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.
Dendritic tree extraction from noisy maximum intensity projection images in C. elegans.
Greenblum, Ayala; Sznitman, Raphael; Fua, Pascal; Arratia, Paulo E; Oren, Meital; Podbilewicz, Benjamin; Sznitman, Josué
2014-06-12
Maximum Intensity Projections (MIP) of neuronal dendritic trees obtained from confocal microscopy are frequently used to study the relationship between tree morphology and mechanosensory function in the model organism C. elegans. Extracting dendritic trees from noisy images remains however a strenuous process that has traditionally relied on manual approaches. Here, we focus on automated and reliable 2D segmentations of dendritic trees following a statistical learning framework. Our dendritic tree extraction (DTE) method uses small amounts of labelled training data on MIPs to learn noise models of texture-based features from the responses of tree structures and image background. Our strategy lies in evaluating statistical models of noise that account for both the variability generated from the imaging process and from the aggregation of information in the MIP images. These noisy models are then used within a probabilistic, or Bayesian framework to provide a coarse 2D dendritic tree segmentation. Finally, some post-processing is applied to refine the segmentations and provide skeletonized trees using a morphological thinning process. Following a Leave-One-Out Cross Validation (LOOCV) method for an MIP databse with available "ground truth" images, we demonstrate that our approach provides significant improvements in tree-structure segmentations over traditional intensity-based methods. Improvements for MIPs under various imaging conditions are both qualitative and quantitative, as measured from Receiver Operator Characteristic (ROC) curves and the yield and error rates in the final segmentations. In a final step, we demonstrate our DTE approach on previously unseen MIP samples including the extraction of skeletonized structures, and compare our method to a state-of-the art dendritic tree tracing software. Overall, our DTE method allows for robust dendritic tree segmentations in noisy MIPs, outperforming traditional intensity-based methods. Such approach provides a useable segmentation framework, ultimately delivering a speed-up for dendritic tree identification on the user end and a reliable first step towards further morphological characterizations of tree arborization.
Method of inhibiting dislocation generation in silicon dendritic webs
Spitznagel, John A.; Seidensticker, Raymond G.; McHugh, James P.
1990-11-20
A method of tailoring the heat balance of the outer edge of the dendrites adjacent the meniscus to produce thinner, smoother dendrites, which have substantially less dislocation sources contiguous with the dendrites, by changing the view factor to reduce radiation cooling or by irradiating the dendrites with light from a quartz lamp or a laser to raise the temperature of the dendrites.
Ultrastructure of antennal sensilla of the peach aphid Myzus persicae Sulzer, 1776.
Ban, Li-Ping; Sun, Yin-Peng; Wang, Ying; Tu, Xiong-Bing; Zhang, Shan-Gan; Zhang, Yun-Ting; Wu, Yun-Sheng; Zhang, Ze-Hua
2015-02-01
The antennal sensilla of alate Myzus persicae were mapped using transmission electron microscopy and the ultrastructure of sensilla trichoidea, coeloconica, and placoidea are described. Trichoid sensilla, located on the tip of the antennae, are innervated by 2-4 neurons, with some outer dendrites reaching the distal end of the hair. Coeloconic sensilla in primary rhinaria are of two morphological types, both equipped with two dendrites. Dendrites of Type II coeloconic sensilla are enveloped in the dendrite sheath, containing the sensillum lymph. In sensilla coeloconica of Type I, instead, dendrites are enclosed by an electron opaque solid cuticle, with no space left for the sensillum lymph. The ultrastructure of big placoid sensillum reveals the presence of three groups of neurons, with 2-3 dendrites in each neuron group, while both small placoid sensilla are equipped with a single group of neurons, consisting of three dendrites. Both large and small placoid sensilla bear multiple pores on the outer cuticle. The function of these sensilla is also discussed. © 2014 Wiley Periodicals, Inc.
Alp, Murat; Cucinotta, Francis A.
2017-01-01
Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (>100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. PMID:28554507
NASA Astrophysics Data System (ADS)
Alp, Murat; Cucinotta, Francis A.
2017-05-01
Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch.
Alp, Murat; Cucinotta, Francis A
2017-05-01
Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100µm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3 He and 12 C particles at energies corresponding to a distance of 1cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. Copyright © 2017. Published by Elsevier Ltd.
Meckelin 3 Is Necessary for Photoreceptor Outer Segment Development in Rat Meckel Syndrome
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
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.
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.
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.
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.
Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D
2008-02-01
Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.
[Sulfhydryl group distribution along the axis of the rod outer segment in the frog].
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.
Steeghs, Liana; van Vliet, Sandra J; Uronen-Hansson, Heli; van Mourik, Andries; Engering, Anneke; Sanchez-Hernandez, Martha; Klein, Nigel; Callard, Robin; van Putten, Jos P M; van der Ley, Peter; van Kooyk, Yvette; van de Winkel, Jan G J
2006-02-01
Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T-cell responses driven by DC towards T helper type 1 activity. Thus, the use of lgtB LPS may provide a powerful instrument to selectively induce the desired arm of the immune response and potentially increase vaccine efficacy.
En face spectral domain optical coherence tomography analysis of lamellar macular holes.
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.
Michalikova, Martina; Remme, Michiel W H; Kempter, Richard
2017-01-01
Spikelets are small spike-like depolarizations that can be measured in somatic intracellular recordings. Their origin in pyramidal neurons remains controversial. To explain spikelet generation, we propose a novel single-cell mechanism: somato-dendritic input generates action potentials at the axon initial segment that may fail to activate the soma and manifest as somatic spikelets. Using mathematical analysis and numerical simulations of compartmental neuron models, we identified four key factors controlling spikelet generation: (1) difference in firing threshold, (2) impedance mismatch, and (3) electrotonic separation between the soma and the axon initial segment, as well as (4) input amplitude. Because spikelets involve forward propagation of action potentials along the axon while they avoid full depolarization of the somato-dendritic compartments, we conjecture that this mode of operation saves energy and regulates dendritic plasticity while still allowing for a read-out of results of neuronal computations.
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
Dendrodendritic Synapses in the Mouse Olfactory Bulb External Plexiform Layer
Bartel, Dianna L.; Rela, Lorena; Hsieh, Lawrence; Greer, Charles A.
2014-01-01
Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. In electron micrographs the M/T to granule cell synapse appeared to predominate and were equivalent in both the outer and inner EPL. However, the dendrodendritic synapses from granule cell spines onto M/T dendrites, were more prevalent in the outer EPL. In contrast, individual gephyrin-IR puncta, a postsynaptic scaffolding protein at inhibitory synapses used here as a proxy for the granule to M/T dendritic synapse was equally distributed throughout the EPL. Of significance to the organization of intrabulbar circuits, gephyrin-IR synapses are not uniformly distributed along M/T secondary dendrites. Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated with an increase in synaptic density. PMID:25420934
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.
The morphology and electrical geometry of rat jaw-elevator motoneurones.
Moore, J A; Appenteng, K
1991-01-01
1. The aim of this work was to quantify both the morphology and electrical geometry of the dendritic trees of jaw-elevator motoneurones. To do this we have made intracellular recordings from identified motoneurones in anaesthetized rats, determined their membrane properties and then filled them with horseradish peroxidase by ionophoretic ejection. Four neurones were subsequently fully reconstructed and the lengths and diameters of all the dendritic segments measured. 2. The mean soma diameter was 25 microns and values of mean dendritic length for individual cells ranged from 514 to 773 microns. Dendrites branched on average 9.1 times to produce 10.2 end-terminations. Dendritic segments could be represented as constant diameter cylinders between branch points. Values of dendritic surface area ranged from 1.08 to 2.52 x 10(5) microns 2 and values of dendritic to total surface area from 98 to 99%. 3. At branch points the ratio of the summed diameters of the daughter dendrites to the 3/2 power against the parent dendrite to the 3/2 power was exactly 1.0. Therefore the individual branch points could be collapsed into a single cylinder. Furthermore for an individual dendrite the diameter of this cylinder remained constant with increasing electrical distance from the soma. Thus individual dendrites can be represented electrically as cylinders of constant diameter. 4. However dendrites of a given neurone terminated at different electrical distances from the soma. The equivalent-cylinder diameter of the combined dendritic tree remained constant over the proximal half and then showed a pronounced reduction over the distal half. The reduction in equivalent diameter could be ascribed to the termination of dendrites at differing electrical distances from the soma. Therefore the complete dendritic tree of these motoneurones is best represented as a cylinder over the proximal half of their electrical length but as a cone over the distal half. PMID:1804966
Hamada, Mustafa S.; Goethals, Sarah; de Vries, Sharon I.; Brette, Romain
2016-01-01
In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies. PMID:27930291
Cooled turbine vane with endcaps
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
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
Correlation between spectral-domain OCT findings and visual acuity in X-linked retinoschisis.
Yang, Hyun Seung; Lee, Jung Bok; Yoon, Young Hee; Lee, Joo Yong
2014-05-08
To investigate the tomographic characteristics of the outer retina and choroid and their relationship with visual acuity in X-linked juvenile retinoschisis (XLRS) patients using spectral-domain optical coherence tomography (SD-OCT). In this retrospective, observational, case-control study, we analyzed 20 eyes of 10 patients with XLRS using SD-OCT. The clinical and tomographic features of the outer retina, including the external limiting membrane (ELM), inner segment/outer segment (IS/OS) junction, cone cell outer segment tips (COST) line, photoreceptor outer segment (PROS) length, and choroid, were evaluated. As controls, 40 age-, sex-, and refraction-matched healthy eyes (1:2 matched) were randomly selected and imaged in parallel. The most prevalent area of abnormality in the outer retina layer of our patients was the outer plexiform layer (OPL; 60% of all affected eyes) and COST line (75% of all affected eyes). On average, the subfoveal choroid and PROS lengths were 35 μm thicker and 19 μm thinner, respectively, in XLRS patients (P = 0.084 and P < 0.001, respectively). A dominant IS/OS junction, COST line defects, and PROS length were related to patient best-corrected visual acuity (BCVA; P = 0.029, P = 0.001, and P < 0.001, respectively) by univariate analysis. Cone cell outer segment tips line defect and PROS length were the only factors related to BCVA in multivariate analysis (P = 0.028 and 0.003, respectively). Outer plexiform layer and photoreceptor microstructure defects are frequent in XLRS patients. Cone cell outer segment tips line defects and shortened PROS lengths as well as other photoreceptor microstructure defects may be closely related to poor vision in XLRS.
Usher syndrome type 1–associated cadherins shape the photoreceptor outer segment
Parain, Karine; Aghaie, Asadollah; Picaud, Serge
2017-01-01
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal. PMID:28495838
Usher syndrome type 1-associated cadherins shape the photoreceptor outer segment.
Schietroma, Cataldo; Parain, Karine; Estivalet, Amrit; Aghaie, Asadollah; Boutet de Monvel, Jacques; Picaud, Serge; Sahel, José-Alain; Perron, Muriel; El-Amraoui, Aziz; Petit, Christine
2017-06-05
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis , these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23 , encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15-containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal. © 2017 Schietroma et al.
Pre-stressed/pre-compressed gas turbine nozzle
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.
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.
Functional significance of the taper of vertebrate cone photoreceptors
Hárosi, Ferenc I.
2012-01-01
Vertebrate photoreceptors are commonly distinguished based on the shape of their outer segments: those of cones taper, whereas the ones from rods do not. The functional advantages of cone taper, a common occurrence in vertebrate retinas, remain elusive. In this study, we investigate this topic using theoretical analyses aimed at revealing structure–function relationships in photoreceptors. Geometrical optics combined with spectrophotometric and morphological data are used to support the analyses and to test predictions. Three functions are considered for correlations between taper and functionality. The first function proposes that outer segment taper serves to compensate for self-screening of the visual pigment contained within. The second function links outer segment taper to compensation for a signal-to-noise ratio decline along the longitudinal dimension. Both functions are supported by the data: real cones taper more than required for these compensatory roles. The third function relates outer segment taper to the optical properties of the inner compartment whereby the primary determinant is the inner segment’s ability to concentrate light via its ellipsoid. In support of this idea, the rod/cone ratios of primarily diurnal animals are predicted based on a principle of equal light flux gathering between photoreceptors. In addition, ellipsoid concentration factor, a measure of ellipsoid ability to concentrate light onto the outer segment, correlates positively with outer segment taper expressed as a ratio of characteristic lengths, where critical taper is the yardstick. Depending on a light-funneling property and the presence of focusing organelles such as oil droplets, cone outer segments can be reduced in size to various degrees. We conclude that outer segment taper is but one component of a miniaturization process that reduces metabolic costs while improving signal detection. Compromise solutions in the various retinas and retinal regions occur between ellipsoid size and acuity, on the one hand, and faster response time and reduced light sensitivity, on the other. PMID:22250013
Biophysics of object segmentation in a collision-detecting neuron
Dewell, Richard Burkett
2018-01-01
Collision avoidance is critical for survival, including in humans, and many species possess visual neurons exquisitely sensitive to objects approaching on a collision course. Here, we demonstrate that a collision-detecting neuron can detect the spatial coherence of a simulated impending object, thereby carrying out a computation akin to object segmentation critical for proper escape behavior. At the cellular level, object segmentation relies on a precise selection of the spatiotemporal pattern of synaptic inputs by dendritic membrane potential-activated channels. One channel type linked to dendritic computations in many neural systems, the hyperpolarization-activated cation channel, HCN, plays a central role in this computation. Pharmacological block of HCN channels abolishes the neuron's spatial selectivity and impairs the generation of visually guided escape behaviors, making it directly relevant to survival. Additionally, our results suggest that the interaction of HCN and inactivating K+ channels within active dendrites produces neuronal and behavioral object specificity by discriminating between complex spatiotemporal synaptic activation patterns. PMID:29667927
Method of fabricating a prestressed cast iron vessel
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.
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).
Sidman, Richard L.
1957-01-01
Fragments of freshly obtained retinas of several vertebrate species were studied by refractometry, with reference to the structure of the rods and cones. The findings allowed a reassessment of previous descriptions based mainly on fixed material. The refractometric method was used also to measure the refractice indices and to calculate the concentrations of solids and water in the various cell segments. The main quantitative data were confirmed by interference microscopy. When examined by the method of refractometry the outer segments of freshly prepared retinal rods appear homogeneous. Within a few minutes a single eccentric longitudinal fiber appears, and transverse striations may develop. These changes are attributed to imbibition of water and swelling in structures normally too small for detection by light microscopy. The central "core" of outer segments and the chromophobic disc between outer and inner segments appear to be artifacts resulting from shrinkage during dehydration. The fresh outer segments of cones, and the inner segments of rods and cones also are described and illustrated. The volumes, refractive indices, concentrations of solids, and wet and dry weights of various segments of the photoreceptor cells were tabulated. Rod outer segments of the different species vary more than 100-fold in volume and mass but all have concentrations of solids of 40 to 43 per cent. Cone outer segments contain only about 30 per cent solids. The myoids, paraboloids, and ellipsoids of the inner segments likewise have characteristic refractive indices and concentrations of solids. Some of the limitations and particular virtues of refractometry as a method for quantitative analysis of living cells are discussed in comparison with more conventional biochemical techniques. Also the shapes and refractive indices of the various segments of photoreceptor cells are considered in relation to the absorption and transmission of light. The Stiles-Crawford effect can be accounted for on the basis of the structure of cone cells. PMID:13416308
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.
Molecular basis for photoreceptor outer segment architecture
Goldberg, Andrew F. X.; Moritz, Orson L.; Williams, David S.
2016-01-01
To serve vision, vertebrate rod and cone photoreceptors must detect photons, convert the light stimuli into cellular signals, and then convey the encoded information to downstream neurons. Rods and cones are sensory neurons that each rely on specialized ciliary organelles to detect light. These organelles, called outer segments, possess elaborate architectures that include many hundreds of light-sensitive membranous disks arrayed one atop another in precise register. These stacked disks capture light and initiate the chain of molecular and cellular events that underlie normal vision. Outer segment organization is challenged by an inherently dynamic nature; these organelles are subject to a renewal process that replaces a significant fraction of their disks (up to ~10%) on a daily basis. In addition, a broad range of environmental and genetic insults can disrupt outer segment morphology to impair photoreceptor function and viability. In this chapter, we survey the major progress that has been made for understanding the molecular basis of outer segment architecture. We also discuss key aspects of organelle lipid and protein composition, and highlight distributions, interactions, and potential structural functions of key OS-resident molecules, including: kinesin-2, actin, RP1, prominin-1, protocadherin 21, peripherin-2/rds, rom-1, glutamic acid-rich proteins, and rhodopsin. Finally, we identify key knowledge gaps and challenges that remain for understanding how normal outer segment architecture is established and maintained. PMID:27260426
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
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
Leaf seal for inner and outer casings of a turbine
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.
2010-01-01
Background Typhoid, which is caused by Salmonella enterica serovar Typhimurium, remains a major health concern worldwide. Multidrug-resistant strains of Salmonella have emerged which exhibit increased survivability and virulence, thus leading to increased morbidity. However, little is known about the protective immune response against this microorganism. The outer membrane protein (Omp)A of bacteria plays an important role in pathogenesis. Results We purified OmpA from S. enterica serovar Typhimurium (OmpA-sal) and characterized the role of OmpA-sal in promoting adaptive and innate immune responses. OmpA-sal functionally activated bone marrow-derived dendritic cells by augmenting expression of CD80, CD86, and major histocompatibility complex classes I and II. Interestingly, OmpA-sal induced production of interferon-γ from T cells in mixed lymphocyte reactions, thus indicating Th1-polarizing capacity. The expression of surface markers and cytokine production in dendritic cells was mediated by the TLR4 signaling pathway in a TLR4 Knock-out system. Conclusions Our findings suggest that OmpA-sal modulates the adaptive immune responses to S. enterica serovar Typhimurium by activating dendritic cells and driving Th1 polarization, which are important properties to consider in the development of effective S. enterica serovar Typhimurium vaccines and immunotherapy adjuvant. PMID:20950448
Harris, Kristen M.; Spacek, Josef; Bell, Maria Elizabeth; Parker, Patrick H.; Lindsey, Laurence F.; Baden, Alexander D.; Vogelstein, Joshua T.; Burns, Randal
2015-01-01
Resurgent interest in synaptic circuitry and plasticity has emphasized the importance of 3D reconstruction from serial section electron microscopy (3DEM). Three volumes of hippocampal CA1 neuropil from adult rat were imaged at X-Y resolution of ~2 nm on serial sections of ~50–60 nm thickness. These are the first densely reconstructed hippocampal volumes. All axons, dendrites, glia, and synapses were reconstructed in a cube (~10 μm3) surrounding a large dendritic spine, a cylinder (~43 μm3) surrounding an oblique dendritic segment (3.4 μm long), and a parallelepiped (~178 μm3) surrounding an apical dendritic segment (4.9 μm long). The data provide standards for identifying ultrastructural objects in 3DEM, realistic reconstructions for modeling biophysical properties of synaptic transmission, and a test bed for enhancing reconstruction tools. Representative synapses are quantified from varying section planes, and microtubules, polyribosomes, smooth endoplasmic reticulum, and endosomes are identified and reconstructed in a subset of dendrites. The original images, traces, and Reconstruct software and files are freely available and visualized at the Open Connectome Project (Data Citation 1). PMID:26347348
Ling, Changying; Hendrickson, Michael L; Kalil, Ronald E
2012-01-01
The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN) of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA) injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60-340 µm(2). Labeled projection neurons supported 7-55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0 × 10(4) µm(2). Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short "tufted" appendages arise mainly from the distal branches of dendrites; "spine-like" appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and "grape-like" appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole.
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.
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
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.
Random Positions of Dendritic Spines in Human Cerebral Cortex
Morales, Juan; Benavides-Piccione, Ruth; Dar, Mor; Fernaud, Isabel; Rodríguez, Angel; Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier
2014-01-01
Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits. PMID:25057209
Glycolytic reliance promotes anabolism in photoreceptors
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
The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones
Sato, Shinya; Frederiksen, Rikard; Cornwall, M. Carter; Kefalov, Vladimir J.
2017-01-01
Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle. However, the molecular identity of the cis retinol oxidase in cones remains unclear. Here, as a first step in characterizing this enzymatic reaction, we sought to determine the subcellular localization of this activity in salamander red cones. We found that the onset of dark adaptation of isolated salamander red cones was substantially faster when exposing directly their outer vs. their inner segment to 9-cis retinol, an analogue of 11-cis retinol. In contrast, this difference was not observed when treating the outer vs. inner segment with 9-cis retinal, a chromophore analogue which can directly support pigment regeneration. These results suggest, surprisingly, that the cis-retinol oxidation occurs in the outer segments of cone photoreceptors. Confirming this notion, pigment regeneration with exogenously added 9-cis retinol was directly observed in the truncated outer segments of cones, but not in rods. We conclude that the enzymatic machinery required for the oxidation of recycled cis retinol as part of the retina visual cycle is present in the outer segments of cones. PMID:28359344
Duménieu, Maël; Oulé, Marie; Kreutz, Michael R.; Lopez-Rojas, Jeffrey
2017-01-01
Neurons are highly polarized cells with apparent functional and morphological differences between dendrites and axon. A critical determinant for the molecular and functional identity of axonal and dendritic segments is the restricted expression of voltage-gated ion channels (VGCs). Several studies show an uneven distribution of ion channels and their differential regulation within dendrites and axons, which is a prerequisite for an appropriate integration of synaptic inputs and the generation of adequate action potential (AP) firing patterns. This review article will focus on the signaling pathways leading to segmented expression of voltage-gated potassium and sodium ion channels at the neuronal plasma membrane and the regulatory mechanisms ensuring segregated functions. We will also discuss the relevance of proper ion channel targeting for neuronal physiology and how alterations in polarized distribution contribute to neuronal pathology. PMID:28484374
Fortier, Pierre A; Bray, Chelsea
2013-04-16
Previous studies revealed mechanisms of dendritic inputs leading to action potential initiation at the axon initial segment and backpropagation into the dendritic tree. This interest has recently expanded toward the communication between different parts of the dendritic tree which could preprocess information before reaching the soma. This study tested for effects of asymmetric voltage attenuation between different sites in the dendritic tree on summation of synaptic inputs and action potential initiation using the NEURON simulation environment. Passive responses due to the electrical equivalent circuit of the three-dimensional neuron architecture with leak channels were examined first, followed by the responses after adding voltage-gated channels and finally synaptic noise. Asymmetric attenuation of voltage, which is a function of asymmetric input resistance, was seen between all pairs of dendritic sites but the transfer voltages (voltage recorded at the opposite site from stimulation among a pair of dendritic sites) were equal and also summed linearly with local voltage responses during simultaneous stimulation of both sites. In neurons with voltage-gated channels, we reproduced the observations where a brief stimulus to the proximal ascending dendritic branch of a pyramidal cell triggers a local action potential but a long stimulus triggers a somal action potential. Combined stimulation of a pair of sites in this proximal dendrite did not alter this pattern. The attraction of the action potential onset toward the soma with a long stimulus in the absence of noise was due to the higher density of voltage-gated sodium channels at the axon initial segment. This attraction was, however, negligible at the most remote distal dendritic sites and was replaced by an effect due to high input resistance. Action potential onset occurred at the dendritic site of higher input resistance among a pair of remote dendritic sites, irrespective of which of these two sites received the synaptic input. Exploration of the parameter space showed how the gradient of voltage-gated channel densities and input resistances along a dendrite could draw the action potential onset away from the stimulation site. The attraction of action potential onset toward the higher density of voltage-gated channels in the soma during stimulation of the proximal dendrite was, however, reduced after the addition of synaptic noise. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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.
Cruce, W L
1975-01-01
Descending fiber projections to the lizard spinal cord were studied using anterograde axonal degeneration. Following hemisection of the cord at the first spinal segment, degeneration was found in the white and gray matter as far down as the 31st (caudal) segment. Degenerating fibers in the white matter were confined to the ipsilateral side and were found in the medial longitudinal fasiculus and the outer half ot the lateral and ventral funiculi. Degeneration was more intense in the dorsolateral and ventromedial funiculi than in the ventrolateral funiculus. In the gray matter, REXED's criteria were applied to Nissl-stained material to delimit boundaries of ten laminae. Degeneration of suprospinal axons was most intense in the medial part of VII, dorsal and ventral commissures to ramify contralaterally in the medial part of VII, in VII, and in medial IX. No degeneration was present in the lateral part of the spinal gray on the contralateral side. In Golgi-stained material, dendrites of lateral IX cells were seen to extend into lamina VII, the dorsolateral part of VII, and the lateral funiculus. Thus, fibers of the ventromedial supraspinal pathway may make axodendritic contact with motoneurons of lateral IX as well as medial IX, ipsilaterally. In addition, there is a possibility of a crossed connection to contralateral motoneurons.
[Role of oxidative mechanisms in the pathogenesis of age-related macular degeneration].
Janik-Papis, Katarzyna; Ulińska, Magdalena; Krzyzanowska, Anna; Stoczyńska, Ewelina; Borucka, Anna I; Woźniak, Katarzyna; Małgorzata, Zaras; Szaflik, Jacek P; Blasiak, Janusz
2009-01-01
Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells are prone to reactive oxygen species (ROS) arising during the stress due to intense oxygen metabolism and a high oxygen pressure. Additionally, the cells can be exposed to ROS as a consequence of accumulation of iron ions in these cells, sunlight exposure and tobacco smoke. There are several defense systems against RTF in the cell, including antioxidant enzymes, low-molecular weight antioxidants and DNA repair pathways. RPE cells display phagocytic activity towards outer segments of photoreceptors and this activity can be associated with additional oxidative stress since the segments are rich in long chain, polyunsaturated fatty acids (PUFA). The oxidation of PUFA leads to the production of additional ROS. Moreover, oxidized PUFA are not correctly cleaved in the lysosomes of RPE and are accumulated in the form of lipofuscin, which is deposited in Bruch's membrane in the form of drusen and in this way it stimulates immune responses, including phagocytosis, associated with the recruiting of macrophages and dendritic cells. In this time, RPE cells are exposed to ROS, produced in oxygen burst associated with phagocytosis. Further studies, both clinical/epidemiological and in vitro, are needed to better understand relationship between AMD and oxidative stress.
Ahn, Seong Joon; Ahn, Jeeyun; Woo, Se Joon; Park, Kyu Hyung
2014-01-01
To compare the postoperative photoreceptor status and visual outcome after epiretinal membrane removal with or without additional internal limiting membrane (ILM) peeling. Medical records of 40 eyes from 37 patients undergoing epiretinal membrane removal with residual ILM peeling (additional ILM peeling group) and 69 eyes from 65 patients undergoing epiretinal membrane removal without additional ILM peeling (no additional peeling group) were reviewed. The length of defects in cone outer segment tips, inner segment/outer segment junction, and external limiting membrane line were measured using spectral domain optical coherence tomography images of the fovea before and at 1, 3, 6, and 12 months after the surgery. Cone outer segment tips and inner segment/outer segment junction line defects were most severe at postoperative 1 month and gradually restored at 12 months postoperatively. The cone outer segment tips line defect in the additional ILM peeling group was significantly greater than that in the no additional peeling group at postoperative 1 month (P = 0.006), and best-corrected visual acuity was significantly worse in the former group at the same month (P = 0.001). There was no significant difference in the defect size and best-corrected visual acuity at subsequent visits and recurrence rates between the two groups. Patients who received epiretinal membrane surgery without additional ILM peeling showed better visual and anatomical outcome than those with additional ILM peeling at postoperative 1 month. However, surgical outcomes were comparable between the two groups, thereafter. In terms of visual outcome and photoreceptor integrity, additional ILM peeling may not be an essential procedure.
Hofmann, H; Braun, K
1995-05-26
The persistence of morphological features of neurons in slice cultures of the imprinting-relevant forebrain area MNH (mediorostral neostriatum and hyperstriatum ventrale) of the domestic chick was analysed at 7, 14, 21 and 28 days in vitro. After having been explanted and kept in culture the neurons in vitro have larger soma areas, longer and more extensively branched dendritic trees and lower spine frequencies compared to the neurons in vivo. During the analyzed culturing period, the parameters soma area, total and mean dendritic length, number of dendrites, number of dendritic nodes per dendrite and per neuron as well as the spine densities in different dendritic segments showed no significant differences between early and late periods. Highly correlated in every age group were the total dendritic length and the number of dendritic nodes per neuron, indicating regular ramification during dendritic growth. Since these morphological parameters remain stable during the first 4 weeks in vitro, this culture system may provide a suitable model to investigate experimentally induced morphological changes.
Turbine nozzle/nozzle support structure
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
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
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
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
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
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.
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.
Random positions of dendritic spines in human cerebral cortex.
Morales, Juan; Benavides-Piccione, Ruth; Dar, Mor; Fernaud, Isabel; Rodríguez, Angel; Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Yuste, Rafael
2014-07-23
Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits. Copyright © 2014 the authors 0270-6474/14/3410078-07$15.00/0.
Segmented inlet nozzle for gas turbine, and methods of installation
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.
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
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.
The localization of guanylyl cyclase-activating proteins in the mammalian retina.
Cuenca, N; Lopez, S; Howes, K; Kolb, H
1998-06-01
To explore the distribution of guanylyl cylase-activating proteins 1 and 2 (GCAP1 and GCAP2) in the mammalian retina. Cryostat and vibratome vertical sections and wholemount retinas from mouse, rat, cat, bovine, monkey, and human eyes were prepared for immunocytochemistry and viewing by light and confocal microscopy. In all mammalian retinas investigated, intense GCAP1 immunoreactivity (GCAP1-IR) was seen in cone photoreceptor inner and outer segments, cell bodies, and synaptic regions. Intensity of the GCAP1-IR was strong in inner segments of rods in all species but weaker in outer segments-particularly so in primates and cats. GCAP2 immunoreactivity (GCAP2-IR) was weak in bovine, mouse, and rat cones but was intense in human and monkey cones. In all species except primates, GCAP2 staining was intense in rod inner and outer segments. In primates GCAP2-IR was intense in the rod inner segment but faint in the rod outer segment. A striking difference from the GCAP1 pattern of immunoreactivity was seen with GCAP2 antibodies as far as the inner retina was concerned. GCAP2-IR was evident in certain populations of bipolar, amacrine, and ganglion cells in all species. GCAP1 and GCAP2, which are involved in Ca2+-dependent stimulation and inhibition of photoreceptor guanylyl cyclase, can be detected in mammalian photoreceptor inner and outer segments, consistent with their physiological function. The occurrence of both GCAPs in the synaptic region of the photoreceptors indicates participation of these proteins in pathways other than regulation of phototransduction. The occurrence of GCAP2 in inner retinal neurons is indicative of second-messenger chemical transduction, possibly in metabotropic glutamate, gamma-aminobutyric acid (GABA) receptor, and nitric oxide-activated neural circuits.
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.
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
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.
Histological techniques for study of photoreceptor orientation.
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.
The sensory dorsal organs of crustaceans.
Lerosey-Aubril, Rudy; Meyer, Roland
2013-05-01
The cuticle of crustaceans bears numerous organs, of which the functions of many are unknown. One of these, the sensory dorsal organ (SDO), is present in a wide diversity of taxa. Here we critically review the variability, ultrastructure, distribution, and possible function of this enigmatic cuticular organ. Previous data are complemented by new observations on larvae and adults of various malacostracans. The SDO is composed of four sensors arranged as the corners of a square, the centre of which is occupied by a gland. Pores or pegs surrounding this central complex may also form part of the organ. The arrangement and the external aspect of the five main elements varies greatly, but this apparently has little impact on their ultrastructural organisation. The sensors and the gland are associated with a particularly thin cuticle. Each sensor contains four outer dendritic segments and the central gland is made of a single large cell. It is not yet known what this large cell secretes. The SDO is innervated from the tritocerebrum and therefore belongs to the third cephalic segment. A similar organ, here called the posterior SDO, has been repeatedly observed more posteriorly on the carapace. It resembles the SDO but has a greater number of sensors (usually six, but up to ten) apparently associated with only two outer dendritic segments. The SDO and the posterior SDO are known in the Eumalacostraca, the Hoplocarida, and the Phyllocarida. Some branchiopods also possess a 'dorsal organ' resembling both the SDO and the ion-transporting organ more typical of this group. This may indicate a common origin for these two functionally distinct groups of organs. New observations on the posterior SDO support the hypothesis that the SDO and the posterior SDO are homologous to the lattice organ complexes of the costracans. However, the relationship between the SDO and the dorsal cephalic hump of calanoid copepods remains unclear. No correlation can be demonstrated between the presence of a SDO and a particular ecological or biological trait. In fossils, the most convincing examples of SDO-like organs are found in some Late Cambrian arthropods from the Alum Shale of southern Sweden. They suggest that related organs might have been present in non-crustacean Cambrian arthropods. The distribution of the SDO and posterior SDO in extant and fossil crustaceans strongly suggests that these organs originated early in the history of the group, and are crucial to the functioning of these organisms. However, except for knowing that the sensors are chemoreceptors and that in a given organ a functional relationship probably exists between them and the gland, little is known about this function. The description of a SDO in freshwater carideans, which can be easily reared in a laboratory, opens the way for behavioural and physiological experiments to be undertaken that could prove crucial for the determination of this function. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.
Actin and microtubule-based cytoskeletal cues direct polarized targeting of proteins in neurons
Arnold, Don B.
2010-01-01
Neuronal proteins are transported to either the axon or dendrites through the action of kinesin motors; however understanding of how cytoskeletal elements steer these cargo-motor complexes to one compartment or the other has remained elusive. Three recent developments, the discovery of an actin-based filter within the axon initial segment, the identification of the pivotal role played by myosin motors in dendritic targeting, and the determination of the properties of a kinesin motor that cause it to prefer axonal to dendritic microtubules, have now provided a structural framework for understanding polarized targeting in neurons. PMID:19671926
Wedge edge ceramic combustor tile
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
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.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, Kang Min; Kim, Yeon Sung; Yang, Hae Woong
2015-01-15
An investigation of the coating structure formed on Mg–3 wt.%Al–1 wt.%Zn alloy sample subjected to plasma electrolytic oxidation was examined by field-emission transmission electron microscopy. The plasma electrolytic oxidation process was conducted in a phosphoric acid electrolyte containing K{sub 2}ZrF{sub 6} for 600 s. Microstructural observations showed that the coating consisting of MgO, MgF{sub 2}, and ZrO{sub 2} phases was divided into three distinctive parts, the barrier, intermediate, and outer layers. Nanocrystalline MgO and MgF{sub 2} compounds were observed mainly in the barrier layer of ~ 1 μm thick near to the substrate. From the intermediate to outer layers, variousmore » ZrO{sub 2} polymorphs appeared due to the effects of the plasma arcing temperature on the phase transition of ZrO{sub 2} compounds during the plasma electrolytic oxidation process. In the outer layer, MgO compound grew in the form of a dendrite-like structure surrounded by cubic ZrO{sub 2}. - Highlights: • The barrier layer containing MgO and MgF{sub 2} was observed near to the Mg substrate. • In the intermediate layer, m-, t-, and o-ZrO{sub 2} compounds were additionally detected. • The outer layer contained MgO with the dendrite-like structure surrounded by c-ZrO{sub 2}. • The grain sizes of compounds in oxide layer increased from barrier to outer layer.« less
Stream network and stream segment temperature models software
Bartholow, John
2010-01-01
This set of programs simulates steady-state stream temperatures throughout a dendritic stream network handling multiple time periods per year. The software requires a math co-processor and 384K RAM. Also included is a program (SSTEMP) designed to predict the steady state stream temperature within a single stream segment for a single time period.
Active action potential propagation but not initiation in thalamic interneuron dendrites
Casale, Amanda E.; McCormick, David A.
2012-01-01
Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033
Calcium homeostasis in the outer segments of retinal rods from the tiger salamander.
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
Oriented Markov random field based dendritic spine segmentation for fluorescence microscopy images.
Cheng, Jie; Zhou, Xiaobo; Miller, Eric L; Alvarez, Veronica A; Sabatini, Bernardo L; Wong, Stephen T C
2010-10-01
Dendritic spines have been shown to be closely related to various functional properties of the neuron. Usually dendritic spines are manually labeled to analyze their morphological changes, which is very time-consuming and susceptible to operator bias, even with the assistance of computers. To deal with these issues, several methods have been recently proposed to automatically detect and measure the dendritic spines with little human interaction. However, problems such as degraded detection performance for images with larger pixel size (e.g. 0.125 μm/pixel instead of 0.08 μm/pixel) still exist in these methods. Moreover, the shapes of detected spines are also distorted. For example, the "necks" of some spines are missed. Here we present an oriented Markov random field (OMRF) based algorithm which improves spine detection as well as their geometric characterization. We begin with the identification of a region of interest (ROI) containing all the dendrites and spines to be analyzed. For this purpose, we introduce an adaptive procedure for identifying the image background. Next, the OMRF model is discussed within a statistical framework and the segmentation is solved as a maximum a posteriori estimation (MAP) problem, whose optimal solution is found by a knowledge-guided iterative conditional mode (KICM) algorithm. Compared with the existing algorithms, the proposed algorithm not only provides a more accurate representation of the spine shape, but also improves the detection performance by more than 50% with regard to reducing both the misses and false detection.
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.
Calretinin immunoreactivity in the claustrum of the rat
Druga, Rastislav; Salaj, Martin; Barinka, Filip; Edelstein, Lawrence; Kubová, Hana
2015-01-01
The claustrum is a telencephalic structure which consists of dorsal segment adjoining the insular cortex and a ventral segment termed also endopiriform nucleus (END). The dorsal segment (claustrum) is divided into a dorsal and ventral zone, while the END is parcellated into dorsal, ventral and intermediate END. The claustrum and the END consist of glutamatergic projection neurons and GABAergic local interneurons coexpressing calcium binding proteins. Among neurons expressing calcium binding proteins the calretinin (CR)-immunoreactive interneurons exert specific functions in neuronal circuits, including disinhibition of excitatory neurons. Previous anatomical data indicate extensive and reciprocally organized claustral projections with cerebral cortex. We asked if the distribution of cells immunoreactive for CR delineates anatomical or functional subdivisions in the claustrum and in the END. Both segments of the claustrum and all subdivisions of the END contained CR immunoreactive neurons with varying distribution. The ventral zone of the claustrum exhibited weak labeling with isolated cell bodies and thin fibers and is devoid of immunoreactive puncta. Within the medial margin of the intermediate END we noted a group of strongly positive neurons. Cells immunoreactive for CR in all subdivisions of the claustrum and END were bipolar, multipolar and oval with smooth, beaded aspiny dendrites. Small number of CR-immunoreactive neurons displayed thin dendrites which enter to adjoining structures. Penetration of dendrites was reciprocal. These results show an inhomogenity over the claustrum and the END in distribution and types of CR immunoreactive neurons. The distribution of the CR-immunoreactive neurons respects the anatomical but not functional zones of the claustral complex. PMID:25653596
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.
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.
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
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.
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.
Jonnal, Ravi S; Gorczynska, Iwona; Migacz, Justin V; Azimipour, Mehdi; Zawadzki, Robert J; Werner, John S
2017-09-01
Optical coherence tomography's (OCT) third outer retinal band has been attributed to the zone of interdigitation between RPE cells and cone outer segments. The purpose of this paper is to investigate the structure of this band with adaptive optics (AO)-OCT. Using AO-OCT, images were obtained from two subjects. Axial structure was characterized by measuring band 3 thickness and separation between bands 2 and 3 in segmented cones. Lateral structure was characterized by correlation of band 3 with band 2 and comparison of their power spectra. Band thickness and separation were also measured in a clinical OCT image of one subject. Band 3 thickness ranged from 4.3 to 6.4 μm. Band 2 correlations ranged between 0.35 and 0.41 and power spectra of both bands confirmed peak frequencies that agree with histologic density measurements. In clinical images, band 3 thickness was between 14 and 19 μm. Measurements of AO-OCT of interband distance were lower than our corresponding clinical OCT measurements. Band 3 originates from a structure with axial extent similar to a single surface. Correlation with band 2 suggests an origin within the cone photoreceptor. These two observations indicate that band 3 corresponds predominantly to cone outer segment tips (COST). Conventional OCT may overestimate both the thickness of band 3 and outer segment length.
Jonnal, Ravi S.; Gorczynska, Iwona; Migacz, Justin V.; Azimipour, Mehdi; Zawadzki, Robert J.; Werner, John S.
2017-01-01
Purpose Optical coherence tomography's (OCT) third outer retinal band has been attributed to the zone of interdigitation between RPE cells and cone outer segments. The purpose of this paper is to investigate the structure of this band with adaptive optics (AO)-OCT. Methods Using AO-OCT, images were obtained from two subjects. Axial structure was characterized by measuring band 3 thickness and separation between bands 2 and 3 in segmented cones. Lateral structure was characterized by correlation of band 3 with band 2 and comparison of their power spectra. Band thickness and separation were also measured in a clinical OCT image of one subject. Results Band 3 thickness ranged from 4.3 to 6.4 μm. Band 2 correlations ranged between 0.35 and 0.41 and power spectra of both bands confirmed peak frequencies that agree with histologic density measurements. In clinical images, band 3 thickness was between 14 and 19 μm. Measurements of AO-OCT of interband distance were lower than our corresponding clinical OCT measurements. Conclusions Band 3 originates from a structure with axial extent similar to a single surface. Correlation with band 2 suggests an origin within the cone photoreceptor. These two observations indicate that band 3 corresponds predominantly to cone outer segment tips (COST). Conventional OCT may overestimate both the thickness of band 3 and outer segment length. PMID:28877320
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.
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▿ †
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
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
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
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.
Distinct functions for IFT140 and IFT20 in opsin transport.
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
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.
Garlipp, Mary Alice; Gonzalez-Fernandez, Federico
2013-08-01
The close packing of vertebrate photoreceptors presents a challenge to the exchange of molecules between the outer segments, retinal pigmented epithelium (RPE), and Müller glia. An extracellular hyaluronan scaffold separates these cells while soluble interphotoreceptor matrix (IPM) proteins traffic visual cycle retinoids, fatty acids, and other molecules between them. In the IPM, retinoids and fatty acids are carried by interphotoreceptor retinoid-binding protein (IRBP). The fact that much of the retina's IRBP can be extracted by saline wash has led to the notion that IRBP does not bind to the retina, but freely distributes itself within the subretinal space. In this study, we challenge this idea by asking if there are specialized IPM domains that bind IRBP, perhaps facilitating its ability to target delivery/uptake of its ligands. Xenopus is an ideal animal model to study the role of the IPM in RPE-photoreceptor interactions. Here, we took advantage of the large size of its photoreceptors, ability to detach the retina in light, sustainability of the retina in short term organ culture, and the availability of recombinant full-length Xenopus IRBP and antisera directed against Xenopus IRBP. We compared the distribution of wash resistant native IRBP, and that of IRBP-Alexa 647 binding in Xenopus retina. IRBP and cone opsin were localized using anti-Xenopus IRBP serum, and monoclonal COS-1 respectively. Cone matrix sheath proteoglycans were localized with wheat germ agglutinin (WGA), and diffuse IPM proteoglycans with peanut agglutinin (PNA). Wholemounts and frozen sections were compared by immunofluorescence from retinas detached under Ringer's followed by additional washes, or detached directly under 4% paraformaldehyde without Ringer's wash. Undetached Lowicryl embedded retinas were subjected to IRBP immunogold electron microscopy (EM). Immunogold labeled a diffuse network of filamentous structures, and a separate distinct flocculant material directly coating the outer segments, filling the rod periciliary ridge, and associated with Müller microvilli. By immunofluorescence, Ringer's wash removed most of the diffuse IRBP, but not that coating the outer segments. IRBP-Alexa 647 bound to the cone outer segments and Müller villi region, and comparably less to rod outer segments. Co-incubation with unlabeled IRBP markedly reduced this binding; ovalbumin-Alexa 647 and Alexa 647 dye alone showed no binding. Our data suggest that the pericellular matrix of the cone outer segments and Müller microvilli provide specialized domains that facilitate IRBP's functions. Copyright © 2013 Elsevier Ltd. All rights reserved.
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.
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.
Partially segmented deformable mirror
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
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.
Cameron, Michael C.; Zhan, Ren-Zhi; Nadler, J. Victor
2014-01-01
After pilocarpine-induced status epilepticus, many granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) are hyperexcitable and may therefore increase circuit excitability. This study determined the distribution of their axons and dendrites. HEGCs and normotopic granule cells were filled with biocytin during whole-cell patch clamp recording in hippocampal slices from pilocarpine-treated rats. The apical dendrite of 86% of the biocytin-labeled HEGCs extended to the outer edge of the dentate molecular layer. The total length and branching of HEGC apical dendrites that penetrated the molecular layer were significantly reduced compared with apical dendrites of normotopic granule cells. HEGCs were much more likely to have a hilar basal dendrite than normotopic granule cells. They were about as likely as normotopic granule cells to project to CA3 pyramidal cells within the slice, but were much more likely to send at least one recurrent mossy fiber into the molecular layer. HEGCs with burst capability had less well-branched apical dendrites than nonbursting HEGCs, their dendrites were more likely to be confined to the hilus, and some exhibited dendritic features similar to those of immature granule cells. HEGCs thus have many paths along which to receive synchronized activity from normotopic granule cells and to transmit their own hyperactivity to both normotopic granule cells and CA3 pyramidal cells. They may therefore contribute to the highly interconnected granule cell hubs that have been proposed as crucial to development of a hyperexcitable, potentially seizure-prone circuit. PMID:21455997
Acute Zonal Cone Photoreceptor Outer Segment Loss.
