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

PubMed Central

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

2007-01-01

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

The ureteric bud epithelium: morphogenesis and roles in metanephric kidney patterning.

PubMed

Nagalakshmi, Vidya K; Yu, Jing

2015-03-01

The mammalian metanephric kidney is composed of two epithelial components, the collecting duct system and the nephron epithelium, that differentiate from two different tissues -the ureteric bud epithelium and the nephron progenitors, respectively-of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis, whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return, the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is physiologically divided along the corticomedullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here, we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortico-medullary patterning of the metanephric kidney. © 2015 Wiley Periodicals, Inc.

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

PubMed

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

2016-08-01

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

Cooled turbine vane with endcaps

DOEpatents

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

2002-01-01

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

STRUCTURAL ASSESSMENT OF HYPERAUTOFLUORESCENT RING IN PATIENTS WITH RETINITIS PIGMENTOSA

PubMed Central

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

2009-01-01

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

Correlation between spectral-domain OCT findings and visual acuity in X-linked retinoschisis.

PubMed

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

PubMed Central

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.

PubMed

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.

Exploring the interaction network of the Bacillus subtilis outer coat and crust proteins.

PubMed

Krajčíková, Daniela; Forgáč, Vladimír; Szabo, Adam; Barák, Imrich

2017-11-01

Bacillus subtilis spores, representatives of an exceptionally resistant dormant cell type, are encircled by a thick proteinaceous layer called the spore coat. More than 80 proteins assemble into four distinct coat layers: a basement layer, an inner coat, an outer coat and a crust. As the spore develops inside the mother cell, spore coat proteins synthesized in the cytoplasm are gradually deposited onto the prespore surface. A small set of morphogenetic proteins necessary for spore coat morphogenesis are thought to form a scaffold to which the rest of the coat proteins are attached. Extensive localization and proteomic studies using wild type and mutant spores have revealed the arrangement of individual proteins within the spore coat layers. In this study we examined the interactions between the proteins localized to the outer coat and crust using a bacterial two hybrid system. These two layers are composed of at least 25 components. Self-interactions were observed for most proteins and numerous novel interactions were identified. The most interesting contacts are those made with the morphogenetic proteins CotE, CotY and CotZ; these could serve as a basis for understanding the specific roles of particular proteins in spore coat morphogenesis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Pre-stressed/pre-compressed gas turbine nozzle

DOEpatents

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

2002-01-01

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

The membrane current of single rod outer segments.

PubMed

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

1979-03-01

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

Functional significance of the taper of vertebrate cone photoreceptors

PubMed Central

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

Method of fabricating a prestressed cast iron vessel

DOEpatents

Lampe, Robert F.

1982-01-01

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

THE STRUCTURE AND CONCENTRATION OF SOLIDS IN PHOTORECEPTOR CELLS STUDIED BY REFRACTOMETRY AND INTERFERENCE MICROSCOPY

PubMed Central

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

Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish.

PubMed

Lovely, C Ben; Swartz, Mary E; McCarthy, Neil; Norrie, Jacqueline L; Eberhart, Johann K

2016-06-01

The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. © 2016. Published by The Company of Biologists Ltd.

Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish

PubMed Central

Swartz, Mary E.; McCarthy, Neil; Norrie, Jacqueline L.; Eberhart, Johann K.

2016-01-01

The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171

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

PubMed

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

2012-04-01

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

Molecular basis for photoreceptor outer segment architecture

PubMed Central

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

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

PubMed

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

2012-10-15

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

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

PubMed Central

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

2012-01-01

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

Epithelial organization and cyst lumen expansion require efficient Sec13-Sec31-driven secretion.

PubMed

Townley, Anna K; Schmidt, Katy; Hodgson, Lorna; Stephens, David J

2012-02-01

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.

Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion

PubMed Central

Townley, Anna K.; Schmidt, Katy; Hodgson, Lorna; Stephens, David J.

2012-01-01

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13–Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture. PMID:22331354

Leaf seal for inner and outer casings of a turbine

DOEpatents

Schroder, Mark Stewart; Leach, David

2002-01-01

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

Electronically transparent graphene replicas of diatoms: a new technique for the investigation of frustule morphology

PubMed Central

Pan, Zhengwei; Lerch, Sarah J. L.; Xu, Liang; Li, Xufan; Chuang, Yen-Jun; Howe, Jane Y.; Mahurin, Shannon M.; Dai, Sheng; Hildebrand, Mark

2014-01-01

The morphogenesis of the silica cell walls (called frustules) of unicellular algae known as diatoms is one of the most intriguing mysteries of the diatoms. To study frustule morphogenesis, optical, electron and atomic force microscopy has been extensively used to reveal the frustule morphology. However, since silica frustules are opaque, past observations were limited to outer and fracture surfaces, restricting observations of interior structures. Here we show that opaque silica frustules can be converted into electronically transparent graphene replicas, fabricated using chemical vapor deposition of methane. Chemical vapor deposition creates a continuous graphene coating preserving the frustule's shape and fine, complicated internal features. Subsequent dissolution of the silica with hydrofluoric acid yields a free-standing replica of the internal and external native frustule morphologies. Electron microscopy renders these graphene replicas highly transparent, revealing previously unobserved, complex, three-dimensional, interior frustule structures, which lend new insights into the investigation of frustule morphogenesis. PMID:25135739

Reactor coolant pump flywheel

DOEpatents

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

2013-11-26

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

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

PubMed Central

1983-01-01

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

Morphogenesis of the second pharyngeal arch cartilage (Reichert's cartilage) in human embryos

PubMed Central

Rodríguez-Vázquez, J F; Mérida-Velasco, J R; Verdugo-López, S; Sánchez-Montesinos, I; Mérida-Velasco, J A

2006-01-01

This study was performed on 50 human embryos and fetuses between 7 and 17 weeks of development. Reichert's cartilage is formed in the second pharyngeal arch in two segments. The longer cranial or styloid segment is continuous with the otic capsule; its inferior end is angulated and is situated very close to the oropharynx. The smaller caudal segment is in contact with the body and greater horn of the hyoid cartilaginous structure. No cartilage forms between these segments. The persistent angulation of the inferior end of the cranial or styloid segment of Reichert's cartilage and its important neurovascular relationships may help explain the symptomatology of Eagle's syndrome. PMID:16441562

Glycolytic reliance promotes anabolism in photoreceptors

PubMed Central

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

2017-01-01

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

The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones

PubMed Central

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

Autocrine and paracrine Shh signaling are necessary for tooth morphogenesis, but not tooth replacement in snakes and lizards (Squamata).

PubMed

Handrigan, Gregory R; Richman, Joy M

2010-01-01

Here we study the role of Shh signaling in tooth morphogenesis and successional tooth initiation in snakes and lizards (Squamata). By characterizing the expression of Shh pathway receptor Ptc1 in the developing dentitions of three species (Eublepharis macularius, Python regius, and Pogona vitticeps) and by performing gain- and loss-of-function experiments, we demonstrate that Shh signaling is active in the squamate tooth bud and is required for its normal morphogenesis. Shh apparently mediates tooth morphogenesis by separate paracrine- and autocrine-mediated functions. According to this model, paracrine Shh signaling induces cell proliferation in the cervical loop, outer enamel epithelium, and dental papilla. Autocrine signaling within the stellate reticulum instead appears to regulate cell survival. By treating squamate dental explants with Hh antagonist cyclopamine, we induced tooth phenotypes that closely resemble the morphological and differentiation defects of vestigial, first-generation teeth in the bearded dragon P. vitticeps. Our finding that these vestigial teeth are deficient in epithelial Shh signaling further corroborates that Shh is needed for the normal development of teeth in snakes and lizards. Finally, in this study, we definitively refute a role for Shh signaling in successional dental lamina formation and conclude that other pathways regulate tooth replacement in squamates.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Spore formation in Myxococcus xanthus is tied to cytoskeleton functions and polysaccharide spore coat deposition

PubMed Central

Müller, Frank D.; Schink, Christian W.; Hoiczyk, Egbert; Cserti, Emöke; Higgs, Penelope I.

2011-01-01

Summary Myxococcus xanthus is a Gram-negative bacterium that differentiates into environmentally resistant spores. Spore differentiation involves septation-independent remodelling of the rod-shaped vegetative cell into a spherical spore and deposition of a thick and compact spore coat outside of the outer membrane. Our analyses suggest that spore coat polysaccharides are exported to the cell surface by the Exo outer membrane polysaccharide export/polysaccharide co-polymerase 2a (OPX/PCP-2a) machinery. Conversion of the capsule-like polysaccharide layer into a compact spore coat layer requires the Nfs proteins which likely form a complex in the cell envelope. Mutants in either nfs, exo, or two other genetic loci encoding homologs of polysaccharide synthesis enzymes, fail to complete morphogenesis from rods to spherical spores and instead produce a transient state of deformed cell morphology before reversion into typical rods. We additionally provide evidence that the cell cytoskeletal protein, MreB, plays an important role in rod to spore morphogenesis and for spore outgrowth. These studies provide evidence that this novel gram-negative differentiation process is tied to cytoskeleton functions and polysaccharide spore coat deposition. PMID:22188356

Automated Image Analysis of Lung Branching Morphogenesis from Microscopic Images of Fetal Rat Explants

PubMed Central

Rodrigues, Pedro L.; Rodrigues, Nuno F.; Duque, Duarte; Granja, Sara; Correia-Pinto, Jorge; Vilaça, João L.

2014-01-01

Background. Regulating mechanisms of branching morphogenesis of fetal lung rat explants have been an essential tool for molecular research. This work presents a new methodology to accurately quantify the epithelial, outer contour, and peripheral airway buds of lung explants during cellular development from microscopic images. Methods. The outer contour was defined using an adaptive and multiscale threshold algorithm whose level was automatically calculated based on an entropy maximization criterion. The inner lung epithelium was defined by a clustering procedure that groups small image regions according to the minimum description length principle and local statistical properties. Finally, the number of peripheral buds was counted as the skeleton branched ends from a skeletonized image of the lung inner epithelia. Results. The time for lung branching morphometric analysis was reduced in 98% in contrast to the manual method. Best results were obtained in the first two days of cellular development, with lesser standard deviations. Nonsignificant differences were found between the automatic and manual results in all culture days. Conclusions. The proposed method introduces a series of advantages related to its intuitive use and accuracy, making the technique suitable to images with different lighting characteristics and allowing a reliable comparison between different researchers. PMID:25250057

Photoreceptor change and visual outcome after idiopathic epiretinal membrane removal with or without additional internal limiting membrane peeling.

PubMed

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.

ACME: Automated Cell Morphology Extractor for Comprehensive Reconstruction of Cell Membranes

PubMed Central

Mosaliganti, Kishore R.; Noche, Ramil R.; Xiong, Fengzhu; Swinburne, Ian A.; Megason, Sean G.

2012-01-01

The quantification of cell shape, cell migration, and cell rearrangements is important for addressing classical questions in developmental biology such as patterning and tissue morphogenesis. Time-lapse microscopic imaging of transgenic embryos expressing fluorescent reporters is the method of choice for tracking morphogenetic changes and establishing cell lineages and fate maps in vivo. However, the manual steps involved in curating thousands of putative cell segmentations have been a major bottleneck in the application of these technologies especially for cell membranes. Segmentation of cell membranes while more difficult than nuclear segmentation is necessary for quantifying the relations between changes in cell morphology and morphogenesis. We present a novel and fully automated method to first reconstruct membrane signals and then segment out cells from 3D membrane images even in dense tissues. The approach has three stages: 1) detection of local membrane planes, 2) voting to fill structural gaps, and 3) region segmentation. We demonstrate the superior performance of the algorithms quantitatively on time-lapse confocal and two-photon images of zebrafish neuroectoderm and paraxial mesoderm by comparing its results with those derived from human inspection. We also compared with synthetic microscopic images generated by simulating the process of imaging with fluorescent reporters under varying conditions of noise. Both the over-segmentation and under-segmentation percentages of our method are around 5%. The volume overlap of individual cells, compared to expert manual segmentation, is consistently over 84%. By using our software (ACME) to study somite formation, we were able to segment touching cells with high accuracy and reliably quantify changes in morphogenetic parameters such as cell shape and size, and the arrangement of epithelial and mesenchymal cells. Our software has been developed and tested on Windows, Mac, and Linux platforms and is available publicly under an open source BSD license (https://github.com/krm15/ACME). PMID:23236265

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, Gary L.; Shaffer, James E.

1997-01-01

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

Turbine nozzle/nozzle support structure

DOEpatents

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

1997-01-07

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

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, Gary L.; Shaffer, James E.

1996-01-01

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

Turbine nozzle/nozzle support structure

DOEpatents

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

1996-09-10

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

Turbine nozzle/nozzle support structure

DOEpatents

Boyd, Gary L.; Shaffer, James E.

1995-01-01

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

Turbine nozzle/nozzle support structure

DOEpatents

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

1995-08-15

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

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

NASA Astrophysics Data System (ADS)

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

2008-03-01

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

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

NASA Technical Reports Server (NTRS)

Schreur, Julian J.

1999-01-01

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

Segmented inlet nozzle for gas turbine, and methods of installation

DOEpatents

Klompas, Nicholas

1985-01-01

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

The localization of guanylyl cyclase-activating proteins in the mammalian retina.

PubMed

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.

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

PubMed

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

2017-07-01

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

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.

PubMed

Laties, A M

1969-01-01

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

ACR4, a putative receptor kinase gene of Arabidopsis thaliana, that is expressed in the outer cell layers of embryos and plants, is involved in proper embryogenesis.

PubMed

Tanaka, Hirokazu; Watanabe, Masaru; Watanabe, Daisuke; Tanaka, Toshihiro; Machida, Chiyoko; Machida, Yasunori

2002-04-01

The surfaces of higher plants are characterized by epidermis, which usually consists of a single layer of cells. The epidermis is derived from the outer cell layer of the embryo or protoderm, which arises as a result of periclinal cell division. After seed germination, most of the epidermal cells of the aerial parts of plants are derived from the outer cell layer of the shoot apical meristem (the L1 layer). Thus, knowledge of how the protoderm and/or L1 layer is established is fundamental to understanding the morphogenesis of higher plants. Here, we report the isolation of a gene encoding an Arabidopsis homologue (ACR4) of the maize putative receptor kinase CRINKLY4 (CR4), which is involved in epidermal differentiation. The domain organization of the predicted amino acid sequence of ACR4 is essentially identical to that of CR4. ACR4-GFP fusion protein localized to the cell surface when expressed in tobacco cell (BY-2) culture. ACR4 transcripts were detected in all the organs of the Arabidopsis plant. In developing embryos and shoot apices, ACR4 transcripts accumulated in protoderm and epidermis at relatively higher levels than in the inner tissues. Over-expression of antisense ACR4 in Arabidopsis plants resulted in malformation of embryos to varying degrees. These results suggest that ACR4 is, at a minimum, involved in the normal morphogenesis of embryos, most likely through properly differentiating protoderm cells.

Wedge edge ceramic combustor tile

DOEpatents

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

1997-06-10

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

Wedge edge ceramic combustor tile

DOEpatents

Shaffer, James E.; Holsapple, Allan C.

1997-01-01

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

Structural Inheritance of the Actin Cytoskeletal Organization Determines the Body Axis in Regenerating Hydra.

PubMed

Livshits, Anton; Shani-Zerbib, Lital; Maroudas-Sacks, Yonit; Braun, Erez; Keren, Kinneret

2017-02-07

Understanding how mechanics complement bio-signaling in defining patterns during morphogenesis is an outstanding challenge. Here, we utilize the multicellular polyp Hydra to investigate the role of the actomyosin cytoskeleton in morphogenesis. We find that the supra-cellular actin fiber organization is inherited from the parent Hydra and determines the body axis in regenerating tissue segments. This form of structural inheritance is non-trivial because of the tissue folding and dynamic actin reorganization involved. We further show that the emergence of multiple body axes can be traced to discrepancies in actin fiber alignment at early stages of the regeneration process. Mechanical constraints induced by anchoring regenerating Hydra on stiff wires suppressed the emergence of multiple body axes, highlighting the importance of mechanical feedbacks in defining and stabilizing the body axis. Together, these results constitute an important step toward the development of an integrated view of morphogenesis that incorporates mechanics. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2004-07-01

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

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

PubMed Central

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

1992-01-01

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

E- and P-cadherin expression during murine hair follicle morphogenesis and cycling.

PubMed

Müller-Röver, S; Tokura, Y; Welker, P; Furukawa, F; Wakita, H; Takigawa, M; Paus, R

1999-08-01

The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR. The expression of both cadherins was strikingly hair cycle-dependent and restricted to distinct anatomical HF compartments. During HF morphogenesis, hair bud keratinocytes displayed strong Ecad and Pcad immunoreactivity (IR). While neonatal epidermis showed Ecad IR in all epidermal layers, Pcad IR was restricted to the basal layer. During later stages of HF morphogenesis and during anagen IV-VI of the adolescent murine hair cycle, the outer root sheath showed strong E- and Pcad IR. Instead, the outermost portion of the hair matrix and the inner root sheath displayed isolated Ecad IR, while the innermost portion of the hair matrix exhibited isolated Pcad IR. During telogen, all epidermal and follicular keratinocytes showed strong Ecad IR. This is in contrast to Pcad, whose IR was stringently restricted to matrix and secondary hair germ keratinocytes which are in closest proximity to the dermal papilla. These findings suggest that isolated or combined E- and/or Pcad expression is involved in follicular pattern formation by segregating HF keratinocytes into functionally distinct subpopulations; most notably, isolated Pcad expression may segregate those hair matrix keratinocytes into one functional epithelial tissue unit, which is particularly susceptible to growth control by dermal papilla-derived morphogens. The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders.

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.

Pulse joining cartridges

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

Golovashchenko, Sergey Fedorovich; Bonnen, John Joseph Francis

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

Pulse joining cartridges

DOEpatents

Golovashchenko, Sergey Fedorovich; Bonnen, John Joseph Francis

2016-08-23

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

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

NASA Astrophysics Data System (ADS)

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

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

Leaf seal for gas turbine stator shrouds and a nozzle band

DOEpatents

Burdgick, Steven Sebastian; Sexton, Brendan Francis

2002-01-01

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

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

PubMed

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

2012-02-01

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

The Properties of Outer Retinal Band Three Investigated With Adaptive-Optics Optical Coherence Tomography.

PubMed

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.

The Properties of Outer Retinal Band Three Investigated With Adaptive-Optics Optical Coherence Tomography

PubMed Central

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

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

PubMed

Spaide, Richard F; Curcio, Christine A

2011-09-01

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

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

PubMed

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

2012-04-01

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

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

PubMed Central

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

2009-01-01

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

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

PubMed Central

Falk, G.; Fatt, P.

1966-01-01

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

Branching morphogenesis in the fetal mouse submandibular gland is codependent on growth factors and extracellular matrix.

PubMed

Gresik, Edward W; Koyama, Noriko; Hayashi, Toru; Kashimata, Masanori

2009-01-01

Branching morphogenesis (BrM) is a basic developmental process for the formation of the lung, kidney, and all exocrine glands, including the salivary glands. This process proceeds as follows. An epithelial downgrowth invaginates into underlying mesenchyme, and forms a cleft at its distal end, which is the site of dichotomous branching and elongation; this process of clefting and elongation is repeated many times at the distal ends of the invading epithelium until the desired final extent of branching is reached. The distal ends of the epithelium differentiate into the secretory endpieces, and the elongated segments become the ducts. This presentation is a brief historical review of studies on BrM during the development of the submandibular gland (SMG).

Turbine stator vane segment having internal cooling circuits

DOEpatents

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

2003-01-01

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

Gas turbine row #1 steam cooled vane

DOEpatents

Cunha, Frank J.

2000-01-01

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

Grouper tshβ Promoter-Driven Transgenic Zebrafish Marks Proximal Kidney Tubule Development

PubMed Central

Wang, Yang; Sun, Zhi-Hui; Zhou, Li; Li, Zhi; Gui, Jian-Fang

2014-01-01

Kidney tubule plays a critical role in recovering or secreting solutes, but the detailed morphogenesis remains unclear. Our previous studies have found that grouper tshβ (gtshβ) is also expressed in kidney, however, the distribution significance is still unknown. To understand the gtshβ role and kidney tubule morphogenesis, here, we have generated a transgenic zebrafish line Tg(gtshβ:GFP) with green fluorescent protein driven by the gtshβ promoter. Similar to the endogenous tshβ in zebrafish or in grouper, the gtshβ promoter-driven GFP is expressed in pituitary and kidney, and the developing details of proximal kidney tubule are marked in the transgenic zebrafish line. The gfp initially transcribes at 16 hours post fertilization (hpf) above the dorsal mesentery, and partially co-localizes with pronephric tubular markers slc20a1a and cdh17. Significantly, the GFP specifically localizes in proximal pronephric segments during embryogenesis and resides at kidney duct epithelium in adult fish. To test whether the gtshβ promoter-driven GFP may serve as a readout signal of the tubular development, we have treated the embryos with retinoic acid signaing (RA) reagents, in which exogenous RA addition results in a distal extension of the proximal segments, while RA inhibition induces a weakness and shortness of the proximal segments. Therefore, this transgenic line provides a useful tool for genetic or chemical analysis of kidney tubule. PMID:24905828

Distinct functions for IFT140 and IFT20 in opsin transport.

PubMed Central

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

2014-01-01

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

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

PubMed

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

2018-02-13

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

Fgf10 is required for specification of non-sensory regions of the cochlear epithelium

PubMed Central

Urness, Lisa D.; Wang, Xiaofen; Shibata, Shumei; Ohyama, Takahiro; Mansour, Suzanne L.

2015-01-01

The vertebrate inner ear is a morphologically complex sensory organ comprised of two compartments, the dorsal vestibular apparatus and the ventral cochlear duct, required for motion and sound detection, respectively. Fgf10, in addition to Fgf3, is necessary for the earliest stage of otic placode induction, but continued expression of Fgf10 in the developing otic epithelium, including the prosensory domain and later in Kolliker’s organ, suggests additional roles for this gene during morphogenesis of the labyrinth. While loss of Fgf10 was implicated previously in semicircular canal agenesis, we show that Fgf10−/+ embryos also exhibit a reduction or absence of the posterior semicircular canal, revealing a dosage-sensitive requirement for FGF10 in vestibular development. In addition, we show that Fgf10−/− embryos have previously unappreciated defects of cochlear morphogenesis, including a somewhat shortened duct, and, surprisingly, a substantially narrower duct. The mutant cochlear epithelium lacks Reissner’s membrane and a large portion of the outer sulcus--two non-contiguous, non-sensory domains. Marker gene analyses revealed effects on Reissner’s membrane as early as E12.5–E13.5 and on the outer sulcus by E15.5, stages when Fgf10 is expressed in close proximity to Fgfr2b, but these effects were not accompanied by changes in epithelial cell proliferation or death. These data indicate a dual role for Fgf10 in cochlear development: to regulate outgrowth of the duct and subsequently as a bidirectional signal that sequentially specifies Reissner’s membrane and outer sulcus non-sensory domains. These findings may help to explain the hearing loss sometimes observed in LADD syndrome subjects with FGF10 mutations. PMID:25624266

Cone outer segment and Müller microvilli pericellular matrices provide binding domains for interphotoreceptor retinoid-binding protein (IRBP).

PubMed

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.

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

PubMed

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

2014-01-01

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

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

PubMed

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

2015-12-01

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

Partially segmented deformable mirror

DOEpatents

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

1991-05-21

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

Partially segmented deformable mirror

DOEpatents

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

1991-01-01

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

Caudal migration and proliferation of renal progenitors regulates early nephron segment size in zebrafish.

PubMed

Naylor, Richard W; Dodd, Rachel C; Davidson, Alan J

2016-10-19

The nephron is the functional unit of the kidney and is divided into distinct proximal and distal segments. The factors determining nephron segment size are not fully understood. In zebrafish, the embryonic kidney has long been thought to differentiate in situ into two proximal tubule segments and two distal tubule segments (distal early; DE, and distal late; DL) with little involvement of cell movement. Here, we overturn this notion by performing lineage-labelling experiments that reveal extensive caudal movement of the proximal and DE segments and a concomitant compaction of the DL segment as it fuses with the cloaca. Laser-mediated severing of the tubule, such that the DE and DL are disconnected or that the DL and cloaca do not fuse, results in a reduction in tubule cell proliferation and significantly shortens the DE segment while the caudal movement of the DL is unaffected. These results suggest that the DL mechanically pulls the more proximal segments, thereby driving both their caudal extension and their proliferation. Together, these data provide new insights into early nephron morphogenesis and demonstrate the importance of cell movement and proliferation in determining initial nephron segment size.

Acute Zonal Cone Photoreceptor Outer Segment Loss.

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

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

DOEpatents

Reichner, Philip

1988-01-01

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

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

PubMed

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

1983-01-01

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

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

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

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

1995-05-20

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

HYPERAUTOFLUORESCENT RING IN AUTOIMMUNE RETINOPATHY

PubMed Central

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

2015-01-01

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

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

PubMed

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

2013-10-15

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

Segmentation in cohesive systems constrained by elastic environments

NASA Astrophysics Data System (ADS)

Novak, I.; Truskinovsky, L.

2017-04-01

The complexity of fracture-induced segmentation in elastically constrained cohesive (fragile) systems originates from the presence of competing interactions. The role of discreteness in such phenomena is of interest in a variety of fields, from hierarchical self-assembly to developmental morphogenesis. In this paper, we study the analytically solvable example of segmentation in a breakable mass-spring chain elastically linked to a deformable lattice structure. We explicitly construct the complete set of local minima of the energy in this prototypical problem and identify among them the states corresponding to the global energy minima. We show that, even in the continuum limit, the dependence of the segmentation topology on the stretching/pre-stress parameter in this problem takes the form of a devil's type staircase. The peculiar nature of this staircase, characterized by locking in rational microstructures, is of particular importance for biological applications, where its structure may serve as an explanation of the robustness of stress-driven segmentation. This article is part of the themed issue 'Patterning through instabilities in complex media: theory and applications.'

Omnidirectional wheel

NASA Technical Reports Server (NTRS)

Blumrich, J. F. (Inventor)

1974-01-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2014-01-01

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

Mouse models for human hair loss disorders

PubMed Central

Porter, Rebecca M

2003-01-01

The outer surface of the hand, limb and body is covered by the epidermis, which is elaborated into a number of specialized appendages, evolved not only to protect and reinforce the skin but also for social signalling. The most prominent of these appendages is the hair follicle. Hair follicles are remarkable because of their prolific growth characteristics and their complexity of differentiation. After initial embryonic morphogenesis, the hair follicle undergoes repeated cycles of regression and regeneration throughout the lifetime of the organism. Studies of mouse mutants with hair loss phenotypes have suggested that the mechanisms controlling the hair cycle probably involve many of the major signalling molecules used elsewhere in development, although the complete pathway of hair follicle growth control is not yet understood. Mouse studies have also led to the discovery of genes underlying several human disorders. Future studies of mouse hair-loss mutants are likely to benefit the understanding of human hair loss as well as increasing our knowledge of mechanisms controlling morphogenesis and tumorigenesis. PMID:12587927

The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis

PubMed Central

Lesko, Alyssa C.; Goss, Kathleen H.; Yang, Frank F.; Schwertner, Adam; Hulur, Imge; Onel, Kenan; Prosperi, Jenifer R.

2015-01-01

The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously implicated in the control of apical-basal polarity; yet, the consequence of APC loss-of-function in epithelial polarization and morphogenesis has not been characterized. To test the hypothesis that APC is required for the establishment of normal epithelial polarity and morphogenesis programs, we generated APC-knockdown epithelial cell lines. APC depletion resulted in loss of polarity and multi-layering on permeable supports, and enlarged, filled spheroids with disrupted polarity in 3D culture. Importantly, these effects of APC knockdown were independent of Wnt/β-catenin signaling, but were rescued with either full-length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene expression signature associated with APC knockdown that points to several candidates known to regulate cell-cell and cell-matrix communication. Analysis of epithelial tissues from mice and humans carrying heterozygous APC mutations further support the importance of APC as a regulator of epithelial behavior and tissue architecture. These data also suggest that the initiation of epithelial-derived tumors as a result of APC mutation or gene silencing may be driven by loss of polarity and dysmorphogenesis. PMID:25578398

Intake of high levels of vitamin A and polyunsaturated fatty acids during different developmental periods modifies the expression of morphogenesis genes in European sea bass (Dicentrarchus labrax).

PubMed

Villeneuve, Laure A N; Gisbert, Enric; Moriceau, Jacques; Cahu, Chantal L; Zambonino Infante, José L

2006-04-01

The effect of the feeding period on larval development was investigated in European sea bass larvae by considering the expression level of some genes involved in morphogenesis. Larvae were fed a control diet except during three different periods (period A: from 8 to 13 d post-hatching (dph); period B: from 13 to 18 dph; period C: from 18 to 23 dph) with two compound diets containing high levels of vitamin A or PUFA. European sea bass morphogenesis was affected by these two dietary nutrients during the early stages of development. The genes involved in morphogenesis could be modulated between 8 and 13 dph, and our results indicated that retinoids and fatty acids influenced two different molecular pathways that in turn implicated two different gene cascades, resulting in two different kinds of malformation. Hypervitaminosis A delayed development, reducing the number of vertebral segments and disturbing bone formation in the cephalic region. These malformations were correlated to an upregulation of retinoic acid receptor gamma, retinoid X receptor (RXR) alpha and bone morphogenetic protein (BMP)4. An excess of PUFA accelerated the osteoblast differentiation process through the upregulation of RXRalpha and BMP4, leading to a supernumerary vertebra. These results suggest that the composition of diets devoted to marine fish larvae has a particularly determining effect before 13 dph on the subsequent development of larvae and juvenile fish.

Zone heated diesel particulate filter electrical connection

DOEpatents

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

2010-03-30

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

Acute Zonal Cone Photoreceptor Outer Segment Loss

PubMed Central

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

2017-01-01

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

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

PubMed Central

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

2016-01-01

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

Segmented annular combustor

DOEpatents

Reider, Samuel B.

1979-01-01

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

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

PubMed Central

Vohnsen, Brian

2014-01-01

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

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

PubMed

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

2017-04-10

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

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

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

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

1986-05-10

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

Inner Segment Remodeling and Mitochondrial Translocation in Cone Photoreceptors in Age-Related Macular Degeneration With Outer Retinal Tubulation.

PubMed

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.

Engineering of M13 Bacteriophage for Development of Tissue Engineering Materials.

PubMed

Jin, Hyo-Eon; Lee, Seung-Wuk

2018-01-01

M13 bacteriophages have several qualities that make them attractive candidates as building blocks for tissue regenerating scaffold materials. Through genetic engineering, a high density of functional peptides and proteins can be simultaneously displayed on the M13 bacteriophage's outer coat proteins. The resulting phage can self-assemble into nanofibrous network structures and can guide the tissue morphogenesis through proliferation, differentiation and apoptosis. In this manuscript, we will describe methods to develop major coat-engineered M13 phages as a basic building block and aligned tissue-like matrices to develop regenerative nanomaterials.

Retinal photoreceptors and visual pigments in Boa constrictor imperator.

PubMed

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.

