to be larger than the distance between bands 2 and 3, across subjects and eccentricities, with a significantly larger difference at 5° than 2°. Conclusions. On the basis of these findings, we suggest that ascription of the outer retinal band 2 to the inner segment ellipsoid is unjustified, because the ellipsoid is both too thick and proximally located to produce the band. PMID:25324288

Optics of retinal oil droplets: a model of light collection and polarization detection in the avian retina.

PubMed

Young, S R; Martin, G R

1984-01-01

A wave optical model was used to analyse the scattering properties of avian retinal oil droplets. Computations for the near field region showed that oil droplets perform significant light collection in cone photoreceptors and so enhance outer segment photon capture rates. Scattering by the oil droplet of the principal cone of a double cone pair, combined with accessory cone dichroic absorption under conditions of transverse illumination, may mediate avian polarization sensitivity.

Chromatic detection from cone photoreceptors to V1 neurons to behavior in rhesus monkeys

PubMed Central

Hass, Charles A.; Angueyra, Juan M.; Lindbloom-Brown, Zachary; Rieke, Fred; Horwitz, Gregory D.

2015-01-01

Chromatic sensitivity cannot exceed limits set by noise in the cone photoreceptors. To determine how close neurophysiological and psychophysical chromatic sensitivity come to these limits, we developed a parameter-free model of stimulus encoding in the cone outer segments, and we compared the sensitivity of the model to the psychophysical sensitivity of monkeys performing a detection task and to the sensitivity of individual V1 neurons. Modeled cones had a temporal impulse response and a noise power spectrum that were derived from in vitro recordings of macaque cones, and V1 recordings were made during performance of the detection task. The sensitivity of the simulated cone mosaic, the V1 neurons, and the monkeys were tightly yoked for low-spatiotemporal-frequency isoluminant modulations, indicating high-fidelity signal transmission for this class of stimuli. Under the conditions of our experiments and the assumptions for our model, the signal-to-noise ratio for these stimuli dropped by a factor of ∼3 between the cones and perception. Populations of weakly correlated V1 neurons narrowly exceeded the monkeys' chromatic sensitivity but fell well short of the cones' chromatic sensitivity, suggesting that most of the behavior-limiting noise lies between the cone outer segments and the output of V1. The sensitivity gap between the cones and behavior for achromatic stimuli was larger than for chromatic stimuli, indicating greater postreceptoral noise. The cone mosaic model provides a means to compare visual sensitivity across disparate stimuli and to identify sources of noise that limit visual sensitivity. PMID:26523737

Chromatic detection from cone photoreceptors to V1 neurons to behavior in rhesus monkeys.

PubMed

Hass, Charles A; Angueyra, Juan M; Lindbloom-Brown, Zachary; Rieke, Fred; Horwitz, Gregory D

2015-01-01

Chromatic sensitivity cannot exceed limits set by noise in the cone photoreceptors. To determine how close neurophysiological and psychophysical chromatic sensitivity come to these limits, we developed a parameter-free model of stimulus encoding in the cone outer segments, and we compared the sensitivity of the model to the psychophysical sensitivity of monkeys performing a detection task and to the sensitivity of individual V1 neurons. Modeled cones had a temporal impulse response and a noise power spectrum that were derived from in vitro recordings of macaque cones, and V1 recordings were made during performance of the detection task. The sensitivity of the simulated cone mosaic, the V1 neurons, and the monkeys were tightly yoked for low-spatiotemporal-frequency isoluminant modulations, indicating high-fidelity signal transmission for this class of stimuli. Under the conditions of our experiments and the assumptions for our model, the signal-to-noise ratio for these stimuli dropped by a factor of ∼3 between the cones and perception. Populations of weakly correlated V1 neurons narrowly exceeded the monkeys' chromatic sensitivity but fell well short of the cones' chromatic sensitivity, suggesting that most of the behavior-limiting noise lies between the cone outer segments and the output of V1. The sensitivity gap between the cones and behavior for achromatic stimuli was larger than for chromatic stimuli, indicating greater postreceptoral noise. The cone mosaic model provides a means to compare visual sensitivity across disparate stimuli and to identify sources of noise that limit visual sensitivity.

Meckelin 3 Is Necessary for Photoreceptor Outer Segment Development in Rat Meckel Syndrome

PubMed Central

Tiwari, Sarika; Hudson, Scott; Gattone, Vincent H.; Miller, Caroline; Chernoff, Ellen A. G.; Belecky-Adams, Teri L.

2013-01-01

Ciliopathies lead to multiorgan pathologies that include renal cysts, deafness, obesity and retinal degeneration. Retinal photoreceptors have connecting cilia joining the inner and outer segment that are responsible for transport of molecules to develop and maintain the outer segment process. The present study evaluated meckelin (MKS3) expression during outer segment genesis and determined the consequences of mutant meckelin on photoreceptor development and survival in Wistar polycystic kidney disease Wpk/Wpk rat using immunohistochemistry, analysis of cell death and electron microscopy. MKS3 was ubiquitously expressed throughout the retina at postnatal day 10 (P10) and P21. However, in the mature retina, MKS3 expression was restricted to photoreceptors and the retinal ganglion cell layer. At P10, both the wild type and homozygous Wpk mutant retina had all retinal cell types. In contrast, by P21, cells expressing rod- and cone-specific markers were fewer in number and expression of opsins appeared to be abnormally localized to the cell body. Cell death analyses were consistent with the disappearance of photoreceptor-specific markers and showed that the cells were undergoing caspase-dependent cell death. By electron microscopy, P10 photoreceptors showed rudimentary outer segments with an axoneme, but did not develop outer segment discs that were clearly present in the wild type counterpart. At p21 the mutant outer segments appeared much the same as the P10 mutant outer segments with only a short axoneme, while the wild-type controls had developed outer segments with many well-organized discs. We conclude that MKS3 is not important for formation of connecting cilium and rudimentary outer segments, but is critical for the maturation of outer segment processes. PMID:23516626

Longitudinal assessment of retinal structure and function reveals a rod-cone degeneration in a guinea pig model initially presented as night blind.

PubMed

Racine, Julie; Joly, Sandrine; Lachapelle, Pierre

2011-08-01

We have previously reported a naturally occurring retinopathy in a population of guinea pigs, where the affected animals presented a defect of the rod-mediated vision. The purpose of this study was to investigate if the mutants were affected with a stationary or degenerative retinopathy and to identify the cellular origin of this unique disorder. Electroretinogram (ERG) [postnatal day 1 (P1) to P450], light (LM) and electron microscopy (EM) [P5, P150, P450], and immunohistochemistry [P30, P150, P450] were evaluated from normal and mutant animals. Irrespective of age, the scotopic ERGs of mutants could only be evoked by bright flashes, and the resulting ERGs were of photopic waveform. Interestingly, the amplitude of the cone and the rod/cone a-waves was always of smaller amplitude in mutants, but this difference tended to decrease with age. In contrast, the b-waves were of larger amplitude than normal in photopic ERGs obtained prior to age 25 (days) and prior to age 10 for rod/cone ERGs. LM revealed, in mutants, an absence of the outer segment layer (OSL) with a reduction in the outer nuclear layer (ONL) thickness. EM disclosed the presence of cone outer segment (OS) while no rod OS could be evidenced. Immunohistochemistry revealed the presence of rhodopsin, both cone opsins as well as normal synaptophysin immunoreactivity. Finally, neither the retinal structure nor the function in the mutants achieved normal development. Results suggest that mutant animals are suffering from a degenerative retinal disorder that affects the structure and function of rods and cones.

Abnormal photoreceptor outer segment development and early retinal degeneration in kif3a mutant zebrafish.

PubMed

Raghupathy, Rakesh K; Zhang, Xun; Alhasani, Reem H; Zhou, Xinzhi; Mullin, Margaret; Reilly, James; Li, Wenchang; Liu, Mugen; Shu, Xinhua

2016-08-01

Photoreceptors are highly specialized sensory neurons that possess a modified primary cilium called the outer segment. Photoreceptor outer segment formation and maintenance require highly active protein transport via a process known as intraflagellar transport. Anterograde transport in outer segments is powered by the heterotrimeric kinesin II and coordinated by intraflagellar transport proteins. Here, we describe a new zebrafish model carrying a nonsense mutation in the kinesin II family member 3A (kif3a) gene. Kif3a mutant zebrafish exhibited curved body axes and kidney cysts. Outer segments were not formed in most parts of the mutant retina, and rhodopsin was mislocalized, suggesting KIF3A has a role in rhodopsin trafficking. Both rod and cone photoreceptors degenerated rapidly between 4 and 9 days post fertilization, and electroretinography response was not detected in 7 days post fertilization mutant larvae. Loss of KIF3A in zebrafish also resulted in an intracellular transport defect affecting anterograde but not retrograde transport of organelles. Our results indicate KIF3A plays a conserved role in photoreceptor outer segment formation and intracellular transport. Copyright © 2016 John Wiley & Sons, Ltd.

Cone Structure in Patients With Usher Syndrome Type III and Mutations in the Clarin 1 Gene

PubMed Central

Ratnam, Kavitha; Västinsalo, Hanna; Roorda, Austin; Sankila, Eeva-Marja K.; Duncan, Jacque L.

2015-01-01

Objective To study macular structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). Methods High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. Results CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment-outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where cones were lost. Conclusions Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without cones in patients with CLRN1 mutations. High-resolution measures of retinal structure demonstrate patterns of cone loss associated with CLRN1 mutations. Clinical Relevance These findings provide insight into the effect of CLRN1 mutations on macular cone structure, which has implications for the development of treatments for USH3. Trial Registration clinicaltrials.gov Identifier: NCT00254605 PMID:22964989

Photoreceptors in a primitive mammal, the South American opossum, Didelphis marsupialis aurita: characterization with anti-opsin immunolabeling.

PubMed

Ahnelt, P K; Hokoç, J N; Röhlich, P

1995-01-01

The retinas of placental mammals appear to lack the large number and morphological diversity of cone subtypes found in diurnal reptiles. We have now studied the photoreceptor layer of a South American marsupial (Didelphis marsupialis aurita) by peanut agglutinin labeling of the cone sheath and by labeling of cone outer segments with monoclonal anti-visual pigment antibodies that have been proven to consistently label middle-to-long wavelength (COS-1) and short-wavelength (OS-2) cone subpopulations in placental mammals. Besides a dominant rod population (max. = 400,000/mm2) four subtypes of cones (max. = 3000/mm2) were identified. The outer segments of three cone subtypes were labeled by COS-1: a double cone with a principal cone containing a colorless oil droplet, a single cone with oil droplet, and another single cone. A second group of single cones lacking oil droplets was labeled by OS-2 antibody. The topography of these cone subtypes showed striking anisotropies. The COS-1 labeled single cones without oil droplets were found all over the retina and constituted the dominant population in the area centralis located in the temporal quadrant of the upper, tapetal hemisphere. The population of OS-2 labeled cones was also ubiquitous although slightly higher in the upper hemisphere (200/mm2). The COS-1 labeled cones bearing an oil droplet, including the principal member of double cones, were concentrated (800/mm2) in the inferior, non-tapetal half of the retina. The two spectral types of single cones resemble those of dichromatic photopic systems in most placental mammals. The additional set of COS-1 labeled cones is a distinct marsupial feature. The presence of oil droplets in this cone subpopulation, its absence in the area centralis, and the correlation with the non-tapetal inferior hemisphere suggest a functional specialization, possibly for mesopic conditions. Thus, sauropsid features have been retained but probably with a modified function.

Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice.

PubMed

Sahly, Iman; Dufour, Eric; Schietroma, Cataldo; Michel, Vincent; Bahloul, Amel; Perfettini, Isabelle; Pepermans, Elise; Estivalet, Amrit; Carette, Diane; Aghaie, Asadollah; Ebermann, Inga; Lelli, Andrea; Iribarne, Maria; Hardelin, Jean-Pierre; Weil, Dominique; Sahel, José-Alain; El-Amraoui, Aziz; Petit, Christine

2012-10-15

The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins-myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans-do not display retinal degeneration. We found here that, in macaque photoreceptor cells, all USH1 proteins colocalized at membrane interfaces (i) between the inner and outer segments in rods and (ii) between the microvillus-like calyceal processes and the outer segment basolateral region in rods and cones. This pattern, conserved in humans and frogs, was mediated by the formation of an USH1 protein network, which was associated with the calyceal processes from the early embryonic stages of outer segment growth onwards. By contrast, mouse photoreceptors lacked calyceal processes and had no USH1 proteins at the inner-outer segment interface. We suggest that USH1 proteins form an adhesion belt around the basolateral region of the photoreceptor outer segment in humans, and that defects in this structure cause the retinal degeneration in USH1 patients.

Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice

PubMed Central

Sahly, Iman; Dufour, Eric; Schietroma, Cataldo; Michel, Vincent; Bahloul, Amel; Perfettini, Isabelle; Pepermans, Elise; Estivalet, Amrit; Carette, Diane; Aghaie, Asadollah; Ebermann, Inga; Lelli, Andrea; Iribarne, Maria; Hardelin, Jean-Pierre; Weil, Dominique; Sahel, José-Alain

2012-01-01

The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins—myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans—do not display retinal degeneration. We found here that, in macaque photoreceptor cells, all USH1 proteins colocalized at membrane interfaces (i) between the inner and outer segments in rods and (ii) between the microvillus-like calyceal processes and the outer segment basolateral region in rods and cones. This pattern, conserved in humans and frogs, was mediated by the formation of an USH1 protein network, which was associated with the calyceal processes from the early embryonic stages of outer segment growth onwards. By contrast, mouse photoreceptors lacked calyceal processes and had no USH1 proteins at the inner–outer segment interface. We suggest that USH1 proteins form an adhesion belt around the basolateral region of the photoreceptor outer segment in humans, and that defects in this structure cause the retinal degeneration in USH1 patients. PMID:23045546

The retinal morphology and retinal histochemistry of a twilight fish Corydoras paleatus (J.).

PubMed

Yew, D T; Woo, H H

1976-01-01

1. The retinas of Corydoras paleatus were studied by histology (HE) and histochemistry (PAS and Nucleic acid). 2. Three types of visual cells were observed, namely rod, single cone and twin cone. All of them are PAS positive. 3. The histochemical PAS pattern of these visual cells differs from those species which are not of a twilight habitat. 4. Significant amount of RNA were not detected in the inner segments of visual cells in this species indicating a possible slow renewal of outer segments.

Histological techniques for study of photoreceptor orientation.

PubMed

Laties, A M

1969-01-01

An histological method for the study of photoreceptor orientation in primate eyes is described. To preserve photoreceptor orientation it is necessary to protect the fragile rod and cone outer segments to the maximum extent possible from mechanical deformation and from injury by solvent extraction. To prevent mechanical deformation the eyes are freeze-dried and embedded in plastic with or without prior vapor fixation. Solvent extraction from the lipid-rich outer segment is limited by avoidance or restriction of organic solvents. When large segments of primate eyes are so treated, it is possible to section the plastic blocks along the visual axis, polish the block surface, and view photoreceptor orientation by epi-illumination microscopy. In such specimens a differential orientation of photoreceptors exists with the long axis of photoreceptor inner and outer segments in line with incoming light rays.

Adaptive Optics Microperimetry and OCT Images Show Preserved Function and Recovery of Cone Visibility in Macular Telangiectasia Type 2 Retinal Lesions

PubMed Central

Wang, Qinyun; Tuten, William S.; Lujan, Brandon J.; Holland, Jennifer; Bernstein, Paul S.; Schwartz, Steven D.; Duncan, Jacque L.; Roorda, Austin

2015-01-01

Purpose. To evaluate visual function and disease progression in the retinal structural abnormalities of three patients from two unrelated families with macular telangiectasia (MacTel) type 2. Methods. Adaptive optics scanning laser ophthalmoscopy (AOSLO) and AOSLO microperimetry (AOMP) were used to evaluate the structure and function of macular cones in three eyes with MacTel type 2. Cone spacing was estimated using histogram analysis of intercone distances, and registered spectral-domain optical coherence tomography (SD-OCT) scans were used to evaluate retinal anatomy. AOMP was used to assess visual sensitivity in and around areas of apparent cone loss. Results. Although overall lesion surface area increased, some initially affected regions subsequently showed clear, contiguous, and normally spaced cone mosaics with recovered photoreceptor inner/outer segment (IS/OS) reflectivity (two of two eyes). The AOMP test sites fell within three categories: normal-appearing cones (N), dimly reflecting cones (D), and RPE cell mosaics (R). At N sites, AOMP threshold values (arbitrary units [au]) increased with increasing eccentricity (slope = 0.054 au/degree, r2 = 0.77). The N thresholds ranged from 0.04 to 0.27 au, D thresholds from 0.04 to 0.33 au, and R thresholds from 0.14 to 1.00 au. There was measurable visual sensitivity everywhere except areas without intact external limiting membrane (ELM) and with diffuse scattering in the IS/OS and posterior tips of the outer segments (PTOS) regions on OCT. Conclusions. Visual sensitivity and recovery of cone visibility in areas of apparent focal cone loss suggests that MacTel type 2 lesions with a preserved ELM may contain functioning cones with abnormal scattering and/or waveguiding characteristics. (ClinicalTrials.gov number, NCT00254605.) PMID:25587056

Temporal and spatial characteristics of cone degeneration in RCS rats.

PubMed

Huang, Yan Ming; Yin, Zheng Qin; Liu, Kang; Huo, Shu Jia

2011-03-01

The temporal and spatial characteristics of cone degeneration in the Royal College of Surgeons (RCS) rat were studied to provide information for treatment strategies of retinitis pigmentosa. Nonpigmented dystrophic RCS rats (RCS) and pigmented nondystrophic RCS rats (controls) were used. Cone processes were visualized with peanut agglutinin (PNA). Cone development appears to have been completed by postnatal day 21 (P21) in both the RCS and control rats. Signs of cone degeneration were obvious by P30, with shorter outer segments (OSs) and enlarged inner segments (ISs). At that time, 81.7% of the cones retained stained ISs. The rate of IS density decline was slower in the peripheral, nasal, and superior retina, and only 43.6% of the cones with ISs were present at P45. By P60, PNA-labeled cone ISs were distorted and restricted to the peripheral retina, and by P90, few cone pedicles were detected. Our findings indicate that therapeutic strategies aimed at rescuing cones in the degenerating retina should be applied before P21 and no later than P45 while substantial numbers of cones retain their ISs. Either the middle or peripheral regions of the nasal and superior retina are the best locations for transplantation strategies.

Foveal damage in habitual poppers users.

PubMed

Audo, Isabelle; El Sanharawi, Mohamed; Vignal-Clermont, Catherine; Villa, Antoine; Morin, Annie; Conrath, John; Fompeydie, Dominique; Sahel, José-Alain; Gocho-Nakashima, Kiyoko; Goureau, Olivier; Paques, Michel

2011-06-01

To describe foveal damage in habitual use of poppers, a popular recreational drug. Retrospective observational case series. Six patients with bilateral vision loss after chronic popper inhalation were seen in 4 university-based ophthalmology departments. Symptoms, medical history, ophthalmic examination, and functional and morphological tests are described. All patients experienced progressive bilateral vision loss, with central photopsia in 2 cases. Initial visual acuities ranged from 20/50 to 20/25. In all patients, a bilateral yellow foveal spot was present that, by optical coherence tomography, was associated with disruption of the outer segments of foveal cones. Functional and anatomical damage was restricted to the fovea. The poppers involved were identified as isopropyl nitrite in 3 cases. Four patients showed anatomical and/or functional improvement over several months after discontinuing popper inhalation. Repeated inhalation of poppers may be associated with prolonged bilateral vision loss due to the disruption of foveal cone outer segments. Retinal damage may progressively improve following drug discontinuation.

Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.

PubMed

Gonzalez-Cordero, Anai; Kruczek, Kamil; Naeem, Arifa; Fernando, Milan; Kloc, Magdalena; Ribeiro, Joana; Goh, Debbie; Duran, Yanai; Blackford, Samuel J I; Abelleira-Hervas, Laura; Sampson, Robert D; Shum, Ian O; Branch, Matthew J; Gardner, Peter J; Sowden, Jane C; Bainbridge, James W B; Smith, Alexander J; West, Emma L; Pearson, Rachael A; Ali, Robin R

2017-09-12

Transplantation of rod photoreceptors, derived either from neonatal retinae or pluripotent stem cells (PSCs), can restore rod-mediated visual function in murine models of inherited blindness. However, humans depend more upon cone photoreceptors that are required for daylight, color, and high-acuity vision. Indeed, macular retinopathies involving loss of cones are leading causes of blindness. An essential step for developing stem cell-based therapies for maculopathies is the ability to generate transplantable human cones from renewable sources. Here, we report a modified 2D/3D protocol for generating hPSC-derived neural retinal vesicles with well-formed ONL-like structures containing cones and rods bearing inner segments and connecting cilia, nascent outer segments, and presynaptic structures. This differentiation system recapitulates human photoreceptor development, allowing the isolation and transplantation of a pure population of stage-matched cones. Purified human long/medium cones survive and become incorporated within the adult mouse retina, supporting the potential of photoreceptor transplantation for treating retinal degeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Photosensitivity of Rhodopsin Bleaching and Light-Induced Increases of Fundus Reflectance in Mice Measured In Vivo With Scanning Laser Ophthalmoscopy

PubMed Central

Zhang, Pengfei; Goswami, Mayank; Zawadzki, Robert J.; Pugh, Edward N.

2016-01-01

Purpose To quantify bleaching-induced changes in fundus reflectance in the mouse retina. Methods Light reflected from the fundus of albino (Balb/c) and pigmented (C57Bl/6J) mice was measured with a multichannel scanning laser ophthalmoscopy optical coherence tomography (SLO-OCT) optical system. Serial scanning of small retinal regions was used for bleaching rhodopsin and measuring reflectance changes. Results Serial scanning generated a saturating reflectance increase centered at 501 nm with a photosensitivity of 1.4 × 10−8 per molecule μm2 in both strains, 2-fold higher than expected were irradiance at the rod outer segment base equal to that at the retinal surface. The action spectrum of the reflectance increase corresponds to the absorption spectrum of mouse rhodopsin in situ. Spectra obtained before and after bleaching were fitted with a model of fundus reflectance, quantifying contributions from loss of rhodopsin absorption with bleaching, absorption by oxygenated hemoglobin (HbO2) in the choroid (Balb/c), and absorption by melanin (C57Bl/6J). Both mouse strains exhibited light-induced broadband reflectance changes explained as bleaching-induced reflectivity increases at photoreceptor inner segment/outer segment (IS/OS) junctions and OS tips. Conclusions The elevated photosensitivity of rhodopsin bleaching in vivo is explained by waveguide condensing of light in propagation from rod inner segment (RIS) to rod outer segment (ROS). The similar photosensitivity of rhodopsin in the two strains reveals that little light backscattered from the sclera can enter the ROS. The bleaching-induced increases in reflectance at the IS/OS junctions and OS tips resemble results previously reported in human cones, but are ascribed to rods due to their 30/1 predominance over cones in mice and to the relatively minor amount of cone M-opsin in the regions scanned. PMID:27403994

Cone Photoreceptor Packing Density and the Outer Nuclear Layer Thickness in Healthy Subjects

PubMed Central

Chui, Toco Y. P.; Song, Hongxin; Clark, Christopher A.; Papay, Joel A.; Burns, Stephen A.; Elsner, Ann E.

2012-01-01

Purpose. We evaluated the relationship between cone photoreceptor packing density and outer nuclear layer (ONL) thickness within the central 15 degrees. Methods. Individual differences for healthy subjects in cone packing density and ONL thickness were examined in 8 younger and 8 older subjects, mean age 27.2 versus 56.2 years. Cone packing density was obtained using an adaptive optics scanning laser ophthalmoscope (AOSLO). The ONL thickness measurements included the ONL and the Henle fiber layer (ONL + HFL), and were obtained using spectral domain optical coherence tomography (SDOCT) and custom segmentation software. Results. There were sizeable individual differences in cone packing density and ONL + HFL thickness. Older subjects had on average lower cone packing densities, but thicker ONL + HFL measurements. Cone packing density and ONL + HFL thickness decreased with increasing retinal eccentricity. The ratio of the cone packing density-to-ONL2 was larger for the younger subjects group, and decreased with retinal eccentricity. Conclusions. The individual differences in cone packing density and ONL + HFL thickness are consistent with aging changes, indicating that normative aging data are necessary for fine comparisons in the early stages of disease or response to treatment. Our finding of ONL + HFL thickness increasing with aging is inconsistent with the hypothesis that ONL measurements with SDOCT depend only on the number of functioning cones, since in our older group cones were fewer, but thickness was greater. PMID:22570340

Two-photon excited autofluorescence imaging of freshly isolated frog retinas.

PubMed

Lu, Rong-Wen; Li, Yi-Chao; Ye, Tong; Strang, Christianne; Keyser, Kent; Curcio, Christine A; Yao, Xin-Cheng

2011-06-01

The purpose of this study was to investigate cellular sources of autofluorescence signals in freshly isolated frog (Rana pipiens) retinas. Equipped with an ultrafast laser, a laser scanning two-photon excitation fluorescence microscope was employed for sub-cellular resolution examination of both sliced and flat-mounted retinas. Two-photon imaging of retinal slices revealed autofluorescence signals over multiple functional layers, including the photoreceptor layer (PRL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Using flat-mounted retinas, depth-resolved imaging of individual retinal layers further confirmed multiple sources of autofluorescence signals. Cellular structures were clearly observed at the PRL, ONL, INL, and GCL. At the PRL, the autofluorescence was dominantly recorded from the intracellular compartment of the photoreceptors; while mixed intracellular and extracellular autofluorescence signals were observed at the ONL, INL, and GCL. High resolution autofluorescence imaging clearly revealed mosaic organization of rod and cone photoreceptors; and sub-cellular bright autofluorescence spots, which might relate to connecting cilium, was observed in the cone photoreceptors only. Moreover, single-cone and double-cone outer segments could be directly differentiated.

Relationship Between Foveal Cone Specialization and Pit Morphology in Albinism

PubMed Central

Wilk, Melissa A.; McAllister, John T.; Cooper, Robert F.; Dubis, Adam M.; Patitucci, Teresa N.; Summerfelt, Phyllis; Anderson, Jennifer L.; Stepien, Kimberly E.; Costakos, Deborah M.; Connor, Thomas B.; Wirostko, William J.; Chiang, Pei-Wen; Dubra, Alfredo; Curcio, Christine A.; Brilliant, Murray H.; Summers, C. Gail; Carroll, Joseph

2014-01-01

Purpose. Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism. Methods. We recruited 32 subjects with a clinical diagnosis of albinism. DNA was obtained from 25 subjects, and known albinism genes were analyzed for mutations. Relative inner and outer segment (IS and OS) lengthening (fovea-to-perifovea ratio) was determined from manually segmented spectral domain-optical coherence tomography (SD-OCT) B-scans. Foveal pit morphology was quantified for eight subjects from macular SD-OCT volumes. Ten subjects underwent imaging with adaptive optics scanning light ophthalmoscopy (AOSLO), and cone density was measured. Results. We found mutations in 22 of 25 subjects, including five novel mutations. All subjects lacked complete excavation of inner retinal layers at the fovea, though four subjects had foveal pits with normal diameter and/or volume. Peak cone density and OS lengthening were variable and overlapped with that observed in normal controls. A fifth hyper-reflective band was observed in the outer retina on SD-OCT in the majority of the subjects with albinism. Conclusions. Foveal cone specialization and pit morphology vary greatly in albinism. Normal cone packing was observed in the absence of a foveal pit, suggesting a pit is not required for packing to occur. The degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight on this issue. PMID:24845642

Guanylate cyclase-activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors.

PubMed

Vinberg, Frans; Peshenko, Igor V; Chen, Jeannie; Dizhoor, Alexander M; Kefalov, Vladimir J

2018-05-11

Light adaptation of photoreceptor cells is mediated by Ca 2+ -dependent mechanisms. In darkness, Ca 2+ influx through cGMP-gated channels into the outer segment of photoreceptors is balanced by Ca 2+ extrusion via Na + /Ca 2+ , K + exchangers (NCKXs). Light activates a G protein signaling cascade, which closes cGMP-gated channels and decreases Ca 2+ levels in photoreceptor outer segment because of continuing Ca 2+ extrusion by NCKXs. Guanylate cyclase-activating proteins (GCAPs) then up-regulate cGMP synthesis by activating retinal membrane guanylate cyclases (RetGCs) in low Ca 2+ This activation of RetGC accelerates photoresponse recovery and critically contributes to light adaptation of the nighttime rod and daytime cone photoreceptors. In mouse rod photoreceptors, GCAP1 and GCAP2 both contribute to the Ca 2+ -feedback mechanism. In contrast, only GCAP1 appears to modulate RetGC activity in mouse cones because evidence of GCAP2 expression in cones is lacking. Surprisingly, we found that GCAP2 is expressed in cones and can regulate light sensitivity and response kinetics as well as light adaptation of GCAP1-deficient mouse cones. Furthermore, we show that GCAP2 promotes cGMP synthesis and cGMP-gated channel opening in mouse cones exposed to low Ca 2+ Our biochemical model and experiments indicate that GCAP2 significantly contributes to the activation of RetGC1 at low Ca 2+ when GCAP1 is not present. Of note, in WT mouse cones, GCAP1 dominates the regulation of cGMP synthesis. We conclude that, under normal physiological conditions, GCAP1 dominates the regulation of cGMP synthesis in mouse cones, but if its function becomes compromised, GCAP2 contributes to the regulation of phototransduction and light adaptation of cones. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

A heterozygous putative null mutation in ROM1 without a mutation in peripherin/RDS in a family with retinitis pigmentosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakuma, Hitoshi; Inana, G.; Murakami, Akira

1995-05-20

ROM1 is a 351-amino-acid, 37-kDa outer segment membrane protein of rod photoreceptors. ROM1 is related to peripherin/RDS, another outer segment membrane protein found in both rods and cones. The precise function of ROM1 or peripherin/RDS is not known, but they have been suggested to play important roles in the function and/or structure of the rod photoreceptor outer segment disks. A recent report implicated ROM1 in disease by suggesting that RP can be caused by a heterozygous null mutation in ROM1 but only in combination with another heterozygous mutation in peripherin/RDS. Screening of the ROM1 gene using polymerase chain reaction amplification,more » denaturing gradient gel electrophoresis, and direct DNA sequencing identified the same heterozygous putative null mutation in a family with RP.« less

Highly efficient retinal metabolism in cones

PubMed Central

Miyazono, Sadaharu; Shimauchi-Matsukawa, Yoshie; Tachibanaki, Shuji; Kawamura, Satoru

2008-01-01

After bleaching of visual pigment in vertebrate photoreceptors, all-trans retinal is reduced to all-trans retinol by retinol dehydrogenases (RDHs). We investigated this reaction in purified carp rods and cones, and we found that the reducing activity toward all-trans retinal in the outer segment (OS) of cones is >30 times higher than that of rods. The high activity of RDHs was attributed to high content of RDH8 in cones. In the inner segment (IS) in both rods and cones, RDH8L2 and RDH13 were found to be the major enzymes among RDH family proteins. We further found a previously undescribed and effective pathway to convert 11-cis retinol to 11-cis retinal in cones: this oxidative conversion did not require NADP+ and instead was coupled with reduction of all-trans retinal to all-trans retinol. The activity was >50 times effective than the oxidizing activity of RDHs that require NADP+. These highly effective reactions of removal of all-trans retinal by RDH8 and production of 11-cis retinal by the coupling reaction are probably the underlying mechanisms that ensure effective visual pigment regeneration in cones that function under much brighter light conditions than rods. PMID:18836074

Concentric retinitis pigmentosa: clinicopathologic correlations.

PubMed

Milam, A H; De Castro, E B; Smith, J E; Tang, W X; John, S K; Gorin, M B; Stone, E M; Aguirre, G D; Jacobson, S G

2001-10-01

Progressive concentric (centripetal) loss of vision is one pattern of visual field loss in retinitis pigmentosa. This study provides the first clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell specific antibodies. Unrelated simplex/multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric field loss, normal or near normal rod and cone sensitivity within the preserved visual field, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective or modify photoreceptor degeneration in concentric retinitis pigmentosa.

Photoreceptor disc shedding in the living human eye

PubMed Central

Kocaoglu, Omer P.; Liu, Zhuolin; Zhang, Furu; Kurokawa, Kazuhiro; Jonnal, Ravi S.; Miller, Donald T.

2016-01-01

Cone photoreceptors undergo a daily cycle of renewal and shedding of membranous discs in their outer segments (OS), the portion responsible for light capture. These physiological processes are fundamental to maintaining photoreceptor health, and their dysfunction is associated with numerous retinal diseases. While both processes have been extensively studied in animal models and postmortem eyes, little is known about them in the living eye, in particular human. In this study, we report discovery of the optical signature associated with disc shedding using a method based on adaptive optics optical coherence tomography (AO-OCT) in conjunction with post-processing methods to track and monitor individual cone cells in 4D. The optical signature of disc shedding is characterized by an abrupt transient loss in the cone outer segment tip (COST) reflection followed by its return that is axially displaced anteriorly. Using this signature, we measured the temporal and spatial properties of shedding events in three normal subjects. Average duration of the shedding event was 8.8 ± 13.4 minutes, and average length loss of the OS was 2.1 μm (7.0% of OS length). Prevalence of cone shedding was highest in the morning (14.3%) followed by the afternoon (5.7%) and evening (4.0%), with load distributed across the imaged patch. To the best of our knowledge these are the first images of photoreceptor disc shedding in the living retina. PMID:27895995

Investigation of retinal microstructure in healthy eyes and dry age-related macular degeneration using a combined AO-OCT-SLO system

NASA Astrophysics Data System (ADS)

Wells-Gray, Elaine M.; Choi, Stacey S.; Ohr, Matthew; Cebulla, Colleen M.; Doble, Nathan

2017-02-01

Combined adaptive optics (AO) optical coherence tomography (OCT) scanning laser ophthalmoscopy (SLO) imaging allows simultaneous en face and cross sectional views of the retina. We describe improvements to our AO-OCT-SLO system and highlight its resolution capability and clinical utility by presenting results from 3 control and 4 dry agerelated macular degeneration (AMD) subjects. From a group of subjects with healthy eyes, OCT A-scans were grouped as originating from cones or rods and were averaged. The resulting reflectance profiles were then used to identify the location of cone and rod segments. Results for rods and cones were compared, with the focus on inner segment (IS) and outer segment (OS) structures and where these cells embed into the retinal pigment epithelium (RPE). In the AMD patients, cone IS and OS lengths were measured over and around drusen for two retinal regions (fovea-2° and 2°-4°), and those results were correlated to drusen height. For the fovea-2° region, the drusen height that caused statistically significant shortening of cone ISL and OSL compared to the unaffected adjacent area were 40 μm and 50 μm respectively (p = 0.009, and p < 0.001, respectively). For the 2°-4° region, the equivalent drusen heights that caused significant shortening of segment length were 60 μm for IS (p = 0.017) and 80 μm for OS (p < 0.001)

The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision.

PubMed

Vinberg, Frans; Wang, Tian; De Maria, Alicia; Zhao, Haiqing; Bassnett, Steven; Chen, Jeannie; Kefalov, Vladimir J

2017-06-26

Calcium (Ca 2+ ) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca 2+ controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca 2+ in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na + /Ca 2+ , K + exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision. We show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2: NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca 2+ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promotes their survival.

Localization of visual pigment antigens to photoreceptor cells with different oil droplets in the chicken retina.

PubMed

Szél, A; Röhlich, P

1985-01-01

Frozen semithin sections and unembedded retinal pieces were investigated by immunocytochemistry using two antibodies produced against visual pigments in our laboratory. One was a polyclonal serum (AO) raised against bovine rhodopsin, while the other one was a monoclonal antibody (COS-1) produced against an epitope present in a cone visual pigment. AO stained, as expected, rod outer segments; in addition it also recognized a single cone characterized by a deep yellow oil droplet as well as another single cone with a yellowish green oil droplet. In contrast, COS-1 labelled both members of the double cones; the principal member having a yellowish-green oil droplet and the accessory member. COS-1 also stained a single cone type exhibiting a large red oil droplet.

The structure of anchovy outer retinae (Engraulididae, Clupeiformes) - a comparative light- and electron-microscopic study using museum-stored material.

PubMed

Hess, Martin; Melzer, Roland R; Eser, Roland; Smola, Ulrich

2006-11-01

The outer retinal architecture of Engraulididae is uncommon among vertebrates. In some anchovies, e.g., Anchoa, two cone types are arranged alternating in long photoreceptor chains, i.e., polycones. The cones have radially oriented outer segment lamellae in close contact with a complex guanine tapetum, most probably subserving polarization contrast vision. To clarify the distribution of the aberrant polycone architecture within the Engraulididae and to provide indications about polycone evolution, the outer retina morphology of 16 clupeoid species was investigated by light and electron microscopy, predominantly using museum-stored material. The outgroup representatives of four clupeid subfamilies (Clupeonella cultriventris, Dorosoma cepedianum, Ethmalosa fimbriata, Pellonula leonensis) show a row pattern of double cones, partially with single cones at defined positions and a pigment epithelium with lobopodial protrusions containing melanin. The pristigasterid Ilisha africana has double rows of single cones lying between linear curtains of pigment epithelium processes filled with minute crystallites and melanin concentrated near their vitreal tips. Within the Engraulididae, two main architectures are found: Coilia nasus and Thryssa setirostris have linear multiple cones or polycones separated by long pigment epithelium barriers containing tapetal crystallites and melanin in the tips (also found in Setipinna taty), whereas Anchoviella alleni, Encrasicholina heteroloba, Engraulis encrasicolus, Engraulis mordax, Lycengraulis batesii, and Stolephorus indicus exhibit the typical polycone architecture. Cetengraulis mysticetus and Lycothrissa crocodilus show cone patterns and pigment epithelium morphology differing from the other anchovy species. The sets of characters are compared, corroborated with the previous knowledge on clupeoid retinae and discussed in terms of functional morphology and visual ecology. A scenario on polycone evolution is developed that may serve as an aid for the reconstruction of engraulidid phylogeny. Furthermore, this study demonstrates the suitability of museum material for morphological studies, even at the electron microscopic level. Copyright 2006 Wiley-Liss, Inc.

Stiles—Crawford effect and the bleaching of cone pigments

PubMed Central

Coble, J. R.; Rushton, W. A. H.

1971-01-01

1. The efficiency of light entering the eye through various points in the pupil (Stiles—Crawford effect) was studied using two criteria: (a) visual brightness judged by flicker fusion and (b) the rate of cone pigment bleaching measured by reflexion densitometry. 2. Both measurements were made in the same apparatus with the same geometry of presentation and both gave the same Stiles—Crawford effect. 3. This suggests that the densitometer measures pigment deep in the outer segments of the cones where light is absorbed for vision. 4. Foveal cones seem all to point in the same direction, since the fraction of pigment bleached by light entering the pupil at any one point is the same when measured by light entering anywhere. PMID:5571926

3D Segmentation of Maxilla in Cone-beam Computed Tomography Imaging Using Base Invariant Wavelet Active Shape Model on Customized Two-manifold Topology

PubMed Central

Chang, Yu-Bing; Xia, James J.; Yuan, Peng; Kuo, Tai-Hong; Xiong, Zixiang; Gateno, Jaime; Zhou, Xiaobo

2013-01-01

Recent advances in cone-beam computed tomography (CBCT) have rapidly enabled widepsread applications of dentomaxillofacial imaging and orthodontic practices in the past decades due to its low radiation dose, high spatial resolution, and accessibility. However, low contrast resolution in CBCT image has become its major limitation in building skull models. Intensive hand-segmentation is usually required to reconstruct the skull models. One of the regions affected by this limitation the most is the thin bone images. This paper presents a novel segmentation approach based on wavelet density model (WDM) for a particular interest in the outer surface of anterior wall of maxilla. Nineteen CBCT datasets are used to conduct two experiments. This mode-based segmentation approach is validated and compared with three different segmentation approaches. The results show that the performance of this model-based segmentation approach is better than those of the other approaches. It can achieve 0.25 ± 0.2mm of surface error from ground truth of bone surface. PMID:23694914

Differential distribution of fibroblast growth factor receptors (FGFRs) on foveal cones: FGFR-4 is an early marker of cone photoreceptors.

PubMed

Cornish, Elisa E; Natoli, Riccardo C; Hendrickson, Anita; Provis, Jan M

2004-01-08

Relatively little is known of the expression and distribution of FGF receptors (FGFR) in the primate retina. We investigated expression of FGFRs in developing and adult Macaca monkey retina, paying particular attention to the cone rich, macular region. One fetal human retina was used for diagnostic PCR using primers designed for FGFR1, FGFR2, FGFR3, FGFR4, and FGFR like-protein 1 (FGFrl1) and for probe design to FGFR3, FGFR4, and FGFrl1. Rat cDNA was used to synthesize probes for FGFR1 and FGFR2 with 90% and 93% homology to human, respectively. Paraffin sections of retina from macaque fetuses sacrificed at fetal days (Fd) 64, 73, 85, 105, 115, 120, and 165, and postnatal ages 2.5 and 11 years were used to detect FGF receptors by immunohistochemistry and in situ hybridization. PCR showed each of the FGF receptors are expressed in fetal human retina. In situ hybridization indicated that mRNA for each receptor is expressed in all retinal cell layers during development, but most intensely in the ganglion cell layer (GCL). FGFR2 mRNA is reduced in the adult inner (INL) and outer (ONL) nuclear layers, while FGFrl1 mRNA is virtually absent from the adult ONL. FGFR4 mRNA is particularly intense in fetal and adult cone photoreceptors. Immunoreactivity to FGFR1-FGFR4 was detected in the interphotoreceptor matrix in what appeared to be RPE microvilli associated with developing photoreceptor outer segments, and generally is high in the GCL and low in the INL. Different patterns of FGFR3 and FGFR4 immunoreactivities in the outer plexiform layer (OPL) suggest localization of FGFR3 to horizontal cell processes, with FGFR4 being expressed by both horizontal and bipolar cell processes. FGFR1, FGFR3, and FGFR4 immunoreactivities are present in the inner segments and somata of adult cones. The pedicles of developing and adult cones are FGFR1 and FGFR3 immunoreactive, and the basal, synaptic region is FGFR4 immunoreactive. FGFR4 labels cones almost in their entirety from early in development and is not detected in rods. The fibers of Henle are intensely FGFR4 immunoreactive in adult cones. The results show high levels of FGF receptor expression in developing and adult retina. Differential distribution of FGF receptors across developing and adult photoreceptors suggests specific roles for FGF signalling in development and maintenance of photoreceptors, particularly the specialized cones of the fovea.

Quantification of photoreceptor layer thickness in different macular pathologies using ultrahigh-resolution optical coherence tomography

NASA Astrophysics Data System (ADS)

Drexler, Wolfgang; Hermann, Boris; Unterhuber, Angelika; Sattmann, Harald; Wirtitsch, Matthias; Stur, Michael; Scholda, Christoph; Ergun, Erdem; Anger, Elisabeth; Ko, Tony H.; Schubert, Christian; Ahnelt, Peter K.; Fujimoto, James G.; Fercher, Adolf F.

2004-07-01

In vivo ultrahigh resolution ophthalmic OCT has been performed in more than 300 eyes of 200 patients with several retinal pathologies, demonstrating unprecedented visualization of all major intraretinal layers, in particular the photoreceptor layer. Visualization as well as quantification of the inner and outer segment of the photoreceptor layer especially in the foveal region has been acvhieved. In normal subjects the photoreceptor layer thickness in the center of the fovea is about of 90 μm, approximately equally distributed to the inner and the outer photoreceptor segment. In the parafoveal region this thickness is reduced to ~50 μm (~30 μm for the inner and ~20 μm for the outer segment). This is in good agreement with well known increase of cone outer segments in the central foveal region. Photoreceptor layer impairment in different macular pathologies like macular hole, central serous chorioretinopathy, age related macular degeneration, foveomacular dystrophies, Stargardt dystrophy as well as retinitis pigmentosa has been investigated. Photoreceptor layer loss significantly correlated with visual acuity (R2 = 0.6, p < 0.001) and microperimetry findings for the first time in 22 eyes with Stargardt dystrophy. Visualization and quantification of photoreceptor inner and outer segment using ultrahigh resolution OCT has the potential to improve early ophthalmic diagnosis, contributes to a better understanding of pathogenesis of retinal diseases as well as might have impact in the development and monitoring of novel therapy approaches.

Variability in bleach kinetics and amount of photopigment between individual foveal cones.

PubMed

Bedggood, Phillip; Metha, Andrew

2012-06-20

To study the bleaching dynamics of individual foveal cone photoreceptors using an adaptive optics ophthalmoscope. After dark adaptation, cones were progressively bleached and imaged by a series of flashes of 545-nm to 570-nm light at 12 Hz. Intensity measurements were made within the foveal avascular zone (FAZ) to avoid confounding signals from the inner retinal blood supply. Over 1300 cones in this region were identified and tracked through the imaging sequences. A single subject was used who demonstrated the necessary steady fixation, wide FAZ, and resolvability of cones close to the foveal center. The mean intensity of all cones was well-described by first-order kinetics. Individual cones showed marked differences from the mean, both in rate of bleach and amount of photopigment; there was an inverse correlation between these two parameters. A subset of the cones showed large oscillations in intensity consistent with interference from light scattered within the cone outer segment. These cones also bleached more quickly, implying that rapid bleaching induces greater amounts of scatter. Neighboring cones in the fovea display high variability in their optical properties.

Distinct functions for IFT140 and IFT20 in opsin transport.

PubMed Central

Crouse, Jacquelin A.; Lopes, Vanda S.; SanAgustin, Jovenal T.; Keady, Brian T.; Williams, David S.; Pazour, Gregory J.

2014-01-01

In the vertebrate retina, light is detected by the outer segments of photoreceptor rods and cones, which are highly modified cilia. Like other cilia, outer segments have no protein synthetic capacity and depend on proteins made in the cell body for their formation and maintenance. The mechanism of transport into the outer segment is not fully understood but intraflagellar transport (IFT) is thought to be a major mechanism for moving protein from the cell body into the cilium. In the case of photoreceptor cells, the high density of receptors and the disk turnover that occurs daily necessitates much higher rates of transport than would be required in other cilia. In this work, we show that the IFT complex A protein IFT140 is required for development and maintenance of outer segments. In earlier work we found that acute deletion of Ift20 caused opsin to accumulate at the Golgi complex. In this work we find that acute deletion of Ift140 does not cause opsin to accumulate at the Golgi complex but rather it accumulates in the plasma membrane of the inner segments. This work is strong support of a model of opsin transport where IFT20 is involved in the movement from the Golgi complex to the base of the cilium. Then, once at the base, the opsin is carried through the connecting cilium by an IFT complex that includes IFT140. PMID:24619649

Cone arrestin: deciphering the structure and functions of arrestin 4 in vision.

PubMed

Craft, Cheryl Mae; Deming, Janise D

2014-01-01

Cone arrestin (Arr4) was discovered 20 years ago as a human X-chromosomal gene that is highly expressed in pinealocytes and cone photoreceptors. Subsequently, specific antibodies were developed to identify Arr4 and to distinguish cone photoreceptor morphology in health and disease states. These reagents were used to demonstrate Arr4 translocation from cone inner segments in the dark to outer segments with light stimulation, similarly to Arrestin 1 (Arr1) translocation in rod photoreceptors. A decade later, the Arr4 crystal structure was solved, which provided more clues about Arr4's mechanisms of action. With the creation of genetically engineered visual arrestin knockout mice, one critical function of Arr4 was clarified. In single living cones, both visual arrestins bind to light-activated, G protein receptor kinase 1 (Grk1) phosphorylated cone opsins to desensitize them, and in their absence, mouse cone pigment shutoff is delayed. Still under investigation are additional functions; however, it is clear that Arr4 has non-opsin-binding partners and diverse synaptic roles, including cellular anchoring and trafficking. Recent studies reveal Arr4 is involved in high temporal resolution and contrast sensitivity, which opens up a new direction for research on this intriguing protein. Even more exciting is the potential for therapeutic use of the Arr4 promoter with an AAV-halorhodopsin that was shown to be effective in using the remaining cones in retinal degeneration mouse models to drive inner retinal circuitry for motion detection and light/dark discrimination.

The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision

PubMed Central

Vinberg, Frans; Wang, Tian; De Maria, Alicia; Zhao, Haiqing; Bassnett, Steven; Chen, Jeannie; Kefalov, Vladimir J

2017-01-01

Calcium (Ca2+) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca2+ controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca2+ in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na+/Ca2+, K+ exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision. We show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2: NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca2+ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promotes their survival. DOI: http://dx.doi.org/10.7554/eLife.24550.001 PMID:28650316

Identification of endogenous fluorophores in the photoreceptors using autofluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Zhao, Lingling; Qu, Junle; Niu, Hanben

2007-11-01

In this paper, we present our investigation on the identification of endogenous fluorophores in photoreceptors using autofluorescence spectroscopy, which is performed with an inverted laser scanning confocal microscope equipped with an Argon ion laser and a GreNe laser. In our experiments, individual cones and rods are clearly resolved even in freshly prepared retina samples, without slicing or labeling. The experiment results show that autofluorescence spectrum of the photoreceptors has three peaks approximately at 525nm, 585nm and 665nm. Furthermore, the brightest autofluorescence originates from the photoreceptor outer segments. We can, therefore, come to a conclusion that the peaks at 525nm, 585nm are corresponding to FAD and A2-PE, respectively, which are distributed in the photoreceptor outer segments.

Photoreceptor inner segment ellipsoid band integrity on spectral domain optical coherence tomography

PubMed Central

Saxena, Sandeep; Srivastav, Khushboo; Cheung, Chui M; Ng, Joanne YW; Lai, Timothy YY

2014-01-01

Spectral domain optical coherence tomography cross-sectional imaging of the macula has conventionally been resolved into four bands. However, some doubts were raised regarding authentication of the existence of these bands. Recently, a number of studies have suggested that the second band appeared to originate from the inner segment ellipsoids of the foveal cone photoreceptors, and therefore the previously called inner segment-outer segment junction is now referred to as inner segment ellipsoidband. Photoreceptor dysfunction may be a significant predictor of visual acuity in a spectrum of surgical and medical retinal diseases. This review aims to provide an overview and summarizes the role of the photoreceptor inner segment ellipsoid band in the management and prognostication of various vitreoretinal diseases. PMID:25525329

Constituents of Bile, Bilirubin and TUDCA, Protect Against Oxidative Stress-Induced Retinal Degeneration

PubMed Central

Oveson, Brian C.; Iwase, Takeshi; Hackett, Sean F.; Lee, Sun Young; Usui, Shinichi; Sedlak, Thomas W.; Snyder, Solomon H.; Campochiaro, Peter A.; Sung, Jennifer U.

2014-01-01

Two constituents of bile, bilirubin and tauroursodeoxycholic acid (TUDCA), have antioxidant activity. However, bilirubin can also cause damage to some neurons and glial cells, particularly immature neurons. In this study, we tested the effects of bilirubin and TUDCA in two models in which oxidative stress contributes to photoreceptor cell death, prolonged light exposure and rd10+/+ mice. In albino BALB/c mice, intraperitoneal (IP) injection of 5 mg/kg of bilirubin or 500 mg/kg of TUDCA prior to exposure to 5,000 lux of white light for 8 hours significantly reduced loss of rod and cone function assessed by electroretinograms (ERGs). Both treatments also reduced light-induced accumulation of superoxide radicals in the outer retina, rod cell death assessed by outer nuclear layer (ONL) thickness, and disruption of cone inner and outer segments. In rd10+/+ mice, IP injections of 5 or 50 mg/kg of bilirubin or 500 mg/kg of TUDCA every 3 days starting at postnatal day (P) 6, caused significant preservation of cone cell number and cone function at P50. Rods were not protected at P50, but both bilirubin and TUDCA provided modest preservation of ONL thickness and rod function at P30. These data suggest that correlation of serum bilirubin levels with rate of vision loss in patients with retinitis pigmentosa (RP) could provide a useful strategy to test the hypothesis that cones die from oxidative damage in patients with RP. If proof-of-concept is established, manipulation of bilirubin levels and administration of TUDCA could be tested in interventional trials. PMID:21054389

Outer Retinal Tubulation in Advanced Age-Related Macular Degeneration: Optical Coherence Tomographic Findings Correspond to Histology

PubMed Central

Schaal, Karen B.; Freund, K. Bailey; Litts, Katie M.; Zhang, Yuhua; Messinger, Jeffrey D.; Curcio, Christine A.

2014-01-01

Purpose To compare optical coherence tomography (OCT) and histology of outer retinal tubulation (ORT) secondary to advanced age-related macular degeneration (AMD) in patients and in post-mortem specimens, with particular attention to the basis of the hyper-reflective border of ORT. Method A private referral practice (imaging) and an academic research laboratory (histology) collaborated on two retrospective case series. High-resolution OCT raster scans of 43 eyes (34 patients) manifesting ORT secondary to advanced AMD were compared to high-resolution histological sections through the fovea and superior perifovea of donor eyes (13 atrophic AMD and 40 neovascular AMD) preserved ≤4 hours after death. Results ORT seen on OCT corresponded to histologic findings of tubular structures comprised largely of cones lacking outer segments (OS) and lacking inner segments (IS). Four phases of cone degeneration were histologically distinguishable in ORT lumenal walls, nascent, mature, degenerate, and end-stage (IS and OS; IS only; no IS; no photoreceptors and only Müller cells forming external limiting membrane, ELM, respectively). Mitochondria, which are normally long and bundled within IS ellipsoids, were small and scattered within shrunken IS and cell bodies of surviving cones. A lumenal border was delimited by an ELM. ORT observed in closed and open configurations were distinguishable from cysts and photoreceptor islands on both OCT and histology. Hyper-reflective lumenal material seen on OCT represents trapped retinal pigment epithelium (RPE) and non-RPE cells. Conclusions The defining OCT features of ORT are location in the outer nuclear layer (ONL), a hyper-reflective band differentiating it from cysts, and RPE that is either dysmorphic or absent. ORT histologic and OCT findings corresponded in regard to composition, location, shape, and stages of formation. The reflectivity of ORT lumenal walls on OCT apparently does not require an OS or an IS/OS junction, indicating an independent reflectivity source, possibly mitochondria, in the IS. PMID:25635579

Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model.

PubMed

Spaide, Richard F; Curcio, Christine A

2011-09-01

To evaluate the validity of commonly used anatomical designations for the four hyperreflective outer retinal bands seen in current-generation optical coherence tomography, a scale model of outer retinal morphology was created using published information for direct comparison with optical coherence tomography scans. Articles and books concerning histology of the outer retina from 1900 until 2009 were evaluated, and data were used to create a scale model drawing. Boundaries between outer retinal tissue compartments described by the model were compared with intensity variations of representative spectral-domain optical coherence tomography scans using longitudinal reflectance profiles to determine the region of origin of the hyperreflective outer retinal bands. This analysis showed a high likelihood that the spectral-domain optical coherence tomography bands attributed to the external limiting membrane (the first, innermost band) and to the retinal pigment epithelium (the fourth, outermost band) are correctly attributed. Comparative analysis showed that the second band, often attributed to the boundary between inner and outer segments of the photoreceptors, actually aligns with the ellipsoid portion of the inner segments. The third band corresponded to an ensheathment of the cone outer segments by apical processes of the retinal pigment epithelium in a structure known as the contact cylinder. Anatomical attributions and subsequent pathophysiologic assessments pertaining to the second and third outer retinal hyperreflective bands may not be correct. This analysis has identified testable hypotheses for the actual correlates of the second and third bands. Nonretinal pigment epithelium contributions to the fourth band (e.g., Bruch membrane) remain to be determined.

Protein sorting, targeting and trafficking in photoreceptor cells

PubMed Central

Pearring, Jillian N.; Salinas, Raquel Y.; Baker, Sheila A.; Arshavsky, Vadim Y.

2013-01-01

Vision is the most fundamental of our senses initiated when photons are absorbed by the rod and cone photoreceptor neurons of the retina. At the distal end of each photoreceptor resides a light-sensing organelle, called the outer segment, which is a modified primary cilium highly enriched with proteins involved in visual signal transduction. At the proximal end, each photoreceptor has a synaptic terminal, which connects this cell to the downstream neurons for further processing of the visual information. Understanding the mechanisms involved in creating and maintaining functional compartmentalization of photoreceptor cells remains among the most fascinating topics in ocular cell biology. This review will discuss how photoreceptor compartmentalization is supported by protein sorting, targeting and trafficking, with an emphasis on the best-studied cases of outer segment-resident proteins. PMID:23562855

Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity*

PubMed Central

Duda, Teresa; Wen, Xiao-Hong; Isayama, Tomoki; Sharma, Rameshwar K.; Makino, Clint L.

2015-01-01

By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca2+]i to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mm for ROS-GC1 and 39 mm for ROS-GC2. The effect required neither Ca2+ nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca2+]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity. PMID:25767116

Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat retina.

PubMed

Goebel, D J; Aurelia, J L; Tai, Q; Jojich, L; Poosch, M S

1998-10-19

Immunocytochemical studies were performed to determine the distribution and cellular localization of the NMDA-R2A receptor subunit (R2A) in the cat retina. R2A-immunoreactivity (R2A-IR) was noted in all layers of the retina, with specific localizations in the outer segments of red/green and blue cone photoreceptors, B-type horizontal cells, several types of amacrine cells, Müller cells and the majority of cells in the ganglion cell layer. In the inner nuclear layer, 48% of all cells residing in the amacrine cell layer were R2A-IR including a cell resembling the GABAergic A17 amacrine cell. Interestingly, the AII rod amacrine cell was devoid of R2A-IR. Although the localization of the R2A subunit was anticipated in ganglion cells, amacrines and Müller cells, the presence of this receptor subunit to the cells in the outer retina was not expected. Here, both the R2A and the R2B subunits were found to be present in the outer segments of cone photoreceptors and to the tips of rod outer segments. Although the function of these receptor subunits in rod and cone photoreceptors remains to be determined, the fact that both R2A and R2B receptor subunits are localized to cone outer segments suggests a possible alternative pathway for calcium entry into a region where this cation plays such a crucial role in the process of phototransduction. To further classify the cells that display NR2A-IR, we performed dual labeling experiments showing the relationship between R2A-labeled cells with GABA. Results showed that all GABAergic-amacrines and displaced amacrines express the R2A-subunit protein. In addition, approximately 11% of the NR2A-labeled amacrines, did not stain for GABA. These findings support pharmacological data showing that NMDA directly facilitates GABA release in retina and retinal cultures [I.L. Ferreira, C.B. Duarte, P.F. Santos, C.M. Carvalho, A.P. Carvalho, Release of [3H]GABA evoked by glutamate receptor agonist in cultured chick retinal cells: effect of Ca2+, Brain Res. 664 (1994) 252-256; G.D. Zeevalk, W.J. Nicklas, Action of the anti-ischemic agent ifenprodil on N-methyl-d-aspartate and kainate-mediated excitotoxicity, Brain Res. 522 (1990) 135-139; R. Huba, H.D. Hofmann, Transmitter-gated currents of GABAergic amacrine-like cells in chick retinal cultures, Vis. Neurosci. 6 (1991) 303-314; M. Yamashita, R. Huba, H.D. Hofmann, Early in vitro development of voltage- and transmitter-gated currents in GABAergic amacrine cells, Dev. Brain Res. 82 (1994) 95-102; R. Ientile, S. Pedale, V. Picciurro, V. Macaione, C. Fabiano, S. Macaione, Nitric oxide mediates NMDA-evoked [3H]GABA release from chick retina cells, FEBS Lett. 417 (1997) 345-348; R.C. Kubrusly, M.C. deMello, F.G. deMello, Aspartate as a selective NMDA agonist in cultured cells from the avian retina, Neurochem. Intl. 32 (1998) 47-52] or reduction of GABA in vivo [N.N. Osborn, A.J. Herrera, The effect of experimental ischaemia and excitatory amino acid agonist on the GABA and serotonin immunoreactivities in the rabbit retina, Neurosci. 59 (1994) 1071-1081]. Since the majority of GABAergic synapses in the inner retina are onto both rod and cone bipolar axon terminals [R.G. Pourcho, M.T. Owzcarzak, Distribution of GABA immunoreactivity in the cat retina: A light and electron-microscopic study, Vis. Neurosci. 2 (1989) 425-435], we hypothesize that the NMDA-receptor plays a crucial role in providing feedback inhibition onto rod and cone bipolar cells. Copyright 1998 Elsevier Science B.V.

Adaptive optics fundus images of cone photoreceptors in the macula of patients with retinitis pigmentosa.

PubMed

Tojo, Naoki; Nakamura, Tomoko; Fuchizawa, Chiharu; Oiwake, Toshihiko; Hayashi, Atsushi

2013-01-01

The purpose of this study was to examine cone photoreceptors in the macula of patients with retinitis pigmentosa using an adaptive optics fundus camera and to investigate any correlations between cone photoreceptor density and findings on optical coherence tomography and fundus autofluorescence. We examined two patients with typical retinitis pigmentosa who underwent ophthalmological examination, including measurement of visual acuity, and gathering of electroretinographic, optical coherence tomographic, fundus autofluorescent, and adaptive optics fundus images. The cone photoreceptors in the adaptive optics images of the two patients with retinitis pigmentosa and five healthy subjects were analyzed. An abnormal parafoveal ring of high-density fundus autofluorescence was observed in the macula in both patients. The border of the ring corresponded to the border of the external limiting membrane and the inner segment and outer segment line in the optical coherence tomographic images. Cone photoreceptors at the abnormal parafoveal ring were blurred and decreased in the adaptive optics images. The blurred area corresponded to the abnormal parafoveal ring in the fundus autofluorescence images. Cone densities were low at the blurred areas and at the nasal and temporal retina along a line from the fovea compared with those of healthy controls. The results for cone spacing and Voronoi domains in the macula corresponded with those for the cone densities. Cone densities were heavily decreased in the macula, especially at the parafoveal ring on high-density fundus autofluorescence in both patients with retinitis pigmentosa. Adaptive optics images enabled us to observe in vivo changes in the cone photoreceptors of patients with retinitis pigmentosa, which corresponded to changes in the optical coherence tomographic and fundus autofluorescence images.

Photoreceptor Cell Death, Proliferation and Formation of Hybrid Rod/S-Cone Photoreceptors in the Degenerating STK38L Mutant Retina

PubMed Central

Berta, Ágnes I.; Boesze-Battaglia, Kathleen; Genini, Sem; Goldstein, Orly; O'Brien, Paul J.; Szél, Ágoston; Acland, Gregory M.; Beltran, William A.; Aguirre, Gustavo D.

2011-01-01

A homozygous mutation in STK38L in dogs impairs the late phase of photoreceptor development, and is followed by photoreceptor cell death (TUNEL) and proliferation (PCNA, PHH3) events that occur independently in different cells between 7–14 weeks of age. During this period, the outer nuclear layer (ONL) cell number is unchanged. The dividing cells are of photoreceptor origin, have rod opsin labeling, and do not label with markers specific for macrophages/microglia (CD18) or Müller cells (glutamine synthetase, PAX6). Nestin labeling is absent from the ONL although it labels the peripheral retina and ciliary marginal zone equally in normals and mutants. Cell proliferation is associated with increased cyclin A1 and LATS1 mRNA expression, but CRX protein expression is unchanged. Coincident with photoreceptor proliferation is a change in the photoreceptor population. Prior to cell death the photoreceptor mosaic is composed of L/M- and S-cones, and rods. After proliferation, both cone types remain, but the majority of rods are now hybrid photoreceptors that express rod opsin and, to a lesser extent, cone S-opsin, and lack NR2E3 expression. The hybrid photoreceptors renew their outer segments diffusely, a characteristic of cones. The results indicate the capacity for terminally differentiated, albeit mutant, photoreceptors to divide with mutations in this novel retinal degeneration gene. PMID:21980341

Effects of ionizing radiation on the light sensing elements of the retina. [Structural and physiological effects of carbon, helium, and neon ions on rods and cones of salamanders and mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malachowski, M.J.

1978-07-01

This investigation was undertaken to quantitate possible morphological and physiological effects of particles of high linear energy transfer on the retina, in comparison with x-ray effects. The particles used were accelerated atomic nuclei of helium, carbon, and neon at kinetic energies of several hundred MeV/nucleon. For morphological studies, scanning and transmission electron microscopy and light microscopy were used. Physiological studies consisted of autoradiographic data of the rate of incorporation of labeled protein in the structures (opsin) of the outer segment of visual cells. Structural changes were found in the nuclei, as well as the inner and outer segments of visualmore » cells, rods and cones. At a low dose of 10 rad, x rays and helium had no statistically significant morphological effects, but carbon and neon beams did cause significant degeneration of individual cells, pointing to the existence of a linear dose--effect relationship. At high doses of several hundred rads, a Pathologic Index determined the relative biological effectiveness of neon against alpha particles to have a value of greater than 6. The severity of effects per particle increased with atomic number. Labeling studies demonstrated a decreased rate of incorporation of labeled proteins in the structural organization of the outer segments of visual rods. The rate of self-renewal of visual rod discs was punctuated by irradiation and the structures themselves were depleted of amino acids. A model of rod discs (metabolic and catabolic) was postulated for correlated early and late effects to high and low doses.« less

Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity.

PubMed

Duda, Teresa; Wen, Xiao-Hong; Isayama, Tomoki; Sharma, Rameshwar K; Makino, Clint L

2015-04-24

By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca(2+)]i to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mM for ROS-GC1 and 39 mM for ROS-GC2. The effect required neither Ca(2+) nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca(2+)]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Effects of Diabetic Retinopathy and Pan-Retinal Photocoagulation on Photoreceptor Cell Function as Assessed by Dark Adaptometry

PubMed Central

Bavinger, J. Clay; Dunbar, Grace E.; Stem, Maxwell S.; Blachley, Taylor S.; Kwark, Leon; Farsiu, Sina; Jackson, Gregory R.; Gardner, Thomas W.

2016-01-01

Purpose The pathophysiology of vision loss in persons with diabetic retinopathy (DR) is complex and incompletely defined. We hypothesized that retinal pigment epithelium (RPE) and rod and cone photoreceptor dysfunction, as measured by dark adaptometry, would increase with severity of DR, and that pan-retinal photocoagulation (PRP) would exacerbate this dysfunction. Methods Dark adaptation (DA) was measured in subjects with diabetes mellitus and healthy controls. Dark adaptation was measured at 5° superior to the fovea following a flash bleach, and the data were analyzed to yield cone and rod sensitivity curves. Retinal layer thicknesses were quantified using spectral-domain optical coherence tomography (OCT). Results The sample consisted of 23 controls and 73 diabetic subjects. Subjects with moderate nonproliferative diabetic retinopathy (NPDR) exhibited significant impairment of rod recovery rate compared with control subjects (P = 0.04). Cone sensitivity was impaired in subjects with proliferative diabetic retinopathy (PDR) (type 1 diabetes mellitus [T1DM]: P = 0.0047; type 2 diabetes mellitus [T2DM]: P < 0.001). Subjects with untreated PDR compared with subjects treated with PRP exhibited similar rod recovery rates and cone sensitivities. Thinner RPE as assessed by OCT was associated with slower rod recovery and lower cone sensitivity, and thinner photoreceptor inner segment/outer segment layer was associated with lower cone sensitivity. Conclusions The results suggest that RPE and photoreceptor cell dysfunction, as assessed by cone sensitivity level and rod- and RPE-mediated dark adaptation, progresses with worsening DR, and rod recovery dysfunction occurs earlier than cone dysfunction. Function was preserved following PRP. The findings suggest multiple defects in retinoid function and provide potential points to improve visual function in persons with PDR. PMID:26803796

Mechanisms of Retinal Damage from Chronic Laser Radiation.

DTIC Science & Technology

1981-07-01

culture. The pigment epithelium is deter- mined to be almost equally susceptible to damage in vitro as in vivo and the same action spectrum is similar in...92 -97 D. Experiment III. Light Damage in Culture of Bovine Retinal Pigment Epithelium 1. Methodology a. Collection of Cells... epithelium : Mild form of damage. Figure 18 Inner segments severely damaged. Figure 19 : Cone pedicle after exposure. Figure 20 Outer plexiform layer

GUCY2D Cone-Rod Dystrophy-6 Is a "Phototransduction Disease" Triggered by Abnormal Calcium Feedback on Retinal Membrane Guanylyl Cyclase 1.

PubMed

Sato, Shinya; Peshenko, Igor V; Olshevskaya, Elena V; Kefalov, Vladimir J; Dizhoor, Alexander M

2018-03-21

The Arg838Ser mutation in retinal membrane guanylyl cyclase 1 (RetGC1) has been linked to autosomal dominant cone-rod dystrophy type 6 (CORD6). It is believed that photoreceptor degeneration is caused by the altered sensitivity of RetGC1 to calcium regulation via guanylyl cyclase activating proteins (GCAPs). To determine the mechanism by which this mutation leads to degeneration, we investigated the structure and function of rod photoreceptors in two transgenic mouse lines, 362 and 379, expressing R838S RetGC1. In both lines, rod outer segments became shorter than in their nontransgenic siblings by 3-4 weeks of age, before the eventual photoreceptor degeneration. Despite the shortening of their outer segments, the dark current of transgenic rods was 1.5-2.2-fold higher than in nontransgenic controls. Similarly, the dim flash response amplitude in R838S + rods was larger, time to peak was delayed, and flash sensitivity was increased, all suggesting elevated dark-adapted free cGMP in transgenic rods. In rods expressing R838S RetGC1, dark-current noise increased and the exchange current, detected after a saturating flash, became more pronounced. These results suggest disrupted Ca 2+ phototransduction feedback and abnormally high free-Ca 2+ concentration in the outer segments. Notably, photoreceptor degeneration, which typically occurred after 3 months of age in R838S RetGC1 transgenic mice in GCAP1,2 +/+ or GCAP1,2 +/- backgrounds, was prevented in GCAP1,2 -/- mice lacking Ca 2+ feedback to guanylyl cyclase. In summary, the dysregulation of guanylyl cyclase in RetGC1-linked CORD6 is a "phototransduction disease," which means it is associated with increased free-cGMP and Ca 2+ levels in photoreceptors. SIGNIFICANCE STATEMENT In a mouse model expressing human membrane guanylyl cyclase 1 (RetGC1, GUCY2D ), a mutation associated with early progressing congenital blindness, cone-rod dystrophy type 6 (CORD6), deregulates calcium-sensitive feedback of phototransduction to the cyclase mediated by guanylyl cyclase activating proteins (GCAPs), which are calcium-sensor proteins. The abnormal calcium sensitivity of the cyclase increases cGMP-gated dark current in the rod outer segments, reshapes rod photoresponses, and triggers photoreceptor death. This work is the first to demonstrate a direct physiological effect of GUCY2D CORD6-linked mutation on photoreceptor physiology in vivo It also identifies the abnormal regulation of the cyclase by calcium-sensor proteins as the main trigger for the photoreceptor death. Copyright © 2018 the authors 0270-6474/18/382990-11$15.00/0.

Spectral sensitivity of cones of the monkey Macaca fascicularis.

PubMed Central

Baylor, D A; Nunn, B J; Schnapf, J L

1987-01-01

1. Spectral sensitivities of cones in the retina of cynomolgus monkeys were determined by recording photocurrents from single outer segments with a suction electrode. 2. The amplitude and shape of the response to a flash depended upon the number of photons absorbed but not the wave-length, so that the 'Principle of Univariance' was obeyed. 3. Spectra were obtained from five 'blue', twenty 'green', and sixteen 'red' cones. The wave-lengths of maximum sensitivity were approximately 430, 531 and 561 nm, respectively. 4. The spectra of the three types of cones had similar shapes when plotted on a log wave number scale, and were fitted by an empirical expression. 5. There was no evidence for the existence of subclasses of cones with different spectral sensitivities. Within a class, the positions of the individual spectra on the wave-length axis showed a standard deviation of less than 1.5 nm. 6. Psychophysical results on human colour matching (Stiles & Burch, 1955; Stiles & Burch, 1959) were well predicted from the spectral sensitivities of the monkey cones. After correction for pre-retinal absorption and pigment self-screening, the spectra of the red and green cones matched the respective pi 5 and pi 4 mechanisms of Stiles (1953, 1959). PMID:3443931

The prenyl-binding protein PrBP/δ: a chaperone participating in intracellular trafficking

PubMed Central

Zhang, Houbin; Constantine, Ryan; Frederick, Jeanne M.; Baehr, Wolfgang

2012-01-01

Expressed ubiquitously, PrBP/δ functions as chaperone/co-factor in the transport of a subset of prenylated proteins. PrBP/δ features an immunoglobulin-like β-sandwich fold for lipid binding, and interacts with diverse partners. PrBP/δ binds both C-terminal C15 and C20 prenyl side chains of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras superfamily. PrBP/δ also interacts with the small GTPases, ARL2 and ARL3, which act as release factors (GDFs) for prenylated cargo. Targeted deletion of the mouse Pde6d gene encoding PrBP/δ resulted in impeded trafficking to the outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and geranylgeranylated, respectively. Rod and cone transducin trafficking was largely unaffected. These trafficking defects produce progressive cone-rod dystrophy in the Pde6d−/− mouse. PMID:22960045

The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility*

PubMed Central

Ding, Xi-Qin; Thapa, Arjun; Ma, Hongwei; Xu, Jianhua; Elliott, Michael H.; Rodgers, Karla K.; Smith, Marci L.; Wang, Jin-Shan; Pittler, Steven J.; Kefalov, Vladimir J.