Aleman, Tomas S; Sandhu, Harpal S; Serrano, Leona W; Traband, Anastasia; Lau, Marisa K; Adamus, Grazyna; Avery, Robert A
2017-05-01
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. To describe the structural and functional associations found in a patient with acute zonal occult photoreceptor loss. A case report of an adolescent boy with acute visual field loss despite a normal fundus examination performed at a university teaching hospital. 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). 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. 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.
Child, Nicholas D; Benarroch, Eduardo E
2014-03-18
Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.
Dinamarca, Margarita C; Guzzetti, Francesca; Karpova, Anna; Lim, Dmitry; Mitro, Nico; Musardo, Stefano; Mellone, Manuela; Marcello, Elena; Stanic, Jennifer; Samaddar, Tanmoy; Burguière, Adeline; Caldarelli, Antonio; Genazzani, Armando A; Perroy, Julie; Fagni, Laurent; Canonico, Pier Luigi; Kreutz, Michael R; Gardoni, Fabrizio; Luca, Monica Di
2016-01-01
Synapses and nuclei are connected by bidirectional communication mechanisms that enable information transfer encoded by macromolecules. Here, we identified RNF10 as a novel synaptonuclear protein messenger. RNF10 is activated by calcium signals at the postsynaptic compartment and elicits discrete changes at the transcriptional level. RNF10 is enriched at the excitatory synapse where it associates with the GluN2A subunit of NMDA receptors (NMDARs). Activation of synaptic GluN2A-containing NMDARs and induction of long term potentiation (LTP) lead to the translocation of RNF10 from dendritic segments and dendritic spines to the nucleus. In particular, we provide evidence for importin-dependent long-distance transport from synapto-dendritic compartments to the nucleus. Notably, RNF10 silencing prevents the maintenance of LTP as well as LTP-dependent structural modifications of dendritic spines. DOI: http://dx.doi.org/10.7554/eLife.12430.001 PMID:26977767
Harper, C E; Roberts, A
1993-04-29
Spinal cord neurons were investigated in embryos of Triturus vulgaris, the smooth newt, just prior to hatching. These embryos can swim if freed from their egg membranes. Horseradish peroxidase (HRP) labelling, together with GABA and glycine immunocytochemistry (ICC), revealed nine distinct anatomical classes of neuron. 1. Ventrolateral motoneurons with mainly dorsal dendrites, sometimes a descending central axon and peripheral axon innervating the trunk muscles. 2. Dorsal primary sensory Rohon-Beard neurons innervating skin and with dorsal ascending and descending axons in spinal cord. 3. Commissural interneurons with mid-cord unipolar soma, glycine-like immunoreactivity, dendrites on initial segment of ventral axon which crosses cord to ascend or branch. 4. Dorsolateral commissural interneurons with multipolar soma in dorsolateral position with dorsal dendrites and ventral axon which crosses and ascends or branches. 5. Giant dorsolateral commissural interneurons with large dorsolateral somata widely spaced (130-250 microns spacing) with process projecting dorsally to other side, dorsolateral dendrites and ventral axon which crosses to ascend and branch. 6. Dorsolateral ascending interneurons in dorsolateral position with multipolar soma and ascending axon on same side. 7. Ascending interneurons with unipolar soma, GABA-like immunoreactivity and ascending axon on same side. 8. Descending interneurons with bi- or multi-polar soma, extensive dorsal and ventral dendrites, and descending axon on same side. They may also have ascending axons. 9. Kolmer-Agduhr cerebrospinal fluid contacting neurons with cilia and microvilli in lateral corners of neural canal. GABA-like immunoreactivity, no dendrites and ascending axon. Eight of the nine cells classes were found to bear a marked resemblance to neurons previously described in zebrafish and Xenopus embryos in terms of their anatomy, distribution and immunoreactivity to GABA and glycine. Homologies and possible functions are discussed. Giant dorsolateral commissural neurons, were not found in Xenopus or teleosts but were present in Ambystoma mexicanum and Neoceratodus. The regular, possibly segmental longitudinal distribution pattern of these cells within the cord is unusual among amphibian spinal neurons.
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
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.
Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment
Tapia, Mónica; Dominguez, Ana; Zhang, Wei; del Puerto, Ana; Ciorraga, María; Benitez, María José; Guaza, Carmen; Garrido, Juan José
2017-01-01
Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown. In this study, we have focused on the role of the type-1 cannabinoid receptor (CB1R), a highly abundant G-protein coupled receptor (GPCR) in the nervous system largely involved in different phases of neuronal development and differentiation. Although CB1R activity modulation has been related to changes in axons or dendrites, its possible role as a modulator of AIS development has not been yet explored. Here we analyzed the potential role of CB1R on neuronal morphology and AIS development using pharmacological and RNA interference approaches in cultured hippocampal neurons. CB1R inhibition, at a very early developmental stage, has no effect on axonal growth, yet CB1R activation can promote it. By contrast, subsequent dendritic growth is impaired by CB1R inhibition, which also reduces ankyrinG density at the AIS. Moreover, our data show a significant correlation between early dendritic growth and ankyrinG density. However, CB1R inhibition in later developmental stages after dendrites are formed only reduces ankyrinG accumulation at the AIS. In conclusion, our data suggest that neuronal CB1R basal activity plays a role in initial development of dendrites and indirectly in AIS proteins accumulation. Based on the lack of CB1R expression at the AIS, we hypothesize that CB1R mediated modulation of dendritic arbor size during early development indirectly determines the accumulation of ankyrinG and AIS development. Further studies will be necessary to determine which CB1R-dependent mechanisms can coordinate these two domains, and what may be the impact of these early developmental changes once neurons mature and are embedded in a functional brain network. PMID:28179879
A Novel Pulse-Chase Paradigm to Visualize the Trafficking of Transport Vesicles in Neurons
NASA Astrophysics Data System (ADS)
Al-Bassam, Sarmad
In neurons transmembrane proteins are targeted to dendrites in vesicles that traffic solely within the somatodendritic compartment. How these vesicles are retained within the somatodendritic domain is unknown. Here we adapt a novel pulse chase system that allows synchronous release of exogenous transmembrane proteins from the endoplasmic reticulum using FKBP12 and Rapamycin. We demonstrate proof-of-concept and establish protein trafficking controls in incremental steps. We demonstrate the utility of this approach in studying protein trafficking and establish parameters for analysis of time-lapse images. We implement this novel pulse-chase strategy to track the movements of post-Golgi transport vesicles. Surprisingly, we found that post-Golgi vesicles carrying dendritic proteins were equally likely to enter axons and dendrites. However, once such vesicles entered the axon they very rarely moved beyond the axon initial segment, but instead either halted or reversed direction in an actin and Myosin Va-dependent manner. In contrast, vesicles carrying either an axonal or a nonspecifically localized protein only rarely halted or reversed and instead generally proceeded to the distal axon. Thus, our results are consistent with the axon initial segment behaving as a vesicle filter that mediates the differential trafficking of transport vesicles.
Localization of antibody binding sites in ultrathin sections of unembedded frog retinal tissue.
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.
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
Monkey extensor digitorum communis motoneuron pool: Proximal dendritic trees and small motoneurons.
Jenny, Arthur B; Cheney, Paul D; Jenny, Andrew K
2018-05-14
Transverse sections of the monkey cervical spinal cord from a previous study (Jenny and Inukai, 1983) were reanalyzed using Neurolucida to create a three-dimensional display of extensor digitorum communis (EDC) motoneurons and proximal dendrites that had been labeled with horse radish peroxidase (HRP). The EDC motoneuron pool was located primarily in the C8 and T1 segments of the spinal cord. Small motoneurons (cell body areas less than 500 μm 2 and presumed to be gamma motoneurons) comprised about ten percent of the motoneurons and were located throughout the length of the motoneuron pool. Most small motoneurons were oblong in shape and had one or two major dendrites originating from the cell body in the transverse plane of section. The majority of the HRP labeled dendritic trees were directed either superiorly, dorsal-medially to the mid zone area between the base of the dorsal horn and the upper portion of the ventral horn, or medially to the ventromedial gray matter. The longer HRP labeled dendrites usually continued in the same radial direction as when originating from the cell body. As such we considered the radial direction of the longer proximal HRP labeled dendrites to be a reasonable estimate of the radial direction of the more distal dendritic tree. Our data suggest that the motoneuron dendritic tree as seen in transverse section has direction-oriented dendrites that extend toward functional terminal regions. Copyright © 2018 Elsevier B.V. All rights reserved.
HYPERAUTOFLUORESCENT RING IN AUTOIMMUNE RETINOPATHY
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
Santuy, A; Rodriguez, J R; DeFelipe, J; Merchan-Perez, A
2018-01-01
Knowing the proportions of asymmetric (excitatory) and symmetric (inhibitory) synapses in the neuropil is critical for understanding the design of cortical circuits. We used focused ion beam milling and scanning electron microscopy (FIB/SEM) to obtain stacks of serial sections from the six layers of the juvenile rat (postnatal day 14) somatosensory cortex (hindlimb representation). We segmented in three-dimensions 6184 synaptic junctions and determined whether they were established on dendritic spines or dendritic shafts. Of all these synapses, 87-94% were asymmetric and 6-13% were symmetric. Asymmetric synapses were preferentially located on dendritic spines in all layers (80-91%) while symmetric synapses were mainly located on dendritic shafts (62-86%). Furthermore, we found that less than 6% of the dendritic spines establish more than one synapse. The vast majority of axospinous synapses were established on the spine head. Synapses on the spine neck were scarce, although they were more common when the dendritic spine established multiple synapses. This study provides a new large quantitative dataset that may contribute not only to the knowledge of the ultrastructure of the cortex, but also towards defining the connectivity patterns through all cortical layers.
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.
Neuron Morphology Influences Axon Initial Segment Plasticity.
Gulledge, Allan T; Bravo, Jaime J
2016-01-01
In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.
Neuron Morphology Influences Axon Initial Segment Plasticity123
2016-01-01
In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation. PMID:27022619
Effect of Dendritic Polymer Architecture on Biological Behaviors of Self-Assembled Nanocarriers
NASA Astrophysics Data System (ADS)
Hsu, Hao-Jui
Polymeric self-assembled nanocarriers represent one of the most versatile platforms for drug delivery. Through tailoring the physiochemical properties of amphiphilic block copolymers, self-assembled nanocarriers with great thermodynamic stability and desired biological properties could be achieved. The PEGylated dendron-based copolymers (PDCs) are one of the novel amphiphilic copolymers that have attracted a great deal of scientific interest due to their unique dendritic structure and properties. While the dendritic polymer architecture of PDC has been shown to enhance the thermodynamic stability of the self-assembling PDCs, dendron micelles, the effect of this polymer architecture on the biological properties of dendron micelles has not yet been studied. Therefore, this dissertation research is focused on understanding the role of dendritic polymer structure on moderating the biological properties of various self-assembled nanocarriers. To systematically investigate this, three studies have been designed and performed. First, we studied whether the dendritic structure of PDC allows dendron micelles to behave non-specific cellular interactions in a similar way that dendrimers would do. Second, cell-specific interactions of dendron micelles mediated by conjugated ligands were investigated. Third, we investigated the influence of dendritic PEG outer shell on micelle-serum protein interactions and its subsequent implication. Our results revealed that both non-specific and specific cellular interactions of dendron micelles were controllable through modulation of the PEG corona length. While the non-specific charge-dependent cellular interactions of dendron micelles were tunable through controlling the length of PEG corona, the use of long PEG tether was found to enhance the ligand-mediated cellular interactions of dendron micelles. With the ligand tethers, a 27-fold enhancement in ligand-mediated cellular interactions can be achieved, compared to non-targeted dendron micelles. Furthermore, we demonstrate that the dense PEG outer shell introduced by its dendritic structure reduced non-specific micelle-serum protein interactions and suppressed the subsequent micelle disintegration or premature drug release, which was not the case for linear block copolymer (LBC)-based micelles. Molecular dynamic (MD) simulation results also supported that dendron micelles exhibited a weaker interaction with serum albumin compared to LBC-based micelles. In the presence of serum proteins, the half-life of dendron micelles was 2-fold longer than that of LBC-based micelles, which could be attributed to their low serum protein interactions. In conclusion, our results provide fundamental understanding on the role of PEG corona and the effect of polymeric architecture on biological properties of polymer micelles, all indicating that dendron micelles have great potential as a novel drug delivery platform.
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.
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.
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.
Szteyn, S; Robak, A; Równiak, M
1997-01-01
The neuronal structure of the somatic oculomotor nucleus (SON) was studied on the basis of Nissl and Golgi preparations, obtained from mesencephalons of 4 European bisons. We distinguished four types of neurons in the investigated nucleus: 1. The large multipolar nerve cells with 5-8 thick dendritic trunks and a thin axon which emerges directly from the soma. These are the most numerous neurons in the SON. 2. The small multipolar neurons. These cells have 4-6 thick dendritic trunks. An axon arises mostly from initial segment of one of the dendrites. This type represents about 8% neurons of SON. 3. The triangular neurons. From perikaryon 3 thick dendritic trunks emerge. A thin axon arises directly from the cell body. These cells make about 10% neurons of SON. 4. The pear-shaped cells which have 1 or 2 dendritic trunks concentrate at one pole of the neurons. In the SON there are about 2% pear-shaped cells. Their features correspond to the features attributed by many authors to the interneurons.
Zone heated diesel particulate filter electrical connection
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.
NASA Astrophysics Data System (ADS)
Mirsafianf, Atefeh S.; Isfahani, Shirin N.; Kasaei, Shohreh; Mobasheri, Hamid
Here we present an approach for processing neural cells images to analyze their growth process in culture environment. We have applied several image processing techniques for: 1- Environmental noise reduction, 2- Neural cells segmentation, 3- Neural cells classification based on their dendrites' growth conditions, and 4- neurons' features Extraction and measurement (e.g., like cell body area, number of dendrites, axon's length, and so on). Due to the large amount of noise in the images, we have used feed forward artificial neural networks to detect edges more precisely.
SAP97 Binding Partner CRIPT Promotes Dendrite Growth In Vitro and In Vivo
Zhang, Lei; Jablonski, Angela Marie; Neve, Rachael; Zhai, JinBin
2017-01-01
Abstract The dendritic tree is a key determinant of neuronal information processing. In the motor system, the dendritic tree of spinal cord neurons undergoes dramatic remodeling in an activity-dependent manner during early postnatal life. This leads to the proper segmental spinal cord connectivity that subserves normal locomotor behavior. One molecular system driving the establishment of dendrite architecture of mammalian motor neurons relies on AMPA receptors (AMPA-Rs) assembled with the GluA1 subunit, and this occurs in an NMDA receptor (NMDA-R)-independent manner. The dendrite growth promoting activity of GluA1-containing AMPA-Rs depends on its intracellular binding partner, SAP97, and SAP97’s PDZ3 domain. We show here that cysteine-rich interactor of PDZ3 (CRIPT) is a bona fide SAP97 PDZ3-domain binding partner, localizes to synapses with GluA1 and SAP97 along the dendritic tree, and is a determinant of the dendritic growth of mammalian spinal cord neurons. We further show that CRIPT has a well-conserved ortholog in the nematode, Caenorhabditis elegans, and animals lacking CRIPT display decreased dendrite branching of the well-studied PVD neuron in vivo. The lack of CRIPT leads to a selective defect in touch perception, and this is rescued by expression of wild-type (WT) human CRIPT (hCRIPT) in the nervous system. This work brings new light into the molecular machinery that drives dendritic growth during development and may prove relevant to the promotion of nervous system plasticity following insult. PMID:29218323
Acute Zonal Cone Photoreceptor Outer Segment Loss
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
Form, shape and function: segmented blood flow in the choriocapillaris
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
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.
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
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.
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
Litts, Katie M; Messinger, Jeffrey D; Freund, K Bailey; Zhang, Yuhua; Curcio, Christine A
2015-04-01
To quantify impressions of mitochondrial translocation in degenerating cones and to determine the nature of accumulated material in the subretinal space with apparent inner segment (IS)-like features by examining cone IS ultrastructure. Human donor eyes with advanced age-related macular degeneration (AMD) were screened for outer retinal tubulation (ORT) in macula-wide, high-resolution digital sections. Degenerating cones inside ORT (ORT cones) and outside ORT (non-ORT cones) from AMD eyes and unaffected cones in age-matched control eyes were imaged using transmission electron microscopy. The distances of mitochondria to the external limiting membrane (ELM), cone IS length, and cone IS width at the ELM were measured. Outer retinal tubulation and non-ORT cones lose outer segments (OS), followed by shortening of IS and mitochondria. In non-ORT cones, IS broaden. Outer retinal tubulation and non-ORT cone IS myoids become undetectable due to mitochondria redistribution toward the nucleus. Some ORT cones were found lacking IS and containing mitochondria in the outer fiber (between soma and ELM). Unlike long, thin IS mitochondria in control cones, ORT and non-ORT IS mitochondria are ovoid or reniform. Shed IS, some containing mitochondria, were found in the subretinal space. In AMD, macula cones exhibit loss of detectable myoid due to IS shortening in addition to OS loss, as described. Mitochondria shrink and translocate toward the nucleus. As reflectivity sources, translocating mitochondria may be detectable using in vivo imaging to monitor photoreceptor degeneration in retinal disorders. These results improve the knowledge basis for interpreting high-resolution clinical retinal imaging.
Contribution of the Axon Initial Segment to Action Potentials Recorded Extracellularly.
Teleńczuk, Maria; Brette, Romain; Destexhe, Alain; Teleńczuk, Bartosz
2018-01-01
Action potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at the onset of an AP the soma and the AIS form a dipole. We study the extracellular signature [the extracellular AP (EAP)] generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. The soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic extracellular potentials recorded in the brain.
Alp, Murat; Cucinotta, Francis A
2018-03-01
Exposure to heavy-ion radiation during cancer treatment or space travel may cause cognitive detriments that have been associated with changes in neuron morphology and plasticity. Observations in mice of reduced neuronal dendritic complexity have revealed a dependence on radiation quality and absorbed dose, suggesting that microscopic energy deposition plays an important role. In this work we used morphological data for mouse dentate granular cell layer (GCL) neurons and a stochastic model of particle track structure and microscopic energy deposition (ED) to develop a predictive model of high-charge and energy (HZE) particle-induced morphological changes to the complex structures of dendritic arbors. We represented dendrites as cylindrical segments of varying diameter with unit aspect ratios, and developed a fast sampling method to consider the stochastic distribution of ED by δ rays (secondary electrons) around the path of heavy ions, to reduce computational times. We introduce probabilistic models with a small number of parameters to describe the induction of precursor lesions that precede dendritic snipping, denoted as snip sites. Predictions for oxygen ( 16 O, 600 MeV/n) and titanium ( 48 Ti, 600 MeV/n) particles with LET of 16.3 and 129 keV/μm, respectively, are considered. Morphometric parameters to quantify changes in neuron morphology are described, including reduction in total dendritic length, number of branch points and branch numbers. Sholl analysis is applied for single neurons to elucidate dose-dependent reductions in dendritic complexity. We predict important differences in measurements from imaging of tissues from brain slices with single neuron cell observations due to the role of neuron death through both soma apoptosis and excessive dendritic length reduction. To further elucidate the role of track structure, random segment excision (snips) models are introduced and a sensitivity study of the effects of the modes of neuron death in predictions of morphometric parameters is described. An important conclusion of this study is that δ rays play a major role in neuron morphological changes due to the large spatial distribution of damage sites, which results in a reduced dependence on LET, including modest difference between 16 O and 48 Ti, compared to damages resulting from ED in localized damage sites.
Retinal photoreceptors and visual pigments in Boa constrictor imperator.
Sillman, A J; Johnson, J L; Loew, E R
2001-09-01
The photoreceptors of Boa constrictor, a boid snake of the subfamily Boinae, were examined with scanning electron microscopy and microspectrophotometry. The retina of B. constrictor is duplex but highly dominated by rods, cones comprising 11% of the photoreceptor population. The rather tightly packed rods have relatively long outer segments with proximal ends that are somewhat tapered. There are two morphologically distinct, single cones. The most common cone by far has a large inner segment and a relatively stout outer segment. The second cone, seen only infrequently, has a substantially smaller inner segment and a finer outer segment. The visual pigments of B. constrictor are virtually identical to those of the pythonine boid, Python regius. Three different visual pigments are present, all based on vitamin A(1.) The visual pigment of the rods has a wavelength of peak absorbance (lambda(max)) at 495 +/- 2 nm. The visual pigment of the more common, large cone has a lambda(max) at 549 +/- 1 nm. The small, rare cone contains a visual pigment with lambda(max) at 357 +/- 2 nm, providing the snake with sensitivity in the ultraviolet. We suggest that B. constrictor might employ UV sensitivity to locate conspecifics and/or to improve hunting efficiency. The data indicate that wavelength discrimination above 430 nm would not be possible without some input from the rods. Copyright 2001 Wiley-Liss, Inc.
Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori
2016-11-28
H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.
Yau, Suk-Yu; Li, Ang; Tong, Jian-Bin; Bostrom, Crystal; Christie, Brian R; Lee, Tatia M C; So, Kwok-Fai
2016-09-21
Our previous work has shown that exposure to the stress hormone corticosterone (40 mg/kg CORT) for two weeks induces dendritic atrophy of pyramidal neurons in the hippocampal CA3 region and behavioral deficits. However, it is unclear whether this treatment also affects the dentate gyrus (DG), a subregion of the hippocampus comprising a heterogeneous population of young and mature neurons. We examined the effect of CORT treatment on the dendritic complexity of mature and young granule cells in the DG. We utilized a Golgi staining method to investigate the dendritic morphology and spine density of young neurons in the inner granular cell layer (GCL) and mature neurons in the outer GCL in response to CORT application. The expressions of glucocorticoid receptors during neuronal maturation were examined using Western blot analysis in a primary hippocampal neuronal culture. Sholl analysis revealed that CORT treatment decreased the number of intersections and shortened the dendritic length in mature, but not young, granule cells. However, the spine density of mature and young neurons was not affected. Western blot analysis showed a progressive increase in the protein levels of glucocorticoid receptors (GRs) in the cultured primary hippocampal neurons during neuronal maturation. These data suggest that mature neurons are likely more vulnerable to chronic exposure to CORT; this may be due to their higher expression of GRs when compared to younger DG neurons.
Amemiya, T
1999-12-01
To examine the effect of vitamins and trace elements on ocular tissue. Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B12, C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyser, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens. Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus. Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B12 deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B12 was found to be related to the circadian rhythm in the retina. Deficiencies of Zn, Cu, Mn, and vitamins A, B12, and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers. In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer. Zn seemed to be necessary for corneal epithelial cell wound healing. Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance. Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B12, C, and E are necessary for maintenance of cellular structure and metabolism.
Amemiya
2000-05-01
Purpose: To examine the effect of vitamins and trace elements on ocular tissue.Materials and Methods: Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B(12), C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyzer, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens.Results: Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus.Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B(12) deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B(12) was found to be related to the circadian rhythm in the retina.Deficiencies of Zn, Cu, Mn, and vitamins A, B(12), and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers.In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer.Zn seemed to be necessary for corneal epithelial cell wound healing.Discussion: Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance.Conclusion: Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B(12), C, and E are necessary for maintenance of cellular structure and metabolism.
Oikonomou, Katerina D.; Short, Shaina M.; Rich, Matthew T.; Antic, Srdjan D.
2012-01-01
Repetitive synaptic stimulation overcomes the ability of astrocytic processes to clear glutamate from the extracellular space, allowing some dendritic segments to become submerged in a pool of glutamate, for a brief period of time. This dynamic arrangement activates extrasynaptic NMDA receptors located on dendritic shafts. We used voltage-sensitive and calcium-sensitive dyes to probe dendritic function in this glutamate-rich location. An excess of glutamate in the extrasynaptic space was achieved either by repetitive synaptic stimulation or by glutamate iontophoresis onto the dendrites of pyramidal neurons. Two successive activations of synaptic inputs produced a typical NMDA spike, whereas five successive synaptic inputs produced characteristic plateau potentials, reminiscent of cortical UP states. While NMDA spikes were coupled with brief calcium transients highly restricted to the glutamate input site, the dendritic plateau potentials were accompanied by calcium influx along the entire dendritic branch. Once initiated, the glutamate-mediated dendritic plateau potentials could not be interrupted by negative voltage pulses. Activation of extrasynaptic NMDA receptors in cellular compartments void of spines is sufficient to initiate and support plateau potentials. The only requirement for sustained depolarizing events is a surplus of free glutamate near a group of extrasynaptic receptors. Highly non-linear dendritic spikes (plateau potentials) are summed in a highly sublinear fashion at the soma, revealing the cellular bases of signal compression in cortical circuits. Extrasynaptic NMDA receptors provide pyramidal neurons with a function analogous to a dynamic range compression in audio engineering. They limit or reduce the volume of “loud sounds” (i.e., strong glutamatergic inputs) and amplify “quiet sounds” (i.e., glutamatergic inputs that barely cross the dendritic threshold for local spike initiation). Our data also explain why consecutive cortical UP states have uniform amplitudes in a given neuron. PMID:22934081
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
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)
Oka, Y
1983-04-01
The local neuronal circuitry of goldfish olfactory bulb was analyzed in Golgi preparations combining light- and electron-microscopy, as well as in routinely prepared ultrastructural preparations. Mitral cells were identified with the light-microscope in Golgi-impregnated thick sections according to the following criteria: (1) cell bodies were distributed irregularly in a wide layer between 100 and 200 micrometer from the surface, (2) cell bodies were larger than other neurons (10-20 micrometer in diameter), and (3) the dendrites were directed toward the superficially-located olfactory nerve layer where they ended as highly branched glomerular tufts. These impregnated cells were examined by electron-microscopy in serial section. The results demonstrate synaptic organization in relation to the mitral cells. (1) Glomerular tufts received afferent input from primary olfactory axons which made Gray's Type I synaptic contacts. These dendrites also had reciprocal dendrodendritic synapses with dendrites of certain non-mitral cells. (2) Dendritic shafts of mitral cells made reciprocal dendritic synapses with dendrites of certain non-mitral cells. (3) Cell bodies and their initial axon segments had reciprocal synapses with certain dendrites but occurred infrequently. In reciprocal synapses, the direction of the Gray Type I (asymmetrical) is away from the mitral cell while those with Gray Type II synapses (symmetrical) are toward the mitral cell. Assuming that the type I synapse is excitatory and Type II is inhibitory, these findings explain the electrophysiological demonstration of self-inhibition discharge found in mitral cells.
Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E; Freedman, Stephen; Schenk, Dale; Young, Warren G; Morrison, John H; Bloom, Floyd E
2004-05-04
Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, beta-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs.
Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E.; Freedman, Stephen; Schenk, Dale; Young, Warren G.; Morrison, John H.; Bloom, Floyd E.
2004-01-01
Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, β-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs. PMID:15118092
Sodium-dependent calcium extrusion and sensitivity regulation in retinal cones of the salamander.
Nakatani, K; Yau, K W
1989-01-01
1. Membrane current was recorded from an isolated, dark-adapted salamander cone by sucking its inner segment into a tight-fitting glass pipette containing Ringer solution. The outer segment of the cell was exposed to a bath solution that could be changed rapidly. 2. After removing Na+ from the bath Ringer solution for a short period of time in darkness (the 'loading period'), a transient inward current was observed upon restoring it in bright light. A similar but longer-lasting current was observed when Na+ was restored in the light after a large Ca2+ influx was induced through the light-sensitive conductance in darkness. 3. The above transient current was not observed if Li+ or guanidinium was substituted for Na+ in the light, or if Ba2+ was substituted for Ca2+ during the dark loading period. However, a current was observed if Sr2+ was the substituting ion for Ca2+ during loading. These observations suggested that the current was associated with an electrogenic Na+-dependent Ca2+ efflux at the cone outer segment. 4. The saturated amplitude of the exchange current was 12-25 pA with a mean around 16 pA. This is very comparable to that measured in the outer segment of a salamander rod under similar conditions. 5. By comparing a known Ca2+ load in a cone outer segment to the subsequent charge transfer through the exchange, we estimated that the stoichiometry of the exchange was near 3Na+:1Ca2+. 6. With a small Ca2+ load, or in the presence of Cs+ around the inner segment, the final temporal decline of the Na+-Ca2+ exchange current was roughly exponential, with a mean time constant of about 100 ms. This decline is about four times faster than that measured in rods. We interpret the shorter time constant in cones to reflect a faster rate of decline of intracellular free Ca2+ in their outer segments resulting from the exchange activity. 7. In the absence of external Na+, and hence any Na+-dependent Ca2+ efflux, the absolute sensitivity of a cone to a dim flash was several times higher than in normal Ringer solution. 8. A roughly similar increase in light sensitivity was observed for a rod under the same conditions. 9. We conclude that the Na+-dependent Ca2+ efflux, through lowering intracellular free Ca2+ in the light, has a role in regulating the absolute light sensitivity in cones as it does in rods.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2479741
Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice
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
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
A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer’s Disease
Somogyi, Attila; Katonai, Zoltán; Alpár, Alán; Wolf, Ervin
2016-01-01
One century after its first description, pathology of Alzheimer’s disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic (TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that AD-related neuronal hyperexcitability cannot be accounted for by altered subthreshold dendritic signaling in these neurons but hyperexcitability is related to changes in active membrane properties and network connectivity. PMID:27378850
A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer's Disease.
Somogyi, Attila; Katonai, Zoltán; Alpár, Alán; Wolf, Ervin
2016-01-01
One century after its first description, pathology of Alzheimer's disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic (TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that AD-related neuronal hyperexcitability cannot be accounted for by altered subthreshold dendritic signaling in these neurons but hyperexcitability is related to changes in active membrane properties and network connectivity.
Dendritic spine dynamics leading to spine elimination after repeated inductions of LTD
Hasegawa, Sho; Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko
2015-01-01
Memory is fixed solidly by repetition. However, the cellular mechanism underlying this repetition-dependent memory consolidation/reconsolidation remains unclear. In our previous study using stable slice cultures of the rodent hippocampus, we found long-lasting synaptic enhancement/suppression coupled with synapse formation/elimination after repeated inductions of chemical LTP/LTD, respectively. We proposed these phenomena as useful model systems for analyzing repetition-dependent memory consolidation. Recently, we analyzed the dynamics of dendritic spines during development of the enhancement, and found that the spines increased in number following characteristic stochastic processes. The current study investigates spine dynamics during the development of the suppression. We found that the rate of spine retraction increased immediately leaving that of spine generation unaltered. Spine elimination occurred independent of the pre-existing spine density on the dendritic segment. In terms of elimination, mushroom-type spines were not necessarily more stable than stubby-type and thin-type spines. PMID:25573377
Thiers, Fabio A; Nadol, Joseph B; Liberman, M Charles
2008-12-01
Cochlear outer hair cells (OHCs) serve both as sensory receptors and biological motors. Their sensory function is poorly understood because their afferent innervation, the type-II spiral ganglion cell, has small unmyelinated axons and constitutes only 5% of the cochlear nerve. Reciprocal synapses between OHCs and their type-II terminals, consisting of paired afferent and efferent specialization, have been described in the primate cochlea. Here, we use serial and semi-serial-section transmission electron microscopy to quantify the nature and number of synaptic interactions in the OHC area of adult cats. Reciprocal synapses were found in all OHC rows and all cochlear frequency regions. They were more common among third-row OHCs and in the apical half of the cochlea, where 86% of synapses were reciprocal. The relative frequency of reciprocal synapses was unchanged following surgical transection of the olivocochlear bundle in one cat, confirming that reciprocal synapses were not formed by efferent fibers. In the normal ear, axo-dendritic synapses between olivocochlear terminals and type-II terminals and/or dendrites were as common as synapses between olivocochlear terminals and OHCs, especially in the first row, where, on average, almost 30 such synapses were seen in the region under a single OHC. The results suggest that a complex local neuronal circuitry in the OHC area, formed by the dendrites of type-II neurons and modulated by the olivocochlear system, may be a fundamental property of the mammalian cochlea, rather than a curiosity of the primate ear. This network may mediate local feedback control of, and bidirectional communication among, OHCs throughout the cochlear spiral.
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
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.
Han, Zhou; Anderson, David W.
2012-01-01
Purpose. Prominin-1 expresses in rod and cone photoreceptors. Mutations in the prominin-1 gene cause retinal degeneration in humans. In this study, the authors investigated the expression and subcellular localization of xlProminin-1 protein, the Xenopus laevis ortholog of prominin-1, in rod and cone photoreceptors of this frog. Methods. Antibodies specific for xlProminin-1 were generated. Immunoblotting was used to study the expression and posttranslational processing of xlProminin-1 protein. Immunocytochemical light and electron microscopy and transgenesis were used to study the subcellular distribution of xlProminin-1. Results. xlProminin-1 is expressed and is subject to posttranslational proteolytic processing in the retina, brain, and kidney. xlProminin-1 is differently expressed and localized in outer segments of rod and cone photoreceptors of X. laevis. Antibodies specific for the N or C termini of xlProminin-1 labeled the open rims of lamellae of cone outer segments (COS) and the open lamellae at the base of rod outer segments (ROS). By contrast, anti–peripherin-2/rds antibody, Xper5A11, labeled the closed rims of cone lamellae adjacent to the ciliary axoneme and the rims of the closed ROS disks. The extent of labeling of the basal ROS by anti–xlProminin-1 antibodies varied with the light cycle in this frog. The entire ROS was also faintly labeled by both antibodies, a result that contrasts with the current notion that prominin-1 localizes only to the basal ROS. Conclusions. These findings suggest that xlProminin-1 may serve as an anti–fusogenic factor in the regulation of disk morphogenesis and may help to maintain the open lamellar structure of basal ROS and COS disks in X. laevis photoreceptors. PMID:22076989
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.
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
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.
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.
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.
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.
DSCAM Localization and Function at the Mouse Cone Synapse
de Andrade, Gabriel Belem; Long, Samuel S.; Fleming, Harrison; Li, Wei; Fuerst, Peter G.
2014-01-01
The Down Syndrome Cell Adhesion Molecule (DSCAM) is required for regulation of cell number, soma spacing and cell type specific dendrite avoidance in many types of retinal ganglion and amacrine cells. In this study we assay the organization of cells making up the outer plexiform layer of the retina in the absence of Dscam. Some types of OFF bipolar cells, type 3b and type 4 bipolar cells, had defects in dendrite arborization in the Dscam mutant retina, while other cell types appeared similar to wild type. The cone synapses that these cells project their dendrites to were intact, as visualized by electron microscopy, and had a distribution and density that was not significantly different than wild type. The spacing of type 3b bipolar cell dendrites was further analyzed by Voronoi domain analysis, Density Recovery Profiling (DRP) analysis and Nearest Neighbor Analysis (NNA). Spacing was found to be significantly different when comparing wild type and mutant type 3b bipolar cell dendrites. Defects in arborization of these bipolar cells could not be attributed to the disorganization of inner plexiform layer cells that occurs in the Dscam mutant retina or an increase in cell number, as they arborized when Dscam was targeted in retinal ganglion cells only or in the bax null retina. Localization of DSCAM was assayed and the protein was localized near to cone synapses in mouse, macaque and ground squirrel retinas. DSCAM protein was detected in several types of bipolar cells, including type 3b and type 4 bipolar cells. PMID:24477985
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.
Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus.
Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D
2008-12-01
The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of approximately 5 m s(-1) and approximately 0.7 m s(-1), respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na(+)] ACSF or the selective Na(v) channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Na(v) channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABA(A) receptors regulates the axonal initiation of action potentials.
Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus
Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D
2008-01-01
The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na+ (Nav) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of ∼5 m s−1 and ∼0.7 m s−1, respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na+] ACSF or the selective Nav channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Nav channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABAA receptors regulates the axonal initiation of action potentials. PMID:18832425
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.
Early photoreceptor outer segment loss and retinoschisis in Cohen syndrome.
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.
Jishkariani, Davit; Lee, Jennifer D; Yun, Hongseok; Paik, Taejong; Kikkawa, James M; Kagan, Cherie R; Donnio, Bertrand; Murray, Christopher B
2017-09-28
The collective magnetic properties of nanoparticle (NP) solid films are greatly affected by inter-particle dipole-dipole interactions and therefore the proximity of the neighboring particles. In this study, a series of dendritic ligands (generations 0 to 3, G0-G3) have been designed and used to cover the surface of magnetic NPs to control the spacings between the NP components in single lattices. The dendrons of different generations introduced here were based on the 2,2-bis(hydroxymethyl)propionic acid (Bis-MPA) scaffold and equipped with an appropriate surface binding group at one end and several fatty acid segments at the other extremity. The surface of the NPs was then modified by partial ligand exchange between the primary stabilizing surfactants and the new dendritic wedges. It was shown that this strategy permitted very precise tuning of inter-particle spacings in the range of 2.9-5.0 nm. As expected, the increase in the inter-particle spacings reduced the dipole-dipole interactions between magnetic NPs and therefore allowed changes in their magnetic permeability. The dendron size and inter-particle distance dependence was studied to reveal the dendritic effect and identify the optimal geometry and generation.
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
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.
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.
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.
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.
Herde, Michel K; Herbison, Allan E
2015-11-01
GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.
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.
Oe, Yuki; Tominaga-Yoshino, Keiko; Hasegawa, Sho; Ogura, Akihiko
2013-01-01
Not only from our daily experience but from learning experiments in animals, we know that the establishment of long-lasting memory requires repeated practice. However, cellular backgrounds underlying this repetition-dependent consolidation of memory remain largely unclear. We reported previously using organotypic slice cultures of rodent hippocampus that the repeated inductions of LTP (long-term potentiation) lead to a slowly developing long-lasting synaptic enhancement accompanied by synaptogenesis distinct from LTP itself, and proposed this phenomenon as a model system suitable for the analysis of the repetition-dependent consolidation of memory. Here we examined the dynamics of individual dendritic spines after repeated LTP-inductions and found the existence of two phases in the spines' stochastic behavior that eventually lead to the increase in spine density. This spine dynamics occurred preferentially in the dendritic segments having low pre-existing spine density. Our results may provide clues for understanding the cellular bases underlying the repetition-dependent consolidation of memory. PMID:23739837
Light-Induced Translocation of RGS9-1 and Gβ5L in Mouse Rod Photoreceptors
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.
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.
Marcos, S; Tornow, R P; Elsner, A E; Navarro, R
1997-07-01
Foveal cone spacing was measured in vivo using an objective technique: ocular speckle interferometry. Cone packing density was computed from cone spacing data. Foveal cone photopigment density difference was measured in the same subjects using retinal densitometry with a scanning laser ophthalmoscope. Both the cone packing density and cone photopigment density difference decreased sharply with increasing retinal eccentricity. From the comparison of both sets of measurements, the computed amounts of photopigment per cone increased slightly with increasing retinal eccentricity. Consistent with previous results, decreases in cone outer segment length are over-compensated by an increase in the outer segment area, at least in retinal eccentricities up to 1 deg.
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.
2013-01-29
Scanning Confocal Microscope (Zeiss- Pascal) using 20x obj. and edited using Zeiss Image Examiner Ver 5.0. The iso-cortical pyramidal layers 1 and 2 are...NeuN immunoreactivity is seen in the neuronal cytoplasm and especially apical dendrites of pyramidal neurons (white arrows), which facilitates the...identification of the pyramidal cell morphology in the outer pyramidal cell layer of neo-cortex (see picture A, depicted as py). Cortical Pyramidal
2016-03-11
50, Immunology. 26 | P a g e blood-borne antigens. The white pulp consists of the periarteriolar lymphoid sheath (PALS) which contain T cells ...and CD8α+ dendritic (DC), and adjacent lymphoid follicles containing mainly circulating B cells , known as follicular B cells (FB). The outer boundary...complexes, for initial priming within the T cell zones of secondary lymphoid organs followed by migration of T cells to the T cell -B cell border. B
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
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
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.
The Cellular Origins of the Outer Retinal Bands in Optical Coherence Tomography Images
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
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.
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
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).
In Vivo Imaging of Human Cone Photoreceptor Inner Segments
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
NASA Astrophysics Data System (ADS)
Xu, Xiaoming; Ding, Hongrui; Li, Yan; Lu, Anhuai; Li, Yan; Wang, Changqiu
2018-03-01
Identification of Mn oxides in natural Mn coatings is very difficult due to their poor crystallinity, fine grains, complex chemistry and tiny amounts. In this work, we investigated three types of Mn coatings including rock varnish, dendrite and soil Fe-Mn cutan from different weathering environments in China. Optical microscope, scanning electron microscope, energy dispersive X-ray spectroscopy and micro-Raman spectrometer were employed to achieve non-destructive, sensitive, in-situ and micro analysis on their mineral assemblages, micromorphological features and elemental distribution characteristics. The observed results suggest that rock varnish and soil cutan comprise birnessite, while dendrite is mainly composed of hollandite. Rock varnish with a layered structure has a clear boundary with its substrate, and microlaminations which arise from the fluctuations in Mn content (6.42-17.07 wt%) within the sample profile are obvious on closer inspection. Branch-like dendrite is rich in Mn (32.53-42.96 wt%) but poor in Si and Al, which shows a pilotaxitic texture with its substrate. Soil Fe-Mn cutan can be further divided into an outer black Mn-rich (8.26-13.58 wt%) belt and an inner yellowish-brown Fe-rich (2.06-4.85 wt%) belt, and a clear border can be identified between these two belts. Mn in the substrate of rock varnish and soil cutan is below detection limit while it can be detected in the substrate of dendrite (1.43-7.83 wt%). Our in-situ analysis provides more precise results than traditional powder test. These mineralogical characteristics indicate that dendrite is most likely endogenic, while rock varnish and soil cutan are external accretion formed under different weathering environments.
The effect of light on outer segment calcium in salamander rods
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
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.
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).
Dorsal motor nucleus of the vagus neurons: a multivariate taxonomy.
Jarvinen, M K; Powley, T L
1999-01-18
The dorsal motor nucleus of the vagus (DMNX) contains neurons with different projections and discrete functions, but little success has been achieved in distinguishing the cells cytoarchitectonically. The present experiment employed multivariate analytical techniques to evaluate DMNX neuronal morphology. Male Sprague-Dawley rats (n = 77) were perfused, and the brainstems were stained en bloc with a Golgi-Cox protocol. DMNX neurons in each of three planes (coronal, sagittal, and horizontal; total sample = 607) were digitized. Three-dimensional features quantified included dendritic length, number of segments, spine density, number of primary dendrites, dendritic orientation, and soma form factor. Cluster analyses of six independent samples of 100+ neurons and of three composite replicate pools of 200+ neurons consistently identified similar sets of four distinct neuronal profiles. One profile (spinous, limited dendrites, small somata) appears to correspond to the interneuron population of the DMNX. In contrast, the other three distinctive profiles (e.g., one is multipolar, with large dendritic fields and large somata) are different types of preganglionic neurons. Each of the four types of neurons is found throughout the DMNX, suggesting that the individual columnar subnuclei and other postulated vagal motorneuron pools are composed of all types of neurons. Within individual motor pools, ensembles of the different neuronal types must cooperatively organize different functions and project to different effectors within a target organ. By extension, specializations of the preganglionic motor pools are more likely to result from their afferent inputs, peripheral target tissues, neurochemistry, or physiological features rather than from any unique morphological profiles.
Reiner, A; Stern, E A; Wilson, C J
2001-01-01
Much of the Wulst and dorsal ventricular ridge (DVR) in birds, which together make up the part of the avian telencephalon functionally resembling mammalian cerebral cortex, projects to the striatum. Those connections arise from neurons projecting additionally to the brainstem as well as from neurons projecting only within the telencephalon. As part of an effort to further characterize corticostriatal-type projection neurons in birds, we recorded intracellularly from neurons of the outer DVR, identified neurons projecting to the striatum by antidromic stimulation from the ipsilateral rostromedial striatum or subsequently by their axonal projection, characterized these neurons physiologically and then filled them with biocytin. As neurons in the outer DVR only project within telencephalon, neurons within it projecting to the striatum are of the intratelencephalically projecting (IT) type. Our studies suggest that: (1) the membrane potentials of avian IT-type neurons fluctuate between two preferred subthreshold values, and action potentials occur only in the 'up' state, (2) avian IT-type neurons show a time-dependent inward rectification in response to hyperpolarization and regular firing in response to constant current injection, (3) the conduction velocity of avian IT-type neurons is slow (about 0.2 m/s), (4) avian IT-type neurons possess radially disposed densely spiny dendrites but no apical dendrite, (5) avian IT-type neurons have local and distant collateral projections within the DVR, and (6) individual avian IT-type neurons give rise to an extensive terminal field within the striatum. Aside from the shape of their dendritic tree, IT-type neurons in birds closely resemble IT-type corticostriatal neurons in mammals in these various aspects, although it is presently uncertain whether this neuron type has been inherited in common by birds and mammals from stem amniotes. Copyright 2002 S. Karger AG, Basel
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.
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.
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.
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.
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.
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
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.
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.
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.
Electrorefining cell with parallel electrode/concentric cylinder cathode
Gay, Eddie C.; Miller, William E.; Laidler, James J.