Three-dimensional visualization of the Autographa californica multiple nucleopolyhedrovirus occlusion-derived virion envelopment process gives new clues as to its mechanism

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

Shi, Yang; Li, Kunpeng; Tang, Peiping

2015-02-15

Baculoviruses produce two virion phenotypes, occlusion-derived virion (ODV) and budded virion (BV). ODV envelopment occurs in the nucleus. Morphogenesis of the ODV has been studied extensively; however, the mechanisms underlying microvesicle formation and ODV envelopment in nuclei remain unclear. In this study, we used electron tomography (ET) together with the conventional electron microscopy to study the envelopment of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ODV. Our results demonstrate that not only the inner but also the outer nuclear membrane can invaginate and vesiculate into microvesicles and that intranuclear microvesicles are the direct source of the ODV membrane. Five main events inmore » the ODV envelopment process are summarized, from which we propose a model to explain this process. - Highlights: • Both the inner and outer nuclear membranes could invaginate. • Both the inner and outer nuclear membranes could vesiculate into microvesicles. • Five main events in the ODV envelopment process are summarized. • A model is proposed to explain this ODV envelopment.« less

Use of border information in the classification of mammographic masses

NASA Astrophysics Data System (ADS)

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

2006-01-01

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

FUEL ELEMENT FOR NUCLEAR REACTORS

DOEpatents

Bassett, C.H.

1961-11-21

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

Segmentation in cohesive systems constrained by elastic environments

PubMed Central

Novak, I.

2017-01-01

The complexity of fracture-induced segmentation in elastically constrained cohesive (fragile) systems originates from the presence of competing interactions. The role of discreteness in such phenomena is of interest in a variety of fields, from hierarchical self-assembly to developmental morphogenesis. In this paper, we study the analytically solvable example of segmentation in a breakable mass–spring chain elastically linked to a deformable lattice structure. We explicitly construct the complete set of local minima of the energy in this prototypical problem and identify among them the states corresponding to the global energy minima. We show that, even in the continuum limit, the dependence of the segmentation topology on the stretching/pre-stress parameter in this problem takes the form of a devil's type staircase. The peculiar nature of this staircase, characterized by locking in rational microstructures, is of particular importance for biological applications, where its structure may serve as an explanation of the robustness of stress-driven segmentation. This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’ PMID:28373383

Sodium-dependent calcium extrusion and sensitivity regulation in retinal cones of the salamander.

PubMed Central

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2017-01-01

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

Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta.

PubMed

Misra, Ashish; Feng, Zhonghui; Zhang, Jiasheng; Lou, Zhi-Yin; Greif, Daniel M

2017-09-12

The aorta is the largest artery in the body. The aortic wall is composed of an inner layer of endothelial cells, a middle layer of alternating elastic lamellae and smooth muscle cells (SMCs), and an outer layer of fibroblasts and extracellular matrix. In contrast to the widespread study of pathological models (e.g., atherosclerosis) in the adult aorta, much less is known about the embryonic and perinatal aorta. Here, we focus on SMCs and provide protocols for the analysis of the morphogenesis and pathogenesis of embryonic and perinatal aortic SMCs in normal development and disease. Specifically, the four protocols included are: i) in vivo embryonic fate mapping and clonal analysis; ii) explant embryonic aorta culture; iii) SMC isolation from the perinatal aorta; and iv) subcutaneous osmotic mini-pump placement in pregnant (or non-pregnant) mice. Thus, these approaches facilitate the investigation of the origin(s), fate, and clonal architecture of SMCs in the aorta in vivo. They allow for modulating embryonic aorta morphogenesis in utero by continuous exposure to pharmacological agents. In addition, isolated aortic tissue explants or aortic SMCs can be used to gain insights into the role of specific gene targets during fundamental processes such as muscularization, proliferation, and migration. These hypothesis-generating experiments on isolated SMCs and the explanted aorta can then be assessed in the in vivo context through pharmacological and genetic approaches.

Hsp47 mediates Cx43-dependent skeletal growth and patterning in the regenerating fin.

PubMed

Bhadra, Joyita; Iovine, M Kathryn

2015-11-01

Skeletal morphogenesis describes how bones achieve their correct shape and size and appropriately position joints. We use the regenerating caudal fin of zebrafish to study this process. Our examination of the fin length mutant short fin (sof (b123)) has revealed that the gap junction protein Cx43 is involved in skeletal morphogenesis by promoting cell proliferation and inhibiting joint formation, thereby coordinating skeletal growth and patterning. Here we demonstrate that serpinh1b is molecularly and functionally downstream of cx43. The gene serpinh1b codes for a protein called Hsp47, a molecular chaperone responsible for proper folding of procollagen molecules. Knockdown of Hsp47 in regenerating fins recapitulates the sof (b123) phenotypes of reduced fin length, reduced segment length and reduced level of cell proliferation. Furthermore, Hsp47 knockdown affects the organization and localization of the collagen-based actinotrichia. Together, our findings reveal that serpinh1b acts in a cx43 dependent manner to regulate cell proliferation and joint formation. We conclude that disruption of the collagen-based extracellular matrix influences signaling events required for cell proliferation, as well as the patterning of skeletal precursor cells that influences segment length. Therefore, we suggest that Hsp47 function is necessary for skeletal growth and patterning during fin regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2010-01-01

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

High temperature control rod assembly

DOEpatents

Vollman, Russell E.

1991-01-01

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

Nrk2b-mediated NAD+ production regulates cell adhesion and is required for muscle morphogenesis in vivo

PubMed Central

Goody, Michelle F.; Kelly, Meghan W.; Lessard, Kevin N.; Khalil, Andre; Henry, Clarissa A.

2010-01-01

Cell-matrix adhesion complexes (CMACs) play fundamental roles during morphogenesis. Given the ubiquitous nature of CMACs and their roles in many cellular processes, one question is how specificity of CMAC function is modulated. The clearly defined cell behaviors that generate segmentally reiterated axial skeletal muscle during zebrafish development comprise an ideal system with which to investigate CMAC function during morphogenesis. We found that Nicotinamide riboside kinase 2b (Nrk2b) cell autonomously modulates the molecular composition of CMACs in vivo. Nrk2b is required for normal Laminin polymerization at the myotendinous junction (MTJ). In Nrk2b-deficient embryos, at MTJ loci where Laminin is not properly polymerized, muscle fibers elongate into adjacent myotomes and are abnormally long. In yeast and human cells, Nrk2 phosphorylates Nicotinamide Riboside and generates NAD+ through an alternative salvage pathway. Exogenous NAD+ treatment rescues MTJ development in Nrk2b-deficient embryos, but not in laminin mutant embryos. Both Nrk2b and Laminin are required for localization of Paxillin, but not β-Dystroglycan, to CMACs at the MTJ. Overexpression of Paxillin in Nrk2b-deficient embryos is sufficient to rescue MTJ integrity. Taken together, these data show that Nrk2b plays a specific role in modulating subcellular localization of discrete CMAC components that in turn play roles in musculoskeletal development. Furthermore, these data suggest that Nrk2b-mediated synthesis of NAD+ is functionally upstream of Laminin adhesion and Paxillin subcellular localization during MTJ development. These results indicate a previously unrecognized complexity to CMAC assembly in vivo and also elucidate a novel role for NAD+ during morphogenesis. PMID:20566368

Notochord segmentation may lay down the pathway for the development of the vertebral bodies in the Atlantic salmon.

PubMed

Grotmol, Sindre; Kryvi, Harald; Nordvik, Kari; Totland, Geir K

2003-12-01

This study indicates that the development of the vertebrae in the Atlantic salmon requires the orchestration of two sources of metameric patterning, derived from the notochord and the somite rows, respectively. Before segmentation of the salmon notochord, chordoblasts exhibit a well-defined cell axis that is uniformly aligned with the cranio-caudal axis. The morphology of these cells is characterised by a foot-like basal projection that rests on the notochordal sheath. Notochordal segments are initially formed within the chordoblast layer by metameric change in the axial orientation of groups of chordoblasts. This process results in the formation of circular bands of chordoblasts, with feet perpendicular to the cranio-caudal axis, the original chordoblast orientation. Each vertebra is defined by two such chordoblast bands, at the cranial and caudal borders, respectively. Formation of the chordoblast segments closely precedes formation of the chordacentra, which form as calcified rings within the adjacent notochordal sheath. Sclerotomal osteoblasts then differentiate on the surface of the chordacentra, using them as foundations for further vertebral growth. Thus, the morphogenesis of the rudiments of the vertebral bodies is initiated by a generation of segments within the chordoblast layer. This dual segmentation model for salmon, in which the segmental patterns of the neural and haemal arches are somite-derived, while the vertebral segments seem to be notochord-derived, contrasts with current models for avians and mammals.

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

PubMed

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

2016-11-18

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

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

PubMed Central

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

2016-01-01

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

Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

PubMed Central

Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

2014-01-01

Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

MorphoGraphX: A platform for quantifying morphogenesis in 4D.

PubMed

Barbier de Reuille, Pierre; Routier-Kierzkowska, Anne-Lise; Kierzkowski, Daniel; Bassel, George W; Schüpbach, Thierry; Tauriello, Gerardo; Bajpai, Namrata; Strauss, Sören; Weber, Alain; Kiss, Annamaria; Burian, Agata; Hofhuis, Hugo; Sapala, Aleksandra; Lipowczan, Marcin; Heimlicher, Maria B; Robinson, Sarah; Bayer, Emmanuelle M; Basler, Konrad; Koumoutsakos, Petros; Roeder, Adrienne H K; Aegerter-Wilmsen, Tinri; Nakayama, Naomi; Tsiantis, Miltos; Hay, Angela; Kwiatkowska, Dorota; Xenarios, Ioannis; Kuhlemeier, Cris; Smith, Richard S

2015-05-06

Morphogenesis emerges from complex multiscale interactions between genetic and mechanical processes. To understand these processes, the evolution of cell shape, proliferation and gene expression must be quantified. This quantification is usually performed either in full 3D, which is computationally expensive and technically challenging, or on 2D planar projections, which introduces geometrical artifacts on highly curved organs. Here we present MorphoGraphX ( www.MorphoGraphX.org), a software that bridges this gap by working directly with curved surface images extracted from 3D data. In addition to traditional 3D image analysis, we have developed algorithms to operate on curved surfaces, such as cell segmentation, lineage tracking and fluorescence signal quantification. The software's modular design makes it easy to include existing libraries, or to implement new algorithms. Cell geometries extracted with MorphoGraphX can be exported and used as templates for simulation models, providing a powerful platform to investigate the interactions between shape, genes and growth.

Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis

PubMed Central

Jackson, Abigail; Kasah, Sahrunizam; Mansour, Suzanne L.; Morrow, Bernice; Basson, M. Albert

2015-01-01

Background The T-box transcription factor Tbx1, is essential for the normal development of multiple organ systems in the embryo. One of the most striking phenotypes in Tbx1−/− embryos is the failure of the caudal pharyngeal pouches to evaginate from the foregut endoderm. Despite considerable interest in the role of Tbx1 in development, the mechanisms whereby Tbx1 controls caudal pouch formation have remained elusive. In particular, the question as to how Tbx1 expression in the pharyngeal endoderm regulates pharyngeal pouch morphogenesis in the mouse embryo is not known. Results To address this question, we produced mouse embryos in which Tbx1 was specifically deleted from the pharyngeal endoderm and as expected, embryos failed to form caudal pharyngeal pouches. To determine the molecular mechanism, we examined expression of Fgf3 and Fgf8 ligands and downstream effectors. Although Fgf8 expression is greatly reduced in Tbx1-deficient endoderm, FGF signaling levels are unaffected. Furthermore, pouch morphogenesis is only partially perturbed by the loss of both Fgf3 and Fgf8 from the endoderm, indicating that neither are required for pouch formation. Conclusions Tbx1 deletion from the pharyngeal endoderm is sufficient to cause caudal pharyngeal arch segmentation defects by FGF-independent effectors that remain to be identified. PMID:24812002

TIGRESS highly-segmented high-purity germanium clover detector

NASA Astrophysics Data System (ADS)

Scraggs, H. C.; Pearson, C. J.; Hackman, G.; Smith, M. B.; Austin, R. A. E.; Ball, G. C.; Boston, A. J.; Bricault, P.; Chakrawarthy, R. S.; Churchman, R.; Cowan, N.; Cronkhite, G.; Cunningham, E. S.; Drake, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hyland, B.; Jones, B.; Leslie, J. R.; Martin, J.-P.; Morris, D.; Morton, A. C.; Phillips, A. A.; Sarazin, F.; Schumaker, M. A.; Svensson, C. E.; Valiente-Dobón, J. J.; Waddington, J. C.; Watters, L. M.; Zimmerman, L.

2005-05-01

The TRIUMF-ISAC Gamma-Ray Escape-Suppressed Spectrometer (TIGRESS) will consist of twelve units of four high-purity germanium (HPGe) crystals in a common cryostat. The outer contacts of each crystal will be divided into four quadrants and two lateral segments for a total of eight outer contacts. The performance of a prototype HPGe four-crystal unit has been investigated. Integrated noise spectra for all contacts were measured. Energy resolutions, relative efficiencies for both individual crystals and for the entire unit, and peak-to-total ratios were measured with point-like sources. Position-dependent performance was measured by moving a collimated source across the face of the detector.

Interaction of 4.1G and cGMP-gated channels in rod photoreceptor outer segments.

PubMed

Cheng, Christiana L; Molday, Robert S

2013-12-15

In photoreceptors, the assembly of signaling molecules into macromolecular complexes is important for phototransduction and maintaining the structural integrity of rod outer segments (ROSs). However, the molecular composition and formation of these complexes are poorly understood. Using immunoprecipitation and mass spectrometry, 4.1G was identified as a new interacting partner for the cyclic-nucleotide gated (CNG) channels in ROSs. 4.1G is a widely expressed multifunctional protein that plays a role in the assembly and stability of membrane protein complexes. Multiple splice variants of 4.1G were cloned from bovine retina. A smaller splice variant of 4.1G selectively interacted with CNG channels not associated with peripherin-2-CNG channel complex. A combination of truncation studies and domain-binding assays demonstrated that CNG channels selectively interacted with 4.1G through their FERM and CTD domains. Using immunofluorescence, labeling of 4.1G was seen to be punctate and partially colocalized with CNG channels in the ROS. Our studies indicate that 4.1G interacts with a subset of CNG channels in the ROS and implicate this protein-protein interaction in organizing the spatial arrangement of CNG channels in the plasma membrane of outer segments.

Analysis of radially cracked ring segments subject to forces and couples

NASA Technical Reports Server (NTRS)

Gross, B.; Srawley, J. E.

1977-01-01

Results of planar boundary collocation analysis are given for ring segment (C-shaped) specimens with radial cracks, subjected to combined forces and couples. Mode I stress intensity factors and crack mouth opening displacements were determined for ratios of outer to inner radius in the range 1.1 to 2.5 and ratios of crack length to segment width in the range 0.1 to 0.8.

Analysis of radially cracked ring segments subject to forces and couples

NASA Technical Reports Server (NTRS)

Gross, B.; Strawley, J. E.

1975-01-01

Results of planar boundary collocation analysis are given for ring segment (C shaped) specimens with radial cracks, subjected to combined forces and couples. Mode I stress intensity factors and crack mouth opening displacements were determined for ratios of outer to inner radius in the range 1.1 to 2.5, and ratios of crack length to segment width in the range 0.1 to 0.8.

Automatic lumen and outer wall segmentation of the carotid artery using deformable three-dimensional models in MR angiography and vessel wall images.

PubMed

van 't Klooster, Ronald; de Koning, Patrick J H; Dehnavi, Reza Alizadeh; Tamsma, Jouke T; de Roos, Albert; Reiber, Johan H C; van der Geest, Rob J

2012-01-01

To develop and validate an automated segmentation technique for the detection of the lumen and outer wall boundaries in MR vessel wall studies of the common carotid artery. A new segmentation method was developed using a three-dimensional (3D) deformable vessel model requiring only one single user interaction by combining 3D MR angiography (MRA) and 2D vessel wall images. This vessel model is a 3D cylindrical Non-Uniform Rational B-Spline (NURBS) surface which can be deformed to fit the underlying image data. Image data of 45 subjects was used to validate the method by comparing manual and automatic segmentations. Vessel wall thickness and volume measurements obtained by both methods were compared. Substantial agreement was observed between manual and automatic segmentation; over 85% of the vessel wall contours were segmented successfully. The interclass correlation was 0.690 for the vessel wall thickness and 0.793 for the vessel wall volume. Compared with manual image analysis, the automated method demonstrated improved interobserver agreement and inter-scan reproducibility. Additionally, the proposed automated image analysis approach was substantially faster. This new automated method can reduce analysis time and enhance reproducibility of the quantification of vessel wall dimensions in clinical studies. Copyright © 2011 Wiley Periodicals, Inc.

Radio Frequency Trap for Containment of Plasmas in Antimatter Propulsion Systems Using Rotating Wall Electric Fields

NASA Technical Reports Server (NTRS)

Sims, William Herbert, III (Inventor); Martin, James Joseph (Inventor); Lewis, Raymond A. (Inventor)

2003-01-01

A containment apparatus for containing a cloud of charged particles comprises a cylindrical vacuum chamber having a longitudinal axis. Within the vacuum chamber is a containment region. A magnetic field is aligned with the longitudinal axis of the vacuum chamber. The magnetic field is time invariant and uniform in strength over the containment region. An electric field is also aligned with the longitudinal axis of the vacuum chamber and the magnetic field. The electric field is time invariant, and forms a potential well over the containment region. One or more means are disposed around the cloud of particles for inducing a rotating electric field internal to the vacuum chamber. The rotating electric field imparts energy to the charged particles within the containment region and compress the cloud of particles. The means disposed around the outer surface of the vacuum chamber for inducing a rotating electric field are four or more segments forming a segmented ring, the segments conforming to the outer surface of the vacuum chamber. Each of the segments is energized by a separate alternating voltage. The sum of the voltages imposed on each segment establishes the rotating field. When four segments form a ring, the rotating field is obtained by a signal generator applying a sinusoidal signal phase delayed by 90,180 and 270 degrees in sequence to the four segments.

Increasing the efficiency of designing hemming processes by using an element-based metamodel approach

NASA Astrophysics Data System (ADS)

Kaiser, C.; Roll, K.; Volk, W.

2017-09-01

In the automotive industry, the manufacturing of automotive outer panels requires hemming processes in which two sheet metal parts are joined together by bending the flange of the outer part over the inner part. Because of decreasing development times and the steadily growing number of vehicle derivatives, an efficient digital product and process validation is necessary. Commonly used simulations, which are based on the finite element method, demand significant modelling effort, which results in disadvantages especially in the early product development phase. To increase the efficiency of designing hemming processes this paper presents a hemming-specific metamodel approach. The approach includes a part analysis in which the outline of the automotive outer panels is initially split into individual segments. By doing a para-metrization of each of the segments and assigning basic geometric shapes, the outline of the part is approximated. Based on this, the hemming parameters such as flange length, roll-in, wrinkling and plastic strains are calculated for each of the geometric basic shapes by performing a meta-model-based segmental product validation. The metamodel is based on an element similar formulation that includes a reference dataset of various geometric basic shapes. A random automotive outer panel can now be analysed and optimized based on the hemming-specific database. By implementing this approach into a planning system, an efficient optimization of designing hemming processes will be enabled. Furthermore, valuable time and cost benefits can be realized in a vehicle’s development process.

Early photoreceptor outer segment loss and retinoschisis in Cohen syndrome.

PubMed

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

2018-06-01

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

Advanced two-layer level set with a soft distance constraint for dual surfaces segmentation in medical images

NASA Astrophysics Data System (ADS)

Ji, Yuanbo; van der Geest, Rob J.; Nazarian, Saman; Lelieveldt, Boudewijn P. F.; Tao, Qian

2018-03-01

Anatomical objects in medical images very often have dual contours or surfaces that are highly correlated. Manually segmenting both of them by following local image details is tedious and subjective. In this study, we proposed a two-layer region-based level set method with a soft distance constraint, which not only regularizes the level set evolution at two levels, but also imposes prior information on wall thickness in an effective manner. By updating the level set function and distance constraint functions alternatingly, the method simultaneously optimizes both contours while regularizing their distance. The method was applied to segment the inner and outer wall of both left atrium (LA) and left ventricle (LV) from MR images, using a rough initialization from inside the blood pool. Compared to manual annotation from experience observers, the proposed method achieved an average perpendicular distance (APD) of less than 1mm for the LA segmentation, and less than 1.5mm for the LV segmentation, at both inner and outer contours. The method can be used as a practical tool for fast and accurate dual wall annotations given proper initialization.

Three-axis asymmetric radiation detector system

DOEpatents

Martini, Mario Pierangelo; Gedcke, Dale A.; Raudorf, Thomas W.; Sangsingkeow, Pat

2000-01-01

A three-axis radiation detection system whose inner and outer electrodes are shaped and positioned so that the shortest path between any point on the inner electrode and the outer electrode is a different length whereby the rise time of a pulse derived from a detected radiation event can uniquely define the azimuthal and radial position of that event, and the outer electrode is divided into a plurality of segments in the longitudinal axial direction for locating the axial location of a radiation detection event occurring in the diode.

ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina.

PubMed

Duncker, Tobias; Lee, Winston; Jiang, Fan; Ramachandran, Rithambara; Hood, Donald C; Tsang, Stephen H; Sparrow, Janet R; Greenstein, Vivienne C

2018-01-01

To assess structure and function across the transition zone (TZ) between relatively healthy and diseased retina in acute zonal occult outer retinopathy. Six patients (6 eyes; age 22-71 years) with acute zonal occult outer retinopathy were studied. Spectral-domain optical coherence tomography, fundus autofluorescence, near-infrared reflectance, color fundus photography, and fundus perimetry were performed and images were registered to each other. The retinal layers of the spectral-domain optical coherence tomography scans were segmented and the thicknesses of two outer retinal layers, that is, the total receptor and outer segment plus layers, and the retinal nerve fiber layer were measured. All eyes showed a TZ on multimodal imaging. On spectral-domain optical coherence tomography, the TZ was in the nasal retina at varying distances from the fovea. For all eyes, it was associated with loss of the ellipsoid zone band, significant thinning of the two outer retinal layers, and in three eyes with thickening of the retinal nerve fiber layer. On fundus autofluorescence, all eyes had a clearly demarcated peripapillary area of abnormal fundus autofluorescence delimited by a border of high autofluorescence; the latter was associated with loss of the ellipsoid zone band and with a change from relatively normal to markedly decreased or nonrecordable visual sensitivity on fundus perimetry. The results of multimodal imaging clarified the TZ in acute zonal occult outer retinopathy. The TZ was outlined by a distinct high autofluorescence border that correlated with loss of the ellipsoid zone band on spectral-domain optical coherence tomography. However, in fundus areas that seemed healthy on fundus autofluorescence, thinning of the outer retinal layers and thickening of the retinal nerve fiber layer were observed near the TZ. The TZ was also characterized by a decrease in visual sensitivity.

Increasing the feasibility of minimally invasive procedures in type A aortic dissections: a framework for segmentation and quantification.

PubMed

Morariu, Cosmin Adrian; Terheiden, Tobias; Dohle, Daniel Sebastian; Tsagakis, Konstantinos; Pauli, Josef

2016-02-01

Our goal is to provide precise measurements of the aortic dimensions in case of dissection pathologies. Quantification of surface lengths and aortic radii/diameters together with the visualization of the dissection membrane represents crucial prerequisites for enabling minimally invasive treatment of type A dissections, which always also imply the ascending aorta. We seek a measure invariant to luminance and contrast for aortic outer wall segmentation. Therefore, we propose a 2D graph-based approach using phase congruency combined with additional features. Phase congruency is extended to 3D by designing a novel conic directional filter and adding a lowpass component to the 3D Log-Gabor filterbank for extracting the fine dissection membrane, which separates the true lumen from the false one within the aorta. The result of the outer wall segmentation is compared with manually annotated axial slices belonging to 11 CTA datasets. Quantitative assessment of our novel 2D/3D membrane extraction algorithms has been obtained for 10 datasets and reveals subvoxel accuracy in all cases. Aortic inner and outer surface lengths, determined within 2 cadaveric CT datasets, are validated against manual measurements performed by a vascular surgeon on excised aortas of the body donors. This contribution proposes a complete pipeline for segmentation and quantification of aortic dissections. Validation against ground truth of the 3D contour lengths quantification represents a significant step toward custom-designed stent-grafts.

Light-dependent translocation of arrestin in rod photoreceptors is signaled through a phospholipase C cascade and requires ATP.

PubMed

Orisme, Wilda; Li, Jian; Goldmann, Tobias; Bolch, Susan; Wolfrum, Uwe; Smith, W Clay

2010-03-01

Partitioning of cellular components is a critical mechanism by which cells can regulate their activity. In rod photoreceptors, light induces a large-scale translocation of arrestin from the inner segments to the outer segments. The purpose of this project is to elucidate the signaling pathway necessary to initiate arrestin translocation to the outer segments and the mechanism for arrestin translocation. Mouse retinal organotypic cultures and eyes from transgenic Xenopus tadpoles expressing a fusion of GFP and rod arrestin were treated with both activators and inhibitors of proteins in the phosphoinositide pathway. Confocal microscopy was used to image the effects of the pharmacological agents on arrestin translocation in rod photoreceptors. Retinas were also depleted of ATP using potassium cyanide to assess the requirement for ATP in arrestin translocation. In this study, we demonstrate that components of the G-protein-linked phospholipase C (PLC) pathway play a role in initiating arrestin translocation. Our results show that arrestin translocation can be stimulated by activators of PLC and protein kinase C (PKC), and by cholera toxin in the absence of light. Arrestin translocation to the outer segments is significantly reduced by inhibitors of PLC and PKC. Importantly, we find that treatment with potassium cyanide inhibits arrestin translocation in response to light. Collectively, our results suggest that arrestin translocation is initiated by a G-protein-coupled cascade through PLC and PKC signaling. Furthermore, our results demonstrate that at least the initiation of arrestin translocation requires energy input.

Reflections on the pathogenesis of Down syndrome.

PubMed

Opitz, J M; Gilbert-Barness, E F

1990-01-01

Present efforts to identify, isolate, and characterize in molecular terms the "consensus" segment of 21q sufficient to cause most of the major and some of the most characteristic minor manifestations of Down syndrome will soon provide answers to many questions. However, we think that a reductionist approach to explain the Down syndrome phenotype in a "linear" manner from the DNA sequence of the segment will be doomed to failure from the outset because of the open, complex, nonlinear, hierarchical nature of morphogenetic systems. Neo-Darwinism is under strong attack; most genetic changes accumulated over time may very well be of neutral effect, and detailed studies in several related groups of vertebrate species has shown that molecular and organismal evolution are largely independent of one another. It has been pointed out recently that biology lacks a theory of ontogenetic and phylogenetic development, and that a purely "genocentric" view of biology at the expense of the complexly hierarchical intrinsic epigenetic attributes of developmental systems is "out of focus with respect to ... biological organization and morphogenesis," and may be "a residue of nineteenth century romantic idealism." Down syndrome impresses us as a paradigm of increased developmental variability due to a deceleration of the rate of development (neoteny) with many anomalies of incomplete morphogenesis (vestigia), atavisms, increased morphometric variability with many decreased means, increased variances, and increased fluctuating asymmetry. These abnormalities, together with highly increased risk of prenatal death and postnatal morbidity, impaired growth, and abnormal CNS and gonadal structure and function characteristic of most aneuploidy syndromes, suggest to us that the pathogenesis of Down syndrome is best viewed in terms of the mechanisms of speciation. Transgenic experiment involving sequential or overlapping pieces of "the consensus segment" on distal 21q22.1-22.3 may help decide to what extent the Down syndrome phenotype can be resolved into the additive effect of several pleiotropic oligogenes with epistatic interaction or the indirect secondary "mass" effect of a specific segment of 21q with epistatic interaction involving multiple loci on 21q and other chromosomes.

Evolution of Magnetic Rayleigh–Taylor Instability into the Outer Solar Corona and Low Interplanetary Space

NASA Astrophysics Data System (ADS)

Mishra, Sudheer K.; Singh, Talwinder; Kayshap, P.; Srivastava, A. K.

2018-03-01

We analyze the observations from Solar TErrestrial RElations Observatory (STEREO)-A and B/COR-1 of an eruptive prominence in the intermediate corona on 2011 June 7 at 08:45 UT, which consists of magnetic Rayleigh–Taylor (MRT) unstable plasma segments. Its upper-northward segment shows spatio-temporal evolution of MRT instability in form of finger structures up to the outer corona and low interplanetary space. Using the method of Dolei et al., It is estimated that the density in each bright finger is greater than the corresponding dark region lying below it in the surrounding intermediate corona. The instability is evolved due to wave perturbations that are parallel to the magnetic field at the density interface. We conjecture that the prominence plasma is supported by tension component of the magnetic field against gravity. Through the use of linear stability theory, the magnetic field is estimated as 21–40 mG to suppress growth of MRT instability in the observed finger structures. In the southward plasma segment, a horn-like structure is observed at 11:55 UT in the intermediate corona that also indicates MRT instability. Falling blobs are also observed in both of the plasma segments. In the outer corona, up to 6–13 solar radii, the mushroom-like plasma structures have been identified in the upper-northward MRT unstable plasma segment using STEREO-A/COR-2. These structures most likely grew due to the breaking and twisting of fingers at large spatial scales in weaker magnetic fields. In the lower interplanetary space up to 20 solar radii, these structures are fragmented into various small-scale localized plasma spikes, most likely due to turbulent mixing.

Light-Induced Translocation of RGS9-1 and Gβ5L in Mouse Rod Photoreceptors

PubMed Central

Tian, Mei; Zallocchi, Marisa; Wang, Weimin; Chen, Ching-Kang; Palczewski, Krzysztof; Delimont, Duane; Cosgrove, Dominic; Peng, You-Wei

2013-01-01

The transducin GTPase-accelerating protein complex, which determines the photoresponse duration of photoreceptors, is composed of RGS9-1, Gβ5L and R9AP. Here we report that RGS9-1 and Gβ5L change their distribution in rods during light/dark adaptation. Upon prolonged dark adaptation, RGS9-1 and Gβ5L are primarily located in rod inner segments. But very dim-light exposure quickly translocates them to the outer segments. In contrast, their anchor protein R9AP remains in the outer segment at all times. In the dark, Gβ5L's interaction with R9AP decreases significantly and RGS9-1 is phosphorylated at S475 to a significant degree. Dim light exposure leads to quick de-phosphorylation of RGS9-1. Furthermore, after prolonged dark adaptation, RGS9-1 and transducin Gα are located in different cellular compartments. These results suggest a previously unappreciated mechanism by which prolonged dark adaptation leads to increased light sensitivity in rods by dissociating RGS9-1 from R9AP and redistributing it to rod inner segments. PMID:23555598

Live-Cell Imaging of Phagosome Motility in Primary Mouse RPE Cells.

PubMed

Hazim, Roni; Jiang, Mei; Esteve-Rudd, Julian; Diemer, Tanja; Lopes, Vanda S; Williams, David S

2016-01-01

The retinal pigment epithelium (RPE) is a post-mitotic epithelial monolayer situated between the light-sensitive photoreceptors and the choriocapillaris. Given its vital functions for healthy vision, the RPE is a primary target for insults that result in blinding diseases, including age-related macular degeneration (AMD). One such function is the phagocytosis and digestion of shed photoreceptor outer segments. In the present study, we examined the process of trafficking of outer segment disk membranes in live cultures of primary mouse RPE, using high speed spinning disk confocal microscopy. This approach has enabled us to track phagosomes, and determine parameters of their motility, which are important for their efficient degradation.

Foveal cone spacing and cone photopigment density difference: objective measurements in the same subjects.