2016-01-01

Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability. As cones comprise only 2–3% of the total photoreceptor population in the wild-type mouse retina, we used Cngb3−/−/Nrl−/− mice with CNGB3 deficiency on a cone-dominant background in our study. We found that, in the absence of CNGB3, CNGA3 was able to travel to the outer segments, co-localize with cone opsin, and form tetrameric complexes. Electroretinogram analyses revealed reduced cone light response amplitude/sensitivity and slower response recovery in Cngb3−/−/Nrl−/− mice compared with Nrl−/− mice. Absence of CNGB3 expression altered the adaptation capacity of cones and severely compromised function in bright light. Biochemical analysis demonstrated that CNGA3 channels lacking CNGB3 were more resilient to proteolysis than CNGA3/CNGB3 channels, suggesting a hindered structural flexibility. Thus, CNGB3 regulates cone light response kinetics and the channel structural flexibility. This work advances our understanding of the biochemical and functional role of CNGB3 in cone photoreceptors. PMID:26893377

Micro-cone targets for producing high energy and low divergence particle beams

DOEpatents

Le Galloudec, Nathalie

2013-09-10

The present invention relates to micro-cone targets for producing high energy and low divergence particle beams. In one embodiment, the micro-cone target includes a substantially cone-shaped body including an outer surface, an inner surface, a generally flat and round, open-ended base, and a tip defining an apex. The cone-shaped body tapers along its length from the generally flat and round, open-ended base to the tip defining the apex. In addition, the outer surface and the inner surface connect the base to the tip, and the tip curves inwardly to define an outer surface that is concave, which is bounded by a rim formed at a juncture where the outer surface meets the tip.

A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy

PubMed Central

1991-01-01

Cancer-associated retinopathy (CAR), a paraneoplastic syndrome, is characterized by the degeneration of retinal photoreceptors under conditions where the tumor and its metastases have not invaded the eye. The retinopathy often is apparent before the diagnosis of cancer and may be associated with autoantibodies that react with specific sites in the retina. We have examined the sera from patients with CAR to further characterize the retinal antigen. Western blot analysis of human retinal proteins reveals a prominent band at 26 kD that is labeled by the CAR antisera. Antibodies to the 26-kD protein were affinity- purified from complex CAR antisera and used for EM-immunocytochemical localization of the protein to the nuclei, inner and outer segments of both rod and cone cells. Other antibodies obtained from the CAR sera did not label photoreceptors. Using the affinity-purified antibodies for detection, the 26-kD protein, designated p26, was purified to homogeneity from the outer segments of bovine rod photoreceptor cells by Phenyl-Sepharose and ion exchange chromatography. Partial amino acid sequence of p26 was determined by gas phase Edman degradation and revealed extensive homology with a cone-specific protein, visinin. Based upon structural relatedness, both the p26 rod protein and visinin are members of the calmodulin family and contain calcium binding domains of the E-F hand structure. PMID:1999465

Early photoreceptor outer segment loss and retinoschisis in Cohen syndrome.

PubMed

Uyhazi, Katherine E; Binenbaum, Gil; Carducci, Nicholas; Zackai, Elaine H; Aleman, Tomas S

2018-06-01

To describe early structural and functional retinal changes in a patient with Cohen syndrome. A 13-month-old Caucasian girl of Irish and Spanish ancestry was noted to have micrognathia and laryngomalacia at birth, which prompted a genetic evaluation that revealed biallelic deletions in COH1 (VPS13B) (a maternally inherited 60-kb deletion involving exons 26-32 and a paternally inherited 3.5-kb deletion within exon 17) consistent with Cohen syndrome. She underwent a complete ophthalmic examination, full-field flash electroretinography and retinal imaging with spectral domain optical coherence tomography. Central vision was central, steady, and maintained. There was bilateral myopic astigmatic refractive error. Fundus exam was notable for dark foveolar pigmentation, but no obvious abnormalities of either eye. Spectral domain optical coherence tomography cross sections through the fovea revealed a normal appearing photoreceptor outer nuclear layer but loss of the interdigitation signal between the photoreceptor outer segments and the apical retinal pigment epithelium. Retinoschisis involving the inner nuclear layer of both eyes and possible ganglion cell layer thinning were also noted. There was a detectable electroretinogram with similarly reduced amplitudes of rod- (white, 0.01 cd.s.m -2 ) and cone-mediated (3 cd.s.m -2 , 30 Hz) responses. Photoreceptor outer segment abnormalities and retinoschisis may represent the earliest structural retinal change detected by spectral domain optical coherence tomography in patients with Cohen syndrome, suggesting a complex pathophysiology with primary involvement of the photoreceptor cilium and disorganization of the structural integrity of the inner retina.

Late-onset cone photoreceptor degeneration induced by R172W mutation in Rds and partial rescue by gene supplementation.

PubMed

Conley, Shannon; Nour, May; Fliesler, Steven J; Naash, Muna I

2007-12-01

R172W is a common mutation in the human retinal degeneration slow (RDS) gene, associated with a late-onset dominant macular dystrophy. In this study, the authors characterized a mouse model that closely mimics the human phenotype and tested the feasibility of gene supplementation as a disease treatment strategy. Transgenic mouse lines carrying the R172W mutation were generated. The retinal phenotype associated with this mutation in a low-expresser line (L-R172W) was examined, both structurally (histology with correlative immunohistochemistry) and functionally (electroretinography). By examining animals over time and with various rds genetic backgrounds, the authors evaluated the dominance of the defect. To assess the efficacy of gene transfer therapy as a treatment for this defect, a previously characterized transgenic line expressing the normal mouse peripherin/Rds (NMP) was crossed with a higher-expresser Rds line harboring the R172W mutation (H-R172W). Functional, structural, and biochemical analyses were used to assess rescue of the retinal disease phenotype. In the wild-type (WT) background, L-R172W mice exhibited late-onset (12-month) dominant cone degeneration without any apparent effect on rods. The degeneration was slightly accelerated (9 months) in the rds(+/-) background. L-R172W retinas did not form outer segments in the absence of endogenous Rds. With use of the H-R172W line on an rds(+/-) background for proof-of-principle genetic supplementation studies, the NMP transgene product rescued rod and cone functional defects and supported outer segment integrity up to 3 months of age, but the rescue effect did not persist in older (11-month) animals. The R172W mutation leads to dominant cone degeneration in the mouse model, regardless of the expression level of the transgene. In contrast, effects of the mutation on rods are dose dependent, underscoring the usefulness of the L-R172W line as a faithful model of the human phenotype. This model may prove helpful in future studies on the mechanisms of cone degeneration and for elucidating the different roles of Rds in rods and cones. This study provides evidence that Rds genetic supplementation can be used to partially rescue visual function. Although this strategy is capable of rescuing haploinsufficiency, it does not rescue the long-term degeneration associated with a gain-of-function mutation.

Cone and Rod Loss in Stargardt Disease Revealed by Adaptive Optics Scanning Light Ophthalmoscopy

PubMed Central

Song, Hongxin; Rossi, Ethan A.; Latchney, Lisa; Bessette, Angela; Stone, Edwin; Hunter, Jennifer J.; Williams, David R.; Chung, Mina

2015-01-01

Importance Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy. Observations Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P <.001) with a dark cone appearance. No foveal cones were detected in the older brother. In the younger brother, foveal cones were enlarged with low density (peak cone density, 48.3 × 103 cones/mm2). The ratio of cone to rod spacing was increased in both patients, with greater divergence from normal approaching the foveal center, indicating that cone loss predominates centrally and rod loss increases peripherally. Both parents had normal photoreceptor mosaics. Genetic testing revealed 3 disease-causing mutations. Conclusions and Relevance This study provides in vivo images of rods and cones in STGD1. Although the primary clinical features of STGD1 are retinal pigment epithelial lesions, adaptive optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1. PMID:26247787

Adaptive optics optical coherence tomography for measuring phase and reflectance dynamics of photoreceptors

NASA Astrophysics Data System (ADS)

Kocaoglu, Omer P.; Jonnal, Ravi S.; Lee, Sangyeol; Wang, Qiang; Liu, Zhuolin; Miller, Donald T.

2012-03-01

Optical coherence tomography with adaptive optics (AO-OCT) is a noninvasive method for imaging the living retina at the microscopic level. We used AO-OCT technology to follow changes in cone photoreceptor outer segment (OS) length and reflectance. To substantially increase sensitivity of the length measurements, a novel phase retrieval technique was demonstrated, capable of detecting changes on a nanometer scale. We acquired volume videos of 0.65°x0.65° retinal patches at 1.5° temporal to the fovea over 75 and 105 minutes in two subjects. Volumes were dewarped and registered, after which the cone intensity, OS length, and referenced phase difference were tracked over time. The reflections from inner segment/OS junction (IS/OS) and posterior tips of OS (PT) showed significant intensity variations over time. In contrast, the OS length as measured from the intensity images did not change, indicative of a highly stable OS length at least down to the level of the system's axial resolution (3μm). Smaller axial changes, however, were detected with our phase retrieval technique. Specifically, the PT-IS/OS phase difference for the same cones showed significant variation, suggesting real sub-wavelength changes in OS length of 125+/-46 nm/hr for the 22 cones followed. We believe these length changes are due to the normal renewal process of the cone OS that elongate the OS at a rate of about 100 nm/hr. The phase difference measurements were strongly correlated among Alines within the same cone (0.65 radians standard deviation) corresponding to a length sensitivity of 31 nm, or ~100 times smaller than the axial resolution of our system.

Evolution, Development and Function of Vertebrate Cone Oil Droplets

PubMed Central

Toomey, Matthew B.; Corbo, Joseph C.

2017-01-01

To distinguish colors, the nervous system must compare the activity of distinct subtypes of photoreceptors that are maximally sensitive to different portions of the light spectrum. In vertebrates, a variety of adaptations have arisen to refine the spectral sensitivity of cone photoreceptors and improve color vision. In this review article, we focus on one such adaptation, the oil droplet, a unique optical organelle found within the inner segment of cone photoreceptors of a diverse array of vertebrate species, from fish to mammals. These droplets, which consist of neutral lipids and carotenoid pigments, are interposed in the path of light through the photoreceptor and modify the intensity and spectrum of light reaching the photosensitive outer segment. In the course of evolution, the optical function of oil droplets has been fine-tuned through changes in carotenoid content. Species active in dim light reduce or eliminate carotenoids to enhance sensitivity, whereas species active in bright light precisely modulate carotenoid double bond conjugation and concentration among cone subtypes to optimize color discrimination and color constancy. Cone oil droplets have sparked the curiosity of vision scientists for more than a century. Accordingly, we begin by briefly reviewing the history of research on oil droplets. We then discuss what is known about the developmental origins of oil droplets. Next, we describe recent advances in understanding the function of oil droplets based on biochemical and optical analyses. Finally, we survey the occurrence and properties of oil droplets across the diversity of vertebrate species and discuss what these patterns indicate about the evolutionary history and function of this intriguing organelle. PMID:29276475

Photoreceptor Layer Thickness Changes During Dark Adaptation Observed With Ultrahigh-Resolution Optical Coherence Tomography.

PubMed

Lu, Chen D; Lee, ByungKun; Schottenhamml, Julia; Maier, Andreas; Pugh, Edward N; Fujimoto, James G

2017-09-01

To examine outer retinal band changes after flash stimulus and subsequent dark adaptation with ultrahigh-resolution optical coherence tomography (UHR-OCT). Five dark-adapted left eyes of five normal subjects were imaged with 3-μm axial-resolution UHR-OCT during 30 minutes of dark adaptation following 96%, 54%, 23%, and 0% full-field and 54% half-field rhodopsin bleach. We identified the ellipsoid zone inner segment/outer segment (EZ[IS/OS]), cone interdigitation zone (CIZ), rod interdigitation zone (RIZ), retinal pigment epithelium (RPE), and Bruch's membrane (BM) axial positions and generated two-dimensional thickness maps of the EZ(IS/OS) to the four bands. The average thickness over an area of the thickness map was compared against that of the dark-adapted baselines. The time-dependent thickness changes (photoresponses) were statistically compared against 0% bleach. Dark adaptometry was performed with the same bleaching protocol. The EZ(IS/OS)-CIZ photoresponse was significantly different at 96% (P < 0.0001) and 54% (P = 0.006) bleach. At all three bleaching levels, the EZ(IS/OS)-RIZ, -RPE, and -BM responses were significantly different (P < 0.0001). The EZ(IS/OS)-CIZ and EZ(IS/OS)-RIZ time courses were similar to the recovery of rod- and cone-mediated sensitivity, respectively, measured with dark adaptometry. The maximal EZ(IS/OS)-CIZ and EZ(IS/OS)-RIZ response magnitudes doubled from 54% to 96% bleach. Both EZ(IS/OS)-RPE and EZ(IS/OS)-BM responses resembled dampened oscillations that were graded in amplitude and duration with bleaching intensity. Half-field photoresponses were localized to the stimulated retina. With noninvasive, near-infrared UHR-OCT, we characterized three distinct, spatially localized photoresponses in the outer retinal bands. These photoresponses have potential value as physical correlates of photoreceptor function.

Outer Retinal Changes Including the Ellipsoid Zone Band in Usher Syndrome 1B due to MYO7A Mutations.

PubMed

Sumaroka, Alexander; Matsui, Rodrigo; Cideciyan, Artur V; McGuigan, David B; Sheplock, Rebecca; Schwartz, Sharon B; Jacobson, Samuel G

2016-07-01

To study transition zones from normal to abnormal retina in Usher syndrome IB (USH1B) caused by myosin 7A (MYO7A) mutations. Optical coherence tomography (OCT) scattering layers in outer retina were segmented in patients (n = 16, ages 2-42; eight patients had serial data, average interval 4.5 years) to quantify outer nuclear layer (ONL) and outer segments (OS) as well as the locus of EZ (ellipsoid zone) edge and its extent from the fovea. Static perimetry was measured under dark-adapted (DA) and light-adapted (LA) conditions. Ellipsoid zone edge in USH1B-MYO7A could be located up to 23° from the fovea. Ellipsoid zone extent constricted at a rate of 0.51°/year with slower rates at smaller eccentricities. A well-defined EZ line could be associated with normal or abnormal ONL and/or OS thickness; detectable ONL extended well beyond EZ edge. At the EZ edge, the local slope of LA sensitivity loss was 2.6 (±1.7) dB/deg for central transition zones. At greater eccentricities, the local slope of cone sensitivity loss was shallower (1.1 ± 0.4 dB/deg for LA) than that of rod sensitivity loss (2.8 ± 1.2 dB/deg for DA). In USH1B-MYO7A, constriction rate of EZ extent depends on the initial eccentricity of the transition. Ellipsoid zone edges in the macula correspond to large local changes in cone vision, but extramacular EZ edges show more pronounced losses on rod-based vision tests. It is advisable to use not only the EZ line but also other structural and functional parameters for estimating natural history of disease and possible therapeutic effects in future clinical trials of USH1B-MYO7A.

Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive retinitis pigmentosa.

PubMed

Lam, Byron L; Züchner, Stephan L; Dallman, Julia; Wen, Rong; Alfonso, Eduardo C; Vance, Jeffery M; Peričak-Vance, Margaret A

2014-01-01

A single-nucleotide mutation in the gene that encodes DHDDS has been identified by whole exome sequencing as the cause of the non-syndromic recessive retinitis pigmentosa (RP) in a family of Ashkenazi Jewish origin in which three of the four siblings have early onset retinal degeneration. The peripheral retinal degeneration in the affected siblings was evident in the initial examination in 1992 and only one had detectable electroretinogram (ERG) that suggested cone-rod dysfunction. The pigmentary retinal degeneration subsequently progressed rapidly. The identified mutation changes the highly conserved residue Lys42 to Glu, resulting in lower catalytic efficiency. Patterns of plasma transferrin isoelectric focusing gel were normal in all family members, indicating no significant abnormality in protein glycosylation. Dolichols have been shown to influence the fluidity and of the membrane and promote vesicle fusion. Considering that photoreceptor outer segments contain stacks of membrane discs, we believe that the mutation may lead to low dolichol levels in photoreceptor outer segments, resulting in unstable membrane structure that leads to photoreceptor degeneration.

Oil droplets of bird eyes: microlenses acting as spectral filters

PubMed Central

Stavenga, Doekele G.; Wilts, Bodo D.

2014-01-01

An important component of the cone photoreceptors of bird eyes is the oil droplets located in front of the visual-pigment-containing outer segments. The droplets vary in colour and are transparent, clear, pale or rather intensely yellow or red owing to various concentrations of carotenoid pigments. Quantitative modelling of the filter characteristics using known carotenoid pigment spectra indicates that the pigments’ absorption spectra are modified by the high concentrations that are present in the yellow and red droplets. The high carotenoid concentrations not only cause strong spectral filtering but also a distinctly increased refractive index at longer wavelengths. The oil droplets therefore act as powerful spherical microlenses, effectively channelling the spectrally filtered light into the photoreceptor's outer segment, possibly thereby compensating for the light loss caused by the spectral filtering. The spectral filtering causes narrow-band photoreceptor spectral sensitivities, which are well suited for spectral discrimination, especially in birds that have feathers coloured by carotenoid pigments. PMID:24395968

Phosphorylation-independent Suppression of Light-activated Visual Pigment by Arrestin in Carp Rods and Cones*

PubMed Central

Tomizuka, Junko; Tachibanaki, Shuji; Kawamura, Satoru

2015-01-01

Visual pigment in photoreceptors is activated by light. Activated visual pigment (R*) is believed to be inactivated by phosphorylation of R* with subsequent binding of arrestin. There are two types of photoreceptors, rods and cones, in the vertebrate retina, and they express different subtypes of arrestin, rod and cone type. To understand the difference in the function between rod- and cone-type arrestin, we first identified the subtype of arrestins expressed in rods and cones in carp retina. We found that two rod-type arrestins, rArr1 and rArr2, are co-expressed in a rod and that a cone-type arrestin, cArr1, is expressed in blue- and UV-sensitive cones; the other cone-type arrestin, cArr2, is expressed in red- and green-sensitive cones. We quantified each arrestin subtype and estimated its concentration in the outer segment of a rod or a cone in the dark; they were ∼0.25 mm (rArr1 plus rArr2) in a rod and 0.6–0.8 mm (cArr1 or cArr2) in a cone. The effect of each arrestin was examined. In contrast to previous studies, both rod and cone arrestins suppressed the activation of transducin in the absence of visual pigment phosphorylation, and all of the arrestins examined (rArr1, rArr2, and cArr2) bound transiently to most probably nonphosphorylated R*. One rod arrestin, rArr2, bound firmly to phosphorylated pigment, and the other two, rArr1 and cArr2, once bound to phosphorylated R* but dissociated from it during incubation. Our results suggested a novel mechanism of arrestin effect on the suppression of the R* activity in both rods and cones. PMID:25713141

The prenyl-binding protein PrBP/δ: a chaperone participating in intracellular trafficking.

PubMed

Zhang, Houbin; Constantine, Ryan; Frederick, Jeanne M; Baehr, Wolfgang

2012-12-15

Expressed ubiquitously, PrBP/δ functions as chaperone/co-factor in the transport of a subset of prenylated proteins. PrBP/δ features an immunoglobulin-like β-sandwich fold for lipid binding, and interacts with diverse partners. PrBP/δ binds both C-terminal C15 and C20 prenyl side chains of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras superfamily. PrBP/δ also interacts with the small GTPases, ARL2 and ARL3, which act as release factors (GDFs) for prenylated cargo. Targeted deletion of the mouse Pde6d gene encoding PrBP/δ resulted in impeded trafficking to the outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and geranylgeranylated, respectively. Rod and cone transducin trafficking was largely unaffected. These trafficking defects produce progressive cone-rod dystrophy in the Pde6d(-/-) mouse. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gene replacement therapy for retinal CNG channelopathies.

PubMed

Schön, Christian; Biel, Martin; Michalakis, Stylianos

2013-10-01

Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

Multimodal Imaging of Photoreceptor Structure in Choroideremia

PubMed Central

Johnson, Ryan D.; Williams, Vesper; Summerfelt, Phyllis; Dubra, Alfredo; Weinberg, David V.; Stepien, Kimberly E.; Fishman, Gerald A.; Carroll, Joseph

2016-01-01

Purpose Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions. Methods Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques. Results Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina. Conclusions Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors. PMID:27936069

Multimodal Imaging of Photoreceptor Structure in Choroideremia.

PubMed

Sun, Lynn W; Johnson, Ryan D; Williams, Vesper; Summerfelt, Phyllis; Dubra, Alfredo; Weinberg, David V; Stepien, Kimberly E; Fishman, Gerald A; Carroll, Joseph

2016-01-01

Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions. Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques. Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina. Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors.

Influence of margin segmentation and anomalous volcanism upon the break-up of the Hatton Bank rifted margin, west of the UK

NASA Astrophysics Data System (ADS)

Elliott, G. M.; Parson, L. M.

2007-12-01

The Hatton Bank margin, flanking the Iceland Basin is a widely cited example of a volcanic rifted margin. Prior to this study insights into the break-up history of the margin have been limited to profiles in the north and south, yet whilst valuable, the along margin tectono-magmatic variability has not been revealed. Over 5660 line km of high quality reflection seismic profiles with supplementary multibeam bathymetry were collected to support the UK's claim to Hatton region under the United Nations Convention on Law of the Sea (UNCLOS). Integration of this new data with existing profiles, allowed the margin to be divided into three segments, each of which are flanked by oceanic crust with a smooth upper surface and internal dipping reflectors. The southernmost segment is characterised by a series of inner and outer seaward dipping reflector (SDR) packages, which are separated by an outer high feature. The outer SDR are truncated by Endymion Spur, a chain of steep sided, late stage volcanic cones linked with necks. The central sector has no inner SDR package and is characterised by the presence of a highly intruded continental block, the Hatton Bank Block (HBB). The northern sector is adjacent to Lousy Bank, with a wider region of SDR recognised than to the south and a high amount of volcanic cones imaged. The variations in the distribution of the SDR's along the margin, the presence of the HBB and Endymion Spur all suggest that the break-up process was not uniform alongstrike. The division of the margin into three sectors reveals that structural segmentation played an important role in producing the variations along the margin. Break- up initiated in the south and progressed north producing the SDR packages witnessed, when the HBB was encountered the focus of break-up moved seaward of the block. The northern sector was closer to the Iceland Hotspot and hence a greater amount of volcanism is encountered. The smooth oceanic basement also indicates a high thermal flux leading to high melt production and subsidence rates forming the dipping reflectors. Shortly after break-up the eruption of Endymion Spur occurred. The nature of the magma erupted is unknown but from the steepness of the cones, it is inferred to be viscous and considering the setting, mostly likely a tholeiitic cumulate. A possible trigger for the Endymion Spur is the passage of a pulse of hotter than normal asthenospheric material along the margin, which interacted with lower crustal material to produce melt to feed the volcanic centres. Enhanced asthenospheric heat flow has been invoked to explain the V-shaped ridges along the present day Reykjanes Ridge and it is probable that the Endymion Spur represents previous such pulses along the margin/spreading axis. The location of the enhanced volcanism is itself controlled by crustal segmentation, with the Endymion Spur limited to the southern sector. The crustal thickness in this sector is approx. 2 to 3 km thinner than that found in the central segment, in which Endymion Spur is absent. The role of the segmentation along the margin has influenced the break-up style (presence or absence of SDR) and also the location and nature of post break-up volcanism.

Late-Onset Cone Photoreceptor Degeneration Induced by R172W Mutation in Rds and Partial Rescue by Gene Supplementation

PubMed Central

Conley, Shannon; Nour, May; Fliesler, Steven J.; Naash, Muna I.

2008-01-01

Purpose R172W is a common mutation in the human retinal degeneration slow (RDS) gene, associated with a late-onset dominant macular dystrophy. In this study, the authors characterized a mouse model that closely mimics the human phenotype and tested the feasibility of gene supplementation as a disease treatment strategy. Methods Transgenic mouse lines carrying the R172W mutation were generated. The retinal phenotype associated with this mutation in a low-expresser line (L-R172W) was examined, both structurally (histology with correlative immunohistochemistry) and functionally (electroretinography). By examining animals over time and with various rds genetic backgrounds, the authors evaluated the dominance of the defect. To assess the efficacy of gene transfer therapy as a treatment for this defect, a previously characterized transgenic line expressing the normal mouse peripherin/Rds (NMP) was crossed with a higher-expresser Rds line harboring the R172W mutation (H-R172W). Functional, structural, and biochemical analyses were used to assess rescue of the retinal disease phenotype. Results In the wild-type (WT) background, L-R172W mice exhibited late-onset (12-month) dominant cone degeneration without any apparent effect on rods. The degeneration was slightly accelerated (9 months) in the rds+/− background. L-R172W retinas did not form outer segments in the absence of endogenous Rds. With use of the H-R172W line on an rds+/− background for proof-of-principle genetic supplementation studies, the NMP transgene product rescued rod and cone functional defects and supported outer segment integrity up to 3 months of age, but the rescue effect did not persist in older (11-month) animals. Conclusions The R172W mutation leads to dominant cone degeneration in the mouse model, regardless of the expression level of the transgene. In contrast, effects of the mutation on rods are dose dependent, underscoring the usefulness of the L-R172W line as a faithful model of the human phenotype. This model may prove helpful in future studies on the mechanisms of cone degeneration and for elucidating the different roles of Rds in rods and cones. This study provides evidence that Rds genetic supplementation can be used to partially rescue visual function. Although this strategy is capable of rescuing haplo-insufficiency, it does not rescue the long-term degeneration associated with a gain-of-function mutation. PMID:18055786

Numerical simulation of axisymmetric valve operation for different outer cone angle

NASA Astrophysics Data System (ADS)

Smyk, Emil

One of the method of flow separation control is application of axisymmetric valve. It is composed of nozzle with core. Normally the main flow is attached to inner cone and flow by preferential collector to primary flow pipe. If through control nozzle starts flow jet (control jet) the main flow is switched to annular secondary collector. In both situation the main flow is deflected to inner or outer cone (placed at the outlet of the valve's nozzle) by Coanda effect. The paper deals with the numerical simulation of this axisymetric annular nozzle with integrated synthetic jet actuator. The aim of the work is influence examination of outer cone angle on deflection on main stream.

Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy.

PubMed

Katschke, Kenneth J; Xi, Hongkang; Cox, Christian; Truong, Tom; Malato, Yann; Lee, Wyne P; McKenzie, Brent; Arceo, Rommel; Tao, Jianhua; Rangell, Linda; Reichelt, Mike; Diehl, Lauri; Elstrott, Justin; Weimer, Robby M; Campagne, Menno van Lookeren

2018-05-09

Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA. When exposed to human serum following outer blood-retinal barrier breakdown, POS act as potent activators of the classical and alternative complement pathway. In mouse models of retinal degeneration, classical and alternative pathway complement activation on photoreceptors contributed to the loss of photoreceptor function. This was dependent on C5a-mediated recruitment of peripheral blood monocytes but independent of resident microglia. Genetic or pharmacologic inhibition of both classical and alternative complement C3 and C5 convertases was required to reduce progressive degeneration of photoreceptor rods and cones. Our study implicates systemic classical and alternative complement proteins and peripheral blood monocytes as critical effectors of localized retinal degeneration with potential relevance for the contribution of complement activation to GA.

The limit of photoreceptor sensitivity: molecular mechanisms of dark noise in retinal cones.

PubMed

Holcman, David; Korenbrot, Juan I

2005-06-01

Detection threshold in cone photoreceptors requires the simultaneous absorption of several photons because single photon photocurrent is small in amplitude and does not exceed intrinsic fluctuations in the outer segment dark current (dark noise). To understand the mechanisms that limit light sensitivity, we characterized the molecular origin of dark noise in intact, isolated bass single cones. Dark noise is caused by continuous fluctuations in the cytoplasmic concentrations of both cGMP and Ca(2+) that arise from the activity in darkness of both guanylate cyclase (GC), the enzyme that synthesizes cGMP, and phosphodiesterase (PDE), the enzyme that hydrolyzes it. In cones loaded with high concentration Ca(2+) buffering agents, we demonstrate that variation in cGMP levels arise from fluctuations in the mean PDE enzymatic activity. The rates of PDE activation and inactivation determine the quantitative characteristics of the dark noise power density spectrum. We developed a mathematical model based on the dynamics of PDE activity that accurately predicts this power spectrum. Analysis of the experimental data with the theoretical model allows us to determine the rates of PDE activation and deactivation in the intact photoreceptor. In fish cones, the mean lifetime of active PDE at room temperature is approximately 55 ms. In nonmammalian rods, in contrast, active PDE lifetime is approximately 555 ms. This remarkable difference helps explain why cones are noisier than rods and why cone photocurrents are smaller in peak amplitude and faster in time course than those in rods. Both these features make cones less light sensitive than rods.

Acute tissue reactions, inner segment pathology, and effects of the antioxidant α1-microglobulin in an in vitro model of retinal detachment.

PubMed

Ghosh, Fredrik; Åkerström, Bo; Bergwik, Jesper; Abdshill, Hodan; Gefors, Lina; Taylor, Linnéa

2018-04-18

The purpose of this study was to explore acute tissue reactions, ultrastructural photoreceptor morphology with emphasis on inner segments, and the effect of antioxidant treatment in an in vitro model of rhegmatogenous retinal detachment (RRD). A previously described method of RRD simulation was used with adult retinal porcine explants kept free-floating in culture medium with or without treatment with the radical scavenger α 1 -microglobulin (A1M). Explants were examined at 5 time points from 1 to 24 h using transmission electron microscopy as well as quantitative real-time PCR (RT-PCR) to quantify gene expression of the cell stress marker heat shock protein 70 (Hsp70) and oxidative stress marker heme oxygenase (HO-1). The culture medium level of the cell damage marker lactate dehydrogenase (LDH) and oxidative stress DNA damage marker 8-Oxo-2'-deoxyguanosine (8-OHdG) was also assessed at each time point. We found that the levels of Hsp70 and LDH rapidly increased in both groups, and at 3 and 6 h, Hsp70 was significantly higher in A1M treated retinas. At 24 h, Hsp70 and LDH, as well as 8-OHdG were significantly lower compared with controls, whereas the tissue level of HO-1 was significantly higher. Progressive ultrastructural photoreceptor changes were seen in untreated control explants from 1 h and onwards including outer segment shortening and loss, disruption of organelles within the inner segments and loss of perikarya in the outer nuclear layer. Inner segment pathology was more rapid and extensive in rods compared with in cones. In A1M treated counterparts, damage to rod inner segment mitochondria was significantly higher after 1 h of culture, but after this time, no statistical difference was found. At 24 h, cone inner segment mitochondrial disruption was significantly higher in control retinas and the number of surviving perikarya lower. From our results, we conclude that retinal explants elicit acute cell stress reactions when placed in culture without physical support simulating a detached retina floating in the vitreous space. Photoreceptors rapidly display degenerative changes including extensive damage to inner segment mitochondria indicating loss of energy transduction as an early key event. A1M increases initial mitochondrial stress in the rods, however, subsequent pathology is attenuated by the treatment, highlighting the dynamics of protective as well as disruptive oxidative stress reactions in the detached retina. Copyright © 2018 Elsevier Ltd. All rights reserved.

Photoreceptor Layer Thickness Changes During Dark Adaptation Observed With Ultrahigh-Resolution Optical Coherence Tomography

PubMed Central

Lu, Chen D.; Lee, ByungKun; Schottenhamml, Julia; Maier, Andreas; Pugh, Edward N.; Fujimoto, James G.

2017-01-01

Purpose To examine outer retinal band changes after flash stimulus and subsequent dark adaptation with ultrahigh-resolution optical coherence tomography (UHR-OCT). Methods Five dark-adapted left eyes of five normal subjects were imaged with 3-μm axial-resolution UHR-OCT during 30 minutes of dark adaptation following 96%, 54%, 23%, and 0% full-field and 54% half-field rhodopsin bleach. We identified the ellipsoid zone inner segment/outer segment (EZ[IS/OS]), cone interdigitation zone (CIZ), rod interdigitation zone (RIZ), retinal pigment epithelium (RPE), and Bruch's membrane (BM) axial positions and generated two-dimensional thickness maps of the EZ(IS/OS) to the four bands. The average thickness over an area of the thickness map was compared against that of the dark-adapted baselines. The time-dependent thickness changes (photoresponses) were statistically compared against 0% bleach. Dark adaptometry was performed with the same bleaching protocol. Results The EZ(IS/OS)-CIZ photoresponse was significantly different at 96% (P < 0.0001) and 54% (P = 0.006) bleach. At all three bleaching levels, the EZ(IS/OS)-RIZ, -RPE, and -BM responses were significantly different (P < 0.0001). The EZ(IS/OS)-CIZ and EZ(IS/OS)-RIZ time courses were similar to the recovery of rod- and cone-mediated sensitivity, respectively, measured with dark adaptometry. The maximal EZ(IS/OS)-CIZ and EZ(IS/OS)-RIZ response magnitudes doubled from 54% to 96% bleach. Both EZ(IS/OS)-RPE and EZ(IS/OS)-BM responses resembled dampened oscillations that were graded in amplitude and duration with bleaching intensity. Half-field photoresponses were localized to the stimulated retina. Conclusions With noninvasive, near-infrared UHR-OCT, we characterized three distinct, spatially localized photoresponses in the outer retinal bands. These photoresponses have potential value as physical correlates of photoreceptor function. PMID:28898357

High-voltage R-F feedthrough bushing

DOEpatents

Grotz, G.F.

1982-09-03

Described is a multi-element, high voltage radio frequency bushing for transmitting rf energy to an antenna located in a vacuum container. The bushing includes a center conductor of complex geometrical shape, an outer coaxial shield conductor, and a thin-walled hollow truncated cone insulator disposed between central and outer conductors. The shape of the center conductor, which includes a reverse curvature portion formed of a radially inwardly directed shoulder and a convex portion, controls the uniformity of the axial surface gradient on the insulator cone. The outer shield has a first substantially cylindrical portion and a second radially inwardly extending truncated cone portion.

High voltage RF feedthrough bushing

DOEpatents

Grotz, Glenn F.

1984-01-01

Described is a multi-element, high voltage radio frequency bushing for trmitting RF energy to an antenna located in a vacuum container. The bushing includes a center conductor of complex geometrical shape, an outer coaxial shield conductor, and a thin-walled hollow truncated cone insulator disposed between central and outer conductors. The shape of the center conductor, which includes a reverse curvature portion formed of a radially inwardly directed shoulder and a convex portion, controls the uniformity of the axial surface gradient on the insulator cone. The outer shield has a first substantially cylindrical portion and a second radially inwardly extending truncated cone portion.

Functional Optical Coherence Tomography Enables In Vivo Physiological Assessment of Retinal Rod and Cone Photoreceptors

PubMed Central

Zhang, Qiuxiang; Lu, Rongwen; Wang, Benquan; Messinger, Jeffrey D.; Curcio, Christine A.; Yao, Xincheng

2015-01-01

Transient intrinsic optical signal (IOS) changes have been observed in retinal photoreceptors, suggesting a unique biomarker for eye disease detection. However, clinical deployment of IOS imaging is challenging due to unclear IOS sources and limited signal-to-noise ratios (SNRs). Here, by developing high spatiotemporal resolution optical coherence tomography (OCT) and applying an adaptive algorithm for IOS processing, we were able to record robust IOSs from single-pass measurements. Transient IOSs, which might reflect an early stage of light phototransduction, are consistently observed in the photoreceptor outer segment almost immediately (<4 ms) after retinal stimulation. Comparative studies of dark- and light-adapted retinas have demonstrated the feasibility of functional OCT mapping of rod and cone photoreceptors, promising a new method for early disease detection and improved treatment of diseases such as age-related macular degeneration (AMD) and other eye diseases that can cause photoreceptor damage. PMID:25901915

Functional Optical Coherence Tomography Enables In Vivo Physiological Assessment of Retinal Rod and Cone Photoreceptors

NASA Astrophysics Data System (ADS)

Zhang, Qiuxiang; Lu, Rongwen; Wang, Benquan; Messinger, Jeffrey D.; Curcio, Christine A.; Yao, Xincheng

2015-04-01

Transient intrinsic optical signal (IOS) changes have been observed in retinal photoreceptors, suggesting a unique biomarker for eye disease detection. However, clinical deployment of IOS imaging is challenging due to unclear IOS sources and limited signal-to-noise ratios (SNRs). Here, by developing high spatiotemporal resolution optical coherence tomography (OCT) and applying an adaptive algorithm for IOS processing, we were able to record robust IOSs from single-pass measurements. Transient IOSs, which might reflect an early stage of light phototransduction, are consistently observed in the photoreceptor outer segment almost immediately (<4 ms) after retinal stimulation. Comparative studies of dark- and light-adapted retinas have demonstrated the feasibility of functional OCT mapping of rod and cone photoreceptors, promising a new method for early disease detection and improved treatment of diseases such as age-related macular degeneration (AMD) and other eye diseases that can cause photoreceptor damage.

Phosphorylation-independent suppression of light-activated visual pigment by arrestin in carp rods and cones.

PubMed

Tomizuka, Junko; Tachibanaki, Shuji; Kawamura, Satoru

2015-04-10

Visual pigment in photoreceptors is activated by light. Activated visual pigment (R*) is believed to be inactivated by phosphorylation of R* with subsequent binding of arrestin. There are two types of photoreceptors, rods and cones, in the vertebrate retina, and they express different subtypes of arrestin, rod and cone type. To understand the difference in the function between rod- and cone-type arrestin, we first identified the subtype of arrestins expressed in rods and cones in carp retina. We found that two rod-type arrestins, rArr1 and rArr2, are co-expressed in a rod and that a cone-type arrestin, cArr1, is expressed in blue- and UV-sensitive cones; the other cone-type arrestin, cArr2, is expressed in red- and green-sensitive cones. We quantified each arrestin subtype and estimated its concentration in the outer segment of a rod or a cone in the dark; they were ∼0.25 mm (rArr1 plus rArr2) in a rod and 0.6-0.8 mm (cArr1 or cArr2) in a cone. The effect of each arrestin was examined. In contrast to previous studies, both rod and cone arrestins suppressed the activation of transducin in the absence of visual pigment phosphorylation, and all of the arrestins examined (rArr1, rArr2, and cArr2) bound transiently to most probably nonphosphorylated R*. One rod arrestin, rArr2, bound firmly to phosphorylated pigment, and the other two, rArr1 and cArr2, once bound to phosphorylated R* but dissociated from it during incubation. Our results suggested a novel mechanism of arrestin effect on the suppression of the R* activity in both rods and cones. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Photoreceptor Outer Segment on Internal Limiting Membrane after Macular Hole Surgery: Implications for Pathogenesis.

PubMed

Grinton, Michael E; Sandinha, Maria T; Steel, David H W

2015-01-01

This report presents a case, which highlights key principles in the pathophysiology of macular holes. It has been hypothesized that anteroposterior (AP) and tangential vitreous traction on the fovea are the primary underlying factors causing macular holes [Nischal and Pearson; in Kanski and Bowling: Clinical Ophthalmology: A Systemic Approach, 2011, pp 629-631]. Spectral domain optical coherence tomography (OCT) has subsequently corroborated this theory in part but shown that AP vitreofoveal traction is the more common scenario [Steel and Lotery: Eye 2013;27:1-21]. This study was conducted as a single case report. A 63-year old female presented to her optician with blurred and distorted vision in her left eye. OCT showed a macular hole with a minimum linear diameter of 370 µm, with persistent broad vitreofoveal attachment on both sides of the hole edges. The patient underwent combined left phacoemulsification and pars plana vitrectomy, internal limiting membrane (ILM) peel and gas injection. The ILM was examined by electron microscopy and showed the presence of a cone outer segment on the retinal side. Post-operative OCT at 11 weeks showed a closed hole with recovery of the foveal contour and good vision. Our case shows the presence of a photoreceptor outer segment on the retinal side of the ILM and reinforces the importance of tangential traction in the development of some macula holes. The case highlights the theory of transmission of inner retinal forces to the photoreceptors via Müller cells and how a full thickness macular hole defect can occur in the absence of AP vitreomacular traction.

Dysflective cones: Visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis.

PubMed

Tu, Joanna H; Foote, Katharina G; Lujan, Brandon J; Ratnam, Kavitha; Qin, Jia; Gorin, Michael B; Cunningham, Emmett T; Tuten, William S; Duncan, Jacque L; Roorda, Austin

2017-09-01

Confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images provide a sensitive measure of cone structure. However, the relationship between structural findings of diminished cone reflectivity and visual function is unclear. We used fundus-referenced testing to evaluate visual function in regions of apparent cone loss identified using confocal AOSLO images. A patient diagnosed with acute bilateral foveolitis had spectral-domain optical coherence tomography (SD-OCT) (Spectralis HRA + OCT system [Heidelberg Engineering, Vista, CA, USA]) images indicating focal loss of the inner segment-outer segment junction band with an intact, but hyper-reflective, external limiting membrane. Five years after symptom onset, visual acuity had improved from 20/80 to 20/25, but the retinal appearance remained unchanged compared to 3 months after symptoms began. We performed structural assessments using SD-OCT, directional OCT (non-standard use of a prototype on loan from Carl Zeiss Meditec) and AOSLO (custom-built system). We also administered fundus-referenced functional tests in the region of apparent cone loss, including analysis of preferred retinal locus (PRL), AOSLO acuity, and microperimetry with tracking SLO (TSLO) (prototype system). To determine AOSLO-corrected visual acuity, the scanning laser was modulated with a tumbling E consistent with 20/30 visual acuity. Visual sensitivity was assessed in and around the lesion using TSLO microperimetry. Complete eye examination, including standard measures of best-corrected visual acuity, visual field tests, color fundus photos, and fundus auto-fluorescence were also performed. Despite a lack of visible cone profiles in the foveal lesion, fundus-referenced vision testing demonstrated visual function within the lesion consistent with cone function. The PRL was within the lesion of apparent cone loss at the fovea. AOSLO visual acuity tests were abnormal, but measurable: for trials in which the stimulus remained completely within the lesion, the subject got 48% correct, compared to 78% correct when the stimulus was outside the lesion. TSLO microperimetry revealed reduced, but detectible, sensitivity thresholds within the lesion. Fundus-referenced visual testing proved useful to identify functional cones despite apparent photoreceptor loss identified using AOSLO and SD-OCT. While AOSLO and SD-OCT appear to be sensitive for the detection of abnormal or absent photoreceptors, changes in photoreceptors that are identified with these imaging tools do not correlate completely with visual function in every patient. Fundus-referenced vision testing is a useful tool to indicate the presence of cones that may be amenable to recovery or response to experimental therapies despite not being visible on confocal AOSLO or SD-OCT images.

IQCB1 and PDE6B Mutations Cause Similar Early Onset Retinal Degenerations in Two Closely Related Terrier Dog Breeds

PubMed Central

Goldstein, Orly; Mezey, Jason G.; Schweitzer, Peter A.; Boyko, Adam R.; Gao, Chuan; Bustamante, Carlos D.; Jordan, Julie Ann; Aguirre, Gustavo D.; Acland, Gregory M.

2013-01-01

Purpose. To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively. Methods. Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the “MAGIC” genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease. Results. Structural photoreceptor abnormalities were observed in crd1-affected dogs as young as 11-weeks old. Rod and cone inner segment (IS) and outer segments (OS) were abnormal in size, shape, and number. In crd2-affected dogs, rod and cone IS and OS were abnormal as early as 3 weeks of age, progressing with age to severe loss of the OS, and thinning of the outer nuclear layer (ONL) by 12 weeks of age. Genome-wide association study (GWAS) identified association at the telomeric end of CFA3 in crd1-affected dogs and on CFA33 in crd2-affected dogs. Candidate gene evaluation identified a three bases deletion in exon 21 of PDE6B in crd1-affected dogs, and a cytosine insertion in exon 10 of IQCB1 in crd2-affected dogs. Conclusions. Identification of the mutations responsible for these two early-onset retinal degenerations provides new large animal models for comparative disease studies and evaluation of potential therapeutic approaches for the homologous human diseases. PMID:24045995

Dysfunction of outer segment guanylate cyclase caused by retinal disease related mutations

PubMed Central

Zägel, Patrick; Koch, Karl-Wilhelm

2014-01-01

Membrane bound guanylate cyclases are expressed in rod and cone cells of the vertebrate retina and mutations in several domains of rod outer segment guanylate cyclase 1 (ROS-GC1 encoded by the gene GUCY2D) correlate with different forms of retinal degenerations. In the present work we investigated the biochemical consequences of three point mutations, one is located in position P575L in the juxtamembrane domain close to the kinase homology domain and two are located in the cyclase catalytic domain at H1019P and P1069R. These mutations correlate with various retinal diseases like autosomal dominant progressive cone degeneration, e.g., Leber Congenital Amaurosis and a juvenile form of retinitis pigmentosa. Wildtype and mutant forms of ROS-GC1 were heterologously expressed in HEK cells, their cellular distribution was investigated and activity profiles in the presence and absence of guanylate cyclase-activating proteins were measured. The mutant P575L was active under all tested conditions, but it displayed a twofold shift in the Ca2+-sensitivity, whereas the mutant P1069R remained inactive despite normal expression levels. The mutation H1019P caused the cyclase to become more labile. The different biochemical consequences of these mutations seem to reflect the different clinical symptoms. The mutation P575L induces a dysregulation of the Ca2+-sensitive cyclase activation profile causing a slow progression of the disease by the distortion of the Ca2+-cGMP homeostasis. In contrast, a strong reduction in cGMP synthesis due to an inactive or structurally unstable ROS-GC1 would trigger more severe forms of retinal diseases. PMID:24616660

Applying microCT and 3D visualization to Jurassic silicified conifer seed cones: A virtual advantage over thin-sectioning.

PubMed

Gee, Carole T

2013-11-01

As an alternative to conventional thin-sectioning, which destroys fossil material, high-resolution X-ray computed tomography (also called microtomography or microCT) integrated with scientific visualization, three-dimensional (3D) image segmentation, size analysis, and computer animation is explored as a nondestructive method of imaging the internal anatomy of 150-million-year-old conifer seed cones from the Late Jurassic Morrison Formation, USA, and of recent and other fossil cones. • MicroCT was carried out on cones using a General Electric phoenix v|tome|x s 240D, and resulting projections were processed with visualization software to produce image stacks of serial single sections for two-dimensional (2D) visualization, 3D segmented reconstructions with targeted structures in color, and computer animations. • If preserved in differing densities, microCT produced images of internal fossil tissues that showed important characters such as seed phyllotaxy or number of seeds per cone scale. Color segmentation of deeply embedded seeds highlighted the arrangement of seeds in spirals. MicroCT of recent cones was even more effective. • This is the first paper on microCT integrated with 3D segmentation and computer animation applied to silicified seed cones, which resulted in excellent 2D serial sections and segmented 3D reconstructions, revealing features requisite to cone identification and understanding of strobilus construction.

Raman Backscatter as a Remote Laser Power Sensor in High-Energy-Density Plasmas [Stimulated Scattering as a Remote Laser Power Sensor in High-Density and Temperature Plasmas

DOE PAGES

Moody, J. D.; Strozzi, D. J.; Divol, L.; ...

2013-07-09

Stimulated Raman backscatter is used as a remote sensor to quantify the instantaneous laser power after transfer from outer to inner cones that cross in a National Ignition Facility (NIF) gas-filled hohlraum plasma. By matching stimulated Raman backscatter between a shot reducing outer versus a shot reducing inner power we infer that about half of the incident outer-cone power is transferred to inner cones, for the specific time and wavelength configuration studied. Furthermore, this is the first instantaneous nondisruptive measure of power transfer in an indirect drive NIF experiment using optical measurements.

A key role for cyclic nucleotide gated (CNG) channels in cGMP-related retinitis pigmentosa.

PubMed

Paquet-Durand, François; Beck, Susanne; Michalakis, Stylianos; Goldmann, Tobias; Huber, Gesine; Mühlfriedel, Regine; Trifunović, Dragana; Fischer, M Dominik; Fahl, Edda; Duetsch, Gabriele; Becirovic, Elvir; Wolfrum, Uwe; van Veen, Theo; Biel, Martin; Tanimoto, Naoyuki; Seeliger, Mathias W

2011-03-01

The rd1 natural mutant is one of the first and probably the most commonly studied mouse model for retinitis pigmentosa (RP), a severe and frequently blinding human retinal degeneration. In several decades of research, the link between the increase in photoreceptor cGMP levels and the extremely rapid cell death gave rise to a number of hypotheses. Here, we provide clear evidence that the presence of cyclic nucleotide gated (CNG) channels in the outer segment membrane is the key to rod photoreceptor loss. In Cngb1(-/-) × rd1 double mutants devoid of regular CNG channels, cGMP levels are still pathologically high, but rod photoreceptor viability and outer segment morphology are greatly improved. Importantly, cone photoreceptors, the basis for high-resolution daylight and colour vision, survived and remained functional for extended periods of time. These findings strongly support the hypothesis of deleterious calcium (Ca(2+))-influx as the cause of rapid rod cell death and highlight the importance of CNG channels in this process. Furthermore, our findings suggest that targeting rod CNG channels, rather than general Ca(2+)-channel blockade, is a most promising symptomatic approach to treat otherwise incurable forms of cGMP-related RP.

Clinical characteristics of occult macular dystrophy in family with mutation of RP1l1 gene.

PubMed

Tsunoda, Kazushige; Usui, Tomoaki; Hatase, Tetsuhisa; Yamai, Satoshi; Fujinami, Kaoru; Hanazono, Gen; Shinoda, Kei; Ohde, Hisao; Akahori, Masakazu; Iwata, Takeshi; Miyake, Yozo

2012-06-01

To report the clinical characteristics of occult macular dystrophy (OMD) in members of one family with a mutation of the RP1L1 gene. Fourteen members with a p.Arg45Trp mutation in the RP1L1 gene were examined. The visual acuity, visual fields, fundus photographs, fluorescein angiograms, full-field electroretinograms, multifocal electroretinograms, and optical coherence tomographic images were examined. The clinical symptoms and signs and course of the disease were documented. All the members with the RP1L1 mutation except one woman had ocular symptoms and signs of OMD. The fundus was normal in all the patients during the entire follow-up period except in one patient with diabetic retinopathy. Optical coherence tomography detected the early morphologic abnormalities both in the photoreceptor inner/outer segment line and cone outer segment tip line. However, the multifocal electroretinograms were more reliable in detecting minimal macular dysfunction at an early stage of OMD. The abnormalities in the multifocal electroretinograms and optical coherence tomography observed in the OMD patients of different durations strongly support the contribution of RP1L1 mutation to the presence of this disease.

Assembly for directing combustion gas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Charron, Richard C.; Little, David A.; Snyder, Gary D.

2016-04-12

An arrangement is provided for delivering gases from a plurality of combustors of a can-annular gas turbine combustion engine to a first row of turbine blades including a first row of turbine blades. The arrangement includes a gas path cylinder, a cone and an integrated exit piece (IEP) for each combustor. Each IEP comprises an inlet chamber for receiving a gas flow from a respective combustor, and includes a connection segment. The IEPs are connected together to define an annular chamber extending circumferentially and concentric to an engine longitudinal axis, for delivering the gas flow to the first row ofmore » blades. A radiused joint extends radially inward from a radially outer side of the inlet chamber to an outer boundary of the annular chamber, and a flared fillet extends radially inward from a radially inner side of the inlet chamber to an inner boundary of the annular chamber.« less

Integrity of the Cone Photoreceptor Mosaic in Oligocone Trichromacy

PubMed Central

Rha, Jungtae; Dees, Elise W.; Baraas, Rigmor C.; Wagner-Schuman, Melissa L.; Mollon, John D.; Dubis, Adam M.; Andersen, Mette K. G.; Rosenberg, Thomas; Larsen, Michael; Moore, Anthony T.

2011-01-01

Purpose. Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these patients have a reduced number of normal functioning cones (oligocone). This paper has sought to evaluate the integrity of the cone photoreceptor mosaic in four patients previously described as having OT. Methods. Retinal images were obtained from two brothers (13 and 15 years) and two unrelated subjects, one male (47 years) and one female (24 years). High-resolution images of the cone mosaic were obtained using high-speed adaptive optics (AO) fundus cameras. Visible structures were analyzed for density using custom software. Additional retinal images were obtained using spectral domain optical coherence tomography (SD-OCT), and the four layers of the photoreceptor-retinal pigment epithelium complex (ELM, IS/OS, RPE1, RPE2) were evaluated. Cone photoreceptor length and the thickness of intraretinal layers were measured and compared to previously published normative data. Results. The adult male subject had infantile onset nystagmus while the three other patients did not. In the adult male patient, a normal appearing cone mosaic was observed. However, the three other subjects had a sparse mosaic of cones remaining at the fovea, with no structure visible outside the central fovea. On SD-OCT, the adult male subject had a very shallow foveal pit, with all major retinal layers being visible, and both inner segment (IS) and outer segment (OS) length were within normal limits. In the other three patients, while all four layers were visible in the central fovea and IS length was within normal limits, the OS length was significantly decreased. Peripherally the IS/OS layer decreased in intensity, and the RPE1 layer was no longer discernable, in keeping with the lack of cone structure observed on AO imaging outside the central fovea. Conclusions. Findings are consistent with the visual deficits being caused by a reduced number of healthy cones in the two brothers and the adult female. In the unrelated adult subject, no structural basis for the disorder was found. These data suggest two distinct groups on the basis of structural imaging. It is proposed that the former group with evidence of a reduction in cone numbers is more in keeping with typical OT, with the latter group representing an OT-like phenotype. These two groups may be difficult to readily discern on the basis of phenotypic features alone, and high-resolution imaging may be an effective way to distinguish between these phenotypes. PMID:21436275

Targeted Ablation of the Pde6h Gene in Mice Reveals Cross-species Differences in Cone and Rod Phototransduction Protein Isoform Inventory*

PubMed Central

Brennenstuhl, Christina; Tanimoto, Naoyuki; Burkard, Markus; Wagner, Rebecca; Bolz, Sylvia; Trifunovic, Dragana; Kabagema-Bilan, Clement; Paquet-Durand, Francois; Beck, Susanne C.; Huber, Gesine; Seeliger, Mathias W.; Ruth, Peter; Wissinger, Bernd; Lukowski, Robert

2015-01-01

Phosphodiesterase-6 (PDE6) is a multisubunit enzyme that plays a key role in the visual transduction cascade in rod and cone photoreceptors. Each type of photoreceptor utilizes discrete catalytic and inhibitory PDE6 subunits to fulfill its physiological tasks, i.e. the degradation of cyclic guanosine-3′,5′-monophosphate at specifically tuned rates and kinetics. Recently, the human PDE6H gene was identified as a novel locus for autosomal recessive (incomplete) color blindness. However, the three different classes of cones were not affected to the same extent. Short wave cone function was more preserved than middle and long wave cone function indicating that some basic regulation of the PDE6 multisubunit enzyme was maintained albeit by a unknown mechanism. To study normal and disease-related functions of cone Pde6h in vivo, we generated Pde6h knock-out (Pde6h−/−) mice. Expression of PDE6H in murine eyes was restricted to both outer segments and synaptic terminals of short and long/middle cone photoreceptors, whereas Pde6h−/− retinae remained PDE6H-negative. Combined in vivo assessment of retinal morphology with histomorphological analyses revealed a normal overall integrity of the retinal organization and an unaltered distribution of the different cone photoreceptor subtypes upon Pde6h ablation. In contrast to human patients, our electroretinographic examinations of Pde6h−/− mice suggest no defects in cone/rod-driven retinal signaling and therefore preserved visual functions. To this end, we were able to demonstrate the presence of rod PDE6G in cones indicating functional substitution of PDE6. The disparities between human and murine phenotypes caused by mutant Pde6h/PDE6H suggest species-to-species differences in the vulnerability of biochemical and neurosensory pathways of the visual signal transduction system. PMID:25739440

Applying microCT and 3D visualization to Jurassic silicified conifer seed cones: A virtual advantage over thin-sectioning1

PubMed Central

Gee, Carole T.

2013-01-01

• Premise of the study: As an alternative to conventional thin-sectioning, which destroys fossil material, high-resolution X-ray computed tomography (also called microtomography or microCT) integrated with scientific visualization, three-dimensional (3D) image segmentation, size analysis, and computer animation is explored as a nondestructive method of imaging the internal anatomy of 150-million-year-old conifer seed cones from the Late Jurassic Morrison Formation, USA, and of recent and other fossil cones. • Methods: MicroCT was carried out on cones using a General Electric phoenix v|tome|x s 240D, and resulting projections were processed with visualization software to produce image stacks of serial single sections for two-dimensional (2D) visualization, 3D segmented reconstructions with targeted structures in color, and computer animations. • Results: If preserved in differing densities, microCT produced images of internal fossil tissues that showed important characters such as seed phyllotaxy or number of seeds per cone scale. Color segmentation of deeply embedded seeds highlighted the arrangement of seeds in spirals. MicroCT of recent cones was even more effective. • Conclusions: This is the first paper on microCT integrated with 3D segmentation and computer animation applied to silicified seed cones, which resulted in excellent 2D serial sections and segmented 3D reconstructions, revealing features requisite to cone identification and understanding of strobilus construction. PMID:25202495

Cone-like rhodopsin expressed in the all-cone retina of the colubrid pine snake as a potential adaptation to diurnality.

PubMed

Bhattacharyya, Nihar; Darren, Benedict; Schott, Ryan K; Tropepe, Vincent; Chang, Belinda S W

2017-07-01

Colubridae is the largest and most diverse family of snakes, with visual systems that reflect this diversity, encompassing a variety of retinal photoreceptor organizations. The transmutation theory proposed by Walls postulates that photoreceptors could evolutionarily transition between cell types in squamates, but few studies have tested this theory. Recently, evidence for transmutation and rod-like machinery in an all-cone retina has been identified in a diurnal garter snake ( Thamnophis ), and it appears that the rhodopsin gene at least may be widespread among colubrid snakes. However, functional evidence supporting transmutation beyond the existence of the rhodopsin gene remains rare. We examined the all-cone retina of another colubrid, Pituophis melanoleucus , thought to be more secretive/burrowing than Thamnophis We found that P. melanoleucus expresses two cone opsins (SWS1, LWS) and rhodopsin (RH1) within the eye. Immunohistochemistry localized rhodopsin to the outer segment of photoreceptors in the all-cone retina of the snake and all opsin genes produced functional visual pigments when expressed in vitro Consistent with other studies, we found that P. melanoleucus rhodopsin is extremely blue-shifted. Surprisingly, P. melanoleucus rhodopsin reacted with hydroxylamine, a typical cone opsin characteristic. These results support the idea that the rhodopsin-containing photoreceptors of P. melanoleucus are the products of evolutionary transmutation from rod ancestors, and suggest that this phenomenon may be widespread in colubrid snakes. We hypothesize that transmutation may be an adaptation for diurnal, brighter-light vision, which could result in increased spectral sensitivity and chromatic discrimination with the potential for colour vision. © 2017. Published by The Company of Biologists Ltd.

Redistribution of insoluble interphotoreceptor matrix components during photoreceptor differentiation in the mouse retina.

PubMed

Mieziewska, K; Szél, A; Van Veen, T; Aguirre, G D; Philp, N

1994-07-01

The development of the nervous system is largely influenced by the extracellular matrix (ECM). In the neural retina, the photoreceptors are surrounded by a unique ECM, the interphotoreceptor matrix (IPM). The IPM plays a central and possibly crucial role in the development, maintenance and specific function of the photoreceptors. Therefore, the characterization of IPM components is necessary to understand the mechanisms regulating photoreceptor differentiation. The IPM in the mouse retina was examined during photoreceptor morphogenesis with the monoclonal antibody (MAb) F22, which recognizes a 250 kDa component of the interphotoreceptor matrix. The binding pattern of MAb F22 revealed a striking redistribution in the expression of the 250 kDa F22 antigen in late stage of postnatal photoreceptor differentiation in the mouse retina. The F22 staining was detectable in the IPM around the inner segments on the third postnatal day (P3). The MAb F22 initially labeled the region around inner segments, but as the outer segments elongated, the F22 distribution became concentrated to the matrix around the rod and cone outer segments until P16-17. At P17, the F22 label around rods began to disappear, while the label around cones became more defined. The shift in label distribution was largely completed by P20. Residual rod-associated label disappeared within a few days. In the adult animal, the F22 antibody labeled the cone-associated matrix only, and this labeling pattern remained stationary. The change in the distribution of MAb F22 demonstrated by immunolabeling was not accompanied by changes in the size of the molecule; F22 antigen isolated from the IPM of P13-15, and from adult IPM migrated with the same molecular weight on SDS gels. The distribution of MAb F22 was compared to that of chondroitin sulfate proteoglycans which are abundant in the IPM. The labeling patterns of MAbs CS-56, C6-S and C4-S were distinct from that of MAb F22. A general decrease of the label intensity was seen with two chondroitin sulfate MAbs (CS-56 and C4-S) between 16 days and 4 months, but a total loss of rod-associated label was not observed. All three chondroitin sulfate MAbs labeled the retina at embryonic day (E) 11.5-13.5, a time of outgrowth of ganglion cell axons, but the F22 antigen was not detected in the retina at this stage of development. The results demonstrate that the F22 and the chondroitin sulfate antibodies are recognizing different molecules that have distinct roles in retinal morphogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic remodeling generates synchronous oscillations in the degenerated outer mouse retina

PubMed Central

Haq, Wadood; Arango-Gonzalez, Blanca; Zrenner, Eberhart; Euler, Thomas; Schubert, Timm

2014-01-01

During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs) establish contacts with remnant cone photoreceptors (cones) as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca2+ imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs), we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from interneurons such as HCs and/or possibly interplexiform cells. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type) cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates) the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells. PMID:25249942

Retinal Degeneration in a Rodent Model of Smith-Lemli-Opitz Syndrome

PubMed Central

Fliesler, Steven J.; Peachey, Neal S.; Richards, Michael J.; Nagel, Barbara A.; Vaughan, Dana K.

2010-01-01

Objective To assess the electrophysiologic, histologic, and biochemical features of an animal model of Smith-Lemli-Opitz syndrome (SLOS). Methods Sprague-Dawley rats were treated with AY9944, a selective inhibitor of 3β-hydroxysterol-Δ7-reductase (the affected enzyme in SLOS). Dark- and light-adapted electroretinograms were obtained from treated and control animals. From each animal, 1 retina was analyzed by microscopy, and the contralateral retina plus serum samples were analyzed for sterol composition. The main outcome measures were rod and cone electroretinographic amplitudes and implicit times, outer nuclear layer (ONL) thickness, rod outer segment length, pyknotic ONL nucleus counts, and the 7-dehydrocholesterol/ cholesterol mole ratio in the retina and serum. Results By 10 weeks’ postnatal age, rod and cone electroretinographic wave amplitudes in AY9944-treated animals were significantly reduced and implicit times were significantly increased relative to controls. Maximal rod photoresponse and gain values were reduced approximately 2-fold in treated animals relative to controls. The ONL thickness and average rod outer segment length were reduced by approximately 18% and 33%, respectively, and ONL pyknotic nucleus counts were approximately 4.5-fold greater in treated animals relative to controls. The retinal pigment epithelium of treated animals contained massive amounts of membranous/lipid inclusions not routinely observed in controls. The 7-dehydrocholesterol/cholesterol mole ratios in treated retinas and serum samples were approximately 5:1 and 9:1, respectively, whereas the ratios in control tissues were essentially zero. Conclusions This rodent model exhibits the key biochemical hallmarks associated with SLOS and displays electrophysiologic deficits comparable to or greater than those observed in the human disease. Clinical Relevance These results predict retinal degeneration in patients with SLOS, particularly those with the more severe (type II) form of the disease, and may be more broadly relevant to other inborn errors of cholesterol biosynthesis. This animal model may also be of use in evaluating therapeutic treatments for SLOS and in understanding the slow phototransduction kinetics observed in patients with SLOS. PMID:15302661

Platelet-Derived Growth Factor-BB Lessens Light-Induced Rod Photoreceptor Damage in Mice.

PubMed

Takahashi, Kei; Shimazawa, Masamitsu; Izawa, Hiroshi; Inoue, Yuki; Kuse, Yoshiki; Hara, Hideaki

2017-12-01

Platelet-derived growth factor (PDGF)-BB is known to have neuroprotective effects against various neurodegenerative disorders. The purpose of this study was to determine whether PDGF-BB can be neuroprotective against light-induced photoreceptor damage in mice. Mice were exposed to 8000-lux luminance for 3 hours to induce phototoxicity. Two hours before light exposure, the experimental mice were injected with PDGF-BB intravitreally, and the control mice were injected with phosphate-buffered saline. The light-exposed PDGF-BB-injected mice and saline-injected mice were evaluated electroretinographically and histologically. The site and expression levels of PDGFR-β and PDGF-BB were determined by immunostaining and Western blotting, respectively. The effect of PDGF-BB on light-induced cone and rod photoreceptor damage was also evaluated in vitro in 661W cells, a murine cone photoreceptor cell line, and in primary retinal cell cultures. An intravitreal injection of PDGF-BB significantly reduced the decrease in the amplitudes of the electroretinograms (ERGs) and the thinning of the outer nuclear layer (ONL) induced by the light exposure. It also reduced the number of TUNEL-positive cells in the ONL. PDGFR-β was expressed in the rod outer segments (OSs) but not the cone OSs. The levels of PDGF-BB and PDGFR-β were decreased after light irradiation. In addition, PDGF-BB had protective effects against light-induced damage to cells of rod photoreceptors but had no effect on the 661W cells in vitro. These findings indicate that PDGF-BB reduces the degree of light-induced retinal damage by activating PDGFR-β in rod photoreceptors. These findings suggest that PDGF-BB could play a role in the prevention of degeneration in eyes susceptible to phototoxicity.

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

PubMed

Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

2012-02-07

Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

Force dependence of phagosome trafficking in retinal pigment epithelial cells

NASA Astrophysics Data System (ADS)

Daniel, Rebekah; Koll, Andrew T.; Altman, David

2014-09-01

Retinal pigment epithelial (RPE) cells play an integral role in the renewal of photoreceptor disk membranes. As rod and cone cells shed their outer segments, they are phagocytosed and degraded by the RPE, and a failure in this process can result in retinal degeneration. We have studied the role of myosin VI in nonspecific phagocytosis in a human RPE primary cell line (ARPE-19), testing the hypothesis that this motor generates the forces required to traffic phagosomes in these cells. Experiments were conducted in the presence of forces through the use of in vivo optical trapping. Our results support a role for myosin VI in phagosome trafficking and demonstrate that applied forces modulate rates of phagosome trafficking.

Particle trap for compressed gas insulated transmission systems

DOEpatents

Cookson, A.H.

1984-04-26

A particle trap is provided for gas insulated transmission lines having a central high voltage conductor supported within an outer coaxial conductive sheath by a dielectric support member. A cavity between the inner conductor and outer sheath is filled with a dielectric insulating gas. A cone-like particle deflector, mounted to the inner conductor, deflects moving particles away from the support member, to radially outer portions of the cavity. A conductive shield is disposed adjacent the outer sheath to form a field-free region in radially outer portions of the cavity, between the shield and the sheath. Particles traveling along the cavity are deflected by the cone-like deflector into the field-free region where they are held immobile. In a vertical embodiment, particles enter the field-free region through an upper end of a gap formed between shield and sheath members. In a horizontal embodiment, the deflector cone has a base which is terminated radially internally of the shield. Apertures in the shield located adjacent the deflector allow passage of deflected particles into the field-free region. The dielectric support member is thereby protected from contaminating particles that may otherwise come to rest thereon.

Particle trap for compressed gas insulated transmission systems

DOEpatents

Cookson, Alan H.

1985-01-01

A particle trap is provided for gas insulated transmission lines having a central high voltage conductor supported within an outer coaxial conductive sheath by a dielectric support member. A cavity between the inner conductor and outer sheath is filled with a dielectric insulating gas. A cone-like particle deflector, mounted to the inner conductor, deflects moving particles away from the support member, to radially outer portions of the cavity. A conductive shield is disposed adjacent the outer sheath to form a field-free region in radially outer portions of the cavity, between the shield and the sheath. Particles traveling along the cavity are deflected by the cone-like deflector into the field-free region where they are held immobile. In a vertical embodiment, particles enter the field-free region through an upper end of a gap formed between shield and sheath members. In a horizontal embodiment, the deflector cone has a base which is terminated radially internally of the shield. Apertures in the shield located adjacent the deflector allow passage of deflected particles into the field-free region. The dielectric support member is thereby protected from contaminating particles that may otherwise come to rest thereon.

Cone Photoreceptor Abnormalities Correlate with Vision Loss in Patients with Stargardt Disease

PubMed Central

Chen, Yingming; Ratnam, Kavitha; Sundquist, Sanna M.; Lujan, Brandon; Ayyagari, Radha; Gudiseva, V. Harini; Roorda, Austin

2011-01-01

Purpose. To study the relationship between macular cone structure, fundus autofluorescence (AF), and visual function in patients with Stargardt disease (STGD). Methods. High-resolution images of the macula were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography in 12 patients with STGD and 27 age-matched healthy subjects. Measures of retinal structure and AF were correlated with visual function, including best-corrected visual acuity, color vision, kinetic and static perimetry, fundus-guided microperimetry, and full-field electroretinography. Mutation analysis of the ABCA4 gene was completed in all patients. Results. Patients were 15 to 55 years old, and visual acuity ranged from 20/25–20/320. Central scotomas were present in all patients, although the fovea was spared in three patients. The earliest cone spacing abnormalities were observed in regions of homogeneous AF, normal visual function, and normal outer retinal structure. Outer retinal structure and AF were most normal near the optic disc. Longitudinal studies showed progressive increases in AF followed by reduced AF associated with losses of visual sensitivity, outer retinal layers, and cones. At least one disease-causing mutation in the ABCA4 gene was identified in 11 of 12 patients studied; 1 of 12 patients showed no disease-causing ABCA4 mutations. Conclusions. AOSLO imaging demonstrated abnormal cone spacing in regions of abnormal fundus AF and reduced visual function. These findings provide support for a model of disease progression in which lipofuscin accumulation results in homogeneously increased AF with cone spacing abnormalities, followed by heterogeneously increased AF with cone loss, then reduced AF with cone and RPE cell death. (ClinicalTrials.gov number, NCT00254605.) PMID:21296825

Cloning and Immunocytochemical Localization of a Cyclic Nucleotide–Gated Channel α-Subunit to All Cone Photoreceptors in the Mouse Retina

PubMed Central

HIRANO, ARLENE A.; HACK, IRIS; WÄSSLE, HEINZ; DUVOISIN, ROBERT M.

2010-01-01

Cyclic nucleotide–gated channels (CNGC) are ligand-gated ion channels that open and close in response to changes in the intracellular concentration of the second messengers, 3′,5′-cyclic adenosine monophosphate and 3′,5′-cyclic guanosine monophosphate. Most notably, they transduce the chemical signal produced by the absorption of light in photoreceptors into a membrane potential change, which is then transmitted to the ascending visual pathway. CNGCs have also been implicated in the signal transduction of other neurons downstream of the photoreceptors, in particular the ON-bipolar cells, as well as in other areas of the central nervous system. We therefore undertook a search for additional cyclic nucleotide–gated channels expressed in the retina. Following a degenerate reverse transcription polymerase chain reaction approach to amplify low-copy number messages, a cDNA encoding a new splice variant of CNGC α-subunit was isolated from mouse retina and classified as mCNG3. An antiserum raised against the carboxy-terminal sequence identified the retinal cell type expressing mCNG3 as cone photoreceptors. Preembedding immunoelectron microscopy demonstrated its membrane localization in the outer segments, consistent with its role in phototransduction. Double-labeling experiments with cone-specific markers indicated that all cone photoreceptors in the murid retina use the same or a highly conserved cyclic nucleotide–gated channel. Therefore, defects in this channel would be predicted to severely impair photopic vision. PMID:10813773

Characterization of photoreceptor degeneration in the rhodopsin P23H transgenic rat line 2 using optical coherence tomography.