1997-01-01
A cathode-anode arrangement for use in an electrolytic cell is adapted for electrochemically refining spent nuclear fuel from a nuclear reactor and recovering purified uranium for further treatment and possible recycling as a fresh blanket or core fuel in a nuclear reactor. The arrangement includes a plurality of inner anodic dissolution baskets that are each attached to a respective support rod, are submerged in a molten lithium halide salt, and are rotationally displaced. An inner hollow cylindrical-shaped cathode is concentrically disposed about the inner anodic dissolution baskets. Concentrically disposed about the inner cathode in a spaced manner are a plurality of outer anodic dissolution baskets, while an outer hollow cylindrical-shaped is disposed about the outer anodic dissolution baskets. Uranium is transported from the anode baskets and deposited in a uniform cylindrical shape on the inner and outer cathode cylinders by rotating the anode baskets within the molten lithium halide salt. Scrapers located on each anode basket abrade and remove the spent fuel deposits on the surfaces of the inner and outer cathode cylinders, with the spent fuel falling to the bottom of the cell for removal. Cell resistance is reduced and uranium deposition rate enhanced by increasing the electrode area and reducing the anode-cathode spacing. Collection efficiency is enhanced by trapping and recovery of uranium dendrites scrapped off of the cylindrical cathodes which may be greater in number than two.
Electrorefining cell with parallel electrode/concentric cylinder cathode
Gay, E.C.; Miller, W.E.; Laidler, J.J.
1997-07-22
A cathode-anode arrangement for use in an electrolytic cell is adapted for electrochemically refining spent nuclear fuel from a nuclear reactor and recovering purified uranium for further treatment and possible recycling as a fresh blanket or core fuel in a nuclear reactor. The arrangement includes a plurality of inner anodic dissolution baskets that are each attached to a respective support rod, are submerged in a molten lithium halide salt, and are rotationally displaced. An inner hollow cylindrical-shaped cathode is concentrically disposed about the inner anodic dissolution baskets. Concentrically disposed about the inner cathode in a spaced manner are a plurality of outer anodic dissolution baskets, while an outer hollow cylindrical-shaped is disposed about the outer anodic dissolution baskets. Uranium is transported from the anode baskets and deposited in a uniform cylindrical shape on the inner and outer cathode cylinders by rotating the anode baskets within the molten lithium halide salt. Scrapers located on each anode basket abrade and remove the spent fuel deposits on the surfaces of the inner and outer cathode cylinders, with the spent fuel falling to the bottom of the cell for removal. Cell resistance is reduced and uranium deposition rate enhanced by increasing the electrode area and reducing the anode-cathode spacing. Collection efficiency is enhanced by trapping and recovery of uranium dendrites scrapped off of the cylindrical cathodes which may be greater in number than two. 12 figs.
Photoreceptor inner segment ellipsoid band integrity on spectral domain optical coherence tomography
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
Ha, Sangdeuk; Baver, Scott; Huo, Lihong; Gata, Adriana; Hairston, Joyce; Huntoon, Nicholas; Li, Wenjing; Zhang, Thompson; Benecchi, Elizabeth J.; Ericsson, Maria; Hentges, Shane T.; Bjørbæk, Christian
2013-01-01
Leptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP)/Neuropeptide Y (NPY)/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin receptor (LepRb). Despite progress in the understanding of LepRb signaling and function, the sub-cellular localization of LepRb in target neurons has not been determined, primarily due to lack of sensitive anti-LepRb antibodies. Here we applied light microscopy (LM), confocal-laser scanning microscopy (CLSM), and electron microscopy (EM) to investigate LepRb localization and signaling in mice expressing a HA-tagged LepRb selectively in POMC or AgRP/NPY/GABA neurons. We report that LepRb receptors exhibit a somato-dendritic expression pattern. We further show that LepRb activates STAT3 phosphorylation in neuronal fibers within several hypothalamic and hindbrain nuclei of wild-type mice and rats, and specifically in dendrites of arcuate POMC and AgRP/NPY/GABA neurons of Leprb +/+ mice and in Leprb db/db mice expressing HA-LepRb in a neuron specific manner. We did not find evidence of LepRb localization or STAT3-signaling in axon-fibers or nerve-terminals of POMC and AgRP/NPY/GABA neurons. Three-dimensional serial EM-reconstruction of dendritic segments from POMC and AgRP/NPY/GABA neurons indicates a high density of shaft synapses. In addition, we found that the leptin activates STAT3 signaling in proximity to synapses on POMC and AgRP/NPY/GABA dendritic shafts. Taken together, these data suggest that the signaling-form of the leptin receptor exhibits a somato-dendritic expression pattern in POMC and AgRP/NPY/GABA neurons. Dendritic LepRb signaling may therefore play an important role in leptin’s central effects on energy balance, possibly through modulation of synaptic activity via post-synaptic mechanisms. PMID:24204898
Multicenter reliability of semiautomatic retinal layer segmentation using OCT
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
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.
Silverman, A J; Hou-Yu, A; Zimmerman, E A
1983-05-01
The ultrastructure of the vasopressin neurons of the paraventricular nucleus of the hypothalamus was studied by immunocytochemical techniques. Tissue antigen was detected in unembedded tissue sections using a monoclonal antibody that recognizes vasopressin but not oxytocin or vasotocin. At the light-microscopic level, reaction product was seen to fill the cytoplasm of the neuron cell body as well as large portions of the dendrite and axon. Immunoreactive spines were seen on both somatic and dendritic surfaces and their presence was confirmed at the ultrastructural level. In the light-microscope, axonal processes do not have spines and are thinner and more varicose than dendritic processes. At the electron-microscopic level, both axons and dendrites of the vasopressin cells are filled with reactive neurosecretory granules. The presence of large numbers of these organelles made it difficult to distinguish proximal dendrites from Herring bodies (axonal swellings). At the ultrastructural level, reaction product was also observed in the cytoplasm of all segments of the vasopressin cells. The presence of reaction product outside of membranous compartments is undoubtably due to disruption of membranes by detergent treatment or exposure to basic pH. However, the staining procedure used did allow us to examine the synaptic input to the vasopressin cells. All portions of the vasopressin neuron receive a diverse innervation. The somata have synapses on their surfaces and on spines. These axo-somatic terminals are primarily, but not exclusively, symmetrical and the presynaptic elements contain spherical or elongate vesicles. On the dendrites, terminals again were observed on the surface or on spines. these axo-dendritic synapses were usually asymmetrical. The presynaptic elements contained clear spherical, elongate or pleomorphic vesicles. Occasional varicosities with dense-core granules were seen to make en passant contacts with dendrites; these contacts did not have obvious membrane specializations. Input to vasopressin axons was studied both along the paraventricular-neurohypophysial tract and in the median eminence. Vasopressin axons receive a synaptic input (axo-axonic), predominately of the asymmetric variety with clear, spherical vesicles in the presynaptic element. These findings demonstrate that the vasopressin neurons of the paraventricular nucleus receive a diverse innervation.
Turbine nozzle stage having thermocouple guide tube
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.
Calcium and magnesium fluxes across the plasma membrane of the toad rod outer segment.
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
Lee, Jun Sik; Lee, Je Chul; Lee, Chang-Min; Jung, In Duk; Jeong, Young-Il; Seong, Eun-Young; Chung, Hae-Young; Park, Yeong-Min
2007-06-30
Acinetobacter baumannii is an increasing hospital-acquired pathogen that causes a various type of infections, but little is known about the protective immune response to this microorganism. Outer membrane protein A of A. baumannii (AbOmpA) is a major porin protein and plays an important role in pathogenesis. We analyzed interaction between AbOmpA and dendritic cells (DCs) to characterize the role of this protein in promoting innate and adaptive immune responses. AbOmpA functionally activates bone marrow-derived DCs by augmenting expression of the surface markers, CD40, CD54, B7 family (CD80 and CD86) and major histocompatibility complex class I and II. AbOmpA induces production of Th1-promoting interleukin-12 from DCs and augments the syngeneic and allogeneic immunostimulatory capacity of DCs. AbOmpA stimulates production of interferon-gamma from T cells in mixed lymphocyte reactions, which suggesting Th1-polarizing capacity. CD4(+) T cells stimulated by AbOmpA-stimulated DCs show a Th1-polarizing cytokine profile. The expression of surface markers on DCs is mediated by both mitogen-activated protein kinases and NF-kappaB pathways. Our findings suggest that AbOmpA induces maturation of DCs and drives Th1 polarization, which are important properties for determining the nature of immune response against A. baumannii.
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
Architecture of kangaroo rat inner medulla: segmentation of descending thin limb of Henle's loop.
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.
Protein sorting, targeting and trafficking in photoreceptor cells
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
Macular telangiectasia type 2 (MacTel) in a 34-year-old patient.
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
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.
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.
Loss, Omar; Stephenson, F Anne
2015-07-01
Neuronal function requires regulated anterograde and retrograde trafficking of mitochondria along microtubules by using the molecular motors kinesin and dynein. Previous work has established that trafficking kinesin proteins (TRAKs),TRAK1 and TRAK2, are kinesin adaptor proteins that link mitochondria to kinesin motor proteins via an acceptor protein in the mitochondrial outer membrane, etc. the Rho GTPase Miro. Recent studies have shown that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons by virtue of its binding to both kinesin and dynein motor proteins, whereas TRAK2 controls mitochondrial transport in dendrites resulting from its binding to dynein. This study further investigates the subcellular localization of TRAK1 and TRAK2 in primary cultures of hippocampal and cortical neurons by using both commercial antibodies and anti-TRAK1 and anti-TRAK2 antibodies raised in our own laboratory (in-house). Whereas TRAK1 was prevalently localized in axons of hippocampal and cortical neurons, TRAK2 was more prevalent in dendrites of hippocampal neurons. In cortical neurons, TRAK2 was equally distributed between axons and dendrites. Some qualitative differences were observed between commercial and in-house-generated antibody immunostaining. © 2015 Wiley Periodicals, Inc.
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.
A univocal definition of the neuronal soma morphology using Gaussian mixture models.
Luengo-Sanchez, Sergio; Bielza, Concha; Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Larrañaga, Pedro
2015-01-01
The definition of the soma is fuzzy, as there is no clear line demarcating the soma of the labeled neurons and the origin of the dendrites and axon. Thus, the morphometric analysis of the neuronal soma is highly subjective. In this paper, we provide a mathematical definition and an automatic segmentation method to delimit the neuronal soma. We applied this method to the characterization of pyramidal cells, which are the most abundant neurons in the cerebral cortex. Since there are no benchmarks with which to compare the proposed procedure, we validated the goodness of this automatic segmentation method against manual segmentation by neuroanatomists to set up a framework for comparison. We concluded that there were no significant differences between automatically and manually segmented somata, i.e., the proposed procedure segments the neurons similarly to how a neuroanatomist does. It also provides univocal, justifiable and objective cutoffs. Thus, this study is a means of characterizing pyramidal neurons in order to objectively compare the morphometry of the somata of these neurons in different cortical areas and species.
Höfflin, Felix; Jack, Alexander; Riedel, Christian; Mack-Bucher, Julia; Roos, Johannes; Corcelli, Corinna; Schultz, Christian; Wahle, Petra; Engelhardt, Maren
2017-01-01
The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin. Consequently, the AIS is separated from the soma. Recent in vitro and in vivo studies have shown that cellular excitability is a function of AIS length/position and somatodendritic morphology, undermining a potentially significant impact of AIS heterogeneity for neuronal function. We therefore investigated neocortical axon morphology and AIS composition, hypothesizing that the initial observation of seemingly homogeneous AIS is inadequate and needs to take into account neuronal cell types. Here, we biolistically transfected cortical neurons in organotypic cultures to visualize the entire neuron and classify cell types in combination with immunolabeling against AIS markers. Using confocal microscopy and morphometric analysis, we investigated axon origin, AIS position, length, diameter as well as distance to the soma. We find a substantial AIS heterogeneity in visual cortical neurons, classified into three groups: (I) axons with somatic origin with proximal AIS at the axon hillock; (II) axons with somatic origin with distal AIS, with a discernible gap between the AIS and the soma; and (III) axons with dendritic origin (axon-carrying dendrite cell, AcD cell) and an AIS either starting directly at the axon origin or more distal to that point. Pyramidal cells have significantly longer AIS than interneurons. Interneurons with vertical columnar axonal projections have significantly more distal AIS locations than all other cells with their prevailing phenotype as an AcD cell. In contrast, neurons with perisomatic terminations display most often an axon originating from the soma. Our data contribute to the emerging understanding that AIS morphology is highly variable, and potentially a function of the cell type. PMID:29170630
Relationship between photoreceptor outer segment length and visual acuity in diabetic macular edema.
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.
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.
Automatic segmentation and reconstruction of the cortex from neonatal MRI.
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.
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
Zinc electrode and rechargeable zinc-air battery
Ross, Jr., Philip N.
1989-01-01
An improved zinc electrode is disclosed for a rechargeable zinc-air battery comprising an outer frame and a porous foam electrode support within the frame which is treated prior to the deposition of zinc thereon to inhibit the formation of zinc dendrites on the external surface thereof. The outer frame is provided with passageways for circulating an alkaline electrolyte through the treated zinc-coated porous foam. A novel rechargeable zinc-air battery system is also disclosed which utilizes the improved zinc electrode and further includes an alkaline electrolyte within said battery circulating through the passageways in the zinc electrode and an external electrolyte circulation means which has an electrolyte reservoir external to the battery case including filter means to filter solids out of the electrolyte as it circulates to the external reservoir and pump means for recirculating electrolyte from the external reservoir to the zinc electrode.
The phototransduction machinery in the rod outer segment has a strong efficacy gradient
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.
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.
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.
Impaired Dendritic Development and Memory in Sorbs2 Knock-Out Mice
Zhang, Qiangge; Gao, Xian; Li, Chenchen; Feliciano, Catia; Wang, Dongqing; Zhou, Dingxi; Mei, Yuan; Monteiro, Patricia; Anand, Michelle; Itohara, Shigeyoshi; Dong, Xiaowei; Fu, Zhanyan
2016-01-01
Intellectual disability is a common neurodevelopmental disorder characterized by impaired intellectual and adaptive functioning. Both environmental insults and genetic defects contribute to the etiology of intellectual disability. Copy number variations of SORBS2 have been linked to intellectual disability. However, the neurobiological function of SORBS2 in the brain is unknown. The SORBS2 gene encodes ArgBP2 (Arg/c-Abl kinase binding protein 2) protein in non-neuronal tissues and is alternatively spliced in the brain to encode nArgBP2 protein. We found nArgBP2 colocalized with F-actin at dendritic spines and growth cones in cultured hippocampal neurons. In the mouse brain, nArgBP2 was highly expressed in the cortex, amygdala, and hippocampus, and enriched in the outer one-third of the molecular layer in dentate gyrus. Genetic deletion of Sorbs2 in mice led to reduced dendritic complexity and decreased frequency of AMPAR-miniature spontaneous EPSCs in dentate gyrus granule cells. Behavioral characterization revealed that Sorbs2 deletion led to a reduced acoustic startle response, and defective long-term object recognition memory and contextual fear memory. Together, our findings demonstrate, for the first time, an important role for nArgBP2 in neuronal dendritic development and excitatory synaptic transmission, which may thus inform exploration of neurobiological basis of SORBS2 deficiency in intellectual disability. SIGNIFICANCE STATEMENT Copy number variations of the SORBS2 gene are linked to intellectual disability, but the neurobiological mechanisms are unknown. We found that nArgBP2, the only neuronal isoform encoded by SORBS2, colocalizes with F-actin at neuronal dendritic growth cones and spines. nArgBP2 is highly expressed in the cortex, amygdala, and dentate gyrus in the mouse brain. Genetic deletion of Sorbs2 in mice leads to impaired dendritic complexity and reduced excitatory synaptic transmission in dentate gyrus granule cells, accompanied by behavioral deficits in acoustic startle response and long-term memory. This is the first study of Sorbs2 function in the brain, and our findings may facilitate the study of neurobiological mechanisms underlying SORBS2 deficiency in the development of intellectual disability. PMID:26888934
Rhodopsin expression in the zebrafish pineal gland from larval to adult stage.
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.
Element for use in an inductive coupler for downhole components
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.
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.
Spectral domain optical coherence tomography findings in tamoxifen retinopathy--a case report.
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.
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
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
Biomorphic networks: approach to invariant feature extraction and segmentation for ATR
NASA Astrophysics Data System (ADS)
Baek, Andrew; Farhat, Nabil H.
1998-10-01
Invariant features in two dimensional binary images are extracted in a single layer network of locally coupled spiking (pulsating) model neurons with prescribed synapto-dendritic response. The feature vector for an image is represented as invariant structure in the aggregate histogram of interspike intervals obtained by computing time intervals between successive spikes produced from each neuron over a given period of time and combining such intervals from all neurons in the network into a histogram. Simulation results show that the feature vectors are more pattern-specific and invariant under translation, rotation, and change in scale or intensity than achieved in earlier work. We also describe an application of such networks to segmentation of line (edge-enhanced or silhouette) images. The biomorphic spiking network's capabilities in segmentation and invariant feature extraction may prove to be, when they are combined, valuable in Automated Target Recognition (ATR) and other automated object recognition systems.
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
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
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.
Neuillé, Marion; Morgans, Catherine W.; Cao, Yan; Orhan, Elise; Michiels, Christelle; Sahel, José-Alain; Audo, Isabelle; Duvoisin, Robert M.; Martemyanov, Kirill A.; Zeitz, Christina
2016-01-01
Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). The exact role of LRIT3 in ON-bipolar cell signaling cascade remains to be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3 (no b-wave 6, (Lrit3nob6/nob6)), which displays similar abnormalities as patients with cCSNB with LRIT3 mutations. Here we compare the localization of components of the ON-bipolar cell signaling cascade in wild-type and Lrit3nob6/nob6 retinal sections by immunofluorescence confocal microscopy. An anti-LRIT3 antibody was generated. Immunofluorescent staining of LRIT3 in wild-type mice revealed a specific punctate labeling in the outer plexiform layer (OPL), which was absent in Lrit3nob6/nob6 mice. LRIT3 did not colocalize with ribeye or calbindin but colocalized with mGluR6. TRPM1 staining was severely decreased at the dendritic tips of all depolarizing bipolar cells in Lrit3nob6/nob6 mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3nob6/nob6 mice, while it was present at the dendritic tips of rod bipolar cells. Furthermore, PNA labeling was severely reduced in the OPL in Lrit3nob6/nob6 mice. This study confirmed the localization of LRIT3 at the dendritic tips of depolarizing bipolar cells in mouse retina and demonstrated the dependence of TRPM1 localization on the presence of LRIT3. Since tested components of the ON-bipolar cell signaling cascade and PNA revealed disrupted localization, an additional function of LRIT3 in cone synapse formation is suggested. These results point to a possibly different regulation of the mGluR6 signaling cascade between rod and cone ON-bipolar cells. PMID:25997951
Side wall cooling for nozzle segments for a gas turbine
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.
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.
Poznanski, Roman R
2010-02-01
An assumption commonly used in cable theory is revised by taking into account electrical amplification due to intracellular capacitive effects in passive dendritic cables. A generalized cable equation for a cylindrical volume representation of a dendritic segment is derived from Maxwell's equations under assumptions: (i) the electric-field polarization is restricted longitudinally along the cable length; (ii) extracellular isopotentiality; (iii) quasielectrostatic conditions; and (iv) homogeneous medium with constant conductivity and permittivity. The generalized cable equation is identical to Barenblatt's equation arising in the theory of infiltration in fissured strata with a known analytical solution expressed in terms of a definite integral involving a modified Bessel function and the solution to a linear one-dimensional classical cable equation. Its solution is used to determine the impact of thermal noise on voltage attenuation with distance at any particular time. A regular perturbation expansion for the membrane potential about the linear one-dimensional classical cable equation solution is derived in terms of a Green's function in order to describe the dynamics of free charge within the Debye layer of endogenous structures in passive dendritic cables. The asymptotic value of the first perturbative term is explicitly evaluated for small values of time to predict how the slowly fluctuating (in submillisecond range) electric field attributed to intracellular capacitive effects alters the amplitude of the membrane potential. It was found that capacitive effects are almost negligible for cables with electrotonic lengths L>0.5 , contributes up to 10% of the signal for cables with electrotonic lengths in the range between 0.25
Debris-less method and apparatus for forming apertures in hollow metallic articles
Jordan, C.L.; Chodelka, E.J.
1980-06-24
This invention is a method for forming an aperture in a wall of a hollow metallic article without introducing metallic debris therein. In a typical operation, an annular groove is formed in an exterior portion of the wall. The groove defines an annular wall segment, and the bottom of the groove is shaped to slope downwardly away from the segment to form a tapered annular web which connects the segment to the wall. Any suitable coupling is attached to the outer face of the segment, as by welding. Pull then is applied to the coupling to effect circumferential breakage of the web, thus forming a removable single-piece wall fragment consisting of the web and segment. The fragment and the coupling member attached thereto then are removed from the wall.
Wang, Shijie; Huang, Weiwei; Li, Kui; Yao, Yufeng; Yang, Xu; Bai, Hongmei; Sun, Wenjia; Liu, Cunbao; Ma, Yanbing
2017-01-01
Currently, therapeutic tumor vaccines under development generally lack significant effects in human clinical trials. Exploring a powerful antigen delivery system is a potential approach to improve vaccine efficacy. We sought to explore engineered bacterial outer membrane vesicles (OMVs) as a new vaccine carrier for efficiently delivering tumor antigens and provoking robust antitumor immune responses. First, the tumoral antigen human papillomavirus type 16 early protein E7 (HPV16E7) was presented on Escherichia coli -derived OMVs by genetic engineering methods, acquiring the recombinant OMV vaccine. Second, the ability of recombinant OMVs delivering their components and the model antigen green fluorescent protein to antigen-presenting cells was investigated in the macrophage Raw264.7 cells and in bone marrow-derived dendritic cells in vitro. Third, it was evaluated in TC-1 graft tumor model in mice that the recombinant OMVs displaying HPV16E7 stimulated specific cellular immune response and intervened the growth of established tumor. E. coli DH5α-derived OMVs could be taken up rapidly by dendritic cells, for which vesicle structure has been proven to be important. OMVs significantly stimulated the expression of dendritic cellmaturation markers CD80, CD86, CD83 and CD40. The HPV16E7 was successfully embedded in engineered OMVs through gene recombinant techniques. Subcutaneous immunization with the engineered OMVs induced E7 antigen-specific cellular immune responses, as shown by the increased numbers of interferon-gamma-expressing splenocytes by enzyme-linked immunospot assay and interferon-gamma-expressing CD4 + and CD8 + cells by flow cytometry analyses. Furthermore, the growth of grafted TC-1 tumors in mice was significantly suppressed by therapeutic vaccination. The recombinant E7 proteins presented by OMVs were more potent than those mixed with wild-type OMVs or administered alone for inducing specific cellular immunity and suppressing tumor growth. The results indicated that the nano-grade OMVs might be a useful vaccine platform for antigen delivery in cancer immunotherapy.
Denoising and segmentation of retinal layers in optical coherence tomography images
NASA Astrophysics Data System (ADS)
Dash, Puspita; Sigappi, A. N.
2018-04-01
Optical Coherence Tomography (OCT) is an imaging technique used to localize the intra-retinal boundaries for the diagnostics of macular diseases. Due to speckle noise, low image contrast and accurate segmentation of individual retinal layers is difficult. Due to this, a method for retinal layer segmentation from OCT images is presented. This paper proposes a pre-processing filtering approach for denoising and segmentation methods for segmenting retinal layers OCT images using graph based segmentation technique. These techniques are used for segmentation of retinal layers for normal as well as patients with Diabetic Macular Edema. The algorithm based on gradient information and shortest path search is applied to optimize the edge selection. In this paper the four main layers of the retina are segmented namely Internal limiting membrane (ILM), Retinal pigment epithelium (RPE), Inner nuclear layer (INL) and Outer nuclear layer (ONL). The proposed method is applied on a database of OCT images of both ten normal and twenty DME affected patients and the results are found to be promising.
Gröbner, Sabine; Adkins, Irena; Schulz, Sebastian; Richter, Kathleen; Borgmann, Stefan; Wesselborg, Sebastian; Ruckdeschel, Klaus; Micheau, Olivier; Autenrieth, Ingo B
2007-10-01
Yersinia outer protein P (YopP) is injected by Y. enterocolitica into host cells thereby inducing apoptotic and necrosis-like cell death in dendritic cells (DC). Here we show the pathways involved in DC death caused by the catalytic activity of YopP. Infection with Yersinia enterocolitica, translocating catalytically active YopP into DC, triggered procaspase-8 cleavage and c-FLIPL degradation. YopP-dependent caspase-8 activation was, however, not mediated by tumor necrosis factor (TNF) receptor family members since the expression of both CD95/Fas/APO-1 and TRAIL-R2 on DC was low, and DC were resistant to apoptosis induced by agonistic anti-CD95 antibodies or TNF-related apoptosis-inducing ligand (TRAIL). Moreover, DC from TNF-Rp55-/- mice were not protected against YopP-induced cell death demonstrating that TNF-R1 is also not involved in this process. Activation of caspase-8 was further investigated by coimmunoprecitation of FADD from Yersinia-infected DC. We found that both cleaved caspase-8 and receptor interacting protein 1 (RIP1) were associated with the Fas-associated death domain (FADD) indicating the formation of an atypical death-inducing signaling complex (DISC). Furthermore, degradation of RIP mediated by the Hsp90 inhibitor geldanamycin significantly impaired YopP-induced cell death. Altogether our findings indicate that Yersinia-induced DC death is independent of death domain containing receptors, but mediated by RIP and caspase-8 at the level of DISC.
Somatic and neuritic spines on tyrosine hydroxylase–immunopositive cells of rat retina
Fasoli, Anna; Dang, James; Johnson, Jeffrey S.; Gouw, Aaron H.; Iseppe, Alex Fogli; Ishida, Andrew T.
2018-01-01
Dopamine- and tyrosine hydroxylase–immunopositive cells (TH cells) modulate visually driven signals as they flow through retinal photoreceptor, bipolar, and ganglion cells. Previous studies suggested that TH cells release dopamine from varicose axons arborizing in the inner and outer plexiform layers after glutamatergic synapses depolarize TH cell dendrites in the inner plexiform layer and these depolarizations propagate to the varicosities. Although it has been proposed that these excitatory synapses are formed onto appendages resembling dendritic spines, spines have not been found on TH cells of most species examined to date or on TH cell somata that release dopamine when exposed to glutamate receptor agonists. By use of protocols that preserve proximal retinal neuron morphology, we have examined the shape, distribution, and synapse-related immunoreactivity of adult rat TH cells. We report here that TH cell somata, tapering and varicose inner plexiform layer neurites, and varicose outer plexiform layer neurites all bear spines, that some of these spines are immunopositive for glutamate receptor and postsynaptic density proteins (viz., GluR1, GluR4, NR1, PSD-95, and PSD-93), that TH cell somata and tapering neurites are also immunopositive for a γ-aminobutyric acid (GABA) receptor subunit (GABAARα1), and that a synaptic ribbon-specific protein (RIBEYE) is found adjacent to some colocalizations of GluR1 and TH in the inner plexiform layer. These results identify previously undescribed sites at which glutamatergic and GABAergic inputs may stimulate and inhibit dopamine release, especially at somata and along varicose neurites that emerge from these somata and arborize in various levels of the retina. PMID:28035673
Ona-Jodar, Tiffany; Gerkau, Niklas J; Sara Aghvami, S; Rose, Christine R; Egger, Veronica
2017-01-01
Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca 2+ imaging. Here, we used two-photon Na + imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types. To this end, neurons in acute slices from juvenile rat bulbs were filled with 1 mM SBFI via whole-cell patch-clamp. Calibration of SBFI signals revealed that a change in fluorescence Δ F / F by 10% corresponded to a Δ[Na + ] i of ∼22 mM. We then imaged proximal axon segments of MCs during somatically evoked APs (sAP). While single sAPs were detectable in ∼50% of axons, trains of 20 sAPs at 50 Hz always resulted in substantial Δ F / F of ∼15% (∼33 mM Δ[Na + ] i ). Δ F / F was significantly larger for 80 Hz vs. 50 Hz trains, and decayed with half-durations τ 1/2 ∼0.6 s for both frequencies. In MC lateral dendrites, AP trains yielded small Δ F / F of ∼3% (∼7 mM Δ[Na + ] i ). In GC apical dendrites and adjacent spines, single sAPs were not detectable. Trains resulted in an average dendritic Δ F / F of 7% (16 mM Δ[Na + ] i ) with τ 1/2 ∼1 s, similar for 50 and 80 Hz. Na + transients were indistinguishable between large GC spines and their adjacent dendrites. Cell-wise analysis revealed two classes of GCs with the first showing a decrease in Δ F / F along the dendrite with distance from the soma and the second an increase. These classes clustered with morphological parameters. Simulations of Δ[Na + ] i replicated these behaviors via negative and positive gradients in Na + current density, assuming faithful AP backpropagation. Such specializations of dendritic excitability might confer specific temporal processing capabilities to bulbar principal cell-GC subnetworks. In conclusion, we show that Na + imaging provides a valuable tool for characterizing AP invasion of MC axons and GC dendrites and spines.
Ona-Jodar, Tiffany; Gerkau, Niklas J.; Sara Aghvami, S.; Rose, Christine R.; Egger, Veronica
2017-01-01
Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca2+ imaging. Here, we used two-photon Na+ imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types. To this end, neurons in acute slices from juvenile rat bulbs were filled with 1 mM SBFI via whole-cell patch-clamp. Calibration of SBFI signals revealed that a change in fluorescence ΔF/F by 10% corresponded to a Δ[Na+]i of ∼22 mM. We then imaged proximal axon segments of MCs during somatically evoked APs (sAP). While single sAPs were detectable in ∼50% of axons, trains of 20 sAPs at 50 Hz always resulted in substantial ΔF/F of ∼15% (∼33 mM Δ[Na+]i). ΔF/F was significantly larger for 80 Hz vs. 50 Hz trains, and decayed with half-durations τ1/2 ∼0.6 s for both frequencies. In MC lateral dendrites, AP trains yielded small ΔF/F of ∼3% (∼7 mM Δ[Na+]i). In GC apical dendrites and adjacent spines, single sAPs were not detectable. Trains resulted in an average dendritic ΔF/F of 7% (16 mM Δ[Na+]i) with τ1/2 ∼1 s, similar for 50 and 80 Hz. Na+ transients were indistinguishable between large GC spines and their adjacent dendrites. Cell-wise analysis revealed two classes of GCs with the first showing a decrease in ΔF/F along the dendrite with distance from the soma and the second an increase. These classes clustered with morphological parameters. Simulations of Δ[Na+]i replicated these behaviors via negative and positive gradients in Na+ current density, assuming faithful AP backpropagation. Such specializations of dendritic excitability might confer specific temporal processing capabilities to bulbar principal cell-GC subnetworks. In conclusion, we show that Na+ imaging provides a valuable tool for characterizing AP invasion of MC axons and GC dendrites and spines. PMID:28293175
Rhee, Taek Kwan; Han, Jung Il
2014-02-01
Dengue fever is a viral disease that is transmitted by mosquitoes and affects humans. In rare cases, dengue fever can cause visual impairment, which usually occurs within 1 month after contracting dengue fever and ranges from mild blurring of vision to severe blindness. Visual impairment due to dengue fever can be detected through angiography, retinography, optical coherence tomography (OCT) imaging, electroretinography, event electroencephalography (visually evoked potentials), and visual field analysis. The purpose of this study is to report changes in the eye captured using fluorescein angiography, indocyanine green, and OCT in 3 cases of dengue fever visual impairment associated with consistent visual symptoms and similar retinochoroidopathic changes. The OCT results of the three patients with dengue fever showed thinning of the outer retinal layer and disruption of the inner segment/outer segment (IS/OS) junction. While thinning of the retina outer layer is an irreversible process, disruption of IS/OS junction is reported to be reversible. Follow-up examination of individuals with dengue fever and associated visual impairment should involve the use of OCT to evaluate visual acuity and visual field changes in patients with acute choroidal ischemia.
Chen, Ding; Xu, Tao; Tu, Mengjun; Xu, Jinlin; Zhou, Chenchen; Cheng, Lulu; Yang, Ruqing; Yang, Tanchu; Zheng, Weiwei; He, Xiubin; Deng, Ruzhi; Ge, Xianglian; Li, Jin; Song, Zongming; Zhao, Junzhao; Gu, Feng
2017-01-01
X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation ( RS1 , p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1 -KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1 -KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice ( RS1 -KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.
Shaffer, James E.; Norton, Paul F.
1996-01-01
A turbine nozzle and shroud assembly having a preestablished rate of thermal expansion is positioned in a gas turbine engine and being attached to conventional metallic components. The metallic components having a preestablished rate of thermal expansion being greater than the preestablished rate of thermal expansion of the turbine nozzle vane assembly. The turbine nozzle vane assembly includes a plurality of segmented vane defining a first vane segment and a second vane segment. Each of the first and second vane segments having a vertical portion. Each of the first vane segments and the second vane segments being positioned in functional relationship one to another within a recess formed within an outer shroud and an inner shroud. The turbine nozzle and shroud assembly provides an economical, reliable and effective ceramic component having a preestablished rate of thermal expansion being less than the preestablished rate of thermal expansion of the other component.
Shaffer, J.E.; Norton, P.F.
1996-12-17
A turbine nozzle and shroud assembly having a preestablished rate of thermal expansion is positioned in a gas turbine engine and being attached to conventional metallic components. The metallic components have a preestablished rate of thermal expansion greater than the preestablished rate of thermal expansion of the turbine nozzle vane assembly. The turbine nozzle vane assembly includes a plurality of segmented vane defining a first vane segment and a second vane segment, each of the first and second vane segments having a vertical portion, and each of the first vane segments and the second vane segments being positioned in functional relationship one to another within a recess formed within an outer shroud and an inner shroud. The turbine nozzle and shroud assembly provides an economical, reliable and effective ceramic component having a preestablished rate of thermal expansion being less than the preestablished rate of thermal expansion of the other component. 4 figs.
Spine Patterning Is Guided by Segmentation of the Notochord Sheath.
Wopat, Susan; Bagwell, Jennifer; Sumigray, Kaelyn D; Dickson, Amy L; Huitema, Leonie F A; Poss, Kenneth D; Schulte-Merker, Stefan; Bagnat, Michel
2018-02-20
The spine is a segmented axial structure made of alternating vertebral bodies (centra) and intervertebral discs (IVDs) assembled around the notochord. Here, we show that, prior to centra formation, the outer epithelial cell layer of the zebrafish notochord, the sheath, segments into alternating domains corresponding to the prospective centra and IVD areas. This process occurs sequentially in an anteroposterior direction via the activation of Notch signaling in alternating segments of the sheath, which transition from cartilaginous to mineralizing domains. Subsequently, osteoblasts are recruited to the mineralized domains of the notochord sheath to form mature centra. Tissue-specific manipulation of Notch signaling in sheath cells produces notochord segmentation defects that are mirrored in the spine. Together, our findings demonstrate that notochord sheath segmentation provides a template for vertebral patterning in the zebrafish spine. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
Foveal damage in habitual poppers users.
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.
Method of controlling the side wall thickness of a turbine nozzle segment for improved cooling
Burdgick, Steven Sebastian
2002-01-01
A gas turbine nozzle segment has outer and inner bands and a vane extending therebetween. Each band has a side wall, a cover and an impingement plate between the cover and nozzle wall defining two cavities on opposite sides of the impingement plate. Cooling steam is supplied to one cavity for flow through apertures of the impingement plate to cool the nozzle wall. The side wall of the band has an inturned flange defining with the nozzle wall an undercut region. The outer surface of the side wall is provided with a step prior to welding the cover to the side wall. A thermal barrier coating is applied in the step and, after the cover is welded to the side wall, the side wall is finally machined to a controlled thickness removing all, some or none of the coating.
Köhler, Silvia Domingo; Weber, Annemarie; Howard, S Peter; Welte, Wolfram; Drescher, Malte
2010-01-01
TonB from Escherichia coli and its homologues are critical for the uptake of siderophores through the outer membrane of Gram-negative bacteria using chemiosmotic energy. When different models for the mechanism of TonB mediated energy transfer from the inner to the outer membrane are discussed, one of the key questions is whether TonB spans the periplasm. In this article, we use long range distance measurements by spin-label pulsed EPR (Double Electron–Electron Resonance, DEER) and CD spectroscopy to show that the proline-rich segment of TonB exists in a PPII-like conformation. The result implies that the proline-rich segment of TonB possesses a length of more than 15 nm, sufficient to span the periplasm of Gram-negative bacteria. PMID:20095050
NASA Astrophysics Data System (ADS)
Muhd Suberi, Anis Azwani; Wan Zakaria, Wan Nurshazwani; Tomari, Razali; Lau, Mei Xia
2016-07-01
Identification of Dendritic Cell (DC) particularly in the cancer microenvironment is a unique disclosure since fighting tumor from the harnessing immune system has been a novel treatment under investigation. Nowadays, the staining procedure in sorting DC can affect their viability. In this paper, a computer aided system is proposed for automatic classification of DC in peripheral blood mononuclear cell (PBMC) images. Initially, the images undergo a few steps in preprocessing to remove uneven illumination and artifacts around the cells. In segmentation, morphological operators and Canny edge are implemented to isolate the cell shapes and extract the contours. Following that, information from the contours are extracted based on Fourier descriptors, derived from one dimensional (1D) shape signatures. Eventually, cells are classified as DC by comparing template matching (TM) of established template and target images. The results show that the proposed scheme is reliable and effective to recognize DC.
Holographic photolysis of caged neurotransmitters
Lutz, Christoph; Otis, Thomas S.; DeSars, Vincent; Charpak, Serge; DiGregorio, David A.; Emiliani, Valentina
2009-01-01
Stimulation of light-sensitive chemical probes has become a powerful tool for the study of dynamic signaling processes in living tissue. Classically, this approach has been constrained by limitations of lens–based and point-scanning illumination systems. Here we describe a novel microscope configuration that incorporates a nematic liquid crystal spatial light modulator (LC-SLM) to generate holographic patterns of illumination. This microscope can produce illumination spots of variable size and number and patterns shaped to precisely match user-defined elements in a specimen. Using holographic illumination to photolyse caged glutamate in brain slices, we demonstrate that shaped excitation on segments of neuronal dendrites and simultaneous, multi-spot excitation of different dendrites enables precise spatial and rapid temporal control of glutamate receptor activation. By allowing the excitation volume shape to be tailored precisely, the holographic microscope provides an extremely flexible method for activation of various photosensitive proteins and small molecules. PMID:19160517
2008-11-06
CAPE CANAVERAL, Fla. – Inside the Vehicle Assembly Building high bay 4 at NASA's Kennedy Space Center in Florida, these Ares I-X upper stage simulator segments have shed their protective blue shrink-wrapped covers used for shipping. The upper stage simulator will be used in the test flight identified as Ares I-X in 2009. The segments will simulate the mass and the outer mold line and will be more than 100 feet of the total vehicle height of 327 feet. The simulator comprises 11 segments that are approximately 18 feet in diameter. Most of the segments will be approximately 10 feet high, ranging in weight from 18,000 to 60,000 pounds, for a total of approximately 450,000 pounds. Photo credit: NASA/Troy Cryder
2008-11-06
CAPE CANAVERAL, Fla. – Inside the Vehicle Assembly Building high bay 4 at NASA's Kennedy Space Center in Florida, these Ares I-X upper stage simulator segments have shed their protective blue shrink-wrapped covers used for shipping. The upper stage simulator will be used in the test flight identified as Ares I-X in 2009. The segments will simulate the mass and the outer mold line and will be more than 100 feet of the total vehicle height of 327 feet. The simulator comprises 11 segments that are approximately 18 feet in diameter. Most of the segments will be approximately 10 feet high, ranging in weight from 18,000 to 60,000 pounds, for a total of approximately 450,000 pounds. Photo credit: NASA/Troy Cryder
2008-11-06
CAPE CANAVERAL, Fla. – Inside the Vehicle Assembly Building high bay 4 at NASA's Kennedy Space Center in Florida, these Ares I-X upper stage simulator segments have shed their protective blue shrink-wrapped covers used for shipping. The upper stage simulator will be used in the test flight identified as Ares I-X in 2009. The segments will simulate the mass and the outer mold line and will be more than 100 feet of the total vehicle height of 327 feet. The simulator comprises 11 segments that are approximately 18 feet in diameter. Most of the segments will be approximately 10 feet high, ranging in weight from 18,000 to 60,000 pounds, for a total of approximately 450,000 pounds. Photo credit: NASA/Troy Cryder
Burkholder, Bryn M; Leung, Theresa G; Ostheimer, Trucian A; Butler, Nicholas J; Thorne, Jennifer E; Dunn, James P
2014-01-27
We describe the spectral domain optical coherence tomography (SD-OCT) findings in three patients with acute syphilitic posterior placoid chorioretinitis (ASPPC). The SD-OCT images demonstrate the pathologic changes in ASPPC with a high level of anatomic detail and may provide information about the pathophysiology of the disease. We report a series of three consecutive patients seen at the Wilmer Eye Institute in 2012 and 2013 who presented with clinical and laboratory findings consistent with a diagnosis of unilateral ASPPC. Two of the three patients had HIV co-infection with good immune recovery. SD-OCT images from their initial (pre-treatment) presentation demonstrated thickening and hyperreflective nodularity of the choroid-retinal pigment epithelium (RPE) complex, with focal disruption of the overlying photoreceptor inner segment-outer segment junction in the areas corresponding to the retinal lesions seen on clinical examination. These changes improved with intravenous antibiotic treatment over a 3-month period of follow-up. SD-OCT imaging in ASPPC demonstrates reversible, focal thickening, and nodularity of the RPE with disruption of the overlying photoreceptor inner segment-outer segment junction. We believe that these SD-OCT images support the concept that ASPPC involves an inflammatory process at the level of the choroid-RPE with resultant structural and functional changes in the retinal photoreceptors. Further study with OCT imaging may be helpful in better understanding this disease.
Kang, Eui Chun; Seo, Yuri; Byeon, Suk Ho
2016-10-01
To describe the characteristics of an unfamiliar disease entity, diabetic retinal pigment epitheliopathy (DRPE), using fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT). This retrospective study included 17 eyes from 10 proliferative diabetic retinopathy (PDR) patients with granular hypo-autofluorescence and/or variable hyper-autofluorescence on FAF (DRPE group) and 17 eyes from 10 age- and sex-matched PDR patients without abnormal autofluorescence (PDR group). Eyes with diabetic macular edema were excluded. Visual acuity (VA), retinal thickness (RT), and choroidal thickness (CT) were compared between the groups. Eyes in the DRPE group had worse logMAR VA than eyes in the PDR group (0.369 ± 0.266 vs. 0.185 ± 0.119; P = 0.026). The thickness of the retinal pigment epithelium plus the inner segment/outer segment of the photoreceptors was reduced to a greater degree in the DRPE group than the PDR group (P < 0.001). Moreover, the thickness of the outer nuclear layer plus the outer plexiform layer was thinner in the DRPE group than in the PDR (P = 0.013). However, the thickness of the inner retina showed no differences between the two groups. CT was significantly thicker in the DRPE group than in the PDR group (329.00 ± 33.76 vs. 225.62 ± 37.47 μm; P < 0.001). Eyes with DRPE showed reduced VA, a thinner outer retina, and thicker choroid in comparison with eyes with PDR. Alterations of autofluorescence on FAF and changes in the outer retinal thickness and CT on SD-OCT can be helpful for differentiating DRPE in patients with PDR.
Berkowitz, Bruce A; Gorgis, Jawan; Patel, Ankit; Baameur, Faiza; Gurevich, Vsevolod V; Craft, Cheryl M; Kefalov, Vladimir J; Roberts, Robin
2015-02-01
Rod tetrameric arrestin 1 (tet-ARR1), stored in the outer nuclear layer/inner segments in the dark, modulates photoreceptor synaptic activity; light exposure stimulates a reduction via translocation to the outer segments for terminating G-protein coupled phototransduction signaling. Here, we test the hypothesis that intraretinal spin-lattice relaxation rate in the rotating frame (1/T1ρ), an endogenous MRI contrast mechanism, has high potential for evaluating rod tet-ARR1 and its reduction via translocation. Dark- and light-exposed mice (null for the ARR1 gene, overexpressing ARR1, diabetic, or wild type with or without treatment with Mn2+, a calcium channel probe) were studied using 1/T1ρ MRI. Immunohistochemistry and single-cell recordings of the retinas were also performed. In wild-type mice with or without treatment with Mn2+, 1/T1ρ of avascular outer retina (64% to 72% depth) was significantly (P < 0.05) greater in the dark than in the light; a significant (P < 0.05) but opposite pattern was noted in the inner retina (<50% depth). Light-evoked outer retina Δ1/T1ρ was absent in ARR1-null mice and supernormal in overexpressing mice. In diabetic mice, the outer retinal Δ1/T1ρ pattern suggested normal dark-to-light tet-ARR1 translocation and chromophore content, conclusions confirmed ex vivo. Light-stimulated Δ1/T1ρ in inner retina was linked to changes in blood volume. Our data support 1/T1ρ MRI for noninvasively assessing rod tet-ARR1 and its reduction via protein translocation, which can be combined with other metrics of retinal function in vivo. © FASEB.
2008-11-06
CAPE CANAVERAL, Fla. – Inside the Vehicle Assembly Building high bay 4 at NASA's Kennedy Space Center in Florida, Ares I-X upper stage simulator segments are lined up. Their protective blue shrink-wrapped covers used for shipping are being removed, as seen on the segments at left and in the back. The upper stage simulator will be used in the test flight identified as Ares I-X in 2009. The segments will simulate the mass and the outer mold line and will be more than 100 feet of the total vehicle height of 327 feet. The simulator comprises 11 segments that are approximately 18 feet in diameter. Most of the segments will be approximately 10 feet high, ranging in weight from 18,000 to 60,000 pounds, for a total of approximately 450,000 pounds. Photo credit: NASA/Troy Cryder
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.