PubMed

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.

Shoreline configuration and shoreline dynamics: A mesoscale analysis. [Assateague Island and Outer Banks of North Carolina

NASA Technical Reports Server (NTRS)

Dolan, R. (Principal Investigator); Hayden, B. P.; Heywood, J. E.

1975-01-01

The author has identified the following significant results. Atlantic coast barrier island shorelines are seldom straight, but rather sinuous. These shoreline curvatures range in size from cusps to capes. Significant relationships exist between the orientation of shoreline segments within the larger of these sinuous features and shoreline dynamics, with coefficients ranging up to .9. Orientation of the shoreline segments of Assateague Island (60 km) and the Outer Banks of North Carolina (130 km) was measured from LANDSAT 2 imagery (1:80,000) and high altitude aerial photography (1:120,000). Long term trends in shoreline dynamics were established by mapping shoreline and storm-surge penetration changes.

Live Imaging of LysoTracker-Labelled Phagolysosomes Tracks Diurnal Phagocytosis of Photoreceptor Outer Segment Fragments in Rat RPE Tissue Ex Vivo.

PubMed

Mao, Yingyu; Finnemann, Silvia C

2016-01-01

Renewal of rod photoreceptor outer segments in the mammalian eye involves synchronized diurnal shedding after light onset of spent distal outer segment fragments (POS) linked to swift clearance of shed POS from the subretinal space by the adjacent retinal pigment epithelium (RPE). Engulfed POS phagosomes in RPE cells mature to acidified phagolysosomes, which accomplish enzymatic degradation of POS macromolecules. Here, we used an acidophilic fluorophore LysoTracker to label acidic organelles in freshly dissected, live rat RPE tissue flat mounts. We observed that all RPE cells imaged contained numerous acidified POS phagolysosomes whose abundance per cell was dramatically increased 2 h after light onset as compared to either 1 h before or 4 h after light onset. Lack of organelles of similar diameter (of 1-2 μm) in phagocytosis-defective mutant RCS rat RPE confirmed that LysoTracker live imaging detected POS phagolysosomes. Lack of increase in lysosomal membrane protein LAMP-1 in RPE/choroid during the diurnal phagocytic burst suggests that formation of POS phagolysosomes in RPE in situ may not involve extra lysosome membrane biogenesis. Taken together, we report a new imaging approach that directly detects POS phagosome acidification and allows rapid tracking and quantification of POS phagocytosis by live RPE -tissue ex situ.

Recirculating electric air filter

DOEpatents

Bergman, Werner

1986-01-01

An electric air filter cartridge has a cylindrical inner high voltage eleode, a layer of filter material, and an outer ground electrode formed of a plurality of segments moveably connected together. The outer electrode can be easily opened to remove or insert filter material. Air flows through the two electrodes and the filter material and is exhausted from the center of the inner electrode.

Recirculating electric air filter

DOEpatents

Bergman, W.

1985-01-09

An electric air filter cartridge has a cylindrical inner high voltage electrode, a layer of filter material, and an outer ground electrode formed of a plurality of segments moveably connected together. The outer electrode can be easily opened to remove or insert filter material. Air flows through the two electrodes and the filter material and is exhausted from the center of the inner electrode.

Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities

PubMed Central

Levin, Michael

2013-01-01

Transformative impact in regenerative medicine requires more than the reprogramming of individual cells: advances in repair strategies for birth defects or injuries, tumor normalization, and the construction of bioengineered organs and tissues all require the ability to control large-scale anatomical shape. Much recent work has focused on the transcriptional and biochemical regulation of cell behaviour and morphogenesis. However, exciting new data reveal that bioelectrical properties of cells and their microenvironment exert a profound influence on cell differentiation, proliferation, and migration. Ion channels and pumps expressed in all cells, not just excitable nerve and muscle, establish resting potentials that vary across tissues and change with significant developmental events. Most importantly, the spatio-temporal gradients of these endogenous transmembrane voltage potentials (Vmem) serve as instructive patterning cues for large-scale anatomy, providing organ identity, positional information, and prepattern template cues for morphogenesis. New genetic and pharmacological techniques for molecular modulation of bioelectric gradients in vivo have revealed the ability to initiate complex organogenesis, change tissue identity, and trigger regeneration of whole vertebrate appendages. A large segment of the spatial information processing that orchestrates individual cells’ programs towards the anatomical needs of the host organism is electrical; this blurs the line between memory and decision-making in neural networks and morphogenesis in non-neural tissues. Advances in cracking this bioelectric code will enable the rational reprogramming of shape in whole tissues and organs, revolutionizing regenerative medicine, developmental biology, and synthetic bioengineering. PMID:23897652

Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities.

PubMed

Levin, Michael

2013-01-01

Transformative impact in regenerative medicine requires more than the reprogramming of individual cells: advances in repair strategies for birth defects or injuries, tumor normalization, and the construction of bioengineered organs and tissues all require the ability to control large-scale anatomical shape. Much recent work has focused on the transcriptional and biochemical regulation of cell behavior and morphogenesis. However, exciting new data reveal that bioelectrical properties of cells and their microenvironment exert a profound influence on cell differentiation, proliferation, and migration. Ion channels and pumps expressed in all cells, not just excitable nerve and muscle, establish resting potentials that vary across tissues and change with significant developmental events. Most importantly, the spatiotemporal gradients of these endogenous transmembrane voltage potentials (Vmem ) serve as instructive patterning cues for large-scale anatomy, providing organ identity, positional information, and prepattern template cues for morphogenesis. New genetic and pharmacological techniques for molecular modulation of bioelectric gradients in vivo have revealed the ability to initiate complex organogenesis, change tissue identity, and trigger regeneration of whole vertebrate appendages. A large segment of the spatial information processing that orchestrates individual cells' programs toward the anatomical needs of the host organism is electrical; this blurs the line between memory and decision-making in neural networks and morphogenesis in nonneural tissues. Advances in cracking this bioelectric code will enable the rational reprogramming of shape in whole tissues and organs, revolutionizing regenerative medicine, developmental biology, and synthetic bioengineering. Copyright © 2013 Wiley Periodicals, Inc.

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

PubMed Central

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

2014-01-01

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

Automated segmentation of mouse OCT volumes (ASiMOV): Validation & clinical study of a light damage model.

PubMed

Antony, Bhavna Josephine; Kim, Byung-Jin; Lang, Andrew; Carass, Aaron; Prince, Jerry L; Zack, Donald J

2017-01-01

The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study.

Automated segmentation of mouse OCT volumes (ASiMOV): Validation & clinical study of a light damage model

PubMed Central

Lang, Andrew; Carass, Aaron; Prince, Jerry L.; Zack, Donald J.

2017-01-01

The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study. PMID:28817571

Automatic plaque characterization and vessel wall segmentation in magnetic resonance images of atherosclerotic carotid arteries

NASA Astrophysics Data System (ADS)

Adame, Isabel M.; van der Geest, Rob J.; Wasserman, Bruce A.; Mohamed, Mona; Reiber, Johan H. C.; Lelieveldt, Boudewijn P. F.

2004-05-01

Composition and structure of atherosclerotic plaque is a primary focus of cardiovascular research. In vivo MRI provides a meanse to non-invasively image and assess the morphological features of athersclerotic and normal human carotid arteries. To quantitatively assess the vulnerability and the type of plaque, the contours of the lumen, outer boundary of the vessel wall and plaque components, need to be traced. To achieve this goal, we have developed an automated contou detection technique, which consists of three consecutive steps: firstly, the outer boundary of the vessel wall is detected by means of an ellipse-fitting procedure in order to obtain smoothed shapes; secondly, the lumen is segnented using fuzzy clustering. Thre region to be classified is that within the outer vessel wall boundary obtained from the previous step; finally, for plaque detection we follow the same approach as for lumen segmentation: fuzzy clustering. However, plaque is more difficult to segment, as the pixel gray value can differ considerably from one region to another, even when it corresponds to the same type of tissue. That makes further processing necessary. All these three steps might be carried out combining information from different sequences (PD-, T2-, T1-weighted images, pre- and post-contrast), to improve the contour detection. The algorithm has been validated in vivo on 58 high-resolution PD and T1 weighted MR images (19 patients). The results demonstrate excellent correspondence between automatic and manual area measurements: lumen (r=0.94), outer (r=0.92), and acceptable for fibrous cap thickness (r=0.76).

In Vivo Imaging of Human Cone Photoreceptor Inner Segments

PubMed Central

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

2014-01-01

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

The effect of light on outer segment calcium in salamander rods

PubMed Central

Matthews, Hugh R; Fain, Gordon L

2003-01-01

Calcium acts as a second messenger in vertebrate rods, regulating the recovery phase of the light response and modulating sensitivity during light-adaptation. Since light not only decreases the outer segment calcium concentration ([Ca2+]i) by closing cyclic nucleotide-gated channels but can also increase [Ca2+]i by releasing Ca2+ from buffer sites or intracellular stores, we examined in detail the effect of light and circulating current on [Ca2+]i by making simultaneous measurements of suction pipette current and [Ca2+]i from isolated rods of the salamander Ambystoma tigrinum after incorporation of the fluorescent dye fluo-5F. When the release of Ca2+ is measured in 0 Ca2+−0 Na+ solution, minimising fluxes of Ca2+ across the plasma membrane, it is substantial only for light bright enough to bleach a significant fraction of the photopigment and is restricted to the part of the outer segment in which the bleach occurred. It is unlikely, therefore, to make a large contribution to [Ca2+]i for most of the physiological operating range of the rod. Nevertheless, since release is half-maximal for a bleach of less than 10 %, it cannot be produced by a simple mechanism such as a change in the affinity of a binding site on rhodopsin itself but must instead require some more complex interaction. In Ringer solution, the Ca2+ in the light-releasable pool can be discharged merely by the decrease in [Ca2+]i that occurs as the outer segment channels close. In steady background light or after exposure to saturating illumination, the fraction of Ca2+ in the pool decreases essentially in proportion to [Ca2+]i as if Ca2+ were being removed from a buffer site within the cytoplasm. Furthermore, [Ca2+]i itself changes in proportion to the circulating current, with little evidence for a contribution from Ca2+ release or other mechanisms of Ca2+ homeostasis. This indicates that flux of Ca2+ across the plasma membrane is the major determinant of outer segment Ca2+ concentration within the rod's normal operating light intensity range. Once Ca2+ has been discharged from the releasable pool, it is restored following dim illumination apparently as the simple result of the subsequent restoration of dark [Ca2+]i and the rebinding of Ca2+ to its release site, but after brighter light perhaps also as a consequence of regeneration of the photopigment. PMID:12949220

Pyrometer mount for a closed-circuit thermal medium cooled gas turbine

DOEpatents

Jones, Raymond Joseph; Kirkpatrick, Francis Lawrence; Burns, James Lee; Fulton, John Robert

2002-01-01

A steam-cooled second-stage nozzle segment has an outer band and an outer cover defining a plenum therebetween for receiving cooling steam for flow through the nozzles to the inner band and cover therefor and return flow through the nozzles. To measure the temperature of the buckets of the stage forwardly of the nozzle stage, a pyrometer boss is electron beam-welded in an opening through the outer band and TIG-welded to the outer cover plate. By machining a hole through the boss and seating a linearly extending tube in the boss, a line of sight between a pyrometer mounted on the turbine frame and the buckets is provided whereby the temperature of the buckets can be ascertained. The welding of the boss to the outer band and outer cover enables steam flow through the plenum without leakage, while providing a line of sight through the outer cover and outer band to measure bucket temperature.

Inner and outer coronary vessel wall segmentation from CCTA using an active contour model with machine learning-based 3D voxel context-aware image force

NASA Astrophysics Data System (ADS)

Sivalingam, Udhayaraj; Wels, Michael; Rempfler, Markus; Grosskopf, Stefan; Suehling, Michael; Menze, Bjoern H.

2016-03-01

In this paper, we present a fully automated approach to coronary vessel segmentation, which involves calcification or soft plaque delineation in addition to accurate lumen delineation, from 3D Cardiac Computed Tomography Angiography data. Adequately virtualizing the coronary lumen plays a crucial role for simulating blood ow by means of fluid dynamics while additionally identifying the outer vessel wall in the case of arteriosclerosis is a prerequisite for further plaque compartment analysis. Our method is a hybrid approach complementing Active Contour Model-based segmentation with an external image force that relies on a Random Forest Regression model generated off-line. The regression model provides a strong estimate of the distance to the true vessel surface for every surface candidate point taking into account 3D wavelet-encoded contextual image features, which are aligned with the current surface hypothesis. The associated external image force is integrated in the objective function of the active contour model, such that the overall segmentation approach benefits from the advantages associated with snakes and from the ones associated with machine learning-based regression alike. This yields an integrated approach achieving competitive results on a publicly available benchmark data collection (Rotterdam segmentation challenge).

Rho-associated kinase activity is required for proper morphogenesis of the inner cell mass in the mouse blastocyst.

PubMed

Laeno, Arlene May A; Tamashiro, Dana Ann A; Alarcon, Vernadeth B

2013-11-01

The blastocyst consists of the outer layer of trophectoderm and pluripotent inner cell mass (ICM), the precursor of the placenta and fetus, respectively. During blastocyst expansion, the ICM adopts a compact, ovoidal shape, whose proper morphology is crucial for normal embryogenesis. Rho-associated kinase (ROCK), an effector of small GTPase RHO signaling, mediates the diverse cellular processes of morphogenesis, but its role in ICM morphogenesis is unclear. Here, we demonstrate that ROCK is required for cohesion of ICM cells and formation of segregated tissues called primitive endoderm (PrE) and epiblast (Epi) in the ICM of the mouse blastocyst. Blastocyst treatment with ROCK inhibitors Y-27632 and Fasudil caused widening or spreading of the ICM, and intermingling of PrE and Epi. Widening of ICM was independent of trophectoderm because isolated ICMs as well as colonies of mouse embryonic stem cells (mESC) also spread upon Y-27632 treatment. PrE, Epi, and trophectoderm cell numbers were similar between control and treated blastocysts, suggesting that ROCK inhibition affected ICM morphology but not lineage differentiation. Rock1 and Rock2 knockdown via RNA interference in mESC also induced spreading, supporting the conclusion that morphological defects caused by the pharmacological inhibitors were due to ROCK inactivation. When blastocysts were transferred into surrogates, implantation efficiencies were unaffected by ROCK inhibition, but treated blastocysts yielded greater fetal loss. These results show that proper ICM morphology is dependent on ROCK activity and is crucial for fetal development. Our studies have wider implication for improving efficiencies of human assisted reproductive technologies that diminish pregnancy loss and promote successful births.

MorphoGraphX: A platform for quantifying morphogenesis in 4D

PubMed Central

Barbier de Reuille, Pierre; Routier-Kierzkowska, Anne-Lise; Kierzkowski, Daniel; Bassel, George W; Schüpbach, Thierry; Tauriello, Gerardo; Bajpai, Namrata; Strauss, Sören; Weber, Alain; Kiss, Annamaria; Burian, Agata; Hofhuis, Hugo; Sapala, Aleksandra; Lipowczan, Marcin; Heimlicher, Maria B; Robinson, Sarah; Bayer, Emmanuelle M; Basler, Konrad; Koumoutsakos, Petros; Roeder, Adrienne HK; Aegerter-Wilmsen, Tinri; Nakayama, Naomi; Tsiantis, Miltos; Hay, Angela; Kwiatkowska, Dorota; Xenarios, Ioannis; Kuhlemeier, Cris; Smith, Richard S

2015-01-01

Morphogenesis emerges from complex multiscale interactions between genetic and mechanical processes. To understand these processes, the evolution of cell shape, proliferation and gene expression must be quantified. This quantification is usually performed either in full 3D, which is computationally expensive and technically challenging, or on 2D planar projections, which introduces geometrical artifacts on highly curved organs. Here we present MorphoGraphX (www.MorphoGraphX.org), a software that bridges this gap by working directly with curved surface images extracted from 3D data. In addition to traditional 3D image analysis, we have developed algorithms to operate on curved surfaces, such as cell segmentation, lineage tracking and fluorescence signal quantification. The software's modular design makes it easy to include existing libraries, or to implement new algorithms. Cell geometries extracted with MorphoGraphX can be exported and used as templates for simulation models, providing a powerful platform to investigate the interactions between shape, genes and growth. DOI: http://dx.doi.org/10.7554/eLife.05864.001 PMID:25946108

Serial imaging and structure-function correlates of high-density rings of fundus autofluorescence in retinitis pigmentosa.

PubMed

Robson, Anthony G; Tufail, Adnan; Fitzke, Fred; Bird, Alan C; Moore, Anthony T; Holder, Graham E; Webster, Andrew R

2011-09-01

To document the evolution and functional and structural significance of parafoveal rings of high-density fundus autofluorescence (AF) in patients with retinitis pigmentosa and preserved visual acuity. Fifty-two patients with nonsyndromic retinitis pigmentosa or Usher syndrome, who had a parafoveal ring of high-density AF and a visual acuity of 20/30 or better, were ascertained. All had international standard full-field electroretinography and pattern electroretinography. Autofluorescence imaging was repeated in 30 patients after periods of up to 9.3 years. Of the 52 patients, 35 underwent optical coherence tomography. Progressive constriction of the ring was detected in 17 patients. Ring radius reduced by up to 40% at a mean rate of between 0.8% and 15.8% per year. In 1 patient, a small ring was replaced by irregular AF; visual acuity deteriorated over the same period. There was a high correspondence between the lateral extent of the preserved optical coherence tomography inner segment/outer segment band and the diameter of the ring along the same optical coherence tomographic scan plane (slope, 0.9; r = 0.97; P < 0.005; n = 35) and between preserved inner segment/outer segment lamina and the pattern electroretinography P50 measure of macular function (R = 0.72; P < 0.005; n = 34). Rings of increased AF surround areas of preserved outer retina and preserved photopic function. Serial fundus AF may provide prognostic indicators for preservation of central acuity and potentially assist in the identification and evaluation of patients suitable for treatment aimed at preservation of remaining function.

Improving image segmentation performance and quantitative analysis via a computer-aided grading methodology for optical coherence tomography retinal image analysis.

PubMed

Debuc, Delia Cabrera; Salinas, Harry M; Ranganathan, Sudarshan; Tátrai, Erika; Gao, Wei; Shen, Meixiao; Wang, Jianhua; Somfai, Gábor M; Puliafito, Carmen A

2010-01-01

We demonstrate quantitative analysis and error correction of optical coherence tomography (OCT) retinal images by using a custom-built, computer-aided grading methodology. A total of 60 Stratus OCT (Carl Zeiss Meditec, Dublin, California) B-scans collected from ten normal healthy eyes are analyzed by two independent graders. The average retinal thickness per macular region is compared with the automated Stratus OCT results. Intergrader and intragrader reproducibility is calculated by Bland-Altman plots of the mean difference between both gradings and by Pearson correlation coefficients. In addition, the correlation between Stratus OCT and our methodology-derived thickness is also presented. The mean thickness difference between Stratus OCT and our methodology is 6.53 microm and 26.71 microm when using the inner segment/outer segment (IS/OS) junction and outer segment/retinal pigment epithelium (OS/RPE) junction as the outer retinal border, respectively. Overall, the median of the thickness differences as a percentage of the mean thickness is less than 1% and 2% for the intragrader and intergrader reproducibility test, respectively. The measurement accuracy range of the OCT retinal image analysis (OCTRIMA) algorithm is between 0.27 and 1.47 microm and 0.6 and 1.76 microm for the intragrader and intergrader reproducibility tests, respectively. Pearson correlation coefficients demonstrate R(2)>0.98 for all Early Treatment Diabetic Retinopathy Study (ETDRS) regions. Our methodology facilitates a more robust and localized quantification of the retinal structure in normal healthy controls and patients with clinically significant intraretinal features.

Improving image segmentation performance and quantitative analysis via a computer-aided grading methodology for optical coherence tomography retinal image analysis

NASA Astrophysics Data System (ADS)

Cabrera Debuc, Delia; Salinas, Harry M.; Ranganathan, Sudarshan; Tátrai, Erika; Gao, Wei; Shen, Meixiao; Wang, Jianhua; Somfai, Gábor M.; Puliafito, Carmen A.

2010-07-01

We demonstrate quantitative analysis and error correction of optical coherence tomography (OCT) retinal images by using a custom-built, computer-aided grading methodology. A total of 60 Stratus OCT (Carl Zeiss Meditec, Dublin, California) B-scans collected from ten normal healthy eyes are analyzed by two independent graders. The average retinal thickness per macular region is compared with the automated Stratus OCT results. Intergrader and intragrader reproducibility is calculated by Bland-Altman plots of the mean difference between both gradings and by Pearson correlation coefficients. In addition, the correlation between Stratus OCT and our methodology-derived thickness is also presented. The mean thickness difference between Stratus OCT and our methodology is 6.53 μm and 26.71 μm when using the inner segment/outer segment (IS/OS) junction and outer segment/retinal pigment epithelium (OS/RPE) junction as the outer retinal border, respectively. Overall, the median of the thickness differences as a percentage of the mean thickness is less than 1% and 2% for the intragrader and intergrader reproducibility test, respectively. The measurement accuracy range of the OCT retinal image analysis (OCTRIMA) algorithm is between 0.27 and 1.47 μm and 0.6 and 1.76 μm for the intragrader and intergrader reproducibility tests, respectively. Pearson correlation coefficients demonstrate R2>0.98 for all Early Treatment Diabetic Retinopathy Study (ETDRS) regions. Our methodology facilitates a more robust and localized quantification of the retinal structure in normal healthy controls and patients with clinically significant intraretinal features.

Fully automated calculation of cardiothoracic ratio in digital chest radiographs

NASA Astrophysics Data System (ADS)

Cong, Lin; Jiang, Luan; Chen, Gang; Li, Qiang

2017-03-01

The calculation of Cardiothoracic Ratio (CTR) in digital chest radiographs would be useful for cardiac anomaly assessment and heart enlargement related disease indication. The purpose of this study was to develop and evaluate a fully automated scheme for calculation of CTR in digital chest radiographs. Our automated method consisted of three steps, i.e., lung region localization, lung segmentation, and CTR calculation. We manually annotated the lung boundary with 84 points in 100 digital chest radiographs, and calculated an average lung model for the subsequent work. Firstly, in order to localize the lung region, generalized Hough transform was employed to identify the upper, lower, and outer boundaries of lung by use of Sobel gradient information. The average lung model was aligned to the localized lung region to obtain the initial lung outline. Secondly, we separately applied dynamic programming method to detect the upper, lower, outer and inner boundaries of lungs, and then linked the four boundaries to segment the lungs. Based on the identified outer boundaries of left lung and right lung, we corrected the center and the declination of the original radiography. Finally, CTR was calculated as a ratio of the transverse diameter of the heart to the internal diameter of the chest, based on the segmented lungs. The preliminary results on 106 digital chest radiographs showed that the proposed method could obtain accurate segmentation of lung based on subjective observation, and achieved sensitivity of 88.9% (40 of 45 abnormalities), and specificity of 100% (i.e. 61 of 61 normal) for the identification of heart enlargements.

Contrast visual acuity in patients with retinitis pigmentosa assessed by a contrast sensitivity tester.

PubMed

Oishi, Maho; Nakamura, Hajime; Hangai, Masanori; Oishi, Akio; Otani, Atsushi; Yoshimura, Nagahisa

2012-01-01

To assess contrast visual acuity (CVA) in patients with retinitis pigmentosa (RP) and compare the result with standard visual acuity (VA), retinal thickness, status of inner segment/outer segment junction, and central visual field. Thirty-nine eyes of 39 patients with RP and 39 eyes of 39 healthy individuals were studied. To see the difference in CVA between RP patients and normal controls, only subjects with standard VA of 1.0 (20/20) or better were included. This was a cross-sectional study. CVA in various light conditions was measured with CAT-2000 and was compared between patients and controls. CVA of patients was further analyzed for association with other parameters including foveal retinal thickness, outer nuclear layer thickness, the status of inner segment/outer segment junction measured with optical coherence tomography (OCT), and visual field mean deviation (MD) measured with Humphrey field analyzer 10-2 program. CVA impairment was evident in RP patients compared to controls (P < 0.01, in all measurement conditions). Multivariate analysis showed association of logarithm of the minimum angle of resolution (logMAR) with CVAs in several conditions. None of the OCT measurements was associated with CVA. When patients were divided into three groups based on MD, the most advanced group (MD worse than or equal to -20 dB) showed impairment of mesopic CVA (P < 0.05, under mesopic condition of 100% without glare, with glare, and 25% without glare). CVA impairment was confirmed in RP patients, especially in advanced cases. CVA measured with CAT-2000 may be a useful tool for assessing foveal function in RP patients.

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.

Ocular Phenotype of Fbn2-Null Mice

PubMed Central

Shi, Yanrong; Tu, Yidong; Mecham, Robert P.; Bassnett, Steven

2013-01-01

Purpose. Fibrillin-2 (Fbn2) is the dominant fibrillin isoform expressed during development of the mouse eye. To test its role in morphogenesis, we examined the ocular phenotype of Fbn2−/− mice. Methods. Ocular morphology was assessed by confocal microscopy using antibodies against microfibril components. Results. Fbn2−/− mice had a high incidence of anterior segment dysgenesis. The iris was the most commonly affected tissue. Complete iridal coloboma was present in 37% of eyes. Dyscoria, corectopia and pseudopolycoria were also common (43% combined incidence). In wild-type (WT) mice, fibrillin-2-rich microfibrils are prominent in the pupillary membrane (PM) during development. In Fbn2-null mice, the absence of Fbn2 was partially compensated for by increased expression of fibrillin-1, although the resulting PM microfibrils were disorganized, compared with WTs. In colobomatous adult Fbn2−/− eyes, the PM failed to regress normally, especially beneath the notched region of the iris. Segments of the ciliary body were hypoplastic, and zonular fibers, although relatively plentiful, were unevenly distributed around the lens equator. In regions where the zonular fibers were particularly disturbed, the synchronous differentiation of the underlying lens fiber cells was affected. Conclusions. Fbn2 has an indispensable role in ocular morphogenesis in mice. The high incidence of iris coloboma in Fbn2-null animals implies a previously unsuspected role in optic fissure closure. The observation that fiber cell differentiation was disturbed in Fbn2−/− mice raises the possibility that the attachment of zonular fibers to the lens surface may help specify the equatorial margin of the lens epithelium. PMID:24130178

A semi-automatic computer-aided method for surgical template design

NASA Astrophysics Data System (ADS)

Chen, Xiaojun; Xu, Lu; Yang, Yue; Egger, Jan

2016-02-01

This paper presents a generalized integrated framework of semi-automatic surgical template design. Several algorithms were implemented including the mesh segmentation, offset surface generation, collision detection, ruled surface generation, etc., and a special software named TemDesigner was developed. With a simple user interface, a customized template can be semi- automatically designed according to the preoperative plan. Firstly, mesh segmentation with signed scalar of vertex is utilized to partition the inner surface from the input surface mesh based on the indicated point loop. Then, the offset surface of the inner surface is obtained through contouring the distance field of the inner surface, and segmented to generate the outer surface. Ruled surface is employed to connect inner and outer surfaces. Finally, drilling tubes are generated according to the preoperative plan through collision detection and merging. It has been applied to the template design for various kinds of surgeries, including oral implantology, cervical pedicle screw insertion, iliosacral screw insertion and osteotomy, demonstrating the efficiency, functionality and generality of our method.

A semi-automatic computer-aided method for surgical template design

PubMed Central

Chen, Xiaojun; Xu, Lu; Yang, Yue; Egger, Jan

2016-01-01

This paper presents a generalized integrated framework of semi-automatic surgical template design. Several algorithms were implemented including the mesh segmentation, offset surface generation, collision detection, ruled surface generation, etc., and a special software named TemDesigner was developed. With a simple user interface, a customized template can be semi- automatically designed according to the preoperative plan. Firstly, mesh segmentation with signed scalar of vertex is utilized to partition the inner surface from the input surface mesh based on the indicated point loop. Then, the offset surface of the inner surface is obtained through contouring the distance field of the inner surface, and segmented to generate the outer surface. Ruled surface is employed to connect inner and outer surfaces. Finally, drilling tubes are generated according to the preoperative plan through collision detection and merging. It has been applied to the template design for various kinds of surgeries, including oral implantology, cervical pedicle screw insertion, iliosacral screw insertion and osteotomy, demonstrating the efficiency, functionality and generality of our method. PMID:26843434

A semi-automatic computer-aided method for surgical template design.

PubMed

Chen, Xiaojun; Xu, Lu; Yang, Yue; Egger, Jan

2016-02-04

This paper presents a generalized integrated framework of semi-automatic surgical template design. Several algorithms were implemented including the mesh segmentation, offset surface generation, collision detection, ruled surface generation, etc., and a special software named TemDesigner was developed. With a simple user interface, a customized template can be semi- automatically designed according to the preoperative plan. Firstly, mesh segmentation with signed scalar of vertex is utilized to partition the inner surface from the input surface mesh based on the indicated point loop. Then, the offset surface of the inner surface is obtained through contouring the distance field of the inner surface, and segmented to generate the outer surface. Ruled surface is employed to connect inner and outer surfaces. Finally, drilling tubes are generated according to the preoperative plan through collision detection and merging. It has been applied to the template design for various kinds of surgeries, including oral implantology, cervical pedicle screw insertion, iliosacral screw insertion and osteotomy, demonstrating the efficiency, functionality and generality of our method.

A New Species of Hyperbenthic Cyclopoid Copepod from Japan: First Record of the Genus Cyclopicina in the Indo-Pacific Region.

PubMed

Ohtsuka, Susumu; Tanaka, Hayato; Boxshall, Geoffrey A

2016-12-01

A new species of the cyclopinid genus Cyclopicina, C. toyoshioae sp. nov., was collected from the hyperbenthic layer off northern Kyushu Island, Japan; its description is based on two adult female specimens. This is the first record of the genus from the Indo-Pacific region. The new species can be distinguished from its two known congeners in: (1) the relatively short antennules which do not reach the posterior margin of the dorsal cephalothoracic shield; (2) the shape of seminal receptacles; (3) the segmentation and armature of the cephalothoracic appendages; (4) the shape of the basal protrusion between the rami of legs 1-4; (5) the presence of three outer spines on the third exopodal segment of leg 4; and (6) the presence or absence of outer setae on the free exopodal segment of leg 5. The genus Cyclopicina shows a wide but scattered distribution in hyperbenthic layers, from the continental shelves to deep-sea basins, in the northern hemisphere.

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

PubMed Central

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

2014-01-01

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

Multicenter reliability of semiautomatic retinal layer segmentation using OCT

PubMed Central

Oberwahrenbrock, Timm; Traber, Ghislaine L.; Lukas, Sebastian; Gabilondo, Iñigo; Nolan, Rachel; Songster, Christopher; Balk, Lisanne; Petzold, Axel; Paul, Friedemann; Villoslada, Pablo; Brandt, Alexander U.; Green, Ari J.