PubMed

Monai, Natsuki; Yamauchi, Kodai; Tanabu, Reiko; Gonome, Takayuki; Ishiguro, Sei-Ichi; Nakazawa, Mitsuru

2018-01-01

To characterize the optical coherence tomography (OCT) appearances of photoreceptor degeneration in the rhodopsin P23H transgenic rat (line 2) in relation to the histological, ultrastructural, and electroretinography (ERG) findings. Homozygous rhodopsin P23H transgenic albino rats (line 2, very-slow degeneration model) were employed. Using OCT (Micron IV®; Phoenix Research Labs, Pleasanton, CA, USA), the natural course of photoreceptor degeneration was recorded from postnatal day (P) 15 to P 287. The OCT images were qualitatively observed by comparing them to histological and ultrastructural findings at P 62 and P 169. In addition, each retinal layer was quantitatively analyzed longitudinally during degeneration, compared it to that observed in wild type Sprague-Dawley (SD) rats. The relationships between the ERG (full-field combined rod-cone response, 3.0 cds/m2 stimulation) findings and OCT images were also analyzed. In the qualitative study, the two layers presumably corresponding to the photoreceptor inner segment ellipsoid zone (EZ) and interdigitation zone (IZ) were identified in the P23H rat until PN day 32. However, the photoreceptor inner and outer segment (IS/OS) layer became diffusely hyperreflective on OCT after P 46, and the EZ and IZ zones could no longer be identified on OCT. In contrast, in the SD rats, the EZ and IZ were clearly distinguished until at least P 247. The ultrastructural study showed partial disarrangements of the photoreceptor outer segment discs in the P23H rats at P 62, although a light-microscopic histological study detected almost no abnormality in the outer segment. In the quantitative study, the outer retinal layer including the outer plexiform layer (OPL) and the outer nuclear layer (ONL) became significantly thinner in the P23H rats than in the SD rats after P 71. The thickness of the IS/OS layer was maintained in the P23H rats until P 130, and it became statistically thinner than in the SD rats at P 237. The longitudinal attenuation in the amplitude of the a- and b-waves of ERG was significantly correlated with the thickness of the combined OPL and ONL but not with that of the IS/OS layer. OCT showed the degenerated photoreceptor IS/OS layer in rhodopsin P23H transgenic rats (line 2) as a diffuse hyperreflective zone, even in the early stage, with the partially disarranged and destabilized OS discs recognizable by ultrastructural assessment but not by a histological study. The amplitude of the a- and b-waves mainly depends on the thickness of the OPL and ONL layer rather than the thickness of the photoreceptor IS/OS layer in P23H rats.

Early-onset, slow progression of cone photoreceptor dysfunction and degeneration in CNG channel subunit CNGB3 deficiency.

PubMed

Xu, Jianhua; Morris, Lynsie; Fliesler, Steven J; Sherry, David M; Ding, Xi-Qin

2011-06-01

To investigate the progression of cone dysfunction and degeneration in CNG channel subunit CNGB3 deficiency. Retinal structure and function in CNGB3(-/-) and wild-type (WT) mice were evaluated by electroretinography (ERG), lectin cytochemistry, and correlative Western blot analysis of cone-specific proteins. Cone and rod terminal integrity was assessed by electron microscopy and synaptic protein immunohistochemical distribution. Cone ERG amplitudes (photopic b-wave) in CNGB3(-/-) mice were reduced to approximately 50% of WT levels by postnatal day 15, decreasing further to approximately 30% of WT levels by 1 month and to approximately 20% by 12 months of age. Rod ERG responses (scotopic a-wave) were not affected in CNGB3(-/-) mice. Average CNGB3(-/-) cone densities were approximately 80% of WT levels at 1 month and declined slowly thereafter to only approximately 50% of WT levels by 12 months. Expression levels of M-opsin, cone transducin α-subunit, and cone arrestin in CNGB3(-/-) mice were reduced by 50% to 60% by 1 month and declined to 35% to 45% of WT levels by 9 months. In addition, cone opsin mislocalized to the outer nuclear layer and the outer plexiform layer in the CNGB3(-/-) retina. Cone and rod synaptic marker expression and terminal ultrastructure were normal in the CNGB3(-/-) retina. These findings are consistent with an early-onset, slow progression of cone functional defects and cone loss in CNGB3(-/-) mice, with the cone signaling deficits arising from disrupted phototransduction and cone loss rather than from synaptic defects.

BBSome function is required for both the morphogenesis and maintenance of the photoreceptor outer segment

PubMed Central

Hsu, Ying; Kim, Gunhee; Zhang, Qihong; Datta, Poppy; Seo, Seongjin

2017-01-01

Genetic mutations disrupting the structure and function of primary cilia cause various inherited retinal diseases in humans. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic ciliopathy characterized by retinal degeneration, obesity, postaxial polydactyly, intellectual disability, and genital and renal abnormalities. To gain insight into the mechanisms of retinal degeneration in BBS, we developed a congenital knockout mouse of Bbs8, as well as conditional mouse models in which function of the BBSome (a protein complex that mediates ciliary trafficking) can be temporally inactivated or restored. We demonstrate that BBS mutant mice have defects in retinal outer segment morphogenesis. We further demonstrate that removal of Bbs8 in adult mice affects photoreceptor function and disrupts the structural integrity of the outer segment. Notably, using a mouse model in which a gene trap inhibiting Bbs8 gene expression can be removed by an inducible FLP recombinase, we show that when BBS8 is restored in immature retinas with malformed outer segments, outer segment extension can resume normally and malformed outer segment discs are displaced distally by normal outer segment structures. Over time, the retinas of the rescued mice become morphologically and functionally normal, indicating that there is a window of plasticity when initial retinal outer segment morphogenesis defects can be ameliorated. PMID:29049287

Autofluorescence from the outer retina and subretinal space: hypothesis and review.

PubMed

Spaide, Richard

2008-01-01

To review the pathophysiologic principles underlying increased autofluorescence from the outer retina and subretinal space using selected diseases as examples. The ocular imaging information and histopathologic features, when known, were integrated for diseases causing increased autofluorescence from the outer retina and subretinal space. Inferences were taken from this information and used to create a classification scheme. These diseases are principally those that cause separation of the outer retina from the retinal pigment epithelium, thereby preventing proper phagocytosis of photoreceptor outer segments. The separation can arise from increased exudation into the subretinal space or inadequate removal of fluid from the subretinal space. Lack of normal outer segment processing initially leads to increased accumulation of outer segments on the outer retina and subretinal space. Over time, this material is visible as an increasingly thick coating on the outer retina, is yellow, and is autofluorescent. Over time, atrophy develops with thinning of the deposited material and decreasing autofluorescence. The accumulated material is ultimately capable of inducing damage to the retinal pigment epithelium. Diseases causing accumulation of the material include central serous chorioretinopathy, vitelliform macular dystrophy, acute exudative polymorphous vitelliform maculopathy, choroidal tumors, and vitreomacular traction syndrome. The physical separation of the retinal outer segments from the retinal pigment epithelium hinders proper phagocytosis of the outer segments. Accumulation of the shed but not phagocytized outer segments plays a role in disease manifestations for a number of macular diseases.

3D printed phantoms of retinal photoreceptor cells for evaluating adaptive optics imaging modalities

NASA Astrophysics Data System (ADS)

Kedia, Nikita; Liu, Zhuolin; Sochol, Ryan; Hammer, Daniel X.; Agrawal, Anant

2018-02-01

Adaptive optics-enabled optical coherence tomography (AO-OCT) and scanning laser ophthalmoscopy (AO-SLO) devices can resolve retinal cones and rods in three dimensions. To evaluate the improved resolution of AO-OCT and AO-SLO, a phantom that mimics retinal anatomy at the cellular level is required. We used a two-photon polymerization approach to fabricate three-dimensional (3D) photoreceptor phantoms modeled on the central foveal cones. By using a femtosecond laser to selectively photocure precise locations within a liquid-based photoresist via two-photon absorption, we produced high-resolution phantoms with μm-level dimensions similar to true anatomy. In this work, we present two phantoms to evaluate the resolution limits of an AO imaging system: one that models only the outer segments of the photoreceptor cells at varying retinal eccentricities and another that contains anatomically relevant features of the full-length photoreceptor. With these phantoms we are able to quantitatively estimate transverse resolution of an AO system and produce images that are comparable to those found in the human retina.

Early-Onset, Slow Progression of Cone Photoreceptor Dysfunction and Degeneration in CNG Channel Subunit CNGB3 Deficiency

PubMed Central

Xu, Jianhua; Morris, Lynsie; Fliesler, Steven J.; Sherry, David M.

2011-01-01

Purpose. To investigate the progression of cone dysfunction and degeneration in CNG channel subunit CNGB3 deficiency. Methods. Retinal structure and function in CNGB3−/− and wild-type (WT) mice were evaluated by electroretinography (ERG), lectin cytochemistry, and correlative Western blot analysis of cone-specific proteins. Cone and rod terminal integrity was assessed by electron microscopy and synaptic protein immunohistochemical distribution. Results. Cone ERG amplitudes (photopic b-wave) in CNGB3−/− mice were reduced to approximately 50% of WT levels by postnatal day 15, decreasing further to approximately 30% of WT levels by 1 month and to approximately 20% by 12 months of age. Rod ERG responses (scotopic a-wave) were not affected in CNGB3−/− mice. Average CNGB3−/− cone densities were approximately 80% of WT levels at 1 month and declined slowly thereafter to only approximately 50% of WT levels by 12 months. Expression levels of M-opsin, cone transducin α-subunit, and cone arrestin in CNGB3−/− mice were reduced by 50% to 60% by 1 month and declined to 35% to 45% of WT levels by 9 months. In addition, cone opsin mislocalized to the outer nuclear layer and the outer plexiform layer in the CNGB3−/− retina. Cone and rod synaptic marker expression and terminal ultrastructure were normal in the CNGB3−/− retina. Conclusions. These findings are consistent with an early-onset, slow progression of cone functional defects and cone loss in CNGB3−/− mice, with the cone signaling deficits arising from disrupted phototransduction and cone loss rather than from synaptic defects. PMID:21273547

LONG-TERM SD-OCT/SLO IMAGING OF NEURORETINA AND RETINAL PIGMENT EPITHELIUM AFTER SUB-THRESHOLD INFRARED LASER TREATMENT OF DRUSEN

PubMed Central

MOJANA, FRANCESCA; BRAR, MANPREET; CHENG, LINGYUN; BARTSCH, DIRK-UWE G.; FREEMAN, WILLIAM R.

2012-01-01

PURPOSE To determine the long-term effect of sub-threshold diode laser treatment for drusen in patients with non-exudative age-related macular degeneration (AMD) with spectral domain optical coherence tomography combined with simultaneous scanning laser ophthalmoscope (SD-OCT/SLO). METHODS 8 eyes of 4 consecutive AMD patients with bilateral drusen previously treated with sub-threshold diode laser were imaged with SD-OCT/SLO. Abnormalities in the outer retina layers reflectivity as seen with SD-OCT/SLO were retrospectively analyzed and compared with color fundus pictures and autofluorescence images (AF) acquired immediately before and after the laser treatment. RESULTS A focal discrete disruptions in the reflectivity of the outer retinal layers was noted in 29% of the laser lesions. The junction in between the inner and outer segment of the photoreceptor was more frequently affected, with associated focal damage of the outer nuclear layer. Defects of the RPE were occasionally detected. These changes did not correspond to threshold burns on color fundus photography, but corresponded to focal areas of increased AF in the majority of the cases. CONCLUSIONS Sub-threshold diode laser treatment causes long-term disruption of the retinal photoreceptor layer as analyzed by SD-OCT/SLO. The concept that sub-threshold laser treatment can achieve a selected RPE effect without damage to rods and cones may be flawed. PMID:21157398

A new mouse model for stationary night blindness with mutant Slc24a1 explains the pathophysiology of the associated human disease

PubMed Central

Vinberg, Frans; Wang, Tian; Molday, Robert S.; Chen, Jeannie; Kefalov, Vladimir J.

2015-01-01

Mutations that affect calcium homeostasis (Ca2+) in rod photoreceptors are linked to retinal degeneration and visual disorders such as retinitis pigmentosa and congenital stationary night blindness (CSNB). It is thought that the concentration of Ca2+ in rod outer segments is controlled by a dynamic balance between influx via cGMP-gated (CNG) channels and extrusion via Na+/Ca2+, K+ exchangers (NCKX1). The extrusion-driven lowering of rod [Ca2+]i following light exposure controls their light adaptation and response termination. Mutant NCKX1 has been linked to autosomal-recessive stationary night blindness. However, whether NCKX1 contributes to light adaptation has not been directly tested and the mechanisms by which human NCKX1 mutations cause night blindness are not understood. Here, we report that the deletion of NCKX1 in mice results in malformed outer segment disks, suppressed expression and function of rod CNG channels and a subsequent 100-fold reduction in rod responses, while preserving normal cone responses. The compensating loss of CNG channel function in the absence of NCKX1-mediated Ca2+ extrusion may prevent toxic Ca2+ buildup and provides an explanation for the stationary nature of the associated disorder in humans. Surprisingly, the lack of NCKX1 did not compromise rod background light adaptation, suggesting additional Ca2+-extruding mechanisms exist in these cells. PMID:26246500

Planar torsion spring

NASA Technical Reports Server (NTRS)

Ihrke, Chris A. (Inventor); Parsons, Adam H. (Inventor); Mehling, Joshua S. (Inventor); Griffith, Bryan Kristian (Inventor)

2012-01-01

A torsion spring comprises an inner mounting segment. An outer mounting segment is located concentrically around the inner mounting segment. A plurality of splines extends from the inner mounting segment to the outer mounting segment. At least a portion of each spline extends generally annularly around the inner mounting segment.

Facilitative glucose transporter Glut1 is actively excluded from rod outer segments.

PubMed

Gospe, Sidney M; Baker, Sheila A; Arshavsky, Vadim Y

2010-11-01

Photoreceptors are among the most metabolically active cells in the body, relying on both oxidative phosphorylation and glycolysis to satisfy their high energy needs. Local glycolysis is thought to be particularly crucial in supporting the function of the photoreceptor's light-sensitive outer segment compartment, which is devoid of mitochondria. Accordingly, it has been commonly accepted that the facilitative glucose transporter Glut1 responsible for glucose entry into photoreceptors is localized in part to the outer segment plasma membrane. However, we now demonstrate that Glut1 is entirely absent from the rod outer segment and is actively excluded from this compartment by targeting information present in its cytosolic C-terminal tail. Our data indicate that glucose metabolized in the outer segment must first enter through other parts of the photoreceptor cell. Consequently, the entire energy supply of the outer segment is dependent on diffusion of energy-rich substrates through the thin connecting cilium that links this compartment to the rest of the cell.

Cryptochrome 1 in Retinal Cone Photoreceptors Suggests a Novel Functional Role in Mammals

PubMed Central

Nießner, Christine; Denzau, Susanne; Malkemper, Erich Pascal; Gross, Julia Christina; Burda, Hynek; Winklhofer, Michael; Peichl, Leo

2016-01-01

Cryptochromes are a ubiquitous group of blue-light absorbing flavoproteins that in the mammalian retina have an important role in the circadian clock. In birds, cryptochrome 1a (Cry1a), localized in the UV/violet-sensitive S1 cone photoreceptors, is proposed to be the retinal receptor molecule of the light-dependent magnetic compass. The retinal localization of mammalian Cry1, homologue to avian Cry1a, is unknown, and it is open whether mammalian Cry1 is also involved in magnetic field sensing. To constrain the possible role of retinal Cry1, we immunohistochemically analysed 90 mammalian species across 48 families in 16 orders, using an antiserum against the Cry1 C-terminus that in birds labels only the photo-activated conformation. In the Carnivora families Canidae, Mustelidae and Ursidae, and in some Primates, Cry1 was consistently labeled in the outer segment of the shortwave-sensitive S1 cones. This finding would be compatible with a magnetoreceptive function of Cry1 in these taxa. In all other taxa, Cry1 was not detected by the antiserum that likely also in mammals labels the photo-activated conformation, although Western blots showed Cry1 in mouse retinal cell nuclei. We speculate that in the mouse and the other negative-tested mammals Cry1 is involved in circadian functions as a non-light-responsive protein. PMID:26898837

Cryptochrome 1 in Retinal Cone Photoreceptors Suggests a Novel Functional Role in Mammals.

PubMed

Nießner, Christine; Denzau, Susanne; Malkemper, Erich Pascal; Gross, Julia Christina; Burda, Hynek; Winklhofer, Michael; Peichl, Leo

2016-02-22

Cryptochromes are a ubiquitous group of blue-light absorbing flavoproteins that in the mammalian retina have an important role in the circadian clock. In birds, cryptochrome 1a (Cry1a), localized in the UV/violet-sensitive S1 cone photoreceptors, is proposed to be the retinal receptor molecule of the light-dependent magnetic compass. The retinal localization of mammalian Cry1, homologue to avian Cry1a, is unknown, and it is open whether mammalian Cry1 is also involved in magnetic field sensing. To constrain the possible role of retinal Cry1, we immunohistochemically analysed 90 mammalian species across 48 families in 16 orders, using an antiserum against the Cry1 C-terminus that in birds labels only the photo-activated conformation. In the Carnivora families Canidae, Mustelidae and Ursidae, and in some Primates, Cry1 was consistently labeled in the outer segment of the shortwave-sensitive S1 cones. This finding would be compatible with a magnetoreceptive function of Cry1 in these taxa. In all other taxa, Cry1 was not detected by the antiserum that likely also in mammals labels the photo-activated conformation, although Western blots showed Cry1 in mouse retinal cell nuclei. We speculate that in the mouse and the other negative-tested mammals Cry1 is involved in circadian functions as a non-light-responsive protein.

Detailed functional and structural phenotype of Bietti crystalline dystrophy associated with mutations in CYP4V2 complicated by choroidal neovascularization.

PubMed

Fuerst, Nicole M; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Maguire, Albert M; Leroy, Bart P; Kim, Benjamin J; Aleman, Tomas S

2016-12-01

To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin ® ; Genentech/Roche). A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA). Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in the peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod > cone sensitivity loss surrounded fixation and extended to ~10° of eccentricity corresponding to regions of photoreceptor outer segment-retinal pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co-localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of BCVA to baseline (20/25). crystals in BCD were predominantly located within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie the relatively extensive retinal dysfunction observed in relatively early-stage BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting.

[Sulfhydryl group distribution along the axis of the rod outer segment in the frog].

PubMed

Derevianchenko, T G; Fedorovich, I B; Ostrovskiĭ, M A

1985-10-01

The existence of SH-group concentration axial gradient in frog's retinal rod outer segments has been shown. A diminution of SH-groups in the outer segment apical part points to a damage of the vision pigment during the life span of the rod disks.

Correlation of outer nuclear layer thickness with cone density values in patients with retinitis pigmentosa and healthy subjects.

PubMed

Menghini, Moreno; Lujan, Brandon J; Zayit-Soudry, Shiri; Syed, Reema; Porco, Travis C; Bayabo, Kristine; Carroll, Joseph; Roorda, Austin; Duncan, Jacque L

2014-12-16

We studied the correlation between outer nuclear layer (ONL) thickness and cone density in normal eyes and eyes with retinitis pigmentosa (RP). Spectral-domain optical coherence tomography (SD-OCT) scans were acquired using a displaced pupil entry position of the scanning beam to distinguish Henle's fiber layer from the ONL in 20 normal eyes (10 subjects) and 12 eyes with RP (7 patients). Cone photoreceptors were imaged using adaptive optics scanning laser ophthalmoscopy. The ONL thickness and cone density were measured at 0.5° intervals along the horizontal meridian through the fovea nasally and temporally. The ONL thickness and cone density were correlated using Spearman's rank correlation coefficient r. Cone densities averaged over the central 6° were lower in eyes with RP than normal, but showed high variability in both groups. The ONL thickness and cone density were significantly correlated when all retinal eccentricities were combined (r = 0.74); the correlation for regions within 0.5° to 1.5° eccentricity was stronger (r = 0.67) than between 1.5° and 3.0° eccentricity (r = 0.23). Although cone densities were lower between 0.5° and 1.5° in eyes with RP, ONL thickness measures at identical retinal locations were similar in the two groups (P = 0.31), and interindividual variation was high for ONL and cone density measures. Although ONL thickness and retinal eccentricity were important predictors of cone density, eccentricity was over 3 times more important. The ONL thickness and cone density were correlated in normal eyes and eyes with RP, but both were strongly correlated with retinal eccentricity, precluding estimation of cone density from ONL thickness. (ClinicalTrials.gov number, NCT00254605.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Correlation of Outer Nuclear Layer Thickness With Cone Density Values in Patients With Retinitis Pigmentosa and Healthy Subjects

PubMed Central

Menghini, Moreno; Lujan, Brandon J.; Zayit-Soudry, Shiri; Syed, Reema; Porco, Travis C.; Bayabo, Kristine; Carroll, Joseph; Roorda, Austin; Duncan, Jacque L.

2015-01-01

Purpose. We studied the correlation between outer nuclear layer (ONL) thickness and cone density in normal eyes and eyes with retinitis pigmentosa (RP). Methods. Spectral-domain optical coherence tomography (SD-OCT) scans were acquired using a displaced pupil entry position of the scanning beam to distinguish Henle's fiber layer from the ONL in 20 normal eyes (10 subjects) and 12 eyes with RP (7 patients). Cone photoreceptors were imaged using adaptive optics scanning laser ophthalmoscopy. The ONL thickness and cone density were measured at 0.5° intervals along the horizontal meridian through the fovea nasally and temporally. The ONL thickness and cone density were correlated using Spearman's rank correlation coefficient r. Results. Cone densities averaged over the central 6° were lower in eyes with RP than normal, but showed high variability in both groups. The ONL thickness and cone density were significantly correlated when all retinal eccentricities were combined (r = 0.74); the correlation for regions within 0.5° to 1.5° eccentricity was stronger (r = 0.67) than between 1.5° and 3.0° eccentricity (r = 0.23). Although cone densities were lower between 0.5° and 1.5° in eyes with RP, ONL thickness measures at identical retinal locations were similar in the two groups (P = 0.31), and interindividual variation was high for ONL and cone density measures. Although ONL thickness and retinal eccentricity were important predictors of cone density, eccentricity was over 3 times more important. Conclusions. The ONL thickness and cone density were correlated in normal eyes and eyes with RP, but both were strongly correlated with retinal eccentricity, precluding estimation of cone density from ONL thickness. (ClinicalTrials.gov number, NCT00254605.) PMID:25515570

Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina.

PubMed

Deming, Janise D; Pak, Joseph S; Shin, Jung-A; Brown, Bruce M; Kim, Moon K; Aung, Moe H; Lee, Eun-Jin; Pardue, Machelle T; Craft, Cheryl Mae

2015-12-01

Previous studies discovered cone phototransduction shutoff occurs normally for Arr1-/- and Arr4-/-; however, it is defective when both visual arrestins are simultaneously not expressed (Arr1-/-Arr4-/-). We investigated the roles of visual arrestins in an all-cone retina (Nrl-/-) since each arrestin has differential effects on visual function, including ARR1 for normal light adaptation, and ARR4 for normal contrast sensitivity and visual acuity. We examined Nrl-/-, Nrl-/-Arr1-/-, Nrl-/-Arr4-/-, and Nrl-/-Arr1-/-Arr4-/- mice with photopic electroretinography (ERG) to assess light adaptation and retinal responses, immunoblot and immunohistochemical localization analysis to measure retinal expression levels of M- and S-opsin, and optokinetic tracking (OKT) to measure the visual acuity and contrast sensitivity. Study results indicated that Nrl-/- and Nrl-/-Arr4-/- mice light adapted normally, while Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- mice did not. Photopic ERG a-wave, b-wave, and flicker amplitudes followed a general pattern in which Nrl-/-Arr4-/- amplitudes were higher than the amplitudes of Nrl-/-, while the amplitudes of Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- were lower. All three visual arrestin knockouts had faster implicit times than Nrl-/- mice. M-opsin expression is lower when ARR1 is not expressed, while S-opsin expression is lower when ARR4 is not expressed. Although M-opsin expression is mislocalized throughout the photoreceptor cells, S-opsin is confined to the outer segments in all genotypes. Contrast sensitivity is decreased when ARR4 is not expressed, while visual acuity was normal except in Nrl-/-Arr1-/-Arr4-/-. Based on the opposite visual phenotypes in an all-cone retina in the Nrl-/-Arr1-/- and Nrl-/-Arr4-/- mice, we conclude that ARR1 and ARR4 perform unique modulatory roles in cone photoreceptors.

Tracking dynamics of photoreceptor disc shedding with adaptive optics-optical coherence tomography

NASA Astrophysics Data System (ADS)

Zhang, Furu; Liu, Zhuolin; Kurokawa, Kazuhiro; Miller, Donald T.

2017-02-01

Absorption of light by photoreceptors initiates vision, but also leads to accumulation of toxic photo-oxidative compounds in the photoreceptor outer segment (OS). To prevent this buildup, small packets of OS discs are periodically pruned from the distal end of the OS, a process called disc shedding. Unfortunately dysfunction in any part of the shedding event can lead to photoreceptor and RPE dystrophy, and has been implicated in numerous retinal diseases, including age related macular degeneration and retinitis pigmentosa. While much is known about the complex molecular and signaling pathways that underpin shedding, all of these advancements have occurred in animal models using postmortem eyes. How these translate to the living retina and to humans remain major obstacles. To that end, we have recently discovered the optical signature of cone OS disc shedding in the living human retina, measured noninvasively using optical coherence tomography equipped with adaptive optics in conjunction with post processing methods to track and monitor individual cones in 4D. In this study, we improve on this method in several key areas: increasing image acquisition up to MHz A-scan rates, improving reliability to detect disc shedding events, establishing system precision, and developing cone tracking for use across the entire awake cycle. Thousands of cones were successfully imaged and tracked over the 17 hour period in two healthy subjects. Shedding events were detected in 79.5% and 77.4% of the tracked cones. Similar to previous animal studies, shedding prevalence exhibited a diurnal rhythm. But we were surprised to find that for these two subjects shedding occurred across the entire day with broad, elevated frequency in the morning and decreasing frequency as the day progressed. Consistent with this, traces of the average cone OS length revealed shedding dominated in the morning and afternoon and renewal in the evening.

Automatic detection of cone photoreceptors in split detector adaptive optics scanning light ophthalmoscope images.

PubMed

Cunefare, David; Cooper, Robert F; Higgins, Brian; Katz, David F; Dubra, Alfredo; Carroll, Joseph; Farsiu, Sina

2016-05-01

Quantitative analysis of the cone photoreceptor mosaic in the living retina is potentially useful for early diagnosis and prognosis of many ocular diseases. Non-confocal split detector based adaptive optics scanning light ophthalmoscope (AOSLO) imaging reveals the cone photoreceptor inner segment mosaics often not visualized on confocal AOSLO imaging. Despite recent advances in automated cone segmentation algorithms for confocal AOSLO imagery, quantitative analysis of split detector AOSLO images is currently a time-consuming manual process. In this paper, we present the fully automatic adaptive filtering and local detection (AFLD) method for detecting cones in split detector AOSLO images. We validated our algorithm on 80 images from 10 subjects, showing an overall mean Dice's coefficient of 0.95 (standard deviation 0.03), when comparing our AFLD algorithm to an expert grader. This is comparable to the inter-observer Dice's coefficient of 0.94 (standard deviation 0.04). To the best of our knowledge, this is the first validated, fully-automated segmentation method which has been applied to split detector AOSLO images.

Morphological evidence of neurotoxicity in retina after methylmercury exposure.

PubMed

Mela, Maritana; Grötzner, Sonia Regina; Legeay, Alexia; Mesmer-Dudons, Nathalie; Massabuau, Jean-Charles; Ventura, Dora Fix; de Oliveira Ribeiro, Ciro Alberto

2012-06-01

The visual system is particularly sensitive to methylmercury (MeHg) exposure and, therefore, provides a useful model for investigating the fundamental mechanisms that direct toxic effects. During a period of 70 days, adult of a freshwater fish species Hoplias malabaricus were fed with fish prey previously labeled with two different doses of methylmercury (0.075 and 0.75 μgg(-1)) to determine the mercury distribution and morphological changes in the retina. Mercury deposits were found in the photoreceptor layer, in the inner plexiform layer and in the outer plexiform layer, demonstrating a dose-dependent bioaccumulation. The ultrastructure analysis of retina revealed a cellular deterioration in the photoreceptor layer, morphological changes in the inner and outer segments of rods, structural changes in the plasma membrane of rods and double cones, changes in the process of removal of membranous discs and a structural discontinuity. These results lead to the conclusion that methylmercury is able to cross the blood-retina barrier, accumulate in the cells and layers of retina and induce changes in photoreceptors of H. malabaricus even under subchronic exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

Lateral interactions in the outer retina

PubMed Central

Thoreson, Wallace B.; Mangel, Stuart C.

2012-01-01

Lateral interactions in the outer retina, particularly negative feedback from horizontal cells to cones and direct feed-forward input from horizontal cells to bipolar cells, play a number of important roles in early visual processing, such as generating center-surround receptive fields that enhance spatial discrimination. These circuits may also contribute to post-receptoral light adaptation and the generation of color opponency. In this review, we examine the contributions of horizontal cell feedback and feed-forward pathways to early visual processing. We begin by reviewing the properties of bipolar cell receptive fields, especially with respect to modulation of the bipolar receptive field surround by the ambient light level and to the contribution of horizontal cells to the surround. We then review evidence for and against three proposed mechanisms for negative feedback from horizontal cells to cones: 1) GABA release by horizontal cells, 2) ephaptic modulation of the cone pedicle membrane potential generated by currents flowing through hemigap junctions in horizontal cell dendrites, and 3) modulation of cone calcium currents (ICa) by changes in synaptic cleft proton levels. We also consider evidence for the presence of direct horizontal cell feed-forward input to bipolar cells and discuss a possible role for GABA at this synapse. We summarize proposed functions of horizontal cell feedback and feed-forward pathways. Finally, we examine the mechanisms and functions of two other forms of lateral interaction in the outer retina: negative feedback from horizontal cells to rods and positive feedback from horizontal cells to cones. PMID:22580106

Diffuser/ejector system for a very high vacuum environment

NASA Technical Reports Server (NTRS)

Riggs, K. E.; Wojciechowski, C. J. (Inventor)

1984-01-01

Turbo jet engines are used to furnish the necessary high temperature, high volume, medium pressure gas to provide a high vacuum test environment at comparatively low cost for space engines at sea level. Moreover, the invention provides a unique way by use of the variable area ratio ejectors with a pair of meshing cones are used. The outer cone is arranged to translate fore and aft, and the inner cone is interchangeable with other cones having varying angles of taper.

Turbine exhaust diffuser with a gas jet producing a coanda effect flow control

DOEpatents

Orosa, John; Montgomery, Matthew

2014-02-11

An exhaust diffuser system and method for a turbine engine includes an inner boundary and an outer boundary with a flow path defined therebetween. The inner boundary is defined at least in part by a hub structure that has an upstream end and a downstream end. The outer boundary may include a region in which the outer boundary extends radially inward toward the hub structure and may direct at least a portion of an exhaust flow in the diffuser toward the hub structure. The hub structure includes at least one jet exit located on the hub structure adjacent to the upstream end of the tail cone. The jet exit discharges a flow of gas substantially tangential to an outer surface of the tail cone to produce a Coanda effect and direct a portion of the exhaust flow in the diffuser toward the inner boundary.

A FRAP-Based Method for Monitoring Molecular Transport in Ciliary Photoreceptor Cells In Vivo.

PubMed

Wunderlich, Kirsten A; Wolfrum, Uwe

2016-01-01

The outer segment of rod and cone photoreceptor cells represents a highly modified primary sensory cilium. It renews on a daily basis throughout lifetime and effective vectorial transport to the cilium is essential for the maintenance of the photoreceptor cell function. Defects in molecules of transport modules lead to severe retinal ciliopathies. We have recently established a fluorescence recovery after photobleaching (FRAP)-based method to monitor molecular trafficking in living rodent photoreceptor cells. We irreversibly bleach the fluorescence of tagged molecules (e.g. eGFP-Rhodopsin) in photoreceptor cells of native vibratome sections through the retina by high laser intensity. In the laser scanning microscope, the recovery of the fluorescent signal is monitored over time and the kinetics of movements of molecules can be quantitatively ascertained.

KCNQ5/Kv7.5 potassium channel expression and subcellular localization in primate retinal pigment epithelium and neural retina

PubMed Central

Zhang, Xiaoming; Yang, Dongli

2011-01-01

Previous studies identified in retinal pigment epithelial (RPE) cells an M-type K+ current, which in many other cell types is mediated by channels encoded by KCNQ genes. The aim of this study was to assess the expression of KCNQ genes in the monkey RPE and neural retina. Application of the specific KCNQ channel blocker XE991 eliminated the M-type current in freshly isolated monkey RPE cells, indicating that KCNQ subunits contribute to the underlying channels. RT-PCR analysis revealed the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in the RPE and all five KCNQ transcripts in the neural retina. At the protein level, KCNQ5 was detected in the RPE, whereas both KCNQ4 and KCNQ5 were found in neural retina. In situ hybridization in frozen monkey retinal sections revealed KCNQ5 gene expression in the ganglion cell layer and the inner and outer nuclear layers of the neural retina, but results in the RPE were inconclusive due to the presence of melanin. Immunohistochemistry revealed KCNQ5 in the inner and outer plexiform layers, in cone and rod photoreceptor inner segments, and near the basal membrane of the RPE. The data suggest that KCNQ5 channels contribute to the RPE basal membrane K+ conductance and, thus, likely play an important role in active K+ absorption. The distribution of KCNQ5 in neural retina suggests that these channels may function in the shaping of the photoresponses of cone and rod photoreceptors and the processing of visual information by retinal neurons. PMID:21795522

En face spectral domain optical coherence tomography analysis of lamellar macular holes.

PubMed

Clamp, Michael F; Wilkes, Geoff; Leis, Laura S; McDonald, H Richard; Johnson, Robert N; Jumper, J Michael; Fu, Arthur D; Cunningham, Emmett T; Stewart, Paul J; Haug, Sara J; Lujan, Brandon J

2014-07-01

To analyze the anatomical characteristics of lamellar macular holes using cross-sectional and en face spectral domain optical coherence tomography. Forty-two lamellar macular holes were retrospectively identified for analysis. The location, cross-sectional length, and area of lamellar holes were measured using B-scans and en face imaging. The presence of photoreceptor inner segment/outer segment disruption and the presence or absence of epiretinal membrane formation were recorded. Forty-two lamellar macular holes were identified. Intraretinal splitting occurred within the outer plexiform layer in 97.6% of eyes. The area of intraretinal splitting in lamellar holes did not correlate with visual acuity. Eyes with inner segment/outer segment disruption had significantly worse mean logMAR visual acuity (0.363 ± 0.169; Snellen = 20/46) than in eyes without inner segment/outer segment disruption (0.203 ± 0.124; Snellen = 20/32) (analysis of variance, P = 0.004). Epiretinal membrane was present in 34 of 42 eyes (81.0%). En face imaging allowed for consistent detection and quantification of intraretinal splitting within the outer plexiform layer in patients with lamellar macular holes, supporting the notion that an area of anatomical weakness exists within Henle's fiber layer, presumably at the synaptic connection of these fibers within the outer plexiform layer. However, the en face area of intraretinal splitting did not correlate with visual acuity, disruption of the inner segment/outer segment junction was associated with significantly worse visual acuity in patients with lamellar macular holes.

Phase-sensitive imaging of the outer retina using optical coherence tomography and adaptive optics

PubMed Central

Jonnal, Ravi S.; Kocaoglu, Omer P.; Wang, Qiang; Lee, Sangyeol; Miller, Donald T.

2011-01-01

The cone photoreceptor’s outer segment (OS) experiences changes in optical path length, both in response to visible stimuli and as a matter of its daily course of renewal and shedding. These changes are of interest, to quantify function in healthy cells and assess dysfunction in diseased ones. While optical coherence tomography (OCT), combined with adaptive optics (AO), has permitted unprecedented three-dimensional resolution in the living retina, it has not generally been able to measure these OS dynamics, whose scale is smaller than OCT’s axial resolution of a few microns. A possible solution is to take advantage of the phase information encoded in the OCT signal. Phase-sensitive implementations of spectral-domain optical coherence tomography (SD-OCT) have been demonstrated, capable of resolving sample axial displacements much smaller than the imaging wavelength, but these have been limited to ex vivo samples. In this paper we present a novel technique for retrieving phase information from OCT volumes of the outer retina. The key component of our technique is quantification of phase differences within the retina. We provide a quantitative analysis of such phase information and show that–when combined with appropriate methods for filtering and unwrapping–it can improve the sensitivity to OS length change by more than an order of magnitude, down to 45 nm, slightly thicker than a single OS disc. We further show that phase sensitivity drops off with retinal eccentricity, and that the best location for phase imaging is close to the fovea. We apply the technique to the measurement of sub-resolution changes in the OS over matters of hours. Using custom software for registration and tracking, these microscopic changes are monitored in hundreds of cones over time. In two subjects, the OS was found to have average elongation rates of 150 nm/hr, values which agree with our previous findings. PMID:22254172

High-Speed Ultra-High-Resolution Optical Coherence Tomography Findings in Hydroxychloroquine Retinopathy

PubMed Central

Rodriguez-Padilla, Julio A.; Hedges, Thomas R.; Monson, Bryan; Srinivasan, Vivek; Wojtkowski, Maciej; Reichel, Elias; Duker, Jay S.; Schuman, Joel S.; Fujimoto, James G.

2007-01-01

Objectives To compare structural changes in the retina seen on high-speed ultra–high-resolution optical coherence tomography (hsUHR-OCT) with multifocal electroretinography (mfERG) and automated visual fields in patients receiving hydroxychloroquine. Methods Fifteen patients receiving hydroxychloroquine were evaluated clinically with hsUHR-OCT, mfERG, and automated visual fields. Six age-matched subjects were imaged with hsUHR-OCT and served as controls. Results Distinctive discontinuity of the perifoveal photoreceptor inner segment/outer segment junction and thinning of the outer nuclear layer were seen with hsUHR-OCT in patients with mild retinal toxic effects. Progression to complete loss of the inner segment/outer segment junction and hyperscattering at the outer segment level were seen in more advanced cases. The mfERG abnormalities correlated with the hsUHR-OCT findings. Asymptomatic patients had normal hsUHR-OCT and mfERG results. Conclusion Distinctive abnormalities in the perifoveal photoreceptor inner segment/outer segment junction were seen on hsUHR-OCT in patients receiving hydroxychloroquine who also were symptomatic and had abnormalities on automated visual fields and mfERG. PMID:17562988

Mef2d is essential for the maturation and integrity of retinal photoreceptor and bipolar cells.

PubMed

Omori, Yoshihiro; Kitamura, Tamiki; Yoshida, Satoyo; Kuwahara, Ryusuke; Chaya, Taro; Irie, Shoichi; Furukawa, Takahisa

2015-05-01

Mef2 transcription factors play a crucial role in cardiac and skeletal muscle differentiation. We found that Mef2d is highly expressed in the mouse retina and its loss causes photoreceptor degeneration similar to that observed in human retinitis pigmentosa patients. Electroretinograms (ERGs) were severely impaired in Mef2d-/- mice. Immunohistochemistry showed that photoreceptor and bipolar cell synapse protein levels severely decreased in the Mef2d-/- retina. Expression profiling by microarray analysis showed that Mef2d is required for the expression of various genes in photoreceptor and bipolar cells, including cone arrestin, Guca1b, Pde6h and Cacna1s, which encode outer segment and synapse proteins. We also observed that Mef2d synergistically activates the cone arrestin (Arr3) promoter with Crx, suggesting that functional cooperation between Mef2d and Crx is important for photoreceptor cell gene regulation. Taken together, our results show that Mef2d is essential for photoreceptor and bipolar cell gene expression, either independently or cooperatively with Crx. © 2015 Institution for Protein Research. Genes to Cells published by Wiley Publishing Asia Pty Ltd and the Molecular Biology Society of Japan.

C2orf71a/pcare1 is important for photoreceptor outer segment morphogenesis and visual function in zebrafish.

PubMed

Corral-Serrano, Julio C; Messchaert, Muriël; Dona, Margo; Peters, Theo A; Kamminga, Leonie M; van Wijk, Erwin; Collin, Rob W J

2018-06-26

Mutations in C2orf71 are causative for autosomal recessive retinitis pigmentosa and occasionally cone-rod dystrophy. We have recently discovered that the protein encoded by this gene is important for modulation of the ciliary membrane through the recruitment of an actin assembly module, and have therefore renamed the gene to PCARE (photoreceptor cilium actin regulator). Here, we report on the identification of two copies of the c2orf71/pcare gene in zebrafish, pcare1 and pcare2. To study the role of the gene most similar to human PCARE, pcare1, we have generated a stable pcare1 mutant zebrafish model (designated pcare1 rmc100/rmc100 ) in which the coding sequence was disrupted using CRISPR/Cas9 technology. Retinas of both embryonic (5 dpf) and adult (6 mpf) pcare1 rmc100/rmc100 zebrafish display a clear disorganization of photoreceptor outer segments, resembling the phenotype observed in Pcare -/- mice. Optokinetic response and visual motor response measurements indicated visual impairment in pcare1 rmc100/rmc100 zebrafish larvae at 5 dpf. In addition, electroretinogram measurements showed decreased b-wave amplitudes in pcare1 rmc100/rmc100 zebrafish as compared to age- and strain-matched wild-type larvae, indicating a defect in the transretinal current. Altogether, our data show that lack of pcare1 causes a retinal phenotype in zebrafish and indicate that the function of the PCARE gene is conserved across species.

Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

PubMed Central

Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

2012-01-01

In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance between excitation and inhibition in the outer retina needs to be adaptable. How this is achieved is unknown. Using electrophysiological techniques in the isolated retina of the goldfish, it was found that opening Ca2+-dependent Cl− channels in recorded cones reduced the size of feedback responses measured in both cones and HCs. Furthermore, we show that cones express Cl− channels that are gated by GABA released from HCs. Similar to activation of ICl(Ca), opening of these GABA-gated Cl− channels reduced the size of light-induced feedback responses both in cones and HCs. Conversely, application of picrotoxin, a blocker of GABAA and GABAC receptors, had the opposite effect. In addition, reducing GABA release from HCs by blocking GABA transporters also led to an increase in the size of feedback. Because the independent manipulation of Ca2+-dependent Cl− currents in individual cones yielded results comparable to bath-applied GABA, it was concluded that activation of either Cl− current by itself is sufficient to reduce the size of HC feedback. However, additional effects of GABA on outer retinal processing cannot be excluded. These results can be accounted for by an ephaptic feedback model in which a cone Cl− current shunts the current flow in the synaptic cleft. The Ca2+-dependent Cl− current might be essential to set the initial balance between the feedforward and the feedback signals active in the cone HC synapse. It prevents that strong feedback from HCs to cones flood the cone with Ca2+. Modulation of the feedback strength by GABA might play a role during light/dark adaptation, adjusting the amount of negative feedback to the signal to noise ratio of the cone output. PMID:22890705

The retinal phenotype of Usher syndrome: pathophysiological insights from animal models.

PubMed

El-Amraoui, Aziz; Petit, Christine

2014-03-01

The Usher syndrome (USH) is the most prevalent cause of inherited deaf-blindness. Three clinical subtypes, USH1-3, have been defined, and ten USH genes identified. The hearing impairment due to USH gene defects has been shown to result from improper organisation of the hair bundle, the sound receptive structure of sensory hair cells. In contrast, the cellular basis of the visual defect is less well understood as this phenotype is absent in almost all the USH mouse models that faithfully mimic the human hearing impairment. Structural and molecular interspecies discrepancies regarding photoreceptor calyceal processes and the association with the distribution of USH1 proteins have recently been unravelled, and have led to the conclusion that a defect in the USH1 protein complex-mediated connection between the photoreceptor outer segment and the surrounding calyceal processes (in both rods and cones), and the inner segment (in rods only), probably causes the USH1 retinal dystrophy in humans. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Experimental chloroquine retinopathy.

PubMed

Matsumura, M; Ohkuma, M; Tsukahara, I

1986-01-01

Chloroquine retinopathy was produced experimentally in the eye of the albino corydoras (one of the tropical fish) by daily administration of chloroquine (0.1 mg per os). The enucleated eyes were examined from the 14th day to 3 months after the beginning of drug administration under light and electron microscopy. The first change of retina was the appearance of membraneous cytoplasmic body (MCB) in the cytoplasm of ganglion, amacrine, bipolar and horizontal cells. MCB might be degenerated lysosome. They showed lamellar figures or crystalline lattice-like structures. Secondarily, these MCB appeared in the inner segments of photoreceptor cells. The outer segments of rod cells disappeared, and then those of cone cells. Although photoreceptor cells were diminished in number in advanced degeneration, the cells of inner nuclear layer and ganglion cells were maintained in number. The presence of MCB dose not mean death of cells. The retinal pigment epithelial cells contained MCB in its cytoplasm only in severe degenerative cases, and did not show other remarkable changes. MCB also appeared in the cytoplasm of pericytes of retinal vessels. Chloroquine is considered to damage directly photoreceptor cells most severely.

Cooled turbine vane with endcaps

DOEpatents

Cunha, Frank J.; Schiavo, Jr., Anthony L.; Nordlund, Raymond Scott; Malow, Thomas; McKinley, Barry L.

2002-01-01

A turbine vane assembly which includes an outer endcap having a plurality of generally straight passages and passage segments therethrough, an inner endcap having a plurality of passages and passage segments therethrough, and a vane assembly having an outer shroud, an airfoil body, and an inner shroud. The outer shroud, airfoil body and inner shroud each have a plurality of generally straight passages and passage segments therethrough as well. The outer endcap is coupled to the outer shroud so that outer endcap passages and said outer shroud passages form a fluid circuit. The inner endcap is coupled to the inner shroud so that the inner end cap passages and the inner shroud passages from a fluid circuit. Passages in the vane casting are in fluid communication with both the outer shroud passages and the inner shroud passages. Passages in the outer endcap may be coupled to a cooling system that supplies a coolant and takes away the heated exhaust.

STRUCTURAL ASSESSMENT OF HYPERAUTOFLUORESCENT RING IN PATIENTS WITH RETINITIS PIGMENTOSA

PubMed Central

LIMA, LUIZ H.; CELLA, WENER; GREENSTEIN, VIVIENNE C.; WANG, NAN-KAI; BUSUIOC, MIHAI; THEODORE SMITH, R.; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.

2009-01-01

Purpose To analyze the retinal structure underlying the hyperautofluorescent ring visible on fundus autofluorescence in patients with retinitis pigmentosa. Methods Twenty-four eyes of 13 patients with retinitis pigmentosa, aged 13 years to 67 years, were studied. The integrity of the photoreceptor cilia, also known as the inner/outer segment junction of the photoreceptors, the outer nuclear layer, and retinal pigment epithelium, was evaluated outside, across, and inside the ring with spectral-domain optical coherence tomography (OCT). Results Inside the foveal area, fundus autofluorescence did not detect abnormalities. Outside the ring, fundus autofluorescence revealed hypoautofluorescence compatible with the photoreceptor/retinal pigment epithelium degeneration. Spectral-domain OCT inside the ring, in the area of normal foveal fundus autofluorescence, revealed an intact retinal structure in all eyes and total retinal thickness values that were within normal limits. Across the ring, inner/outer segment junction disruption was observed and the outer nuclear layer was decreased in thickness in a centrifugal direction in all eyes. Outside the hyperautofluorescent ring, the inner/outer segment junction and the outer nuclear layer appeared to be absent and there were signs of retinal pigment epithelium degeneration. Conclusion Disruption of the inner/outer segment junction and a decrease in outer retinal thickness were found across the central hyperautofluorescent ring seen in retinitis pigmentosa. Outer segment phagocytosis by retinal pigment epithelium is necessary for the formation of an hyperautofluorescent ring. PMID:19584660

Automated method for structural segmentation of nasal airways based on cone beam computed tomography

NASA Astrophysics Data System (ADS)

Tymkovych, Maksym Yu.; Avrunin, Oleg G.; Paliy, Victor G.; Filzow, Maksim; Gryshkov, Oleksandr; Glasmacher, Birgit; Omiotek, Zbigniew; DzierŻak, RóŻa; Smailova, Saule; Kozbekova, Ainur

2017-08-01

The work is dedicated to the segmentation problem of human nasal airways using Cone Beam Computed Tomography. During research, we propose a specialized approach of structured segmentation of nasal airways. That approach use spatial information, symmetrisation of the structures. The proposed stages can be used for construction a virtual three dimensional model of nasal airways and for production full-scale personalized atlases. During research we build the virtual model of nasal airways, which can be used for construction specialized medical atlases and aerodynamics researches.

Postembryonic development of Antygomonas incomitata (Kinorhyncha: Cyclorhagida).

PubMed

Sørensen, Martin V; Accogli, Gianluca; Hansen, Jesper G

2010-07-01

Postembryonic development in the kinorhynch species Antygomonas incomitata was examined using scanning electron microscopy. The morphology of the six juvenile stages, J-1 to J-6, varies at numerous details, but they can also be distinguished by a few key characters. Juvenile stage 1 by its composition of only nine trunk segments; J-2 by the combination of possessing 10 trunk segments, but no cuspidate spines on segment 9; J-3 by the presence of cuspidate spines on segment 9, but only one pair of cuspidate spines on segment 8; J-4 by the combination of 10 trunk segments only, but having two pairs of cuspidate spines on segment 8; J-5 by possessing 11 trunk segments and same spine compositions as adults but is still maintaining postmarginal spiculae; J-6 specimens closely resemble adults and are most easily identified by their reduced trunk lengths. New segments are formed in a growth zone in the anterior part of the terminal segment. The complete number of segments is reached in J-5. Development of cuticular head and trunk structures are described through all postembryonic stages and following developmental patterns could be outlined: the mouth cone possesses outer oral styles from J-1, but in J-1 to J-3, the styles alternate in size. Scalids of the introvert are added after each molt, and scalids appear earliest in the anterior rings, whereas scalids in more posterior rings are added in older postembryonic stages. The early J-1 stage is poor in spines and sensory spots and both structures increase in number after each molt. The complete spine composition is reached in J-4, whereas new sensory spots appear after all molts, inclusive the final one from J-6 to adult. Sensory spots in the paraventral positions often appear as Type 3 sensory spots but are through development transformed to Type 2. This transformation happens earliest on the anterior segments.

Investigation into aerodynamic and heat transfer of annular channel with inner and outer surface of the shape truncated cone and swirling fluid flow

NASA Astrophysics Data System (ADS)

Leukhin, Yu L.; Pankratov, E. V.; Karpov, S. V.

2017-11-01

We have carried out Investigation into aerodynamic and convective heat transfer of the annular channel. Inner or outer surface of annular channel has shape of blunt-nosed cone tapering to outlet end. Truncated cone connects to a cyclone swirling flow generator. Asymmetric and unsteady flow from the swirling generator in the shape of periodic process gives rise to the formation of secondary flows of the type Taylor-Görtler vortices. These vortices occupy the whole space of the annular channel, with the axes, which coincide with the motion direction of the major stream. Contraction of cross-sectional area of channel (in both cases 52%) causes a marked increase in total velocity of flow, primarily due to its axial component and promotes a more intensive vortex generation. Vortex structures have a significant influence on both average heat transfer and surface distribution. At cross-sections of the annular channel we observe similarity of curves describing distribution of total velocity about wall and heat flux density on the surface. The coordinates of maximum and minimum values of velocity and heat flux coincide. At the average cross-section channel of maximum value of heat transfer is greater than minimum of about by a factor of 2.7 times for outer heat transfer surface and about by a factor of 1.7 times for inner heat transfer surface. Taper channel has a much higher influence on heat transfer of the inner surface than the outer surface and manifests itself at lower values of dimensionless axial coordinate. For the investigated taper cone geometry of the annular channel the heat transfer coefficient of inner surface increases at the outlet section and exceeds value in comparison with straight-line section by 91 … 98%. Heat transfer of the outer cylinder in the same section increases only by 5 … 11%. The increase in average heat transfer over the surfaces is 36% and 4% respectively.

Pre-stressed/pre-compressed gas turbine nozzle

DOEpatents

Jang, Hoyle; Itzel, Gary Michael; Yu, Yufeng Phillip

2002-01-01

A method of increasing low cycle fatigue life of a turbine nozzle comprising a plurality of stationary airfoils extending between radially inner and outer ring segments comprising a) providing at least one radial passage in each of the plurality of airfoils; b) installing a rod in the radial passage extending between the radially inner and outer ring segments and fixing one end of the rod to one of the inner and outer rings; and c) pre-loading the rod to compress the airfoil between the inner and outer ring segments.

The membrane current of single rod outer segments.

PubMed

Baylor, D A; Lamb, T D; Yau, K W

1979-03-01

1. Outer segments of individual rods in the retina of the toad, Bufo marinus, were drawn into a glass pipette to record the membrane current. 2. Light flashes evoked transient outward currents. The peak response amplitude was related to flash intensity by a Michaelis equation with half-saturating intensity about 1 photon mum-2. 3. The saturating response amplitude ranged up to 27 pA and corresponded closely to complete suppression of the steady inward current present in darkness. 4. For a given cell the saturating response amplitude varied linearly with the length of outer segment within the pipette. This is consistent with a uniform density of light-sensitive channels and negligible gradient of membrane potential along the outer segment. 5. Responses to bright flashes never showed the relaxation from an initial peak seen previously in intracellular voltage recordings, suggesting that the conductance change responsible for the relaxation does not occur in the outer segment. 6. Responses to local illumination of only the recorded outer segment were very similar to those obtained with diffuse light at the same intensity, indicating that peripheral rods made little contribution to the responses. 7. The spectral sensitivity of 'red' rods was consistent with a retinal1-based pigment with lambda max = 498 +/- 2 nm. 8. The kinetics of the response were consistent with four stages of delay affecting action of the internal transmitter. Responses were faster at the basal end of the outer segment than at the distal tip. 9. Background light reduced the sensitivity to a superposed dim test flash and shortened the time course of the response, indicating that adapting light modifies the kinetics and gain of the transduction mechanism within the outer segment. 10. Responses to dim lights exhibited pronounced fluctuations which are attributed in the succeeding paper (Baylor, Lamb & Yau, 1979) to the quantal nature of light.

3D imaging of cone photoreceptors over extended time periods using optical coherence tomography with adaptive optics

NASA Astrophysics Data System (ADS)

Kocaoglu, Omer P.; Lee, Sangyeol; Jonnal, Ravi S.; Wang, Qiang; Herde, Ashley E.; Besecker, Jason; Gao, Weihua; Miller, Donald T.

2011-03-01

Optical coherence tomography with adaptive optics (AO-OCT) is a highly sensitive, noninvasive method for 3D imaging of the microscopic retina. The purpose of this study is to advance AO-OCT technology by enabling repeated imaging of cone photoreceptors over extended periods of time (days). This sort of longitudinal imaging permits monitoring of 3D cone dynamics in both normal and diseased eyes, in particular the physiological processes of disc renewal and phagocytosis, which are disrupted by retinal diseases such as age related macular degeneration and retinitis pigmentosa. For this study, the existing AO-OCT system at Indiana underwent several major hardware and software improvements to optimize system performance for 4D cone imaging. First, ultrahigh speed imaging was realized using a Basler Sprint camera. Second, a light source with adjustable spectrum was realized by integration of an Integral laser (Femto Lasers, λc=800nm, ▵λ=160nm) and spectral filters in the source arm. For cone imaging, we used a bandpass filter with λc=809nm and ▵λ=81nm (2.6 μm nominal axial resolution in tissue, and 167 KHz A-line rate using 1,408 px), which reduced the impact of eye motion compared to previous AO-OCT implementations. Third, eye motion artifacts were further reduced by custom ImageJ plugins that registered (axially and laterally) the volume videos. In two subjects, cone photoreceptors were imaged and tracked over a ten day period and their reflectance and outer segment (OS) lengths measured. High-speed imaging and image registration/dewarping were found to reduce eye motion to a fraction of a cone width (1 μm root mean square). The pattern of reflections in the cones was found to change dramatically and occurred on a spatial scale well below the resolution of clinical instruments. Normalized reflectance of connecting cilia (CC) and OS posterior tip (PT) of an exemplary cone was 54+/-4, 47+/-4, 48+/-6, 50+/-5, 56+/-1% and 46+/-4, 53+/-4, 52+/-6, 50+/-5, 44+/-1% for days #1,3,6,8,10 respectively. OS length of the same cone was 28.9, 26.4, 26.4, 30.6, and 28.1 ìm for days #1,3,6,8,10 respectively. It is plausible these changes are an optical correlate of the natural process of OS renewal and shedding.

Enhanced depth imaging optical coherence tomography of choroidal metastasis in 14 eyes.

PubMed

Al-Dahmash, Saad A; Shields, Carol L; Kaliki, Swathi; Johnson, Timothy; Shields, Jerry A

2014-08-01

To describe the imaging features of choroidal metastasis using enhanced depth imaging optical coherence tomography (EDI-OCT). This retrospective observational case series included 31 eyes with choroidal metastasis. Spectral domain EDI-OCT was performed using Heidelberg Spectralis HRA + OCT. The main outcome measures were imaging features by EDI-OCT. Of 31 eyes with choroidal metastasis imaged with EDI-OCT, 14 (45%) eyes displayed image detail suitable for study. The metastasis originated from carcinoma of the breast (n = 7, 50%), lung (n = 5, 36%), pancreas (n = 1, 7%), and thyroid gland (n = 1, 7%). The mean tumor basal diameter was 6.4 mm, and mean thickness was 2.3 mm by B-scan ultrasonography. The tumor location was submacular in 6 (43%) eyes and extramacular in 8 (57%) eyes. By EDI-OCT, the mean tumor thickness was 987 μm. The most salient EDI-OCT features of the metastasis included anterior compression/obliteration of the overlying choriocapillaris (n = 13, 93%), an irregular (lumpy bumpy) anterior contour (n = 9, 64%), and posterior shadowing (n = 12, 86%). Overlying retinal pigment epithelial abnormalities were noted (n = 11, 78%). Outer retinal features included structural loss of the interdigitation of the cone outer segment tips (n = 9, 64%), the ellipsoid portion of photoreceptors (n = 8, 57%), external limiting membrane (n = 4, 29%), outer nuclear layer (n = 1, 7%), and outer plexiform layer (n = 1, 7%). The inner retinal layers (inner nuclear layer to nerve fiber layer) were normal. Subretinal fluid (n = 11, 79%), subretinal lipofuscin pigment (n = 1, 7%), and intraretinal edema (n = 2, 14%) were identified. The EDI-OCT of choroidal metastasis shows a characteristic lumpy bumpy anterior tumor surface and outer retinal layer disruption with preservation of inner retinal layers.

Toward a Next Generation Solar Coronagraph: Diffracted Light Simulation and Test Results for a Cone Occulter with Tapered Surface

NASA Astrophysics Data System (ADS)

Yang, Heesu; Bong, Su-Chan; Cho, Kyung-Suk; Choi, Seonghwan; Park, Jongyeob; Kim, Jihun; Baek, Ji-Hye; Nah, Jakyoung; Sun, Mingzhe; Gong, Qian

2018-04-01

In a solar coronagraph, the most important component is an occulter to block the direct light from the disk of the sun Because the intensity of the solar outer corona is 10-6 to 10-10 times of that of the solar disk (\\ir), it is necessary to minimize scattering at the optical elements and diffraction at the occulter. Using a Fourier optic simulation and a stray light test, we investigated the performance of a compact coronagraph that uses an external truncated-cone occulter without an internal occulter and Lyot stop. In the simulation, the diffracted light was minimized to the order of 7.6×10-10 \\ir when the cone angle θc was about 0.39°. The performance of the cone occulter was then tested by experiment. The level of the diffracted light reached the order of 6×10-9 \\ir at θc=0.40°. This is sufficient to observe the outer corona without additional optical elements such as a Lyot stop or inner occulter. We also found the manufacturing tolerance of the cone angle to be 0.05°, the lateral alignment tolerance was 45 \\um, and the angular alignment tolerance was 0.043°. Our results suggest that the physical size of coronagraphs can be shortened significantly by using a cone occulter.

Method of fabricating a prestressed cast iron vessel

DOEpatents

Lampe, Robert F.

1982-01-01

A method of fabricating a prestressed cast iron vessel wherein double wall cast iron body segments each have an arcuate inner wall and a spaced apart substantially parallel outer wall with a plurality of radially extending webs interconnecting the inner wall and the outer wall, the bottom surface and the two exposed radial side surfaces of each body segment are machined and eight body segments are formed into a ring. The top surfaces and outer surfaces of the outer walls are machined and keyways are provided across the juncture of adjacent end walls of the body segments. A liner segment complementary in shape to a selected inner wall of one of the body segments is mounted to each of the body segments and again formed into a ring. The liner segments of each ring are welded to form unitary liner rings and thereafter the cast iron body segments are prestressed to complete the ring assembly. Ring assemblies are stacked to form the vessel and adjacent unitary liner rings are welded. A top head covers the top ring assembly to close the vessel and axially extending tendons retain the top and bottom heads in place under pressure.

KCNQ and KCNE Potassium Channel Subunit Expression in Bovine Retinal Pigment Epithelium

PubMed Central

Zhang, Xiaoming; Hughes, Bret A.

2013-01-01

Human, monkey, and bovine retinal pigment epithelial (RPE) cells exhibit an M-type K+ current, which in many other cell types is mediated by channels composed of KCNQ α-subunits and KCNE auxiliary subunits. Recently, we demonstrated the expression of KCNQ1, KCNQ4, and KCNQ5 in the monkey RPE. Here, we investigated the expression of KCNQ and KCNE subunits in native bovine RPE. RT-PCR analysis revealed the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in the RPE, but, in Western blot analysis of RPE plasma membranes, only KCNQ5 was detected. Among the five members of the KCNE gene family, transcripts for KCNE1, KCNE2, KCNE3, and KCNE4 were detected in bovine RPE, but only KCNE1 and KCNE2 proteins were detected. Immunohistochemistry of frozen bovine retinal sections revealed KCNE1 expression near the apical and basal membranes of the RPE, in cone outer segments, in the outer nuclear layer, and throughout the inner retina. The localization of KCNE1 in the RPE basal membrane, where KCNQ5 was previously found to be present, suggests that this β-subunit may contribute to M-type K+ channels in this membrane. PMID:24416770

Role of subunit assembly in autosomal dominant retinitis pigmentosa linked to mutations in peripherin 2.

PubMed

Molday, Robert S; Molday, Laurie L; Loewen, Christopher J R

2004-01-01

Peripherin 2 is a photoreceptor-specific membrane protein implicated in outer segment disk morphogenesis and linked to various retinopathies including autosomal dominant retinitis pigmentosa (ADRP). Peripherin 2 and ROM1 assemble as a mixture of core noncovalent homomeric and heteromeric tetramers that further link together through disulfide bonds to form higher order oligomers. These complexes are critical for disk rim formation and outer segment structure through interaction with the cGMP-gated channel and other photoreceptor proteins. We have examined the role of subunit assembly in peripherin 2 targeting to disks, outer segment structure, and photoreceptor degeneration by examining molecular and cellular properties of peripherin 2 mutants in COS-1 cells and transgenic Xenopus laevis rod photoreceptors. Wild-type (WT) and the ADRP-linked P216L mutant were transported and incorporated into newly formed outer segment disks of transgenic X. laevis. The P216L mutant, however, induced progressive outer segment instability and photoreceptor degeneration possibly through the introduction of a new N-linked oligosaccharide chain. In contrast, the C214S and L185P disease-linked, tetramerization-defective mutants, were retained in the inner segment, but did not affect outer segment structure or induce photoreceptor degeneration. Together, these results indicate that peripherin 2 mutations can cause ADRP either through a deficiency in WT peripherin 2 (C214S, 1.185P) or by a dominant negative effect on disk stability (P216L).

Extra-mitochondrial aerobic metabolism in retinal rod outer segments: new perspectives in retinopathies.

PubMed

Panfoli, I; Calzia, D; Ravera, S; Morelli, A M; Traverso, C E

2012-04-01

Vertebrate retinal rods are photoreceptors for dim-light vision. They display extreme sensitivity to light thanks to a specialized subcellular organelle, the rod outer segment. This is filled with a stack of membranous disks, expressing the proteins involved in visual transduction, a very energy demanding process. Our previous proteomic and biochemical studies have shed new light on the chemical energy processes that supply ATP to the outer segment, suggesting the presence of an extra-mitochondrial aerobic metabolism in rod outer segment, devoid of mitochondria, which would account for a quantitatively adequate ATP supply for phototransduction. Here the functional presence of an oxidative phosphorylation in the rod outer limb is examined for its relationship to many physiological and pathological data on the rod outer segment. We hypothesize that the rod outer limb is at risk of oxidative stress, in any case of impairment in the respiratory chain functioning, or of blood supply. In fact, the electron transfer chain is a major source of reactive O(2) species, known to produce severe alteration to the membrane lipids, especially those of the outer segment that are rich in polyunsaturated fatty acids. We propose that the disk membrane may become the target of reactive oxygen species that may be released by the electron transport chain under pathologic conditions. For example, during aging reactive oxygen species production increases, while cellular antioxidant capacity decreases. Also the apoptosis of the rod observed after exposure to bright or continuous illumination can be explained considering that an overfunctioning of phototransduction may damage the disk membrane to a point at which cytochrome c escapes from the intradiskal space, where it is presently supposed to be, activating a putative caspase 9 and the apoptosome. A pathogenic mechanism for many inherited and acquired retinal degenerations, representing a major problem in clinical ophthalmology, is proposed: a number of rod pathologies would be promoted by impairment of energy supply and/or oxidative stress in the rod outer segment. In conclusion we suppose that the damaging role of oxygen, be it hypoxia or hyperoxia invoked in most of the blinding diseases, acquired and even hereditary is to be seeked for inside the photoreceptor outer segment that would conceal a potential for cell death that is still to be recognized. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Displacement of the posterior part of the eyeball in myopia].

PubMed

Akizawa, Yasuko; Masahiro, Ida

2006-12-01

The principal aim of this study was to investigate displacement of the posterior part of the eyeball within the muscle cone in myopic eyes, particularly in moderately myopic subjects as well as in high myopes. Secondly, the correlation of the amount of displacement and the outer axial length of the globe was studied. The direction of displacement was also examined to clarify whether the eyeball tends to shift toward a certain direction. Seven patients with moderate myopia (moderate myopia group), fifteen patients with high myopia without esotropia (high myopia group), five patients with high myopia and esotropia (myopic esotropia group), and twenty-two controls (control group) were examined. Using magnetic resonance imaging, the outer axial length and the displacement of the posterior portion of the eyeball in the muscle cone were measured. In order to eliminate interindividual differences in the facial configuration, the coronal scanning was done perpendicularly to the orbital axis. The displacement was measured in a plane 4 mm anterior to the globe-optic nerve junction. The displacement was represented by the distance and direction of the globe center from the center of the muscle cone. In the moderate myopia group, there was no displacement of the posterior part of the eyeball in the muscle cone. It was the same as in the control group. But among the three groups, the displacement (mean standard deviation) was significantly greater in the myopic esotropia group (1.53 +/- 0.49 mm) and the high myopia group (0.94 +/- 0.52 mm) than in the control group (0.11 +/- 0.18 mm) (one way ANOVA and multiple comparison). The outer axial length and the distance of the displacement in all cases was significantly correlated (r = 0.87, p = 0.01). Moreover, the posterior part of the eyeball of the myopic esotropia group and the high myopia group was displaced superiorly and temporally. The posterior part of the eyeball of myopic eyes was displaced superotemporally in the muscle cone regardless of the presence of esotropia, and the amount of displacement was significantly correlated with the outer axial length. The more the eyeball expanded, the farther it was displaced. In the end, it was thought that the most elongated high myopic eyes would dislocate out of the muscle cone.

Development of an Advanced Aidman Vision Screener (AVS) for selective assessment of outer and inner laser induced retinal injury

NASA Astrophysics Data System (ADS)

Boye, Michael W.; Zwick, Harry; Stuck, Bruce E.; Edsall, Peter R.; Akers, Andre

2007-02-01

The need for tools that can assist in evaluating visual function is an essential and a growing requirement as lasers on the modern battlefield mature and proliferate. The requirement for rapid and sensitive vision assessment under field conditions produced the USAMRD Aidman Vision Screener (AVS), designed to be used as a field diagnostic tool for assessing laser induced retinal damage. In this paper, we describe additions to the AVS designed to provide a more sensitive assessment of laser induced retinal dysfunction. The AVS incorporates spectral LogMar Acuity targets without and with neural opponent chromatic backgrounds. Thus, it provides the capability of detecting selective photoreceptor damage and its functional consequences at the level of both the outer and inner retina. Modifications to the original achromatic AVS have been implemented to detect selective cone system dysfunction by providing LogMar acuity Landolt rings associated with the peak spectral absorption regions of the S (short), M (middle), and L (long) wavelength cone photoreceptor systems. Evaluation of inner retinal dysfunction associated with selective outer cone damage employs LogMar spectral acuity charts with backgrounds that are neurally opponent. Thus, the AVS provides the capability to assess the effect of selective cone dysfunction on the normal neural balance at the level of the inner retinal interactions. Test and opponent background spectra have been optimized by using color space metrics. A minimal number of three AVS evaluations will be utilized to provide an estimate of false alarm level.

Leaf seal for inner and outer casings of a turbine

DOEpatents

Schroder, Mark Stewart; Leach, David

2002-01-01

A plurality of arcuate, circumferentially extending leaf seal segments form an annular seal spanning between annular sealing surfaces of inner and outer casings of a turbine. The ends of the adjoining seal segments have circumferential gaps to enable circumferential expansion and contraction of the segments. The end of a first segment includes a tab projecting into a recess of a second end of a second segment. Edges of the tab seal against the sealing surfaces of the inner and outer casings have a narrow clearance with opposed edges of the recess. An overlying cover plate spans the joint. Leakage flow is maintained at a minimum because of the reduced gap between the radially spaced edges of the tab and recess, while the seal segments retain the capacity to expand and contract circumferentially.

Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk.

PubMed

Vollrath, D; Feng, W; Duncan, J L; Yasumura, D; D'Cruz, P M; Chappelow, A; Matthes, M T; Kay, M A; LaVail, M M

2001-10-23

The Royal College of Surgeons (RCS) rat is a widely studied animal model of retinal degeneration in which the inability of the retinal pigment epithelium (RPE) to phagocytize shed photoreceptor outer segments leads to a progressive loss of rod and cone photoreceptors. We recently used positional cloning to demonstrate that the gene Mertk likely corresponds to the retinal dystrophy (rdy) locus of the RCS rat. In the present study, we sought to determine whether gene transfer of Mertk to a RCS rat retina would result in correction of the RPE phagocytosis defect and preservation of photoreceptors. We used subretinal injection of a recombinant replication-deficient adenovirus encoding rat Mertk to deliver the gene to the eyes of young RCS rats. Electrophysiological assessment of animals 30 days after injection revealed an increased sensitivity of treated eyes to low-intensity light. Histologic and ultrastructural assessment demonstrated substantial sparing of photoreceptors, preservation of outer segment structure, and correction of the RPE phagocytosis defect in areas surrounding the injection site. Our results provide definitive evidence that mutation of Mertk underlies the RCS retinal dystrophy phenotype, and that the phenotype can be corrected by treatment of juvenile animals. To our knowledge, this is the first demonstration of complementation of both a functional cellular defect (phagocytosis) and a photoreceptor degeneration by gene transfer to the RPE. These results, together with the recent discovery of MERTK mutations in individuals with retinitis pigmentosa, emphasize the importance of the RCS rat as a model for gene therapy of diseases that arise from RPE dysfunction.

Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome.

PubMed

Sun, Lynn W; Johnson, Ryan D; Langlo, Christopher S; Cooper, Robert F; Razeen, Moataz M; Russillo, Madia C; Dubra, Alfredo; Connor, Thomas B; Han, Dennis P; Pennesi, Mark E; Kay, Christine N; Weinberg, David V; Stepien, Kimberly E; Carroll, Joseph

2016-05-01

The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO. Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse. Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.

Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome

PubMed Central

Sun, Lynn W.; Johnson, Ryan D.; Langlo, Christopher S.; Cooper, Robert F.; Razeen, Moataz M.; Russillo, Madia C.; Dubra, Alfredo; Connor, Thomas B.; Han, Dennis P.; Pennesi, Mark E.; Kay, Christine N.; Weinberg, David V.; Stepien, Kimberly E.; Carroll, Joseph

2016-01-01

Purpose The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). Methods Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO. Results Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse. Conclusions Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology. PMID:27145477

Activation and quenching of the phototransduction cascade in retinal cones as inferred from electrophysiology and mathematical modeling

PubMed Central

Astakhova, Luba; Firsov, Michael

2015-01-01

Purpose To experimentally identify and quantify factors responsible for the lower sensitivity of retinal cones compared to rods. Methods Electrical responses of frog rods and fish (Carassius) cones to short flashes of light were recorded using the suction pipette technique. A fast solution changer was used to apply a solution that fixed intracellular Ca2+ concentration at the prestimulus level, thereby disabling Ca2+ feedback, to the outer segment (OS). The results were analyzed with a specially designed mathematical model of phototransduction. The model included all basic processes of activation and quenching of the phototransduction cascade but omitted unnecessary mechanistic details of each step. Results Judging from the response versus intensity curves, Carassius cones were two to three orders of magnitude less sensitive than frog rods. There was a large scatter in sensitivity among individual cones, with red-sensitive cones being on average approximately two times less sensitive than green-sensitive ones. The scatter was mostly due to different signal amplification, since the kinetic parameters of the responses among cones were far less variable than sensitivity. We argue that the generally accepted definition of the biochemical amplification in phototransduction cannot be used for comparing amplification in rods and cones, since it depends on an irrelevant factor, that is, the cell’s volume. We also show that the routinely used simplified parabolic curve fitting to an initial phase of the response leads to a few-fold underestimate of the amplification. We suggest a new definition of the amplification that only includes molecular parameters of the cascade activation, and show how it can be derived from experimental data. We found that the mathematical model with unrestrained parameters can yield an excellent fit to experimental responses. However, the fits with wildly different sets of parameters can be virtually indistinguishable, and therefore cannot provide meaningful data on underlying mechanisms. Based on results of Ca2+-clamp experiments, we developed an approach to strongly constrain the values of many key parameters that set the time course and sensitivity of the photoresponse (such as the dark turnover rate of cGMP, rates of turnoffs of the photoactivated visual pigment and phosphodiesterase, and kinetics of Ca2+ feedback). We show that applying these constraints to our mathematical model enables accurate determination of the biochemical amplification in phototransduction. It appeared that, contrary to many suggestions, maximum biochemical amplification derived for “best” Carassius cones was as high as in frog rods. On the other hand, all turnoff and recovery reactions in cones proceeded approximately 10 times faster than in rods. Conclusions The main cause of the differing sensitivity of rods and cones is cones’ ability to terminate their photoresponse faster. PMID:25866462

Detailed Functional and Structural Phenotype of Bietti Crystalline Dystrophy Associated with Mutations in CYP4V2 Complicated by Choroidal Neovascularization

PubMed Central

Fuerst, Nicole M.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Maguire, Albert M.; Leroy, Bart P.; Kim, Benjamin J.; Aleman, Tomas S.