Rod Photopigment Kinetics After Photodisruption of the Retinal Pigment Epithelium
Masella, Benjamin D.; Hunter, Jennifer J.; Williams, David R.
2014-01-01
Purpose. Advances in retinal imaging have led to the discovery of long-lasting retinal changes caused by light exposures below published safety limits, including disruption of the RPE. To investigate the functional consequences of RPE disruption, we combined adaptive optics ophthalmoscopy with retinal densitometry. Methods. A modified adaptive optics scanning light ophthalmoscope (AOSLO) measured the apparent density and regeneration rate of rhodopsin in two macaques before and after four different 568-nm retinal radiant exposures (RREs; 400–3200 J/cm2). Optical coherence tomography (OCT) was used to measure the optical path length through the photoreceptor outer segments before and after RPE disruption. Results. All tested RREs caused visible RPE disruption. Apparent rhodopsin density was significantly reduced following 1600 (P = 0.01) and 3200 J/cm2 (P = 0.007) exposures. No significant change in apparent density was observed in response to 800 J/cm2. Surprisingly, exposure to 400 J/cm2 showed a significant increase in apparent density (P = 0.047). Rhodopsin recovery rate was not significantly affected by these RREs. Optical coherence tomography measurements showed a significant decrease in the optical path length through the photoreceptor outer segments for RREs above 800 J/cm2 (P < 0.001). Conclusions. At higher RREs, optical path length through the outer segments was reduced. However, the rate of photopigment regeneration was unchanged. While some ambiguity remains as to the correlation between measured reflectivity and absolute rhodopsin density; at the lowest RREs, RPE disruption appears not to be accompanied by a loss of apparent rhodopsin density, which would have been indicative of functional loss. PMID:25316724
Chew, Avenell L.; Lamey, Tina; McLaren, Terri; De Roach, John
2016-01-01
Purpose To present en face optical coherence tomography (OCT) images generated by graph-search theory algorithm-based custom software and examine correlation with other imaging modalities. Methods En face OCT images derived from high density OCT volumetric scans of 3 healthy subjects and 4 patients using a custom algorithm (graph-search theory) and commercial software (Heidelberg Eye Explorer software (Heidelberg Engineering)) were compared and correlated with near infrared reflectance, fundus autofluorescence, adaptive optics flood-illumination ophthalmoscopy (AO-FIO) and microperimetry. Results Commercial software was unable to generate accurate en face OCT images in eyes with retinal pigment epithelium (RPE) pathology due to segmentation error at the level of Bruch’s membrane (BM). Accurate segmentation of the basal RPE and BM was achieved using custom software. The en face OCT images from eyes with isolated interdigitation or ellipsoid zone pathology were of similar quality between custom software and Heidelberg Eye Explorer software in the absence of any other significant outer retinal pathology. En face OCT images demonstrated angioid streaks, lesions of acute macular neuroretinopathy, hydroxychloroquine toxicity and Bietti crystalline deposits that correlated with other imaging modalities. Conclusions Graph-search theory algorithm helps to overcome the limitations of outer retinal segmentation inaccuracies in commercial software. En face OCT images can provide detailed topography of the reflectivity within a specific layer of the retina which correlates with other forms of fundus imaging. Our results highlight the need for standardization of image reflectivity to facilitate quantification of en face OCT images and longitudinal analysis. PMID:27959968
Hossain, Waheeda A; Antic, Srdjan D; Yang, Yang; Rasband, Matthew N; Morest, D Kent
2005-07-20
The origin of the action potential in the cochlea has been a long-standing puzzle. Because voltage-dependent Na+ (Nav) channels are essential for action potential generation, we investigated the detailed distribution of Nav1.6 and Nav1.2 in the cochlear ganglion, cochlear nerve, and organ of Corti, including the type I and type II ganglion cells. In most type I ganglion cells, Nav1.6 was present at the first nodes flanking the myelinated bipolar cell body and at subsequent nodes of Ranvier. In the other ganglion cells, including type II, Nav1.6 clustered in the initial segments of both of the axons that flank the unmyelinated bipolar ganglion cell bodies. In the organ of Corti, Nav1.6 was localized in the short segments of the afferent axons and their sensory endings beneath each inner hair cell. Surprisingly, the outer spiral fibers and their sensory endings were well labeled beneath the outer hair cells over their entire trajectory. In contrast, Nav1.2 in the organ of Corti was localized to the unmyelinated efferent axons and their endings on the inner and outer hair cells. We present a computational model illustrating the potential role of the Nav channel distribution described here. In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion. Together, these results suggest that distinct Nav channels generate and regenerate action potentials at multiple sites along the cochlear ganglion cells and nerve fibers, including the afferent endings, ganglionic initial segments, and nodes of Ranvier.
Saleh, Mohamed G A; Campbell, John Peter; Yang, Paul; Lin, Phoebe
2017-03-01
To determine the ultra-wide-field fundus autofluorescence (UWFFAF) and optical coherence tomography (OCT) features of syphilitic outer retinopathy (SOR). Retrospective chart review. Three patients with SOR were investigated. Treatment with parenteral penicillin led to improvement of outer retinopathy, visual acuity, and symptoms. UWFFAF showed speckled hyperautofluorescence, hypoautofluorescence, and normal autofluorescence, similar to what has been described as a trizonal pattern in acute zonal occult outer retinopathy (AZOOR) in the chronic case of SOR, but with hyperautofluorescent areas in the two acute cases. OCT showed disruption of the photoreceptor outer segment ellipsoid zone and external limiting membrane, which improved after penicillin treatment, and corresponded to normalization of the hyperautofluorescent areas on UWFFAF. There was irregularity and nodular thickening of retinal pigment epithelium on OCT in areas of mottled hyperautofluorescence. SOR can present similarly to AZOOR on UWFFAF and should be highly suspected in cases presenting like AZOOR. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:208-215. ]. Copyright 2017, SLACK Incorporated.
Film cooling air pocket in a closed loop cooled airfoil
Yu, Yufeng Phillip; Itzel, Gary Michael; Osgood, Sarah Jane; Bagepalli, Radhakrishna; Webbon, Waylon Willard; Burdgick, Steven Sebastian
2002-01-01
Turbine stator vane segments have radially inner and outer walls with vanes extending between them. The inner and outer walls are compartmentalized and have impingement plates. Steam flowing into the outer wall plenum passes through the impingement plate for impingement cooling of the outer wall upper surface. The spent impingement steam flows into cavities of the vane having inserts for impingement cooling the walls of the vane. The steam passes into the inner wall and through the impingement plate for impingement cooling of the inner wall surface and for return through return cavities having inserts for impingement cooling of the vane surfaces. To provide for air film cooing of select portions of the airfoil outer surface, at least one air pocket is defined on a wall of at least one of the cavities. Each air pocket is substantially closed with respect to the cooling medium in the cavity and cooling air pumped to the air pocket flows through outlet apertures in the wall of the airfoil to cool the same.
Coronagraphic Wavefront Control for the ATLAST-9.2m Telescope
NASA Technical Reports Server (NTRS)
Lyon, RIchard G.; Oegerle, William R.; Feinberg, Lee D.; Bolcar, Matthew R.; Dean, Bruce H.; Mosier, Gary E.; Postman, Marc
2010-01-01
The Advanced Technology for Large Aperture Space Telescope (ATLAST) concept was assessed as one of the NASA Astrophysics Strategic Mission Concepts (ASMC) studies. Herein we discuss the 9.2-meter diameter segmented aperture version and its wavefront sensing and control (WFSC) with regards to coronagraphic detection and spectroscopic characterization of exoplanets. The WFSC would consist of at least two levels of sensing and control: (i) an outer coarser level of sensing and control to phase and control the segments and secondary mirror in a manner similar to the James Webb Space Telescope but operating at higher temporal bandwidth, and (ii) an inner, coronagraphic instrument based, fine level of sensing and control for both amplitude and wavefront errors operating at higher temporal bandwidths. The outer loop would control rigid-body actuators on the primary and secondary mirrors while the inner loop would control one or more segmented deformable mirror to suppress the starlight within the coronagraphic field-of view. Herein we discuss the visible nulling coronagraph (VNC) and the requirements it levies on wavefront sensing and control and show the results of closed-loop simulations to assess performance and evaluate the trade space of system level stability versus control bandwidth.
The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis.
Baylor, D A; Nunn, B J; Schnapf, J L
1984-01-01
Visual transduction in rods of the cynomolgus monkey, Macaca fascicularis, was studied by recording membrane current from single outer segments projecting from small pieces of retina. Light flashes evoked transient outward-going photocurrents with saturating amplitudes of up to 34 pA. A flash causing twenty to fifty photoisomerizations gave a response of half the saturating amplitude. The response-stimulus relation was of the form 1-e-x where x is flash strength. The response to a dim flash usually had a time to peak of 150-250 ms and resembled the impulse response of a series of six low-pass filters. From the average spectral sensitivity of ten rods the rhodopsin was estimated to have a peak absorption near 491 nm. The spectral sensitivity of the rods was in good agreement with the average human scotopic visibility curve determined by Crawford (1949), when the human curve was corrected for lens absorption and self-screening of rhodopsin. Fluctuations in the photocurrent evoked by dim lights were consistent with a quantal event about 0.7 pA in peak amplitude. A steady light causing about 100 photoisomerizations s-1 reduced the flash sensitivity to half the dark-adapted value. At higher background levels the rod rapidly saturated. These results support the idea that dim background light desensitizes human scotopic vision by a mechanism central to the rod outer segments while scotopic saturation may occur within the outer segments. Recovery of the photocurrent after bright flashes was marked by quantized step-like events. The events had the properties expected if bleached rhodopsin in the disks occasionally caused an abrupt blockage of the dark current over about one-twentieth of the length of the outer segment. It is suggested that superposition of these events after bleaching may contribute to the threshold elevation measured psychophysically. The current in darkness showed random fluctuations which disappeared in bright light. The continuous component of the noise had a variance of about 0.03 pA2 and a power spectrum that fell to half near 3 Hz. A second component, consisting of discrete events resembling single-photon responses, was estimated to occur at a rate of 0.006 s-1. It is suggested that the continuous component of the noise may be removed from scotopic vision by a thresholding operation near the rod output. PMID:6512705
The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis.
Baylor, D A; Nunn, B J; Schnapf, J L
1984-12-01
Visual transduction in rods of the cynomolgus monkey, Macaca fascicularis, was studied by recording membrane current from single outer segments projecting from small pieces of retina. Light flashes evoked transient outward-going photocurrents with saturating amplitudes of up to 34 pA. A flash causing twenty to fifty photoisomerizations gave a response of half the saturating amplitude. The response-stimulus relation was of the form 1-e-x where x is flash strength. The response to a dim flash usually had a time to peak of 150-250 ms and resembled the impulse response of a series of six low-pass filters. From the average spectral sensitivity of ten rods the rhodopsin was estimated to have a peak absorption near 491 nm. The spectral sensitivity of the rods was in good agreement with the average human scotopic visibility curve determined by Crawford (1949), when the human curve was corrected for lens absorption and self-screening of rhodopsin. Fluctuations in the photocurrent evoked by dim lights were consistent with a quantal event about 0.7 pA in peak amplitude. A steady light causing about 100 photoisomerizations s-1 reduced the flash sensitivity to half the dark-adapted value. At higher background levels the rod rapidly saturated. These results support the idea that dim background light desensitizes human scotopic vision by a mechanism central to the rod outer segments while scotopic saturation may occur within the outer segments. Recovery of the photocurrent after bright flashes was marked by quantized step-like events. The events had the properties expected if bleached rhodopsin in the disks occasionally caused an abrupt blockage of the dark current over about one-twentieth of the length of the outer segment. It is suggested that superposition of these events after bleaching may contribute to the threshold elevation measured psychophysically. The current in darkness showed random fluctuations which disappeared in bright light. The continuous component of the noise had a variance of about 0.03 pA2 and a power spectrum that fell to half near 3 Hz. A second component, consisting of discrete events resembling single-photon responses, was estimated to occur at a rate of 0.006 s-1. It is suggested that the continuous component of the noise may be removed from scotopic vision by a thresholding operation near the rod output.
Cobbs, W H; Pugh, E N
1987-01-01
1. Membrane currents initiated by intense, 20 microseconds flashes (photocurrents) were recorded from isolated salamander rods by combined extracellular suction electrodes and intracellular tight-seal electrodes either in current or voltage clamp mode. The magnitudes (mean +/- 2 S.E.M.) of the maximal photoresponses recorded by the suction and by the intracellular electrode respectively were 40 +/- 5 pA (n = 18) and 35 +/- 7 mV (n = 8) for current clamp at zero current; 43 +/- 9 pA and 66 +/- 13 (n = 11) pA for voltage clamp at the zero-current holding potential, -24 +/- 3 mV. 2. Photocurrents initiated by flashes isomerizing 0.1% or more of the outer segment's rhodopsin achieved a saturated velocity and were 95% complete in less than 50 ms. The effect of incrementing flash intensity above 0.1% isomerization can be described as a translation of the photocurrent along the time axis towards the origin. Within the interval 0-50 ms the latter two-thirds of the velocity-saturated photocurrent is well described as a single-exponential decay. The decay was much faster in voltage clamp (2.8 +/- 1.2 ms, n = 11) than in current clamp mode (17 +/- 5 ms, n = 17). 3. The initial third of the velocity-saturated photocurrent, occurring over the interval from the flash to the onset of exponential decay, followed about the same time course in current and voltage clamp. The time interval occupied by this initial 'latent' phase decreased with increasing flash intensity and attained an apparent minimum of about 7 ms in response to flashes isomerizing 10% or more of the rhodopsin at ca. 22 degrees C. 4. The hypothesis that the decay of outer segment light-sensitive membrane current is the same in current and voltage clamp was supported by an analysis of the difference between outer segment currents measured successively in the two recording modes. First, the tail of the difference current decayed exponentially with a time constant approximately equal to R x C, where R and C are independently estimated slope resistance and capacitance of the rod. Secondly, the integral of the difference current, when divided by outer segment capacitance, closely approximated the hyperpolarizing light response measured under current clamp. Thus, displacement current accounted for the difference between photocurrents measured in current and voltage clamp.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2832596
Fine structure of the retinal photoreceptors of the great horned owl (Bubo virginianus).
Braekevelt, C R
1993-01-01
The retinal photoreceptors of the great horned owl (Bubo virginianus) consist of rods, single cones and unequal double cones present in a ratio of about 30:1.2. In the light-adapted state the rods are stout cells which are not felt to undergo retinomotor movements. The rod outer segment consists of a stack of scalloped membranous discs enclosed by the cell membrane. The rod inner segment shows an ellipsoid of mitochondria and a wealth of rough endoplasmic reticulum (RER) and polysomes, Golgi zones and autophagic vacuoles but not hyperboloid of glycogen. Single cones show a slightly tapered outer segment, a heterogenous oil droplet and an ellipsoid of mitochondria at the apex of the inner segment. Double cones consist of a larger chief member which also displays an oil droplet and a slightly smaller accessory member which does not. Both members of the double cone as well as the single cone show a prominent ellipsoid, plentiful polysomes and RER and Golgi zones in the inner segment. Neither single nor double cones possess a condensed paraboloid of glycogen but instead show plentiful scattered glycogen particles. Along the contiguous membranes between accessory and chief cones a few presumed junctional complexes are seen near the external limiting membrane. Judging by their morphology in light-adaptation the cones of this species do not undergo photomechanical movements. Rods and cones (both types) have both invaginated (ribbon) and numerous superficial (conventional) synaptic sites. Rods are more numerous in this nocturnally active bird than is usually noted in avian species.
FUEL ELEMENT FOR NUCLEAR REACTORS
Bassett, C.H.
1961-05-01
A nuclear reactor fuel element comprising high density ceramic fissionable material enclosed in a tubular cladding of corrosion-resistant material is described. The fissionable material is in the form of segments of a tube which have cooperating tapered interfaces which produce outward radial displacement when the segments are urged axially together. A resilient means is provided within the tubular housing to constantly urge the fuel segments axially. This design maintains the fuel material in tight contacting engagement against the inner surface of the outer cladding tube to eliminate any gap therebetween which may be caused by differential thermal expansion between the fuel material and the material of the tube.
Burdgick, Steven Sebastian; Itzel, Gary Michael
2001-01-01
A gas turbine nozzle segment has outer and inner bands. Each band includes a side wall, a cover and an impingement plate between the cover and nozzle wall defining two cavities on opposite sides of the impingement plate. Cooling steam is supplied to one cavity for flow through apertures of the impingement plate to cool the nozzle wall. The side wall of the band and inturned flange define with the nozzle wall an undercut region. The inturned flange has a plurality of apertures for directing cooling steam to cool the side wall between adjacent nozzle segments.
Load-resistant coaxial transmission line
Hall, David R.; Fox, Joe
2006-01-03
A transmission line for downhole tools that make up all or part of a tool string for drilling and production of oil, gas, and geothermal wells that can withstand the dynamic gravitational forces and other accelerations associated with downhole excavations. The transmission line has a metal tube, or outer conductor, that houses a coaxial wire inner conductor. A non-metallic dielectric material is interposed between the inner and outer conductors. The outer and inner conductors and the dielectric are sufficiently compressed together so that independent motion between them is abated. Compression of the components of the transmission line may be achieved by drawing the transmission through one or more dies in order to draw down the outer conductor onto the dielectric, or by expanding the inner conductor against the dielectric using a mandrel or hydraulic pressure. Non-metallic bead segments may be used in aid of the compression necessary to resist the dynamic forces and accelerations of drilling.
A hybrid method for airway segmentation and automated measurement of bronchial wall thickness on CT.
Xu, Ziyue; Bagci, Ulas; Foster, Brent; Mansoor, Awais; Udupa, Jayaram K; Mollura, Daniel J
2015-08-01
Inflammatory and infectious lung diseases commonly involve bronchial airway structures and morphology, and these abnormalities are often analyzed non-invasively through high resolution computed tomography (CT) scans. Assessing airway wall surfaces and the lumen are of great importance for diagnosing pulmonary diseases. However, obtaining high accuracy from a complete 3-D airway tree structure can be quite challenging. The airway tree structure has spiculated shapes with multiple branches and bifurcation points as opposed to solid single organ or tumor segmentation tasks in other applications, hence, it is complex for manual segmentation as compared with other tasks. For computerized methods, a fundamental challenge in airway tree segmentation is the highly variable intensity levels in the lumen area, which often causes a segmentation method to leak into adjacent lung parenchyma through blurred airway walls or soft boundaries. Moreover, outer wall definition can be difficult due to similar intensities of the airway walls and nearby structures such as vessels. In this paper, we propose a computational framework to accurately quantify airways through (i) a novel hybrid approach for precise segmentation of the lumen, and (ii) two novel methods (a spatially constrained Markov random walk method (pseudo 3-D) and a relative fuzzy connectedness method (3-D)) to estimate the airway wall thickness. We evaluate the performance of our proposed methods in comparison with mostly used algorithms using human chest CT images. Our results demonstrate that, on publicly available data sets and using standard evaluation criteria, the proposed airway segmentation method is accurate and efficient as compared with the state-of-the-art methods, and the airway wall estimation algorithms identified the inner and outer airway surfaces more accurately than the most widely applied methods, namely full width at half maximum and phase congruency. Copyright © 2015. Published by Elsevier B.V.
Cerebrovascular plaque segmentation using object class uncertainty snake in MR images
NASA Astrophysics Data System (ADS)
Das, Bipul; Saha, Punam K.; Wolf, Ronald; Song, Hee Kwon; Wright, Alexander C.; Wehrli, Felix W.
2005-04-01
Atherosclerotic cerebrovascular disease leads to formation of lipid-laden plaques that can form emboli when ruptured causing blockage to cerebral vessels. The clinical manifestation of this event sequence is stroke; a leading cause of disability and death. In vivo MR imaging provides detailed image of vascular architecture for the carotid artery making it suitable for analysis of morphological features. Assessing the status of carotid arteries that supplies blood to the brain is of primary interest to such investigations. Reproducible quantification of carotid artery dimensions in MR images is essential for plaque analysis. Manual segmentation being the only method presently makes it time consuming and sensitive to inter and intra observer variability. This paper presents a deformable model for lumen and vessel wall segmentation of carotid artery from MR images. The major challenges of carotid artery segmentation are (a) low signal-to-noise ratio, (b) background intensity inhomogeneity and (c) indistinct inner and/or outer vessel wall. We propose a new, effective object-class uncertainty based deformable model with additional features tailored toward this specific application. Object-class uncertainty optimally utilizes MR intensity characteristics of various anatomic entities that enable the snake to avert leakage through fuzzy boundaries. To strengthen the deformable model for this application, some other properties are attributed to it in the form of (1) fully arc-based deformation using a Gaussian model to maximally exploit vessel wall smoothness, (2) construction of a forbidden region for outer-wall segmentation to reduce interferences by prominent lumen features and (3) arc-based landmark for efficient user interaction. The algorithm has been tested upon T1- and PD- weighted images. Measures of lumen area and vessel wall area are computed from segmented data of 10 patient MR images and their accuracy and reproducibility are examined. These results correspond exceptionally well with manual segmentation completed by radiology experts. Reproducibility of the proposed method is estimated for both intra- and inter-operator studies.
Impaired Dendritic Development and Memory in Sorbs2 Knock-Out Mice.
Zhang, Qiangge; Gao, Xian; Li, Chenchen; Feliciano, Catia; Wang, Dongqing; Zhou, Dingxi; Mei, Yuan; Monteiro, Patricia; Anand, Michelle; Itohara, Shigeyoshi; Dong, Xiaowei; Fu, Zhanyan; Feng, Guoping
2016-02-17
Intellectual disability is a common neurodevelopmental disorder characterized by impaired intellectual and adaptive functioning. Both environmental insults and genetic defects contribute to the etiology of intellectual disability. Copy number variations of SORBS2 have been linked to intellectual disability. However, the neurobiological function of SORBS2 in the brain is unknown. The SORBS2 gene encodes ArgBP2 (Arg/c-Abl kinase binding protein 2) protein in non-neuronal tissues and is alternatively spliced in the brain to encode nArgBP2 protein. We found nArgBP2 colocalized with F-actin at dendritic spines and growth cones in cultured hippocampal neurons. In the mouse brain, nArgBP2 was highly expressed in the cortex, amygdala, and hippocampus, and enriched in the outer one-third of the molecular layer in dentate gyrus. Genetic deletion of Sorbs2 in mice led to reduced dendritic complexity and decreased frequency of AMPAR-miniature spontaneous EPSCs in dentate gyrus granule cells. Behavioral characterization revealed that Sorbs2 deletion led to a reduced acoustic startle response, and defective long-term object recognition memory and contextual fear memory. Together, our findings demonstrate, for the first time, an important role for nArgBP2 in neuronal dendritic development and excitatory synaptic transmission, which may thus inform exploration of neurobiological basis of SORBS2 deficiency in intellectual disability. Copy number variations of the SORBS2 gene are linked to intellectual disability, but the neurobiological mechanisms are unknown. We found that nArgBP2, the only neuronal isoform encoded by SORBS2, colocalizes with F-actin at neuronal dendritic growth cones and spines. nArgBP2 is highly expressed in the cortex, amygdala, and dentate gyrus in the mouse brain. Genetic deletion of Sorbs2 in mice leads to impaired dendritic complexity and reduced excitatory synaptic transmission in dentate gyrus granule cells, accompanied by behavioral deficits in acoustic startle response and long-term memory. This is the first study of Sorbs2 function in the brain, and our findings may facilitate the study of neurobiological mechanisms underlying SORBS2 deficiency in the development of intellectual disability. Copyright © 2016 the authors 0270-6474/16/362248-14$15.00/0.
Hájos, N; Papp, E C; Acsády, L; Levey, A I; Freund, T F
1998-01-01
In previous studies m2 muscarinic acetylcholine receptor-immunoreactive interneurons and various types of m2-positive axon terminals have been described in the hippocampal formation. The aim of the present study was to identify the types of interneurons expressing m2 receptor and to examine whether the somadendritic and axonal m2 immunostaining labels the same or distinct cell populations. In the CA1 subfield, neurons immunoreactive for m2 have horizontal dendrites, they are located at the stratum oriens/alveus border and have an axon that project to the dendritic region of pyramidal cells. In the CA3 subfield and the hilus, m2-positive neurons are multipolar and are scattered in all layers except stratum lacunosum-moleculare. In stratum pyramidale of the CA1 and CA3 regions, striking axon terminal staining for m2 was observed, surrounding the somata and axon initial segments of pyramidal cells in a basket-like manner. The co-localization of m2 with neurochemical markers and GABA was studied using the "mirror" technique and fluorescent double-immunostaining at the light microscopic level and with double-labelling using colloidal gold-conjugated antisera and immunoperoxidase reaction (diaminobenzidine) at the electron microscopic level. GABA was shown to be present in the somata of most m2-immunoreactive interneurons, as well as in the majority of m2-positive terminals in all layers. The calcium-binding protein parvalbumin was absent from practically all m2-immunoreactive cell bodies and dendrites. In contrast, many of the terminals synapsing on pyramidal cell somata and axon initial segments co-localized parvalbumin and m2, suggesting a differential distribution of m2 receptor immunoreactivity on the axonal and somadendritic membrane of parvalbumin-containing basket and axo-axonic cells. The co-existence of m2 receptors with the calcium-binding protein calbindin and the neuropeptides cholecystokinin and vasoactive intestinal polypeptide was rare throughout the hippocampal formation. Only calretinin and somatostatin showed an appreciable degree of co-localization with m2 (20% and 15%, respectively). Using retrograde tracing, some of the m2-positive cells in stratum oriens were shown to project to the medial septum, accouting for 38% of all projection neurons. The present results demonstrate that there is a differential distribution of m2 receptor immunoreactivity on the axonal vs the somadendritic membranes of distinct interneuron types and suggest that acetylcholine via m2 receptors may reduce GABA release presynaptically from the terminals of perisomatic inhibitory cells, while it may act to increase the activity of another class of interneuron, which innervates the dendritic region of pyramidal cells.
2008-11-06
CAPE CANAVERAL, Fla. – Inside the Vehicle Assembly Building high bay 4 at NASA's Kennedy Space Center in Florida, workers from NASA's Glenn Research Center remove the blue shrink-wrapped covers on these Ares I-X upper stage simulator segments. The protective covers were used for shipping. The upper stage simulator will be used in the test flight identified as Ares I-X in 2009. The segments will simulate the mass and the outer mold line and will be more than 100 feet of the total vehicle height of 327 feet. The simulator comprises 11 segments that are approximately 18 feet in diameter. Most of the segments will be approximately 10 feet high, ranging in weight from 18,000 to 60,000 pounds, for a total of approximately 450,000 pounds. Photo credit: NASA/Troy Cryder
2008-11-06
CAPE CANAVERAL, Fla. – Inside the Vehicle Assembly Building high bay 4 at NASA's Kennedy Space Center in Florida, workers from NASA's Glenn Research Center remove the blue shrink-wrapped covers on these Ares I-X upper stage simulator segments. The protective covers were used for shipping. The upper stage simulator will be used in the test flight identified as Ares I-X in 2009. The segments will simulate the mass and the outer mold line and will be more than 100 feet of the total vehicle height of 327 feet. The simulator comprises 11 segments that are approximately 18 feet in diameter. Most of the segments will be approximately 10 feet high, ranging in weight from 18,000 to 60,000 pounds, for a total of approximately 450,000 pounds. Photo credit: NASA/Troy Cryder
2008-11-06
CAPE CANAVERAL, Fla. – Inside the Vehicle Assembly Building high bay 4 at NASA's Kennedy Space Center in Florida, workers from NASA's Glenn Research Center remove the blue shrink-wrapped covers on these Ares I-X upper stage simulator segments. The protective covers were used for shipping. The upper stage simulator will be used in the test flight identified as Ares I-X in 2009. The segments will simulate the mass and the outer mold line and will be more than 100 feet of the total vehicle height of 327 feet. The simulator comprises 11 segments that are approximately 18 feet in diameter. Most of the segments will be approximately 10 feet high, ranging in weight from 18,000 to 60,000 pounds, for a total of approximately 450,000 pounds. Photo credit: NASA/Troy Cryder
2008-11-06
CAPE CANAVERAL, Fla. – Inside the Vehicle Assembly Building high bay 4 at NASA's Kennedy Space Center in Florida, workers from NASA's Glenn Research Center remove the blue shrink-wrapped covers on these Ares I-X upper stage simulator segments. The protective covers were used for shipping. The upper stage simulator will be used in the test flight identified as Ares I-X in 2009. The segments will simulate the mass and the outer mold line and will be more than 100 feet of the total vehicle height of 327 feet. The simulator comprises 11 segments that are approximately 18 feet in diameter. Most of the segments will be approximately 10 feet high, ranging in weight from 18,000 to 60,000 pounds, for a total of approximately 450,000 pounds. Photo credit: NASA/Troy Cryder
NASA Technical Reports Server (NTRS)
Quintana, Rolando
2002-01-01
Four high-pressure gas tanks, the basis of this study, were especially made by a private contractor and tested before being delivered to NASA Kennedy Space Center. In order to insure 100% reliability of each individual tank the staff at KSC decided to again submit the four tanks under more rigorous tests. These tests were conducted during a period from April 10 through May 8 at KSC. This application further validates the predictive safety model for accident prevention and system failure in the testing of four high-pressure gas tanks at Kennedy Space Center, called Continuous Hazard Tracking and Failure Prediction Methodology (CHTFPM). It is apparent from the variety of barriers available for a hazard control that some barriers will be more successful than others in providing protection. In order to complete the Barrier Analysis of the system, a Task Analysis and a Biomechanical Study were performed to establish the relationship between the degree of biomechanical non-conformities and the anomalies found within the system on particular joints of the body. This relationship was possible to obtain by conducting a Regression Analysis to the previously generated data. From the information derived the body segment with the lowest percentage of non-conformities was the neck flexion with 46.7%. Intense analysis of the system was conducted including Preliminary Hazard Analysis (PHA), Failure Mode and Effect Analysis (FMEA), and Barrier Analysis. These analyses resulted in the identification of occurrences of conditions, which may be becoming hazardous in the given system. These conditions, known as dendritics, may become hazards and could result in an accident, system malfunction, or unacceptable risk conditions. A total of 56 possible dendritics were identified. Work sampling was performed to observe the occurrence each dendritic. The out of control points generated from a Weighted c control chart along with a Pareto analysis indicate that the dendritics "Personnel not Wearing Proper Protective and Hose/tubing located in high-traffic area" which account for 59.18% of total dendritic frequency need to be addressed to reduce the chance of a hazard from occurring. However, the occurrences of some dendritics are more important than others. As a result immediate, from a Weighted c perspective, corrective action should be taken to ameliorate the cause of the Class A dendritic "Personnel located under suspended or moving loads" rather than just the most commonly occurring dendritics. In any case the vast majority of data obtained indicates that testing operations possess a relatively high degree of safety.
Environmental enrichment alters dentate granule cell morphology in oldest-old rat.
Darmopil, Sanja; Petanjek, Zdravko; Mohammed, Abdul H; Bogdanović, Nenad
2009-08-01
The hippocampus of aged rats shows marked age-related morphological changes that could cause memory deficits. Experimental evidence has established that environmental enrichment attenuates memory deficits in aged rats. We therefore studied whether environmental enrichment produces morphological changes on the dentate granule cells of aged rats. Fifteen male Sprague-Dawley rats, 24 months of age, were randomly distributed in two groups that were housed under standard (n = 7) or enriched (n = 8) environmental conditions for 26 days. Quantitative data of dendritic morphology from dentate gyrus granule cells were obtained on Golgi-Cox stained sections. Environmental enrichment significantly increased the complexity and size of dendritic tree (total number of segments increased by 61% and length by 116%), and spine density (88% increase). There were large interindividual differences within the enriched group, indicating differential individual responses to environmental stimulation. Previous studies in young animals have shown changes produced by environmental enrichment in the morphology of dentate gyrus granule cells. The results of the present study show that environmental enrichment can also produce changes in dentate granule cell morphology in the senescent brain. In conclusion, the hippocampus retains its neuroplastic capacity during aging, and enriched environmental housing conditions can attenuate age-related dendritic regression and synaptic loss, thus preserving memory functions.
Litts, Katie M.; Wang, Xiaolin; Clark, Mark E.; Owsley, Cynthia; Freund, K. Bailey; Curcio, Christine A.; Zhang, Yuhua
2016-01-01
Purpose To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO). Methods Four eyes of 4 subjects with advanced AMD underwent color fundus photography, infrared reflectance imaging, SD-OCT, and AOSLO with a high-resolution research instrument. ORT was identified in closely spaced (11 μm) SD-OCT volume scans. Results ORT in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by AOSLO was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors. Conclusion Lack of ORT cone reflectivity by AOSLO indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in OCT. PMID:27584549
Retinal pigment epithelial dystrophy in Briard dogs.
Lightfoot, R M; Cabral, L; Gooch, L; Bedford, P G; Boulton, M E
1996-01-01
The eyes of normal Briard dogs, Briards affected with inherited retinal pigment epithelial dystrophy (RPED) and a range of normal crossbred and beagle dogs were examined and the histopathology of RPED in the Briard was compared with the histopathological features of ageing in the normal canine retina. RPED was characterised by the accumulation of auto-fluorescent lipofuscin-like inclusions in the retinal pigment epithelium (RPE), which initially involved only non-pigmented RPE cells overlying the tapetum but subsequently spread to all pigmented RPE cells. Secondary neuro-retinal degeneration was characterised by a gradual loss of the outer nuclear layer and the subsequent atrophy and degeneration of the inner retina. The loss of primary photoreceptors in the peripheral retina was accompanied by the migration of photoreceptor nuclei and appeared to resemble severe changes due to ageing. Intra-vitreal radiolabelled leucine was used to examine the rate of turnover of the outer segments of the rods in some Briards, but no significant variations were found. The activity of acid phosphatase in RPE was assayed in vitro and showed comparable regional variations in Briard and crossbred dogs. The results suggest that RPED in the Briard is unlikely to be due either to an increased rate of turnover of rod outer segments (and thus an increased phagocytic load) or to a primary insufficiency of lysosomal enzyme.
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.
Virtanen, Mari A; Lacoh, Claudia Marvine; Fiumelli, Hubert; Kosel, Markus; Tyagarajan, Shiva; de Roo, Mathias; Vutskits, Laszlo
2018-05-01
Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons. Using this technique and focusing on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto these cells between postnatal days 10 and 20. While the spatial distribution of gephyrin clusters was not affected by the distance from the cell body at postnatal day 10, we found that distal dendritic segments appeared to have a higher gephyrin density at later developmental stages. We also show a transient increase around postnatal day 20 in the percentage of spines that are carrying a gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the precise spatial arrangement of synaptic inputs is an important determinant of neuronal responses, we believe that the method described in this work may allow a better understanding of how inhibition settles together with excitation, and serve as basics for further modelling studies focusing on the geometry of dendritic inhibition during development.
Morphology of the utricular otolith organ in the toadfish, Opsanus tau.
Boyle, Richard; Ehsanian, Reza; Mofrad, Alireza; Popova, Yekaterina; Varelas, Joseph
2018-06-15
The utricle provides the vestibular reflex pathways with the sensory codes of inertial acceleration of self-motion and head orientation with respect to gravity to control balance and equilibrium. Here we present an anatomical description of this structure in the adult oyster toadfish and establish a morphological basis for interpretation of subsequent functional studies. Light, scanning, and transmission electron microscopy techniques were applied to visualize the sensory epithelium at varying levels of detail, its neural innervation and its synaptic organization. Scanning electron microscopy was used to visualize otolith mass and morphological polarization patterns of hair cells. Afferent nerve fibers were visualized following labeling with biocytin, and light microscope images were used to make three-dimensional (3-D) reconstructions of individual labeled afferents to identify dendritic morphology with respect to epithelial location. Transmission electron micrographs were compiled to create a serial 3-D reconstruction of a labeled afferent over a segment of its dendritic field and to examine the cell-afferent synaptic contacts. Major observations are: a well-defined striola, medial and lateral extra-striolar regions with a zonal organization of hair bundles; prominent lacinia projecting laterally; dependence of hair cell density on macular location; narrow afferent dendritic fields that follow the hair bundle polarization; synaptic specializations issued by afferents are typically directed towards a limited number of 7-13 hair cells, but larger dendritic fields in the medial extra-striola can be associated with > 20 hair cells also; and hair cell synaptic bodies can be confined to only an individual afferent or can synapse upon several afferents. © 2018 Wiley Periodicals, Inc.
Deep learning and shapes similarity for joint segmentation and tracing single neurons in SEM images
NASA Astrophysics Data System (ADS)
Rao, Qiang; Xiao, Chi; Han, Hua; Chen, Xi; Shen, Lijun; Xie, Qiwei
2017-02-01
Extracting the structure of single neurons is critical for understanding how they function within the neural circuits. Recent developments in microscopy techniques, and the widely recognized need for openness and standardization provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons. In order to look into the fine structure of neurons, we use the Automated Tape-collecting Ultra Microtome Scanning Electron Microscopy (ATUM-SEM) to get images sequence of serial sections of animal brain tissue that densely packed with neurons. Different from other neuron reconstruction method, we propose a method that enhances the SEM images by detecting the neuronal membranes with deep convolutional neural network (DCNN) and segments single neurons by active contour with group shape similarity. We joint the segmentation and tracing together and they interact with each other by alternate iteration that tracing aids the selection of candidate region patch for active contour segmentation while the segmentation provides the neuron geometrical features which improve the robustness of tracing. The tracing model mainly relies on the neuron geometrical features and is updated after neuron being segmented on the every next section. Our method enables the reconstruction of neurons of the drosophila mushroom body which is cut to serial sections and imaged under SEM. Our method provides an elementary step for the whole reconstruction of neuronal networks.
Kandaswamy, Umasankar; Rotman, Ziv; Watt, Dana; Schillebeeckx, Ian; Cavalli, Valeria; Klyachko, Vitaly
2013-01-01
High-resolution live-cell imaging studies of neuronal structure and function are characterized by large variability in image acquisition conditions due to background and sample variations as well as low signal-to-noise ratio. The lack of automated image analysis tools that can be generalized for varying image acquisition conditions represents one of the main challenges in the field of biomedical image analysis. Specifically, segmentation of the axonal/dendritic arborizations in brightfield or fluorescence imaging studies is extremely labor-intensive and still performed mostly manually. Here we describe a fully automated machine-learning approach based on textural analysis algorithms for segmenting neuronal arborizations in high-resolution brightfield images of live cultured neurons. We compare performance of our algorithm to manual segmentation and show that it combines 90% accuracy, with similarly high levels of specificity and sensitivity. Moreover, the algorithm maintains high performance levels under a wide range of image acquisition conditions indicating that it is largely condition-invariable. We further describe an application of this algorithm to fully automated synapse localization and classification in fluorescence imaging studies based on synaptic activity. Textural analysis-based machine-learning approach thus offers a high performance condition-invariable tool for automated neurite segmentation. PMID:23261652
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
Hanneken, Anne; Neikirk, Thomas; Johnson, Jennifer; Kono, Masahiro
2017-08-01
To test the hypothesis that delayed dark adaptation in patients with macular degeneration is due to an excess of free unliganded opsin (apo-opsin) and a deficiency of the visual chromophore, 11 -cis retinal, in rod outer segments. A total of 50 human autopsy eyes were harvested from donors with and without macular degeneration within 2-24 hrs. postmortem. Protocols were developed which permitted dark adaptation of normal human eyes after death and enucleation. Biochemical methods of purifying rod outer segments were optimized and the concentration of rhodopsin and apo-opsin was measured with UV-visible scanning spectroscopy. The presence of apo-opsin was calculated by measuring the difference in the rhodopsin absorption spectra before and after the addition of 11 -cis retinal. A total of 20 normal eyes and 16 eyes from donors with early, intermediate and advanced stages of macular degeneration were included in the final analysis. Dark adaptation was achieved by harvesting whole globes in low light, transferring into dark (light-proof) canisters and dissecting the globes using infrared light and image converters for visualization. Apo-opsin was readily detected in positive controls after the addition of 11 -cis retinal. Normal autopsy eyes showed no evidence of apo-opsin. Eyes with macular degeneration also showed no evidence of apo-opsin, regardless of the severity of disease. Methods have been developed to study dark adaptation in human autopsy eyes. Eyes with age-related macular degeneration do not show a deficiency of 11 -cis retinal or an excess of apo-opsin within rod outer segments.
Milstein, Michelle L; Kimler, Victoria A; Ghatak, Chiranjib; Ladokhin, Alexey S; Goldberg, Andrew F X
2017-05-12
Peripherin-2/rds is required for biogenesis of vertebrate photoreceptor outer segment organelles. Its localization at the high-curvature rim domains of outer segment disk membranes suggests that it may act to shape these structures; however, the molecular function of this protein is not yet resolved. Here, we apply biochemical, biophysical, and imaging techniques to elucidate the role(s) played by the protein's intrinsically disordered C-terminal domain and an incipient amphipathic α-helix contained within it. We investigated a deletion mutant lacking only this α-helix in stable cell lines and Xenopus laevis photoreceptors. We also studied a soluble form of the full-length ∼7-kDa cytoplasmic C terminus in cultured cells and purified from Escherichia coli The α-helical motif was not required for protein biosynthesis, tetrameric subunit assembly, tetramer polymerization, localization at disk rims, interaction with GARP2, or the generation of membrane curvature. Interestingly, however, loss of the helical motif up-regulated membrane curvature generation in cellulo , introducing the possibility that it may regulate this activity in photoreceptors. Furthermore, the incipient α-helix (within the purified soluble C terminus) partitioned into membranes only when its acidic residues were neutralized by protonation. This suggests that within the context of full-length peripherin-2/rds, partitioning would most likely occur at a bilayer interfacial region, potentially adjacent to the protein's transmembrane domains. In sum, this study significantly strengthens the evidence that peripherin-2/rds functions directly to shape the high-curvature rim domains of the outer segment disk and suggests that the protein's C terminus may modulate membrane curvature-generating activity present in other protein domains. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Blakeley, Lorie R; Chen, Chunhe; Chen, Ching-Kang; Chen, Jeannie; Crouch, Rosalie K; Travis, Gabriel H; Koutalos, Yiannis
2011-06-01
The reactive aldehyde all-trans retinal is released in rod photoreceptor outer segments by photoactivated rhodopsin and is eliminated through reduction to all-trans retinol. This study was undertaken to determine whether all-trans retinol formation depends on Abca4, arrestin, rhodopsin kinase, and the palmitylation of rhodopsin, all of which are factors that affect the release and sequestration of all-trans retinal. Experiments were performed in isolated retinas and single living rods derived from 129/sv wild-type mice and Abca4-, arrestin-, and rhodopsin kinase-deficient mice and in genetically modified mice containing unpalmitylated rhodopsin. Formation of all-trans retinol was measured by imaging its fluorescence and by HPLC of retina extracts. The release of all-trans retinal from photoactivated rhodopsin was measured in purified rod outer segment membranes according to the increase in tryptophan fluorescence. All experiments were performed at 37°C. The kinetics of all-trans retinol formation in the different types of genetically modified mice are in reasonable agreement with those in wild-type animals. The kinetics of all-trans retinol formation in 129/sv mice are similar to those in C57BL/6, although the latter are known to regenerate rhodopsin much more slowly. The release of all-trans retinal from rhodopsin in purified membranes is significantly faster than the formation of all-trans retinol in intact cells and is independent of the presence of the palmitate groups. The regeneration of rhodopsin and the recycling of its chromophore are not strongly coupled. Neither the activities of Abca4, rhodopsin kinase, and arrestin, nor the palmitylation of rhodopsin affects the formation of all-trans retinol.
Concentric retinitis pigmentosa: clinicopathologic correlations.
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.
Wong, Bernice H.; Chan, Jia Pei; Cazenave-Gassiot, Amaury; Poh, Rebecca W.; Foo, Juat Chin; Galam, Dwight L. A.; Ghosh, Sujoy; Nguyen, Long N.; Barathi, Veluchamy A.; Yeo, Sia W.; Luu, Chi D.; Wenk, Markus R.; Silver, David L.
2016-01-01
Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth. Here we demonstrate that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of Mfsd2a expression in the eye. Eyes from whole body Mfsd2a-deficient (KO) mice, but not endothelium-specific Mfsd2a-deficient mice, were DHA-deficient and had significantly reduced LPC/DHA transport in vivo. Fluorescein angiography indicated normal blood-retinal barrier function. Histological and electron microscopic analysis indicated that Mfsd2a KO mice exhibited a specific reduction in outer rod segment length, disorganized outer rod segment discs, and mislocalization of and reduction in rhodopsin early in postnatal development without loss of photoreceptors. Minor photoreceptor cell loss occurred in adult Mfsd2a KO mice, but electroretinography indicated visual function was normal. The developing eyes of Mfsd2a KO mice had activated microglia and up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of LPC transport. These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs. PMID:27008858
New algorithm for detecting smaller retinal blood vessels in fundus images
NASA Astrophysics Data System (ADS)
LeAnder, Robert; Bidari, Praveen I.; Mohammed, Tauseef A.; Das, Moumita; Umbaugh, Scott E.