2018-01-01

Objective To evaluate the inter-rater reliability of semiautomated segmentation of spectral domain optical coherence tomography (OCT) macular volume scans. Methods Macular OCT volume scans of left eyes from 17 subjects (8 patients with MS and 9 healthy controls) were automatically segmented by Heidelberg Eye Explorer (v1.9.3.0) beta-software (Spectralis Viewing Module v6.0.0.7), followed by manual correction by 5 experienced operators from 5 different academic centers. The mean thicknesses within a 6-mm area around the fovea were computed for the retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer (OPL), and outer nuclear layer (ONL). Intraclass correlation coefficients (ICCs) were calculated for mean layer thickness values. Spatial distribution of ICC values for the segmented volume scans was investigated using heat maps. Results Agreement between raters was good (ICC > 0.84) for all retinal layers, particularly inner retinal layers showed excellent agreement across raters (ICC > 0.96). Spatial distribution of ICC showed highest values in the perimacular area, whereas the ICCs were poorer for the foveola and the more peripheral macular area. The automated segmentation of the OPL and ONL required the most correction and showed the least agreement, whereas differences were less prominent for the remaining layers. Conclusions Automated segmentation with manual correction of macular OCT scans is highly reliable when performed by experienced raters and can thus be applied in multicenter settings. Reliability can be improved by restricting analysis to the perimacular area and compound segmentation of GCL and IPL. PMID:29552598

Hox control of Drosophila larval anatomy; The Alary and Thoracic Alary-Related Muscles.

PubMed

Bataillé, Laetitia; Frendo, Jean-Louis; Vincent, Alain

2015-11-01

The body plan of arthropods and vertebrates involves the formation of repetitive segments, which subsequently diversify to give rise to different body parts along the antero-posterior/rostro-caudal body axis. Anatomical variations between body segments are crucial for organ function and organismal fitness. Pioneering work in Drosophila has established that Hox transcription factors play key roles both in endowing initially identical segments with distinct identities and organogenesis. The focus of this review is on Alary Muscles (AMs) and the newly discovered Thoracic Alary-Related Muscles (TARMs). AMs and TARMs are thin muscles which together connect the circulatory system and different midgut regions to the exoskeleton, while intertwining with the respiratory tubular network. They were hypothesized to represent a new type of muscles with spring-like properties, maintaining internal organs in proper anatomical positions during larval locomotion. Both the morphology of TARMs relative to AMs, and morphogenesis of connected tissues is under Hox control, emphasizing the key role of Hox proteins in coordinating the anatomical development of the larva. Copyright © 2015 Elsevier B.V. All rights reserved.

Reconstituted TOM core complex and Tim9/Tim10 complex of mitochondria are sufficient for translocation of the ADP/ATP carrier across membranes.

PubMed

Vasiljev, Andreja; Ahting, Uwe; Nargang, Frank E; Go, Nancy E; Habib, Shukry J; Kozany, Christian; Panneels, Valérie; Sinning, Irmgard; Prokisch, Holger; Neupert, Walter; Nussberger, Stephan; Rapaport, Doron

2004-03-01

Precursor proteins of the solute carrier family and of channel forming Tim components are imported into mitochondria in two main steps. First, they are translocated through the TOM complex in the outer membrane, a process assisted by the Tim9/Tim10 complex. They are passed on to the TIM22 complex, which facilitates their insertion into the inner membrane. In the present study, we have analyzed the function of the Tim9/Tim10 complex in the translocation of substrates across the outer membrane of mitochondria. The purified TOM core complex was reconstituted into lipid vesicles in which purified Tim9/Tim10 complex was entrapped. The precursor of the ADP/ATP carrier (AAC) was found to be translocated across the membrane of such lipid vesicles. Thus, these components are sufficient for translocation of AAC precursor across the outer membrane. Peptide libraries covering various substrate proteins were used to identify segments that are bound by Tim9/Tim10 complex upon translocation through the TOM complex. The patterns of binding sites on the substrate proteins suggest a mechanism by which portions of membrane-spanning segments together with flanking hydrophilic segments are recognized and bound by the Tim9/Tim10 complex as they emerge from the TOM complex into the intermembrane space.

Turbine nozzle stage having thermocouple guide tube

DOEpatents

Schotsch, Margaret Jones; Kirkpatrick, Francis Lawrence; Lapine, Eric Michael

2002-01-01

A guide tube is fixed adjacent opposite ends in outer and inner covers of a nozzle stage segment. The guide tube is serpentine in shape between the outer and inner covers and extends through a nozzle vane. An insert is disposed in the nozzle vane and has apertures to accommodate serpentine portions of the guide tube. Cooling steam is also supplied through chambers of the insert on opposite sides of a central insert chamber containing the guide tube. The opposite ends of the guide tube are fixed to sleeves, in turn fixed to the outer and inner covers.

The host outer membrane proteins OmpA and OmpC are associated with the Shigella phage Sf6 virion

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

Zhao Haiyan, E-mail: zhaohy@ku.ed; Sequeira, Reuben D., E-mail: sequen@ku.ed; Galeva, Nadezhda A., E-mail: galeva@ku.ed

2011-01-20

Assembly of dsDNA bacteriophage is a precisely programmed process. Potential roles of host cell components in phage assembly haven't been well understood. It was previously reported that two unidentified proteins were present in bacteriophage Sf6 virion (Casjens et al, 2004, J.Mol.Biol. 339, 379-394, Fig. 2A). Using tandem mass spectrometry, we have identified the two proteins as outer membrane proteins (OMPs) OmpA and OmpC from its host Shigella flexneri. The transmission electron cryo-microscopy structure of Sf6 shows significant density at specific sites at the phage capsid inner surface. This density fit well with the characteristic beta-barrel domains of OMPs, thus maymore » be due to the two host proteins. Locations of this density suggest a role in Sf6 morphogenesis reminiscent of phage-encoded cementing proteins. These data indicate a new, OMP-related phage:host linkage, adding to previous knowledge that some lambdoid bacteriophage genomes contain OmpC-like genes that express phage-encoded porins in the lysogenic state.« less

Calcium and magnesium fluxes across the plasma membrane of the toad rod outer segment.

PubMed Central

Nakatani, K; Yau, K W

1988-01-01

1. Membrane current was recorded from an isolated, dark-adapted toad rod by sucking either its inner segment or outer segment into a tight-fitting glass pipette containing Ringer solution. The remainder of the cell was exposed to bath solution which could be changed rapidly. 2. In normal Ringer solution the current response of a cell to a saturating flash or step of light showed a small secondary rise at its initial peak. The profile of this secondary rise (i.e. amplitude and time course) was independent of both the intensity and the duration of illumination once the light response had reached a plateau level. 3. This secondary rise disappeared when external Na+ around the outer segment was replaced by Li+ or guanidinium, suggesting that it represented an electrogenic Na+-dependent Ca2+ efflux which was declining after the onset of light. 4. This Na+-Ca2+ exchange activity showed a roughly exponential decline, with a time constant of about 0.5 s. Exponential extrapolation of the exchange current to the time at half-height of the light response gave an initial amplitude of about 2 pA. Using La3+ as a blocker, we did not detect any steady exchange current after the initial exponential decline. 5. An intense flash superposed on a just-saturating steady background light failed to produce any incremental exchange current transient. 6. Our interpretation of the above results is that in darkness there are counterbalancing levels of Ca2+ influx (through the light-sensitive conductance) and efflux (through the Na+-Ca2+ exchange) across the plasma membrane of the rod outer segment. The exchange current transient at the onset of light merely represents the unidirectional Ca2+ efflux which becomes revealed as a result of the stoppage of the Ca2+ influx, rather than a de novo Ca2+ efflux triggered by light. 7. Consistent with this interpretation, a test light delivered soon after a saturating, conditioning light elicited little exchange current, which then gradually recovered to control value with a time course parallel to the restoration of the dark current. Conversely, when the dark current was increased above its physiological level by IBMX (isobutylmethylxanthine) the exchange current transient became larger than control.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 8 PMID:2457685

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

PubMed Central

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

2016-01-01

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

Architecture of kangaroo rat inner medulla: segmentation of descending thin limb of Henle's loop.

PubMed

Urity, Vinoo B; Issaian, Tadeh; Braun, Eldon J; Dantzler, William H; Pannabecker, Thomas L

2012-03-15

We hypothesize that the inner medulla of the kangaroo rat Dipodomys merriami, a desert rodent that concentrates its urine to more than 6,000 mosmol/kgH(2)O water, provides unique examples of architectural features necessary for production of highly concentrated urine. To investigate this architecture, inner medullary nephron segments in the initial 3,000 μm below the outer medulla were assessed with digital reconstructions from physical tissue sections. Descending thin limbs of Henle (DTLs), ascending thin limbs of Henle (ATLs), and collecting ducts (CDs) were identified by immunofluorescence using antibodies that label segment-specific proteins associated with transepithelial water flux (aquaporin 1 and 2, AQP1 and AQP2) and chloride flux (the chloride channel ClC-K1); all tubules and vessels were labeled with wheat germ agglutinin. In the outer 3,000 μm of the inner medulla, AQP1-positive DTLs lie at the periphery of groups of CDs. ATLs lie inside and outside the groups of CDs. Immunohistochemistry and reconstructions of loops that form their bends in the outer 3,000 μm of the inner medulla show that, relative to loop length, the AQP1-positive segment of the kangaroo rat is significantly longer than that of the Munich-Wistar rat. The length of ClC-K1 expression in the prebend region at the terminal end of the descending side of the loop in kangaroo rat is about 50% shorter than that of the Munich-Wistar rat. Tubular fluid of the kangaroo rat DTL may approach osmotic equilibrium with interstitial fluid by water reabsorption along a relatively longer tubule length, compared with Munich-Wistar rat. A relatively shorter-length prebend segment may promote a steeper reabsorptive driving force at the loop bend. These structural features predict functionality that is potentially significant in the production of a high urine osmolality in the kangaroo rat.

Protein sorting, targeting and trafficking in photoreceptor cells

PubMed Central

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

2013-01-01

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

Macular telangiectasia type 2 (MacTel) in a 34-year-old patient.

PubMed

Nicolai, Heleen; Wirix, Mieke; Spielberg, Leigh; Leys, Anita

2014-09-23

We report macular telangiectasia type 2 (MacTel) in a 34-year-old man, the youngest patient so far published with MacTel type 2. The patient presented with metamorphopsia and impaired reading ability. Diagnosis was based on bilateral abnormal macular autofluorescence, perifoveal telangiectasia with fluorescein angiographic hyperfluorescence without cystoid oedema, a small foveal avascular zone, asymmetric configuration of the foveal pit, disruptions in the inner segment/outer segment layer and hyper-reflective haze and spots in the outer nuclear layer. Although MacTel usually manifests with a slowly progressive decrease in visual acuity in the fifth to seventh decades of life, younger patients may occasionally be diagnosed with the disease. Awareness of subtle signs of the condition is essential for early diagnosis. 2014 BMJ Publishing Group Ltd.

Macular telangiectasia type 2 (MacTel) in a 34-year-old patient

PubMed Central

Nicolai, Heleen; Wirix, Mieke; Spielberg, Leigh; Leys, Anita

2014-01-01

We report macular telangiectasia type 2 (MacTel) in a 34-year-old man, the youngest patient so far published with MacTel type 2. The patient presented with metamorphopsia and impaired reading ability. Diagnosis was based on bilateral abnormal macular autofluorescence, perifoveal telangiectasia with fluorescein angiographic hyperfluorescence without cystoid oedema, a small foveal avascular zone, asymmetric configuration of the foveal pit, disruptions in the inner segment/outer segment layer and hyper-reflective haze and spots in the outer nuclear layer. Although MacTel usually manifests with a slowly progressive decrease in visual acuity in the fifth to seventh decades of life, younger patients may occasionally be diagnosed with the disease. Awareness of subtle signs of the condition is essential for early diagnosis. PMID:25249218

A perspective of gene therapy in the glaucomas.

PubMed

Kaufman, P L; Jia, W W; Tan, J; Chen, Z; Gabelt, B T; Booth, V; Tufaro, F; Cynader, M

1999-06-01

Gene therapy in the anterior and posterior segment tissues may have the potential to favorably influence aqueous hydrodynamics and retinal ganglion cell biology, thereby preventing, delaying, or minimizing glaucomatous damage to the optic nerve. We demonstrated the feasibility of using a herpes viral vector (ribonucleotide reductase defective HSV-1, hrR3) to deliver the lacZ reporter gene to living cat and rat eyes. Cats received injections into the anterior chamber and rats into the vitreous cavity. In cats, lacZ expression was detectable at 1 to 2 days in the anterior outer portion of the ciliary muscle and the lining of the intertrabecular spaces of the corneoscleral and uveal meshwork. Rat eyes showed lacZ expression in the retinal pigment epithelium and photoreceptor outer segments 2 days after injection.

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.

Why are enteric ganglia so small? Role of differential adhesion of enteric neurons and enteric neural crest cells.

PubMed Central

Rollo, Benjamin N.; Zhang, Dongcheng; Simkin, Johanna E.; Menheniott, Trevelyan R.; Newgreen, Donald F.

2015-01-01

The avian enteric nervous system (ENS) consists of a vast number of unusually small ganglia compared to other peripheral ganglia. Each ENS ganglion at mid-gestation has a core of neurons and a shell of mesenchymal precursor/glia-like enteric neural crest (ENC) cells. To study ENS cell ganglionation we isolated midgut ENS cells by HNK-1 fluorescence-activated cell sorting (FACS) from E5 and E8 quail embryos, and from E9 chick embryos. We performed cell-cell aggregation assays which revealed a developmentally regulated functional increase in ENS cell adhesive function, requiring both Ca 2+ -dependent and independent adhesion. This was consistent with N-cadherin and NCAM labelling. Neurons sorted to the core of aggregates, surrounded by outer ENC cells, showing that neurons had higher adhesion than ENC cells. The outer surface of aggregates became relatively non-adhesive, correlating with low levels of NCAM and N-cadherin on this surface of the outer non-neuronal ENC cells. Aggregation assays showed that ENS cells FACS selected for NCAM-high and enriched for enteric neurons formed larger and more coherent aggregates than unsorted ENS cells. In contrast, ENS cells of the NCAM-low FACS fraction formed small, disorganised aggregates.  This suggests a novel mechanism for control of ENS ganglion morphogenesis where i) differential adhesion of ENS neurons and ENC cells controls the core/shell ganglionic structure and ii) the ratio of neurons to ENC cells dictates the equilibrium ganglion size by generation of an outer non-adhesive surface. PMID:26064478

Morphoelastic control of gastro-intestinal organogenesis: Theoretical predictions and numerical insights

NASA Astrophysics Data System (ADS)

Balbi, V.; Kuhl, E.; Ciarletta, P.

2015-05-01

With nine meters in length, the gastrointestinal tract is not only our longest, but also our structurally most diverse organ. During embryonic development, it evolves as a bilayered tube with an inner endodermal lining and an outer mesodermal layer. Its inner surface displays a wide variety of morphological patterns, which are closely correlated to digestive function. However, the evolution of these intestinal patterns remains poorly understood. Here we show that geometric and mechanical factors can explain intestinal pattern formation. Using the nonlinear field theories of mechanics, we model surface morphogenesis as the instability problem of constrained differential growth. To allow for internal and external expansion, we model the gastrointestinal tract with homogeneous Neumann boundary conditions. To establish estimates for the folding pattern at the onset of folding, we perform a linear stability analysis supplemented by the perturbation theory. To predict pattern evolution in the post-buckling regime, we perform a series of nonlinear finite element simulations. Our model explains why longitudinal folds emerge in the esophagus with a thick and stiff outer layer, whereas circumferential folds emerge in the jejunum with a thinner and softer outer layer. In intermediate regions like the feline esophagus, longitudinal and circumferential folds emerge simultaneously. Our model could serve as a valuable tool to explain and predict alterations in esophageal morphology as a result of developmental disorders or certain digestive pathologies including food allergies.

Spatiotemporal distribution of extracellular matrix changes during mouse duodenojejunal flexure formation.

PubMed

Onouchi, Sawa; Ichii, Osamu; Nakamura, Teppei; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

2016-08-01

Although gut flexures characterize gut morphology, the mechanisms underlying flexure formation remain obscure. Previously, we analyzed the mouse duodenojejunal flexure (DJF) as a model for its formation and reported asymmetric morphologies between the inner and outer bending sides of the fetal mouse DJF, implying their contribution to DJF formation. We now present the extracellular matrix (ECM) as an important factor for gut morphogenesis. We investigate ECM distribution during mouse DJF formation by histological techniques. In the intercellular space of the gut wall, high Alcian-Blue positivity for proteoglycans shifted from the outer to the inner side of the gut wall during DJF formation. Immunopositivity for fibronectin, collagen I, or pan-tenascin was higher at the inner than at the outer side. Collagen IV and laminins localized to the epithelial basement membrane. Beneath the mesothelium at the pre-formation stage, collagen IV and laminin immunopositivity showed inverse results, corresponding to the different cellular characteristics at this site. At the post-formation stage, however, laminin positivity beneath the mesothelium was the reverse of that observed during the pre-formation stage. High immunopositivity for collagen IV and laminins at the inner gut wall mesenchyme of the post-formation DJF implied a different blood vessel distribution. We conclude that ECM distribution changes spatiotemporally during mouse DJF formation, indicating ECM association with the establishment of asymmetric morphologies during this process.

Reduced Abd-B Hox function during kidney development results in lineage infidelity.

PubMed

Magella, Bliss; Mahoney, Robert; Adam, Mike; Potter, S Steven

2018-06-15

Hox genes can function as key drivers of segment identity, with Hox mutations in Drosophila often resulting in dramatic homeotic transformations. In addition, however, they can serve other essential functions. In mammals, the study of Hox gene roles in development is complicated by the presence of four Hox clusters with a total of 39 genes showing extensive functional overlap. In this study, in order to better understand shared core Hox functions, we examined kidney development in mice with frameshift mutations of multiple Abd-B type Hox genes. The resulting phenotypes included dramatically reduced branching morphogenesis of the ureteric bud, premature depletion of nephron progenitors and abnormal development of the stromal compartment. Most unexpected, however, we also observed a cellular level lineage infidelity in nephron segments. Scattered cells within the proximal tubules, for example, expressed genes normally expressed only in collecting ducts. Multiple combinations of inappropriate nephron segment specific marker expression were found. In some cases, cells within a tubule showed incorrect identity, while in other cases cells showed ambiguous character, with simultaneous expression of genes associated with more than one nephron segment. These results give evidence that Hox genes have an overlapping core function at the cellular level in driving and/or maintaining correct differentiation decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

Accelerated eruption of rat lower incisor. Relationship between impeded and unimpeded eruption rates, rate of attrition, tooth length, and production of dentin and enamel.

PubMed

Risnes, S; Septier, D; Goldberg, M

1995-01-01

The present investigation studies the effects of persistently cutting one lower rat incisor out of occlusion. Within four days, the rate of eruption of the cut (unimpeded) incisor increased to 216% and that of the uncut (impeded) contralateral to 136% of the baseline rate. While the former remained high, the latter decreased gradually to about 90% within three weeks. The rate of attrition of the impeded incisor increased to 233% of the baseline rate within two days, then fell abruptly, and remained at a slightly lower level than the rate of eruption. Accordingly, the length of the erupted part of the impeded incisor decreased initially, but increased gradually after about four days. Measurements made on SEM micrographs of the series of transverse tooth segments obtained when cutting the incisor out of occlusion, showed that growth-related increase in mesiodistal tooth width was arrested from the 10th segment, dentin thickness decreased gradually to about 50% in the 12th segment, and enamel thickness, after an initial increase, decreased to about 80% in the 11th segment. The present study provides experimental evidence that accelerated eruption affects morphogenesis and histogenesis of the rat lower incisor. An impeded incisor, especially the contralateral, may not serve as an ideal control.

Relationship between photoreceptor outer segment length and visual acuity in diabetic macular edema.

PubMed

Forooghian, Farzin; Stetson, Paul F; Meyer, Scott A; Chew, Emily Y; Wong, Wai T; Cukras, Catherine; Meyerle, Catherine B; Ferris, Frederick L

2010-01-01

The purpose of this study was to quantify photoreceptor outer segment (PROS) length in 27 consecutive patients (30 eyes) with diabetic macular edema using spectral domain optical coherence tomography and to describe the correlation between PROS length and visual acuity. Three spectral domain-optical coherence tomography scans were performed on all eyes during each session using Cirrus HD-OCT. A prototype algorithm was developed for quantitative assessment of PROS length. Retinal thicknesses and PROS lengths were calculated for 3 parameters: macular grid (6 x 6 mm), central subfield (1 mm), and center foveal point (0.33 mm). Intrasession repeatability was assessed using coefficient of variation and intraclass correlation coefficient. The association between retinal thickness and PROS length with visual acuity was assessed using linear regression and Pearson correlation analyses. The main outcome measures include intrasession repeatability of macular parameters and correlation of these parameters with visual acuity. Mean retinal thickness and PROS length were 298 mum to 381 microm and 30 microm to 32 mum, respectively, for macular parameters assessed in this study. Coefficient of variation values were 0.75% to 4.13% for retinal thickness and 1.97% to 14.01% for PROS length. Intraclass correlation coefficient values were 0.96 to 0.99 and 0.73 to 0.98 for retinal thickness and PROS length, respectively. Slopes from linear regression analyses assessing the association of retinal thickness and visual acuity were not significantly different from 0 (P > 0.20), whereas the slopes of PROS length and visual acuity were significantly different from 0 (P < 0.0005). Correlation coefficients for macular thickness and visual acuity ranged from 0.13 to 0.22, whereas coefficients for PROS length and visual acuity ranged from -0.61 to -0.81. Photoreceptor outer segment length can be quantitatively assessed using Cirrus HD-OCT. Although the intrasession repeatability of PROS measurements was less than that of macular thickness measurements, the stronger correlation of PROS length with visual acuity suggests that the PROS measures may be more directly related to visual function. Photoreceptor outer segment length may be a useful physiologic outcome measure, both clinically and as a direct assessment of treatment effects.

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

PubMed

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

2018-01-01

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

The spatial and temporal expression of Ch-en, the engrailed gene in the polychaete Chaetopterus, does not support a role in body axis segmentation

NASA Technical Reports Server (NTRS)

Seaver, E. C.; Paulson, D. A.; Irvine, S. Q.; Martindale, M. Q.

2001-01-01

We are interested in understanding whether the annelids and arthropods shared a common segmented ancestor and have approached this question by characterizing the expression pattern of the segment polarity gene engrailed (en) in a basal annelid, the polychaete Chaetopterus. We have isolated an en gene, Ch-en, from a Chaetopterus cDNA library. Genomic Southern blotting suggests that this is the only en class gene in this animal. The predicted protein sequence of the 1.2-kb cDNA clone contains all five domains characteristic of en proteins in other taxa, including the en class homeobox. Whole-mount in situ hybridization reveals that Ch-en is expressed throughout larval life in a complex spatial and temporal pattern. The Ch-en transcript is initially detected in a small number of neurons associated with the apical organ and in the posterior portion of the prototrochophore. At later stages, Ch-en is expressed in distinct patterns in the three segmented body regions (A, B, and C) of Chaetopterus. In all segments, Ch-en is expressed in a small set of segmentally iterated cells in the CNS. In the A region, Ch-en is also expressed in a small group of mesodermal cells at the base of the chaetal sacs. In the B region, Ch-en is initially expressed broadly in the mesoderm that then resolves into one band/segment coincident with morphological segmentation. The mesodermal expression in the B region is located in the anterior region of each segment, as defined by the position of ganglia in the ventral nerve cord, and is involved in the morphogenesis of segment-specific feeding structures late in larval life. We observe banded mesodermal and ectodermal staining in an anterior-posterior sequence in the C region. We do not observe a segment polarity pattern of expression of Ch-en in the ectoderm, as is observed in arthropods. Copyright 2001 Academic Press.

Automatic segmentation and reconstruction of the cortex from neonatal MRI.

PubMed

Xue, Hui; Srinivasan, Latha; Jiang, Shuzhou; Rutherford, Mary; Edwards, A David; Rueckert, Daniel; Hajnal, Joseph V

2007-11-15

Segmentation and reconstruction of cortical surfaces from magnetic resonance (MR) images are more challenging for developing neonates than adults. This is mainly due to the dynamic changes in the contrast between gray matter (GM) and white matter (WM) in both T1- and T2-weighted images (T1w and T2w) during brain maturation. In particular in neonatal T2w images WM typically has higher signal intensity than GM. This causes mislabeled voxels during cortical segmentation, especially in the cortical regions of the brain and in particular at the interface between GM and cerebrospinal fluid (CSF). We propose an automatic segmentation algorithm detecting these mislabeled voxels and correcting errors caused by partial volume effects. Our results show that the proposed algorithm corrects errors in the segmentation of both GM and WM compared to the classic expectation maximization (EM) scheme. Quantitative validation against manual segmentation demonstrates good performance (the mean Dice value: 0.758+/-0.037 for GM and 0.794+/-0.078 for WM). The inner, central and outer cortical surfaces are then reconstructed using implicit surface evolution. A landmark study is performed to verify the accuracy of the reconstructed cortex (the mean surface reconstruction error: 0.73 mm for inner surface and 0.63 mm for the outer). Both segmentation and reconstruction have been tested on 25 neonates with the gestational ages ranging from approximately 27 to 45 weeks. This preliminary analysis confirms previous findings that cortical surface area and curvature increase with age, and that surface area scales to cerebral volume according to a power law, while cortical thickness is not related to age or brain growth.

Platform-Independent Cirrus and Spectralis Thickness Measurements in Eyes with Diabetic Macular Edema Using Fully Automated Software

PubMed Central

Willoughby, Alex S.; Chiu, Stephanie J.; Silverman, Rachel K.; Farsiu, Sina; Bailey, Clare; Wiley, Henry E.; Ferris, Frederick L.; Jaffe, Glenn J.

2017-01-01

Purpose We determine whether the automated segmentation software, Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can measure, in a platform-independent manner, retinal thickness on Cirrus and Spectralis spectral domain optical coherence tomography (SD-OCT) images in eyes with diabetic macular edema (DME) under treatment in a clinical trial. Methods Automatic segmentation software was used to segment the internal limiting membrane (ILM), inner retinal pigment epithelium (RPE), and Bruch's membrane (BM) in SD-OCT images acquired by Cirrus and Spectralis commercial systems, from the same eye, on the same day during a clinical interventional DME trial. Mean retinal thickness differences were compared across commercial and DOCTRAP platforms using intraclass correlation (ICC) and Bland-Altman plots. Results The mean 1 mm central subfield thickness difference (standard error [SE]) comparing segmentation of Spectralis images with DOCTRAP versus HEYEX was 0.7 (0.3) μm (0.2 pixels). The corresponding values comparing segmentation of Cirrus images with DOCTRAP versus Cirrus software was 2.2 (0.7) μm. The mean 1 mm central subfield thickness difference (SE) comparing segmentation of Cirrus and Spectralis scan pairs with DOCTRAP using BM as the outer retinal boundary was −2.3 (0.9) μm compared to 2.8 (0.9) μm with inner RPE as the outer boundary. Conclusions DOCTRAP segmentation of Cirrus and Spectralis images produces validated thickness measurements that are very similar to each other, and very similar to the values generated by the corresponding commercial software in eyes with treated DME. Translational Relevance This software enables automatic total retinal thickness measurements across two OCT platforms, a process that is impractical to perform manually. PMID:28180033

The phototransduction machinery in the rod outer segment has a strong efficacy gradient

PubMed Central

Mazzolini, Monica; Facchetti, Giuseppe; Andolfi, Laura; Proietti Zaccaria, Remo; Tuccio, Salvatore; Treu, Johannes; Altafini, Claudio; Di Fabrizio, Enzo M.; Lazzarino, Marco; Rapp, Gert; Torre, Vincent

2015-01-01

Rod photoreceptors consist of an outer segment (OS) and an inner segment. Inside the OS a biochemical machinery transforms the rhodopsin photoisomerization into electrical signal. This machinery has been treated as and is thought to be homogenous with marginal inhomogeneities. To verify this assumption, we developed a methodology based on special tapered optical fibers (TOFs) to deliver highly localized light stimulations. By using these TOFs, specific regions of the rod OS could be stimulated with spots of light highly confined in space. As the TOF is moved from the OS base toward its tip, the amplitude of saturating and single photon responses decreases, demonstrating that the efficacy of the transduction machinery is not uniform and is 5–10 times higher at the base than at the tip. This gradient of efficacy of the transduction machinery is attributed to a progressive depletion of the phosphodiesterase along the rod OS. Moreover we demonstrate that, using restricted spots of light, the duration of the photoresponse along the OS does not increase linearly with the light intensity as with diffuse light. PMID:25941368

Drive system for the retraction/extension of variable diameter rotor systems

NASA Technical Reports Server (NTRS)

Gmirya, Yuriy (Inventor)

2003-01-01

A drive system for a variable diameter rotor (VDR) system includes a plurality of rotor blade assemblies with inner and outer rotor blade segments. The outer blade segment being telescopically mounted to the inner blade segment. The VDR retraction/extension system includes a drive housing mounted at the root of each blade. The housing supports a spool assembly, a harmonic gear set and an electric motor. The spool assembly includes a pair of counter rotating spools each of which drive a respective cable which extends through the interior of the inboard rotor blade section and around a pulley mounted to the outboard rotor blade section. In operation, the electric motor drives the harmonic gear set which rotates the counter rotating spools. Rotation of the spools causes the cables to be wound onto or off their respective spool consequently effecting retraction/extension of the pulley and the attached outboard rotor blade section relative the inboard rotor blade section. As each blade drive system is independently driven by a separate electrical motor, each independent VDR blade assembly is independently positionable.

Pineal organs of deep-sea fish: photopigments and structure.

PubMed

Bowmaker, James K; Wagner, Hans-Joachim

2004-06-01

We have examined the morphology and photopigments of the pineal organs from a number of mesopelagic fish, including representatives of the hatchet fish (Sternoptychidae), scaly dragon-fish (Chauliodontidae) and bristlemouths (Gonostomidae). Although these fish were caught at depths of between 500 and 1000 m, the morphological organisation of their pineal organs is remarkably similar to that of surface-dwelling fish. Photoreceptor inner and outer segments protrude into the lumen of the pineal vesicle, and the outer segment is composed of a stack of up to 20 curved disks that form a cap-like cover over the inner segment. In all species, the pineal photopigment was spectrally distinct from the retinal rod pigment, with lambdamax displaced to longer wavelengths, between approximately 485 and 503 nm. We also investigated the pineal organ of the deep demersal eel, Synaphobranchus kaupi, caught at depths below 2000 m, which possesses a rod visual pigment with lambdamax at 478 nm, but the pineal pigment has lambdamax at approximately 515 nm. In one species of hatchet fish, Argyropelecus affinis, two spectral classes of pinealocyte were identified, both spectrally distinct from the retinal rod photopigment.

Retinal degeneration in cats fed casein. IV. The early receptor potential.

PubMed

Berson, E L; Watson, G; Grasse, K L; Szamier, R B

1981-08-01

Electroretinographic studies of casein-fed cats with retinal taurine deficiency revealed that the early receptor potential (ERP) was initially normal in amplitude at a time when the a-wave and b-wave of the electroretinogram were substantially reduced or even nondetectable. The preserved ERP's in these taurine-deficient cats could be correlated with the histologic finding that their outer segments were relatively intact over 90% of the retinal area subtended by the test flash. The sequence of electroretinographic changes in these taurine-deficient cats was also consistent with previous biochemical studies on the normal cat retina that have shown a relatively low concentration of taurine at the level of the outer segments and a higher concentration at the level of the inner segments. The responses in early stages from taurine-deficient cats differed from the responses obtained from vitamin A--deficient cats but resembled those from cats that received an intravitreal injection of ouabain. Similarities and a difference between the responses of taurine-deficient cats and those of patients with early retinitis pigmentosa are considered.