2016-01-01

Purpose To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin ®; Genentech/Roche). Methods A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA). Results Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod > cone sensitivity loss surrounded fixation and extended to ~10° of eccentricity corresponding to regions of photoreceptor outer segment-retinal pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co-localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of BCVA to baseline (20/25). Conclusion Crystals in BCD were predominantly located within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie the relatively extensive retinal dysfunction observed in relatively early-stage BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting. PMID:27028354

Direct estimation of human trabecular bone stiffness using cone beam computed tomography.

PubMed

Klintström, Eva; Klintström, Benjamin; Pahr, Dieter; Brismar, Torkel B; Smedby, Örjan; Moreno, Rodrigo

2018-04-10

The aim of this study was to evaluate the possibility of estimating the biomechanical properties of trabecular bone through finite element simulations by using dental cone beam computed tomography data. Fourteen human radius specimens were scanned in 3 cone beam computed tomography devices: 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan), NewTom 5 G (QR Verona, Verona, Italy), and Verity (Planmed, Helsinki, Finland). The imaging data were segmented by using 2 different methods. Stiffness (Young modulus), shear moduli, and the size and shape of the stiffness tensor were studied. Corresponding evaluations by using micro-CT were regarded as the reference standard. The 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan) showed good performance in estimating stiffness and shear moduli but was sensitive to the choice of segmentation method. NewTom 5 G (QR Verona, Verona, Italy) and Verity (Planmed, Helsinki, Finland) yielded good correlations, but they were not as strong as Accuitomo 80 (J. Morita MFG., Kyoto, Japan). The cone beam computed tomography devices overestimated both stiffness and shear compared with the micro-CT estimations. Finite element-based calculations of biomechanics from cone beam computed tomography data are feasible, with strong correlations for the Accuitomo 80 scanner (J. Morita MFG., Kyoto, Japan) combined with an appropriate segmentation method. Such measurements might be useful for predicting implant survival by in vivo estimations of bone properties. Copyright © 2018 Elsevier Inc. All rights reserved.

Observation of hohlraum-wall motion with spectrally selective x-ray imaging at the National Ignition Facility

NASA Astrophysics Data System (ADS)

Izumi, N.; Meezan, N. B.; Divol, L.; Hall, G. N.; Barrios, M. A.; Jones, O.; Landen, O. L.; Kroll, J. J.; Vonhof, S. A.; Nikroo, A.; Jaquez, J.; Bailey, C. G.; Hardy, C. M.; Ehrlich, R. B.; Town, R. P. J.; Bradley, D. K.; Hinkel, D. E.; Moody, J. D.

2016-11-01

The high fuel capsule compression required for indirect drive inertial confinement fusion requires careful control of the X-ray drive symmetry throughout the laser pulse. When the outer cone beams strike the hohlraum wall, the plasma ablated off the hohlraum wall expands into the hohlraum and can alter both the outer and inner cone beam propagations and hence the X-ray drive symmetry especially at the final stage of the drive pulse. To quantitatively understand the wall motion, we developed a new experimental technique which visualizes the expansion and stagnation of the hohlraum wall plasma. Details of the experiment and the technique of spectrally selective x-ray imaging are discussed.

Observation of hohlraum-wall motion with spectrally selective x-ray imaging at the National Ignition Facility.

PubMed

Izumi, N; Meezan, N B; Divol, L; Hall, G N; Barrios, M A; Jones, O; Landen, O L; Kroll, J J; Vonhof, S A; Nikroo, A; Jaquez, J; Bailey, C G; Hardy, C M; Ehrlich, R B; Town, R P J; Bradley, D K; Hinkel, D E; Moody, J D

2016-11-01

The high fuel capsule compression required for indirect drive inertial confinement fusion requires careful control of the X-ray drive symmetry throughout the laser pulse. When the outer cone beams strike the hohlraum wall, the plasma ablated off the hohlraum wall expands into the hohlraum and can alter both the outer and inner cone beam propagations and hence the X-ray drive symmetry especially at the final stage of the drive pulse. To quantitatively understand the wall motion, we developed a new experimental technique which visualizes the expansion and stagnation of the hohlraum wall plasma. Details of the experiment and the technique of spectrally selective x-ray imaging are discussed.

Reactor coolant pump flywheel

DOEpatents

Finegan, John Raymond; Kreke, Francis Joseph; Casamassa, John Joseph

2013-11-26

A flywheel for a pump, and in particular a flywheel having a number of high density segments for use in a nuclear reactor coolant pump. The flywheel includes an inner member and an outer member. A number of high density segments are provided between the inner and outer members. The high density segments may be formed from a tungsten based alloy. A preselected gap is provided between each of the number of high density segments. The gap accommodates thermal expansion of each of the number of segments and resists the hoop stress effect/keystoning of the segments.

Freeze-fracture studies of photoreceptor membranes: new observations bearing upon the distribution of cholesterol

PubMed Central

1983-01-01

We performed electron microscopy of replicas from freeze-fractured retinas exposed during or after fixation to the cholesterol-binding antibiotic, filipin. We observed characteristic filipin-induced perturbations throughout the disk and plasma membranes of retinal rod outer segments of various species. It is evident that a prolonged exposure to filipin in fixative enhances rather than reduces presumptive cholesterol detection in the vertebrate photoreceptor cell. In agreement with the pattern seen in our previous study (Andrews, L.D., and A. I. Cohen, 1979, J. Cell Biol., 81:215-228), filipin- binding in membranes exhibiting particle-free patches seemed largely confined to these patches. Favorably fractured photoreceptors exhibited marked filipin-binding in apical inner segment plasma membrane topologically confluent with and proximate to the outer segment plasma membrane, which was comparatively free of filipin binding. A possible boundary between these differing membrane domains was suggested in a number of replicas exhibiting lower filipin binding to the apical plasma membrane of the inner segment in the area surrounding the cilium. This area contains a structure (Andrews, L. D., 1982, Freeze- fracture studies of vertebrate photoreceptors, In Structure of the Eye, J. G. Hollyfield and E. Acosta Vidrio, editors, Elsevier/North-Holland, New York, 11-23) that resembles the active zones of the nerve terminals for the frog neuromuscular junction. These observations lead us to hypothesize that these structures may function to direct vesicle fusion to occur near them, in a domain of membrane more closely resembling outer than inner segment plasma membrane. The above evidence supports the views that (a) all disk membranes contain cholesterol, but the particle-free patches present in some disks trap cholesterol from contiguous particulate membrane regions; (b) contiguous inner and outer segment membranes may greatly differ in cholesterol content; and (c) the suggested higher cholesterol in the inner segment than in the outer segment plasma membrane may help direct newly inserted photopigment molecules to the outer segment. PMID:6411740

Numerical simulation study on the optimization design of the crown shape of PDC drill bit.

PubMed

Ju, Pei; Wang, Zhenquan; Zhai, Yinghu; Su, Dongyu; Zhang, Yunchi; Cao, Zhaohui

The design of bit crown is an important part of polycrystalline diamond compact (PDC) bit design, although predecessors have done a lot of researches on the design principles of PDC bit crown, the study of the law about rock-breaking energy consumption according to different bit crown shape is not very systematic, and the mathematical model of design is over-simplified. In order to analyze the relation between rock-breaking energy consumption and bit crown shape quantificationally, the paper puts forward an idea to take "per revolution-specific rock-breaking work" as objective function, and analyzes the relationship between rock properties, inner cone angle, outer cone arc radius, and per revolution-specific rock-breaking work by means of explicit dynamic finite element method. Results show that the change law between per revolution-specific rock-breaking work and the radius of gyration is similar for rocks with different properties, it is beneficial to decrease rock-breaking energy consumption by decreasing inner cone angle or outer cone arc radius. Of course, we should also consider hydraulic structure and processing technology in the optimization design of PDC bit crown.

ARL2BP, a protein linked to Retinitis Pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure.

PubMed

Moye, Abigail R; Singh, Ratnesh; Kimler, Victoria A; Dilan, Tanya L; Munezero, Daniella; Saravanan, Thamaraiselvi; Goldberg, Andrew F X; Ramamurthy, Visvanathan

2018-05-02

The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous discs that contain the proteins needed for phototransduction and vision. Though cilia formation and function has been well characterized, little is known about the role of cilia in the development of photoreceptor OS. Nevertheless, progress has been made by studying mutations in ciliary proteins which often result in malformed outer segments and lead to blinding diseases. To investigate how ciliary proteins contribute to outer segment formation, we generated a knockout mouse model for ARL2BP, a ciliary protein linked to Retinitis Pigmentosa. The knockout mice display an early and progressive reduction in visual response. Prior to photoreceptor degeneration we observed disorganization of the photoreceptor OS, with vertically aligned discs and shortened axonemes. Interestingly, ciliary doublet microtubule structure was also impaired, displaying open B-tubule doublets, paired with loss of singlet microtubules. Based on results from this study, we conclude that ARL2BP is necessary for photoreceptor cilia doublet formation and axoneme elongation, which is required for outer segment morphogenesis and vision.

Calcium Homeostasis and Cone Signaling Are Regulated by Interactions between Calcium Stores and Plasma Membrane Ion Channels

PubMed Central

Bartoletti, Theodore M.; Huang, Wei; Akopian, Abram; Thoreson, Wallace B.; Krizaj, David

2009-01-01

Calcium is a messenger ion that controls all aspects of cone photoreceptor function, including synaptic release. The dynamic range of the cone output extends beyond the activation threshold for voltage-operated calcium entry, suggesting another calcium influx mechanism operates in cones hyperpolarized by light. We have used optical imaging and whole-cell voltage clamp to measure the contribution of store-operated Ca2+ entry (SOCE) to Ca2+ homeostasis and its role in regulation of neurotransmission at cone synapses. Mn2+ quenching of Fura-2 revealed sustained divalent cation entry in hyperpolarized cones. Ca2+ influx into cone inner segments was potentiated by hyperpolarization, facilitated by depletion of intracellular Ca2+ stores, unaffected by pharmacological manipulation of voltage-operated or cyclic nucleotide-gated Ca2+ channels and suppressed by lanthanides, 2-APB, MRS 1845 and SKF 96365. However, cation influx through store-operated channels crossed the threshold for activation of voltage-operated Ca2+ entry in a subset of cones, indicating that the operating range of inner segment signals is set by interactions between store- and voltage-operated Ca2+ channels. Exposure to MRS 1845 resulted in ∼40% reduction of light-evoked postsynaptic currents in photopic horizontal cells without affecting the light responses or voltage-operated Ca2+ currents in simultaneously recorded cones. The spatial pattern of store-operated calcium entry in cones matched immunolocalization of the store-operated sensor STIM1. These findings show that store-operated channels regulate spatial and temporal properties of Ca2+ homeostasis in vertebrate cones and demonstrate their role in generation of sustained excitatory signals across the first retinal synapse. PMID:19696927

Glycolytic reliance promotes anabolism in photoreceptors

PubMed Central

Chinchore, Yashodhan; Begaj, Tedi; Wu, David; Drokhlyansky, Eugene; Cepko, Constance L

2017-01-01

Vertebrate photoreceptors are among the most metabolically active cells, exhibiting a high rate of ATP consumption. This is coupled with a high anabolic demand, necessitated by the diurnal turnover of a specialized membrane-rich organelle, the outer segment, which is the primary site of phototransduction. How photoreceptors balance their catabolic and anabolic demands is poorly understood. Here, we show that rod photoreceptors in mice rely on glycolysis for their outer segment biogenesis. Genetic perturbations targeting allostery or key regulatory nodes in the glycolytic pathway impacted the size of the outer segments. Fibroblast growth factor signaling was found to regulate glycolysis, with antagonism of this pathway resulting in anabolic deficits. These data demonstrate the cell autonomous role of the glycolytic pathway in outer segment maintenance and provide evidence that aerobic glycolysis is part of a metabolic program that supports the biosynthetic needs of a normal neuronal cell type. DOI: http://dx.doi.org/10.7554/eLife.25946.001 PMID:28598329

S-cone discrimination in the presence of two adapting fields: data and model

PubMed Central

Cao, Dingcai

2014-01-01

This study investigated S-cone discrimination using a test annulus surrounded by an inner and outer adapting field with systematic manipulation of the adapting l = L/(L + M) or s = S/(L + M) chromaticities. The results showed that different adapting l chromaticities altered S-cone discrimination for a high adapting s chromaticity due to parvocellular input to the koniocellular pathway. In addition, S-cone discrimination was determined by the combined spectral signals arising from both adapting fields. The “white” adapting field or an adapting field with a different l chromaticity from the other fields was more likely to have a stronger influence on discrimination thresholds. These results indicated that the two cardinal axes are not independent in S-cone discrimination, and the two adapting fields jointly contribute to S-cone discrimination through a cortical summation mechanism. PMID:24695204

Observation of hohlraum-wall motion with spectrally selective x-ray imaging at the National Ignition Facility

DOE PAGES

Izumi, N.; Meezan, N. B.; Divol, L.; ...

2016-08-12

The high fuel capsule compression required for indirect drive inertial confinement fusion (ICF) requires careful control of the X-raydrive symmetry throughout the laser pulse. When the outer cone beams strike the hohlraum wall, the plasma ablated off the hohlraum wall expands into the hohlraum and can alter both the outer and inner cone beam propagation and hencethe X-raydrive symmetry especially at thefinal stage of the drive pulse. In order to quantitatively understand the wall motion, we developed a new experimental technique which visualizes the expansion and stagnation of the hohlraum wall plasma. Finally, we discuss details of the experiment andmore » the technique of spectrally selectivex-ray imaging.« less

Observation of hohlraum-wall motion with spectrally selective x-ray imaging at the National Ignition Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izumi, N., E-mail: izumi2@llnl.gov; Meezan, N. B.; Divol, L.

The high fuel capsule compression required for indirect drive inertial confinement fusion requires careful control of the X-ray drive symmetry throughout the laser pulse. When the outer cone beams strike the hohlraum wall, the plasma ablated off the hohlraum wall expands into the hohlraum and can alter both the outer and inner cone beam propagations and hence the X-ray drive symmetry especially at the final stage of the drive pulse. To quantitatively understand the wall motion, we developed a new experimental technique which visualizes the expansion and stagnation of the hohlraum wall plasma. Details of the experiment and the techniquemore » of spectrally selective x-ray imaging are discussed.« less

Observation of hohlraum-wall motion with spectrally selective x-ray imaging at the National Ignition Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izumi, N.; Meezan, N. B.; Divol, L.

The high fuel capsule compression required for indirect drive inertial confinement fusion (ICF) requires careful control of the X-raydrive symmetry throughout the laser pulse. When the outer cone beams strike the hohlraum wall, the plasma ablated off the hohlraum wall expands into the hohlraum and can alter both the outer and inner cone beam propagation and hencethe X-raydrive symmetry especially at thefinal stage of the drive pulse. In order to quantitatively understand the wall motion, we developed a new experimental technique which visualizes the expansion and stagnation of the hohlraum wall plasma. Finally, we discuss details of the experiment andmore » the technique of spectrally selectivex-ray imaging.« less

KSC-2009-2225

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. – The NASA Railroad hauls cars carrying the Ares I-X motor segments and nozzle exit cone over a river bridge to NASA's Kennedy Space Center in Florida. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2227

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. – The NASA Railroad hauls cars carrying the Ares I-X motor segments and nozzle exit cone over a river bridge to NASA's Kennedy Space Center in Florida. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2228

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. – A close-up of the NASA Railroad locomotive #3, and the EMDSW-1500 switcher, that is hauling the Ares I-X motor segments and nozzle exit cone to NASA's Kennedy Space Center in Florida. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2229

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. – After switching out the box cars on the train, the NASA Railroad hauls the Ares I-X motor segments and nozzle exit cone to NASA's Kennedy Space Center in Florida. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

KSC-2009-2226

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. – The NASA Railroad hauls cars carrying the Ares I-X motor segments and nozzle exit cone over a river bridge to NASA's Kennedy Space Center in Florida. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

S-net : Construction of large scale seafloor observatory network for tsunamis and earthquakes along the Japan Trench

NASA Astrophysics Data System (ADS)

Mochizuki, M.; Uehira, K.; Kanazawa, T.; Shiomi, K.; Kunugi, T.; Aoi, S.; Matsumoto, T.; Sekiguchi, S.; Yamamoto, N.; Takahashi, N.; Nakamura, T.; Shinohara, M.; Yamada, T.

2017-12-01

NIED has launched the project of constructing a seafloor observatory network for tsunamis and earthquakes after the occurrence of the 2011 Tohoku Earthquake to enhance reliability of early warnings of tsunamis and earthquakes. The observatory network was named "S-net". The S-net project has been financially supported by MEXT.The S-net consists of 150 seafloor observatories which are connected in line with submarine optical cables. The total length of submarine optical cable is about 5,500 km. The S-net covers the focal region of the 2011 Tohoku Earthquake and its vicinity regions. Each observatory equips two units of a high sensitive pressure gauges as a tsunami meter and four sets of three-component seismometers. The S-net is composed of six segment networks. Five of six segment networks had been already installed. Installation of the last segment network covering the outer rise area have been finally finished by the end of FY2016. The outer rise segment has special features like no other five segments of the S-net. Those features are deep water and long distance. Most of 25 observatories on the outer rise segment are located at the depth of deeper than 6,000m WD. Especially, three observatories are set on the seafloor of deeper than about 7.000m WD, and then the pressure gauges capable of being used even at 8,000m WD are equipped on those three observatories. Total length of the submarine cables of the outer rise segment is about two times longer than those of the other segments. The longer the cable system is, the higher voltage supply is needed, and thus the observatories on the outer rise segment have high withstanding voltage characteristics. We employ a dispersion management line of a low loss formed by combining a plurality of optical fibers for the outer rise segment cable, in order to achieve long-distance, high-speed and large-capacity data transmission Installation of the outer rise segment was finished and then full-scale operation of S-net has started. All the data from 150 seafloor observatories are being transferred to and stored in the Tsukuba DC. Some data are being transmitted directly to JMA and have been used for monitoring of earthquakes and tsunamis. We will report construction and operation of the S-net system as well as the outline of the obtained data in this presentation.

N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR).

PubMed

Beharry, Seelochan; Zhong, Ming; Molday, Robert S

2004-12-24

ABCA4, a member of the family of ATP binding cassette (ABC) proteins found in rod and cone photoreceptors, has been implicated in the transport of retinoid compounds across the outer segment disk membrane following the photoactivation of rhodopsin. Mutations in the ABCA4 gene are responsible for Stargardt macular dystrophy and related retinal degenerative diseases that cause a loss in vision. To identify the retinoid substrate that interacts with ABCA4, we have isolated ABCA4 from rod outer segment disk membranes on an immunoaffinity matrix and analyzed retinoid compounds that bind to ABCA4 using high performance liquid chromatography and radiolabeling methods. When all-trans-retinal was added to ABCA4 in the presence of phosphatidylethanolamine, approximately 0.9 mol of N-retinylidene-phosphatidylethanolamine and 0.3 mol of all-trans-retinal were bound per mol of ABCA4 with an apparent K(d) of 2-5 microm. ATP and GTP released these retinoids from ABCA4, whereas ADP, GDP, and nonhydrolyzable derivatives, adenosine 5'-(beta,gamma-imido)triphosphate and guanosine 5'-(beta,gamma-imido)triphosphate, were ineffective. One mole of N-retinyl-phosphatidylethanolamine, the reduced form of N-retinylidene-phosphatidylethanolamine, bound per mol of ABCA4, whereas 0.3 mol of all-trans-retinal were bound in the absence of phosphatidylethanolamine. No binding of all-trans-retinol to ABCA4 was observed. Our results indicate that ABCA4 preferentially binds N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP. Our studies further suggest that ATP binding and hydrolysis induces a protein conformational change that causes N-retinylidene-phosphatidylethanolamine to dissociate from ABCA4.

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, Gary L.; Shaffer, James E.

1997-01-01

An axial flow turbine's nozzle/nozzle support structure having a cantilevered nozzle outer structure including an outer shroud and airfoil vanes extending radially inwardly therefrom, an inner shroud radially adjacent the inner end of the airfoil vanes and cooperatively disposed relative to the outer shroud to provide an annular fluid flow path, an inner and an outer support ring respectively arranged radially inside the inner shroud and axially adjacent a portion of the outer shroud, and pins extending through such portion and into the outer support ring. The inner support ring or inner shroud has a groove therein bounded by end walls for receiving and being axially abuttable with a locating projection from the adjacent airfoil vane, inner shroud, or inner support ring. The nozzle outer structure may comprise segments each of which has a single protrusion which is axially engageable with the outer support ring or, alternatively, a first and second protrusion which are arcuately and axially separated and which include axial openings therein whereby first and second protrusions on respective, arcuately adjacent nozzle segments have axial openings therein which are alignable with connector openings in the outer support ring and within each of such aligned openings a pin is receivable. The inner shroud may, likewise, comprise segments which, when assembled in operating configuration, have a 360 degree expanse.

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, G.L.; Shaffer, J.E.

1997-01-07

An axial flow turbine`s nozzle/nozzle support structure is described having a cantilevered nozzle outer structure including an outer shroud and airfoil vanes extending radially inwardly therefrom, an inner shroud radially adjacent the inner end of the airfoil vanes and cooperatively disposed relative to the outer shroud to provide an annular fluid flow path, an inner and an outer support ring respectively arranged radially inside the inner shroud and axially adjacent a portion of the outer shroud, and pins extending through such portion and into the outer support ring. The inner support ring or inner shroud has a groove therein bounded by end walls for receiving and being axially abuttable with a locating projection from the adjacent airfoil vane, inner shroud, or inner support ring. The nozzle outer structure may comprise segments each of which has a single protrusion which is axially engageable with the outer support ring or, alternatively, a first and second protrusion which are arcuately and axially separated and which include axial openings therein whereby first and second protrusions on respective, arcuately adjacent nozzle segments have axial openings therein which are alignable with connector openings in the outer support ring and within each of such aligned openings a pin is receivable. The inner shroud may, likewise, comprise segments which, when assembled in operating configuration, have a 360 degree expanse. 6 figs.

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, Gary L.; Shaffer, James E.

1996-01-01

An axial flow turbine's nozzle/nozzle support structure having a cantilevered nozzle outer structure including an outer shroud and airfoil vanes extending radially inwardly therefrom, an inner shroud radially adjacent the inner end of the airfoil vanes and cooperatively disposed relative to the outer shroud to provide an annular fluid flow path, an inner and an outer support ring respectively arranged radially inside the inner shroud and axially adjacent a portion of the outer shroud, and pins extending through such portion and into the outer support ring. The inner support ring or inner shroud has a groove therein bounded by end walls for receiving and being axially abuttable with a locating projection from the adjacent airfoil vane, inner shroud, or inner support ring. The nozzle outer structure may comprise segments each of which has a single protrusion which is axially engageable with the outer support ring or, alternatively, a first and second protrusion which are arcuately and axially separated and which include axial openings therein whereby first and second protrusions on respective, arcuately adjacent nozzle segments have axial openings therein which are alignable with connector openings in the outer support ring and within each of such aligned openings a pin is receivable. The inner shroud may, likewise, comprise segments which, when assembled in operating configuration, have a 360 degree expanse.

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, G.L.; Shaffer, J.E.

1996-09-10

An axial flow turbine`s nozzle/nozzle support structure is described having a cantilevered nozzle outer structure including an outer shroud and airfoil vanes extending radially inwardly therefrom, an inner shroud radially adjacent the inner end of the airfoil vanes and cooperatively disposed relative to the outer shroud to provide an annular fluid flow path, an inner and an outer support ring respectively arranged radially inside the inner shroud and axially adjacent a portion of the outer shroud, and pins extending through such portion and into the outer support ring. The inner support ring or inner shroud has a groove therein bounded by end walls for receiving and being axially abuttable with a locating projection from the adjacent airfoil vane, inner shroud, or inner support ring. The nozzle outer structure may comprise segments each of which has a single protrusion which is axially engageable with the outer support ring or, alternatively, a first and second protrusion which are arcuately and axially separated and which include axial openings therein whereby first and second protrusions on respective, arcuately adjacent nozzle segments have axial openings therein which are alignable with connector openings in the outer support ring and within each of such aligned openings a pin is receivable. The inner shroud may, likewise, comprise segments which, when assembled in operating configuration, have a 360 degree expanse. 6 figs.

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, Gary L.; Shaffer, James E.

1995-01-01

An axial flow turbine's nozzle/nozzle support structure having a cantilevered nozzle outer structure including an outer shroud and airfoil vanes extending radially inwardly therefrom, an inner shroud radially adjacent the inner end of the airfoil vanes and cooperatively disposed relative to the outer shroud to provide an annular fluid flow path, an inner and an outer support ring respectively arranged radially inside the inner shroud and axially adjacent a portion of the outer shroud, and pins extending through such portion and into the outer support ring. The inner support ring or inner shroud has a groove therein bounded by end walls for receiving and being axially abuttable with a locating projection from the adjacent airfoil vane, inner shroud, or inner support ring. The nozzle outer structure may comprise segments each of which has a single protrusion which is axially engageable with the outer support ring or, alternatively, a first and second protrusion which are arcuately and axially separated and which include axial openings therein whereby first and second protrusions on respective, arcuately adjacent nozzle segments have axial openings therein which are alignable with connector openings in the outer support ring and within each of such aligned openings a pin is receivable. The inner shroud may, likewise, comprise segments which, when assembled in operating configuration, have a 360 degree expanse.

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, G.L.; Shaffer, J.E.

1995-08-15

An axial flow turbine`s nozzle/nozzle support structure is described having a cantilevered nozzle outer structure including an outer shroud and airfoil vanes extending radially inwardly therefrom, an inner shroud radially adjacent the inner end of the airfoil vanes and cooperatively disposed relative to the outer shroud to provide an annular fluid flow path, an inner and an outer support ring respectively arranged radially inside the inner shroud and axially adjacent a portion of the outer shroud, and pins extending through such portion and into the outer support ring. The inner support ring or inner shroud has a groove therein bounded by end walls for receiving and being axially abuttable with a locating projection from the adjacent airfoil vane, inner shroud, or inner support ring. The nozzle outer structure may comprise segments each of which has a single protrusion which is axially engageable with the outer support ring or, alternatively, a first and second protrusion which are arcuately and axially separated and which include axial openings therein whereby first and second protrusions on respective, arcuately adjacent nozzle segments have axial openings therein which are alignable with connector openings in the outer support ring and within each of such aligned openings a pin is receivable. The inner shroud may, likewise, comprise segments which, when assembled in operating configuration, have a 360 degree expanse. 6 figs.

Apparatus for measuring charged particle beam

NASA Technical Reports Server (NTRS)

Gregory, D. A.; Stocks, C. D. (Inventor)

1984-01-01

An apparatus to measure the incident charged particle beam flux while effectively eliminating losses to reflection and/or secondary emission of the charged particle beam being measured is described. It comprises a sense cup through which the charged particle beam enters. A sense cone forms the rear wall of the interior chamber with the cone apex adjacent the entry opening. An outer case surrounds the sense cup and is electrically insulated therefrom. Charged particles entering the interior chamber are trapped and are absorbed by the sense cup and cone and travel through a current measuring device to ground.

Pharmacological Amelioration of Cone Survival and Vision in a Mouse Model for Leber Congenital Amaurosis

PubMed Central

Li, Songhua; Samardzija, Marijana; Yang, Zhihui; Grimm, Christian

2016-01-01

RPE65, an abundant membrane-associate protein in the retinal pigment epithelium (RPE), is a key retinoid isomerase of the visual cycle necessary for generating 11-cis-retinal that functions not only as a molecular switch for activating cone and rod visual pigments in response to light stimulation, but also as a chaperone for normal trafficking of cone opsins to the outer segments. Many mutations in RPE65 are associated with Leber congenital amaurosis (LCA). A R91W substitution, the most frequent LCA-associated mutation, results in a severe decrease in protein level and enzymatic activity of RPE65, causing cone opsin mislocalization and early cone degeneration in the mutation knock-in mouse model of LCA. Here we show that R91W RPE65 undergoes ubiquitination-dependent proteasomal degradation in the knock-in mouse RPE due to misfolding. The 26S proteasome non-ATPase regulatory subunit 13 mediated degradation specifically of misfolded R91W RPE65. The mutation disrupted membrane-association and colocalization of RPE65 with lecithin:retinol acyltransferase (LRAT) that provides the hydrophobic substrate for RPE65. Systemic administration of sodium 4-phenylbutyrate (PBA), a chemical chaperone, increased protein stability, enzymatic activity, membrane-association, and colocalization of R91W RPE65 with LRAT. This rescue effect increased synthesis of 11-cis-retinal and 9-cis-retinal, a functional iso-chromophore of the visual pigments, led to alleviation of S-opsin mislocalization and cone degeneration in the knock-in mice. Importantly, PBA-treatment also improved cone-mediated vision in the mutant mice. These results indicate that PBA, a U.S. Food and Drug Administration-approved safe oral medication, may provide a noninvasive therapeutic intervention that delays daylight vision loss in patients with RPE65 mutations. SIGNIFICANCE STATEMENT LCA is a severe early onset retinal dystrophy. Recent clinical trials of gene therapy have implicated the need of an alternative or combination therapy to improve cone survival and function in patients with LCA caused by RPE65 mutations. Using a mouse model carrying the most frequent LCA-associated mutation (R91W), we found that the mutant RPE65 underwent ubiquitination-dependent proteasomal degradation due to misfolding. Treatment of the mice with a chemical chaperone partially corrected stability, enzymatic activity, and subcellular localization of R91W RPE65, which was also accompanied by improvement of cone survival and vision. These findings identify an in vivo molecular pathogenic mechanism for R91W mutation and provide a feasible pharmacological approach that can delay vision loss in patients with RPE65 mutations. PMID:27225770

Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina

PubMed Central

Deming, Janise D.; Pak, Joseph S.; Shin, Jung-a; Brown, Bruce M.; Kim, Moon K.; Aung, Moe H.; Lee, Eun-Jin; Pardue, Machelle T.; Craft, Cheryl Mae

2015-01-01

Purpose Previous studies discovered cone phototransduction shutoff occurs normally for Arr1−/− and Arr4−/−; however, it is defective when both visual arrestins are simultaneously not expressed (Arr1−/−Arr4−/−). We investigated the roles of visual arrestins in an all-cone retina (Nrl−/−) since each arrestin has differential effects on visual function, including ARR1 for normal light adaptation, and ARR4 for normal contrast sensitivity and visual acuity. Methods We examined Nrl−/−, Nrl−/−Arr1−/−, Nrl−/−Arr4−/−, and Nrl−/−Arr1−/−Arr4−/− mice with photopic electroretinography (ERG) to assess light adaptation and retinal responses, immunoblot and immunohistochemical localization analysis to measure retinal expression levels of M- and S-opsin, and optokinetic tracking (OKT) to measure the visual acuity and contrast sensitivity. Results Study results indicated that Nrl−/− and Nrl−/−Arr4−/− mice light adapted normally, while Nrl−/−Arr1−/− and Nrl−/−Arr1−/−Arr4−/− mice did not. Photopic ERG a-wave, b-wave, and flicker amplitudes followed a general pattern in which Nrl−/−Arr4−/− amplitudes were higher than the amplitudes of Nrl−/−, while the amplitudes of Nrl−/−Arr1−/− and Nrl−/−Arr1−/−Arr4−/− were lower. All three visual arrestin knockouts had faster implicit times than Nrl−/− mice. M-opsin expression is lower when ARR1 is not expressed, while S-opsin expression is lower when ARR4 is not expressed. Although M-opsin expression is mislocalized throughout the photoreceptor cells, S-opsin is confined to the outer segments in all genotypes. Contrast sensitivity is decreased when ARR4 is not expressed, while visual acuity was normal except in Nrl−/−Arr1−/−Arr4−/−. Conclusions Based on the opposite visual phenotypes in an all-cone retina in the Nrl−/−Arr1−/− and Nrl−/−Arr4−/− mice, we conclude that ARR1 and ARR4 perform unique modulatory roles in cone photoreceptors. PMID:26624493

High-Resolution Images of Retinal Structure in Patients with Choroideremia

PubMed Central

Syed, Reema; Sundquist, Sanna M.; Ratnam, Kavitha; Zayit-Soudry, Shiri; Zhang, Yuhua; Crawford, J. Brooks; MacDonald, Ian M.; Godara, Pooja; Rha, Jungtae; Carroll, Joseph; Roorda, Austin; Stepien, Kimberly E.; Duncan, Jacque L.

2013-01-01

Purpose. To study retinal structure in choroideremia patients and carriers using high-resolution imaging techniques. Methods. Subjects from four families (six female carriers and five affected males) with choroideremia (CHM) were characterized with best-corrected visual acuity (BCVA), kinetic and static perimetry, full-field electroretinography, and fundus autofluorescence (FAF). High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT). Coding regions of the CHM gene were sequenced. Results. Molecular analysis of the CHM gene identified a deletion of exons 9 to 15 in family A, a splice site mutation at position 79+1 of exon 1 in family B, deletion of exons 6 to 8 in family C, and a substitution at position 106 causing a premature stop in family D. BCVA ranged from 20/16 to 20/63 in carriers and from 20/25 to 5/63 in affected males. FAF showed abnormalities in all subjects. SD-OCT showed outer retinal layer loss, outer retinal tubulations at the margin of outer retinal loss, and inner retinal microcysts. Patchy cone loss was present in two symptomatic carriers. In two affected males, cone mosaics were disrupted with increased cone spacing near the fovea but more normal cone spacing near the edge of atrophy. Conclusions. High-resolution retinal images in CHM carriers and affected males demonstrated RPE and photoreceptor cell degeneration. As both RPE and photoreceptor cells were affected, these cell types may degenerate simultaneously in CHM. These findings provide insight into the effect of CHM mutations on macular retinal structure, with implications for the development of treatments for CHM. (ClinicalTrials.gov number, NCT00254605.) PMID:23299470

High-resolution images of retinal structure in patients with choroideremia.

PubMed

Syed, Reema; Sundquist, Sanna M; Ratnam, Kavitha; Zayit-Soudry, Shiri; Zhang, Yuhua; Crawford, J Brooks; MacDonald, Ian M; Godara, Pooja; Rha, Jungtae; Carroll, Joseph; Roorda, Austin; Stepien, Kimberly E; Duncan, Jacque L

2013-02-01

To study retinal structure in choroideremia patients and carriers using high-resolution imaging techniques. Subjects from four families (six female carriers and five affected males) with choroideremia (CHM) were characterized with best-corrected visual acuity (BCVA), kinetic and static perimetry, full-field electroretinography, and fundus autofluorescence (FAF). High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT). Coding regions of the CHM gene were sequenced. Molecular analysis of the CHM gene identified a deletion of exons 9 to 15 in family A, a splice site mutation at position 79+1 of exon 1 in family B, deletion of exons 6 to 8 in family C, and a substitution at position 106 causing a premature stop in family D. BCVA ranged from 20/16 to 20/63 in carriers and from 20/25 to 5/63 in affected males. FAF showed abnormalities in all subjects. SD-OCT showed outer retinal layer loss, outer retinal tubulations at the margin of outer retinal loss, and inner retinal microcysts. Patchy cone loss was present in two symptomatic carriers. In two affected males, cone mosaics were disrupted with increased cone spacing near the fovea but more normal cone spacing near the edge of atrophy. High-resolution retinal images in CHM carriers and affected males demonstrated RPE and photoreceptor cell degeneration. As both RPE and photoreceptor cells were affected, these cell types may degenerate simultaneously in CHM. These findings provide insight into the effect of CHM mutations on macular retinal structure, with implications for the development of treatments for CHM. (ClinicalTrials.gov number, NCT00254605.).

Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human-like macula.

PubMed

Hammoum, Imane; Benlarbi, Maha; Dellaa, Ahmed; Szabó, Klaudia; Dékány, Bulcsú; Csaba, Dávid; Almási, Zsuzsanna; Hajdú, Rozina I; Azaiz, Rached; Charfeddine, Ridha; Lukáts, Ákos; Ben Chaouacha-Chekir, Rafika

2017-09-01

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases. © 2017 Wiley Periodicals, Inc.

Detection and visualization of endoleaks in CT data for monitoring of thoracic and abdominal aortic aneurysm stents

NASA Astrophysics Data System (ADS)

Lu, J.; Egger, J.; Wimmer, A.; Großkopf, S.; Freisleben, B.

2008-03-01

In this paper we present an efficient algorithm for the segmentation of the inner and outer boundary of thoratic and abdominal aortic aneurysms (TAA & AAA) in computed tomography angiography (CTA) acquisitions. The aneurysm segmentation includes two steps: first, the inner boundary is segmented based on a grey level model with two thresholds; then, an adapted active contour model approach is applied to the more complicated outer boundary segmentation, with its initialization based on the available inner boundary segmentation. An opacity image, which aims at enhancing important features while reducing spurious structures, is calculated from the CTA images and employed to guide the deformation of the model. In addition, the active contour model is extended by a constraint force that prevents intersections of the inner and outer boundary and keeps the outer boundary at a distance, given by the thrombus thickness, to the inner boundary. Based upon the segmentation results, we can measure the aneurysm size at each centerline point on the centerline orthogonal multiplanar reformatting (MPR) plane. Furthermore, a 3D TAA or AAA model is reconstructed from the set of segmented contours, and the presence of endoleaks is detected and highlighted. The implemented method has been evaluated on nine clinical CTA data sets with variations in anatomy and location of the pathology and has shown promising results.

Segmented Mirror Image Degradation Due to Surface Dust, Alignment and Figure

NASA Technical Reports Server (NTRS)

Schreur, Julian J.

1999-01-01

In 1996 an algorithm was developed to include the effects of surface roughness in the calculation of the point spread function of a telescope mirror. This algorithm has been extended to include the effects of alignment errors and figure errors for the individual elements, and an overall contamination by surface dust. The final algorithm builds an array for a guard-banded pupil function of a mirror that may or may not have a central hole, a central reflecting segment, or an outer ring of segments. The central hole, central reflecting segment, and outer ring may be circular or polygonal, and the outer segments may have trimmed comers. The modeled point spread functions show that x-tilt and y-tilt, or the corresponding R-tilt and theta-tilt for a segment in an outer ring, is readily apparent for maximum wavefront errors of 0.1 lambda. A similar sized piston error is also apparent, but integral wavelength piston errors are not. Severe piston error introduces a focus error of the opposite sign, so piston could be adjusted to compensate for segments with varying focal lengths. Dust affects the image principally by decreasing the Strehl ratio, or peak intensity of the image. For an eight-meter telescope a 25% coverage by dust produced a scattered light intensity of 10(exp -9) of the peak intensity, a level well below detectability.

The IBEX Flight Segment

NASA Astrophysics Data System (ADS)

Scherrer, J.; Carrico, J.; Crock, J.; Cross, W.; Delossantos, A.; Dunn, A.; Dunn, G.; Epperly, M.; Fields, B.; Fowler, E.; Gaio, T.; Gerhardus, J.; Grossman, W.; Hanley, J.; Hautamaki, B.; Hawes, D.; Holemans, W.; Kinaman, S.; Kirn, S.; Loeffler, C.; McComas, D. J.; Osovets, A.; Perry, T.; Peterson, M.; Phillips, M.; Pope, S.; Rahal, G.; Tapley, M.; Tyler, R.; Ungar, B.; Walter, E.; Wesley, S.; Wiegand, T.

2009-08-01

IBEX provides the observations needed for detailed modeling and in-depth understanding of the interstellar interaction (McComas et al. in Physics of the Outer Heliosphere, Third Annual IGPP Conference, pp. 162-181, 2004; Space Sci. Rev., 2009a, this issue). From mission design to launch and acquisition, this goal drove all flight system development. This paper describes the management, design, testing and integration of IBEX’s flight system, which successfully launched from Kwajalein Atoll on October 19, 2008. The payload is supported by a simple, Sun-pointing, spin-stabilized spacecraft with no deployables. The spacecraft bus consists of the following subsystems: attitude control, command and data handling, electrical power, hydrazine propulsion, RF, thermal, and structures. A novel 3-step orbit approach was employed to put IBEX in its highly elliptical, 8-day final orbit using a Solid Rocket Motor, which provided large delta-V after IBEX separated from the Pegasus launch vehicle; an adapter cone, which interfaced between the SRM and Pegasus; Motorized Lightbands, which performed separation from the Pegasus, ejection of the adapter cone, and separation of the spent SRM from the spacecraft; a ShockRing isolation system to lower expected launch loads; and the onboard Hydrazine Propulsion System. After orbit raising, IBEX transitioned from commissioning to nominal operations and science acquisition. At every phase of development, the Systems Engineering and Mission Assurance teams supervised the design, testing and integration of all IBEX flight elements.

The Neural Retina in Retinopathy of Prematurity

PubMed Central

Hansen, Ronald M.; Moskowitz, Anne; Akula, James D.; Fulton, Anne B.

2016-01-01

Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP. PMID:27671171

Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration

PubMed Central

Zhang, Lijuan; Du, Jianhai; Justus, Sally; Hsu, Chun-Wei; Bonet-Ponce, Luis; Wu, Wen-Hsuan; Tsai, Yi-Ting; Wu, Wei-Pu; Jia, Yading; Duong, Jimmy K.; Mahajan, Vinit B.; Lin, Chyuan-Sheng; Wang, Shuang; Hurley, James B.

2016-01-01

Retinitis pigmentosa (RP) encompasses a diverse group of Mendelian disorders leading to progressive degeneration of rods and then cones. For reasons that remain unclear, diseased RP photoreceptors begin to deteriorate, eventually leading to cell death and, consequently, loss of vision. Here, we have hypothesized that RP associated with mutations in phosphodiesterase-6 (PDE6) provokes a metabolic aberration in rod cells that promotes the pathological consequences of elevated cGMP and Ca2+, which are induced by the Pde6 mutation. Inhibition of sirtuin 6 (SIRT6), a histone deacetylase repressor of glycolytic flux, reprogrammed rods into perpetual glycolysis, thereby driving the accumulation of biosynthetic intermediates, improving outer segment (OS) length, enhancing photoreceptor survival, and preserving vision. In mouse retinae lacking Sirt6, effectors of glycolytic flux were dramatically increased, leading to upregulation of key intermediates in glycolysis, TCA cycle, and glutaminolysis. Both transgenic and AAV2/8 gene therapy–mediated ablation of Sirt6 in rods provided electrophysiological and anatomic rescue of both rod and cone photoreceptors in a preclinical model of RP. Due to the extensive network of downstream effectors of Sirt6, this study motivates further research into the role that these pathways play in retinal degeneration. Because reprogramming metabolism by enhancing glycolysis is not gene specific, this strategy may be applicable to a wide range of neurodegenerative disorders. PMID:27841758

Segmented inlet nozzle for gas turbine, and methods of installation

DOEpatents

Klompas, Nicholas

1985-01-01

A gas turbine nozzle guide vane assembly is formed of individual arcuate nozzle segments. The arcuate nozzle segments are elastically joined to each other to form a complete ring, with edges abutted to prevent leakage. The resultant nozzle ring is included within the overall gas turbine stationary structure and secured by a mounting arrangement which permits relative radial movement at both the inner and outer mountings. A spline-type outer mounting provides circumferential retention. A complete rigid nozzle ring with freedom to "float" radially results. Specific structures are disclosed for the inner and outer mounting arrangements. A specific tie-rod structure is also disclosed for elastically joining the individual nozzle segments. Also disclosed is a method of assembling the nozzle ring subassembly-by-subassembly into a gas turbine employing temporary jacks.

Stratovolcano stability assessment methods and results from Citlaltepetl, Mexico

USGS Publications Warehouse

Zimbelman, D.R.; Watters, R.J.; Firth, I.R.; Breit, G.N.; Carrasco-Nunez, Gerardo

2004-01-01

Citlaltépetl volcano is the easternmost stratovolcano in the Trans-Mexican Volcanic Belt. Situated within 110 km of Veracruz, it has experienced two major collapse events and, subsequent to its last collapse, rebuilt a massive, symmetrical summit cone. To enhance hazard mitigation efforts we assess the stability of Citlaltépetl's summit cone, the area thought most likely to fail during a potential massive collapse event. Through geologic mapping, alteration mineralogy, geotechnical studies, and stability modeling we provide important constraints on the likelihood, location, and size of a potential collapse event. The volcano's summit cone is young, highly fractured, and hydrothermally altered. Fractures are most abundant within 5–20-m wide zones defined by multiple parallel to subparallel fractures. Alteration is most pervasive within the fracture systems and includes acid sulfate, advanced argillic, argillic, and silicification ranks. Fractured and altered rocks both have significantly reduced rock strengths, representing likely bounding surfaces for future collapse events. The fracture systems and altered rock masses occur non-uniformly, as an orthogonal set with N–S and E–W trends. Because these surfaces occur non-uniformly, hazards associated with collapse are unevenly distributed about the volcano. Depending on uncertainties in bounding surfaces, but constrained by detailed field studies, potential failure volumes are estimated to range between 0.04–0.5 km3. Stability modeling was used to assess potential edifice failure events. Modeled failure of the outer portion of the cone initially occurs as an "intact block" bounded by steeply dipping joints and outwardly dipping flow contacts. As collapse progresses, more of the inner cone fails and the outer "intact" block transforms into a collection of smaller blocks. Eventually, a steep face develops in the uppermost and central portion of the cone. This modeled failure morphology mimics collapse amphitheaters

Alterations of the outer retina in non-arteritic anterior ischaemic optic neuropathy detected using spectral-domain optical coherence tomography.

PubMed

Ackermann, Philipp; Brachert, Maike; Albrecht, Philipp; Ringelstein, Marius; Finis, David; Geerling, Gerd; Aktas, Orhan; Guthoff, Rainer

2017-07-01

A characteristic disease pattern may be reflected by retinal layer thickness changes in non-arteritic anterior ischaemic optic neuropathy measured using spectraldomain optical coherence tomography. Retinal layer segmentation is enabled by advanced software. In this study, retinal layer thicknesses in acute and chronic non-arteritic anterior ischaemic optic neuropathy were compared. A single-centre cross-sectional analysis was used. A total of 27 patients (20 age-matched healthy eyes) were included: 14 with acute (<7 days) and 13 patients with chronic non-arteritic anterior ischaemic optic neuropathy. Macular volume and 12° peripapillary ring optical coherence tomography scans were used. The peripapillary thicknesses of the following layers were determined by manual segmentation: retinal nerve fibres, ganglion cells + inner plexiform layer, inner nuclear layer + outer plexiform layer, outer nuclear layer + inner segments of the photoreceptors and outer segments of the photoreceptors to Bruch's membrane. Macular retinal layer thicknesses were automatically determined in volume cubes centred on the fovea. Peripapillary retinal swelling in acute nonarteritic anterior ischaemic optic neuropathy was attributable to retinal nerve fibre layer, ganglion cell layer/inner plexiform layer and outer nuclear layer/segments of the photoreceptors thickening. In chronic cases, peripapillary retinal nerve fibre layer, macular ganglion cell layer and inner plexiform layer thinning were observed. In acute non-arteritic anterior ischaemic optic neuropathy, the inner and outer peripapillary retinal layers are affected by thickness changes. In chronic cases, atrophy of the ganglion cells and their axons and dendrites is evident by inner retinal layer thinning. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Analysis of electrical noise in turtle cones

PubMed Central

Lamb, T. D.; Simon, E. J.

1977-01-01

1. Properties of the light-sensitive voltage noise in cones in the retina of the turtle, Pseudemys scripta elegans, have been studied by intracellular recording. 2. Suppression of the noise by light was a function of the hyperpolarizing response of a cone but not of the size or pattern of illumination. 3. Power density spectra of the noise were fitted in many cones by the product of two Lorentzians with characteristic time constants τ1 and τ2 averaging 40 and 7 msec respectively. The spectra of some cells were peaked and could be fitted by a resonance curve. 4. Spectra in dim light exhibited decreased low frequency power. They could often be fitted by a product of two Lorentzians using the same value of τ2 as used in darkness but decreasing τ1 and the zero frequency asymptote. An e-fold reduction in τ1 occurred with lights which hyperpolarized by 4-7 mV. 5. Injection of hyperpolarizing currents of about 0·1-0·2 nA into weakly coupled cones reduced the noise, and also reduced the sensitivity to dim flashes. 6. The variance-voltage relation during steady illumination of different intensities differed from cone to cone. Dim lights increased the noise in some cells and decreased it in others, but moderately bright lights which gave steady responses of more than about one third maximal reduced the noise in all cells. 7. When the cell was transiently depolarized during the differentiated component following steady illumination, the noise was less than it was after prolonged darkness. 8. In the after-effect of bright light, the time course of recovery of noise was the same as that of flash sensitivity and voltage. The noise was reduced e-fold for hyperpolarizations averaging 3 mV while for sensitivity this reduction occurred for 1·3 mV. For a given hyperpolarization the noise was lower during the after-effect than during steady dim illumination. 9. When a series of dim flashes was delivered to a cone, no significant increase in variance over the dark noise was detected during the photo-response. This implies that each photoisomerization evokes no more than about 1·5 μV at the peak of the response in a coupled cone, corresponding to about 50 μV in an isolated cone. 10. The elementary shot events underlying the noise are about 100 μV in amplitude in an isolated cone, have a characteristic time constant of 16-60 msec and reflect unit conductance fluctuations of about 16 pS (S, Siemen ≡ Ω-1). 11. It is concluded that the noise source is internal to the cones. We postulate that the noise arises from opening and closing of the light-sensitive ionic channels in the outer segment, and that in darkness there is a residual concentration of the blocking substance which on average closes up to about one third of the channels. It seems likely that the unit event involves a considerable number of blocking molecules and ionic channels. PMID:592199

System for supporting a bundled tube fuel injector within a combustor

DOE Office of Scientific and Technical Information (OSTI.GOV)

LeBegue, Jeffrey Scott; Melton, Patrick Benedict; Westmoreland, III, James Harold

A combustor includes an end cover having an outer side and an inner side, an outer barrel having a forward end that is adjacent to the inner side of the end cover and an aft end that is axially spaced from the forward end. An inner barrel is at least partially disposed concentrically within the outer barrel and is fixedly connected to the outer barrel. A fluid conduit extends downstream from the end cover. A first bundled tube fuel injector segment is disposed concentrically within the inner barrel. The bundled tube fuel injector segment includes a fuel plenum that ismore » in fluid communication with the fluid conduit and a plurality of parallel tubes that extend axially through the fuel plenum. The bundled tube fuel injector segment is fixedly connected to the inner barrel.« less

STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF BENIGN FLECK RETINA USING MULTIMODAL IMAGING.

PubMed

Neriyanuri, Srividya; Rao, Chetan; Raman, Rajiv

2017-01-01

To report structural and functional features in a case series of benign fleck retina using multimodal imaging. Four cases with benign fleck retina underwent complete ophthalmic examination that included detailed history, visual acuity, and refractive error testing, FM-100 hue test, dilated fundus evaluation, full field electroretinogram, fundus photography with autofluorescence, fundus fluorescein angiography, and swept-source optical coherence tomography. Age group of the cases ranged from 19 years to 35 years (3 males and 1 female). Parental consanguinity was reported in two cases. All of them were visually asymptomatic with best-corrected visual acuity of 20/20 (moderate astigmatism) in both the eyes. Low color discrimination was seen in two cases. Fundus photography showed pisciform flecks which were compactly placed on posterior pole and were discrete, diverging towards periphery. Lesions were seen as smaller dots within 1500 microns from fovea and were hyperfluorescent on autofluorescence. Palisading retinal pigment epithelium defects were seen in posterior pole on fundus fluorescein angiography imaging; irregular hyper fluorescence was also noted. One case had reduced cone responses on full field electroretinogram; the other three cases had normal electroretinogram. On optical coherence tomography, level of lesions varied from retinal pigment epithelium, inner segment to outer segment extending till external limiting membrane. Functional and structural deficits in benign fleck retina were picked up using multimodal imaging.

Comparison of the Diagnostic Image Quality of the Canine Maxillary Dentoalveolar Structures Obtained by Cone Beam Computed Tomography and 64-Multidetector Row Computed Tomography.

PubMed

Soukup, Jason W; Drees, Randi; Koenig, Lisa J; Snyder, Christopher J; Hetzel, Scott; Miles, Chanda R; Schwarz, Tobias

2015-01-01

The objective of this blinded study was to validate the use of cone beam computed tomography (C) for imaging of the canine maxillary dentoalveolar structures by comparing its diagnostic image quality with that of 64-multidetector row CT Sagittal slices of a tooth-bearing segment of the maxilla of a commercially purchased dog skull embedded in methylmethacrylate were obtained along a line parallel with the dental arch using a commercial histology diamond saw. The slice of tooth-bearing bone that best depicted the dentoalveolar structures was chosen and photographed. The maxillary segment was imaged with cone beam CT and 64-multidetector row CT. Four blinded evaluators compared the cone beam CT and 64-multidetector row CT images and image quality was scored as it related to the anatomy of dentoalveolar structures. Trabecular bone, enamel, dentin, pulp cavity, periodontal ligament space, and lamina dura were scored In addition, a score depicting the evaluators overall impression of the image was recorded. Images acquired with cone beam CT were found to be significantly superior in image quality to images acquired with 64-multidetector row CT overall, and in all scored categories. In our study setting cone beam CT was found to be a valid and clinically superior imaging modality for the canine maxillary dentoalveolar structures when compared to 64-multidetector row CT.

Comparison of the Diagnostic Image Quality of the Canine Maxillary Dentoalveolar Structures Obtained by Cone Beam Computed Tomography and 64-Multidetector Row Computed Tomography

PubMed Central

Soukup, Jason W.; Drees, Randi; Koenig, Lisa J.; Snyder, Christopher J.; Hetzel, Scott; Miles, Chanda R.; Schwarz, Tobias

2016-01-01

Summary The objective of this blinded study was to validate the use of cone beam computed tomography (CT) for imaging of the canine maxillary dentoalveolar structures by comparing its diagnostic image quality with that of 64-multidetector row CT. Sagittal slices of a tooth-bearing segment of the maxilla of a commercially purchased dog skull embedded in methyl methacrylate were obtained along a line parallel with the dental arch using a commercial histology diamond saw. The slice of tooth-bearing bone that best depicted the dentoalveolar structures was chosen and photographed. The maxilla segment was imaged with cone beam CT and 64-multidetector row CT. Four blinded evaluators compared the cone beam CT and 64-multidetector row CT images and image quality was scored as it related to the anatomy of dentoalveolar structures. Trabecular bone, enamel, dentin, pulp cavity, periodontal ligament space, and lamina dura were scored. In addition, a score depicting the evaluators overall impression of the image was recorded. Images acquired with cone beam CT were found to be significantly superior in image quality to images acquired with 64-multidetector row CT overall, and in all scored categories. In our study setting, cone beam CT was found to be a valid and clinically superior imaging modality for the canine maxillary dentoalveolar structures when compared to 64-multidetector row CT. PMID:26415384

Segmented trapped vortex cavity

NASA Technical Reports Server (NTRS)

Grammel, Jr., Leonard Paul (Inventor); Pennekamp, David Lance (Inventor); Winslow, Jr., Ralph Henry (Inventor)

2010-01-01

An annular trapped vortex cavity assembly segment comprising includes a cavity forward wall, a cavity aft wall, and a cavity radially outer wall there between defining a cavity segment therein. A cavity opening extends between the forward and aft walls at a radially inner end of the assembly segment. Radially spaced apart pluralities of air injection first and second holes extend through the forward and aft walls respectively. The segment may include first and second expansion joint features at distal first and second ends respectively of the segment. The segment may include a forward subcomponent including the cavity forward wall attached to an aft subcomponent including the cavity aft wall. The forward and aft subcomponents include forward and aft portions of the cavity radially outer wall respectively. A ring of the segments may be circumferentially disposed about an axis to form an annular segmented vortex cavity assembly.

Development of a full ice-cream cone model for halo CME structures

NASA Astrophysics Data System (ADS)

Na, Hyeonock; Moon, Yong-Jae

2015-04-01

The determination of three dimensional parameters (e.g., radial speed, angular width, source location) of Coronal Mass Ejections (CMEs) is very important for space weather forecast. To estimate these parameters, several cone models based on a flat cone or a shallow ice-cream cone with spherical front have been suggested. In this study, we investigate which cone model is proper for halo CME morphology using 33 CMEs which are identified as halo CMEs by one spacecraft (SOHO or STEREO-A or B) and as limb CMEs by the other ones. From geometrical parameters of these CMEs such as their front curvature, we find that near full ice-cream cone CMEs (28 events) are dominant over shallow ice-cream cone CMEs (5 events). So we develop a new full ice-cream cone model by assuming that a full ice-cream cone consists of many flat cones with different heights and angular widths. This model is carried out by the following steps: (1) construct a cone for given height and angular width, (2) project the cone onto the sky plane, (3) select points comprising the outer boundary, (4) minimize the difference between the estimated projection points with the observed ones. We apply this model to several halo CMEs and compare the results with those from other methods such as a Graduated Cylindrical Shell model and a geometrical triangulation method.

Short-wavelength cone-opponent retinal ganglion cells in mammals.

PubMed

Marshak, David W; Mills, Stephen L

2014-03-01

In all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages.

KSC-07pd1167

NASA Image and Video Library

2007-05-14

KENNEDY SPACE CENTER, FLA. -- Solid rocket motor segments and two aft exit cone segments arrive by rail at NASA's Kennedy Space Center. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/George Shelton

KSC-07pd1162

NASA Image and Video Library

2007-05-14

KENNEDY SPACE CENTER, FLA. -- Solid rocket motor segments and two aft exit cone segments arrive by rail at NASA's Kennedy Space Center. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/Kim Shiflett

KSC-07pd1168

NASA Image and Video Library

2007-05-14

KENNEDY SPACE CENTER, FLA. -- Solid rocket motor segments and two aft exit cone segments arrive by rail at NASA's Kennedy Space Center. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/George Shelton

HISTOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Multilayer Approach.

PubMed

Li, Miaoling; Huisingh, Carrie; Messinger, Jeffrey; Dolz-Marco, Rosa; Ferrara, Daniela; Freund, K Bailey; Curcio, Christine A

2018-05-03

To systematically characterize histologic features of multiple chorioretinal layers in eyes with geographic atrophy, or complete retinal pigment epithelium (RPE) and outer retinal atrophy, secondary to age-related macular degeneration, including Henle fiber layer and outer nuclear layer; and to compare these changes to those in the underlying RPE-Bruch membrane-choriocapillaris complex and associated extracellular deposits. Geographic atrophy was delimited by the external limiting membrane (ELM) descent towards Bruch membrane. In 13 eyes, histologic phenotypes and/or thicknesses of Henle fiber layer, outer nuclear layer, underlying supporting tissues, and extracellular deposits at four defined locations on the non-atrophic and atrophic sides of the ELM descent were assessed and compared across other tissue layers, with generalized estimating equations and logit models. On the non-atrophic side of the ELM descent, distinct Henle fiber layer and outer nuclear layer became dyslaminated, cone photoreceptor inner segment myoids shortened, photoreceptor nuclei and mitochondria translocated inward, and RPE was dysmorphic. On the atrophic side of the ELM descent, all measures of photoreceptor health declined to zero. Henle fiber layer/outer nuclear layer thickness halved, and only Müller cells remained, in the absence of photoreceptors. Sub-RPE deposits remained, Bruch membrane thinned, and choriocapillaris density decreased. The ELM descent sharply delimits an area of marked gliosis and near-total photoreceptor depletion clinically defined as Geographic atrophy (or outer retinal atrophy), indicating severe and potentially irreversible tissue damage. Degeneration of supporting tissues across this boundary is gradual, consistent with steady age-related change and suggesting that RPE and Müller cells subsequently respond to a threshold of stress. Novel clinical trial endpoints should be sought at age-related macular degeneration stages before intense gliosis and thick deposits impede therapeutic intervention.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Wedge edge ceramic combustor tile

DOEpatents

Shaffer, J.E.; Holsapple, A.C.

1997-06-10

A multipiece combustor has a portion thereof being made of a plurality of ceramic segments. Each of the plurality of ceramic segments have an outer surface and an inner surface. Each of the plurality of ceramic segments have a generally cylindrical configuration and including a plurality of joints. The joints define joint portions, a first portion defining a surface being skewed to the outer surface and the inner surface. The joint portions have a second portion defining a surface being skewed to the outer surface and the inner surface. The joint portions further include a shoulder formed intermediate the first portion and the second portion. The joints provide a sealing interlocking joint between corresponding ones of the plurality of ceramic segments. Thus, the multipiece combustor having the plurality of ceramic segment with the plurality of joints reduces the physical size of the individual components and the degradation of the surface of the ceramic components in a tensile stress zone is generally eliminated reducing the possibility of catastrophic failures. 7 figs.

Wedge edge ceramic combustor tile

DOEpatents

Shaffer, James E.; Holsapple, Allan C.

1997-01-01

A multipiece combustor has a portion thereof being made of a plurality of ceramic segments. Each of the plurality of ceramic segments have an outer surface and an inner surface. Each of the plurality of ceramic segments have a generally cylindrical configuration and including a plurality of joints. The joints define joint portions, a first portion defining a surface being skewed to the outer surface and the inner surface. The joint portions have a second portion defining a surface being skewed to the outer surface and the inner surface. The joint portions further include a shoulder formed intermediate the first portion and the second portion. The joints provide a sealing interlocking joint between corresponding ones of the plurality of ceramic segments. Thus, the multipiece combustor having the plurality of ceramic segment with the plurality of joints reduces the physical size of the individual components and the degradation of the surface of the ceramic components in a tensile stress zone is generally eliminated reducing the possibility of catastrophic failures.

Determination of HCME 3-D parameters using a full ice-cream cone model

NASA Astrophysics Data System (ADS)

Na, Hyeonock; Moon, Yong-Jae; Lee, Harim

2016-05-01

It is very essential to determine three dimensional parameters (e.g., radial speed, angular width, source location) of Coronal Mass Ejections (CMEs) for space weather forecast. Several cone models (e.g., an elliptical cone model, an ice-cream cone model, an asymmetric cone model) have been examined to estimate these parameters. In this study, we investigate which cone type is close to a halo CME morphology using 26 CMEs: halo CMEs by one spacecraft (SOHO or STEREO-A or B) and as limb CMEs by the other ones. From cone shape parameters of these CMEs such as their front curvature, we find that near full ice-cream cone type CMEs are much closer to observations than shallow ice-cream cone type CMEs. Thus we develop a new cone model in which a full ice-cream cone consists of many flat cones with different heights and angular widths. This model is carried out by the following steps: (1) construct a cone for given height and angular width, (2) project the cone onto the sky plane, (3) select points comprising the outer boundary, and (4) minimize the difference between the estimated projection speeds with the observed ones. By applying this model to 12 SOHO/LASCO halo CMEs, we find that 3-D parameters from our method are similar to those from other stereoscopic methods (a geometrical triangulation method and a Graduated Cylindrical Shell model) based on multi-spacecraft data. We are developing a general ice-cream cone model whose front shape is a free parameter determined by observations.

Calcium homeostasis in the outer segments of retinal rods from the tiger salamander.

PubMed Central

Lagnado, L; Cervetto, L; McNaughton, P A

1992-01-01

1. The processes regulating intracellular calcium in the outer segments of salamander rods have been investigated. The main preparation used was the isolated rod loaded with the Ca(2+)-sensitive photoprotein aequorin, from which outer segment membrane current and free [Ca2+]i could be recorded simultaneously. Two other preparations were also used: outer segment membrane current was recorded from intact, isolated rods using a suction pipette, and from detached outer segments using a whole-cell pipette. 2. Measurements of free intracellular [Ca2+] in Ringer solution were obtained from two aequorin-loaded rods. Mean [Ca2+]i in darkness was 0.41 microM, and after a bright flash [Ca2+]i fell to below detectable levels ( < 0.3 microM). No release of intracellular Ca2+ by a bright flash of light could be detected ( < 0.2 microM). 3. Application of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) caused an increase in the size of the light-sensitive current and a rise in [Ca2+]i, but application of IBMX either when the light-sensitive channels had been closed by a bright light or in the absence of external Ca2+ caused no detectable rise in [Ca2+]i. It is concluded that IBMX increases [Ca2+]i by opening light-sensitive channels, and does not release Ca2+ from stores within the outer segment. 4. Removal of external Na+ caused a rise in [Ca2+]i to around 2 microM and completely suppressed the light-sensitive current. 5. The Na(+)-Ca2+, K+ exchange current in aequorin-loaded rods was activated in first-order manner by internal free calcium, with a mean Michaelis constant, KCa, of 1.6 microM. 6. The KCa of the Na(+)-Ca2+, K+ exchange was increased by elevating internal [Na+]. 7. The Michaelis relation between [Ca2+]i and the activity of the Na(+)-Ca2+, K+ exchange was used to calculate the change in [Ca2+]i occurring during the response to a bright light. In aequorin-loaded rods in Ringer solution the mean change in free [Ca2+]i after a bright flash was 0.34 microM. In these rods 10% of the dark current was carried by Ca2+. 8. Most of the calcium entering the outer segment was taken up rapidly and reversibly by buffer systems. The time constant of equilibration between free and rapidly bound Ca2+ was less than 20 ms. No slow component of calcium uptake was detected. 9. Two components of calcium buffering could be distinguished in the outer segments of aequorin-loaded rods.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1282928

A model for radial dike emplacement in composite cones based on observations from Summer Coon volcano, Colorado, USA

USGS Publications Warehouse

Poland, Michael P.; Moats, W.P.; Fink, J.H.

2008-01-01

We mapped the geometry of 13 silicic dikes at Summer Coon, an eroded Oligocene stratovolcano in southern Colorado, to investigate various characteristics of radial dike emplacement in composite volcanoes. Exposed dikes are up to about 7 km in length and have numerous offset segments along their upper peripheries. Surprisingly, most dikes at Summer Coon increase in thickness with distance from the center of the volcano. Magma pressure in a dike is expected to lessen away from the pressurized source region, which would encourage a blade-like dike to decrease in thickness with distance from the center of the volcano. We attribute the observed thickness pattern as evidence of a driving pressure gradient, which is caused by decreasing host rock shear modulus and horizontal stress, both due to decreasing emplacement depths beneath the sloping flanks of the volcano. Based on data from Summer Coon, we propose that radial dikes originate at depth below the summit of a host volcano and follow steeply inclined paths towards the surface. Near the interface between volcanic cone and basement, which may represent a neutral buoyancy surface or stress barrier, magma is transported subhorizontally and radially away from the center of the volcano in blade-like dikes. The dikes thicken with increasing radial distance, and offset segments and fingers form along the upper peripheries of the intrusions. Eruptions may occur anywhere along the length of the dikes, but the erupted volume will generally be greater for dike-fed eruptions far from the center of the host volcano owing to the increase in driving pressure with distance from the source. Observed eruptive volumes, vent locations, and vent-area intrusions from inferred post-glacial dike-fed eruptions at Mount Adams, Washington, USA, support the proposed model. Hazards associated with radial dike emplacement are therefore greater for longer dikes that propagate to the outer flanks of a volcano. ?? Springer-Verlag 2007.

Morphological changes in the anterior segment of the Abyssinian cat eye with hereditary rod-cone degeneration.

PubMed

May, Chr Albrecht; Lütjen-Drecoll, Elke; Narfström, Kristina

2005-10-01

The purpose of this study was to investigate morphological changes of the anterior segment of the eye in Abyssinian cats with progressive rod-cone degeneration and to correlate them with blood flow data obtained in the same animals. Sections of the left eyes of six normal cats and of eight cats with different stages of hereditary retinal degeneration were prepared for transmission and scanning electron microscopy. Tangential and sagittal sections were also stained with antibodies against substance P, tyrosine hydroxylase, panneuronal marker PGP9.5, nitric oxide synthase, synaptophysin, and smooth muscle alpha-actin. In Abyssinian cats with hereditary rod-cone degeneration, significant changes were observed in the iris consisting of irregularities in the vascular wall of smaller arteries without changes in their innervation pattern. The ciliary processes were shorter than in normal cats, and their structure appeared more compact and retracted. Slight changes were also observed in the anterior part of the ciliary epithelium. The anterior chamber angle region did not appear to be affected. Clear morphological correlations to the physiological blood flow data were observed in the anterior eye segment, pointing not only to functional but also morphological vascular abnormalities in this animal model for retinitis pigmentosa.

Reduction of foveal bulges and other anatomical changes in fellow eyes of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes.

PubMed

Delas, Barbara; Julio, Gemma; Fernández-Vega, Álvaro; Casaroli-Marano, Ricardo P; Nadal, Jeroni

2017-11-01

To compare the foveal characteristics in fellow eyes (FE) of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes with eyes of healthy controls. Forty-seven FE and 52 eyes of 52 age- and sex-matched healthy controls were studied. Quantitative assessment of the dome-shaped appearance of the hyperreflective lines that represent external limiting membrane (ELM_bulge) and inner outer segment junctions (IS/OS_bulge) were made by optical coherence tomography (OCT) images. Inner retinal complex thickness (IRCT) was quantitatively assessed at 1000 and 2000 μm of the foveal center in nasal and temporal quadrants. Presence of alterations in the inner retinal outer layers and central foveal thickness (CFT) were also analyzed. Significantly lower ELM_bulge (p < 0.0001; Mann-Whitney test) and IS/OS_bulge (p < 0.001; student t test) and higher cases with COST alterations, expressed as a diffuse line (p < 0.006; Chi 2 test) were found in FE than control eyes. IRCT were significantly reduced in FE at all the studied locations when comparing to control eyes (p < 0.05; student t test), maintaining anatomical proportionality among locations. FE without pathologic vitreomacular interactions seems to present some central cone alterations that may be related to other causes than vitreomacular traction.

Computer-aided detection of human cone photoreceptor inner segments using multi-scale circular voting

NASA Astrophysics Data System (ADS)

Liu, Jianfei; Dubra, Alfredo; Tam, Johnny

2016-03-01

Cone photoreceptors are highly specialized cells responsible for the origin of vision in the human eye. Their inner segments can be noninvasively visualized using adaptive optics scanning light ophthalmoscopes (AOSLOs) with nonconfocal split detection capabilities. Monitoring the number of cones can lead to more precise metrics for real-time diagnosis and assessment of disease progression. Cell identification in split detection AOSLO images is hindered by cell regions with heterogeneous intensity arising from shadowing effects and low contrast boundaries due to overlying blood vessels. Here, we present a multi-scale circular voting approach to overcome these challenges through the novel combination of: 1) iterative circular voting to identify candidate cells based on their circular structures, 2) a multi-scale strategy to identify the optimal circular voting response, and 3) clustering to improve robustness while removing false positives. We acquired images from three healthy subjects at various locations on the retina and manually labeled cell locations to create ground-truth for evaluating the detection accuracy. The images span a large range of cell densities. The overall recall, precision, and F1 score were 91±4%, 84±10%, and 87±7% (Mean±SD). Results showed that our method for the identification of cone photoreceptor inner segments performs well even with low contrast cell boundaries and vessel obscuration. These encouraging results demonstrate that the proposed approach can robustly and accurately identify cells in split detection AOSLO images.

Light induces a rapid and transient increase in inositol-trisphosphate in toad rod outer segments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, J.E.; Blazynski, C.; Cohen, A.I.

1987-08-14

The sub-second time course of changes in the content of (/sup 3/H)inositol-1,4,5-trisphosphate was determined in rod outer segments from very rapidly frozen Bufo retinas that had been incubated with (/sup 3/H)inositol. Rod outer segments were cut off frozen specimens with a cryostat microtome and the water soluble extracts were analyzed. The content of (/sup 3/H)inositol-1,4,5-trisphosphate rose after approximately 250 msec of bright illumination, but returned to the unstimulated level after 1 sec, whether the stimulus remained on or not. That is, there was rapid but transient change in the content of (/sup 3/H)inositol-1,4,5-trisphosphate after the onset of stimulation.

Fully automatic segmentation of arbitrarily shaped fiducial markers in cone-beam CT projections

NASA Astrophysics Data System (ADS)

Bertholet, J.; Wan, H.; Toftegaard, J.; Schmidt, M. L.; Chotard, F.; Parikh, P. J.; Poulsen, P. R.