2010-03-01
About 4.1 million Americans suffer from diabetic retinopathy. To help automatically diagnose various stages of the disease, a new blood-vessel-segmentation algorithm based on spatial high-pass filtering was developed to automatically segment blood vessels, including the smaller ones, with low noise. Methods: Image database: Forty, 584 x 565-pixel images were collected from the DRIVE image database. Preprocessing: Green-band extraction was used to obtain better contrast, which facilitated better visualization of retinal blood vessels. A spatial highpass filter of mask-size 11 was applied. A histogram stretch was performed to enhance contrast. A median filter was applied to mitigate noise. At this point, the gray-scale image was converted to a binary image using a binary thresholding operation. Then, a NOT operation was performed by gray-level value inversion between 0 and 255. Postprocessing: The resulting image was AND-ed with its corresponding ring mask to remove the outer-ring (lens-edge) artifact. At this point, the above algorithm steps had extracted most of the major and minor vessels, with some intersections and bifurcations missing. Vessel segments were reintegrated using the Hough transform. Results: After applying the Hough transform, both the average peak SNR and the RMS error improved by 10%. Pratt's Figure of Merit (PFM) was decreased by 6%. Those averages were better than [1] by 10-30%. Conclusions: The new algorithm successfully preserved the details of smaller blood vessels and should prove successful as a segmentation step for automatically identifying diseases that affect retinal blood vessels.
High-Resolution Gamma-Ray Imaging Measurements Using Externally Segmented Germanium Detectors
NASA Technical Reports Server (NTRS)
Callas, J.; Mahoney, W.; Skelton, R.; Varnell, L.; Wheaton, W.
1994-01-01
Fully two-dimensional gamma-ray imaging with simultaneous high-resolution spectroscopy has been demonstrated using an externally segmented germanium sensor. The system employs a single high-purity coaxial detector with its outer electrode segmented into 5 distinct charge collection regions and a lead coded aperture with a uniformly redundant array (URA) pattern. A series of one-dimensional responses was collected around 511 keV while the system was rotated in steps through 180 degrees. A non-negative, linear least-squares algorithm was then employed to reconstruct a 2-dimensional image. Corrections for multiple scattering in the detector, and the finite distance of source and detector are made in the reconstruction process.
NASA Technical Reports Server (NTRS)
Gross, B.; Srawley, J. E.
1983-01-01
The boudary collocation method was used to generate Mode 1 stress intensity and crack mouth displacement coefficients for internally and externally radially cracked ring segments (arc bend specimens) subjected to three point radial loading. Numerical results were obtained for ring segment outer to inner radius ratios (R sub o/ R sub i) ranging from 1.10 to 2.50 and crack length to width ratios (a/W) ranging from 0.1 to 0.8. Stress intensity and crack mouth displacement coefficients were found to depend on the ratios R sub o/R sub i and a/W as well as the included angle between the directions of the reaction forces.
Architecture of the human renal inner medulla and functional implications
Wei, Guojun; Rosen, Seymour; Dantzler, William H.
2015-01-01
The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. PMID:26290371
Chen, Eric; Brown, David M; Benz, Matthew S; Fish, Richard H; Wong, Tien P; Kim, Rosa Y; Major, James C
2010-10-21
While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage. Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers. Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the "flying saucer" sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none. Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.
Nti, Akosua A; Serrano, Leona W; Sandhu, Harpal S; Uyhazi, Katherine E; Edelstein, Ilaina D; Zhou, Elaine J; Bowman, Scott; Song, Delu; Gangadhar, Tara C; Schuchter, Lynn M; Mitnick, Sheryl; Huang, Alexander; Nichols, Charles W; Amaravadi, Ravi K; Kim, Benjamin J; Aleman, Tomas S
2018-01-10
To assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma. Patients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment. There were no clinically significant ocular events; there was no ocular inflammation. The only medication-related change was a separation of the photoreceptor outer segment tip from the apical retinal pigment epithelium that could be traced from the fovea to the perifoveal retina noted in 9/11 (82%) of the patients. There were no changes in retinal pigment epithelium melanization or lipofuscin content by near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence, respectively. There were no inner retinal or outer nuclear layer changes. Visual acuities and sensitivities were unchanged. BRAFi (trametinib) + MEKi (dabrafenib) + HCQ causes very frequent, subclinical separation of the photoreceptor outer segment from the apical retinal pigment epithelium without inner retinal changes or signs of inflammation. The changes suggest interference with the maintenance of the outer retinal barrier and/or phagocytic/pump functions of the retinal pigment epithelium by effective MEK inhibition.
Segmented lasing tube for high temperature laser assembly
Sawicki, Richard H.; Alger, Terry W.; Finucane, Raymond G.; Hall, Jerome P.
1996-01-01
A high temperature laser assembly capable of withstanding operating temperatures in excess of 1500.degree. C. is described comprising a segmented cylindrical ceramic lasing tube having a plurality of cylindrical ceramic lasing tube segments of the same inner and outer diameters non-rigidly joined together in axial alignment; insulation of uniform thickness surround the walls of the ceramic lasing tube; a ceramic casing, preferably of quartz, surrounding the insulation; and a fluid cooled metal jacket surrounds the ceramic casing. In a preferred embodiment, the inner surface of each of the ceramic lasing tube segments are provided with a pair of oppositely spaced grooves in the wall thereof parallel to the center axis of the segmented cylindrical ceramic lasing tube, and both of the grooves and the center axis of the segmented cylindrical ceramic lasing tube lie in a common plane, with the grooves in each ceramic lasing tube segment in circumferential alignment with the grooves in the adjoining ceramic lasing tube segments; and one or more ceramic plates, all lying in a common plane to one another and with the central axis of the segmented ceramic lasing tube, are received in the grooves to provide additional wall area in the segmented ceramic lasing tube for collision and return to ground state of metastable metal atoms within the segmented ceramic lasing tube.
Cooling circuit for steam and air-cooled turbine nozzle stage
Itzel, Gary Michael; Yu, Yufeng
2002-01-01
The turbine vane segment includes inner and outer walls with a vane extending therebetween. The vane includes leading and trailing edge cavities and intermediate cavities. An impingement plate is spaced from the outer wall to impingement-cool the outer wall. Post-impingement cooling air flows through holes in the outer wall to form a thin air-cooling film along the outer wall. Cooling air is supplied an insert sleeve with openings in the leading edge cavity for impingement-cooling the leading edge. Holes through the leading edge afford thin-film cooling about the leading edge. Cooling air is provided the trailing edge cavity and passes through holes in the side walls of the vane for thin-film cooling of the trailing edge. Steam flows through a pair of intermediate cavities for impingement-cooling of the side walls. Post-impingement steam flows to the inner wall for impingement-cooling of the inner wall and returns the post-impingement cooling steam through inserts in other intermediate cavities for impingement-cooling the side walls of the vane.
Adaptations in rod outer segment disc membranes in response to environmental lighting conditions.
Rakshit, Tatini; Senapati, Subhadip; Parmar, Vipul M; Sahu, Bhubanananda; Maeda, Akiko; Park, Paul S-H
2017-10-01
The light-sensing rod photoreceptor cell exhibits several adaptations in response to the lighting environment. While adaptations to short-term changes in lighting conditions have been examined in depth, adaptations to long-term changes in lighting conditions are less understood. Atomic force microscopy was used to characterize the structure of rod outer segment disc membranes, the site of photon absorption by the pigment rhodopsin, to better understand how photoreceptor cells respond to long-term lighting changes. Structural properties of the disc membrane changed in response to housing mice in constant dark or light conditions and these adaptive changes required output from the phototransduction cascade initiated by rhodopsin. Among these were changes in the packing density of rhodopsin in the membrane, which was independent of rhodopsin synthesis and specifically affected scotopic visual function as assessed by electroretinography. Studies here support the concept of photostasis, which maintains optimal photoreceptor cell function with implications in retinal degenerations. Copyright © 2017 Elsevier B.V. All rights reserved.
Growth Mechanism of a Unique Hierarchical Vaterite Structure
NASA Astrophysics Data System (ADS)
Ma, Guobin; Xu, Yifei; Wang, Mu
2013-03-01
Calcium carbonate is one of the most significant minerals in nature as well as in biogenic sources. Calcium carbonate occurs naturally in three crystalline polymorphs, i.e., calcite, aragonite, and vaterite. Although it has been attracted much research attention to understanding of the formation mechanisms of the material, the properties of the vaterite polymorph is not well known. Here we report synthesis and formation mechanism of a unique hierarchical structure of vaterite. The material is grown by a controlled diffusion method. The structure possesses a core and an outer part. The core is convex lens-like and is formed by vaterite nanocrystals that have small misorientations. The outer part is separated into six garlic clove-like segments. Each segment possesses piles of plate-like vaterite crystals, and the orientations of the plates continuously change from pile to pile. Based on real-time experimental results and the structural analysis, a growth mechanism is presented. Work supported by NSFC (Grant No. 51172104) and MOST of China (Grant No. 2101CB630705)
A smart sensor architecture based on emergent computation in an array of outer-totalistic cells
NASA Astrophysics Data System (ADS)
Dogaru, Radu; Dogaru, Ioana; Glesner, Manfred
2005-06-01
A novel smart-sensor architecture is proposed, capable to segment and recognize characters in a monochrome image. It is capable to provide a list of ASCII codes representing the recognized characters from the monochrome visual field. It can operate as a blind's aid or for industrial applications. A bio-inspired cellular model with simple linear neurons was found the best to perform the nontrivial task of cropping isolated compact objects such as handwritten digits or characters. By attaching a simple outer-totalistic cell to each pixel sensor, emergent computation in the resulting cellular automata lattice provides a straightforward and compact solution to the otherwise computationally intensive problem of character segmentation. A simple and robust recognition algorithm is built in a compact sequential controller accessing the array of cells so that the integrated device can provide directly a list of codes of the recognized characters. Preliminary simulation tests indicate good performance and robustness to various distortions of the visual field.
Posterior Segment Toxicity Following Gemcitabine and Docetaxel Chemotherapy
Valeshabad, Ali Kord; Mieler, William F.; Setlur, Vikram; Thomas, Merina; Shahidi, Mahnaz
2015-01-01
Purpose To report outer retinal disruption and uveal effusion following gemcitabine and docetaxel combination therapy. Case Report A 78-year-old woman presented with blurry vision following two cycles of gemcitabine and docetaxel combination chemotherapy for stage IV sarcoma. At presentation, visual acuity (VA) was finger counting and 20/25 in the right and left eyes, respectively. Slit lamp examination and B scan ultrasonography revealed severe uveal effusion in the right eye and choroidal folds in the left eye. Spectral domain optical coherence tomography showed disruption of photoreceptor inner segment ellipsoid band in the right eye. The patient was monitored weekly with ophthalmic examination and B scan ultrasonography, while continuing with gemcitabine monotherapy. At 8 weeks follow up, uveal effusion improved considerably and VA was 20/40 and 20/20 in the right and left eyes, respectively. Conclusions Uveal effusion and outer retinal disruption were reported following gemcitabine and docetaxel chemotherapy. Early detection and close ophthalmic monitoring may allow concurrent cancer treatment and prevention of possible chemotherapy-induced ocular side effects. PMID:25822016
Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive retinitis pigmentosa.
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
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
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
Gao, Shan; van 't Klooster, Ronald; Brandts, Anne; Roes, Stijntje D; Alizadeh Dehnavi, Reza; de Roos, Albert; Westenberg, Jos J M; van der Geest, Rob J
2017-01-01
To develop and evaluate a method that can fully automatically identify the vessel wall boundaries and quantify the wall thickness for both common carotid artery (CCA) and descending aorta (DAO) from axial magnetic resonance (MR) images. 3T MRI data acquired with T 1 -weighted gradient-echo black-blood imaging sequence from carotid (39 subjects) and aorta (39 subjects) were used to develop and test the algorithm. The vessel wall segmentation was achieved by respectively fitting a 3D cylindrical B-spline surface to the boundaries of lumen and outer wall. The tube-fitting was based on the edge detection performed on the signal intensity (SI) profile along the surface normal. To achieve a fully automated process, Hough Transform (HT) was developed to estimate the lumen centerline and radii for the target vessel. Using the outputs of HT, a tube model for lumen segmentation was initialized and deformed to fit the image data. Finally, lumen segmentation was dilated to initiate the adaptation procedure of outer wall tube. The algorithm was validated by determining: 1) its performance against manual tracing; 2) its interscan reproducibility in quantifying vessel wall thickness (VWT); 3) its capability of detecting VWT difference in hypertensive patients compared with healthy controls. Statistical analysis including Bland-Altman analysis, t-test, and sample size calculation were performed for the purpose of algorithm evaluation. The mean distance between the manual and automatically detected lumen/outer wall contours was 0.00 ± 0.23/0.09 ± 0.21 mm for CCA and 0.12 ± 0.24/0.14 ± 0.35 mm for DAO. No significant difference was observed between the interscan VWT assessment using automated segmentation for both CCA (P = 0.19) and DAO (P = 0.94). Both manual and automated segmentation detected significantly higher carotid (P = 0.016 and P = 0.005) and aortic (P < 0.001 and P = 0.021) wall thickness in the hypertensive patients. A reliable and reproducible pipeline for fully automatic vessel wall quantification was developed and validated on healthy volunteers as well as patients with increased vessel wall thickness. This method holds promise for helping in efficient image interpretation for large-scale cohort studies. 4 J. Magn. Reson. Imaging 2017;45:215-228. © 2016 International Society for Magnetic Resonance in Medicine.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wiebe, David J.
A transition duct system (10) for delivering hot-temperature gases from a plurality of combustors in a combustion turbine engine is provided. The system includes an exit piece (16) for each combustor. The exit piece may include a straight path segment (26) and an arcuate connecting segment (36). A respective straight metal liner (92) and an arcuate metal liner (94) may be each inwardly disposed onto a metal outer shell (38) along the straight path segment and the arcuate connecting segment (36) of the exit piece. Structural arrangements are provided to securely attach the respective liners in the presence of substantialmore » flow path pressurization. Cost-effective serviceability of the transition duct systems is realizable since the liners can be readily removed and replaced as needed.« less
Moyers, S.M.
1975-12-16
A device for gripping the exterior surface of a pipe or rod is described which has a plurality of wedges, each having a concave face which engages the outer surface of the pipe and each having a smooth face opposing the concave face. The wedges are seated on and their grooved concave faces are maintained in circular alignment by tapered axial segments of an opening extending through a wedge-seating member. The wedges are allowed to slide across the tapered axial segments so that such a sliding movement acts to vary the diameter of the circular alignment.
The retinal morphology and retinal histochemistry of a twilight fish Corydoras paleatus (J.).
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.
State and location dependence of action potential metabolic cost in cortical pyramidal neurons.
Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P
2012-06-03
Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.
Modeling brain circuitry over a wide range of scales.
Fua, Pascal; Knott, Graham W
2015-01-01
If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation.
Modeling brain circuitry over a wide range of scales
Fua, Pascal; Knott, Graham W.
2015-01-01
If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation. PMID:25904852
NASA Astrophysics Data System (ADS)
Andrade, V.; Rajendran, K.
2010-12-01
The response of subduction zones to large earthquakes varies along their strike, both during the interseismic and post-seismic periods. The December 26, 2004 earthquake nucleated at 3° N latitude and its rupture propagated northward, along the Andaman-Sumatra subduction zone, terminating at 15°N. Rupture speed was estimated at about 2.0 km per second in the northern part under the Andaman region and 2.5 - 2.7 km per second under southern Nicobar and North Sumatra. We have examined the pre and post-2004 seismicity to understand the stress transfer processes within the subducting plate, in the Andaman (10° - 15° N ) and Nicobar (5° - 10° N) segments. The seismicity pattern in these segments shows distinctive characteristics associated with the outer rise, accretionary prism and the spreading ridge, all of which are relatively better developed in the Andaman segment. The Ninety East ridge and the Sumatra Fault System are significant tectonic features in the Nicobar segment. The pre-2004 seismicity in both these segments conform to the steady-state conditions wherein large earthquakes are fewer and compressive stresses dominate along the plate interface. Among the pre-2004 great earthquakes are the 1881 Nicobar and 1941 Andaman events. The former is considered to be a shallow thrust event that generated a small tsunami. Studies in other subduction zones suggest that large outer-rise tensional events follow great plate boundary breaking earthquakes due to the the up-dip transfer of stresses within the subducting plate. The seismicity of the Andaman segment (1977-2004) concurs with the steady-state stress conditions where earthquakes occur dominantly by thrust faulting. The post-2004 seismicity shows up-dip migration along the plate interface, with dominance of shallow normal faulting, including a few outer rise events and some deeper (> 100 km) strike-slip faulting events within the subducting plate. The September 13, 2002, Mw 6.5 thrust faulting earthquake at Diglipur (depth: 21 km) and the August 10, 2009, Mw 7.5 normal faulting earthquake near Coco Island (depth: 22 km), within the northern terminus of the 2004 rupture are cited as examples of the alternating pre and post earthquake stress conditions. The major pre and post 2004 clusters were associated with the Andaman Spreading Ridge (ASR). In the Nicobar segment, the most recent earthquake on June 12, 2010, Mw 7.5 (focal depth: 35 km) occurred very close to the plate boundary, through left lateral strike-slip faulting. A segment that does not feature any active volcanoes unlike its northern and southern counterparts, this part of the plate boundary has generated several right lateral strike-slip earthquakes, mostly on the Sumatra Fault System. The left-lateral strike-slip faulting associated with the June 12 event on a nearly N-S oriented fault plane consistent with the trend of the Ninety East ridge and the occasional left-lateral earthquakes prior to the 2004 mega-thrust event suggest the involvement of the Ninety East ridge in the subduction process.
Eybalin, M; Pujol, R
1987-01-01
Using anatomical criteria, the olivo-cochlear fibers ending in the organ of Corti (efferent fibers) have recently been separated into two systems: a lateral system innervating principally the inner hair cell (IHC) area and a medial system innervating mainly the outer hair cells (OHCs). Electrophysiological and biochemical experiments suggest that acetylcholine may be a neurotransmitter of these efferent fibers. However, efferent synapses that use acetylcholine as neurotransmitter have not yet been identified at the electron microscopic level. Using a pre-embedding immunoelectron microscopic technique with a monoclonal antibody against choline acetyltransferase (ChAT), we localized ChAT-immunostained fibers below both the IHCs and OHCs. In the inner spiral bundle, one type of ChAT-immunostained fibers was vesiculated and formed axo-dendritic synapses with the afferent auditory dendrites contacting the inner hair cells. A second type of ChAT-immunostained fibers seen in the inner spiral bundle was unvesiculated. Unstained vesiculated varicosities synapsing with the auditory dendrites were also seen in the inner spiral bundle. At the OHC level, ChAT immunostaining was found in nearly all the terminals synapsing with the OHCs. The finding of two types of ChAT-immunostained efferent synapses in the organ of Corti, i.e. axo-dendritic synapses in the inner spiral bundle and axo-somatic synapses with the OHCs, supports the hypothesis that both the lateral and the medial olivo-cochlear systems use acetylcholine as a neurotransmitter. The finding of numerous unstained synapses in the inner spiral bundle, and some below OHCs, together with previous data about putative cochlear neurotransmitters, suggests the possibility of additional non-cholinergic olivo-cochlear systems. It might soon appear useful to reclassify efferents according to the nature of the different neurotransmitters/co-transmitters found in the various efferent synapses of the organ of Corti.
Histologic development of the human fovea from midgestation to maturity.
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.
Berkowitz, Bruce A.; Gorgis, Jawan; Patel, Ankit; Baameur, Faiza; Gurevich, Vsevolod V.; Craft, Cheryl M.; Kefalov, Vladimir J.; Roberts, Robin
2015-01-01
Rod tetrameric arrestin 1 (tet-ARR1), stored in the outer nuclear layer/inner segments in the dark, modulates photoreceptor synaptic activity; light exposure stimulates a reduction via translocation to the outer segments for terminating G-protein coupled phototransduction signaling. Here, we test the hypothesis that intraretinal spin-lattice relaxation rate in the rotating frame (1/T1ρ), an endogenous MRI contrast mechanism, has high potential for evaluating rod tet-ARR1 and its reduction via translocation. Dark- and light-exposed mice (null for the ARR1 gene, overexpressing ARR1, diabetic, or wild type with or without treatment with Mn2+, a calcium channel probe) were studied using 1/T1ρ MRI. Immunohistochemistry and single-cell recordings of the retinas were also performed. In wild-type mice with or without treatment with Mn2+, 1/T1ρ of avascular outer retina (64% to 72% depth) was significantly (P < 0.05) greater in the dark than in the light; a significant (P < 0.05) but opposite pattern was noted in the inner retina (<50% depth). Light-evoked outer retina Δ1/T1ρ was absent in ARR1-null mice and supernormal in overexpressing mice. In diabetic mice, the outer retinal Δ1/T1ρ pattern suggested normal dark-to-light tet-ARR1 translocation and chromophore content, conclusions confirmed ex vivo. Light-stimulated Δ1/T1ρ in inner retina was linked to changes in blood volume. Our data support 1/T1ρ MRI for noninvasively assessing rod tet-ARR1 and its reduction via protein translocation, which can be combined with other metrics of retinal function in vivo.—Berkowitz, B. A., Gorgis, J., Patel, A., Baameur, F., Gurevich, V. V., Craft, C. M., Kefalov, V. J., Roberts, R. Development of an MRI biomarker sensitive to tetrameric visual arrestin 1 and its reduction via light-evoked translocation in vivo. PMID:25351983
Fragmentation alters stream fish community structure in dendritic ecological networks.
Perkin, Joshuah S; Gido, Keith B
2012-12-01
Effects of fragmentation on the ecology of organisms occupying dendritic ecological networks (DENs) have recently been described through both conceptual and mathematical models, but few hypotheses have been tested in complex, real-world ecosystems. Stream fishes provide a model system for assessing effects of fragmentation on the structure of communities occurring within DENs, including how fragmentation alters metacommunity dynamics and biodiversity. A recently developed habitat-availability measure, the "dendritic connectivity index" (DCI), allows for assigning quantitative measures of connectivity in DENs regardless of network extent or complexity, and might be used to predict fish community response to fragmentation. We characterized stream fish community structure in 12 DENs in the Great Plains, USA, during periods of dynamic (summer) and muted (fall) discharge regimes to test the DCI as a predictive model of fish community response to fragmentation imposed by road crossings. Results indicated that fish communities in stream segments isolated by road crossings had reduced species richness (alpha diversity) relative to communities that maintained connectivity with the surrounding DEN during summer and fall. Furthermore, isolated communities had greater dissimilarity (beta diversity) to downstream sites notisolated by road crossings during summer and fall. Finally, dissimilarity among communities within DENs decreased as a function of increased habitat connectivity (measured using the DCI) for summer and fall, suggesting that communities within highly connected DENs tend to be more homogeneous. Our results indicate that the DCI is sensitive to community effects of fragmentation in riverscapes and might be used by managers to predict ecological responses to changes in habitat connectivity. Moreover, our findings illustrate that relating structural connectivity of riverscapes to functional connectivity among communities might aid in maintaining metacommunity dynamics and biodiversity in complex dendritic ecosystems.
Automatic segmentation of equine larynx for diagnosis of laryngeal hemiplegia
NASA Astrophysics Data System (ADS)
Salehin, Md. Musfequs; Zheng, Lihong; Gao, Junbin
2013-10-01
This paper presents an automatic segmentation method for delineation of the clinically significant contours of the equine larynx from an endoscopic image. These contours are used to diagnose the most common disease of horse larynx laryngeal hemiplegia. In this study, hierarchal structured contour map is obtained by the state-of-the-art segmentation algorithm, gPb-OWT-UCM. The conic-shaped outer boundary of equine larynx is extracted based on Pascal's theorem. Lastly, Hough Transformation method is applied to detect lines related to the edges of vocal folds. The experimental results show that the proposed approach has better performance in extracting the targeted contours of equine larynx than the results of using only the gPb-OWT-UCM method.
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Exposure to the organophosphorous insecticide fenthion has been associated with retinal degeneration in occupational studies. It has also been associated with pigmentary changes of the retina. Because retinal degeneration and pigmentary changes may be due to dysfunction of t...
Greenstein, Vivienne C.; Duncker, Tobias; Holopigian, Karen; Carr, Ronald E.; Greenberg, Jonathan; Tsang, Stephen H.; Hood, Donald C.
2013-01-01
Purpose To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa (RP). Methods Twenty -one RP patients (21 eyes) with rings/arcs and 21 normals (21 eyes) were studied. Visual sensitivity in the central 10° was measured with microperimetry. Retinal structure was evaluated with spectral domain optical coherence tomography (SD-OCT). 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 (RPE) complex (R+), and outer segment plus RPE complex (OS+) layers were measured. Results were compared to measurements of the distance from the fovea to the inner and outer borders of the ring/arc seen on fundus autofluorescence (FAF). Results Disruption/loss of the IS/OS junction occurred closer to the inner border of the ring/arc and it was closer to the fovea in 8 eyes. For 19 eyes, OS+ and R+ 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. Conclusions Structural and functional changes can occur inside the hyperfluorescent ring/arc in RP. PMID:21909055
Allam, Riham S. H. M.; Ahmed, Rania A.
2015-01-01
Purpose. To study features of the lower punctum in normal subjects using spectral domain anterior segment optical coherence tomography (SD AS-OCT). Methods. Observational cross-sectional study that included 147 punctae (76 subjects). Punctae were evaluated clinically for appearance, position, and size. AS-OCT was used to evaluate the punctal shape, contents, and junction with the vertical canaliculus. Inner and outer diameters as well as depth were measured. Results. 24 males and 52 females (mean age 44 ± 14.35 y) were included. Lower punctum was perceived by OCT to be an area with an outer diameter (mean 412.16 ± 163 μm), inner diameter (mean 233.67 ± 138.73 μm), and depth (mean 251.7 ± 126.58 μm). The OCT measured outer punctum diameter was significantly less than that measured clinically (P: 0.000). Seven major shapes were identified. The junction with the vertical canaliculus was detectable in 44%. Fluid was detected in 34%, one of which had an air bubble; however, 63% of punctae showed no contents and 4% had debris. Conclusions. AS-OCT can be a useful tool in understanding the anatomy of the punctum and distal lacrimal system as well as tear drainage physiology. Measuring the punctum size may play a role in plugs fitting. PMID:26090219
A new fractional order derivative based active contour model for colon wall segmentation
NASA Astrophysics Data System (ADS)
Chen, Bo; Li, Lihong C.; Wang, Huafeng; Wei, Xinzhou; Huang, Shan; Chen, Wensheng; Liang, Zhengrong
2018-02-01
Segmentation of colon wall plays an important role in advancing computed tomographic colonography (CTC) toward a screening modality. Due to the low contrast of CT attenuation around colon wall, accurate segmentation of the boundary of both inner and outer wall is very challenging. In this paper, based on the geodesic active contour model, we develop a new model for colon wall segmentation. First, tagged materials in CTC images were automatically removed via a partial volume (PV) based electronic colon cleansing (ECC) strategy. We then present a new fractional order derivative based active contour model to segment the volumetric colon wall from the cleansed CTC images. In this model, the regionbased Chan-Vese model is incorporated as an energy term to the whole model so that not only edge/gradient information but also region/volume information is taken into account in the segmentation process. Furthermore, a fractional order differentiation derivative energy term is also developed in the new model to preserve the low frequency information and improve the noise immunity of the new segmentation model. The proposed colon wall segmentation approach was validated on 16 patient CTC scans. Experimental results indicate that the present scheme is very promising towards automatically segmenting colon wall, thus facilitating computer aided detection of initial colonic polyp candidates via CTC.
Compensating Faraday Depolarization by Magnetic Helicity in the Solar Corona
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brandenburg, Axel; Ashurova, Mohira B.; Jabbari, Sarah, E-mail: brandenb@nordita.org
A turbulent dynamo in spherical geometry with an outer corona is simulated to study the sign of magnetic helicity in the outer parts. In agreement with earlier studies, the sign in the outer corona is found to be opposite to that inside the dynamo. Line-of-sight observations of polarized emission are synthesized to explore the feasibility of using the local reduction of Faraday depolarization to infer the sign of helicity of magnetic fields in the solar corona. This approach was previously identified as an observational diagnostic in the context of galactic magnetic fields. Based on our simulations, we show that thismore » method can be successful in the solar context if sufficient statistics are gathered by using averages over ring segments in the corona separately for the regions north and south of the solar equator.« less
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
Biological effects of blocking blue and other visible light on the mouse retina.
Narimatsu, Toshio; Ozawa, Yoko; Miyake, Seiji; Kubota, Shunsuke; Yuki, Kenya; Nagai, Norihiro; Tsubota, Kazuo
2014-08-01
To elucidate the biological effects of blocking fluorescent light on the retina using specific blocking materials. Seven- to 8-week-old BALB/c mice were divided into three groups and placed in one of the three boxes: one blocked ultraviolet and violet wavelengths of light (violet blockade), one blocked ultraviolet, violet, blue and some other visible wavelengths (blue-plus blockade), and one allowed most visible light to pass through (control). They were then exposed to a white fluorescent lamp for 1 h at 5.65E-05 mW/cm(2) /s. After treatment, the electroretinogram, retinal outer nuclear layer thickness and retinal outer segment length were measured. In addition, retinal apoptotic cells were quantified by TdT-mediated dUTP nick-end labelling assay and c-Fos messenger RNA, and protein levels were measured by real-time reverse-transcription polymerase chain reaction and immunoblot analyses, respectively. The blue-plus blockade group retained a significantly better electroretinogram response following light exposure than the control or violet blockade groups. The blue-plus blockade group also exhibited greater outer nuclear layer thickness and greater outer-segment length, and fewer apoptotic cells after light exposure than the other groups. The c-Fos messenger RNA and protein levels were substantially reduced in the blue-plus blockade group and reduced to a lesser extent in the violet blockade group. The blockade of blue plus additional visible wavelengths of light was most effective in protecting the retina from light-induced damage. The blockade of violet light alone was also effective in reducing intracellular molecular responses, but these effects were not sufficient for attenuating retinal degeneration. © 2013 Royal Australian and New Zealand College of Ophthalmologists.
Characteristics of intraretinal deposits in acute central serous chorioretinopathy.
Plateroti, Andrea M; Witmer, Matthew T; Kiss, Szilárd; D'Amico, Donald J
2014-01-01
To describe the temporal and spatial characteristics of intraretinal deposits in patients with acute central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (OCT). We retrospectively reviewed the medical records of all patients that presented with acute CSC to Weill Cornell Medical College from January 2012 to May 2013. Acute CSC was defined as a diagnosis of CSC within 4 months of the onset of symptoms. Only one eye per patient was included in the study. Each patient was imaged with spectral domain OCT at the initial office visit. The decision to reimage these patients was made by the treating physician. A total of 25 patients (25 eyes; 17 men and eight nonpregnant women) were included in this review. Seven of 25 patients (28%) demonstrated intraretinal deposits within the outer plexiform layer during the initial OCT, with deposits appearing as early as the same day as the onset of symptoms. A total of 25 of 25 patients (100%) demonstrated intraretinal deposits in the outer nuclear layer upon initial (76%) or follow-up OCT, as early as 2 days after the onset of symptoms. A total of 24 of 25 patients (96%) demonstrated deposits in the external limiting membrane upon a follow-up OCT, as early as 7 days from symptoms appearing. A total of 24 of 25 patients (96%) developed intraretinal deposits in the inner segment/outer segment layer upon follow-up OCT, appearing as early as 14 days after symptom onset. At the time of resolution of subretinal fluid, 20 of 25 patients (80%) demonstrated intraretinal deposits. Intraretinal deposits are present in the outer retinal layers in patients with acute CSC, with the deposits appearing progressively deeper within the retina as the condition evolves. Upon resolution of subretinal fluid, the deposits slowly resolve.
Architecture of the human renal inner medulla and functional implications.
Wei, Guojun; Rosen, Seymour; Dantzler, William H; Pannabecker, Thomas L
2015-10-01
The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. Copyright © 2015 the American Physiological Society.
Neurons of the Dentate Molecular Layer in the Rabbit Hippocampus
Sancho-Bielsa, Francisco J.; Navarro-López, Juan D.; Alonso-Llosa, Gregori; Molowny, Asunción; Ponsoda, Xavier; Yajeya, Javier; López-García, Carlos
2012-01-01
The molecular layer of the dentate gyrus appears as the main entrance gate for information into the hippocampus, i.e., where the perforant path axons from the entorhinal cortex synapse onto the spines and dendrites of granule cells. A few dispersed neuronal somata appear intermingled in between and probably control the flow of information in this area. In rabbits, the number of neurons in the molecular layer increases in the first week of postnatal life and then stabilizes to appear permanent and heterogeneous over the individuals’ life span, including old animals. By means of Golgi impregnations, NADPH histochemistry, immunocytochemical stainings and intracellular labelings (lucifer yellow and biocytin injections), eight neuronal morphological types have been detected in the molecular layer of developing adult and old rabbits. Six of them appear as interneurons displaying smooth dendrites and GABA immunoreactivity: those here called as globoid, vertical, small horizontal, large horizontal, inverted pyramidal and polymorphic. Additionally there are two GABA negative types: the sarmentous and ectopic granular neurons. The distribution of the somata and dendritic trees of these neurons shows preferences for a definite sublayer of the molecular layer: small horizontal, sarmentous and inverted pyramidal neurons are preferably found in the outer third of the molecular layer; vertical, globoid and polymorph neurons locate the intermediate third, while large horizontal and ectopic granular neurons occupy the inner third or the juxtagranular molecular layer. Our results reveal substantial differences in the morphology and electrophysiological behaviour between each neuronal archetype in the dentate molecular layer, allowing us to propose a new classification for this neural population. PMID:23144890
Neurons of the dentate molecular layer in the rabbit hippocampus.
Sancho-Bielsa, Francisco J; Navarro-López, Juan D; Alonso-Llosa, Gregori; Molowny, Asunción; Ponsoda, Xavier; Yajeya, Javier; López-García, Carlos
2012-01-01
The molecular layer of the dentate gyrus appears as the main entrance gate for information into the hippocampus, i.e., where the perforant path axons from the entorhinal cortex synapse onto the spines and dendrites of granule cells. A few dispersed neuronal somata appear intermingled in between and probably control the flow of information in this area. In rabbits, the number of neurons in the molecular layer increases in the first week of postnatal life and then stabilizes to appear permanent and heterogeneous over the individuals' life span, including old animals. By means of Golgi impregnations, NADPH histochemistry, immunocytochemical stainings and intracellular labelings (lucifer yellow and biocytin injections), eight neuronal morphological types have been detected in the molecular layer of developing adult and old rabbits. Six of them appear as interneurons displaying smooth dendrites and GABA immunoreactivity: those here called as globoid, vertical, small horizontal, large horizontal, inverted pyramidal and polymorphic. Additionally there are two GABA negative types: the sarmentous and ectopic granular neurons. The distribution of the somata and dendritic trees of these neurons shows preferences for a definite sublayer of the molecular layer: small horizontal, sarmentous and inverted pyramidal neurons are preferably found in the outer third of the molecular layer; vertical, globoid and polymorph neurons locate the intermediate third, while large horizontal and ectopic granular neurons occupy the inner third or the juxtagranular molecular layer. Our results reveal substantial differences in the morphology and electrophysiological behaviour between each neuronal archetype in the dentate molecular layer, allowing us to propose a new classification for this neural population.
Otto Friedrich Karl Deiters (1834-1863).
Deiters, Vera S; Guillery, R W
2013-06-15
Otto Deiters, for whom the lateral vestibular nucleus and the supporting cells of the outer auditory hair cells were named, died in 1863 aged 29. He taught in the Bonn Anatomy Department, had an appointment in the University Clinic, and ran a small private practice. He published articles on the cell theory, the structure and development of muscle fibers, the inner ear, leukaemia, and scarlet fever. He was the second of five surviving children in an academic family whose private correspondence revealed him to be a young man with limited social skills and high ambitions to complete a deeply original study of the brainstem and spinal cord. However, first his father and then his younger brother died, leaving him and his older brother responsible for a suddenly impecunious family as he failed to gain academic promotion. Otto died of typhus two years after his younger brother's death, leaving his greatest scientific achievement to be published posthumously. He showed that most nerve cells have a single axon and several dendrites; he recognized the possibility that nerve cells might be functionally polarized and produced the first illustrations of synaptic inputs to dendrites from what he termed a second system of nerve fibers. Copyright © 2012 Wiley Periodicals, Inc.
Burgess, Stacey L; Buonomo, Erica; Carey, Maureen; Cowardin, Carrie; Naylor, Caitlin; Noor, Zannatun; Wills-Karp, Marsha; Petri, William A
2014-11-04
There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica is a major cause of amebic diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolytica infection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB(+) to an SFB(-) mouse was sufficient to provide protection against E. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells. Entamoeba histolytica is the causative agent of amebiasis, an infectious disease that contributes significantly to morbidity and mortality due to diarrhea in the developing world. We showed in a murine model that colonization with the commensal members of the Clostridia known as SFB provides protection against E. histolytica and that dendritic cells from SFB-colonized mice alone can recapitulate protection. Understanding interactions between enteropathogens, commensal intestinal bacteria, and the mucosal immune response, including dendritic cells, will help in the development of effective treatments for this disease and other infectious and inflammatory diseases. The demonstration of immune-mediated protection due to communication from the microbiome to the bone marrow represents an emerging field of study that will yield unique approaches to the development of these treatments. Copyright © 2014 Burgess et al.
Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity*
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
Tsina, Efthymia; Chen, Chunhe; Koutalos, Yiannis; Ala-Laurila, Petri; Tsacopoulos, Marco; Wiggert, Barbara; Crouch, Rosalie K.; Cornwall, M. Carter
2004-01-01
The visual cycle comprises a sequence of reactions that regenerate the visual pigment in photoreceptors during dark adaptation, starting with the reduction of all-trans retinal to all-trans retinol and its clearance from photoreceptors. We have followed the reduction of retinal and clearance of retinol within bleached outer segments of red rods isolated from salamander retina by measuring its intrinsic fluorescence. Following exposure to a bright light (bleach), increasing fluorescence intensity was observed to propagate along the outer segments in a direction from the proximal region adjacent to the inner segment toward the distal tip. Peak retinol fluorescence was achieved after ∼30 min, after which it declined very slowly. Clearance of retinol fluorescence is considerably accelerated by the presence of the exogenous lipophilic substances IRBP (interphotoreceptor retinoid binding protein) and serum albumin. We have used simultaneous fluorometric and electrophysiological measurements to compare the rate of reduction of all-trans retinal to all-trans retinol to the rate of recovery of flash response amplitude in these cells in the presence and absence of IRBP. We find that flash response recovery in rods is modestly accelerated in the presence of extracellular IRBP. These results suggest such substances may participate in the clearance of retinoids from rod photoreceptors, and that this clearance, at least in rods, may facilitate dark adaptation by accelerating the clearance of photoproducts of bleaching. PMID:15452202
Airfoil nozzle and shroud assembly
Shaffer, James E.; Norton, Paul F.
1997-01-01
An airfoil and nozzle assembly including an outer shroud having a plurality of vane members attached to an inner surface and having a cantilevered end. The assembly further includes a inner shroud being formed by a plurality of segments. Each of the segments having a first end and a second end and having a recess positioned in each of the ends. The cantilevered end of the vane member being positioned in the recess. The airfoil and nozzle assembly being made from a material having a lower rate of thermal expansion than that of the components to which the airfoil and nozzle assembly is attached.
CHEN, ROYCE W. S.; GREENBERG, JONATHAN P.; LAZOW, MARGOT A.; RAMACHANDRAN, RITHU; LIMA, LUIZ H.; HWANG, JOHN C.; SCHUBERT, CARL; BRAUNSTEIN, ALEXANDRA; ALLIKMETS, RANDO; TSANG, STEPHEN H.
2015-01-01
PURPOSE To test the hypothesis that the evaluation of retinal structure can have diagnostic value in differentiating between incomplete congenital stationary night blindness (CSNB2) and retinitis pigmentosa (RP). To compare retinal thickness differences between patients with CSNB2 and myopic controls. DESIGN Prospective cross-sectional study. METHODS Ten eyes of 5 patients diagnosed with CSNB2 (4 X-linked recessive, 1 autosomal recessive) and 6 eyes of 3 patients with RP (2 autosomal dominant, 1 autosomal recessive) were evaluated with spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF). Diagnoses of CSNB2 and RP were confirmed by full-field electroretinography (ERG). Manual segmentation of retinal layers, aided by a computer program, was performed by 2 professional segmenters on SD OCT images of all CSNB2 patients and 4 age-similar, normal myopic controls. Seven patients were screened for mutations with congenital stationary night blindness and RP genotyping arrays. RESULTS Patients with CSNB2 had specific findings on SD OCT and FAF that were distinct from those found in RP. CSNB2 patients showed qualitatively normal SD OCT results with preserved photoreceptor inner segment/outer segment junction, whereas this junction was lost in RP patients. In addition, CSNB2 patients had normal FAF images, whereas patients with RP demonstrated a ring of increased autofluorescence around the macula. On SD OCT segmentation, the inner and outer retinal layers of both X-linked recessive and autosomal recessive CSNB2 patients were thinner compared with those of normal myopic controls, with means generally outside of normal 95% confidence intervals. The only layers that demonstrated similar thickness between CSNB2 patients and the controls were the retinal nerve fiber layer and, temporal to the fovea, the combined outer segment layer and retinal pigment epithelium. A proband and his 2 affected brothers from a family segregating X-linked recessive CSNB2 had a mutation, p.R614X, in the gene encoding calcium channel, α 1F subunit. CONCLUSIONS CSNB2 patients (X-linked recessive and autosomal recessive) had significantly thinner retinas than myopic controls. However, they demonstrated qualitatively normal SD OCT and FAF images, and therefore can be differentiated from RP patients with these techniques. Although ERG testing remains the gold standard for the diagnosis of these conditions, FAF and SD OCT systems are more widely available to community ophthalmologists, offer shorter acquisition times, and, unlike ERG, can be performed on the same day as the initial clinic visit. Therefore, as a supplement to ERG and genetic testing, we advocate the use of FAF and SD OCT in the examination of patients with CSNB2 and RP. PMID:21920492
McIntire, William R.
1983-01-01
A cylindrical radiant energy collector is provided which includes a reflector spaced apart from an energy absorber. The reflector is of a particular shape which ideally eliminates gap losses. The reflector includes a plurality of adjacent facets of V shaped segments sloped so as to reflect all energy entering between said absorber and said reflector onto said absorber. The outer arms of each facet are sloped to reflect one type of extremal ray in a line substantially tangent to the lowermost extremity of the energy absorber. The inner arms of the facets are sloped to reflect onto the absorber all rays either falling directly thereon or as a result of reflection from an outer arm.
Glaucoma diagnosis by mapping macula with Fourier domain optical coherence tomography
NASA Astrophysics Data System (ADS)
Tan, Ou; Lu, Ake; Chopra, Vik; Varma, Rohit; Hiroshi, Ishikawa; Schuman, Joel; Huang, David
2008-03-01
A new image segmentation method was developed to detect macular retinal sub-layers boundary on newly-developed Fourier-Domain Optical Coherence Tomography (FD-OCT) with macular grid scan pattern. The segmentation results were used to create thickness map of macular ganglion cell complex (GCC), which contains the ganglion cell dendrites, cell bodies and axons. Overall average and several pattern analysis parameters were defined on the GCC thickness map and compared for the diagnosis of glaucoma. Intraclass correlation (ICC) is used to compare the reproducibility of the parameters. Area under receiving operative characteristic curve (AROC) was calculated to compare the diagnostic power. The result is also compared to the output of clinical time-domain OCT (TD-OCT). We found that GCC based parameters had good repeatability and comparable diagnostic power with circumpapillary nerve fiber layer (cpNFL) thickness. Parameters based on pattern analysis can increase the diagnostic power of GCC macular mapping.
Pang, Jincheng; Özkucur, Nurdan; Ren, Michael; Kaplan, David L; Levin, Michael; Miller, Eric L
2015-11-01
Phase Contrast Microscopy (PCM) is an important tool for the long term study of living cells. Unlike fluorescence methods which suffer from photobleaching of fluorophore or dye molecules, PCM image contrast is generated by the natural variations in optical index of refraction. Unfortunately, the same physical principles which allow for these studies give rise to complex artifacts in the raw PCM imagery. Of particular interest in this paper are neuron images where these image imperfections manifest in very different ways for the two structures of specific interest: cell bodies (somas) and dendrites. To address these challenges, we introduce a novel parametric image model using the level set framework and an associated variational approach which simultaneously restores and segments this class of images. Using this technique as the basis for an automated image analysis pipeline, results for both the synthetic and real images validate and demonstrate the advantages of our approach.
16 CFR 305.3 - Description of covered products.
Code of Federal Regulations, 2011 CFR
2011-01-01
... operation. Some models may require user intervention to initiate these different segments of the cycle after... inner reflective coating on the outer bulb to direct the light, an R, PAR, or similar bulb shapes... bulb to direct the light, an R, PAR, ER, BR, BPAR, or similar bulb shapes with E26 medium screw bases...