Rhodopsin expression in the zebrafish pineal gland from larval to adult stage.

PubMed

Magnoli, Domenico; Zichichi, Rosalia; Laurà, Rosaria; Guerrera, Maria Cristina; Campo, Salvatore; de Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

2012-03-09

The zebrafish pineal gland plays an important role in different physiological functions including the regulation of the circadian clock. In the fish pineal gland the pinealocytes are made up of different segments: outer segment, inner segment and basal pole. Particularly, in the outer segment the rhodopsin participates in the external environment light reception that represents the first biochemical step in the melatonin production. It is well known that the rhodopsin in the adult zebrafish is well expressed in the pineal gland but both the expression and the cellular localization of this protein during development remain still unclear. In this study using qRT-PCR, sequencing and immunohistochemistry the expression as well as the protein localization of the rhodopsin in the zebrafish from larval (10 dpf) to adult stage (90 dpf) were demonstrated. The rhodopsin mRNA expression presents a peak of expression at 10 dpf, a further reduction to 50 dpf before increasing again in the adult stage. Moreover, the cellular localization of the rhodopsin-like protein was always localized in the pinealocyte at all ages examined. Our results demonstrated the involvement of the rhodopsin in the zebrafish pineal gland physiology particularly in the light capture during the zebrafish lifespan. Copyright © 2012 Elsevier B.V. All rights reserved.

Element for use in an inductive coupler for downhole components

DOEpatents

Hall, David R [Provo, UT; Fox, Joe [Spanish Fork, UT

2009-03-31

An element for use in an inductive coupler for downhole components comprises an annular housing having a generally circular recess. The element further comprises a plurality of generally linear, magnetically conductive segments. Each segment includes a bottom portion, an inner wall portion, and an outer wall portion. The portions together define a generally linear trough from a first end to a second end of each segment. The segments are arranged adjacent to each other within the housing recess to form a generally circular trough. The ends of at least half of the segments are shaped such that the first end of one of the segments is complementary in form to the second end of an adjacent segment. In one embodiment, all of the ends are angled. Preferably, the first ends are angled with the same angle and the second ends are angled with the complementary angle.

Learning-based automated segmentation of the carotid artery vessel wall in dual-sequence MRI using subdivision surface fitting.

PubMed

Gao, Shan; van 't Klooster, Ronald; Kitslaar, Pieter H; Coolen, Bram F; van den Berg, Alexandra M; Smits, Loek P; Shahzad, Rahil; Shamonin, Denis P; de Koning, Patrick J H; Nederveen, Aart J; van der Geest, Rob J

2017-10-01

The quantification of vessel wall morphology and plaque burden requires vessel segmentation, which is generally performed by manual delineations. The purpose of our work is to develop and evaluate a new 3D model-based approach for carotid artery wall segmentation from dual-sequence MRI. The proposed method segments the lumen and outer wall surfaces including the bifurcation region by fitting a subdivision surface constructed hierarchical-tree model to the image data. In particular, a hybrid segmentation which combines deformable model fitting with boundary classification was applied to extract the lumen surface. The 3D model ensures the correct shape and topology of the carotid artery, while the boundary classification uses combined image information of 3D TOF-MRA and 3D BB-MRI to promote accurate delineation of the lumen boundaries. The proposed algorithm was validated on 25 subjects (48 arteries) including both healthy volunteers and atherosclerotic patients with 30% to 70% carotid stenosis. For both lumen and outer wall border detection, our result shows good agreement between manually and automatically determined contours, with contour-to-contour distance less than 1 pixel as well as Dice overlap greater than 0.87 at all different carotid artery sections. The presented 3D segmentation technique has demonstrated the capability of providing vessel wall delineation for 3D carotid MRI data with high accuracy and limited user interaction. This brings benefits to large-scale patient studies for assessing the effect of pharmacological treatment of atherosclerosis by reducing image analysis time and bias between human observers. © 2017 American Association of Physicists in Medicine.

Segmentation of the common carotid artery with active shape models from 3D ultrasound images

NASA Astrophysics Data System (ADS)

Yang, Xin; Jin, Jiaoying; He, Wanji; Yuchi, Ming; Ding, Mingyue

2012-03-01

Carotid atherosclerosis is a major cause of stroke, a leading cause of death and disability. In this paper, we develop and evaluate a new segmentation method for outlining both lumen and adventitia (inner and outer walls) of common carotid artery (CCA) from three-dimensional ultrasound (3D US) images for carotid atherosclerosis diagnosis and evaluation. The data set consists of sixty-eight, 17× 2× 2, 3D US volume data acquired from the left and right carotid arteries of seventeen patients (eight treated with 80mg atorvastain and nine with placebo), who had carotid stenosis of 60% or more, at baseline and after three months of treatment. We investigate the use of Active Shape Models (ASMs) to segment CCA inner and outer walls after statin therapy. The proposed method was evaluated with respect to expert manually outlined boundaries as a surrogate for ground truth. For the lumen and adventitia segmentations, respectively, the algorithm yielded Dice Similarity Coefficient (DSC) of 93.6%+/- 2.6%, 91.8%+/- 3.5%, mean absolute distances (MAD) of 0.28+/- 0.17mm and 0.34 +/- 0.19mm, maximum absolute distances (MAXD) of 0.87 +/- 0.37mm and 0.74 +/- 0.49mm. The proposed algorithm took 4.4 +/- 0.6min to segment a single 3D US images, compared to 11.7+/-1.2min for manual segmentation. Therefore, the method would promote the translation of carotid 3D US to clinical care for the fast, safety and economical monitoring of the atherosclerotic disease progression and regression during therapy.

Intrinsic properties of limb bud cells can be differentially reset.

PubMed

Saiz-Lopez, Patricia; Chinnaiya, Kavitha; Towers, Matthew; Ros, Maria A

2017-02-01

An intrinsic timing mechanism specifies the positional values of the zeugopod (i.e. radius/ulna) and then autopod (i.e. wrist/digits) segments during limb development. Here, we have addressed whether this timing mechanism ensures that patterning events occur only once by grafting GFP-expressing autopod progenitor cells to the earlier host signalling environment of zeugopod progenitor cells. We show by detecting Hoxa13 expression that early and late autopod progenitors fated for the wrist and phalanges, respectively, both contribute to the entire host autopod, indicating that the autopod positional value is irreversibly determined. We provide evidence that Hoxa13 provides an autopod-specific positional value that correctly allocates cells into the autopod, most likely through the control of cell-surface properties as shown by cell-cell sorting analyses. However, we demonstrate that only the earlier autopod cells can adopt the host proliferation rate to permit normal morphogenesis. Therefore, our findings reveal that the ability of embryonic cells to differentially reset their intrinsic behaviours confers robustness to limb morphogenesis. We speculate that this plasticity could be maintained beyond embryogenesis in limbs with regenerative capacity. © 2017. Published by The Company of Biologists Ltd.

Spectral domain optical coherence tomography findings in tamoxifen retinopathy--a case report.

PubMed

Nair, Sandhya Narayanan; Anantharaman, Giridhar; Gopalakrishnan, Mahesh; Vyas, Jyothiprakash

2013-01-01

To report spectral domain optical coherence tomography findings in a case of typical tamoxifen retinopathy. In this observational case report, a patient with tamoxifen retinopathy was imaged with spectral domain optical coherence tomography and fundus auto fluorescence. Spectral domain optical coherence tomography showed numerous hyperreflective spots within the retina, mainly in the inner retinal layers in both the eyes. The external limiting membrane, the Inner Segment-Outer Segment junction, and the photoreceptors were not discernable at the fovea in the right eye. In the left eye, there was foveal atrophy with total loss of photoreceptors. The autofluorescent images showed macular hypofluorescence with foveal hyperfluorescence. Spectral domain optical coherence tomography demonstrated abnormalities in the outer retinal layers in tamoxifen retinopathy. There were also characteristic alterations in the autofluorescence pattern at the macula in tamoxifen retinopathy.

Stimulus-evoked outer segment changes in rod photoreceptors

NASA Astrophysics Data System (ADS)

Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Lu, Yiming; Gai, Shaoyan; Yao, Xincheng

2016-06-01

Rod-dominated transient retinal phototropism (TRP) has been recently observed in freshly isolated mouse and frog retinas. Comparative confocal microscopy and optical coherence tomography revealed that the TRP was predominantly elicited from the rod outer segment (OS). However, the biophysical mechanism of rod OS dynamics is still unknown. Mouse and frog retinal slices, which displayed a cross-section of retinal photoreceptors and other functional layers, were used to test the effect of light stimulation on rod OSs. Time-lapse microscopy revealed stimulus-evoked conformational changes of rod OSs. In the center of the stimulated region, the length of the rod OS shrunk, while in the peripheral region, the rod OS swung toward the center region. Our experimental observation and theoretical analysis suggest that the TRP may reflect unbalanced rod disc-shape changes due to localized visible light stimulation.

Comparative investigation of stimulus-evoked rod outer segment movement and retinal electrophysiological activity

NASA Astrophysics Data System (ADS)

Lu, Yiming; Wang, Benquan; Yao, Xincheng

2017-02-01

Transient retinal phototropism (TRP) has been observed in rod photoreceptors activated by oblique visible light flashes. Time-lapse confocal microscopy and optical coherence tomography (OCT) revealed rod outer segment (ROS) movements as the physical source of TRP. However, the physiological source of TRP is still not well understood. In this study, concurrent TRP and electroretinogram (ERG) measurements disclosed a remarkably earlier onset time of the ROS movements (<=10 ms) than that ( 38 ms) of the ERG a-wave. Furthermore, low sodium treatment reversibly blocked the photoreceptor ERG a-wave, which is known to reflect hyperpolarization of retinal photoreceptors, but preserved the TRP associated rod OS movements well. Our experimental results and theoretical analysis suggested that the physiological source of TRP might be attributed to early stages of phototransduction, before the hyperpolarization of retinal photoreceptors.

Stimulus-evoked outer segment changes in rod photoreceptors

PubMed Central

Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Lu, Yiming; Gai, Shaoyan; Yao, Xincheng

2016-01-01

Abstract. Rod-dominated transient retinal phototropism (TRP) has been recently observed in freshly isolated mouse and frog retinas. Comparative confocal microscopy and optical coherence tomography revealed that the TRP was predominantly elicited from the rod outer segment (OS). However, the biophysical mechanism of rod OS dynamics is still unknown. Mouse and frog retinal slices, which displayed a cross-section of retinal photoreceptors and other functional layers, were used to test the effect of light stimulation on rod OSs. Time-lapse microscopy revealed stimulus-evoked conformational changes of rod OSs. In the center of the stimulated region, the length of the rod OS shrunk, while in the peripheral region, the rod OS swung toward the center region. Our experimental observation and theoretical analysis suggest that the TRP may reflect unbalanced rod disc-shape changes due to localized visible light stimulation. PMID:27334933

Evidence of early ultrastructural photoreceptor abnormalities in light-induced retinal degeneration using spectral domain optical coherence tomography.

PubMed

Aziz, Mehak K; Ni, Aiguo; Esserman, Denise A; Chavala, Sai H

2014-07-01

To study spatiotemporal in vivo changes in retinal morphology and quantify thickness of retinal layers in a mouse model of light-induced retinal degeneration using spectral domain optical coherence tomography (SD-OCT). BALB/c mice were exposed to 5000 lux of constant light for 3 h. SD-OCT images were taken 3 h, 24 h, 3 days, 1 week and 1 month after light exposure and were compared with histology at the same time points. SD-OCT images were also taken at 0, 1 and 2 h after light exposure in order to analyse retinal changes at the earliest time points. The thickness of retinal layers was measured using the Bioptigen software InVivoVue Diver. SD-OCT demonstrated progressive outer retinal thinning. 3 h after light exposure, the outer nuclear layer converted from hyporeflective to hyper-reflective. At 24 h, outer retinal bands and nuclear layer demonstrated similar levels of hyper-reflectivity. Significant variations in outer retinal thickness, vitreous opacities and retinal detachments occurred within days of injury. Thinning of the retina was observed at 1 month after injury. It was also determined that outer nuclear layer changes precede photoreceptor segment structure disintegration and the greatest change in segment structure occurs between 1 and 2 h after light exposure. Longitudinal SD-OCT reveals intraretinal changes that cannot be observed by histopathology at early time points in the light injury model. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

High-gradient compact linear accelerator

DOEpatents

Carder, B.M.

1998-05-26

A high-gradient linear accelerator comprises a solid-state stack in a vacuum of five sets of disc-shaped Blumlein modules each having a center hole through which particles are sequentially accelerated. Each Blumlein module is a sandwich of two outer conductive plates that bracket an inner conductive plate positioned between two dielectric plates with different thicknesses and dielectric constants. A third dielectric core in the shape of a hollow cylinder forms a casing down the series of center holes, and it has a dielectric constant different that the two dielectric plates that sandwich the inner conductive plate. In operation, all the inner conductive plates are charged to the same DC potential relative to the outer conductive plates. Next, all the inner conductive plates are simultaneously shorted to the outer conductive plates at the outer diameters. The signal short will propagate to the inner diameters at two different rates in each Blumlein module. A faster wave propagates quicker to the third dielectric core across the dielectric plates with the closer spacing and lower dielectric constant. When the faster wave reaches the inner extents of the outer and inner conductive plates, it reflects back outward and reverses the field in that segment of the dielectric core. All the field segments in the dielectric core are then in unipolar agreement until the slower wave finally propagates to the third dielectric core across the dielectric plates with the wider spacing and higher dielectric constant. During such unipolar agreement, particles in the core are accelerated with gradients that exceed twenty megavolts per meter. 10 figs.

High-gradient compact linear accelerator

DOEpatents

Carder, Bruce M.

1998-01-01

A high-gradient linear accelerator comprises a solid-state stack in a vacuum of five sets of disc-shaped Blumlein modules each having a center hole through which particles are sequentially accelerated. Each Blumlein module is a sandwich of two outer conductive plates that bracket an inner conductive plate positioned between two dielectric plates with different thicknesses and dielectric constants. A third dielectric core in the shape of a hollow cylinder forms a casing down the series of center holes, and it has a dielectric constant different that the two dielectric plates that sandwich the inner conductive plate. In operation, all the inner conductive plates are charged to the same DC potential relative to the outer conductive plates. Next, all the inner conductive plates are simultaneously shorted to the outer conductive plates at the outer diameters. The signal short will propagate to the inner diameters at two different rates in each Blumlein module. A faster wave propagates quicker to the third dielectric core across the dielectric plates with the closer spacing and lower dielectric constant. When the faster wave reaches the inner extents of the outer and inner conductive plates, it reflects back outward and reverses the field in that segment of the dielectric core. All the field segments in the dielectric core are then in unipolar agreement until the slower wave finally propagates to the third dielectric core across the dielectric plates with the wider spacing and higher dielectric constant. During such unipolar agreement, particles in the core are accelerated with gradients that exceed twenty megavolts per meter.

Side wall cooling for nozzle segments for a gas turbine

DOEpatents

Burdgick, Steven Sebastian

2002-01-01

A nozzle vane segment includes outer and inner band portions with a vane extending therebetween and defining first and second cavities separated by an impingement plate for flowing cooling medium for impingement cooling of nozzle side walls. The side wall of each nozzle segment has an undercut region. The impingement plate has an inturned flange with a plurality of openings. Cooling inserts or receptacles having an open end are received in the openings and the base and side walls of the receptacles have apertures for receiving cooling medium from the first cavity and directing the cooling medium for impingement cooling of the side wall of the nozzle segment and a portion of the nozzle wall.

Respiratory potential in sapwood of old versus young ponderosa pine trees in the Pacific Northwest.

PubMed

Pruyn, Michele L; Gartner, Barbara L; Harmon, Mark E

2002-02-01

Our primary objective was to present and test a new technique for in vitro estimation of respiration of cores taken from old trees to determine respiratory trends in sapwood. Our secondary objective was to quantify effects of tree age and stem position on respiratory potential (rate of CO2 production of woody tissue under standardized laboratory conditions). We extracted cores from one to four vertical positions in boles of +200-, +50- and +15-year-old Pinus ponderosa Dougl. ex Laws. trees. Cores were divided into five segments corresponding to radial depths of inner bark; outer, middle and inner sapwood; and heartwood. Data suggested that core segment CO2 production was an indicator of its respiratory activity, and that potential artifacts caused by wounding and extraction were minimal. On a dry mass basis, respiratory potential of inner bark was 3-15 times greater than that of sapwood at all heights for all ages (P < 0.0001). Within sapwood at all heights and in all ages of trees, outer sapwood had a 30-60% higher respiratory potential than middle or inner sapwood (P < 0.005). Heartwood had only 2-10% of the respiratory potential of outer sapwood. For all ages of trees, sapwood rings produced in the same calendar year released over 50% more CO2 at treetops than at bases (P < 0.0001). When scaled to the whole-tree level on a sapwood volume basis, sapwood of younger trees had higher respiratory potential than sapwood of older trees. In contrast, the trend was reversed when using the outer-bark surface area of stems as a basis for comparing respiratory potential. The differences observed in respiratory potential calculated on a core dry mass, sapwood volume, or outer-bark surface area basis clearly demonstrate that the resulting trends within and among trees are determined by the way in which the data are expressed. Although these data are based on core segments rather than in vivo measurements, we conclude that the relative differences are probably valid even if the absolute differences are not.

Membrane curvature generation by a C-terminal amphipathic helix in peripherin-2/rds, a tetraspanin required for photoreceptor sensory cilium morphogenesis

PubMed Central

Khattree, Nidhi; Ritter, Linda M.; Goldberg, Andrew F. X.

2013-01-01

Summary Vertebrate vision requires photon absorption by photoreceptor outer segments (OSs), structurally elaborate membranous organelles derived from non-motile sensory cilia. The structure and function of OSs depends on a precise stacking of hundreds of membranous disks. Each disk is fully (as in rods) or partially (as in cones) bounded by a rim, at which the membrane is distorted into an energetically unfavorable high-curvature bend; however, the mechanism(s) underlying disk rim structure is (are) not established. Here, we demonstrate that the intrinsically disordered cytoplasmic C-terminus of the photoreceptor tetraspanin peripherin-2/rds (P/rds) can directly generate membrane curvature. A P/rds C-terminal domain and a peptide mimetic of an amphipathic helix contained within it each generated curvature in liposomes with a composition similar to that of OS disks and in liposomes generated from native OS lipids. Association of the C-terminal domain with liposomes required conical phospholipids, and was promoted by membrane curvature and anionic surface charge, results suggesting that the P/rds C-terminal amphipathic helix can partition into the cytosolic membrane leaflet to generate curvature by a hydrophobic insertion (wedging) mechanism. This activity was evidenced in full-length P/rds by its induction of small-diameter tubulovesicular membrane foci in cultured cells. In sum, the findings suggest that curvature generation by the P/rds C-terminus contributes to the distinctive structure of OS disk rims, and provide insight into how inherited defects in P/rds can disrupt organelle structure to cause retinal disease. They also raise the possibility that tethered amphipathic helices can function for shaping cellular membranes more generally. PMID:23886945

Role of notochord cells and sclerotome-derived cells in vertebral column development in fugu, Takifugu rubripes: histological and gene expression analyses.

PubMed

Kaneko, Takamasa; Freeha, Khalid; Wu, Xiaoming; Mogi, Makoto; Uji, Susumu; Yokoi, Hayato; Suzuki, Tohru

2016-10-01

Despite the common structure of vertebrates, the development of the vertebral column differs widely between teleosts and tetrapods in several respects, including the ossification of the centrum and the function of the notochord. In contrast to tetrapods, vertebral development in teleosts is not fully understood, particularly for large fish with highly ossified bones. We therefore examined the histology and gene expression profile of vertebral development in fugu, Takifugu rubripes, a model organism for genomic research. Ossification of the fugu centrum is carried out by outer osteoblasts expressing col1a1, col2a1, and sparc, and the growing centra completely divide the notochord into double cone-shaped segments that function as intercentral joints. In this process, the notochord basal cells produce a thick notochord sheath exhibiting Alcian-blue-reactive cartilaginous properties and composing the intercentral ligament in cooperation with the external ligament connective tissue. Synthesis of the matrix by the basal cells was ascertained by an in vitro test. Expression of twist2 indicates that this connective tissue is descended from the embryonic sclerotome. Notochord basal cells express sox9, ihhb, shh, and col2a1a, suggesting that the signaling system involved in chondrocyte proliferation and matrix production also functions in notochord cells for notochord sheath formation. We further found that the notochord expression of both ntla and shh is maintained in the fugu vertebral column, whereas it is turned off after embryogenesis in zebrafish. Thus, our results demonstrate that, in contrast to zebrafish, a dynamic morphogenesis and molecular network continues to function in fugu until the establishment of the adult vertebral column.

Debris-less method and apparatus for forming apertures in hollow metallic articles

DOEpatents

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.

Msx homeobox gene family and craniofacial development.

PubMed

Alappat, Sylvia; Zhang, Zun Yi; Chen, Yi Ping

2003-12-01

Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene. These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development. Inductive interactions mediated by the Msx genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice, as manifested by the phenotypic abnormalities shown in knockout mice and in humans. This review summarizes studies on the expression, regulation, and functional analysis of Msx genes that bear relevance to craniofacial development in humans and mice. Key words: Msx genes, craniofacial, tooth, cleft palate, suture, development, transcription factor, signaling molecule.

Wnt-regulated dynamics of positional information in zebrafish somitogenesis

PubMed Central

Bajard, Lola; Morelli, Luis G.; Ares, Saúl; Pécréaux, Jacques; Jülicher, Frank; Oates, Andrew C.

2014-01-01

How signaling gradients supply positional information in a field of moving cells is an unsolved question in patterning and morphogenesis. Here, we ask how a Wnt signaling gradient regulates the dynamics of a wavefront of cellular change in a flow of cells during somitogenesis. Using time-controlled perturbations of Wnt signaling in the zebrafish embryo, we changed segment length without altering the rate of somite formation or embryonic elongation. This result implies specific Wnt regulation of the wavefront velocity. The observed Wnt signaling gradient dynamics and timing of downstream events support a model for wavefront regulation in which cell flow plays a dominant role in transporting positional information. PMID:24595291

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.

Daughters of the Enamel Organ: Development, Fate, and Function of the Stratum Intermedium, Stellate Reticulum, and Outer Enamel Epithelium

PubMed Central

Liu, Hui; Yan, Xiulin; Pandya, Mirali; Luan, Xianghong

2016-01-01

The tooth enamel organ (EO) is a complex epithelial cell assembly involved in multiple aspects of tooth development, including amelogenesis. The present study focuses on the role of the nonameloblast layers of the EO, the stratum intermedium, the stellate reticulum, and the outer enamel epithelium (OEE). The secretory stage stratum intermedium was distinguished by p63-positive epithelial stem cell marks, highly specific alkaline phosphatase labeling, as well as multiple desmosomes and gap junctions. At the location of the presecretory stage stellate reticulum, the pre-eruption EO prominently featured the papillary layer (PL) as a keratin immunopositive network of epithelial strands between tooth crowns and oral epithelium. PL cell strands contained numerous p63-positive epithelial stem cells, while BrdU proliferative cells were detected at the outer boundaries of the PL, suggesting that the stellate reticulum/PL epithelial cell sheath proliferated to facilitate an epithelial seal during tooth eruption. Comparative histology studies demonstrated continuity between the OEE and the general lamina of continuous tooth replacement in reptiles, and the outer layer of Hertwig's epithelial root sheath in humans, implicating the OEE as the formative layer for continuous tooth replacement and tooth root extension. Cell fate studies in organ culture verified that the cervical portion of the mouse molar EO gave rise to Malassez rest-like cell islands. Together, these studies indicate that the nonameloblast layers of the EO play multiple roles during odontogenesis, including the maintenance of several p63-positive stem cell reservoirs, a role during tooth root morphogenesis and tooth succession, a stabilizing function for the ameloblast layer, the facilitation of ion transport from the EO capillaries to the enamel layer, as well as safe and seamless tooth eruption. PMID:27611344

Daughters of the Enamel Organ: Development, Fate, and Function of the Stratum Intermedium, Stellate Reticulum, and Outer Enamel Epithelium.

PubMed

Liu, Hui; Yan, Xiulin; Pandya, Mirali; Luan, Xianghong; Diekwisch, Thomas G H

2016-09-09

The tooth enamel organ (EO) is a complex epithelial cell assembly involved in multiple aspects of tooth development, including amelogenesis. The present study focuses on the role of the nonameloblast layers of the EO, the stratum intermedium, the stellate reticulum, and the outer enamel epithelium (OEE). The secretory stage stratum intermedium was distinguished by p63-positive epithelial stem cell marks, highly specific alkaline phosphatase labeling, as well as multiple desmosomes and gap junctions. At the location of the presecretory stage stellate reticulum, the pre-eruption EO prominently featured the papillary layer (PL) as a keratin immunopositive network of epithelial strands between tooth crowns and oral epithelium. PL cell strands contained numerous p63-positive epithelial stem cells, while BrdU proliferative cells were detected at the outer boundaries of the PL, suggesting that the stellate reticulum/PL epithelial cell sheath proliferated to facilitate an epithelial seal during tooth eruption. Comparative histology studies demonstrated continuity between the OEE and the general lamina of continuous tooth replacement in reptiles, and the outer layer of Hertwig's epithelial root sheath in humans, implicating the OEE as the formative layer for continuous tooth replacement and tooth root extension. Cell fate studies in organ culture verified that the cervical portion of the mouse molar EO gave rise to Malassez rest-like cell islands. Together, these studies indicate that the nonameloblast layers of the EO play multiple roles during odontogenesis, including the maintenance of several p63-positive stem cell reservoirs, a role during tooth root morphogenesis and tooth succession, a stabilizing function for the ameloblast layer, the facilitation of ion transport from the EO capillaries to the enamel layer, as well as safe and seamless tooth eruption.

Use of optical coherence tomography to evaluate visual acuity and visual field changes in dengue fever.

PubMed

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.

Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation.

PubMed

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.

Localization of type IV collagen a 1 to a 6 chains in basement membrane during mouse molar germ development.

PubMed

Nagai, N; Nakano, K; Sado, Y; Naito, I; Gunduz, M; Tsujigiwa, H; Nagatsuka, H; Ninomiya, Y; Siar, C H

2001-10-01

The dental basement membrane (BM) putatively mediates epithelial-mesenchymal interactions during tooth morphogenesis and cytodifferentiation. Type IV collagen alpha chains, a major network-forming protein of the dental BM, was studied and results disclosed distinct expression patterns at different stages of mouse molar germ development. At the dental placode and bud stage, the BM of the oral epithelium expressed alpha 1, alpha 2, alpha 5 and alpha 6 chains while the gubernaculum dentis, in addition to the above four chains, also expressed a 4 chain. An asymmetrical expression for alpha 4, alpha 5 and alpha 6 chains was observed at the bud stage. At the early bell stage, the BM associated with the inner enamel epithelium (IEE) of molar germ expressed alpha 1, alpha 2 and alpha 4 chains while the BM of the outer enamel epithelium (OEE) expressed only alpha 1 and a 2 chains. With the onset of dentinogenesis, the collagen a chain profile of the IEE BM gradually disappeared. Howeverfrom the early to late bell stage, the gubernaculum dentis consistently expressed alpha 1, alpha 2, alpha 5 and a 6 chains resembling fetal oral mucosa. These findings suggest that stage- and position-specific distribution of type IV collagen alpha subunits occur during molar germ development and that these changes are essential for molar morphogenesis and cytodifferentiation.

Ceramic turbine nozzle

DOEpatents

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.

Ceramic turbine nozzle

DOEpatents

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.

PubMed

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.

PubMed

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

2011-06-01

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

Method of controlling the side wall thickness of a turbine nozzle segment for improved cooling

DOEpatents

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.

The proline-rich domain of TonB possesses an extended polyproline II-like conformation of sufficient length to span the periplasm of Gram-negative bacteria

PubMed Central

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

KSC-08pd3565

NASA Image and Video Library

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

KSC-08pd3564

NASA Image and Video Library

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

KSC-08pd3570

NASA Image and Video Library

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

Differential growth of pavement cells of Arabidopsis thaliana leaf epidermis as revealed by microbead labeling.

PubMed

Elsner, Joanna; Lipowczan, Marcin; Kwiatkowska, Dorota

2018-02-01

In numerous vascular plants, pavement cells of the leaf epidermis are shaped like a jigsaw-puzzle piece. Knowledge about the subcellular pattern of growth that accompanies morphogenesis of such a complex shape is crucial for studies of the role of the cytoskeleton, cell wall and phytohormones in plant cell development. Because the detailed growth pattern of the anticlinal and periclinal cell walls remains unknown, our aim was to measure pavement cell growth at a subcellular resolution. Using fluorescent microbeads applied to the surface of the adaxial leaf epidermis of Arabidopsis thaliana as landmarks for growth computation, we directly assessed the growth rates for the outer periclinal and anticlinal cell walls at a subcellular scale. We observed complementary tendencies in the growth pattern of the outer periclinal and anticlinal cell walls. Central portions of periclinal walls were characterized by relatively slow growth, while growth of the other wall portions was heterogeneous. Local growth of the periclinal walls accompanying lobe development after initiation was relatively fast and anisotropic, with maximal extension usually in the direction along the lobe axis. This growth pattern of the periclinal walls was complemented by the extension of the anticlinal walls, which was faster on the lobe sides than at the tips. Growth of the anticlinal and outer periclinal walls of leaf pavement cells is heterogeneous. The growth of the lobes resembles cell elongation via diffuse growth rather than tip growth. © 2018 Botanical Society of America.

Nervous systems in 3D: a comparison of Caridean, anomuran, and brachyuran zoea-I (Decapoda).

PubMed

Geiselbrecht, Hannes; Melzer, Roland R

2013-12-01

Using serial semi-thin sections and digital 3D-reconstructions we studied the nervous systems of zoea-I larvae in three decapod species, Hippolyte inermis (Leach, 1815), Porcellana platycheles (Pennant, 1777), and Pachygrapsus marmoratus (Fabricius, 1787). These taxa represent three decapod lineages, that is, Caridea, Anomura, and Brachyura, each characterized by specific zoea-I morphology. Special attention was paid to development of ganglia, neuropil composition, and segmental nerves. In all zoeae studied, the overall elements, for example, the segmental ganglia, their neuropils and most of the nerves of the adult decapod nervous system are present. Ongoing differentiation processes are observable as well, most obvious in segments with well-developed limbs the ganglia are in a more advanced stage of differentiation and more voluminous compared to segments with only limb buds or without externally visible limb anlagen. Intra- and interspecific comparisons indicate that neuromere differentiation thus deviates from a simple anterior-posterior gradient as, for example, posterior thoracic neuromeres are less developed than those of the pleon. In addition, the differences in the progress of the development of ganglia between the studied taxa can best be attributed to heterochronic mechanisms. Taxon and stage-specific morphologies indicate that neuronal architecture reflects both, morphogenesis to the adult stage and specific larval adaptions, and provides sets of characters relevant to understanding the corresponding phylogeny. © 2013 Wiley Periodicals, Inc.

Spectral domain optical coherence tomography findings in acute syphilitic posterior placoid chorioretinitis.

PubMed

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.