2017-02-01

Radio-opaque fiducial markers of different shapes are often implanted in or near abdominal or thoracic tumors to act as surrogates for the tumor position during radiotherapy. They can be used for real-time treatment adaptation, but this requires a robust, automatic segmentation method able to handle arbitrarily shaped markers in a rotational imaging geometry such as cone-beam computed tomography (CBCT) projection images and intra-treatment images. In this study, we propose a fully automatic dynamic programming (DP) assisted template-based (TB) segmentation method. Based on an initial DP segmentation, the DPTB algorithm generates and uses a 3D marker model to create 2D templates at any projection angle. The 2D templates are used to segment the marker position as the position with highest normalized cross-correlation in a search area centered at the DP segmented position. The accuracy of the DP algorithm and the new DPTB algorithm was quantified as the 2D segmentation error (pixels) compared to a manual ground truth segmentation for 97 markers in the projection images of CBCT scans of 40 patients. Also the fraction of wrong segmentations, defined as 2D errors larger than 5 pixels, was calculated. The mean 2D segmentation error of DP was reduced from 4.1 pixels to 3.0 pixels by DPTB, while the fraction of wrong segmentations was reduced from 17.4% to 6.8%. DPTB allowed rejection of uncertain segmentations as deemed by a low normalized cross-correlation coefficient and contrast-to-noise ratio. For a rejection rate of 9.97%, the sensitivity in detecting wrong segmentations was 67% and the specificity was 94%. The accepted segmentations had a mean segmentation error of 1.8 pixels and 2.5% wrong segmentations.

Rotary high power transfer apparatus

NASA Technical Reports Server (NTRS)

Jacobson, Peter E. (Inventor); Porter, Ryan S. (Inventor)

1987-01-01

An apparatus for reducing terminal-to-terminal circuit resistance and enhancing heat transfer in a rotary power transfer apparatus of the roll ring type comprising a connecting thimble for attaching an external power cable to a cone shaped terminal which is attached to a tab integral to an outer ring. An inner ring having a spherical recess mates with the spherical end of a tie connector. A cone shaped terminal is fitted to a second connecting thimble for attaching a second external power cable.

Pulse joining cartridges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golovashchenko, Sergey Fedorovich; Bonnen, John Joseph Francis

A pulsed joining tool includes a tool body that defines a cavity that receives an inner tubular member and an outer tubular member and a pulse joining cartridge. The tubular members are nested together with the cartridge being disposed around the outer tubular member. The cartridge includes a conductor, such as a wire or foil, that extends around the outer tubular member and is insulated to separate a supply segment from a return segment. A source of stored electrical energy is discharged through the conductor to join the tubular members with an electromagnetic force pulse.

Pulse joining cartridges

DOEpatents

Golovashchenko, Sergey Fedorovich; Bonnen, John Joseph Francis

2016-08-23

A pulsed joining tool includes a tool body that defines a cavity that receives an inner tubular member and an outer tubular member and a pulse joining cartridge. The tubular members are nested together with the cartridge being disposed around the outer tubular member. The cartridge includes a conductor, such as a wire or foil, that extends around the outer tubular member and is insulated to separate a supply segment from a return segment. A source of stored electrical energy is discharged through the conductor to join the tubular members with an electromagnetic force pulse.

Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity

PubMed Central

Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

2016-01-01

The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer nuclear layer (ONL), an outer plexiform layer (OPL), an inner nuclear layer (INL), an inner plexiform layer (IPL), and a ganglion cell layer (GCL). By immunohistochemistry, the number of melanopsin (mRGCs) and non-melanopsin bearing retinal ganglion cells was analyzed in detail. Using the ganglion cell marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm2). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly in the GCL with projections forming two dendritic plexuses located in the inner part of the IPL and in the OPL. Few melanopsin dendrites were also found in the ONL. The Spalax retina is rich in rhodopsin and long/middle wave (L/M) cone opsin bearing photoreceptor cells. By using Ctbp2 as a marker for ribbon synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells contain calretinin. The calretinin expressing amacrine cells seemed to form synaptic contacts with rhodopsin containing photoreceptor cells in the OPL and contacts with melanopsin cell bodies and dendrites in the IPL. The study demonstrates the complex retinal circuitry used by the Spalax to detect light, and provides evidence for both melanopsin and non-melanopsin projecting pathways to the brain. PMID:27375437

Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity.

PubMed

Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

2016-01-01

The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer nuclear layer (ONL), an outer plexiform layer (OPL), an inner nuclear layer (INL), an inner plexiform layer (IPL), and a ganglion cell layer (GCL). By immunohistochemistry, the number of melanopsin (mRGCs) and non-melanopsin bearing retinal ganglion cells was analyzed in detail. Using the ganglion cell marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm(2)). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly in the GCL with projections forming two dendritic plexuses located in the inner part of the IPL and in the OPL. Few melanopsin dendrites were also found in the ONL. The Spalax retina is rich in rhodopsin and long/middle wave (L/M) cone opsin bearing photoreceptor cells. By using Ctbp2 as a marker for ribbon synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells contain calretinin. The calretinin expressing amacrine cells seemed to form synaptic contacts with rhodopsin containing photoreceptor cells in the OPL and contacts with melanopsin cell bodies and dendrites in the IPL. The study demonstrates the complex retinal circuitry used by the Spalax to detect light, and provides evidence for both melanopsin and non-melanopsin projecting pathways to the brain.

Study on a New Combination Method and High Efficiency Outer Rotor Type Permanent Magnet Motors

NASA Astrophysics Data System (ADS)

Enomoto, Yuji; Kitamura, Masashi; Motegi, Yasuaki; Andoh, Takashi; Ochiai, Makoto; Abukawa, Toshimi

The segment stator core, high space factor coil, and high efficiency magnet are indispensable technologies in the development of compact and a high efficiency motors. But adoption of the segment stator core and high space factor coil has not progressed in the field of outer rotor type motors, for the reason that the inner components cannot be laser welded together. Therefore, we have examined a segment stator core combination technology for the purposes of getting a large increase in efficiency and realizing miniaturization. We have also developed a characteristic estimation method which provides the most suitable performance for segment stator core motors.

Leaf seal for gas turbine stator shrouds and a nozzle band

DOEpatents

Burdgick, Steven Sebastian; Sexton, Brendan Francis

2002-01-01

A leaf seal assembly is secured to the trailing edge of a shroud segment for sealing between the shroud segment and the leading edge side wall of a nozzle outer band. The leaf seal includes a circumferentially elongated seal plate biased by a pair of spring clips disposed in a groove along the trailing edge of the shroud segment to maintain the seal plate in engagement with the flange on the leading edge side wall of the nozzle outer band. The leaf seal plate and spring clips receive pins tack-welded to the shroud segment to secure the leaf seal assembly in place.

Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa.

PubMed

Greenstein, Vivienne C; Duncker, Tobias; Holopigian, Karen; Carr, Ronald E; Greenberg, Jonathan P; Tsang, Stephen H; Hood, Donald C

2012-02-01

To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa. Twenty-one retinitis pigmentosa patients (21 eyes) with rings/arcs and 21 normal individuals (21 eyes) were studied. Visual sensitivity in the central 10° was measured with microperimetry. Retinal structure was evaluated with spectral-domain optical coherence tomography. The distance from the fovea to disruption/loss of the inner outer segment (IS/OS) junction and thicknesses of the total receptor plus retinal pigment epithelial complex and outer segment plus retinal pigment epithelial complex layers were measured. Results were compared with measurements of the distance from the fovea to the inner and outer borders of the ring/arc seen on fundus autofluorescence. Disruption/loss of the inner outer segment junction occurred closer to the inner border of the ring/arc and it was closer to the fovea in eight eyes. For 19 eyes, outer segment plus and receptor plus RPE complex thicknesses were significantly decreased at locations closer to the fovea than the appearance of the inner border of hyperautofluorescence. Mean visual sensitivity was decreased inside, across, and outside the ring/arc by 3.5 ± 3.8, 8.9 ± 4.8, and 17.0 ± 2.4 dB, respectively. Structural and functional changes can occur inside the hyperfluorescent ring/arc in retinitis pigmentosa.

Substrate specificity and subcellular localization of the aldehyde-alcohol redox-coupling reaction in carp cones.

PubMed

Sato, Shinya; Fukagawa, Takashi; Tachibanaki, Shuji; Yamano, Yumiko; Wada, Akimori; Kawamura, Satoru

2013-12-20

Our previous study suggested the presence of a novel cone-specific redox reaction that generates 11-cis-retinal from 11-cis-retinol in the carp retina. This reaction is unique in that 1) both 11-cis-retinol and all-trans-retinal were required to produce 11-cis-retinal; 2) together with 11-cis-retinal, all-trans-retinol was produced at a 1:1 ratio; and 3) the addition of enzyme cofactors such as NADP(H) was not necessary. This reaction is probably part of the reactions in a cone-specific retinoid cycle required for cone visual pigment regeneration with the use of 11-cis-retinol supplied from Müller cells. In this study, using purified carp cone membrane preparations, we first confirmed that the reaction is a redox-coupling reaction between retinals and retinols. We further examined the substrate specificity, reaction mechanism, and subcellular localization of this reaction. Oxidation was specific for 11-cis-retinol and 9-cis-retinol. In contrast, reduction showed low specificity: many aldehydes, including all-trans-, 9-cis-, 11-cis-, and 13-cis-retinals and even benzaldehyde, supported the reaction. On the basis of kinetic studies of this reaction (aldehyde-alcohol redox-coupling reaction), we found that formation of a ternary complex of a retinol, an aldehyde, and a postulated enzyme seemed to be necessary, which suggested the presence of both the retinol- and aldehyde-binding sites in this enzyme. A subcellular fractionation study showed that the activity is present almost exclusively in the cone inner segment. These results suggest the presence of an effective production mechanism of 11-cis-retinal in the cone inner segment to regenerate visual pigment.

Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa

PubMed Central

Scott, Patrick A.; de Castro, Juan P. Fernandez; DeMarco, Paul J.; Ross, Jason W.; Njoka, Josephat; Walters, Eric; Prather, Randall S.; McCall, Maureen A.; Kaplan, Henry J.

2017-01-01

Purpose We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy. Methods The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age. Miniswine were euthanized and their retinas processed for morphologic evaluation at the light and electron microscopic level. Retinal morphology of a 36-month-old Tg miniswine also was examined. Results Wild type littermates reached mature scotopic and photopic retinal function by 3 months, while TgP23H miniswine showed abnormal scotopic ffERGs at the earliest time point, 1 month, and depressed photopic ffERGs after 2 months. Rod and cone photoreceptors (PR) exhibited morphologic abnormalities and dropout from the outer nuclear layer at 1 month, with only a monolayer of cone PR somata remaining after 2 months. The retinas showed progressive neural remodeling of the outer retina that included dendritic retraction of rod bipolar cells and glial seal formation by Müller cells. The TgP23H founder miniswine showed cone PR with relatively intact morphology exclusive to the area centralis. Conclusions The F1 Tg miniswine and the TgP23H founder miniswine exhibit similar retinopathy. Translational Relevance TgP23H miniswine are a useful large-eye model to study pathogenesis and preservation cone PRs in humans with retinitis pigmentosa. PMID:28316877

Early simultaneous fundus autofluorescence and optical coherence tomography features after pars plana vitrectomy for primary rhegmatogenous retinal detachment.

PubMed

Dell'Omo, Roberto; Mura, Marco; Lesnik Oberstein, Sarit Y; Bijl, Heico; Tan, H Stevie

2012-04-01

To describe fundus autofluorescence and optical coherence tomography (OCT) features of the macula after pars plana vitrectomy for rhegmatogenous retinal detachment. Thirty-three eyes of 33 consecutive patients with repaired rhegmatogenous retinal detachment with or without the involvement of the macula were prospectively investigated with simultaneous fundus autofluorescence and OCT imaging using the Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) within a few weeks after the operation. Fundus autofluorescence imaging of the macula showed lines of increased and decreased autofluorescence in 19 cases (57.6%). On OCT, these lines corresponded to the following abnormalities: outer retinal folds, inner retinal folds, and skip reflectivity abnormalities of the photoreceptor inner segment/outer segment band. Other OCT findings, not related to abnormal lines on fundus autofluorescence, consisted of disruption of photoreceptor inner segment/outer segment band and collection of intraretinal or subretinal fluid. The presence of outer retinal folds significantly related to metamorphopsia but did not relate to poor postoperative visual acuity. Partial-thickness retinal folds occur commonly after vitrectomy for rhegmatogenous retinal detachment repair and may represent an important anatomical substrate for postoperative metamorphopsia. Fundus autofluorescence and OCT are both sensitive techniques for the detection of these abnormalities.

DYF-1 Is Required for Assembly of the Axoneme in Tetrahymena thermophila▿ †

PubMed Central

Dave, Drashti; Wloga, Dorota; Sharma, Neeraj; Gaertig, Jacek

2009-01-01

In most cilia, the axoneme can be subdivided into three segments: proximal (the transition zone), middle (with outer doublet microtubules), and distal (with singlet extensions of outer doublet microtubules). How the functionally distinct segments of the axoneme are assembled and maintained is not well understood. DYF-1 is a highly conserved ciliary protein containing tetratricopeptide repeats. In Caenorhabditis elegans, DYF-1 is specifically needed for assembly of the distal segment (G. Ou, O. E. Blacque, J. J. Snow, M. R. Leroux, and J. M. Scholey. Nature. 436:583-587, 2005). We show that Tetrahymena cells lacking an ortholog of DYF-1, Dyf1p, can assemble only extremely short axoneme remnants that have structural defects of diverse natures, including the absence of central pair and outer doublet microtubules and incomplete or absent B tubules on the outer microtubules. Thus, in Tetrahymena, DYF-1 is needed for either assembly or stability of the entire axoneme. Our observations support the conserved function for DYF-1 in axoneme assembly or stability but also show that the consequences of loss of DYF-1 for axoneme segments are organism specific. PMID:19581442

Rapid hydrogen ion uptake of rod outer segments and rhodopsin solutions on illumination

PubMed Central

Falk, G.; Fatt, P.

1966-01-01

1. Flash illumination of a suspension of frog rod outer segments or rhodopsin solution in contact with a platinum electrode produces a rapidly developing negative displacement of potential of the electrode (with respect to a reversible electrode). 2. The amplitude of the potential change varies inversely with the H+ buffering capacity of the medium. It is inferred that the response is due to an uptake of H+ by the rod outer segments or rhodopsin, with the platinum surface acting as a pH electrode. 3. Determination of the action spectrum shows that the response depends on the absorption of light by rhodopsin. 4. In frog rods one acid-binding group with a pK of about 7·9 is produced for each molecule of rhodopsin bleached, consistent with a rhodopsin concentration in frog rods of 1·7 mM. 5. It is suggested that the time course of the response with rhodopsin solutions reflects the kinetics of the conversion of metarhodopsin I to metarhodopsin II. 6. A slower time course of voltage change observed for suspensions of outer segments is attributable to the time required for the diffusion of H+ buffer out of the rods. PMID:5945249

Turbine stator vane segment having internal cooling circuits

DOEpatents

Jones, Raymond Joseph; Burns, James Lee; Bojappa, Parvangada Ganapathy; Jones, Schotsch Margaret

2003-01-01

A turbine stator vane includes outer and inner walls each having outer and inner chambers and a vane extending between the outer and inner walls. The vane includes first, second, third, fourth and fifth cavities for flowing a cooling medium. The cooling medium enters the outer chamber of the outer wall, flows through an impingement plate for impingement cooling of the outer band wall defining in part the hot gas path and through openings in the first, second and fourth cavities for flow radially inwardly, cooling the vane. The spent cooling medium flows into the inner wall and inner chamber for flow through an impingement plate radially outwardly to cool the inner wall. The spent cooling medium flows through the third cavity for egress from the turbine vane segment from the outer wall. The first, second or third cavities contain inserts having impingement openings for impingement cooling of the vane walls. The fifth cavity provides air cooling for the trailing edge.

Gas turbine row #1 steam cooled vane

DOEpatents

Cunha, Frank J.

2000-01-01

A design for a vane segment having a closed-loop steam cooling system is provided. The vane segment comprises an outer shroud, an inner shroud and an airfoil, each component having a target surface on the inside surface of its walls. A plurality of rectangular waffle structures are provided on the target surface to enhance heat transfer between each component and cooling steam. Channel systems are provided in the shrouds to improve the flow of steam through the shrouds. Insert legs located in cavities in the airfoil are also provided. Each insert leg comprises outer channels located on a perimeter of the leg, each outer channel having an outer wall and impingement holes on the outer wall for producing impingement jets of cooling steam to contact the airfoil's target surface. Each insert leg further comprises a plurality of substantially rectangular-shaped ribs located on the outer wall and a plurality of openings located between outer channels of the leg to minimize cross flow degradation.

Optical properties of photoreceptor and retinal pigment epithelium cells investigated with adaptive optics optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, Zhuolin

Human vision starts when photoreceptors collect and respond to light. Photoreceptors do not function in isolation though, but share close interdependence with neighboring photoreceptors and underlying retinal pigment epithelium (RPE) cells. These cellular interactions are essential for normal function of the photoreceptor-RPE complex, but methods to assess these in the living human eye are limited. One approach that has gained increased promise is high-resolution retinal imaging that has undergone tremendous technological advances over the last two decades to probe the living retina at the cellular level. Pivotal in these advances has been adaptive optics (AO) and optical coherence tomography (OCT) that together allow unprecedented spatial resolution of retinal structures in all three dimensions. Using these high-resolution systems, cone photoreceptor are now routinely imaged in healthy and diseased retina enabling fundamental structural properties of cones to be studied such as cell spacing, packing arrangement, and alignment. Other important cell properties, however, have remained elusive to investigation as even better imaging performance is required and thus has resulted in an incomplete understanding of how cells in the photoreceptor-RPE complex interact with light. To address this technical bottleneck, we expanded the imaging capability of AO-OCT to detect and quantify more accurately and completely the optical properties of cone photoreceptor and RPE cells at the cellular level in the living human retina. The first objective of this thesis was development of a new AO-OCT method that is more precise and sensitive, thus enabling a more detailed view of the 3D optical signature of the photoreceptor-RPE complex than was previously possible (Chapter 2). Using this new system, the second objective was quantifying the waveguide properties of individual cone photoreceptor inner and outer segments across the macula (Chapter 3). The third objective extended the AO-OCT method to RPE cell imaging. This entailed using AO-OCT in conjunction with organelle motility as a novel contrast mechanism to visualize RPE cells and to characterize their 3D reflectance profile (Chapter 4).

Measuring In Vivo Free Radical Production by the Outer Retina

PubMed Central

Berkowitz, Bruce A.; Bredell, Bryce X.; Davis, Christopher; Samardzija, Marijana; Grimm, Christian; Roberts, Robin

2015-01-01

Purpose Excessive and continuously produced free radicals in the outer retina are implicated in retinal aging and the pathogenesis of sight-threatening retinopathies, yet measuring outer retinal oxidative stress in vivo remains a challenge. Here, we test the hypothesis that continuously produced paramagnetic free radicals from the outer retina can be measured in vivo using high-resolution (22-μm axial resolution) 1/T1magnetic resonance imaging (MRI) without and with a confirmatory quench (quench-assisted MRI). Methods Low-dose sodium iodate–treated and diabetic C57Bl6/J mice (and their controls), and rod-dominated (129S6) or cone-only R91W;Nrl−/− mice were studied. In dark-adapted groups, 1/T1 was mapped transretinally in vivo without or with (1) the antioxidant combination of methylene blue (MB) and α-lipoic acid (LPA), or (2) light exposure; in subgroups, retinal superoxide production was measured ex vivo (lucigenin). Results In the sodium iodate model, retinal superoxide production and outer retina-specific 1/T1 values were both significantly greater than normal and corrected to baseline with MB+LPA therapy. Nondiabetic mice at two ages and 1.2-month diabetic mice (before the appearance of oxidative stress) had similar transretinal 1/T1 profiles. By 2.3 months of diabetes, only outer retinal 1/T1 values were significantly greater than normal and were corrected to baseline with MB+LPA therapy. In mice with healthy photoreceptors, a light quench caused 1/T1 of rods, but not cones, to significantly decrease from their values in the dark. Conclusions Quench-assisted MRI is a feasible method for noninvasively measuring normal and pathologic production of free radicals in photoreceptors/RPE in vivo. PMID:26670830

Severity and presence of atherosclerosis signs within the segments of internal carotid artery: CBCT's contribution.

PubMed

Damaskos, Spyros; da Silveira, Heraldo L D; Berkhout, Erwin W R

2016-07-01

This study aims to assess with cone-beam computed tomography the distribution and interrelation of the presence of calcifications along the course of the internal carotid artery and to associate their severity with their allocation within the segments of internal carotid artery, gender, and age. Using a documented visual scale, 161 cone-beam computed tomography scans were evaluated on the allocation and severity of intracranial calcifications within the segments of the internal carotid artery. Calcifications were detected along the petrous (C2: 11.8%), lacerum (C3: 23.6%), cavernous (C4: 92.5%), and ophthalmic-clinoid (C5/C6: 65.8%) segments. The Friedman test showed significant differences in severity distribution among these segments; the highest degree was found in the C4 segment (P < .05). The Wilcoxon signed-rank test showed no significant differences between calcifications on the right or left side or between severities within the C1 (extracranial) and C5/C6 segments. The Chi-square test showed that the severity and allocation of calcifications are not influenced by gender; it also showed that their severity increases with age (P < .05). In the cohort studied, the incidence of calcifications increased throughout the C1, C5/C6, and C4 segments. More severe calcifications were found at the C4, C1, and C5/C6 segments in decreasing order but increased with age, regardless of gender. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular determinants of Guanylate Cyclase Activating Protein subcellular distribution in photoreceptor cells of the retina.

PubMed

López-Begines, Santiago; Plana-Bonamaisó, Anna; Méndez, Ana

2018-02-13

Retinal guanylate cyclase (RetGC) and guanylate cyclase activating proteins (GCAPs) play an important role during the light response in photoreceptor cells. Mutations in these proteins are linked to distinct forms of blindness. RetGC and GCAPs exert their role at the ciliary outer segment where phototransduction takes place. We investigated the mechanisms governing GCAP1 and GCAP2 distribution to rod outer segments by expressing selected GCAP1 and GCAP2 mutants as transient transgenes in the rods of GCAP1/2 double knockout mice. We show that precluding GCAP1 direct binding to RetGC (K23D/GCAP1) prevented its distribution to rod outer segments, while preventing GCAP1 activation of RetGC post-binding (W94A/GCAP1) did not. We infer that GCAP1 translocation to the outer segment strongly depends on GCAP1 binding affinity for RetGC, which points to GCAP1 requirement to bind to RetGC to be transported. We gain further insight into the distinctive regulatory steps of GCAP2 distribution, by showing that a phosphomimic at position 201 is sufficient to retain GCAP2 at proximal compartments; and that the bovine equivalent to blindness-causative mutation G157R/GCAP2 results in enhanced phosphorylation in vitro and significant retention at the inner segment in vivo, as likely contributing factors to the pathophysiology.

Two new methods used to simulate the circumferential solar flux density concentrated on the absorber of a parabolic trough solar collector

NASA Astrophysics Data System (ADS)

Guo, Minghuan; Wang, Zhifeng; Sun, Feihu

2016-05-01

The optical efficiencies of a solar trough concentrator are important to the whole thermal performance of the solar collector, and the outer surface of the tube absorber is a key interface of energy flux. So it is necessary to simulate and analyze the concentrated solar flux density distributions on the tube absorber of a parabolic trough solar collector for various sun beam incident angles, with main optical errors considered. Since the solar trough concentrators are linear focusing, it is much of interest to investigate the solar flux density distribution on the cross-section profile of the tube absorber, rather than the flux density distribution along the focal line direction. Although a few integral approaches based on the "solar cone" concept were developed to compute the concentrated flux density for some simple trough concentrator geometries, all those integral approaches needed special integration routines, meanwhile, the optical parameters and geometrical properties of collectors also couldn't be changed conveniently. Flexible Monte Carlo ray trace (MCRT) methods are widely used to simulate the more accurate concentrated flux density distribution for compound parabolic solar trough concentrators, while generally they are quite time consuming. In this paper, we first mainly introduce a new backward ray tracing (BRT) method combined with the lumped effective solar cone, to simulate the cross-section flux density on the region of interest of the tube absorber. For BRT, bundles of rays are launched at absorber-surface points of interest, directly go through the glass cover of the absorber, strike on the uniformly sampled mirror segment centers in the close-related surface region of the parabolic reflector, and then direct to the effective solar cone around the incident sun beam direction after the virtual backward reflection. All the optical errors are convoluted into the effective solar cone. The brightness distribution of the effective solar cone is supposed to be circular Gaussian type. Then a parabolic trough solar collector of Euro Trough 150 is used as an example object to apply this BRT method. Euro Trough 150 is composed of RP3 mirror facets, with the focal length of 1.71m, aperture width of 5.77m, outer tube diameter of 0.07m. Also to verify the simulated flux density distributions, we establish a modified MCRT method. For this modified MCRT method, the random rays with weighted energy elements are launched in the close-related rectangle region in the aperture plane of the parabolic concentrator and the optical errors are statistically modeled in the stages of forward ray tracing process. Given the same concentrator geometric parameters and optical error values, the simulated results from these two ray tracing methods are in good consistence. The two highlights of this paper are the new optical simulation method, BRT, and figuring out the close-related mirror surface region for BRT and the close-related aperture region for MCRT in advance to effectively simulate the solar flux distribution on the absorber surface of a parabolic trough collector.

Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish

PubMed Central

Hagerman, Gordon F.; Noel, Nicole C. L.; Cao, Sylvia Y.; DuVal, Michèle G.; Oel, A. Phillip; Allison, W. Ted

2016-01-01

Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (P<0.05). We further assessed ocular photoreception by measuring the effects of UV light on body pigmentation, and observed that photoreceptor deficits and recovery occurred (p<0.01) with a timeline coincident to the OMR results. This corroborated and extended previous conclusions that UV cones are required photoreceptors for modulating body pigmentation, addressing assumptions that were unavoidable in previous experiments. Functional vision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual recovery occurs following ablation of some, but not all, cone subtypes, suggesting an opportunity to contrast and dissect the sources and mechanisms of outer retinal recovery during cone photoreceptor death and regeneration. PMID:27893779

KSC-07pd1171

NASA Image and Video Library

2007-05-14

KENNEDY SPACE CENTER, FLA. -- The locomotive and rail cars carrying solid rocket booster motor segments and two aft exit cone segments cross a road on Kennedy Space Center. These cars are headed for the SRB Assembly and Refurbishment Facility. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/George Shelton

KSC-07pd1170

NASA Image and Video Library

2007-05-14

KENNEDY SPACE CENTER, FLA. -- The locomotive and rail cars carrying solid rocket booster motor segments and two aft exit cone segments cross a road on Kennedy Space Center. These cars are headed for the SRB Assembly and Refurbishment Facility. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/George Shelton

KSC-07pd1169

NASA Image and Video Library

2007-05-14

KENNEDY SPACE CENTER, FLA. -- The locomotive and rail cars carrying solid rocket booster motor segments and two aft exit cone segments cross a road on Kennedy Space Center. These cars are headed for the SRB Assembly and Refurbishment Facility. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/George Shelton

Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health.

PubMed

Deming, Janise D; Pak, Joseph S; Brown, Bruce M; Kim, Moon K; Aung, Moe H; Eom, Yun Sung; Shin, Jung-A; Lee, Eun-Jin; Pardue, Machelle T; Craft, Cheryl Mae

2015-08-01

Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4-/-) compared with age-matched control, wild-type mice. When 2-month-old Arr4-/- mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4-/- mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4-/- mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. Our study demonstrates that Arr4-/- mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy.

Rescue of compromised lysosomes enhances degradation of photoreceptor outer segments and reduces lipofuscin-like autofluorescence in retinal pigmented epithelial cells.

PubMed

Guha, Sonia; Liu, Ji; Baltazar, Gabe; Laties, Alan M; Mitchell, Claire H

2014-01-01

Healthful cell maintenance requires the efficient degradative processing and removal of waste material. Retinal pigmented epithelial (RPE) cells have the onerous task of degrading both internal cellular debris generated through autophagy as well as phagocytosed photoreceptor outer segments. We propose that the inadequate processing material with the resulting accumulation of cellular waste contributes to the downstream pathologies characterized as age-related macular degeneration (AMD). The lysosomal enzymes responsible for clearance function optimally over a narrow range of acidic pH values; elevation of lysosomal pH by compounds like chloroquine or A2E can impair degradative enzyme activity and lead to a lipofuscin-like autofluorescence. Restoring acidity to the lysosomes of RPE cells can enhance activity of multiple degradative enzymes and is therefore a logical target in early AMD. We have identified several approaches to reacidify lysosomes of compromised RPE cells; stimulation of beta-adrenergic, A2A adenosine and D5 dopamine receptors each lowers lysosomal pH and improves degradation of outer segments. Activation of the CFTR chloride channel also reacidifies lysosomes and increases degradation. These approaches also restore the lysosomal pH of RPE cells from aged ABCA4(-/-) mice with chronically high levels of A2E, suggesting that functional signaling pathways to reacidify lysosomes are retained in aged cells like those in patients with AMD. Acidic nanoparticles transported to RPE lysosomes also lower pH and improve degradation of outer segments. In summary, the ability of diverse approaches to lower lysosomal pH and enhance outer segment degradation support the proposal that lysosomal acidification can prevent the accumulation of lipofuscin-like material in RPE cells.

Wind Turbine With Concentric Ducts

NASA Technical Reports Server (NTRS)

Muhonen, A. J.

1983-01-01

Wind Turbine device is relatively compact and efficient. Converging inner and outer ducts increase pressure difference across blades of wind turbine. Turbine shaft drives alternator housed inside exit cone. Suitable for installation on such existing structures as water towers, barns, houses, and commercial buildings.

Comparison of in vivo 3D cone-beam computed tomography tooth volume measurement protocols.

PubMed

Forst, Darren; Nijjar, Simrit; Flores-Mir, Carlos; Carey, Jason; Secanell, Marc; Lagravere, Manuel

2014-12-23

The objective of this study is to analyze a set of previously developed and proposed image segmentation protocols for precision in both intra- and inter-rater reliability for in vivo tooth volume measurements using cone-beam computed tomography (CBCT) images. Six 3D volume segmentation procedures were proposed and tested for intra- and inter-rater reliability to quantify maxillary first molar volumes. Ten randomly selected maxillary first molars were measured in vivo in random order three times with 10 days separation between measurements. Intra- and inter-rater agreement for all segmentation procedures was attained using intra-class correlation coefficient (ICC). The highest precision was for automated thresholding with manual refinements. A tooth volume measurement protocol for CBCT images employing automated segmentation with manual human refinement on a 2D slice-by-slice basis in all three planes of space possessed excellent intra- and inter-rater reliability. Three-dimensional volume measurements of the entire tooth structure are more precise than 3D volume measurements of only the dental roots apical to the cemento-enamel junction (CEJ).

Joint segmentation of lumen and outer wall from femoral artery MR images: Towards 3D imaging measurements of peripheral arterial disease.

PubMed

Ukwatta, Eranga; Yuan, Jing; Qiu, Wu; Rajchl, Martin; Chiu, Bernard; Fenster, Aaron

2015-12-01

Three-dimensional (3D) measurements of peripheral arterial disease (PAD) plaque burden extracted from fast black-blood magnetic resonance (MR) images have shown to be more predictive of clinical outcomes than PAD stenosis measurements. To this end, accurate segmentation of the femoral artery lumen and outer wall is required for generating volumetric measurements of PAD plaque burden. Here, we propose a semi-automated algorithm to jointly segment the femoral artery lumen and outer wall surfaces from 3D black-blood MR images, which are reoriented and reconstructed along the medial axis of the femoral artery to obtain improved spatial coherence between slices of the long, thin femoral artery and to reduce computation time. The developed segmentation algorithm enforces two priors in a global optimization manner: the spatial consistency between the adjacent 2D slices and the anatomical region order between the femoral artery lumen and outer wall surfaces. The formulated combinatorial optimization problem for segmentation is solved globally and exactly by means of convex relaxation using a coupled continuous max-flow (CCMF) model, which is a dual formulation to the convex relaxed optimization problem. In addition, the CCMF model directly derives an efficient duality-based algorithm based on the modern multiplier augmented optimization scheme, which has been implemented on a GPU for fast computation. The computed segmentations from the developed algorithm were compared to manual delineations from experts using 20 black-blood MR images. The developed algorithm yielded both high accuracy (Dice similarity coefficients ≥ 87% for both the lumen and outer wall surfaces) and high reproducibility (intra-class correlation coefficient of 0.95 for generating vessel wall area), while outperforming the state-of-the-art method in terms of computational time by a factor of ≈ 20. Copyright © 2015 Elsevier B.V. All rights reserved.

CNGA3 deficiency affects cone synaptic terminal structure and function and leads to secondary rod dysfunction and degeneration.

PubMed

Xu, Jianhua; Morris, Lynsie M; Michalakis, Stylianos; Biel, Martin; Fliesler, Steven J; Sherry, David M; Ding, Xi-Qin

2012-03-01

To investigate rod function and survival after cone dysfunction and degeneration in a mouse model of cone cyclic nucleotide-gated (CNG) channel deficiency. Rod function and survival in mice with cone CNG channel subunit CNGA3 deficiency (CNGA3-/- mice) were evaluated by electroretinographic (ERG), morphometric, and Western blot analyses. The arrangement, integrity, and ultrastructure of photoreceptor terminals were investigated by immunohistochemistry and electron microscopy. The authors found loss of cone function and cone death accompanied by impairment of rods and rod-driven signaling in CNGA3-/- mice. Scotopic ERG b-wave amplitudes were reduced by 15% at 1 month, 30% at 6 months, and 40% at 9 months and older, while scotopic a-wave amplitudes were decreased by 20% at 9 months, compared with ERGs of age-matched wild-type mice. Outer nuclear layer thickness in CNGA3-/- retina was reduced by 15% at 12 months compared with age-matched wild-type controls. This was accompanied by a 30%-40% reduction in expression of rod-specific proteins, including rhodopsin, rod transducin α-subunit, and glutamic acid-rich protein (GARP). Cone terminals in the CNGA3-/- retina showed a progressive loss of neurochemical and ultrastructural integrity. Abnormalities were observed as early as 1 month. Disorganized rod terminal ultrastructure was noted by 12 months. These findings demonstrate secondary rod impairment and degeneration after cone degeneration in mice with cone CNG channel deficiency. Loss of cone phototransduction accompanies the compromised integrity of cone terminals. With time, rod synaptic structure, function, and viability also become compromised.

Observation of Dirac-like band dispersion in LaAgSb 2

DOE PAGES

Shi, X.; Richard, P.; Wang, Kefeng; ...

2016-02-16

In this paper, we present a combined angle-resolved photoemission spectroscopy (ARPES) and first-principles calculations study of the electronic structure of LaAgSb 2 in the entire first Brillouin zone. We observe a Dirac-cone-like structure in the vicinity of the Fermi level formed by the crossing of two linear energy bands, as well as the nested segments of a Fermi surface pocket emerging from the cone. In conclusion, our ARPES results show the close relationship of the Dirac cone to the charge-density-wave ordering, providing consistent explanations for exotic behaviors in this material.

Partially segmented deformable mirror

DOEpatents

Bliss, E.S.; Smith, J.R.; Salmon, J.T.; Monjes, J.A.

1991-05-21

A partially segmented deformable mirror is formed with a mirror plate having a smooth and continuous front surface and a plurality of actuators to its back surface. The back surface is divided into triangular areas which are mutually separated by grooves. The grooves are deep enough to make the plate deformable and the actuators for displacing the mirror plate in the direction normal to its surface are inserted in the grooves at the vertices of the triangular areas. Each actuator includes a transducer supported by a receptacle with outer shells having outer surfaces. The vertices have inner walls which are approximately perpendicular to the mirror surface and make planar contacts with the outer surfaces of the outer shells. The adhesive which is used on these contact surfaces tends to contract when it dries but the outer shells can bend and serve to minimize the tendency of the mirror to warp. 5 figures.

Partially segmented deformable mirror

DOEpatents

Bliss, Erlan S.; Smith, James R.; Salmon, J. Thaddeus; Monjes, Julio A.

1991-01-01

A partially segmented deformable mirror is formed with a mirror plate having a smooth and continuous front surface and a plurality of actuators to its back surface. The back surface is divided into triangular areas which are mutually separated by grooves. The grooves are deep enough to make the plate deformable and the actuators for displacing the mirror plate in the direction normal to its surface are inserted in the grooves at the vertices of the triangular areas. Each actuator includes a transducer supported by a receptacle with outer shells having outer surfaces. The vertices have inner walls which are approximately perpendicular to the mirror surface and make planar contacts with the outer surfaces of the outer shells. The adhesive which is used on these contact surfaces tends to contract when it dries but the outer shells can bend and serve to minimize the tendency of the mirror to warp.

Temporal and spatial characteristics of male cone development in Metasequoia glyptostroboides Hu et Cheng

PubMed Central

Jin, Biao; Tang, Liang; Lu, Yan; Wang, Di; Zhang, Min; Ma, Jiuxia

2012-01-01

Metasequoia glyptostroboides, a famous relic species of conifer that survived in China, has been successfully planted in large numbers across the world. However, limited information on male cone development in the species is available. In this study, we observed the morphological and anatomical changes that occur during male cone development in M. glyptostroboides using semi-thin sections and scanning electron microscopy. The male cones were borne oppositely on one-year-old twigs that were mainly located around the outer and sunlit parts of crown. Male cones were initiated from early September and shed pollen in the following February. Each cone consisted of spirally arranged microsporophylls subtended by decussate sterile scales, and each microsporophyll commonly consisted of three microsporangia and a phylloclade. The microsporangial wall was composed of an epidermis, endothecium, and tapetum. In mid-February, the endothecium and tapetum layers disintegrated, and in the epidermal layer the cell walls were thickened with inner protrusions. Subsequently, dehiscence of the microsporangia occurred through rupturing of the microsporangial wall along the dehiscence line. These results suggest that the structure, morphology, architecture and arrangement of male cones of M. glyptostroboides are mainly associated with the production, protection and dispersal of pollen for optimization of wind pollination. PMID:23221679

Temporal and spatial characteristics of male cone development in Metasequoia glyptostroboides Hu et Cheng.

PubMed

Jin, Biao; Tang, Liang; Lu, Yan; Wang, Di; Zhang, Min; Ma, Jiuxia

2012-12-01

Metasequoia glyptostroboides, a famous relic species of conifer that survived in China, has been successfully planted in large numbers across the world. However, limited information on male cone development in the species is available. In this study, we observed the morphological and anatomical changes that occur during male cone development in M. glyptostroboides using semi-thin sections and scanning electron microscopy. The male cones were borne oppositely on one-year-old twigs that were mainly located around the outer and sunlit parts of crown. Male cones were initiated from early September and shed pollen in the following February. Each cone consisted of spirally arranged microsporophylls subtended by decussate sterile scales, and each microsporophyll commonly consisted of three microsporangia and a phylloclade. The microsporangial wall was composed of an epidermis, endothecium, and tapetum. In mid-February, the endothecium and tapetum layers disintegrated, and in the epidermal layer the cell walls were thickened with inner protrusions. Subsequently, dehiscence of the microsporangia occurred through rupturing of the microsporangial wall along the dehiscence line. These results suggest that the structure, morphology, architecture and arrangement of male cones of M. glyptostroboides are mainly associated with the production, protection and dispersal of pollen for optimization of wind pollination.

Effects of acidic amino acid antagonists upon the spectral properties of carp horizontal cells: circuitry of the outer retina.

PubMed

Mangel, S C; Ariel, M; Dowling, J E

1985-11-01

The acidic amino acid receptor antagonists, alpha-methylglutamate and alpha-aminoadipate, were applied to the carp retina to study their effects upon the spectral properties of horizontal cells and to elucidate the synaptic connections between horizontal cells and cones. Application of these antagonists strongly hyperpolarized the L-type cone horizontal cells and reduced the responses of these horizontal cells to red light more than to blue light. Application of Co2+ ions to the retina, a procedure which decreases transmitter release, also hyperpolarized the L-type cone horizontal cells but reduced the response of these horizontal cells to red and blue lights equally. These results suggest that red- or long wavelength-sensitive cones release a different transmitter onto L-type cone horizontal cells than do short wavelength-sensitive cones. Application of the acidic amino acid antagonists also revealed details of the feedback pathway from L-type cone horizontal cells to cones. Previous studies have shown that feedback varies directly with stimulus size and that the effects of feedback on the responses of cones are observed as a transient waveform at response onset (a large, hyperpolarizing potential that is quickly followed by a smaller plateau potential). Application of the acidic amino acid antagonists at a dose which partially hyperpolarized the horizontal cells selectively enhanced the response of the cells to blue lights, when full field, and not spot, stimuli were used. The antagonists also eliminated the transient at response onset. These findings are consistent with the presence of a feedback pathway from L-type cone horizontal cells to short wavelength cones but not to long (red-sensitive) cones.

Tissue inhibitor of metalloproteinases 1 enhances rod survival in the rd1 mouse retina.

PubMed

Kim, Hwa Sun; Vargas, Andrew; Eom, Yun Sung; Li, Justin; Yamamoto, Kyra L; Craft, Cheryl Mae; Lee, Eun-Jin

2018-01-01

Retinitis pigmentosa (RP), an inherited retinal degenerative disease, is characterized by a progressive loss of rod photoreceptors followed by loss of cone photoreceptors. Previously, when tissue inhibitor of metalloproteinase 1 (TIMP1), a key extracellular matrix (ECM) regulator that binds to and inhibits activation of Matrix metallopeptidase 9 (MMP9) was intravitreal injected into eyes of a transgenic rhodopsin rat model of RP, S334ter-line3, we discovered cone outer segments are partially protected. In parallel, we reported that a specific MMP9 and MMP2 inhibitor, SB-3CT, interferes with mechanisms leading to rod photoreceptor cell death in an MMP9 dependent manner. Here, we extend our initial rat studies to examine the potential of TIMP1 as a treatment in retinal degeneration by investigating neuroprotective effects in a classic mouse retinal degeneration model, rdPde6b-/- (rd1). The results clearly demonstrate that intravitreal injections of TIMP1 produce extended protection to delay rod photoreceptor cell death. The mean total number of rods in whole-mount retinas was significantly greater in TIMP-treated rd1 retinas (postnatal (P) 30, P35 (P<0.0001) and P45 (P<0.05) than in saline-treated rd1 retinas. In contrast, SB-3CT did not delay rod cell death, leading us to further investigate alternative pathways that do not involve MMPs. In addition to inducing phosphorylated ERK1/2, TIMP1 significantly reduces BAX activity and delays attenuation of the outer nuclear layer (ONL). Physiological responses using scotopic electroretinograms (ERG) reveal b-wave amplitudes from TIMP1-treated retinas are significantly greater than from saline-treated rd1 retinas (P<0.05). In later degenerative stages of rd1 retinas, photopic b-wave amplitudes from TIMP1-treated rd1 retinas are significantly larger than from saline-treated rd1 retinas (P<0.05). Our findings demonstrate that TIMP1 delays photoreceptor cell death. Furthermore, this study provides new insights into how TIMP1 works in the mouse animal model of RP.

Patellar segmentation from 3D magnetic resonance images using guided recursive ray-tracing for edge pattern detection

NASA Astrophysics Data System (ADS)

Cheng, Ruida; Jackson, Jennifer N.; McCreedy, Evan S.; Gandler, William; Eijkenboom, J. J. F. A.; van Middelkoop, M.; McAuliffe, Matthew J.; Sheehan, Frances T.

2016-03-01

The paper presents an automatic segmentation methodology for the patellar bone, based on 3D gradient recalled echo and gradient recalled echo with fat suppression magnetic resonance images. Constricted search space outlines are incorporated into recursive ray-tracing to segment the outer cortical bone. A statistical analysis based on the dependence of information in adjacent slices is used to limit the search in each image to between an outer and inner search region. A section based recursive ray-tracing mechanism is used to skip inner noise regions and detect the edge boundary. The proposed method achieves higher segmentation accuracy (0.23mm) than the current state-of-the-art methods with the average dice similarity coefficient of 96.0% (SD 1.3%) agreement between the auto-segmentation and ground truth surfaces.

Cell and current collector felt arrangement for solid oxide electrochemical cell combinations

DOEpatents

Reichner, Philip

1988-01-01

A solid electrolyte electrochemical cell combination 1 is made, comprising an annular, axially elongated, inner electrode 2 containing at least one interior gas feed conduit 3; annular solid electrolyte segments 4 around and covering portions of the inner electrode; annular outer electrode segments 6 around and covering portions of the electrolyte segments; electronically conducting, non-porous, interconnection material 5 disposed between electrolyte segments and in contact with the inner electrode, and electronically conducting, porous, metal fiber current collector felts 7 disposed on top of the non-porous interconnect material and outer electrode segments, where both the non-porous interconnect material and the porous metal felts are disposed circumferentially about the cell, transversely to the axial length of the cell and the inner electrode is continuous for the entire axial length of the cell combination.

Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health

PubMed Central

Deming, Janise D.; Pak, Joseph S.; Brown, Bruce M.; Kim, Moon K.; Aung, Moe H.; Eom, Yun Sung; Shin, Jung-a; Lee, Eun-Jin; Pardue, Machelle T.; Craft, Cheryl Mae

2015-01-01

Purpose Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. Methods A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4−/−) compared with age-matched control, wild-type mice. Results When 2-month-old Arr4−/− mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4−/− mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4−/− mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. Conclusions Our study demonstrates that Arr4−/− mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy. PMID:26284544

Neurobiological hypothesis of color appearance and hue perception

PubMed Central

Schmidt, Brian P.; Neitz, Maureen; Neitz, Jay

2014-01-01

DeValois and DeValois (1993) showed that to explain hue appearance, S-cone signals have to be combined with M vs. L opponent signals in two different ways to produce red-green and yellow-blue axes respectively. Recently, it has been shown that color appearance is normal for individuals with genetic mutations that block S-cone input to blue-on ganglion cells. This is inconsistent with the DeValois hypothesis in which S-opponent konio-geniculate signals are combined with L−M signals at a 3rd processing stage in cortex. Instead, here we show that color appearance, including individual differences never explained before, are predicted by a model in which S-cone signals are combined with L vs. M signals in the outer retina. PMID:24695170

HYPERAUTOFLUORESCENT RING IN AUTOIMMUNE RETINOPATHY

PubMed Central

LIMA, LUIZ H.; GREENBERG, JONATHAN P.; GREENSTEIN, VIVIENNE C.; SMITH, R. THEODORE; SALLUM, JULIANA M. F.; THIRKILL, CHARLES; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.

2015-01-01

Purpose To report the presence of a hyperautofluorescent ring and corresponding spectral-domain optical coherence tomography (SD-OCT) features seen in patients with autoimmune retinopathy. Methods All eyes were evaluated by funduscopic examination, full-fleld electroretinography, fundus autofluorescence, and SD-OCT. Further confirmation of the diagnosis was obtained with immunoblot and immunohistochemistry testing of the patient’s serum. Humphrey visual fields and microperimetry were also performed. Results Funduscopic examination showed atrophic retinal pigment epithelium (RPE) associated with retinal artery narrowing but without pigment deposits. The scotopic and photopic full-field electroretinograms were nondetectable in three patients and showed a cone–rod pattern of dysfunction in one patient. Fundus autofluorescence revealed a hyperautofluorescent ring in the parafoveal region, and the corresponding SD-OCT demonstrated loss of the photoreceptor inner segment–outer segment junction with thinning of the outer nuclear layer from the region of the hyperautofluorescent ring toward the retinal periphery. The retinal layers were generally intact within the hyperautofluorescent ring, although the inner segment–outer segment junction was disrupted, and the outer nuclear layer and photoreceptor outer segment layer were thinned. Conclusion This case series revealed the structure of the hyperautofluorescent ring in autoimmune retinopathy using SD-OCT. Fundus autofluorescence and SD-OCT may aid in the diagnosis of autoimmune retinopathy and may serve as a tool to monitor its progression. PMID:22218149

Segmentation of large periapical lesions toward dental computer-aided diagnosis in cone-beam CT scans

NASA Astrophysics Data System (ADS)

Rysavy, Steven; Flores, Arturo; Enciso, Reyes; Okada, Kazunori

2008-03-01

This paper presents an experimental study for assessing the applicability of general-purpose 3D segmentation algorithms for analyzing dental periapical lesions in cone-beam computed tomography (CBCT) scans. In the field of Endodontics, clinical studies have been unable to determine if a periapical granuloma can heal with non-surgical methods. Addressing this issue, Simon et al. recently proposed a diagnostic technique which non-invasively classifies target lesions using CBCT. Manual segmentation exploited in their study, however, is too time consuming and unreliable for real world adoption. On the other hand, many technically advanced algorithms have been proposed to address segmentation problems in various biomedical and non-biomedical contexts, but they have not yet been applied to the field of dentistry. Presented in this paper is a novel application of such segmentation algorithms to the clinically-significant dental problem. This study evaluates three state-of-the-art graph-based algorithms: a normalized cut algorithm based on a generalized eigen-value problem, a graph cut algorithm implementing energy minimization techniques, and a random walks algorithm derived from discrete electrical potential theory. In this paper, we extend the original 2D formulation of the above algorithms to segment 3D images directly and apply the resulting algorithms to the dental CBCT images. We experimentally evaluate quality of the segmentation results for 3D CBCT images, as well as their 2D cross sections. The benefits and pitfalls of each algorithm are highlighted.

CNGA3 Deficiency Affects Cone Synaptic Terminal Structure and Function and Leads to Secondary Rod Dysfunction and Degeneration

PubMed Central

Xu, Jianhua; Morris, Lynsie M.; Michalakis, Stylianos; Biel, Martin; Fliesler, Steven J.; Sherry, David M.

2012-01-01

Purpose. To investigate rod function and survival after cone dysfunction and degeneration in a mouse model of cone cyclic nucleotide-gated (CNG) channel deficiency. Methods. Rod function and survival in mice with cone CNG channel subunit CNGA3 deficiency (CNGA3−/− mice) were evaluated by electroretinographic (ERG), morphometric, and Western blot analyses. The arrangement, integrity, and ultrastructure of photoreceptor terminals were investigated by immunohistochemistry and electron microscopy. Results. The authors found loss of cone function and cone death accompanied by impairment of rods and rod-driven signaling in CNGA3−/− mice. Scotopic ERG b-wave amplitudes were reduced by 15% at 1 month, 30% at 6 months, and 40% at 9 months and older, while scotopic a-wave amplitudes were decreased by 20% at 9 months, compared with ERGs of age-matched wild-type mice. Outer nuclear layer thickness in CNGA3−/− retina was reduced by 15% at 12 months compared with age-matched wild-type controls. This was accompanied by a 30%–40% reduction in expression of rod-specific proteins, including rhodopsin, rod transducin α-subunit, and glutamic acid-rich protein (GARP). Cone terminals in the CNGA3−/− retina showed a progressive loss of neurochemical and ultrastructural integrity. Abnormalities were observed as early as 1 month. Disorganized rod terminal ultrastructure was noted by 12 months. Conclusions. These findings demonstrate secondary rod impairment and degeneration after cone degeneration in mice with cone CNG channel deficiency. Loss of cone phototransduction accompanies the compromised integrity of cone terminals. With time, rod synaptic structure, function, and viability also become compromised. PMID:22247469

Phagocytosis of photoreceptor outer segments by transplanted human neural stem cells as a neuroprotective mechanism in retinal degeneration.

PubMed

Cuenca, Nicolás; Fernández-Sánchez, Laura; McGill, Trevor J; Lu, Bin; Wang, Shaomei; Lund, Raymond; Huhn, Stephen; Capela, Alexandra

2013-10-15

Transplantation of human central nervous system stem cells (HuCNS-SC) into the subretinal space of Royal College of Surgeons (RCS) rats preserves photoreceptors and visual function. To explore possible mechanism(s) of action underlying this neuroprotective effect, we performed a detailed morphologic and ultrastructure analysis of HuCNS-SC transplanted retinas. The HuCNS-SC were transplanted into the subretinal space of RCS rats. Histologic examination of the transplanted retinas was performed by light and electron microscopy. Areas of the retina adjacent to HuCNS-SC graft (treated regions) were analyzed and compared to control sections obtained from the same retina, but distant from the transplant site (untreated regions). The HuCNS-SC were detected as a layer of STEM 121 immunopositive cells in the subretinal space. In treated regions, preserved photoreceptor nuclei, as well as inner and outer segments were identified readily. In contrast, classic signs of degeneration were observed in the untreated regions. Interestingly, detailed ultrastructure analysis revealed a striking preservation of the photoreceptor-bipolar-horizontal cell synaptic contacts in the outer plexiform layer (OPL) of treated areas, in stark contrast with untreated areas. Finally, the presence of phagosomes and vesicles exhibiting the lamellar structure of outer segments also was detected within the cytosol of HuCNS-SC, indicating that these cells have phagocytic capacity in vivo. This study reveals the novel finding that preservation of specialized synaptic contacts between photoreceptors and second order neurons, as well as phagocytosis of photoreceptor outer segments, are potential mechanism(s) of HuCNS-SC transplantation, mediating functional rescue in retinal degeneration.

Multiple-Cone Sunshade for a Spaceborne Telescope

NASA Technical Reports Server (NTRS)

Cafferty, Terry; Ford, Virginia

2008-01-01

A document describes a sunshade assembly for the spaceborne telescope of the Terrestrial Planet Finder Coronagraph mission. During operation, the telescope is aimed at target stars in the semihemisphere away from the Earth's Sun. The observatory rotates about its pointing axis during a single star observation, resulting in relative movement of the Sun. The sunshade assembly protects the telescope against excessive solar-induced thermal distortions for times long enough to complete observations. The assembly includes a cylindrical baffle immediately surrounding the telescope, and a series of coaxial conical shields at half-cone angle increments of between 3 and 6. The black inner surface of the cylindrical baffle suppresses stray light. The outer surface of the cylindrical baffle and all the surfaces of the conical shields except the outermost one are specular and highly reflective in the infrared. The outer surface of the outer shield is a material with low solar absorptance and high infrared emittance, such as silverized Teflon or white paint. This arrangement strongly radiatively couples each shield layer more effectively to cold space than to adjacent shield layers. The result is that the solar-driven temperature gradients in the cylindrical baffle are nearly negated, and only weakly communicated to the highly-infrared-reflective face of the primary telescope mirror.

Omnidirectional wheel

NASA Technical Reports Server (NTRS)

Blumrich, J. F. (Inventor)

1974-01-01

The apparatus consists of a wheel having a hub with radially disposed spokes which are provided with a plurality of circumferential rim segments. These rim segments carry, between the spokes, rim elements which are rigid relative to their outer support surfaces, and defined in their outer contour to form a part of the circle forming the wheel diameter. The rim segments have provided for each of the rim elements an independent drive means selectively operable when the element is in ground contact to rotatably drive the rim element in a direction of movement perpendicularly lateral to the normal plane of rotation and movement of the wheel. This affords the wheel omnidirectional movement.

Theoretical Elastic Stress Distributions Arising from Discontinuities and Edge Loads in Several Shell-Type Structures

NASA Technical Reports Server (NTRS)

Johns, Robert H.; Orange, Thomas W.

1961-01-01

The deformation and complete stress distribution are determined for each of the following edge loaded thin shells of revolution: (1) a right circular cylinder, (2) a frustum of a right circular cone, and (3) a portion of a sphere. The locations of the maximum circumferential and meridional stresses on both the inner and outer surfaces are also found. The basic equations for the above were selected from the published literature on the subject and expanded to produce to resultant-stress equations in closed from where practicable to do so. Equations are also developed for the discontinuity shear force and bending moment at each of the following junction: (1) axial change of thickness in a circular cylinder, (2) axial change of thickness in a cone, (3) change of thickness in a portion of a sphere, (4) a cylinder and a cone, (5) a cylinder and a portion of a sphere(6) a cylinder and a flat head, and (7) a cone and a portion of a sphere.

Blue light-induced retinal lesions, intraretinal vascular leakage and edema formation in the all-cone mouse retina

PubMed Central

Geiger, P; Barben, M; Grimm, C; Samardzija, M

2015-01-01

Little is known about the mechanisms underlying macular degenerations, mainly for the scarcity of adequate experimental models to investigate cone cell death. Recently, we generated R91W;Nrl−/− double-mutant mice, which display a well-ordered all-cone retina with normal retinal vasculature and a strong photopic function that generates useful vision. Here we exposed R91W;Nrl−/− and wild-type (wt) mice to toxic levels of blue light and analyzed their retinas at different time points post illumination (up to 10 days). While exposure of wt mice resulted in massive pyknosis in a focal region of the outer nuclear layer (ONL), the exposure of R91W;Nrl−/− mice led to additional cell death detected within the inner nuclear layer. Microglia/macrophage infiltration at the site of injury was more pronounced in the all-cone retina of R91W;Nrl−/− than in wt mice. Similarly, vascular leakage was abundant in the inner and outer retina in R91W;Nrl−/− mice, whereas it was mild and restricted to the subretinal space in wt mice. This was accompanied by retinal swelling and the appearance of cystoid spaces in both inner and ONLs of R91W;Nrl−/− mice indicating edema in affected areas. In addition, basal expression levels of tight junction protein-1 encoding ZO1 were lower in R91W;Nrl−/− than in wt retinas. Collectively, our data suggest that exposure of R91W;Nrl−/− mice to blue light not only induces cone cell death but also disrupts the inner blood–retinal barrier. Macular edema in humans is a result of diffuse capillary leakage and microaneurysms in the macular region. Blue light exposure of the R91W;Nrl−/− mouse could therefore be used to study molecular events preceding edema formation in a cone-rich environment, and thus potentially help to develop treatment strategies for edema-based complications in macular degenerations. PMID:26583326

Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell

PubMed Central

Lei, Lei; Tzekov, Radouil; Li, Huapeng; McDowell, J. Hugh; Gao, Guangping; Smith, W. Clay; Tang, Shibo; Kaushal, Shalesh

2017-01-01

The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and the autofluorescence was detected by fluorescence-activated cell sorting. Supplementation with different types of rod outer segments increased lipofuscin-like autofluorescence (LLAF) after the inhibition of autophagy, while the induction of autophagy (e.g., application of rapamycin) decreased LLAF. The effects of autophagy induction were further confirmed by Western blotting, which showed the conversion of LC3-I to LC3-II, and by immunofluorescence microscopy, which detected the lysosomal activity of the autophagy inducers. We also monitored LLAF after the application of several autophagy inhibitors by RNA-interference and confocal microscopy. The results showed that, in general, the inhibition of the autophagy-related proteins resulted in an increase in LLAF when cells were fed with rod outer segments, which further confirms the effect of autophagy in the fate of RPE lipofuscin degradation. These results emphasize the complex role of autophagy in modulating RPE autofluorescence and confirm the possibility of the pharmacological clearance of RPE lipofuscin by small molecules. PMID:28353645

Transient spectral domain optical coherence tomography findings in classic MEWDS: a case report.

PubMed

Lavigne, Luciana Castro; Isaac, David Leonardo Cruvinel; Duarte Júnior, José Osório; Avila, Marcos Pereira de

2014-01-01

The purpose of this study was to describe a patient with multiple evanescent white dot syndrome (MEWDS) who presented with classic retinal findings and transient changes in outer retinal anatomy. A 20-year-old man presented with mild blurred vision in the left eye, reporting flu-like symptoms 1 week before the visual symptoms started. Fundus examination of the left eye revealed foveal granularity and multiple scattered spots deep to the retina in the posterior pole. Fluorescein angiography and indocyanine green angiography showed typical MEWDS findings. Spectral Domain Optical Coherence Tomography has shown transient changes in outer retinal anatomy with disappearance of inner segment-outer segment junction and mild attenuation of external limiting membrane. Six months later, Spectral Domain Optical Coherence Tomography has shown complete resolution with recovery of normal outer retinal aspect.

Zone heated diesel particulate filter electrical connection

DOEpatents

Gonze, Eugene V.; Paratore, Jr., Michael J.

2010-03-30

An electrical connection system for a particulate filter is provided. The system includes: a particulate filter (PF) disposed within an outer shell wherein the PF is segmented into a plurality of heating zones; an outer mat disposed between the particulate filter and the outer shell; an electrical connector coupled to the outer shell of the PF; and a plurality of printed circuit connections that extend along the outer surface of the PF from the electrical connector to the plurality of heating zones.

Ocular anatomy of the black pacu (Colossoma macropomum): gross, histologic, and diagnostic imaging.

PubMed

Gustavsen, Kate A; Paul-Murphy, Joanne R; Weber, Ernest Scott; Zwingenberger, Allison L; Dunker, Freeland H; Dubielzig, Richard R; Reilly, Christopher M; Murphy, Christopher J

2018-01-30

To describe the ocular anatomy of the black pacu (Colossoma macropomum), a freshwater teleost fish of the Amazon River basin, including an unusual choroid laden with adipose tissue. Three adult black pacu were anesthetized and examined clinically and with ocular ultrasonography, then euthanized. Three fish were euthanized and their heads imaged immediately postmortem using computed tomography. One fish was euthanized and its exenterated eyes imaged by high-resolution magnetic resonance imaging. The exenterated eyes of all seven fish were fixed in formalin; eyes from three fish were examined grossly and histologically. Additionally, archived histologic sections from two smaller black pacu specimens were examined. Findings were consistent among the ocular imaging modalities used. Intrinsic to the sclera were circumferential ossicles and scleral cartilage. The lens was spherical and protruded through the ovoid pupil with an aphakic space inferiorly when the accommodative mechanism was relaxed under anesthesia. Both a small falciform process and epiretinal vasculature were present in the posterior segment. The retina was cone-rich, and processes of the retinal pigment epithelium enveloped the photoreceptor outer segments. Remarkably, the choroid occupied one-third of the anteroposterior length of the globe; histology confirmed that the bulk of the choroid was composed of adipose tissue. The eye of the pacu overall is typical of teleosts but has the notable and consistent finding of a substantive store of choroidal fat of unknown function. © 2018 American College of Veterinary Ophthalmologists.

Cone Structure in Retinal Degeneration Associated with Mutations in the peripherin/RDS Gene

PubMed Central

Talcott, Katherine E.; Ratnam, Kavitha; Sundquist, Sanna M.; Lucero, Anya S.; Day, Shelley; Zhang, Yuhua; Roorda, Austin

2011-01-01

Purpose. To study cone photoreceptor structure and function associated with mutations in the second intradiscal loop region of peripherin/RDS. Methods. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in four patients with peripherin/RDS mutations and 27 age-similar healthy subjects. Measures of retinal structure and fundus autofluorescence (AF) were correlated with visual function, including best-corrected visual acuity (BCVA), kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The coding regions of the peripherin/RDS gene were sequenced in each patient. Results. Heterozygous mutations in peripherin/RDS were predicted to affect protein structure in the second intradiscal domain in each patient (Arg172Trp, Gly208Asp, Pro210Arg and Cys213Tyr). BCVA was at least 20/32 in the study eye of each patient. Diffuse cone-greater-than-rod dysfunction was present in patient 1, while rod-greater-than-cone dysfunction was present in patient 4; macular outer retinal dysfunction was present in all patients. Macular AF was heterogeneous, and the photoreceptor-retinal pigment epithelial (RPE) junction layer showed increased reflectivity at the fovea in all patients except patient 1, who showed cone-rod dystrophy. Cone packing was irregular, and cone spacing was significantly increased (z-scores >2) at most locations throughout the central 4° in each patient. Conclusions. peripherin/RDS mutations produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction, and increased cone spacing, consistent with cone loss in the macula. The abnormalities observed suggest that the integrity of the second intradiscal domain of peripherin/RDS is critical for normal macular cone structure. PMID:21071739

Development of a Full Ice-cream Cone Model for Halo Coronal Mass Ejections

NASA Astrophysics Data System (ADS)

Na, Hyeonock; Moon, Y.-J.; Lee, Harim

2017-04-01

It is essential to determine three-dimensional parameters (e.g., radial speed, angular width, and source location) of coronal mass ejections (CMEs) for the space weather forecast. In this study, we investigate which cone type represents a halo CME morphology using 29 CMEs (12 Solar and Heliospheric Observatory (SOHO)/Large Angle and Spectrometric Coronagraph (LASCO) halo CMEs and 17 Solar Terrestrial Relations Observatory (STEREO)/Sun-Earth Connection Coronal and Heliospheric Investigation COR2 halo CMEs) from 2010 December to 2011 June. These CMEs are identified as halo CMEs by one spacecraft (SOHO or one of STEREO A and B) and limb ones by the other spacecraft (One of STEREO A and B or SOHO). From cone shape parameters of these CMEs, such as their front curvature, we find that the CME observational structures are much closer to a full ice-cream cone type than a shallow ice-cream cone type. Thus, we develop a full ice-cream cone model based on a new methodology that the full ice-cream cone consists of many flat cones with different heights and angular widths to estimate the three-dimensional parameters of the halo CMEs. This model is constructed by carrying out the following steps: (1) construct a cone for a given height and angular width, (2) project the cone onto the sky plane, (3) select points comprising the outer boundary, and (4) minimize the difference between the estimated projection speeds with the observed ones. By applying this model to 12 SOHO/LASCO halo CMEs, we find that 3D parameters from our method are similar to those from other stereoscopic methods (I.e., a triangulation method and a Graduated Cylindrical Shell model).

Development of a Full Ice-cream Cone Model for Halo Coronal Mass Ejections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Na, Hyeonock; Moon, Y.-J.; Lee, Harim, E-mail: nho0512@khu.ac.kr, E-mail: moonyj@khu.ac.kr

It is essential to determine three-dimensional parameters (e.g., radial speed, angular width, and source location) of coronal mass ejections (CMEs) for the space weather forecast. In this study, we investigate which cone type represents a halo CME morphology using 29 CMEs (12 Solar and Heliospheric Observatory (SOHO) /Large Angle and Spectrometric Coronagraph (LASCO) halo CMEs and 17 Solar Terrestrial Relations Observatory ( STEREO )/Sun–Earth Connection Coronal and Heliospheric Investigation COR2 halo CMEs) from 2010 December to 2011 June. These CMEs are identified as halo CMEs by one spacecraft ( SOHO or one of STEREO A and B ) and limbmore » ones by the other spacecraft (One of STEREO A and B or SOHO ). From cone shape parameters of these CMEs, such as their front curvature, we find that the CME observational structures are much closer to a full ice-cream cone type than a shallow ice-cream cone type. Thus, we develop a full ice-cream cone model based on a new methodology that the full ice-cream cone consists of many flat cones with different heights and angular widths to estimate the three-dimensional parameters of the halo CMEs. This model is constructed by carrying out the following steps: (1) construct a cone for a given height and angular width, (2) project the cone onto the sky plane, (3) select points comprising the outer boundary, and (4) minimize the difference between the estimated projection speeds with the observed ones. By applying this model to 12 SOHO /LASCO halo CMEs, we find that 3D parameters from our method are similar to those from other stereoscopic methods (i.e., a triangulation method and a Graduated Cylindrical Shell model).« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hajian, Hodjat, E-mail: hodjat.hajian@bilkent.edu.tr; Ozbay, Ekmel; Department of Physics, Bilkent University, 06800 Ankara

Certain types of photonic crystals with Dirac cones at the Γ point of their band structure have a zero effective index of refraction at Dirac cone frequency. Here, by an appropriate design of the photonic structure, we obtain a strong coupling between modes around the Dirac cone frequency of an all-dielectric zero-index photonic crystal and the guided ones supported by a photonic crystal waveguide. Consequently, we experimentally demonstrate that the presence of the zero-index photonic crystal at the inner side of the photonic crystal waveguide leads to an enhancement in the transmission of some of the guided waves passing throughmore » this hybrid system. Moreover, those electromagnetic waves extracted from the structure with enhanced transmission exhibit high directional beaming due to the presence of the zero-index photonic crystal at the outer side of the photonic crystal waveguide.« less

In vitro comparison of gutta-percha-filled area percentages in root canals instrumented and obturated with different techniques.

PubMed

Yilmaz, Ayca; Karagoz-Kucukay, Isil

2017-01-01

To evaluate the efficacy of different obturation techniques in root canals instrumented either by hand or rotary instruments with regard to the percentage of gutta- percha-filled area (PGFA). One hundred and sixty extracted mandibular premolars with single, straight root canals were studied. Root canals were prepared to an apical size of 30 by hand with a modified crown-down technique or the ProTaper and HEROShaper systems. Teeth were divided into eight groups (n=20) according to the following instrumentation and obturation techniques: G1: Hand files+lateral condensation (LC), G2: Hand files+Thermafil, G3: ProTaper+LC, G4: ProTaper+single-cone, G5: ProTaper+ProTaper-Obturator, G6: HEROShaper+LC, G7: HEROShaper+single-cone, G8: HEROShaper+HEROfill. Horizontal sections were cut at 1, 3, 5, 7, 9, 11 and 13 mm from the apical foramen. A total of 1120 sections obtained were digitally photographed under a stereomicroscope set at 48X magnification. The cross-sectional area of the canal and the gutta-percha was measured by digital image analysis and the PGFA was calculated for each section. The mean of the PGFA in Thermafil (G2), ProTaper-Obturator (G5) and HEROfill (G8) groups was significantly higher than the other groups. In G3 and G4, PGFA showed no significant difference in the apical segments whereas PGFA was significantly higher at the middle and coronal segments in G3. In G6 and G7, PGFA showed no significant difference in the apical and middle segments whereas PGFA was significantly higher at the coronal segments in G6. The carrier-based gutta-percha obturation systems revealed significantly higher PGFA in comparison to single-cone and lateral condensation techniques.

Form, shape and function: segmented blood flow in the choriocapillaris

PubMed Central

Zouache, M. A.; Eames, I.; Klettner, C. A.; Luthert, P. J.

2016-01-01

The development of fluid transport systems was a key event in the evolution of animals and plants. While within vertebrates branched geometries predominate, the choriocapillaris, which is the microvascular bed that is responsible for the maintenance of the outer retina, has evolved a planar topology. Here we examine the flow and mass transfer properties associated with this unusual geometry. We show that as a result of the form of the choriocapillaris, the blood flow is decomposed into a tessellation of functional vascular segments of various shapes delineated by separation surfaces across which there is no flow, and in the vicinity of which the transport of passive substances is diffusion-limited. The shape of each functional segment is determined by the distribution of arterioles and venules and their respective relative flow rates. We also show that, remarkably, the mass exchange with the outer retina is a function of the shape of each functional segment. In addition to introducing a novel framework in which the structure and function of the metabolite delivery system to the outer retina may be investigated in health and disease, the present work provides a general characterisation of the flow and transfers in multipole Hele-Shaw configurations. PMID:27779198

Segmented annular combustor

DOEpatents

Reider, Samuel B.

1979-01-01

An industrial gas turbine engine includes an inclined annular combustor made up of a plurality of support segments each including inner and outer walls of trapezoidally configured planar configuration extents and including side flanges thereon interconnected by means of air cooled connector bolt assemblies to form a continuous annular combustion chamber therebetween and wherein an air fuel mixing chamber is formed at one end of the support segments including means for directing and mixing fuel within a plenum and a perforated header plate for directing streams of air and fuel mixture into the combustion chamber; each of the outer and inner walls of each of the support segments having a ribbed lattice with tracks slidably supporting porous laminated replaceable panels and including pores therein for distributing combustion air into the combustion chamber while cooling the inner surface of each of the panels by transpiration cooling thereof.

Directional sensitivity of the retina: A layered scattering model of outer-segment photoreceptor pigments

PubMed Central

Vohnsen, Brian

2014-01-01

Photoreceptor outer segments have been modeled as stacked arrays of discs or membrane infoldings containing visual pigments with light-induced dipole moments. Waveguiding has been excluded so fields diffract beyond the physical boundaries of each photoreceptor cell. Optical reciprocity is used to argue for identical radiative and light gathering properties of pigments to model vision. Two models have been introduced: one a macroscopic model that assumes a uniform pigment density across each layer and another microscopic model that includes the spatial location of each pigment molecule within each layer. Both models result in highly similar directionality at the pupil plane which proves to be insensitive to the exact details of the outer-segment packing being predominantly determined by the first and last contributing layers as set by the fraction of bleaching. The versatility of the microscopic model is demonstrated with an array of examples that includes the Stiles-Crawford effect, visibility of a focused beam of light and the role of defocus. PMID:24877016

Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.

PubMed

Wahlin, Karl J; Maruotti, Julien A; Sripathi, Srinivasa R; Ball, John; Angueyra, Juan M; Kim, Catherine; Grebe, Rhonda; Li, Wei; Jones, Bryan W; Zack, Donald J

2017-04-10

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro.

Influence of bacterial toxins on the GTPase activity of transducin from bovine retinal rod outer segments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rybin, V.O.; Gureeva, A.A.

1986-05-10

The action of cholera toxin, capable of ADP-ribosylation of the activator N/sub s/ protein, and pertussis toxin, capable of ADP-ribosylation of the inhibitor N/sub i/ protein of the adenylate cyclase complex, on transducin, the GTP-binding protein of the rod outer segments of the retina, was investigated. It was shown that under the action of pertussis and cholera toxins, the GTPase activity of transducin is inhibited. Pertussin toxin inhibits the GTPase of native retinal rod outer segments by 30-40%, while GTPase of homogeneous transducin produces a 70-80% inhibition. The action of toxins on transducin depends on the presence and nature ofmore » the guanylic nucleotide with which incubation is performed. On the basis of the data obtained it is suggested that pertussis toxin interacts with pretransducin and with the transducin-GDP complex, while cholera toxin ADP-ribosylates the transducin-GTP complex and does not act on transducin lacking GTP.« less

Synthesis of stiffened shells of revolution

NASA Technical Reports Server (NTRS)

Thornton, W. A.

