RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations

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Li eJiang

2014-04-01

Full Text Available RNA interference (RNAi knockdown is an efficacious therapeutic strategy for silencing genes causative for dominant retinal dystrophies. To test this, we used self-complementary (sc AAV2/8 vector to develop an RNAi-based therapy in two dominant retinal degeneration mouse models. The allele-specific model expresses transgenic bovine GCAP1(Y99C establishing a rapid RP-like phenotype, whereas the nonallele-specific model expresses mouse GCAP1(L151F producing a slowly progressing cone/rod dystrophy (CORD. The late onset GCAP1(L151F-CORD mimics the dystrophy observed in human GCAP1-CORD patients. Subretinal injection of scAAV2/8 carrying shRNA expression cassettes specific for bovine or mouse GCAP1 showed strong expression at one week post-injection. In both allele-specific (GCAP1(Y99C-RP and nonallele-specific (GCAP1(L151F-CORD models of dominant retinal dystrophy, RNAi-mediated gene silencing enhanced photoreceptor survival, delayed onset of degeneration and improved visual function. Such results provide a proof of concept toward effective RNAi-based gene therapy mediated by scAAV2/8 for dominant retinal disease based on GCAP1 mutation. Further, nonallele-specific RNAi knockdown of GCAP1 may prove generally applicable toward the rescue of any human GCAP1-based dominant cone-rod dystrophy.

Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

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Klevering, B Jeroen; Blankenagel, Anita; Maugeri, Alessandra; Cremers, Frans P M; Hoyng, Carel B; Rohrschneider, Klaus

2002-06-01

To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were reviewed after molecular analysis revealed mutations in the ABCA4 gene. In two of the patients both the photopic and scotopic electroretinogram were nonrecordable. In the remainder, the photopic cone b-wave amplitudes appeared to be more seriously affected than the scotopic rod b-wave amplitudes. Although the clinical presentation was heterogeneous, all patients experienced visual loss early in life, impaired color vision, and a central scotoma. Fundoscopy revealed evidence of early-onset maculopathy, sometimes accompanied by involvement of the retinal periphery in the later stages of the disease. Mutations in the ABCA4 gene are the pathologic cause of the CRD-like dystrophy in these patients, and the resultant clinical pictures are complex and heterogeneous. Given this wide clinical spectrum of CRD-like phenotypes associated with ABCA4 mutations, detailed clinical subclassifications are difficult and may not be very useful.

Alteration of rod and cone function in children with Usher syndrome.

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Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Stone, Edwin S; Andréasson, Sten

2011-01-01

To evaluate the retinal function, with emphasis on phenotype and rate of progression, in infants and children with different genotypes of Usher syndrome. Fourteen children (2-10 years of age) with retinitis pigmentosa and hearing impairment were examined with full-field electroretinography (ERG) during general anesthesia, ophthalmologic examination, and genetic analysis. Five children were repeatedly examined (follow-up 5-10 years) with full-field ERG under local anesthesia and in 2 children multifocal ERG and optical coherence tomography (OCT) were performed. These results were compared to full-field ERG data from 58 children without retinal eye disorder. Six children were genotyped as Usher 1B, 2A, and 3A. Full-field ERG demonstrated early alterations corresponding to a rod-cone dystrophy in all children. A remaining rod function could be verified in the majority of the children up to 4 years of age. After 4 years of age, there was a further deterioration of the rod function; the progress was severe in Usher types 1 and 2 and moderate in Usher type 3. In all children, the cone function was moderately reduced, in a few cases almost normal. The results from the 58 children without retinal disorder confirm that full-field ERG during general anesthesia is reliable. Multifocal ERG confirmed a preserved central cone function and in OCT there were discrete structural alterations. Full-field ERG during general anesthesia in children with Usher syndrome demonstrates variable phenotypes and different degrees in rate of progression during childhood.

Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses.

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Johnson, Jerry E; Perkins, Guy A; Giddabasappa, Anand; Chaney, Shawntay; Xiao, Weimin; White, Andrew D; Brown, Joshua M; Waggoner, Jenna; Ellisman, Mark H; Fox, Donald A

2007-06-15

stained for PMCA, whereas the larger cone pedicles preferentially stained for NCX1 at their active zones and PMCA near their mitochondria. EM and ET revealed that mitochondria in rod spherules and cone pedicles differed markedly in their number, location, size, volume, and total cristae surface area, and cristae junction diameter. Rod spherules had one large ovoid mitochondrion located near its active zone, whereas cone pedicles averaged five medium-sized mitochondria clustered far from their active zones. Most spherules had one ribbon synapse, whereas pedicles contained numerous ribbon synapses. Fluo-3 imaging studies revealed that during darkness rod spherules maintained a lower [Ca2+] than cone pedicles, whereas during light adaptation pedicles rapidly lowered their [Ca2+] below that observed in spherules. These findings indicate that ATP demand and mitochondrial ATP production are greater in cone pedicles than rod spherules. Rod spherules employ high affinity/low turnover PMCA and their mitochondrion to maintain a relatively low [Ca2+] in darkness, which increases their sensitivity and signal-to-noise ratio. In contrast, cone pedicles utilize low affinity/high turnover NCX to rapidly lower their high [Ca2+] during light adaptation, which increases their response kinetics. Spatiotemporal fluo-3-Ca2+ imaging results support our immunocytochemical results. The clustering of cone pedicle mitochondria likely provides increased protection from Ca2+ overload and permeability transition. In summary, these novel studies reveal that several integrated cellular and subcellular components interact to regulate ATP and Ca2+ dynamics in rod and cone synaptic terminals. These results should provide a greater understanding of in vivo photoreceptor synaptic terminal exocytosis/endocytosis, Ca2+ overload and therapies for retinal degenerations.

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

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Nikopoulos, Konstantinos; Farinelli, Pietro; Giangreco, Basilio; Tsika, Chrysanthi; Royer-Bertrand, Beryl; Mbefo, Martial K; Bedoni, Nicola; Kjellström, Ulrika; El Zaoui, Ikram; Di Gioia, Silvio Alessandro; Balzano, Sara; Cisarova, Katarina; Messina, Andrea; Decembrini, Sarah; Plainis, Sotiris; Blazaki, Styliani V; Khan, Muhammad Imran; Micheal, Shazia; Boldt, Karsten; Ueffing, Marius; Moulin, Alexandre P; Cremers, Frans P M; Roepman, Ronald; Arsenijevic, Yvan; Tsilimbaris, Miltiadis K; Andréasson, Sten; Rivolta, Carlo

2016-09-01

Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa

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Clérin Emmanuelle

2011-12-01

Full Text Available Abstract Background Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. Methods An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. Results The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. Conclusion The automated

℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa.

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Clérin, Emmanuelle; Wicker, Nicolas; Mohand-Saïd, Saddek; Poch, Olivier; Sahel, José-Alain; Léveillard, Thierry

2011-12-20

Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs) as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. The automated platform ℮-conome used here for retinal disease is a tool that

Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function.

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Nishiguchi, Koji M; Friedman, James S; Sandberg, Michael A; Swaroop, Anand; Berson, Eliot L; Dryja, Thaddeus P

2004-12-21

Mice lacking the transcription factor Nrl have no rod photoreceptors and an increased number of short-wavelength-sensitive cones. Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa; however, the phenotype associated with the loss of NRL function in humans has not been reported. We identified two siblings who carried two allelic mutations: a predicted null allele (L75fs) and a missense mutation (L160P) altering a highly conserved residue in the domain involved in DNA-binding-site recognition. In vitro luciferase reporter assays demonstrated that the NRL-L160P mutant had severely reduced transcriptional activity compared with the WT NRL protein, consistent with a severe loss of function. The affected patients had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short-wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium (clumped pigmentary retinal degeneration). Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in NRL.

Correlated cone noise decreases rod signal contributions to the post-receptoral pathways.

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Hathibelagal, Amithavikram R; Feigl, Beatrix; Zele, Andrew J

2018-04-01

This study investigated how invisible extrinsic temporal white noise that correlates with the activity of one of the three [magnocellular (MC), parvocellular (PC), or koniocellular (KC)] post-receptoral pathways alters mesopic rod signaling. A four-primary photostimulator provided independent control of the rod and three cone photoreceptor excitations. The rod contributions to the three post-receptoral pathways were estimated by perceptually matching a 20% contrast rod pulse by independently varying the LMS (MC pathway), +L-M (PC pathway), and S-cone (KC pathway) excitations. We show that extrinsic cone noise caused a predominant decrease in the overall magnitude and ratio of the rod contributions to each pathway. Thus, the relative cone activity in the post-receptoral pathways determines the relative mesopic rod inputs to each pathway.

Clinical Course, Genetic Etiology, and Visual Outcome in Cone and Cone-Rod Dystrophy

NARCIS (Netherlands)

Thiadens, Alberta A. H. J.; Phan, T. My Lan; Zekveld-Vroon, Renate C.; Leroy, Bart P.; van den Born, L. Ingeborgh; Hoyng, Carel B.; Klaver, Caroline C. W.; Roosing, Susanne; Pott, Jan-Willem R.; van Schooneveld, Mary J.; van Moll-Ramirez, Norka; van Genderen, Maria M.; Boon, Camiel J. F.; den Hollander, Anneke I.; Bergen, Arthur A. B.; De Baere, Elfride; Cremers, Frans P. M.; Lotery, Andrew J.

Objective: To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD). Design: Clinic-based, longitudinal, multicenter study. Participants: Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N =

Genetics Home Reference: cone-rod dystrophy

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... common cause of autosomal recessive cone-rod dystrophy , accounting for 30 to 60 percent of cases. At ... dystrophy play essential roles in the structure and function of specialized light receptor cells (photoreceptors) in the ...

Ultrastructural and ERG findings in progressive rod-cone dystrophy in a litter of Labrador retrievers.

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Raitta, C; Kommonen, B; Ulshafer, R; Karhunen, U

1991-02-01

Early ultrastructural findings of a progressive photoreceptor dystrophy and corresponding ERG findings are reported in 3 Labrador Retrievers from a litter of 7 pups bred from 2 dogs clinically and electroretinographically affected with generalized progressive retinal dystrophy. The pups were euthanized at 5, 11 and 15 months post partum. The most prominent ultrastructural finding was photoreceptor dystrophy. At 5 months the outer nuclear layer (ONL) consisted of 8-10 layers and seemed reduced in thickness, pyknotic nuclei were seen in this layer. The receptor outer segments (OS) were short and swollen. Some disorientation of OS discs occurred. In the 11-months specimen 7-8 ONL layers were identified. Overall thinning of the neuro-retina had occurred and fewer receptors compared to the 5-months specimen were present. By 15 months the ONL was further reduced to about 4 layers. Enlarged internuclear spaces were present in the ONL as well as around inner segments (IS). Phagocytic cells were frequent among remains of OS. The pigment epithelium appeared normal. The dark adapted ERG b-wave amplitudes and photopic 30 Hz flicker responses were low in comparison to controls of the same breed, and decreased with age. The condition represents a progressive rod-cone dystrophy which shares similarities with primary receptor dystrophy in man such as retinitis pigmentosa.

Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision.

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Seeliger, Mathias W; Brombas, Arne; Weiler, Reto; Humphries, Peter; Knop, Gabriel; Tanimoto, Naoyuki; Müller, Frank

2011-11-08

Retinal photoreceptors permit visual perception over a wide range of lighting conditions. Rods work best in dim, and cones in bright environments, with considerable functional overlap at intermediate (mesopic) light levels. At many sites in the outer and inner retina where rod and cone signals interact, gap junctions, particularly those containing Connexin36, have been identified. However, little is known about the dynamic processes associated with the convergence of rod and cone system signals into ON- and OFF-pathways. Here we show that proper cone vision under mesopic conditions requires rapid adaptational feedback modulation of rod output via hyperpolarization-activated and cyclic nucleotide-gated channels 1. When these channels are absent, sustained rod responses following bright light exposure saturate the retinal network, resulting in a loss of downstream cone signalling. By specific genetic and pharmacological ablation of key signal processing components, regular cone signalling can be restored, thereby identifying the sites involved in functional rod-cone interactions.

Molecular and phenotypic analysis of a family with autosomal recessive cone-rod dystrophy and Stargardt disease.

NARCIS (Netherlands)

Ijzer, Suzanne; Born, L.I. van den; Zonneveld, M.N.; Lopez, I.; Ayyagari, R.; Teye-Botchway, L.; Mota-Vieira, L.; Cremers, F.P.M.; Koenekoop, R.K.

2007-01-01

PURPOSE: To identify the causative gene mutations in three siblings with severe progressive autosomal recessive cone-rod dystrophy (arCRD) and their fifth paternal cousin with Stargardt disease (STGD1) and to specify the phenotypes. METHODS: We evaluated eight sibs of one family, three family

NMNAT1 variants cause cone and cone-rod dystrophy.

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Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

2018-03-01

Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

Restoration of vision in the pde6β-deficient dog, a large animal model of rod-cone dystrophy.

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Petit, Lolita; Lhériteau, Elsa; Weber, Michel; Le Meur, Guylène; Deschamps, Jack-Yves; Provost, Nathalie; Mendes-Madeira, Alexandra; Libeau, Lyse; Guihal, Caroline; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

2012-11-01

Defects in the β subunit of rod cGMP phosphodiesterase 6 (PDE6β) are associated with autosomal recessive retinitis pigmentosa (RP), a childhood blinding disease with early retinal degeneration and vision loss. To date, there is no treatment for this pathology. The aim of this preclinical study was to test recombinant adeno-associated virus (AAV)-mediated gene addition therapy in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model of naturally occurring PDE6β deficiency that strongly resembles the human pathology. A total of eight rcd1 dogs were injected subretinally with AAV2/5RK.cpde6β (n = 4) or AAV2/8RK.cpde6β (n = 4). In vivo and post-mortem morphological analysis showed a significant preservation of the retinal structure in transduced areas of both AAV2/5RK.cpde6β- and AAV2/8RK.cpde6β-treated retinas. Moreover, substantial rod-derived electroretinography (ERG) signals were recorded as soon as 1 month postinjection (35% of normal eyes) and remained stable for at least 18 months (the duration of the study) in treated eyes. Rod-responses were undetectable in untreated contralateral eyes. Most importantly, dim-light vision was restored in all treated rcd1 dogs. These results demonstrate for the first time that gene therapy effectively restores long-term retinal function and vision in a large animal model of autosomal recessive rod-cone dystrophy, and provide great promise for human treatment.

Identification of a Novel Homozygous Nonsense Mutation Confirms the Implication of GNAT1 in Rod-Cone Dystrophy.

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Cécile Méjécase

Full Text Available GNAT1, encoding the transducin subunit Gα, is an important element of the phototransduction cascade. Mutations in this gene have been associated with autosomal dominant and autosomal recessive congenital stationary night blindness. Recently, a homozygous truncating GNAT1 mutation was identified in a patient with late-onset rod-cone dystrophy. After exclusion of mutations in genes underlying progressive inherited retinal disorders, by targeted next generation sequencing, a 32 year-old male sporadic case with severe rod-cone dystrophy and his unaffected parents were investigated by whole exome sequencing. This led to the identification of a homozygous nonsense variant, c.963C>A p.(Cys321* in GNAT1, which was confirmed by Sanger sequencing. The mother was heterozygous for this variant whereas the variant was absent in the father. c.963C>A p.(Cys321* is predicted to produce a shorter protein that lacks critical sites for the phototransduction cascade. Our work confirms that the phenotype and the mode of inheritance associated with GNAT1 variants can vary from autosomal dominant, autosomal recessive congenital stationary night blindness to autosomal recessive rod-cone dystrophy.

Cone visual pigments are present in gecko rod cells.

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Kojima, D; Okano, T; Fukada, Y; Shichida, Y; Yoshizawa, T; Ebrey, T G

1992-08-01

The Tokay gecko (Gekko gekko), a nocturnal lizard, has two kinds of visual pigments, P467 and P521. In spite of the pure-rod morphology of the photoreceptor cells, the biochemical properties of P521 and P467 resemble those of iodopsin (the chicken red-sensitive cone visual pigment) and rhodopsin, respectively. We have found that the amino acid sequence of P521 deduced from the cDNA was very similar to that of iodopsin. In addition, P467 has the highest homology with the chicken green-sensitive cone visual pigment, although it also has a relatively high homology with rhodopsins. These results give additional strength to the transmutation theory of Walls [Walls, G. L. (1934) Am. J. Ophthalmol. 17, 892-915], who proposed that the rod-shaped photoreceptor cells of lizards have been derived from ancestral cone-like photoreceptors. Apparently amino acid sequences of visual pigments are less changeable than the morphology of the photoreceptor cells in the course of evolution.

Pushing the limits of photoreception in twilight conditions: The rod-like cone retina of the deep-sea pearlsides

KAUST Repository

Busserolles, Fanny de

2017-11-09

Most vertebrates have a duplex retina comprising two photoreceptor types, rods for dim-light (scotopic) vision and cones for bright-light (photopic) and color vision. However, deep-sea fishes are only active in dim-light conditions; hence, most species have lost their cones in favor of a simplex retina composed exclusively of rods. Although the pearlsides, Maurolicus spp., have such a pure rod retina, their behavior is at odds with this simplex visual system. Contrary to other deep-sea fishes, pearlsides are mostly active during dusk and dawn close to the surface, where light levels are intermediate (twilight or mesopic) and require the use of both rod and cone photoreceptors. This study elucidates this paradox by demonstrating that the pearlside retina does not have rod photoreceptors only; instead, it is composed almost exclusively of transmuted cone photoreceptors. These transmuted cells combine the morphological characteristics of a rod photoreceptor with a cone opsin and a cone phototransduction cascade to form a unique photoreceptor type, a rod-like cone, specifically tuned to the light conditions of the pearlsides\\' habitat (blue-shifted light at mesopic intensities). Combining properties of both rods and cones into a single cell type, instead of using two photoreceptor types that do not function at their full potential under mesopic conditions, is likely to be the most efficient and economical solution to optimize visual performance. These results challenge the standing paradigm of the function and evolution of the vertebrate duplex retina and emphasize the need for a more comprehensive evaluation of visual systems in general.

Pushing the limits of photoreception in twilight conditions: The rod-like cone retina of the deep-sea pearlsides

KAUST Repository

Busserolles, Fanny de; Cortesi, Fabio; Helvik, Jon Vidar; Davies, Wayne I. L.; Templin, Rachel M.; Sullivan, Robert K. P.; Michell, Craig T.; Mountford, Jessica K.; Collin, Shaun P.; Irigoien, Xabier; Kaartvedt, Stein; Marshall, Justin

2017-01-01

retina does not have rod photoreceptors only; instead, it is composed almost exclusively of transmuted cone photoreceptors. These transmuted cells combine the morphological characteristics of a rod photoreceptor with a cone opsin and a cone

Declines in arrestin and rhodopsin in the macula with progression of age-related macular degeneration.

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Ethen, Cheryl M; Feng, Xiao; Olsen, Timothy W; Ferrington, Deborah A

2005-03-01

Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.

Rod and cone interactions in the retina [version 1; referees: 4 approved

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Gordon Fain

2018-05-01

Full Text Available We have long known that rod and cone signals interact within the retina and can even contribute to color vision, but the extent of these influences has remained unclear. New results with more powerful methods of RNA expression profiling, specific cell labeling, and single-cell recording have provided greater clarity and are showing that rod and cone signals can mix at virtually every level of signal processing. These interactions influence the integration of retinal signals and make an important contribution to visual perception.

NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP).

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Schorderet, Daniel F; Escher, Pascal

2009-11-01

NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients is night blindness, rudimental or absent rod function, and hyperfunction of the "blue" S-cones. A single p.G56R mutation is inherited in a dominant manner and causes retinitis pigmentosa (RP). We have established a new locus-specific database for NR2E3 (www.LOVD.nl/eye), containing all reported mutations, polymorphisms, and unclassified sequence variants, including novel ones. A high proportion of mutations are located in the evolutionarily-conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) of NR2E3. Based on homology modeling of these NR2E3 domains, we propose a structural localization of mutated residues. The high variability of clinical phenotypes observed in patients affected by NR2E3-linked retinal degenerations may be caused by different disease mechanisms, including absence of DNA-binding, altered interactions with transcriptional coregulators, and differential activity of modifier genes.

Further delineation of spondylometaphyseal dysplasia with cone-rod dystrophy

NARCIS (Netherlands)

Sousa, Sérgio B.; Russell-Eggitt, Isabelle; Hall, Christine; Hall, Bryan D.; Hennekam, Raoul C. M.

2008-01-01

There are several entities that combine a skeletal dysplasia with a retinal dystrophy. Recently, another possibly autosomal recessive entity was added to this group characterized by a specific spondylometaphyseal dysplasia and a cone-rod dystrophy, without other significant impairments. The entity

Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

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Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

2015-01-01

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307–316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod–cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone–rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. PMID:25324231

Progress in light cone physics

International Nuclear Information System (INIS)

Preparata, G.

1973-01-01

A very brief review is given of the progress made in the physics of the light cone in the past year. Included are the light cone expansion, gauge invariance and the consequences of precocious scaling near threshold, the light cone description of the muon pair experiment, light cone expansions, and the assessment and exploitation of analyticity properties in both mass and energy of light cone amplitudes. (U.S.)

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

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

2015-04-01

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

Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa.

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Petit, Lolita; Ma, Shan; Cipi, Joris; Cheng, Shun-Yun; Zieger, Marina; Hay, Nissim; Punzo, Claudio

2018-05-29

Aerobic glycolysis accounts for ∼80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis. In contrast, cones adapt without increased mitochondrial number but require HK2 to adapt to metabolic stress conditions such as those encountered in retinitis pigmentosa, where the loss of rods causes a nutrient shortage in cones. The data support a model where aerobic glycolysis in PRs is not a necessity but rather a metabolic choice that maximizes PR function and adaptability to nutrient stress conditions. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Cone photopigment in older subjects: decreased optical density in early age-related macular degeneration

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Elsner, Ann E.; Burns, Stephen A.; Weiter, John J.

2002-01-01

We measured changes to cone photoreceptors in patients with early age-related macular degeneration. The data of 53 patients were compared with normative data for color matching measurements of long- and middle-wavelength-sensitive cones in the central macula. A four-parameter model quantified cone photopigment optical density and kinetics. Cone photopigment optical density was on average less for the patients than for normal subjects and was uncorrelated with visual acuity. More light was needed to reduce the photopigment density by 50% in the steady state for patients. These results imply that cone photopigment optical density is reduced by factors other than slowed kinetics.

Necrotic enlargement of cone photoreceptor cells and the release of high-mobility group box-1 in retinitis pigmentosa

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Murakami, Y; Ikeda, Y; Nakatake, S; Tachibana, T; Fujiwara, K; Yoshida, N; Notomi, S; Nakao, S; Hisatomi, T; Miller, J W; Vavvas, DG; Sonoda, KH; Ishibashi, T

2015-01-01

Retinitis pigmentosa (RP) refers to a group of inherited retinal degenerations resulting form rod and cone photoreceptor cell death. The rod cell death due to deleterious genetic mutations has been shown to occur mainly through apoptosis, whereas the mechanisms and features of the secondary cone cell death have not been fully elucidated. Our previous study showed that the cone cell death in rd10 mice, an animal model of RP, involves necrotic features and is partly mediated by the receptor interacting protein kinase. However, the relevancy of necrotic cone cell death in human RP patients remains unknown. In the present study, we showed that dying cone cells in rd10 mice exhibited cellular enlargement, along with necrotic changes such as cellular swelling and mitochondrial rupture. In human eyes, live imaging of cone cells by adaptive optics scanning laser ophthalmoscopy revealed significantly increased percentages of enlarged cone cells in the RP patients compared with the control subjects. The vitreous of the RP patients contained significantly higher levels of high-mobility group box-1, which is released extracellularly associated with necrotic cell death. These findings suggest that necrotic enlargement of cone cells is involved in the process of cone degeneration, and that necrosis may be a novel target to prevent or delay the loss of cone-mediated central vision in RP. PMID:27551484

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

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

2015-01-01

Importance Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy. Observations Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1. PMID:26247787

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

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Sharif, Ali Sakawa

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

Moderate Light-Induced Degeneration of Rod Photoreceptors with Delayed Transducin Translocation in shaker1 Mice

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Zallocchi, Marisa; Wang, Wei-Min; Delimont, Duane; Cosgrove, Dominic

2011-01-01

Purpose. Usher syndrome is characterized by congenital deafness associated with retinitis pigmentosa (RP). Mutations in the myosin VIIa gene (MYO7A) cause a common and severe subtype of Usher syndrome (USH1B). Shaker1 mice have mutant MYO7A. They are deaf and have vestibular dysfunction but do not develop photoreceptor degeneration. The goal of this study was to investigate abnormalities of photoreceptors in shaker1 mice. Methods. Immunocytochemistry and hydroethidine-based detection of intracellular superoxide production were used. Photoreceptor cell densities under various conditions of light/dark exposures were evaluated. Results. In shaker1 mice, the rod transducin translocation is delayed because of a shift of its light activation threshold to a higher level. Even moderate light exposure can induce oxidative damage and significant rod degeneration in shaker1 mice. Shaker1 mice reared under a moderate light/dark cycle develop severe retinal degeneration in less than 6 months. Conclusions. These findings show that, contrary to earlier studies, shaker1 mice possess a robust retinal phenotype that may link to defective rod protein translocation. Importantly, USH1B animal models are likely vulnerable to light-induced photoreceptor damage, even under moderate light. PMID:21447681

[Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

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Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

2017-02-10

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

Negative electroretinograms in pericentral pigmentary retinal degeneration.

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Hotta, Kazuki; Kondo, Mineo; Nakamura, Makoto; Hotta, Junko; Terasaki, Hiroko; Miyake, Yozo; Hida, Tetsuo

2006-01-01

The clinical presentation and electrophysiological findings are described of three consecutive cases with pericentral pigmentary retinal degeneration. The responses to bright flashes after dark adaptation showed negative waveform shape in all cases. Rod responses were strongly reduced compared with cone responses. Cone electroretinograms elicited by long-duration stimuli showed greater loss of the on-response than the off-response. The ratio of the on-response amplitude to off-response amplitude of these patients (0.52 +/- 0.12; mean +/- SD, n = 6) was significantly smaller than that of normal subject (0.83 +/- 0.21; mean +/- SD, n = 8) (Mann-Whitney U-test, P retinal function, especially in transmission between photoreceptors and depolarizing bipolar cells.

Multiple rod–cone and cone–rod photoreceptor transmutations in snakes: Evidence from visual opsin gene expression

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Simoe, Bruno F; Sampaio, Filipa L.; Loew, Ellis R.; Sanders, Kate L.; Fisher, Robert N.; Hart, Nathan S.; Hunt, David M.; Partridge, Julian C.; Gower, David J.

2016-01-01

In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor ‘transmutation’. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels.

Visual function in patients with cone-rod dystrophy (CRD) associated with mutations in the ABCA4(ABCR) gene.

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Birch, D G; Peters, A Y; Locke, K L; Spencer, R; Megarity, C F; Travis, G H

2001-12-01

Mutations in the ABCA4(ABCR) gene cause autosomal recessive Stargardt disease (STGD). ABCR mutations were identified in patients with cone-rod dystrophy (CRD) and retinitis pigmentosa (RP) by direct sequencing of all 50 exons in 40 patients. Of 10 patients with RP, one contained two ABCR mutations suggesting a compound heterozygote. This patient had a characteristic fundus appearance with attenuated vessels, pale disks and bone-spicule pigmentation. Rod electroretinograms (ERGs) were non-detectable, cone ERGs were greatly reduced in amplitude and delayed in implicit time, and visual fields were constricted to 10 degrees diameter. Eleven of 30 (37%) patients with CRD had mutations in ABCR. In general, these patients showed reduced but detectable rod ERG responses, reduced and delayed cone responses, and poor visual acuity. Rod photoresponses to high intensity flashes were of reduced maximum amplitude but showed normal values for the gain of phototransduction. Most CRD patients with mutations in ABCR showed delayed recovery of sensitivity (dark adaptation) following exposure to bright light. Pupils were also significantly smaller in these patients compared to controls at 30 min following light exposure, consistent with a persistent 'equivalent light' background due to the accumulation of a tentatively identified 'noisy' photoproduct. Copyright 2001 Academic Press.

An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy.

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Eidinger, Osnat; Leibu, Rina; Newman, Hadas; Rizel, Leah; Perlman, Ido; Ben-Yosef, Tamar

2015-01-01

To investigate the genetic basis for autosomal recessive cone-rod dystrophy (CRD) in a consanguineous Israeli Jewish family. Patients underwent a detailed ophthalmic evaluation, including eye examination, visual field testing, optical coherence tomography (OCT), and electrophysiological tests, electroretinography (ERG) and visual evoked potential (VEP). Genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array was performed to identify homozygous regions shared among two of the affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico and in vitro analyses were used to predict the effect of the identified mutation on splicing. The affected family members are three siblings who have various degrees of progressive visual deterioration, glare, color vision abnormalities, and night vision difficulties. Visual field tests revealed central scotomas of different extension. Cone and rod ERG responses were reduced, with cones more severely affected. Homozygosity mapping revealed several homozygous intervals shared among two of the affected individuals. One included the PROM1 gene. Sequence analysis of the 26 coding exons of PROM1 in one affected individual revealed no mutations in the coding sequence or in intronic splice sites. However, in intron 21, proximate to the intron-exon junction, we observed a homozygous 10 bp deletion between positions -26 and -17 (c.2281-26_-17del). The deletion was linked to a known SNP, c.2281-6C>G. The deletion cosegregated with the disease in the family, and was not detected in public databases or in 101 ethnically-matched control individuals. In silico analysis predicted that this deletion would lead to altered intron 21 splicing. Bioinformatic analysis predicted that a recognition site for the SRSF2 splicing factor is located within the deleted sequence. The in vitro splicing assay demonstrated that c.2281-26_-17del leads to complete exon 22 skipping. A novel

Digoxin-induced retinal degeneration depends on rhodopsin.

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Landfried, Britta; Samardzija, Marijana; Barben, Maya; Schori, Christian; Klee, Katrin; Storti, Federica; Grimm, Christian

2017-03-16

Na,K-ATPases are energy consuming ion pumps that are required for maintaining ion homeostasis in most cells. In the retina, Na,K-ATPases are especially important to sustain the dark current in photoreceptor cells needed for rapid hyperpolarization of rods and cones in light. Cardiac glycosides like digoxin inhibit the activity of Na,K-ATPases by targeting their catalytic alpha subunits. This leads to a disturbed ion balance, which can affect cellular function and survival. Here we show that the treatment of wild-type mice with digoxin leads to severe retinal degeneration and loss of vision. Digoxin induced cell death specifically in photoreceptor cells with no or only minor effects in other retinal cell types. Photoreceptor-specific cytotoxicity depended on the presence of bleachable rhodopsin. Photoreceptors of Rpe65 knockouts, which have no measurable rhodopsin and photoreceptors of Rpe65 R91W mice that have treatment. Similarly, cones in the all-cone retina of Nrl knockout mice were also not affected. Digoxin induced expression of several genes involved in stress signaling and inflammation. It also activated proteins such as ERK1/2, AKT, STAT1, STAT3 and CASP1 during a period of up to 10 days after treatment. Activation of signaling genes and proteins, as well as the dependency on bleachable rhodopsin resembles mechanisms of light-induced photoreceptor degeneration. Digoxin-mediated photoreceptor cell death may thus be used as an inducible model system to study molecular mechanisms of retinal degeneration.

Vitamin A and Vision.

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Saari, John C

2016-01-01

Visual systems detect light by monitoring the effect of photoisomerization of a chromophore on the release of a neurotransmitter from sensory neurons, known as rod and cone photoreceptor cells in vertebrate retina. In all known visual systems, the chromophore is 11-cis-retinal complexed with a protein, called opsin, and photoisomerization produces all-trans-retinal. In mammals, regeneration of 11-cis-retinal following photoisomerization occurs by a thermally driven isomerization reaction. Additional reactions are required during regeneration to protect cells from the toxicity of aldehyde forms of vitamin A that are essential to the visual process. Photochemical and phototransduction reactions in rods and cones are identical; however, reactions of the rod and cone visual pigment regeneration cycles differ, and perplexingly, rod and cone regeneration cycles appear to use different mechanisms to overcome the energy barrier involved in converting all-trans- to 11-cis-retinoid. Abnormal processing of all-trans-retinal in the rod regeneration cycle leads to retinal degeneration, suggesting that excessive amounts of the retinoid itself or its derivatives are toxic. This line of reasoning led to the development of various approaches to modifying the activity of the rod visual cycle as a possible therapeutic approach to delay or prevent retinal degeneration in inherited retinal diseases and perhaps in the dry form of macular degeneration (geographic atrophy). In spite of great progress in understanding the functioning of rod and cone regeneration cycles at a molecular level, resolution of a number of remaining puzzling issues will offer insight into the amelioration of several blinding retinal diseases.

Cone-rod dystrophy and amelogenesis imperfecta (Jalili syndrome): phenotypes and environs.

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Jalili, I K

2010-11-01

To report a new phenotype with additional data on the oculo-dental syndrome of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) caused by mutations on CNNM4, a metal transporter, with linkage at achromatopsia locus 2q11 (Jalili syndrome). Three siblings aged 5, 6, and 10 years from a six-generation Arab family in Gaza City underwent full systemic, ophthalmic, and dental examinations, investigations and detailed genealogy. Subjects presented at early childhood with visual impairment and abnormal dentition together with photophobia and fine nystagmus increasing under photopic conditions, in the presence of normal fundi. Electrophysiologically, photopic flicker responses were impaired; scotopic responses were extinguished at the age of 10 years. Anterior open bite accompanied AI in all siblings. The syndrome formed 83% of CRD cases in the Gaza Strip, which has a prevalence of 1 : 10,000. On the basis of clinical features and electrophysiology, two phenotypes exist: an infancy onset form with progressive macular lesion and an early childhood onset form with normal fundi. More prevalent than previously thought, Jalili syndrome presents a model of the effect of different mutations of the same genetic defect, observations of the same phenotype at different stages of the natural history of the disease, and the influence of epigenetic and tissue-specific factors as causes of phenotypic variability. The paper calls for action to tackle consanguinity in endogamous communities, addresses the possible role of high fluoride levels in groundwater as a trigger for genetic mutations, and the use of red-tinted filter in cone disorders.

Synaptic Remodeling Generates Synchronous Oscillations in the Degenerated Outer Mouse Retina

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Wadood eHaq

2014-09-01

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

Dietary supplement enriched in antioxidants and omega-3 protects from progressive light-induced retinal degeneration.

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Ramchani-Ben Othman, Khaoula; Cercy, Christine; Amri, Mohamed; Doly, Michel; Ranchon-Cole, Isabelle

2015-01-01

In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG) followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD). For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA), 142% for docosapentaenoic acid (DPA) and 19% for docosahexaenoic acid (DHA) and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration.

Dietary supplement enriched in antioxidants and omega-3 protects from progressive light-induced retinal degeneration.

Directory of Open Access Journals (Sweden)

Khaoula Ramchani-Ben Othman

Full Text Available In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD. For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA, 142% for docosapentaenoic acid (DPA and 19% for docosahexaenoic acid (DHA and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration.

Progression of Fatty Muscle Degeneration in Atraumatic Rotator Cuff Tears.

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Hebert-Davies, Jonah; Teefey, Sharlene A; Steger-May, Karen; Chamberlain, Aaron M; Middleton, William; Robinson, Kathryn; Yamaguchi, Ken; Keener, Jay D

2017-05-17

The purpose of this prospective study was to examine the progression of fatty muscle degeneration over time in asymptomatic shoulders with degenerative rotator cuff tears. Subjects with an asymptomatic rotator cuff tear in 1 shoulder and pain due to rotator cuff disease in the contralateral shoulder were enrolled in a prospective cohort. Subjects were followed annually with shoulder ultrasonography, which evaluated tear size, location, and fatty muscle degeneration. Tears that were either full-thickness at enrollment or progressed to a full-thickness defect during follow-up were examined. A minimum follow-up of 2 years was necessary for eligibility. One hundred and fifty-six shoulders with full-thickness rotator cuff tears were potentially eligible. Seventy shoulders had measurable fatty muscle degeneration of at least 1 rotator cuff muscle at some time point. Patients with fatty muscle degeneration in the shoulder were older than those without degeneration (mean, 65.8 years [95% confidence interval (CI), 64.0 to 67.6 years] compared with 61.0 years [95% CI, 59.1 to 62.9 years]; p tears at baseline was larger in shoulders with degeneration than in shoulders that did not develop degeneration (13 and 10 mm wide, respectively, and 13 and 10 mm long; p Tears with fatty muscle degeneration were more likely to have enlarged during follow-up than were tears that never developed muscle degeneration (79% compared with 58%; odds ratio, 2.64 [95% CI, 1.29 to 5.39]; p muscle degeneration occurred more frequently in shoulders with tears that had enlarged (43%; 45 of 105) than in shoulders with tears that had not enlarged (20%; 10 of 51; p tears with enlargement and progression of muscle degeneration were more likely to extend into the anterior supraspinatus than were those without progression (53% and 17%, respectively; p tear size (p = 0.56). The median time from tear enlargement to progression of fatty muscle degeneration was 1.0 year (range, -2.0 to 6.9 years) for the

Association of a homozygous nonsense mutation in the ABCA4 (ABCR) gene with cone-rod dystrophy phenotype in an Italian family.

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Simonelli, Francesca; Testa, Francesco; Zernant, Jana; Nesti, Anna; Rossi, Settimio; Rinaldi, Ernesto; Allikmets, Rando

2004-01-01

Genetic variation in the ABCA4 (ABCR) gene has been associated with several distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), retinitis pigmentosa (RP) and age-related macular degeneration. The current model of genotype/phenotype association suggests that patients harboring deleterious mutations in both ABCR alleles would develop RP-like retinal pathology. Here we describe ABCA4-associated phenotypes, including a proband with a homozygous nonsense mutation in a family from Southern Italy. The proband had been originally diagnosed with STGD. Ophthalmologic examination included kinetic perimetry, electrophysiological studies and fluorescein angiography. DNA of the affected individual and family members was analyzed for variants in all 50 exons of the ABCA4 gene by screening on the ABCR400 microarray. A homozygous nonsense mutation 2971G>T (G991X) was detected in a patient initially diagnosed with STGD based on funduscopic evidence, including bull's eye depigmentation of the fovea and flecks at the posterior pole extending to the mid-peripheral retina. Since this novel nucleotide substitution results in a truncated, nonfunctional, ABCA4 protein, the patient was examined in-depth for the severity of the disease phenotype. Indeed, subsequent electrophysiological studies determined severely reduced cone amplitude as compared to the rod amplitude, suggesting the diagnosis of CRD. ABCR400 microarray is an efficient tool for determining causal genetic variation, including new mutations. A homozygous protein-truncating mutation in ABCA4 can cause a phenotype ranging from STGD to CRD as diagnosed at an early stage of the disease. Only a combination of comprehensive genotype/phenotype correlation studies will determine the proper diagnosis and prognosis of ABCA4-associated pathology. Copyright 2004 S. Karger AG, Basel

[ERG diagnosis and differential diagnosis: results of examination over 6 years].

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Stemeyer, G; Stähli, P

1996-05-01

This study reviews the patient material first from the point of view of referral diagnosis. Secondly, we focus on difficulties in selective differential diagnoses. 1501 patients underwent electroretinographic (ERG) testing from 1989 to 1994, amounting to 1815 ERG recordings, including follow-up examinations. The technique applied is full-field, single flash ERG with selective stimulation of the rod- and of the cone-systems. In 3.8% (57 cases) the ERG was performed under general anesthesia in outpatients. Tapetoretinal degenerations, toxic retinal side effects, inflammatory disease and ocular trauma represented, in this order, the major groups of referral diagnoses aside from unclear visual loss. The documentation or the exclusion of tapetoretinal degeneration represented the largest share (57%) of the application of the diagnostic procedure. 171 cases of isolated retinitis pigmentosa (RP) and 33 cases of syndromic RP were identified. Frequent and rare diagnostic entities and their differential diagnoses within this group are discussed. Inevitably, a number of diagnostic decisions remain problematic, in particular at the first examination. These diagnostic difficulties are addressed also and include the differentiation between RP sine pigmento and congenital amaurosis Leber in infants, RP with macular involvement vs. cone-rod degeneration, unilateral RP vs. postinflammatory conditions, and progressive cone dystrophy vs. achromatopsia, cone-rod degeneration or Stargardt's disease. Frequent and meaningful indications for ERG recording and difficult diagnostic decisions arise from this review of a relatively large group of patients. A number of diagnoses can hardly, if not at all be established without ERG testing. These include retinal cause of visual loss in infants, congenital amaurosis Leber, RP sine pigmento, early stages of RP, carrier status in XL RP and in choroideremia, progressive cone dystrophy, toxic retinopathy without fundus changes, retinal involvement

Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration

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Kamil Kruczek

2017-06-01

Full Text Available The loss of cone photoreceptors that mediate daylight vision represents a leading cause of blindness, for which cell replacement by transplantation offers a promising treatment strategy. Here, we characterize cone differentiation in retinas derived from mouse embryonic stem cells (mESCs. Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive precursors and, subsequently, photoreceptors exhibiting cone-specific phototransduction-related proteins. We establish that stage-specific inhibition of the Notch pathway increases cone cell differentiation, while retinoic acid signaling regulates cone maturation, comparable with their actions in vivo. MESC-derived cones can be isolated in large numbers and transplanted into adult mouse eyes, showing capacity to survive and mature in the subretinal space of Aipl1−/− mice, a model of end-stage retinal degeneration. Together, this work identifies a robust, renewable cell source for cone replacement by purified cell suspension transplantation.

Longitudinal ophthalmic findings in a child with Helsmoortel-Van der Aa Syndrome

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Michael J. Gale

2018-06-01

Full Text Available Purpose: We present the first detailed ophthalmic description of a child with Helsmoortel-Van der Aa Syndrome (HVDAS, including longitudinal follow-up and analysis. Observations: After extensive workup, a young child with poor visual behavior, hypotonic cerebral palsy, intellectual disability, and global developmental delay was found to have a heterozygous de novo mutation in the ADNP gene and diagnosed with HVDAS. Ophthalmic findings were remarkable for progressive nystagmus, macular pigment mottling, mild foveal hypoplasia with abnormal macular laminations, persistent rod dysfunction with electronegative waveform, and progressive cone degeneration. Conclusions and importance: Patients with HVDAS are known to have abnormal visual behavior due to refractive or cortical impairment. However, we present the first description, to our knowledge, of an association with retinal mal-development and degeneration. Thus, patients with HVDAS should be referred for ophthalmic genetics evaluation, and HVDAS should be on the differential diagnosis for young children with global developmental delay who present with nystagmus, rod and cone dysfunction with electronegative waveform, and relative lack of severe structural degeneration on optical coherence tomography. Keywords: Helsmoortel-Van der Aa Syndrome, HVDAS, Activity-dependent neuroprotective protein, ADNP, Nystagmus, Retinal degeneration, Electronegative waveform, Optical coherence tomography

[From gene to disease: from the ABCA4 gene to Stargardt disease, cone-rod dystrophy and retinitis pigmentosa

NARCIS (Netherlands)

Cremers, F.P.M.; Maugeri, A.; Klevering, B.J.; Hoefsloot, L.H.; Hoyng, C.B.