The vacuole within

PubMed Central

Ellis, Kathryn; Hoffman, Brenton D.; Bagnat, Michel

2013-01-01

The notochord is an evolutionarily conserved structure that has long been known to play an important role in patterning during embryogenesis. Structurally, the notochord is composed of two cell layers: an outer epithelial-like sheath, and an inner core of cells that contain large fluid-filled vacuoles. We have recently shown these notochord vacuoles are lysosome-related organelles that form through Rab32a and vacuolar-type proton-ATPase-dependent acidification. Disruption of notochord vacuoles results in a shortened embryo along the anterior-posterior axis. Interestingly, we discovered that notochord vacuoles are also essential for proper spine morphogenesis and that vacuole defects lead to scoliosis of the spine. Here we discuss the cellular organization of the notochord and how key features of its architecture allow the notochord to function in embryonic axis elongation and spine formation. PMID:23887209

Diabetic retinal pigment epitheliopathy: fundus autofluorescence and spectral-domain optical coherence tomography findings.

PubMed

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.

Development of an MRI biomarker sensitive to tetrameric visual arrestin 1 and its reduction via light-evoked translocation in vivo.

PubMed

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.

KSC-08pd3571

NASA Image and Video Library

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

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

PubMed

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

2015-01-01

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

Rod Photopigment Kinetics After Photodisruption of the Retinal Pigment Epithelium

PubMed Central

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

Enhanced Visualization of Subtle Outer Retinal Pathology by En Face Optical Coherence Tomography and Correlation with Multi-Modal Imaging

PubMed Central

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

Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea.

PubMed

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.

Ultra-Wide-Field Fundus Autofluorescence and Spectral-Domain Optical Coherence Tomography Findings in Syphilitic Outer Retinitis.

PubMed

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

DOEpatents

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.

PubMed Central

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.

PubMed

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.

Kinetics and components of the flash photocurrent of isolated retinal rods of the larval salamander, Ambystoma tigrinum.

PubMed Central

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

Cellular phosphoinositides and the maturation of bluetongue virus, a non-enveloped capsid virus

PubMed Central

2013-01-01

Background Bluetongue virus (BTV), a member of Orbivirus genus in the Reoviridae family is a double capsid virus enclosing a genome of 10 double-stranded RNA segments. A non-structural protein of BTV, NS3, which is associated with cellular membranes and interacts with outer capsid proteins, has been shown to be involved in virus morphogenesis in infected cells. In addition, studies have also shown that during the later stages of virus infection NS3 behaves similarly to HIV protein Gag, an enveloped viral protein. Since Gag protein is known to interact with membrane lipid phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2] and one of the known binding partners of NS3, cellular protein p11 also interacts with annexin a PI(4,5)P2 interacting protein, this study was designed to understand the role of this negatively charged membrane lipid in BTV assembly and maturation. Methods Over expression of cellular enzymes that either depleted cells of PI(4,5)P2 or altered the distribution of PI(4,5)P2, were used to analyze the effect of the lipid on BTV maturation at different times post-infection. The production of mature virus particles was monitored by plaque assay. Microscopic techniques such as confocal microscopy and electron microscopy (EM) were also undertaken to study localization of virus proteins and virus particles in cells, respectively. Results Initially, confocal microscopic analysis demonstrated that PI(4,5)P2 not only co-localized with NS3, but it also co-localized with VP5, one of the outer capsid proteins of BTV. Subsequently, experiments involving depletion of cellular PI(4,5)P2 or its relocation demonstrated an inhibitory effect on normal BTV maturation and it also led to a redistribution of BTV proteins within the cell. The data was supported further by EM visualization showing that modulation of PI(4,5)P2 in cells indeed resulted in less particle production. Conclusion This study to our knowledge, is the first report demonstrating involvement of PI(4,5)P2 in a non-enveloped virus assembly and release. As BTV does not have lipid envelope, this finding is unique for this group of viruses and it suggests that the maturation of capsid and enveloped viruses may be more closely related than previously thought. PMID:23497128

Fine structure of the retinal photoreceptors of the great horned owl (Bubo virginianus).

PubMed

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

DOEpatents

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.

Apparatus and methods for impingement cooling of an undercut region adjacent a side wall of a turbine nozzle segment

DOEpatents

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

DOEpatents

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.

PubMed

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.

Essential roles for lines in mediating leg and antennal proximodistal patterning and generating a stable Notch signaling interface at segment borders.

PubMed

Greenberg, Lina; Hatini, Victor

2009-06-01

The Drosophila leg imaginal disc provides a paradigm with which to understand the fundamental developmental mechanisms that generate an intricate appendage structure. Leg formation depends on the subdivision of the leg proximodistal (PD) axis into broad domains by the leg gap genes. The leg gap genes act combinatorially to initiate the expression of the Notch ligands Delta (Dl) and Serrate (Ser) in a segmental pattern. Dl and Ser induce the expression of a set of transcriptional regulators along the segment border, which mediate leg segment growth and joint morphogenesis. Here we show that Lines accumulates in nuclei in the presumptive tarsus and the inter-joints of proximal leg segments and governs the formation of these structures by destabilizing the nuclear protein Bowl. Across the presumptive tarsus, lines modulates the opposing expression landscapes of the leg gap gene dachshund (dac) and the tarsal PD genes, bric-a-brac 2 (bab), apterous (ap) and BarH1 (Bar). In this manner, lines inhibits proximal tarsal fates and promotes medial and distal tarsal fates. Across proximal leg segments, lines antagonizes bowl to promote Dl expression by relief-of-repression. In turn, Dl signals asymmetrically to stabilize Bowl in adjacent distal cells. Bowl, then, acts cell-autonomously, together with one or more redundant factors, to repress Dl expression. Together, lines and bowl act as a binary switch to generate a stable Notch signaling interface between Dl-expressing cells and adjacent distal cell. lines plays analogous roles in developing antennae, which are serially homologous to legs, suggesting evolutionarily conserved roles for lines in ventral appendage formation.

The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95).

PubMed

Wu, Qian; DiBona, Victoria L; Bernard, Laura P; Zhang, Huaye

2012-08-31

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95.

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration

NASA Astrophysics Data System (ADS)

Gibbs, Holly C.; Dodson, Colin R.; Bai, Yuqiang; Lekven, Arne C.; Yeh, Alvin T.

2014-12-01

During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration.

PubMed

Gibbs, Holly C; Dodson, Colin R; Bai, Yuqiang; Lekven, Arne C; Yeh, Alvin T

2014-12-01

During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

KSC-08pd3567

NASA Image and Video Library

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

KSC-08pd3566

NASA Image and Video Library

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

KSC-08pd3568

NASA Image and Video Library

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

KSC-08pd3569

NASA Image and Video Library

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

Exploring photoreceptor reflectivity via multimodal imaging of outer retinal tubulation in advanced age-related macular degeneration

PubMed Central

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.

PubMed

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.

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

PubMed

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

2018-05-09

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

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

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

Malachowski, M.J.

1978-07-01

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

Biochemical Measurements of Free Opsin in Macular Degeneration Eyes: Examining the 11-CIS Retinal Deficiency Hypothesis of Delayed Dark Adaptation (An American Ophthalmological Society Thesis).

PubMed

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.

An inducible amphipathic helix within the intrinsically disordered C terminus can participate in membrane curvature generation by peripherin-2/rds.

PubMed

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.

Rod outer segment retinol formation is independent of Abca4, arrestin, rhodopsin kinase, and rhodopsin palmitylation.

PubMed

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.

PubMed

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

2001-10-01

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

Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development*

PubMed Central

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.

The Polarity Protein Partitioning-defective 1 (PAR-1) Regulates Dendritic Spine Morphogenesis through Phosphorylating Postsynaptic Density Protein 95 (PSD-95)*

PubMed Central

Wu, Qian; DiBona, Victoria L.; Bernard, Laura P.; Zhang, Huaye

2012-01-01

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95. PMID:22807451

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.

Stress intensity and displacement coefficients for radially cracked ring segments subject to three-point bending

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.

MreB drives de novo rod morphogenesis in Caulobacter crescentus via remodeling of the cell wall.

PubMed

Takacs, Constantin N; Poggio, Sebastian; Charbon, Godefroid; Pucheault, Mathieu; Vollmer, Waldemar; Jacobs-Wagner, Christine

2010-03-01

MreB, the bacterial actin-like cytoskeleton, is required for the rod morphology of many bacterial species. Disruption of MreB function results in loss of rod morphology and cell rounding. Here, we show that the widely used MreB inhibitor A22 causes MreB-independent growth inhibition that varies with the drug concentration, culture medium conditions, and bacterial species tested. MP265, an A22 structural analog, is less toxic than A22 for growth yet equally efficient for disrupting the MreB cytoskeleton. The action of A22 and MP265 is enhanced by basic pH of the culture medium. Using this knowledge and the rapid reversibility of drug action, we examined the restoration of rod shape in lemon-shaped Caulobacter crescentus cells pretreated with MP265 or A22 under nontoxic conditions. We found that reversible restoration of MreB function after drug removal causes extensive morphological changes including a remarkable cell thinning accompanied with elongation, cell branching, and shedding of outer membrane vesicles. We also thoroughly characterized the composition of C. crescentus peptidoglycan by high-performance liquid chromatography and mass spectrometry and showed that MreB disruption and recovery of rod shape following restoration of MreB function are accompanied by considerable changes in composition. Our results provide insight into MreB function in peptidoglycan remodeling and rod shape morphogenesis and suggest that MreB promotes the transglycosylase activity of penicillin-binding proteins.

Architecture of the human renal inner medulla and functional implications

PubMed Central

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

Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign).

PubMed

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.

FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial.

PubMed

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

DOEpatents

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

DOEpatents

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.

PubMed

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

PubMed Central

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.

PubMed

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

2014-01-01

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

Oil droplets of bird eyes: microlenses acting as spectral filters

PubMed Central

Stavenga, Doekele G.; Wilts, Bodo D.

2014-01-01

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

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

PubMed Central

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

2017-01-01

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

Quantification of common carotid artery and descending aorta vessel wall thickness from MR vessel wall imaging using a fully automated processing pipeline.

PubMed

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.

Transition duct system with metal liners for delivering hot-temperature gases in a combustion turbine engine

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

Nowa, a novel protein with minicollagen Cys-rich domains, is involved in nematocyst formation in Hydra.

PubMed

Engel, Ulrike; Ozbek, Suat; Streitwolf-Engel, Ruth; Petri, Barbara; Lottspeich, Friedrich; Holstein, Thomas W; Oezbek, Suat; Engel, Ruth

2002-10-15

The novel protein Nowa was identified in nematocysts, explosive organelles of Hydra, jellyfish, corals and other CNIDARIA: Biogenesis of these organelles is complex and involves assembly of proteins inside a post-Golgi vesicle to form a double-layered capsule with a long tubule. Nowa is the major component of the outer wall, which is formed very early in morphogenesis. The high molecular weight glycoprotein has a modular structure with an N-terminal sperm coating glycoprotein domain, a central C-type lectin-like domain, and an eightfold repeated cysteine-rich domain at the C-terminus. Interestingly, the cysteine-rich domains are homologous to the cysteine-rich domains of minicollagens. We have previously shown that the cysteines of these minicollagen cysteine-rich domains undergo an isomerization process from intra- to intermolecular disulfide bonds, which mediates the crosslinking of minicollagens to networks in the inner wall of the capsule. The minicollagen cysteine-rich domains present in both proteins provide a potential link between Nowa in the outer wall and minicollagens in the inner wall. We propose a model for nematocyst formation that integrates cytoskeleton rearrangements around the post-Golgi vesicle and protein assembly inside the vesicle to generate a complex structure that is stabilized by intermolecular disulfide bonds.

Pipe gripper

DOEpatents

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.).

PubMed

Yew, D T; Woo, H H

1976-01-01

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

Stress Transfer Processes during Great Plate Boundary Thrusting Events: A Study from the Andaman and Nicobar Segments

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.

Histologic development of the human fovea from midgestation to maturity.

PubMed

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

2012-11-01

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

Development of an MRI biomarker sensitive to tetrameric visual arrestin 1 and its reduction via light-evoked translocation in vivo

PubMed Central

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

Physics and the canalization of morphogenesis: a grand challenge in organismal biology

PubMed Central

von Dassow, Michelangelo; Davidson, Lance A.

2011-01-01

Morphogenesis takes place in a background of organism-to-organism and environmental variation. Therefore, a fundamental question in the study of morphogenesis is how the mechanical processes of tissue movement and deformation are affected by that variability, and in turn, how the mechanics of the system modulates phenotypic variation. We highlight a few key factors, including environmental temperature, embryo size, and environmental chemistry that might perturb the mechanics of morphogenesis in natural populations. Then we discuss several ways in which mechanics – including feedback from mechanical cues – might influence intra-specific variation in morphogenesis. To understand morphogenesis it will be necessary to consider whole-organism, environment, and evolutionary scales because these larger scales present the challenges that developmental mechanisms have evolved to cope with. Studying the variation organisms express and the variation organisms experience will aid in deciphering the causes of birth defects. PMID:21750364

Free space-planning solutions in the architecture of multi-storey buildings

NASA Astrophysics Data System (ADS)

Ibragimov, Alexander; Danilov, Alexander

2018-03-01

Here some aspects of the development of steel frame structure design from the standpoint of geometry and morphogenesis of bearing steel structures of civil engineering objects. An alternative approach to forming constructive schemes may be application of curved steel elements in the main load-bearing system. As an example, it may be circular and parabolic arches or segments of varying outline and orientation. The considered approach implies creating large internal volumes without loss in the load-bearing capacity of the frame. The basic concept makes possible a wide variety of layout and design solutions. The presence of free internal spaces of large volume in buildings of a "skyscraper" type contributes to resolving a great number of problems, including those of communicative nature.

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.

THE ORGANOPHOSPHOROUS INSECTICIDE FENTHION DOES NOT AFFECT PHAGOCYTOSIS OF ROD OUTER SEGMENTS BY RETINAL PIGMENT EPITHELIUM CELLS IN CULTURE.

EPA Science Inventory

:
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...

Structural and Functional Changes Associated with Normal and Abnormal Fundus Autofluorescence in Patients with Retinitis Pigmentosa

PubMed Central

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

Evaluation of the Lower Punctum Parameters and Morphology Using Spectral Domain Anterior Segment Optical Coherence Tomography

PubMed Central

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

Normal morphogenesis of epithelial tissues and progression of epithelial tumors

PubMed Central

Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

2011-01-01

Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

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

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

PubMed Central

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

2013-01-01

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

Biological effects of blocking blue and other visible light on the mouse retina.

PubMed

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.

PubMed

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.

PubMed

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.

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

PubMed Central

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

2015-01-01

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

Physiological and Microfluorometric Studies of Reduction and Clearance of Retinal in Bleached Rod Photoreceptors

PubMed Central

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

DOEpatents

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.

Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae.

PubMed Central

Cid, V J; Durán, A; del Rey, F; Snyder, M P; Nombela, C; Sánchez, M

1995-01-01

In fungi and many other organisms, a thick outer cell wall is responsible for determining the shape of the cell and for maintaining its integrity. The budding yeast Saccharomyces cerevisiae has been a useful model organism for the study of cell wall synthesis, and over the past few decades, many aspects of the composition, structure, and enzymology of the cell wall have been elucidated. The cell wall of budding yeasts is a complex and dynamic structure; its arrangement alters as the cell grows, and its composition changes in response to different environmental conditions and at different times during the yeast life cycle. In the past few years, we have witnessed a profilic genetic and molecular characterization of some key aspects of cell wall polymer synthesis and hydrolysis in the budding yeast. Furthermore, this organism has been the target of numerous recent studies on the topic of morphogenesis, which have had an enormous impact on our understanding of the intracellular events that participate in directed cell wall synthesis. A number of components that direct polarized secretion, including those involved in assembly and organization of the actin cytoskeleton, secretory pathways, and a series of novel signal transduction systems and regulatory components have been identified. Analysis of these different components has suggested pathways by which polarized secretion is directed and controlled. Our aim is to offer an overall view of the current understanding of cell wall dynamics and of the complex network that controls polarized growth at particular stages of the budding yeast cell cycle and life cycle. PMID:7565410

Solo and keratin filaments regulate epithelial tubule morphology.

PubMed

Nishimura, Ryosuke; Kato, Kagayaki; Fujiwara, Sachiko; Ohashi, Kazumasa; Mizuno, Kensaku

2018-04-28

Epithelial tubules, consisting of the epithelial cell sheet with a central lumen, are the basic structure of many organs. Mechanical forces play an important role in epithelial tubulogenesis; however, little is known about the mechanisms controlling the mechanical forces during epithelial tubule morphogenesis. Solo (also known as ARHGEF40) is a RhoA-targeting guanine-nucleotide exchange factor that is involved in mechanical force-induced RhoA activation and stress fiber formation. Solo binds to keratin-8/keratin-18 (K8/K18) filaments, and this interaction plays a crucial role in mechanotransduction. In this study, we examined the roles of Solo and K8/K18 filaments in epithelial tubulogenesis using MDCK cells cultured in 3D collagen gels. Knockdown of either Solo or K18 resulted in rounder tubules with increased lumen size, indicating that Solo and K8/K18 filaments play critical roles in forming the elongated morphology of epithelial tubules. Moreover, knockdown of Solo or K18 decreased the level of diphosphorylated myosin light chain (a marker of contractile force) at the luminal and outer surfaces of tubules, suggesting that Solo and K8/K18 filaments are involved in the generation of the myosin II-mediated contractile force during epithelial tubule morphogenesis. In addition, K18 filaments were normally oriented along the long axis of the tubule, but knockdown of Solo perturbed their orientation. These results suggest that Solo plays crucial roles in forming the elongated morphology of epithelial tubules and in regulating myosin II activity and K18 filament organization during epithelial tubule formation.

Autofluorescence Imaging and Spectral-Domain Optical Coherence Tomography in Incomplete Congenital Stationary Night Blindness and Comparison with Retinitis Pigmentosa

PubMed Central

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

Radiant energy collector

DOEpatents

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.

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

PubMed Central

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

Uncoupling phototoxicity-elicited neural dysmorphology and death by insidious function and selective impairment of Ran-binding protein 2 (Ranbp2).

PubMed

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.

Tegument Protein ORF45 Plays an Essential Role in Virion Morphogenesis of Murine Gammaherpesvirus 68

PubMed Central

Jia, Xing; Shen, Sheng; Lv, Ying; Zhang, Ziwei; Guo, Haitao

2016-01-01

Tegument proteins play critical roles in herpesvirus morphogenesis. ORF45 is a conserved tegument protein of gammaherpesviruses; however, its role in virion morphogenesis is largely unknown. In this work, we determined the ultrastructural localization of murine gammaherpesvirus 68 (MHV-68) ORF45 and found that this protein was incorporated into virions around the site of host-derived vesicles. Notably, the absence of ORF45 inhibited nucleocapsid egress and blocked cytoplasmic virion maturation, demonstrating that ORF45 is essential for MHV-68 virion morphogenesis. PMID:27226376

Apparatus and methods for impingement cooling of a side wall of a turbine nozzle segment

DOEpatents

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

DOEpatents

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.

Cytologic appearance of retinal cells included in a fine-needle aspirate of a meningioma around the optic nerve of a dog.

PubMed

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

PubMed Central

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

Morphology of immature stages of blow fly, Lucilia sinensis Aubertin (Diptera: Calliphoridae), a potential species of forensic importance.

PubMed

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.

PubMed

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.

Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development.

PubMed

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.

PubMed

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.

PubMed

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.

PubMed

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.

A highly efficient protocol for micropropagation of Begonia tuberous.

PubMed

Duong, Tan Nhut; Nguyen, Thanh Hai; Mai, Xuan Phan

2010-01-01

A protocol for micropropagation of begonia was established utilizing a thin cell layer (TCL) system. This system has been employed to produce several thousand shoots per sample. Explant size and position, and plant growth regulators (PGRs) contribute to the tissue morphogenesis. By optimizing the size of the tissue and applying an improved selection procedure, shoots were elongated in 8 weeks of culture, with an average number of 210 +/- 9.7 shoots per segment. This system has facilitated a number of studies using TCL as a model for micropropagation and will enable the large-scale production of begonia. On an average, the best treatment would allow production of about 10,000 plantlets by the micropropagation of the axillary buds of one plant with five petioles, within a period of 8 months.

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

PubMed

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

2018-03-21

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

The Pea Seedling as a Model of Normal and Abnormal Morphogenesis

ERIC Educational Resources Information Center

Kurkdjian, Armen; And Others

1974-01-01

Describes several simple and inexpensive experiments designed to facilitate the study of normal and abnormal morphogenesis in the biology laboratory. Seedlings of the common garden pea are used in the experiments, and abnormal morphogenesis (tumors) are induced by a virulent strain of the crown-gall organism, Agrobacterium tumefaciens. (JR)

Film cooling for a closed loop cooled airfoil

DOEpatents

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.

Exit chimney joint and method of forming the joint for closed circuit steam cooled gas turbine nozzles

DOEpatents

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

DOEpatents

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.

MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis.

PubMed

Rebustini, Ivan T; Myers, Christopher; Lassiter, Keyonica S; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G; Hoffman, Matthew P

2009-10-01

Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here, we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA treatment, increasing MT-MMP and proproliferative gene expression via beta1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis.

Developmental expression of Hsp90, Hsp70 and HSF during morphogenesis in the vetigastropod Haliotis asinina.

PubMed

Gunter, Helen M; Degnan, Bernard M

2007-08-01

Heat shock proteins (Hsps) have dual functions, participating in both the stress response and a broad range of developmental processes. At physiological temperatures, it has been demonstrated in deuterostomes (vertebrates) and ecdysozoans (insects) that Hsps are expressed in tissues that are undergoing differentiation and morphogenesis. Here we investigate the developmental expression of Hsp70, Hsp90 and their regulatory transcription factor heat shock transcription factor (HSF) in the marine gastropod Haliotis asinina, a representative of the 3rd major lineage of bilaterian animals, the Lophotrochozoa. HasHsp70, HasHsp90 and HasHSF are maternally expressed in H. asinina and are progressively restricted to the micromere lineage during cleavage. During larval morphogenesis, they are expressed in unique and overlapping patterns in the prototroch, foot, and mantle. Hsp expression peaked in these tissues during periods of cell differentiation and morphogenesis, returning to lower levels after morphogenesis was complete. These patterns of Hsp and HSF expression in H. asinina are akin to those observed in ecdysozoans and deuterostomes, with Hsps being activated in cells and tissues undergoing morphogenesis.

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

PubMed

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

2013-01-01

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

Expression and function of glycogen synthase kinase-3 in human hair follicles.

PubMed

Yamauchi, Koichi; Kurosaka, Akira

2010-05-01

Beta-catenin is involved in the hair follicle morphogenesis and stem cell differentiation, and inhibition of glycogen synthase kinase-3 (GSK-3) increases beta-catenin concentration in the cytoplasm. To examine the effects of GSK-3 inhibition on the hair follicle epithelium, we first examined the expression of GSK-3 in plucked human hair follicles by RT-PCR and found GSK-3 expression in hair follicles. Western blotting with a GSK-3beta-specific antibody, Y174, also demonstrated GSK-3beta expression in the follicles. Moreover, GSK-3beta immunostaining with Y174 showed that GSK-3beta colocalized with hair follicle bulge markers. Contrary to GSK-3beta, GSK-3 alpha was widely expressed throughout the follicles when immunostained with a specific antibody, EP793Y. We then investigated the influence of GSK-3 inhibition. A GSK-3 inhibitor, BIO, promoted the growth of human outer root sheath cells, which could be cultured for up to four passages. The BIO-treated cells exhibited smaller and more undifferentiated morphology than control cells. Moreover, in organ culture of plucked human hair, outer root sheath cells in the middle of a hair follicle proliferated when cultured with BIO. These results indicate that GSK-3beta is expressed in hair bulge stem cells and BIO promotes the growth of ORS cells, possibly by regulating the GSK-3 signaling pathway.

CYTODIFFERENTIATION DURING SPERMIOGENESIS IN LUMBRICUS TERRESTRIS

PubMed Central

Anderson, W. A.; Weissman, A.; Ellis, R. A.

1967-01-01

The structural changes during spermiogenesis were studied on developing spermatids in seminal vesicles and receptacles of Lumbricus terrestris fixed in glutaraldehyde-osmium tetroxide and embedded in Epon-Araldite. The centriole plays a prominent role in the morphogenesis and organization of the microtubules of the manchette and flagellum. Microtubules arising from the centriole extend anteriorly to encase the developing middle piece, the nucleus, and the acrosome. The manchette not only provides a supporting framework for the cell during elongation, but also may provide the motive force for the elimination of both nucleoplasm and cytoplasm. The manchette participates in segregation and elimination of the nuclear vesicle that contains the nonchromatin nucleoplasm. Compartmentalization and conservation may also be a function of the manchette since those elements which remain within the framework of microtubules are retained, while all the cytoplasm outside the manchette is discarded. At maturation, the endoplasmic reticulum plays a key role in dismantling the manchette and reducing the cytoplasm external to it. During the early stages of middle-piece formation, six ovoid mitochondria aggregate at the posterior pole of the spermatid nucleus. Concurrent with manchette formation, the mitochondria are compressed laterally into elongate wedge-shaped components, and their outer limiting membranes fuse to form an hexagonal framework that surrounds the dense intramitochondrial matrices. Dense glycogen granules are arranged linearly between the peripheral flagellar tubules and the outer membrane of the mature sperm tail. PMID:10976199

Regulated efflux of photoreceptor outer segment-derived cholesterol by human RPE cells.

PubMed

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)

PubMed Central

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

Alterations in Retinal Layer Thickness and Reflectance at Different Stages of Diabetic Retinopathy by En Face Optical Coherence Tomography

PubMed Central

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

The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

PubMed

Marti-Figueroa, Carlos R; Ashton, Randolph S

2017-05-01

Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis to generate organoids with biomimicry at all scales. Such advancements would enable the use of organoids as a basis for 'next-generation' tissue engineering of functional, anatomically mimetic human tissues and potentially novel organ transplants. Here, we discuss critical aspects of organoid morphogenesis where application of innovative tissue engineering methodologies would yield significant advancement towards this goal. Copyright © 2017. Published by Elsevier Ltd.

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

Whole abdominal wall segmentation using augmented active shape models (AASM) with multi-atlas label fusion and level set

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

DOEpatents

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.

Interference by 2,3,7,8-tetrachlorodibenzo-p-dioxin with cultured mouse submandibular gland branching morphogenesis involves reduced epidermal growth factor receptor signaling

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

Kiukkonen, Anu; Sahlberg, Carin; Partanen, Anna-Maija

2006-05-01

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to mouse embryonic teeth, sharing features of early development with salivary glands in common, involves enhanced apoptosis and depends on the expression of epidermal growth factor (EGF) receptor. EGF receptor signaling, on the other hand, is essential for salivary gland branching morphogenesis. To see if TCDD impairs salivary gland morphogenesis and if the impairment is associated with EGF receptor signaling, we cultured mouse (NMRI) E13 submandibular glands with TCDD or TCDD in combination with EGF or fibronectin (FN), both previously found to enhance branching morphogenesis. Explants were examined stereomicroscopically and processed to paraffin sections. TCDD exposuremore » impaired epithelial branching and cleft formation, resulting in enlarged buds. The glands were smaller than normal. EGF and FN alone concentration-dependently stimulated or inhibited branching morphogenesis but when co-administered with TCDD, failed to compensate for its effect. TCDD induced cytochrome P4501A1 expression in the glandular epithelium, indicating activation of the aryl hydrocarbon receptor. TCDD somewhat increased epithelial apoptosis as observed by terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labeling method but the increase could not be correlated with morphological changes. The frequency of proliferating cells was not altered. Corresponding to the reduced cleft sites in TCDD-exposed explants, FN immunoreactivity in the epithelium was reduced. The results show that TCDD, comparably with EGF and FN at morphogenesis-inhibiting concentrations, impaired salivary gland branching morphogenesis in vitro. Together with the failure of EGF and FN at morphogenesis-stimulating concentrations to compensate for the effect of TCDD this implies that TCDD toxicity to developing salivary gland involves reduced EGF receptor signaling.« less

Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

PubMed Central

Ivanovitch, Kenzo; Temiño, Susana

2017-01-01

During vertebrate heart development, two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here, we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development. PMID:29202929

Nonmuscle Myosin II Regulates the Morphogenesis of Metanephric Mesenchyme–Derived Immature Nephrons

PubMed Central

Recuenco, Mariam C.; Ohmori, Tomoko; Tanigawa, Shunsuke; Taguchi, Atsuhiro; Fujimura, Sayoko; Conti, Mary Anne; Wei, Qize; Kiyonari, Hiroshi; Abe, Takaya; Adelstein, Robert S.

2015-01-01

The kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud. The mesenchyme transforms into epithelia and forms complicated nephron structures, whereas the ureteric bud extends its pre-existing epithelial ducts. Although the roles are well established for extracellular stimuli, such as Wnt and Notch, it is unclear how the intracellular cytoskeleton regulates these morphogenetic processes. Myh9 and Myh10 encode nonmuscle myosin II heavy chains, and Myh9 mutations in humans are implicated in congenital kidney diseases and focal segmental glomerulosclerosis in adults. Here, we analyzed the roles of Myh9 and Myh10 in the developing kidney. Ureteric bud-specific depletion of Myh9 resulted in no apparent phenotypes, whereas mesenchyme-specific Myh9 deletion caused proximal tubule dilations and renal failure. Mesenchyme-specific Myh9/Myh10 mutant mice died shortly after birth and showed a severe defect in nephron formation. The nascent mutant nephrons failed to form a continuous lumen, which likely resulted from impaired apical constriction of the elongating tubules. In addition, nephron progenitors lacking Myh9/Myh10 or the possible interactor Kif26b were less condensed at midgestation and reduced at birth. Taken together, nonmuscle myosin II regulates the morphogenesis of immature nephrons derived from the metanephric mesenchyme and the maintenance of nephron progenitors. Our data also suggest that Myh9 deletion in mice results in failure to maintain renal tubules but not in glomerulosclerosis. PMID:25168025

Displacement coefficients along the inner boundaries of radially cracked ring segments subject to forces and couples

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

DOEpatents

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

DOEpatents

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

DOEpatents

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.

Un(MaSC)ing Stem Cell Dynamics in Mammary Branching Morphogenesis.

PubMed

Greenwood, Erin; Wrenn, Emma D; Cheung, Kevin J

2017-02-27

The properties of stem cells that participate in mammary gland branching morphogenesis remain contested. Reporting in Nature, Scheele et al. (2017) establish a model for post-pubertal mammary branching morphogenesis in which position-dependent, lineage-restricted stem cells undergo cell mixing in order to contribute to long-term growth. Copyright © 2017 Elsevier Inc. All rights reserved.

MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis

PubMed Central

Rebustini, Ivan T.; Myers, Christopher; Lassiter, Keyonica S.; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G.; Hoffman, Matthew P.