Magnetic Field Analysis of Lorentz Motors Using a Novel Segmented Magnetic Equivalent Circuit Method
Qian, Junbing; Chen, Xuedong; Chen, Han; Zeng, Lizhan; Li, Xiaoqing
2013-01-01
A simple and accurate method based on the magnetic equivalent circuit (MEC) model is proposed in this paper to predict magnetic flux density (MFD) distribution of the air-gap in a Lorentz motor (LM). In conventional MEC methods, the permanent magnet (PM) is treated as one common source and all branches of MEC are coupled together to become a MEC network. In our proposed method, every PM flux source is divided into three sub-sections (the outer, the middle and the inner). Thus, the MEC of LM is divided correspondingly into three independent sub-loops. As the size of the middle sub-MEC is small enough, it can be treated as an ideal MEC and solved accurately. Combining with decoupled analysis of outer and inner MECs, MFD distribution in the air-gap can be approximated by a quadratic curve, and the complex calculation of reluctances in MECs can be avoided. The segmented magnetic equivalent circuit (SMEC) method is used to analyze a LM, and its effectiveness is demonstrated by comparison with FEA, conventional MEC and experimental results. PMID:23358368
Cho, Kyoung-in; Haney, Victoria; Yoon, Dosuk; Hao, Yin; Ferreira, Paulo A
2015-12-21
Morphological disintegration of neurons is coupled invariably to neural death. In particular, disruption of outer segments of photoreceptor neurons triggers photoreceptor death regardless of the pathological stressors. We show that Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) mice with mutations in SUMO-binding motif (SBM) of cyclophilin-like domain (CLD) of Ran-binding protein 2 (Ranbp2) expressed in a null Ranbp2 background lack untoward effects in photoreceptors in the absence of light-stress. However, compared to wild type photoreceptors, light-stress elicits profound disintegration of outer segments of Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) with paradoxical age-dependent resistance of photoreceptors to death and genotype-independent activation of caspases. Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) exhibit photoreceptor death-independent changes in ubiquitin-proteasome system (UPS), but death-dependent increase of ubiquitin carrier protein 9(ubc9) levels. Hence, insidious functional impairment of SBM of Ranbp2's CLD promotes neuroprotection and uncoupling of photoreceptor degeneration and death against phototoxicity. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Apparatus and methods for impingement cooling of a side wall of a turbine nozzle segment
Burdgick, Steven Sebastian
2002-01-01
A gas turbine nozzle segment has outer and inner bands and a vane therebetween. Each band includes a nozzle wall, a side wall, a cover and an impingement plate between the cover and the nozzle wall defining two cavities on opposite sides of the impingement plate. Cooling steam is supplied to one cavity for flow through apertures of the impingement plate to cool the nozzle wall. The side wall of the band and inturned flange define with the nozzle wall an undercut region. The impingement plate has a turned flange welded to the inturned flange. A backing plate overlies the turned flange and aligned apertures are formed through the backing plate and turned flange to direct and focus cooling flow onto the side wall of the nozzle segment.
Support pedestals for interconnecting a cover and nozzle band wall in a gas turbine nozzle segment
Yu, Yufeng Phillip; Itzel, Gary Michael; Webbon, Waylon Willard; Bagepalli, Radhakrishna; Burdgick, Steven Sebastian; Kellock, Iain Robertson
2002-01-01
A gas turbine nozzle segment has outer and inner band portions. Each band portion includes a nozzle wall, a cover and an impingement plate between the cover and nozzle wall defining two cavities on opposite sides of the impingement plate. Cooling steam is supplied to one cavity for flow through the apertures of the impingement plate to cool the nozzle wall. Structural pedestals interconnect the cover and nozzle wall and pass through holes in the impingement plate to reduce localized stress otherwise resulting from a difference in pressure within the chamber of the nozzle segment and the hot gas path and the fixed turbine casing surrounding the nozzle stage. The pedestals may be cast or welded to the cover and nozzle wall.
Tvedten, Harold; Hillström, Anna
2013-06-01
A 6-year-old Wirehair Dachshund had a meningioma around the optic nerve that caused exophthalmos. A benign mesenchymal tumor was suspected based on the cytologic pattern of a fine-needle aspirate, and a meningioma was diagnosed by histopathologic examination. In addition to the meningioma cells, the cytologic smears included groups of cells from apparently 4 layers of normal retina. In particular, uniform rod-shaped structures in the cytologic sample could suggest rod-shaped bacteria, but these structures were identified as cylindrical outer segments of photoreceptor rod cells. Other retinal structures recognized included pigmented epithelial layer cells with their uniquely formed pigment granules, the characteristic bi-lobed, cleaved nuclei from the outer nuclear layer, and nerve tissue likely from the outer plexiform layer of the retina. © 2013 American Society for Veterinary Clinical Pathology.
Three-dimensional spectral domain optical coherence tomography in X linked foveal retinoschisis
Saxena, Sandeep; Manisha; Meyer, Carsten H
2013-01-01
Spectral domain optical coherence tomography (SD-OCT) was performed in two cases of bilateral X linked foveal retinoschisis of different age groups. On fundus examination spoke wheel and honeycomb pattern of cysts were observed along with retinal nerve fibre layer (RNFL) defects. On SD-OCT, schisis was observed in the outer plexiform layer. External limiting membrane disruption was observed in the subfoveal area, along with disruption of outer nuclear layer (ONL) and inner–outer segment junction. Elevation of ONL due to tractional pull of central palisade was a novel observation. Retinoschisis extended beyond the optic disc up to the nasal region. Extracted RNFL tomogram presented an unprecedented visualisation of schisis along 360° of the optic disc. Tractional elevation in the foveal area and schisis involving nasal region, not observed upon clinical examination, was highlighted on SD-OCT. This investigative modality is an important adjunct in the assessment of foveal retinoschisis. PMID:23563673
Sanit, Sangob; Sukontason, Kom; Kurahashi, Hiromu; Tomberlin, Jeffery K; Wannasan, Anchalee; Kraisittipanit, Rungroj; Sukontason, Kabkaew L
2017-12-01
Lucilia sinensis Aubertin (Diptera: Calliphoridae) is a blow fly species of potential forensic importance since adults are attracted to, and colonize, decomposing vertebrate remains. Blow fly larvae associated with human corpses can be useful evidence in forensic investigations; however, their use is dependent in most cases on proper species identification and availability of developmental data. For identification, morphological information on each life stage is traditionally used. We used scanning electron microscopy (SEM) to examine the ultrastructure of eggs, all instars, and puparia, of L. sinensis. The important characteristics used to differentiate L. sinensis from other species are provided. Distinctive features of the eggs are the slight widening median area extending almost the entire length. The last abdominal segment of the first instar bears elongated outer ventral tubercles along the rim of the last abdominal segment. These tubercles, as well as the well developed median and outer dorsal tubercles, are more prominent in the second and third instars. The surface integument of the tubercles is equipped with circular rows of microtrichia. Pairs of inner dorsal tubercle are absent. Each anterior spiracle is comprised of 9-12 papillae arrange in a single row in the second and third instars. As for the third instar, the dorsal spines between the first and second thoracic segments are delicate, narrow, small, and close together (as row or set). The peristigmatic tufts adjacent to the posterior spiracle of the third instar are moderately branches of short, fine hairs, but minute in puparia. In conclusion, the prominent outer ventral tubercle in all instars and puparia is a new diagnostic feature of L. sinensis and helpful in differentiating it from other Lucilia species that are forensically important. The description of immature L. sinensis in this study will be useful for forensic entomologists in countries where this species exists. Copyright © 2017 Elsevier B.V. All rights reserved.
Role of Caspase-3 in acute light damage to retina of rats.
Wang, Xiao; Hu, Shi-Xing; Li, Wei; Lin, Shao-Chun
2007-03-01
To investigate the role of Caspase-3 in retinal damage caused by light exposure in rats. Light injury to retina was induced by persistent exposure to illumination (intensity: 30 000 +/- 50 lux) of operating microscope for 30 minutes in the right eyes of Sprague-Dawley rats. The pathological changes of retina were observed under optical and electron microscopies at different time points, which were 6 hours, 1, 3, 7, and 15 days after the light exposure. Apoptosis of retinal cells was analyzed by flow cytometry. The activity of Caspase-3 was evaluated by using the Caspase-3 assay kit. At the same time, the expression of Caspase-3 protease was determined with Western blot analysis. The examination results of optical and transmission electron microscopes showed that edema of inner and outer segments of the retina, especially the chondriosome inside the inner segment, became obvious 6 hours after the light exposure. The change was deteriorated along with the increasing time. The structures of the discoidal valve dissociated in the outer segment simultaneously. Disorderly arranged nuclei, karyopycnosis, and thinning in the outer nuclear layer were observed. The retinal pigment epithelium almost disappeared during the later stage. The staining results of Annexin-V combined with PI demonstrated that the proportion of apoptotic cells increased with time. The proportion between 7th day (82.7%) and 15th day (80.4%), however, showed no significant difference. Caspase-3 became remarkably active with the lapse of time, which increased from 0.02 at 6th hour to the peak of 9.8 at 7th day before it started to descend. The Western blot detected a expression of the active form of Caspase-3 at 7th day and 15th day. Apoptosis of photoreceptor cells is markedly involved in the light damage and Caspase-3 protease may play an important role in the apoptotic process of the retina after light exposure in rats.
Wong, Bernice H; Chan, Jia Pei; Cazenave-Gassiot, Amaury; Poh, Rebecca W; Foo, Juat Chin; Galam, Dwight L A; Ghosh, Sujoy; Nguyen, Long N; Barathi, Veluchamy A; Yeo, Sia W; Luu, Chi D; Wenk, Markus R; Silver, David L
2016-05-13
Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth. Here we demonstrate that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of Mfsd2a expression in the eye. Eyes from whole body Mfsd2a-deficient (KO) mice, but not endothelium-specific Mfsd2a-deficient mice, were DHA-deficient and had significantly reduced LPC/DHA transport in vivo Fluorescein angiography indicated normal blood-retinal barrier function. Histological and electron microscopic analysis indicated that Mfsd2a KO mice exhibited a specific reduction in outer rod segment length, disorganized outer rod segment discs, and mislocalization of and reduction in rhodopsin early in postnatal development without loss of photoreceptors. Minor photoreceptor cell loss occurred in adult Mfsd2a KO mice, but electroretinography indicated visual function was normal. The developing eyes of Mfsd2a KO mice had activated microglia and up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of LPC transport. These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Lateral diffusion of rhodopsin in photoreceptor membrane: a reappraisal.
Govardovskii, Victor I; Korenyak, Darya A; Shukolyukov, Sergei A; Zueva, Lidia V
2009-08-28
In a series of works between 1972 and 1984, it was established that rhodopsin undergoes rotational and lateral Brownian motion in the plane of photoreceptor membrane. The concept of free movement of proteins of phototransduction cascade is an essential principle of the present scheme of vertebrate phototransduction. This has recently been challenged by findings that show that in certain conditions rhodopsin in the membrane may be dimeric and form extended areas of paracrystalline organization. Such organization seems incompatible with earlier data on free rhodopsin diffusion. Thus we decided to reinvestigate lateral diffusion of rhodopsin and products of its photolysis in photoreceptor membrane specifically looking for indications of possible oligomeric organization. Diffusion exchange by rhodopsin and its photoproducts between bleached and unbleached halves of rod outer segment was traced using high-speed dichroic microspectrophotometer. Measurements were conducted on amphibian (frog, toad, and salamander) and gecko rods. We found that the curves that are supposed to reflect the process of diffusion equilibration of rhodopsin in nonuniformly bleached outer segment largely show production of long-lived bleaching intermediate, metarhodopsin III (Meta III). After experimental elimination of Meta III contribution, we observed rhodopsin equilibration time constant was threefold to tenfold longer than estimated previously. However, after proper correction for the geometry of rod discs, it translates into generally accepted value of diffusion constant of approximately 5 x 10(-9) cm(2) s(-1). Yet, we found that there exists an immobile rhodopsin fraction whose size can vary from virtually zero to 100%, depending on poorly defined factors. Controls suggest that the formation of the immobile fraction is not due to fragmentation of rod outer segment discs but supposedly reflects oligomerization of rhodopsin. Implications of the new findings for the present model of phototransduction are discussed. We hypothesize that formation of paracrystalline areas, if controlled physiologically, could be an extra mechanism of cascade regulation.
The role of the notochord in amniote vertebral column segmentation.
Ward, Lizzy; Pang, Angel S W; Evans, Susan E; Stern, Claudio D
2018-07-01
The vertebral column is segmented, comprising an alternating series of vertebrae and intervertebral discs along the head-tail axis. The vertebrae and outer portion (annulus fibrosus) of the disc are derived from the sclerotome part of the somites, whereas the inner nucleus pulposus of the disc is derived from the notochord. Here we investigate the role of the notochord in vertebral patterning through a series of microsurgical experiments in chick embryos. Ablation of the notochord causes loss of segmentation of vertebral bodies and discs. However, the notochord cannot segment in the absence of the surrounding sclerotome. To test whether the notochord dictates sclerotome segmentation, we grafted an ectopic notochord. We find that the intrinsic segmentation of the sclerotome is dominant over any segmental information the notochord may possess, and no evidence that the chick notochord is intrinsically segmented. We propose that the segmental pattern of vertebral bodies and discs in chick is dictated by the sclerotome, which first signals to the notochord to ensure that the nucleus pulposus develops in register with the somite-derived annulus fibrosus. Later, the notochord is required for maintenance of sclerotome segmentation as the mature vertebral bodies and intervertebral discs form. These results highlight differences in vertebral development between amniotes and teleosts including zebrafish, where the notochord dictates the segmental pattern. The relative importance of the sclerotome and notochord in vertebral patterning has changed significantly during evolution. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Towards Artificial Speech Therapy: A Neural System for Impaired Speech Segmentation.
Iliya, Sunday; Neri, Ferrante
2016-09-01
This paper presents a neural system-based technique for segmenting short impaired speech utterances into silent, unvoiced, and voiced sections. Moreover, the proposed technique identifies those points of the (voiced) speech where the spectrum becomes steady. The resulting technique thus aims at detecting that limited section of the speech which contains the information about the potential impairment of the speech. This section is of interest to the speech therapist as it corresponds to the possibly incorrect movements of speech organs (lower lip and tongue with respect to the vocal tract). Two segmentation models to detect and identify the various sections of the disordered (impaired) speech signals have been developed and compared. The first makes use of a combination of four artificial neural networks. The second is based on a support vector machine (SVM). The SVM has been trained by means of an ad hoc nested algorithm whose outer layer is a metaheuristic while the inner layer is a convex optimization algorithm. Several metaheuristics have been tested and compared leading to the conclusion that some variants of the compact differential evolution (CDE) algorithm appears to be well-suited to address this problem. Numerical results show that the SVM model with a radial basis function is capable of effective detection of the portion of speech that is of interest to a therapist. The best performance has been achieved when the system is trained by the nested algorithm whose outer layer is hybrid-population-based/CDE. A population-based approach displays the best performance for the isolation of silence/noise sections, and the detection of unvoiced sections. On the other hand, a compact approach appears to be clearly well-suited to detect the beginning of the steady state of the voiced signal. Both the proposed segmentation models display outperformed two modern segmentation techniques based on Gaussian mixture model and deep learning.
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.
Film cooling for a closed loop cooled airfoil
Burdgick, Steven Sebastian; Yu, Yufeng Phillip; Itzel, Gary Michael
2003-01-01
Turbine stator vane segments have radially inner and outer walls with vanes extending therebetween. The inner and outer walls are compartmentalized and have impingement plates. Steam flowing into the outer wall plenum passes through the impingement plate for impingement cooling of the outer wall upper surface. The spent impingement steam flows into cavities of the vane having inserts for impingement cooling the walls of the vane. The steam passes into the inner wall and through the impingement plate for impingement cooling of the inner wall surface and for return through return cavities having inserts for impingement cooling of the vane surfaces. At least one film cooling hole is defined through a wall of at least one of the cavities for flow communication between an interior of the cavity and an exterior of the vane. The film cooling hole(s) are defined adjacent a potential low LCF life region, so that cooling medium that bleeds out through the film cooling hole(s) reduces a thermal gradient in a vicinity thereof, thereby the increase the LCF life of that region.
Burdgick, Steven Sebastian; Burns, James Lee
2002-01-01
A nozzle segment for a gas turbine includes inner and outer band portions and a vane extending between the band portions. The inner and outer band portions are each divided into first and second plenums separated by an impingement plate. Cooling steam is supplied to the first cavity for flow through the apertures to cool the outer nozzle wall. The steam flows through a leading edge cavity in the vane into the first cavity of the inner band portion for flow through apertures of the impingement plate to cool the inner nozzle wall. Spent cooling steam flows through a plurality of cavities in the vane, exiting through an exit chimney in the outer band. The exit chimney is secured at its inner end directly to the nozzle vane wall surrounding the exit cavities, to the margin of the impingement plate at a location intermediate the ends of the exit chimney and to margins of an opening through the cover whereby each joint is externally accessible for joint formation and for subsequent inspection.
Steam exit flow design for aft cavities of an airfoil
Storey, James Michael; Tesh, Stephen William
2002-01-01
Turbine stator vane segments have inner and outer walls with vanes extending therebetween. The inner and outer walls have impingement plates. Steam flowing into the outer wall passes through the impingement plate for impingement cooling of the outer wall surface. The spent impingement steam flows into cavities of the vane having inserts for impingement cooling the walls of the vane. The steam passes into the inner wall and through the impingement plate for impingement cooling of the inner wall surface and for return through return cavities having inserts for impingement cooling of the vane surfaces. A skirt or flange structure is provided for shielding the steam cooling impingement holes adjacent the inner wall aerofoil fillet region of the nozzle from the steam flow exiting the aft nozzle cavities. Moreover, the gap between the flash rib boss and the cavity insert is controlled to minimize the flow of post impingement cooling media therebetween. This substantially confines outflow to that exiting via the return channels, thus furthermore minimizing flow in the vicinity of the aerofoil fillet region that may adversely affect impingement cooling thereof.
Cone structure in patients with usher syndrome type III and mutations in the Clarin 1 gene.
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.
Regulated efflux of photoreceptor outer segment-derived cholesterol by human RPE cells.
Storti, Federica; Raphael, Gabriele; Griesser, Vera; Klee, Katrin; Drawnel, Faye; Willburger, Carolin; Scholz, Rebecca; Langmann, Thomas; von Eckardstein, Arnold; Fingerle, Jürgen; Grimm, Christian; Maugeais, Cyrille
2017-12-01
Genetic studies have linked age-related macular degeneration (AMD) to genes involved in high-density lipoprotein (HDL) metabolism, including ATP-binding cassette transporter A1 (ABCA1). The retinal pigment epithelium (RPE) handles large amounts of lipids, among others cholesterol, partially derived from internalized photoreceptor outer segments (OS) and lipids physiologically accumulate in the aging eye. To analyze the potential function of ABCA1 in the eye, we measured cholesterol efflux, the first step of HDL generation, in RPE cells. We show the expression of selected genes related to HDL metabolism in mouse and human eyecups as well as in ARPE-19 and human primary RPE cells. Immunofluorescence staining revealed localization of ABCA1 on both sides of polarized RPE cells. This was functionally confirmed by directional efflux to apolipoprotein AI (ApoA-I) of 3 H-labeled cholesterol given to the cells via serum or via OS. ABCA1 expression and activity was modulated using a liver-X-receptor (LXR) agonist and an ABCA1 neutralizing antibody, demonstrating that the efflux was ABCA1-dependent. We concluded that the ABCA1-mediated lipid efflux pathway, and hence HDL biosynthesis, is functional in RPE cells towards both the basal (choroidal) and apical (subretinal) space. Impaired activity of the pathway might cause age-related perturbations of lipid homeostasis in the outer retina and thus may contribute to disease development and/or progression. Copyright © 2017 Elsevier Ltd. All rights reserved.
Quantification of Peripapillary Sparing and Macular Involvement in Stargardt Disease (STGD1)
Rhee, David W.; Smith, R. Theodore; Tsang, Stephen H.; Allikmets, Rando; Chang, Stanley; Lazow, Margot A.; Hood, Donald C.; Greenstein, Vivienne C.
2011-01-01
Purpose. To quantify and compare structure and function across the macula and peripapillary area in Stargardt disease (STGD1). Methods. Twenty-seven patients (27 eyes) and 12 age-similar controls (12 eyes) were studied. Patients were classified on the basis of full-field electroretinogram (ERG) results. Fundus autofluorescence (FAF) and spectral domain-optical coherence tomography (SD-OCT) horizontal line scans were obtained through the fovea and peripapillary area. The thicknesses of the outer nuclear layer plus outer plexiform layer (ONL+), outer segment (OS), and retinal pigment epithelium (RPE) were measured through the fovea, and peripapillary areas from 1° to 4° temporal to the optic disc edge using a computer-aided, manual segmentation technique. Visual sensitivities in the central 10° were assessed using microperimetry and related to retinal layer thicknesses. Results. Compared to the central macula, the differences between controls and patients in ONL+, OS, and RPE layer thicknesses were less in the nasal and temporal macula. Relative sparing of the ONL+ and/or OS layers was detected in the nasal (i.e., peripapillary) macula in 8 of 13 patients with extramacular disease on FAF; relative functional sparing was also detected in this subgroup. All 14 patients with disease confined to the central macula, as detected on FAF, showed ONL+ and OS layer thinning in regions of normal RPE thickness. Conclusions. Relative peripapillary sparing was detected in STGD1 patients with extramacular disease on FAF. Photoreceptor thinning may precede RPE degeneration in STGD1. PMID:21873672
Wanek, Justin; Blair, Norman P.; Chau, Felix Y.; Lim, Jennifer I.; Leiderman, Yannek I.; Shahidi, Mahnaz
2016-01-01
Purpose This article reports a method for en face optical coherence tomography (OCT) imaging and quantitative assessment of alterations in both thickness and reflectance of individual retinal layers at different stages of diabetic retinopathy (DR). Methods High-density OCT raster volume scans were acquired in 29 diabetic subjects divided into no DR (NDR) or non-proliferative DR (NPDR) groups and 22 control subjects (CNTL). A customized image segmentation method identified eight retinal layer interfaces and generated en face thickness maps and reflectance images for nerve fiber layer (NFL), ganglion cell and inner plexiform layers (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE). Mean thickness and intensity values were calculated in nine macular subfields for each retinal layer. Results En face thickness maps and reflectance images of retinal layers in CNTL subjects corresponded to normal retinal anatomy. Total retinal thickness correlated negatively with age in nasal subfields (R ≤−0.31; P ≤ 0.03, N = 51). In NDR subjects, NFL and OPL thickness were decreased (P = 0.05), and ONL thickness was increased (P = 0.04) compared to CNTL. In NPDR subjects, GCLIPL thickness was increased in perifoveal subfields (P < 0.05) and INL intensity was higher in all macular subfields (P = 0.04) compared to CNTL. Conclusions Depth and spatially resolved retinal thickness and reflectance measurements are potential biomarkers for assessment and monitoring of DR. PMID:27409491
CT volumetry of the skeletal tissues
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brindle, James M.; Alexandre Trindade, A.; Pichardo, Jose C.
2006-10-15
Computed tomography (CT) is an important and widely used modality in the diagnosis and treatment of various cancers. In the field of molecular radiotherapy, the use of spongiosa volume (combined tissues of the bone marrow and bone trabeculae) has been suggested as a means to improve the patient-specificity of bone marrow dose estimates. The noninvasive estimation of an organ volume comes with some degree of error or variation from the true organ volume. The present study explores the ability to obtain estimates of spongiosa volume or its surrogate via manual image segmentation. The variation among different segmentation raters was exploredmore » and found not to be statistically significant (p value >0.05). Accuracy was assessed by having several raters manually segment a polyvinyl chloride (PVC) pipe with known volumes. Segmentation of the outer region of the PVC pipe resulted in mean percent errors as great as 15% while segmentation of the pipe's inner region resulted in mean percent errors within {approx}5%. Differences between volumes estimated with the high-resolution CT data set (typical of ex vivo skeletal scans) and the low-resolution CT data set (typical of in vivo skeletal scans) were also explored using both patient CT images and a PVC pipe phantom. While a statistically significant difference (p value <0.002) between the high-resolution and low-resolution data sets was observed with excised femoral heads obtained following total hip arthroplasty, the mean difference between high-resolution and low-resolution data sets was found to be only 1.24 and 2.18 cm{sup 3} for spongiosa and cortical bone, respectively. With respect to differences observed with the PVC pipe, the variation between the high-resolution and low-resolution mean percent errors was a high as {approx}20% for the outer region volume estimates and only as high as {approx}6% for the inner region volume estimates. The findings from this study suggest that manual segmentation is a reasonably accurate and reliable means for the in vivo estimation of spongiosa volume. This work also provides a foundation for future studies where spongiosa volumes are estimated by various raters in more comprehensive CT data sets.« less
In vitro suppression of dendritic cells by Helicobacter pylori OipA.
Teymournejad, Omid; Mobarez, Ashraf M; Hassan, Zuhair M; Moazzeni, Seyed M; Ahmadabad, Hassan N
2014-04-01
Outer inflammatory protein A (OipA) has an important role in Helicobacter pylori pathogenesis. In this study, we purified the outer membrane protein and evaluated the effects of this protein on maturation and cytokine production by dendritic cells (DCs). The oipA gene was inserted into pET28a, and this construct was transformed into Escherichia coli BL21 (DE3). Purification of the recombinant protein was performed by Ni-NTA affinity chromatography. Immature DCs were purified from spleen of C57BL/6 mice with more than 90% purity and were treated with several concentrations of OipA (1-20 μg/mL) overnight. Expression of maturation markers (CD86, CD40, and MHC-II) on the surface of DCs and production of IL-10 and IL-12 were assessed by flow cytometry and ELISA, respectively. The expression of DC maturation markers CD40, CD86, and MHC-II was downregulated on the surface of OipA-treated DCs at concentrations of 10 and 20 μg/mL compared with negative control. Production of IL-10 decreases with increasing OipA concentration at a concentration of 5 μg/mL, but we detected no change in IL-12 production. Inability to eliminate H. pylori from stomach is partly due to the evasion of the bacteria from the immune response. DCs are central mediators between innate and adaptive immunity, and DC cytokines direct the types of adaptive immune response. This study indicated that OipA of H. pylori is a DC maturation suppression factor. Previous studies have shown that H. pylori manage tolerogenic programming in DCs leading to long-time gastric colonization. In conclusion, H. pylori OipA helps the establishment of chronic infection with reduction in IL-10 and suppression of DC maturation. © 2014 John Wiley & Sons Ltd.
Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes
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
Corson, James A.; Erisir, Alev
2014-01-01
While physiological studies suggested convergence of chorda tympani and glossopharyngeal afferent axons onto single neurons of the rostral nucleus of the solitary tract (rNTS), anatomical evidence has been elusive. The current study uses high-magnification confocal microscopy to identify putative synaptic contacts from afferent fibers of the two nerves onto individual projection neurons. Imaged tissue is re-visualized with electron microscopy, confirming that overlapping fluorescent signals in confocal z-stacks accurately identify appositions between labeled terminal and dendrite pairs. Monte Carlo modeling reveals that the probability of overlapping fluorophores is stochastically unrelated to the density of afferent label suggesting that convergent innervation in the rNTS is selective rather than opportunistic. Putative synaptic contacts from each nerve are often compartmentalized onto dendrite segments of convergently innervated neurons. These results have important implications for orosensory processing in the rNTS, and the techniques presented here have applications in investigations of neural microcircuitry with an emphasis on innervation patterning. PMID:23640852
NASA Astrophysics Data System (ADS)
Xu, Zhoubing; Baucom, Rebeccah B.; Abramson, Richard G.; Poulose, Benjamin K.; Landman, Bennett A.
2016-03-01
The abdominal wall is an important structure differentiating subcutaneous and visceral compartments and intimately involved with maintaining abdominal structure. Segmentation of the whole abdominal wall on routinely acquired computed tomography (CT) scans remains challenging due to variations and complexities of the wall and surrounding tissues. In this study, we propose a slice-wise augmented active shape model (AASM) approach to robustly segment both the outer and inner surfaces of the abdominal wall. Multi-atlas label fusion (MALF) and level set (LS) techniques are integrated into the traditional ASM framework. The AASM approach globally optimizes the landmark updates in the presence of complicated underlying local anatomical contexts. The proposed approach was validated on 184 axial slices of 20 CT scans. The Hausdorff distance against the manual segmentation was significantly reduced using proposed approach compared to that using ASM, MALF, and LS individually. Our segmentation of the whole abdominal wall enables the subcutaneous and visceral fat measurement, with high correlation to the measurement derived from manual segmentation. This study presents the first generic algorithm that combines ASM, MALF, and LS, and demonstrates practical application for automatically capturing visceral and subcutaneous fat volumes.
Ceramic turbine stator vane and shroud support
Glenn, Robert G.
1981-01-01
A support system for supporting the stationary ceramic vanes and ceramic outer shrouds which define the motive fluid gas path in a gas turbine engine is shown. Each individual segment of the ceramic component whether a vane or shroud segment has an integral radially outwardly projecting stem portion. The stem is enclosed in a split collet member of a high-temperature alloy material having a cavity configured to interlock with the stem portion. The generally cylindrical external surface of the collet engages a mating internal cylindrical surface of an aperture through a supporting arcuate ring segment with mating camming surfaces on the two facing cylindrical surfaces such that radially outward movement of the collet relative to the ring causes the internal cavity of the collet to be reduced in diameter to tightly engage the ceramic stem disposed therein. A portion of the collet extends outwardly through the ring segment opposite the ceramic piece and is threaded for receiving a nut and a compression washer for retaining the collet in the ring segment under a continuous biasing force urging the collet radially outwardly.
Microstructures of ancient and modern cast silver–copper alloys
DOE Office of Scientific and Technical Information (OSTI.GOV)
Northover, S.M., E-mail: s.m.northover@open.ac.uk; Northover, J.P., E-mail: peter.northover@materials.ox.ac.uk
The microstructures of modern cast Sterling silver and of cast silver objects about 2500 years old have been compared using optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), energy dispersive X-ray microanalysis (EDX) and electron backscatter diffraction (EBSD). Microstructures of both ancient and modern alloys were typified by silver-rich dendrites with a few pools of eutectic and occasional cuprite particles with an oxidised rim on the outer surface. EBSD showed the dendrites to have a complex internal structure, often involving extensive twinning. There was copious intragranular precipitation within the dendrites, in themore » form of very fine copper-rich rods which TEM, X-ray diffraction (XRD), SEM and STEM suggest to be of a metastable face-centred-cubic (FCC) phase with a cube–cube orientation relationship to the silver-rich matrix but a higher silver content than the copper-rich β in the eutectic. Samples from ancient objects displayed a wider range of microstructures including a fine scale interpenetration of the adjoining grains not seen in the modern material. Although this study found no unambiguous evidence that this resulted from microstructural change produced over archaeological time, the copper supersaturation remaining after intragranular precipitation suggests that such changes, previously proposed for wrought and annealed material, may indeed occur in ancient silver castings. - Highlights: • Similar twinned structures and oxidised surfaces seen in ancient and modern cast silver • General precipitation of fine Cu-rich rods apparently formed by discontinuous precipitation is characteristic of as-cast silver. • The fine rods are cube-cube related to the matrix in contrast with the eutectic. • The silver-rich phase remains supersaturated with copper. • Possibly age-related grain boundary features seen in ancient cast silver.« less
NASA Technical Reports Server (NTRS)
Gross, B.
1978-01-01
Displacement results of plane boundary collocation analysis are given for various locations on the inner boundaries of radially cracked ring segments (C-shaped specimens) subject to two complementary types of loading. Results are presented for ratios of outer to inner radius in the range of 1.1 to 2.5 and ratios a/W in the range 0.1 to 0.8, where a is the crack length for a specimen of wall thickness W. By combination of these results the resultant displacement coefficient or the corresponding influence coefficient can be obtained for any practical load line location of a pin-loaded specimen.
Airfoil nozzle and shroud assembly
Shaffer, J.E.; Norton, P.F.
1997-06-03
An airfoil and nozzle assembly are disclosed including an outer shroud having a plurality of vane members attached to an inner surface and having a cantilevered end. The assembly further includes a inner shroud being formed by a plurality of segments. Each of the segments having a first end and a second end and having a recess positioned in each of the ends. The cantilevered end of the vane member being positioned in the recess. The airfoil and nozzle assembly being made from a material having a lower rate of thermal expansion than that of the components to which the airfoil and nozzle assembly is attached. 5 figs.
Nozzle insert for mixed mode fuel injector
Lawrence, Keith E [Peoria, IL
2006-11-21
A fuel injector includes a homogenous charge nozzle outlet set and a conventional nozzle outlet set controlled respectively, by first and second needle valve members. The homogeneous charged nozzle outlet set is defined by a nozzle insert that is attached to an injector body, which defines the conventional nozzle outlet set. The nozzle insert is a one piece metallic component with a large diameter segment separated from a small diameter segment by an annular engagement surface. One of the needle valve members is guided on an outer surface of the nozzle insert, and the nozzle insert has an interference fit attachment to the injector body.
Pressure actuated film riding seals for turbo machinery
Bidkar, Rahul Anil; Thatte, Azam Mihir; Gibson, Nathan Evan McCurdy; Giametta, Andrew Paul
2015-08-25
A seal assembly for a rotary machine is provided. The seal assembly includes multiple sealing device segments disposed circumferentially intermediate to a stationary housing and a rotor. Each of the sealing device segments includes a stator interface element, a shoe plate having an extended portion having one or more labyrinth teeth facing the rotor and a load bearing portion, wherein the shoe plate is configured to generate an aerodynamic force between the shoe plate and the rotor. The sealing device segment further includes a secondary seal configured to be in contact with the stator interface element at a radially outer end and configured to be in contact with an elevated nose section of the extended portion of the shoe plate on a radially inner end; and multiple flexible elements attached to the shoe plate and to the stator interface element.
NASA Astrophysics Data System (ADS)
Kumar, Arjun S.
Over the last fifteen years, there has been a rapid growth in the use of high resolution X-ray computed tomography (HRXCT) imaging in material science applications. We use it at nanoscale resolutions up to 50 nm (nano-CT) for key research problems in large scale operation of polymer electrolyte membrane fuel cells (PEMFC) and lithium-ion (Li-ion) batteries in automotive applications. PEMFC are clean energy sources that electrochemically react with hydrogen gas to produce water and electricity. To reduce their costs, capturing their electrode nanostructure has become significant in modeling and optimizing their performance. For Li-ion batteries, a key challenge in increasing their scope for the automotive industry is Li metal dendrite growth. Li dendrites are structures of lithium with 100 nm features of interest that can grow chaotically within a battery and eventually lead to a short-circuit. HRXCT imaging is an effective diagnostics tool for such applications as it is a non-destructive method of capturing the 3D internal X-ray absorption coefficient of materials from a large series of 2D X-ray projections. Despite a recent push to use HRXCT for quantitative information on material samples, there is a relative dearth of computational tools in nano-CT image processing and analysis. Hence, we focus on developing computational methods for nano-CT image analysis of fuel cell and battery materials as required by the limitations in material samples and the imaging environment. The first problem we address is the segmentation of nano-CT Zernike phase contrast images. Nano-CT instruments are equipped with Zernike phase contrast optics to distinguish materials with a low difference in X-ray absorption coefficient by phase shifting the X-ray wave that is not diffracted by the sample. However, it creates image artifacts that hinder the use of traditional image segmentation techniques. To restore such images, we setup an inverse problem by modeling the X-ray phase contrast optics. We solve for the artifact-free images through an optimization function that uses novel edge detection and fast image interpolation methods. We use this optics-based segmentation method in two main research problems - 1) the characterization of a failure mechanism in the internal structure of Li-ion battery electrodes and 2) the measurement of Li metal dendrite morphology for different current and temperature parameters of Li-ion battery cell operation. The second problem we address is the development of a space+time (4D) reconstruction method for in-operando imaging of samples undergoing temporal change, particularly for X-ray sources with low throughput and nanoscale spatial resolutions. The challenge in using such systems is achieving a sufficient temporal resolution despite exposure times of a 2D projection on the order of 1 minute. We develop a 4D dynamic X-ray computed tomography (CT) reconstruction method, capable of reconstructing a temporal 3D image every 2 to 8 projections. Its novel properties are its projection angle sequence and the probabilistic detection of experimental change. We show its accuracy on phantom and experimental datasets to show its promise in temporally resolving Li metal dendrite growth and in elucidating mitigation strategies.
Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity.
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.
Zhang, M; Liu, J; Jiang, M; Wu, D-M; Sonawane, K; Guy, H R; Tseng, G-N
2005-10-01
Studies on voltage-gated K channels such as Shaker have shown that positive charges in the voltage-sensor (S4) can form salt bridges with negative charges in the surrounding transmembrane segments in a state-dependent manner, and different charge pairings can stabilize the channels in closed or open states. The goal of this study is to identify such charge interactions in the hERG channel. This knowledge can provide constraints on the spatial relationship among transmembrane segments in the channel's voltage-sensing domain, which are necessary for modeling its structure. We first study the effects of reversing S4's positive charges on channel activation. Reversing positive charges at the outer (K525D) and inner (K538D) ends of S4 markedly accelerates hERG activation, whereas reversing the 4 positive charges in between either has no effect or slows activation. We then use the 'mutant cycle analysis' to test whether D456 (outer end of S2) and D411 (inner end of S1) can pair with K525 and K538, respectively. Other positive charges predicted to be able, or unable, to interact with D456 or D411 are also included in the analysis. The results are consistent with predictions based on the distribution of these charged residues, and confirm that there is functional coupling between D456 and K525 and between D411 and K538.
Walker, Ray A.; Reich, Fred R.; Russell, James T.
1978-01-01
An optical extensometer is described using sequentially pulsed light beams for measuring the dimensions of objects by detecting two opposite edges of the object without contacting the object. The light beams may be of different distinguishable light characteristics, such as polarization or wave length, and are time modulated in an alternating manner at a reference frequency. The light characteristics are of substantially the same total light energy and are distributed symmetrically. In the preferred embodiment two light beam segments of one characteristic are on opposite sides of a middle segment of another characteristic. As a result, when the beam segments are scanned sequentially across two opposite edges of the object, they produce a readout signal at the output of a photoelectric detector that is compared with the reference signal by a phase comparator to produce a measurement signal with a binary level transition when the light beams cross an edge. The light beams may be of different cross sectional geometries, including two superimposed and concentric circular beam cross sections of different diameter, or two rectangular cross sections which intersect with each other substantially perpendicular so only their central portions are superimposed. Alternately, a row of three light beams can be used including two outer beams on opposite sides and separate from a middle beam. The three beams may all be of the same light characteristic. However it is preferable that the middle beam be of a different characteristic but of the same total energy as the two outer beams.
Gröbner, Sabine; Autenrieth, Stella E; Soldanova, Irena; Gunst, Dani S J; Schaller, Martin; Bohn, Erwin; Müller, Steffen; Leverkus, Martin; Wesselborg, Sebastian; Autenrieth, Ingo B; Borgmann, Stefan
2006-11-01
Yersinia outer protein P (YopP) is a virulence factor of Yersinia enterocolitica that is injected into the cytosol of host cells where it targets MAP kinase kinases (MKKs) and inhibitor of kappaB kinase (IKK)-beta resulting in inhibition of cytokine production as well as induction of apoptosis in murine macrophages and dendritic cells (DC). Here we show that DC death was only partially prevented by the broad spectrum caspase inhibitor zVAD-fmk, indicating simultaneous caspase-dependent and caspase-independent mechanisms of cell death induction by YopP. Microscopic analyses and measurement of cell size demonstrated necrosis-like morphology of caspase-independent cell death. Application of zVAD-fmk prevented cleavage of procaspases and Bid, decrease of the inner transmembrane mitochondrial potential DeltaPsi(m) and mitochondrial release of cytochrome c. From these data we conclude that YopP-induced activation of the mitochondrial death pathway is mediated upstream via caspases. In conclusion, our results suggest that YopP simultaneously induces caspase-dependent apoptotic and caspase-independent necrosis-like death in DC. However, it has to be resolved if necrosis-like DC death occurs independently from apoptotic events or as an apoptotic epiphenomenon.
Lateral interactions in the outer retina
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
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.
Skrapits, Katalin; Kanti, Vivien; Savanyú, Zsófia; Maurnyi, Csilla; Szenci, Ottó; Horváth, András; Borsay, Beáta Á.; Herczeg, László; Liposits, Zsolt; Hrabovszky, Erik
2015-01-01
Hypophysiotropic projections of gonadotropin-releasing hormone (GnRH)-synthesizing neurons form the final common output way of the hypothalamus in the neuroendocrine control of reproduction. Several peptidergic neuronal systems of the medial hypothalamus innervate human GnRH cells and mediate crucially important hormonal and metabolic signals to the reproductive axis, whereas much less is known about the contribution of the lateral hypothalamic area to the afferent control of human GnRH neurons. Orexin (ORX)- and melanin-concentrating hormone (MCH)-synthesizing neurons of this region have been implicated in diverse behavioral and autonomic processes, including sleep and wakefulness, feeding and other functions. In the present immunohistochemical study, we addressed the anatomical connectivity of these neurons to human GnRH cells in post-mortem hypothalamic samples obtained from autopsies. We found that 38.9 ± 10.3% and 17.7 ± 3.3% of GnRH-immunoreactive (IR) perikarya in the infundibular nucleus of human male subjects received ORX-IR and MCH-IR contacts, respectively. On average, each 1 mm segment of GnRH dendrites received 7.3 ± 1.1 ORX-IR and 3.7 ± 0.5 MCH-IR axo-dendritic appositions. Overall, the axo-dendritic contacts dominated over the axo-somatic contacts and represented 80.5 ± 6.4% of ORX-IR and 76.7 ± 4.6% of MCH-IR inputs to GnRH cells. Based on functional evidence from studies of laboratory animals, the direct axo-somatic and axo-dendritic input from ORX and MCH neurons to the human GnRH neuronal system may convey critical metabolic and other homeostatic signals to the reproducive axis. In this study, we also report the generation and characterization of new antibodies for immunohistochemical detection of GnRH neurons in histological sections. PMID:26388735
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
Outer Retinal Changes Including the Ellipsoid Zone Band in Usher Syndrome 1B due to MYO7A Mutations.
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.
Failure analysis of an aluminum alloy material framework component induced by casting defects
NASA Astrophysics Data System (ADS)
Li, Bo; Hu, Weiye
2017-09-01
Failure analysis on a fractured radome framework component was carried out through visual observations, metallographic examination using optical microscope, fractog-raphy inspections using scanning electron microscope and chemical composition analysis. The failed frame was made of casting Al-Si7-Mg0.4 aluminum alloy. It had suffered a former vi-bration performance tests. It was indicated that the fractures were attributed to fatigue cracks which were induced by casting porosities at the outer surfaces of frame. Failure analysis was carefully conducted for the semi-penetrating crack appearing on the framework. According to the fractography inspected by scanning electron microscope, it was indicated that numerous casting porosities at the outer surface of the framework played the role of multiple fracture sources due to some applied stresses. Optical microstructure observations suggested that the dendrite-shaped casting porosities largely contributed to the crack-initiation. The groove-shaped structure at roots of spatial convex-bodies on the edge of casting porosities supplied the preferred paths of the crack-propagation. Besides, the brittle silicon eutectic particles distrib-uting along grain boundaries induced the intergranular fracture mode in the region of the over-load final fracture surface.
Surgical Treatment of Laser Induced Eye Injuries
1990-12-05
Continue on reverse if necessary and identify by block number) Subretinal blood within the macula may play a causative role in visual loss in a...period. Initial observations included clot organization with retraction of fibrin strands tearing photoreceptor outer segments. Later degeneration ...macular degeneration is the leading cause of permanent blindness in people over age 60 in the industrialized world’. Subretinal hemorrhage from
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wilson, T.; Dominic, J.; Halverson, J.