2002-01-01

Autosomal recessive Stargardt disease is caused by mutations in the ABCA4 gene. Mutations in ABCA4 are also found in two-thirds of cases with autosomal recessive cone-rod dystrophy, and a small fraction of patients with autosomal recessive retinitis pigmentosa. Patients with autosomal recessive

Cone structure imaged with adaptive optics scanning laser ophthalmoscopy in eyes with nonneovascular age-related macular degeneration.

Science.gov (United States)

Zayit-Soudry, Shiri; Duncan, Jacque L; Syed, Reema; Menghini, Moreno; Roorda, Austin J

2013-11-15

To evaluate cone spacing using adaptive optics scanning laser ophthalmoscopy (AOSLO) in eyes with nonneovascular AMD, and to correlate progression of AOSLO-derived cone measures with standard measures of macular structure. Adaptive optics scanning laser ophthalmoscopy images were obtained over 12 to 21 months from seven patients with AMD including four eyes with geographic atrophy (GA) and four eyes with drusen. Adaptive optics scanning laser ophthalmoscopy images were overlaid with color, infrared, and autofluorescence fundus photographs and spectral domain optical coherence tomography (SD-OCT) images to allow direct correlation of cone parameters with macular structure. Cone spacing was measured for each visit in selected regions including areas over drusen (n = 29), at GA margins (n = 14), and regions without drusen or GA (n = 13) and compared with normal, age-similar values. Adaptive optics scanning laser ophthalmoscopy imaging revealed continuous cone mosaics up to the GA edge and overlying drusen, although reduced cone reflectivity often resulted in hyporeflective AOSLO signals at these locations. Baseline cone spacing measures were normal in 13/13 unaffected regions, 26/28 drusen regions, and 12/14 GA margin regions. Although standard clinical measures showed progression of GA in all study eyes, cone spacing remained within normal ranges in most drusen regions and all GA margin regions. Adaptive optics scanning laser ophthalmoscopy provides adequate resolution for quantitative measurement of cone spacing at the margin of GA and over drusen in eyes with AMD. Although cone spacing was often normal at baseline and remained normal over time, these regions showed focal areas of decreased cone reflectivity. These findings may provide insight into the pathophysiology of AMD progression. (ClinicalTrials.gov number, NCT00254605).

Inherited Retinal Degenerative Disease Registry

Science.gov (United States)

2017-09-13

Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging.

Science.gov (United States)

Song, Hongxin; Rossi, Ethan A; Stone, Edwin; Latchney, Lisa; Williams, David; Dubra, Alfredo; Chung, Mina

2018-01-01

Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene. Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A . This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bcl-xL-mediated remodeling of rod and cone synaptic mitochondria after postnatal lead exposure: electron microscopy, tomography and oxygen consumption.

Science.gov (United States)

Perkins, Guy A; Scott, Ray; Perez, Alex; Ellisman, Mark H; Johnson, Jerry E; Fox, Donald A

2012-01-01

Postnatal lead exposure produces rod-selective and Bax-mediated apoptosis, decreased scotopic electroretinograms (ERGs), and scotopic and mesopic vision deficits in humans and/or experimental animals. Rod, but not cone, inner segment mitochondria were considered the primary site of action. However, photoreceptor synaptic mitochondria were not examined. Thus, our experiments investigated the structural and functional effects of environmentally relevant postnatal lead exposure on rod spherule and cone pedicle mitochondria and whether Bcl-xL overexpression provided neuroprotection. C57BL/6N mice pups were exposed to lead only during lactation via dams drinking water containing lead acetate. The blood [Pb] at weaning was 20.6±4.7 µg/dl, which decreased to the control value by 2 months. To assess synaptic mitochondrial structural differences and vulnerability to lead exposure, wild-type and transgenic mice overexpressing Bcl-xL in photoreceptors were used. Electron microscopy, three-dimensional electron tomography, and retinal and photoreceptor synaptic terminal oxygen consumption (QO(2)) studies were conducted in adult control, Bcl-xL, lead, and Bcl-xL/lead mice. The spherule and pedicle mitochondria in lead-treated mice were swollen, and the cristae structure was markedly changed. In the lead-treated mice, the mitochondrial cristae surface area and volume (abundance: measure correlated with ATP (ATP) synthesis) were decreased in the spherules and increased in the pedicles. Pedicles also had an increased number of crista segments per volume. In the lead-treated mice, the number of segments/crista and fraction of cristae with multiple segments (branching) similarly increased in spherule and pedicle mitochondria. Lead-induced remodeling of spherule mitochondria produced smaller cristae with more branching, whereas pedicle mitochondria had larger cristae with more branching and increased crista junction (CJ) diameter. Lead decreased dark- and light-adapted photoreceptor

Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system.

LENUS (Irish Health Repository)

Bhatt, Lavinia

2010-01-01

PURPOSE: The production of reactive oxygen species (ROS) can lead to oxidative stress, which is a strong contributory factor to many ocular diseases. In this study, the removal of trophic factors is used as a model system to investigate the effects of stress in the retina. The aims were to determine if both rod and cone photoreceptor cells produce ROS when they are deprived of trophic factor support and to demonstrate if the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes are responsible for this ROS production. METHODS: Retinas were explanted from mice aged between postnatal days 8-10 and cultured overnight. The following morning, confocal microscopy combined with various fluorescent probes was used to detect the production of ROS. Each time peanut agglutinin (PNA), a cone photoreceptor marker, was used to facilitate orientation of the retina. Dihydroethidium and dihydrorhodamine 123 (DHR123) were used to determine which cells produce ROS. Subsequently, western blots of retinal serial sections were used to detect the presence of Noxs in the different retinal layers. The Nox inhibitor apocynin was then tested to determine if it altered the production of ROS within these cells. RESULTS: Live retinal explants, viewed at high magnifications using confocal microscopy, displayed an increase in the fluorescent products of dihydroethidium and DHR123 upon serum removal when compared to controls. DHR123 fluorescence, once oxidized, localized to mitochondria and was found in the same focal plane as the PNA staining. This showed that cones and rods produced ROS when stressed. Retinal serial sectioning established that the photoreceptor layer expressed Nox4, dual oxidase (Duox) 1, and Duox2 at varying levels. Finally, the Nox inhibitor apocynin decreased the burst stimulated by the stress of serum removal. CONCLUSIONS: Confocal microscopy and PNA staining allowed differentiation of cell types within the outermost layers of the retina, demonstrating

Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal recessive cone-rod dystrophy and retinitis pigmentosa.

NARCIS (Netherlands)

Klevering, B.J.; Ijzer, S.; Rohrschneider, K.; Zonneveld-Vrieling, M.N.; Allikmets, R.; Born, L.I. van den; Maugeri, A.; Hoyng, C.B.; Cremers, F.P.M.

2004-01-01

Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). We employed a recently developed genotyping microarray, the ABCR400-chip, to search for known ABCA4 mutations in patients with isolated or

A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration.

Science.gov (United States)

Chavali, Venkata R M; Khan, Naheed W; Cukras, Catherine A; Bartsch, Dirk-Uwe; Jablonski, Monica M; Ayyagari, Radha

2011-05-15

Late-onset retinal macular degeneration (L-ORD) is an autosomal dominant inherited disorder caused by a single missense mutation (S163R) in the CTRP5/C1QTNF5 protein. Early phenotypic features of L-ORD include: dark adaptation abnormalities, nyctalopia, and drusen deposits in the peripheral macular region. Apart from posterior segment abnormalities, these patients also develop abnormally long anterior lens zonules. In the sixth decade of life the rod and cone function declines, accompanied by electroretinogram (ERG) abnormalities. Some patients also develop choroidal neovascularization and glaucoma. In order to understand the disease pathology and mechanisms involved in retinal dystrophy, we generated a knock-in (Ctrp5(+/-)) mouse model carrying the disease-associated mutation in the mouse Ctrp5/C1QTNF5 gene. These mice develop slower rod-b wave recovery consistent with early dark adaptation abnormalities, accumulation of hyperautofluorescence spots, retinal pigment epithelium abnormalities, drusen, Bruch's membrane abnormalities, loss of photoreceptors, and retinal vascular leakage. The Ctrp5(+/-) mice, which have most of the pathological features of age-related macular degeneration, are unique and may serve as a valuable model both to understand the molecular pathology of late-onset retinal degeneration and to evaluate therapies.

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

Energy Technology Data Exchange (ETDEWEB)

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 visual 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.

Alterations of sodium and potassium channels of RGCs in RCS rat with the development of retinal degeneration.

Science.gov (United States)

Chen, Zhongshan; Song, Yanping; Yao, Junping; Weng, Chuanhuang; Yin, Zheng Qin

2013-11-01

All know that retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases characterized by progressive dysfunction of photoreceptors and associated with progressive cells loss; nevertheless, little is known about how rods and cones loss affects the surviving inner retinal neurons and networks. Retinal ganglion cells (RGCs) process and convey visual information from retina to visual centers in the brain. The healthy various ion channels determine the normal reception and projection of visual signals from RGCs. Previous work on the Royal College of Surgeons (RCS) rat, as a kind of classical RP animal model, indicated that, at late stages of retinal degeneration in RCS rat, RGCs were also morphologically and functionally affected. Here, retrograde labeling for RGCs with Fluorogold was performed to investigate the distribution, density, and morphological changes of RGCs during retinal degeneration. Then, patch clamp recording, western blot, and immunofluorescence staining were performed to study the channels of sodium and potassium properties of RGCs, so as to explore the molecular and proteinic basis for understanding the alterations of RGCs membrane properties and firing functions. We found that the resting membrane potential, input resistance, and capacitance of RGCs changed significantly at the late stage of retinal degeneration. Action potential could not be evoked in a part of RGCs. Inward sodium current and outward potassium current recording showed that sodium current was impaired severely but only slightly in potassium current. Expressions of sodium channel protein were impaired dramatically at the late stage of retinal degeneration. The results suggested that the density of RGCs decreased, process ramification impaired, and sodium ion channel proteins destructed, which led to the impairment of electrophysiological functions of RGCs and eventually resulted in the loss of visual function.

Integrity of the cone photoreceptor mosaic in oligocone trichromacy

DEFF Research Database (Denmark)

Michaelides, Michel; Rha, Jungtae; Dees, Elise W

2011-01-01

Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these......Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed...

EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

Directory of Open Access Journals (Sweden)

David B. McGuigan

2017-07-01

Full Text Available Mutations in the EYS (eyes shut homolog gene are a common cause of autosomal recessive (ar retinitis pigmentosa (RP. Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT, and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit, some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

Progressive neuronal degeneration of childhood with liver disease

International Nuclear Information System (INIS)

Kendall, B.E.; Boyd, S.G.; Egger, J.; Harding, B.N.

1987-01-01

The clinical, electrophysiological and neuroradiological features of thirteen patients suffering from progressive neuronal degeneration of childhood with liver failure are presented. The disease commonly presents very early in life with progressive mental retardation, followed by intractable epilepsy, and should be suspected clinically especially if there is a family history of similar disorder in a sibling. On computed tomography there are low density regions, particularly in the occipital and posterior temporal lobes, involving both cortex and white matter, combined with or followed by progressive atrophy. Typical EEG findings may be confirmatory. (orig.)

Reconstruction-of-difference (RoD) imaging for cone-beam CT neuro-angiography

Science.gov (United States)

Wu, P.; Stayman, J. W.; Mow, M.; Zbijewski, W.; Sisniega, A.; Aygun, N.; Stevens, R.; Foos, D.; Wang, X.; Siewerdsen, J. H.

2018-06-01

Timely evaluation of neurovasculature via CT angiography (CTA) is critical to the detection of pathology such as ischemic stroke. Cone-beam CTA (CBCT-A) systems provide potential advantages in the timely use at the point-of-care, although challenges of a relatively slow gantry rotation speed introduce tradeoffs among image quality, data consistency and data sparsity. This work describes and evaluates a new reconstruction-of-difference (RoD) approach that is robust to such challenges. A fast digital simulation framework was developed to test the performance of the RoD over standard reference reconstruction methods such as filtered back-projection (FBP) and penalized likelihood (PL) over a broad range of imaging conditions, grouped into three scenarios to test the trade-off between data consistency, data sparsity and peak contrast. Two experiments were also conducted using a CBCT prototype and an anthropomorphic neurovascular phantom to test the simulation findings in real data. Performance was evaluated primarily in terms of normalized root mean square error (NRMSE) in comparison to truth, with reconstruction parameters chosen to optimize performance in each case to ensure fair comparison. The RoD approach reduced NRMSE in reconstructed images by up to 50%–53% compared to FBP and up to 29%–31% compared to PL for each scenario. Scan protocols well suited to the RoD approach were identified that balance tradeoffs among data consistency, sparsity and peak contrast—for example, a CBCT-A scan with 128 projections acquired in 8.5 s over a 180°  +  fan angle half-scan for a time attenuation curve with ~8.5 s time-to-peak and 600 HU peak contrast. With imaging conditions such as the simulation scenarios of fixed data sparsity (i.e. varying levels of data consistency and peak contrast), the experiments confirmed the reduction of NRMSE by 34% and 17% compared to FBP and PL, respectively. The RoD approach demonstrated superior performance in 3D angiography

Effects of Subretinal Gene Transfer at Different Time Points in a Mouse Model of Retinal Degeneration.

Science.gov (United States)

Dai, Xufeng; Zhang, Hua; Han, Juanjuan; He, Ying; Zhang, Yangyang; Qi, Yan; Pang, Ji-Jing

2016-01-01

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is necessary for photoreceptors to generate an important lipid component of their membranes. The absence of LPCAT1 results in early and rapid rod and cone degeneration. Retinal degeneration 11 (rd11) mice carry a mutation in the Lpcat1 gene, and are an excellent model of early-onset rapid retinal degeneration (RD). To date, no reports have documented gene therapy administration in the rd11 mouse model at different ages. In this study, the AAV8 (Y733F)-smCBA-Lpcat1 vector was subretinally injected at postnatal day (P) 10, 14, 18, or 22. Four months after injection, immunohistochemistry and analysis of retinal morphology showed that treatment at P10 rescued about 82% of the wild-type retinal thickness. However, the diffusion of the vector and the resulting rescue were limited to an area around the injection site that was only 31% of the total retinal area. Injection at P14 resulted in vector diffusion that covered approximately 84% of the retina, and we found that gene therapy was more effective against RD when exposure to light was limited before and after treatment. We observed long-term preservation of electroretinogram (ERG) responses, and preservation of retinal structure, indicating that early treatment followed by limited light exposure can improve gene therapy effectiveness for the eyes of rd11 mice. Importantly, delayed treatment still partially preserved M-cones, but not S-cones, and M-cones in the rd11 retina appeared to have a longer window of opportunity for effective preservation with gene therapy. These results provide important information regarding the effects of subretinal gene therapy in the mouse model of LPCAT1-deficiency.

Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina.

Directory of Open Access Journals (Sweden)

Tracy Ho

Full Text Available Amyloid precursor protein (APP is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry.

Enhancing the efficacy of AREDS antioxidants in light-induced retinal degeneration.

Science.gov (United States)

Wong, Paul; Markey, M; Rapp, C M; Darrow, R M; Ziesel, A; Organisciak, D T

2017-01-01

Light-induced photoreceptor cell degeneration and disease progression in age-related macular degeneration (AMD) involve oxidative stress and visual cell loss, which can be prevented, or slowed, by antioxidants. Our goal was to test the protective efficacy of a traditional Age-related Eye Disease Study antioxidant formulation (AREDS) and AREDS combined with non-traditional antioxidants in a preclinical animal model of photooxidative retinal damage. Male Sprague-Dawley rats were reared in a low-intensity (20 lux) or high-intensity (200 lux) cyclic light environment for 6 weeks. Some animals received a daily dietary supplement consisting of a small cracker infused with an AREDS antioxidant mineral mixture, AREDS antioxidants minus zinc, or zinc oxide alone. Other rats received AREDS combined with a detergent extract of the common herb rosemary, AREDS plus carnosic acid, zinc oxide plus rosemary, or rosemary alone. Antioxidant efficacy was determined by measuring retinal DNA levels 2 weeks after 6 h of intense exposure to white light (9,000 lux). Western blotting was used to determine visual cell opsin and arrestin levels following intense light treatment. Rhodopsin regeneration was determined after 1 h of exposure to light. Gene array analysis was used to determine changes in the expression of retinal genes resulting from light rearing environment or from antioxidant supplementation. Chronic high-intensity cyclic light rearing resulted in lower levels of rod and cone opsins, retinal S-antigen (S-ag), and medium wavelength cone arrestin (mCAR) than found for rats maintained in low cyclic light. However, as determined by retinal DNA, and by residual opsin and arrestin levels, 2 weeks after acute photooxidative damage, visual cell loss was greater in rats reared in low cyclic light. Retinal damage decreased with AREDS plus rosemary, or with zinc oxide plus rosemary whereas AREDS alone and zinc oxide alone (at their daily recommended levels) were both ineffective. One

Protective effect of sulforaphane against retinal degeneration in the Pde6rd10 mouse model of retinitis pigmentosa.

Science.gov (United States)

Kang, Kai; Yu, Minzhong

2017-12-01

Retinitis pigmentosa (RP) is a group of inherited diseases characterized by the death of rod photoreceptors, followed by the death of cone photoreceptors, progressively leading to partial or complete blindness. Currently no specific treatment is available for RP patients. Sulforaphane (SFN) has been confirmed to be an effective antioxidant in the treatment of many diseases. In this study, we tested the therapeutic effects of SFN against photoreceptor degeneration in Pde6b rd10 mice. rd10 mice and C57/BL6 wild-type (WT) mice were treated with SFN and saline, respectively, from P6 to P20. Electroretinography (ERG), terminal deoxynucleotidyl transferase dUTP nick end labeling and western blot were tested, respectively, at P21 for the analysis of retinal function, retinal cell apoptosis or death and the protein express of GRP78/BiP (TUNEL) as a marker of endoplasmic reticulum (ER) stress. Compared with the saline group, the SFN-treated group showed significantly higher ERG a-wave and b-wave amplitudes, less photoreceptor death, and the downregulation of GRP78/BiP. Our data showed that SFN ameliorated the retinal degeneration of rd10 mice, which is possibly related to the downregulation of GRP78 expression.

Mutations in the ABCA4 (ABCR) Gene Are the Major Cause of Autosomal Recessive Cone-Rod Dystrophy

OpenAIRE

Maugeri, Alessandra; Klevering, B. Jeroen; Rohrschneider, Klaus; Blankenagel, Anita; Brunner, Han G.; Deutman, August F.; Hoyng, Carel B.; Cremers, Frans P. M.

2000-01-01

The photoreceptor cell–specific ATP-binding cassette transporter gene (ABCA4; previously denoted “ABCR”) is mutated in most patients with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients with isolated CRD, all fro...

Concentric retinitis pigmentosa: clinicopathologic correlations.

Science.gov (United States)

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

Fuel Rod Melt Progression Simulation Using Low-Temperature Melting Metal Alloy

International Nuclear Information System (INIS)

Seung Dong Lee; Suh, Kune Y.; GoonCherl Park; Un Chul Lee

2002-01-01

The TMI-2 accident and various severe fuel damage experiments have shown that core damage is likely to proceed through various states before the core slumps into the lower head. Numerous experiments were conducted to address when and how the core can lose its original geometry, what geometries are formed, and in what processes the core materials are transported to the lower plenum of the reactor pressure vessel. Core degradation progresses along the line of clad ballooning, clad oxidation, material interaction, metallic blockage, molten pool formation, melt progression, and relocation to the lower head. Relocation into the lower plenum may occur from the lateral periphery or from the bottom of the core depending upon the thermal and physical states of the pool. Determining the quantities and rate of molten material transfer to the lower head is important since significant amounts of molten material relocated to the lower head can threaten the vessel integrity by steam explosion and thermal and mechanical attack of the melt. In this paper the focus is placed on the melt flow regime on a cylindrical fuel rod utilizing the LAMDA (Lumped Analysis of Melting in Degrading Assemblies) facility at the Seoul National University. The downward relocation of the molten material is a combination of the external film flow and the internal pipe flow. The heater rods are 0.8 m long and are coated by a low-temperature melting metal alloy. The electrical internal heating method is employed during the test. External heating is adopted to simulate the exothermic Zircaloy-steam reaction. Tests are conducted in several quasi-steady-state conditions. Given the variable boundary conditions including the heat flux and the water level, observation is made for the melting location, progression, and the mass of molten material. Finally, the core melt progression model is developed from the visual inspection and quantitative analysis of the experimental data. As the core material relocates

Clinical results from low-level laser therapy in patients with autosomal dominant cone-rod dystrophy

Science.gov (United States)

Koev, K.; Avramov, L.; Borissova, E.

2018-03-01

The objective of this study is to examine long-term effects of low-level laser therapy (LLLT) in patients with autosomal dominant cone-rod dystrophy (CRDs). A He-Ne Laser with continuous emission at 633 nm (01 mW/cm2) was used on five patients with autosomal dominant pedigree of Romani origin with non-syndromic CRDs. The laser radiation was applied transpupillary to the macula six times for three minutes every other day. The experiment was conducted for a period of three years. The clinical evaluation included best corrected visual acuity determination, funduscopy, Humphrey perimetry, Farnsworth Hue-28 color testing, fluorescein angiography, and full-field electroretinogram (ERG). All affected individuals presented reduced visual acuity (0.01 – 0.4) and photophobia. The funduscopic examination and fluorescein angiography revealed advanced changes including bone spicule-like pigment deposits in the midperiphery and the macular area, along with retinal atrophy, narrowing of the vessels, and waxy optic discs. The visual fields demonstrated central scotoma. The electrophysiologic examination of the patients detected an abnormal cone-rod ERG (20 – 30 μV) with photopic amplitudes more markedly reduced than the scotopic. Flicker responses were missing and Farnsworth Hue-28 test found protanopia. There was a statistically significant increase in the visual acuity (p<0.001, end of study versus baseline) for CRDs patients for the period of three years after the treatment with LLLT. Following the LLLT, the central absolute scotoma in CRDs was reduced, as was the prevalence of metamorphopsia in CRDs. This study shows that LLLT may prove be a novel long-lasting therapeutic option for both forms of CRDs. It is a highly effective treatment resulting in a long-term improvement of the visual acuity.

Brain perfusion imaging using a Reconstruction-of-Difference (RoD) approach for cone-beam computed tomography

Science.gov (United States)

Mow, M.; Zbijewski, W.; Sisniega, A.; Xu, J.; Dang, H.; Stayman, J. W.; Wang, X.; Foos, D. H.; Koliatsos, V.; Aygun, N.; Siewerdsen, J. H.

2017-03-01

Purpose: To improve the timely detection and treatment of intracranial hemorrhage or ischemic stroke, recent efforts include the development of cone-beam CT (CBCT) systems for perfusion imaging and new approaches to estimate perfusion parameters despite slow rotation speeds compared to multi-detector CT (MDCT) systems. This work describes development of a brain perfusion CBCT method using a reconstruction of difference (RoD) approach to enable perfusion imaging on a newly developed CBCT head scanner prototype. Methods: A new reconstruction approach using RoD with a penalized-likelihood framework was developed to image the temporal dynamics of vascular enhancement. A digital perfusion simulation was developed to give a realistic representation of brain anatomy, artifacts, noise, scanner characteristics, and hemo-dynamic properties. This simulation includes a digital brain phantom, time-attenuation curves and noise parameters, a novel forward projection method for improved computational efficiency, and perfusion parameter calculation. Results: Our results show the feasibility of estimating perfusion parameters from a set of images reconstructed from slow scans, sparse data sets, and arc length scans as short as 60 degrees. The RoD framework significantly reduces noise and time-varying artifacts from inconsistent projections. Proper regularization and the use of overlapping reconstructed arcs can potentially further decrease bias and increase temporal resolution, respectively. Conclusions: A digital brain perfusion simulation with RoD imaging approach has been developed and supports the feasibility of using a CBCT head scanner for perfusion imaging. Future work will include testing with data acquired using a 3D-printed perfusion phantom currently and translation to preclinical and clinical studies.

Large deletions of the KCNV2 gene are common in patients with cone dystrophy with supernormal rod response

DEFF Research Database (Denmark)

Wissinger, Bernd; Schaich, Simone; Baumann, Britta

2011-01-01

KCNV2 gene and one also includes the adjacent VLDLR gene. Furthermore, we investigated N-terminal amino acid substitution mutations for its effect on interaction with Kv2.1 using yeast two-hybrid technology. We found that these mutations dramatically reduce or abolish this interaction suggesting a lack......Cone dystrophy with supernormal rod response (CDSRR) is considered to be a very rare autosomal recessive retinal disorder. CDSRR is associated with mutations in KCNV2, a gene that encodes a modulatory subunit (Kv8.2) of a voltage-gated potassium channel. In this study, we found that KCNV2 mutations...... are present in a substantial fraction (2.2-4.3%) of a sample of 367 independent patients with a variety of initial clinical diagnoses of cone malfunction, indicating that CDSRR is underdiagnosed and more common than previously thought. In total, we identified 20 different KCNV2 mutations; 15 of them are novel...

Quantitative analysis of cone photoreceptor distribution and its relationship with axial length, age, and early age-related macular degeneration.

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Ryo Obata

Full Text Available PURPOSE: It has not been clarified whether early age-related macular degeneration (AMD is associated with cone photoreceptor distribution. We used adaptive optics fundus camera to examine cone photoreceptors in the macular area of aged patients and quantitatively analyzed its relationship between the presence of early AMD and cone distribution. METHODS: Sixty cases aged 50 or older were studied. The eyes were examined with funduscopy and spectral-domain optical coherence tomography to exclude the eyes with any abnormalities at two sites of measurement, 2° superior and 5° temporal to the fovea. High-resolution retinal images with cone photoreceptor mosaic were obtained with adaptive optics fundus camera (rtx1, Imagine Eyes, France. After adjusting for axial length, cone packing density was calculated and the relationship with age, axial length, or severity of early AMD based on the age-related eye disease study (AREDS classification was analyzed. RESULTS: Patient's age ranged from 50 to 77, and axial length from 21.7 to 27.5 mm. Mean density in metric units and that in angular units were 24,900 cells/mm2, 2,170 cells/deg2 at 2° superior, and 18,500 cells/mm2, 1,570 cels/deg2 at 5° temporal, respectively. Axial length was significantly correlated with the density calculated in metric units, but not with that in angular units. Age was significantly correlated with the density both in metric and angular units at 2° superior. There was no significant difference in the density in metric and angular units between the eyes with AREDS category one and those with categories two or three. CONCLUSION: Axial length and age were significantly correlated with parafoveal cone photoreceptor distribution. The results do not support that early AMD might influence cone photoreceptor density in the area without drusen or pigment abnormalities.

Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease.

Science.gov (United States)

Kuboyama, Tomoharu; Hirotsu, Keisuke; Arai, Tetsuya; Yamasaki, Hiroo; Tohda, Chihiro

2017-01-01

Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia ; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

Clinicopathologic analysis of progressive non-fluent aphasia and corticobasal degeneration:Case report and review

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Paulo Roberto de Brito-Marques

Full Text Available Abstract Objective: To investigate progressive non-fluent aphasia and histopathologically-proven corticobasal degeneration. Methods: We evaluated symptoms, signs, neuropsychological deficits, and radiology data longitudinally, in a patient with autopsy-proven corticobasal degeneration and correlated these observations directly to the neuroanatomic distribution of the disease. Results: At presentation, a specific pattern of cognitive impairment was evident with an extreme extrapyramidal motor abnormality. Follow-up examination revealed persistent impairment of praxis and executive functioning, progressive worsening of language performance, and moderately preserved memory. The motor disorder manifested and worsened as the condition progressed. Many of the residual nerve cells were ballooned and achromatic with eccentric nuclei. Tau-immunoreactive pathology was significantly more prominent in neurons in the frontal and parietal cortices and dentate nuclei than in temporal neocortex, hippocampi and brainstem. Conclusion: The clinical diagnosis of progressive non-fluent aphasia secondary to corticobasal degeneration hinged on a specific pattern of impaired cognition as well as an extrapyramidal motor disorder, reflecting the neuroanatomic distribution of the disease in frontal and anterior temporal cortices and the dentate nuclei.

Clinicopathologic analysis of progressive non-fluent aphasia and corticobasal degeneration: Case report and review.

Science.gov (United States)

de Brito-Marques, Paulo Roberto; Vieira-Mello, Roberto José; Montenegro, Luciano; Aragão, Maria de Fátima Vasco

2011-01-01

To investigate progressive non-fluent aphasia and histopathologically-proven corticobasal degeneration. We evaluated symptoms, signs, neuropsychological deficits, and radiology data longitudinally, in a patient with autopsy-proven corticobasal degeneration and correlated these observations directly to the neuroanatomic distribution of the disease. At presentation, a specific pattern of cognitive impairment was evident with an extreme extrapyramidal motor abnormality. Follow-up examination revealed persistent impairment of praxis and executive functioning, progressive worsening of language performance, and moderately preserved memory. The motor disorder manifested and worsened as the condition progressed. Many of the residual nerve cells were ballooned and achromatic with eccentric nuclei. Tau-immunoreactive pathology was significantly more prominent in neurons in the frontal and parietal cortices and dentate nuclei than in temporal neocortex, hippocampi and brainstem. The clinical diagnosis of progressive non-fluent aphasia secondary to corticobasal degeneration hinged on a specific pattern of impaired cognition as well as an extrapyramidal motor disorder, reflecting the neuroanatomic distribution of the disease in frontal and anterior temporal cortices and the dentate nuclei.

Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits.

Science.gov (United States)

Flynn, Oliver J; Cukras, Catherine A; Jeffrey, Brett G

2018-05-01

To examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity. Participants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning ±18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (±12°). Rod intercept time (RIT) was defined from the time to detect a -3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography. Scotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes. Three rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD.

Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Tomoharu Kuboyama

2017-11-01

Full Text Available Memory impairments in Alzheimer’s disease (AD occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

Retinal cone photoreceptors of the deer mouse Peromyscus maniculatus: development, topography, opsin expression and spectral tuning.

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Patrick Arbogast

Full Text Available A quantitative analysis of photoreceptor properties was performed in the retina of the nocturnal deer mouse, Peromyscus maniculatus, using pigmented (wildtype and albino animals. The aim was to establish whether the deer mouse is a more suitable model species than the house mouse for photoreceptor studies, and whether oculocutaneous albinism affects its photoreceptor properties. In retinal flatmounts, cone photoreceptors were identified by opsin immunostaining, and their numbers, spectral types, and distributions across the retina were determined. Rod photoreceptors were counted using differential interference contrast microscopy. Pigmented P. maniculatus have a rod-dominated retina with rod densities of about 450.000/mm(2 and cone densities of 3000-6500/mm(2. Two cone opsins, shortwave sensitive (S and middle-to-longwave sensitive (M, are present and expressed in distinct cone types. Partial sequencing of the S opsin gene strongly supports UV sensitivity of the S cone visual pigment. The S cones constitute a 5-15% minority of the cones. Different from house mouse, S and M cone distributions do not have dorsoventral gradients, and coexpression of both opsins in single cones is exceptional (<2% of the cones. In albino P. maniculatus, rod densities are reduced by approximately 40% (270.000/mm(2. Overall, cone density and the density of cones exclusively expressing S opsin are not significantly different from pigmented P. maniculatus. However, in albino retinas S opsin is coexpressed with M opsin in 60-90% of the cones and therefore the population of cones expressing only M opsin is significantly reduced to 5-25%. In conclusion, deer mouse cone properties largely conform to the general mammalian pattern, hence the deer mouse may be better suited than the house mouse for the study of certain basic cone properties, including the effects of albinism on cone opsin expression.

Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse.

Science.gov (United States)

Gargini, Claudia; Novelli, Elena; Piano, Ilaria; Biagioni, Martina; Strettoi, Enrica

2017-07-18

Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of Rho Tvrm4 /Rho + rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.

Evidence for RPE65-independent vision in the cone-dominated zebrafish retina.

Science.gov (United States)

Schonthaler, Helia B; Lampert, Johanna M; Isken, Andrea; Rinner, Oliver; Mader, Andreas; Gesemann, Matthias; Oberhauser, Vitus; Golczak, Marcin; Biehlmaier, Oliver; Palczewski, Krzysztof; Neuhauss, Stephan C F; von Lintig, Johannes

2007-10-01

An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all-trans to 11-cis-retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision.

Salamander blue-sensitive cones lost during metamorphosis.

NARCIS (Netherlands)

Chen, Y.; Znoiko, S.; Grip, W.J. de; Crouch, R.K.; Ma, J.X.

2008-01-01

The tiger salamander lives in shallow water with bright light in the aquatic phase, and in dim tunnels or caves in the terrestrial phase. In the aquatic phase, there are five types of photoreceptors--two types of rods and three types of cones. Our previous studies showed that the green rods and

Integrity of the cone photoreceptor mosaic in oligocone trichromacy

DEFF Research Database (Denmark)

Michaelides, Michel; Rha, Jungtae; Dees, Elise W

2011-01-01

Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these...... that these patients have a reduced number of normal functioning cones (oligocone). This paper has sought to evaluate the integrity of the cone photoreceptor mosaic in four patients previously described as having OT....

Correlation between SD-OCT, immunocytochemistry and functional findings in a pigmented animal model of retinal degeneration

Directory of Open Access Journals (Sweden)

Nicolás eCuenca

2014-12-01

Full Text Available Purpose: The P23H rhodopsin mutation is an autosomal dominant cause of retinitis pigmentosa. The degeneration can be tracked using different anatomical and functional methods. In our case, we evaluated the anatomical changes using Spectral-Domain Optical Coherence Tomography (SD-OCT and correlated the findings with retinal thickness values determined by immunocytochemistry.Methods: Pigmented rats heterozygous for the P23H mutation, with ages between P18 and P180 were studied. Function was assessed by means of optomotor testing and ERGs. Retinal thicknesses measurements, autofluorescence and fluorescein angiography were performed using Spectralis OCT. Retinas were studied by means of immunohistochemistry. Results: Between P30 and P180, visual acuity decreased from 0.500 to 0.182 cycles per degree (cyc/deg and contrast sensitivity decreased from 54.56 to 2.98 for a spatial frequency of 0.089 cyc/deg. Only cone-driven b-wave responses reached developmental maturity. Flicker fusions were also comparable at P29 (42 Hz. Double flash-isolated rod-driven responses were already affected at P29. Photopic responses revealed deterioration after P29.A reduction in retinal thicknesses and morphological modifications were seen in OCT sections. Statistically significant differences were found in all evaluated thicknesses. Autofluorescence was seen in P23H rats as sparse dots. Immunocytochemistry showed a progressive decrease in the outer nuclear layer, and morphological changes. Although anatomical thickness measures were significantly lower than OCT values, there was a very strong correlation between the values measured by both techniques.Conclusions: In pigmented P23H rats, a progressive deterioration occurs in both retinal function and anatomy. Anatomical changes can be effectively evaluated using SD-OCT and immunocytochemistry, with a good correlation between their values, thus making SD-OCT an important tool for research in retinal degeneration.

Molecular evolution of the cone visual pigments in the pure rod-retina of the nocturnal gecko, Gekko gekko.

Science.gov (United States)

Yokoyama, S; Blow, N S

2001-10-03

We have isolated a full-length cDNA encoding a putative ultraviolet (UV)-sensitive visual pigment of the Tokay gecko (Gekko gekko). This clone has 57 and 59% sequence similarities to the gecko RH2 and MWS pigment genes, respectively, but it shows 87% similarity to the UV pigment gene of the American chameleon (Anolis carolinensis). The evolutionary rates of amino acid replacement are significantly higher in the three gecko pigments than in the corresponding chameleon pigments. The accelerated evolutionary rates reflect not only the transition from cones to rods in the retina but also the blue-shift in the absorption spectra of the gecko pigments.

Deletion of the Thyroid Hormone-Activating Type 2 Deiodinase Rescues Cone Photoreceptor Degeneration but Not Deafness in Mice Lacking Type 3 Deiodinase.

Science.gov (United States)

Ng, Lily; Liu, Hong; St Germain, Donald L; Hernandez, Arturo; Forrest, Douglas

2017-06-01

Type 2 deiodinase amplifies and type 3 deiodinase depletes levels of the active form of thyroid hormone, triiodothyronine. Given the opposing activities of these enzymes, we tested the hypothesis that they counteract each other's developmental functions by investigating whether deletion of type 2 deiodinase (encoded by Dio2) modifies sensory phenotypes in type 3 deiodinase-deficient (Dio3-/-) mice. Dio3-/- mice display degeneration of retinal cones, the photoreceptors that mediate daylight and color vision. In Dio2-/- mice, cone function was largely normal but deletion of Dio2 in Dio3-/- mice markedly recovered cone numbers and electroretinogram responses, suggesting counterbalancing roles for both enzymes in cone survival. Both Dio3-/- and Dio2-/- strains exhibit deafness with cochlear abnormalities. In Dio3-/-;Dio2-/- mice, deafness was exacerbated rather than alleviated, suggesting unevenly balanced actions by these enzymes during auditory development. Dio3-/- mice also exhibit an atrophic thyroid gland, low thyroxine, and high triiodothyronine levels, but this phenotype was ameliorated in Dio3-/-;Dio2-/- mice, indicating counterbalancing roles for the enzymes in determining the thyroid hormone status. The results suggest that the composite action of these two enzymes is a critical determinant in visual and auditory development and in setting the systemic thyroid hormone status.

New truncation mutation of the NR2E3 gene in a Japanese patient with enhanced S-cone syndrome.

Science.gov (United States)

Kuniyoshi, Kazuki; Hayashi, Takaaki; Sakuramoto, Hiroyuki; Mishima, Hiroshi; Tsuneoka, Hiroshi; Tsunoda, Kazushige; Iwata, Takeshi; Shimomura, Yoshikazu

2016-11-01

The enhanced S-cone syndrome (ESCS) is a rare hereditary retinal degeneration that has enhanced short wavelength-sensitive cone (S-cone) functions. The longitudinal clinical course of this disease has been rarely reported, and the genetic aspects of ESCS have not been well investigated in the Japanese population. In this report, we present our clinical and genetic findings for 2 patients with ESCS. The patients were 2 unrelated Japanese men. Standard ophthalmic examinations and mutation screening for the NR2E3 gene were performed. Patient 1 was a 36-year-old man, and his clinical findings were typical of ESCS. His decimal best-corrected visual acuity (BCVA) was 1.0 OD and 0.5 OS after removal of cataracts. Genetic investigations revealed a homozygous truncation frameshift, the p.I307LfsX33 mutation. Patient 2 was an 11-year-old boy when he was first examined by us. His clinical findings were typical of ESCS except for uveitis in the left eye. His decimal BCVA at the age of 39 years was maintained at 1.5 in each eye, although the retinal degeneration and visual field impairments had progressed during the follow-up period. The genetic investigations revealed homozygous mutations of p.R104Q in the NR2E3 gene. The frameshift mutation, p.I307LfsX33, in the NR2E3 gene is a new causative mutation for ESCS. The clinical observations for patient 2 are the longest ever reported. The retinal degeneration caused by this mutation is slowly progressive, and these patients maintained good vision with maintenance of the foveal structure until their late thirties.

Rip3 knockdown rescues photoreceptor cell death in blind pde6c zebrafish.

Science.gov (United States)

Viringipurampeer, I A; Shan, X; Gregory-Evans, K; Zhang, J P; Mohammadi, Z; Gregory-Evans, C Y

2014-05-01

Achromatopsia is a progressive autosomal recessive retinal disease characterized by early loss of cone photoreceptors and later rod photoreceptor loss. In most cases, mutations have been identified in CNGA3, CNGB3, GNAT2, PDE6C or PDE6H genes. Owing to this genetic heterogeneity, mutation-independent therapeutic schemes aimed at preventing cone cell death are very attractive treatment strategies. In pde6c(w59) mutant zebrafish, cone photoreceptors expressed high levels of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3) kinases, key regulators of necroptotic cell death. In contrast, rod photoreceptor cells were alternatively immunopositive for caspase-3 indicating activation of caspase-dependent apoptosis in these cells. Morpholino gene knockdown of rip3 in pde6c(w59) embryos rescued the dying cone photoreceptors by inhibiting the formation of reactive oxygen species and by inhibiting second-order neuron remodelling in the inner retina. In rip3 morphant larvae, visual function was restored in the cones by upregulation of the rod phosphodiesterase genes (pde6a and pde6b), compensating for the lack of cone pde6c suggesting that cones are able to adapt to their local environment. Furthermore, we demonstrated through pharmacological inhibition of RIP1 and RIP3 activity that cone cell death was also delayed. Collectively, these results demonstrate that the underlying mechanism of cone cell death in the pde6c(w59) mutant retina is through necroptosis, whereas rod photoreceptor bystander death occurs through a caspase-dependent mechanism. This suggests that targeting the RIP kinase signalling pathway could be an effective therapeutic intervention in retinal degeneration patients. As bystander cell death is an important feature of many retinal diseases, combinatorial approaches targeting different cell death pathways may evolve as an important general principle in treatment.

Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia.

Science.gov (United States)

Ueki, Yumi; Ramirez, Grisela; Salcedo, Ernesto; Stabio, Maureen E; Lefcort, Frances

2016-01-01

Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein ( IKBKAP ). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre ( Tα1-Cre ). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients.

Coolant mixing in LMFBR rod bundles and outlet plenum mixing transients. Progress report, March 1, 1977--May 31, 1977

International Nuclear Information System (INIS)

Todreas, N.E.; Golay, M.W.; Wolf, L.

1977-01-01

Progress is summarized in the following tasks: (1) bundle flow studies (wrapped and bare rods); (2) subchannel flow studies (bare rods); (3) LMFBR outlet plenum flow mixing; and (4) theoretical determination of local temperature fields in LMFBR fuel rod bundles

Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope

Science.gov (United States)

Dubra, Alfredo; Sulai, Yusufu; Norris, Jennifer L.; Cooper, Robert F.; Dubis, Adam M.; Williams, David R.; Carroll, Joseph

2011-01-01

The rod photoreceptors are implicated in a number of devastating retinal diseases. However, routine imaging of these cells has remained elusive, even with the advent of adaptive optics imaging. Here, we present the first in vivo images of the contiguous rod photoreceptor mosaic in nine healthy human subjects. The images were collected with three different confocal adaptive optics scanning ophthalmoscopes at two different institutions, using 680 and 775 nm superluminescent diodes for illumination. Estimates of photoreceptor density and rod:cone ratios in the 5°–15° retinal eccentricity range are consistent with histological findings, confirming our ability to resolve the rod mosaic by averaging multiple registered images, without the need for additional image processing. In one subject, we were able to identify the emergence of the first rods at approximately 190 μm from the foveal center, in agreement with previous histological studies. The rod and cone photoreceptor mosaics appear in focus at different retinal depths, with the rod mosaic best focus (i.e., brightest and sharpest) being at least 10 μm shallower than the cones at retinal eccentricities larger than 8°. This study represents an important step in bringing high-resolution imaging to bear on the study of rod disorders. PMID:21750765

Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options

OpenAIRE

Lamb, Ruth; Rohrer, Jonathan D.; Lees, Andrew J.; Morris, Huw R.

2016-01-01

Opinion statement There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specif...

Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options

OpenAIRE

Lamb, R.; Rohrer, J. D.; Lees, A. J.; Morris, H. R.

2016-01-01

There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesi...

Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypic expression

Czech Academy of Sciences Publication Activity Database

Dostál, Jaromír; Hrdlicová, Anna; Horák, Pavel

2011-01-01

Roč. 56, č. 5 (2011), s. 243-247 ISSN 0375-8427 Institutional research plan: CEZ:AV0Z50450515 Keywords : canine * retinitis pigmentosa * autosomal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.748, year: 2011

A theoretically exact reconstruction algorithm for helical cone-beam differential phase-contrast computed tomography

International Nuclear Information System (INIS)

Li Jing; Sun Yi; Zhu Peiping

2013-01-01

Differential phase-contrast computed tomography (DPC-CT) reconstruction problems are usually solved by using parallel-, fan- or cone-beam algorithms. For rod-shaped objects, the x-ray beams cannot recover all the slices of the sample at the same time. Thus, if a rod-shaped sample is required to be reconstructed by the above algorithms, one should alternately perform translation and rotation on this sample, which leads to lower efficiency. The helical cone-beam CT may significantly improve scanning efficiency for rod-shaped objects over other algorithms. In this paper, we propose a theoretically exact filter-backprojection algorithm for helical cone-beam DPC-CT, which can be applied to reconstruct the refractive index decrement distribution of the samples directly from two-dimensional differential phase-contrast images. Numerical simulations are conducted to verify the proposed algorithm. Our work provides a potential solution for inspecting the rod-shaped samples using DPC-CT, which may be applicable with the evolution of DPC-CT equipments. (paper)

A CNGB1 frameshift mutation in Papillon and Phalene dogs with progressive retinal atrophy.

Directory of Open Access Journals (Sweden)

Saija J Ahonen

Full Text Available Progressive retinal degenerations are the most common causes of complete blindness both in human and in dogs. Canine progressive retinal atrophy (PRA or degeneration resembles human retinitis pigmentosa (RP and is characterized by a progressive loss of rod photoreceptor cells followed by a loss of cone function. The primary clinical signs are detected as vision impairment in a dim light. Although several genes have been associated with PRAs, there are still PRAs of unknown genetic cause in many breeds, including Papillons and Phalènes. We have performed a genome wide association and linkage studies in cohort of 6 affected Papillons and Phalènes and 14 healthy control dogs to map a novel PRA locus on canine chromosome 2, with a 1.9 Mb shared homozygous region in the affected dogs. Parallel exome sequencing of a trio identified an indel mutation, including a 1-bp deletion, followed by a 6-bp insertion in the CNGB1 gene. This mutation causes a frameshift and premature stop codon leading to probable nonsense mediated decay (NMD of the CNGB1 mRNA. The mutation segregated with the disease and was confirmed in a larger cohort of 145 Papillons and Phalènes (PFisher = 1.4×10(-8 with a carrier frequency of 17.2 %. This breed specific mutation was not present in 334 healthy dogs from 10 other breeds or 121 PRA affected dogs from 44 other breeds. CNGB1 is important for the photoreceptor cell function its defects have been previously associated with retinal degeneration in both human and mouse. Our study indicates that a frameshift mutation in CNGB1 is a cause of PRA in Papillons and Phalènes and establishes the breed as a large functional animal model for further characterization of retinal CNGB1 biology and possible retinal gene therapy trials. This study enables also the development of a genetic test for breeding purposes.

Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice

International Nuclear Information System (INIS)

Chen, Mo; Wang, Qin; Zhu, Gang-Hua; Hu, Peng; Zhou, Yuan; Wang, Tian; Lai, Ruo-Sha; Xiao, Zi-An; Xie, Ding-Hua

2016-01-01

The TPRN gene encodes taperin, which is prominently present at the taper region of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177–187 in exon 1 of TPRN, which results in a truncated form of taperin protein. Heterozygous TPRN +/− mice showed apparently normal auditory phenotypes to their wide-type (WT) littermates. Homozygous TPRN −/− mice exhibited progressive sensorineural hearing loss as reflected by auditory brainstem response to both click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60). Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell numbers in the cochlea between TPRN −/− mice and WT mice under light microscope. However, scanning electronic microscopy revealed progressive degeneration of inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to scattered absence at P15 and further to substantial loss at P30. The outer hair cell stereocilia also showed progressive degeneration, though much less severe, Collectively, we conclude that taperin plays an important role in maintenance of hair cell stereocilia. Establishment of TPRN knockout mice enables further investigation into the function of this gene. - Highlights: • TPRN −/− mice were generated using TALEN technique. • TPRN −/− mice presented progressive hearing loss. • WT and TPRN −/− mice showed no difference in hair cell numbers. • TPRN −/− mice showed progressive degeneration of hair cell stereocilia.

Rod and cone function in patients with KCNV2 retinopathy.

Directory of Open Access Journals (Sweden)

Ditta Zobor

Full Text Available BACKGROUND: To investigate rod and cone function and disease mechanisms in patients with KCNV2 retinopathy. METHODOLOGY/PRINCIPAL FINDINGS: Psychophysical examinations as well as detailed electrophysiological examinations with Ganzfeld and multifocal electroretinogram (ERG were performed to study response dynamics. Additionally, fundus photography, autofluorescence imaging and spectral domain OCTs were carried out for morphological characterization. Molecular genetic analysis revealed compound heterozygosity in five patients and homozygosity for the KCNV2 gene in one patient. The mutations resulted in complete absence of Kv8.2 subunits in three patients (no protein group, NOP, while the other three patients expressed mutant Kv8.2 subunits resulting in altered Kv2.1/Kv8.2 heteromeric or residual Kv2.1 homomeric potassium channel function (altered protein group, ALP. Although more advanced morphological changes were visible in the NOP group, a clear functional difference between the two groups could not be observed. All patients showed characteristic dynamics of the b-wave intensity-response function, however, scotopic b-wave response amplitudes were within normal limits. We also observed severely reduced oscillatory potentials. CONCLUSIONS/SIGNIFICANCE: A specific genotype-phenotype correlation in retinal function could not be demonstrated. KCNV2 mutations cause a unique form of retinal disorder illustrating the importance of K(+-channels for the resting potential, activation and deactivation of photoreceptors, while phototransduction remains unchanged. The reduced oscillatory potentials further suggest an altered function of the inner retina. Besides the characteristically steep amplitude-versus-intensity relationship, flicker responses at intermediate frequencies (5-15 Hz are significantly reduced and shifted in phase.

2D model for melt progression through rods and debris

International Nuclear Information System (INIS)

Fichot, F.

2001-01-01

During the degradation of a nuclear core in a severe accident scenario, the high temperatures reached lead to the melting of materials. The formation of liquid mixtures at various elevations is followed by the flow of molten materials through the core. Liquid mixture may flow under several configurations: axial relocation along the rods, horizontal motion over a plane surface such as the core support plate or a blockage of material, 2D relocation through a debris bed, etc.. The two-dimensional relocation of molten material through a porous debris bed, implemented for the simulation of late degradation phases, has opened a new way to the elaboration of the relocation model for the flow of liquid mixture along the rods. It is based on a volume averaging method, where wall friction and capillary effects are taken into account by introducing effective coefficients to characterize the solid matrix (rods, grids, debris, etc.). A local description of the liquid flow is necessary to derive the effective coefficients. Heat transfers are modelled in a similar way. The derivation of the conservation equations for the liquid mixture falling flow (momentum) in two directions (axial and radial-horizontal) and for the heat exchanges (energy) are the main points of this new model for simulating melt progression. In this presentation, the full model for the relocation and solidification of liquid materials through a rod bundle or a debris bed is described. It is implemented in the ICARE/CATHARE code, developed by IPSN in Cadarache. The main improvements and advantages of the new model are: A single formulation for liquid mixture relocation, in 2D, either through a rod bundle or a porous debris bed, Extensions to complex structures (grids, by-pass, etc..), The modeling of relocation of a liquid mixture over plane surfaces. (author)

Course of Sodium Iodate-Induced Retinal Degeneration in Albino and Pigmented Mice.

Science.gov (United States)

Chowers, Guy; Cohen, Matan; Marks-Ohana, Devora; Stika, Shelly; Eijzenberg, Ayala; Banin, Eyal; Obolensky, Alexey

2017-04-01

To characterize the course of sodium iodate (SI)-induced retinal degeneration in young adult albino and pigmented mice. Single intraperitoneal (IP) injections of SI (25, 50, and 100 mg/kg) were performed in 7- to 8-week-old BALB/c and C57Bl/6J mice. Retinal function and structure was assessed at baseline, 24 hours, 3 days, 1, 2, 3, and 4 weeks postinjection by optokinetic tracking response, ERG, optical coherence tomography (OCT), and histologic and immunohistochemical techniques. The 50 mg/kg SI dosage was selected after dose ranging due to consistent retinal effects and lack of systemic toxicity. Time-dependent deterioration in retinal function and morphology was consistently observed between 1 and 4 weeks in all measured parameters. These include reduction of ERG responses, thinning of retinal layers as observed by OCT and histology, and loss of RPE nuclei. Immunohistochemistry revealed rapid RPE disorganization with loss of tight junctions and markedly reduced expression of RPE65 and rod opsin, accompanied by mislocalization of cone opsins. Earlier time points displayed variable results, including partial recovery of visual acuity at 1 week and supranormal ERG cone responses at 24 hours, suggesting possible limitations of early intervention and assessment in the SI model. A single IP injection of 50 mg/kg SI leads to severe RPE injury followed by vision impairment, dysfunction, and loss of photoreceptors in both BALB/c and C57Bl/6J mice. This easily induced and reproducible noninherited model may serve as a useful tool for seeking and evaluating novel therapeutic modalities for the treatment of retinal degenerations caused by primary failure of the RPE.

A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

DEFF Research Database (Denmark)

Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper

2010-01-01

The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-)(/)(-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit...... melanopsin neurons or the SCN may be necessary for a normal function of the non-image forming system of the mouse. However, a change in the SCN of the Crx(-/-) mouse might also explain the observed circadian differences between the knock out mouse and wild type mouse....

Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision.

Science.gov (United States)

Cao, Yan; Sarria, Ignacio; Fehlhaber, Katherine E; Kamasawa, Naomi; Orlandi, Cesare; James, Kiely N; Hazen, Jennifer L; Gardner, Matthew R; Farzan, Michael; Lee, Amy; Baker, Sheila; Baldwin, Kristin; Sampath, Alapakkam P; Martemyanov, Kirill A

2015-09-23

In the retina, rod and cone photoreceptors form distinct connections with different classes of downstream bipolar cells. However, the molecular mechanisms responsible for their selective connectivity are unknown. Here we identify a cell-adhesion protein, ELFN1, to be essential for the formation of synapses between rods and rod ON-bipolar cells in the primary rod pathway. ELFN1 is expressed selectively in rods where it is targeted to the axonal terminals by the synaptic release machinery. At the synapse, ELFN1 binds in trans to mGluR6, the postsynaptic receptor on rod ON-bipolar cells. Elimination of ELFN1 in mice prevents the formation of synaptic contacts involving rods, but not cones, allowing a dissection of the contributions of primary and secondary rod pathways to retinal circuit function and vision. We conclude that ELFN1 is necessary for the selective wiring of rods into the primary rod pathway and is required for high sensitivity of vision. Copyright © 2015 Elsevier Inc. All rights reserved.

Double Dirac cones in phononic crystals

KAUST Repository

Li, Yan

2014-07-07

A double Dirac cone is realized at the center of the Brillouin zone of a two-dimensional phononic crystal (PC) consisting of a triangular array of core-shell-structure cylinders in water. The double Dirac cone is induced by the accidental degeneracy of two double-degenerate Bloch states. Using a perturbation method, we demonstrate that the double Dirac cone is composed of two identical and overlapping Dirac cones whose linear slopes can also be accurately predicted from the method. Because the double Dirac cone occurs at a relatively low frequency, a slab of the PC can be mapped onto a slab of zero refractive index material by using a standard retrieval method. Total transmission without phase change and energy tunneling at the double Dirac point frequency are unambiguously demonstrated by two examples. Potential applications can be expected in diverse fields such as acoustic wave manipulations and energy flow control.

Double Dirac cones in phononic crystals

KAUST Repository

Li, Yan; Wu, Ying; Mei, Jun

2014-01-01

A double Dirac cone is realized at the center of the Brillouin zone of a two-dimensional phononic crystal (PC) consisting of a triangular array of core-shell-structure cylinders in water. The double Dirac cone is induced by the accidental degeneracy of two double-degenerate Bloch states. Using a perturbation method, we demonstrate that the double Dirac cone is composed of two identical and overlapping Dirac cones whose linear slopes can also be accurately predicted from the method. Because the double Dirac cone occurs at a relatively low frequency, a slab of the PC can be mapped onto a slab of zero refractive index material by using a standard retrieval method. Total transmission without phase change and energy tunneling at the double Dirac point frequency are unambiguously demonstrated by two examples. Potential applications can be expected in diverse fields such as acoustic wave manipulations and energy flow control.

Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration.

Science.gov (United States)

Ma, Hongwei; Yang, Fan; Butler, Michael R; Belcher, Joshua; Redmond, T Michael; Placzek, Andrew T; Scanlan, Thomas S; Ding, Xi-Qin

2017-08-01

Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, THRA and THRB , encode TRs; THRB 2 has been associated with cone viability. Using TR antagonists and Thrb2 deletion, we examined the effects of TR inhibition. Systemic and ocular treatment with the TR antagonists NH-3 and 1-850 increased cone density by 30-40% in the Rpe65 -/- mouse model of Leber congenital amaurosis and reduced the number of TUNEL + cells. Cone survival was significantly improved in Rpe65 -/- and Cpfl1 (a model of achromatopsia with Pde6c defect) mice with Thrb2 deletion. Ventral cone density in Cpfl1/Thrb2 -/- and Rpe65 -/- / Thrb2 -/- mice was increased by 1- to 4-fold, compared with age-matched controls. Moreover, the expression levels of TR were significantly higher in the cone-degeneration retinas, suggesting locally elevated TR signaling. This work shows that the effects of antithyroid treatment or targeting DIOs were likely mediated by TRs and that suppressing TR protects cones. Our findings support the view that inhibition of TR locally in the retina is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

Progress of stem/progenitor cell-based therapy for retinal degeneration.

Science.gov (United States)

Tang, Zhimin; Zhang, Yi; Wang, Yuyao; Zhang, Dandan; Shen, Bingqiao; Luo, Min; Gu, Ping

2017-05-10

Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE. The sources of stem/progenitor cells are classified into two broad categories in this review, which are (1) ocular-derived progenitor cells, such as retinal progenitor cells, and (2) non-ocular-derived stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stromal cells. Here, we discuss in detail the progress in the study of four predominant stem/progenitor cell types used in animal models of RD. A short overview of clinical trials involving the stem/progenitor cells is also presented. Currently, stem/progenitor cell therapies for RD still have some drawbacks such as inhibited proliferation and/or differentiation in vitro (with the exception of the RPE) and limited long-term survival and function of grafts in vivo. Despite these challenges, stem/progenitor cells represent the most promising strategy for RD treatment in the near future.

The Influence of Psycholinguistic Variables on Articulatory Errors in Naming in Progressive Motor Speech Degeneration

Science.gov (United States)

Code, Chris; Tree, Jeremy; Ball, Martin

2011-01-01

We describe an analysis of speech errors on a confrontation naming task in a man with progressive speech degeneration of 10-year duration from Pick's disease. C.S. had a progressive non-fluent aphasia together with a motor speech impairment and early assessment indicated some naming impairments. There was also an absence of significant…

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

DEFF Research Database (Denmark)

Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

2016-01-01

The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer...... marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm2). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly...... synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells...

Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology.

Directory of Open Access Journals (Sweden)

Shaomei Wang

Full Text Available BACKGROUND: Retinitis pigmentosa (RP is characterized by progressive night blindness, visual field loss, altered vascular permeability and loss of central vision. Currently there is no effective treatment available except gene replacement therapy has shown promise in a few patients with specific gene defects. There is an urgent need to develop therapies that offer generic neuro-and vascular-protective effects with non-invasive intervention. Here we explored the potential of systemic administration of pluripotent bone marrow-derived mesenchymal stem cells (MSCs to rescue vision and associated vascular pathology in the Royal College Surgeons (RCS rat, a well-established animal model for RP. METHODOLOGY/PRINCIPAL FINDINGS: Animals received syngeneic MSCs (1x10(6 cells by tail vein at an age before major photoreceptor loss. PRINCIPAL RESULTS: both rod and cone photoreceptors were preserved (5-6 cells thick at the time when control animal has a single layer of photoreceptors remained; Visual function was significantly preserved compared with controls as determined by visual acuity and luminance threshold recording from the superior colliculus; The number of pathological vascular complexes (abnormal vessels associated with migrating pigment epithelium cells and area of vascular leakage that would ordinarily develop were dramatically reduced; Semi-quantitative RT-PCR analysis indicated there was upregulation of growth factors and immunohistochemistry revealed that there was an increase in neurotrophic factors within eyes of animals that received MSCs. CONCLUSIONS/SIGNIFICANCE: These results underscore the potential application of MSCs in treating retinal degeneration. The advantages of this non-invasive cell-based therapy are: cells are easily isolated and can be expanded in large quantity for autologous graft; hypoimmunogenic nature as allogeneic donors; less controversial in nature than other stem cells; can be readministered with minor discomfort

Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

Science.gov (United States)

Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

2016-12-01

Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

The Effects of Gx, Gy and Gz Forces on Cone Mesopic Vision

Science.gov (United States)

1983-10-01

of duration less than 1.0 seconds (time frame may vary depending on the source referred to). macular degeneration - Atrophy of the macula of the...rela- 7 tive number of cones itrcreases. In the macula , the visual center of the eye, there is virtually only cones. There are other anatomic...the cones in the center of the macula having a 1:1 synaptic ratio). These features allow small stimuli with minimal separated distances to activate

X linked progressive cone dystrophy. Localisation of the gene locus to Xp21-p11.1 by linkage analysis

NARCIS (Netherlands)

Meire, F. M.; Bergen, A. A.; de Rouck, A.; Leys, M.; Delleman, J. W.

1994-01-01

Six affected males, three female carriers, and two possible carriers were evaluated from a three generation pedigree with X linked progressive cone dystrophy. The affected males presented with progressive decrease of visual acuity, impairment of colour vision, and deterioration of electroretinogram,

Correlated and uncorrelated invisible temporal white noise alters mesopic rod signaling.

Science.gov (United States)

Hathibelagal, Amithavikram R; Feigl, Beatrix; Kremers, Jan; Zele, Andrew J

2016-03-01

We determined how rod signaling at mesopic light levels is altered by extrinsic temporal white noise that is correlated or uncorrelated with the activity of one (magnocellular, parvocellular, or koniocellular) postreceptoral pathway. Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. Psychometric (Weibull) functions were measured for incremental rod pulses (50 to 250 ms) in the presence (or absence; control) of perceptually invisible subthreshold extrinsic noise. Uncorrelated (rod) noise facilitates rod detection. Correlated postreceptoral pathway noise produces differential changes in rod detection thresholds and decreases the slope of the psychometric functions. We demonstrate that invisible extrinsic noise changes rod-signaling characteristics within the three retinogeniculate pathways at mesopic illumination depending on the temporal profile of the rod stimulus and the extrinsic noise type.

Temporal Progression of Retinal Progenitor Cell Identity: Implications in Cell Replacement Therapies

Directory of Open Access Journals (Sweden)

Awais Javed

2017-12-01

Full Text Available Retinal degenerative diseases, which lead to the death of rod and cone photoreceptor cells, are the leading cause of inherited vision loss worldwide. Induced pluripotent or embryonic stem cells (iPSCs/ESCs have been proposed as a possible source of new photoreceptors to restore vision in these conditions. The proof of concept studies carried out in mouse models of retinal degeneration over the past decade have highlighted several limitations for cell replacement in the retina, such as the low efficiency of cone photoreceptor production from stem cell cultures and the poor integration of grafted cells in the host retina. Current protocols to generate photoreceptors from stem cells are largely based on the use of extracellular factors. Although these factors are essential to induce the retinal progenitor cell (RPC fate from iPSCs/ESCs, developmental studies have shown that RPCs alter fate output as a function of time (i.e., their temporal identity to generate the seven major classes of retinal cell types, rather than spatial position. Surprisingly, current stem cell differentiation protocols largely ignore the intrinsic temporal identity of dividing RPCs, which we argue likely explains the low efficiency of cone production in such cultures. In this article, we briefly review the mechanisms regulating temporal identity in RPCs and discuss how they could be exploited to improve cone photoreceptor production for cell replacement therapies.

Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress.

Science.gov (United States)

Barben, Maya; Ail, Divya; Storti, Federica; Klee, Katrin; Schori, Christian; Samardzija, Marijana; Michalakis, Stylianos; Biel, Martin; Meneau, Isabelle; Blaser, Frank; Barthelmes, Daniel; Grimm, Christian

2018-04-17

Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process. To model chronically elevated HIF activity and investigate ensuing consequences for photoreceptors, we generated mice lacking von Hippel Lindau (VHL) protein in rods. This activated HIF transcription factors and led to a slowly progressing retinal degeneration in the ageing mouse retina. Importantly, this process depended mainly on HIF1 with only a minor contribution of HIF2. A gene therapy approach using AAV-mediated RNA interference through an anti-Hif1a shRNA significantly mitigated the degeneration suggesting a potential intervention strategy that may be applicable to human patients.

The synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degeneration

Directory of Open Access Journals (Sweden)

Ashleigh M. Byrne

2016-12-01

Full Text Available Retinitis pigmentosa (RP is one of the most common retinal degenerative conditions affecting people worldwide, and is currently incurable. It is characterized by the progressive loss of photoreceptors, in which the death of rod cells leads to the secondary death of cone cells; the cause of eventual blindness. As rod cells die, retinal-oxygen metabolism becomes perturbed, leading to increased levels of reactive oxygen species (ROS and thus oxidative stress; a key factor in the secondary death of cones. In this study, norgestrel, an FDA-approved synthetic analog of progesterone, was found to be a powerful neuroprotective antioxidant, preventing light-induced ROS in photoreceptor cells, and subsequent cell death. Norgestrel also prevented light-induced photoreceptor morphological changes that were associated with ROS production, and that are characteristic of RP. Further investigation showed that norgestrel acts via post-translational modulation of the major antioxidant transcription factor Nrf2; bringing about its phosphorylation, subsequent nuclear translocation, and increased levels of its effector protein superoxide dismutase 2 (SOD2. In summary, these results demonstrate significant protection of photoreceptor cells from oxidative stress, and underscore the potential of norgestrel as a therapeutic option for RP.

CEP250 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in a Japanese family.

Science.gov (United States)

Kubota, Daiki; Gocho, Kiyoko; Kikuchi, Sachiko; Akeo, Keiichiro; Miura, Masahiro; Yamaki, Kunihiko; Takahashi, Hiroshi; Kameya, Shuhei

2018-05-02

CEP250 encodes the C-Nap1 protein which belongs to the CEP family of proteins. C-Nap1 has been reported to be expressed in the photoreceptor cilia and is known to interact with other ciliary proteins. Mutations of CEP250 cause atypical Usher syndrome which is characterized by early-onset sensorineural hearing loss (SNHL) and a relatively mild retinitis pigmentosa. This study tested the hypothesis that the mild cone-rod dystrophy (CRD) and SNHL in a non-consanguineous Japanese family was caused by CEP250 mutations. Detailed ophthalmic and auditory examinations were performed on the proband and her family members. Whole exome sequencing (WES) was used on the DNA obtained from the proband. Electrophysiological analysis revealed a mild CRD in two family members. Adaptive optics (AO) imaging showed reduced cone density around the fovea. Auditory examinations showed a slight SNHL in both patients. WES of the proband identified compound heterozygous variants c.361C>T, p.R121*, and c.562C>T, p.R188* in CEP250. The variants were found to co-segregate with the disease in five members of the family. The variants of CEP250 are both null variants and according to American College of Medical Genetics and Genomics (ACMG) standards and guideline, these variants are classified into the very strong category (PVS1). The criteria for both alleles will be pathogenic. Our data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients. Because the ophthalmological phenotypes were very mild, high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP250-associated disease.

Mapping of the human cone transducin {alpha} subunit (GNAT2) gene to 1p13 and mutation analysis in patients with Stargardt`s disease

Energy Technology Data Exchange (ETDEWEB)

Magovcevic, I.; Weremowicz, S.; Morton, C.C. [Harvard Medical School, Boston, MA (United States)] [and others

1994-09-01

Transducin {alpha} subunits are members of a large family of G-proteins and play an important role in phototransduction in rod and cone photoreceptors. We report the localization of the human cone {alpha} transducin (GNAT2) gene using fluorescence in situ hybridization (FISH) on chromosome 1 in band p13. The recent assignment of a gene for Stargardt`s disease to the same chromosomal region by linkage analysis prompted us to investigate the possible role of GNAT2 in the pathogenesis of this disease. Stargardt`s disease is characterized by degeneration in late childhood or early adulthood of the macula of the retina, a region rich in cones. We screened patients with Stargardt`s disease, with or without peripheral cone involvement as monitored by the full-field ERG, for mutations in this gene. We investigated 66 unrelated patients including 22 with peripheral cone dysfunction for mutations in the coding region of the GNAT2 gene using polymerase chain reaction-single strand conformation polymorphism analysis (SSCP) and direct sequencing. One patient (034-16) was heterozygous for a silent change in exon VI, Asp238Asp (GAT to GAC). Two patients, one (035-005) with peripheral cone involvement and one (071-001) without peripheral cone involvement, were heterozygous for the missense change Val124Met (GTG to ATG) in exon IV. A subsequent screen of 96 unrelated, unaffected controls revealed one individual (N10) who was also heterozygous for the Val124Met alteration. We concluded that Asp238Asp and Val124Met are rare variants not causing Stargardt`s disease. Hence, no disease-specific mutations were found indicating that GNAT2 is probably not involved in the pathogenesis of most cases of Stargardt`s disease.

Cervical Lordosis Actually Increases With Aging and Progressive Degeneration in Spinal Deformity Patients.

Science.gov (United States)

Kim, Han Jo; Lenke, Lawrence G; Oshima, Yasushi; Chuntarapas, Tapanut; Mesfin, Addisu; Hershman, Stuart; Fogelson, Jeremy L; Riew, K Daniel

2014-09-01

Retrospective. The authors hypothesized that cervical lordosis (CL) would decrease with aging and increasing degeneration. It is theorized that with age and degeneration, the cervical spine loses lordosis and becomes progressively more kyphotic; however, no studies support these conclusions in patients with various spinal deformities. The authors performed a radiographic analysis of asymptomatic adults (referring to their cervical spine) of varying ages, with differing forms of spinal deformity to the thoracic/lumbar spine to see how cervical lordosis changes with increasing age. A total of 104 total spine EOS X-rays of adult (aged >18 years) spinal deformity patients without documented neck pain, prior neck surgery, or cervical deformity were reviewed. The researchers only reviewed EOS X-rays because they allow complete visualization from occiput to feet. Cervical lordosis, standard Cobb measurements, sagittal balance parameters, and cervical degeneration were quantified radiographically by the method previously described by Gore et al. Statistical analysis was performed with 1-way analysis of variance to compare significant differences between groups aged 60 years as well as changes in sagittal balance. A p-value 60 years, respectively; p 60 years, respectively; p < .01), with the highest degeneration at the C5-6 and C6-7 disc spaces (3.7 ± 3.3 and 3.2 ± 2.9, respectively; p < .01). This increase did not correlate with the increase in CL seen with aging (r = 0.02; p = .84). Cervical lordosis increased with aging in adult spinal deformity patients. There was no relationship between cervical degeneration and lordosis despite the strong relationship seen between increasing CL in older age groups. Copyright © 2014 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Genotyping microarray (gene chip) for the ABCR (ABCA4) gene.

NARCIS (Netherlands)

Jaakson, K.; Zernant, J.; Kulm, M.; Hutchinson, A.; Tonisson, N.; Glavac, D.; Ravnik-Glavac, M.; Hawlina, M.; Meltzer, M.R.; Caruso, R.C.; Testa, F.; Maugeri, A.; Hoyng, C.B.; Gouras, P.; Simonelli, F.; Lewis, R.A.; Lupski, J.R.; Cremers, F.P.M.; Allikmets, R.

2003-01-01

Genetic variation in the ABCR (ABCA4) gene has been associated with five distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), and age-related macular degeneration (AMD). Comparative genetic analyses of ABCR variation and diagnostics

Transgenic Mice Over-Expressing RBP4 Have RBP4-Dependent and Light-Independent Retinal Degeneration.

Science.gov (United States)

Du, Mei; Phelps, Eric; Balangue, Michael J; Dockins, Aaron; Moiseyev, Gennadiy; Shin, Younghwa; Kane, Shelley; Otalora, Laura; Ma, Jian-Xing; Farjo, Rafal; Farjo, Krysten M

2017-08-01

Transgenic mice overexpressing serum retinol-binding protein (RBP4-Tg) develop progressive retinal degeneration, characterized by microglia activation, yet the precise mechanisms underlying retinal degeneration are unclear. Previous studies showed RBP4-Tg mice have normal ocular retinoid levels, suggesting that degeneration is independent of the retinoid visual cycle or light exposure. The present study addresses whether retinal degeneration is light-dependent and RBP4-dependent by testing the effects of dark-rearing and pharmacological lowering of serum RBP4 levels, respectively. RBP4-Tg mice reared on normal mouse chow in normal cyclic light conditions were directly compared to RBP4-Tg mice exposed to chow supplemented with the RBP4-lowering compound A1120 or dark-rearing conditions. Quantitative retinal histological analysis was conducted to assess retinal degeneration, and electroretinography (ERG) and optokinetic tracking (OKT) tests were performed to assess retinal and visual function. Ocular retinoids and bis-retinoid A2E were quantified. Dark-rearing RBP4-Tg mice effectively reduced ocular bis-retinoid A2E levels, but had no significant effect on retinal degeneration or dysfunction in RBP4-Tg mice, demonstrating that retinal degeneration is light-independent. A1120 treatment lowered serum RBP4 levels similar to wild-type mice, and prevented structural retinal degeneration. However, A1120 treatment did not prevent retinal dysfunction in RBP4-Tg mice. Moreover, RBP4-Tg mice on A1120 diet had significant worsening of OKT response and loss of cone photoreceptors compared to RBP4-Tg mice on normal chow. This may be related to the very significant reduction in retinyl ester levels in the retina of mice on A1120-supplemented diet. Retinal degeneration in RBP4-Tg mice is RBP4-dependent and light-independent.

First-principles study of Dirac and Dirac-like cones in phononic and photonic crystals

KAUST Repository

Mei, Jun; Wu, Ying; Chan, C. T.; Zhang, Zhao-Qing

2012-01-01

By using the k•p method, we propose a first-principles theory to study the linear dispersions in phononic and photonic crystals. The theory reveals that only those linear dispersions created by doubly degenerate states can be described by a reduced Hamiltonian that can be mapped into the Dirac Hamiltonian and possess a Berry phase of -π. Linear dispersions created by triply degenerate states cannot be mapped into the Dirac Hamiltonian and carry no Berry phase, and, therefore should be called Dirac-like cones. Our theory is capable of predicting accurately the linear slopes of Dirac and Dirac-like cones at various symmetry points in a Brillouin zone, independent of frequency and lattice structure. © 2012 American Physical Society.

First-principles study of Dirac and Dirac-like cones in phononic and photonic crystals

KAUST Repository

Mei, Jun

2012-07-24

By using the k•p method, we propose a first-principles theory to study the linear dispersions in phononic and photonic crystals. The theory reveals that only those linear dispersions created by doubly degenerate states can be described by a reduced Hamiltonian that can be mapped into the Dirac Hamiltonian and possess a Berry phase of -π. Linear dispersions created by triply degenerate states cannot be mapped into the Dirac Hamiltonian and carry no Berry phase, and, therefore should be called Dirac-like cones. Our theory is capable of predicting accurately the linear slopes of Dirac and Dirac-like cones at various symmetry points in a Brillouin zone, independent of frequency and lattice structure. © 2012 American Physical Society.

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

Science.gov (United States)

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.

Accidental degeneracy of double Dirac cones in a phononic crystal

KAUST Repository

Chen, Ze-Guo; Ni, Xu; Wu, Ying; He, Cheng; Sun, Xiao-Chen; Zheng, Li-Yang; Lu, Ming-Hui; Chen, Yan-Feng

2014-01-01

Artificial honeycomb lattices with Dirac cone dispersion provide a macroscopic platform to study the massless Dirac quasiparticles and their novel geometric phases. In this paper, a quadruple-degenerate state is achieved at the center of the Brillouin zone in a two-dimensional honeycomb lattice phononic crystal, which is a result of accidental degeneracy of two double-degenerate states. In the vicinity of the quadruple-degenerate state, the dispersion relation is linear. Such quadruple degeneracy is analyzed by rigorous representation theory of groups. Using method, a reduced Hamiltonian is obtained to describe the linear Dirac dispersion relations of this quadruple-degenerate state, which is well consistent with the simulation results. Near such accidental degeneracy, we observe some unique properties in wave propagating, such as defect-insensitive propagating character and the Talbot effect.

Accidental degeneracy of double Dirac cones in a phononic crystal

KAUST Repository

Chen, Ze-Guo

2014-04-09

Artificial honeycomb lattices with Dirac cone dispersion provide a macroscopic platform to study the massless Dirac quasiparticles and their novel geometric phases. In this paper, a quadruple-degenerate state is achieved at the center of the Brillouin zone in a two-dimensional honeycomb lattice phononic crystal, which is a result of accidental degeneracy of two double-degenerate states. In the vicinity of the quadruple-degenerate state, the dispersion relation is linear. Such quadruple degeneracy is analyzed by rigorous representation theory of groups. Using method, a reduced Hamiltonian is obtained to describe the linear Dirac dispersion relations of this quadruple-degenerate state, which is well consistent with the simulation results. Near such accidental degeneracy, we observe some unique properties in wave propagating, such as defect-insensitive propagating character and the Talbot effect.

Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion.

Science.gov (United States)

Hadj-Saïd, Wahiba; Froger, Nicolas; Ivkovic, Ivana; Jiménez-López, Manuel; Dubus, Élisabeth; Dégardin-Chicaud, Julie; Simonutti, Manuel; Quénol, César; Neveux, Nathalie; Villegas-Pérez, María Paz; Agudo-Barriuso, Marta; Vidal-Sanz, Manuel; Sahel, Jose-Alain; Picaud, Serge; García-Ayuso, Diego

2016-09-01

Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S- and L- cones) in an animal model of induced taurine depletion. We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a+ RGCs, and L- and S-opsin+ cones was automatically quantified and their retinal distribution studied using isodensity maps. The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. S-opsin+cones were more affected (36%) than L-opsin+cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed. This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin+cones, L-opsin+cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.

New research progress on the epidemiology of age-related macular degeneration

Directory of Open Access Journals (Sweden)

Ming-Xing Wu

2015-02-01

Full Text Available Age-related macular degeneration(AMDis a kind of age-related blinding degenerative fundus lesions, totally about 30 million patients suffering from AMD all over the world, with about 500 000 people blind for it yearly. As the development of economy and the aging of the population intensified, incidence of AMD indicates a trend of rising year by year, being the third major cause of blindness in our country. At present, the pathogenesis of AMD is not fully clear, as reported it may be related to oxidative stress, inflammatory immune response, VEGF and genetic manipulation. Clinical treatments mainly include photodynamic therapy, drug therapy, radiation therapy, laser photocoagulaory operation, the pupil warm treatments, Chinese medicine and intravitreous injection VEGF antagonists such as Ranibizumab, Conbercept and so on. In this issue, we mainly expound on the progress in the epidemiological studies of AMD, especially elaborate the progress made on genetic manipulation in recent years.

Polyetheretherketone (PEEK) rods: short-term results in lumbar spine degenerative disease.

Science.gov (United States)

Colangeli, S; Barbanti Brodàno, G; Gasbarrini, A; Bandiera, S; Mesfin, A; Griffoni, C; Boriani, S

2015-06-01

Pedicle screw and rod instrumentation has become the preferred technique for performing stabilization and fusion in the surgical treatment of lumbar spine degenerative disease. Rigid fixation leads to high fusion rates but may also contribute to stress shielding and adjacent segment degeneration. Thus, the use of semirigid rods made of polyetheretherketone (PEEK) has been proposed. Although the PEEK rods biomechanical properties, such as anterior load sharing properties, have been shown, there are few clinical studies evaluating their application in the lumbar spine surgical treatment. This study examined a retrospective cohort of patients who underwent posterior lumbar fusion for degenerative disease using PEEK rods, in order to evaluate the clinical and radiological outcomes and the incidence of complications.

Non-syndromic retinitis pigmentosa

NARCIS (Netherlands)

Verbakel, S.K. (Sanne K.); R.A.C. van Huet (Ramon A. C.); C.J.F. Boon (Camiel); A.I. Hollander (Anneke); R.W.J. Collin (Rob); C.C.W. Klaver (Caroline); C. Hoyng (Carel); R. Roepman (Ronald); B.J. Klevering (Jeroen)

2018-01-01

textabstractRetinitis pigmentosa (RP) encompasses a group of inherited retinal dystrophies characterized by the primary degeneration of rod and cone photoreceptors. RP is a leading cause of visual disability, with a worldwide prevalence of 1:4000. Although the majority of RP cases are non-syndromic,

Progressive retinal atrophy in the Polski Owczarek Nizinny dog: a clinical and genetic study.

Science.gov (United States)

Svensson, Marika; Olsén, Lena; Winkler, Paige A; Petersen-Jones, Simon M; Bergström, Tomas; Garncarz, Yacek; Narfström, Kristina

2016-05-01

To describe ophthalmic, functional, structural, and genetical characteristics of progressive retinal atrophy (PRA) in the polski owczarek nizinny (PON) breed of dog. Client-owned PON dogs (n = 82) from Sweden. Routine examination for presumed inherited eye disease was performed in all dogs. Bilateral full-field electroretinography (ERG) was performed in 11 affected and 4 control dogs. Eyes from one affected dog were studied with light microscopy. DNA samples from 34 Swedish and 30 PON dogs collected by Michigan State University (MSU) were tested for the mutations causing the rcd4 and prcd forms of PRA. Sixteen of the eighty-two Swedish dogs were diagnosed with PRA. Slight vascular attenuation, first seen at 4.5 years of age, preceded changes in tapetal reflectivity. The initial ERG changes in affected dogs showed markedly diminished rod responses, while cone responses were barely affected. Eventually, cone responses were also reduced. Retinal morphology showed approximately a 50% reduction of photoreceptor nuclei in the outer nuclear layer. Fourteen of fifteen PRA-affected Swedish dogs and eighteen of twenty of the MSU PRA-affected dogs tested genetically were positive for the rcd4 mutation. All tested dogs were negative for the mutation causing prcd-PRA. PRA of PON dogs is a late-onset degenerative disease with slow progression. There is early loss of rod function, while the cone system deteriorates later. The rcd4 mutation in the C2ORF71 gene was associated with the majority of the PRA cases tested. The possibility of additional forms of PRA in the breed cannot be excluded. © 2015 American College of Veterinary Ophthalmologists.

The distribution and degeneration pattern of the cone opsins in rd11 mice%rd11小鼠视锥细胞变性过程中视蛋白的变化特点

Institute of Scientific and Technical Information of China (English)

韩娟娟; 戴旭锋; 戚艳; 张华; 庞继景

2014-01-01

��鼠视锥细胞中的M-视蛋白和S-视蛋白均随着鼠龄的增长而急剧减少,以S-视蛋白更为明显.随着鼠龄的增长,rd11小鼠M-视蛋白变性从视神经周围区向鼻下方,再向颞上方逐渐进展,而S-视蛋白变性由颞上方向鼻下方逐渐进展.%Background The retinal degeneration 11 (rd11) mouse is a newly discovered naturally occurring recessive animal model with lysophosphatidylcholine acyltransferase 1 (Lpcatl) mutation.Previous studies showed that the photoreceptor cells are characterized by typical rod-cone degeneration pattern in rd1 1 mice,while cone degeneration pattern in rd11 mice is unclcar.Objective Using immunofluorescence staining techniques with retinal wholemount,we aim to clarify the degeneration patterns of cone-function related M-opsin or S-opsin in different ages of rd1 1 mice.Methods A total of thirty rd1 1 and C57BL/6J mice at postnatal (P) day 14,28,42 (five in each age group) were sacrificed and retinal wholemounts were prepared.Immunohistochemistry was performed to identify the expression of M-opsin or S-opsin in retinal wholemounts,which were photographed with a fluorescent microscope.Cone opsins were compared between rd1 1 retinas and age-matched normal C57BL/6J retinas by manually counting the opsin positive cone cells in different quadrants of the retinas.Results The number of M-opsin or S-opsin positive fluorescent dots in each quadrant was similar at all ages of normal C57BL/6J retina.M-opsin positive fluorescent dots in dorsal/temporal,ventral/temporal,dorsal/nasal and ventral/nasal quadrants of rdl 1 retina at P28 were (414±32),(300± 8),(324 ± 22) and (250± 20)/0.037 mm2,which were lower than the age-matched normal C57BL/6J mice (t =4.114,15.225,7.505,17.990,all at P＜0.05).At the same time the S-opsin positive fluorescent dots in P28 rd11 were (8 ±4),(175 ± 16),(74 ± 13) and (315 ±20)/0.037 mm2,with significant decrease in comparison with those in the age-matched normal C57BL/6J mice (t =8.555,17.076,21.637,13.498,all at P＜0.05).With the development of retinal degeneration in rd11 mice,the M-opsin degeneration spread

Loss and gain of cone types in vertebrate ciliary photoreceptor evolution.

Science.gov (United States)

Musser, Jacob M; Arendt, Detlev

2017-11-01

Ciliary photoreceptors are a diverse cell type family that comprises the rods and cones of the retina and other related cell types such as pineal photoreceptors. Ciliary photoreceptor evolution has been dynamic during vertebrate evolution with numerous gains and losses of opsin and phototransduction genes, and changes in their expression. For example, early mammals lost all but two cone opsins, indicating loss of cone receptor types in response to nocturnal lifestyle. Our review focuses on the comparison of specifying transcription factors and cell type-specific transcriptome data in vertebrate retinae to build and test hypotheses on ciliary photoreceptor evolution. Regarding cones, recent data reveal that a combination of factors specific for long-wavelength sensitive opsin (Lws)- cones in non-mammalian vertebrates (Thrb and Rxrg) is found across all differentiating cone photoreceptors in mice. This suggests that mammalian ancestors lost all but one ancestral cone type, the Lws-cone. We test this hypothesis by a correlation analysis of cone transcriptomes in mouse and chick, and find that, indeed, transcriptomes of all mouse cones are most highly correlated to avian Lws-cones. These findings underscore the importance of specifying transcription factors in tracking cell type evolution, and shed new light on the mechanisms of cell type loss and gain in retina evolution. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

NARCIS (Netherlands)

Joachim, N.; Colijn, J.M.; Kifley, A.; Lee, K.E.; Buitendijk, G.H.; Klein, B.E.; Myers, C.E.; Meuer, S.M.; Tan, A.G.; Holliday, E.G.; Attia, J.; Liew, G.; Iyengar, S.K.; Jong, p de; Hofman, A.; Vingerling, J.R.; Mitchell, P.; Klaver, C.C.W.; Klein, R.; Wang, J.J.