1974-01-01

Computer programs for the synthesis of shells of various configurations were developed. The conditions considered are: (1) uniform shells (mainly cones) using a membrane buckling analysis, (2) completely uniform shells (cones, spheres, toroidal segments) using linear bending prebuckling analysis, and (3) revision of second design process to reduce the number of design variables to about 30 by considering piecewise uniform designs. A perturbation formula was derived and this allows exact derivatives of the general buckling load to be computed with little additional computer time.

Use of border information in the classification of mammographic masses

NASA Astrophysics Data System (ADS)

Varela, C.; Timp, S.; Karssemeijer, N.

2006-01-01

We are developing a new method to characterize the margin of a mammographic mass lesion to improve the classification of benign and malignant masses. Towards this goal, we designed features that measure the degree of sharpness and microlobulation of mass margins. We calculated these features in a border region of the mass defined as a thin band along the mass contour. The importance of these features in the classification of benign and malignant masses was studied in relation to existing features used for mammographic mass detection. Features were divided into three groups, each representing a different mass segment: the interior region of a mass, the border and the outer area. The interior and the outer area of a mass were characterized using contrast and spiculation measures. Classification was done in two steps. First, features representing each of the three mass segments were merged into a neural network classifier resulting in a single regional classification score for each segment. Secondly, a classifier combined the three single scores into a final output to discriminate between benign and malignant lesions. We compared the classification performance of each regional classifier and the combined classifier on a data set of 1076 biopsy proved masses (590 malignant and 486 benign) from 481 women included in the Digital Database for Screening Mammography. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of the classifiers. The area under the ROC curve (Az) was 0.69 for the interior mass segment, 0.76 for the border segment and 0.75 for the outer mass segment. The performance of the combined classifier was 0.81 for image-based and 0.83 for case-based evaluation. These results show that the combination of information from different mass segments is an effective approach for computer-aided characterization of mammographic masses. An advantage of this approach is that it allows the assessment of the contribution of regions rather than individual features. Results suggest that the border and the outer areas contained the most valuable information for discrimination between benign and malignant masses.

FUEL ELEMENT FOR NUCLEAR REACTORS

DOEpatents

Bassett, C.H.

1961-11-21

A fuel element is designed which is particularly adapted for reactors of high power density used to generate steam for the production of electricity. The fuel element consists of inner and outer concentric tubes forming an annular chamber within which is contained fissionable fuel pellet segments, wedge members interposed between the fuel segments, and a spring which, acting with wedge members, urges said fuel pellets radially into contact against the inner surface of the outer tube. The wedge members may be a fertile material convertible into fissionable fuel material by absorbing neutrons emitted from the fissionable fuel pellet segments. The costly grinding of cylindrical fuel pellets to close tolerances for snug engagement is reduced because the need to finish the exact size is eliminated. (AEC)

Gluten protein composition in several fractions obtained by shear induced separation of wheat flour.

PubMed

van der Zalm, Elizabeth E J; Grabowska, Katarzyna J; Strubel, Maurice; van der Goot, Atze J; Hamer, Rob J; Boom, Remko M

2010-10-13

Recently, it was found that applying curvilinear shear flow in a cone-cone shearing device to wheat flour dough induces separation, resulting in a gluten-enriched fraction in the apex of the cone and gluten-depleted fraction at the outer part. This article describes whether fractionation of the various proteineous components occurs during and after separation of Soissons wheat flour. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and size-exclusion high performance liquid chromatography (SE-HPLC) were found to be suitable techniques for this. It is concluded that all protein fractions migrate to the center of the cone as a result of which the composition of the gluten-enriched fraction remains rather similar to that in the original flour. However, the larger glutenin polymer fraction migrated faster, as a result of which the concentration of large polymers was increased with a factor 2.4 compared to that of Soissons flour. The concentration of monomers in the gluten-enriched fraction was decreased to 70% of the original concentration in the original wheat flour.

Permeation of internal and external monovalent cations through the catfish cone photoreceptor cGMP-gated channel

PubMed Central

1995-01-01

The permeation of monovalent cations through the cGMP-gated channel of catfish cone outer segments was examined by measuring permeability and conductance ratios under biionic conditions. For monovalent cations presented on the cytoplasmic side of the channel, the permeability ratios with respect to extracellular Na followed the sequence NH4 > K > Li > Rb = Na > Cs while the conductance ratios at +50 mV followed the sequence Na approximately NH4 > K > Rb > Li = Cs. These patterns are broadly similar to the amphibian rod channel. The symmetry of the channel was tested by presenting the test ion on the extracellular side and using Na as the common reference ion on the cytoplasmic side. Under these biionic conditions, the permeability ratios with respect to Na at the intracellular side followed the sequence NH4 > Li > K > Na > Rb > Cs while the conductance ratios at +50 mV followed the sequence NH4 > K approximately Na > Rb > Li > Cs. Thus, the channel is asymmetric with respect to external and internal cations. Under symmetrical 120 mM ionic conditions, the single-channel conductance at +50 mV ranged from 58 pS in NH4 to 15 pS for Cs and was in the order NH4 > Na > K > Rb > Cs. Unexpectedly, the single-channel current-voltage relation showed sufficient outward rectification to account for the rectification observed in multichannel patches without invoking voltage dependence in gating. The concentration dependence of the reversal potential for K showed that chloride was impermeant. Anomalous mole fraction behavior was not observed, nor, over a limited concentration range, were multiple dissociation constants. An Eyring rate theory model with a single binding site was sufficient to explain these observations. PMID:8786344

Imaging human retinal pigment epithelium cells using adaptive optics optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, Zhuolin; Kocaoglu, Omer P.; Turner, Timothy L.; Miller, Donald T.

2016-03-01

Retinal pigment epithelium (RPE) cells are vital to health of the outer retina, but are often compromised in ageing and major ocular diseases that lead to blindness. Early manifestation of RPE disruption occurs at the cellular level, and while biomarkers at this scale hold considerable promise, RPE cells have proven extremely challenging to image in the living human eye. We present a novel method based on optical coherence tomography (OCT) equipped with adaptive optics (AO) that overcomes the associated technical obstacles. The method takes advantage of the 3D resolution of AO-OCT, but more critically sub-cellular segmentation and registration that permit organelle motility to be used as a novel contrast mechanism. With this method, we successfully visualized RPE cells and characterized their 3D reflectance profile in every subject and retinal location (3° and 7° temporal to the fovea) imaged to date. We have quantified RPE packing geometry in terms of cell density, cone-to-RPE ratio, and number of nearest neighbors using Voronoi and power spectra analyses. RPE cell density (cells/mm2) showed no significant difference between 3° (4,892+/-691) and 7° (4,780+/-354). In contrast, cone-to- RPE ratio was significantly higher at 3° (3.88+/-0.52:1) than 7° (2.31+/- 0.23:1). Voronoi analysis also showed most RPE cells have six nearest neighbors, which was significantly larger than the next two most prevalent associations: five and seven. Averaged across the five subjects, prevalence of cells with six neighbors was 51.4+/-3.58% at 3°, and 54.58+/-3.01% at 7°. These results are consistent with histology and in vivo studies using other imaging modalities.

Technical note: suppression of artifacts arising from simultaneous cone-beam imaging and RF transponder tracking in prostate radiotherapy.

PubMed

Poludniowski, Gavin; Webb, Steve; Evans, Philip M

2012-03-01

Artifacts in treatment-room cone-beam reconstructions have been observed at the authors' center when cone-beam acquisition is simultaneous with radio frequency (RF) transponder tracking using the Calypso 4D system (Calypso Medical, Seattle, WA). These artifacts manifest as CT-number modulations and increased CT-noise. The authors present a method for the suppression of the artifacts. The authors propose a three-stage postprocessing technique that can be applied to image volumes previously reconstructed by a cone-beam system. The stages are (1) segmentation of voxels into air, soft-tissue, and bone; (2) application of a 2D spatial-filter in the axial plane to the soft-tissue voxels; and (3) normalization to remove streaking along the axial-direction. The algorithm was tested on patient data acquired with Synergy XVI cone-beam CT systems (Elekta, Crawley, United Kingdom). The computational demands of the suggested correction are small, taking less than 15 s per cone-beam reconstruction on a desktop PC. For a moderate loss of spatial-resolution, the artifacts are strongly suppressed and low-contrast visibility is improved. The correction technique proposed is fast and effective in removing the artifacts caused by simultaneous cone-beam imaging and RF-transponder tracking.

Foveal shape and structure in a normal population.

PubMed

Tick, Sarah; Rossant, Florence; Ghorbel, Itebeddine; Gaudric, Alain; Sahel, José-Alain; Chaumet-Riffaud, Philippe; Paques, Michel

2011-07-29

The shape of the human fovea presents important but still poorly characterized variations. In this study, the variability of the shape and structure of normal foveae were examined. In a group of 110 eyes of 57 healthy adults, the shape and structure of the fovea were analyzed by automated segmentation of retinal layer on high-resolution optical coherence tomography scans. In an additional group of 10 normal eyes of 10 patients undergoing fluorescein angiography, the size of the foveal avascular zone (FAZ) was correlated to foveal shape. From the thickest to the thinnest fovea, there was a structural continuum ranging from a shallow pit with continuity of the inner nuclear layer (INL) over the center (seven eyes; 6.7%), to a complete separation of inner layers overlying a flat and thinner central outer nuclear layer (ONL; eight eyes; 7.3%). Central foveal thickness correlated inversely to the degree of inner layer separation and to the surface of the FAZ. Foveal structure strongly correlates with its neurovascular organization. The findings support a developmental model in which the size of the FAZ determines the extent of centrifugal migration of inner retinal layers, which counteracts in some way the centripetal packing of cone photoreceptors.

Fundamental studies in the molecular basis of laser-induced retinal damage. Annual report, September 1981-August 1982

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis

1982-09-01

This research led to new insights in the fundamental mechanisms involved in laser induced retinal damage and some of the fundamental work on these mechanisms lead to new and exciting avenues in the development of rapidly adjustable molecular light filters with important new possibilities for pulsed-laser eye protection. This report summarizes the significant progress of the past year: (1) Development and Fundamental Mechanism of a Rapidly Adjustable Molecular Filter for Pulsed Laser Eye Protection - this research direction resulted from our investigations on cones of the red-eared swamp turtle, Pseudemys scripta elegans. (2) The Optical Density of Turtle Oil Dropletmore » Solutions - it is important both from a practical and fundamental point of view to determine the optical density of turtle oil-droplet suspensions. In view of the high optical densities in this system, tunable-laser resonance Raman spectroscopy, which is the only technique that has been able to provide high-resolution data, is the only technique that is potentially able to obtain the information. (3) Laser-Induced Molecular Alterations in Turtle Retina. (4) Light Driven Enzymatic Reactions in Photoreceptors. (5) Molecular Cytology of Rod Outer Segments.« less

Adaptive optics and the eye (super resolution OCT).

PubMed

Miller, D T; Kocaoglu, O P; Wang, Q; Lee, S

2011-03-01

The combination of adaptive optics (AO) and optical coherence tomography (OCT) was first reported 8 years ago and has undergone tremendous technological advances since then. The technical benefits of adding AO to OCT (increased lateral resolution, smaller speckle, and enhanced sensitivity) increase the imaging capability of OCT in ways that make it well suited for three-dimensional (3D) cellular imaging in the retina. Today, AO-OCT systems provide ultrahigh 3D resolution (3 × 3 × 3 μm³) and ultrahigh speed (up to an order of magnitude faster than commercial OCT). AO-OCT systems have been used to capture volume images of retinal structures, previously only visible with histology, and are being used for studying clinical conditions. Here, we present representative examples of cellular structures that can be visualized with AO-OCT. We overview three studies from our laboratory that used ultrahigh-resolution AO-OCT to measure the cross-sectional profiles of individual bundles in the retinal nerve fiber layer; the diameters of foveal capillaries that define the terminal rim of the foveal avascular zone; and the spacing and length of individual cone photoreceptor outer segments as close as 0.5° from the fovea center.

Evolution of Vision

NASA Astrophysics Data System (ADS)

Ostrovsky, Mikhail

The evolution of photoreception, giving rise to eye, offers a kaleidoscopic view on selection acting at both the organ and molecular levels. The molecular level is mainly considered in the lecture. The greatest progress to date has been made in relation to the opsin visual pigments. Opsins appeared before eyes did. Two- and three-dimensional organization for rhodopsin in the rod outer segment disk membrane, as well as molecular mechanisms of visual pigments spectral tuning, photoisomerization and also opsin as a G-protein coupled receptor are considered. Molecular mechanisms of visual pigments spectral tuning, namely switching of chromophore (physiological time scale) and amino acid changes in the chromophore site of opsin (evolutionary time scale) is considered in the lecture. Photoisomerization of rhodopsin chromophore, 11-cis retinal is the only photochemical reaction in vision. The reaction is extemely fast (less that 200 fs) and high efficient (. is 0.65). The rhodopsin photolysis and kinetics of the earlier products appearance, photo- and bathorhodopsin, is considered. It is known that light is not only a carrier of information, but also a risk factor of damage to the eye. This photobiological paradox of vision is mainly due to the nature of rhodopsin chromophore. Photooxidation is the base of the paradox. All factors present in the phototrceptor cells to initiate free-radical photooxidation: photosensitizers, oxygen and substrates of oxidation: lipids and proteins (opsin). That is why photoprotective system of the eye structures appeared in the course of evolution. Three lines of protective system to prevent light damage to the retina and retina pigment epithelium is known: permanent renewal of rod and cone outer segment, powerful antioxidant system and optical media as cut-off filters where the lens is a key component. The molecular mechanisms of light damage to the eye and photoprotective system of the eye is considered in the lecture. The molecular mechanisms of phototransduction in vertebrates eye is also briefly considered in the lecture. Evolution of vision is an enormous subject for thought and investigation. In the postgenomic era evolutionary molecular physiology as a whole and evolutionary molecular physiology of vision can be considered as a key approach for understanding how genome is working.

Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice

PubMed Central

Thompson, Stewart; Blodi, Frederick R.; Lee, Swan; Welder, Chris R.; Mullins, Robert F.; Tucker, Budd A.; Stasheff, Steven F.; Stone, Edwin M.

2014-01-01

Purpose. In animal models of degenerative photoreceptor disease, there has been some success in restoring photoreception by transplanting stem cell–derived photoreceptor cells into the subretinal space. However, only a small proportion of transplanted cells develop extended outer segments, considered critical for photoreceptor cell function. The purpose of this study was to determine whether photoreceptor cells that lack a fully formed outer segment could usefully contribute to vision. Methods. Retinal and visual function was tested in wild-type and Rds mice at 90 days of age (RdsP90). Photoreceptor cells of mice homozygous for the Rds mutation in peripherin 2 never develop a fully formed outer segment. The electroretinogram and multielectrode recording of retinal ganglion cells were used to test retinal responses to light. Three distinct visual behaviors were used to assess visual capabilities: the optokinetic tracking response, the discrimination-based visual water task, and a measure of the effect of vision on wheel running. Results. RdsP90 mice had reduced but measurable electroretinogram responses to light, and exhibited light-evoked responses in multiple types of retinal ganglion cells, the output neurons of the retina. In optokinetic and discrimination-based tests, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running test showed that RdsP90 mice needed 3 log units brighter luminance than wild type to support useful vision (10 cd/m2). Conclusions. Photoreceptors that lack fully formed outer segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision. PMID:24569582

Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration

PubMed Central

Athanasiou, Dimitra; Aguila, Monica; Opefi, Chikwado A.; South, Kieron; Bellingham, James; Bevilacqua, Dalila; Munro, Peter M.; Kanuga, Naheed; Mackenzie, Francesca E.; Dubis, Adam M.; Georgiadis, Anastasios; Graca, Anna B.; Pearson, Rachael A.; Ali, Robin R.; Sakami, Sanae; Palczewski, Krzysztof; Sherman, Michael Y.; Reeves, Philip J.

2017-01-01

Abstract Protein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic ‘gain of function’, such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death. The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments. These data suggest that improving the traffic of misfolding rhodopsin mutants is unlikely to be a practical therapy, because of their intrinsic instability and long half-life in the outer segment, but also highlights the potential of altering translation through AMPK to improve protein function in other protein misfolding diseases. PMID:28065882

Lipoprotein Uptake by Neuronal Growth Cones in Vitro

NASA Astrophysics Data System (ADS)

Ignatius, Michael J.; Shooter, Eric M.; Pitas, Robert E.; Mahley, Robert W.

1987-05-01

Macrophages that rapidly enter injured peripheral nerve synthesize and secrete large quantities of apolipoprotein E. This protein may be involved in the redistribution of lipid, including cholesterol released during degeneration, to the regenerating axons. To test this postulate, apolipoprotein E-associated lipid particles released from segments of injured rat sciatic nerve and apolipoprotein E-containing lipoproteins from plasma were used to determine whether sprouting neurites, specifically their growth cones, possessed lipoprotein receptors. Pheochromocytoma (PC12) cells, which can be stimulated to produce neurites in vitro, were used as a model system. Apolipoprotein E-containing lipid particles and lipoproteins, which had been labeled with fluorescent dye, were internalized by the neurites and their growth cones; the unmetabolized dye appeared to be localized to the lysosomes. The rapid rate of accumulation in the growth cones precludes the possibility of orthograde transport of the fluorescent particles from the PC12 cell bodies. Thus, receptor-mediated lipoprotein uptake is performed by the apolipoprotein B,E(LDL) (low density lipoprotein) receptors, and in the regenerating peripheral nerve apolipoprotein E may deliver lipids to the neurites and their growth cones for membrane biosynthesis.

Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type calcium currents in cones but not in rods.

PubMed

Hosoi, Nobutake; Arai, Itaru; Tachibana, Masao

2005-04-20

Light responses of photoreceptors (rods and cones) are transmitted to the second-order neurons (bipolar cells and horizontal cells) via glutamatergic synapses located in the outer plexiform layer of the retina. Although it has been well established that postsynaptic group III metabotropic glutamate receptors (mGluRs) of ON bipolar cells contribute to generating the ON signal, presynaptic roles of group III mGluRs remain to be elucidated at this synaptic connection. We addressed this issue by applying the slice patch-clamp technique to the newt retina. OFF bipolar cells and horizontal cells generate a steady inward current in the dark and a transient inward current at light offset, both of which are mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist, L-2-amino-4-phosphonobutyric acid (L-AP-4), inhibited both the steady and off-transient inward currents but did not affect the glutamate-induced current in these postsynaptic neurons. L-AP-4 inhibited the presynaptic L-type calcium current (ICa) in cones by shifting the voltage dependence of activation to more positive membrane potentials. The inhibition of ICa was most prominent around the physiological range of cone membrane potentials. In contrast, L-AP-4 did not affect L-type ICa in rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed that L-AP-4 inhibited both ICa and glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibited ICa in cones but not in rods. Selective modulation of ICa in cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.

Melanopsin is required for non-image-forming photic responses in blind mice.

PubMed

Panda, Satchidananda; Provencio, Ignacio; Tu, Daniel C; Pires, Susana S; Rollag, Mark D; Castrucci, Ana Maria; Pletcher, Mathew T; Sato, Trey K; Wiltshire, Tim; Andahazy, Mary; Kay, Steve A; Van Gelder, Russell N; Hogenesch, John B

2003-07-25

Although mice lacking rod and cone photoreceptors are blind, they retain many eye-mediated responses to light, possibly through photosensitive retinal ganglion cells. These cells express melanopsin, a photopigment that confers this photosensitivity. Mice lacking melanopsin still retain nonvisual photoreception, suggesting that rods and cones could operate in this capacity. We observed that mice with both outer-retinal degeneration and a deficiency in melanopsin exhibited complete loss of photoentrainment of the circadian oscillator, pupillary light responses, photic suppression of arylalkylamine-N-acetyltransferase transcript, and acute suppression of locomotor activity by light. This indicates the importance of both nonvisual and classical visual photoreceptor systems for nonvisual photic responses in mammals.

A new Permian gnetalean cone as fossil evidence for supporting current molecular phylogeny.

PubMed

Wang, Zi-Qiang

2004-08-01

The order Gnetales has been the central focus of controversy in seed plant phylogeny. Traditional treatment of morphology supports the anthophyte hypothesis with Gnetales sister to angiosperms but current molecular data reject this hypothesis. A new fossil gnetalean cone, Palaeognetaleana auspicia gen. et sp. nov., is reported from the Upper Permian in North China, and its phylogenic implications are considered. Samples of cones from the upper part of the Upper Permian redbeds of Baode section, northwestern Shanxi Province, China, were examined. The cone is characterized by its unusual nature of reproduction that combines features of post-Triassic gnetaleans and some of the Palaeozoic conifers. It is made up of a number of imbricate axillary units, each simply formed by an ovule and a subtending bract, which may be comparable with the axillary seed-scale complex of some of the Palaeozoic conifer cones. The cone exhibits at least a partially bisexual character that appears to have pollen sacs with monosulcate ribbed pollen grains and sessile, asymmetric, and radiospermic ovules. The ovule has an integument of three envelopes: an outer one of pointed scales; a middle sclerified one; and an inner cuticle that extends upward into a micropyle with an oblique tip. The new Permian cone has unequivocal affinity with the Gnetales. The fossil has considerably extended the divergence time of the Gnetales from 140 (210?) back to 270 myr ago and, therefore, provides the first significant fossil evidence to support the current conclusion based on molecular data of seed plants, i.e. monophyletic gymnosperms, comprising the Gnetales are closely related to conifers.

Line plus arc source trajectories and their R-line coverage for long-object cone-beam imaging with a C-arm system

NASA Astrophysics Data System (ADS)

Yu, Zhicong; Wunderlich, Adam; Dennerlein, Frank; Lauritsch, Günter; Noo, Frédéric

2011-06-01

Cone-beam imaging with C-arm systems has become a valuable tool in interventional radiology. Currently, a simple circular trajectory is used, but future applications should use more sophisticated source trajectories, not only to avoid cone-beam artifacts but also to allow extended volume imaging. One attractive strategy to achieve these two goals is to use a source trajectory that consists of two parallel circular arcs connected by a line segment, possibly with repetition. In this work, we address the question of R-line coverage for such a trajectory. More specifically, we examine to what extent R-lines for such a trajectory cover a central cylindrical region of interest (ROI). An R-line is a line segment connecting any two points on the source trajectory. Knowledge of R-line coverage is crucial because a general theory for theoretically exact and stable image reconstruction from axially truncated data is only known for the points in the scanned object that lie on R-lines. Our analysis starts by examining the R-line coverage for the elemental trajectories consisting of (i) two parallel circular arcs and (ii) a circular arc connected orthogonally to a line segment. Next, we utilize our understanding of the R-lines for the aforementioned elemental trajectories to determine the R-line coverage for the trajectory consisting of two parallel circular arcs connected by a tightly fit line segment. For this trajectory, we find that the R-line coverage is insufficient to completely cover any central ROI. Because extension of the line segment beyond the circular arcs helps to increase the R-line coverage, we subsequently propose a trajectory composed of two parallel circular arcs connected by an extended line. We show that the R-lines for this trajectory can fully cover a central ROI if the line extension is long enough. Our presentation includes a formula for the minimum line extension needed to achieve full R-line coverage of an ROI with a specified size, and also includes a preliminary study on the required detector size, showing that the R-lines added by the line extension are not constraining.

Techniques in helical scanning, dynamic imaging and image segmentation for improved quantitative analysis with X-ray micro-CT

NASA Astrophysics Data System (ADS)

Sheppard, Adrian; Latham, Shane; Middleton, Jill; Kingston, Andrew; Myers, Glenn; Varslot, Trond; Fogden, Andrew; Sawkins, Tim; Cruikshank, Ron; Saadatfar, Mohammad; Francois, Nicolas; Arns, Christoph; Senden, Tim

2014-04-01

This paper reports on recent advances at the micro-computed tomography facility at the Australian National University. Since 2000 this facility has been a significant centre for developments in imaging hardware and associated software for image reconstruction, image analysis and image-based modelling. In 2010 a new instrument was constructed that utilises theoretically-exact image reconstruction based on helical scanning trajectories, allowing higher cone angles and thus better utilisation of the available X-ray flux. We discuss the technical hurdles that needed to be overcome to allow imaging with cone angles in excess of 60°. We also present dynamic tomography algorithms that enable the changes between one moment and the next to be reconstructed from a sparse set of projections, allowing higher speed imaging of time-varying samples. Researchers at the facility have also created a sizeable distributed-memory image analysis toolkit with capabilities ranging from tomographic image reconstruction to 3D shape characterisation. We show results from image registration and present some of the new imaging and experimental techniques that it enables. Finally, we discuss the crucial question of image segmentation and evaluate some recently proposed techniques for automated segmentation.

Restoration of outer segments of foveal photoreceptors after resolution of central serous chorioretinopathy.

PubMed

Ojima, Yumiko; Tsujikawa, Akitaka; Yamashiro, Kenji; Ooto, Sotaro; Tamura, Hiroshi; Yoshimura, Nagahisa

2010-01-01

To study morphologically and functionally the prognosis of damaged outer segments of the foveal photoreceptor layer in eyes with resolved central serous chorioretinopathy (CSC). We studied retrospectively the medical records of 70 patients (74 eyes) with resolved CSC. Optical coherence tomography was used to detect the junctions between inner and outer segments of the photoreceptors (IS/OS) as a hallmark of the integrity of the outer photoreceptor layer. In 53 eyes (71.6%), the IS/OS line was clearly detected beneath the fovea immediately after resolution of the retinal detachment, with good visual acuity (VA). In the remaining 21 eyes (28.4%), however, the foveal IS/OS line could not be detected shortly after resolution of CSC, and VA was variable, ranging from 0.1 to 1.5 (median, 0.9). Of these 21 eyes, 15 had a follow-up examination with OCT, and in four the foveal IS/OS line was not detected at the follow-up and vision in these eyes remained poor. However, nine eyes showed recovery of the foveal IS/OS line during follow-up, and these eyes had substantial visual recovery. Immediately after resolution of active CSC, although the IS/OS line cannot be detected beneath the fovea, it often shows restoration over time, with visual recovery, though in some eyes no restoration takes place and the prognosis remains poor.

High temperature control rod assembly

DOEpatents

Vollman, Russell E.

1991-01-01

A high temperature nuclear control rod assembly comprises a plurality of substantially cylindrical segments flexibly joined together in succession by ball joints. The segments are made of a high temperature graphite or carbon-carbon composite. The segment includes a hollow cylindrical sleeve which has an opening for receiving neutron-absorbing material in the form of pellets or compacted rings. The sleeve has a threaded sleeve bore and outer threaded surface. A cylindrical support post has a threaded shaft at one end which is threadably engaged with the sleeve bore to rigidly couple the support post to the sleeve. The other end of the post is formed with a ball portion. A hollow cylindrical collar has an inner threaded surface engageable with the outer threaded surface of the sleeve to rigidly couple the collar to the sleeve. the collar also has a socket portion which cooperates with the ball portion to flexibly connect segments together to form a ball and socket-type joint. In another embodiment, the segment comprises a support member which has a threaded shaft portion and a ball surface portion. The threaded shaft portion is engageable with an inner threaded surface of a ring for rigidly coupling the support member to the ring. The ring in turn has an outer surface at one end which is threadably engageably with a hollow cylindrical sleeve. The other end of the sleeve is formed with a socket portion for engagement with a ball portion of the support member. In yet another embodiment, a secondary rod is slidably inserted in a hollow channel through the center of the segment to provide additional strength. A method for controlling a nuclear reactor utilizing the control rod assembly is also included.

Images of photoreceptors in living primate eyes using adaptive optics two-photon ophthalmoscopy

PubMed Central

Hunter, Jennifer J.; Masella, Benjamin; Dubra, Alfredo; Sharma, Robin; Yin, Lu; Merigan, William H.; Palczewska, Grazyna; Palczewski, Krzysztof; Williams, David R.

2011-01-01

In vivo two-photon imaging through the pupil of the primate eye has the potential to become a useful tool for functional imaging of the retina. Two-photon excited fluorescence images of the macaque cone mosaic were obtained using a fluorescence adaptive optics scanning laser ophthalmoscope, overcoming the challenges of a low numerical aperture, imperfect optics of the eye, high required light levels, and eye motion. Although the specific fluorophores are as yet unknown, strong in vivo intrinsic fluorescence allowed images of the cone mosaic. Imaging intact ex vivo retina revealed that the strongest two-photon excited fluorescence signal comes from the cone inner segments. The fluorescence response increased following light stimulation, which could provide a functional measure of the effects of light on photoreceptors. PMID:21326644

Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes

PubMed Central

HIRANO, ARLENE A.; BRANDSTÄTTER, JOHANN HELMUT; VILA, ALEJANDRO; BRECHA, NICHOLAS C.

2009-01-01

Horizontal cells mediate inhibitory feed-forward and feedback communication in the outer retina; however, mechanisms that underlie transmitter release from mammalian horizontal cells are poorly understood. Toward determining whether the molecular machinery for exocytosis is present in horizontal cells, we investigated the localization of syntaxin-4, a SNARE protein involved in targeting vesicles to the plasma membrane, in mouse, rat, and rabbit retinae using immunocytochemistry. We report robust expression of syntaxin-4 in the outer plexiform layer of all three species. Syntaxin-4 occurred in processes and tips of horizontal cells, with regularly spaced, thicker sandwich-like structures along the processes. Double labeling with syntaxin-4 and calbindin antibodies, a horizontal cell marker, demonstrated syntaxin-4 localization to horizontal cell processes; whereas, double labeling with PKC antibodies, a rod bipolar cell (RBC) marker, showed a lack of co-localization, with syntaxin-4 immunolabeling occurring just distal to RBC dendritic tips. Syntaxin-4 immunolabeling occurred within VGLUT-1-immunoreactive photoreceptor terminals and underneath synaptic ribbons, labeled by CtBP2/RIBEYE antibodies, consistent with localization in invaginating horizontal cell tips at photoreceptor triad synapses. Vertical sections of retina immunostained for syntaxin-4 and peanut agglutinin (PNA) established that the prominent patches of syntaxin-4 immunoreactivity were adjacent to the base of cone pedicles. Horizontal sections through the OPL indicate a one-to-one co-localization of syntaxin-4 densities at likely all cone pedicles, with syntaxin-4 immunoreactivity interdigitating with PNA labeling. Pre-embedding immuno-electron microscopy confirmed the subcellular localization of syntaxin-4 labeling to lateral elements at both rod and cone triad synapses. Finally, co-localization with SNAP-25, a possible binding partner of syntaxin-4, indicated co-expression of these SNARE proteins in the same subcellular compartment of the horizontal cell. Taken together, the strong expression of these two SNARE proteins in the processes and endings of horizontal cells at rod and cone terminals suggests that horizontal cell axons and dendrites are likely sites of exocytotic activity. PMID:17640443

Loss of ift122, a Retrograde Intraflagellar Transport (IFT) Complex Component, Leads to Slow, Progressive Photoreceptor Degeneration Due to Inefficient Opsin Transport.

PubMed

Boubakri, Meriam; Chaya, Taro; Hirata, Hiromi; Kajimura, Naoko; Kuwahara, Ryusuke; Ueno, Akiko; Malicki, Jarema; Furukawa, Takahisa; Omori, Yoshihiro

2016-11-18

In the retina, aberrant opsin transport from cell bodies to outer segments leads to retinal degenerative diseases such as retinitis pigmentosa. Opsin transport is facilitated by the intraflagellar transport (IFT) system that mediates the bidirectional movement of proteins within cilia. In contrast to functions of the anterograde transport executed by IFT complex B (IFT-B), the precise functions of the retrograde transport mediated by IFT complex A (IFT-A) have not been well studied in photoreceptor cilia. Here, we analyzed developing zebrafish larvae carrying a null mutation in ift122 encoding a component of IFT-A. ift122 mutant larvae show unexpectedly mild phenotypes, compared with those of mutants defective in IFT-B. ift122 mutants exhibit a slow onset of progressive photoreceptor degeneration mainly after 7 days post-fertilization. ift122 mutant larvae also develop cystic kidney but not curly body, both of which are typically observed in various ciliary mutants. ift122 mutants display a loss of cilia in the inner ear hair cells and nasal pit epithelia. Loss of ift122 causes disorganization of outer segment discs. Ectopic accumulation of an IFT-B component, ift88, is observed in the ift122 mutant photoreceptor cilia. In addition, pulse-chase experiments using GFP-opsin fusion proteins revealed that ift122 is required for the efficient transport of opsin and the distal elongation of outer segments. These results show that IFT-A is essential for the efficient transport of outer segment proteins, including opsin, and for the survival of retinal photoreceptor cells, rendering the ift122 mutant a unique model for human retinal degenerative diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Loss of ift122, a Retrograde Intraflagellar Transport (IFT) Complex Component, Leads to Slow, Progressive Photoreceptor Degeneration Due to Inefficient Opsin Transport*

PubMed Central

Boubakri, Meriam; Chaya, Taro; Hirata, Hiromi; Kajimura, Naoko; Kuwahara, Ryusuke; Ueno, Akiko; Malicki, Jarema; Furukawa, Takahisa; Omori, Yoshihiro

2016-01-01

In the retina, aberrant opsin transport from cell bodies to outer segments leads to retinal degenerative diseases such as retinitis pigmentosa. Opsin transport is facilitated by the intraflagellar transport (IFT) system that mediates the bidirectional movement of proteins within cilia. In contrast to functions of the anterograde transport executed by IFT complex B (IFT-B), the precise functions of the retrograde transport mediated by IFT complex A (IFT-A) have not been well studied in photoreceptor cilia. Here, we analyzed developing zebrafish larvae carrying a null mutation in ift122 encoding a component of IFT-A. ift122 mutant larvae show unexpectedly mild phenotypes, compared with those of mutants defective in IFT-B. ift122 mutants exhibit a slow onset of progressive photoreceptor degeneration mainly after 7 days post-fertilization. ift122 mutant larvae also develop cystic kidney but not curly body, both of which are typically observed in various ciliary mutants. ift122 mutants display a loss of cilia in the inner ear hair cells and nasal pit epithelia. Loss of ift122 causes disorganization of outer segment discs. Ectopic accumulation of an IFT-B component, ift88, is observed in the ift122 mutant photoreceptor cilia. In addition, pulse-chase experiments using GFP-opsin fusion proteins revealed that ift122 is required for the efficient transport of opsin and the distal elongation of outer segments. These results show that IFT-A is essential for the efficient transport of outer segment proteins, including opsin, and for the survival of retinal photoreceptor cells, rendering the ift122 mutant a unique model for human retinal degenerative diseases. PMID:27681595

Generic method for automatic bladder segmentation on cone beam CT using a patient-specific bladder shape model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoot, A. J. A. J. van de, E-mail: a.j.schootvande@amc.uva.nl; Schooneveldt, G.; Wognum, S.

Purpose: The aim of this study is to develop and validate a generic method for automatic bladder segmentation on cone beam computed tomography (CBCT), independent of gender and treatment position (prone or supine), using only pretreatment imaging data. Methods: Data of 20 patients, treated for tumors in the pelvic region with the entire bladder visible on CT and CBCT, were divided into four equally sized groups based on gender and treatment position. The full and empty bladder contour, that can be acquired with pretreatment CT imaging, were used to generate a patient-specific bladder shape model. This model was used tomore » guide the segmentation process on CBCT. To obtain the bladder segmentation, the reference bladder contour was deformed iteratively by maximizing the cross-correlation between directional grey value gradients over the reference and CBCT bladder edge. To overcome incorrect segmentations caused by CBCT image artifacts, automatic adaptations were implemented. Moreover, locally incorrect segmentations could be adapted manually. After each adapted segmentation, the bladder shape model was expanded and new shape patterns were calculated for following segmentations. All available CBCTs were used to validate the segmentation algorithm. The bladder segmentations were validated by comparison with the manual delineations and the segmentation performance was quantified using the Dice similarity coefficient (DSC), surface distance error (SDE) and SD of contour-to-contour distances. Also, bladder volumes obtained by manual delineations and segmentations were compared using a Bland-Altman error analysis. Results: The mean DSC, mean SDE, and mean SD of contour-to-contour distances between segmentations and manual delineations were 0.87, 0.27 cm and 0.22 cm (female, prone), 0.85, 0.28 cm and 0.22 cm (female, supine), 0.89, 0.21 cm and 0.17 cm (male, supine) and 0.88, 0.23 cm and 0.17 cm (male, prone), respectively. Manual local adaptations improved the segmentation results significantly (p < 0.01) based on DSC (6.72%) and SD of contour-to-contour distances (0.08 cm) and decreased the 95% confidence intervals of the bladder volume differences. Moreover, expanding the shape model improved the segmentation results significantly (p < 0.01) based on DSC and SD of contour-to-contour distances. Conclusions: This patient-specific shape model based automatic bladder segmentation method on CBCT is accurate and generic. Our segmentation method only needs two pretreatment imaging data sets as prior knowledge, is independent of patient gender and patient treatment position and has the possibility to manually adapt the segmentation locally.« less

The I-Raum: A new shaped hohlraum for improved inner beam propagation in indirectly-driven ICF implosions on the National Ignition Facility

NASA Astrophysics Data System (ADS)

Robey, H. F.; Berzak Hopkins, L.; Milovich, J. L.; Meezan, N. B.

2018-01-01

Recent work in indirectly-driven inertial confinement fusion implosions on the National Ignition Facility has indicated that late-time propagation of the inner cones of laser beams (23° and 30°) is impeded by the growth of a "bubble" of hohlraum wall material (Au or depleted uranium), which is initiated by and is located at the location where the higher-intensity outer beams (44° and 50°) hit the hohlraum wall. The absorption of the inner cone beams by this "bubble" reduces the laser energy reaching the hohlraum equator at late time driving an oblate or pancaked implosion, which limits implosion performance. In this article, we present the design of a new shaped hohlraum designed specifically to reduce the impact of this bubble by adding a recessed pocket at the location where the outer cones hit the hohlraum wall. This recessed pocket displaces the bubble radially outward, reducing the inward penetration of the bubble at all times throughout the implosion and increasing the time for inner beam propagation by approximately 1 ns. This increased laser propagation time allows one to drive a larger capsule, which absorbs more energy and is predicted to improve implosion performance. The new design is based on a recent National Ignition Facility shot, N170601, which produced a record neutron yield. The expansion rate and absorption of laser energy by the bubble is quantified for both cylindrical and shaped hohlraums, and the predicted performance is compared.

Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived RPE Cells Following Transplantation

PubMed Central

McGill, Trevor J.; Bohana-Kashtan, Osnat; Stoddard, Jonathan W.; Andrews, Michael D.; Pandit, Neelay; Rosenberg-Belmaker, Lior R.; Wiser, Ofer; Matzrafi, Limor; Banin, Eyal; Reubinoff, Benjamin; Netzer, Nir; Irving, Charles

2017-01-01

Purpose Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. Methods Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells. BSS+ (balanced salt solution) (vehicle) and unoperated eyes served as controls. Optomotor tracking (OKT) behavior was used to quantify functional efficacy. Histology and immunohistochemistry were used to evaluate photoreceptor rescue and transplanted cell survival at 60, 100, 150, and 200 days of age. Results OKT was rescued in a dose-dependent manner. Outer nuclear layer (ONL) was significantly thicker in cell-treated eyes than controls up to P150. Transplanted RPE cells were identified in both the subretinal space and integrated into the host RPE monolayer in animals of all age groups, and often contained internalized photoreceptor outer segments. No pathology was observed. Conclusions OpRegen RPE cells survived, rescued visual function, preserved rod and cone photoreceptors long-term in the RCS rat. Thus, these data support the use of OpRegen RPE cells for the treatment of human RPE cell disorders including AMD. Translational Relevance Our novel xeno-free RPE cells minimize concerns of animal derived contaminants while providing a promising prospective therapy to the diseased retina. PMID:28626601

Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells.

PubMed

el-Amraoui, A; Sahly, I; Picaud, S; Sahel, J; Abitbol, M; Petit, C

1996-08-01

Usher syndrome type 1 (USH1) associates severe congenital deafness, vestibular dysfunction and progressive retinitis pigmentosa leading to blindness. The gene encoding myosin VIIA is responsible for USH1B. Mutations in the murine orthologous gene lead to the shaker-1 phenotype, which manifests cochlear and vestibular dysfunction, without any retinal defect. To address this phenotypic discrepancy, the expression of myosin VIIA in retinal cells was analyzed in human and mouse during embryonic development and adult life. In the human embryo, myosin VIIA was present first in the pigment epithelium cells, and later in these cells as well as in the photoreceptor cells. In the adult human retina, myosin VIIA was present in both cell types. In contrast, in mouse, only pigment epithelium cells expressed the protein throughout development and adult life. Myosin VIIA was also found to be absent in the photoreceptor cells of other rodents (rat and guinea-pig), whereas these cells expressed the protein in amphibians, avians and primates. These observations suggest that retinitis pigmentosa of USH1B results from a primary rod and cone defect. The USH1B/shaker-1 paradigm illustrates a species-specific cell pattern of gene expression as a possible cause for the discrepancy between phenotypes involving defective orthologous genes in man and mouse. Interestingly, in the photoreceptor cells, myosin VIIA is mainly localized in the inner and base of outer segments as well as in the synaptic ending region where it is co-localized with the synaptic vesicles. Therefore, we suggest that myosin VIIA might play a role in the trafficking of ribbon-synaptic vesicle complexes and the renewal processes of the outer photoreceptor disks.

Understanding the Function of Genes Involved in Inherited Retinal Degeneration-Insights into the Pathogenesis and Function of C8ORF37

NASA Astrophysics Data System (ADS)

Sharif, Ali Sakawa

Inherited retinal degenerative diseases (IRD) are a group of disorders that lead to progressive deterioration of mainly the photoreceptors. Retinitis pigmentosa (RP) and cone-rod dystrophy (CRD) are two forms of IRDs. RP is the most common form of IRD and is due to rod photoreceptor degeneration followed by cone photoreceptor loss. CRD, on the other hand, is characterized by the loss of cones or the concurrent degeneration of both cones and rods. Both RP and CRD are presently incurable. More than 200 genes have been identified to cause IRDs and the functions of many of these genes remain unclear. Mutations in a novel gene, C8ORF37, were identified to cause recessive, severe, and early-onset RP and CRD. I, therefore, pioneered in characterizing the role of C8ORF37 in the retina. This dissertation is comprised of four chapters that is organized as follows: (1) summary of an ocular disorder (2) a genetic model of a retinal disorder (3) biochemical/proteomic analysis of C8ORF37 (4) potential clinical applications. A summary of ocular disorders is discussed in Chapter 1, with an emphasis on CRD. Chapter 2 focuses on the generation and characterization of C8orf37 mutant mouse models that recapitulate the retinal pathologies observed in human patients. In C8orf37 knockout retinas, the outer segment (OS) was nonuniform, swollen, and wider in width when compared to the controls. Moreover, many OS membrane proteins were reduced in the retina of C8orf37 knockout, including CNGB1 and RDS, proteins essential for OS disc morphogenesis and alignment. Our findings shed new light on the pathogenesis underlying retinal dysfunction and degeneration in C8ORF37-deficient patients. To determine the function of a novel protein, a powerful approach is by identifying its binding partners. In Chapter 3, I discuss GST pull-down using bovine retinal lysates, yeast-two-hybrid, and immunoprecipitation with mouse retinal lysate in order to identify C8ORF37-interacting proteins. Our pull-downs identified KTN1, RAB28, UCHL1, and PSMD14 suggesting that C8ORF37 may have a role in protein homeostasis. Chapter 4 concludes and discusses the impact of generating and characterizing C8orf37 animal models for future studies in understanding photoreceptor function and in the development of therapeutics against retinal degeneration.

The structure and the formation of egg shells in the parthenogenetic species Dactylobiotus dispar Murray, 1907 (Tardigrada: Eutardigrada).

PubMed

Poprawa, Izabela

2005-01-01

The eggs of Dactylobiotus dispar, similar to other Tardigrada eggs, are covered with two shells: the vitelline envelope and the chorion. Ultrastructural studies have shown that the oocyte actively participates in the formation of both shells. The process of egg capsule formation begins at the midpoint of vitellogenesis. The chorion at first appears as isolated cones resulting from the exocytotic activity of the oocyte and the ovarian epithelium. Subsequently, connections between the cones are formed. Three layers can be distinguished in the completely developed chorion: (1) the inner layer of medium electron density; (2) the middle, labyrinthine layer; (3) the outer layer of medium electron density with cones (future conical processes). After chorion formation, a vitelline envelope is secreted by the oocyte. The Dactylobiotus dispar egg is covered with small, conical processes with hooked tips. The surface of the chorion is covered with a mesh-like network consisting of elongated interstices. The egg capsule has no micropylar opening.

A new species of Condyloderes (Cyclorhagida, Kinorhyncha) from Korea.

PubMed

Sørensen, Martin V; Rho, Hyun Soo; Kim, Dongsung

2010-03-01

A new kinorhynch species, Condyloderes megastigma sp. nov., is described from the Korea Strait. The new species is characterized by the presence of 16 placids with either eight, four, or two knobby projections, middorsal and lateroventral acicular spines on segments 1 to 9, lateroventral cuspidate spines on segment 2 in females only, but otherwise lateroventral cuspidate spines on segments 4 and 5, and 8 and 9 in both sexes. Unique for the new species is furthermore the presence of paired ventromedial appendages on segments 7 and 8, giant ventromedial sensory spots on segment 9, and a terminal segment consisting of one tergal and one sternal plate. The mouth cone and introvert armature are described in detail for the first time for the genus Condyloderes Higgins, 1969. This study reveals similarities in several morphological characters between this genus and species of Campyloderes Zelinka, 1913.

Cone-beam CT image contrast and attenuation-map linearity improvement (CALI) for brain stereotactic radiosurgery procedures

NASA Astrophysics Data System (ADS)

Hashemi, Sayed Masoud; Lee, Young; Eriksson, Markus; Nordström, Hâkan; Mainprize, James; Grouza, Vladimir; Huynh, Christopher; Sahgal, Arjun; Song, William Y.; Ruschin, Mark

2017-03-01

A Contrast and Attenuation-map (CT-number) Linearity Improvement (CALI) framework is proposed for cone-beam CT (CBCT) images used for brain stereotactic radiosurgery (SRS). The proposed framework is used together with our high spatial resolution iterative reconstruction algorithm and is tailored for the Leksell Gamma Knife ICON (Elekta, Stockholm, Sweden). The incorporated CBCT system in ICON facilitates frameless SRS planning and treatment delivery. The ICON employs a half-cone geometry to accommodate the existing treatment couch. This geometry increases the amount of artifacts and together with other physical imperfections causes image inhomogeneity and contrast reduction. Our proposed framework includes a preprocessing step, involving a shading and beam-hardening artifact correction, and a post-processing step to correct the dome/capping artifact caused by the spatial variations in x-ray energy generated by bowtie-filter. Our shading correction algorithm relies solely on the acquired projection images (i.e. no prior information required) and utilizes filtered-back-projection (FBP) reconstructed images to generate a segmented bone and soft-tissue map. Ideal projections are estimated from the segmented images and a smoothed version of the difference between the ideal and measured projections is used in correction. The proposed beam-hardening and dome artifact corrections are segmentation free. The CALI was tested on CatPhan, as well as patient images acquired on the ICON system. The resulting clinical brain images show substantial improvements in soft contrast visibility, revealing structures such as ventricles and lesions which were otherwise un-detectable in FBP-reconstructed images. The linearity of the reconstructed attenuation-map was also improved, resulting in more accurate CT#.

High-Resolution Adaptive Optics Retinal Imaging of Cellular Structure in Choroideremia

PubMed Central

Morgan, Jessica I. W.; Han, Grace; Klinman, Eva; Maguire, William M.; Chung, Daniel C.; Maguire, Albert M.; Bennett, Jean

2014-01-01

Purpose. We characterized retinal structure in patients and carriers of choroideremia using adaptive optics and other high resolution modalities. Methods. A total of 57 patients and 18 carriers of choroideremia were imaged using adaptive optics scanning light ophthalmoscopy (AOSLO), optical coherence tomography (OCT), autofluorescence (AF), and scanning light ophthalmoscopy (SLO). Cone density was measured in 59 eyes of 34 patients where the full cone mosaic was observed. Results. The SLO imaging revealed scalloped edges of RPE atrophy and large choroidal vessels. The AF imaging showed hypo-AF in areas of degeneration, while central AF remained present. OCT images showed outer retinal tubulations and thinned RPE/interdigitation layers. The AOSLO imaging revealed the cone mosaic in central relatively intact retina, and cone density was either reduced or normal at 0.5 mm eccentricity. The border of RPE atrophy showed abrupt loss of the cone mosaic at the same location. The AF imaging in comparison with AOSLO showed RPE health may be compromised before cone degeneration. Other disease features, including visualization of choroidal vessels, hyper-reflective clumps of cones, and unique retinal findings, were tabulated to show the frequency of occurrence and model disease progression. Conclusions. The data support the RPE being one primary site of degeneration in patients with choroideremia. Photoreceptors also may degenerate independently. High resolution imaging, particularly AOSLO in combination with OCT, allows single cell analysis of disease in choroideremia. These modalities promise to be useful in monitoring disease progression, and in documenting the efficacy of gene and cell-based therapies for choroideremia and other diseases as these therapies emerge. (ClinicalTrials.gov number, NCT01866371.) PMID:25190651

Abnormal Cone Structure in Foveal Schisis Cavities in X-Linked Retinoschisis from Mutations in Exon 6 of the RS1 Gene

PubMed Central

Ratnam, Kavitha; Birch, David G.; Sundquist, Sanna M.; Lucero, Anna S.; Zhang, Yuhua; Meltzer, Meira; Smaoui, Nizar; Roorda, Austin

2011-01-01

Purpose. To evaluate macular cone structure in patients with X-linked retinoschisis (XLRS) caused by mutations in exon 6 of the RS1 gene. Methods. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT) in two patients with XLRS and 27 age-similar healthy subjects. Retinal structure was correlated with best-corrected visual acuity, kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The six coding exons and the flanking intronic regions of the RS1 gene were sequenced in each patient. Results. Two unrelated males, ages 14 and 29, with visual acuity ranging from 20/32 to 20/63, had macular schisis with small relative central scotomas in each eye. The mixed scotopic ERG b-wave was reduced more than the a-wave. SD-OCT showed schisis cavities in the outer and inner nuclear and plexiform layers. Cone spacing was increased within the largest foveal schisis cavities but was normal elsewhere. In each patient, a mutation in exon 6 of the RS1 gene was identified and was predicted to change the amino acid sequence in the discoidin domain of the retinoschisin protein. Conclusions. AOSLO images of two patients with molecularly characterized XLRS revealed increased cone spacing and abnormal packing in the macula of each patient, but cone coverage and function were near normal outside the central foveal schisis cavities. Although cone density is reduced, the preservation of wave-guiding cones at the fovea and eccentric macular regions has prognostic and therapeutic implications for XLRS patients with foveal schisis. (Clinical Trials.gov number, NCT00254605.) PMID:22110067

High-resolution adaptive optics retinal imaging of cellular structure in choroideremia.

PubMed

Morgan, Jessica I W; Han, Grace; Klinman, Eva; Maguire, William M; Chung, Daniel C; Maguire, Albert M; Bennett, Jean

2014-09-04

We characterized retinal structure in patients and carriers of choroideremia using adaptive optics and other high resolution modalities. A total of 57 patients and 18 carriers of choroideremia were imaged using adaptive optics scanning light ophthalmoscopy (AOSLO), optical coherence tomography (OCT), autofluorescence (AF), and scanning light ophthalmoscopy (SLO). Cone density was measured in 59 eyes of 34 patients where the full cone mosaic was observed. The SLO imaging revealed scalloped edges of RPE atrophy and large choroidal vessels. The AF imaging showed hypo-AF in areas of degeneration, while central AF remained present. OCT images showed outer retinal tubulations and thinned RPE/interdigitation layers. The AOSLO imaging revealed the cone mosaic in central relatively intact retina, and cone density was either reduced or normal at 0.5 mm eccentricity. The border of RPE atrophy showed abrupt loss of the cone mosaic at the same location. The AF imaging in comparison with AOSLO showed RPE health may be compromised before cone degeneration. Other disease features, including visualization of choroidal vessels, hyper-reflective clumps of cones, and unique retinal findings, were tabulated to show the frequency of occurrence and model disease progression. The data support the RPE being one primary site of degeneration in patients with choroideremia. Photoreceptors also may degenerate independently. High resolution imaging, particularly AOSLO in combination with OCT, allows single cell analysis of disease in choroideremia. These modalities promise to be useful in monitoring disease progression, and in documenting the efficacy of gene and cell-based therapies for choroideremia and other diseases as these therapies emerge. (ClinicalTrials.gov number, NCT01866371.). Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

TIGRESS highly-segmented high-purity germanium clover detector

NASA Astrophysics Data System (ADS)

Scraggs, H. C.; Pearson, C. J.; Hackman, G.; Smith, M. B.; Austin, R. A. E.; Ball, G. C.; Boston, A. J.; Bricault, P.; Chakrawarthy, R. S.; Churchman, R.; Cowan, N.; Cronkhite, G.; Cunningham, E. S.; Drake, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hyland, B.; Jones, B.; Leslie, J. R.; Martin, J.-P.; Morris, D.; Morton, A. C.; Phillips, A. A.; Sarazin, F.; Schumaker, M. A.; Svensson, C. E.; Valiente-Dobón, J. J.; Waddington, J. C.; Watters, L. M.; Zimmerman, L.

2005-05-01

The TRIUMF-ISAC Gamma-Ray Escape-Suppressed Spectrometer (TIGRESS) will consist of twelve units of four high-purity germanium (HPGe) crystals in a common cryostat. The outer contacts of each crystal will be divided into four quadrants and two lateral segments for a total of eight outer contacts. The performance of a prototype HPGe four-crystal unit has been investigated. Integrated noise spectra for all contacts were measured. Energy resolutions, relative efficiencies for both individual crystals and for the entire unit, and peak-to-total ratios were measured with point-like sources. Position-dependent performance was measured by moving a collimated source across the face of the detector.

Interaction of 4.1G and cGMP-gated channels in rod photoreceptor outer segments.

PubMed

Cheng, Christiana L; Molday, Robert S

2013-12-15

In photoreceptors, the assembly of signaling molecules into macromolecular complexes is important for phototransduction and maintaining the structural integrity of rod outer segments (ROSs). However, the molecular composition and formation of these complexes are poorly understood. Using immunoprecipitation and mass spectrometry, 4.1G was identified as a new interacting partner for the cyclic-nucleotide gated (CNG) channels in ROSs. 4.1G is a widely expressed multifunctional protein that plays a role in the assembly and stability of membrane protein complexes. Multiple splice variants of 4.1G were cloned from bovine retina. A smaller splice variant of 4.1G selectively interacted with CNG channels not associated with peripherin-2-CNG channel complex. A combination of truncation studies and domain-binding assays demonstrated that CNG channels selectively interacted with 4.1G through their FERM and CTD domains. Using immunofluorescence, labeling of 4.1G was seen to be punctate and partially colocalized with CNG channels in the ROS. Our studies indicate that 4.1G interacts with a subset of CNG channels in the ROS and implicate this protein-protein interaction in organizing the spatial arrangement of CNG channels in the plasma membrane of outer segments.

KSC-2009-2311

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – The first Ares I-X motor segment is in the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

Analytical and experimental studies of natural vibrations modes of ring-stiffened truncated-cone shells with variable theoretical ring fixity

NASA Technical Reports Server (NTRS)

Naumann, E. C.; Catherines, D. S.; Walton, W. C., Jr.

1971-01-01

Experimental and analytical investigations of the vibratory behavior of ring-stiffened truncated-cone shells are described. Vibration tests were conducted on 60 deg conical shells having up to four ring stiffeners and for free-free and clamped-free edge constraints and 9 deg conical shells, for two thicknesses, each with two angle rings and for free-free, free-clamped, and clamped-clamped edge constraints. The analytical method is based on linear thin shell theory, employing the Rayleigh-Ritz method. Discrete rings are represented as composed of one or more segments, each of which is a short truncated-cone shell of uniform thickness. Equations of constraint are used to join a ring and shell along a circumferential line connection. Excellent agreement was obtained for comparisons of experimental and calculated frequencies.

Hartman Testing of X-Ray Telescopes

NASA Technical Reports Server (NTRS)

Saha, Timo T.; Biskasch, Michael; Zhang, William W.

2013-01-01

Hartmann testing of x-ray telescopes is a simple test method to retrieve and analyze alignment errors and low-order circumferential errors of x-ray telescopes and their components. A narrow slit is scanned along the circumference of the telescope in front of the mirror and the centroids of the images are calculated. From the centroid data, alignment errors, radius variation errors, and cone-angle variation errors can be calculated. Mean cone angle, mean radial height (average radius), and the focal length of the telescope can also be estimated if the centroid data is measured at multiple focal plane locations. In this paper we present the basic equations that are used in the analysis process. These equations can be applied to full circumference or segmented x-ray telescopes. We use the Optical Surface Analysis Code (OSAC) to model a segmented x-ray telescope and show that the derived equations and accompanying analysis retrieves the alignment errors and low order circumferential errors accurately.

A new method for recognizing quadric surfaces from range data and its application to telerobotics and automation, final phase

NASA Technical Reports Server (NTRS)

Mielke, Roland; Dcunha, Ivan; Alvertos, Nicolas

1994-01-01

In the final phase of the proposed research a complete top to down three dimensional object recognition scheme has been proposed. The various three dimensional objects included spheres, cones, cylinders, ellipsoids, paraboloids, and hyperboloids. Utilizing a newly developed blob determination technique, a given range scene with several non-cluttered quadric surfaces is segmented. Next, using the earlier (phase 1) developed alignment scheme, each of the segmented objects are then aligned in a desired coordinate system. For each of the quadric surfaces based upon their intersections with certain pre-determined planes, a set of distinct features (curves) are obtained. A database with entities such as the equations of the planes and angular bounds of these planes has been created for each of the quadric surfaces. Real range data of spheres, cones, cylinders, and parallelpipeds have been utilized for the recognition process. The developed algorithm gave excellent results for the real data as well as for several sets of simulated range data.

Analysis of radially cracked ring segments subject to forces and couples

NASA Technical Reports Server (NTRS)

Gross, B.; Srawley, J. E.

1977-01-01

Results of planar boundary collocation analysis are given for ring segment (C-shaped) specimens with radial cracks, subjected to combined forces and couples. Mode I stress intensity factors and crack mouth opening displacements were determined for ratios of outer to inner radius in the range 1.1 to 2.5 and ratios of crack length to segment width in the range 0.1 to 0.8.

Analysis of radially cracked ring segments subject to forces and couples

NASA Technical Reports Server (NTRS)

Gross, B.; Strawley, J. E.

1975-01-01

Results of planar boundary collocation analysis are given for ring segment (C shaped) specimens with radial cracks, subjected to combined forces and couples. Mode I stress intensity factors and crack mouth opening displacements were determined for ratios of outer to inner radius in the range 1.1 to 2.5, and ratios of crack length to segment width in the range 0.1 to 0.8.

Automatic lumen and outer wall segmentation of the carotid artery using deformable three-dimensional models in MR angiography and vessel wall images.

PubMed

van 't Klooster, Ronald; de Koning, Patrick J H; Dehnavi, Reza Alizadeh; Tamsma, Jouke T; de Roos, Albert; Reiber, Johan H C; van der Geest, Rob J

2012-01-01

To develop and validate an automated segmentation technique for the detection of the lumen and outer wall boundaries in MR vessel wall studies of the common carotid artery. A new segmentation method was developed using a three-dimensional (3D) deformable vessel model requiring only one single user interaction by combining 3D MR angiography (MRA) and 2D vessel wall images. This vessel model is a 3D cylindrical Non-Uniform Rational B-Spline (NURBS) surface which can be deformed to fit the underlying image data. Image data of 45 subjects was used to validate the method by comparing manual and automatic segmentations. Vessel wall thickness and volume measurements obtained by both methods were compared. Substantial agreement was observed between manual and automatic segmentation; over 85% of the vessel wall contours were segmented successfully. The interclass correlation was 0.690 for the vessel wall thickness and 0.793 for the vessel wall volume. Compared with manual image analysis, the automated method demonstrated improved interobserver agreement and inter-scan reproducibility. Additionally, the proposed automated image analysis approach was substantially faster. This new automated method can reduce analysis time and enhance reproducibility of the quantification of vessel wall dimensions in clinical studies. Copyright © 2011 Wiley Periodicals, Inc.

Radio Frequency Trap for Containment of Plasmas in Antimatter Propulsion Systems Using Rotating Wall Electric Fields

NASA Technical Reports Server (NTRS)

Sims, William Herbert, III (Inventor); Martin, James Joseph (Inventor); Lewis, Raymond A. (Inventor)

2003-01-01

A containment apparatus for containing a cloud of charged particles comprises a cylindrical vacuum chamber having a longitudinal axis. Within the vacuum chamber is a containment region. A magnetic field is aligned with the longitudinal axis of the vacuum chamber. The magnetic field is time invariant and uniform in strength over the containment region. An electric field is also aligned with the longitudinal axis of the vacuum chamber and the magnetic field. The electric field is time invariant, and forms a potential well over the containment region. One or more means are disposed around the cloud of particles for inducing a rotating electric field internal to the vacuum chamber. The rotating electric field imparts energy to the charged particles within the containment region and compress the cloud of particles. The means disposed around the outer surface of the vacuum chamber for inducing a rotating electric field are four or more segments forming a segmented ring, the segments conforming to the outer surface of the vacuum chamber. Each of the segments is energized by a separate alternating voltage. The sum of the voltages imposed on each segment establishes the rotating field. When four segments form a ring, the rotating field is obtained by a signal generator applying a sinusoidal signal phase delayed by 90,180 and 270 degrees in sequence to the four segments.

Increasing the efficiency of designing hemming processes by using an element-based metamodel approach

NASA Astrophysics Data System (ADS)

Kaiser, C.; Roll, K.; Volk, W.

2017-09-01

In the automotive industry, the manufacturing of automotive outer panels requires hemming processes in which two sheet metal parts are joined together by bending the flange of the outer part over the inner part. Because of decreasing development times and the steadily growing number of vehicle derivatives, an efficient digital product and process validation is necessary. Commonly used simulations, which are based on the finite element method, demand significant modelling effort, which results in disadvantages especially in the early product development phase. To increase the efficiency of designing hemming processes this paper presents a hemming-specific metamodel approach. The approach includes a part analysis in which the outline of the automotive outer panels is initially split into individual segments. By doing a para-metrization of each of the segments and assigning basic geometric shapes, the outline of the part is approximated. Based on this, the hemming parameters such as flange length, roll-in, wrinkling and plastic strains are calculated for each of the geometric basic shapes by performing a meta-model-based segmental product validation. The metamodel is based on an element similar formulation that includes a reference dataset of various geometric basic shapes. A random automotive outer panel can now be analysed and optimized based on the hemming-specific database. By implementing this approach into a planning system, an efficient optimization of designing hemming processes will be enabled. Furthermore, valuable time and cost benefits can be realized in a vehicle’s development process.

Advanced two-layer level set with a soft distance constraint for dual surfaces segmentation in medical images

NASA Astrophysics Data System (ADS)

Ji, Yuanbo; van der Geest, Rob J.; Nazarian, Saman; Lelieveldt, Boudewijn P. F.; Tao, Qian

2018-03-01

Anatomical objects in medical images very often have dual contours or surfaces that are highly correlated. Manually segmenting both of them by following local image details is tedious and subjective. In this study, we proposed a two-layer region-based level set method with a soft distance constraint, which not only regularizes the level set evolution at two levels, but also imposes prior information on wall thickness in an effective manner. By updating the level set function and distance constraint functions alternatingly, the method simultaneously optimizes both contours while regularizing their distance. The method was applied to segment the inner and outer wall of both left atrium (LA) and left ventricle (LV) from MR images, using a rough initialization from inside the blood pool. Compared to manual annotation from experience observers, the proposed method achieved an average perpendicular distance (APD) of less than 1mm for the LA segmentation, and less than 1.5mm for the LV segmentation, at both inner and outer contours. The method can be used as a practical tool for fast and accurate dual wall annotations given proper initialization.

Three-axis asymmetric radiation detector system

DOEpatents

Martini, Mario Pierangelo; Gedcke, Dale A.; Raudorf, Thomas W.; Sangsingkeow, Pat

2000-01-01

A three-axis radiation detection system whose inner and outer electrodes are shaped and positioned so that the shortest path between any point on the inner electrode and the outer electrode is a different length whereby the rise time of a pulse derived from a detected radiation event can uniquely define the azimuthal and radial position of that event, and the outer electrode is divided into a plurality of segments in the longitudinal axial direction for locating the axial location of a radiation detection event occurring in the diode.

ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina.

PubMed

Duncker, Tobias; Lee, Winston; Jiang, Fan; Ramachandran, Rithambara; Hood, Donald C; Tsang, Stephen H; Sparrow, Janet R; Greenstein, Vivienne C

2018-01-01

To assess structure and function across the transition zone (TZ) between relatively healthy and diseased retina in acute zonal occult outer retinopathy. Six patients (6 eyes; age 22-71 years) with acute zonal occult outer retinopathy were studied. Spectral-domain optical coherence tomography, fundus autofluorescence, near-infrared reflectance, color fundus photography, and fundus perimetry were performed and images were registered to each other. The retinal layers of the spectral-domain optical coherence tomography scans were segmented and the thicknesses of two outer retinal layers, that is, the total receptor and outer segment plus layers, and the retinal nerve fiber layer were measured. All eyes showed a TZ on multimodal imaging. On spectral-domain optical coherence tomography, the TZ was in the nasal retina at varying distances from the fovea. For all eyes, it was associated with loss of the ellipsoid zone band, significant thinning of the two outer retinal layers, and in three eyes with thickening of the retinal nerve fiber layer. On fundus autofluorescence, all eyes had a clearly demarcated peripapillary area of abnormal fundus autofluorescence delimited by a border of high autofluorescence; the latter was associated with loss of the ellipsoid zone band and with a change from relatively normal to markedly decreased or nonrecordable visual sensitivity on fundus perimetry. The results of multimodal imaging clarified the TZ in acute zonal occult outer retinopathy. The TZ was outlined by a distinct high autofluorescence border that correlated with loss of the ellipsoid zone band on spectral-domain optical coherence tomography. However, in fundus areas that seemed healthy on fundus autofluorescence, thinning of the outer retinal layers and thickening of the retinal nerve fiber layer were observed near the TZ. The TZ was also characterized by a decrease in visual sensitivity.

Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel.

PubMed

Patel, Kirti A; Bartoli, Kristen M; Fandino, Richard A; Ngatchou, Anita N; Woch, Gustaw; Carey, Jannette; Tanaka, Jacqueline C

2005-07-01

Achromatopsia 2, an inherited retinal disorder resulting in attenuation or loss of cone function, is caused by mutations in the alpha subunit of the cone cyclic nucleotide-gated (CNG) channel gene CNGA3. Examination of mutations that cluster in the first transmembrane segment of the protein may provide insight into its role in CNG channel structure, function, biogenesis, and pathophysiology. The human CNGA3 gene was tagged at the C terminus with green fluorescent protein. Four mutations, Y181C, N182Y, L186F, and C191Y, were expressed in human embryonic kidney cells. Protein expression was evaluated with immunoblot analysis and cellular localization was determined by immunocytochemistry. Channel function was evaluated by patch-clamp electrophysiology. All the mutations result in loss of channel function, as determined by the failure of cGMP to activate wild-type currents in excised patches. Full-length mutant proteins were synthesized but retained in the endoplasmic reticulum. Glycerol treatment did not rescue channel function nor did coexpression with CNGB3, a subunit of native hetero-tetrameric cone channels. A control mutant, C191S, exhibited cGMP current activation with significantly reduced cooperativity, suggesting that mutations in the first transmembrane domain alter in inter- or intrasubunit communication. The results implicate the first transmembrane segment in both maturation and function of CNG channels. The defects are not reversed with glycerol, a chemical chaperone that rescues channel function in some channelopathies. Molecular analysis of achromatopsia 2 mutations may be useful in evaluating potential therapeutic approaches for treatment of this channelopathy.

Regenerator seal design

DOEpatents

Eckart, Francis H.

1982-01-01

A rotary regenerator disc matrix has a face seal with a cross arm and arcuate rim segments joined by prestress clamps to prestrain the arcuate rim seals so as to compensate seal rim twisting or coning and resultant disc face seal leakage as produced by operating thermal gradients across the seal.

The evolution of rod photoreceptors

PubMed Central

Morshedian, Ala

2017-01-01

Photoreceptors in animals are generally of two kinds: the ciliary or c-type and the rhabdomeric or r-type. Although ciliary photoreceptors are found in many phyla, vertebrates seem to be unique in having two distinct kinds which together span the entire range of vision, from single photons to bright light. We ask why the principal photoreceptors of vertebrates are ciliary and not rhabdomeric, and how rods evolved from less sensitive cone-like photoreceptors to produce our duplex retina. We suggest that the principal advantage of vertebrate ciliary receptors is that they use less ATP than rhabdomeric photoreceptors. This difference may have provided sufficient selection pressure for the development of a completely ciliary eye. Although many of the details of rod evolution are still uncertain, present evidence indicates that (i) rods evolved very early before the split between the jawed and jawless vertebrates, (ii) outer-segment discs make no contribution to rod sensitivity but may have evolved to increase the efficiency of protein renewal, and (iii) evolution of the rod was incremental and multifaceted, produced by the formation of several novel protein isoforms and by changes in protein expression, with no one alteration having more than a few-fold effect on transduction activation or inactivation. This article is part of the themed issue ‘Vision in dim light’. PMID:28193819

The evolution of rod photoreceptors.

PubMed

Morshedian, Ala; Fain, Gordon L

2017-04-05

Photoreceptors in animals are generally of two kinds: the ciliary or c-type and the rhabdomeric or r-type. Although ciliary photoreceptors are found in many phyla, vertebrates seem to be unique in having two distinct kinds which together span the entire range of vision, from single photons to bright light. We ask why the principal photoreceptors of vertebrates are ciliary and not rhabdomeric, and how rods evolved from less sensitive cone-like photoreceptors to produce our duplex retina. We suggest that the principal advantage of vertebrate ciliary receptors is that they use less ATP than rhabdomeric photoreceptors. This difference may have provided sufficient selection pressure for the development of a completely ciliary eye. Although many of the details of rod evolution are still uncertain, present evidence indicates that (i) rods evolved very early before the split between the jawed and jawless vertebrates, (ii) outer-segment discs make no contribution to rod sensitivity but may have evolved to increase the efficiency of protein renewal, and (iii) evolution of the rod was incremental and multifaceted, produced by the formation of several novel protein isoforms and by changes in protein expression, with no one alteration having more than a few-fold effect on transduction activation or inactivation.This article is part of the themed issue 'Vision in dim light'. © 2017 The Author(s).

Sculpting Silica Colloids by Etching Particles with Nonuniform Compositions

PubMed Central

2017-01-01

We present the synthesis of new shapes of colloidal silica particles by manipulating their chemical composition and subsequent etching. Segments of silica rods, prepared by the ammonia catalyzed hydrolysis and condensation of tetraethylorthosilicate (TEOS) from polyvinylpyrrolidone loaded water droplets, were grown under different conditions. Upon decreasing temperature, delaying ethanol addition, or increasing monomer concentration, the rate of dissolution of the silica segment subsequently formed decreased. A watery solution of NaOH (∼mM) selectively etched these segments. Further tuning the conditions resulted in rod–cone or cone–cone shapes. Deliberately modulating the composition along the particle’s length by delayed addition of (3-aminopropyl)-triethoxysilane (APTES) also allowed us to change the composition stepwise. The faster etching of this coupling agent in neutral conditions or HF afforded an even larger variety of particle morphologies while in addition changing the chemical functionality. A comparable step in composition was applied to silica spheres. Biamine functional groups used in a similar way as APTES caused a charge inversion during the growth, causing dumbbells and higher order aggregates to form. These particles etched more slowly at the neck, resulting in a biconcave silica ring sandwiched between two silica spheres, which could be separated by specifically etching the functionalized layer using HF. PMID:28413261

Increasing the feasibility of minimally invasive procedures in type A aortic dissections: a framework for segmentation and quantification.

PubMed

Morariu, Cosmin Adrian; Terheiden, Tobias; Dohle, Daniel Sebastian; Tsagakis, Konstantinos; Pauli, Josef

2016-02-01

Our goal is to provide precise measurements of the aortic dimensions in case of dissection pathologies. Quantification of surface lengths and aortic radii/diameters together with the visualization of the dissection membrane represents crucial prerequisites for enabling minimally invasive treatment of type A dissections, which always also imply the ascending aorta. We seek a measure invariant to luminance and contrast for aortic outer wall segmentation. Therefore, we propose a 2D graph-based approach using phase congruency combined with additional features. Phase congruency is extended to 3D by designing a novel conic directional filter and adding a lowpass component to the 3D Log-Gabor filterbank for extracting the fine dissection membrane, which separates the true lumen from the false one within the aorta. The result of the outer wall segmentation is compared with manually annotated axial slices belonging to 11 CTA datasets. Quantitative assessment of our novel 2D/3D membrane extraction algorithms has been obtained for 10 datasets and reveals subvoxel accuracy in all cases. Aortic inner and outer surface lengths, determined within 2 cadaveric CT datasets, are validated against manual measurements performed by a vascular surgeon on excised aortas of the body donors. This contribution proposes a complete pipeline for segmentation and quantification of aortic dissections. Validation against ground truth of the 3D contour lengths quantification represents a significant step toward custom-designed stent-grafts.