2009-01-01

Summary Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Importantly, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA-treatment, increasing MT-MMP and pro-proliferative gene expression via β1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA-treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis. PMID:19853562

Melatonin Inhibits Embryonic Salivary Gland Branching Morphogenesis by Regulating Both Epithelial Cell Adhesion and Morphology

PubMed Central

Miura, Jiro; Sakai, Manabu; Uchida, Hitoshi; Nakamura, Wataru; Nohara, Kanji; Maruyama, Yusuke; Hattori, Atsuhiko; Sakai, Takayoshi

2015-01-01

Many organs, including salivary glands, lung, and kidney, are formed by epithelial branching during embryonic development. Branching morphogenesis occurs via either local outgrowths or the formation of clefts that subdivide epithelia into buds. This process is promoted by various factors, but the mechanism of branching morphogenesis is not fully understood. Here we have defined melatonin as a potential negative regulator or “brake” of branching morphogenesis, shown that the levels of it and its receptors decline when branching morphogenesis begins, and identified the process that it regulates. Melatonin has various physiological functions, including circadian rhythm regulation, free-radical scavenging, and gonadal development. Furthermore, melatonin is present in saliva and may have an important physiological role in the oral cavity. In this study, we found that the melatonin receptor is highly expressed on the acinar epithelium of the embryonic submandibular gland. We also found that exogenous melatonin reduces salivary gland size and inhibits branching morphogenesis. We suggest that this inhibition does not depend on changes in either proliferation or apoptosis, but rather relates to changes in epithelial cell adhesion and morphology. In summary, we have demonstrated a novel function of melatonin in organ formation during embryonic development. PMID:25876057

Rac1/RhoA antagonism defines cell-to-cell heterogeneity during epidermal morphogenesis in nematodes

PubMed Central

Ouellette, Marie-Hélène

2016-01-01

The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo. Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells. In these contexts, protrusions adopt lamellipodia or an amoeboid morphology. We propose that lamella formation may reduce tension building at cell–cell junctions during morphogenesis. Cell-autonomous antagonism between these pathways enables cells to switch between Rac1- and RhoA-like morphogenetic programs. This study identifies the first case of cell-to-cell heterogeneity controlled by Rac1/RhoA antagonism during epidermal morphogenesis. PMID:27821782

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

PubMed

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

2015-04-24

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

Interactions between charged residues in the transmembrane segments of the voltage-sensing domain in the hERG channel.

PubMed

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.

Optical extensometer

DOEpatents

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.

Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure.

PubMed

Hamblet, Natasha S; Lijam, Nardos; Ruiz-Lozano, Pilar; Wang, Jianbo; Yang, Yasheng; Luo, Zhenge; Mei, Lin; Chien, Kenneth R; Sussman, Daniel J; Wynshaw-Boris, Anthony

2002-12-01

The murine dishevelled 2 (Dvl2) gene is an ortholog of the Drosophila segment polarity gene Dishevelled, a member of the highly conserved Wingless/Wnt developmental pathway. Dvl2-deficient mice were produced to determine the role of Dvl2 in mammalian development. Mice containing null mutations in Dvl2 present with 50% lethality in both inbred 129S6 and in a hybrid 129S6-NIH Black Swiss background because of severe cardiovascular outflow tract defects, including double outlet right ventricle, transposition of the great arteries and persistent truncus arteriosis. The majority of the surviving Dvl2(-/-) mice were female, suggesting that penetrance was influenced by sex. Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow tract formation. In addition, approximately 90% of Dvl2(-/-) mice have vertebral and rib malformations that affect the proximal as well as the distal parts of the ribs. These skeletal abnormalities were more pronounced in mice deficient for both Dvl1 and Dvl2. Somite differentiation markers used to analyze Dvl2(-/-) and Dvl1(-/-);Dvl2(-/-) mutant embryos revealed mildly aberrant expression of Uncx4.1, delta 1 and myogenin, suggesting defects in somite segmentation. Finally, 2-3% of Dvl2(-/-) embryos displayed thoracic spina bifida, while virtually all Dvl1/2 double mutant embryos displayed craniorachishisis, a completely open neural tube from the midbrain to the tail. Thus, Dvl2 is essential for normal cardiac morphogenesis, somite segmentation and neural tube closure, and there is functional redundancy between Dvl1 and Dvl2 in some phenotypes.

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

PubMed

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

2018-04-18

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

Simple rules for a "simple" nervous system? Molecular and biomathematical approaches to enteric nervous system formation and malformation.

PubMed

Newgreen, Donald F; Dufour, Sylvie; Howard, Marthe J; Landman, Kerry A

2013-10-01

We review morphogenesis of the enteric nervous system from migratory neural crest cells, and defects of this process such as Hirschsprung disease, centering on cell motility and assembly, and cell adhesion and extracellular matrix molecules, along with cell proliferation and growth factors. We then review continuum and agent-based (cellular automata) models with rules of cell movement and logistical proliferation. Both movement and proliferation at the individual cell level are modeled with stochastic components from which stereotyped outcomes emerge at the population level. These models reproduced the wave-like colonization of the intestine by enteric neural crest cells, and several new properties emerged, such as colonization by frontal expansion, which were later confirmed biologically. These models predict a surprising level of clonal heterogeneity both in terms of number and distribution of daughter cells. Biologically, migrating cells form stable chains made up of unstable cells, but this is not seen in the initial model. We outline additional rules for cell differentiation into neurons, axon extension, cell-axon and cell-cell adhesions, chemotaxis and repulsion which can reproduce chain migration. After the migration stage, the cells re-arrange as a network of ganglia. Changes in cell adhesion molecules parallel this, and we describe additional rules based on Steinberg's Differential Adhesion Hypothesis, reflecting changing levels of adhesion in neural crest cells and neurons. This was able to reproduce enteric ganglionation in a model. Mouse mutants with disturbances of enteric nervous system morphogenesis are discussed, and these suggest future refinement of the models. The modeling suggests a relatively simple set of cell behavioral rules could account for complex patterns of morphogenesis. The model has allowed the proposal that Hirschsprung disease is mostly an enteric neural crest cell proliferation defect, not a defect of cell migration. In addition, the model suggests an explanations for zonal and skip segment variants of Hirschsprung disease, and also gives a novel stochastic explanation for the observed discordancy of Hirschsprung disease in identical twins. © 2013 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2016-07-01

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

Surgical Treatment of Laser Induced Eye Injuries

DTIC Science & Technology

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

Oil-spill risk analysis: Cook inlet outer continental shelf lease sale 149. Volume 1. The analysis. Final report

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

PubMed Central

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

A distance measurement between specific sites on the cytoplasmic surface of bovine rhodopsin in rod outer segment disk membranes.

PubMed

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.

PubMed

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.

PubMed

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.

PubMed

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.

PubMed

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

2011-03-01

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

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

PubMed

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

2012-06-01

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

Analysis of in vivo single cell behavior by high throughput, human-in-the-loop segmentation of three-dimensional images.

PubMed

Chiang, Michael; Hallman, Sam; Cinquin, Amanda; de Mochel, Nabora Reyes; Paz, Adrian; Kawauchi, Shimako; Calof, Anne L; Cho, Ken W; Fowlkes, Charless C; Cinquin, Olivier

2015-11-25

Analysis of single cells in their native environment is a powerful method to address key questions in developmental systems biology. Confocal microscopy imaging of intact tissues, followed by automatic image segmentation, provides a means to conduct cytometric studies while at the same time preserving crucial information about the spatial organization of the tissue and morphological features of the cells. This technique is rapidly evolving but is still not in widespread use among research groups that do not specialize in technique development, perhaps in part for lack of tools that automate repetitive tasks while allowing experts to make the best use of their time in injecting their domain-specific knowledge. Here we focus on a well-established stem cell model system, the C. elegans gonad, as well as on two other model systems widely used to study cell fate specification and morphogenesis: the pre-implantation mouse embryo and the developing mouse olfactory epithelium. We report a pipeline that integrates machine-learning-based cell detection, fast human-in-the-loop curation of these detections, and running of active contours seeded from detections to segment cells. The procedure can be bootstrapped by a small number of manual detections, and outperforms alternative pieces of software we benchmarked on C. elegans gonad datasets. Using cell segmentations to quantify fluorescence contents, we report previously-uncharacterized cell behaviors in the model systems we used. We further show how cell morphological features can be used to identify cell cycle phase; this provides a basis for future tools that will streamline cell cycle experiments by minimizing the need for exogenous cell cycle phase labels. High-throughput 3D segmentation makes it possible to extract rich information from images that are routinely acquired by biologists, and provides insights - in particular with respect to the cell cycle - that would be difficult to derive otherwise.

36th Annual David W. Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2015 annual meeting.

PubMed

Gripp, Karen W; Adam, Margaret P; Hudgins, Louanne; Carey, John C

2016-07-01

The 36th Annual David W Smith Workshop on Malformations and Morphogenesis was held on August 14-19, 2015 at the Harbourtowne Conference Center in St. Michaels Maryland. The Workshop, which honors the legacy of David W Smith, brought together over 120 clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis. As is the tradition of the meeting, the Workshop highlighted five themes besides mechanisms of morphogenesis: Rasopathies, Eye Malformations, Therapeutics, Prenatal Diagnosis, and Disorders of Sex Development. This Conference Report includes the abstracts presented at the 2015 Workshop. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Extracellular matrix motion and early morphogenesis

PubMed Central

Loganathan, Rajprasad; Rongish, Brenda J.; Smith, Christopher M.; Filla, Michael B.; Czirok, Andras; Bénazéraf, Bertrand

2016-01-01

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale ‘total’ cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. PMID:27302396

FGF8 coordinates tissue elongation and cell epithelialization during early kidney tubulogenesis

PubMed Central

Atsuta, Yuji; Takahashi, Yoshiko

2015-01-01

When a tubular structure forms during early embryogenesis, tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner. We here demonstrate, using the Wolffian duct (WD) of early chicken embryos, that this coordination is regulated by the expression of FGF8, which shifts posteriorly during body axis elongation. FGF8 acts as a chemoattractant on the leader cells of the elongating WD and prevents them from epithelialization, whereas static (‘rear’) cells that receive progressively less FGF8 undergo epithelialization to form a lumen. Thus, FGF8 acts as a binary switch that distinguishes tubular elongation from lumen formation. The posteriorly shifting FGF8 is also known to regulate somite segmentation, suggesting that multiple types of tissue morphogenesis are coordinately regulated by macroscopic changes in body growth. PMID:26130757

Differentiation of Swine iPSC into Rod Photoreceptors and Their Integration into the Retina

PubMed Central

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

Polycystin-1 Binds Par3/aPKC and Controls Convergent Extension During Renal Tubular Morphogenesis

PubMed Central

Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

2013-01-01

Several organs, including lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintanance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1 (PC-1), a large receptor of unknown function. Here we demonstrate that PC-1 plays an essential role in establishment of correct tubular diameter during nephron development. PC-1 associates with Par3 favoring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a program of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis and in renal cyst formation. Our data define PC-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis. PMID:24153433

Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis

NASA Astrophysics Data System (ADS)

Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

2013-10-01

Several organs, including the lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintenance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1, a large receptor of unknown function. Here we demonstrate that PC-1 has an essential role in the establishment of correct tubular diameter during nephron development. Polycystin-1 associates with Par3 favouring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a programme of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis, and in renal cyst formation. Our data define Polycystin-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis.

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.

Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE?

PubMed

Fossati, Sara Maria; Candiani, Simona; Nödl, Marie-Therese; Maragliano, Luca; Pennuto, Maria; Domingues, Pedro; Benfenati, Fabio; Pestarino, Mario; Zullo, Letizia

2015-08-01

Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non-cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis.

An animal model for Norrie disease (ND): gene targeting of the mouse ND gene.

PubMed

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.

Patterns of muscular strain in the embryonic heart wall.

PubMed

Damon, Brooke J; Rémond, Mathieu C; Bigelow, Michael R; Trusk, Thomas C; Xie, Wenjie; Perucchio, Renato; Sedmera, David; Denslow, Stewart; Thompson, Robert P

2009-06-01

The hypothesis that inner layers of contracting muscular tubes undergo greater strain than concentric outer layers was tested by numerical modeling and by confocal microscopy of strain within the wall of the early chick heart. We modeled the looped heart as a thin muscular shell surrounding an inner layer of sponge-like trabeculae by two methods: calculation within a two-dimensional three-variable lumped model and simulated expansion of a three-dimensional, four-layer mesh of finite elements. Analysis of both models, and correlative microscopy of chamber dimensions, sarcomere spacing, and membrane leaks, indicate a gradient of strain decreasing across the wall from highest strain along inner layers. Prediction of wall thickening during expansion was confirmed by ultrasonography of beating hearts. Degree of stretch determined by radial position may thus contribute to observed patterns of regional myocardial conditioning and slowed proliferation, as well as to the morphogenesis of ventricular trabeculae and conduction fascicles. Developmental Dynamics 238:1535-1546, 2009. (c) 2009 Wiley-Liss, Inc.

An application of a vulnerability index to oil spill modeling in the Gulf of Mexico

USGS Publications Warehouse

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.

Ceramic Cerami Turbine Nozzle

DOEpatents

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.

Displacement coefficients along the inner boundaries of radially cracked ring segments subject to forces and couples

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.

Transition duct system with arcuate ceramic liner for delivering hot-temperature gases in a combustion turbine engine

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

Extracellular matrix motion and early morphogenesis.

PubMed

Loganathan, Rajprasad; Rongish, Brenda J; Smith, Christopher M; Filla, Michael B; Czirok, Andras; Bénazéraf, Bertrand; Little, Charles D

2016-06-15

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale 'total' cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. © 2016. Published by The Company of Biologists Ltd.

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.

SU-E-J-123: Assessing Segmentation Accuracy of Internal Volumes and Sub-Volumes in 4D PET/CT of Lung Tumors Using a Novel 3D Printed Phantom

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.

PubMed

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.

A global sensitivity analysis approach for morphogenesis models.

PubMed

Boas, Sonja E M; Navarro Jimenez, Maria I; Merks, Roeland M H; Blom, Joke G

2015-11-21

Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such 'black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all 'black-box' models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

Extracellular matrix and growth factors in branching morphogenesis

NASA Technical Reports Server (NTRS)

Hardman, P.; Spooner, B. S.

1993-01-01

The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.

Genetic Interaction of Centrosomin and Bazooka in Apical Domain Regulation in Drosophila Photoreceptor

PubMed Central

Chen, Geng; Rogers, Alicia K.; League, Garrett P.; Nam, Sang-Chul

2011-01-01

Background Cell polarity genes including Crumbs (Crb) and Par complexes are essential for controlling photoreceptor morphogenesis. Among the Crb and Par complexes, Bazooka (Baz, Par-3 homolog) acts as a nodal component for other cell polarity proteins. Therefore, finding other genes interacting with Baz will help us to understand the cell polarity genes' role in photoreceptor morphogenesis. Methodology/Principal Findings Here, we have found a genetic interaction between baz and centrosomin (cnn). Cnn is a core protein for centrosome which is a major microtubule-organizing center. We analyzed the effect of the cnn mutation on developing eyes to determine its role in photoreceptor morphogenesis. We found that Cnn is dispensable for retinal differentiation in eye imaginal discs during the larval stage. However, photoreceptors deficient in Cnn display dramatic morphogenesis defects including the mislocalization of Crumbs (Crb) and Bazooka (Baz) during mid-stage pupal eye development, suggesting that Cnn is specifically required for photoreceptor morphogenesis during pupal eye development. This role of Cnn in apical domain modulation was further supported by Cnn's gain-of-function phenotype. Cnn overexpression in photoreceptors caused the expansion of the apical Crb membrane domain, Baz and adherens junctions (AJs). Conclusions/Significance These results strongly suggest that the interaction of Baz and Cnn is essential for apical domain and AJ modulation during photoreceptor morphogenesis, but not for the initial photoreceptor differentiation in the Drosophila photoreceptor. PMID:21253601

Mis-expression of grainyhead-like transcription factors in zebrafish leads to defects in enveloping layer (EVL) integrity, cellular morphogenesis and axial extension.

PubMed

Miles, Lee B; Darido, Charbel; Kaslin, Jan; Heath, Joan K; Jane, Stephen M; Dworkin, Sebastian

2017-12-14

The grainyhead-like (grhl) transcription factors play crucial roles in craniofacial development, epithelial morphogenesis, neural tube closure, and dorso-ventral patterning. By utilising the zebrafish to differentially regulate expression of family members grhl2b and grhl3, we show that both genes regulate epithelial migration, particularly convergence-extension (CE) type movements, during embryogenesis. Genetic deletion of grhl3 via CRISPR/Cas9 results in failure to complete epiboly and pre-gastrulation embryonic rupture, whereas morpholino (MO)-mediated knockdown of grhl3 signalling leads to aberrant neural tube morphogenesis at the midbrain-hindbrain boundary (MHB), a phenotype likely due to a compromised overlying enveloping layer (EVL). Further disruptions of grhl3-dependent pathways (through co-knockdown of grhl3 with target genes spec1 and arhgef19) confirm significant MHB morphogenesis and neural tube closure defects. Concomitant MO-mediated disruption of both grhl2b and grhl3 results in further extensive CE-like defects in body patterning, notochord and somite morphogenesis. Interestingly, over-expression of either grhl2b or grhl3 also leads to numerous phenotypes consistent with disrupted cellular migration during gastrulation, including embryo dorsalisation, axial duplication and impaired neural tube migration leading to cyclopia. Taken together, our study ascribes novel roles to the Grhl family in the context of embryonic development and morphogenesis.

A possible source mechanism of the 1946 Unimak Alaska far-field tsunami, uplift of the mid-slope terrace above a splay fault zone

USGS Publications Warehouse

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.

A Possible Source Mechanism of the 1946 Unimak Alaska Far-Field Tsunami: Uplift of the Mid-Slope Terrace Above a Splay Fault Zone

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.

Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis

PubMed Central

Rodríguez-Fraticelli, Alejo E.; Auzan, Muriel; Alonso, Miguel A.; Bornens, Michel

2012-01-01

Epithelial organ morphogenesis involves sequential acquisition of apicobasal polarity by epithelial cells and development of a functional lumen. In vivo, cells perceive signals from components of the extracellular matrix (ECM), such as laminin and collagens, as well as sense physical conditions, such as matrix stiffness and cell confinement. Alteration of the mechanical properties of the ECM has been shown to promote cell migration and invasion in cancer cells, but the effects on epithelial morphogenesis have not been characterized. We analyzed the effects of cell confinement on lumen morphogenesis using a novel, micropatterned, three-dimensional (3D) Madin-Darby canine kidney cell culture method. We show that cell confinement, by controlling cell spreading, limits peripheral actin contractility and promotes centrosome positioning and lumen initiation after the first cell division. In addition, peripheral actin contractility is mediated by master kinase Par-4/LKB1 via the RhoA–Rho kinase–myosin II pathway, and inhibition of this pathway restores lumen initiation in minimally confined cells. We conclude that cell confinement controls nuclear–centrosomal orientation and lumen initiation during 3D epithelial morphogenesis. PMID:22965908

Wnt/β-Catenin Regulates the Activity of Epiprofin/Sp6, SHH, FGF, and BMP to Coordinate the Stages of Odontogenesis

PubMed Central

Aurrekoetxea, Maitane; Irastorza, Igor; García-Gallastegui, Patricia; Jiménez-Rojo, Lucia; Nakamura, Takashi; Yamada, Yoshihiko; Ibarretxe, Gaskon; Unda, Fernando J.

2016-01-01

Background: We used an in vitro tooth development model to investigate the effects of overactivation of the Wnt/β-catenin pathway during odontogenesis by bromoindirubin oxime reagent (BIO), a specific inhibitor of GSK-3 activity. Results: Overactivating the Wnt/β-catenin pathway at tooth initiation upregulated and ectopically expressed the epithelial markers Sonic Hedgehog (Shh), Epiprofin (Epfn), and Fibroblast growth factor8 (Fgf8), which are involved in the delimitation of odontogenic fields in the oral ectoderm. This result indicated an ectopic extension of the odontogenic potential. During tooth morphogenesis, Fibroblast growth factor4 (Fgf4), Fibroblast growth factor10 (Fgf10), Muscle segment homeobox 1 (Msx-1), Bone Morphogenetic protein 4 (Bmp4), and Dickkopf WNT signaling pathway inhibitor 1 (Dkk-1) were overexpressed in first molars cultured with BIO. Conversely, the expression levels of Wingless integration site 10b (Wnt-10b) and Shh were reduced. Additionally, the odontoblast differentiation markers Nestin and Epfn showed ectopic overexpression in the dental mesenchyme of BIO-treated molars. Moreover, alkaline phosphatase activity increased in the dental mesenchyme, again suggesting aberrant, ectopic mesenchymal cell differentiation. Finally, Bmp4 downregulated Epfn expression during dental morphogenesis. Conclusions: We suggest the presence of a positive feedback loop wherein Epfn and β-catenin activate each other. The balance of the expression of these two molecules is essential for proper tooth development. We propose a possible link between Wnt, Bmp, and Epfn that would critically determine the correct patterning of dental cusps and the differentiation of odontoblasts and ameloblasts. PMID:27066482

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

NASA Astrophysics Data System (ADS)

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

2007-12-01

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

Common and Distinct Capsid and Surface Protein Requirements for Secretion of Complete and Genome-free Hepatitis B Virions.

PubMed

Ning, Xiaojun; Luckenbaugh, Laurie; Liu, Kuancheng; Bruss, Volker; Sureau, Camille; Hu, Jianming

2018-05-09

During the morphogenesis of hepatitis B virus (HBV), an enveloped virus, two types of virions are secreted: (1) a minor population of complete virions containing a mature nucleocapsid with the characteristic, partially double-stranded, relaxed circular DNA genome and (2) a major population containing an empty capsid with no DNA or RNA (empty virions). Secretion of both types of virions requires interactions between the HBV capsid or core protein (HBc) and the viral surface or envelope proteins. We have studied the requirements from both HBc and envelope proteins for empty virion secretion, in comparison with those for secretion of complete virions. Substitutions within the N-terminal domain of HBc that block secretion of DNA-containing virions reduced but did not prevent secretion of empty virions. The HBc C-terminal domain was not essential for empty virion secretion. Among the three viral envelope proteins, the smallest, S, alone was sufficient for empty virion secretion at a basal level. The largest protein, L, essential for complete virion secretion, was not required for, but could stimulate empty virion secretion. Also, substitutions in L that eliminate secretion of complete virions reduced but did not eliminate empty virion secretion. S mutations that block secretion of the hepatitis D virus (HDV), an HBV satellite, did not block secretion of either empty or complete HBV virions. Together, these results indicate that both common and distinct signals on empty capsids vs. mature nucleocapsids interact with the S and L proteins during the formation of complete vs. empty virions. IMPORTANCE Hepatitis B virus (HBV) is a major cause of severe liver diseases including cirrhosis and cancer. In addition to the complete infectious virion particle, which contains an outer envelope layer and an interior capsid that, in turn, encloses a DNA genome, HBV infected cells also secrete non-infectious, incomplete viral particles in large excess over the complete virions. In particular, the empty (or genome-free) virion share with the complete virion the outer envelope and interior capsid but contain no genome. We have carried out a comparative study on the capsid and envelope requirements for the secretion of these two types of virion particles and uncovered both shared and distinct determinants on the capsid and envelope for their secretion. These results provide new information on HBV morphogenesis, and have implications for efforts to develop empty HBV virions as a novel biomarker and a new generation of HBV vaccine. Copyright © 2018 American Society for Microbiology.

Synthetic Morphogenesis.

PubMed

Teague, Brian P; Guye, Patrick; Weiss, Ron

2016-09-01

Throughout biology, function is intimately linked with form. Across scales ranging from subcellular to multiorganismal, the identity and organization of a biological structure's subunits dictate its properties. The field of molecular morphogenesis has traditionally been concerned with describing these links, decoding the molecular mechanisms that give rise to the shape and structure of cells, tissues, organs, and organisms. Recent advances in synthetic biology promise unprecedented control over these molecular mechanisms; this opens the path to not just probing morphogenesis but directing it. This review explores several frontiers in the nascent field of synthetic morphogenesis, including programmable tissues and organs, synthetic biomaterials and programmable matter, and engineering complex morphogenic systems de novo. We will discuss each frontier's objectives, current approaches, constraints and challenges, and future potential. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea.

PubMed

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.

S-net project: Construction of large scale seafloor observatory network for tsunamis and earthquakes in Japan

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

PubMed Central

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

2015-01-01

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

Provenance of sand on the Poverty Bay shelf, the link between source and sink sectors of the Waipaoa River sedimentary system

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.

The Drosophila Extradenticle and Homothorax selector proteins control branchless/FGF expression in mesodermal bridge-cells.

PubMed

Merabet, Samir; Ebner, Andreas; Affolter, Markus

2005-08-01

The stereotyped outgrowth of tubular branches of the Drosophila tracheal system is orchestrated by the local and highly dynamic expression profile of branchless (bnl), which encodes a secreted fibroblast growth factor (FGF)-like molecule. Despite the importance of the spatial and temporal bnl regulation, little is known about the upstream mechanisms that establish its complex expression pattern. Here, we show that the Extradenticle and Homothorax selector proteins control bnl transcription in a single cell per segment, the mesodermal bridge-cell. In addition, we observed that a key determinant of bridge-cell specification, the transcription factor Hunchback, is also required for bnl expression. Therefore, we propose that one of the functions of the bridge-cell is to synthesize and secrete the chemoattractant Bnl. These findings provide a hitherto unknown and interesting link between combinatorial inputs of transcription factors, cell-specific ligand expression and organ morphogenesis.

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

PubMed

Racine, Julie; Joly, Sandrine; Lachapelle, Pierre

2011-08-01

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

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

PubMed

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

2016-12-01

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

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

PubMed

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

2017-09-01

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

Automatic segmentation of the facial nerve and chorda tympani in pediatric CT scans.

PubMed

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.

DTIC Science & Technology

1981-07-01

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

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.

Comparative study of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) as a treatment for retinal dystrophies

PubMed Central

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

Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival.

PubMed

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.

Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival

PubMed Central

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.

Calorimetric Studies of Bovine Rod Outer Segment Disk Membranes Support a Monomeric Unit for Both Rhodopsin and Opsin

PubMed Central

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.

PubMed

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

PubMed Central

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

Reactive oxygen species in the presence of high glucose alter ureteric bud morphogenesis.

PubMed

Zhang, Shao-Ling; Chen, Yun-Wen; Tran, Stella; Chenier, Isabelle; Hébert, Marie-Josée; Ingelfinger, Julie R

2007-07-01

Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal d-glucose (5 mM) or high d-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high d-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as d-mannitol, l-glucose, and 2-deoxy-d-glucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.

A System for Modelling Cell–Cell Interactions during Plant Morphogenesis

PubMed Central

Dupuy, Lionel; Mackenzie, Jonathan; Rudge, Tim; Haseloff, Jim

2008-01-01

Background and aims During the development of multicellular organisms, cells are capable of interacting with each other through a range of biological and physical mechanisms. A description of these networks of cell–cell interactions is essential for an understanding of how cellular activity is co-ordinated in regionalized functional entities such as tissues or organs. The difficulty of experimenting on living tissues has been a major limitation to describing such systems, and computer modelling appears particularly helpful to characterize the behaviour of multicellular systems. The experimental difficulties inherent to the multitude of parallel interactions that underlie cellular morphogenesis have led to the need for computer models. Methods A new generic model of plant cellular morphogenesis is described that expresses interactions amongst cellular entities explicitly: the plant is described as a multi-scale structure, and interactions between distinct entities is established through a topological neighbourhood. Tissues are represented as 2D biphasic systems where the cell wall responds to turgor pressure through a viscous yielding of the cell wall. Key Results This principle was used in the development of the CellModeller software, a generic tool dedicated to the analysis and modelling of plant morphogenesis. The system was applied to three contrasting study cases illustrating genetic, hormonal and mechanical factors involved in plant morphogenesis. Conclusions Plant morphogenesis is fundamentally a cellular process and the CellModeller software, through its underlying generic model, provides an advanced research tool to analyse coupled physical and biological morphogenetic mechanisms. PMID:17921524

Synthesis and morphogenesis of organic and inorganic polymers by means of biominerals and biomimetic materials.

PubMed

Kijima, Misako; Oaki, Yuya; Munekawa, Yurika; Imai, Hiroaki

2013-02-11

We have studied the simultaneous synthesis and morphogenesis of polymer materials with hierarchical structures from nanoscopic to macroscopic scales. The morphologies of the original materials can be replicated to the polymer materials. In general, it is not easy to achieve the simultaneous synthesis and morphogenesis of polymer material even using host materials. In the present work, four biominerals and three biomimetic mesocrystal structures are used as the host materials or templates and polypyrrole, poly(3-hexylthiopehene), and silica were used as the precursors for the simultaneous syntheses and morphogenesis of polymer materials. The host materials with the hierarchical structure possess the nanospace for the incorporation of the monomers. After the incorporation of the monomers, the polymerization reaction proceeds in the nanospace with addition of the initiator agents. Then, the dissolution of the host materials leads to the formation and morphogenesis of the polymer materials. The scheme of the replication can be classified into the three types based on the structures of the host materials (types I-III). The type I template facilitates the hierarchical replication of the whole host material, type II mediates the hierarchical surface replication, and type III induces the formation of the two-dimensional nanosheets. Based on these results, the approach for the coupled synthesis and morphogenesis can be applied to a variety of combinations of the templates and polymer materials. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anatomy-guided joint tissue segmentation and topological correction for 6-month infant brain MRI with risk of autism.

PubMed

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.

Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis

PubMed Central

Cavodeassi, Florencia; Ivanovitch, Kenzo; Wilson, Stephen W.

2013-01-01

During forebrain morphogenesis, there is extensive reorganisation of the cells destined to form the eyes, telencephalon and diencephalon. Little is known about the molecular mechanisms that regulate region-specific behaviours and that maintain the coherence of cell populations undergoing specific morphogenetic processes. In this study, we show that the activity of the Eph/Ephrin signalling pathway maintains segregation between the prospective eyes and adjacent regions of the anterior neural plate during the early stages of forebrain morphogenesis in zebrafish. Several Ephrins and Ephs are expressed in complementary domains in the prospective forebrain and combinatorial abrogation of their activity results in incomplete segregation of the eyes and telencephalon and in defective evagination of the optic vesicles. Conversely, expression of exogenous Ephs or Ephrins in regions of the prospective forebrain where they are not usually expressed changes the adhesion properties of the cells, resulting in segregation to the wrong domain without changing their regional fate. The failure of eye morphogenesis in rx3 mutants is accompanied by a loss of complementary expression of Ephs and Ephrins, suggesting that this pathway is activated downstream of the regional fate specification machinery to establish boundaries between domains undergoing different programmes of morphogenesis. PMID:24026122

Postembryonic development of Antygomonas incomitata (Kinorhyncha: Cyclorhagida).

PubMed

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

2010-07-01

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

The perforating branches of the P1 segment of the posterior cerebral artery.

PubMed

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.

The control of branching morphogenesis

PubMed Central

Iber, Dagmar; Menshykau, Denis

2013-01-01

Many organs of higher organisms are heavily branched structures and arise by an apparently similar process of branching morphogenesis. Yet the regulatory components and local interactions that have been identified differ greatly in these organs. It is an open question whether the regulatory processes work according to a common principle and how far physical and geometrical constraints determine the branching process. Here, we review the known regulatory factors and physical constraints in lung, kidney, pancreas, prostate, mammary gland and salivary gland branching morphogenesis, and describe the models that have been formulated to analyse their impacts. PMID:24004663

Programming Morphogenesis through Systems and Synthetic Biology.

PubMed

Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

2018-04-01

Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Remodeling a tissue: subtraction adds insight.

PubMed

Axelrod, Jeffrey D

2012-11-27

Sculpting a body plan requires both patterning of gene expression and translating that pattern into morphogenesis. Developmental biologists have made remarkable strides in understanding gene expression patterning, but despite a long history of fascination with the mechanics of morphogenesis, knowledge of how patterned gene expression drives the emergence of even simple shapes and forms has grown at a slower pace. The successful merging of approaches from cell biology, developmental biology, imaging, engineering, and mathematical and computational sciences is now accelerating progress toward a fuller and better integrated understanding of the forces shaping morphogenesis.

Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

PubMed

Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

2018-05-16

Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our results suggest that proper control of TGF-β/Smads/CRMP2 signaling pathways is critical for the precise execution of neuronal morphogenesis, whose impairment eventually results in neurodevelopmental disorders. Copyright © 2018 the authors 0270-6474/18/384791-20$15.00/0.

Novel Hg2+-Induced Nephropathy in Rats and Mice Lacking Mrp2: Evidence of Axial Heterogeneity in the Handling of Hg2+ Along the Proximal Tubule

PubMed Central

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

Geology along the Fairweather-Queen Charlotte fault system off southeast Alaska and British Columbia from GLORIA images and seismic-reflection data

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

Interaction of Arrestin with Enolase1 in Photoreceptors

PubMed Central

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.

PubMed

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.

Perithecium morphogenesis in Sordaria macrospora.

PubMed

Lord, Kathryn M; Read, Nick D

2011-04-01

The perithecium of the self-fertile ascomycete Sordaria macrospora provides an excellent model in which to analyse fungal multicellular development. This study provides a detailed analysis of perithecium morphogenesis in the wild type and eight developmental mutants of S. macrospora, using a range of correlative microscopical techniques. Fundamentally, perithecia and other complex multicellular structures produced by fungi arise by hyphal aggregation and adhesion, and these processes are followed by specialization and septation of hyphal compartments within the aggregates. Perithecial morphogenesis can be divided into the ascogonial, protoperithecial, and perithecial stages of development. At least 13 specialized, morphologically distinct cell-types are involved in perithecium morphogenesis, and these fall into three basic classes: hyphae, conglutinate cells and spores. Conglutinate cells arise from hyphal adhesion and certain perithecial hyphae develop from conglutinate cells. Various hypha-conglutinate cell transitions play important roles during the development of the perithecial wall and neck. Copyright © 2010. Published by Elsevier Inc.

Histological features of the gastrointestinal tract of wild Indonesian shortfin eel, Anguilla bicolor bicolor (McClelland, 1844), captured in Peninsular Malaysia.

PubMed

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.

Changes in Inner and Outer Retinal Layer Thicknesses after Vitrectomy for Idiopathic Macular Hole: Implications for Visual Prognosis

PubMed Central

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

In vivo and in vitro heterogeneity of segment length changes in the semimembranosus muscle of the toad

PubMed Central

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

Human Development VI: Supracellular Morphogenesis. The Origin of Biological and Cellular Order

PubMed Central

Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

2006-01-01

Uninterrupted morphogenesis shows the informational potentials of biological organisms. Experimentally disturbed morphogenesis shows the compensational dynamics of the biological informational system, which is the rich informational redundancy. In this paper, we use these data to describe morphogenesis in terms of the development of supracellular levels of the organism, and we define complex epigenesis and supracellular differentiation. We review the phenomena of regeneration and induction of Hydra and amphibians, and the higher animals informational needs for developing their complex nervous systems. We argue, also building on the NO-GO theorem for ontogenesis as chemistry, that the traditional chemical explanations of high-level informational events in ontogenesis, such as transmutation, regeneration, and induction, are insufficient. We analyze the informational dynamics of three embryonic compensatory reactions to different types of disturbances: (1) transmutations of the imaginal discs of insects, (2) regeneration after removal of embryonic tissue, and (3) embryonic induction, where two tissues that normally are separated experimentally are made to influence each other. We describe morphogenesis as a complex bifurcation, and the resulting morphological levels of the organism as organized in a fractal manner and supported by positional information. We suggest that some kind of real nonchemical phenomenon must be taking form in living organisms as an information-carrying dynamic fractal field, causing morhogenesis and supporting the organisms morphology through time. We argue that only such a phenomenon that provides information-directed self-organization to the organism is able to explain the observed dynamic distribution of biological information through morphogenesis and the organism's ability to rejuvenate and heal. PMID:17115082

Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut

PubMed Central

Chung, Mei-I; Nascone-Yoder, Nanette M.; Grover, Stephanie A.; Drysdale, Thomas A.; Wallingford, John B.

2010-01-01

Individual cell shape changes are essential for epithelial morphogenesis. A transcriptional network for epithelial cell shape change is emerging in Drosophila, but this area remains largely unexplored in vertebrates. The distinction is important as so far, key downstream effectors of cell shape change in Drosophila appear not to be conserved. Rather, Shroom3 has emerged as a central effector of epithelial morphogenesis in vertebrates, driving both actin- and microtubule-based cell shape changes. To date, the morphogenetic role of Shroom3 has been explored only in the neural epithelium, so the broad expression of this gene raises two important questions: what are the requirements for Shroom3 in non-neural tissues and what factors control Shroom3 transcription? Here, we show in Xenopus that Shroom3 is essential for cell shape changes and morphogenesis in the developing vertebrate gut and that Shroom3 transcription in the gut requires the Pitx1 transcription factor. Moreover, we show that Pitx proteins directly activate Shroom3 transcription, and we identify Pitx-responsive regulatory elements in the genomic DNA upstream of Shroom3. Finally, we show that ectopic expression of Pitx proteins is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change. These data demonstrate new breadth to the requirements for Shroom3 in morphogenesis, and they also provide a cell-biological basis for the role of Pitx transcription factors in morphogenesis. More generally, these results provide a foundation for deciphering the transcriptional network that underlies epithelial cell shape change in developing vertebrates. PMID:20332151

Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis

PubMed Central

Hielscher, Abigail; Ellis, Kim; Qiu, Connie; Porterfield, Josh; Gerecht, Sharon

2016-01-01

The extracellular matrix (ECM) has been demonstrated to facilitate angiogenesis. In particular, fibronectin has been documented to activate endothelial cells, resulting in their transition from a quiescent state to an active state in which the cells exhibit enhanced migration and proliferation. The goal of this study is to examine the role of polymerized fibronectin during vascular tubulogenesis using a 3 dimensional (3D) cell-derived de-cellularized matrix. A fibronectin-rich 3D de-cellularized ECM was used as a scaffold to study vascular morphogenesis of endothelial cells (ECs). Confocal analyses of several matrix proteins reveal high intra- and extra-cellular deposition of fibronectin in formed vascular structures. Using a small peptide inhibitor of fibronectin polymerization, we demonstrate that inhibition of fibronectin fibrillogenesis in ECs cultured atop de-cellularized ECM resulted in decreased vascular morphogenesis. Further, immunofluorescence and ultrastructural analyses reveal decreased expression of stromal matrix proteins in the absence of polymerized fibronectin with high co-localization of matrix proteins found in association with polymerized fibronectin. Evaluating vascular kinetics, live cell imaging showed that migration, migration velocity, and mean square displacement, are disrupted in structures grown in the absence of polymerized fibronectin. Additionally, vascular organization failed to occur in the absence of a polymerized fibronectin matrix. Consistent with these observations, we tested vascular morphogenesis following the disruption of EC adhesion to polymerized fibronectin, demonstrating that block of integrins α5β1 and αvβ3, abrogated vascular morphogenesis. Overall, fibronectin deposition in a 3D cell-derived de-cellularized ECM appears to be imperative for matrix assembly and vascular morphogenesis. PMID:26811931

Optimization of Soft Tissue Management, Spacer Design, and Grafting Strategies for Large Segmental Bone Defects using the Chronic Caprine Tibial Defect Model

DTIC Science & Technology

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

The laryngeal primordium and epithelial lamina. A new interpretation.

PubMed Central

Sañudo, J R; Domenech-Mateu, J M

1990-01-01

The laryngeal primordium is present in both the laryngotracheal sulcus (LTS) and the primitive pulmonary sac (PPS). Its early period of development may be subdivided into two phases. The first phase (Stage 11) is represented by what is traditionally referred to as the LTS, located directly beneath the PP4 on the ventral wall of the foregut (primary segment), and by the PPS which is situated at its caudal end. The LTS will represent the primordium of the upper or membranous infraglottic cavity region; whereas the PPS, will give rise not only to the bronchial tree, but also to the primordium of the trachea and the lower or cartilaginous region of the infraglottic cavity. The second phase (Stages 13 and 14) is distinguished by the cranial growth of the LTS above the PP4 and therefore by its absorption into the floor of the primitive pharynx in the mesobranchial area (secondary segment), which will develop into the primordium of the vestibule of the larynx. Similarly, we observed that in the development of the laryngeal cavity there are two temporally and spatially separate epithelial structures: the epithelial septum and the epithelial lamina. In this respect we differ from other authors who are of the opinion that there is a single structure (the epithelial lamina). The epithelial septum is a primary structure responsible for the final configuration of the LTS, as it contributes to the development of the lower end of the primary segment of the LTS and also to the creation of the secondary segment. The epithelial lamina is a secondary structure which appears inside the LTS as a result of pressure exerted by the mesenchyme on its lateral walls, without having any effect on the morphogenesis of the LTS. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:2081706

The eggshell of the cherry fly Rhagoletis cerasi.

PubMed

Mouzaki, D G; Margaritis, L H

1991-01-01

One of the major pests in Greek cherry orchards is the cherry fly Rhagoletis cerasi (Diptera: Tephritidae). In order to complete our comparative work on the chorion assembly of other representatives of the fruit flies (e.g. Ceratitis capitata and Dacus oleae) we studied eggshell morphogenesis in the cherry fly. The oocyte is surrounded by several distinct layers which are produced during choriogenesis. The eggshell consists of the vitelline membrane, a fibrous layer of possible water-proofing function, an innermost chorionic layer, endochorionic and exochorionic layers. The endochorion shows a branched configuration with irregular cavities, and the exochorion consists of inner and outer layers for better embryo protection. At the anterior region of the follicle, the hexagonal borders of the follicle cells are created by endochorionic material, covered by both inner and outer exochorion. This area resembles the D. melanogaster chorionic appendages and therefore can serve for plastron respiration. The structural results support the phylogenetic relationships among the tephritids (Rhagoletis is closer to Ceratitis than Dacus). The presence of peroxidase in the endochorion, detected by diaminobenzidine, is consistent with the eggshell hardening at the end of choriogenesis, following the same pattern with the other fruit flies studied so far. Two major chorionic proteins are found both in R. cerasi and in C. capitata and therefore general conclusions can be drawn from this study, concerning the pattern of choriogenesis, which all dipteran insects follow, in order to create a resistant and functional eggshell, and the high conservation of the proteinaceous components of the chorion among species in the order.

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.

PubMed

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.

Early events in Agrobacterium-mediated genetic transformation of citrus explants.

PubMed

Peña, Leandro; Pérez, Rosa M; Cervera, Magdalena; Juárez, José A; Navarro, Luis

2004-07-01

Genetic transformation of plants relies on two independent but concurrent processes: integration of foreign DNA into plant cells and regeneration of whole plants from these transformed cells. Cell competence for regeneration and for transformation does not always fall into the same cell type/developmental stage, and this is one of the main causes of the so-called recalcitrance for transformation of certain plant species. In this study, a detailed examination of the first steps of morphogenesis from citrus explants after co-cultivation with Agrobacterium tumefaciens was performed, and an investigation into which cells and tissues are competent for regeneration and transformation was carried out. Moreover, the role of phytohormones in the co-cultivation medium as possible enhancers of gene transfer was also studied. A highly responsive citrus genotype and well-established culture conditions were used to perform a histological analysis of morphogenesis and cell competence for transformation after co-cultivation of citrus epicotyl segments with A. tumefaciens. In addition, the role of phytohormones as transformation enhancers was investigated by flow cytometry. It is demonstrated that cells competent for transformation are located in the newly formed callus growing from the cambial ring. Conditions conducive to further development of this callus, such as treatment of explants in a medium rich in auxins, resulted in a more pronounced formation of cambial callus and a slower shoot regeneration process, both in Agrobacterium-inoculated and non-inoculated explants. Furthermore, co- cultivation in a medium rich in auxins caused a significant increase in the rate of actively dividing cells in S-phase, the stage in which cells are more prone to integrate foreign DNA. Use of proper co-cultivation medium and conditions led to a higher number of stably transformed cells and to an increase in the final number of regenerated transgenic plants.

The Congested-like Tracheae Gene of Drosophila Melanogaster Encodes a Member of the Mitochondrial Carrier Family Required for Gas-Filling of the Tracheal System and Expansion of the Wings after Eclosion

PubMed Central

Hartenstein, K.; Sinha, P.; Mishra, A.; Schenkel, H.; Torok, I.; Mechler, B. M.

1997-01-01

A recessive semi-lethal mutation resulting from the insertion of a P-lacW transposon at the cytological position 23A on the polytene chromosomes of Drosophila melanogaster was found to affect the unfolding and expansion of the wings resulting in a loss of venation and a marked decrease in their size. Lethality was polyphasic with numerous animals dying during early larval development and displaying apparently collapsed tracheal trees. The gene was therefore designated as congested-like tracheae, or colt. The colt mutation resulted from the insertion of a P-lacW transposon within the coding region of a 1.4-kb transcript. Wild-type function was restored by inducing a precise excision of the P-lacW transposon, while a deletion of the colt locus, produced by imprecise excision of the P element, showed a phenotype similar to that of the original P insert. The colt gene consists of a single exon and encodes a protein of 306 amino acids made of three tandem repeats, each characterized by two predicted transmembrane segments and a loop domain. The COLT protein shares extensive homology with proteins in the mitochondrial carrier family and particularly with the DIF-1 protein of Caenorhabditis elegans, which has been shown to be maternally required for embryonic tissue differentiation. Our analysis revealed that zygotic colt function is dispensable for normal embryonic morphogenesis but is required for gas-filling of the tracheal system at hatching time of the embryo and for normal epithelial morphogenesis of the wings. PMID:9409834

Multicellular Models of Morphogenesis

EPA Science Inventory

EPA’s Virtual Embryo project (v-Embryo™), in collaboration with developers of CompuCell3D, aims to create computer models of morphogenesis that can be used to address the effects of chemical perturbation on embryo development at the cellular level. Such computational (in silico) ...

Morphogenesis in Plants: Modeling the Shoot Apical Meristem, and Possible Applications

NASA Technical Reports Server (NTRS)

Mjolsness, Eric; Gor, Victoria; Meyerowitz, Elliot; Mann, Tobias

1998-01-01

A key determinant of overall morphogenesis in flowering plants such as Arabidopsis thaliana is the shoot apical meristem (growing tip of a shoot). Gene regulation networks can be used to model this system. We exhibit a very preliminary two-dimensional model including gene regulation and intercellular signaling, but omitting cell division and dynamical geometry. The model can be trained to have three stable regions of gene expression corresponding to the central zone, peripheral zone, and rib meristem. We also discuss a space-engineering motivation for studying and controlling the morphogenesis of plants using such computational models.

The Ron Receptor Tyrosine Kinase Negatively Regulates Mammary Gland Branching Morphogenesis

PubMed Central

Meyer, Sara E.; Zinser, Glendon M.; Stuart, William D.; Pathrose, Peterson; Waltz, Susan E.

2009-01-01

The Ron receptor tyrosine kinase is expressed in normal breast tissue and is overexpressed in approximately 50% of human breast cancers. Despite the recent studies on Ron in breast cancer, nothing is known about the importance of this protein during breast development. To investigate the functional significance of Ron in the normal mammary gland, we compared mammary gland development in wild-type mice to mice containing a targeted ablation of the tyrosine kinase (TK) signaling domain of Ron (TK−/−). Mammary glands from RonTK−/− mice exhibited accelerated pubertal development including significantly increased ductal extension and branching morphogenesis. While circulating levels of estrogen, progesterone, and overall rates of epithelial cell turnover were unchanged, significant increases in phosphorylated MAPK, which predominantly localized to the epithelium, were associated with increased branching morphogenesis. Additionally, purified RonTK−/− epithelial cells cultured ex vivo exhibited enhanced branching morphogenesis, which was reduced upon MAPK inhibition. Microarray analysis of pubertal RonTK−/− glands revealed 393 genes temporally impacted by Ron expression with significant changes observed in signaling networks regulating development, morphogenesis, differentiation, cell motility, and adhesion. In total, these studies represent the first evidence of a role for the Ron receptor tyrosine kinase as a critical negative regulator of mammary development. PMID:19576199

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.

Role of Geologic Framework, Paleotopography, Sediment Supply, and Human Modification in the Evolutionary Development of the Northeastern North Carolina Barrier Island System

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.

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

Transition duct system with straight ceramic liner for delivering hot-temperature gases in a combustion turbine engine

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

A Curriculum Vitae of Teeth: Evolution, Generation, Regeneration

PubMed Central

Koussoulakou, Despina S.; Margaritis, Lukas H.; Koussoulakos, Stauros L.

2009-01-01

The ancestor of recent vertebrate teeth was a tooth-like structure on the outer body surface of jawless fishes. Over the course of 500,000,000 years of evolution, many of those structures migrated into the mouth cavity. In addition, the total number of teeth per dentition generally decreased and teeth morphological complexity increased. Teeth form mainly on the jaws within the mouth cavity through mutual, delicate interactions between dental epithelium and oral ectomesenchyme. These interactions involve spatially restricted expression of several, teeth-related genes and the secretion of various transcription and signaling factors. Congenital disturbances in tooth formation, acquired dental diseases and odontogenic tumors affect millions of people and rank human oral pathology as the second most frequent clinical problem. On the basis of substantial experimental evidence and advances in bioengineering, many scientists strongly believe that a deep knowledge of the evolutionary relationships and the cellular and molecular mechanisms regulating the morphogenesis of a given tooth in its natural position, in vivo, will be useful in the near future to prevent and treat teeth pathologies and malformations and for in vitro and in vivo teeth tissue regeneration. PMID:19266065

Fgf Signaling is Required for Photoreceptor Maintenance in the Adult Zebrafish Retina

PubMed Central

Hochmann, Sarah; Kaslin, Jan; Hans, Stefan; Weber, Anke; Machate, Anja; Geffarth, Michaela; Funk, Richard H. W.; Brand, Michael

2012-01-01

Fibroblast growth factors (Fgf) are secreted signaling molecules that have mitogenic, patterning, neurotrophic and angiogenic properties. Their importance during embryonic development in patterning and morphogenesis of the vertebrate eye is well known, but less is known about the role of Fgfs in the adult vertebrate retina. To address Fgf function in adult retina, we determined the spatial distribution of components of the Fgf signaling pathway in the adult zebrafish retina. We detected differential expression of Fgf receptors, ligands and downstream Fgf targets within specific retinal layers. Furthermore, we blocked Fgf signaling in the retina, by expressing a dominant negative variant of Fgf receptor 1 conditionally in transgenic animals. After blocking Fgf signaling we observe a fast and progressive photoreceptor degeneration and disorganization of retinal tissue, coupled with cell death in the outer nuclear layer. Following the degeneration of photoreceptors, a profound regeneration response is triggered that starts with proliferation in the inner nuclear layer. Ultimately, rod and cone photoreceptors are regenerated completely. Our study reveals the requirement of Fgf signaling to maintain photoreceptors and for proliferation during regeneration in the adult zebrafish retina. PMID:22291943

Establishment of the Vertebrate Germ Layers.

PubMed

Tseng, Wei-Chia; Munisha, Mumingjiang; Gutierrez, Juan B; Dougan, Scott T

2017-01-01

The process of germ layer formation is a universal feature of animal development. The germ layers separate the cells that produce the internal organs and tissues from those that produce the nervous system and outer tissues. Their discovery in the early nineteenth century transformed embryology from a purely descriptive field into a rigorous scientific discipline, in which hypotheses could be tested by observation and experimentation. By systematically addressing the questions of how the germ layers are formed and how they generate overall body plan, scientists have made fundamental contributions to the fields of evolution, cell signaling, morphogenesis, and stem cell biology. At each step, this work was advanced by the development of innovative methods of observing cell behavior in vivo and in culture. Here, we take an historical approach to describe our current understanding of vertebrate germ layer formation as it relates to the long-standing questions of developmental biology. By comparing how germ layers form in distantly related vertebrate species, we find that highly conserved molecular pathways can be adapted to perform the same function in dramatically different embryonic environments.

Stress and strain analysis of contractions during ramp distension in partially obstructed guinea pig jejunal segments

PubMed Central

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

Integrated profiling of three dimensional cell culture models and 3D microscopy

PubMed Central

Bilgin, Cemal Cagatay; Kim, Sun; Leung, Elle; Chang, Hang; Parvin, Bahram

2013-01-01

Motivation: Our goal is to develop a screening platform for quantitative profiling of colony organizations in 3D cell culture models. The 3D cell culture models, which are also imaged in 3D, are functional assays that mimic the in vivo characteristics of the tissue architecture more faithfully than the 2D cultures. However, they also introduce significant computational challenges, with the main barriers being the effects of growth conditions, fixations and inherent complexities in segmentation that need to be resolved in the 3D volume. Results: A segmentation strategy has been developed to delineate each nucleus in a colony that overcomes (i) the effects of growth conditions, (ii) variations in chromatin distribution and (iii) ambiguities formed by perceptual boundaries from adjacent nuclei. The strategy uses a cascade of geometric filters that are insensitive to spatial non-uniformity and partitions a clump of nuclei based on the grouping of points of maximum curvature at the interface of two neighboring nuclei. These points of maximum curvature are clustered together based on their coplanarity and proximity to define dissecting planes that separate the touching nuclei. The proposed curvature-based partitioning method is validated with both synthetic and real data, and is shown to have a superior performance against previous techniques. Validation and sensitivity analysis are coupled with the experimental design that includes a non-transformed cell line and three tumorigenic cell lines, which covers a wide range of phenotypic diversity in breast cancer. Colony profiling, derived from nuclear segmentation, reveals distinct indices for the morphogenesis of each cell line. Availability: All software are developed in ITK/VTK and are available at https://vision.lbl.gov/Software/3DMorphometry. Contact: b_parvin@lbl.gov or hchang@lbl.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24045773

Adenosine kinase modulates root gravitropism and cap morphogenesis in Arabidopsis.

PubMed

Young, Li-Sen; Harrison, Benjamin R; Narayana Murthy, U M; Moffatt, Barbara A; Gilroy, Simon; Masson, Patrick H

2006-10-01

Adenosine kinase (ADK) is a key enzyme that regulates intra- and extracellular levels of adenosine, thereby modulating methyltransferase reactions, production of polyamines and secondary compounds, and cell signaling in animals. Unfortunately, little is known about ADK's contribution to the regulation of plant growth and development. Here, we show that ADK is a modulator of root cap morphogenesis and gravitropism. Upon gravistimulation, soluble ADK levels and activity increase in the root tip. Mutation in one of two Arabidopsis (Arabidopsis thaliana) ADK genes, ADK1, results in cap morphogenesis defects, along with alterations in root sensitivity to gravistimulation and slower kinetics of root gravitropic curvature. The kinetics defect can be partially rescued by adding spermine to the growth medium, whereas the defects in cap morphogenesis and gravitropic sensitivity cannot. The root morphogenesis and gravitropism defects of adk1-1 are accompanied by altered expression of the PIN3 auxin efflux facilitator in the cap and decreased expression of the auxin-responsive DR5-GUS reporter. Furthermore, PIN3 fails to relocalize to the bottom membrane of statocytes upon gravistimulation. Consequently, adk1-1 roots cannot develop a lateral auxin gradient across the cap, necessary for the curvature response. Interestingly, adk1-1 does not affect gravity-induced cytoplasmic alkalinization of the root statocytes, suggesting either that ADK1 functions between cytoplasmic alkalinization and PIN3 relocalization in a linear pathway or that the pH and PIN3-relocalization responses to gravistimulation belong to distinct branches of the pathway. Our data are consistent with a role for ADK and the S-adenosyl-L-methionine pathway in the control of root gravitropism and cap morphogenesis.

Adenosine Kinase Modulates Root Gravitropism and Cap Morphogenesis in Arabidopsis1[W][OA

PubMed Central

Young, Li-Sen; Harrison, Benjamin R.; U.M., Narayana Murthy; Moffatt, Barbara A.; Gilroy, Simon; Masson, Patrick H.

2006-01-01

Adenosine kinase (ADK) is a key enzyme that regulates intra- and extracellular levels of adenosine, thereby modulating methyltransferase reactions, production of polyamines and secondary compounds, and cell signaling in animals. Unfortunately, little is known about ADK's contribution to the regulation of plant growth and development. Here, we show that ADK is a modulator of root cap morphogenesis and gravitropism. Upon gravistimulation, soluble ADK levels and activity increase in the root tip. Mutation in one of two Arabidopsis (Arabidopsis thaliana) ADK genes, ADK1, results in cap morphogenesis defects, along with alterations in root sensitivity to gravistimulation and slower kinetics of root gravitropic curvature. The kinetics defect can be partially rescued by adding spermine to the growth medium, whereas the defects in cap morphogenesis and gravitropic sensitivity cannot. The root morphogenesis and gravitropism defects of adk1-1 are accompanied by altered expression of the PIN3 auxin efflux facilitator in the cap and decreased expression of the auxin-responsive DR5-GUS reporter. Furthermore, PIN3 fails to relocalize to the bottom membrane of statocytes upon gravistimulation. Consequently, adk1-1 roots cannot develop a lateral auxin gradient across the cap, necessary for the curvature response. Interestingly, adk1-1 does not affect gravity-induced cytoplasmic alkalinization of the root statocytes, suggesting either that ADK1 functions between cytoplasmic alkalinization and PIN3 relocalization in a linear pathway or that the pH and PIN3-relocalization responses to gravistimulation belong to distinct branches of the pathway. Our data are consistent with a role for ADK and the S-adenosyl-l-methionine pathway in the control of root gravitropism and cap morphogenesis. PMID:16891550

Expression Pattern of the Pro-apoptotic Gene PAR-4 During the Morphogenesis of MCF-10A Human Mammary Epithelial Cells.

PubMed

de Bessa Garcia, Simone A; Pereira, Michelly C; Nagai, Maria A

2010-12-21

The histological organization of the mammary gland involves a spatial interaction of epithelial and myoepithelial cells with the specialized basement membrane (BM), composed of extra-cellular matrix (ECM) proteins, which is disrupted during the tumorigenic process. The interactions between mammary epithelial cells and ECM components play a major role in mammary gland branching morphogenesis. Critical signals for mammary epithelial cell proliferation, differentiation, and survival are provided by the ECM proteins. Three-dimensional (3D) cell culture was developed to establish a system that simulates several features of the breast epithelium in vivo; 3D cell culture of the spontaneously immortalized cell line, MCF10A, is a well-established model system to study breast epithelial cell biology and morphogenesis. Mammary epithelial cells grown in 3D form spheroids, acquire apicobasal polarization, and form lumens that resemble acini structures, processes that involve cell death. Using this system, we evaluated the expression of the pro-apoptotic gene PAWR (PKC apoptosis WT1 regulator; also named PAR-4, prostate apoptosis response-4) by immunofluorescence and quantitative real time PCR (qPCR). A time-dependent increase in PAR-4 mRNA expression was found during the process of MCF10A acinar morphogenesis. Confocal microscopy analysis also showed that PAR-4 protein was highly expressed in the MCF10A cells inside the acini structure. During the morphogenesis of MCF10A cells in 3D cell culture, the cells within the lumen showed caspase-3 activation, indicating apoptotic activity. PAR-4 was only partially co-expressed with activated caspase-3 on these cells. Our results provide evidence, for the first time, that PAR-4 is differentially expressed during the process of MCF10A acinar morphogenesis.

Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids.

PubMed

Linch, Mark; Sanz-Garcia, Marta; Rosse, Carine; Riou, Philippe; Peel, Nick; Madsen, Chris D; Sahai, Erik; Downward, Julian; Khwaja, Asim; Dillon, Christian; Roffey, Jon; Cameron, Angus J M; Parker, Peter J

2014-02-01

Protein kinase C iota (PKCι), a serine/threonine kinase required for cell polarity, proliferation and migration, is commonly up- or downregulated in cancer. PKCι is a human oncogene but whether this is related to its role in cell polarity and what repertoire of oncogenes acts in concert with PKCι is not known. We developed a panel of candidate oncogene expressing Madin-Darby canine kidney (MDCK) cells and demonstrated that H-Ras, ErbB2 and phosphatidylinositol 3-kinase transformation led to non-polar spheroid morphogenesis (dysplasia), whereas MDCK spheroids expressing c-Raf or v-Src were largely polarized. We show that small interfering RNA (siRNA)-targeting PKCι decreased the size of all spheroids tested and partially reversed the aberrant polarity phenotype in H-Ras and ErbB2 spheroids only. This indicates distinct requirements for PKCι and moreover that different thresholds of PKCι activity are required for these phenotypes. By manipulating PKCι function using mutant constructs, siRNA depletion or chemical inhibition, we have demonstrated that PKCι is required for polarization of parental MDCK epithelial cysts in a 3D matrix and that there is a threshold of PKCι activity above and below which, disorganized epithelial morphogenesis results. Furthermore, treatment with a novel PKCι inhibitor, CRT0066854, was able to restore polarized morphogenesis in the dysplastic H-Ras spheroids. These results show that tightly regulated PKCι is required for normal-polarized morphogenesis in mammalian cells and that H-Ras and ErbB2 cooperate with PKCι for loss of polarization and dysplasia. The identification of a PKCι inhibitor that can restore polarized morphogenesis has implications for the treatment of Ras and ErbB2 driven malignancies.

Sucrose Synthase Is Associated with the Cell Wall of Tobacco Pollen Tubes1[W

PubMed Central

Persia, Diana; Cai, Giampiero; Del Casino, Cecilia; Faleri, Claudia; Willemse, Michiel T.M.; Cresti, Mauro

2008-01-01

Sucrose synthase (Sus; EC 2.4.1.13) is a key enzyme of sucrose metabolism in plant cells, providing carbon for respiration and for the synthesis of cell wall polymers and starch. Since Sus is important for plant cell growth, insights into its structure, localization, and features are useful for defining the relationships between nutrients, growth, and cell morphogenesis. We used the pollen tube of tobacco (Nicotiana tabacum) as a cell model to characterize the main features of Sus with regard to cell growth and cell wall synthesis. Apart from its role during sexual reproduction, the pollen tube is a typical tip-growing cell, and the proper construction of its cell wall is essential for correct shaping and direction of growth. The outer cell wall layer of pollen tubes consists of pectins, but the inner layer is composed of cellulose and callose; both polymers require metabolic precursors in the form of UDP-glucose, which is synthesized by Sus. We identified an 88-kD polypeptide in the soluble, plasma membrane and Golgi fraction of pollen tubes. The protein was also found in association with the cell wall. After purification, the protein showed an enzyme activity similar to that of maize (Zea mays) Sus. Distribution of Sus was affected by brefeldin A and depended on the nutrition status of the pollen tube, because an absence of metabolic sugars in the growth medium caused Sus to distribute differently during tube elongation. Analysis by bidimensional electrophoresis indicated that Sus exists as two isoforms, one of which is phosphorylated and more abundant in the cytoplasm and cell wall and the other of which is not phosphorylated and is specific to the plasma membrane. Results indicate that the protein has a role in the construction of the extracellular matrix and thus in the morphogenesis of pollen tubes. PMID:18344420

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

PubMed

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

1998-10-19

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

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

PubMed Central

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

2012-01-01

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

Accurate quantification of local changes for carotid arteries in 3D ultrasound images using convex optimization-based deformable registration

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.

Strain measurements and the potential for a great subduction earthquake off the coast of washington.

PubMed

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.

Band-notched spiral antenna

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.

High-resolution optical coherence tomography, autofluorescence, and infrared reflectance imaging in Sjögren reticular dystrophy.

PubMed

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.

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

PubMed Central

1991-01-01

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