2017-01-01

PURPOSE: To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. DESIGN: Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. METHODS:

Five-year progression of unilateral age-related macular degeneration to bilateral involvement : the Three Continent AMD Consortium report

NARCIS (Netherlands)

Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E; Buitendijk, Gabriëlle H S; Klein, Barbara E K; Myers, Chelsea E; Meuer, Stacy M; Tan, Ava G; Holliday, Elizabeth G; Attia, John; Liew, Gerald; Iyengar, Sudha K; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Klein, Ronald; Wang, Jie Jin

2017-01-01

PURPOSE: To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. DESIGN: Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. METHODS:

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

NARCIS (Netherlands)

Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E.; Buitendijk, Gabriëlle H. S.; Klein, Barbara E. K.; Myers, Chelsea E.; Meuer, Stacy M.; Tan, Ava G.; Holliday, Elizabeth G.; Attia, John; Liew, Gerald; Iyengar, Sudha K.; de Jong, Paulus T. V. M.; Hofman, Albert; Vingerling, Johannes R.; Mitchell, Paul; Klaver, Caroline C. W.; Klein, Ronald; Wang, Jie Jin

2017-01-01

Purpose To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. Design Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. Methods Retinal

Feasibility of using cone penetrometer truck (CPT) to install time domain reflectometry (TDR) and fiber optic slope failure detectors in pavement structures.

Science.gov (United States)

2011-02-01

A new method of cable installation using a heavy-duty Cone Penetration Test : (CPT) truck was developed and practiced successfully in this study. The coaxial and fiber : optic cables were pushed along with the cone rods by the hydraulic system integr...

Optimal Control for the Degenerate Elliptic Logistic Equation

International Nuclear Information System (INIS)

Delgado, M.; Montero, J.A.; Suarez, A.

2002-01-01

We consider the optimal control of harvesting the diffusive degenerate elliptic logistic equation. Under certain assumptions, we prove the existence and uniqueness of an optimal control. Moreover, the optimality system and a characterization of the optimal control are also derived. The sub-supersolution method, the singular eigenvalue problem and differentiability with respect to the positive cone are the techniques used to obtain our results

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

Science.gov (United States)

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

2016-01-01

Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (Pvision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual recovery occurs following ablation of some, but not all, cone subtypes, suggesting an opportunity to contrast and dissect the sources and mechanisms of outer retinal recovery during cone photoreceptor death and regeneration. PMID:27893779

Genome-wide analysis of disease progression in age-related macular degeneration.

Science.gov (United States)

Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

2018-03-01

Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration.

Science.gov (United States)

Rojas-Fernandez, Carlos H; Tyber, Kevin

2017-03-01

To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene ( CFH) and age-related maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.

Infantile onset progressive cerebellar atrophy and anterior horn cell degeneration--a late onset variant of PCH-1?

Science.gov (United States)

Lev, Dorit; Michelson-Kerman, Marina; Vinkler, Chana; Blumkin, Lubov; Shalev, Stavit A; Lerman-Sagie, Tally

2008-03-01

Despite major recent advances in our understanding of developmental cerebellar disorders, classification and delineation of these disorders remains difficult. The term pontocerebellar hypoplasia is used when there is a structural defect, originating in utero of both pons and cerebellar hemispheres. The term olivopontocerebellar atrophy is used when the disorder starts later in life and the process is a primary degeneration of cerebellar neurons. Pontocerebellar hypoplasia type 1 is associated with spinal anterior horn cell degeneration, congenital contractures, microcephaly, polyhydramnion and respiratory insufficiency leading to early death. However, anterior horn cell degeneration has also been described in cases with later onset pontocerebellar atrophy and recently the spectrum has even been further extended to include the association of anterior horn cell degeneration and cerebellar atrophy without pontine involvement. We describe two siblings from a consanguineous Moslem Arabic family who presented with progressive degeneration of both the cerebellum and the anterior horn cells. The patients presented after 1 year of age with a slow neurodegenerative course that included both cognitive and motor functions. There is considerable phenotypic variability; the sister shows a much milder course. Both children are still alive at 6 and 9 years. The sister could still crawl and speak two word sentences at the age of 3 years while the brother was bedridden and only uttered guttural sounds at the same age. Our cases further extend the phenotype of the cerebellar syndromes with anterior horn cell involvement to include a childhood onset and protracted course and further prove that this neurodegenerative disorder may start in utero or later in life.

Increased proliferation of late-born retinal progenitor cells by gestational lead exposure delays rod and bipolar cell differentiation.

Science.gov (United States)

Chaney, Shawnta Y; Mukherjee, Shradha; Giddabasappa, Anand; Rueda, Elda M; Hamilton, W Ryan; Johnson, Jerry E; Fox, Donald A

2016-01-01

or protein expression, a marker for late-born Müller glial cells, were observed in the developing retinas. In the retinas from the GLE mice, anti-PKCα, - Chx10 (Vsx2) and -secretagogin antibodies revealed a two- to three-day delay in the differentiation of rod and cone BCs, whereas the expression of the proneural and BC genes Otx2 and Chx10 , respectively, increased. In addition, confocal studies of proteins associated with functional synapses (e.g., vesicular glutamate transporter 1 [VGluT1], plasma membrane calcium ATPase [PMCA], transient receptor potential channel M1 [TRPM1], and synaptic vesicle glycoprotein 2B [SV2B]) revealed a two-day delay in the formation of the outer and inner plexiform layers of the GLE retinas. Moreover, several markers revealed that the initiation of the differentiation and intensity of the labeling of early-born cells in the retinal ganglion cell and inner plexiform layers were not different in the control retinas. Our combined gene, confocal, and immunoblot findings revealed that the onset of rod and BC differentiation and their subsequent synaptic development is delayed by two to three days in GLE retinas. These results suggest that perturbations during the early proliferative stages of late-born RPCs fated to be rods and BCs ultimately alter the coordinated time-dependent progression of rod and BC differentiation and synaptic development. These GLE effects were selective for late-born neurons. Although the molecular mechanisms are unknown, alterations in soluble neurotrophic factors and/or their receptors are likely to play a role. Since neurodevelopmental delays and altered synaptic connectivity are associated with neuropsychiatric and behavioral disorders as well as cognitive deficits, future work is needed to determine if similar effects occur in the brains of GLE mice and whether children with GLE experience similar delays in retinal and brain neuronal differentiation and synaptic development.

Volumetric imaging of rod and cone photoreceptor structure with a combined adaptive optics-optical coherence tomography-scanning laser ophthalmoscope

Science.gov (United States)

Wells-Gray, Elaine M.; Choi, Stacey S.; Zawadzki, Robert J.; Finn, Susanna C.; Greiner, Cherry; Werner, John S.; Doble, Nathan

2018-03-01

We have designed and implemented a dual-mode adaptive optics (AO) imaging system that combines spectral domain optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) for in vivo imaging of the human retina. The system simultaneously acquires SLO frames and OCT B-scans at 60 Hz with an OCT volume acquisition time of 4.2 s. Transverse eye motion measured from the SLO is used to register the OCT B-scans to generate three-dimensional (3-D) volumes. Key optical design considerations include: minimizing system aberrations through the use of off-axis relay telescopes, conjugate pupil plane requirements, and the use of dichroic beam splitters to separate and recombine the OCT and SLO beams around the nonshared horizontal scanning mirrors. To demonstrate system performance, AO-OCT-SLO images and measurements are taken from three normal human subjects ranging in retinal eccentricity from the fovea out to 15-deg temporal and 20-deg superior. Also presented are en face OCT projections generated from the registered 3-D volumes. The ability to acquire high-resolution 3-D images of the human retina in the midperiphery and beyond has clinical importance in diseases, such as retinitis pigmentosa and cone-rod dystrophy.

Association of weight change with progression of meniscal intrasubstance degeneration over 48 months. Data from the Osteoarthritis Initiative

Energy Technology Data Exchange (ETDEWEB)

Brandao Guimaraes, Julio [University of California, Musculoskeletal and Quantitative Imaging Research Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Federal University of Sao Paulo (UNIFESP), Department of Radiology, Sao Paulo (Brazil); DASA Laboratory, Department of Radiology, Sao Paulo (Brazil); Nevitt, Michael C.; McCulloch, Charles E.; Liu, Felix [University of California, Department of Epidemiology and Biostatistics, San Francisco, CA (United States); Schwaiger, Benedikt J.; Gersing, Alexandra S.; Facchetti, Luca; Bucknor, Matthew D.; Chanchek, Nattagan; Joseph, Gabby B.; Link, Thomas M. [University of California, Musculoskeletal and Quantitative Imaging Research Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

2018-03-15

To investigate the association of weight change over 48 months with progression of meniscal intrasubstance degeneration (MID). We studied 487 subjects with MID at baseline and after 48 months using 3-T MRI with the same protocol (FSE sequences with and without fat suppression). These participants lost weight (≥3%, n = 141), had moderate weight gain (3-10%, n = 77), substantial weight gain (>10%, n = 15) or maintained stable weight (n = 254). Progression of MID to a meniscal tear was assessed using the WORMS grading system and compared among weight change groups using logistic regression. ANOVA and chi-square tests were used to study the differences in subjects' characteristics. Progression of MID increased from weight loss to substantial weight gain (p < 0.001) and was significantly more likely with both moderate weight gain (odds ratio [OR], 4.9; 95% confidence interval [CI] 2.4-8.9) and substantial weight gain (OR, 9.5; 95% CI 3.2-28.5) compared to stable weight. Results were similar in both menisci for moderate weight gain (medial: OR, 6.8; 95% CI 3.5-11.3; lateral: OR, 2.6; 95% CI 1.1-6.6) and substantial weight gain (medial: OR, 21.0; 95% CI 5.1-80.7; lateral: OR, 9.7; 95% CI 0.95-100.2). Weight gain is associated with an increased likelihood that meniscal intrasubstance degeneration will progress with the risk increasing with greater weight gain. (orig.)

Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.

Science.gov (United States)

Maugeri, A; Klevering, B J; Rohrschneider, K; Blankenagel, A; Brunner, H G; Deutman, A F; Hoyng, C B; Cremers, F P

2000-10-01

The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.

A Novel Method to Simulate the Progression of Collagen Degeneration of Cartilage in the Knee: Data from the Osteoarthritis Initiative

Science.gov (United States)

Mononen, Mika E.; Tanska, Petri; Isaksson, Hanna; Korhonen, Rami K.

2016-02-01

We present a novel algorithm combined with computational modeling to simulate the development of knee osteoarthritis. The degeneration algorithm was based on excessive and cumulatively accumulated stresses within knee joint cartilage during physiological gait loading. In the algorithm, the collagen network stiffness of cartilage was reduced iteratively if excessive maximum principal stresses were observed. The developed algorithm was tested and validated against experimental baseline and 4-year follow-up Kellgren-Lawrence grades, indicating different levels of cartilage degeneration at the tibiofemoral contact region. Test groups consisted of normal weight and obese subjects with the same gender and similar age and height without osteoarthritic changes. The algorithm accurately simulated cartilage degeneration as compared to the Kellgren-Lawrence findings in the subject group with excess weight, while the healthy subject group’s joint remained intact. Furthermore, the developed algorithm followed the experimentally found trend of cartilage degeneration in the obese group (R2 = 0.95, p osteoarthritis (0-2 years, p  0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis.

Macular Pigment and Lutein Supplementation in ABCA4-associated Retinal Degenerations

Science.gov (United States)

Aleman, Tomas S.; Cideciyan, Artur V.; Windsor, Elizabeth A. M.; Schwartz, Sharon B.; Swider, Malgorzata; Chico, John D.; Sumaroka, Alexander; Pantelyat, Alexander Y.; Duncan, Keith G.; Gardner, Leigh M.; Emmons, Jessica M.; Steinberg, Janet D.; Stone, Edwin M.; Jacobson, Samuel G.

2008-01-01

PURPOSE To determine macular pigment (MP) optical density (OD) in patients with ABCA4-associated retinal degenerations (ABCA4-RD) and the response of MP and vision to supplementation with lutein. METHODS Stargardt disease or cone-rod dystrophy patients with foveal fixation and with known or suspected disease-causing mutations in the ABCA4 gene were included. MPOD profiles were measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity and retinal thickness were quantified. Changes in MPOD and central vision were determined in a subset of patients receiving oral supplementation with lutein for 6 months. RESULTS MPOD in patients ranged from normal to markedly abnormal. As a group, ABCA4-RD patients had reduced foveal MPOD and there was strong correlation with retinal thickness. Average foveal tissue concentration of MP, estimated by dividing MPOD by retinal thickness, was normal in patients whereas serum concentration of lutein and zeaxanthin was significantly lower than normal. After oral lutein supplementation for 6 months, 91% of the patients showed significant increases in serum lutein and 63% of the patient eyes showed a significant augmentation in MPOD. The retinal responders tended to be female, and have lower serum lutein and zeaxanthin, lower MPOD and greater retinal thickness at baseline. Responding eyes had significantly lower baseline MP concentration compared to non-responding eyes. Central vision was unchanged after the period of supplementation. CONCLUSIONS MP is strongly affected by the stage of ABCA4 disease leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in some patients. There was no change in central vision after 6 months of lutein supplementation. Long-term influences on the natural history of this supplement on macular degenerations require further study. PMID:17325179

Accounting for disagreements on average cone loss rates in retinitis pigmentosa with a new kinetic model: Its relevance for clinical trials.

Science.gov (United States)

Baumgartner, W A; Baumgartner, A M

2016-04-01

Since 1985, at least nine studies of the average rate of cone loss in retinitis pigmentosa (RP) populations have yielded conflicting average rate constant values (-k), differing by 90-160%. This is surprising, since, except for the first two investigations, the Harvard or Johns Hopkins' protocols used in these studies were identical with respect to: use of the same exponential decline model, calculation of average -k from individual patient k values, monitoring patients over similarly large time frames, and excluding data exhibiting floor and ceiling effects. A detailed analysis of Harvard's and Hopkins' protocols and data revealed two subtle differences: (i) Hopkins' use of half-life t0.5 (or t(1/e)) for expressing patient cone-loss rates rather than k as used by Harvard; (ii) Harvard obtaining substantially more +k from improving fields due to dormant-cone recovery effects and "small -k" values than Hopkins' ("small -k" is defined as less than -0.040 year(-1)), e.g., 16% +k, 31% small -k, vs. Hopkins' 3% and 6% respectively. Since t0.5=0.693/k, it follows that when k=0, or is very small, t0.5 (or t(1/e)) is respectively infinity or a very large number. This unfortunate mathematical property (which also prevents t0.5 (t(1/e)) histogram construction corresponding to -k to +k) caused Hopkins' to delete all "small -k" and all +k due to "strong leverage". Naturally this contributed to Hopkins' larger average -k. Difference (ii) led us to re-evaluate the Harvard/Hopkins' exponential unchanging -k model. In its place we propose a model of increasing biochemical stresses from dying rods on cones during RP progression: increasing oxidative stresses and trophic factor deficiencies (e.g., RdCVF), and RPE malfunction. Our kinetic analysis showed rod loss to follow exponential kinetics with unchanging -k due to constant genetic stresses, thereby providing a theoretical basis for Clarke et al.'s empirical observation of such kinetics with eleven animal models of RP. In

Multiple cone pathways are involved in photic regulation of retinal dopamine.

Science.gov (United States)

Qiao, Sheng-Nan; Zhang, Zhijing; Ribelayga, Christophe P; Zhong, Yong-Mei; Zhang, Dao-Qi

2016-06-30

Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina.

Surgical Treatment of Acute Submacular Hemorrhages and Advanced Exudative Age-related Macular Degeneration

NARCIS (Netherlands)

E.J.T. van Zeeburg (Elsbeth)

2014-01-01

markdownabstract__Abstract__ Located behind the cornea, iris and lens, the vitreous is a clear gel in the center of the eye (figure 1). The inner surface of the eye is lined with retina, a multi-layered sensory tissue. In the retina the photoreceptors, rods and cones, are capable of

Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health.

Science.gov (United States)

Owsley, Cynthia; Huisingh, Carrie; Clark, Mark E; Jackson, Gregory R; McGwin, Gerald

2016-01-01

To compare the ability of several visual functional tests in terms of the strength of their associations with the earliest phases of age-related macular degeneration (AMD), which bears on their potential to serve as functional endpoints in evaluating treatments for early AMD and prevention strategies. Eyes from adults ≥60 years old were identified as being in normal macular health or in the earliest stages of AMD (steps 2, 3 or 4) through grading of color stereo-fundus photos by an experienced grader masked to all other study variables who used the 9-step Age-Related Eye Disease Study (AREDS) classification system for AMD severity. Visual function was assessed using the following tests: best-corrected visual acuity, low luminance visual acuity, spatial contrast sensitivity, macular cone-mediated light sensitivity and rod-mediated dark adaptation. A total of 1260 eyes were tested from 640 participants; 1007 eyes were in normal macular health (defined as step 1 in AREDS system) and 253 eyes had early AMD (defined as steps 2, 3 or 4). Adjusting for age and gender, early AMD eyes had two times the odds of having delayed rod-mediated dark adaptation than eyes in normal macular health (p = 0.0019). Visual acuity, low luminance acuity, spatial contrast sensitivity and macular light sensitivity did not differ between normal eyes and early AMD eyes. Eyes in the earliest phases of AMD were two times more likely to have delayed rod-mediated dark adaptation, as assessed by the rod-intercept, as compared to older eyes in normal macular health, whereas there was no difference in early AMD versus normal eyes in tests of visual acuity, low luminance acuity, macular light sensitivity and spatial contrast sensitivity.

Molecular analysis of retinal fascin gene 2 (FSCN2), a candidate gene for progressive rod-cone degeneration in dogs

Czech Academy of Sciences Publication Activity Database

Horák, Pavel; Knoll, Aleš

2006-01-01

Roč. 9, Mimoriadne číslo (2006), s. 62-64 ISSN 1335-258X. [XXII. dni genetiky. 12.09.2006-14.09.2006, Nitra] Institutional research plan: CEZ:AV0Z50450515 Keywords : pig * polymorphism * LEPR and H-FABP genes Subject RIV: EB - Genetics ; Molecular Biology

Self-cleaning threaded rod spinneret for high-efficiency needleless electrospinning

Science.gov (United States)

Zheng, Gaofeng; Jiang, Jiaxin; Wang, Xiang; Li, Wenwang; Zhong, Weizheng; Guo, Shumin

2018-07-01

High-efficiency production of nanofibers is the key to the application of electrospinning technology. This work focuses on multi-jet electrospinning, in which a threaded rod electrode is utilized as the needless spinneret to achieve high-efficiency production of nanofibers. A slipper block, which fits into and moves through the threaded rod, is designed to transfer polymer solution evenly to the surface of the rod spinneret. The relative motion between the slipper block and the threaded rod electrode promotes the instable fluctuation of the solution surface, thus the rotation of threaded rod electrode decreases the critical voltage for the initial multi-jet ejection and the diameter of nanofibers. The residual solution on the surface of threaded rod is cleaned up by the moving slipper block, showing a great self-cleaning ability, which ensures the stable multi-jet ejection and increases the productivity of nanofibers. Each thread of the threaded rod electrode serves as an independent spinneret, which enhances the electric field strength and constrains the position of the Taylor cone, resulting in high productivity of uniform nanofibers. The diameter of nanofibers decreases with the increase of threaded rod rotation speed, and the productivity increases with the solution flow rate. The rotation of electrode provides an excess force for the ejection of charged jets, which also contributes to the high-efficiency production of nanofibers. The maximum productivity of nanofibers from the threaded rod spinneret is 5-6 g/h, about 250-300 times as high as that from the single-needle spinneret. The self-cleaning threaded rod spinneret is an effective way to realize continuous multi-jet electrospinning, which promotes industrial applications of uniform nanofibrous membrane.

Long-Term Protection of Genetically Ablated Rabbit Retinal Degeneration by Sustained Transscleral Unoprostone Delivery.

Science.gov (United States)

Nagai, Nobuhiro; Koyanagi, Eri; Izumida, Yasuko; Liu, Junjun; Katsuyama, Aya; Kaji, Hirokazu; Nishizawa, Matsuhiko; Osumi, Noriko; Kondo, Mineo; Terasaki, Hiroko; Mashima, Yukihiko; Nakazawa, Toru; Abe, Toshiaki

2016-12-01

To evaluate the long-term protective effects of transscleral unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation). The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry. In situ hybridization and immunohistochemistry evaluated the retinal distribution of big potassium (BK) channels, and RT-PCR evaluated the expressions of BK channels and m-opsin at 1 week after URD treatment. The URD released UNO at a rate of 10.2 ±1.0 μg/d, and the release rate and amount of UNO decreased during 32 weeks. Higher ERG amplitudes were observed in the URD-treated Tg rabbits compared with the placebo-URD, or nontreated controls. At 24 weeks after implantation into the URD-treated Tg rabbits, OCT images showed preservation of retinal thickness, and histologic examinations (44 weeks) showed greater thickness of outer nuclear layers. Unoprostone was detected in the retina, choroid, and plasma of Wt rabbits. Retina/plasma ratio of UNO levels were 38.0 vs. 0.68 ng UNO*hour/mL in the URD-treated group versus control (topical UNO), respectively. Big potassium channels were observed in cone, cone ON-bipolar, and rod bipolar cells. Reverse-transcriptase PCR demonstrated BK channels and m-opsins increased in URD-treated eyes. In Tg rabbits, URD use slowed the decline of retinal function for more than 32 weeks, and therefore provides a promising tool for long-term treatment of RP.

Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

Science.gov (United States)

Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

2015-01-01

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

Astrocytes and Müller cells changes during retinal degeneration in a transgenic rat model of retinitis pigmentosa.

Directory of Open Access Journals (Sweden)

Laura eFernández-Sánchez

2015-12-01

Full Text Available Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer of P23H versus SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.

What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD?

Directory of Open Access Journals (Sweden)

Willich, Stefan N.

2006-12-01

Full Text Available Background: The cataract (Cataracta senilis is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology – can be seen as routine surgery. The age related macular degeneration (AMD is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing number of patients will suffer from cataract and AMD at the same time. This coincidence leads to a greater interest in the question of a mutual influence of both diseases, respectively their therapies, on each other. Objectives: The aim of this report was the evaluation of the medical and health economic effects of cataract operations on the development and progression of an age related macular degeneration (AMD. It was differentiated between first manifestations of AMD, progression of early stages of AMD and influence on further impairment in late stages of AMD. Methods: The relevant publications for this report were identified by DIMDI via structured database enquiry as well as common, self-made enquiry and were evaluated, based on the criteria of evidence based medicine. The present report included German and English literature published since 1983. Results: The database enquiry generated a record of 2769 issue-related publications. Eight medical publications were eligible for analysis in the course of the present HTA report. No relevant studies on health economical, ethical, social or legal issues could be included. Three epidemiological cohort studies provided some evidence for a promoting influence of cataract extractions on the progression of early types of AMD. Two of the epidemiological studies assessed the risk of first manifestation of AMD after cataract extraction. Both came up with up with increased incidences that did not reach statistical

Natural history of seminiferous tubule degeneration in Klinefelter syndrome

DEFF Research Database (Denmark)

Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

2006-01-01

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...... summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome....

Dietary fatty acids and lipoproteins on progression of age-related macular degeneration

International Nuclear Information System (INIS)

Montserrat-de la Paz, S.; Naranjo, M.C.; Bermúdez, B.; López, S.; Abia, R.; Muriana, F.J.G.

2017-01-01

Age-related macular degeneration (AMD) is a medical condition of central loss vision and blindness. Numerous studies have revealed that changes on certain dietary fatty acids (FAs) could have useful for AMD management. This review summarizes the effects of dietary omega-3 long-chain PUFAs, MUFAs, and SFAs, and lipoproteins on AMD. Findings are consistent with the beneficial role of dietary omega-3 long-chain PUFAs, while the effects of dietary MUFAs and SFAs appeared to be ambiguous with respect to the possible protection from MUFAs and to the possible adverse impact from SFAs on AMD. Some of the pathological mechanisms associated with lipoproteins on AMD share those observed previously in cardiovascular diseases. It was also noticed that the effects of FAs in the diet and lipoprotein on AMD could be modulated by genetic variants. From a population health perspective, the findings of this review are in favour of omega-3 long-chain FAs recommendations in a preventive and therapeutic regimen to attain lower AMD occurrence and progression rates. Additional long-term and short-term nutrigenomic studies are required to clearly establish the role and the relevance of interaction of dietary FAs, lipoproteins, and genes in the genesis and progression of AMD. [es

Dietary fatty acids and lipoproteins on progression of age-related macular degeneration

Directory of Open Access Journals (Sweden)

S. Montserrat-de la Paz

2017-06-01

Full Text Available Age-related macular degeneration (AMD is a medical condition of central loss vision and blindness. Numerous studies have revealed that changes on certain dietary fatty acids (FAs could have useful for AMD management. This review summarizes the effects of dietary omega-3 long-chain PUFAs, MUFAs, and SFAs, and lipoproteins on AMD. Findings are consistent with the beneficial role of dietary omega-3 long-chain PUFAs, while the effects of dietary MUFAs and SFAs appeared to be ambiguous with respect to the possible protection from MUFAs and to the possible adverse impact from SFAs on AMD. Some of the pathological mechanisms associated with lipoproteins on AMD share those observed previously in cardiovascular diseases. It was also noticed that the effects of FAs in the diet and lipoprotein on AMD could be modulated by genetic variants. From a population health perspective, the findings of this review are in favour of omega-3 long-chain FAs recommendations in a preventive and therapeutic regimen to attain lower AMD occurrence and progression rates. Additional long-term and short-term nutrigenomic studies are required to clearly establish the role and the relevance of interaction of dietary FAs, lipoproteins, and genes in the genesis and progression of AMD.

Natural history of seminiferous tubule degeneration in Klinefelter syndrome

DEFF Research Database (Denmark)

Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

2006-01-01

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...

Rayleigh-Love model of longitudinal vibrations of conical and exponential rods: Exact solutions and numerical simulation by the method of lines

CSIR Research Space (South Africa)

Shatalov, M

2011-07-01

Full Text Available of conical surface of the rod is described by equation ( ) ( )pr x k x x kx= ? = , where px is coordinate of the pole of the cone, px x x= ? , then ( ) 2 2S x k xpi= , ( ) 4 4 2pI x k xpi= and equation (2) is rewritten as follows: ( ) ( ) ( ) ( ) ( ) 2... rod in accordance with the classi- cal theory, and 2 k c ? ?? = is the wavenumber of the conical rod which has dimension 1m? . Introducing new dimensionless variable z x?= , considering new function ( ) zV z U ? ? ? = ? ?? ? ( )W z z...

Cadmium safety rod thermal tests

International Nuclear Information System (INIS)

Thomas, J.K.; Iyer, N.C.; Peacock, H.B.

1992-01-01

Thermal testing of cadmium safety rods was conducted as part of a program to define the response of Savannah River Site (SRS) production reactor core components to a hypothetical LOCA leading to a drained reactor tank. The safety rods are present in the reactor core only during shutdown and are not used as a control mechanism during operation; thus, their response to the conditions predicted for the LOCA is only of interest to the extent that it could impact the progression of the accident. This document provides a description of this testing

Urocortin 2 treatment is protective in excitotoxic retinal degeneration.

Science.gov (United States)

Szabadfi, K; Kiss, P; Reglodi, D; Fekete, E M; Tamas, A; Danyadi, B; Atlasz, T; Gabriel, R

2014-03-01

Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced retinal degeneration by routine histology and to investigate cell-type specific effects by immunohistochemistry. Rat pups received MSG applied on postnatal days 1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was determined for glial fibrillary acidic protein, vesicular glutamate transporter 1, protein kinase Cα, calbindin, parvalbumin and calretinin. Retinal tissue from animals treated with MSG showed severe degeneration compared to normal retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal structure both at histological and neurochemical levels: distinct inner retinal layers and rescued inner retinal cells (different types of amacrine and rod bipolar cells) could be observed. These findings support the neuroprotective function of Ucn 2 in MSG-induced retinal degeneration.

Vibrational characteristics and wear of fuel rods

International Nuclear Information System (INIS)

Schmugar, K.L.

1977-01-01

Fuel rod wear, due to vibration, is a continuing concern in the design of liquid-cooled reactors. In my report, the methodology and models that are used to predict fuel rod vibrational response and vibratory wear, in a light water reactor environment, are discussed. This methodology is being followed at present in the design of Westinghouse Nuclear Fuel. Fuel rod vibrations are expressed as the normal bending modes, and sources of rod vibration are examined with special emphasis on flow-induced mechanisms in the stable flow region. In a typical Westinghouse PWR fuel assembly design, each fuel rod is supported at multiple locations along the rod axis by a square-shaped 'grid cell'. For a fuel rod /grid support system, the development of small oscillatory motions, due to fluid flow at the rod/grid interface, results in material wear. A theoretical wear mode is developed using the Archard Theory of Adhesive Wear as the basis. Without question certainty, fretting wear becomes a serious problem if it progresses to the stage where the fuel cladding is penetrated and fuel is exposed to the coolant. Westinghouse fuel is designed to minimize fretting wear by limiting the relative motion between the fuel rod and its supports. The wear producing motion between the fuel rod and its supports occurs when the vibration amplitude exceeds the slippage threshold amplitude

The giant mottled eel, Anguilla marmorata, uses blue-shifted rod photoreceptors during upstream migration.

Science.gov (United States)

Wang, Feng-Yu; Fu, Wen-Chun; Wang, I-Li; Yan, Hong Young; Wang, Tzi-Yuan

2014-01-01

Catadromous fishes migrate between ocean and freshwater during particular phases of their life cycle. The dramatic environmental changes shape their physiological features, e.g. visual sensitivity, olfactory ability, and salinity tolerance. Anguilla marmorata, a catadromous eel, migrates upstream on dark nights, following the lunar cycle. Such behavior may be correlated with ontogenetic changes in sensory systems. Therefore, this study was designed to identify changes in spectral sensitivity and opsin gene expression of A. marmorata during upstream migration. Microspectrophotometry analysis revealed that the tropical eel possesses a duplex retina with rod and cone photoreceptors. The λmax of rod cells are 493, 489, and 489 nm in glass, yellow, and wild eels, while those of cone cells are 508, and 517 nm in yellow, and wild eels, respectively. Unlike European and American eels, Asian eels exhibited a blue-shifted pattern of rod photoreceptors during upstream migration. Quantitative gene expression analyses of four cloned opsin genes (Rh1f, Rh1d, Rh2, and SWS2) revealed that Rh1f expression is dominant at all three stages, while Rh1d is expressed only in older yellow eel. Furthermore, sequence comparison and protein modeling studies implied that a blue shift in Rh1d opsin may be induced by two known (N83, S292) and four putative (S124, V189, V286, I290) tuning sites adjacent to the retinal binding sites. Finally, expression of blue-shifted Rh1d opsin resulted in a spectral shift in rod photoreceptors. Our observations indicate that the giant mottled eel is color-blind, and its blue-shifted scotopic vision may influence its upstream migration behavior and habitat choice.

[Clinical features and prognosis of retinal lattice degeneration].

Science.gov (United States)

Guo, X R

1990-07-01

110 cases (110 eyes) of retinal lattice degeneration were clinically observed and followed up for 3-8 years. Most lesions were located in the superotemporal quadrant, band-shaped, and parallel to the ora serrata. 80.9% of the lesions presented various degrees of pigmentation, 67.1% yellowish white spots, and 83.6% white lines. 32.9% of the eyes developed retinal holes. Most lattice degenerations were accompanied by vitreous degeneration and vitreoretinal traction. The disease progressed only slowly, though in a few cases it tended to expand.

ERG and other discriminators between advanced hydroxychloroquine retinopathy and retinitis pigmentosa.

Science.gov (United States)

Nair, Archana A; Marmor, Michael F

2017-06-01

To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance. We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared. Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP. While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam's razor).

Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration.

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Jillian N Pearring

2017-04-01

Full Text Available Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway. More recently, Arf4 was also implicated in regulating ciliary trafficking, however, this has not been comprehensively tested in vivo. To directly address Arf4's role in ciliary transport, we deleted Arf4 specifically in either rod photoreceptor cells, kidney, or globally during the early postnatal period. Arf4 deletion in photoreceptors did not cause protein mislocalization or retinal degeneration, as expected if Arf4 played a role in protein transport to the ciliary outer segment. Likewise, Arf4 deletion in kidney did not cause cystic disease, as expected if Arf4 were involved in general ciliary trafficking. In contrast, global Arf4 deletion in the early postnatal period resulted in growth restriction, severe pancreatic degeneration and early death. These findings are consistent with Arf4 playing a critical role in endomembrane trafficking, particularly in the pancreas, but not in ciliary function.

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).

Science.gov (United States)

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.

Electrophysiolocal findings in Mohr-Tranebjærg syndrome

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Regina Halfeld Furtado de Mendonça

2015-04-01

Full Text Available Mohr-Tranebjærg syndrome (MTS is an X-liked recessive rare syndrome also known as deafness-dystonia syndrome. The severity of the symptoms may vary, but they progress usually to severe deafness and dystonia and sometimes they are accompanied by cortical deterioration of vision and mental deterioration. The purpose of this paper is to illustrate a very interesting case of Mohr-Tranebjærg syndrome. A 24-year-old italian man with Mohr-Tranebjærg syndrome underwent full field electroretinography (ERG and visual evoked potentials (VEPs. Fundus examination showed apparently normal retina with pallor of the optic disc. Pattern reversal VEP and flash VEP responses were non-recordable. ERG showed amplitude reduction of the fotopic, scotopic and 30 Hz flicker responses revealing generalized retinal dysfunction with reduction of cone and rod responses. The progressive neurodegeneration in Mohr-Tranebjærg syndrome can be also associated with a retinal degeneration.

Identification of a Novel Mutation in the ABCA4 Gene in a Chinese Family with Retinitis Pigmentosa Using Exome Sequencing.

Science.gov (United States)

Huang, Xiangjun; Yuan, Lamei; Xu, Hongbo; Zheng, Wen; Cao, Yanna; Yi, Junhui; Guo, Yi; Yang, Zhijian; Li, Yu; Deng, Hao

2018-02-05

Retinitis pigmentosa (RP) is a group of hereditary, degenerative retinal disorders characterized by progressive retinal dysfunction, outer retina cell loss, and retinal tissue atrophy. It eventually leads to tunnel vision and legal, or total blindness. Here we aimed to reveal the causal gene and mutation contributing to the development of autosomal recessive RP (arRP) in a consanguineous family. A novel homozygous mutation, c.4845delT (p.K1616Rfs*46), in the ATP-binding cassette subfamily A member 4gene ( ABCA4 ) was identified. It may reduce ABCA4 protein activity, leading to progressive degeneration of both rod and cone photoreceptors. The study extends the arRP genotypic spectrum and confirms a genotype-phenotype relationship. This study may also disclose some new clues for RP genetic causes and pathogenesis, as well as clinical and genetic diagnosis. The research findings may contribute to improvement in clinical care, therapy, genetic screening, and counseling. ©2018 The Author(s).

Polyetheretherketone (PEEK) Rods in Lumbar Spine Degenerative Disease: A Case Series.

Science.gov (United States)

Ormond, D Ryan; Albert, Ladislau; Das, Kaushik

2016-08-01

Retrospective case series. The purpose of our study was to retrospectively review the results of posterior lumbar fusion using polyetheretherketone (PEEK) rods. Pedicle screw and rod instrumentation has become the preferred technique for performing stabilization and fusion in the lumbar spine for degenerative disease. Rigid fixation with titanium rods leads to high fusion rates, but may also contribute to stress shielding and adjacent segment degeneration (ASD). Thus, some have advocated using semirigid rods made of PEEK. Although the biomechanical properties of PEEK rods have shown improved stress-shielding characteristics and anterior load-sharing properties, there are very few clinical studies evaluating their application in the lumbar spine. We evaluated a retrospective cohort of 42 patients who underwent posterior lumbar fusion from 2007 to 2009 for the treatment of lumbar spine degenerative disease using PEEK rods. Reoperation rate was the primary outcome evaluated. Fusion rate was also evaluated. Eight of the 42 patients with PEEK rods required reoperation. Reasons for reoperation mainly included ASD (5/8) and nonunion with cage migration (3/8). Radiographically, documented fusion rate was 86%. Mean follow-up was 31.4 months. No statistical differences were found in fusion rates or reoperation between age above 55 years and younger than 55 years (P=1.00), male and female (P=0.110), single or multilevel fusion (P=0.67), and fusion with and without an interbody graft (P=0.69). Smokers showed a trend towards increased risk of reoperation for ASD or instrumentation failure (P=0.056). PEEK rods demonstrate a similar fusion and reoperation rate in comparison to other instrumentation modalities in the treatment of degenerative lumbar spine disease.

LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

Science.gov (United States)

Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A

2016-12-01

To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms. Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.

Retinal pigment epithelial detachments and tears, and progressive retinal degeneration in light chain deposition disease.

Science.gov (United States)

Spielberg, Leigh H; Heckenlively, John R; Leys, Anita M

2013-05-01

Light-chain deposition disease (LCDD) is a rare condition characterised by deposition of monoclonal immunoglobulin light chains (LCs) in tissues, resulting in varying degrees of organ dysfunction. This study reports the characteristic clinical ocular findings seen in advanced LCDD upon development of ocular fundus changes. This is the first report to describe this entity in vivo in a series of patients. A case series of ocular fundus changes in three patients with kidney biopsy-proven LCDD. All patients underwent best corrected visual acuity (BCVA) exam, perimetry, colour fundus photography and fluorescein angiography; two patients underwent indocyanine green angiography, optical coherence tomography, ultrasound and electroretinography; and one patient underwent fundus autofluorescence. Three patients, 53-60 years old at initial presentation, were studied. All three presented with night blindness, poor dark adaptation, metamorphopsia and visual loss. Examination revealed serous and serohaemorrhagic detachments, multiple retinal pigment epithelial (RPE) tears, diffuse RPE degeneration and progressive fibrotic changes. Neither choroidal neovascularisation nor other vascular abnormalities were present. Final best corrected visual acuity (BCVA) ranged from 20/40 to 20/300. Progressive LC deposition in the fundus seems to damage RPE pump function with flow disturbance between choroid and retina. This pathogenesis can explain the evolution to RPE detachments and subsequent rips and progressive retinal malfunction.

Process and equipment for locating defective fuel rods of a reactor fuel element

International Nuclear Information System (INIS)

Jester, A.; Honig, H.

1977-01-01

By this equipment, well-known processes for determining defective fuel rods of a reactor fuel element are improved in such a fashion that defective fuel rods can be located individually, so that it is possible to replace them. The equipment consists of a cylindrical test vessel open above, which accommodates the element to be tested, so that an annular space is left between the latter's external circumference and the wall of the vessel, and so that the fuel rods project above the vessel. A bell in the shape of a frustrum of a cone is inverted over the test vessel, which has an infra-red measuring equipment at a certain distance above the tops of the fuel rods. The fuel element to be tested together with the test vessel and hood are immersed in a basin full of water, which displaces water by means of gas from the hood. The post-shutdown heat increases the temperature in the water space of the test vessel, which is stabilised at 100 0 C. In each defective fuel rod the water which has penetrated the defective fuel rod previously, or does so now, starts to boil. The steam rising in the fuel rod raises the temperature of the defective fuel rod compared to all the sound ones. The subsequent measurement easily determines this. Where one can expect interference with the measurement by appreciable amounts of gamma rays, the measuring equipment is removed from the path of radiation by mirror deflection in a suitably shaped measuring hood. (FW) [de

Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study

Directory of Open Access Journals (Sweden)

Marion Fusellier

2016-01-01

Full Text Available Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi, radiography (IVD height index, and histology (NP area and Boos’ scoring. The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos’ scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration.

Modeling retinal degeneration using patient-specific induced pluripotent stem cells.

Directory of Open Access Journals (Sweden)

Zi-Bing Jin

Full Text Available Retinitis pigmentosa (RP is the most common inherited human eye disease resulting in night blindness and visual defects. It is well known that the disease is caused by rod photoreceptor degeneration; however, it remains incurable, due to the unavailability of disease-specific human photoreceptor cells for use in mechanistic studies and drug screening. We obtained fibroblast cells from five RP patients with distinct mutations in the RP1, RP9, PRPH2 or RHO gene, and generated patient-specific induced pluripotent stem (iPS cells by ectopic expression of four key reprogramming factors. We differentiated the iPS cells into rod photoreceptor cells, which had been lost in the patients, and found that they exhibited suitable immunocytochemical features and electrophysiological properties. Interestingly, the number of the patient-derived rod cells with distinct mutations decreased in vitro; cells derived from patients with a specific mutation expressed markers for oxidation or endoplasmic reticulum stress, and exhibited different responses to vitamin E than had been observed in clinical trials. Overall, patient-derived rod cells recapitulated the disease phenotype and expressed markers of cellular stresses. Our results demonstrate that the use of patient-derived iPS cells will help to elucidate the pathogenic mechanisms caused by genetic mutations in RP.

The giant mottled eel, Anguilla marmorata, uses blue-shifted rod photoreceptors during upstream migration.

Directory of Open Access Journals (Sweden)

Feng-Yu Wang

Full Text Available Catadromous fishes migrate between ocean and freshwater during particular phases of their life cycle. The dramatic environmental changes shape their physiological features, e.g. visual sensitivity, olfactory ability, and salinity tolerance. Anguilla marmorata, a catadromous eel, migrates upstream on dark nights, following the lunar cycle. Such behavior may be correlated with ontogenetic changes in sensory systems. Therefore, this study was designed to identify changes in spectral sensitivity and opsin gene expression of A. marmorata during upstream migration. Microspectrophotometry analysis revealed that the tropical eel possesses a duplex retina with rod and cone photoreceptors. The λmax of rod cells are 493, 489, and 489 nm in glass, yellow, and wild eels, while those of cone cells are 508, and 517 nm in yellow, and wild eels, respectively. Unlike European and American eels, Asian eels exhibited a blue-shifted pattern of rod photoreceptors during upstream migration. Quantitative gene expression analyses of four cloned opsin genes (Rh1f, Rh1d, Rh2, and SWS2 revealed that Rh1f expression is dominant at all three stages, while Rh1d is expressed only in older yellow eel. Furthermore, sequence comparison and protein modeling studies implied that a blue shift in Rh1d opsin may be induced by two known (N83, S292 and four putative (S124, V189, V286, I290 tuning sites adjacent to the retinal binding sites. Finally, expression of blue-shifted Rh1d opsin resulted in a spectral shift in rod photoreceptors. Our observations indicate that the giant mottled eel is color-blind, and its blue-shifted scotopic vision may influence its upstream migration behavior and habitat choice.

Rapid Retinal Release from a Cone Visual Pigment Following Photoactivation*

Science.gov (United States)

Chen, Min-Hsuan; Kuemmel, Colleen; Birge, Robert R.; Knox, Barry E.