Light-dependent translocation of arrestin in rod photoreceptors is signaled through a phospholipase C cascade and requires ATP.

PubMed

Orisme, Wilda; Li, Jian; Goldmann, Tobias; Bolch, Susan; Wolfrum, Uwe; Smith, W Clay

2010-03-01

Partitioning of cellular components is a critical mechanism by which cells can regulate their activity. In rod photoreceptors, light induces a large-scale translocation of arrestin from the inner segments to the outer segments. The purpose of this project is to elucidate the signaling pathway necessary to initiate arrestin translocation to the outer segments and the mechanism for arrestin translocation. Mouse retinal organotypic cultures and eyes from transgenic Xenopus tadpoles expressing a fusion of GFP and rod arrestin were treated with both activators and inhibitors of proteins in the phosphoinositide pathway. Confocal microscopy was used to image the effects of the pharmacological agents on arrestin translocation in rod photoreceptors. Retinas were also depleted of ATP using potassium cyanide to assess the requirement for ATP in arrestin translocation. In this study, we demonstrate that components of the G-protein-linked phospholipase C (PLC) pathway play a role in initiating arrestin translocation. Our results show that arrestin translocation can be stimulated by activators of PLC and protein kinase C (PKC), and by cholera toxin in the absence of light. Arrestin translocation to the outer segments is significantly reduced by inhibitors of PLC and PKC. Importantly, we find that treatment with potassium cyanide inhibits arrestin translocation in response to light. Collectively, our results suggest that arrestin translocation is initiated by a G-protein-coupled cascade through PLC and PKC signaling. Furthermore, our results demonstrate that at least the initiation of arrestin translocation requires energy input.

Evolution of Magnetic Rayleigh–Taylor Instability into the Outer Solar Corona and Low Interplanetary Space

NASA Astrophysics Data System (ADS)

Mishra, Sudheer K.; Singh, Talwinder; Kayshap, P.; Srivastava, A. K.

2018-03-01

We analyze the observations from Solar TErrestrial RElations Observatory (STEREO)-A and B/COR-1 of an eruptive prominence in the intermediate corona on 2011 June 7 at 08:45 UT, which consists of magnetic Rayleigh–Taylor (MRT) unstable plasma segments. Its upper-northward segment shows spatio-temporal evolution of MRT instability in form of finger structures up to the outer corona and low interplanetary space. Using the method of Dolei et al., It is estimated that the density in each bright finger is greater than the corresponding dark region lying below it in the surrounding intermediate corona. The instability is evolved due to wave perturbations that are parallel to the magnetic field at the density interface. We conjecture that the prominence plasma is supported by tension component of the magnetic field against gravity. Through the use of linear stability theory, the magnetic field is estimated as 21–40 mG to suppress growth of MRT instability in the observed finger structures. In the southward plasma segment, a horn-like structure is observed at 11:55 UT in the intermediate corona that also indicates MRT instability. Falling blobs are also observed in both of the plasma segments. In the outer corona, up to 6–13 solar radii, the mushroom-like plasma structures have been identified in the upper-northward MRT unstable plasma segment using STEREO-A/COR-2. These structures most likely grew due to the breaking and twisting of fingers at large spatial scales in weaker magnetic fields. In the lower interplanetary space up to 20 solar radii, these structures are fragmented into various small-scale localized plasma spikes, most likely due to turbulent mixing.

KSC-2009-2308

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – The NASA Railroad hauls one of the cars with the first Ares I-X segment to the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida. Four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments are being delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

KSC-2009-2307

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – The NASA Railroad hauls one of the cars with the first Ares I-X segment to the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida. Four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments are being delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

KSC-2009-2310

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – The NASA Railroad delivers the first Ares I-X segment to the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida. Four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments are being delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

KSC-2009-2212

NASA Image and Video Library

2009-03-19

CAPE CANAVERAL, Fla. – The NASA Railroad makes the exchange with the Florida East Coast Railway cars carrying the booster segments for the Ares I-X test rocket. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to the Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2309

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – The NASA Railroad delivers the first Ares I-X segment to the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida. Four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments are being delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

Light-Induced Translocation of RGS9-1 and Gβ5L in Mouse Rod Photoreceptors

PubMed Central

Tian, Mei; Zallocchi, Marisa; Wang, Weimin; Chen, Ching-Kang; Palczewski, Krzysztof; Delimont, Duane; Cosgrove, Dominic; Peng, You-Wei

2013-01-01

The transducin GTPase-accelerating protein complex, which determines the photoresponse duration of photoreceptors, is composed of RGS9-1, Gβ5L and R9AP. Here we report that RGS9-1 and Gβ5L change their distribution in rods during light/dark adaptation. Upon prolonged dark adaptation, RGS9-1 and Gβ5L are primarily located in rod inner segments. But very dim-light exposure quickly translocates them to the outer segments. In contrast, their anchor protein R9AP remains in the outer segment at all times. In the dark, Gβ5L's interaction with R9AP decreases significantly and RGS9-1 is phosphorylated at S475 to a significant degree. Dim light exposure leads to quick de-phosphorylation of RGS9-1. Furthermore, after prolonged dark adaptation, RGS9-1 and transducin Gα are located in different cellular compartments. These results suggest a previously unappreciated mechanism by which prolonged dark adaptation leads to increased light sensitivity in rods by dissociating RGS9-1 from R9AP and redistributing it to rod inner segments. PMID:23555598

Live-Cell Imaging of Phagosome Motility in Primary Mouse RPE Cells.

PubMed

Hazim, Roni; Jiang, Mei; Esteve-Rudd, Julian; Diemer, Tanja; Lopes, Vanda S; Williams, David S

2016-01-01

The retinal pigment epithelium (RPE) is a post-mitotic epithelial monolayer situated between the light-sensitive photoreceptors and the choriocapillaris. Given its vital functions for healthy vision, the RPE is a primary target for insults that result in blinding diseases, including age-related macular degeneration (AMD). One such function is the phagocytosis and digestion of shed photoreceptor outer segments. In the present study, we examined the process of trafficking of outer segment disk membranes in live cultures of primary mouse RPE, using high speed spinning disk confocal microscopy. This approach has enabled us to track phagosomes, and determine parameters of their motility, which are important for their efficient degradation.

Shoreline configuration and shoreline dynamics: A mesoscale analysis. [Assateague Island and Outer Banks of North Carolina

NASA Technical Reports Server (NTRS)

Dolan, R. (Principal Investigator); Hayden, B. P.; Heywood, J. E.

1975-01-01

The author has identified the following significant results. Atlantic coast barrier island shorelines are seldom straight, but rather sinuous. These shoreline curvatures range in size from cusps to capes. Significant relationships exist between the orientation of shoreline segments within the larger of these sinuous features and shoreline dynamics, with coefficients ranging up to .9. Orientation of the shoreline segments of Assateague Island (60 km) and the Outer Banks of North Carolina (130 km) was measured from LANDSAT 2 imagery (1:80,000) and high altitude aerial photography (1:120,000). Long term trends in shoreline dynamics were established by mapping shoreline and storm-surge penetration changes.

Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype.

PubMed

Schwartz, Sharon B; Aleman, Tomas S; Cideciyan, Artur V; Windsor, Elizabeth A M; Sumaroka, Alexander; Roman, Alejandro J; Rane, Tej; Smilko, Elaine E; Bennett, Jean; Stone, Edwin M; Kimberling, William J; Liu, Xue-Zhong; Jacobson, Samuel G

2005-02-01

To investigate the retinal disease expression in USH2C, the subtype of Usher syndrome type 2 recently shown to be caused by mutation in the VLGR1 gene, and compare results with those from USH2A, a more common cause of Usher syndrome. Three siblings with USH2C and 14 patients with USH2A were studied. Visual function was measured by kinetic perimetry, static chromatic perimetry, and electroretinography (ERG). Central retinal microstructure was studied with optical coherence tomography (OCT). The siblings with VLGR1 mutation showed abnormal photoreceptor-mediated function in all retinal regions, and there was greater rod than cone dysfunction. USH2A had a wider spectrum of disease expression and included patients with normal function in some retinal regions. When abnormalities were detected, there was more rod than cone dysfunction. Retinal microstructure in both USH2C and USH2A shared the abnormality of loss of outer nuclear layer thickness. Central retinal structure in both genotypes was complicated by cystic macular lesions. A coincidental finding in an USH2C patient was that oral intake of antihistamines was associated with temporary resolution of the macular cystic change. USH2C and USH2A manifest photoreceptor disease with rod- and cone-mediated visual losses and thinning of the outer nuclear layer. An orderly progression through disease stages was estimated from cross-sectional and limited longitudinal data. Intrafamilial and interfamilial variation in retinal severity in USH2A, however, suggests that genetic or nongenetic modifiers may be involved in the disease expression.

KSC-2009-2320

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, technicians check the fit of the end cover on the Ares I-X motor segment. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2321

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, the open end of the Ares I-X motor segment is seen without the end cover. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2319

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, a technician begins propellant grain inspection of the interior of the Ares I-X motor segment. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2316

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, the Ares I-X motor segment waits for inspection after removal of the shipping container. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2322

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, a technician performs propellant grain inspection of the inside of the Ares I-X motor segment. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2314

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, the rail car cover is moved away from the first Ares I-X motor segment. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2315

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, the Ares I-X motor segment is revealed after removal of the rail car cover. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2313

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, the rail car cover is removed from the first Ares I-X motor segment. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2312

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, the rail car cover is removed from the first Ares I-X motor segment. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

Symmetry control in subscale near-vacuum hohlraums

NASA Astrophysics Data System (ADS)

Turnbull, D.; Berzak Hopkins, L. F.; Le Pape, S.; Divol, L.; Meezan, N.; Landen, O. L.; Ho, D. D.; Mackinnon, A.; Zylstra, A. B.; Rinderknecht, H. G.; Sio, H.; Petrasso, R. D.; Ross, J. S.; Khan, S.; Pak, A.; Dewald, E. L.; Callahan, D. A.; Hurricane, O.; Hsing, W. W.; Edwards, M. J.

2016-05-01

Controlling the symmetry of indirect-drive inertial confinement fusion implosions remains a key challenge. Increasing the ratio of the hohlraum diameter to the capsule diameter (case-to-capsule ratio, or CCR) facilitates symmetry tuning. By varying the balance of energy between the inner and outer cones as well as the incident laser pulse length, we demonstrate the ability to tune from oblate, through round, to prolate at a CCR of 3.2 in near-vacuum hohlraums at the National Ignition Facility, developing empirical playbooks along the way for cone fraction sensitivity of various laser pulse epochs. Radiation-hydrodynamic simulations with enhanced inner beam propagation reproduce most experimental observables, including hot spot shape, for a majority of implosions. Specular reflections are used to diagnose the limits of inner beam propagation as a function of pulse length.

Directing collagen fibers using counter-rotating cone extrusion.

PubMed

Hoogenkamp, Henk R; Bakker, Gert-Jan; Wolf, Louis; Suurs, Patricia; Dunnewind, Bertus; Barbut, Shai; Friedl, Peter; van Kuppevelt, Toin H; Daamen, Willeke F

2015-01-01

The bio-inspired engineering of tissue equivalents should take into account anisotropic morphology and the mechanical properties of the extracellular matrix. This especially applies to collagen fibrils, which have various, but highly defined, orientations throughout tissues and organs. There are several methods available to control the alignment of soluble collagen monomers, but the options to direct native insoluble collagen fibers are limited. Here we apply a controlled counter-rotating cone extrusion technology to engineer tubular collagen constructs with defined anisotropy. Driven by diverging inner and outer cone rotation speeds, collagen fibrils from bovine skin were extruded and precipitated onto mandrels as tubes with oriented fibers and bundles, as examined by second harmonic generation microscopy and quantitative image analysis. A clear correlation was found whereby the direction and extent of collagen fiber alignment during extrusion were a function of the shear forces caused by a combination of the cone rotation and flow direction. A gradual change in the fiber direction, spanning +50 to -40°, was observed throughout the sections of the sample, with an average decrease ranging from 2.3 to 2.6° every 10μm. By varying the cone speeds, the collagen constructs showed differences in elasticity and toughness, spanning 900-2000kPa and 19-35mJ, respectively. Rotational extrusion presents an enabling technology to create and control the (an)isotropic architecture of collagen constructs for application in tissue engineering and regenerative medicine. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The application of cone-beam CT in the aging of bone calluses: a new perspective?

PubMed

Cappella, A; Amadasi, A; Gaudio, D; Gibelli, D; Borgonovo, S; Di Giancamillo, M; Cattaneo, C

2013-11-01

In the forensic and anthropological fields, the assessment of the age of a bone callus can be crucial for a correct analysis of injuries in the skeleton. To our knowledge, the studies which have focused on this topic are mainly clinical and still leave much to be desired for forensic purposes, particularly in looking for better methods for aging calluses in view of criminalistic applications. This study aims at evaluating the aid cone-beam CT can give in the investigation of the inner structure of fractures and calluses, thus acquiring a better knowledge of the process of bone remodeling. A total of 13 fractures (three without callus formation and ten with visible callus) of known age from cadavers were subjected to radiological investigations with digital radiography (DR) (conventional radiography) and cone-beam CT with the major aim of investigating the differences between DR and tomographic images when studying the inner and outer structures of bone healing. Results showed how with cone-beam CT the structure of the callus is clearly visible with higher specificity and definition and much more information on mineralization in different sections and planes. These results could lay the foundation for new perspectives on bone callus evaluation and aging with cone-beam CT, a user-friendly and skillful technique which in some instances can also be used extensively on the living (e.g., in cases of child abuse) with reduced exposition to radiation.

Comparative retinal morphology of the platypus.

PubMed

Zeiss, Caroline J; Schwab, Ivan R; Murphy, Christopher J; Dubielzig, Richard W

2011-08-01

The purpose of this study is to identify evolutionary origin and fate of anatomic features of the duck-billed platypus eye. Eyes from the duck-billed platypus and four key evolutionary basal vertebrates (Pacific hagfish, north hemisphere sea lamprey, and Australian and South American lungfishes) were prepared for light microscopy. In addition to a standard panel of stains, tissues were immunostained against a variety of rod and cone opsins. Finally, published opsin sequences of platypus and several other vertebrate species were aligned and compared with immunohistochemical results. A complete scleral cartilage similar to that seen in birds, reptiles and amphibians encloses the platypus eye. This feature is present in sharks and rays, and in extant relatives of tetrapods, the lungfishes. The choroid lacks a tapetum. The retina is largely avascular and is rod-dominated, with a minority of red- and blue- cone immunoreactive photoreceptors. Like marsupials and many nonmammalian vertebrates, cones contain clear inner segment droplets. Double cones were present, a feature not found in eutherian mammals or marsupials. Evaluation of opsins indicates that red and blue immunoreactive cone opsins, but not rhodopsin, are present in the most basal of the extant species examined, the Pacific hagfish. Rhodopsin appears in the Australian and South American lungfishes, establishing emergence of this pigment in an extant relative of tetrapods. Unlike eyes of eutherian mammals, the platypus eye has retained morphologic features present in early tetrapods such as amphibians and their evolutionarily basal sister group, the lungfishes. These include scleral cartilage, double cones and cone droplets. In the platypus, as in other mammals, rod rhodopsin is the predominant photoreceptor pigment, at expense of the cone system. Copyright © 2011 Wiley-Liss, Inc.

An Ambulatory Surgery Service Feasibility Study at Madigan Army Medical Center, Tacoma, Washington

DTIC Science & Technology

1978-08-01

sturmdorf) Benign Intraoral lesions Cervical cone Branchial arch appendages, Colpotomy, diagnostic excision Cryotherapy (alone)" Basla cell CA...petrous pyramid, atti- ceantrotomy, closure of fistula, exteneeration of air cells of petrous pyramid, mastoid antrotomy, removal of outer attic wall...here admission forms will be filled out. Patients will then take those forms to the Admissions Office and return to that clinic for stamin up of 1

Live Imaging of LysoTracker-Labelled Phagolysosomes Tracks Diurnal Phagocytosis of Photoreceptor Outer Segment Fragments in Rat RPE Tissue Ex Vivo.

PubMed

Mao, Yingyu; Finnemann, Silvia C

2016-01-01

Renewal of rod photoreceptor outer segments in the mammalian eye involves synchronized diurnal shedding after light onset of spent distal outer segment fragments (POS) linked to swift clearance of shed POS from the subretinal space by the adjacent retinal pigment epithelium (RPE). Engulfed POS phagosomes in RPE cells mature to acidified phagolysosomes, which accomplish enzymatic degradation of POS macromolecules. Here, we used an acidophilic fluorophore LysoTracker to label acidic organelles in freshly dissected, live rat RPE tissue flat mounts. We observed that all RPE cells imaged contained numerous acidified POS phagolysosomes whose abundance per cell was dramatically increased 2 h after light onset as compared to either 1 h before or 4 h after light onset. Lack of organelles of similar diameter (of 1-2 μm) in phagocytosis-defective mutant RCS rat RPE confirmed that LysoTracker live imaging detected POS phagolysosomes. Lack of increase in lysosomal membrane protein LAMP-1 in RPE/choroid during the diurnal phagocytic burst suggests that formation of POS phagolysosomes in RPE in situ may not involve extra lysosome membrane biogenesis. Taken together, we report a new imaging approach that directly detects POS phagosome acidification and allows rapid tracking and quantification of POS phagocytosis by live RPE -tissue ex situ.

Recirculating electric air filter

DOEpatents

Bergman, Werner

1986-01-01

An electric air filter cartridge has a cylindrical inner high voltage eleode, a layer of filter material, and an outer ground electrode formed of a plurality of segments moveably connected together. The outer electrode can be easily opened to remove or insert filter material. Air flows through the two electrodes and the filter material and is exhausted from the center of the inner electrode.

Recirculating electric air filter

DOEpatents

Bergman, W.

1985-01-09

An electric air filter cartridge has a cylindrical inner high voltage electrode, a layer of filter material, and an outer ground electrode formed of a plurality of segments moveably connected together. The outer electrode can be easily opened to remove or insert filter material. Air flows through the two electrodes and the filter material and is exhausted from the center of the inner electrode.

Comparative myoanatomy of Echinoderes (Kinorhyncha): a comprehensive investigation by CLSM and 3D reconstruction.

PubMed

Herranz, María; Boyle, Michael J; Pardos, Fernando; Neves, Ricardo C

2014-04-05

Kinorhyncha is a clade of marine invertebrate meiofauna. Their body plan includes a retractable introvert bearing rings of cuticular spines, and a limbless trunk with distinct segmentation of nervous, muscular and epidermal organ systems. As derived members within the basal branch of Ecdysozoa, kinorhynchs may provide an important example of convergence on the evolution of segmentation within one of three bilaterian superclades. We describe the myoanatomy of Echinoderes, the most specious kinorhynch genus, and build upon historical studies of kinorhynch ultrastructure and gross morphology. This is the first multi-species comparison of a complete organ system by confocal microscopy and three-dimensional reconstruction within Kinorhyncha. Myoanatomy of adult Echinoderes is composed of the following: Head with two mouth cone circular muscles, nine pairs of oral style muscles, ten introvert retractors, one introvert circular muscle, and fourteen introvert circular muscle retractors; Neck with one circular muscle; Trunk showing distinct pairs of ventral and dorsal muscles within segments 1-10, dorsoventral muscles within segments 3-10, diagonal muscles within segments 1-8, longitudinal fibers spanning segments 1-9, three pairs of terminal spine muscles, and one pair of male penile spine muscles; Gut showing a pharynx with ten alternating rings of radial and circular muscle fibers enclosed in a complex sheath of protractors and retractors, an orthogonal grid of longitudinal and circular fibers surrounding the intestine, and paired hindgut dilators. Myoanatomy is highly conserved between species of Echinoderes. Interspecific variation is observed in the arrangement and number of introvert fibers and the composition of pharyngeal muscles. Segmented trunk musculature facilitates the movements of articulated cuticular plates along the anterior-posterior axis. Intersegmental muscle fibers assist with dorsoventral and lateral trunk movements. Protractors, retractors and circular muscles coordinate eversion and retraction of the introvert and mouth cone, and relocation of the pharynx during locomotion and feeding behaviors. Pairs of posterior fibers suggest independent movements of terminal spines, and male penile spines. Within Scalidophora, myoanatomy is more similar between Kinorhyncha and Loricifera, than either group is to Priapulida. Kinorhynch myoanatomy may reflect a convergent transition from vermiform to segmented body plans during the early radiation of Ecdysozoa.

Point spread function modeling and image restoration for cone-beam CT

NASA Astrophysics Data System (ADS)

Zhang, Hua; Huang, Kui-Dong; Shi, Yi-Kai; Xu, Zhe

2015-03-01

X-ray cone-beam computed tomography (CT) has such notable features as high efficiency and precision, and is widely used in the fields of medical imaging and industrial non-destructive testing, but the inherent imaging degradation reduces the quality of CT images. Aimed at the problems of projection image degradation and restoration in cone-beam CT, a point spread function (PSF) modeling method is proposed first. The general PSF model of cone-beam CT is established, and based on it, the PSF under arbitrary scanning conditions can be calculated directly for projection image restoration without the additional measurement, which greatly improved the application convenience of cone-beam CT. Secondly, a projection image restoration algorithm based on pre-filtering and pre-segmentation is proposed, which can make the edge contours in projection images and slice images clearer after restoration, and control the noise in the equivalent level to the original images. Finally, the experiments verified the feasibility and effectiveness of the proposed methods. Supported by National Science and Technology Major Project of the Ministry of Industry and Information Technology of China (2012ZX04007021), Young Scientists Fund of National Natural Science Foundation of China (51105315), Natural Science Basic Research Program of Shaanxi Province of China (2013JM7003) and Northwestern Polytechnical University Foundation for Fundamental Research (JC20120226, 3102014KYJD022)

The electrical response of turtle cones to flashes and steps of light.

PubMed

Baylor, D A; Hodgkin, A L; Lamb, T D

1974-11-01

1. The linear response of turtle cones to weak flashes or steps of light was usually well fitted by equations based on a chain of six or seven reactions with time constants varying over about a 6-fold range.2. The temperature coefficient (Q(10)) of the reciprocal of the time to peak of the response to a flash was 1.8 (15-25 degrees C), corresponding to an activation energy of 10 kcal/mole.3. Electrical measurements with one internal electrode and a balancing circuit gave the following results on red-sensitive cones of high resistance: resistance across cell surface in dark 50-170 MOmega; time constant in dark 4-6.5 msec. The effect of a bright light was to increase the resistance and time constant by 10-30%.4. If the cell time constant, resting potential and maximum hyperpolarization are known, the fraction of ionic channels blocked by light at any instant can be calculated from the hyperpolarization and its rate of change. At times less than 50 msec the shape of this relation is consistent with the idea that the concentration of a blocking molecule which varies linearly with light intensity is in equilibrium with the fraction of ionic channels blocked.5. The rising phase of the response to flashes and steps of light covering a 10(5)-fold range of intensities is well fitted by a theory in which the essential assumptions are that (i) light starts a linear chain of reactions leading to the production of a substance which blocks ionic channels in the outer segment, (ii) an equilibrium between the blocking molecules and unblocked channels is established rapidly, and (iii) the electrical properties of the cell can be represented by a simple circuit with a time constant in the dark of about 6 msec.6. Deviations from the simple theory which occur after 50 msec are attributed partly to a time-dependent desensitization mechanism and partly to a change in saturation potential resulting from a voltage-dependent change in conductance.7. The existence of several components in the relaxation of the potential to its resting level can be explained by supposing that the ;substance' which blocks light sensitive ionic channels is inactivated in a series of steps.

The saturation of monochromatic lights obliquely incident on the retina.

PubMed Central

Alpern, M; Tamaki, R

1983-01-01

Foveal dark-adaptation undertaken to test the hypothesis that the excitation of rods causes the desaturation of 'yellow' lights in a 1 degree field traversing the margin of the pupil, fails to exclude that possibility. The desaturation is largest for a 1 degree outside diameter annular test, is still measurable with a 0.5 degree circular disk, but disappears for a 0.29 degree disk. The supersaturation of obliquely incident 501.2 nm test light follows the opposite pattern; it disappears with an annulus and is largest for a 0.29 degree circular field. It is unlikely that rods replace short-wave sensitive cones in the trichromatic match of an obliquely incident test with normally incident primaries. If rods as well as all three cones species are involved, the matches might not be trichromatic in the strong sense. Grassmann's law of scalar multiplication was tested and shown not to hold for the match of an obliquely incident test with normally incident primaries, though it remains valid whenever, both primaries and test strike the retina at the same angle of incidence (independent of that angle). The result in section 3 (above) cannot be due to rod intrusion. It persists (and becomes more conspicuous) on backgrounds (4.0 log scotopic td) which saturate rods. Moreover obliquely incident 'yellow' lights remain desaturated in intervals in the dark after a full bleach, whilst the test field is below rod threshold. The amount of desaturation does not differ appreciably from that normally found. The assumption of the unified theory of Alpern, Kitahara & Tamaki (1983) that the outer segments of only a single set of three cone species (with acceptance angles wide enough to include the entire exit pupil) contain the visual pigments absorbing both the normally incident primaries and the obliquely incident test is disproved by these results. Failure of Grassmann's law is most conspicuous under the conditions for which the changes in saturation upon changing from normal to oblique incidence are greatest and least when the saturation changes are the smallest. Either all unified theories of the Stiles-Crawford effects are wrong or all the effects of oblique incidence operate at a stage in the visual process at which the effects of radiation of different wave-lengths are no longer compounded by the simple linear laws. PMID:6875976

Automated segmentation of mouse OCT volumes (ASiMOV): Validation & clinical study of a light damage model.

PubMed

Antony, Bhavna Josephine; Kim, Byung-Jin; Lang, Andrew; Carass, Aaron; Prince, Jerry L; Zack, Donald J

2017-01-01

The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study.

Automated segmentation of mouse OCT volumes (ASiMOV): Validation & clinical study of a light damage model

PubMed Central

Lang, Andrew; Carass, Aaron; Prince, Jerry L.; Zack, Donald J.

2017-01-01

The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study. PMID:28817571

Automatic plaque characterization and vessel wall segmentation in magnetic resonance images of atherosclerotic carotid arteries

NASA Astrophysics Data System (ADS)

Adame, Isabel M.; van der Geest, Rob J.; Wasserman, Bruce A.; Mohamed, Mona; Reiber, Johan H. C.; Lelieveldt, Boudewijn P. F.

2004-05-01

Composition and structure of atherosclerotic plaque is a primary focus of cardiovascular research. In vivo MRI provides a meanse to non-invasively image and assess the morphological features of athersclerotic and normal human carotid arteries. To quantitatively assess the vulnerability and the type of plaque, the contours of the lumen, outer boundary of the vessel wall and plaque components, need to be traced. To achieve this goal, we have developed an automated contou detection technique, which consists of three consecutive steps: firstly, the outer boundary of the vessel wall is detected by means of an ellipse-fitting procedure in order to obtain smoothed shapes; secondly, the lumen is segnented using fuzzy clustering. Thre region to be classified is that within the outer vessel wall boundary obtained from the previous step; finally, for plaque detection we follow the same approach as for lumen segmentation: fuzzy clustering. However, plaque is more difficult to segment, as the pixel gray value can differ considerably from one region to another, even when it corresponds to the same type of tissue. That makes further processing necessary. All these three steps might be carried out combining information from different sequences (PD-, T2-, T1-weighted images, pre- and post-contrast), to improve the contour detection. The algorithm has been validated in vivo on 58 high-resolution PD and T1 weighted MR images (19 patients). The results demonstrate excellent correspondence between automatic and manual area measurements: lumen (r=0.94), outer (r=0.92), and acceptable for fibrous cap thickness (r=0.76).

Generating high-power short terahertz electromagnetic pulses with a multifoil radiator.

PubMed

Vinokurov, Nikolay A; Jeong, Young Uk

2013-02-08

We describe a multifoil cone radiator capable of generating high-field short terahertz pulses using short electron bunches. Round flat conducting foil plates with successively decreasing radii are stacked, forming a truncated cone with the z axis. The gaps between the foil plates are equal and filled with some dielectric (or vacuum). A short relativistic electron bunch propagates along the z axis. At sufficiently high particle energy, the energy losses and multiple scattering do not change the bunch shape significantly. When passing by each gap between the foil plates, the electron bunch emits some energy into the gap. Then, the radiation pulses propagate radially outward. For transverse electromagnetic waves with a longitudinal (along the z axis) electric field and an azimuthal magnetic field, there is no dispersion in these radial lines; therefore, the radiation pulses conserve their shapes (time dependence). At the outer surface of the cone, we have synchronous circular radiators. Their radiation field forms a conical wave. Ultrashort terahertz pulses with gigawatt-level peak power can be generated with this device.

The effect of light on outer segment calcium in salamander rods

PubMed Central

Matthews, Hugh R; Fain, Gordon L

2003-01-01

Calcium acts as a second messenger in vertebrate rods, regulating the recovery phase of the light response and modulating sensitivity during light-adaptation. Since light not only decreases the outer segment calcium concentration ([Ca2+]i) by closing cyclic nucleotide-gated channels but can also increase [Ca2+]i by releasing Ca2+ from buffer sites or intracellular stores, we examined in detail the effect of light and circulating current on [Ca2+]i by making simultaneous measurements of suction pipette current and [Ca2+]i from isolated rods of the salamander Ambystoma tigrinum after incorporation of the fluorescent dye fluo-5F. When the release of Ca2+ is measured in 0 Ca2+−0 Na+ solution, minimising fluxes of Ca2+ across the plasma membrane, it is substantial only for light bright enough to bleach a significant fraction of the photopigment and is restricted to the part of the outer segment in which the bleach occurred. It is unlikely, therefore, to make a large contribution to [Ca2+]i for most of the physiological operating range of the rod. Nevertheless, since release is half-maximal for a bleach of less than 10 %, it cannot be produced by a simple mechanism such as a change in the affinity of a binding site on rhodopsin itself but must instead require some more complex interaction. In Ringer solution, the Ca2+ in the light-releasable pool can be discharged merely by the decrease in [Ca2+]i that occurs as the outer segment channels close. In steady background light or after exposure to saturating illumination, the fraction of Ca2+ in the pool decreases essentially in proportion to [Ca2+]i as if Ca2+ were being removed from a buffer site within the cytoplasm. Furthermore, [Ca2+]i itself changes in proportion to the circulating current, with little evidence for a contribution from Ca2+ release or other mechanisms of Ca2+ homeostasis. This indicates that flux of Ca2+ across the plasma membrane is the major determinant of outer segment Ca2+ concentration within the rod's normal operating light intensity range. Once Ca2+ has been discharged from the releasable pool, it is restored following dim illumination apparently as the simple result of the subsequent restoration of dark [Ca2+]i and the rebinding of Ca2+ to its release site, but after brighter light perhaps also as a consequence of regeneration of the photopigment. PMID:12949220

Pyrometer mount for a closed-circuit thermal medium cooled gas turbine

DOEpatents

Jones, Raymond Joseph; Kirkpatrick, Francis Lawrence; Burns, James Lee; Fulton, John Robert

2002-01-01

A steam-cooled second-stage nozzle segment has an outer band and an outer cover defining a plenum therebetween for receiving cooling steam for flow through the nozzles to the inner band and cover therefor and return flow through the nozzles. To measure the temperature of the buckets of the stage forwardly of the nozzle stage, a pyrometer boss is electron beam-welded in an opening through the outer band and TIG-welded to the outer cover plate. By machining a hole through the boss and seating a linearly extending tube in the boss, a line of sight between a pyrometer mounted on the turbine frame and the buckets is provided whereby the temperature of the buckets can be ascertained. The welding of the boss to the outer band and outer cover enables steam flow through the plenum without leakage, while providing a line of sight through the outer cover and outer band to measure bucket temperature.

Model-based segmentation in orbital volume measurement with cone beam computed tomography and evaluation against current concepts.

PubMed

Wagner, Maximilian E H; Gellrich, Nils-Claudius; Friese, Karl-Ingo; Becker, Matthias; Wolter, Franz-Erich; Lichtenstein, Juergen T; Stoetzer, Marcus; Rana, Majeed; Essig, Harald

2016-01-01

Objective determination of the orbital volume is important in the diagnostic process and in evaluating the efficacy of medical and/or surgical treatment of orbital diseases. Tools designed to measure orbital volume with computed tomography (CT) often cannot be used with cone beam CT (CBCT) because of inferior tissue representation, although CBCT has the benefit of greater availability and lower patient radiation exposure. Therefore, a model-based segmentation technique is presented as a new method for measuring orbital volume and compared to alternative techniques. Both eyes from thirty subjects with no known orbital pathology who had undergone CBCT as a part of routine care were evaluated (n = 60 eyes). Orbital volume was measured with manual, atlas-based, and model-based segmentation methods. Volume measurements, volume determination time, and usability were compared between the three methods. Differences in means were tested for statistical significance using two-tailed Student's t tests. Neither atlas-based (26.63 ± 3.15 mm(3)) nor model-based (26.87 ± 2.99 mm(3)) measurements were significantly different from manual volume measurements (26.65 ± 4.0 mm(3)). However, the time required to determine orbital volume was significantly longer for manual measurements (10.24 ± 1.21 min) than for atlas-based (6.96 ± 2.62 min, p < 0.001) or model-based (5.73 ± 1.12 min, p < 0.001) measurements. All three orbital volume measurement methods examined can accurately measure orbital volume, although atlas-based and model-based methods seem to be more user-friendly and less time-consuming. The new model-based technique achieves fully automated segmentation results, whereas all atlas-based segmentations at least required manipulations to the anterior closing. Additionally, model-based segmentation can provide reliable orbital volume measurements when CT image quality is poor.

Inner and outer coronary vessel wall segmentation from CCTA using an active contour model with machine learning-based 3D voxel context-aware image force

NASA Astrophysics Data System (ADS)

Sivalingam, Udhayaraj; Wels, Michael; Rempfler, Markus; Grosskopf, Stefan; Suehling, Michael; Menze, Bjoern H.

2016-03-01

In this paper, we present a fully automated approach to coronary vessel segmentation, which involves calcification or soft plaque delineation in addition to accurate lumen delineation, from 3D Cardiac Computed Tomography Angiography data. Adequately virtualizing the coronary lumen plays a crucial role for simulating blood ow by means of fluid dynamics while additionally identifying the outer vessel wall in the case of arteriosclerosis is a prerequisite for further plaque compartment analysis. Our method is a hybrid approach complementing Active Contour Model-based segmentation with an external image force that relies on a Random Forest Regression model generated off-line. The regression model provides a strong estimate of the distance to the true vessel surface for every surface candidate point taking into account 3D wavelet-encoded contextual image features, which are aligned with the current surface hypothesis. The associated external image force is integrated in the objective function of the active contour model, such that the overall segmentation approach benefits from the advantages associated with snakes and from the ones associated with machine learning-based regression alike. This yields an integrated approach achieving competitive results on a publicly available benchmark data collection (Rotterdam segmentation challenge).

Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina

PubMed Central

Osada, Hideto; Okamoto, Tomohiro; Kawashima, Hirohiko; Toda, Eriko; Miyake, Seiji; Nagai, Norihiro; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

2017-01-01

Excessive exposure to light promotes degenerative and blinding retinal diseases such as age-related macular degeneration and retinitis pigmentosa. However, the underlying mechanisms of photo-induced retinal degeneration are not fully understood, and a generalizable preventive intervention has not been proposed. Bilberry extract is an antioxidant-rich supplement that ameliorates ocular symptoms. However, its effects on photo-stressed retinas have not been clarified. In this study, we examined the neuroprotective effects of bilberry extract against photo-stress in murine retinas. Light-induced visual function impairment recorded by scotopic and phototopic electroretinograms showing respective rod and cone photoreceptor function was attenuated by oral administration of bilberry extract through a stomach tube in Balb/c mice (750 mg/kg body weight). Bilberry extract also suppressed photo-induced apoptosis in the photoreceptor cell layer and shortening of the outer segments of rod and cone photoreceptors. Levels of photo-induced reactive oxygen species (ROS), oxidative and endoplasmic reticulum (ER) stress markers, as measured by real-time reverse transcriptase polymerase chain reaction, were reduced by bilberry extract treatment. Reduction of ROS by N-acetyl-L-cysteine, a well-known antioxidant also suppressed ER stress. Immunohistochemical analysis of activating transcription factor 4 expression showed the presence of ER stress in the retina, and at least in part, in Müller glial cells. The photo-induced disruption of tight junctions in the retinal pigment epithelium was also attenuated by bilberry extract, repressing an oxidative stress marker, although ER stress markers were not repressed. Our results suggest that bilberry extract attenuates photo-induced apoptosis and visual dysfunction most likely, and at least in part, through ROS reduction, and subsequent ER stress attenuation in the retina. This study can help understand the mechanisms of photo-stress and contribute to developing a new, potentially useful therapeutic approach using bilberry extract for preventing retinal photo-damage. PMID:28570634

Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina.

PubMed

Osada, Hideto; Okamoto, Tomohiro; Kawashima, Hirohiko; Toda, Eriko; Miyake, Seiji; Nagai, Norihiro; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

2017-01-01

Excessive exposure to light promotes degenerative and blinding retinal diseases such as age-related macular degeneration and retinitis pigmentosa. However, the underlying mechanisms of photo-induced retinal degeneration are not fully understood, and a generalizable preventive intervention has not been proposed. Bilberry extract is an antioxidant-rich supplement that ameliorates ocular symptoms. However, its effects on photo-stressed retinas have not been clarified. In this study, we examined the neuroprotective effects of bilberry extract against photo-stress in murine retinas. Light-induced visual function impairment recorded by scotopic and phototopic electroretinograms showing respective rod and cone photoreceptor function was attenuated by oral administration of bilberry extract through a stomach tube in Balb/c mice (750 mg/kg body weight). Bilberry extract also suppressed photo-induced apoptosis in the photoreceptor cell layer and shortening of the outer segments of rod and cone photoreceptors. Levels of photo-induced reactive oxygen species (ROS), oxidative and endoplasmic reticulum (ER) stress markers, as measured by real-time reverse transcriptase polymerase chain reaction, were reduced by bilberry extract treatment. Reduction of ROS by N-acetyl-L-cysteine, a well-known antioxidant also suppressed ER stress. Immunohistochemical analysis of activating transcription factor 4 expression showed the presence of ER stress in the retina, and at least in part, in Müller glial cells. The photo-induced disruption of tight junctions in the retinal pigment epithelium was also attenuated by bilberry extract, repressing an oxidative stress marker, although ER stress markers were not repressed. Our results suggest that bilberry extract attenuates photo-induced apoptosis and visual dysfunction most likely, and at least in part, through ROS reduction, and subsequent ER stress attenuation in the retina. This study can help understand the mechanisms of photo-stress and contribute to developing a new, potentially useful therapeutic approach using bilberry extract for preventing retinal photo-damage.

KSC-2009-2209

NASA Image and Video Library

2009-03-19

CAPE CANAVERAL, Fla. – – The NASA Railroad (right) is ready for the exchange of the Florida East Coast Railway cars carrying the booster segments for the Ares I-X test rocket. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to the Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2233

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. –The NASA Railroad is hauling one of the cars with an Ares I-X segment to the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

KSC-2209-2205

NASA Image and Video Library

2009-03-19

CAPE CANAVERAL, Fla. – The Florida East Coast Railway train arrives at the Jay Jay Rail Yard with the booster segments for the Ares I-X test rocket for interchange with the NASA Railroad (left). The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to the Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2203

NASA Image and Video Library

2009-03-19

CAPE CANAVERAL, Fla. – The Florida East Coast Railway train arrives at the Jay Jay Rail Yard with the booster segments for the Ares I-X test rocket for interchange with the NASA Railroad. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to the Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2208

NASA Image and Video Library

2009-03-19

CAPE CANAVERAL, Fla. – The NASA Railroad (right) is ready for the exchange of the Florida East Coast Railway cars carrying the booster segments for the Ares I-X test rocket. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to the Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2204

NASA Image and Video Library

2009-03-19

CAPE CANAVERAL, Fla. – The Florida East Coast Railway train arrives at the Jay Jay Rail Yard with the booster segments for the Ares I-X test rocket for interchange with the NASA Railroad. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to the Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2201

NASA Image and Video Library

2009-03-19

CAPE CANAVERAL, Fla. – The Florida East Coast Railway train arrives at the Jay Jay Rail Yard with the booster segments for the Ares I-X test rocket for interchange with the NASA Railroad. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to the Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2232

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. –This NASA Railroad engine is hauling one of the cars with an Ares I-X segment to the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

Serial imaging and structure-function correlates of high-density rings of fundus autofluorescence in retinitis pigmentosa.

PubMed

Robson, Anthony G; Tufail, Adnan; Fitzke, Fred; Bird, Alan C; Moore, Anthony T; Holder, Graham E; Webster, Andrew R

2011-09-01

To document the evolution and functional and structural significance of parafoveal rings of high-density fundus autofluorescence (AF) in patients with retinitis pigmentosa and preserved visual acuity. Fifty-two patients with nonsyndromic retinitis pigmentosa or Usher syndrome, who had a parafoveal ring of high-density AF and a visual acuity of 20/30 or better, were ascertained. All had international standard full-field electroretinography and pattern electroretinography. Autofluorescence imaging was repeated in 30 patients after periods of up to 9.3 years. Of the 52 patients, 35 underwent optical coherence tomography. Progressive constriction of the ring was detected in 17 patients. Ring radius reduced by up to 40% at a mean rate of between 0.8% and 15.8% per year. In 1 patient, a small ring was replaced by irregular AF; visual acuity deteriorated over the same period. There was a high correspondence between the lateral extent of the preserved optical coherence tomography inner segment/outer segment band and the diameter of the ring along the same optical coherence tomographic scan plane (slope, 0.9; r = 0.97; P < 0.005; n = 35) and between preserved inner segment/outer segment lamina and the pattern electroretinography P50 measure of macular function (R = 0.72; P < 0.005; n = 34). Rings of increased AF surround areas of preserved outer retina and preserved photopic function. Serial fundus AF may provide prognostic indicators for preservation of central acuity and potentially assist in the identification and evaluation of patients suitable for treatment aimed at preservation of remaining function.

Improving image segmentation performance and quantitative analysis via a computer-aided grading methodology for optical coherence tomography retinal image analysis.

PubMed

Debuc, Delia Cabrera; Salinas, Harry M; Ranganathan, Sudarshan; Tátrai, Erika; Gao, Wei; Shen, Meixiao; Wang, Jianhua; Somfai, Gábor M; Puliafito, Carmen A

2010-01-01

We demonstrate quantitative analysis and error correction of optical coherence tomography (OCT) retinal images by using a custom-built, computer-aided grading methodology. A total of 60 Stratus OCT (Carl Zeiss Meditec, Dublin, California) B-scans collected from ten normal healthy eyes are analyzed by two independent graders. The average retinal thickness per macular region is compared with the automated Stratus OCT results. Intergrader and intragrader reproducibility is calculated by Bland-Altman plots of the mean difference between both gradings and by Pearson correlation coefficients. In addition, the correlation between Stratus OCT and our methodology-derived thickness is also presented. The mean thickness difference between Stratus OCT and our methodology is 6.53 microm and 26.71 microm when using the inner segment/outer segment (IS/OS) junction and outer segment/retinal pigment epithelium (OS/RPE) junction as the outer retinal border, respectively. Overall, the median of the thickness differences as a percentage of the mean thickness is less than 1% and 2% for the intragrader and intergrader reproducibility test, respectively. The measurement accuracy range of the OCT retinal image analysis (OCTRIMA) algorithm is between 0.27 and 1.47 microm and 0.6 and 1.76 microm for the intragrader and intergrader reproducibility tests, respectively. Pearson correlation coefficients demonstrate R(2)>0.98 for all Early Treatment Diabetic Retinopathy Study (ETDRS) regions. Our methodology facilitates a more robust and localized quantification of the retinal structure in normal healthy controls and patients with clinically significant intraretinal features.

Improving image segmentation performance and quantitative analysis via a computer-aided grading methodology for optical coherence tomography retinal image analysis

NASA Astrophysics Data System (ADS)

Cabrera Debuc, Delia; Salinas, Harry M.; Ranganathan, Sudarshan; Tátrai, Erika; Gao, Wei; Shen, Meixiao; Wang, Jianhua; Somfai, Gábor M.; Puliafito, Carmen A.

2010-07-01

We demonstrate quantitative analysis and error correction of optical coherence tomography (OCT) retinal images by using a custom-built, computer-aided grading methodology. A total of 60 Stratus OCT (Carl Zeiss Meditec, Dublin, California) B-scans collected from ten normal healthy eyes are analyzed by two independent graders. The average retinal thickness per macular region is compared with the automated Stratus OCT results. Intergrader and intragrader reproducibility is calculated by Bland-Altman plots of the mean difference between both gradings and by Pearson correlation coefficients. In addition, the correlation between Stratus OCT and our methodology-derived thickness is also presented. The mean thickness difference between Stratus OCT and our methodology is 6.53 μm and 26.71 μm when using the inner segment/outer segment (IS/OS) junction and outer segment/retinal pigment epithelium (OS/RPE) junction as the outer retinal border, respectively. Overall, the median of the thickness differences as a percentage of the mean thickness is less than 1% and 2% for the intragrader and intergrader reproducibility test, respectively. The measurement accuracy range of the OCT retinal image analysis (OCTRIMA) algorithm is between 0.27 and 1.47 μm and 0.6 and 1.76 μm for the intragrader and intergrader reproducibility tests, respectively. Pearson correlation coefficients demonstrate R2>0.98 for all Early Treatment Diabetic Retinopathy Study (ETDRS) regions. Our methodology facilitates a more robust and localized quantification of the retinal structure in normal healthy controls and patients with clinically significant intraretinal features.

Fully automated calculation of cardiothoracic ratio in digital chest radiographs

NASA Astrophysics Data System (ADS)

Cong, Lin; Jiang, Luan; Chen, Gang; Li, Qiang

2017-03-01

The calculation of Cardiothoracic Ratio (CTR) in digital chest radiographs would be useful for cardiac anomaly assessment and heart enlargement related disease indication. The purpose of this study was to develop and evaluate a fully automated scheme for calculation of CTR in digital chest radiographs. Our automated method consisted of three steps, i.e., lung region localization, lung segmentation, and CTR calculation. We manually annotated the lung boundary with 84 points in 100 digital chest radiographs, and calculated an average lung model for the subsequent work. Firstly, in order to localize the lung region, generalized Hough transform was employed to identify the upper, lower, and outer boundaries of lung by use of Sobel gradient information. The average lung model was aligned to the localized lung region to obtain the initial lung outline. Secondly, we separately applied dynamic programming method to detect the upper, lower, outer and inner boundaries of lungs, and then linked the four boundaries to segment the lungs. Based on the identified outer boundaries of left lung and right lung, we corrected the center and the declination of the original radiography. Finally, CTR was calculated as a ratio of the transverse diameter of the heart to the internal diameter of the chest, based on the segmented lungs. The preliminary results on 106 digital chest radiographs showed that the proposed method could obtain accurate segmentation of lung based on subjective observation, and achieved sensitivity of 88.9% (40 of 45 abnormalities), and specificity of 100% (i.e. 61 of 61 normal) for the identification of heart enlargements.

Contrast visual acuity in patients with retinitis pigmentosa assessed by a contrast sensitivity tester.

PubMed

Oishi, Maho; Nakamura, Hajime; Hangai, Masanori; Oishi, Akio; Otani, Atsushi; Yoshimura, Nagahisa

2012-01-01

To assess contrast visual acuity (CVA) in patients with retinitis pigmentosa (RP) and compare the result with standard visual acuity (VA), retinal thickness, status of inner segment/outer segment junction, and central visual field. Thirty-nine eyes of 39 patients with RP and 39 eyes of 39 healthy individuals were studied. To see the difference in CVA between RP patients and normal controls, only subjects with standard VA of 1.0 (20/20) or better were included. This was a cross-sectional study. CVA in various light conditions was measured with CAT-2000 and was compared between patients and controls. CVA of patients was further analyzed for association with other parameters including foveal retinal thickness, outer nuclear layer thickness, the status of inner segment/outer segment junction measured with optical coherence tomography (OCT), and visual field mean deviation (MD) measured with Humphrey field analyzer 10-2 program. CVA impairment was evident in RP patients compared to controls (P < 0.01, in all measurement conditions). Multivariate analysis showed association of logarithm of the minimum angle of resolution (logMAR) with CVAs in several conditions. None of the OCT measurements was associated with CVA. When patients were divided into three groups based on MD, the most advanced group (MD worse than or equal to -20 dB) showed impairment of mesopic CVA (P < 0.05, under mesopic condition of 100% without glare, with glare, and 25% without glare). CVA impairment was confirmed in RP patients, especially in advanced cases. CVA measured with CAT-2000 may be a useful tool for assessing foveal function in RP patients.

Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.

PubMed

Phillips, M Joseph; Otteson, Deborah C; Sherry, David M

2010-06-01

The Pde6b(rd10) (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6b(rd10) (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well-known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5. (c) 2010 Wiley-Liss, Inc.

Progression of Neuronal and Synaptic Remodeling in the rd10 Mouse Model of Retinitis Pigmentosa

PubMed Central

Phillips, M. Joseph; Otteson, Deborah C.; Sherry, David M.

2010-01-01

The Pde6brd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6brd10 (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5. PMID:20394059

Computer program for definition of transonic axial-flow compressor blade rows

NASA Technical Reports Server (NTRS)

Crouse, J. E.

1975-01-01

Particular type of blade element used has two segments which have centerlines and surfaces described by constant change of angle with path distance on cone. Program is result of rework of earlier program to give major gains in accuracy, reliability and speed. It also covers more steps of overall compressor design procedure.

The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic

PubMed Central

Carroll, Joseph; Dubra, Alfredo; Gardner, Jessica C.; Mizrahi-Meissonnier, Liliana; Cooper, Robert F.; Dubis, Adam M.; Nordgren, Rick; Genead, Mohamed; Connor, Thomas B.; Stepien, Kimberly E.; Sharon, Dror; Hunt, David M.; Banin, Eyal; Hardcastle, Alison J.; Moore, Anthony T.; Williams, David R.; Fishman, Gerald; Neitz, Jay; Neitz, Maureen; Michaelides, Michel

2012-01-01

Purpose. To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations. Methods. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array. Results. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with “L/M interchange” mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic. Conclusions. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy. PMID:23139274

Contrasting types of surtseyan tuff cones on Marion and Prince Edward islands, southwest Indian Ocean

NASA Astrophysics Data System (ADS)

Verwoerd, W. J.; Chevallier, L.

1987-02-01

Ten surtseyan tuff cones on Marion island (46° 54' S, 37° 46' E) and seven on Prince Edward island (46° 38' S, 37° 57' E) were erupted on shallow submerged coastal plains related to normal faulting. They range from Pleistocene to Holocene in age and exhibit a variable degree of erosion by the sea. Fundamental differences, irrespective of age, exist between two types: Type I cones have diameters of 1 1.5 km, rim heights of about 200 m and steep (27°) outer slopes. Deposits are plastered against nearby cliffs. Beds are thin, including layers of accretionary lapilli and less than 10 % lithic clasts. Numerous bomb sags, soft sediment deformation structures and gravity slides occur. On one of these cones mudflows formed small tunnels which resemble lava tubes, associated with channels sometimes having oversteepened walls. These cones reflect comparatively low energy conditions and probably resulted from extremely wet surges interspersed with mudflows and ballistic falls. Type II cones have smaller diameters (˜0.5 km) but widespread fallout/surge aprons. Rim heights are about 100 m and average slope angles are 18°. Bedding is massive with variable lapilli/matrix ratio and more than 10 % lithic clasts without bomb sags. These cones formed under drier, perhaps hotter and more violently explosive conditions than Type I, though not as energetic as the phreatomagmatic eruptions of terrestrial tuff rings. The two types of surtseyan eruptions are explained by invoking not only different water/magma ratios in the conduit but also different mechanisms of water/magma interaction. The slurry model of Kokelaar is favoured for Type I and a fuel-coolant model for Type II. The decisive factor is considered to be rate of effusion, with rim closure and exclusion of sea water playing a secondary role.

A semi-automatic computer-aided method for surgical template design

NASA Astrophysics Data System (ADS)

Chen, Xiaojun; Xu, Lu; Yang, Yue; Egger, Jan

2016-02-01

This paper presents a generalized integrated framework of semi-automatic surgical template design. Several algorithms were implemented including the mesh segmentation, offset surface generation, collision detection, ruled surface generation, etc., and a special software named TemDesigner was developed. With a simple user interface, a customized template can be semi- automatically designed according to the preoperative plan. Firstly, mesh segmentation with signed scalar of vertex is utilized to partition the inner surface from the input surface mesh based on the indicated point loop. Then, the offset surface of the inner surface is obtained through contouring the distance field of the inner surface, and segmented to generate the outer surface. Ruled surface is employed to connect inner and outer surfaces. Finally, drilling tubes are generated according to the preoperative plan through collision detection and merging. It has been applied to the template design for various kinds of surgeries, including oral implantology, cervical pedicle screw insertion, iliosacral screw insertion and osteotomy, demonstrating the efficiency, functionality and generality of our method.

A semi-automatic computer-aided method for surgical template design

PubMed Central

Chen, Xiaojun; Xu, Lu; Yang, Yue; Egger, Jan

2016-01-01

This paper presents a generalized integrated framework of semi-automatic surgical template design. Several algorithms were implemented including the mesh segmentation, offset surface generation, collision detection, ruled surface generation, etc., and a special software named TemDesigner was developed. With a simple user interface, a customized template can be semi- automatically designed according to the preoperative plan. Firstly, mesh segmentation with signed scalar of vertex is utilized to partition the inner surface from the input surface mesh based on the indicated point loop. Then, the offset surface of the inner surface is obtained through contouring the distance field of the inner surface, and segmented to generate the outer surface. Ruled surface is employed to connect inner and outer surfaces. Finally, drilling tubes are generated according to the preoperative plan through collision detection and merging. It has been applied to the template design for various kinds of surgeries, including oral implantology, cervical pedicle screw insertion, iliosacral screw insertion and osteotomy, demonstrating the efficiency, functionality and generality of our method. PMID:26843434

A semi-automatic computer-aided method for surgical template design.

PubMed

Chen, Xiaojun; Xu, Lu; Yang, Yue; Egger, Jan

2016-02-04

This paper presents a generalized integrated framework of semi-automatic surgical template design. Several algorithms were implemented including the mesh segmentation, offset surface generation, collision detection, ruled surface generation, etc., and a special software named TemDesigner was developed. With a simple user interface, a customized template can be semi- automatically designed according to the preoperative plan. Firstly, mesh segmentation with signed scalar of vertex is utilized to partition the inner surface from the input surface mesh based on the indicated point loop. Then, the offset surface of the inner surface is obtained through contouring the distance field of the inner surface, and segmented to generate the outer surface. Ruled surface is employed to connect inner and outer surfaces. Finally, drilling tubes are generated according to the preoperative plan through collision detection and merging. It has been applied to the template design for various kinds of surgeries, including oral implantology, cervical pedicle screw insertion, iliosacral screw insertion and osteotomy, demonstrating the efficiency, functionality and generality of our method.

A New Species of Hyperbenthic Cyclopoid Copepod from Japan: First Record of the Genus Cyclopicina in the Indo-Pacific Region.

PubMed

Ohtsuka, Susumu; Tanaka, Hayato; Boxshall, Geoffrey A

2016-12-01

A new species of the cyclopinid genus Cyclopicina, C. toyoshioae sp. nov., was collected from the hyperbenthic layer off northern Kyushu Island, Japan; its description is based on two adult female specimens. This is the first record of the genus from the Indo-Pacific region. The new species can be distinguished from its two known congeners in: (1) the relatively short antennules which do not reach the posterior margin of the dorsal cephalothoracic shield; (2) the shape of seminal receptacles; (3) the segmentation and armature of the cephalothoracic appendages; (4) the shape of the basal protrusion between the rami of legs 1-4; (5) the presence of three outer spines on the third exopodal segment of leg 4; and (6) the presence or absence of outer setae on the free exopodal segment of leg 5. The genus Cyclopicina shows a wide but scattered distribution in hyperbenthic layers, from the continental shelves to deep-sea basins, in the northern hemisphere.

KSC-2009-2318

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. –In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, the end of the Ares I-X motor segment is removed to allow propellant grain inspection of the interior. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

KSC-2009-2317

NASA Image and Video Library

2009-03-26

CAPE CANAVERAL, Fla. – In the Rotation, Processing and Surge Facility at NASA's Kennedy Space Center in Florida, technicians prepare to remove the cover from the end of the Ares I-X motor segment for propellant grain inspection of the interior. It is one of four reusable motor segments and nozzle exit cone shipped by the Ares I first-stage prime contractor Alliant Techsystems Inc. for final processing and integration in the facility. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming flight test this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jim Grossmann

3D tumor measurement in cone-beam CT breast imaging

NASA Astrophysics Data System (ADS)

Chen, Zikuan; Ning, Ruola

2004-05-01

Cone-beam CT breast imaging provides a digital volume representation of a breast. With a digital breast volume, the immediate task is to extract the breast tissue information, especially for suspicious tumors, preferably in an automatic manner or with minimal user interaction. This paper reports a program for three-dimensional breast tissue analysis. It consists of volumetric segmentation (by globally thresholding), subsegmentation (connection-based separation), and volumetric component measurement (volume, surface, shape, and other geometrical specifications). A combination scheme of multi-thresholding and binary volume morphology is proposed to fast determine the surface gradients, which may be interpreted as the surface evolution (outward growth or inward shrinkage) for a tumor volume. This scheme is also used to optimize the volumetric segmentation. With a binary volume, we decompose the foreground into components according to spatial connectedness. Since this decomposition procedure is performed after volumetric segmentation, it is called subsegmentation. The subsegmentation brings the convenience for component visualization and measurement, in the whole support space, without interference from others. Upon the tumor component identification, we measure the following specifications: volume, surface area, roundness, elongation, aspect, star-shapedness, and location (centroid). A 3D morphological operation is used to extract the cluster shell and, by delineating the corresponding volume from the grayscale volume, to measure the shell stiffness. This 3D tissue measurement is demonstrated with a tumor-borne breast specimen (a surgical part).

Symmetry control in subscale near-vacuum hohlraums

DOE PAGES

Turnbull, D.; Berzak Hopkins, L. F.; Le Pape, S.; ...

2016-05-18

Controlling the symmetry of indirect-drive inertial confinement fusion implosions remains a key challenge. Increasing the ratio of the hohlraum diameter to the capsule diameter (case-to-capsule ratio, or CCR) facilitates symmetry tuning. By varying the balance of energy between the inner and outer cones as well as the incident laser pulse length, we demonstrate the ability to tune from oblate, through round, to prolate at a CCR of 3.2 in near-vacuum hohlraums at the National Ignition Facility, developing empirical playbooks along the way for cone fraction sensitivity of various laser pulse epochs. Radiation-hydrodynamic simulations with enhanced inner beam propagation reproduce mostmore » experimental observables, including hot spot shape, for a majority of implosions. In conclusion, specular reflections are used to diagnose the limits of inner beam propagation as a function of pulse length.« less

Multicenter reliability of semiautomatic retinal layer segmentation using OCT

PubMed Central

Oberwahrenbrock, Timm; Traber, Ghislaine L.; Lukas, Sebastian; Gabilondo, Iñigo; Nolan, Rachel; Songster, Christopher; Balk, Lisanne; Petzold, Axel; Paul, Friedemann; Villoslada, Pablo; Brandt, Alexander U.; Green, Ari J.

2018-01-01

Objective To evaluate the inter-rater reliability of semiautomated segmentation of spectral domain optical coherence tomography (OCT) macular volume scans. Methods Macular OCT volume scans of left eyes from 17 subjects (8 patients with MS and 9 healthy controls) were automatically segmented by Heidelberg Eye Explorer (v1.9.3.0) beta-software (Spectralis Viewing Module v6.0.0.7), followed by manual correction by 5 experienced operators from 5 different academic centers. The mean thicknesses within a 6-mm area around the fovea were computed for the retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer (OPL), and outer nuclear layer (ONL). Intraclass correlation coefficients (ICCs) were calculated for mean layer thickness values. Spatial distribution of ICC values for the segmented volume scans was investigated using heat maps. Results Agreement between raters was good (ICC > 0.84) for all retinal layers, particularly inner retinal layers showed excellent agreement across raters (ICC > 0.96). Spatial distribution of ICC showed highest values in the perimacular area, whereas the ICCs were poorer for the foveola and the more peripheral macular area. The automated segmentation of the OPL and ONL required the most correction and showed the least agreement, whereas differences were less prominent for the remaining layers. Conclusions Automated segmentation with manual correction of macular OCT scans is highly reliable when performed by experienced raters and can thus be applied in multicenter settings. Reliability can be improved by restricting analysis to the perimacular area and compound segmentation of GCL and IPL. PMID:29552598

Reconstituted TOM core complex and Tim9/Tim10 complex of mitochondria are sufficient for translocation of the ADP/ATP carrier across membranes.

PubMed

Vasiljev, Andreja; Ahting, Uwe; Nargang, Frank E; Go, Nancy E; Habib, Shukry J; Kozany, Christian; Panneels, Valérie; Sinning, Irmgard; Prokisch, Holger; Neupert, Walter; Nussberger, Stephan; Rapaport, Doron

2004-03-01

Precursor proteins of the solute carrier family and of channel forming Tim components are imported into mitochondria in two main steps. First, they are translocated through the TOM complex in the outer membrane, a process assisted by the Tim9/Tim10 complex. They are passed on to the TIM22 complex, which facilitates their insertion into the inner membrane. In the present study, we have analyzed the function of the Tim9/Tim10 complex in the translocation of substrates across the outer membrane of mitochondria. The purified TOM core complex was reconstituted into lipid vesicles in which purified Tim9/Tim10 complex was entrapped. The precursor of the ADP/ATP carrier (AAC) was found to be translocated across the membrane of such lipid vesicles. Thus, these components are sufficient for translocation of AAC precursor across the outer membrane. Peptide libraries covering various substrate proteins were used to identify segments that are bound by Tim9/Tim10 complex upon translocation through the TOM complex. The patterns of binding sites on the substrate proteins suggest a mechanism by which portions of membrane-spanning segments together with flanking hydrophilic segments are recognized and bound by the Tim9/Tim10 complex as they emerge from the TOM complex into the intermembrane space.

A hypersonic aeroheating calculation method based on inviscid outer edge of boundary layer parameters

NASA Astrophysics Data System (ADS)

Meng, ZhuXuan; Fan, Hu; Peng, Ke; Zhang, WeiHua; Yang, HuiXin

2016-12-01

This article presents a rapid and accurate aeroheating calculation method for hypersonic vehicles. The main innovation is combining accurate of numerical method with efficient of engineering method, which makes aeroheating simulation more precise and faster. Based on the Prandtl boundary layer theory, the entire flow field is divided into inviscid and viscid flow at the outer edge of the boundary layer. The parameters at the outer edge of the boundary layer are numerically calculated from assuming inviscid flow. The thermodynamic parameters of constant-volume specific heat, constant-pressure specific heat and the specific heat ratio are calculated, the streamlines on the vehicle surface are derived and the heat flux is then obtained. The results of the double cone show that at the 0° and 10° angle of attack, the method of aeroheating calculation based on inviscid outer edge of boundary layer parameters reproduces the experimental data better than the engineering method. Also the proposed simulation results of the flight vehicle reproduce the viscid numerical results well. Hence, this method provides a promising way to overcome the high cost of numerical calculation and improves the precision.

Turbine nozzle stage having thermocouple guide tube

DOEpatents

Schotsch, Margaret Jones; Kirkpatrick, Francis Lawrence; Lapine, Eric Michael

2002-01-01

A guide tube is fixed adjacent opposite ends in outer and inner covers of a nozzle stage segment. The guide tube is serpentine in shape between the outer and inner covers and extends through a nozzle vane. An insert is disposed in the nozzle vane and has apertures to accommodate serpentine portions of the guide tube. Cooling steam is also supplied through chambers of the insert on opposite sides of a central insert chamber containing the guide tube. The opposite ends of the guide tube are fixed to sleeves, in turn fixed to the outer and inner covers.

Heat shield characterization: Outer planet atmospheric entry probe

NASA Technical Reports Server (NTRS)

Mezines, S. A.; Rusert, E. L.; Disser, E. F.

1976-01-01

A full scale carbon phenolic heat shield was fabricated for the Outer Planet Probe in order to demonstrate the feasibility of molding large carbon phenolic parts with a new fabrication processing method (multistep). The sphere-cone heat shield was molded as an integral unit with the nose cap plies configured into a double inverse chevron shape to achieve the desired ply orientation. The fabrication activity was successful and the feasibility of the multistep processing technology was established. Delaminations or unbonded plies were visible on the heat shield and resulted from excessive loss of resin and lack of sufficient pressure applied on the part during the curing cycle. A comprehensive heat shield characterization test program was conducted, including: nondestructive tests with the full scale heat shield and thermal and mechanical property tests with small test specimen.

Calcium and magnesium fluxes across the plasma membrane of the toad rod outer segment.

PubMed Central

Nakatani, K; Yau, K W

1988-01-01

1. Membrane current was recorded from an isolated, dark-adapted toad rod by sucking either its inner segment or outer segment into a tight-fitting glass pipette containing Ringer solution. The remainder of the cell was exposed to bath solution which could be changed rapidly. 2. In normal Ringer solution the current response of a cell to a saturating flash or step of light showed a small secondary rise at its initial peak. The profile of this secondary rise (i.e. amplitude and time course) was independent of both the intensity and the duration of illumination once the light response had reached a plateau level. 3. This secondary rise disappeared when external Na+ around the outer segment was replaced by Li+ or guanidinium, suggesting that it represented an electrogenic Na+-dependent Ca2+ efflux which was declining after the onset of light. 4. This Na+-Ca2+ exchange activity showed a roughly exponential decline, with a time constant of about 0.5 s. Exponential extrapolation of the exchange current to the time at half-height of the light response gave an initial amplitude of about 2 pA. Using La3+ as a blocker, we did not detect any steady exchange current after the initial exponential decline. 5. An intense flash superposed on a just-saturating steady background light failed to produce any incremental exchange current transient. 6. Our interpretation of the above results is that in darkness there are counterbalancing levels of Ca2+ influx (through the light-sensitive conductance) and efflux (through the Na+-Ca2+ exchange) across the plasma membrane of the rod outer segment. The exchange current transient at the onset of light merely represents the unidirectional Ca2+ efflux which becomes revealed as a result of the stoppage of the Ca2+ influx, rather than a de novo Ca2+ efflux triggered by light. 7. Consistent with this interpretation, a test light delivered soon after a saturating, conditioning light elicited little exchange current, which then gradually recovered to control value with a time course parallel to the restoration of the dark current. Conversely, when the dark current was increased above its physiological level by IBMX (isobutylmethylxanthine) the exchange current transient became larger than control.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 8 PMID:2457685

KSC-2009-2231

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. –The cars on the NASA Railroad are separated for different destinations at NASA's Kennedy Space Center in Florida. They carry Ares I-X segments. One of the cars is going to the Rotation, Processing and Surge Facility. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

KSC-2009-2202

NASA Image and Video Library

2009-03-19

CAPE CANAVERAL, Fla. – The Florida East Coast Railway train arrives at the Jay Jay Rail Yard with the booster segments for the Ares I-X test rocket for interchange with the NASA Railroad. Officials from Alliant Techsystems Inc. and NASA accompany the train. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to the Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Kim Shiflett

KSC-2009-2230

NASA Image and Video Library

2009-03-20

CAPE CANAVERAL, Fla. – The NASA Railroad leaves four of the cars with Ares I-X segments at Suspect siding on NASA's Kennedy Space Center in Florida and continues on with the remaining car to the Rotation, Processing and Surge Facility. The four reusable motor segments and the nozzle exit cone, manufactured by the Ares I first-stage prime contractor Alliant Techsystems Inc., or ATK, departed Utah March 12 on the seven-day, cross-country trip to Florida. The segments will be delivered to Kennedy's Rotation, Processing and Surge Facility for final processing and integration. The booster used for the Ares I-X launch is being modified by adding new forward structures and a fifth segment simulator. The motor is the final hardware needed for the rocket's upcoming test flight this summer. The stacking operations are scheduled to begin in the Vehicle Assembly Building in April. Photo credit: NASA/Jack Pfaller

Machine learning in soil classification.

PubMed

Bhattacharya, B; Solomatine, D P

2006-03-01

In a number of engineering problems, e.g. in geotechnics, petroleum engineering, etc. intervals of measured series data (signals) are to be attributed a class maintaining the constraint of contiguity and standard classification methods could be inadequate. Classification in this case needs involvement of an expert who observes the magnitude and trends of the signals in addition to any a priori information that might be available. In this paper, an approach for automating this classification procedure is presented. Firstly, a segmentation algorithm is developed and applied to segment the measured signals. Secondly, the salient features of these segments are extracted using boundary energy method. Based on the measured data and extracted features to assign classes to the segments classifiers are built; they employ Decision Trees, ANN and Support Vector Machines. The methodology was tested in classifying sub-surface soil using measured data from Cone Penetration Testing and satisfactory results were obtained.

Architecture of kangaroo rat inner medulla: segmentation of descending thin limb of Henle's loop.

PubMed

Urity, Vinoo B; Issaian, Tadeh; Braun, Eldon J; Dantzler, William H; Pannabecker, Thomas L

2012-03-15

We hypothesize that the inner medulla of the kangaroo rat Dipodomys merriami, a desert rodent that concentrates its urine to more than 6,000 mosmol/kgH(2)O water, provides unique examples of architectural features necessary for production of highly concentrated urine. To investigate this architecture, inner medullary nephron segments in the initial 3,000 μm below the outer medulla were assessed with digital reconstructions from physical tissue sections. Descending thin limbs of Henle (DTLs), ascending thin limbs of Henle (ATLs), and collecting ducts (CDs) were identified by immunofluorescence using antibodies that label segment-specific proteins associated with transepithelial water flux (aquaporin 1 and 2, AQP1 and AQP2) and chloride flux (the chloride channel ClC-K1); all tubules and vessels were labeled with wheat germ agglutinin. In the outer 3,000 μm of the inner medulla, AQP1-positive DTLs lie at the periphery of groups of CDs. ATLs lie inside and outside the groups of CDs. Immunohistochemistry and reconstructions of loops that form their bends in the outer 3,000 μm of the inner medulla show that, relative to loop length, the AQP1-positive segment of the kangaroo rat is significantly longer than that of the Munich-Wistar rat. The length of ClC-K1 expression in the prebend region at the terminal end of the descending side of the loop in kangaroo rat is about 50% shorter than that of the Munich-Wistar rat. Tubular fluid of the kangaroo rat DTL may approach osmotic equilibrium with interstitial fluid by water reabsorption along a relatively longer tubule length, compared with Munich-Wistar rat. A relatively shorter-length prebend segment may promote a steeper reabsorptive driving force at the loop bend. These structural features predict functionality that is potentially significant in the production of a high urine osmolality in the kangaroo rat.

Macular telangiectasia type 2 (MacTel) in a 34-year-old patient.

PubMed

Nicolai, Heleen; Wirix, Mieke; Spielberg, Leigh; Leys, Anita

2014-09-23

We report macular telangiectasia type 2 (MacTel) in a 34-year-old man, the youngest patient so far published with MacTel type 2. The patient presented with metamorphopsia and impaired reading ability. Diagnosis was based on bilateral abnormal macular autofluorescence, perifoveal telangiectasia with fluorescein angiographic hyperfluorescence without cystoid oedema, a small foveal avascular zone, asymmetric configuration of the foveal pit, disruptions in the inner segment/outer segment layer and hyper-reflective haze and spots in the outer nuclear layer. Although MacTel usually manifests with a slowly progressive decrease in visual acuity in the fifth to seventh decades of life, younger patients may occasionally be diagnosed with the disease. Awareness of subtle signs of the condition is essential for early diagnosis. 2014 BMJ Publishing Group Ltd.

Macular telangiectasia type 2 (MacTel) in a 34-year-old patient

PubMed Central

Nicolai, Heleen; Wirix, Mieke; Spielberg, Leigh; Leys, Anita

2014-01-01

We report macular telangiectasia type 2 (MacTel) in a 34-year-old man, the youngest patient so far published with MacTel type 2. The patient presented with metamorphopsia and impaired reading ability. Diagnosis was based on bilateral abnormal macular autofluorescence, perifoveal telangiectasia with fluorescein angiographic hyperfluorescence without cystoid oedema, a small foveal avascular zone, asymmetric configuration of the foveal pit, disruptions in the inner segment/outer segment layer and hyper-reflective haze and spots in the outer nuclear layer. Although MacTel usually manifests with a slowly progressive decrease in visual acuity in the fifth to seventh decades of life, younger patients may occasionally be diagnosed with the disease. Awareness of subtle signs of the condition is essential for early diagnosis. PMID:25249218

A perspective of gene therapy in the glaucomas.