1996-04-10
Drainage patterns observed in the Appalachian Valley and Ridge and Plateau provinces exhibit distinctly different patterns. The patterns appear to be controlled by varying influences of local structural and lithologic variability. Drainage patterns in the Valley and Ridge study area can be classified as a combination of dendritic and trellis arrangements. The patterns vary over short distances in both the strike and dip directions. In the Granny Creek area of the Appalachian Plateau drainage patterns are predominantly dendritic. The possibility that these drainage patterns have fractal characteristics was evaluated by box-counting. Results obtained from box counting do not yield amore » well defined fractal regime in either areas. In the Valley and Ridge a space-filling, or random regime (D=2) is observed for boxes with side-lengths of 300 meters and greater. Below 300 meters, large changes in D occur between consecutively smaller box sizes. From side lengths of 300 to 150m, 150 to 75m, and 75 to 38m, D is measured at 1.77, 1.39, and 1.08 respectively. For box sizes less than 38m the fractal dimension is 1 or less. While the l0g-log response of the box counting data is nonlinear and does not define a fractal regime, the curves offer the possibility of characterizing non-fractal patterns. The rate at which D drops outside the random regime correlates to drainage density. D in areas with a smaller density of drainage segments fell toward saturation (D=1) more abruptly. The break-away point from the random regime and the transition to the saturated regime may provide useful information about the relative lengths of stream segments.« less
Zempel, Hans; Dennissen, Frank J A; Kumar, Yatender; Luedtke, Julia; Biernat, Jacek; Mandelkow, Eva-Maria; Mandelkow, Eckhard
2017-07-21
Subcellular mislocalization of the microtubule-associated protein Tau is a hallmark of Alzheimer disease (AD) and other tauopathies. Six Tau isoforms, differentiated by the presence or absence of a second repeat or of N-terminal inserts, exist in the human CNS, but their physiological and pathological differences have long remained elusive. Here, we investigated the properties and distributions of human and rodent Tau isoforms in primary forebrain rodent neurons. We found that the Tau diffusion barrier (TDB), located within the axon initial segment (AIS), controls retrograde (axon-to-soma) and anterograde (soma-to-axon) traffic of Tau. Tau isoforms without the N-terminal inserts were sorted efficiently into the axon. However, the longest isoform (2N4R-Tau) was partially retained in cell bodies and dendrites, where it accelerated spine and dendrite growth. The TDB (located within the AIS) was impaired when AIS components (ankyrin G, EB1) were knocked down or when glycogen synthase kinase-3β (GSK3β; an AD-associated kinase tethered to the AIS) was overexpressed. Using superresolution nanoscopy and live-cell imaging, we observed that microtubules within the AIS appeared highly dynamic, a feature essential for the TDB. Pathomechanistically, amyloid-β insult caused cofilin activation and F-actin remodeling and decreased microtubule dynamics in the AIS. Concomitantly with these amyloid-β-induced disruptions, the AIS/TDB sorting function failed, causing AD-like Tau missorting. In summary, we provide evidence that the human and rodent Tau isoforms differ in axodendritic sorting and amyloid-β-induced missorting and that the axodendritic distribution of Tau depends on AIS integrity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Fohlmeister, Jürgen F; Cohen, Ethan D; Newman, Eric A
2010-03-01
Trains of action potentials of rat and cat retinal ganglion cells (RGCs) were recorded intracellularly across a temperature range of 7-37 degrees C. Phase plots of the experimental impulse trains were precision fit using multicompartment simulations of anatomically reconstructed rat and cat RGCs. Action potential excitation was simulated with a "Five-channel model" [Na, K(delayed rectifier), Ca, K(A), and K(Ca-activated) channels] and the nonspace-clamped condition of the whole cell recording was exploited to determine the channels' distribution on the dendrites, soma, and proximal axon. At each temperature, optimal phase-plot fits for RGCs occurred with the same unique channel distribution. The "waveform" of the electrotonic current was found to be temperature dependent, which reflected the shape changes in the experimental action potentials and confirmed the channel distributions. The distributions are cell-type specific and adequate for soma and dendritic excitation with a safety margin. The highest Na-channel density was found on an axonal segment some 50-130 microm distal to the soma, as determined from the temperature-dependent "initial segment-somadendritic (IS-SD) break." The voltage dependence of the gating rate constants remains invariant between 7 and 23 degrees C and between 30 and 37 degrees C, but undergoes a transition between 23 and 30 degrees C. Both gating-kinetic and ion-permeability Q10s remain virtually constant between 23 and 37 degrees C (kinetic Q10s = 1.9-1.95; permeability Q10s = 1.49-1.64). The Q10s systematically increase for T <23 degrees C (kinetic Q10 = 8 at T = 8 degrees C). The Na channels were consistently "sleepy" (non-Arrhenius) for T <8 degrees C, with a loss of spiking for T <7 degrees C.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Johnson, W.R.; Marshall, C.F.; Anderson, C.M.
1994-08-01
This report summarizes results of an oil-spill risk analysis (OSRA) conducted for the proposed lower Cook Inlet Outer Continental Shelf (OCS) Lease Sale 149. The objective of this analysis was to estimate relative oil-spill risks associated with oil and gas production from the leasing alternatives proposed for the lease sale. The Minerals Management Service (MMS) will consider the analysis in the environmental impact statement (EIS) prepared for the lease sale. The analysis for proposed OCS Lease Sale 149 was conducted in three parts corresponding to different aspects of the overall problem. The first part dealt with the probability of oil-spillmore » occurrence. The second dealt with trajectories of oil spills from potential spill sites to various environmental resources or land segments. The third part combined the results of the first two parts to give estimates of the overall oil-spill risk if there is oil production as a result of the lease sale. To aid the analysis, conditional risk contour maps of seasonal conditional probabilities of spill contact were generated for each environmental resource or land segment in the study area (see vol. 2).« less
Exploration of the pore structure of a peptide-gated Na+channel
Poët, Mallorie; Tauc, Michel; Lingueglia, Eric; Cance, Peggy; Poujeol, Philippe; Lazdunski, Michel; Counillon, Laurent
2001-01-01
The FMRF-amide-activated sodium channel (FaNaC), a member of the ENaC/Degenerin family, is a homotetramer, each subunit containing two transmembrane segments. We changed independently every residue of the first transmembrane segment (TM1) into a cysteine and tested each position’s accessibility to the cysteine covalent reagents MTSET and MTSES. Eleven mutants were accessible to the cationic MTSET, showing that TM1 faces the ion translocation pathway. This was confirmed by the accessibility of cysteines present in the acid-sensing ion channels and other mutations introduced in FaNaC TM1. Modification of accessibilities for positions 69, 71 and 72 in the open state shows that the gating mechanism consists of the opening of a constriction close to the intracellular side. The anionic MTSES did not penetrate into the channel, indicating the presence of a charge selectivity filter in the outer vestibule. Furthermore, amiloride inhibition resulted in the channel occlusion in the middle of the pore. Summarizing, the ionic pore of FaNaC includes a large aqueous cavity, with a charge selectivity filter in the outer vestibule and the gate close to the interior. PMID:11598003
Albert, A D; Watts, A; Spooner, P; Groebner, G; Young, J; Yeagle, P L
1997-08-14
Structural information on mammalian integral membrane proteins is scarce. As part of work on an alternative approach to the structure of bovine rhodopsin, a method was devised to obtain an intramolecular distance between two specific sites on rhodopsin while in the rod outer segment disk membrane. In this report, the distance between the rhodopsin kinase phosphorylation site(s) on the carboxyl terminal and the top of the third transmembrane helix was measured on native rhodopsin. Rhodopsin was labeled with a nuclear spin label (31P) by limited phosphorylation with rhodopsin kinase. Major phosphorylation occurs at serines 343 and 338 on the carboxyl terminal. The phosphorylated rhodopsin was then specifically labeled on cysteine 140 with an electron spin label. Magic angle spinning 31P-nuclear magnetic resonance revealed the resonance arising from the phosphorylated protein. The enhancement of the transverse relaxation of this resonance by the paramagnetic spin label was observed. The strength of this perturbation was used to determine the through-space distance between the phosphorylation site(s) and the spin label position. A distance of 18 +/- 3 A was obtained.
Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6.
Hall, M O; Prieto, A L; Obin, M S; Abrams, T A; Burgess, B L; Heeb, M J; Agnew, B J
2001-10-01
The function and viability of vertebrate photoreceptors requires the daily phagocytosis of photoreceptor outer segments (OS) by the adjacent retinal pigment epithelium (RPE). We demonstrate here a critical role in this process for Gas6 and by implication one of its receptor protein tyrosine kinases (RTKs), Mertk (Mer). Gas6 specifically and selectively stimulates the phagocytosis of OS by normal cultured rat RPE cells. The magnitude of the response is dose-dependent and shows an absolute requirement for calcium. By contrast the Royal College of Surgeons (RCS) rat RPE cells, in which a mutation in the gene Mertk results in the expression of a truncated, non-functional receptor, does not respond to Gas6. These data strongly suggest that activation of Mertk by its ligand, Gas6, is the specific signaling pathway responsible for initiating the ingestion of shed OS. Moreover, photoreceptor degeneration in the RCS rat retina, which lacks Mertk, and in humans with a mutation in Mertk, strongly suggests that the Gas6/Mertk signaling pathway is essential for photoreceptor viability. We believe that this is the first demonstration of a specific function for Gas6 in the eye. Copyright 2001 Academic Press.
Inner and outer segment junction (IS/OS line) integrity in ocular Behçet's disease.
Yüksel, Harun; Türkcü, Fatih M; Sahin, Muhammed; Cinar, Yasin; Cingü, Abdullah K; Ozkurt, Zeynep; Sahin, Alparslan; Ari, Seyhmus; Caça, Ihsan
2014-08-01
In this study, we examined the spectral domain optical coherence tomography (OCT) findings of ocular Behçet's disease (OB) in patients with inactive uveitis. Specifically, we analyzed the inner and outer segment junction (IS/OS line) integrity and the effect of disturbed IS/OS line integrity on visual acuity. Patient files and OCT images of OB patients who had been followed-up between January and June of the year 2013 at the Dicle University Eye Clinic were evaluated retrospectively. Sixty-six eyes of 39 patients were included the study. OCT examination of the patients with inactive OB revealed that approximately 25% of the patients had disturbed IS/OS and external limiting membrane (EML) line integrity, lower visual acuity (VA), and lower macular thickness than others. Linear regression analysis revealed that macular thickness was not an independent variable for VA. In contrast, the IS/OS line integrity was an independent variable for VA in inactive OB patients. In this study, we showed that the IS/OS line integrity was an independent variable for VA in inactive OB patients. Further prospective studies are needed to evaluate the integrity of the IS/OS line in OB patients.
Type 3 Neovascularization Associated with Retinitis Pigmentosa.
Sayadi, Jihene; Miere, Alexandra; Souied, Eric H; Cohen, Salomon Y
2017-01-01
To report a case of type 3 neovascular lesion in a patient with retinitis pigmentosa (RP) complicated by macular edema. A 78-year-old man with a long follow-up for RP was referred for painless visual acuity decrease in the right eye. Best-corrected visual acuity was 20/125 in the right eye and 20/40 in the left. Fundus examination showed typical RP and macular edema in both eyes. In the right eye, spectral domain optical coherence tomography revealed a marked cystic macular edema associated with disruption of the Bruch membrane/retinal pigment epithelium complex overlying a pigmentary epithelium detachment, with a vascular structure which appeared to originate from the deep capillary plexus and to be connected with the subretinal pigment epithelium space. Optical coherence tomography angiography showed a high-flow vessel infiltrating the outer retinal layers in the deep capillary plexus segmentation, and a tuft-shaped, bright, high-flow network that seemed to be connected with the subretinal pigment epithelium space in the outer retinal layer segmentation. This presentation was consistent with an early type 3 neovascular lesion in the right eye. Type 3 neovascularization may be considered a possible complication of RP.
A key role for cyclic nucleotide gated (CNG) channels in cGMP-related retinitis pigmentosa.
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.
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.
Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons
Serrano-Velez, Jose L.; Rodriguez-Alvarado, Melanie; Torres-Vazquez, Irma I.; Fraser, Scott E.; Yasumura, Thomas; Vanderpool, Kimberly G.; Rash, John E.; Rosa-Molinar, Eduardo
2014-01-01
“Dye-coupling”, whole-mount immunohistochemistry for gap junction channel protein connexin 35 (Cx35), and freeze-fracture replica immunogold labeling (FRIL) reveal an abundance of electrical synapses/gap junctions at glutamatergic mixed synapses in the 14th spinal segment that innervates the adult male gonopodium of Western Mosquitofish, Gambusia affinis (Mosquitofish). To study gap junctions’ role in fast motor behavior, we used a minimally-invasive neural-tract-tracing technique to introduce gap junction-permeant or -impermeant dyes into deep muscles controlling the gonopodium of the adult male Mosquitofish, a teleost fish that rapidly transfers (complete in <20 mS) spermatozeugmata into the female reproductive tract. Dye-coupling in the 14th spinal segment controlling the gonopodium reveals coupling between motor neurons and a commissural primary ascending interneuron (CoPA IN) and shows that the 14th segment has an extensive and elaborate dendritic arbor and more gap junctions than do other segments. Whole-mount immunohistochemistry for Cx35 results confirm dye-coupling and show it occurs via gap junctions. Finally, FRIL shows that gap junctions are at mixed synapses and reveals that >50 of the 62 gap junctions at mixed synapses are in the 14th spinal segment. Our results support and extend studies showing gap junctions at mixed synapses in spinal cord segments involved in control of genital reflexes in rodents, and they suggest a link between mixed synapses and fast motor behavior. The findings provide a basis for studies of specific roles of spinal neurons in the generation/regulation of sex-specific behavior and for studies of gap junctions’ role in regulating fast motor behavior. Finally, the CoPA IN provides a novel candidate neuron for future studies of gap junctions and neural control of fast motor behaviors. PMID:25018700
Differentiation of Swine iPSC into Rod Photoreceptors and Their Integration into the Retina
Zhou, Liang; Wang, Wei; Liu, Yongqing; de Castro, Juan Fernandez; Ezashi, Toshihiko; Telugu, Bhanu Prakash V.L.; Roberts, R. Michael; Kaplan, Henry J.; Dean, Douglas C.
2014-01-01
Absence of a regenerative pathway for damaged retina following injury or disease has led to experiments utilizing stem cell transplantation for retinal repair, and encouraging results have been obtained in rodents. The swine eye is a closer anatomical and physiological match to the human eye, but embryonic stem cells have not been isolated from pig, and photoreceptor differentiation has not been demonstrated with swine induced pluripotent stem cells (iPSC). Here, we subjected swine iPSC to a rod photoreceptor differentiation protocol consisting of floating culture as embryoid bodies followed by differentiation in adherent culture. Real time PCR and immunostaining of differentiated cells demonstrated loss of expression of the pluripotent genes POU5F1, NANOG and SOX2 and induction of rod photoreceptor genes RCVRN, NRL, RHO and ROM1. While these differentiated cells displayed neuronal morphology, culturing on a Matrigel substratum triggered a further morphological change resulting in concentration of RHO and ROM1 in outer segment-like projections resembling those on primary cultures of rod photoreceptors. The differentiated cells were transplanted into the subretinal space of pigs treated with iodoacetic acid to eliminate rod photoreceptors. Three weeks after transplantation, engrafted RHO+ cells were evident in the outer nuclear layer where photoreceptors normally reside. A portion of these transplanted cells had generated projections resembling outer segments. These results demonstrate that swine iPSC can differentiate into photoreceptors in culture and these cells can integrate into the damaged swine neural retina thus laying a foundation for future studies using the pig as a model for retinal stem cell transplantation. PMID:21491544
Model-based segmentation of the facial nerve and chorda tympani in pediatric CT scans
NASA Astrophysics Data System (ADS)
Reda, Fitsum A.; Noble, Jack H.; Rivas, Alejandro; Labadie, Robert F.; Dawant, Benoit M.
2011-03-01
In image-guided cochlear implant surgery an electrode array is implanted in the cochlea to treat hearing loss. Access to the cochlea is achieved by drilling from the outer skull to the cochlea through the facial recess, a region bounded by the facial nerve and the chorda tympani. To exploit existing methods for computing automatically safe drilling trajectories, the facial nerve and chorda tympani need to be segmented. The effectiveness of traditional segmentation approaches to achieve this is severely limited because the facial nerve and chorda are small structures (~1 mm and ~0.3 mm in diameter, respectively) and exhibit poor image contrast. We have recently proposed a technique to achieve this task in adult patients, which relies on statistical models of the structures. These models contain intensity and shape information along the central axes of both structures. In this work we use the same method to segment pediatric scans. We show that substantial differences exist between the anatomy of children and the anatomy of adults, which lead to poor segmentation results when an adult model is used to segment a pediatric volume. We have built a new model for pediatric cases and we have applied it to ten scans. A leave-one-out validation experiment was conducted in which manually segmented structures were compared to automatically segmented structures. The maximum segmentation error was 1 mm. This result indicates that accurate segmentation of the facial nerve and chorda in pediatric scans is achievable, thus suggesting that safe drilling trajectories can also be computed automatically.
An animal model for Norrie disease (ND): gene targeting of the mouse ND gene.
Berger, W; van de Pol, D; Bächner, D; Oerlemans, F; Winkens, H; Hameister, H; Wieringa, B; Hendriks, W; Ropers, H H
1996-01-01
In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.
PTEN knockdown alters dendritic spine/protrusion morphology, not density
Haws, Michael E.; Jaramillo, Thomas C.; Espinosa-Becerra, Felipe; Widman, Allie; Stuber, Garret D.; Sparta, Dennis R.; Tye, Kay M.; Russo, Scott J.; Parada, Luis F.; Kaplitt, Michael; Bonci, Antonello; Powell, Craig M.
2014-01-01
Mutations in phosphatase and tensin homolog deleted on chromosome ten (PTEN) are implicated in neuropsychiatric disorders including autism. Previous studies report that PTEN knockdown in neurons in vivo leads to increased spine density and synaptic activity. To better characterize synaptic changes in neurons lacking PTEN, we examined the effects of shRNA knockdown of PTEN in basolateral amygdala neurons on synaptic spine density and morphology using fluorescent dye confocal imaging. Contrary to previous studies in dentate gyrus, we find that knockdown of PTEN in basolateral amygdala leads to a significant decrease in total spine density in distal dendrites. Curiously, this decreased spine density is associated with increased miniature excitatory post-synaptic current frequency and amplitude, suggesting an increase in number and function of mature spines. These seemingly contradictory findings were reconciled by spine morphology analysis demonstrating increased mushroom spine density and size with correspondingly decreased thin protrusion density at more distal segments. The same analysis of PTEN conditional deletion in dentate gyrus demonstrated that loss of PTEN does not significantly alter total density of dendritic protrusions in the dentate gyrus, but does decrease thin protrusion density and increases density of more mature mushroom spines. These findings suggest that, contrary to previous reports, PTEN knockdown may not induce de novo spinogenesis, but instead may increase synaptic activity by inducing morphological and functional maturation of spines. Furthermore, behavioral analysis of basolateral amygdala PTEN knockdown suggests that these changes limited only to the basolateral amygdala complex may not be sufficient to induce increased anxiety-related behaviors. PMID:24264880
An application of a vulnerability index to oil spill modeling in the Gulf of Mexico
LaBelle, R.P.; Rainey, Gail; Lanfear, K.J.
1982-01-01
An analysis was made of the relative impact to the shoreline of the Gulf of Mexico from proposed Federal Outer Continental Shelf oil and gas leasing activity. An oil spill trajectory model was coupled with a land segment vulnerability characterization to predict the risks to the shoreline. Such a technique allows spatial and temporal variability in oil spill sensitivity to be represented and combined with the likelihood of oil spill contact to specific coastal segments in the study area. Predicted relative impact was greatest along the coastlines of Louisiana, Mississippi, and Alabama. Useful information is provided for environmental impact analysis, as well as oil spill response planning.
Boyd, Gary L.
1997-04-01
A turbine nozzle vane assembly having a preestablished rate of thermal expansion is positioned in a gas turbine engine and being attached to conventional metallic components. The metallic components having a preestablished rate of thermal expansion being greater than the preestablished rate of thermal expansion of the turbine nozzle vane assembly. The turbine nozzle vane assembly includes an outer shroud and an inner shroud having a plurality of horizontally segmented vanes therebetween being positioned by a connecting member positioning segmented vanes in functional relationship one to another. The turbine nozzle vane assembly provides an economical, reliable and effective ceramic component having a preestablished rate of thermal expansion being greater than the preestablished rate of thermal expansion of the other component.
NASA Technical Reports Server (NTRS)
Gross, B.
1977-01-01
Displacement results of plane boundary collocation analysis are given for various locations on the inner boundaries of radially cracked ring segments (C-shaped specimens) subject to two complementary types of loading. Results are presented for ratios of outer to inner radius R sub o/R sub i in the range of 1.1 to 2.5, and ratios a/W in the range 0.1 to 0.8 where a is the crack length for a specimen of wall thickness W. By combination of these results the resultant displacement coefficient delta or the corresponding influence coefficient, can be obtained for any practical load line location of a pin loaded specimen.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wiebe, David J.
A transition duct system (10) for delivering hot-temperature gases from a plurality of combustors in a combustion turbine engine is provided. The system includes an exit piece (16) for each combustor. The exit piece may include an arcuate connecting segment (36). An arcuate ceramic liner (60) may be inwardly disposed onto a metal outer shell (38) along the arcuate connecting segment of the exit piece. Structural arrangements are provided to securely attach the ceramic liner in the presence of substantial flow path pressurization. Cost-effective serviceability of the transition duct systems is realizable since the liner can be readily removed andmore » replaced as needed.« less
Three-dimensional choroidal segmentation in spectral OCT volumes using optic disc prior information
NASA Astrophysics Data System (ADS)
Hu, Zhihong; Girkin, Christopher A.; Hariri, Amirhossein; Sadda, SriniVas R.
2016-03-01
Recently, much attention has been focused on determining the role of the peripapillary choroid - the layer between the outer retinal pigment epithelium (RPE)/Bruchs membrane (BM) and choroid-sclera (C-S) junction, whether primary or secondary in the pathogenesis of glaucoma. However, the automated choroidal segmentation in spectral-domain optical coherence tomography (SD-OCT) images of optic nerve head (ONH) has not been reported probably due to the fact that the presence of the BM opening (BMO, corresponding to the optic disc) can deflect the choroidal segmentation from its correct position. The purpose of this study is to develop a 3D graph-based approach to identify the 3D choroidal layer in ONH-centered SD-OCT images using the BMO prior information. More specifically, an initial 3D choroidal segmentation was first performed using the 3D graph search algorithm. Note that varying surface interaction constraints based on the choroidal morphological model were applied. To assist the choroidal segmentation, two other surfaces of internal limiting membrane and innerouter segment junction were also segmented. Based on the segmented layer between the RPE/BM and C-S junction, a 2D projection map was created. The BMO in the projection map was detected by a 2D graph search. The pre-defined BMO information was then incorporated into the surface interaction constraints of the 3D graph search to obtain more accurate choroidal segmentation. Twenty SD-OCT images from 20 healthy subjects were used. The mean differences of the choroidal borders between the algorithm and manual segmentation were at a sub-voxel level, indicating a high level segmentation accuracy.
Exciton confinement in organic dendrimer quantum wells for opto-electronic applications
NASA Astrophysics Data System (ADS)
Lupton, J. M.; Samuel, I. D. W.; Burn, P. L.; Mukamel, S.
2002-01-01
Organic dendrimers are a fascinating new class of materials for opto-electronic applications. We present coupled electronic oscillator calculations on novel nanoscale conjugated dendrimers for use in organic light-emitting diodes. Strong confinement of excitations at the center of the dendrimers is observed, which accounts for the dependence of intermolecular interactions and charge transport on the degree of branching of the dendrimer. The calculated absorption spectra are in excellent agreement with the measured data and show that benzene rings are shared between excitations on the linear segments of the hyperbranched molecules. The coupled electronic oscillator approach is ideally suited to treat large dendritic molecules.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Soultan, D; Murphy, J; James, C
2015-06-15
Purpose: To assess the accuracy of internal target volume (ITV) segmentation of lung tumors for treatment planning of simultaneous integrated boost (SIB) radiotherapy as seen in 4D PET/CT images, using a novel 3D-printed phantom. Methods: The insert mimics high PET tracer uptake in the core and 50% uptake in the periphery, by using a porous design at the periphery. A lung phantom with the insert was placed on a programmable moving platform. Seven breathing waveforms of ideal and patient-specific respiratory motion patterns were fed to the platform, and 4D PET/CT scans were acquired of each of them. CT images weremore » binned into 10 phases, and PET images were binned into 5 phases following the clinical protocol. Two scenarios were investigated for segmentation: a gate 30–70 window, and no gating. The radiation oncologist contoured the outer ITV of the porous insert with on CT images, while the internal void volume with 100% uptake was contoured on PET images for being indistinguishable from the outer volume in CT images. Segmented ITVs were compared to the expected volumes based on known target size and motion. Results: 3 ideal breathing patterns, 2 regular-breathing patient waveforms, and 2 irregular-breathing patient waveforms were used for this study. 18F-FDG was used as the PET tracer. The segmented ITVs from CT closely matched the expected motion for both no gating and gate 30–70 window, with disagreement of contoured ITV with respect to the expected volume not exceeding 13%. PET contours were seen to overestimate volumes in all the cases, up to more than 40%. Conclusion: 4DPET images of a novel 3D printed phantom designed to mimic different uptake values were obtained. 4DPET contours overestimated ITV volumes in all cases, while 4DCT contours matched expected ITV volume values. Investigation of the cause and effects of the discrepancies is undergoing.« less
Retinal Layer Abnormalities as Biomarkers of Schizophrenia.
Samani, Niraj N; Proudlock, Frank A; Siram, Vasantha; Suraweera, Chathurie; Hutchinson, Claire; Nelson, Christopher P; Al-Uzri, Mohammed; Gottlob, Irene
2018-06-06
Schizophrenia is associated with several brain deficits, as well as visual processing deficits, but clinically useful biomarkers are elusive. We hypothesized that retinal layer changes, noninvasively visualized using spectral-domain optical coherence tomography (SD-OCT), may represent a possible "window" to these abnormalities. A Leica EnvisuTM SD-OCT device was used to obtain high-resolution central foveal B-scans in both eyes of 35 patients with schizophrenia and 50 demographically matched controls. Manual retinal layer segmentation was performed to acquire individual and combined layer thickness measurements in 3 macular regions. Contrast sensitivity was measured at 3 spatial frequencies in a subgroup of each cohort. Differences were compared using adjusted linear models and significantly different layer measures in patients underwent Spearman Rank correlations with contrast sensitivity, quantified symptoms severity, disease duration, and antipsychotic medication dose. Total retinal and photoreceptor complex thickness was reduced in all regions in patients (P < .0001). Segmentation revealed consistent thinning of the outer nuclear layer (P < .001) and inner segment layer (P < .05), as well as a pattern of parafoveal ganglion cell changes. Low spatial frequency contrast sensitivity was reduced in patients (P = .002) and correlated with temporal parafoveal ganglion cell complex thinning (R = .48, P = .01). Negative symptom severity was inversely correlated with foveal photoreceptor complex thickness (R = -.54, P = .001) and outer nuclear layer thickness (R = -.47, P = .005). Our novel findings demonstrate considerable retinal layer abnormalities in schizophrenia that are related to clinical features and visual function. With time, SD-OCT could provide easily-measurable biomarkers to facilitate clinical assessment and further our understanding of the disease.
von Huene, Roland E.; Miller, John J.; Klaeschen, Dirk; Dartnell, Peter
2016-01-01
In 1946, megathrust seismicity along the Unimak segment of the Alaska subduction zone generated the largest ever recorded Alaska/Aleutian tsunami. The tsunami severely damaged Pacific islands and coastal areas from Alaska to Antarctica. It is the charter member of “tsunami” earthquakes that produce outsized far-field tsunamis for the recorded magnitude. Its source mechanisms were unconstrained by observations because geophysical data for the Unimak segment were sparse and of low resolution. Reprocessing of legacy geophysical data reveals a deep water, high-angle reverse or splay thrust fault zone that leads megathrust slip upward to the mid-slope terrace seafloor rather than along the plate boundary toward the trench axis. Splay fault uplift elevates the outer mid-slope terrace and its inner area subsides. Multibeam bathymetry along the splay fault zone shows recent but undated seafloor disruption. The structural configuration of the nearby Semidi segment is similar to that of the Unimak segment, portending generation of a future large tsunami directed toward the US West coast.
NASA Astrophysics Data System (ADS)
von Huene, Roland; Miller, John J.; Klaeschen, Dirk; Dartnell, Peter
2016-12-01
In 1946, megathrust seismicity along the Unimak segment of the Alaska subduction zone generated the largest ever recorded Alaska/Aleutian tsunami. The tsunami severely damaged Pacific islands and coastal areas from Alaska to Antarctica. It is the charter member of "tsunami" earthquakes that produce outsized far-field tsunamis for the recorded magnitude. Its source mechanisms were unconstrained by observations because geophysical data for the Unimak segment were sparse and of low resolution. Reprocessing of legacy geophysical data reveals a deep water, high-angle reverse or splay thrust fault zone that leads megathrust slip upward to the mid-slope terrace seafloor rather than along the plate boundary toward the trench axis. Splay fault uplift elevates the outer mid-slope terrace and its inner area subsides. Multibeam bathymetry along the splay fault zone shows recent but undated seafloor disruption. The structural configuration of the nearby Semidi segment is similar to that of the Unimak segment, portending generation of a future large tsunami directed toward the US West coast.
Cyclic nucleotide- and inositol phosphate-gated ion channels in lobster olfactory receptor neurons.
Hatt, H; Ache, B W
1994-01-01
The idea of having two second messenger pathways in olfaction, one mediated by cAMP and the other by inositol 1,4,5-trisphosphate, is supported by evidence that both second messengers directly activate distinct ion channels in the outer dendrite of lobster olfactory receptor neurons. Evidence that both types of second messenger-gated channels can occur in the same patch of membrane suggests that channels of both types can be expressed in one neuron. Evidence of more than one type of inositol phosphate-gated channel in this highly specialized region of the neuron furthers the idea that the output of individual olfactory receptor cells is regulated through multiple effectors and allows that effector diversity may contribute to functional diversity among olfactory receptor cells. Images PMID:7517547
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.
de Sisternes, Luis; Hu, Julia; Rubin, Daniel L; Marmor, Michael F
2015-05-01
To evaluate the relative involvement of inner and outer retina in hydroxychloroquine (HCQ) retinopathy while on the drug, and after drug cessation, using data from spectral-domain optical coherence tomography (SD-OCT). A total of 102 SD-OCT scans were obtained from 11 patients (classified as having early, moderate, or severe stages of toxicity) over a period of 4 years after cessation of HCQ. The inner and outer retina boundaries were identified automatically to measure thickness and characterize progression topographically. The segmentation of retinal layers was verified in SD-OCT cross-sections for all eyes and scans included in this study (a total of 102 scans). Topographic analysis showed that inner retina was not involved in HCQ toxicity to any meaningful degree, either between stages of retinopathy or after the drug is stopped. The characteristic bull's eye pattern of outer macula thinning appears when comparing moderate retinopathy (before any RPE damage) to the early stage. Later damage, as toxicity evolved to a severe stage, was diffuse across most of the macula. If the drug was stopped at an early or moderate stage, progression was limited to the first year and occurred diffusely without parafoveal localization. Hydroxychloroquine retinopathy primarily involves outer retina (photoreceptors). Outer retinal thinning while using HCQ initially involves the parafovea, but becomes diffuse across the macula as damage progresses or after drug cessation. When HCQ is stopped at an early or moderate stage (before RPE damage), progression seems to be limited to the first year.
NASA Astrophysics Data System (ADS)
Mochizuki, M.; Kanazawa, T.; Uehira, K.; Shimbo, T.; Shiomi, K.; Kunugi, T.; Aoi, S.; Matsumoto, T.; Sekiguchi, S.; Yamamoto, N.; Takahashi, N.; Shinohara, M.; Yamada, T.
2016-12-01
National Research Institute for Earth Science and Disaster Resilience ( NIED ) has launched the project of constructing an observatory network for tsunamis and earthquakes on the seafloor. The observatory network was named "S-net, Seafloor Observation Network for Earthquakes and Tsunamis along the Japan Trench". 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 5,700 km. The S-net system extends along Kuril and Japan trenches around Japan islands from north to south covering the area between southeast off island of Hokkaido and off the Boso Peninsula, Chiba Prefecture. The project has been financially supported by MEXT Japan. An observatory package is 34cm in diameter and 226cm long. Each observatory equips two units of a high sensitive water-depth sensor as a tsunami meter and four sets of three-component seismometers. The water-depth sensor has measurement resolution of sub-centimeter level. Combination of multiple seismometers secures wide dynamic range and robustness of the observation that are needed for early earthquake warning. The S-net is composed of six segment networks that consists of about 25 observatories and 800-1,600km length submarine optical cable. Five of six segment networks except the one covering the outer rise area of the Japan Trench has been already installed. The data from the observatories on those five segment networks are being transferred to the data center at NIED on a real-time basis, and then verification of data integrity are being carried out at the present moment. Installation of the last segment network of the S-net, that is, the outer rise one is scheduled to be finished within FY2016. Full-scale operation of the S-net will start at FY2017. We will report construction and operation of the S-net submarine cable system as well as the outline of the obtained data in this presentation.
Texture analysis improves level set segmentation of the anterior abdominal wall
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Zhoubing; Allen, Wade M.; Baucom, Rebeccah B.
2013-12-15
Purpose: The treatment of ventral hernias (VH) has been a challenging problem for medical care. Repair of these hernias is fraught with failure; recurrence rates ranging from 24% to 43% have been reported, even with the use of biocompatible mesh. Currently, computed tomography (CT) is used to guide intervention through expert, but qualitative, clinical judgments, notably, quantitative metrics based on image-processing are not used. The authors propose that image segmentation methods to capture the three-dimensional structure of the abdominal wall and its abnormalities will provide a foundation on which to measure geometric properties of hernias and surrounding tissues and, therefore,more » to optimize intervention.Methods: In this study with 20 clinically acquired CT scans on postoperative patients, the authors demonstrated a novel approach to geometric classification of the abdominal. The authors’ approach uses a texture analysis based on Gabor filters to extract feature vectors and follows a fuzzy c-means clustering method to estimate voxelwise probability memberships for eight clusters. The memberships estimated from the texture analysis are helpful to identify anatomical structures with inhomogeneous intensities. The membership was used to guide the level set evolution, as well as to derive an initial start close to the abdominal wall.Results: Segmentation results on abdominal walls were both quantitatively and qualitatively validated with surface errors based on manually labeled ground truth. Using texture, mean surface errors for the outer surface of the abdominal wall were less than 2 mm, with 91% of the outer surface less than 5 mm away from the manual tracings; errors were significantly greater (2–5 mm) for methods that did not use the texture.Conclusions: The authors’ approach establishes a baseline for characterizing the abdominal wall for improving VH care. Inherent texture patterns in CT scans are helpful to the tissue classification, and texture analysis can improve the level set segmentation around the abdominal region.« less
Cone Structure in Patients With Usher Syndrome Type III and Mutations in the Clarin 1 Gene
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
NASA Astrophysics Data System (ADS)
Parra, Julie G.; Marsaglia, Kathleen M.; Rivera, Kevin S.; Dawson, Shelby T.; Walsh, J. P.
2012-12-01
The Poverty Shelf, North Island, New Zealand, is a segment of the Waipaoa Sedimentary System (WSS), a MARGINS Source-to-Sink focus site. Our petrographic analysis of sand from shelf core samples indicates that the sand fraction is mainly derived from intra- and potentially extrabasinal sources, but surprisingly, the major fluvial system that drains into Poverty Bay, the Waipaoa River (mean %QFL = xQyFzL), is not the dominant source. Only one vibracore at the mouth of Poverty Bay contained sand (%QFL = xQyFzL) potentially derived from the Waipaoa River. The shelf sand (mean %QFL = xQyFzL) more strongly resembles beach sand (mean %QFL = xQyFzL) collected along the coast, which is likely sourced from pervasive local cliff erosion of Miocene-Pliocene sedimentary units that exhibit similar sandstone detrital modes (mean %QFL = xQyFzL). Texturally, coarser, more poorly sorted and more angular sand is located along the outer shelf, while finer, well-sorted sand characterizes the mid-shelf. These findings suggest a shorter transport history for the material near the outer-shelf bathymetric high areas, and this observation along with the composition data suggests that they were sourced by erosion of locally exposed Miocene-Pliocene units. A potential extrabasinal source of shelf sediment is indicated by anomalous prolate and equant-shaped greywacke (Torlesse) and minor red chert pebbles collected in two outer-shelf box cores on the Lachlan anticline; these are not lithologies found within the terrestrial segment of the WSS or strata comprising the outer-shelf highs. The clast shapes are also distinctly different from the oblate-shaped, pebble-sized greywacke gravel clasts on beaches in Hawke Bay. Rather, these sediments are more similar to Torlesse stream gravel. Seismic and multibeam data support the possibility that during the most recent sea-level lowstand, the Hawke Bay fluvial system flowed into Poverty Canyon, bringing these unique gravels onto what is now the Poverty outer shelf. The presence of the Torlesse gravel is significant in that it highlights how the WSS was not a closed sedimentary system in the past, just as recent sedimentary research has shown in the case today.
Type I interferon dependence of plasmacytoid dendritic cell activation and migration
Asselin-Paturel, Carine; Brizard, Géraldine; Chemin, Karine; Boonstra, Andre; O'Garra, Anne; Vicari, Alain; Trinchieri, Giorgio
2005-01-01
Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration. PMID:15795237
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.
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.
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.
Automatic segmentation of the facial nerve and chorda tympani in pediatric CT scans.
Reda, Fitsum A; Noble, Jack H; Rivas, Alejandro; McRackan, Theodore R; Labadie, Robert F; Dawant, Benoit M
2011-10-01
Cochlear implant surgery is used to implant an electrode array in the cochlea to treat hearing loss. The authors recently introduced a minimally invasive image-guided technique termed percutaneous cochlear implantation. This approach achieves access to the cochlea by drilling a single linear channel from the outer skull into the cochlea via the facial recess, a region bounded by the facial nerve and chorda tympani. To exploit existing methods for computing automatically safe drilling trajectories, the facial nerve and chorda tympani need to be segmented. The goal of this work is to automatically segment the facial nerve and chorda tympani in pediatric CT scans. The authors have proposed an automatic technique to achieve the segmentation task in adult patients that relies on statistical models of the structures. These models contain intensity and shape information along the central axes of both structures. In this work, the authors attempted to use the same method to segment the structures in pediatric scans. However, the authors learned that substantial differences exist between the anatomy of children and that of adults, which led to poor segmentation results when an adult model is used to segment a pediatric volume. Therefore, the authors built a new model for pediatric cases and used it to segment pediatric scans. Once this new model was built, the authors employed the same segmentation method used for adults with algorithm parameters that were optimized for pediatric anatomy. A validation experiment was conducted on 10 CT scans in which manually segmented structures were compared to automatically segmented structures. The mean, standard deviation, median, and maximum segmentation errors were 0.23, 0.17, 0.18, and 1.27 mm, respectively. The results indicate that accurate segmentation of the facial nerve and chorda tympani in pediatric scans is achievable, thus suggesting that safe drilling trajectories can also be computed automatically.
Mechanisms of Retinal Damage from Chronic Laser Radiation.
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
This pineal gland does not mediate phase shifts in the disc shedding rhythm of the rat retina
DOE Office of Scientific and Technical Information (OSTI.GOV)
Goldman, A.I.
Albino rats were subjected to pinealectomy, superior cervical ganglionectomy, or the appropriate sham preparation and were placed in lighting conditions so that light onset was advanced by 10 hr. After 6 days of this regimen, all animals exhibited a complete shift in their outer segment disc shedding rhythm, indicating that the pineal gland is not a factor in mediating such a shift.
Riera, Marina; Fontrodona, Laura; Albert, Silvia; Ramirez, Diana Mora; Seriola, Anna; Salas, Anna; Muñoz, Yolanda; Ramos, David; Villegas-Perez, Maria Paz; Zapata, Miguel Angel; Raya, Angel; Ruberte, Jesus; Veiga, Anna; Garcia-Arumi, Jose
2016-01-01
Retinal dystrophies (RD) are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE) cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC)-based therapies. We differentiated RPE from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) and transplanted them into the subretinal space of the Royal College of Surgeons (RCS) rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD. PMID:27006969
Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa
2010-12-28
Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.
Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa
2010-01-01
Cilia function as cell sensors in many organs, and their disorders are referred to as “ciliopathies.” Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors. PMID:21148103
Keywords image retrieval in historical handwritten Arabic documents
NASA Astrophysics Data System (ADS)
Saabni, Raid; El-Sana, Jihad
2013-01-01
A system is presented for spotting and searching keywords in handwritten Arabic documents. A slightly modified dynamic time warping algorithm is used to measure similarities between words. Two sets of features are generated from the outer contour of the words/word-parts. The first set is based on the angles between nodes on the contour and the second set is based on the shape context features taken from the outer contour. To recognize a given word, the segmentation-free approach is partially adopted, i.e., continuous word parts are used as the basic alphabet, instead of individual characters or complete words. Additional strokes, such as dots and detached short segments, are classified and used in a postprocessing step to determine the final comparison decision. The search for a keyword is performed by the search for its word parts given in the correct order. The performance of the presented system was very encouraging in terms of efficiency and match rates. To evaluate the presented system its performance is compared to three different systems. Unfortunately, there are no publicly available standard datasets with ground truth for testing Arabic key word searching systems. Therefore, a private set of images partially taken from Juma'a Al-Majid Center in Dubai for evaluation is used, while using a slightly modified version of the IFN/ENIT database for training.
Edrington, Thomas C.; Bennett, Michael; Albert, Arlene D.
2008-01-01
The photoreceptor rhodopsin is a G-protein coupled receptor that has recently been proposed to exist as a dimer or higher order oligomer, in contrast to the previously described monomer, in retinal rod outer segment disk membranes. Rhodopsin exhibits considerably greater thermal stability than opsin (the bleached form of the receptor), which is reflected in an ∼15°C difference in the thermal denaturation temperatures (Tm) of rhodopsin and opsin as measured by differential scanning calorimetry. Here we use differential scanning calorimetry to investigate the effect of partial bleaching of disk membranes on the Tm of rhodopsin and of opsin in native disk membranes, as well as in cross-linked disk membranes in which rhodopsin dimers are known to be present. The Tms of rhodopsin and opsin are expected to be perturbed if mixed oligomers are present. The Tm remained constant for rhodopsin and opsin in native disks regardless of the level of bleaching. In contrast, the Tm of cross-linked rhodopsin in disk membranes was dependent on the extent of bleaching. The energy of activation for denaturation of rhodopsin and cross-linked rhodopsin was calculated. Cross-linking rhodopsin significantly decreased the energy of activation. We conclude that in native disk membranes, rhodopsin behaves predominantly as a monomer. PMID:18586850
A variant of arrestin-1 binds rod outer segment membranes in a light-independent manner.
Uzcanga, Graciela L; Becerra, Aniuska R; Perdomo, Deisy; Bubis, José
2011-03-15
A 50-kDa-polypeptide band peripherally bound to retinal rod outer segment (ROS) membranes was purified by anion-exchange chromatography. When the 50-kDa protein was compared with purified arrestin-1, it was observed that: (1) both proteins comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and were recognized by either anti-50-kDa protein polyclonal antibodies or anti-arrestin-1 monoclonal antibodies; (2) protein fragments and peptide fingerprint maps obtained following limited and complete proteolysis with specific proteases were very similar for both molecules; and (3) several chromatographically-purified tryptic peptides from the 50-kDa protein possessed the same amino acid composition as tryptic peptides deduced from the reported arrestin-1 primary structure. Consequently, arrestin-1 and the purified 50-kDa protein must correspond to variants of the same molecule. However, in contrast to arrestin-1 that associated to the ROS membranes only in the presence of light and ATP, the 50-kDa protein interacted with the ROS membranes in a light-independent manner, either in the presence or absence of ATP. These results clearly established that phosphorylated and illuminated rhodopsin is not the membrane anchor for this variant of arrestin-1. Copyright © 2010 Elsevier Inc. All rights reserved.
Aneurysm of the Left Atrial Appendage
Victor, Solomon; Nayak, Vijaya M.
2001-01-01
A 43-year-old woman underwent excision of an aneurysm of the left atrial appendage, which had been causing cerebrovascular embolic episodes. We attribute the aneurysm to congenital dysplasia of the musculi pectinati in the left atrial appendage and of the bands of atrial muscle from which they arise. In Appendix I, we draw attention to the morphologically similar arrangements of inner and outer bands that emanate from a common transverse interatrial band and yield morphologically similar medial, descending, and ascending palm-leaf arrangements of musculi pectinati. In addition, we observe that the strap-like arrangements of musculi in both atria connect the outer band with the para-annular segment of the inner band. In Appendix II, we briefly review the literature concerning musculi pectinati and related bands. PMID:11453121
Wang, Li; Li, Gang; Adeli, Ehsan; Liu, Mingxia; Wu, Zhengwang; Meng, Yu; Lin, Weili; Shen, Dinggang
2018-06-01
Tissue segmentation of infant brain MRIs with risk of autism is critically important for characterizing early brain development and identifying biomarkers. However, it is challenging due to low tissue contrast caused by inherent ongoing myelination and maturation. In particular, at around 6 months of age, the voxel intensities in both gray matter and white matter are within similar ranges, thus leading to the lowest image contrast in the first postnatal year. Previous studies typically employed intensity images and tentatively estimated tissue probabilities to train a sequence of classifiers for tissue segmentation. However, the important prior knowledge of brain anatomy is largely ignored during the segmentation. Consequently, the segmentation accuracy is still limited and topological errors frequently exist, which will significantly degrade the performance of subsequent analyses. Although topological errors could be partially handled by retrospective topological correction methods, their results may still be anatomically incorrect. To address these challenges, in this article, we propose an anatomy-guided joint tissue segmentation and topological correction framework for isointense infant MRI. Particularly, we adopt a signed distance map with respect to the outer cortical surface as anatomical prior knowledge, and incorporate such prior information into the proposed framework to guide segmentation in ambiguous regions. Experimental results on the subjects acquired from National Database for Autism Research demonstrate the effectiveness to topological errors and also some levels of robustness to motion. Comparisons with the state-of-the-art methods further demonstrate the advantages of the proposed method in terms of both segmentation accuracy and topological correctness. © 2018 Wiley Periodicals, Inc.
Mittal, Rahul; Krishnan, Subramanian; Gonzalez-Gomez, Ignacio; Prasadarao, Nemani V
2011-01-21
Outer membrane protein A (OmpA) has been implicated as an important virulence factor in several gram-negative bacterial infections such as Escherichia coli K1, a leading cause of neonatal meningitis associated with significant mortality and morbidity. In this study, we generated E. coli K1 mutants that express OmpA in which three or four amino acids from various extracellular loops were changed to alanines, and we examined their ability to survive in several immune cells. We observed that loop regions 1 and 2 play an important role in the survival of E. coli K1 inside neutrophils and dendritic cells, and loop regions 1 and 3 are needed for survival in macrophages. Concomitantly, E. coli K1 mutants expressing loop 1 and 2 mutations were unable to cause meningitis in a newborn mouse model. Of note, mutations in loop 4 of OmpA enhance the severity of the pathogenesis by allowing the pathogen to survive better in circulation and to produce high bacteremia levels. These results demonstrate, for the first time, the roles played by different regions of extracellular loops of OmpA of E. coli K1 in the pathogenesis of meningitis and may help in designing effective preventive strategies against this deadly disease.