2012-01-01

As part of the visual cycle, the retinal chromophore in both rod and cone visual pigments undergoes reversible Schiff base hydrolysis and dissociation following photobleaching. We characterized light-activated retinal release from a short-wavelength sensitive cone pigment (VCOP) in 0.1% dodecyl maltoside using fluorescence spectroscopy. The half-time (t1/2) of retinal release from VCOP was 7.1 s, 250-fold faster than rhodopsin. VCOP exhibited pH-dependent release kinetics, with the t1/2 decreasing from 23 s to 4 s with pH 4.1 to 8, respectively. However, the Arrhenius activation energy (Ea) for VCOP derived from kinetic measurements between 4° and 20°C was 17.4 kcal/mol, similar to 18.5 kcal/mol for rhodopsin. There was a small kinetic isotope (D2O) effect in VCOP, but less than that observed in rhodopsin. Mutation of the primary Schiff base counterion (VCOPD108A) produced a pigment with an unprotonated chromophore (⌊max = 360 nm) and dramatically slowed (t1/2 ~ 6.8 min) light-dependent retinal release. Using homology modeling, a VCOP mutant with two substitutions (S85D/ D108A) was designed to move the counterion one alpha helical turn into the transmembrane region from the native position. This double mutant had a UV-visible absorption spectrum consistent with a protonated Schiff base (⌊max = 420 nm). Moreover, VCOPS85D/D108A mutant had retinal release kinetics (t1/2 = 7 s) and Ea (18 kcal/mol) similar to the native pigment exhibiting no pH-dependence. By contrast, the single mutant VCOPS85D had a ~3-fold decrease in retinal release rate compared to the native pigment. Photoactivated VCOPD108A had kinetics comparable to a rhodopsin counterion mutant, RhoE113Q, both requiring hydroxylamine to fully release retinal. These results demonstrate that the primary counterion of cone visual pigments is necessary for efficient Schiff base hydrolysis. We discuss how the large differences in retinal release rates between rod and cone visual pigments arise, not from

ROLE OF DIETARY SUPPLEMENTATION IN PREVENTING PROGRESSION OF AGE-RELATED MACULAR DEGENERATION

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N. A. Ermakova

2016-01-01

Full Text Available Age-related macular degeneration (AMD is a chronic, progressive, degenerative eye disease affecting the central retina. It is the leading cause of blindness among individuals of 65 years and older. In the early stage patients have drusen and/or alterations of pigmentation in the macular region. This disease can progress to geographic atrophy and/or choroidal neovascularization. It has been shown that oxidative stress and hypoxia are important in the pathogenesis of AMD. Patients may gain some visual improvement with inhibitors of vascular endothelial growth factor, but complete restoration of visual function is achieved only in small cases. No effective therapies are known for atrophic AMD. Many large observational studies have shown that dietary antioxidant supplementation is beneficial in preventing the progression of AMD from early to late stages. The Age-Related Eye Disease Study (AREDS demonstrated that daily oral supplementation with vitamins C (500 mg and E (400 IU, beta carotene (15 mg, zinc (80 mg and copper (2 mg reduced the risk of progression to advanced AMD by 25% at 5 years. In primary analyses AREDS II failed to show further reduce of this risk by addition of lutein (10 mg and zeaxanthin (2mg, or/and omega-3 long-chain polyunsaturated fatty acids [docosahexaenoic acid (350 mg DHA and eicosapentaenoic acid 650 mg (EPA] to the AREDS formulation. But there was no true placebo group. The simultaneous administration of beta carotene, lutein and zeaxanthin may suppress tissue level of the both laters because of competitive absorption of carotenoids. Subgroup analyses revealed that dietary supplementation with lutein, zeaxanthin and AREDS formulation without beta carotene may reduce the risk of progression to advanced AMD.The LUNA (Lutein nutrition effects measured by autofluorescence study demonstrated that supplementation with lutein (12 mg, zeaxanthin (1 mg, vitamin C (120 mg, vitamin E (17,6 mg, zinc (10 mg, selenium (40 mg resulted

Nontraumatic tibial polyethylene insert cone fracture in mobile-bearing posterior-stabilized total knee arthroplasty

OpenAIRE

Tanikake, Yohei; Hayashi, Koji; Ogawa, Munehiro; Inagaki, Yusuke; Kawate, Kenji; Tomita, Tetsuya; Tanaka, Yasuhito

2016-01-01

A 72-year-old male patient underwent mobile-bearing posterior-stabilized total knee arthroplasty for osteoarthritis. He experienced a nontraumatic polyethylene tibial insert cone fracture 27 months after surgery. Scanning electron microscopy of the fracture surface of the tibial insert cone suggested progress of ductile breaking from the posterior toward the anterior of the cone due to repeated longitudinal bending stress, leading to fatigue breaking at the anterior side of the cone, followed...

Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.

Science.gov (United States)

Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

2016-08-11

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.

Hypoxic preconditioning protects photoreceptors against light damage independently of hypoxia inducible transcription factors in rods.

Science.gov (United States)

Kast, Brigitte; Schori, Christian; Grimm, Christian

2016-05-01

Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used rod-specific Hif2a single and Hif1a;Hif2a double knockout mice to investigate the potential involvement of HIF2 in rods for protection after hypoxic preconditioning. To identify potential HIF2 target genes in rods we determined the retinal transcriptome of hypoxic control and rod-specific Hif2a knockouts by RNA sequencing. We show that rods do not need HIF2 for hypoxia-induced increased survival after light exposure. The transcriptomic analysis revealed a number of genes that are potentially regulated by HIF2 in rods; among those were Htra1, Timp3 and Hmox1, candidates that are interesting due to their connection to human degenerative diseases of the retina. We conclude that neither HIF1 nor HIF2 are required in photoreceptors for protection by hypoxic preconditioning. We hypothesize that HIF transcription factors may be needed in other cells to produce protective factors acting in a paracrine fashion on photoreceptor cells. Alternatively, hypoxic preconditioning induces a rod-intrinsic response that is independent of HIF transcription factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

Science.gov (United States)

Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

2014-01-01

Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration.

Science.gov (United States)

Shroyer, N F; Lewis, R A; Yatsenko, A N; Wensel, T G; Lupski, J R

2001-11-01

Mutations in ABCR (ABCA4) have been reported to cause a spectrum of autosomal recessively inherited retinopathies, including Stargardt disease (STGD), cone-rod dystrophy and retinitis pigmentosa. Individuals heterozygous for ABCR mutations may be predisposed to develop the multifactorial disorder age-related macular degeneration (AMD). We hypothesized that some carriers of STGD alleles have an increased risk to develop AMD. We tested this hypothesis in a cohort of families that manifest both STGD and AMD. With a direct-sequencing mutation detection strategy, we found that AMD-affected relatives of STGD patients are more likely to be carriers of pathogenic STGD alleles than predicted based on chance alone. We further investigated the role of AMD-associated ABCR mutations by testing for expression and ATP-binding defects in an in vitro biochemical assay. We found that mutations associated with AMD have a range of assayable defects ranging from no detectable defect to apparent null alleles. Of the 21 missense ABCR mutations reported in patients with AMD, 16 (76%) show abnormalities in protein expression, ATP-binding or ATPase activity. We infer that carrier relatives of STGD patients are predisposed to develop AMD.

Apparatus for inspecting a irradiated nuclear fuel rod

International Nuclear Information System (INIS)

Saura, Hideaki; Yonemura, Eizo.

1975-01-01

Object: To increase safety and inspection efficiency by operating irradiated fuel rods, which are accommodated in a water-filled pool after being taken out from the reactor. Structure: When making inspection of irradiated fuel rods, particularly the cladding tube thereof, a fuel box which stores irradiated fuel rods in a water pool is secured to a securement mechanism with slime removal apparatus and inspection apparatus on either side capable of being vertically moved, and it is then stopped at a water depth of about 2 meters. When the lid of the box is opened, irradiated fuel rods are taken out with gripping means and then secured together with the gripping means to an operation base provided on the outside of the pool. Thereafter, the box is lowered by operating pedals on the operation base to completely pull out the irradiated fuel rods from the box, and the irradiated fuel rods are then horizontally moved and then held in a suspended state. Next a slime removal apparatus in raised by operating pedals and an inspection element assembly are progressively raised for inspection of the state of the cladding tube of each fuel rod after removal of slime therefrom. (Nakamura, S.)

Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity.

Science.gov (United States)

Omori, Yoshihiro; Kubo, Shun; Kon, Tetsuo; Furuhashi, Mayu; Narita, Hirotaka; Kominami, Taro; Ueno, Akiko; Tsutsumi, Ryotaro; Chaya, Taro; Yamamoto, Haruka; Suetake, Isao; Ueno, Shinji; Koseki, Haruhiko; Nakagawa, Atsushi; Furukawa, Takahisa

2017-09-26

Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7- null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7 -deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity.

Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle.

Science.gov (United States)

Frederick, David W; Loro, Emanuele; Liu, Ling; Davila, Antonio; Chellappa, Karthikeyani; Silverman, Ian M; Quinn, William J; Gosai, Sager J; Tichy, Elisia D; Davis, James G; Mourkioti, Foteini; Gregory, Brian D; Dellinger, Ryan W; Redpath, Philip; Migaud, Marie E; Nakamaru-Ogiso, Eiko; Rabinowitz, Joshua D; Khurana, Tejvir S; Baur, Joseph A

2016-08-09

NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function. Copyright © 2016 Elsevier Inc. All rights reserved.

Retinal function in patients with the neuronal ceroid lipofuscinosis phenotype

Directory of Open Access Journals (Sweden)

Elizabeth Maria Aparecida Barasnevicius Quagliato

Full Text Available ABSTRACT Purpose: To analyze the clinical features, visual acuity, and full-field electroretinogram (ERG findings of 15 patients with the neuronal ceroid lipofuscinosis (NCL phenotype and to establish the role of ERG testing in NCL diagnosis. Methods: The medical records of five patients with infantile NCL, five with Jansky-Bielschowsky disease, and five with juvenile NCL who underwent full-field ERG testing were retrospectively analyzed. Results: Progressive vision loss was the initial symptom in 66.7% of patients and was isolated or associated with ataxia, epilepsy, and neurodevelopmental involution. Epilepsy was present in 93.3% of patients, of whom 86.6% presented with neurodevelopmental involution. Fundus findings ranged from normal to pigmentary/atrophic abnormalities. Cone-rod, rod-cone, and both types of dysfunction were observed in six, one, and eight patients, respectively. Conclusion: In our study, all patients with the NCL phenotype had abnormal ERG findings, and the majority exhibited both cone-rod and rod-cone dysfunction. We conclude that ERG is a valuable tool for the characterization of visual dysfunction in patients with the NCL phenotype and is useful for diagnosis.

The dual rod system of amphibians supports colour discrimination at the absolute visual threshold.

Science.gov (United States)

Yovanovich, Carola A M; Koskela, Sanna M; Nevala, Noora; Kondrashev, Sergei L; Kelber, Almut; Donner, Kristian

2017-04-05

The presence of two spectrally different kinds of rod photoreceptors in amphibians has been hypothesized to enable purely rod-based colour vision at very low light levels. The hypothesis has never been properly tested, so we performed three behavioural experiments at different light intensities with toads ( Bufo ) and frogs ( Rana ) to determine the thresholds for colour discrimination. The thresholds of toads were different in mate choice and prey-catching tasks, suggesting that the differential sensitivities of different spectral cone types as well as task-specific factors set limits for the use of colour in these behavioural contexts. In neither task was there any indication of rod-based colour discrimination. By contrast, frogs performing phototactic jumping were able to distinguish blue from green light down to the absolute visual threshold, where vision relies only on rod signals. The remarkable sensitivity of this mechanism comparing signals from the two spectrally different rod types approaches theoretical limits set by photon fluctuations and intrinsic noise. Together, the results indicate that different pathways are involved in processing colour cues depending on the ecological relevance of this information for each task.This article is part of the themed issue 'Vision in dim light'. © 2017 The Authors.

Nontraumatic tibial polyethylene insert cone fracture in mobile-bearing posterior-stabilized total knee arthroplasty

Directory of Open Access Journals (Sweden)

Yohei Tanikake

2016-12-01

Full Text Available A 72-year-old male patient underwent mobile-bearing posterior-stabilized total knee arthroplasty for osteoarthritis. He experienced a nontraumatic polyethylene tibial insert cone fracture 27 months after surgery. Scanning electron microscopy of the fracture surface of the tibial insert cone suggested progress of ductile breaking from the posterior toward the anterior of the cone due to repeated longitudinal bending stress, leading to fatigue breaking at the anterior side of the cone, followed by the tibial insert cone fracture at the anterior side of the cone, resulting in fracture at the base of the cone. This analysis shows the risk of tibial insert cone fracture due to longitudinal stress in mobile-bearing posterior-stabilized total knee arthroplasty in which an insert is designed to highly conform to the femoral component.

French LMFBR's control rods experience and development

International Nuclear Information System (INIS)

Arnaud, G.; Guigon, A.; Verset, L.

1983-06-01

Since the last ten years, the French program has been, first of all, directed to the setting up, and then the development of, at once, the Phenix control rods, and next, the Super-Phenix ones. The vented pin design, with porous plug and sodium bonding, which allows the choices of large diameters, has been taken, since the Rapsodie experience was decisive. The absorber material is sintered, 10 B enriched, boron carbide. The can is made of 316 type stainless steel, stabilised, or not, with titanium. The experience gained in Phenix up to now is important, and deals with about six loads of control rods. Results confirm the validity of the design of the absorber pins. Some difficulties has been encountered for the guiding devices, due to the swelling of the steel. They have required design and material improvements. Such difficulties are discarded by a new design of the bearing, for the Super-Phenix control rods. The other parts of these rods, from the Primary Shut-Down System, are strictly derived from Phenix. The design of the rods from the Secondary Shut-Down System is rather different, but it's not the case for the design of the absorber pins: in many a way, they are derived from Phenix pins and from Rapsodie control rods. Both types of rods irradiation tests are in progress in Phenix [fr

Control rod

International Nuclear Information System (INIS)

Kawakami, Kazuo; Shimoshige, Takanori; Nishimura, Akira

1979-01-01

Purpose: A control rod has been developed, which provided a plurality of through-holes in the vicinity of the sheath fitting position, in order to flatten burn-up, of fuel rods in positions confronting a control rod. Thereby to facilitate the manufacture of the control rods and prevent fuel rod failures. Constitution: A plurality of through-holes are formed in the vicinity of the sheath fitting position of a central support rod to which a sheath for the control rod is fitted. These through-holes are arranged in the axial direction of the central support rod. Accordingly, burn-up of fuel rods confronting the control rods can be reduced by through-holes and fuel rod failures can be prevented. (Yoshino, Y.)

Choice of Cell Source in Cell-Based Therapies for Retinal Damage due to Age-Related Macular Degeneration: A Review

Directory of Open Access Journals (Sweden)

Sudhakar John

2013-01-01

Full Text Available Background. Age-related macular degeneration (AMD is a complex disorder that affects primarily the macula involving the retinal pigment epithelium (RPE but also to a certain extent the photoreceptor layer and the retinal neurons. Cell transplantation is a promising option for AMD and clinical trials are underway using different cell types. Methods. We hypothesize that instead of focusing on a particular cell source for concurrent regeneration of all the retinal layers and also to prevent exhaustive research on an array of cell sources for regeneration of each layer, the choice should depend on, precisely, which layer is damaged. Results. Thus, for a damage limited to the retinal pigment epithelial (RPE layer, the choice we suggest would be RPE cells. When the damage extends to rods and cones, the choice would be bone marrow stem cells and when retinal neurons are involved, relatively immature stem cell populations with an inherent capacity to yield neuronal lineage such as hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells can be tried. Conclusion. This short review will prove to be a valuable guideline for those working on cell therapy for AMD to plan their future directions of research and therapy for this condition.

Rod Migration Into the Spinal Canal After Posterior Instrumented Fusion Causing Late-Onset Neurological Symptoms.

Science.gov (United States)

Canavese, Federico; Dmitriev, Petru; Deslandes, Jacques; Samba, Antoine; Dimeglio, Alain; Mansour, Mounira; Rousset, Marie; Dubousset, Jean

2017-01-01

Rod migration into the spinal canal after posterior instrumented fusion is a rare complication causing late-onset neurological symptoms. The purpose of the present study is to report a case of a 13-year-old boy with spastic cerebral palsy and related neuromuscular kyphoscoliosis who developed late-onset neurological deterioration secondary to progressive implant migration into the spinal canal over a 5-year period. A decision was made to remove both rods to achieve decompression. Intraoperative findings were consistent with information gained from preoperative imaging. The rods were found to have an intracanal trajectory at T9-T10 for the right rod and T12-L2 for the left rod. The cause of implant migration, with progressive laminar erosion slow enough to generate a solid mass behind, was progressive kyphosis in a skeletally immature patient with neuromuscular compromise. Fixation type, early surgery, and spasticity management contributed significantly to the presenting condition. Mechanical factors and timing of surgery played a decisive role in this particular presentation. Level IV--Case report and review of the literature.

Intramuscular degeneration process in Duchenne muscular dystrophy

International Nuclear Information System (INIS)

Hasegawa, Takeshi; Matsumra, Kiichiro; Hashimoto, Takahiro; Ikehira, Hiroo; Fukuda, Hiroshi; Tateno, Yukio.

1992-01-01

Intramuscular degeneration process of Duchenne dystrophy skeletal muscles was investigated by longitudinal skeletal muscle imaging with high-field-strength NMR-CT of 1.5 Tesla. Thigh muscles in 10 cases ranging in age from 4 to 19 years were examined by T 1 -weighted longitudinal images (TR=215∼505 ms, TE=19∼20 ms). The following results were obtained. Skeletal muscle degeneration was depicted as high signal intensity area reflecting its high fat contents. These high signal intensity areas had a longitudinally streaky appearance in parallel direction with myofibers. These findings were more prominent toward myotendon junction than muscle bellies. Skeletal muscle degeneration progressed rapidly between 7 to 10 years of age, and reached a plateau after that. (author)

Radioactive lightning rods waste treatment

International Nuclear Information System (INIS)

Vicente, Roberto; Dellamano, Jose C.; Hiromoto, Goro

2008-01-01

Full text: In this paper, we present alternative processes that could be adopted for the management of radioactive waste that arises from the replacement of lightning rods with attached Americium-241 sources. Lightning protectors, with Americium-241 sources attached to the air terminals, were manufactured in Brazil until 1989, when the regulatory authority overthrew the license for fabrication, commerce, and installation of radioactive lightning rods. It is estimated that, during the license period, about 75,000 such devices were set up in public, commercial and industrial buildings, including houses and schools. However, the policy of CNEN in regard to the replacement of the installed radioactive rods, has been to leave the decision to municipal governments under local building regulations, requiring only that the replaced rods be sent immediately to one of its research institutes to be treated as radioactive waste. As a consequence, the program of replacement proceeds in a low pace and until now only about twenty thousand rods have reached the waste treatment facilities The process of management that was adopted is based primarily on the assumption that the Am-241 sources will be disposed of as radioactive sealed sources, probably in a deep borehole repository. The process can be described broadly by the following steps: a) Receive and put the lightning rods in initial storage; b) Disassemble the rods and pull out the sources; c) Decontaminate and release the metal parts to metal recycling; d) Store the sources in intermediate storage; e) Package the sources in final disposal packages; and f) Send the sources for final disposal. Up to now, the disassembled devices gave rise to about 90,000 sources which are kept in storage while the design of the final disposal package is in progress. (author)

Degenerate mixing of plasma waves on cold, magnetized single-species plasmas

International Nuclear Information System (INIS)

Anderson, M. W.; O'Neil, T. M.; Dubin, D. H. E.; Gould, R. W.

2011-01-01

In the cold-fluid dispersion relation ω=ω p /[1+(k perpendicular /k z ) 2 ] 1/2 for Trivelpiece-Gould waves on an infinitely long magnetized plasma cylinder, the transverse and axial wavenumbers appear only in the combination k perpendicular /k z . As a result, for any frequency ω p , there are infinitely many degenerate waves, all having the same value of k perpendicular /k z . On a cold finite-length plasma column, these degenerate waves reflect into one another at the ends; thus, each standing-wave normal mode of the bounded plasma is a mixture of many degenerate waves, not a single standing wave as is often assumed. A striking feature of the many-wave modes is that the short-wavelength waves often add constructively along resonance cones given by dz/dr=±(ω p 2 /ω 2 -1) 1/2 . Also, the presence of short wavelengths in the admixture for a predominantly long-wavelength mode enhances the viscous damping beyond what the single-wave approximation would predict. Here, numerical solutions are obtained for modes of a cylindrical plasma column with rounded ends. Exploiting the fact that the modes of a spheroidal plasma are known analytically (the Dubin modes), a perturbation analysis is used to investigate the mixing of low-order, nearly degenerate Dubin modes caused by small deformations of a plasma spheroid.

Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

Science.gov (United States)

Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

2017-09-01

There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.

Degenerate mixing of plasma waves on cold, magnetized single-species plasmas

Science.gov (United States)

Anderson, M. W.; O'Neil, T. M.; Dubin, D. H. E.; Gould, R. W.

2011-10-01

In the cold-fluid dispersion relation ω =ωp/[1+(k⊥/kz)2]1/2 for Trivelpiece-Gould waves on an infinitely long magnetized plasma cylinder, the transverse and axial wavenumbers appear only in the combination k⊥/kz. As a result, for any frequency ω plasma column, these degenerate waves reflect into one another at the ends; thus, each standing-wave normal mode of the bounded plasma is a mixture of many degenerate waves, not a single standing wave as is often assumed. A striking feature of the many-wave modes is that the short-wavelength waves often add constructively along resonance cones given by dz /dr=±(ωp2/ω2-1)1/2. Also, the presence of short wavelengths in the admixture for a predominantly long-wavelength mode enhances the viscous damping beyond what the single-wave approximation would predict. Here, numerical solutions are obtained for modes of a cylindrical plasma column with rounded ends. Exploiting the fact that the modes of a spheroidal plasma are known analytically (the Dubin modes), a perturbation analysis is used to investigate the mixing of low-order, nearly degenerate Dubin modes caused by small deformations of a plasma spheroid.

Light-cone quantized QCD and novel hadron phenomenology

International Nuclear Information System (INIS)

Brodsky, S.J.

1997-09-01

The authors reviews progress made in solving gauge theories such as collinear quantum chromodynamics using light-cone Hamiltonian methods. He also shows how the light-cone Fock expansion for hadron wavefunctions can be used to compute operator matrix elements such as decay amplitudes, form factors, distribution amplitudes, and structure functions, and how it provides a tool for exploring novel features of QCD. The author also reviews commensurate scale relations, leading-twist identities which relate physical observables to each other, thus eliminating renormalization scale and scheme ambiguities in perturbative QCD predictions

Cone Algorithm of Spinning Vehicles under Dynamic Coning Environment

Directory of Open Access Journals (Sweden)

Shuang-biao Zhang

2015-01-01

Full Text Available Due to the fact that attitude error of vehicles has an intense trend of divergence when vehicles undergo worsening coning environment, in this paper, the model of dynamic coning environment is derived firstly. Then, through investigation of the effect on Euler attitude algorithm for the equivalency of traditional attitude algorithm, it is found that attitude error is actually the roll angle error including drifting error and oscillating error, which is induced directly by dynamic coning environment and further affects the pitch angle and yaw angle through transferring. Based on definition of the cone frame and cone attitude, a cone algorithm is proposed by rotation relationship to calculate cone attitude, and the relationship between cone attitude and Euler attitude of spinning vehicle is established. Through numerical simulations with different conditions of dynamic coning environment, it is shown that the induced error of Euler attitude fluctuates by the variation of precession and nutation, especially by that of nutation, and the oscillating frequency of roll angle error is twice that of pitch angle error and yaw angle error. In addition, the rotation angle is more competent to describe the spinning process of vehicles under coning environment than Euler angle gamma, and the real pitch angle and yaw angle are calculated finally.

Modeling the Flexural Rigidity of Rod Photoreceptors

Science.gov (United States)

Haeri, Mohammad; Knox, Barry E.; Ahmadi, Aphrodite

2013-01-01

In vertebrate eyes, the rod photoreceptor has a modified cilium with an extended cylindrical structure specialized for phototransduction called the outer segment (OS). The OS has numerous stacked membrane disks and can bend or break when subjected to mechanical forces. The OS exhibits axial structural variation, with extended bands composed of a few hundred membrane disks whose thickness is diurnally modulated. Using high-resolution confocal microscopy, we have observed OS flexing and disruption in live transgenic Xenopus rods. Based on the experimental observations, we introduce a coarse-grained model of OS mechanical rigidity using elasticity theory, representing the axial OS banding explicitly via a spring-bead model. We calculate a bending stiffness of ∼105 nN⋅μm2, which is seven orders-of-magnitude larger than that of typical cilia and flagella. This bending stiffness has a quadratic relation to OS radius, so that thinner OS have lower fragility. Furthermore, we find that increasing the spatial frequency of axial OS banding decreases OS rigidity, reducing its fragility. Moreover, the model predicts a tendency for OS to break in bands with higher spring number density, analogous to the experimental observation that transgenic rods tended to break preferentially in bands of high fluorescence. We discuss how pathological alterations of disk membrane properties by mutant proteins may lead to increased OS rigidity and thus increased breakage, ultimately contributing to retinal degeneration. PMID:23442852

Transgenic Expression of Constitutively Active RAC1 Disrupts Mouse Rod Morphogenesis

Science.gov (United States)

Song, Hongman; Bush, Ronald A.; Vijayasarathy, Camasamudram; Fariss, Robert N.; Kjellstrom, Sten; Sieving, Paul A.

2014-01-01

Purpose. Dominant-active RAC1 rescues photoreceptor structure in Drosophila rhodopsin-null mutants, indicating an important role in morphogenesis. This report assesses the morphogenetic effect of activated RAC1 during mammalian rod photoreceptor development using transgenic mice that express constitutively active (CA) RAC1. Methods. Transgenic mice were generated by expressing CA RAC1 under control of the Rhodopsin promoter, and morphological features of the photoreceptors were evaluated by histology, immunohistochemistry, and transmission electron microscopy. Function was evaluated by electroretinography. Potential protein partners of CA RAC1 were identified by co-immunoprecipitation of retinal extracts. Results. Constitutively active RAC1 expression in differentiating rods disrupted outer retinal lamination as early as postnatal day (P)6, and many photoreceptor cell nuclei were displaced apically into the presumptive subretinal space. These photoreceptors did not develop normal inner and outer segments and had abnormal placement of synaptic elements. Some photoreceptor nuclei were also mislocalized into the inner nuclear layer. Extensive photoreceptor degeneration was subsequently observed in the adult animal. Constitutively active RAC1 formed a complex with the polarity protein PAR6 and with microtubule motor dynein in mouse retina. The normal localization of the PAR6 complex was disrupted in CA RAC1-expressing rod photoreceptors. Conclusions. Constitutively active RAC1 had a profound negative effect on mouse rod cell viability and development. Rod photoreceptors in the CA RAC1 retina exhibited a defect in polarity and migration. Constitutively active RAC1 disrupted rod morphogenesis and gave a phenotype resembling that found in the Crumbs mutant. PAR6 and dynein are two potential downstream effectors that may be involved in CA RAC1-mediated defective mouse photoreceptor morphogenesis. PMID:24651551

Corrugated thimble tube for controlling control rod descent in nuclear reactor

International Nuclear Information System (INIS)

Luetzow, H.J.

1981-01-01

A thimble tube construction is described which will provide a controlled descent for a control rod while minimizing the reaction forces which must be absorbed by the thimble tube and reducing the possibility that a foreign particle could interfere with the free descent of a control rod. A thimble tube is formed with helically-corrugate internal walls which cooperate with a control rod contained in the tube in an emergency situation to provide a progressively-increasing hydraulic restraining force as each adjacent corrugation is encountered

Cold knife cone biopsy

Science.gov (United States)

... biopsy; Pap smear - cone biopsy; HPV - cone biopsy; Human papilloma virus - cone biopsy; Cervix - cone biopsy; Colposcopy - cone biopsy Images Female reproductive anatomy Cold cone biopsy Cold cone removal References Baggish ...

Lattice degeneration of the retina and retinal detachment.

Science.gov (United States)

Semes, L P

1992-01-01

Lattice retinal degeneration is considered the most significant peripheral retinal disorder potentially predisposing to retinal breaks and retinal detachment. Lattice degeneration affects the vitreous and inner retinal layers with secondary changes as deep as the retinal pigment epithelium and perhaps the choriocapillaris. Variations in clinical appearance are the rule; geographically, lattice lesions favor the vertical meridians between the equator and the ora serrata. Lattice degeneration begins early in life and has been reported in sequential generations of the same family. Along with its customary bilateral occurrence, lattice shares other characteristics of a dystrophy. The association between the vitreous and retina in lattice lesions may be responsible for the majority of lattice-induced retinal detachments. The tumultuous event of posterior vitreous separation in the presence of abnormally strong vitreoretinal adherence is the trigger for a retinal tear that, in turn, may lead to retinal detachment. Although retinal holes in young patients with lattice degeneration may play a role in the evolution of retinal detachment, the clinical course of lattice degeneration seems to be one of dormancy rather than of progressive change. This discussion outlines the pathophysiology of lattice retinal degeneration and the relationship of pathophysiology to clinical presentation. The epidemiology of lattice degeneration is summarized, as are the possible precursors to retinal detachment. A clinical characterization of the natural history of lattice degeneration is offered, and interventions for complications are described. To conclude, management strategies from a primary-care standpoint are reviewed.

Gender difference in genetic association between IL1A variant and early lumbar disc degeneration

DEFF Research Database (Denmark)

Eskola, Pasi J; Kjær, Per; Sorensen, Joan S

2012-01-01

The purpose of the present study was to analyze the associations between specific genetic markers and early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI)....

Rod rotation and differential rod contouring followed by direct vertebral rotation for treatment of adolescent idiopathic scoliosis: effect on thoracic and thoracolumbar or lumbar curves assessed with intraoperative computed tomography.

Science.gov (United States)

Seki, Shoji; Kawaguchi, Yoshiharu; Nakano, Masato; Makino, Hiroto; Mine, Hayato; Kimura, Tomoatsu

2016-03-01

Although direct vertebral rotation (DVR) is now used worldwide for the surgical treatment of adolescent idiopathic scoliosis (AIS), the benefit of DVR in reducing vertebral body rotation in these patients has not been determined. We investigated a possible additive effect of DVR on further reduction of vertebral body rotation in the axial plane following intraoperative rod rotation or differential rod contouring in patients undergoing surgical treatment for AIS. The study was a prospective computed tomography (CT) image analysis. We analyzed the results of the two intraoperative procedures in 30 consecutive patients undergoing surgery for AIS (Lenke type I or II: 15; Lenke type V: 15). The angle of reduction of vertebral body rotation taken by intraoperative CT scan was measured and analyzed. Pre- and postoperative responses to the Scoliosis Research Society 22 Questionnaire (SRS-22) were also analyzed. To analyze the reduction of vertebral body rotation with rod rotation or DVR, intraoperative cone-beam CT scans of the three apical vertebrae of the major curve of the scoliosis (90 vertebrae) were taken pre-rod rotation (baseline), post-rod rotation with differential rod contouring, and post-DVR in all patients. The angle of vertebral body rotation in these apical vertebrae was measured and analyzed for statistical significance. Additionally, differences between thoracic curve scoliosis (Lenke type I or II; 45 vertebrae) and thoracolumbar or lumbar curve scoliosis (Lenke type V; 45 vertebrae) were analyzed. Pre- and postoperative SRS-22 scores were evaluated in all patients. The mean (90 vertebrae) vertebral body rotation angles at baseline, post-rod rotation or differential rod contouring, and post-rod rotation or differential rod contouring or post-DVR were 17.3°, 11.1°, and 6.9°, respectively. The mean reduction in vertebral body rotation with the rod rotation technique was 6.8° for thoracic curves and 5.7° for thoracolumbar or lumbar curves (pself

Control rod

International Nuclear Information System (INIS)

Igarashi, Takao; Sugawara, Satoshi; Yoshimoto, Yuichiro; Saito, Shozo; Fukumoto, Takashi.

1987-01-01

Purpose: To reduce the weight and thereby obtain satisfactory operationability of control rods by combining absorbing nuclear chain type neutron absorbers and conventional type neutron absorbers in the axial direction of blades. Constitution: Neutron absorber rods and long life type neutron absorber rods are disposed in a tie rod and a sheath. The neutron absorber rod comprises a poison tube made of stainless steels and packed with B 4 C powder. The long life type neutron absorber rod is prepared by packing B-10 enriched boron carbide powder into a hafnium metal rod, hafnium pipe, europium and stainless made poison tube. Since the long life type absorber rod uses HF as the absorbing nuclear chain type neutron absorber, it absorbs neutrons to form new neutron absorbers to increase the nuclear life. (Yoshino, Y.)

Control rods

International Nuclear Information System (INIS)

Maruyama, Hiromi.

1984-01-01

Purpose: To realize effective utilization, cost reduction and weight reduction in neutron absorbing materials. Constitution: Residual amount of neutron absorbing material is averaged between the top end region and other regions of a control rod upon reaching to the control rod working life, by using a single kind of neutron absorbing material and increasing the amount of the neutron absorber material at the top end region of the control rod as compared with that in the other regions. Further, in a case of a control rod having control rod blades such as in a cross-like control rod, the amount of the neutron absorbing material is decreased in the middle portion than in the both end portions of the control rod blade along the transversal direction of the rod, so that the residual amount of the neutron absorbing material is balanced between the central region and both end regions upon reaching the working life of the control rod. (Yoshihara, H.)

Control-rod parametrical studies in the framework of the PRE-RACINE and RACINE programs

International Nuclear Information System (INIS)

Humbert, G.; Ruelle, B.; Daguzan, G.; Stanculescu, A.; Kappler, F.; Scholtyssek, W.; Bouscavet, D.; Martini, M.; Broccoli, U.

1982-01-01

A control-rod experimental program is presented. This program, established in the frame of PRE-RACINE and RACINE common DEBENE, Italian and French experiments at MASURCA facility, is still under progress at the moment. The results, limited to single central rod worth are already available. For these experiments, a parametrical approach has been used. The effects of rod worth, varied separatly by rod side, boron enrichment and core size, on experiment to calculation relative discrepancy (E-C)/C can be drawn out

Control rod calibration including the rod coupling effect

International Nuclear Information System (INIS)

Szilard, R.; Nelson, G.W.

1984-01-01

In a reactor containing more than one control rod, which includes all reactors licensed in the United States, there will be a 'coupling' or 'shadowing' of control rod flux at the location of a control rod as a result of the flux depression caused by another control rod. It was decided to investigate this phenomenon further, and eventually to put calibration table data or formulae in a small computer in the control room, so once could insert the positions of the three control rods and receive the excess reactivity without referring to separate tables. For this to be accomplished, a 'three control- rod reactivity function' would be used which would include the flux coupling between the rods. The function is design and measured data was fitted into it to determine the calibration constants. The input data for fitting the trial functions consisted of 254 data points, each consisting of the position of the reg, shim, and transient rods, and the total excess reactivity. (About 200 of these points were 'critical balance points', that is the rod positions for which reactor was critical, and the remainder were determined by positive period measurements.) Although this may be unrealistic from a physical viewpoint, the function derived gave a very accurate recalculation of the input data, and thus would faithfully give the excess reactivity for any possible combination of the locations of the three control rods. The next step, incorporation of the three-rod function into the minicomputer, will be pursued in the summer and fall of 1984

Progression of retinal pigment epithelial atrophy in antiangiogenic therapy of neovascular age-related macular degeneration.

Science.gov (United States)

Schütze, Christopher; Wedl, Manuela; Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

2015-06-01

To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT). Prospective interventional case series. setting: Clinical practice. Thirty patients (31 eyes) with treatment-naïve neovascular AMD. Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. RPE response, geographic atrophy (GA) progression. Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm(2) at 12 months to 1.10 mm(2) (standard deviation = 1.09 mm(2)) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased. Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

National standards and code compliance for electrical equipment and instruments installed in hazardous locations for the cone penetrometer

International Nuclear Information System (INIS)

Bussell, J.H.

1996-03-01

The cone penetrometer is designed to measure the material properties of waste tank contents at the Hanford Site. The penetrometer system consists of a skid-mounted assembly, a penetrometer assembly (composed of a guide tube and a push rod), an active neutron moisture measurement probe, decontamination unit, and a support trailer containing a diesel-engine-driven hydraulic pump and a generator. The skid-mounted assembly is about 8 feet wide by 23 feet long and 15 feet high. Its nominal weight is about 40,000 pounds with the provisions to add up to 54,500 pounds of additional ballast. This document describes the cone penetrometer electrical instruments and how it complies with national standards

Complement pathway biomarkers and age-related macular degeneration

Science.gov (United States)

Gemenetzi, M; Lotery, A J

2016-01-01

In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

Ubiquitin–Synaptobrevin Fusion Protein Causes Degeneration of Presynaptic Motor Terminals in Mice

Science.gov (United States)

Liu, Yun; Li, Hongqiao; Sugiura, Yoshie; Han, Weiping; Gallardo, Gilbert; Khvotchev, Mikhail; Zhang, Yinan; Kavalali, Ege T.; Südhof, Thomas C.

2015-01-01

Protein aggregates containing ubiquitin (Ub) are commonly observed in neurodegenerative disorders, implicating the involvement of the ubiquitin proteasome system (UPS) in their pathogenesis. Here, we aimed to generate a mouse model for monitoring UPS function using a green fluorescent protein (GFP)-based substrate that carries a “noncleavable” N-terminal ubiquitin moiety (UbG76V). We engineered transgenic mice expressing a fusion protein, consisting of the following: (1) UbG76V, GFP, and a synaptic vesicle protein synaptobrevin-2 (UbG76V-GFP-Syb2); (2) GFP-Syb2; or (3) UbG76V-GFP-Syntaxin1, all under the control of a neuron-specific Thy-1 promoter. As expected, UbG76V-GFP-Syb2, GFP-Syb2, and UbG76V-GFP-Sytaxin1 were highly expressed in neurons, such as motoneurons and motor nerve terminals of the neuromuscular junction (NMJ). Surprisingly, UbG76V-GFP-Syb2 mice developed progressive adult-onset degeneration of motor nerve terminals, whereas GFP-Syb2 and UbG76V-GFP-Syntaxin1 mice were normal. The degeneration of nerve terminals in UbG76V-GFP-Syb2 mice was preceded by a progressive impairment of synaptic transmission at the NMJs. Biochemical analyses demonstrated that UbG76V-GFP-Syb2 interacted with SNAP-25 and Syntaxin1, the SNARE partners of synaptobrevin. Ultrastructural analyses revealed a marked reduction in synaptic vesicle density, accompanying an accumulation of tubulovesicular structures at presynaptic nerve terminals. These morphological defects were largely restricted to motor nerve terminals, as the ultrastructure of motoneuron somata appeared to be normal at the stages when synaptic nerve terminals degenerated. Furthermore, synaptic vesicle endocytosis and membrane trafficking were impaired in UbG76V-GFP-Syb2 mice. These findings indicate that UbG76V-GFP-Syb2 may compete with endogenous synaptobrevin, acting as a gain-of-function mutation that impedes SNARE function, resulting in the depletion of synaptic vesicles and degeneration of the nerve

Control rod drives

International Nuclear Information System (INIS)

Nakamura, Akira.

1984-01-01

Purpose: To enable to monitor the coupling state between a control rod and a control rod drive. Constitution: After the completion of a control rod withdrawal, a coolant pressure is applied to a control rod drive being adjusted so as to raise only the control rod drive and, in a case where the coupling between the control rod drive and the control rod is detached, the former is elevated till it contacts the control rod and then stopped. The actual stopping position is detected by an actual position detection circuit and compared with a predetermined position stored in a predetermined position detection circuit. If both of the positions are not aligned with each other, it is judged by a judging circuit that the control rod and the control rod drives are not combined. (Sekiya, K.)

Analysing the Progression Rates of Macular Lesions with Autofluorescence Imaging Modes in Dry Age-Related Macular Degeneration

Directory of Open Access Journals (Sweden)

Kenan Olcay

2015-12-01

Full Text Available Objectives: In this study we aimed to compare the sensitivity of blue-light fundus autofluorescence (FAF and near-infrared autofluorescence (NI-AF imaging for determining the progression rates of macular lesions in dry age-related macular degeneration (AMD. Materials and Methods: The study was designed retrospectively and included patients diagnosed with intermediate and advanced stage dry AMD. Best corrected visual acuities and FAF and NI-AF images were recorded in 46 eyes of 33 patients. Lesion borders were drawn manually on the images using Heidelberg Eye Explorer software and lesion areas were calculated by using Microsoft Excel software. BCVA and lesion areas were compared with each other. Results: Patients’ mean follow-up time was 30.98±13.30 months. The lesion area progression rates were 0.85±0.93 mm2/y in FAF and 0.93±1.01 mm2/y in NI-AF, showing statistically significant correlation with each other (r=0.883; p<0.01. Both imaging methods are moderately correlated with visual acuity impairment (r=0.362; p<0.05 and r=0.311; p<0.05, respectively. In addition, larger lesions showed higher progression rates than smaller ones in both imaging methods. Conclusion: NI-AF imaging is as important and effective as FAF imaging for follow-up of dry AMD patients.

Control rod assembly

International Nuclear Information System (INIS)

Takahashi, Akio.

1982-01-01

Purpose: To enable reliable insertion and drops of control rods, as well as insure a sufficient flow rate of coolants flowing through the control rods for attaining satisfactory cooling thereof to enable relexation of thermal stress resulted to rectifying mechanisms or the likes. Constitution: To the outer circumference of a control rod contained vertically movably within a control rod guide tube, resistive members are retractably provided in such a way as to project to close the gap between outer circumference of the control rod and the inner surface of the control rod guide tube upon engagement of a gripper of control rod drives, and retract upon release of the engagement of the gripper. Thus, since the resistive members project to provide a greater resistance to the coolants flowing between them and the control rod guide tube in the normal operation where the gripper is engaged to drive the control rod by the control rod drives, a major part of the coolant flowing into the control rod guide tube flows into the control rod. This enables to cool the control rod effectively and make the temperature distribution uniform for the coolant flowing from the upper end of the control rod guide tube to thereby attain the relaxation of the thermal stress resulted in the rectifying mechanisms or the likes. (Moriyama, K.)

Control-rod parametrical studies in the framework of the PRE-RACINE and RACINE programs

International Nuclear Information System (INIS)

Humbert, G.; Ruelle, B.; Daguzan, G.

1982-09-01

The program, established in the frame of PRERACINE and RACINE common DEBENE, Italian and French experiments at MASURCA facility, is still under progress at the moment. The results, limited to single central rod worth are already available. For these experiments, a parametrical approach has been used. The effects of rod worth, varied separatly by rod side, boron enrichment and core size, on experiment to calculation relative discrepancy (E-C)/C can be drawn out

SINGLE-DEGENERATE TYPE Ia SUPERNOVAE ARE PREFERENTIALLY OVERLUMINOUS

International Nuclear Information System (INIS)

Fisher, Robert; Jumper, Kevin

2015-01-01

Recent observational and theoretical progress has favored merging and helium-accreting sub-Chandrasekhar mass white dwarfs (WDs) in the double-degenerate and the double-detonation channels, respectively, as the most promising progenitors of normal Type Ia supernovae (SNe Ia). Thus the fate of rapidly accreting Chandrasekhar mass WDs in the single-degenerate channel remains more mysterious then ever. In this paper, we clarify the nature of ignition in Chandrasekhar-mass single-degenerate SNe Ia by analytically deriving the existence of a characteristic length scale which establishes a transition from central ignitions to buoyancy-driven ignitions. Using this criterion, combined with data from three-dimensional simulations of convection and ignition, we demonstrate that the overwhelming majority of ignition events within Chandrasekhar-mass WDs in the single-degenerate channel are buoyancy-driven, and consequently lack a vigorous deflagration phase. We thus infer that single-degenerate SNe Ia are generally expected to lead to overluminous 1991T-like SNe Ia events. We establish that the rates predicted from both the population of supersoft X-ray sources (SSSs) and binary population synthesis models of the single-degenerate channel are broadly consistent with the observed rates of overluminous SNe Ia, and suggest that the population of SSSs are the dominant stellar progenitors of SNe 1991T-like events. We further demonstrate that the single-degenerate channel contribution to the normal and failed 2002cx-like rates is not likely to exceed 1% of the total SNe Ia rate. We conclude with a range of observational tests of overluminous SNe Ia which will either support or strongly constrain the single-degenerate scenario

Device for coupling a control rod and control rod drive

International Nuclear Information System (INIS)

Nishioka, Kazuya.