PubMed

Kaufman, P L; Jia, W W; Tan, J; Chen, Z; Gabelt, B T; Booth, V; Tufaro, F; Cynader, M

1999-06-01

Gene therapy in the anterior and posterior segment tissues may have the potential to favorably influence aqueous hydrodynamics and retinal ganglion cell biology, thereby preventing, delaying, or minimizing glaucomatous damage to the optic nerve. We demonstrated the feasibility of using a herpes viral vector (ribonucleotide reductase defective HSV-1, hrR3) to deliver the lacZ reporter gene to living cat and rat eyes. Cats received injections into the anterior chamber and rats into the vitreous cavity. In cats, lacZ expression was detectable at 1 to 2 days in the anterior outer portion of the ciliary muscle and the lining of the intertrabecular spaces of the corneoscleral and uveal meshwork. Rat eyes showed lacZ expression in the retinal pigment epithelium and photoreceptor outer segments 2 days after injection.

Growth of Megaspherulites In a Rhyolitic Vitrophyre

NASA Technical Reports Server (NTRS)

Smith, Robert K.; Tremallo, Robin L.; Lofgren, Gary E.

2000-01-01

Megaspherulites occur in the middle zone of a thick sequence of rhyolitic vitrophyre that occupies a small, late Eocene to early Oligocene volcanic-tectonic basin near Silver Cliff, Custer County, Colorado. Diameters of the megaspherulites range from 0.3 m to over 3.66 m, including a clay envelope. The megaspherulites are compound spherulites. consisting of an extremely large number (3.8 x 10(exp 9) to 9.9 x 10(exp 9)) of individual growth cones averaging 3 mm long by 1.25 mm wide at their termination. They are holocrystalline, very fine- to fine-grained, composed of disordered to ordered sanidine (orthoclase) and quartz, and surrounded by a thin K-feldspar, quartz rich rind, an inner clay layer with mordenite, and an outer clay layer composed wholly of 15 A montmorillonite. Whole rock analyses of the megaspherulites show a restricted composition from their core to their outer edge, with an average analyses of 76.3% SiO2, 0.34% CaO, 2.17% Na2O, 6.92% K2O, 0.83% H2O+ compared to the rhyolitic vitrophyre from which they crystallize with 71.07% SiO2, 0.57% CaO, 4.06% Na2O,4.l0% K2O, and 6.40% H2O+. The remaining oxides of Fe2O3 (total Fe), A12O3, MnO,MgO, TiO2, P2O5, Cr2O3, and trace elements show uniform distribution between the megaspherulites and the rhyolitic vitrophyre. Megaspherulite crystallization began soon after the rhyolitic lava ceased to flow as the result of sparse heterogeneous nucleation, under nonequilibrium conditions, due to a high degree of undercooling, delta T. The crystals grow with a fibrous habit which is favored by a large delta T ranging between 245 C and 295 C, despite lowered viscosity, and enhanced diffusion due to the high H2O content, ranging between 5% and 7%. Therefore, megaspherulite growth proceeded in a diffusion controlled manner, where the diffusion, rate lags behind the crystal growth rate at the crystal-liquid interface, restricting fibril lengths and diameters to the 10 micron to 15 micron and 3 micron and 8 micron ranges respectively. Once diffusion reestablishes itself at the crystallization front, a new nucleation event occurs at the terminated tips of the fibril cones and a new cone begins to develop with a similar orientation (small angle branching) to the earlier cones. During crystallization, these fibril cones impinge upon each other, resulting in fibril cone-free areas. These cone-free areas consist of coarser, fine-grained phases, dominated by quartz, which crystallized from the melt as it accumulated between the crystallizing K-feldspar fibrils of the cones. The anhydrous nature of the disordered to ordered sanidine (orthoclase) and quartz, suggests that water in the vitrophyre moved ahead of the crystallization front, resulting in a water rich fluid being enriched in Si, K, Na, Mg, Ca, Sr, Ba, and Y. The clay layers associated with the megaspherulites are therefore, the result of the deuteric alteration between the fractionated water and the vitrophyre, as indicated by the presence of the minerals mordenite and montmorillonite. This silica rich fluid also resulted in the total silicification of the megaspherulites within the upper 3 m of the vitrophyre.

Effect of Conus Eccentricity on Visual Outcomes After Intracorneal Ring Segments Implantation in Keratoconus.

PubMed

Gatzioufas, Zisis; Panos, Georgios D; Elalfy, Mohamed; Khine, Aye; Hamada, Samer; Lake, Damian; Kozeis, Nikos; Balidis, Miltos

2018-03-01

To investigate the potential impact of cone eccentricity on visual outcomes after Keraring (Mediphacos, Belo Horizonte, Brazil) implantation for keratoconus. Nineteen eyes from 19 patients with keratoconus who underwent femtosecond laser-assisted Keraring implantation for keratoconus were included in this retrospective study. Uncorrected visual acuity (UDVA), corrected visual acuity (CDVA), keratometric readings, central corneal thickness, maximum keratometric distance from corneal apex (DKmax), corneal thinnest point from corneal apex (DTh), and coma were evaluated preoperatively and 6 months after the Keraring implantation. DKmax and DTh were used as metrics reflecting the eccentricity of the cone. UDVA, CDVA, keratometric readings, and coma improved at 6 months postoperatively. However, there was no correlation between DKmax or DTh and visual outcomes at 6 months postoperatively. The data did not show any impact of the cone eccentricity on visual outcomes after Keraring implantation for keratoconus at 6 months postoperatively. [J Refract Surg. 2018;34(3):196-200.]. Copyright 2018, SLACK Incorporated.

3D exemplar-based random walks for tooth segmentation from cone-beam computed tomography images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pei, Yuru, E-mail: peiyuru@cis.pku.edu.cn; Ai, Xin

Purpose: Tooth segmentation is an essential step in acquiring patient-specific dental geometries from cone-beam computed tomography (CBCT) images. Tooth segmentation from CBCT images is still a challenging task considering the comparatively low image quality caused by the limited radiation dose, as well as structural ambiguities from intercuspation and nearby alveolar bones. The goal of this paper is to present and discuss the latest accomplishments in semisupervised tooth segmentation with adaptive 3D shape constraints. Methods: The authors propose a 3D exemplar-based random walk method of tooth segmentation from CBCT images. The proposed method integrates semisupervised label propagation and regularization by 3Dmore » exemplar registration. To begin with, the pure random walk method is to get an initial segmentation of the teeth, which tends to be erroneous because of the structural ambiguity of CBCT images. And then, as an iterative refinement, the authors conduct a regularization by using 3D exemplar registration, as well as label propagation by random walks with soft constraints, to improve the tooth segmentation. In the first stage of the iteration, 3D exemplars with well-defined topologies are adapted to fit the tooth contours, which are obtained from the random walks based segmentation. The soft constraints on voxel labeling are defined by shape-based foreground dentine probability acquired by the exemplar registration, as well as the appearance-based probability from a support vector machine (SVM) classifier. In the second stage, the labels of the volume-of-interest (VOI) are updated by the random walks with soft constraints. The two stages are optimized iteratively. Instead of the one-shot label propagation in the VOI, an iterative refinement process can achieve a reliable tooth segmentation by virtue of exemplar-based random walks with adaptive soft constraints. Results: The proposed method was applied for tooth segmentation of twenty clinically captured CBCT images. Three metrics, including the Dice similarity coefficient (DSC), the Jaccard similarity coefficient (JSC), and the mean surface deviation (MSD), were used to quantitatively analyze the segmentation of anterior teeth including incisors and canines, premolars, and molars. The segmentation of the anterior teeth achieved a DSC up to 98%, a JSC of 97%, and an MSD of 0.11 mm compared with manual segmentation. For the premolars, the average values of DSC, JSC, and MSD were 98%, 96%, and 0.12 mm, respectively. The proposed method yielded a DSC of 95%, a JSC of 89%, and an MSD of 0.26 mm for molars. Aside from the interactive definition of label priors by the user, automatic tooth segmentation can be achieved in an average of 1.18 min. Conclusions: The proposed technique enables an efficient and reliable tooth segmentation from CBCT images. This study makes it clinically practical to segment teeth from CBCT images, thus facilitating pre- and interoperative uses of dental morphologies in maxillofacial and orthodontic treatments.« less

3D exemplar-based random walks for tooth segmentation from cone-beam computed tomography images.

PubMed

Pei, Yuru; Ai, Xingsheng; Zha, Hongbin; Xu, Tianmin; Ma, Gengyu

2016-09-01

Tooth segmentation is an essential step in acquiring patient-specific dental geometries from cone-beam computed tomography (CBCT) images. Tooth segmentation from CBCT images is still a challenging task considering the comparatively low image quality caused by the limited radiation dose, as well as structural ambiguities from intercuspation and nearby alveolar bones. The goal of this paper is to present and discuss the latest accomplishments in semisupervised tooth segmentation with adaptive 3D shape constraints. The authors propose a 3D exemplar-based random walk method of tooth segmentation from CBCT images. The proposed method integrates semisupervised label propagation and regularization by 3D exemplar registration. To begin with, the pure random walk method is to get an initial segmentation of the teeth, which tends to be erroneous because of the structural ambiguity of CBCT images. And then, as an iterative refinement, the authors conduct a regularization by using 3D exemplar registration, as well as label propagation by random walks with soft constraints, to improve the tooth segmentation. In the first stage of the iteration, 3D exemplars with well-defined topologies are adapted to fit the tooth contours, which are obtained from the random walks based segmentation. The soft constraints on voxel labeling are defined by shape-based foreground dentine probability acquired by the exemplar registration, as well as the appearance-based probability from a support vector machine (SVM) classifier. In the second stage, the labels of the volume-of-interest (VOI) are updated by the random walks with soft constraints. The two stages are optimized iteratively. Instead of the one-shot label propagation in the VOI, an iterative refinement process can achieve a reliable tooth segmentation by virtue of exemplar-based random walks with adaptive soft constraints. The proposed method was applied for tooth segmentation of twenty clinically captured CBCT images. Three metrics, including the Dice similarity coefficient (DSC), the Jaccard similarity coefficient (JSC), and the mean surface deviation (MSD), were used to quantitatively analyze the segmentation of anterior teeth including incisors and canines, premolars, and molars. The segmentation of the anterior teeth achieved a DSC up to 98%, a JSC of 97%, and an MSD of 0.11 mm compared with manual segmentation. For the premolars, the average values of DSC, JSC, and MSD were 98%, 96%, and 0.12 mm, respectively. The proposed method yielded a DSC of 95%, a JSC of 89%, and an MSD of 0.26 mm for molars. Aside from the interactive definition of label priors by the user, automatic tooth segmentation can be achieved in an average of 1.18 min. The proposed technique enables an efficient and reliable tooth segmentation from CBCT images. This study makes it clinically practical to segment teeth from CBCT images, thus facilitating pre- and interoperative uses of dental morphologies in maxillofacial and orthodontic treatments.

Identification of the two rotavirus genes determining neutralization specificities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Offit, P.A.; Blavat, G.

1986-01-01

Bovine rotavirus NCDV and simian rotavirus SA-11 represent two distinct rotavirus serotypes. A genetic approach was used to determine which viral gene segments segregated with serotype-specific viral neutralization. There were 16 reassortant rotarviruses derived by coinfection of MA-104 cells in vitro with the SA-11 and NCDV strains. The parental origin of reassortant rotavirus double-stranded RNA segments was determined by gene segment mobility in polyacrylamide gels and by hybridization with radioactively labeled parental viral transcripts. The authors found that two rotavirus gene segments found previously to code for outer capsid proteins vp3 and vp7 cosegreated with virus neutralization specificities.

Surface-region context in optimal multi-object graph-based segmentation: robust delineation of pulmonary tumors.

PubMed

Song, Qi; Chen, Mingqing; Bai, Junjie; Sonka, Milan; Wu, Xiaodong

2011-01-01

Multi-object segmentation with mutual interaction is a challenging task in medical image analysis. We report a novel solution to a segmentation problem, in which target objects of arbitrary shape mutually interact with terrain-like surfaces, which widely exists in the medical imaging field. The approach incorporates context information used during simultaneous segmentation of multiple objects. The object-surface interaction information is encoded by adding weighted inter-graph arcs to our graph model. A globally optimal solution is achieved by solving a single maximum flow problem in a low-order polynomial time. The performance of the method was evaluated in robust delineation of lung tumors in megavoltage cone-beam CT images in comparison with an expert-defined independent standard. The evaluation showed that our method generated highly accurate tumor segmentations. Compared with the conventional graph-cut method, our new approach provided significantly better results (p < 0.001). The Dice coefficient obtained by the conventional graph-cut approach (0.76 +/- 0.10) was improved to 0.84 +/- 0.05 when employing our new method for pulmonary tumor segmentation.

Geomorphological features of rootless cones in Myvatn, Iceland in comparison with Martian candidates

NASA Astrophysics Data System (ADS)

Noguchi, R.; Kurita, K.

2015-12-01

Rootless cones (RC) have not been paid much attention so far because of their limited locations and their small size. They are formed by repeated phreatovolcanic explosions by lava-waterlogged sediments interactions. While the distribution is limited on the Earth, they have been pervasively recognized on Mars (e.g., Greeley and Fagents, 2001) and considered as a key marker in identifying lava flow. Although in-depth morphological comparisons are necessary, the terrestrial standard is not sufficient. Recent studies have clarified detailed characteristics of the distribution in the context of lava flow dynamics in Laki, Iceland (Hamilton et al., 2010a,b). However, we are still lacking of sufficient data of the morphology. To construct the terrestrial reference, we performed survey in Myvatn, Iceland.About 2300 years ago, lava flowed into old-Lake Myvatn, then formed RCs (Thorarinsson, 1953). There exists 3 morphological types; Single Cone (SC), a conical edifice with a summit crater, Double Cone (DC), composed of an inner cone with a summit crater within the summit crater of an outer cone, and multiple cone, similar to DC but with several inner cones. Through aerial photo survey, 1154 RCs (1056 are SC, 78 are DC and 20 are multiple one) are identified in this area. To know high-resolution topography of them, we apply kinematic GPS. Constituent materials of RCs are analyzed focusing on their bulk density, vesicularity, and grain size distribution.Geomorphological features of RCs are strongly correlated with its location and constituent materials. The crater diameter/bottom diameter ratio of cone, which is considered as an indicator of the explosivity, is larger around the lake and smaller far way from the lava source. This suggests an importance of available thermal energy as well as the water supply. The edifice morphology is grouped into 5 types; I: constant slopes that reach the repose angle; II: constant slopes lower than the repose angle; III: variable slopes with a step; IV: variable slopes that get steeper with higher altitude; and V: variable and small slope angles. We found these types correspond to their constituent materials and volumes. In this presentation, we show the relationship between RC morphology and other parameters, which can be useful as well as the planetary volcanology.

Interaction of Extracellular Domain 2 of the Human Retina-specific ATP-binding Cassette Transporter (ABCA4) with All-trans-retinal*

PubMed Central

Biswas-Fiss, Esther E.; Kurpad, Deepa S.; Joshi, Kinjalben; Biswas, Subhasis B.

2010-01-01

The retina-specific ATP-binding cassette (ABC) transporter, ABCA4, is essential for transport of all-trans-retinal from the rod outer segment discs in the retina and is associated with a broad range of inherited retinal diseases, including Stargardt disease, autosomal recessive cone rod dystrophy, and fundus flavimaculatus. A unique feature of the ABCA subfamily of ABC transporters is the presence of highly conserved, long extracellular loops or domains (ECDs) with unknown function. The high degree of sequence conservation and mapped disease-associated mutations in these domains suggests an important physiological significance. Conformational analysis using CD spectroscopy of purified, recombinant ECD2 protein demonstrated that it has an ordered and stable structure composed of 27 ± 3% α-helix, 20 ± 3% β-pleated sheet, and 53 ± 3% coil. Significant conformational changes were observed in disease-associated mutant proteins. Using intrinsic tryptophan fluorescence emission spectrum of ECD2 polypeptide and fluorescence anisotropy, we have demonstrated that this domain specifically interacts with all-trans-retinal. Furthermore, the retinal interaction appeared preferential for the all-trans-isomer and was directly measurable through fluorescence anisotropy analysis. Our results demonstrate that the three macular degeneration-associated mutations lead to significant changes in the secondary structure of the ECD2 domain of ABCA4, as well as in its interaction with all-trans-retinal. PMID:20404325

ROLES OF CELL-INTRINSIC AND MICROENVIRONMENTAL FACTORS IN PHOTORECEPTOR CELL DIFFERENTIATION

PubMed Central

Bradford, Rebecca L.; Wang, Chenwei; Zack, Donald J.; Adler, Ruben

2005-01-01

Photoreceptor differentiation requires the coordinated expression of numerous genes. It is unknown whether those genes share common regulatory mechanisms or are independently regulated by distinct mechanisms. To distinguish between these scenarios, we have used in situ hybridization, RT-PCR and real time PCR to analyze the expression of visual pigments and other photoreceptor-specific genes during chick embryo retinal development in ovo, as well as in retinal cell cultures treated with molecules that regulate the expression of particular visual pigments. In ovo, onset of gene expression was asynchronous, becoming detectable at the time of photoreceptor generation (ED 5–8) for some photoreceptor genes, but only around the time of outer segment formation (ED 14–16) for others. Treatment of retinal cell cultures with activin, staurosporine or CNTF selectively induced or down-regulated specific visual pigment genes, but many cognate rod- or cone-specific genes were not affected by the treatments. These results indicate that many photoreceptor genes are independently regulated during development, are consistent with the existence of at least two distinct stages of gene expression during photoreceptor differentiation, suggest that intrinsic, coordinated regulation of a cascade of gene expression triggered by a commitment to the photoreceptor fate is not a general mechanism of photoreceptor differentiation, and imply that using a single photoreceptor-specific “marker” as a proxy to identify photoreceptor cell fate is problematic. PMID:16120439

Melatonin Modulates Prohibitin and Cytoskeleton in the Retinal Pigment Epithelium.

PubMed

Sripathi, Srinivas R; Prigge, Cameron L; Elledge, Beth; He, Weilue; Offor, Johnpaul; Gutsaeva, Diana R; Jahng, Wan Jin

2017-07-01

The retinal pigment epithelium (RPE) plays imperative roles in normal retinal function by photoreceptor protection from light and phagocytosis of rod and cone outer segments during disc shedding. Melatonin is the free radical scavenger and circadian determinant to protect the RPE and retina from oxidative stress and regulate the circadian clock. The current study tested the hypothesis whether melatonin could affect cytoskeletal structure within RPE. Our Western blot analysis demonstrated that melatonin treatment up-regulated prohibitin 3-fold compared to control. β-tubulin levels were also up-regulated by melatonin but to a lesser extent. Initial cell shape of ARPE-19 is epitheloid, however, after 30-minute treatment with melatonin, RPE cells undergo a morphological change to a fusiform shape with spindle outgrowth. Cells return to epitheloid shape after 12 hours in untreated medium. Melatonin treated cells showed increased and dissimilar distribution of prohibitin and β-tubulin compared to non-treated cells, thus altered cytoskeletal and mitochondrial structure in the RPE. Our data implies that melatonin may play a protective role under oxidative stress, which is shown by the marker prohibitin in terms of increased expression and nuclear distribution. During the protective process, cells change their morphology. Our results suggest that melatonin treatment could be beneficial to protect mitochondria under oxidative stress and treat certain ocular diseases, including age-related macular degeneration.

Melatonin Modulates Prohibitin and Cytoskeleton in the Retinal Pigment Epithelium

PubMed Central

Sripathi, Srinivas R.; Prigge, Cameron L.; Elledge, Beth; He, Weilue; Offor, Johnpaul; Gutsaeva, Diana R.; Jahng, Wan Jin

2017-01-01

The retinal pigment epithelium (RPE) plays imperative roles in normal retinal function by photoreceptor protection from light and phagocytosis of rod and cone outer segments during disc shedding. Melatonin is the free radical scavenger and circadian determinant to protect the RPE and retina from oxidative stress and regulate the circadian clock. The current study tested the hypothesis whether melatonin could affect cytoskeletal structure within RPE. Our Western blot analysis demonstrated that melatonin treatment up-regulated prohibitin 3-fold compared to control. β-tubulin levels were also up-regulated by melatonin but to a lesser extent. Initial cell shape of ARPE-19 is epitheloid, however, after 30-minute treatment with melatonin, RPE cells undergo a morphological change to a fusiform shape with spindle outgrowth. Cells return to epitheloid shape after 12 hours in untreated medium. Melatonin treated cells showed increased and dissimilar distribution of prohibitin and β-tubulin compared to non-treated cells, thus altered cytoskeletal and mitochondrial structure in the RPE. Our data implies that melatonin may play a protective role under oxidative stress, which is shown by the marker prohibitin in terms of increased expression and nuclear distribution. During the protective process, cells change their morphology. Our results suggest that melatonin treatment could be beneficial to protect mitochondria under oxidative stress and treat certain ocular diseases, including age-related macular degeneration. PMID:28845390

Comparative myoanatomy of Echinoderes (Kinorhyncha): a comprehensive investigation by CLSM and 3D reconstruction

PubMed Central

2014-01-01

Introduction Kinorhyncha is a clade of marine invertebrate meiofauna. Their body plan includes a retractable introvert bearing rings of cuticular spines, and a limbless trunk with distinct segmentation of nervous, muscular and epidermal organ systems. As derived members within the basal branch of Ecdysozoa, kinorhynchs may provide an important example of convergence on the evolution of segmentation within one of three bilaterian superclades. We describe the myoanatomy of Echinoderes, the most specious kinorhynch genus, and build upon historical studies of kinorhynch ultrastructure and gross morphology. This is the first multi-species comparison of a complete organ system by confocal microscopy and three-dimensional reconstruction within Kinorhyncha. Results Myoanatomy of adult Echinoderes is composed of the following: Head with two mouth cone circular muscles, nine pairs of oral style muscles, ten introvert retractors, one introvert circular muscle, and fourteen introvert circular muscle retractors; Neck with one circular muscle; Trunk showing distinct pairs of ventral and dorsal muscles within segments 1–10, dorsoventral muscles within segments 3–10, diagonal muscles within segments 1–8, longitudinal fibers spanning segments 1–9, three pairs of terminal spine muscles, and one pair of male penile spine muscles; Gut showing a pharynx with ten alternating rings of radial and circular muscle fibers enclosed in a complex sheath of protractors and retractors, an orthogonal grid of longitudinal and circular fibers surrounding the intestine, and paired hindgut dilators. Conclusions Myoanatomy is highly conserved between species of Echinoderes. Interspecific variation is observed in the arrangement and number of introvert fibers and the composition of pharyngeal muscles. Segmented trunk musculature facilitates the movements of articulated cuticular plates along the anterior-posterior axis. Intersegmental muscle fibers assist with dorsoventral and lateral trunk movements. Protractors, retractors and circular muscles coordinate eversion and retraction of the introvert and mouth cone, and relocation of the pharynx during locomotion and feeding behaviors. Pairs of posterior fibers suggest independent movements of terminal spines, and male penile spines. Within Scalidophora, myoanatomy is more similar between Kinorhyncha and Loricifera, than either group is to Priapulida. Kinorhynch myoanatomy may reflect a convergent transition from vermiform to segmented body plans during the early radiation of Ecdysozoa. PMID:24708877

Flight motor set 360L002 (STS-27R). Volume 5: Nozzle component

NASA Technical Reports Server (NTRS)

Meyer, S. A.

1990-01-01

A review of the performance and post-flight condition of the STS-27 Redesigned Solid Rocket Motor (RSRM) nozzles is presented. Thermal/Structural instrumentation data is reviewed, and applicable Discrepancy Reports (DRs) and Process Departures (PDs) are presented. The Nozzle Component Program Team (NCPT) performance evaluation and the Redesign Program Review Board (RPRB) assessment is included. The STS-27 nozzle assemblies were flown on the RSRM Second Flight (Space Shuttle Atlantis) on 2 December 1988. The nozzles were a partially submerged convergent and/or divergent movable design with an aft pivot point flexible bearing. The nozzle assemblies incorporated the following features: RSRM forward exit cone with snubber assembly, RSRM fixed housing, Structural backup Outer Boot Ring (OBR), RSRM cowl ring, RSRM nose inlet assembly, RSRM throat assembly, RSRM aft exit cone assembly with Linear-Shaped Charge (LSC), RTV backfill in Joints 1, 3, and 4, Use of EA913 NA adhesive in place of EA913 adhesive, Redesigned nozzle plug, and Carbon Cloth Phenolic (CCP) with 750 ppm sodium content. The CCP material usage for the STS-27 forward nozzle and aft exit cone assemblies is shown.

Characterization of organic osmolytes in avian renal medulla: a nonurea osmotic gradient system.

PubMed

Lien, Y H; Pacelli, M M; Braun, E J

1993-06-01

We measured the organic osmolytes present in the renal cortex and medullary cones of adult female domestic fowl before and after 48 h of water deprivation. Urine osmolality increased from 198 +/- 82 to 569 +/- 42 mosmol/kgH2O after water deprivation. In water-deprived birds, the major organic osmolytes, myoinositol, betaine, and taurine, in the medullary cones increased by 40, 100, and 24%, respectively, compared with control birds. No sorbitol was detected, and glycerophosphorylcholine (GPC) content was not affected by water deprivation. In the renal cortex, only betaine content increased significantly (4.8 +/- 0.6 vs. 3.1 +/- 0.3 mmol/kg wet wt) after water deprivation. In this study, we demonstrated that birds, like mammals, accumulate organic osmolytes in response to the increased interstitial osmolality that occurs during antidiuresis. Because urea is nearly absent in the avian medullary interstitium, our observation that GPC is not osmoregulated in the avian kidney supports the idea that GPC is the "counteracting osmolyte" for urea in the mammalian kidney. Furthermore, the organic osmolytes present in avian medullary cones are remarkably similar to those of the mammalian outer medulla. This similarity may be relevant to the morphological analogy of the two regions.

Relationship between photoreceptor outer segment length and visual acuity in diabetic macular edema.

PubMed

Forooghian, Farzin; Stetson, Paul F; Meyer, Scott A; Chew, Emily Y; Wong, Wai T; Cukras, Catherine; Meyerle, Catherine B; Ferris, Frederick L

2010-01-01

The purpose of this study was to quantify photoreceptor outer segment (PROS) length in 27 consecutive patients (30 eyes) with diabetic macular edema using spectral domain optical coherence tomography and to describe the correlation between PROS length and visual acuity. Three spectral domain-optical coherence tomography scans were performed on all eyes during each session using Cirrus HD-OCT. A prototype algorithm was developed for quantitative assessment of PROS length. Retinal thicknesses and PROS lengths were calculated for 3 parameters: macular grid (6 x 6 mm), central subfield (1 mm), and center foveal point (0.33 mm). Intrasession repeatability was assessed using coefficient of variation and intraclass correlation coefficient. The association between retinal thickness and PROS length with visual acuity was assessed using linear regression and Pearson correlation analyses. The main outcome measures include intrasession repeatability of macular parameters and correlation of these parameters with visual acuity. Mean retinal thickness and PROS length were 298 mum to 381 microm and 30 microm to 32 mum, respectively, for macular parameters assessed in this study. Coefficient of variation values were 0.75% to 4.13% for retinal thickness and 1.97% to 14.01% for PROS length. Intraclass correlation coefficient values were 0.96 to 0.99 and 0.73 to 0.98 for retinal thickness and PROS length, respectively. Slopes from linear regression analyses assessing the association of retinal thickness and visual acuity were not significantly different from 0 (P > 0.20), whereas the slopes of PROS length and visual acuity were significantly different from 0 (P < 0.0005). Correlation coefficients for macular thickness and visual acuity ranged from 0.13 to 0.22, whereas coefficients for PROS length and visual acuity ranged from -0.61 to -0.81. Photoreceptor outer segment length can be quantitatively assessed using Cirrus HD-OCT. Although the intrasession repeatability of PROS measurements was less than that of macular thickness measurements, the stronger correlation of PROS length with visual acuity suggests that the PROS measures may be more directly related to visual function. Photoreceptor outer segment length may be a useful physiologic outcome measure, both clinically and as a direct assessment of treatment effects.

Scoria Cone and Tuff Ring Stratigraphy Interpreted from Ground Penetrating Radar, Rattlesnake Crater, Arizona

NASA Astrophysics Data System (ADS)

Kruse, S. E.; McNiff, C. M.; Marshall, A. M.; Courtland, L. M.; Connor, C.; Charbonnier, S. J.; Abdollahzadeh, M.; Connor, L.; Farrell, A. K.; Harburger, A.; Kiflu, H. G.; Malservisi, R.; Njoroge, M.; Nushart, N.; Richardson, J. A.; Rookey, K.

2013-12-01

Numerous recent studies have demonstrated that detailed investigation of scoria cone and maar morphology can reveal rich details the eruptive and erosion histories of these volcanoes. A suite of geophysical surveys were conducted to images Rattlesnake Crater in the San Francisco Volcanic Field, AZ, US. We report here the results of ~3.4 km of ground penetrating radar (GPR) surveys that target the processes of deposition and erosion on the pair of cinder cones that overprint the southeast edge of Rattlesnake crater and on the tuff ring that forms the crater rim. Data were collected with 500, 250, 100, and 50 MHz antennas. The profiles were run in a radial direction down the northeast flanks of the cones (~1 km diameter, ~120 meters height) , and on the inner and outer margins of the oblong maar rim (~20-80 meters height). A maximum depth of penetration of GPR signal of ~15m was achieved high on the flanks of scoria cones. A minimum depth of essentially zero penetration occurred in the central crater. We speculate that maximum penetration occurs near the peaks of the cones and crater rim because ongoing erosion limits new soil formation. Soil formation would tend to increase surface conductivity and hence decrease GPR penetration. Soil is probably better developed within the crater, precluding significant radar penetration there. On the northeast side of the gently flattened rim of the easternmost scoria cone, the GPR profile shows internal layering that dips ~20 degrees northeast relative to the current ground surface. This clearly indicates that the current gently dipping surface is not a stratigraphic horizon, but reflects instead an erosive surface into cone strata that formed close to the angle of repose. Along much of the cone flanks GPR profiles show strata dipping ~4-5 degrees more steeply than the current surface, suggesting erosion has occurred over most of the height of the cone. An abrupt change in strata attitude is observed at the gradual slope diminishment at the base of the scoria cone, where the dip of GPR reflectors changes from radially out from the cone to horizontal or radially inward toward the cone. These changes suggest that grain avalanche packages thin at the base of the slope or that cone strata terminate against the pre-existing surface. We do not identify continuous tephra fall deposits extending from the base of the cone, which would be indicative of violent strombolian activity. On one profile strong diffractors at the base of the cone suggest the presence of now-buried ballistics that rolled to the bottom of the slope. A major question to be addressed with the GPR data is whether the scoria cone erosion by downslope granular flow can be modeled using the diffusion-advection equation with constant diffusivity and advection terms, and in contrast, how much of the profile is explained by downslope movement at the time of the eruption. GPR reflecting horizons on the maar rim are smoother in appearance than those on the scoria cone, perhaps indicating finer-grained material and the absence of diffracting blocks. On the west rim layers suggest indicated a paleo-rim with a flat top ~50 meters wide, surrounded on both sides by strata dipping more steeply than the current surface. Radar stratgraphy outside the northeastern maar rim is much more complex.

A new form of Elongatoolithidae, Undulatoolithus pengi oogen. et oosp. nov. from Pingxiang, Jiangxi, China.

PubMed

Wang, Qiang; Zhao, Zikui; Wang, Xiaolin; Li, Ning; Zou, Songlin

2013-12-10

A new oogenus and oospecies of the Elongatoolithidae, Undulatoolithus pengi oogen. et oosp. nov., is described on the basis of specimens from the Upper Cretaceous Zhoutian Formation of the Pingxiang Basin, Jiangxi Province, China. The eggs are slightly asymmetrical, paired, and lay radially-oriented in a circular configuration within the clutch, and most suggestive of Macroolithus of the Elongatoolithidae by medium-sized eggs with average polar axis and equatorial diameter of 19.36 and 8.35 cm, and the ornamentation pattern of nodes and ridges on the outer surface. The new oogenus differs from Macroolithus in its prominent ridges 0.67 mm in height, about half of the entire eggshell thickness, gradational boundary between the cone layer and the overlying columnar layer, cone layer-to-columnar layer thickness ratio of 1/8 or 1/4. This discovery adds new data on the morphology and diversification of Late Cretaceous elongatoolithid ootaxa. 

KSC-07pd1206

NASA Image and Video Library

2007-05-15

KENNEDY SPACE CENTER, FLA. -- The locomotive and rail cars carrying solid rocket booster motor segments and two aft exit cone segments roll to the Rotation, Processing and Surge Facility in Kennedy Space Center's Launch Complex 39 Area. The main facility is used for solid rocket motor receiving, rotation and inspection, and supports aft booster buildup. When live solid rocket motor segments arrive at the processing facility, they are positioned under one of the cranes. Handling slings are then attached to and remove the railcar cover. The segment is inspected while it remains horizontal. The two overhead cranes hoist the segment, rotate it to a vertical position and place it on a fixed stand. The aft handling ring is then removed. The segment is hoisted again and lowered onto a transportation and storage pallet, and the forward handling ring is removed to allow inspections. It is then transported to one of the surge buildings and temporarily stored until it is needed for booster stacking in the VAB. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/George Shelton

KSC-07pd1210

NASA Image and Video Library

2007-05-15

KENNEDY SPACE CENTER, FLA. -- The locomotive and rail cars carrying solid rocket booster motor segments and two aft exit cone segments deliver their cargo to the Rotation, Processing and Surge Facility (RPSF) in Kennedy Space Center's Launch Complex 39 Area. The RPSF is used for solid rocket motor receiving, rotation and inspection, and supports aft booster buildup. When live solid rocket motor segments arrive at the processing facility, they are positioned under one of the cranes. Handling slings are then attached to and remove the railcar cover. The segment is inspected while it remains horizontal. The two overhead cranes hoist the segment, rotate it to a vertical position and place it on a fixed stand. The aft handling ring is then removed. The segment is hoisted again and lowered onto a transportation and storage pallet, and the forward handling ring is removed to allow inspections. It is then transported to one of the surge buildings and temporarily stored until it is needed for booster stacking in the VAB. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/George Shelton

KSC-07pd1208

NASA Image and Video Library

2007-05-15

KENNEDY SPACE CENTER, FLA. -- The locomotive and rail cars carrying solid rocket booster motor segments and two aft exit cone segments roll past the Vehicle Assembly Building to the Rotation, Processing and Surge Facility (RPSF) in Kennedy Space Center's Launch Complex 39 Area. The RPSF is used for solid rocket motor receiving, rotation and inspection, and supports aft booster buildup. When live solid rocket motor segments arrive at the processing facility, they are positioned under one of the cranes. Handling slings are then attached to and remove the railcar cover. The segment is inspected while it remains horizontal. The two overhead cranes hoist the segment, rotate it to a vertical position and place it on a fixed stand. The aft handling ring is then removed. The segment is hoisted again and lowered onto a transportation and storage pallet, and the forward handling ring is removed to allow inspections. It is then transported to one of the surge buildings and temporarily stored until it is needed for booster stacking in the VAB. While enroute, solid rocket motor segments were involved in a derailment in Alabama. The rail cars carrying these segments remained upright and were undamaged. An inspection determined these segment cars could continue on to Florida. The segments themselves will undergo further evaluation at Kennedy before they are cleared for flight. Other segments involved in the derailment will be returned to a plant in Utah for further evaluation. Photo credit: NASA/George Shelton

Comparison of an adaptive local thresholding method on CBCT and µCT endodontic images

NASA Astrophysics Data System (ADS)

Michetti, Jérôme; Basarab, Adrian; Diemer, Franck; Kouame, Denis

2018-01-01

Root canal segmentation on cone beam computed tomography (CBCT) images is difficult because of the noise level, resolution limitations, beam hardening and dental morphological variations. An image processing framework, based on an adaptive local threshold method, was evaluated on CBCT images acquired on extracted teeth. A comparison with high quality segmented endodontic images on micro computed tomography (µCT) images acquired from the same teeth was carried out using a dedicated registration process. Each segmented tooth was evaluated according to volume and root canal sections through the area and the Feret’s diameter. The proposed method is shown to overcome the limitations of CBCT and to provide an automated and adaptive complete endodontic segmentation. Despite a slight underestimation (-4, 08%), the local threshold segmentation method based on edge-detection was shown to be fast and accurate. Strong correlations between CBCT and µCT segmentations were found both for the root canal area and diameter (respectively 0.98 and 0.88). Our findings suggest that combining CBCT imaging with this image processing framework may benefit experimental endodontology, teaching and could represent a first development step towards the clinical use of endodontic CBCT segmentation during pulp cavity treatment.

Automatic segmentation and reconstruction of the cortex from neonatal MRI.

PubMed

Xue, Hui; Srinivasan, Latha; Jiang, Shuzhou; Rutherford, Mary; Edwards, A David; Rueckert, Daniel; Hajnal, Joseph V

2007-11-15

Segmentation and reconstruction of cortical surfaces from magnetic resonance (MR) images are more challenging for developing neonates than adults. This is mainly due to the dynamic changes in the contrast between gray matter (GM) and white matter (WM) in both T1- and T2-weighted images (T1w and T2w) during brain maturation. In particular in neonatal T2w images WM typically has higher signal intensity than GM. This causes mislabeled voxels during cortical segmentation, especially in the cortical regions of the brain and in particular at the interface between GM and cerebrospinal fluid (CSF). We propose an automatic segmentation algorithm detecting these mislabeled voxels and correcting errors caused by partial volume effects. Our results show that the proposed algorithm corrects errors in the segmentation of both GM and WM compared to the classic expectation maximization (EM) scheme. Quantitative validation against manual segmentation demonstrates good performance (the mean Dice value: 0.758+/-0.037 for GM and 0.794+/-0.078 for WM). The inner, central and outer cortical surfaces are then reconstructed using implicit surface evolution. A landmark study is performed to verify the accuracy of the reconstructed cortex (the mean surface reconstruction error: 0.73 mm for inner surface and 0.63 mm for the outer). Both segmentation and reconstruction have been tested on 25 neonates with the gestational ages ranging from approximately 27 to 45 weeks. This preliminary analysis confirms previous findings that cortical surface area and curvature increase with age, and that surface area scales to cerebral volume according to a power law, while cortical thickness is not related to age or brain growth.

Platform-Independent Cirrus and Spectralis Thickness Measurements in Eyes with Diabetic Macular Edema Using Fully Automated Software

PubMed Central

Willoughby, Alex S.; Chiu, Stephanie J.; Silverman, Rachel K.; Farsiu, Sina; Bailey, Clare; Wiley, Henry E.; Ferris, Frederick L.; Jaffe, Glenn J.

2017-01-01

Purpose We determine whether the automated segmentation software, Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can measure, in a platform-independent manner, retinal thickness on Cirrus and Spectralis spectral domain optical coherence tomography (SD-OCT) images in eyes with diabetic macular edema (DME) under treatment in a clinical trial. Methods Automatic segmentation software was used to segment the internal limiting membrane (ILM), inner retinal pigment epithelium (RPE), and Bruch's membrane (BM) in SD-OCT images acquired by Cirrus and Spectralis commercial systems, from the same eye, on the same day during a clinical interventional DME trial. Mean retinal thickness differences were compared across commercial and DOCTRAP platforms using intraclass correlation (ICC) and Bland-Altman plots. Results The mean 1 mm central subfield thickness difference (standard error [SE]) comparing segmentation of Spectralis images with DOCTRAP versus HEYEX was 0.7 (0.3) μm (0.2 pixels). The corresponding values comparing segmentation of Cirrus images with DOCTRAP versus Cirrus software was 2.2 (0.7) μm. The mean 1 mm central subfield thickness difference (SE) comparing segmentation of Cirrus and Spectralis scan pairs with DOCTRAP using BM as the outer retinal boundary was −2.3 (0.9) μm compared to 2.8 (0.9) μm with inner RPE as the outer boundary. Conclusions DOCTRAP segmentation of Cirrus and Spectralis images produces validated thickness measurements that are very similar to each other, and very similar to the values generated by the corresponding commercial software in eyes with treated DME. Translational Relevance This software enables automatic total retinal thickness measurements across two OCT platforms, a process that is impractical to perform manually. PMID:28180033

The phototransduction machinery in the rod outer segment has a strong efficacy gradient

PubMed Central

Mazzolini, Monica; Facchetti, Giuseppe; Andolfi, Laura; Proietti Zaccaria, Remo; Tuccio, Salvatore; Treu, Johannes; Altafini, Claudio; Di Fabrizio, Enzo M.; Lazzarino, Marco; Rapp, Gert; Torre, Vincent

2015-01-01

Rod photoreceptors consist of an outer segment (OS) and an inner segment. Inside the OS a biochemical machinery transforms the rhodopsin photoisomerization into electrical signal. This machinery has been treated as and is thought to be homogenous with marginal inhomogeneities. To verify this assumption, we developed a methodology based on special tapered optical fibers (TOFs) to deliver highly localized light stimulations. By using these TOFs, specific regions of the rod OS could be stimulated with spots of light highly confined in space. As the TOF is moved from the OS base toward its tip, the amplitude of saturating and single photon responses decreases, demonstrating that the efficacy of the transduction machinery is not uniform and is 5–10 times higher at the base than at the tip. This gradient of efficacy of the transduction machinery is attributed to a progressive depletion of the phosphodiesterase along the rod OS. Moreover we demonstrate that, using restricted spots of light, the duration of the photoresponse along the OS does not increase linearly with the light intensity as with diffuse light. PMID:25941368

Drive system for the retraction/extension of variable diameter rotor systems

NASA Technical Reports Server (NTRS)

Gmirya, Yuriy (Inventor)

2003-01-01

A drive system for a variable diameter rotor (VDR) system includes a plurality of rotor blade assemblies with inner and outer rotor blade segments. The outer blade segment being telescopically mounted to the inner blade segment. The VDR retraction/extension system includes a drive housing mounted at the root of each blade. The housing supports a spool assembly, a harmonic gear set and an electric motor. The spool assembly includes a pair of counter rotating spools each of which drive a respective cable which extends through the interior of the inboard rotor blade section and around a pulley mounted to the outboard rotor blade section. In operation, the electric motor drives the harmonic gear set which rotates the counter rotating spools. Rotation of the spools causes the cables to be wound onto or off their respective spool consequently effecting retraction/extension of the pulley and the attached outboard rotor blade section relative the inboard rotor blade section. As each blade drive system is independently driven by a separate electrical motor, each independent VDR blade assembly is independently positionable.

Pineal organs of deep-sea fish: photopigments and structure.

PubMed

Bowmaker, James K; Wagner, Hans-Joachim

2004-06-01

We have examined the morphology and photopigments of the pineal organs from a number of mesopelagic fish, including representatives of the hatchet fish (Sternoptychidae), scaly dragon-fish (Chauliodontidae) and bristlemouths (Gonostomidae). Although these fish were caught at depths of between 500 and 1000 m, the morphological organisation of their pineal organs is remarkably similar to that of surface-dwelling fish. Photoreceptor inner and outer segments protrude into the lumen of the pineal vesicle, and the outer segment is composed of a stack of up to 20 curved disks that form a cap-like cover over the inner segment. In all species, the pineal photopigment was spectrally distinct from the retinal rod pigment, with lambdamax displaced to longer wavelengths, between approximately 485 and 503 nm. We also investigated the pineal organ of the deep demersal eel, Synaphobranchus kaupi, caught at depths below 2000 m, which possesses a rod visual pigment with lambdamax at 478 nm, but the pineal pigment has lambdamax at approximately 515 nm. In one species of hatchet fish, Argyropelecus affinis, two spectral classes of pinealocyte were identified, both spectrally distinct from the retinal rod photopigment.

Retinal degeneration in cats fed casein. IV. The early receptor potential.

PubMed

Berson, E L; Watson, G; Grasse, K L; Szamier, R B

1981-08-01

Electroretinographic studies of casein-fed cats with retinal taurine deficiency revealed that the early receptor potential (ERP) was initially normal in amplitude at a time when the a-wave and b-wave of the electroretinogram were substantially reduced or even nondetectable. The preserved ERP's in these taurine-deficient cats could be correlated with the histologic finding that their outer segments were relatively intact over 90% of the retinal area subtended by the test flash. The sequence of electroretinographic changes in these taurine-deficient cats was also consistent with previous biochemical studies on the normal cat retina that have shown a relatively low concentration of taurine at the level of the outer segments and a higher concentration at the level of the inner segments. The responses in early stages from taurine-deficient cats differed from the responses obtained from vitamin A--deficient cats but resembled those from cats that received an intravitreal injection of ouabain. Similarities and a difference between the responses of taurine-deficient cats and those of patients with early retinitis pigmentosa are considered.

Rhodopsin expression in the zebrafish pineal gland from larval to adult stage.

PubMed

Magnoli, Domenico; Zichichi, Rosalia; Laurà, Rosaria; Guerrera, Maria Cristina; Campo, Salvatore; de Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

2012-03-09

The zebrafish pineal gland plays an important role in different physiological functions including the regulation of the circadian clock. In the fish pineal gland the pinealocytes are made up of different segments: outer segment, inner segment and basal pole. Particularly, in the outer segment the rhodopsin participates in the external environment light reception that represents the first biochemical step in the melatonin production. It is well known that the rhodopsin in the adult zebrafish is well expressed in the pineal gland but both the expression and the cellular localization of this protein during development remain still unclear. In this study using qRT-PCR, sequencing and immunohistochemistry the expression as well as the protein localization of the rhodopsin in the zebrafish from larval (10 dpf) to adult stage (90 dpf) were demonstrated. The rhodopsin mRNA expression presents a peak of expression at 10 dpf, a further reduction to 50 dpf before increasing again in the adult stage. Moreover, the cellular localization of the rhodopsin-like protein was always localized in the pinealocyte at all ages examined. Our results demonstrated the involvement of the rhodopsin in the zebrafish pineal gland physiology particularly in the light capture during the zebrafish lifespan. Copyright © 2012 Elsevier B.V. All rights reserved.

Asymmetric effects of luminance and chrominance in the watercolor illusion

PubMed Central

Coia, Andrew J.; Crognale, Michael A.

2014-01-01

When bounded by a line of sufficient contrast, the desaturated hue of a colored line will spread over an enclosed area, an effect known as the watercolor illusion. The contrast of the two lines can be in luminance, chromaticity, or a combination of both. The effect is most salient when the enclosing line has greater contrast with the background than the line that induces the spreading color. In most prior experiments with watercolor spreading, the luminance of both lines has been lower than the background. An achromatic version of the illusion exists where a dark line will spread while being bounded by either a darker or brighter line. In a previous study we measured the strength of the watercolor effect in which the colored inducing line was isoluminant to the background, and found an illusion for both brighter and darker achromatic outer contours. We also found the strength of spreading is stronger for bluish (+S cone input) colors compared to yellowish (−S cone input) ones, when bounded by a dark line. The current study set out to measure the hue dependence of the watercolor illusion when inducing colors are flanked with brighter (increment) as opposed to darker outer lines. The asymmetry in the watercolor effect with S cone input was enhanced when the inducing contrast was an increment rather than a decrement. Further experiments explored the relationship between the perceived contrast of these chromatic lines when paired with luminance increments and decrements and revealed that the perceived contrast of luminance increments and decrements is dependent on which isoluminant color they are paired with. In addition to known hue asymmetries in the watercolor illusion there are asymmetries between luminance increments and decrements that are also hue dependent. These latter asymmetries may be related to the perceived contrast of the hue/luminance parings. PMID:25309396

Breast density quantification with cone-beam CT: A post-mortem study

PubMed Central

Johnson, Travis; Ding, Huanjun; Le, Huy Q.; Ducote, Justin L.; Molloi, Sabee

2014-01-01

Forty post-mortem breasts were imaged with a flat-panel based cone-beam x-ray CT system at 50 kVp. The feasibility of breast density quantification has been investigated using standard histogram thresholding and an automatic segmentation method based on the fuzzy c-means algorithm (FCM). The breasts were chemically decomposed into water, lipid, and protein immediately after image acquisition was completed. The percent fibroglandular volume (%FGV) from chemical analysis was used as the gold standard for breast density comparison. Both image-based segmentation techniques showed good precision in breast density quantification with high linear coefficients between the right and left breast of each pair. When comparing with the gold standard using %FGV from chemical analysis, Pearson’s r-values were estimated to be 0.983 and 0.968 for the FCM clustering and the histogram thresholding techniques, respectively. The standard error of the estimate (SEE) was also reduced from 3.92% to 2.45% by applying the automatic clustering technique. The results of the postmortem study suggested that breast tissue can be characterized in terms of water, lipid and protein contents with high accuracy by using chemical analysis, which offers a gold standard for breast density studies comparing different techniques. In the investigated image segmentation techniques, the FCM algorithm had high precision and accuracy in breast density quantification. In comparison to conventional histogram thresholding, it was more efficient and reduced inter-observer variation. PMID:24254317

Element for use in an inductive coupler for downhole components

DOEpatents

Hall, David R [Provo, UT; Fox, Joe [Spanish Fork, UT

2009-03-31

An element for use in an inductive coupler for downhole components comprises an annular housing having a generally circular recess. The element further comprises a plurality of generally linear, magnetically conductive segments. Each segment includes a bottom portion, an inner wall portion, and an outer wall portion. The portions together define a generally linear trough from a first end to a second end of each segment. The segments are arranged adjacent to each other within the housing recess to form a generally circular trough. The ends of at least half of the segments are shaped such that the first end of one of the segments is complementary in form to the second end of an adjacent segment. In one embodiment, all of the ends are angled. Preferably, the first ends are angled with the same angle and the second ends are angled with the complementary angle.

Learning-based automated segmentation of the carotid artery vessel wall in dual-sequence MRI using subdivision surface fitting.

PubMed

Gao, Shan; van 't Klooster, Ronald; Kitslaar, Pieter H; Coolen, Bram F; van den Berg, Alexandra M; Smits, Loek P; Shahzad, Rahil; Shamonin, Denis P; de Koning, Patrick J H; Nederveen, Aart J; van der Geest, Rob J

2017-10-01

The quantification of vessel wall morphology and plaque burden requires vessel segmentation, which is generally performed by manual delineations. The purpose of our work is to develop and evaluate a new 3D model-based approach for carotid artery wall segmentation from dual-sequence MRI. The proposed method segments the lumen and outer wall surfaces including the bifurcation region by fitting a subdivision surface constructed hierarchical-tree model to the image data. In particular, a hybrid segmentation which combines deformable model fitting with boundary classification was applied to extract the lumen surface. The 3D model ensures the correct shape and topology of the carotid artery, while the boundary classification uses combined image information of 3D TOF-MRA and 3D BB-MRI to promote accurate delineation of the lumen boundaries. The proposed algorithm was validated on 25 subjects (48 arteries) including both healthy volunteers and atherosclerotic patients with 30% to 70% carotid stenosis. For both lumen and outer wall border detection, our result shows good agreement between manually and automatically determined contours, with contour-to-contour distance less than 1 pixel as well as Dice overlap greater than 0.87 at all different carotid artery sections. The presented 3D segmentation technique has demonstrated the capability of providing vessel wall delineation for 3D carotid MRI data with high accuracy and limited user interaction. This brings benefits to large-scale patient studies for assessing the effect of pharmacological treatment of atherosclerosis by reducing image analysis time and bias between human observers. © 2017 American Association of Physicists in Medicine.

Segmentation of the common carotid artery with active shape models from 3D ultrasound images

NASA Astrophysics Data System (ADS)

Yang, Xin; Jin, Jiaoying; He, Wanji; Yuchi, Ming; Ding, Mingyue

2012-03-01

Carotid atherosclerosis is a major cause of stroke, a leading cause of death and disability. In this paper, we develop and evaluate a new segmentation method for outlining both lumen and adventitia (inner and outer walls) of common carotid artery (CCA) from three-dimensional ultrasound (3D US) images for carotid atherosclerosis diagnosis and evaluation. The data set consists of sixty-eight, 17× 2× 2, 3D US volume data acquired from the left and right carotid arteries of seventeen patients (eight treated with 80mg atorvastain and nine with placebo), who had carotid stenosis of 60% or more, at baseline and after three months of treatment. We investigate the use of Active Shape Models (ASMs) to segment CCA inner and outer walls after statin therapy. The proposed method was evaluated with respect to expert manually outlined boundaries as a surrogate for ground truth. For the lumen and adventitia segmentations, respectively, the algorithm yielded Dice Similarity Coefficient (DSC) of 93.6%+/- 2.6%, 91.8%+/- 3.5%, mean absolute distances (MAD) of 0.28+/- 0.17mm and 0.34 +/- 0.19mm, maximum absolute distances (MAXD) of 0.87 +/- 0.37mm and 0.74 +/- 0.49mm. The proposed algorithm took 4.4 +/- 0.6min to segment a single 3D US images, compared to 11.7+/-1.2min for manual segmentation. Therefore, the method would promote the translation of carotid 3D US to clinical care for the fast, safety and economical monitoring of the atherosclerotic disease progression and regression during therapy.

Bcl-xL-mediated remodeling of rod and cone synaptic mitochondria after postnatal lead exposure: electron microscopy, tomography and oxygen consumption.

PubMed

Perkins, Guy A; Scott, Ray; Perez, Alex; Ellisman, Mark H; Johnson, Jerry E; Fox, Donald A

2012-01-01

Postnatal lead exposure produces rod-selective and Bax-mediated apoptosis, decreased scotopic electroretinograms (ERGs), and scotopic and mesopic vision deficits in humans and/or experimental animals. Rod, but not cone, inner segment mitochondria were considered the primary site of action. However, photoreceptor synaptic mitochondria were not examined. Thus, our experiments investigated the structural and functional effects of environmentally relevant postnatal lead exposure on rod spherule and cone pedicle mitochondria and whether Bcl-xL overexpression provided neuroprotection. C57BL/6N mice pups were exposed to lead only during lactation via dams drinking water containing lead acetate. The blood [Pb] at weaning was 20.6±4.7 µg/dl, which decreased to the control value by 2 months. To assess synaptic mitochondrial structural differences and vulnerability to lead exposure, wild-type and transgenic mice overexpressing Bcl-xL in photoreceptors were used. Electron microscopy, three-dimensional electron tomography, and retinal and photoreceptor synaptic terminal oxygen consumption (QO(2)) studies were conducted in adult control, Bcl-xL, lead, and Bcl-xL/lead mice. The spherule and pedicle mitochondria in lead-treated mice were swollen, and the cristae structure was markedly changed. In the lead-treated mice, the mitochondrial cristae surface area and volume (abundance: measure correlated with ATP (ATP) synthesis) were decreased in the spherules and increased in the pedicles. Pedicles also had an increased number of crista segments per volume. In the lead-treated mice, the number of segments/crista and fraction of cristae with multiple segments (branching) similarly increased in spherule and pedicle mitochondria. Lead-induced remodeling of spherule mitochondria produced smaller cristae with more branching, whereas pedicle mitochondria had larger cristae with more branching and increased crista junction (CJ) diameter. Lead decreased dark- and light-adapted photoreceptor and dark-adapted photoreceptor synaptic terminal QO(2). Bcl-xL partially blocked many of the lead-induced alterations relative to controls. However, spherules still had partially decreased abundance, whereas pedicles still had increased branching, increased crista segments per volume, and increased crista junction diameter. Moreover, photoreceptor and synaptic QO(2) were only partially recovered. These findings reveal cellular and compartmental specific differences in the structure and vulnerability of rod and cone inner segment and synaptic mitochondria to postnatal lead exposure. Spherule and pedicle mitochondria in lead-exposed mice displayed complex and distinguishing patterns of cristae and matrix damage and remodeling consistent with studies showing that synaptic mitochondria are more sensitive to Ca(2+) overload, oxidative stress, and ATP loss than non-synaptic mitochondria. The lead-induced decreases in QO(2) likely resulted from the decreased spherule cristae abundance and smaller cristae, perhaps due to Bax-mediated effects as they occurred in apoptotic rod inner segments. The increase in pedicle cristae abundance and CJ diameter could have resulted from increased Drp1-mediated fission, as small mitochondrial fragments were observed. The mechanisms of Bcl-xL-mediated remodeling might occur via interaction with formation of CJ protein 1 (Fcj1), whereas the partial protection of synaptic QO(2) might result from the enhanced efficiency of energy metabolism via Bcl-xL's direct interaction with the F1F0 ATP synthase and/or regulation of cellular redox status. These lead-induced alterations in photoreceptor synaptic terminal mitochondria likely underlie the persistent scotopic and mesopic deficits in lead-exposed children, workers, and experimental animals. Our findings stress the clinical and scientific importance of examining synaptic dysfunction following injury or disease during development, and developing therapeutic treatments that prevent synaptic degeneration in retinal and neurodegenerative disorders even when apoptosis is blocked.

Brittle Materials Design, High Temperature Gas Turbine

DTIC Science & Technology

1981-03-01

slides and core pins which formed the outer diameter and the hollow struts. Inner inserts were used to form the inside surface of the nose cone...ceramic component development. Figure 1 illustrates this by showing, in turn, ready removal in the test cell of a ceramic regenerator core , combusior...objective. This Executive Summary briefly reviews the highlights of the program. VII ■■■ *»W*w»«»^il»^.3«£*a;-^ -,Al^».t, „ . Regenerator Core Removal

Horizontal cryogenic bushing for the termination of a superconducting power-transmission line

DOEpatents

Minati, K.F.; Morgan, G.H.; McNerney, A.J.; Schauer, F.

1982-07-29

A termination for a superconducting power transmission line is disclosed which is comprised of a standard air entrance insulated vertical bushing with an elbow, a horizontal cryogenic bushing linking the pressurized cryogenic cable environment to the ambient temperature bushing and a stress cone which terminated the cable outer shield and transforms the large radial voltage gradient in the cable dielectric into a much lower radial voltage gradient in the high density helium coolant at the cold end of the cryogenic bushing.

Termination for a superconducting power transmission line including a horizontal cryogenic bushing

DOEpatents

Minati, Kurt F.; Morgan, Gerry H.; McNerney, Andrew J.; Schauer, Felix

1984-01-01

A termination for a superconducting power transmission line is disclosed which is comprised of a standard air entrance insulated vertical bushing with an elbow, a horizontal cryogenic bushing linking the pressurized cryogenic cable environment to the ambient temperature bushing and a stress cone which terminates the cable outer shield and transforms the large radial voltage gradient in the cable dielectric into a much lower radial voltage gradient in the high density helium coolant at the cold end of the cryogenic bushing.

A multi wavelength study of the circumnuclear region of NGC 1365

NASA Astrophysics Data System (ADS)

Kristen, H.; Sandqvist, A. A.; Lindblad, P. O.

We select a sample of five barred spiral galaxies in order to test previous findings concerning NGC 1365. The H I halos of the investigated objects are found to be compact. The effect of companions on the H I extent is illustrated. The central region of NGC 1365 has been mapped in the J = 3-2 CO emission line with the 15-m SEST, which has a HPBW of 15" at the frequency of this transition. The observing grid has a 5"-spacing in the inner and a 10"-spacing in the outer region. A Maximum Entropy Method (MEM) deconvolution has been performed on the inner region observations. A circumnuclear molecular torus with a radius of about 5" is the dominant feature. Molecular emission is also seen coming from various dust streamers in the bar of the galaxy. The velocity field of the molecular region agrees well with predictions of models of gas streaming in the bar and nuclear region. Comparisons with 7"-resolution VLA observations of H I absorption in the nuclear region are discussed. The morphology and kinematics of the high excitation outflow cone in the nuclear region of the Seyfert 1.5 galaxy NGC 1365 is investigated. The opening angle of the cone is 100 degrees, and the orientation such that the line of sight to the Seyfert 1.5 nucleus falls inside the cone. The outflow velocities within the cone are accelerated and fall off towards the edge. An HST FOC exposure of the nuclear region in [OIII] emission shows the cone to contain a large number of discrete clouds. Seen in the B band, a number of star forming regions surround the nucleus, of which the brightest seem to have absolute magnitudes of about -16.6 magnitudes.

Effects of the 2016 Kumamoto earthquakes on the Aso volcanic edifice

NASA Astrophysics Data System (ADS)

Tajima, Yasuhisa; Hasenaka, Toshiaki; Torii, Masayuki

2017-05-01

Large earthquakes occurred in the central part of Kumamoto Prefecture on April 14-16, 2016, causing severe damage to the northern segment of the Hinagu faults and the eastern segment of the Futagawa faults. Earthquake surface ruptures appeared along these faults and on the Aso volcanic edifice, which in turn generated landslides. We conducted landform change analysis of the central cones of Aso volcano by using satellite and aerial photographs. First, we categorized the topographical changes as surface scarps, arc-shaped cracks, and linear cracks. Field survey indicated that landslides caused the scarps and arc-shaped cracks, whereas faulting caused the linear cracks. We discovered a surface rupture concentration zone (RCZ) formed three ruptures bands with many surface ruptures and landslides extending from the west foot to the center of the Aso volcanic edifice. The magmatic volcanic vents that formed during the past 10,000 years are located along the north margin of the RCZ. Moreover, the distribution and dip of the core of rupture concentration zone correspond with the Nakadake craters. We conclude that a strong relationship exists between the volcanic vents and fault structures in the central cones of Aso volcano.[Figure not available: see fulltext.

The role of localised Ultra-Low Frequency waves in energetic electron precipitation

NASA Astrophysics Data System (ADS)

Rae, J.; Murphy, K. R.; Watt, C.; Mann, I. R.; Ozeke, L.; Halford, A. J.; Sibeck, D. G.; Clilverd, M. A.; Rodger, C. J.; Degeling, A. W.; Singer, H. J.

2016-12-01

Electromagnetic waves play pivotal roles in radiation belt dynamics through a variety of different means. Typically, Ultra-Low Frequency (ULF) waves have historically been invoked for radial diffusive transport leading to both acceleration and loss of outer radiation belt electrons. Very-Low Frequency (VLF) and Extremely-Low Frequency (ELF) waves are generally thought to provide a mechanism for localized acceleration and loss through precipitation into the ionosphere. In this study we present a new mechanism for electron loss through precipitation into the ionosphere due to direct modulation of the loss cone via localized compressional ULF waves. Observational evidence is presented demonstrating that modulation of the equatorial loss cone can occur via localized compressional wave activity. We then perform statistical computations of the probability distribution to determine how likely a given magnetic perturbation would produce a given percentage change in the bounce loss-cone (BLC). We discuss the ramifications of the action of coherent, localized compressional ULF waves on drifting electron populations; their precipitation response can be a complex interplay between electron energy, the shape of the phase space density profile at pitch angles close to the loss cone, ionospheric decay timescales, and the time-dependence of the electron source. We present a case study of compressional wave activity in tandem with riometer and balloon-borne electron precipitation across keV-MeV energies to demonstrate that the experimental measurements can be explained by our new enhanced loss cone mechanism. We determine that the two pivotal components not usually considered are localized ULF wave fields and ionospheric decay timescales. We conclude that ULF wave modulation of the loss cone is a viable candidate for direct precipitation of radiation belt electrons without any additional requirement for gyroresonant wave-particle interaction. Additional mechanisms would be complementary and additive in providing means to precipitate electrons from the radiation belts during storm-times.

Spectral domain optical coherence tomography findings in tamoxifen retinopathy--a case report.

PubMed

Nair, Sandhya Narayanan; Anantharaman, Giridhar; Gopalakrishnan, Mahesh; Vyas, Jyothiprakash

2013-01-01

To report spectral domain optical coherence tomography findings in a case of typical tamoxifen retinopathy. In this observational case report, a patient with tamoxifen retinopathy was imaged with spectral domain optical coherence tomography and fundus auto fluorescence. Spectral domain optical coherence tomography showed numerous hyperreflective spots within the retina, mainly in the inner retinal layers in both the eyes. The external limiting membrane, the Inner Segment-Outer Segment junction, and the photoreceptors were not discernable at the fovea in the right eye. In the left eye, there was foveal atrophy with total loss of photoreceptors. The autofluorescent images showed macular hypofluorescence with foveal hyperfluorescence. Spectral domain optical coherence tomography demonstrated abnormalities in the outer retinal layers in tamoxifen retinopathy. There were also characteristic alterations in the autofluorescence pattern at the macula in tamoxifen retinopathy.

Stimulus-evoked outer segment changes in rod photoreceptors

NASA Astrophysics Data System (ADS)

Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Lu, Yiming; Gai, Shaoyan; Yao, Xincheng

2016-06-01

Rod-dominated transient retinal phototropism (TRP) has been recently observed in freshly isolated mouse and frog retinas. Comparative confocal microscopy and optical coherence tomography revealed that the TRP was predominantly elicited from the rod outer segment (OS). However, the biophysical mechanism of rod OS dynamics is still unknown. Mouse and frog retinal slices, which displayed a cross-section of retinal photoreceptors and other functional layers, were used to test the effect of light stimulation on rod OSs. Time-lapse microscopy revealed stimulus-evoked conformational changes of rod OSs. In the center of the stimulated region, the length of the rod OS shrunk, while in the peripheral region, the rod OS swung toward the center region. Our experimental observation and theoretical analysis suggest that the TRP may reflect unbalanced rod disc-shape changes due to localized visible light stimulation.

Comparative investigation of stimulus-evoked rod outer segment movement and retinal electrophysiological activity

NASA Astrophysics Data System (ADS)

Lu, Yiming; Wang, Benquan; Yao, Xincheng

2017-02-01

Transient retinal phototropism (TRP) has been observed in rod photoreceptors activated by oblique visible light flashes. Time-lapse confocal microscopy and optical coherence tomography (OCT) revealed rod outer segment (ROS) movements as the physical source of TRP. However, the physiological source of TRP is still not well understood. In this study, concurrent TRP and electroretinogram (ERG) measurements disclosed a remarkably earlier onset time of the ROS movements (<=10 ms) than that ( 38 ms) of the ERG a-wave. Furthermore, low sodium treatment reversibly blocked the photoreceptor ERG a-wave, which is known to reflect hyperpolarization of retinal photoreceptors, but preserved the TRP associated rod OS movements well. Our experimental results and theoretical analysis suggested that the physiological source of TRP might be attributed to early stages of phototransduction, before the hyperpolarization of retinal photoreceptors.

Stimulus-evoked outer segment changes in rod photoreceptors

PubMed Central

Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Lu, Yiming; Gai, Shaoyan; Yao, Xincheng

2016-01-01

Abstract. Rod-dominated transient retinal phototropism (TRP) has been recently observed in freshly isolated mouse and frog retinas. Comparative confocal microscopy and optical coherence tomography revealed that the TRP was predominantly elicited from the rod outer segment (OS). However, the biophysical mechanism of rod OS dynamics is still unknown. Mouse and frog retinal slices, which displayed a cross-section of retinal photoreceptors and other functional layers, were used to test the effect of light stimulation on rod OSs. Time-lapse microscopy revealed stimulus-evoked conformational changes of rod OSs. In the center of the stimulated region, the length of the rod OS shrunk, while in the peripheral region, the rod OS swung toward the center region. Our experimental observation and theoretical analysis suggest that the TRP may reflect unbalanced rod disc-shape changes due to localized visible light stimulation. PMID:27334933

Evidence of early ultrastructural photoreceptor abnormalities in light-induced retinal degeneration using spectral domain optical coherence tomography.

PubMed

Aziz, Mehak K; Ni, Aiguo; Esserman, Denise A; Chavala, Sai H

2014-07-01

To study spatiotemporal in vivo changes in retinal morphology and quantify thickness of retinal layers in a mouse model of light-induced retinal degeneration using spectral domain optical coherence tomography (SD-OCT). BALB/c mice were exposed to 5000 lux of constant light for 3 h. SD-OCT images were taken 3 h, 24 h, 3 days, 1 week and 1 month after light exposure and were compared with histology at the same time points. SD-OCT images were also taken at 0, 1 and 2 h after light exposure in order to analyse retinal changes at the earliest time points. The thickness of retinal layers was measured using the Bioptigen software InVivoVue Diver. SD-OCT demonstrated progressive outer retinal thinning. 3 h after light exposure, the outer nuclear layer converted from hyporeflective to hyper-reflective. At 24 h, outer retinal bands and nuclear layer demonstrated similar levels of hyper-reflectivity. Significant variations in outer retinal thickness, vitreous opacities and retinal detachments occurred within days of injury. Thinning of the retina was observed at 1 month after injury. It was also determined that outer nuclear layer changes precede photoreceptor segment structure disintegration and the greatest change in segment structure occurs between 1 and 2 h after light exposure. Longitudinal SD-OCT reveals intraretinal changes that cannot be observed by histopathology at early time points in the light injury model. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

High-gradient compact linear accelerator

DOEpatents

Carder, B.M.

1998-05-26

A high-gradient linear accelerator comprises a solid-state stack in a vacuum of five sets of disc-shaped Blumlein modules each having a center hole through which particles are sequentially accelerated. Each Blumlein module is a sandwich of two outer conductive plates that bracket an inner conductive plate positioned between two dielectric plates with different thicknesses and dielectric constants. A third dielectric core in the shape of a hollow cylinder forms a casing down the series of center holes, and it has a dielectric constant different that the two dielectric plates that sandwich the inner conductive plate. In operation, all the inner conductive plates are charged to the same DC potential relative to the outer conductive plates. Next, all the inner conductive plates are simultaneously shorted to the outer conductive plates at the outer diameters. The signal short will propagate to the inner diameters at two different rates in each Blumlein module. A faster wave propagates quicker to the third dielectric core across the dielectric plates with the closer spacing and lower dielectric constant. When the faster wave reaches the inner extents of the outer and inner conductive plates, it reflects back outward and reverses the field in that segment of the dielectric core. All the field segments in the dielectric core are then in unipolar agreement until the slower wave finally propagates to the third dielectric core across the dielectric plates with the wider spacing and higher dielectric constant. During such unipolar agreement, particles in the core are accelerated with gradients that exceed twenty megavolts per meter. 10 figs.

High-gradient compact linear accelerator

DOEpatents

Carder, Bruce M.

1998-01-01

A high-gradient linear accelerator comprises a solid-state stack in a vacuum of five sets of disc-shaped Blumlein modules each having a center hole through which particles are sequentially accelerated. Each Blumlein module is a sandwich of two outer conductive plates that bracket an inner conductive plate positioned between two dielectric plates with different thicknesses and dielectric constants. A third dielectric core in the shape of a hollow cylinder forms a casing down the series of center holes, and it has a dielectric constant different that the two dielectric plates that sandwich the inner conductive plate. In operation, all the inner conductive plates are charged to the same DC potential relative to the outer conductive plates. Next, all the inner conductive plates are simultaneously shorted to the outer conductive plates at the outer diameters. The signal short will propagate to the inner diameters at two different rates in each Blumlein module. A faster wave propagates quicker to the third dielectric core across the dielectric plates with the closer spacing and lower dielectric constant. When the faster wave reaches the inner extents of the outer and inner conductive plates, it reflects back outward and reverses the field in that segment of the dielectric core. All the field segments in the dielectric core are then in unipolar agreement until the slower wave finally propagates to the third dielectric core across the dielectric plates with the wider spacing and higher dielectric constant. During such unipolar agreement, particles in the core are accelerated with gradients that exceed twenty megavolts per meter.

Side wall cooling for nozzle segments for a gas turbine

DOEpatents

Burdgick, Steven Sebastian

2002-01-01

A nozzle vane segment includes outer and inner band portions with a vane extending therebetween and defining first and second cavities separated by an impingement plate for flowing cooling medium for impingement cooling of nozzle side walls. The side wall of each nozzle segment has an undercut region. The impingement plate has an inturned flange with a plurality of openings. Cooling inserts or receptacles having an open end are received in the openings and the base and side walls of the receptacles have apertures for receiving cooling medium from the first cavity and directing the cooling medium for impingement cooling of the side wall of the nozzle segment and a portion of the nozzle wall.

Respiratory potential in sapwood of old versus young ponderosa pine trees in the Pacific Northwest.

PubMed

Pruyn, Michele L; Gartner, Barbara L; Harmon, Mark E

2002-02-01

Our primary objective was to present and test a new technique for in vitro estimation of respiration of cores taken from old trees to determine respiratory trends in sapwood. Our secondary objective was to quantify effects of tree age and stem position on respiratory potential (rate of CO2 production of woody tissue under standardized laboratory conditions). We extracted cores from one to four vertical positions in boles of +200-, +50- and +15-year-old Pinus ponderosa Dougl. ex Laws. trees. Cores were divided into five segments corresponding to radial depths of inner bark; outer, middle and inner sapwood; and heartwood. Data suggested that core segment CO2 production was an indicator of its respiratory activity, and that potential artifacts caused by wounding and extraction were minimal. On a dry mass basis, respiratory potential of inner bark was 3-15 times greater than that of sapwood at all heights for all ages (P < 0.0001). Within sapwood at all heights and in all ages of trees, outer sapwood had a 30-60% higher respiratory potential than middle or inner sapwood (P < 0.005). Heartwood had only 2-10% of the respiratory potential of outer sapwood. For all ages of trees, sapwood rings produced in the same calendar year released over 50% more CO2 at treetops than at bases (P < 0.0001). When scaled to the whole-tree level on a sapwood volume basis, sapwood of younger trees had higher respiratory potential than sapwood of older trees. In contrast, the trend was reversed when using the outer-bark surface area of stems as a basis for comparing respiratory potential. The differences observed in respiratory potential calculated on a core dry mass, sapwood volume, or outer-bark surface area basis clearly demonstrate that the resulting trends within and among trees are determined by the way in which the data are expressed. Although these data are based on core segments rather than in vivo measurements, we conclude that the relative differences are probably valid even if the absolute differences are not.