Postembryonic development of Antygomonas incomitata (Kinorhyncha: Cyclorhagida).
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.
The perforating branches of the P1 segment of the posterior cerebral artery.
Kaya, Ahmet Hilmi; Dagcinar, Adnan; Ulu, Mustafa Onur; Topal, Arif; Bayri, Yasar; Ulus, Aykan; Kopuz, Cem; Sam, Bulent
2010-01-01
The perforating branches of the P1 segment of the posterior cerebral artery are vulnerable to injury. Because of their close proximity to the basilar artery, the vulnerability occurs especially during surgical interventions for vascular pathologies such as basilar apex aneurysms. Therefore, extensive knowledge of the microsurgical anatomy of this area is mandatory to prevent poor post-operative outcomes. We microscopically examined 28 P1 segments obtained from 14 adult fresh cadaver brains (6 silicone injected, 8 freshly examined). The P1 segments ranged between 2.8mm and 12.2mm (mean 6.8mm) in length with a mean outer diameter of 1.85 mm (range 0.8-4.5mm). All 94 thalamoperforating branches identified in 27 P1 segments (mean 3.35 branches per segment) arose from the postero-superior aspect of P1 and were the most proximally originating branch in nearly all specimens (96.4%). In addition in 28 P1s, 12 short circumflex arteries (42.8%; mean 0.42 branches per segment), 16 long circumflex arteries (57.1%; mean 0.57 branches per segment) and 10 medial posterior choroidal arteries (35.7%; mean 0.35 branches per segment) were identified and all originated from the posterior or postero-inferior surface of the P1 segment. When the P1 segment had more than one type of branch, it was the short circumflex arteries that were always more proximal in origin than the others. The medial posterior choroidal arteries were always more distal in origin. All three branches were not observed together in any of the P1 segments. The findings in this, and future, anatomical studies may help to reduce the post-surgical morbidity and mortality rates after surgery for posterior circulation aneurysms. Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Mannosylated polyion complexes for in vivo gene delivery into CD11c(+) dendritic cells.
Raviv, Lior; Jaron-Mendelson, Michal; David, Ayelet
2015-02-02
Dendritic cells (DCs) possess unique abilities in initiating primary immune responses and thus represent prime targets for DNA-based vaccinations. Here, we describe the design and synthesis of mannosylated polyion complexes (PICs) composed of cationic polyethylenimine (PEI) and hydrophilic polyethylene glycol (PEG) segments, and bearing mono- and trivalent mannose as a ligand for targeting mannose receptor (MR/CD206)-positive DCs. Amino-terminated mannose (Man)-containing ligands in mono- and trivalent presentations (Man- and Man3-, respectively) were prepared and conjugated to PEG via an N-hydroxysuccinimide (NHS)-activated terminal. Thiolated PEI was conjugated to the mannosylated PEG via the maleimide (MAL)-activated terminal. The resulting positively charged diblock copolymers bearing mannoses (Man-PEG-b-PEI and Man3-PEG-b-PEI) were self-assembled with DNA to form PICs with lower surface charge than did their PEI building block and mean hydrodynamic diameters in the range of 100-450 nm, depending on the N/P ratio. Man3-PEG-b-PEI demonstrated a 3-4-fold greater transfection efficiency in MR-positive dendritic cell lines (THP-1, DC2.4), relative to Man-PEG-b-PEI, exhibited low cytotoxicity when compared with PEI, and showed low transfection efficiency in nondendritic HeLa cells. In preliminary in vivo experiments, Man-PEG-b-PEI/DNA and Man3-PEG-b-PEI/DNA demonstrated 2-3-fold higher gene delivery efficiency into CD11c(+) DCs collected from inguinal lymph nodes of C57/BL6 mice, when compared to PEI/DNA complexes, as shown by GFP expression measurements, 24 h post subcutaneous injection. The results indicate that the mannosylated PICs are a safe and effective gene delivery system, showing in vivo specificity toward CD11c(+) DCs.
Zalups, Rudolfs K.; Joshee, Lucy; Bridges, Christy C.
2014-01-01
The role of the multi-resistance protein 2 (Mrp2) in the nephropathy induced by inorganic mercuric mercury (Hg2+) was studied in rats (TR−) and mice (Mrp2−/−), which lack functional Mrp2, and control animals. Animals were exposed to nephrotoxic doses of HgCl2. Forty-eight or 24 hours after exposure, tissues were harvested and analyzed for Hg content and markers of injury. Histological analyses revealed that the proximal tubular segments affected pathologically by Hg2+ were significantly different between Mrp2-deficient animals and controls. In the absence of Mrp2, cellular injury localized almost exclusively in proximal tubular segments in the subcapsular (S1) to midcortical regions (early S2) of the kidney. In control animals, cellular death occurred mainly in the proximal tubular segments in the inner cortex (late S2) and outer stripe of the outer medulla (S3). These differences in renal pathology indicate that axial heterogeneity exists along the proximal tubule with respect to how mercuric ions are handled. Total renal and hepatic accumulation of mercury was also greater in animals lacking Mrp2 than in controls, indicating that Mrp2 normally plays a significant role in eliminating mercuric ions from within proximal tubular cells and hepatocytes. Analyses of plasma creatinine, BUN, and renal expression of Kim-1 and Ngal tend to support the severity of the nephropathies detected histologically. Collectively, our findings indicate that a fraction of mercuric ions is normally secreted by Mrp2 in early portions of proximal tubules into the lumen and then is absorbed downstream in straight portions, where mercuric species typically induce toxic effects. PMID:25145654
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bruns, T.R.; Carlson, P.R.; Stevenson, A.J.
1990-06-01
GLORIA images collected in 1989 along southeast Alaska and British Columbia strikingly show the active trace of the Fairweather-Queen Charlotte transform fault system beneath the outer shelf and slope; seismic-reflection data are used to track the fault system across the continental shelf where GLORIA data are not available. From Cross Sound to Chatham Strait, the fault system is comprised of two sets of subparallel fault traces separated by 3 to 6 km. The fault system crosses the shelf from Icy Point to south of Yakobi Valley, then follows the shelf edge to Chatham Strait. Between Chatham Strait and Dixon Entrance,more » a single, sharply defined active fault trace underlies the upper and middle slope. This fault segment is bounded on the seaward side by a high, midslope ridge and by lower slope Quaternary( ) anticlines up to 35 km wide. Southeast of Dixon Entrance, the active fault trace trends back onto the outer shelf until midway along the Queen Charlotte Islands, then cuts back to and stays at midslope to the Tuzo Wilson Knolls south of the Queen Charlotte Islands. The fault steps westward at Tuzo Wilson Knolls, which are likely part of a spreading ridge segment. Major deep-sea fans along southeast Alaska show a southeastward age progression from older to younger and record both point source deposition at Chatham Strait and Dixon Entrance and subsequent (Quaternary ) offset along the fault system. Subsidence of ocean plate now adjacent to the Chatham Strait-Dixon Entrance fault segment initiated development of both Mukluk and Horizon Channels.« less
Molecular Characterization of abLIM, a Novel Actin-binding and Double Zinc Finger Protein
Roof, Dorothy J.; Hayes, Annmarie; Adamian, Michael; Chishti, Athar H.; Li, Tiansen
1997-01-01
Molecules that couple the actin-based cytoskeleton to intracellular signaling pathways are central to the processes of cellular morphogenesis and differentiation. We have characterized a novel protein, the actin-binding LIM (abLIM) protein, which could mediate such interactions between actin filaments and cytoplasmic targets. abLIM protein consists of a COOH-terminal cytoskeletal domain that is fused to an NH2-terminal domain consisting of four double zinc finger motifs. The cytoskeletal domain is ∼50% identical to erythrocyte dematin, an actin-bundling protein of the red cell membrane skeleton, while the zinc finger domains conform to the LIM motif consensus sequence. In vitro expression studies demonstrate that abLIM protein can bind to F-actin through the dematin-like domain. Transcripts corresponding to three distinct isoforms have a widespread tissue distribution. However, a polypeptide corresponding to the full-length isoform is found exclusively in the retina and is enriched in biochemical extracts of retinal rod inner segments. abLIM protein also undergoes extensive phosphorylation in light-adapted retinas in vivo, and its developmental expression in the retina coincides with the elaboration of photoreceptor inner and outer segments. Based on the composite primary structure of abLIM protein, actin-binding capacity, potential regulation via phosphorylation, and isoform expression pattern, we speculate that abLIM may play a general role in bridging the actin-based cytoskeleton with an array of potential LIM protein-binding partners. The developmental time course of abLIM expression in the retina suggests that the retina-specific isoform may have a specialized role in the development or elaboration of photoreceptor inner and outer segments. PMID:9245787
Interaction of Arrestin with Enolase1 in Photoreceptors
Bolch, Susan; Dugger, Donald R.; Li, Jian; Esquenazi, Isi; Arendt, Anatol; Benzenhafer, Del; McDowell, J. Hugh
2011-01-01
Purpose. Arrestin is in disequilibrium in photoreceptors, translocating between inner and outer segments in response to light. The purpose of this project was to identify the cellular component with which arrestin associates in the dark-adapted retina. Methods. Retinas were cross-linked with 2.5 mM dithiobis(succinimidylpropionate) (DSP), and arrestin-containing complexes purified by anion-exchange chromatography. Tandem mass spectrometric analysis was used to identify the protein components in the complex. Enolase localization in photoreceptors was assessed by immunohistochemistry. Confirmation of interacting components was performed using immunoprecipitation and surface plasmon resonance (SPR). Enolase activity was also assessed in the presence of arrestin1. Results. In retinas treated with DSP, arrestin cross-linked in a 125-kDa complex. The principal components of this complex were arrestin1 and enolase1. Both arrestin1 and -4 were pulled down with enolase1 when enolase1 was immunoprecipitated. In the dark-adapted retina, enolase1 co-localized with arrestin1 in the inner segments and outer nuclear layer, but remained in the inner segments when arrestin1 translocated in response to light adaptation. SPR of purified arrestin1 and enolase1 demonstrated direct binding between arrestin1 and enolase1. Arrestin1 modulated the catalytic activity of enolase1, slowing it by as much as 24%. Conclusions. The results show that in the dark-adapted retina, arrestin1 and -4 interact with enolase1. The SPR data show that the interaction between arrestin1 and enolase1 was direct, not requiring a third element to form the complex. Arrestin1 slowed the catalytic activity of enolase1, suggesting that light-driven translocation of arrestin1 may modulate the metabolic activity of photoreceptors. PMID:21051714
Interaction of arrestin with enolase1 in photoreceptors.
Smith, W Clay; Bolch, Susan; Dugger, Donald R; Li, Jian; Esquenazi, Isi; Arendt, Anatol; Benzenhafer, Del; McDowell, J Hugh
2011-03-01
Arrestin is in disequilibrium in photoreceptors, translocating between inner and outer segments in response to light. The purpose of this project was to identify the cellular component with which arrestin associates in the dark-adapted retina. Retinas were cross-linked with 2.5 mM dithiobis(succinimidylpropionate) (DSP), and arrestin-containing complexes purified by anion-exchange chromatography. Tandem mass spectrometric analysis was used to identify the protein components in the complex. Enolase localization in photoreceptors was assessed by immunohistochemistry. Confirmation of interacting components was performed using immunoprecipitation and surface plasmon resonance (SPR). Enolase activity was also assessed in the presence of arrestin1. In retinas treated with DSP, arrestin cross-linked in a 125-kDa complex. The principal components of this complex were arrestin1 and enolase1. Both arrestin1 and -4 were pulled down with enolase1 when enolase1 was immunoprecipitated. In the dark-adapted retina, enolase1 co-localized with arrestin1 in the inner segments and outer nuclear layer, but remained in the inner segments when arrestin1 translocated in response to light adaptation. SPR of purified arrestin1 and enolase1 demonstrated direct binding between arrestin1 and enolase1. Arrestin1 modulated the catalytic activity of enolase1, slowing it by as much as 24%. The results show that in the dark-adapted retina, arrestin1 and -4 interact with enolase1. The SPR data show that the interaction between arrestin1 and enolase1 was direct, not requiring a third element to form the complex. Arrestin1 slowed the catalytic activity of enolase1, suggesting that light-driven translocation of arrestin1 may modulate the metabolic activity of photoreceptors.
Nasruddin, Nurrul Shaqinah; Azmai, Mohammad Noor Amal; Ismail, Ahmad; Saad, Mohd Zamri; Daud, Hassan Mohd; Zulkifli, Syaizwan Zahmir
2014-01-01
This study was conducted to record the histological features of the gastrointestinal tract of wild Indonesian shortfin eel, Anguilla bicolor bicolor (McClelland, 1844), captured in Peninsular Malaysia. The gastrointestinal tract was segmented into the oesophagus, stomach, and intestine. Then, the oesophagus was divided into five (first to fifth), the stomach into two (cardiac and pyloric), and the intestine into four segments (anterior, intermediate, posterior, and rectum) for histological examinations. The stomach had significantly taller villi and thicker inner circular muscles compared to the intestine and oesophagus. The lamina propria was thickest in stomach, significantly when compared with oesophagus, but not with the intestine. However, the intestine showed significantly thicker outer longitudinal muscle while gastric glands were observed only in the stomach. The histological features were closely associated with the functions of the different segments of the gastrointestinal tract. In conclusion, the histological features of the gastrointestinal tract of A. b. bicolor are consistent with the feeding habit of a carnivorous fish.
Manufacture of a 1.7m prototype of the GMT primary mirror segments
NASA Astrophysics Data System (ADS)
Martin, H. M.; Burge, J. H.; Miller, S. M.; Smith, B. K.; Zehnder, R.; Zhao, C.
2006-06-01
We have nearly completed the manufacture of a 1.7 m off-axis mirror as part of the technology development for the Giant Magellan Telescope. The mirror is an off-axis section of a 5.3 m f/0.73 parent paraboloid, making it roughly a 1:5 model of the outer 8.4 m GMT segment. The 1.7 m mirror will be the primary mirror of the New Solar Telescope at Big Bear Solar Observatory. It has a 2.7 mm peak-to-valley departure from the best-fit sphere, presenting a serious challenge in terms of both polishing and measurement. The mirror was polished with a stressed lap, which bends actively to match the local curvature at each point on the mirror surface, and works for asymmetric mirrors as well as symmetric aspheres. It was measured using a hybrid reflective-diffractive null corrector to compensate for the mirror's asphericity. Both techniques will be applied in scaled-up versions to the GMT segments.
Hashimoto, Yuki; Saito, Wataru; Fujiya, Akio; Yoshizawa, Chikako; Hirooka, Kiriko; Mori, Shohei; Noda, Kousuke; Ishida, Susumu
2015-01-01
Purpose To investigate sequential post-operative thickness changes in inner and outer retinal layers in eyes with an idiopathic macular hole (MH). Methods Retrospective case series. Twenty-four eyes of 23 patients who had received pars plana vitrectomy (PPV) for the closure of MH were included in the study. Spectral domain optical coherence tomography C-scan was used to automatically measure the mean thickness of the inner and outer retinal layers pre-operatively and up to 6 months following surgery. The photoreceptor outer segment (PROS) length was measured manually and was used to assess its relationship with best-corrected visual acuity (BCVA). Results Compared with the pre-operative thickness, the inner layers significantly thinned during follow-up (P = 0.02), particularly in the parafoveal (P = 0.01), but not perifoveal, area. The post-operative inner layer thinning ranged from the ganglion cell layer to the inner plexiform layer (P = 0.002), whereas the nerve fiber layer was unaltered. Outer layer thickness was significantly greater post-operatively (P = 0.002), and especially the PROS lengthened not only in the fovea but also in the parafovea (P < 0.001). Six months after surgery, BCVA was significantly correlated exclusively with the elongated foveal PROS (R = 0.42, P = 0.03), but not with any of the other thickness parameters examined. Conclusions Following PPV for MH, retinal inner layers other than the nerve fiber layer thinned, suggestive of subclinical thickening in the inner layers where no cyst was evident pre-operatively. In contrast, retinal outer layer thickness significantly increased, potentially as a result of PROS elongation linking tightly with favorable visual prognosis in MH eyes. PMID:26291526
Regulation of dendrite growth and maintenance by exocytosis
Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.
2015-01-01
ABSTRACT Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop–exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments. PMID:26483382
Ahn, A N; Monti, R J; Biewener, A A
2003-01-01
Many studies examine sarcomere dynamics in single fibres or length–tension dynamics in whole muscles in vivo or in vitro, but few studies link the various levels of organisation. To relate data addressing in vitro muscle segment behaviour with in vivo whole muscle behaviour during locomotion, we measured in vivo strain patterns of muscle segments using three sonomicrometry crystals implanted along a fascicle of the semimembranosus muscle in the American toad (Bufo americanus; n = 6) during hopping. The centre crystal emitted an ultrasonic signal, while the outer crystals received the signal allowing the instantaneous measurement of lengths from two adjacent muscle segments. On the first day, we recorded from the central and distal segments. On the second day of recordings, the most distal crystal was moved to a proximal position to record from a proximal segment and the same central segment. When the toads hopped a distance of two body lengths, the proximal and central segments strained −15.1 ± 6.1 and −14.0 ± 4.9 % (i.e. shortening), respectively. Strain of the distal segment, however, was significantly lower and more variable in pattern, often lengthening before shortening during a hop. From rest length, the distal segment initially lengthened by 2.6 ± 2.0 % before shortening by 6.5 ± 3.2 % at the same hop distance. Under in vitro conditions, the central segment always shortened more than the distal segment, except when passively cycled, during which the segments strained similarly. When the whole muscle was cycled sinusoidally and stimulated phasically in vitro, the two adjacent segments strained in opposite directions over much (up to 34 %) of the cycle. These differences in strain amplitude and direction imply that two adjacent segments can not only produce and/or absorb varying amounts of mechanical energy, but can also operate on different regions of their force–length and force–velocity relationships when activated by the same neural signal. Understanding regional differences in contractile dynamics within muscles is therefore important to linking our understanding of sarcomere behaviour with whole muscle behaviour during locomotion. PMID:12717006
2015-10-01
Several target genes such as Oct4, Sox2, TGFB, and Col1A1 were generally up-regulated in all sections. In distal sections, VWF, PDGFB, and EGFR were...TGFB, and Col1A1 in all sections. No significant main effects were found for target gene fold-change between outer or inner membrane position or distal
NASA Astrophysics Data System (ADS)
Wang, Fu; Wu, Zining; Huang, Can; Ma, Dexin; Jakumeit, Jürgen; Bührig-Polaczek, Andreas
2017-12-01
The effect of withdrawal rates on the three-dimensional dendrite growth within the shrouds of single crystal blades during directional solidification was studied by both experiments and numerical simulations. The results showed that at given withdrawal rates, the dendrite pattern within the shrouds comprised three zones: primary dendrite zone, secondary dendrite spread zone, and a higher-order dendrite branched zone. With increasing withdrawal rate, the average primary dendrite arm spacing in the primary dendrite zone and the average secondary dendrite arm spacings in both the secondary dendrite spread zone and the higher-order dendrite branched zone were reduced. Independent of the variation in withdrawal rate, two analogous dendrite growth routes were observed within the shrouds of the employed blade geometry. These routes originated from the primary dendrites in the primary dendrite zone and filled in the shrouds by directly spreading secondary or successively branching higher-order dendrites. Except for a withdrawal rate of 6 mm min-1, these dendrites impinged at the shroud's highest extremity and could be explained by the simulated moving isotherms. As the withdrawal rate was increased to 2.5 mm min-1, undercooling and contraction stress-related equiaxed grains were observed in the interdendritic region at the lowest shroud extremity. With increasing withdrawal rate, the amount of the defects was increased. Since the defects destroy the integrity of single crystal blades, the solidification condition within the shroud should be controlled to avoid their occurrence. Along the dendrite growth route, an accumulated misorientation of the dendrites was observed. At the same positions, this accumulation increased with increasing withdrawal rate.
Drescher, M J; Drescher, D G; Khan, K M; Hatfield, J S; Ramakrishnan, N A; Abu-Hamdan, M D; Lemonnier, L A
2006-09-29
Pituitary adenylyl cyclase-activating polypeptide (PACAP), via its specific receptor pituitary adenylyl cyclase-activating polypeptide receptor 1 (PAC1-R), is known to have roles in neuromodulation and neuroprotection associated with glutamatergic and cholinergic neurotransmission, which, respectively, are believed to form the primary basis for afferent and efferent signaling in the organ of Corti. Previously, we identified transcripts for PACAP preprotein and multiple splice variants of its receptor, PAC1-R, in microdissected cochlear subfractions. In the present work, neural localizations of PACAP and PAC1-R within the organ of Corti and spiral ganglion were examined, defining sites of PACAP action. Immunolocalization of PACAP and PAC1-R in the organ of Corti and spiral ganglion was compared with immunolocalization of choline acetyltransferase (ChAT) and synaptophysin as efferent neuronal markers, and glutamate receptor 2/3 (GluR2/3) and neurofilament 200 as afferent neuronal markers, for each of the three cochlear turns. Brightfield microscopy giving morphological detail for individual immunolocalizations was followed by immunofluorescence detection of co-localizations. PACAP was found to be co-localized with ChAT in nerve fibers of the intraganglionic spiral bundle and beneath the inner and outer hair cells within the organ of Corti. Further, evidence was obtained that PACAP is expressed in type I afferent axons leaving the spiral ganglion en route to the auditory nerve, potentially serving as a neuromodulator in axonal terminals. In contrast to the efferent localization of PACAP within the organ of Corti, PAC1-R immunoreactivity was co-localized with afferent dendritic neuronal marker GluR2/3 in nerve fibers passing beneath and lateral to the inner hair cell and in fibers at supranuclear and basal sites on outer hair cells. Given the known association of PACAP with catecholaminergic neurotransmission in sympathoadrenal function, we also re-examined the issue of whether the organ of Corti receives adrenergic innervation. We now demonstrate the existence of nerve fibers within the organ of Corti which are immunoreactive for the adrenergic marker dopamine beta-hydroxylase (DBH). DBH immunoreactivity was particularly prominent in nerve fibers both at the base and near the cuticular plate of outer hair cells of the apical turn, extending to the non-sensory Hensen's cell region. Evidence was obtained for limited co-localization of DBH with PAC1-R and PACAP. In the process of this investigation, we obtained evidence that efferent and afferent nerve fibers, in addition to adrenergic nerve fibers, are present at supranuclear sites on outer hair cells and distributed within the non-sensory epithelium of the apical cochlear turn for rat, based upon immunoreactivity for the corresponding neuronal markers. Overall, PACAP is hypothesized to act within the organ of Corti as an efferent neuromodulator of afferent signaling via PAC1-R that is present on type I afferent dendrites, in position to afford protection from excitotoxicity. Additionally, PACAP/PAC1-R may modulate secretion of catecholamines from adrenergic terminals within the organ of Corti.
Mishchenko, Yuriy
2009-01-30
We describe an approach for automation of the process of reconstruction of neural tissue from serial section transmission electron micrographs. Such reconstructions require 3D segmentation of individual neuronal processes (axons and dendrites) performed in densely packed neuropil. We first detect neuronal cell profiles in each image in a stack of serial micrographs with multi-scale ridge detector. Short breaks in detected boundaries are interpolated using anisotropic contour completion formulated in fuzzy-logic framework. Detected profiles from adjacent sections are linked together based on cues such as shape similarity and image texture. Thus obtained 3D segmentation is validated by human operators in computer-guided proofreading process. Our approach makes possible reconstructions of neural tissue at final rate of about 5 microm3/manh, as determined primarily by the speed of proofreading. To date we have applied this approach to reconstruct few blocks of neural tissue from different regions of rat brain totaling over 1000microm3, and used these to evaluate reconstruction speed, quality, error rates, and presence of ambiguous locations in neuropil ssTEM imaging data.
Ng, Julian; Browning, Alyssa; Lechner, Lorenz; Terada, Masako; Howard, Gillian; Jefferis, Gregory S. X. E.
2016-01-01
Large dimension, high-resolution imaging is important for neural circuit visualisation as neurons have both long- and short-range patterns: from axons and dendrites to the numerous synapses at terminal endings. Electron Microscopy (EM) is the favoured approach for synaptic resolution imaging but how such structures can be segmented from high-density images within large volume datasets remains challenging. Fluorescent probes are widely used to localise synapses, identify cell-types and in tracing studies. The equivalent EM approach would benefit visualising such labelled structures from within sub-cellular, cellular, tissue and neuroanatomical contexts. Here we developed genetically-encoded, electron-dense markers using miniSOG. We demonstrate their ability in 1) labelling cellular sub-compartments of genetically-targeted neurons, 2) generating contrast under different EM modalities, and 3) segmenting labelled structures from EM volumes using computer-assisted strategies. We also tested non-destructive X-ray imaging on whole Drosophila brains to evaluate contrast staining. This enabled us to target specific regions for EM volume acquisition. PMID:27958322
Optimization of GaAs Nanowire Pin Junction Array Solar Cells by Using AlGaAs/GaAs Heterojunctions
NASA Astrophysics Data System (ADS)
Wu, Yao; Yan, Xin; Wei, Wei; Zhang, Jinnan; Zhang, Xia; Ren, Xiaomin
2018-04-01
We optimized the performance of GaAs nanowire pin junction array solar cells by introducing AlGaAs/GaAs heterejunctions. AlGaAs is used for the p type top segment for axial junctions and the p type outer shell for radial junctions. The AlGaAs not only serves as passivation layers for GaAs nanowires but also confines the optical generation in the active regions, reducing the recombination loss in heavily doped regions and the minority carrier recombination at the top contact. The results show that the conversion efficiency of GaAs nanowires can be greatly enhanced by using AlGaAs for the p segment instead of GaAs. A maximum efficiency enhancement of 8.42% has been achieved in this study. And for axial nanowire, by using AlGaAs for the top p segment, a relatively long top segment can be employed without degenerating device performance, which could facilitate the fabrication and contacting of nanowire array solar cells. While for radial nanowires, AlGaAs/GaAs nanowires show better tolerance to p-shell thickness and surface condition.
Optimization of GaAs Nanowire Pin Junction Array Solar Cells by Using AlGaAs/GaAs Heterojunctions.
Wu, Yao; Yan, Xin; Wei, Wei; Zhang, Jinnan; Zhang, Xia; Ren, Xiaomin
2018-04-25
We optimized the performance of GaAs nanowire pin junction array solar cells by introducing AlGaAs/GaAs heterejunctions. AlGaAs is used for the p type top segment for axial junctions and the p type outer shell for radial junctions. The AlGaAs not only serves as passivation layers for GaAs nanowires but also confines the optical generation in the active regions, reducing the recombination loss in heavily doped regions and the minority carrier recombination at the top contact. The results show that the conversion efficiency of GaAs nanowires can be greatly enhanced by using AlGaAs for the p segment instead of GaAs. A maximum efficiency enhancement of 8.42% has been achieved in this study. And for axial nanowire, by using AlGaAs for the top p segment, a relatively long top segment can be employed without degenerating device performance, which could facilitate the fabrication and contacting of nanowire array solar cells. While for radial nanowires, AlGaAs/GaAs nanowires show better tolerance to p-shell thickness and surface condition.
Hall, Alicia M.; Throesch, Benjamin T.; Buckingham, Susan C.; Markwardt, Sean J.; Peng, Yin; Wang, Qin
2015-01-01
Neuronal hyperexcitability occurs early in the pathogenesis of Alzheimer's disease (AD) and contributes to network dysfunction in AD patients. In other disorders with neuronal hyperexcitability, dysfunction in the dendrites often contributes, but dendritic excitability has not been directly examined in AD models. We used dendritic patch-clamp recordings to measure dendritic excitability in the CA1 region of the hippocampus. We found that dendrites, more so than somata, of hippocampal neurons were hyperexcitable in mice overexpressing Aβ. This dendritic hyperexcitability was associated with depletion of Kv4.2, a dendritic potassium channel important for regulating dendritic excitability and synaptic plasticity. The antiepileptic drug, levetiracetam, blocked Kv4.2 depletion. Tau was required, as crossing with tau knock-out mice also prevented both Kv4.2 depletion and dendritic hyperexcitability. Dendritic hyperexcitability induced by Kv4.2 deficiency exacerbated behavioral deficits and increased epileptiform activity in hAPP mice. We conclude that increased dendritic excitability, associated with changes in dendritic ion channels including Kv4.2, may contribute to neuronal dysfunction in early stages AD. PMID:25878292
Absolute measurements of large mirrors
NASA Astrophysics Data System (ADS)
Su, Peng
The ability to produce mirrors for large astronomical telescopes is limited by the accuracy of the systems used to test the surfaces of such mirrors. Typically the mirror surfaces are measured by comparing their actual shapes to a precision master, which may be created using combinations of mirrors, lenses, and holograms. The work presented here develops several optical testing techniques that do not rely on a large or expensive precision, master reference surface. In a sense these techniques provide absolute optical testing. The Giant Magellan Telescope (GMT) has been designed with a 350 m 2 collecting area provided by a 25 m diameter primary mirror made out from seven circular independent mirror segments. These segments create an equivalent f/0.7 paraboloidal primary mirror consisting of a central segment and six outer segments. Each of the outer segments is 8.4 m in diameter and has an off-axis aspheric shape departing 14.5 mm from the best-fitting sphere. Much of the work in this dissertation is motivated by the need to measure the surfaces or such large mirrors accurately, without relying on a large or expensive precision reference surface. One method for absolute testing describing in this dissertation uses multiple measurements relative to a reference surface that is located in different positions with respect to the test surface of interest. The test measurements are performed with an algorithm that is based on the maximum likelihood (ML) method. Some methodologies for measuring large flat surfaces in the 2 m diameter range and for measuring the GMT primary mirror segments were specifically developed. For example, the optical figure of a 1.6-m flat mirror was determined to 2 nm rms accuracy using multiple 1-meter sub-aperture measurements. The optical figure of the reference surface used in the 1-meter sub-aperture measurements was also determined to the 2 nm level. The optical test methodology for a 1.7-m off axis parabola was evaluated by moving several times the mirror under test in relation to the test system. The result was a separation of errors in the optical test system to those errors from the mirror under test. This method proved to be accurate to 12nm rms. Another absolute measurement technique discussed in this dissertation utilizes the property of a paraboloidal surface of reflecting rays parallel to its optical axis, to its focal point. We have developed a scanning pentaprism technique that exploits this geometry to measure off-axis paraboloidal mirrors such as the GMT segments. This technique was demonstrated on a 1.7 m diameter prototype and proved to have a precision of about 50 nm rms.
NASA Astrophysics Data System (ADS)
Riggs, S. R.; Thieler, E. R.; Mallinson, D. A.; Culver, S. J.; Corbett, D. R.; Hoffman, C. W.
2002-12-01
The NE North Carolina coastal system contains an exceptionally thick and well preserved Quaternary stratigraphic record that is the focus of a five-year Cooperative Coastal Geology Program between the USGS, several academic institutions, and state agencies. The major goal is to map this Quaternary section on the inner continental shelf, Outer Banks barrier islands, Albemarle-Pamlico estuarine system, and adjacent land areas. The program objectives are to define the geologic framework, develop the detailed evolutionary history, and understand the ongoing process dynamics driving this large, complex, and rapidly changing, high-energy coastal system. Preliminary data synthesis demonstrates that the major controls dictating the present health and future evolution of this coastal system include the following. 1) The regional late Pleistocene morphology constitutes the underlying geologic framework that the Holocene system has inherited. 2) The controlling paleotopography is a series of lowstand drainage basins consisting of trunk and tributary streams and associated interstream divides that are being drowned. 3) Three major sediment sources dictate the highly variable sand resources available to specific barrier segments and include riverine channel and deltaic deposits associated with lowstand trunk streams, the large cross-shelf cape shoal sand deposits, and sand-rich units occurring within the adjacent shoreface and inner-self strata. 4) Wherever large sand supplies have historically been available, the barrier segments occur as complex islands with large sand volumes producing high and wide barriers, whereas barrier segments without adequate sand supplies are sediment starved and occur as simple overwash barriers. 5) Human modification of the barrier islands over the past seven decades represents a major force that has significantly changed the barrier island dynamics and evolution. 6) The Albemarle Embayment appears to have a slightly higher rate of sea-level rise than adjacent regions due to a slow rate of regional subsidence. Consequently, if the ongoing pattern of storm activity and sea-level rise either continues or increases during the next few decades to centuries, several simple overwash barrier segments on the Outer Banks, that are currently disintegrating, will ultimately collapse into Pamlico Sound. These barrier segments will likely back-step across the open marine Pamlico Embayment and reform on the landward side. A few sand-rich complex barrier segments will persist as isolated, but perched and eroding islands for some longer period of time. In contrast, simple overwash barrier segments that have received minimal human modification and are associated with narrow and shallow back-barrier sounds, appear to be maintaining themselves in their upward and landward migration in response to ongoing storms and sea-level rise.
Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.
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
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
Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.
Muñoz, Fabián; Fuentealba, Pablo
2012-01-01
Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.
Morphology of the Vestibular Utricule in Toadfish, Opsanus Tau
NASA Technical Reports Server (NTRS)
Bass, L.; Smith, J.; Twombly, A.; Boyle, Richard; Varelas, Ehsanian J.; Johanson, C.
2003-01-01
The uticle is an otolith organ in the vertebrate inner ear that provides gravitoinertial acceleration information into the vestibular reflex pathways. The aim of the present study was to provide an anatomical description of this structure in the adult oyster toadfish, and establish a morphological basis for interpretation of subsequent functional studies. Light, scanning electron and transmission electron microscopy were applied to visualize the sensory epithelium and its neural innervation. Electrophysiological techniques were used to identify utricular afferents by their response to translation stimuli. Similar to nerve afferents supplying the semicircular canals and lagena, utricular afferents commonly exhibit a short-latency increase of firing rate in response to electrical activation of the central efferent pathway. Afferents were labeled with biocytin either intraaxonally or with extracellular bulk deposits. Light microscope images of serial thick sections were used to make three-dimensional reconstructions of individual labeled afferents to identify the dendritic morphology with respect to epithelial location. Scanning electron microscopy was used to visualize the surface of the otolith mass facing the otolith membrane, and the hair cell polarization patterns of strioler and extrastriolar regions. Transmission electron micrographs of serial thin sections were compiled to create a three-dimensional reconstruction of the labeled afferent over a segment of its dendritic field and to examine the hair cell-afferent synaptic contacts.
Contralateral Breast Dose After Whole-Breast Irradiation: An Analysis by Treatment Technique
DOE Office of Scientific and Technical Information (OSTI.GOV)
Williams, Terence M.; Moran, Jean M., E-mail: jmmoran@med.umich.edu; Hsu, Shu-Hui
2012-04-01
Purpose: To investigate the contralateral breast dose (CBD) across a continuum of breast-conservation therapy techniques. Methods and Materials: An anthropomorphic phantom was CT-simulated, and six treatment plans were generated: open tangents, tangents with an external wedge on the lateral beam, tangents with lateral and medial external wedges, a simple segment plan (three segments per tangent), a complex segmental intensity-modulated radiotherapy (IMRT) plan (five segments per tangent), and a beamlet IMRT plan (>100 segments). For all techniques, the breast on the phantom was irradiated to 5000 cGy. Contralateral breast dose was measured at a uniform depth at the center and eachmore » quadrant using thermoluminescent detectors. Results: Contralateral breast dose varied with position and was 50 {+-} 7.3 cGy in the inner half, 24 {+-} 4.1 cGy at the center, and 16 {+-} 2.2 cGy in the outer half for the open tangential plan. Compared with an average dose of 31 cGy across all points for the open field, the average doses were simple segment 32 cGy (range, 99-105% compared with open technique), complex segment 34 cGy (range, 103-117% compared with open technique), beamlet IMRT 34 cGy (range, 103-124% compared with open technique), lateral wedge only 46 cGy (range, 133-175% compared with open technique), and medial and lateral wedge 96 cGy (range, 282-370% compared with open technique). Conclusions: Single or dual wedge techniques resulted in the highest CBD increases compared with open tangents. To obtain the desired homogeneity to the treated breast while minimizing CBD, segmental and IMRT techniques should be encouraged over external physical compensators.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wiebe, David J.
A transition duct system (10) for delivering hot-temperature gases from a plurality of combustors in a combustion turbine engine is provided. The system includes an exit piece (16) for each combustor. The exit piece may include a straight path segment (26) for receiving a gas flow from a respective combustor. A straight ceramic liner (40) may be inwardly disposed onto a metal outer shell (38) along the straight path segment of the exit piece. Structural arrangements are provided to securely attach the ceramic liner in the presence of substantial flow path pressurization. Cost-effective serviceability of the transition duct systems ismore » realizable since the liner can be readily removed and replaced as needed.« less
Farley, Jennifer R.; Sterritt, Jeffrey R.; Crane, Andrés B.; Wallace, Christopher S.
2017-01-01
Astroglia play key roles in the development of neurons, ranging from regulating neuron survival to promoting synapse formation, yet basic questions remain about whether astrocytes might be involved in forming the dendritic arbor. Here, we used cultured hippocampal neurons as a simple in vitro model that allowed dendritic growth and geometry to be analyzed quantitatively under conditions where the extent of interactions between neurons and astrocytes varied. When astroglia were proximal to neurons, dendrites and dendritic filopodia oriented toward them, but the general presence of astroglia significantly reduced overall dendrite growth. Further, dendritic arbors in partial physical contact with astroglia developed a pronounced pattern of asymmetrical growth, because the dendrites in direct contact were significantly smaller than the portion of the arbor not in contact. Notably, thrombospondin, the astroglial factor shown previously to promote synapse formation, did not inhibit dendritic growth. Thus, while astroglia promoted the formation of presynaptic contacts onto dendrites, dendritic growth was constrained locally within a developing arbor at sites where dendrites contacted astroglia. Taken together, these observations reveal influences on spatial orientation of growth as well as influences on morphogenesis of the dendritic arbor that have not been previously identified. PMID:28081563
Zhao, Jingbo; Liao, Donghua; Yang, Jian; Gregersen, Hans
2011-01-01
Previous studies have demonstrated morphological and biomechanical remodeling in the intestine proximal to an obstruction. The present study aimed to obtain stress and strain thresholds to initiate contraction and the maximal contraction stress and strain in partially obstructed guinea pig jejunal segments. Partial obstruction and sham operations were surgically created in mid-jejunum of male guinea pigs. The animals survived 2, 4, 7, and 14 days, respectively. Animals not being operated on served as normal controls. The segments were used for no-load state, zero-stress state and distension analyses. The segment was inflated to 10 cmH2O pressure in an organ bath containing 37°C Krebs solution and the outer diameter change was monitored. The stress and strain at the contraction threshold and at maximum contraction were computed from the diameter, pressure and the zero-stress state data. Young’s modulus was determined at the contraction threshold. The muscle layer thickness in obstructed intestinal segments increased up to 300%. Compared with sham-obstructed and normal groups, the contraction stress threshold, the maximum contraction stress and the Young’s modulus at the contraction threshold increased whereas the strain threshold and maximum contraction strain decreased after 7 days obstruction (P<0.05 and 0.01). In conclusion, in the partially obstructed intestinal segments, a larger distension force was needed to evoke contraction likely due to tissue remodeling. Higher contraction stresses were produced and the contraction deformation (strain) became smaller. PMID:21632056
Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat retina.
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.
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
NASA Astrophysics Data System (ADS)
Cheng, Jieyu; Qiu, Wu; Yuan, Jing; Fenster, Aaron; Chiu, Bernard
2016-03-01
Registration of longitudinally acquired 3D ultrasound (US) images plays an important role in monitoring and quantifying progression/regression of carotid atherosclerosis. We introduce an image-based non-rigid registration algorithm to align the baseline 3D carotid US with longitudinal images acquired over several follow-up time points. This algorithm minimizes the sum of absolute intensity differences (SAD) under a variational optical-flow perspective within a multi-scale optimization framework to capture local and global deformations. Outer wall and lumen were segmented manually on each image, and the performance of the registration algorithm was quantified by Dice similarity coefficient (DSC) and mean absolute distance (MAD) of the outer wall and lumen surfaces after registration. In this study, images for 5 subjects were registered initially by rigid registration, followed by the proposed algorithm. Mean DSC generated by the proposed algorithm was 79:3+/-3:8% for lumen and 85:9+/-4:0% for outer wall, compared to 73:9+/-3:4% and 84:7+/-3:2% generated by rigid registration. Mean MAD of 0:46+/-0:08mm and 0:52+/-0:13mm were generated for lumen and outer wall respectively by the proposed algorithm, compared to 0:55+/-0:08mm and 0:54+/-0:11mm generated by rigid registration. The mean registration time of our method per image pair was 143+/-23s.
Effect of Solute Diffusion on Dendrite Growth in the Molten Pool of Al-Cu Alloy
NASA Astrophysics Data System (ADS)
Zhan, Xiaohong; Gu, Cheng; Liu, Yun; Wei, Yanhong
2017-10-01
A cellular automaton (CA)-finite difference model is developed to simulate dendrite growth and solute diffusion during solidification process in the molten pool of Al-Cu alloy. In order to explain the interaction between the dendritic growth and solute distribution, a series of CA simulations with different solute diffusion velocity coefficients are carried out. It is concluded that the solute concentration increases with dendrite growing and solute accumulation in the dendrite tip. Converged value of the dendrite tip growth velocity is about 480 μm/s if the mesh size is refined to 2 μm or less. Growth of the primary dendrite and the secondary dendrite is mainly influenced by solute diffusion at the dendrite tips. And growth of secondary and tertiary dendrites is mainly influenced by solute diffusion at interdendrite.
Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo
2010-06-01
Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease.
Strain measurements and the potential for a great subduction earthquake off the coast of washington.
Savage, J C; Lisowski, M
1991-04-05
Geodetic measurements of deformation in northwestern Washington indicate that strain is accumulating at a rate close to that predicted by a model of the Cascadia subduction zone in which the plate interface underlying the continental slope and outer continental shelf is currently locked but the remainder of the interface slips continuously. Presumably this locked segment will eventually rupture in a great thrust earthquake with a down-dip extent greater than 100 kilometers.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeon, Jae; Chang, John
A band-notched spiral antenna having one or more spiral arms extending from a radially inner end to a radially outer end for transmitting or receiving electromagnetic radiation over a frequency range, and one or more resonance structures positioned adjacent one or more segments of the spiral arm associated with a notch frequency band or bands of the frequency range so as to resonate and suppress the transmission or reception of electromagnetic radiation over said notch frequency band or bands.
Update on the Ares V to Support Heavy Lift for U.S. Space Exploration Policy
NASA Technical Reports Server (NTRS)
Creech, Steve
2008-01-01
The focus of design efforts in the near future will be on the primary Lunar mission. We are currently just beginning to integrate the design functions from the various centers for this mission. We appreciate all thoughts and ideas for different ways to use the Ares V platform. The Ares V can support an order of magnitude more science instrumentation for outer planetary exploration missions. It can also reach outer planets such as Neptune and other high energy insertion destinations. Current Ares V Point-of-Departure (51.00.48) exceeds Saturn mass capability by approx.40%. Ares V Lunar Capabilities Concept Review analysis focused on meeting lunar requirements and developing margin. Ares V is sensitive to Loiter, Attitude, Power, and Altitude requirements in addition to payload performance. LCCR-approved 51.00.48 POD 5.5-segment steel case booster/6 engine core) Ares V can meet current Human Lunar Return requirements with approx.6 mT of Margin. LCCR-approved 51.00.47 option maintained (5 segment HTPB composite case booster/6 engine core) can meet HLR requirement with more than 9 mT Margin. Ares V team is actively reaching out to external organizations during this early concept phase to ensure that the Ares V vehicle can be leveraged for national security, scientific and commercial development needs.
Schauwvlieghe, Pieter-Paul; Torre, Kara Della; Coppieters, Frauke; Van Hoey, Anneleen; De Baere, Elfride; De Zaeytijd, Julie; Leroy, Bart P; Brodie, Scott E
2013-01-01
To describe the phenotype of three cases of Sjögren reticular dystrophy in detail, including high-resolution optical coherence tomography, autofluorescence imaging, and near-infrared reflectance imaging. Two unrelated teenagers were independently referred for ophthalmologic evaluation. Both underwent a full ophthalmologic workup, including electrophysiologic and extensive imaging with spectral-domain optical coherence tomography, autofluorescence imaging, and near-infrared reflectance imaging. In addition, mutation screening of ABCA4, PRPH2, and the mitochondrial tRNA gene was performed in Patient 1. Subsequently, the teenage sister of Patient 2 was examined. Strikingly similar phenotypes were present in these three patients. Fundoscopy showed bilateral foveal pigment alterations, and a lobular network of deep retinal, pigmented deposits throughout the posterior pole, tapering toward the midperiphery, with relative sparing of the immediate perifoveal macula and peripapillary area. This network is mildly to moderately hyperautofluorescent on autofluorescence and bright on near-infrared reflectance imaging. Optical coherence tomography showed abnormalities of the retinal pigment epithelium-Bruch membrane complex, photoreceptor outer segments, and photoreceptor inner/outer segment interface. The results of retinal function test were entirely normal. No molecular cause was detected in Patient 1. Imaging suggested that the lobular network of deep retinal deposits in Sjögren reticular dystrophy is the result of accumulation of both pigment and lipofuscin between photoreceptors and retinal pigment epithelium, as well as within the retinal pigment epithelium.
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