1975-01-01

Object: To obtain simple and reliable coupling between a control rod and control rod drive by equipping the lower end of the control rod with an extension provided with lateral protuberances and forming the upper end of an index tube with a recess provided with lateral holes. Structure: The tapering central extension of the control rod is inserted into the recess by lowering the control rod, and then it is further inserted by causing frictional movement of the inclined surfaces of lateral protuberances in frictional contact with guide surfaces. When the lateral protuberances are brought into contact with a stepped portion, the control rod is rotated to fit the lateral protuberances into the lateral holes. In this way, the control rod is coupled to the index tube of the control rod drive. (Yoshino, Y.)

Control rod displacement

International Nuclear Information System (INIS)

Nakazato, S.

1987-01-01

This patent describes a nuclear reactor including a core, cylindrical control rods, a single support means supporting the control rods from their upper ends in spaced apart positions and movable for displacing the control rods in their longitudinal direction between a first end position in which the control rods are fully inserted into the core and a second end position in which the control rods are retracted from the core, and guide means contacting discrete regions of the outer surface of each control rod at least when the control rods are in the vicinity of the second end position. The control rods are supported by the support means for longitudinal movement without rotation into and out of the core relative to the guide means to thereby cause the outer surface of the control rods to experience wear as a result of sliding contact with the guide means. The support means are so arranged with respect to the core and the guide means that it is incapable of rotation relative to the guide means. The improvement comprises displacement means being operatively coupled to a respective one of the control rods for periodically rotating the control rod in a single angular direction through an angle selected to change the locations on the outer surfaces of the control rods at which the control rods are contacted by the guide means during subsequent longitudinal movement of the control rods

The role of 11-cis-retinyl esters in vertebrate cone vision.

Science.gov (United States)

Babino, Darwin; Perkins, Brian D; Kindermann, Aljoscha; Oberhauser, Vitus; von Lintig, Johannes

2015-01-01

A cycle of cis-to-trans isomerization of the chromophore is intrinsic to vertebrate vision where rod and cone photoreceptors mediate dim- and bright-light vision, respectively. Daylight illumination can greatly exceed the rate at which the photoproduct can be recycled back to the chromophore by the canonical visual cycle. Thus, an additional supply pathway(s) must exist to sustain cone-dependent vision. Two-photon microscopy revealed that the eyes of the zebrafish (Danio rerio) contain high levels of 11-cis-retinyl esters (11-REs) within the retinal pigment epithelium. HPLC analyses demonstrate that 11-REs are bleached by bright light and regenerated in the dark. Pharmacologic treatment with all-trans-retinylamine (Ret-NH2), a potent and specific inhibitor of the trans-to-cis reisomerization reaction of the canonical visual cycle, impeded the regeneration of 11-REs. Intervention with 11-cis-retinol restored the regeneration of 11-REs in the presence of all-trans-Ret-NH2. We used the XOPS:mCFP transgenic zebrafish line with a functional cone-only retina to directly demonstrate that this 11-RE cycle is critical to maintain vision under bright-light conditions. Thus, our analyses reveal that a dark-generated pool of 11-REs helps to supply photoreceptors with the chromophore under the varying light conditions present in natural environments. © FASEB.

Morphoelastic rods. Part I: A single growing elastic rod

KAUST Repository

Moulton, D.E.

2013-02-01

A theory for the dynamics and statics of growing elastic rods is presented. First, a single growing rod is considered and the formalism of three-dimensional multiplicative decomposition of morphoelasticity is used to describe the bulk growth of Kirchhoff elastic rods. Possible constitutive laws for growth are discussed and analysed. Second, a rod constrained or glued to a rigid substrate is considered, with the mismatch between the attachment site and the growing rod inducing stress. This stress can eventually lead to instability, bifurcation, and buckling. © 2012 Elsevier Ltd. All rights reserved.

Morphoelastic rods. Part I: A single growing elastic rod

KAUST Repository

Moulton, D.E.; Lessinnes, T.; Goriely, A.

2013-01-01

A theory for the dynamics and statics of growing elastic rods is presented. First, a single growing rod is considered and the formalism of three-dimensional multiplicative decomposition of morphoelasticity is used to describe the bulk growth of Kirchhoff elastic rods. Possible constitutive laws for growth are discussed and analysed. Second, a rod constrained or glued to a rigid substrate is considered, with the mismatch between the attachment site and the growing rod inducing stress. This stress can eventually lead to instability, bifurcation, and buckling. © 2012 Elsevier Ltd. All rights reserved.

Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-β1 signaling in a mouse model of osteoarthritis.

Science.gov (United States)

Chen, Rebecca; Mian, Michelle; Fu, Martin; Zhao, Jing Ying; Yang, Liang; Li, Yefu; Xu, Lin

2015-11-01

Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-β1 signaling protects adult knee joints in mice against the development of osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Degree of tendon degeneration and stage of rotator cuff disease.

Science.gov (United States)

Jo, Chris Hyunchul; Shin, Won Hyoung; Park, Ji Wan; Shin, Ji Sun; Kim, Ji Eun

2017-07-01

While tendon degeneration has been known to be an important cause of rotator cuff disease, few studies have objectively proven the association of tendon degeneration and rotator cuff disease. The purpose of this study was to investigate changes of tendon degeneration with respect to the stage of rotator cuff disease. A total of 48 patients were included in the study: 12 with tendinopathy, 12 with a partial-thickness tear (pRCT), 12 with a full-thickness tear (fRCT), and 12 as the control. A full-thickness supraspinatus tendon sample was harvested en bloc from the middle portion between the lateral edge and the musculotendinous junction of the tendon using a biopsy punch with a diameter of 3 mm. Harvested samples were evaluated using a semi-quantitative grading scale with 7 parameters after haematoxylin and eosin staining. There was no significant difference in age, gender, symptom duration, and Kellgren-Lawrence grade between the groups except for the global fatty degeneration index. All of the seven parameters were significantly different between the groups and could be categorized as follows: early responders (fibre structure and arrangement), gradual responder (rounding of the nuclei), after-tear responders (cellularity, vascularity, and stainability), and late responder (hyalinization). The total degeneration scores were not significantly different between the control (6.08 ± 1.16) and tendinopathy (6.67 ± 1.83) (n.s.). However, the score of pRCT group (10.42 ± 1.31) was greater than that of tendinopathy (P rotator cuff disease progresses from tendinopathy to pRCT, and then to fRCT. The degree of degeneration of tendinopathy was not different from that of normal but aged tendons, and significant tendon degeneration began from the stage of pRCT. The clinical relevance of the study is that strategies and goals of the treatment for rotator cuff disease should be specific to its stage, in order to prevent disease progression for tendinopathy and pRCT, as

Control rod drive

International Nuclear Information System (INIS)

Hawke, B.C.

1986-01-01

A reactor core, one or more control rods, and a control rod drive are described for selectively inserting and withdrawing the one or more control rods into and from the reactor core, which consists of: a support structure secured beneath the reactor core; control rod positioning means supported by the support structure for movably supporting the control rod for movement between a lower position wherein the control rod is located substantially beneath the reactor core and an upper position wherein at least an upper portion of the control rod extends into the reactor core; transmission means; primary drive means connected with the control rod positioning means by the transmission means for positioning the control rod under normal operating conditions; emergency drive means for moving the control rod from the lower position to the upper position under emergency conditions, the emergency drive means including a weight movable between an upper and a lower position, means for movably supporting the weight, and means for transmitting gravitational force exerted on the weight to the control rod positioning means to move the control rod upwardly when the weight is pulled downwardly by gravity; the transmission means connecting the control rod positioning means with the emergency drive means so that the primary drive means effects movement of the weight and the control rod in opposite directions under normal conditions, thus providing counterbalancing to reduce the force required for upward movement of the control rod under normal conditions; and restraint means for restraining the fall of the weight under normal operating conditions and disengaging the primary drive means to release the weight under emergency conditions

Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women.

Science.gov (United States)

Lou, Chao; Xiang, Guangheng; Weng, Qiaoyou; Chen, Zhaojie; Chen, Deheng; Wang, Qingqing; Zhang, Di; Zhou, Bin; He, Dengwei; Chen, Hongliang

2016-11-01

The purpose of this study was to investigate the association between menopause and severity of knee joint cartilage degeneration using a magnetic resonance imaging-based six-level grading system, with six cartilage surfaces, the medial and lateral femoral condyle, the femoral trochlea, the medial and lateral tibia plateau, and the patella. The study cohort comprised 860 healthy women (age 36-83 y), and 5,160 cartilage surfaces were analyzed. Age, weight, height, age at natural menopause, and years since menopause (YSM) were obtained. Cartilage degeneration was assessed using a magnetic resonance imaging-based six-level grading system. After removing the age, height, and weight effects, postmenopausal women had more severe cartilage degeneration than pre- and perimenopausal women (P  0.05). No significant difference was observed in lateral tibia plateau and lateral femoral condyle in postmenopausal women. Menopause is associated with cartilage degeneration of knee joint. After menopause, cartilage showed progressive severe degeneration that occurred in the first 25 YSM, suggesting estrogen deficiency might be a risk factor of cartilage degeneration of the knee joint. Further studies are needed to investigate whether age or menopause plays a more important role in the progression of cartilage degeneration in the knee joint.

Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice.

Science.gov (United States)

Miyazaki, Kazunori; Masamoto, Kazuto; Morimoto, Nobutoshi; Kurata, Tomoko; Mimoto, Takahumi; Obata, Takayuki; Kanno, Iwao; Abe, Koji

2012-03-01

The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow-metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow-metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS.

Recovery of 233U from irradiated J rods - operating experience

International Nuclear Information System (INIS)

Lakshmanan, K.; Natarajan, D.; Muthukumar, M.; Halder, Surajit; Jayakrishnan, G.; Selvarasan, M.; Kuppusamy, V.; Ganesan, V.; Vijayakumar, V.

2000-01-01

The first campaign of reprocessing was completed in 1988 and 233 U was delivered for fabrication of fuel for KAMINI. After revamping the facility, the second campaign was started in Dec 1998 and has processed some of the high density thoria rods from CIRUS successfully. Currently the campaign is in progress and it is planned to process the irradiated thorium rods from Dhruva. Interim 23 process selective to 233 U is adopted for separation of uranium from thorium and fission products

Serum levels of lipid metabolites in age-related macular degeneration

OpenAIRE

Orban, Tivadar; Johnson, William M.; Dong, Zhiqian; Maeda, Tadao; Maeda, Akiko; Sakai, Tsutomu; Tsuneoka, Hiroshi; Mieyal, John J.; Palczewski, Krzysztof

2015-01-01

Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4−/−Rdh8−/− mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decrea...

Variation in rhodopsin kinase expression alters the dim flash response shut off and the light adaptation in rod photoreceptors.

Science.gov (United States)

Sakurai, Keisuke; Young, Joyce E; Kefalov, Vladimir J; Khani, Shahrokh C

2011-08-29

Rod photoreceptors are exquisitely sensitive light detectors that function in dim light. The timely inactivation of their light responses is critical for the ability of rods to reliably detect and count photons. A key step in the inactivation of the rod transduction is the phosphorylation of the rod visual pigment, rhodopsin, catalyzed by G-protein-dependent receptor kinase 1 (GRK1). Absence of GRK1 greatly prolongs the photoreceptors' light response and enhances their susceptibility to degeneration. This study examined the light responses from mouse rods expressing various levels of GRK1 to evaluate how their function is modulated by rhodopsin inactivation. Transretinal and single-cell rod electrophysiological recordings were obtained from several strains of mice expressing GRK1 at 0.3- to 3-fold the wild-type levels. The effect of GRK1 expression level on the function of mouse rods was examined in darkness and during background adaptation. Altering the expression of GRK1 from 0.3- to 3-fold that in wild-type rods had little effect on the single photon response amplitude. Notably, increasing the expression level of GRK1 accelerated the dim flash response shut off but had no effect on the saturated response shut off. Additionally, GRK1 excess abolished the acceleration of saturated responses shut off during light adaptation. These results demonstrate that rhodopsin inactivation can modulate the kinetics of recovery from dim light stimulation. More importantly, the ratio of rhodopsin kinase to its modulator recoverin appears critical for the proper adaptation of rods and the acceleration of their response shut off in background light.

Material Exchange in Photoreceptor Transplantation: Updating Our Understanding of Donor/Host Communication and the Future of Cell Engraftment Science.

Science.gov (United States)

Nickerson, Philip E B; Ortin-Martinez, Arturo; Wallace, Valerie A

2018-01-01

Considerable research effort has been invested into the transplantation of mammalian photoreceptors into healthy and degenerating mouse eyes. Several platforms of rod and cone fluorescent reporting have been central to refining the isolation, purification and transplantation of photoreceptors. The tracking of engrafted cells, including identifying the position, morphology and degree of donor cell integration post-transplant is highly dependent on the use of fluorescent protein reporters. Improvements in imaging and analysis of transplant recipients have revealed that donor cell fluorescent reporters can transfer into host tissue though a process termed material exchange (ME). This recent discovery has chaperoned a new era of interpretation when reviewing the field's use of dissociated donor cell preparations, and has prompted scientists to re-examine how we use and interpret the information derived from fluorescence-based tracking tools. In this review, we describe the status of our understanding of ME in photoreceptor transplantation. In addition, we discuss the impact of this discovery on several aspects of historical rod and cone transplantation data, and provide insight into future standards and approaches to advance the field of cell engraftment.

Evaluation of cone function by a handheld non-mydriatic flicker electroretinogram device

Directory of Open Access Journals (Sweden)

Nakamura N

2016-06-01

Full Text Available Natsuko Nakamura,1 Kaoru Fujinami,1 Yoshinobu Mizuno,2 Toru Noda,2 Kazushige Tsunoda11Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, 2Department of Ophthalmology, National Hospital Organization, National Tokyo Medical Center, Tokyo, JapanPurpose: Full-field electroretinograms (ERGs are used to evaluate retinal function in patients with various types of hereditary and acquired retinal diseases. However, ERG recordings require relatively invasive procedures, including pupillary dilation and the use of contact lens electrodes. Thus, it would be helpful to have a simpler and noninvasive screening method. The purpose of this study was to determine whether a new, handheld, portable ERG device, RETeval™, can be used to screen patients for cone dysfunction.Patients and methods: Thirty-five eyes of 35 patients who had reduced cone responses ascertained by a conventional ERG system using contact lens electrodes were studied. The causative diseases included achromatopsia, cone dystrophy, cone-rod dystrophy, retinitis pigmentosa, choroidal dystrophy, autoimmune retinopathy, and Stargardt disease. The flicker ERGs were recorded with the RETeval™ under undilated conditions with skin electrodes (stimulus strength, 3.0 cd·s/m2; frequency, 28.3 Hz, and the responses were compared to that of 50 healthy eyes. The amplitudes and implicit times of the fundamental component of the flicker ERGs were analyzed in three age groups: Group A, ≤20 years; Group B, 21–40 years; and Group C, ≥41 years.Results: In all of the age groups, the amplitudes of the ERGs were significantly smaller and the implicit times significantly longer in patients with cone dysfunction than in the control eyes. All but one of the patients had flicker amplitudes lower than the mean −2.0 standard deviation of control eyes.Conclusion: The RETeval™ has a potential of being used to screen for cone dysfunction. The entire examination

Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement

OpenAIRE

Cideciyan, Artur V.; Jacobson, Samuel G.; Beltran, William A.; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J.; Olivares, Melani B.; Schwartz, Sharon B.; Komáromy, András M.; Hauswirth, William W.; Aguirre, Gustavo D.

2013-01-01

The first retinal gene therapy in human blindness from RPE65 mutations has focused on safety and efficacy, as defined by improved vision. The disease component not studied, however, has been the fate of photoreceptors in this progressive retinal degeneration. We show that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans. In the canine model, the same result occurs when treatment is at the disease stage equivalent to humans. The study ...

Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.

Directory of Open Access Journals (Sweden)

Hong Hao

Full Text Available A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.

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

Science.gov (United States)

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

Replacement rod

International Nuclear Information System (INIS)

Hatfield, S.C.

1989-01-01

This patent describes in an elongated replacement rod for use with fuel assemblies of the type having two end fittings connected by guide tubes with a plurality of rod and guide tube cell defining spacer grids containing rod support features and mixing vanes. The grids secured to the guide tubes in register between the end fittings at spaced intervals. The fuel rod comprising: an asymmetrically beveled tip; a shank portion having a straight centerline; and a permanently diverging portion between the tip and the shank portion

Geomorphometric variability of "monogenetic" volcanic cones: Evidence from Mauna Kea, Lanzarote and experimental cones

Science.gov (United States)

Kervyn, M.; Ernst, G. G. J.; Carracedo, J.-C.; Jacobs, P.

2012-01-01

Volcanic cones are the most common volcanic constructs on Earth. Their shape can be quantified using two morphometric ratios: the crater/cone base ratio (W cr/W co) and the cone height/width ratio (H co/W co). The average values for these ratios obtained over entire cone fields have been explained by the repose angle of loose granular material (i.e. scoria) controlling cone slopes. The observed variability in these ratios between individual cones has been attributed to the effect of erosional processes or contrasting eruptive conditions on cone morphometry. Using a GIS-based approach, high spatial resolution Digital Elevation Models and airphotos, two new geomorphometry datasets for cone fields at Mauna Kea (Hawaii, USA) and Lanzarote (Canary Islands, Spain) are extracted and analyzed here. The key observation in these datasets is the great variability in morphometric ratios, even for simple-shape and well-preserved cones. Simple analog experiments are presented to analyze factors influencing the morphometric ratios. The formation of a crater is simulated within an analog cone (i.e. a sand pile) by opening a drainage conduit at the cone base. Results from experiments show that variability in the morphometric ratios can be attributed to variations in the width, height and horizontal offset of the drainage point relative to the cone symmetry axis, to the dip of the underlying slope or to the influence of a small proportion of fine cohesive material. GIS analysis and analog experiments, together with specific examples of cones documented in the field, suggest that the morphometric ratios for well-preserved volcanic cones are controlled by a combination of 1) the intrinsic cone material properties, 2) time-dependent eruption conditions, 3) the local setting, and 4) the method used to estimate the cone height. Implications for interpreting cone morphometry solely as either an age or as an eruption condition indicator are highlighted.

Scanning laser densitometry and color perimetry demonstrate reduced photopigment density and sensitivity in two patients with retinal degeneration.

Science.gov (United States)

Tornow, R P; Stilling, R; Zrenner, E

1999-10-01

To test the feasibility of scanning laser densitometry with a modified Rodenstock scanning laser ophthalmoscope (SLO) to measure the rod and cone photopigment distribution in patients with retinal diseases. Scanning laser densitometry was performed using a modified Rodenstock scanning laser ophthalmoscope. The distribution of the photopigments was calculated from dark adapted and bleached images taken with the 514 nm laser of the SLO. This wavelength is absorbed by rod and cone photopigments. Discrimination is possible due to their different spatial distribution. Additionally, to measure retinal sensitivity profiles, dark adapted two color static perimetry with a Tübinger manual perimeter was performed along the horizontal meridian with 1 degree spacing. A patient with retinitis pigmentosa had slightly reduced photopigment density within the central +/- 5 degrees but no detectable photopigment for eccentricities beyond 5 degrees. A patient with cone dystrophy had nearly normal pigment density beyond +/- 5 degrees, but considerably reduced photopigment density within the central +/- 5 degrees. Within the central +/- 5 degrees, the patient with retinitis pigmentosa had normal sensitivity for the red stimulus and reduced sensitivity for the green stimulus. There was no measurable function beyond 7 degrees. The patient with cone dystrophy had normal sensitivity for the green stimulus outside the foveal center and reduced sensitivity for the red stimulus at the foveal center. The results of color perimetry for this patient with a central scotoma were probably influenced by eccentric fixation. Scanning laser densitometry with a modified Rodenstock SLO is a useful method to assess the human photopigment distribution. Densitometry results were confirmed by dark adapted two color static perimetry. Photopigment distribution and retinal sensitivity profiles can be measured with high spatial resolution. This may help to measure exactly the temporal development of retinal

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

Science.gov (United States)

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.

Water rod

International Nuclear Information System (INIS)

Kashiwai, Shin-ichi; Yokomizo, Osamu; Orii, Akihito.

1992-01-01

In a reactor core of a BWR type reactor, the area of a flow channel in a lower portion of a downcoming pipe for downwardly releasing steams present at the top portion in a water rod is increased. Further, a third coolant flow channel (an inner water rod) is disposed in an uprising having an exit opened near the inlet of the water rod and an inlet opened at the outside near the top portion of the water and having an increase flow channel area in the upper portion. The downcoming pipe in the water rod is filled with steams, and the void ratio is increased by so much as the flow channel area of the downcoming pipe is increased. Since the pressure difference between the inlet and the exit of the inner water rod is greater than the pressure difference between the inlet and the exit of the water rod, most of water flown into the inner water rod is discharged out of the exit in the form of water as it is. Since the area of the flow channel is increased in the portion of the inner water rod, void efficiency in the upper portion of the reactor core is decreased by so much. Since the void ratio is thus increased in the lower portion and the void efficiency is decreased in the upper portion of the reactor core, axial void distribution can be flattened. (N.H.)

Transsynaptic neuronal degeneration of optic nerves associated with bilateral occipital lesions

Directory of Open Access Journals (Sweden)

Sachdev Mahipal

1990-01-01

Full Text Available A case is reported of a 9-year old male who presented with abnormal behaviour and progressive diminution of vision. Pupils were middilated in both eyes but the pupillary reflexes were preserved. Fundus examination revealed a bilateral optic atrophy and radiological investigations showed a bilateral occipital calcification. We hereby document a case of retrograde transsynaptic neuronal degeneration of the visual system secondary to bilateral occipital lesions. Transsynapptic neuronal degeneration of optic nerves consequent to occipital lobe lesions is a rare phenomenon. Experimentally occipital lobe ablation in non-human primates has been shown to result in optic atrophy. Herein, we document a case of retrograde transsynaptic neuronal degeneration of the visual system secondary to bilateral occipital lesions.

Hydrodynamic prediction of multidimensional single- and two-phase flow in rod arrays. Progress report, January 1-December 31, 1983

International Nuclear Information System (INIS)

Ebeling-Koning, D.B.; Robinson, J.T.; Todreas, N.E.

1984-01-01

The objective of this research is to develop comprehensive constitutive models for multidimensional two-phase flow in rod arrays. The constitutive parameters are the solid-fluid flow resistance and the gas-liquid interfacial momentum exchange force. This report covers work in four areas: (1) a correlation for flow resistance across banks of tubes which is independent of rod arrangement has been developed. The correlation was developed from data from three rod arrangements covering a Reynolds number range (based on superficial velocity) of 1 to 40,000; (2) complete pressure drop data for water flows in the laminar region in crossflow and 45 0 inclined rod arrays were taken; (3) the development of a model for the interfacial momentum exchange force in bubbly flows has been completed. This model has been validated against single bubble velocity data in inclined rod arrays. The model has been cast in a form suitable for implementation to two-fluid computer codes; and (4) rise velocities of bubbles in 0 0 , 45 0 , and 90 0 inclined rod arrays have been measured. This data should prove useful for the development of a bubble drag coefficient model for rod arrays

Progression of transsynaptic retinal degeneration with spectral-domain optical coherence tomography

Directory of Open Access Journals (Sweden)

Stephen G. Schwartz

2017-04-01

Conclusions and importance: Retrograde transsynaptic retinal degeneration may occur in patients with homonymous visual field loss caused by post-geniculate neurologic disease. This is best detected as homonymous thinning of the retina, corresponding to the pattern of visual field loss, using SD-OCT of the GCC and macula. The retinal changes occur at a variable time following the onset of neurologic disease.

Computational algebraic geometry for statistical modeling FY09Q2 progress.

Energy Technology Data Exchange (ETDEWEB)

Thompson, David C.; Rojas, Joseph Maurice; Pebay, Philippe Pierre

2009-03-01

This is a progress report on polynomial system solving for statistical modeling. This is a progress report on polynomial system solving for statistical modeling. This quarter we have developed our first model of shock response data and an algorithm for identifying the chamber cone containing a polynomial system in n variables with n+k terms within polynomial time - a significant improvement over previous algorithms, all having exponential worst-case complexity. We have implemented and verified the chamber cone algorithm for n+3 and are working to extend the implementation to handle arbitrary k. Later sections of this report explain chamber cones in more detail; the next section provides an overview of the project and how the current progress fits into it.

Cerebral blood flow SPECT may be helpful in establishing the diagnosis of progressive supranuclear palsy and corticobasal degeneration

International Nuclear Information System (INIS)

Slawek, J.; Lass, P.; Derejko, M.; Dubaniewicz, M.

2001-01-01

We present 4 cases, which illustrate the usefulness of neuroimaging studies in atypical forms of Parkinsonism. Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD) are rare neurodegenerative progressive disorders of the central nervous system of unknown cause. The clinical accuracy in this diagnosis is not very high even in centres specialising in movement disorders. Functional imaging can be helpful in diagnosing PSP and CBD. We present the results of cerebral blood flow (CBF) SPECT scanning in 2 patients with PSP and 2 patients with CBD. This was performed using a triple-head gammacamera and 99m Tc-HMPAO. In PSP patients a diffuse frontal perfusion deficit was seen, eventually with striatal and occipital hypoperfusion. CT/MRI was either normal or showed a diffuse cortical-subcortical atrophy. In CBD patients left fronto-parieto-temporal cortex and a striatal hypoperfusion were shown. CT scanning was normal in one case and showed an asymmetrical temporo-parietal atrophy in second one. The pattern of diffuse frontal perfusions deficit in PSP and asymmetrical, contralateral to symptoms of CBD, cortico-subcortical hypoperfusion may be helpful in establishing the correct diagnosis. (author)

Control rod

International Nuclear Information System (INIS)

Igarashi, Takao; Yoshimoto, Yuichiro; Sugawara, Satoshi; Fukumoto, Takashi; Endo, Zen-ichiro; Saito, Shozo; Shinpo, Katsutoshi; Nishimura, Akira; Ozawa, Michihiro

1988-01-01

Purpose: To provide a sufficient shutdown margin upon reactor shutdown, prevent sheath deformation without decreasing neutron absorbents and prevent impact shocks exerted to structural materials. Constitution: The control rod of the present invention comprises a neutron absorption region, a sheath deformation means attached to the side wall and means for restricting and supporting axial movement of the neutron absorbent rod. Then, the amount of absorptive nuclei chained absorbents in the lower region is reduced than that in the upper region. In this way, effective neutron absorbing performance can be obtained relative to the neutron importance distribution during reactor shutdown. In addition, since the operationability is improved by reducing the weight of the control rod and the absorptive nuclei chained neutron abosrbers are used, mechanical nuclear life of the control rod can be increased. Thus, it is possible to prevent the outward deformation of the sheath, as well as prevent collision between the neutron absorber rod and the structural material on the side of inserting the control rod generated upon reactor scram by a simple structure. (Kamimura, M.)

Risk factors of age-related macular degeneration in Argentina

Directory of Open Access Journals (Sweden)

María Eugenia Nano

2013-04-01

Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

Fasudil, a Clinically Used ROCK Inhibitor, Stabilizes Rod Photoreceptor Synapses after Retinal Detachment.

Science.gov (United States)

Townes-Anderson, Ellen; Wang, Jianfeng; Halász, Éva; Sugino, Ilene; Pitler, Amy; Whitehead, Ian; Zarbin, Marco

2017-06-01

Retinal detachment disrupts the rod-bipolar synapse in the outer plexiform layer by retraction of rod axons. We showed that breakage is due to RhoA activation whereas inhibition of Rho kinase (ROCK), using Y27632, reduces synaptic damage. We test whether the ROCK inhibitor fasudil, used for other clinical applications, can prevent synaptic injury after detachment. Detachments were made in pigs by subretinal injection of balanced salt solution (BSS) or fasudil (1, 10 mM). In some animals, fasudil was injected intravitreally after BSS-induced detachment. After 2 to 4 hours, retinae were fixed for immunocytochemistry and confocal microscopy. Axon retraction was quantified by imaging synaptic vesicle label in the outer nuclear layer. Apoptosis was analyzed using propidium iodide staining. For biochemical analysis by Western blotting, retinal explants, detached from retinal pigmented epithelium, were cultured for 2 hours. Subretinal injection of fasudil (10 mM) reduced retraction of rod spherules by 51.3% compared to control detachments ( n = 3 pigs, P = 0.002). Intravitreal injection of 10 mM fasudil, a more clinically feasible route of administration, also reduced retraction (28.7%, n = 5, P ROCK, was decreased with 30 μM fasudil ( n = 8-10 explants, P ROCK signaling with fasudil reduced photoreceptor degeneration and preserved the rod-bipolar synapse after retinal detachment. These results support the possibility, previously tested with Y27632, that ROCK inhibition may attenuate synaptic damage in iatrogenic detachments.

Quotient normed cones

Indian Academy of Sciences (India)

general setting of the space CL(X, Y ) of all continuous linear mappings from a normed cone (X, p) to a normed cone (Y, q), extending several well-known results related to open continuous linear mappings between normed linear spaces. Keywords. Normed cone; extended quasi-metric; continuous linear mapping; bicom-.

Control rod drives

International Nuclear Information System (INIS)

Futatsugi, Masao.

1980-01-01

Purpose: To secure the reactor operation safety by the provision of a fluid pressure detecting section for control rod driving fluid and a control rod interlock at the midway of the flow pass for supplying driving fluid to the control rod drives. Constitution: Between a driving line and a direction control valve are provided a pressure detecting portion, an alarm generating device, and a control rod inhibition interlock. The driving fluid from a driving fluid source is discharged by way of a pump and a manual valve into the reactor in which the control rods and reactor fuels are contained. In addition, when the direction control valve is switched and the control rods are inserted and extracted by the control rod drives, the pressure in the driving line is always detected by the pressure detection section, whereby if abnormal pressure is resulted, the alarm generating device is actuated to warn the abnormality and the control rod inhibition interlock is actuated to lock the direction control valve thereby secure the safety operation of the reactor. (Seki, T.)

Control rod drives

International Nuclear Information System (INIS)

Oonuki, Koji.

1981-01-01

Purpose: To increase the driving speed of control rods at rapid insertion with an elongate control rod and an extension pipe while ensuring sufficient buffering performance in a short buffering distance, by providing a plurality of buffers to an extension pipe between a control rod drive source and a control rod in LMFBR type reactor. Constitution: First, second and third buffers are respectively provided to an acceleration piston, an extension pipe and a control rod respectively and the insertion positions for each of the buffers are displaced orderly from above to below. Upon disconnection of energizing current for an electromagnet, the acceleration piston, the extension pipe and the control rod are rapidly inserted in one body. The first, second and third buffers are respectively actuated at each of their falling strokes upon rapid insertion respectively, and the acceleration piston, the extension pipe and the control rod receive the deceleration effect in the order correspondingly. Although the compression force is applied to the control rod only near the stroke end, it does not cause deformation. (Kawakami, Y.)

Light Cone 2017 : Frontiers in Light Front Hadron Physics : Theory and Experiment.

CERN Document Server

2018-01-01

LC2017 belongs to a series of Light-Cone conferences, which started in 1991. Light Cone conferences are held each year under the auspices of the International Light Cone Advisory Committee (ILCAC) (http://www.ilcacinc.org). The main objective of the Light Cone conference series is to provide a timely update of the progress in light-front theory and its phenomenological applications. Light-front theory provides a suitable framework to calculate observables such as scattering amplitudes, decay rates, spin effects, parton distributions, and other hadronic observables. One of the themes of the conference will be the interface between theory and experiment in hadron physics. The main topics of the program are: o Hadron Physics at present and future colliders o Light Front Field Theory in QED and QCD o AdS/QCD, D Branes and Strings o Hadron Structure : TMDs, GPDs and PDFs o Lattice QCD o QCD at high temperature and density o Higher order QCD corrections

Clinical and Rehabilitative Management of Retinitis Pigmentosa: Up-to-Date

Science.gov (United States)

Parmeggiani, Francesco; Sato, Giovanni; De Nadai, Katia; Romano, Mario R; Binotto, Andrea; Costagliola, Ciro

2011-01-01

The term retinitis pigmentosa (RP) indicates a heterogeneous group of genetic rare ocular diseases in which either rods or cones are prevalently damaged. RP represents the most common hereditary cause of blindness in people from 20 to 60 years old. In general, the different RP forms consist of progressive photo-receptorial neuro-degenerations, which are characterized by variable visual disabilities and considerable socio-sanitary burden. Sometimes, RP patients do not become visually impaired or legally blind until their 40-50 years of age and/or maintain a quite acceptable sight for all their life. Other individuals with RP become completely blind very early or in middle childhood. Although there is no treatment that can effectively cure RP, in some case-series the disease’s progression seems to be reducible by specific preventive approaches. In the most part of RP patients, the quality of vision can be considerably increased by means of nanometer-controlled filters. In the present review, the main aspects of the routine clinical and rehabilitative managements for RP patients are described, particularly focusing on the importance of specific referral Centers to practice a real multidisciplinary governance of these dramatic diseases. PMID:22131870

Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study.

Science.gov (United States)

Teraguchi, M; Yoshimura, N; Hashizume, H; Yamada, H; Oka, H; Minamide, A; Nagata, K; Ishimoto, Y; Kagotani, R; Kawaguchi, H; Tanaka, S; Akune, T; Nakamura, K; Muraki, S; Yoshida, M

2017-07-01

The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Tuning topological phase transitions in hexagonal photonic lattices made of triangular rods

Science.gov (United States)

Chan, Hsun-Chi; Guo, Guang-Yu

2018-01-01

In this paper we study topological phases in a two-dimensional photonic crystal with broken time (T ) and parity (P ) symmetries by performing calculations of band structures, Berry curvatures, Chern numbers, edge states, and also numerical simulations of light propagation in the edge modes. Specifically, we consider a hexagonal lattice consisting of triangular gyromagnetic rods. Here the gyromagnetic material breaks T symmetry while the triangular rods break P symmetry. Interestingly, we find that the crystal could host quantum anomalous Hall (QAH) phases with different gap Chern numbers (Cg) including | Cg|>1 as well as quantum valley Hall (QVH) phases with contrasting valley Chern numbers (Cv), depending on the orientation of the triangular rods. Furthermore, phase transitions among these topological phases, such as from QAH to QVH and vice versa, can be engineered by a simple rotation of the rods. Our band theoretical analyses reveal that the Dirac nodes at the K and K' valleys in the momentum space are produced and protected by the mirror symmetry (my) instead of the P symmetry, and they become gapped when either T or my symmetry is broken, resulting in a QAH or QVH phase, respectively. Moreover, a high Chern number (Cg=-2 ) QAH phase is generated by gapping triply degenerate nodal points rather than pairs of Dirac points by breaking T symmetry. Our proposed photonic crystal thus provides a platform for investigating intriguing topological phenomena which may be challenging to realize in electronic systems, and also has promising potentials for device applications in photonics such as reflection-free one-way waveguides and topological photonic circuits.

Light Cone 2016 : Challenges for Theory and Experiment in Hadron and Nuclear Physics on the Light Front

CERN Document Server

Pena, Teresa

2018-01-01

The Light-Cone 2016 conference, held in September 2016 in Lisbon, Portugal, belongs to a series of yearly Light-Cone meetings that started in 1991. As its predecessors, this conference was guided by the objectives defined by the International Light Cone Advisory Committee, namely to “advance research in quantum field theory, particularly light-cone quantization methods applicable to the solution of physical problems”. This volume compiles selected papers presented at the conference by experts from all over the world, which describe recent progress in theoretical research, and new results and planned activities at leading experimental facilities, with special emphasis on the physics of hadrons and nuclei.

Rod-like microglia are restricted to eyes with laser-induced ocular hypertension but absent from the microglial changes in the contralateral untreated eye.

Directory of Open Access Journals (Sweden)

Rosa de Hoz

Full Text Available In the mouse model of unilateral laser-induced ocular hypertension (OHT the microglia in both the treated and the normotensive untreated contralateral eye have morphological signs of activation and up-regulation of MHC-II expression in comparison with naïve. In the brain, rod-like microglia align to less-injured neurons in an effort to limit damage. We investigate whether: i microglial activation is secondary to laser injury or to a higher IOP and; ii the presence of rod-like microglia is related to OHT. Three groups of mice were used: age-matched control (naïve, n=15; and two lasered: limbal (OHT, n=15; and non-draining portion of the sclera (scleral, n=3. In the lasered animals, treated eyes as well as contralateral eyes were analysed. Retinal whole-mounts were immunostained with antibodies against, Iba-1, NF-200, MHC-II, CD86, CD68 and Ym1. In the scleral group (normal ocular pressure no microglial signs of activation were found. Similarly to naïve eyes, OHT-eyes and their contralateral eyes had ramified microglia in the nerve-fibre layer related to the blood vessel. However, only eyes with OHT had rod-like microglia that aligned end-to-end, coupling to form trains of multiple cells running parallel to axons in the retinal surface. Rod-like microglia were CD68+ and were related to retinal ganglion cells (RGCs showing signs of degeneration (NF-200+RGCs. Although MHC-II expression was up-regulated in the microglia of the NFL both in OHT-eyes and their contralateral eyes, no expression of CD86 and Ym1 was detected in ramified or in rod-like microglia. After 15 days of unilateral lasering of the limbal and the non-draining portion of the sclera, activated microglia was restricted to OHT-eyes and their contralateral eyes. However, rod-like microglia were restricted to eyes with OHT and degenerated NF-200+RGCs and were absent from their contralateral eyes. Thus, rod-like microglia seem be related to the neurodegeneration associated with HTO.

ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Querques, Giuseppe; Kamami-Levy, Cynthia; Georges, Anouk; Pedinielli, Alexandre; Capuano, Vittorio; Blanco-Garavito, Rocio; Poulon, Fanny; Souied, Eric H

2016-02-01

To describe adaptive optics (AO) imaging of foveal sparing in geographic atrophy (GA) secondary to age-related macular degeneration. Flood-illumination AO infrared (IR) fundus images were obtained in four consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes). Adaptive optics IR images were overlaid with confocal scanning laser ophthalmoscope near-IR autofluorescence images to allow direct correlation of en face AO features with areas of foveal sparing. Adaptive optics appearance of GA and foveal sparing, preservation of functional photoreceptors, and cone densities in areas of foveal sparing were investigated. In 5 eyes of 4 patients (all female; mean age 74.2 ± 11.9 years), a total of 5 images, sized 4° × 4°, of foveal sparing visualized on confocal scanning laser ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face AO images revealed GA as regions of inhomogeneous hyperreflectivity with irregularly dispersed hyporeflective clumps. By direct comparison with adjacent regions of GA, foveal sparing appeared as well-demarcated areas of reduced reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of note, in these areas, en face AO IR images revealed cone photoreceptors as hyperreflective dots over the background reflectivity (mean cone density 3,271 ± 1,109 cones per square millimeter). Microperimetry demonstrated residual function in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence. Adaptive optics allows the appreciation of differences in reflectivity between regions of GA and foveal sparing. Preservation of functional cone photoreceptors was demonstrated on en face AO IR images in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence.

[Retinal pigmentary degeneration--clinical features, diagnostics and possibilities of treatment].

Science.gov (United States)

Grześk, Magdalena; Malukiewicz-Wiśniewska, Grazyna

2007-01-01

The purpose of this study was to evaluate clinical course of retinitis pigmentosa taking into consideration models of inheritance and possible treatment. Retinitis pigmentosa belongs to heterogeneous group of hereditary disorders, which are connected with gradual loss of the photoreceptor function, firstly rod cells subsequently cones, which is accompanied by the retinal pigmentary epithelium disorder. Retinitis pigmentosa connected with X chromosome is one of the most severe form of this disease that in polish population takes place with frequency at average 10-15% which is similar to ADRP--10-20%. Course of RP, despite many similarities may differ from each other and prognosis depends on model of inheritance. Unfortunately, in spite of many efforts, nowadays medicine do not have successful treatment for patients with RP.

Ardnamurchan 3D cone-sheet architecture explained by a single elongate magma chamber.

Science.gov (United States)

Burchardt, Steffi; Troll, Valentin R; Mathieu, Lucie; Emeleus, Henry C; Donaldson, Colin H

2013-10-08

The Palaeogene Ardnamurchan central igneous complex, NW Scotland, was a defining place for the development of the classic concepts of cone-sheet and ring-dyke emplacement and has thus fundamentally influenced our thinking on subvolcanic structures. We have used the available structural information on Ardnamurchan to project the underlying three-dimensional (3D) cone-sheet structure. Here we show that a single elongate magma chamber likely acted as the source of the cone-sheet swarm(s) instead of the traditionally accepted model of three successive centres. This proposal is supported by the ridge-like morphology of the Ardnamurchan volcano and is consistent with the depth and elongation of the gravity anomaly underlying the peninsula. Our model challenges the traditional model of cone-sheet emplacement at Ardnamurchan that involves successive but independent centres in favour of a more dynamical one that involves a single, but elongate and progressively evolving magma chamber system.

Control rod cluster with removable rods for nuclear fuel assembly

International Nuclear Information System (INIS)

Denizou, J.P.

1989-01-01

For each removable control rod, the open end section of the sleeve has a certain length of reduced diameter with openings in its wall. The top end of the rod is joined to an extension tube that surrounds the shaft over part of its lenght. This extension tube fits over the reduced part of the sleeve when the shaft is screwed into the bore of the sleeve. Rotation of the rod in the sleeve is prevented by deforming the extension tube locally in the openings of the end part of the sleeve. The rod is dismantled by exerting a torque on it using a gripping area near the end of the rod [fr

[Short-term curative effects of Tantalum rod treatment in early avascular necrosis].

Science.gov (United States)

Ye, Fu-Sheng; Ni, Zhe-Ji; Chu, Xiao-Bing; He, Bang-Jian; Li, Ju; Tong, Pei-Jian

2013-08-01

To explore the recent clinical curative effect of Tantalum rod in treating the early avascular necrosis. From January 2008 to November 2008, the 25 patients (39 hips) with early avascular necrosis accepted tantalum rod placement and included 9 males (11 hips) and 16 females (28 hips) with an average age of 37 years old ranging from 18 to 74 years old. Four patients (6 hips) caused by Alcoholic, 6 patients (8 hips) by hormone, 2 cases (2 hips) by traumatic, 13 cases (23 hips) by idiopathic. Steinberg preoperative stage involved 7 hips in period I, 24 hips in period II, 8 hips in period III. Curative effect analysis included preoperative and postoperative Harris score, radiographic changes and hip replacement for follow-up to accept the end of the femoral head survival rate. All patients were followed up for 6 to 47 months (averaged 37.4 months). All 12 hips imaging appeard progress,including tantalum rod exit in 1 hip, hip hemiarthroplasty collapse in 3 hips, the area increased to avascular necrosis in 8 hips. Six hips accepted total hip replacement, including imaging progress in 5 hips (41.7%, 5/12), no imaging progress in 1 hip (3.7%,1/27). All hips' Kaplan-Meier survival curves showed 6-month survival rate was (97.4 +/- 2.5)% after tantalum stick insertion, 1-year survival rate was (94.7 +/- 3.6), and 2-year survival rate was (88.6 +/- 5.4)%, 3-year survival rate was (72.5 +/- 11.2). It is effective for treatment of avascular necrosis of femoral head in Steinberg I and II by Tantalum rod, and it can effectively relieve femoral head replacement time.

Control rod drive mechanism

International Nuclear Information System (INIS)

Nakamura, Akira.

1981-01-01

Purpose: To ensure the scram operation of a control rod by the reliable detection for the position of control rods. Constitution: A permanent magnet is provided to the lower portion of a connecting rod in engagement with a control rod and a tube having a plurality of lead switches arranged axially therein in a predetermined pitch is disposed outside of the control rod drives. When the control rod moves upwardly in the scram operation, the lead switches are closed successively upon passage of the permanent magnet to operate the electrical circuit provided by way of each of the lead switches. Thus, the position for the control rod during the scram can reliably be determined and the scram characteristic of the control rod can be recognized. (Furukawa, Y.)

New approaches and potential treatments for dry age-related macular degeneration

Directory of Open Access Journals (Sweden)

Francisco Max Damico

2012-02-01

Full Text Available Emerging treatments for dry age-related macular degeneration (AMD and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged retinoic acid exposure

Directory of Open Access Journals (Sweden)

Cameron David A

2011-08-01

Full Text Available Abstract Background Retinoic acid (RA is important for vertebrate eye morphogenesis and is a regulator of photoreceptor development in the retina. In the zebrafish, RA treatment of postmitotic photoreceptor precursors has been shown to promote the differentiation of rods and red-sensitive cones while inhibiting the differentiation of blue- and UV-sensitive cones. The roles played by RA and its receptors in modifying photoreceptor fate remain to be determined. Results Treatment of zebrafish embryos with RA, beginning at the time of retinal progenitor cell proliferation and prior to photoreceptor terminal mitosis, resulted in a significant alteration of rod and cone mosaic patterns, suggesting an increase in the production of rods at the expense of red cones. Quantitative pattern analyses documented increased density of rod photoreceptors and reduced local spacing between rod cells, suggesting rods were appearing in locations normally occupied by cone photoreceptors. Cone densities were correspondingly reduced and cone photoreceptor mosaics displayed expanded and less regular spacing. These results were consistent with replacement of approximately 25% of positions normally occupied by red-sensitive cones, with additional rods. Analysis of embryos from a RA-signaling reporter line determined that multiple retinal cell types, including mitotic cells and differentiating rods and cones, are capable of directly responding to RA. The RA receptors RXRγ and RARαb are expressed in patterns consistent with mediating the effects of RA on photoreceptors. Selective knockdown of RARαb expression resulted in a reduction in endogenous RA signaling in the retina. Knockdown of RARαb also caused a reduced production of rods that was not restored by simultaneous treatments with RA. Conclusions These data suggest that developing retinal cells have a dynamic sensitivity to RA during retinal neurogenesis. In zebrafish RA may influence the rod vs. cone cell fate

Light adaptation alters the source of inhibition to the mouse retinal OFF pathway

Science.gov (United States)

Mazade, Reece E.

2013-01-01

Sensory systems must avoid saturation to encode a wide range of stimulus intensities. One way the retina accomplishes this is by using both dim-light-sensing rod and bright-light-sensing cone photoreceptor circuits. OFF cone bipolar cells are a key point in this process, as they receive both excitatory input from cones and inhibitory input from AII amacrine cells via the rod pathway. However, in addition to AII amacrine cell input, other inhibitory inputs from cone pathways also modulate OFF cone bipolar cell light signals. It is unknown how these inhibitory inputs to OFF cone bipolar cells change when switching between rod and cone pathways or whether all OFF cone bipolar cells receive rod pathway input. We found that one group of OFF cone bipolar cells (types 1, 2, and 4) receive rod-mediated inhibitory inputs that likely come from the rod-AII amacrine cell pathway, while another group of OFF cone bipolar cells (type 3) do not. In both cases, dark-adapted rod-dominant light responses showed a significant contribution of glycinergic inhibition, which decreased with light adaptation and was, surprisingly, compensated by an increase in GABAergic inhibition. As GABAergic input has distinct timing and spatial spread from glycinergic input, a shift from glycinergic to GABAergic inhibition could significantly alter OFF cone bipolar cell signaling to downstream OFF ganglion cells. Larger GABAergic input could reflect an adjustment of OFF bipolar cell spatial inhibition, which may be one mechanism that contributes to retinal spatial sensitivity in the light. PMID:23926034

Localization of a novel X-linked congenital stationary night blindness locus: close linkage to the RP3 type retinitis pigmentosa gene region

NARCIS (Netherlands)

Bergen, A. A.; ten Brink, J. B.; Riemslag, F.; Schuurman, E. J.; Tijmes, N.

1995-01-01

X-linked congenital stationary night blindness (CSNBX) is a non-progressive retinal disorder characterized by decreased visual acuity and loss of night vision. CSNBX is clinically heterogeneous with respect to the involvement of retinal rods and/or cones in the disease. In this study, we localize a

Rebirth of a control rod at the Phenix power plant

International Nuclear Information System (INIS)

De Carvalho, Corinne; Vignau, Bernard; Masson, Marc

2007-01-01

This paper outlines the operations involved in cleaning the control rod for the complementary shutdown system in the Phenix Power Plant, the French sodium-cooled fast reactor. The Phenix reactor is controlled by six control rods and a complementary shutdown system. The latter comprises a control rod and a mechanism maintaining the rod in position by means of an electromagnet. The electromagnet is continuously supplied with power and holds the rod control assembly in position by magnetisation on a plane circular surface made from pure iron. The bearing capacity of the mechanism on the rod was initially 80 daN with a rod weight of 26.3 daN. This deteriorated progressively over time. The bearing surface of the rod and the electromagnet became contaminated with a deposit of sodium oxides and metallic particles, thus creating an air gap. This reached a figure of 36 daN in 2005 and was deemed not to be sufficient to prevent the rod from dropping at the wrong time during reactor operation. The Power Plant thus decided to replace the rod mechanism in the reactor in an initial phase, followed by the control rod itself. As the Phenix Power Plant had no spare control rods left, they initiated a 'salvage' plan, over two stages, for the rod removed from the reactor and placed in the fuel storage drum: - Inspection of the bearing surface of the rod by means of a borescope to check whether the rod could be salvaged, - A cleaning operation on the bearing face and checks on the bearing capacity of the rod. The operation is subject to very stringent requirements: the rod must not be taken out of the sodium to ensure that it can be reused in the reactor. The operation must thus take place in the fuel storage drum where there are no facilities for such an operation and where operating conditions are very hostile: high temperatures (the sodium in the fuel storage drum is at a temperature of 150 deg. C, high dose rate (3 mGy/h on the bearing surface) and the bearing surface is submerged

Method of inserting fuel rod

International Nuclear Information System (INIS)

Kamimoto, Shuji; Imoo, Makoto; Tsuchida, Kenji.

1991-01-01

The present invention concerns a method of inserting a fuel rod upon automatic assembling, automatic dismantling and reassembling of a fuel assembly in a light water moderated reactor, as well as a device and components used therefor. That is, a fuel rod is inserted reliably to an aimed point of insertion by surrounding the periphery of the fuel rod to be inserted with guide rods, and thereby suppressing the movement of the fuel rod during insertion. Alternatively, a fuel rod is inserted reliably to a point of insertion by inserting guide rods at the periphery of the point of insertion for the fuel rod to be inserted thereby surrounding the point of insertion with the guide rods or fuel rods. By utilizing fuel rods already present in the fuel assembly as the guide rods described above, the fuel rod can be inserted reliably to the point of insertion with no additional devices. Dummy fuel rods are previously inserted in a fuel assembly which are then utilized as the above-mentioned guide rods to accurately insert the fuel rod to the point of insertion. (I.S.)

Post-test examination of the VVER-1000 fuel rod bundle CORA-W2

International Nuclear Information System (INIS)

Hofmann, P.; Noack, V.; Burbach, J.; Metzger, H.; Schanz, G.; Hagen, S.; Sepold, L.

1995-01-01

The upper half of the bundle is completely oxidized, the lower half has kept the fuel rods relatively intact. The post-test examination results show the strong impact of the B 4 C absorber rod and the stainless steel grid spacers on the 'low-temperature' bundle damage initiation and progression. The B 4 C absorber rod completely disappeared in the upper half of the bundle. The multicomponent melts relocated and formed coolant channel blockages on solidification with a maximum extent of about 30% in the lower part of the bundle. At temperatures above the melting point of the ZrNb1 cladding extensive fuel dissolution occured. (orig./HP)

Post-test examination of the VVER-1000 fuel rod bundle CORA-W2

Energy Technology Data Exchange (ETDEWEB)

Hofmann, P.; Noack, V.; Burbach, J.; Metzger, H.; Schanz, G.; Hagen, S.; Sepold, L.

1995-08-01

The upper half of the bundle is completely oxidized, the lower half has kept the fuel rods relatively intact. The post-test examination results show the strong impact of the B{sub 4}C absorber rod and the stainless steel grid spacers on the `low-temperature` bundle damage initiation and progression. The B{sub 4}C absorber rod completely disappeared in the upper half of the bundle. The multicomponent melts relocated and formed coolant channel blockages on solidification with a maximum extent of about 30% in the lower part of the bundle. At temperatures above the melting point of the ZrNb1 cladding extensive fuel dissolution occured. (orig./HP)

Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats.

Science.gov (United States)

Schraermeyer, U; Thumann, G; Luther, T; Kociok, N; Armhold, S; Kruttwig, K; Andressen, C; Addicks, K; Bartz-Schmidt, K U

2001-01-01

The Royal College of Surgeons (RCS) rat is an animal model for retinal degeneration such as the age-related macular degeneration. The RCS rat undergoes a progressive retinal degeneration during the early postnatal period. A potential treatment to prevent this retinal degeneration is the transplantation into the subretinal space of cells that would replace functions of the degenerating retinal pigment epithelium (RPE) cells or may form neurotrophic factors. In this study we have investigated the potential of subretinally transplanted embryonic stem cells to prevent the genetically determined photoreceptor cell degeneration in the RCS rat. Embryonic stem cells from the inner cell mass of the mouse blastocyst were allowed to differentiate to neural precursor cells in vitro and were then transplanted into the subretinal space of 20-day-old RCS rats. Transplanted and sham-operated rats were sacrificed 2 months following cell transplantation. The eyes were enucleated and photoreceptor degeneration was quantified by analyzing and determining the thickness of the outer nuclear layer by light and electron microscopy. In the eyes transplanted with embryonic cells up to 8 rows of photoreceptor cell nuclei were observed, whereas in nontreated control eyes the outer nuclear layer had degenerated completely. Transplantation of embryonic stem cells appears to delay photoreceptor cell degeneration in RCS rats.

Control rod drives

International Nuclear Information System (INIS)

Hayakawa, Hiroyasu.

1979-01-01

Purpose: To enable rapid control in a simple circuit by providing a motor control device having an electric capacity capable of simultaneously driving all of the control rods rapidly only in the inserting direction as well as a motor controlling device capable of fine control for the insertion and extraction at usual operation. Constitution: The control rod drives comprise a first motor control device capable of finely controlling the control rods both in inserting and extracting directions, a second motor control device capable of rapidly driving the control rods only in the inserting direction, and a first motor switching circuit and a second motor switching circuit switched by switches. Upon issue of a rapid insertion instruction for the control rods, the second motor switching circuit is closed by the switch and the second motor control circuit and driving motors are connected. Thus, each of the control rod driving motors is driven at a high speed in the inserting direction to rapidly insert all of the control rods. (Yoshino, Y.)

Frontotemporal Degeneration in a Child.

Science.gov (United States)

Terrill, Tyler; Pascual, Juan M

2017-07-01

There is a predilection for the frontal and temporal lobes in certain cases of dementia in the adult, leading to the syndrome of frontotemporal dementia. However, this syndrome has seemed to elude the developing brain until now. We describe an example of apparently selective neurodegeneration of the frontal and temporal regions during development associated with some of the clinical, magnetic resonance imaging, and fludeoxyglucose positron emission tomography (FDG PET) scan features of canonical frontotemporal dementia in the adult. This patient does not have any of the common frontotemporal dementia-causing mutations or known progressive brain disorders of children. This patient illustrates that symptomatic, selective, and progressive vulnerability of the frontal and temporal lobes is not restricted to adulthood, expanding the phenotype of frontotemporal degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Prescreening whole exome sequencing results from patients with retinal degeneration for variants in genes associated with retinal degeneration

Directory of Open Access Journals (Sweden)

Bryant L

2017-12-01

heterozygous mutation identified that would cause recessive disease and 13% had no obviously pathogenic variants and no family members available to perform segregation analysis. Eleven subjects are good candidates for novel gene discovery. Two de novo mutations were identified that resulted in dominant retinal degeneration.Conclusion: Whole exome sequencing allows for thorough genetic analysis of candidate genes as well as novel gene discovery. It allows for an unbiased analysis of genetic variants to reduce the chance that the pathogenic mutation will be missed due to incomplete or inaccurate family history or analysis at the early stage of a syndromic form of retinal degeneration. Keywords: retinal degeneration, genetic diagnosis, retinitis pigmentosa, Leber congenital amaurosis, cone–rod dystrophy, whole exome sequencing

Berkeley Lighting Cone

Energy Technology Data Exchange (ETDEWEB)

Lask, Kathleen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gadgil, Ashok [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2016-10-24

A lighting cone is a simple metal cone placed on the fuel bed of a stove during ignition to act as a chimney, increasing the draft through the fuel bed. Many stoves tend to be difficult to light due to poor draft through the fuel bed, so lighting cones are used in various parts of the world as an inexpensive accessory to help with ignition.

Acute Zonal Cone Photoreceptor Outer Segment Loss.

Science.gov (United States)

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

Luminescence- and nanoparticle-mediated increase of light absorption by photoreceptor cells: Converting UV light to visible light.

Science.gov (United States)

Li, Lei; Sahi, Sunil K; Peng, Mingying; Lee, Eric B; Ma, Lun; Wojtowicz, Jennifer L; Malin, John H; Chen, Wei

2016-02-10

We developed new optic devices - singly-doped luminescence glasses and nanoparticle-coated lenses that convert UV light to visible light - for improvement of visual system functions. Tb(3+) or Eu(3+) singly-doped borate glasses or CdS-quantum dot (CdS-QD) coated lenses efficiently convert UV light to 542 nm or 613 nm wavelength narrow-band green or red light, or wide-spectrum white light, and thereby provide extra visible light to the eye. In zebrafish (wild-type larvae and adult control animals, retinal degeneration mutants, and light-induced photoreceptor cell degeneration models), the use of Tb(3+) or Eu(3+) doped luminescence glass or CdS-QD coated glass lenses provide additional visible light to the rod and cone photoreceptor cells, and thereby improve the visual system functions. The data provide proof-of-concept for the future development of optic devices for improvement of visual system functions in patients who suffer from photoreceptor cell degeneration or related retinal diseases.

Fission reactor control rod

International Nuclear Information System (INIS)

Irie, Tomoo.

1991-01-01

The present invention concerns a control rod in a PWR type reactor. A control rod has an inner cladding tube and an outer cladding tube disposed coaxially, and a water draining hole is formed at the inside of the inner cladding tube. Neutron absorbers are filled in an annular gap between the outer cladding tube and the inner cladding tube. The water draining hole opens at the lower end thereof to the top end of the control rod and at the upper end thereof to the side of the upper end plug of the control rod. If the control rod is dropped to a control rod guide thimble for reactor scram, coolants from the control rod guide thimble are flown from the lower end of the water draining hole and discharged from the upper end passing through the water draining hole. In this way, water from the control rod guide thimble is removed easily when the control rod is dropped. Further, the discharging amount of water itself is reduced by the provision of the water draining hole. Accordingly, sufficient control rod dropping speed can be attained. (I.N.)

Fuel rod simulator effects in flooding experiments single rod tests

International Nuclear Information System (INIS)

Nishida, M.

1984-09-01

The influence of a gas filled gap between cladding and pellet on the quenching behavior of a PWR fuel rod during the reflood phase of a LOCA has been investigated. Flooding experiments were conducted with a short length electrically heated single fuel rod simulator surrounded by glass housing. The gap of 0.05 mm width between the Zircaloy cladding and the internal Al 2 O 3 pellets of the rod was filled either wit helium or with argon to vary the radial heat resistance across the gap. This report presents some typical data and an evaluation of the reflood behavior of the fuel rod simulator used. The results show that the quench front propagates faster for increasing heat resistance in the gap between cladding and heat source of the rod. (orig.) [de

Alstr?m Syndrome: Genetics and Clinical Overview

OpenAIRE

Marshall, Jan D; Maffei, Pietro; Collin, Gayle B; Naggert, J?rgen K

2011-01-01

Alstr?m syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinic...

Volumetric MRI for evaluation of regional pattern and progression of neocortical degeneration in Alzheimer's disease

International Nuclear Information System (INIS)

Leinsinger, G.; Teipel, S.; Pruessner, J.; Hampel, H.; Wismueller, A.; Born, C.; Meindl, T.; Flatz, W.; Schoenberg, S.; Reiser, M.

2003-01-01

Volumetric analysis of the corpus callosum and hippocampus using MRI in Alzheimer's disease (AD) to evaluate the regional pattern and progression of neocortical neurodegeneration. In subsequent studies we investigated patients with AD and healthy controls. Volumetry was based on MRI-data from a sagittal 3D T1w-gradient echo sequence. The corpus callosum (CC) was measured in a midsagittal slice, and subdivided into 5 subregions. Volumetry of the hippocampus/amygdala-formation (HAF) was performed by segmentation in coronary reoriented slices. In AD patients we found a significant atrophy in the rostrum und splenium of CC. The atrophy was correlated with the severity of dementia, but no correlation was found with the load of white matter lesions. In comparison with 18 FDG-PET, we found a significant correlation of regional CC-atrophy with the regional decline of cortical glucose metabolism. A ROC-analysis demonstrated no significant differences in the diagostic accuracy of HAF volumetry and regional CC volumetry of the splenium (region C5) even in mild stages of dementia. Regional atrophy of CC can be used as a marker of neocortical degeneration even in early stages of dementia in AD. (orig.) [de

Maximum/minimum asymmetric rod detection

International Nuclear Information System (INIS)

Huston, J.T.

1990-01-01

This patent describes a system for determining the relative position of each control rod within a control rod group in a nuclear reactor. The control rod group having at least three control rods therein. It comprises: means for producing a signal representative of a position of each control rod within the control rod group in the nuclear reactor; means for establishing a signal representative of the highest position of a control rod in the control rod group in the nuclear reactor; means for establishing a signal representative of the lowest position of a control rod in the control rod group in the nuclear reactor; means for determining a difference between the signal representative of the position of the highest control rod and the signal representative of the position of the lowest control rod; means for establishing a predetermined limit for the difference between the signal representative of the position of the highest control rod and the signal representative of the position of the lowest control rod; and means for comparing the difference between the signals with the predetermined limit. The comparing means producing an output signal when the difference between the signals exceeds the predetermined limit

Ejecta evolution during cone impact

KAUST Repository

Marston, Jeremy

2014-07-07

We present findings from an experimental investigation into the impact of solid cone-shaped bodies onto liquid pools. Using a variety of cone angles and liquid physical properties, we show that the ejecta formed during the impact exhibits self-similarity for all impact speeds for very low surface tension liquids, whilst for high-surface tension liquids similarity is only achieved at high impact speeds. We find that the ejecta tip can detach from the cone and that this phenomenon can be attributed to the air entrainment phenomenon. We analyse of a range of cone angles, including some ogive cones, and impact speeds in terms of the spatiotemporal evolution of the ejecta tip. Using superhydrophobic cones, we also examine the entry of cones which entrain an air layer.

Percussion drilling cone penetrometer with wireless operating in-tip gaschromatograph

Energy Technology Data Exchange (ETDEWEB)

Bracht, C.; Matz, G. [Technische Univ. Hamburg-Harburg, Hamburg (Germany)

2003-07-01

Percussion drilling cone penetrometric analysis is the fast alternative to soil sampling and laboratory analyses. Online detection enables the characterization of a large variety of contaminants in soil. This becomes very important in the reactivation of contaminated sites. Therefore a new system has been constructed, which avoids tedious harness handling through the penetrometer drill rods and minimizes the time for an analysis down to 30 minutes per drill hole. This system enables the in-situ analysis of soil gases up to a depth of 10 to 15 meters. This system consists of a remote controlled in-tip mounted gaschromatograph, a special gas inlet module and a data transfer unit including a rechargeable battery pack. The modules are shock proved to be suitable for percussion drilling techniques and can be removed easily for maintenance. A PDA (Pocket PC) controls the subsoil gaschromatograph unit, calculates and displays the concentration of the detected compounds and stores the acquired data. The gaschromatograph until is optimized to analyze VOCs e.g. BTEX within 10 seconds per analysis. It consists of a loop inlet, a capillary column and a Photo Ionization Detector. It is microcontroller operated and battery powered. The inlet module is optimized soil gases. It includes a sensor and solenoid valve system for water protection and humidity acquisition while drilling. A completely charged battery pack provides up to three hours of analyses. It could be exchanged fast and easy to enable continuous analyses. Digital data transfer between subsoil unit and surface is provided wireless by IR light through the rods. On surface data is transferred wireless by BLUETOOTH radio link to the PDA. The depth of the penetrometer, global position and local time are acquired on-line onto the surface and are transferred on request by BLUETOOTH radio link to the PDA. The wireless data transfer and battery powered modules avoid time consuming cable handling and enable this cone

Control rod drives

International Nuclear Information System (INIS)

Hayakawa, Hiroyasu; Kawamura, Atsuo.

1979-01-01

Purpose: To reduce pellet-clad mechanical interactions, as well as improve the fuel safety. Constitution: In the rod drive of a bwr type reactor, an electric motor operated upon intermittent input such as of pulse signals is connected to a control rod. A resolver for converting the rotational angle of the motor to electric signals is connected to the rotational shaft of the motor and the phase difference between the output signal from the resolver and a reference signal is adapted to detect by a comparator. Based on the detection result, the controller is actuated to control a motor for control rod drive so that fine control for the movement of the control rod is made possible. This can reduce the moving distance of the control rod, decrease the thermal stress applied to the control rod and decrease the pellet clad mechanical interaction failures due to thermal expansion between the cladding tube and the pellets caused by abrupt changes in the generated power. (Furukawa, Y.)

Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

Science.gov (United States)

Evans, Jennifer R; Lawrenson, John G

2017-07-31

It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of age-related macular degeneration (AMD). The objective of this review was to assess the effects of antioxidant vitamin or mineral supplementation on the progression of AMD in people with AMD. We searched CENTRAL (2017, Issue 2), MEDLINE Ovid (1946 to March 2017), Embase Ovid (1947 to March 2017), AMED (1985 to March 2017), OpenGrey (System for Information on Grey Literature in Europe, the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 March 2017. We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation (alone or in combination) to placebo or no intervention, in people with AMD. Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We graded the certainty of the evidence using GRADE. We included 19 studies conducted in USA, Europe, China, and Australia. We judged the trials that contributed data to the review to be at low or unclear risk of bias.Nine studies compared multivitamins with placebo (7 studies) or no treatment (2 studies) in people with early and moderate AMD. The duration of supplementation and follow-up ranged from nine months to six years; one trial followed up beyond two years. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio

Development of partial ontogenic resistance to powdery mildew in hop cones and its management implications.

Directory of Open Access Journals (Sweden)

Megan C Twomey

Full Text Available Knowledge of processes leading to crop damage is central to devising rational approaches to disease management. Multiple experiments established that infection of hop cones by Podosphaera macularis was most severe if inoculation occurred within 15 to 21 days after bloom. This period of infection was associated with the most pronounced reductions in alpha acids, cone color, and accelerated maturation of cones. Susceptibility of cones to powdery mildew decreased progressively after the transition from bloom to cone development, although complete immunity to the disease failed to develop. Maturation of cone tissues was associated with multiple significant affects on the pathogen manifested as reduced germination of conidia, diminished frequency of penetration of bracts, lengthening of the latent period, and decreased sporulation. Cones challenged with P. macularis in juvenile developmental stages also led to greater frequency of colonization by a complex of saprophytic, secondary fungi. Since no developmental stage of cones was immune to powdery mildew, the incidence of powdery mildew continued to increase over time and exceeded 86% by late summer. In field experiments with a moderately susceptible cultivar, the incidence of cones with powdery mildew was statistically similar when fungicide applications were made season-long or targeted only to the juvenile stages of cone development. These studies establish that partial ontogenic resistance develops in hop cones and may influence multiple phases of the infection process and pathogen reproduction. The results further reinforce the concept that the efficacy of a fungicide program may depend largely on timing of a small number of sprays during a relatively brief period of cone development. However in practice, targeting fungicide and other management tactics to periods of enhanced juvenile susceptibility may be complicated by a high degree of asynchrony in cone development and other factors that are

The treatment effect of porous titanium alloy rod on the early stage talar osteonecrosis of sheep.

Directory of Open Access Journals (Sweden)

Xiao-Kang Li

Full Text Available Osteonecrosis of the talus (ONT may severely affect the function of the ankle joint. Most orthopedists believe that ONT should be treated at an early stage, but a concise and effective surgical treatment is lacking. In this study, porous titanium alloy rods were prepared and implanted into the tali of sheep with early-stage ONT (IM group. The curative effect of the rods was compared to treatment by core decompression (DC group. No significant differences in bone reconstruction were observed between the two groups at 1 month after intervention. After 3 months, the macroscopic view of gross specimens of the IM group showed ordinary contours, but the specimens of the DC group showed obvious partial bone defects and cartilage degeneration. Quantitative analysis of the reconstructed trabeculae by micro-CT and histological study suggested that the curative effect of the IM group was superior to that of the DC group at 3 months after intervention. These favorable short-term results of the implantation of porous titanium alloy rods into the tali of sheep with early-stage ONT may provide insight into an innovative surgical treatment for ONT.

Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice

Directory of Open Access Journals (Sweden)

Hernán H. Dieguez

2018-02-01

Full Text Available Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age

Metallosis: A complication in the guided growing rod system used in treatment of scoliosis

Directory of Open Access Journals (Sweden)

Jae Hyuk Yang

2017-01-01

Full Text Available Soft tissue reaction following metallic debris formation with the use of guided growing rod system has not been previously reported in human. The purpose of this study is to report complications caused by metallosis in a guided growing rod system. A 9-year-old female patient, who underwent treatment for the progressive idiopathic scoliosis (with Cobb's angle of 71° with the guided growing rod system. Her Cobb's angle was corrected to 13° with the index surgery. During the 5 years postoperative period, she manifested recurrent episodes of skin irritation and progressive worsening of lateral curvature of the spine to an angle of 57°. Furthermore, at her final followup, Risser stage 4 with a gain in height of 26.4 cm was achieved. Considering adequate growth attainment and deterioration in the curvature, revision surgery with fusion was performed. Postoperative Cobb's angle of 23° was achieved with the final correction. During the revisional surgery, signs of implant wear and metallosis were observed at the location of the unconstrained screws. On histological evaluation, chronic inflammation with foreign body granules was seen. However, titanium level in the body was within normal range. She was discharged without any complications. More research on implant wear as a complication in the guided growing rod system is necessary before its widespread use. The occurrence of metallosis with the use of guided growing rod system in growing young children should be considered, when designing the implants.

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

Science.gov (United States)

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

2012-12-15

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

Immunology of age-related macular degeneration

Science.gov (United States)

Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

2014-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

Correlation Between Cone Penetration Rate And Measured Cone Penetration Parameters In Silty Soils

DEFF Research Database (Denmark)

Poulsen, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

2013-01-01

This paper shows, how a change in cone penetration rate affects the cone penetration measurements, hence the cone resistance, pore pressure, and sleeve friction in silty soil. The standard rate of penetration is 20 mm/s, and it is generally accepted that undrained penetration occurs in clay while...... drained penetration occurs in sand. When lowering the penetration rate, the soil pore water starts to dissipate and a change in the drainage condition is seen. In intermediate soils such as silty soils, the standard cone penetration rate may result in a drainage condition that could be undrained......, partially or fully drained. However, lowering the penetration rate in silty soils has a great significance because of the soil permeability, and only a small change in penetration rate will result in changed cone penetration measurements. In this paper, analyses will be done on data from 15 field cone...

Status of rod consolidation

International Nuclear Information System (INIS)

Bailey, W.J.

1985-04-01

Two of the factors that need to be taken into account with rod consolidation are (1) the effects on rods from their removal from the fuel assembly and (2) the effects on rods as a result of the consolidation process. Potential components of both factors are described in the report. Discussed under (1) are scratches on the fuel rod surfaces, rod breakage, crud, extended burnup, and possible cladding embrittlement due to hydrogen injection at BWRs. Discussed under (2) are the increased water temperature (less than 10 0 C) because of closer packing of the rods, formation of crevices between rods in the close-packed mode, contact with dissimilar metals, and the potential for rapid heating of fuel rods following the loss of water from a spent fuel storage pool. Another factor that plays an important role in rod consolidation is the cost of disposal of the nonfuel-bearing components of the fuel assembly. Also, the dose rate from the components - especially Inconel spacer grids - can affect the handling procedures. Several licensing issues that exist are described. A list of recommendations is provided. 98 refs., 5 figs., 5 tabs

Material Exchange in Photoreceptor Transplantation: Updating Our Understanding of Donor/Host Communication and the Future of Cell Engraftment Science

Directory of Open Access Journals (Sweden)

Philip E. B. Nickerson

2018-03-01

Full Text Available Considerable research effort has been invested into the transplantation of mammalian photoreceptors into healthy and degenerating mouse eyes. Several platforms of rod and cone fluorescent reporting have been central to refining the isolation, purification and transplantation of photoreceptors. The tracking of engrafted cells, including identifying the position, morphology and degree of donor cell integration post-transplant is highly dependent on the use of fluorescent protein reporters. Improvements in imaging and analysis of transplant recipients have revealed that donor cell fluorescent reporters can transfer into host tissue though a process termed material exchange (ME. This recent discovery has chaperoned a new era of interpretation when reviewing the field’s use of dissociated donor cell preparations, and has prompted scientists to re-examine how we use and interpret the information derived from fluorescence-based tracking tools. In this review, we describe the status of our understanding of ME in photoreceptor transplantation. In addition, we discuss the impact of this discovery on several aspects of historical rod and cone transplantation data, and provide insight into future standards and approaches to advance the field of cell engraftment.

Higher-twist effects in the B → π transition form factor from QCD light-cone sum rules

Energy Technology Data Exchange (ETDEWEB)

Khodjamirian, Alexander; Rusov, Aleksey [Universitaet Siegen (Germany). Fakultaet IV, Department Physik, Theoretische Physik 1 Walter-Flex-Strasse 3 57068 Siegen

2016-07-01

I report on the progress in calculating new higher-twist corrections to the QCD light-cone sum rule for the B → π transition form factor. First, the expansion of the massive heavy-quark propagator in the external gluonic field near the light-cone was extended to include new terms containing the gluon-field strength derivatives. The resulting analytical expressions for the twist-5 and twist-6 contributions to the correlation function were obtained in a factorized approximation, expressed via the product of the quark-condensate density and the lower-twist pion distribution amplitudes. The numerical analysis of new higher-twist effects is in progress.

Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

Science.gov (United States)

Yonekawa, Yoshihiro; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. PMID:25280900

Decreased Expression of DREAM Promotes the Degeneration of Retinal Neurons

Science.gov (United States)

Chintala, Shravan; Cheng, Mei; Zhang, Xiao

2015-01-01

The intrinsic mechanisms that promote the degeneration of retinal ganglion cells (RGCs) following the activation of N-Methyl-D-aspartic acid-type glutamate receptors (NMDARs) are unclear. In this study, we have investigated the role of downstream regulatory element antagonist modulator (DREAM) in NMDA-mediated degeneration of the retina. NMDA, phosphate-buffered saline (PBS), and MK801 were injected into the vitreous humor of C57BL/6 mice. At 12, 24, and 48 hours after injection, expression of DREAM in the retina was determined by immunohistochemistry, western blot analysis, and electrophoretic mobility-shift assay (EMSA). Apoptotic death of cells in the retina was determined by terminal deoxynucleotidyl transferace dUTP nick end labeling (TUNEL) assays. Degeneration of RGCs in cross sections and in whole mount retinas was determined by using antibodies against Tuj1 and Brn3a respectively. Degeneration of amacrine cells and bipolar cells was determined by using antibodies against calretinin and protein kinase C (PKC)-alpha respectively. DREAM was expressed constitutively in RGCs, amacrine cells, bipolar cells, as well as in the inner plexiform layer (IPL). NMDA promoted a progressive decrease in DREAM levels in all three cell types over time, and at 48 h after NMDA-treatment very low DREAM levels were evident in the IPL only. DREAM expression in retinal nuclear proteins was decreased progressively after NMDA-treatment, and correlated with its decreased binding to the c-fos-DRE oligonucleotides. A decrease in DREAM expression correlated significantly with apoptotic death of RGCs, amacrine cells and bipolar cells. Treatment of eyes with NMDA antagonist MK801, restored DREAM expression to almost normal levels in the retina, and significantly decreased NMDA-mediated apoptotic death of RGCs, amacrine cells, and bipolar cells. Results presented in this study show for the first time that down-regulation of DREAM promotes the degeneration of RGCs, amacrine cells, and

Control rod drive

International Nuclear Information System (INIS)

Okutani, Tetsuro.

1988-01-01

Purpose: To provide a simple and economical control rod drive using a control circuit requiring no pulse circuit. Constitution: Control rods in a BWR type reactor are driven by hydraulic pressure and inserted or withdrawn in the direction of applying the hydraulic pressure. The direction of the hydraulic pressure is controlled by a direction control valve. Since the driving for the control rod is extremely important in view of the operation, a self diagnosis function is disposed for rapid inspection of possible abnormality. In the present invention, two driving contacts are disposed each by one between the both ends of a solenoid valve of the direction control valve for driving the control rod and the driving power source, and diagnosis is conducted by alternately operating them. Therefore, since it is only necessary that the control circuit issues a driving instruction only to one of the two driving contacts, the pulse circuit is no more required. Further, since the control rod driving is conducted upon alignment of the two driving instructions, the reliability of the control rod drive can be improved. (Horiuchi, T.)

Control rod withdrawal monitoring device

International Nuclear Information System (INIS)

Ebisuya, Mitsuo.

1984-01-01

Purpose: To prevent the power ramp even if a plurality of control rods are subjected to withdrawal operation at a time, by reducing the reactivity applied to the reactor. Constitution: The control rod withdrawal monitoring device is adapted to monitor and control the withdrawal of the control rods depending on the reactor power and the monitoring region thereof is divided into a control rod group monitoring region a transition region and a control group monitoring not interfere region. In a case if the distance between a plurality of control rods for which the withdrawal positions are selected is less than a limiting value, the coordinate for the control rods, distance between the control rods and that the control rod distance is shorter are displayed on a display panel, and the withdrawal for the control rods are blocked. Accordingly, even if a plurality of control rods are subjected successively to the withdrawal operation contrary to the control rod withdrawal sequence upon high power operation of the reactor, the power ramp can be prevented. (Kawakami, Y.)

Feasibility of telemedicine in detecting diabetic retinopathy and age-related macular degeneration.

Science.gov (United States)

Vaziri, Kamyar; Moshfeghi, Darius M; Moshfeghi, Andrew A

2015-03-01

Age-related macular degeneration and diabetic retinopathy are important causes of visual impairment and blindness in the world. Because of recent advances and newly available treatment modalities along with the devastating consequences associated with late stages of these diseases, much attention has been paid to the importance of early detection and improving patient access to specialist care. Telemedicine or, more specifically, digital retinal imaging utilizing telemedical technology has been proposed as an important alternative screening and management strategy to help meet this demand. In this paper, we perform a literature review and analysis that evaluates the validity and feasibility of telemedicine in detecting diabetic retinopathy and age-related macular degeneration. Understanding both the progress and barriers to progress that have been demonstrated in these two areas is important for future telemedicine research projects and innovations in telemedicine technology.

Cataract surgery and age-related macular degeneration. An evidence-based update

DEFF Research Database (Denmark)

Kessel, Line; Erngaard, Ditte; Flesner, Per

2015-01-01

PURPOSE: Age-related macular degeneration (AMD) and cataract often coexist in patients and concerns that cataract surgery is associated with an increased risk of incidence or progression of existing AMD has been raised. This systematic review and meta-analysis is focused on presenting the evidence...

Cone Responses in Usher Syndrome Types 1 and 2 by Microvolt Electroretinography

OpenAIRE

Zein, Wadih M.; Falsini, Benedetto; Tsilou, Ekaterina T.; Turriff, Amy E.; Schultz, Julie M.; Friedman, Thomas B.; Brewer, Carmen C.; Zalewski, Christopher K.; King, Kelly A.; Muskett, Julie A.; Rehman, Atteeq U.; Morell, Robert J.; Griffith, Andrew J.; Sieving, Paul A.

2015-01-01

Cone electroretinography signals in Usher (USH) syndrome demonstrate poor signal-to-noise ratio when measured by standard methodology. The cycle-by-cycle ERG provides for a more reliable measurement with potential as an indicator of disease progression and as an outcome measure in USH treatment trials.

NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

Science.gov (United States)

Song, Hongman; Vijayasarathy, Camasamudram; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Wu, Zhijian; Sieving, Paul A.

2016-01-01

Purpose The active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1. Methods Transgenic (Tg)–CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP. Results Transgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a- and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP–transduced retinas. Conclusions Constitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway. PMID:27233035

Thermal behavior simulation of a nuclear fuel rod through an eletrically heated rod

International Nuclear Information System (INIS)

Lima, R. de C.F. de.

1984-01-01

In thermalhydraulic loops the nuclear industry often uses electrically heated rods to simulate power transients, which occur in nuclear fuel rods. The development and design of a electrically heated rod, by supplying the dimensions and materials which should be used in order to yeld the same temperature and heat flux at the surfaces of the nuclear rod and the electrically heated rod are presented. To a given nuclear transient this equality was obtained by fitting the linear power through the lumped parameters technique. (Author) [pt

The Overexpression of TDP-43 Protein in the Neuron and Oligodendrocyte Cells Causes the Progressive Motor Neuron Degeneration in the SOD1 G93A Transgenic Mouse Model of Amyotrophic Lateral Sclerosis.

Science.gov (United States)

Lu, Yi; Tang, Chunyan; Zhu, Lei; Li, Jiao; Liang, Huiting; Zhang, Jie; Xu, Renshi

2016-01-01

The recent investigation suggested that the TDP-43 protein was closely related to the motor neuron degeneration in amyotrophic lateral sclerosis (ALS), but the pathogenesis contributed to motor neuron degeneration largely remained unknown. Therefore, we detected the alteration of TDP-43 expression and distribution in the adult spinal cord of the SOD1 G93A transgenic mouse model for searching the possible pathogenesis of ALS. We examined the TDP-43 expression and distribution in the different anatomic regions, segments and neural cells in the adult spinal cord at the different stages of the SOD1 wild-type and G93A transgenic model by the fluorescent immunohistochemical technology. We revealed that the amount of TDP-43 positive cell was cervical>lumbar>thoracic segment, that in the ventral horn was more than that in the dorsal horn, a few of TDP-43 protein sparsely expressed and distributed in the other regions, the TDP-43 protein weren't detected in the white matter and the central canal. The TDP-43 protein was mostly expressed and distributed in the nuclear of neuron cells and the cytoplasm of oligodendrocyte cells of the gray matter surrounding the central canal of spinal cord by the granular shape in the SOD1 wild-type and G93A transgenic mice. The amount of TDP-43 positive cell significantly increased at the onset and progression stages of ALS following with the increase of neuron death in spinal cord, particularly in the ventral horn of cervical segment at the progression stage. Our results suggested that the overexpression of TDP-43 protein in the neuron and oligodendrocyte cell causes the progressive motor neuron degeneration in the ALS-like mouse model.

Nuclear fuel rod loading apparatus

International Nuclear Information System (INIS)

King, H.B.; Macivergan, R.; Mckenzie, G.W.

1980-01-01

An apparatus incorporating a microprocessor control is provided for automatically loading nuclear fuel pellets into fuel rods commonly used in nuclear reactor cores. The apparatus comprises a split ''v'' trough for assembling segments of fuel pellets in rows and a shuttle to receive the fuel pellets from the split ''v'' trough when the two sides of the split ''v'' trough are opened. The pellets are weighed while in the shuttle, and the shuttle then moves the pellets into alignment with a fuel rod. A guide bushing is provided to assist the transfer of the pellets into the fuel rod. A rod carousel which holds a plurality of fuel rods presents the proper rod to the guide bushing at the appropriate stage in the loading sequence. The bushing advances to engage the fuel rod, and the shuttle advances to engage the guide bushing. The pellets are then loaded into the fuel rod by a motor operated push rod. The guide bushing includes a photocell utilized in conjunction with the push rod to measure the length of the row of fuel pellets inserted in the fuel rod

Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

Science.gov (United States)

Dieguez, Hernán H; Romeo, Horacio E; González Fleitas, María F; Aranda, Marcos L; Milne, Georgia A; Rosenstein, Ruth E; Dorfman, Damián

2018-02-07

Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and

Control rod shutdown system

International Nuclear Information System (INIS)

Miyamoto, Yoshiyuki; Higashigawa, Yuichi.

1996-01-01

The present invention provides a control rod terminating system in a BWR type nuclear power plant, which stops an induction electric motor as rapidly as possible to terminate the control rods. Namely, the control rod stopping system controls reactor power by inserting/withdrawing control rods into a reactor by driving them by the induction electric motor. The system is provided with a control device for controlling the control rods and a control device for controlling the braking device. The control device outputs a braking operation signal for actuating the braking device during operation of the control rods to stop the operation of the control rods. Further, the braking device has at least two kinds of breaks, namely, a first and a second brakes. The two kinds of brakes are actuated by receiving the brake operation signals at different timings. The brake device is used also for keeping the control rods after the stopping. Even if a stopping torque of each of the breaks is small, different two kinds of brakes are operated at different timings thereby capable of obtaining a large stopping torque as a total. (I.S.)

Cerebral blood flow SPECT scanning in cortico-basal degeneration

International Nuclear Information System (INIS)

Slawek, J.; Walczak, A.; Krupa-Olchawa, J.; Lass, P.; Dubaniewicz, M.

1999-01-01

Idiopathic Parkinson's disease accounts for ca. 75% of all cases of Parkinsonism. Corticobasal degeneration is a relatively rare example of the so-called ''Parkinson-plus'' syndrome. The authors present the case of a 56-year-old woman with rigidity and atypical tremor of upper extremity followed by gait apraxia, dysarthria, bilateral pyramidal signs and myoclonus. There was no improvement after treatment with L-dopa. The disease has progressed, but the patient is still alive. On the basis of clinical data a diagnosis of corticobasal degeneration has been established. Cerebral blood flow SPECT scanning revealed diffuse hypoperfusion of left frontal lobe, antero-inferior part of the left temporal lobe and left basal ganglia. The case illustrates the usefulness of brain SPECT in atypical forma of Parkinson's disease. (author)

Fuel rod leak detector

International Nuclear Information System (INIS)

Womack, R.E.

1978-01-01

A typical embodiment of the invention detects leaking fuel rods by means of a radiation detector that measures the concentration of xenon-133 ( 133 Xe) within each individual rod. A collimated detector that provides signals related to the energy of incident radiation is aligned with one of the ends of a fuel rod. A statistically significant sample of the gamma radiation (γ-rays) that characterize 133 Xe is accumulated through the detector. The data so accumulated indicates the presence of a concentration of 133 Xe appropriate to a sound fuel rod, or a significantly different concentration that reflects a leaking fuel rod

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

Science.gov (United States)

Lambertus, Stanley; Bax, Nathalie M; Fakin, Ana; Groenewoud, Joannes M M; Klevering, B Jeroen; Moore, Anthony T; Michaelides, Michel; Webster, Andrew R; van der Wilt, Gert Jan; Hoyng, Carel B

2017-01-01

Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease progression in

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

Directory of Open Access Journals (Sweden)

Stanley Lambertus

Full Text Available Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration.We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14 and the United Kingdom (external validation cohort, n = 18. The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52. Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904. These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872. We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients.These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease

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

Science.gov (United States)

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

2012-01-01

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

Fuel rods

International Nuclear Information System (INIS)

Hattori, Shinji; Kajiwara, Koichi.

1980-01-01

Purpose: To ensure the safety for the fuel rod failures by adapting plenum springs to function when small forces such as during transportation of fuel rods is exerted and not to function the resilient force when a relatively great force is exerted. Constitution: Between an upper end plug and a plenum spring in a fuel rod, is disposed an insertion member to the lower portion of which is mounted a pin. This pin is kept upright and causes the plenum spring to function resiliently to the pellets against the loads due to accelerations and mechanical vibrations exerted during transportation of the fuel rods. While on the other hand, if a compression force of a relatively high level is exerted to the plenum spring during reactor operation, the pin of the insertion member is buckled and the insertion member is inserted to the inside of the plenum spring, whereby the pellets are allowed to expand freely and the failures in the fuel elements can be prevented. (Moriyama, K.)

Cone responses in Usher syndrome types 1 and 2 by microvolt electroretinography.

Science.gov (United States)

Zein, Wadih M; Falsini, Benedetto; Tsilou, Ekaterina T; Turriff, Amy E; Schultz, Julie M; Friedman, Thomas B; Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Muskett, Julie A; Rehman, Atteeq U; Morell, Robert J; Griffith, Andrew J; Sieving, Paul A

2014-11-25

Progressive decline of psychophysical cone-mediated measures has been reported in type 1 (USH1) and type 2 (USH2) Usher syndrome. Conventional cone electroretinogram (ERG) responses in USH demonstrate poor signal-to-noise ratio. We evaluated cone signals in USH1 and USH2 by recording microvolt level cycle-by-cycle (CxC) ERG. Responses of molecularly genotyped USH1 (n = 18) and USH2 (n = 24) subjects (age range, 15-69 years) were compared with those of controls (n = 12). A subset of USH1 (n = 9) and USH2 (n = 9) subjects was examined two to four times over 2 to 8 years. Photopic CxC ERG and conventional 30-Hz flicker ERG were recorded on the same visits. Usher syndrome subjects showed considerable cone flicker ERG amplitude losses and timing phase delays (P Usher subjects showed abnormal ERG response latency, but this changed less than amplitude with time. In USH syndrome, CxC ERG is more sensitive than conventional ERG and warrants consideration as an outcome measure in USH treatment trials. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

The Preliminary Study for Numerical Computation of 37 Rod Bundle in CANDU Reactor

International Nuclear Information System (INIS)

Jeon, Yu Mi; Bae, Jun Ho; Park, Joo Hwan

2010-01-01

A typical CANDU 6 fuel bundle consists of 37 fuel rods supported by two endplates and separated by spacer pads at various locations. In addition, the bearing pads are brazed to each outer fuel rod with the aim of reducing the contact area between the fuel bundle and the pressure tube. Although the recent progress of CFD methods has provided opportunities for computing the thermal-hydraulic phenomena inside of a fuel channel, it is yet impossible to reflect the detailed shape of rod bundle on the numerical computation due to a lot of computing mesh and memory capacity. Hence, the previous studies conducted a numerical computation for smooth channels without considering spacers, bearing pads. But, it is well known that these components are an important factor to predict the pressure drop and heat transfer rate in a channel. In this study, the new computational method is proposed to solve the complex geometry such as a fuel rod bundle. In front of applying the method to the problem of 37 rod bundle, the validity and the accuracy of the method are tested by applying the method to the simple geometry. Based on the present result, the calculation for the fully shaped 37-rod bundle is scheduled for the future works

Critical condition for the transformation from Taylor cone to cone-jet

International Nuclear Information System (INIS)

Wei Cheng; Zhao Yang; Gang Tie-Qiang; Chen Li-Jie

2014-01-01

An energy method is proposed to investigate the critical transformation condition from a Taylor cone to a cone-jet. Based on the kinetic theorem, the system power allocation and the electrohydrodynamics stability are discussed. The numerical results indicate that the energy of the liquid cone tip experiences a maximum value during the transformation. With the proposed jetting energy, we give the critical transformation condition under which the derivative of jetting energy with respect to the surface area is greater than or equal to the energy required to form a unit of new liquid surface

Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons.

Science.gov (United States)

Fallini, Claudia; Donlin-Asp, Paul G; Rouanet, Jeremy P; Bassell, Gary J; Rossoll, Wilfried

2016-03-30

Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite outgrowth and stabilization

Multiple fuel rod gripper

International Nuclear Information System (INIS)

Shields, E.P.

1987-01-01

An apparatus is described for gripping an array of rods comprising: (a) gripping members grippingly engageable with the rods, each of which has a hollow portion terminating in an open end for receiving the end of one of the rods; (b) a closing means for causing the hollow portion of each of the gripping members to apply substantially the same gripping force onto the end of its respective rod, including (i) a locking plate having a plurality of tapered holes registrable with the array of rods, wherein the exterior of each of the gripping members is tapered and nested within one of the tapered holes, (ii) a withdrawing means having a hydraulic plunger operatively connected to each of the gripping members for applying a substantially identical withdrawing force on each of the gripping members, whereby the hollow portion of each of the gripping members applies substantially the same gripping force on its respective rod, and (c) means for detecting whether each of the gripping members has grippingly engaged its respective rod

Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options.

Science.gov (United States)

Lamb, Ruth; Rohrer, Jonathan D; Lees, Andrew J; Morris, Huw R

2016-09-01

There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesia and rigidity) in PSP and CBD; however, evidence is conflicting and where present, benefits are often negligible and short lived. In fact, "poor" response to levodopa forms part of the NINDS-SPSP criteria for the diagnosis of PSP and consensus criteria for the diagnosis of CBD (Lang Mov Disord. 20 Suppl 1:S83-91, 2005; Litvan et al. Neurology. 48:119-25, 1997; Armstrong et al. Neurology. 80(5):496-503, 2013). There is some evidence that intrasalivery gland botulinum toxin is useful in managing problematic sialorrhea and that intramuscular botulinum toxin and baclofen are helpful in reducing dystonia, including blepharospasm. Benzodiazepines may also be useful in managing dystonia. Myoclonus may be managed using levetiracetam and benzodiazepines. Pharmacological agents licensed for Alzheimer's disease (such as acetylcholinesterase inhibitors and N-Methyl-D-aspartate receptor antagonists) have been used off-label in PSP, CBD, and other tauopathies with the aim of improving cognition; however, there is limited evidence that they are effective and risk of adverse effects may outweigh benefits. The use of atypical antipsychotics for behavioural symptoms is not recommended in the elderly or those with demetia associated conditions and most antipsychotics will worsen Parkinsonism. Antidepressants may be useful for behavioral symptoms and depression but are often poorly tolerated due to adverse effects. In the absence of an effective drug treatment to target the underlying cause of

Review on resonance cone fields

International Nuclear Information System (INIS)

Ohnuma, Toshiro.

1980-02-01

Resonance cone fields and lower hybrid heating are reviewed in this report. The resonance cone fields were reported by Fisher and Gould, and they proposed the use of the measurement of resonance cones and structure as a diagnostic tool to determine the plasma density and electron temperature in magnetoplasma. After the resonance cone, a wave-like disturbance persists. Ohnuma et al. have measured bending, reflection and ducting of resonance cones in detail. The thermal modes in inhomogeneous magnetoplasma were seen. The reflection of thermal mode near an electron plasma frequency layer and an insulating plate has been observed. The non-linear effects of resonance cones is reported. Monochromatic electron beam produces the noise of broad band whistler mode. Lower hybrid waves have been the subject of propagation from the edge of plasma to the lower hybrid layer. Linear lower hybrid waves were studied. The lower hybrid and ion acoustic waves radiated from a point source were observed. The parametric decay of finite-extent, cold electron plasma waves was studied. The lower hybrid cone radiated from a point source going along magnetic field lines was observed. Several experimental data on the lower hybrid heating in tokamak devices have been reported. The theories on resonance cones and lower hybrid waves are introduced in this report. (Kato, T.)

High-yield production of hydrophobins RodA and RodB from Aspergillus fumigatus in Pichia pastoris

DEFF Research Database (Denmark)

Pedersen, Mona Højgaard; Borodina, Irina; Moresco, Jacob Lange

2011-01-01

A as well as rRodB were able to convert a glass surface from hydrophilic to hydrophobic similar to native RodA, but only rRodB was able to decrease the hydrophobicity of a Teflon-like surface to the same extent as native RodA, while rRodA showed this ability to a lesser extent. Recombinant RodA and native...

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

Science.gov (United States)

Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

2015-01-01

Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis.

Science.gov (United States)

Dörken, Veit Martin; Rudall, Paula J

2018-01-01

Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales). The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

Comparison of the load-sharing characteristics between pedicle-based dynamic and rigid rod devices

International Nuclear Information System (INIS)

Ahn, Yoon-Ho; Chen, W-M; Lee, Kwon-Yong; Park, Kyung-Woo; Lee, Sung-Jae

2008-01-01

Recently, numerous types of posterior dynamic stabilization (PDS) devices have been introduced as an alternative to the fusion devices for the surgical treatment of degenerative lumbar spine. It is hypothesized that the use of 'compliant' materials such as Nitinol (Ni-Ti alloy, elastic modulus = 75 GPa) or polyether-etherketone (PEEK, elastic modulus = 3.2 GPa) in PDS can restore stability of the lumbar spine without adverse stress-shielding effects that have often been found with 'rigid' fusion devices made of 'rigid' Ti alloys (elastic modulus = 114 GPa). Previous studies have shown that suitably designed PDS devices made of more compliant material may be able to help retain kinematic behavior of the normal spine with optimal load sharing between the anterior and posterior spinal elements. However, only a few studies on their biomechanical efficacies are available. In this study, we conducted a finite-element (FE) study to investigate changes in load-sharing characteristics of PDS devices. The implanted models were constructed after modifying the previously validated intact model of L3-4 spine. Posterior lumbar fusion with three different types of pedicle screw systems was simulated: a conventional rigid fixation system (Ti6Al4V, Φ = 6.0 mm) and two kinds of PDS devices (one with Nitinol rod with a three-coiled turn manner, Φ = 4.0 mm; the other with PEEK rod with a uniform cylindrical shape, Φ = 6.0 mm). To simulate the load on the lumbar spine in a neutral posture, an axial compressive load (400 N) was applied. Subsequently, the changes in load-sharing characteristics and stresses were investigated. When the compressive load was applied on the implanted models (Nitinol rod, PEEK rod, Ti-alloy rod), the predicted axial compressive loads transmitted through the devices were 141.8 N, 109.8 N and 266.8 N, respectively. Axial forces across the PDS devices (Nitinol rod, PEEK rod) and rigid system (Ti-alloy rod) with facet joints were predicted to take over 41%, 33

Intraspinal canal rod migration causing late-onset paraparesis 8 years after scoliosis surgery.

Science.gov (United States)

Obeid, Ibrahim; Vital, Jean-Marc; Aurouer, Nicolas; Hansen, Steve; Gangnet, Nicolas; Pointillart, Vincent; Gille, Olivier; Boissiere, Louis; Quraishi, Nasir A

2016-07-01

Complete intraspinal canal rod migration with posterior bone reconstitution has never been described in the adolescent idiopathic scoliosis (AIS) population. We present an unusual but significant delayed neurological complication after spinal instrumentation surgery. A 24-year-old woman presented with lower limb weakness (ASIA D) 8 years after posterior instrumentation from T2 to L4 for AIS. CT scan and MRI demonstrated intra-canal rod migration with complete laminar reconstitution. The C-reactive protein was slightly elevated (fluctuated between 10 and 20 mg/l). Radiographs showed the convex rod had entered the spinal canal. The patient was taken into the operating room for thoracic spinal decompression and removal of the convex rod. This Cotrel-Dubousset rod, which had been placed on the convexity of the thoracic curve had completely entered the canal from T5 to T10 and was totally covered by bone with the eroded laminae entirely healed and closed. There was no pseudarthrosis. Intra-operatively, the fusion mass was opened along the whole length of this rod and the rod carefully removed and the spinal cord decompressed. The bacteriological cultures returned positive for Propionibacterium acnes. The patient recovered fully within 2 months post-operatively. We opine that the progressive laminar erosion with intra-canal rod migration resulted from mechanical and infectious-related factors. The very low virulence of the strain of Propionibacterium acnes is probably involved in this particular presentation where the rod was trapped in the canal, owing to the quite extensive laminar reconstitution.

Cones for dental radiography

Energy Technology Data Exchange (ETDEWEB)

Butler, M J [National Radiological Protection Board, Harwell (UK)

1977-04-01

Dental radiographic techniques are summarized. The advantages and disadvantages of the use of both the conventional plastic pointer cone and the open-ended cylinders or divergent cones favoured both by the ICRP (Protection against Ionizing Radiation from External Sources, Oxford, Pergamon Press, 1973, ICRP Publication 15), and in the Code of Practice for the Protection of Persons against Ionizing Radiation arising from Medical and Dental Use (1972, 3rd edition, London, HMSO) are discussed. The use of the word 'should' in these recommendations to signify a desirable requirement, not an essential one, is noted. This wording is currently of interest both nationally and internationally in relation to regulations, standards and notes for guidance. The National Radiological Protection Board (NRPB) has been reviewing the position, and has concluded that open-ended cones have disadvantages which may sometimes outweigh their advantages. Although open-ended cones are preferable under some circumstances, the recommendation that they should be used ought not to be followed without an understanding of the issues involved. The hazards associated with the use of interchangeable cones are considered. The NRPB now proposes that the requirement for the replacement of pointer cones (for both new and existing equipment) should be withdrawn.

Control rod drive for vertical movement

International Nuclear Information System (INIS)

Suskov, I.I.; Gorjunov, V.S.; Zajcev, B.I.; Derevjankin, N.E.; Petrov, V.A.; Istomin, S.D.; Kovalencik, D.I.; Archipov, E.A.; Serebrjakov, V.I.; Kacalin, V.S.

1982-01-01

The control of the rod repositioning gear unit and the control unit of the profile grab of the control rod drive for the alkali metal-cooled fast breeder reactor is achieved by an electromotor being arranged outside the hermetic drive casing. The guide tube is directly repositioned by the rod repositioning gear unit. Coupling control of the drive with the control rod is done in the lower operative position of the control rod and that because of the interaction of the tie rod arranged on the spring-mounted control rod with the induction transmitter for the lower position of the control rod. In the transfer position the rod is fixed within the guide tube. (orig.)

Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis

Directory of Open Access Journals (Sweden)

Veit Martin Dörken

2018-06-01

Full Text Available Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales. The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

Safety rod driving device

International Nuclear Information System (INIS)

Murakami, Kiyonobu; Kurosaki, Akira.

1988-01-01

Purpose: To rapidly insert safety rods for a criticality experiment device into a reactor core container to stop the criticality reaction thereby prevent reactivity accidents. Constitution: A cylinder device having a safety rod as a cylinder rod attached with a piston at one end is constituted. The piston is elevated by pressurized air and attracted and fixed by an electromagnet which is a stationary device disposed at the upper portion of the cylinder. If the current supply to the electromagnet is disconnected, the safety rod constituting the cylinder rod is fallen together with the piston to the lower portion of the cylinder. Since the cylinder rod driving device has neither electrical motor nor driving screw as in the conventional device, necessary space can be reduced and the weight is decreased. In addition, since the inside of the nuclear reactor can easily be shielded completely from the external atmosphere, leakage of radioactive materials can be prevented. (Horiuchi, T.)

Rimonabant, a selective cannabinoid1 receptor antagonist, protects against light-induced retinal degeneration in vitro and in vivo.

Science.gov (United States)

Imamura, Tomoyo; Tsuruma, Kazuhiro; Inoue, Yuki; Otsuka, Tomohiro; Ohno, Yuta; Ogami, Shiho; Yamane, Shinsaku; Shimazawa, Masamitsu; Hara, Hideaki

2017-05-15

The endocannabinoid system is involved in some neurodegenerative diseases such as Alzheimer's disease. An endogenous constellation of proteins related to cannabinoid 1 receptor signaling, including free fatty acids, diacylglycerol lipase, and N-acylethanolamine-hydrolyzing acid amidase, are localized in the murine retina. Moreover, the expression levels of endogenous agonists of cannabinoid receptors are changed in the vitreous fluid. However, the role of the endocannabinoid system in the retina, particularly in the light-induced photoreceptor degeneration, remains unknown. Therefore, we investigated involvement of the cannabinoid 1 receptor in light-induced retinal degeneration using in vitro and in vivo models. To evaluate the effect of cannabinoid 1 receptors in light irradiation-induced cell death, the mouse retinal cone-cell line (661W) was treated with a cannabinoid 1 receptor antagonist, rimonabant. Time-dependent changes of expression and localization of retinal cannabinoid 1 receptors were measured using Western blot and immunostaining. Retinal damage was induced in mice by exposure to light, followed by intravitreal injection of rimonabant. Electroretinograms and histologic analyses were performed. Rimonabant suppressed light-induced photoreceptor cell death. Cannabinoid 1 receptor expression was upregulated by light exposure. Treatment with rimonabant improved both a- and b-wave amplitudes and the thickness of the outer nuclear layer. These results suggest that the cannabinoid 1 receptor is involved in light-induced retinal degeneration and it may represent a therapeutic target in the light-induced photoreceptor degeneration related diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Light-cone quantization of quantum chromodynamics

International Nuclear Information System (INIS)

Brodsky, S.J.; Pauli, H.C.

1991-06-01

We discuss the light-cone quantization of gauge theories from two perspectives: as a calculational tool for representing hadrons as QCD bound-states of relativistic quarks and gluons, and also as a novel method for simulating quantum field theory on a computer. The light-cone Fock state expansion of wavefunctions at fixed light cone time provides a precise definition of the parton model and a general calculus for hadronic matrix elements. We present several new applications of light-cone Fock methods, including calculations of exclusive weak decays of heavy hadrons, and intrinsic heavy-quark contributions to structure functions. A general nonperturbative method for numerically solving quantum field theories, ''discretized light-cone quantization,'' is outlined and applied to several gauge theories, including QCD in one space and one time dimension, and quantum electrodynamics in physical space-time at large coupling strength. The DLCQ method is invariant under the large class of light-cone Lorentz transformations, and it can be formulated such at ultraviolet regularization is independent of the momentum space discretization. Both the bound-state spectrum and the corresponding relativistic light-cone wavefunctions can be obtained by matrix diagonalization and related techniques. We also discuss the construction of the light-cone Fock basis, the structure of the light-cone vacuum, and outline the renormalization techniques required for solving gauge theories within the light-cone Hamiltonian formalism

Light-cone quantization of quantum chromodynamics

Energy Technology Data Exchange (ETDEWEB)

Brodsky, S.J. (Stanford Linear Accelerator Center, Menlo Park, CA (USA)); Pauli, H.C. (Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany, F.R.))

1991-06-01

We discuss the light-cone quantization of gauge theories from two perspectives: as a calculational tool for representing hadrons as QCD bound-states of relativistic quarks and gluons, and also as a novel method for simulating quantum field theory on a computer. The light-cone Fock state expansion of wavefunctions at fixed light cone time provides a precise definition of the parton model and a general calculus for hadronic matrix elements. We present several new applications of light-cone Fock methods, including calculations of exclusive weak decays of heavy hadrons, and intrinsic heavy-quark contributions to structure functions. A general nonperturbative method for numerically solving quantum field theories, discretized light-cone quantization,'' is outlined and applied to several gauge theories, including QCD in one space and one time dimension, and quantum electrodynamics in physical space-time at large coupling strength. The DLCQ method is invariant under the large class of light-cone Lorentz transformations, and it can be formulated such at ultraviolet regularization is independent of the momentum space discretization. Both the bound-state spectrum and the corresponding relativistic light-cone wavefunctions can be obtained by matrix diagonalization and related techniques. We also discuss the construction of the light-cone Fock basis, the structure of the light-cone vacuum, and outline the renormalization techniques required for solving gauge theories within the light-cone Hamiltonian formalism.

Direct interaction of the inhibitory gamma-subunit of Rod cGMP phosphodiesterase (PDE6) with the PDE6 GAFa domains.

Science.gov (United States)

Muradov, Khakim G; Granovsky, Alexey E; Schey, Kevin L; Artemyev, Nikolai O

2002-03-26

Retinal rod and cone cGMP phosphodiesterases (PDE6 family) function as the effector enzyme in the vertebrate visual transduction cascade. The activity of PDE6 catalytic subunits is controlled by the Pgamma-subunits. In addition to the inhibition of cGMP hydrolysis at the catalytic sites, Pgamma is known to stimulate a noncatalytic binding of cGMP to the regulatory GAFa-GAFb domains of PDE6. The latter role of Pgamma has been attributed to its polycationic region. To elucidate the structural basis for the regulation of cGMP binding to the GAF domains of PDE6, a photoexcitable peptide probe corresponding to the polycationic region of Pgamma, Pgamma-21-45, was specifically cross-linked to rod PDE6alphabeta. The site of Pgamma-21-45 cross-linking was localized to Met138Gly139 within the PDE6alpha GAFa domain using mass spectrometric analysis. Chimeras between PDE5 and cone PDE6alpha', containing GAFa and/or GAFb domains of PDE6alpha' have been generated to probe a potential role of the GAFb domains in binding to Pgamma. Analysis of the inhibition of the PDE5/PDE6alpha' chimeras by Pgamma supported the role of PDE6 GAFa but not GAFb domains in the interaction with Pgamma. Our results suggest that a direct binding of the polycationic region of Pgamma to the GAFa domains of PDE6 may lead to a stabilization of the noncatalytic cGMP-binding sites.

Guided-Wave Testing of Trunnion Rods at Greenup Lock and Dam, Kentucky

Science.gov (United States)

2014-04-01

fatigue cracks which go through opening and closing periods during their progression, microcracks in post-tension trunnion anchor rods are believed to be...produce undesired interference effects. A new 1.5 in. diameter, medium-damped lead zirconate titanate ( PZT ), ceramic-based crystal (i.e., an Accuscan

[Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

Science.gov (United States)

Machalińska, Anna

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

Testing device for control rod drives

International Nuclear Information System (INIS)

Hayakawa, Toshifumi.

1992-01-01

A testing device for control rod drives comprises a logic measuring means for measuring an output signal from a control rod drive logic generation circuit, a control means for judging the operation state of a control rod and a man machine interface means for outputting the result of the judgement. A driving instruction outputted from the control rod operation device is always monitored by the control means, and if the operation instruction is stopped, a testing signal is outputted to the control rod control device to simulate a control rod operation. In this case, the output signal of the control rod drive logic generation circuit is held in a control rod drive memory means and intaken into a logic analysis means for measurement and an abnormality is judged by the control means. The stopping of the control rod drive instruction is monitored and the operation abnormality of the control rod is judged, to mitigate the burden of an operator. Further, the operation of the control rod drive logic generation circuit can be confirmed even during a nuclear plant operation by holding the control rod drive instruction thereby enabling to improve maintenance efficiency. (N.H.)

Imaging geographic atrophy in age-related macular degeneration.

Science.gov (United States)

Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

2011-01-01

Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized. Copyright © 2011 S. Karger AG, Basel.

Acquired retinal pigmentary degeneration in a child with 13q deletion syndrome.

Science.gov (United States)

Aguilera, Zenia P; Belin, Peter J; Cavuoto, Kara M; Jayakar, Parul; McKeown, Craig A

2015-10-01

Orbeli syndrome, or 13q deletion syndrome, is a rare condition caused by a distal deletion in the long arm of chromosome 13. The syndrome is characterized by severe physical malformations and developmental delays and has been associated with numerous ocular manifestations. We report the case of a 10-year-old boy with 13q deletion syndrome, who was evaluated for impaired vision and found to have bilateral retinal pigmentary changes resembling those seen in retinitis pigmentosa. There has only been one other case of retinal pigment variation in association with 13q deletion syndrome; however, this represents the first case of bilateral symmetric retinal pigmentary changes with corresponding rod and cone dysfunction on electroretinography. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Failed fuel rod detector

Energy Technology Data Exchange (ETDEWEB)

Uchida, Katsuya; Matsuda, Yasuhiko

1984-05-02

The purpose of the project is to enable failed fuel rod detection simply with no requirement for dismantling the fuel assembly. A gamma-ray detection section is arranged so as to attend on the optional fuel rods in the fuel assembly. The fuel assembly is adapted such that a gamma-ray shielding plate is detachably inserted into optional gaps of the fuel rods or, alternatively, the fuel assembly can detachably be inserted to the gamma-ray shielding plate. In this way, amount of gaseous fission products accumulated in all of the plenum portions in the fuel rods as the object of the measurement can be determined without dismantling the fuel assembly. Accordingly, by comparing the amounts of the gaseous fission products, the failed fuel rod can be detected.

RodPilotR - The Innovative and Cost-Effective Digital Control Rod Drive Control System for PWRs

International Nuclear Information System (INIS)

Baron, Clemens

2008-01-01

With RodPilot, AREVA NP offers an innovative and cost-effective system for controlling control rods in Pressurized Water Reactors. RodPilot controls the three operating coils of the control rod drive mechanism (lift, moveable gripper and stationary gripper coil). The rods are inserted into or withdrawn from the core as required by the Reactor Control System. The system combines modern components, state-of-the-art logic and a proven electronic control rod drive control principle to provide enhanced reliability and lower maintenance costs. (author)

Integrated control rod monitoring device

International Nuclear Information System (INIS)

Saito, Katsuhiro

1997-01-01

The present invention provides a device in which an entire control rod driving time measuring device and a control rod position support device in a reactor building and a central control chamber are integrated systematically to save hardwares such as a signal input/output device and signal cables between boards. Namely, (1) functions of the entire control rod driving time measuring device for monitoring control rods which control the reactor power and a control rod position indication device are integrated into one identical system. Then, the entire devices can be made compact by the integration of the functions. (2) The functions of the entire control rod driving time measuring device and the control rod position indication device are integrated in a central operation board and a board in the site. Then, the place for the installation of them can be used in common in any of the cases. (3) The functions of the entire control rod driving time measuring device and the control rod position indication device are integrated to one identical system to save hardware to be used. Then, signal input/output devices and drift branching panel boards in the site and the central operation board can be saved, and cables for connecting both of the boards is no more necessary. (I.S.)

Progressive irreversible hearing loss is caused by stria vascularis degeneration in an Slc26a4-insufficient mouse model of large vestibular aqueduct syndrome.

Science.gov (United States)

Ito, T; Nishio, A; Wangemann, P; Griffith, A J

2015-12-03

Hearing loss of patients with enlargement of the vestibular aqueduct (EVA) can fluctuate or progress, with overall downward progression. The most common detectable cause of EVA is mutations of SLC26A4. We previously described a transgenic Slc26a4-insufficient mouse model of EVA in which Slc26a4 expression is controlled by doxycycline administration. Mice that received doxycycline from conception until embryonic day 17.5 (DE17.5; doxycycline discontinued at embryonic day 17.5) had fluctuating hearing loss between 1 and 6 months of age with an overall downward progression after 6 months of age. In this study, we characterized the cochlear functional and structural changes underlying irreversible hearing loss in DE17.5 mice at 12 months of age. The endocochlear potential was decreased and inversely correlated with auditory brainstem response thresholds. The stria vascularis was thickened and edematous in ears with less severe hearing loss, and thinned and atrophic in ears with more severe hearing loss. There were pathologic changes in marginal cell morphology and gene expression that were not observed at 3 months. We conclude that strial dysfunction and degeneration are the primary causes of irreversible progressive hearing loss in our Slc26a4-insufficient mouse model of EVA. This model of primary strial atrophy may be used to explore the mechanisms of progressive hearing loss due to strial dysfunction. Published by Elsevier Ltd.

Rod drive and latching mechanism

International Nuclear Information System (INIS)

Veronesi, L.; Sherwood, D.G.

1982-01-01

Hydraulic drive and latching mechanisms for driving reactivity control mechanisms in nuclear reactors are described. Preferably, the pressurized reactor coolant is utilized to raise the drive rod into contact with and to pivot the latching mechanism so as to allow the drive rod to pass the latching mechanism. The pressure in the housing may then be equalized which allows the drive rod to move downwardly into contact with the latching mechanism but to hold the shaft in a raised position with respect to the reactor core. Once again, the reactor coolant pressure may be utilized to raise the drive rod and thus pivot the latching mechanism so that the drive rod passes above the latching mechanism. Again, the mechanism pressure can be equalized which allows the drive rod to fall and pass by the latching mechanism so that the drive rod approaches the reactor core. (author)

Age-Related Macular Degeneration: Pathogenesis, Genetic Background, and the Role of Nutritional Supplements

Directory of Open Access Journals (Sweden)

Marilita M. Moschos

2014-01-01

Full Text Available Age-related macular degeneration (ARMD is the leading cause of severe vision loss and blindness worldwide, mainly affecting people over 65 years old. Dry and wet ARDM are the main types of the disease, which seem to have a multifactorial background. The aim of this review is to summarize the mechanisms of ARMD pathogenesis and exhibit the role of diet and nutritional supplements in the onset and progression of the disease. Environmental factors, such as smoking, alcohol, and, diet appear to interact with mutations in nuclear and mitochondrial DNA, contributing to the pathogenesis of ARMD. Inflammatory mediators and oxidative stress, induced by the daily exposure of retina to high pressure of oxygen and light radiation, have been also associated with ARMD lesions. Other than medical and surgical therapies, nutritional supplements hold a significant role in the prevention and treatment of ARMD, eliminating the progression of macular degeneration.

Control rods

International Nuclear Information System (INIS)

Koga, Isao; Masuoka, Ryuzo.

1979-01-01

Purpose: To prevent fuel element failures during power conditioning by removing liquid absorbents in poison tubes of control rods in a fast power up step and extracting control rods to slightly increase power in a medium power up step. Constitution: A plurality of poison tubes are disposed in a coaxial or plate-like arrangement and divided into a region capable of compensating the reactivity from the initial state at low temperature to 40% power operation and a region capable of compensating the reactivity in the power up above 40% power operation. Soluble poisons are used as absorbers in the poison tubes corresponding to above 40% power operation and they are adapted to be removed independently from the driving of control rods. The poison tubes filled with the soluble absorbers are responsible for the changes in the reactivity from the initial state at low temperature to the medium power region and the reactivity control is conducted by the elimination of liquid absorbers from the poison tubes. In the succeeding slight power up region above the medium power, power up is proceeding by extracting the control rods having remaining poison tubes filled with solid or liquid absorbers. (Seki, T.)

Simulation of nuclear fuel rods by using process computer-controlled power for indirect electrically heated rods

International Nuclear Information System (INIS)

Malang, S.

1975-11-01

An investigation was carried out to determine how the simulation of nuclear fuel rods with indirect electrically heated rods could be improved by use of a computer to control the electrical power during a loss-of-coolant accident (LOCA). To aid in the experiment, a new version of the HETRAP code was developed which simulates a LOCA with heater rod power controlled by a computer that adjusts rod power during a blowdown to minimize the difference in heat flux of the fuel and heater rods. Results show that without computer control of heater rod power, only the part of a blowdown up to the time when the heat transfer mode changes from nucleate boiling to transition or film boiling can be simulated well and then only for short times. With computer control, the surface heat flux and temperature of an electrically heated rod can be made nearly identical to that of a reactor fuel rod with the same cooling conditions during much of the LOCA. A small process control computer can be used to achieve close simulation of a nuclear fuel rod with an indirect electrically heated rod

Macular degeneration (image)

Science.gov (United States)

... macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

TMJ degeneration in SAMP8 mice is accompanied by deranged Ihh signaling.

Science.gov (United States)

Ishizuka, Y; Shibukawa, Y; Nagayama, M; Decker, R; Kinumatsu, T; Saito, A; Pacifici, M; Koyama, E

2014-03-01

The temporomandibular joint (TMJ) functions as a load-bearing diarthrodial joint during mastication, and its continuous use and stress can lead to degeneration over age. Using senescence-accelerated (SAMP8) mice that develop early osteoarthritis-like changes in synovial joints at high frequency, we analyzed possible molecular mechanisms of TMJ degeneration and tested whether and how malocclusion may accelerate it. Condylar articular cartilage in young SAMP8 mice displayed early-onset osteoarthritic changes that included reductions in superficial/chondroprogenitor cell number, proteoglycan/collagen content, and Indian hedgehog (Ihh)-expressing chondrocytes. Following malocclusion induced by tooth milling, the SAMP8 condyles became morphologically defective, displayed even lower proteoglycan levels, and underwent abnormal chondrocyte maturation compared with malocclusion-treated condyles in wild-type mice. Malocclusion also induced faster progression of pathologic changes with increasing age in SAMP8 condyles as indicated by decreased PCNA-positive proliferating chondroprogenitors and increased TUNEL-positive apoptotic cells. These changes were accompanied by steeper reductions in Ihh signaling and by expression of matrix metalloproteinase 13 at the chondro-osseous junction in SAMP8 articular cartilage. In sum, we show for the first time that precocious TMJ degeneration in SAMP8 mice is accompanied by--and possibly attributable to--altered Ihh signaling and that occlusal dysfunction accelerates progression toward degenerative TMJ disease in this model.

Fuel rod technology

International Nuclear Information System (INIS)

Bezold, H.; Romeiser, H.J.

1979-07-01

By extensive mechanization and automation of the fuel rod production, also at increasing production numbers, an efficient production shall be secured, simultaneously corresponding to the high quality standard of the fuel rods. The works done up to now concentrated on the lay out of a rough concept for a mechanized production course. Detail-studies were made for the problems of fuel rod humidity, filling and resistance welding. Further promotion of this project and thus further report will be stopped, since the main point of these works is the production technique. (orig.) [de

Realization of non-symmorphic Dirac cones in PbFCl materials

Science.gov (United States)

Schoop, Leslie

While most 3D Dirac semimetals require two bands with different orbital character to be protected, there is also the possibility to find 3D Dirac semimetals that are guaranteed to exist in certain space groups. Those are resulting from the non-symmoprhic symmetry of the space group, which forces the bands to degenerate at high symmetry points in the Brillouin zone. Non-symmorphic space groups can force three- four, six and eight fold degeneracies which led to the proposal to find 3D Dirac Semimetals as well as new quasiparticles in such space groups. Problematic for realizing this types of Dirac materials is that they require and odd band filling in order to have the Fermi level located at or also near by the band crossing points. Therefore, although the first prediction for using non-symmoprhic symmetry to create a Dirac material was made in 2012, it took almost four years for an experimental verification of this type of Dirac crossing. In this talk I will introduce the material ZrSiS that has, besides other Dirac features, a Dirac cone protected by non-symmorphic symmetry at about 0.5 eV below the Fermi level and was the first material where this type of Dirac cone was imaged with ARPES. I will then proceed to discuss ways to shift this crossing to the Fermi edge and finally show an experimental verification of a fourfold Dirac crossing, protected by non-symmorphic symmetry, at the Fermi energy.

Digital control rod blocking monitor

International Nuclear Information System (INIS)

Funayama, Yoshio.

1996-01-01

The present invention system is used for monitoring of a power region of a reactor, and used for monitoring of simultaneous withdrawal of a plurality of control rods without increasing the size or complicating the system. Namely, the system processes signals from a neutron flux detectors at the periphery of control rods controlled for withdrawal. As a result of the processing, the digital monitoring system generates an alarm when the reactor power at the periphery of the control rods fluctuates exceeding an allowable range. In the system, a control rod information forming means prepares frame data comprising front data, positions of the control rods to be withdrawn, frame numbers and completion data. A serial data transmitting means transmits the frame data successively as repeating frame data rows. A control rod information receiving means takes up the frame data of each of control rods to be withdrawn from the transmitted frame data rows. Since the system of the present invention can monitor the withdrawal of a plurality of control rods simultaneously without increasing the size or complicating the system, cost can be saved and the maintenance can be improved. (I.S.)

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease

Science.gov (United States)

Bax, Nathalie M.; Fakin, Ana; Groenewoud, Joannes M. M.; Klevering, B. Jeroen; Moore, Anthony T.; Michaelides, Michel; Webster, Andrew R.; van der Wilt, Gert Jan; Hoyng, Carel B.

2017-01-01

Background Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options—including gene therapy—are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. Methods and findings We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30–0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33–0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. Conclusions These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a

Focal degeneration of basal cells and the resultant auto-immunoreactions: a novel mechanism for prostate tumor progression and invasion.

Science.gov (United States)

Man, Yan-Gao; Gardner, William A

2008-01-01

The development of human prostate cancer is believed to be a multistep process, progressing sequentially from normal, to hyperplasia, to prostatic intraepithelial neoplasia (PIN), and to invasive and metastatic lesions. High grade PIN has been generally considered as the direct precursor of invasive lesions, and the progression of PIN is believed to be triggered primarily, if not solely, by the overproduction of proteolytic enzymes predominately by cancer cells, which result in the degradation of the basement membrane. These theories, however, are hard to reconcile with two main facts: (1) only about 30% untreated PIN progress to invasive stage, while none of the current approaches could accurately identify the specific PIN or individuals at greater risk for progression, and (2) results from recent world-wide clinical trials with a wide variety of proteolytic enzyme inhibitors have been very disappointing, casting doubt on the validity of the proteolytic enzyme theory. Since over 90% of prostate cancer-related deaths result from invasion-related illness and the incidence of PIN could be up to 16.5-25% in routine or ultrasound guided prostate biopsy, there is an urgent need to uncover the intrinsic mechanism of prostate tumor invasion. Promoted by the facts that the basal cell population is the source of several tumor suppressors and the absence of the basal cell layer is the most distinct feature of invasive lesions, our recent studies have intended to identify the early alterations of basal cell layers and their impact on tumor invasion using multidisciplinary approaches. Our studies revealed that a subset of pre-invasive tumors contained focal disruptions (the absence of basal cells resulting in a gap greater than the combined size of at least three epithelial cells) in surrounding basal cell layers. Compared to their non-disrupted counterparts, focally disrupted basal cell layers had several unique features: (1) significantly lower proliferation; (2

Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

DEFF Research Database (Denmark)

Patterson, Emily J.; Wilk, Melissa; Langlo, Christopher S.

2016-01-01

encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants......PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations...... to clarify the link between color vision deficiency and cone dysfunction.  METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone...

Translocation of "rod-coil" polymers: probing the structure of single molecules within nanopores.

Science.gov (United States)

de Haan, Hendrick W; Slater, Gary W

2013-01-25

Using simulation and analytical techniques, we demonstrate that it is possible to extract structural information about biological molecules by monitoring the dynamics as they translocate through nanopores. From Langevin dynamics simulations of polymers exhibiting discrete changes in flexibility (rod-coil polymers), distinct plateaus are observed in the progression towards complete translocation. Characterizing these dynamics via an incremental mean first passage approach, the large steps are shown to correspond to local barriers preventing the passage of the coils while the rods translocate relatively easily. Analytical replication of the results provides insight into the corrugated nature of the free energy landscape as well as the dependence of the effective barrier heights on the length of the coil sections. Narrowing the width of the pore or decreasing the charge on either the rod or the coil segments are both shown to enhance the resolution of structural details. The special case of a single rod confined within a nanopore is also studied. Here, sufficiently long flexible sections attached to either end are demonstrated to act as entropic anchors which can effectively trap the rod within the pore for an extended period of time. Both sets of results suggest new experimental approaches for the control and study of biological molecules within nanopores.

MR imaging of central nervous system white matter tract degeneration (Wallerian degeneration)

International Nuclear Information System (INIS)

Kuhn, M.J.; Johnson, K.A.; Davis, K.R.

1987-01-01

Wallerian degeneration is readily demonstrated by MR imaging. Twenty-one patients with MR signal abnormalities in various central nervous system (CNS) white matter tracts were evaluated with regard to (1) nature of signal abnormality, (2) MR anatomy of the involved tract, and (3) primary pathology (e.g., infarct, tumor, hemorrhage). Most examples of wallerian degeneration result in a thin, continuous band of long T1, long T2 signal abnormality conforming to the known anatomic pathway of a CNS axonal tract. Old, large cortical infarcts have the greatest propensity to show subsequent white-matter tract degeneration. Corticospinal tract degeneration is the type most readily visualized, often seen extending completely from the cerebral cortex through the medulla

The NLO jet vertex in the small-cone approximation for kt and cone algorithms

International Nuclear Information System (INIS)

Colferai, D.; Niccoli, A.

2015-01-01

We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet “radius” R=0.5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

The NLO jet vertex in the small-cone approximation for kt and cone algorithms

Energy Technology Data Exchange (ETDEWEB)

Colferai, D.; Niccoli, A. [Dipartimento di Fisica e Astronomia, Università di Firenze and INFN, Sezione di Firenze, 50019 Sesto Fiorentino (Italy)

2015-04-15

We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet “radius” R=0.5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

QCD on the light cone

International Nuclear Information System (INIS)

Brodsky, S.J.

1992-09-01

The quantization of gauge theory at fixed light-cone time τ = t - z/c provides new perspectives for solving non-perturbative problems in quantum chromodynamics. The light-cone Fock state expansion provides both a precise definition of the relativistic wavefunctions of hadrons as bound-states of quarks and gluons and a general calculus for predicting QCD processes at the amplitude level. Applications to exclusive processes and weak decay amplitudes are discussed. The problem of computing the hadronic spectrum and the corresponding light-cone wavefunctions of QCD in one space and one time dimension has been successfully reduced to the diagonalization of a discrete representation of the light-cone Hamiltonian. The problems confronting the solution of gauge theories in 3 + 1 dimensions in the light-cone quantization formalism,, including zero modes and non-perturbative renormalization, are reviewed

Thresholds and noise limitations of colour vision in dim light.

Science.gov (United States)

Kelber, Almut; Yovanovich, Carola; Olsson, Peter

2017-04-05

Colour discrimination is based on opponent photoreceptor interactions, and limited by receptor noise. In dim light, photon shot noise impairs colour vision, and in vertebrates, the absolute threshold of colour vision is set by dark noise in cones. Nocturnal insects (e.g. moths and nocturnal bees) and vertebrates lacking rods (geckos) have adaptations to reduce receptor noise and use chromatic vision even in very dim light. In contrast, vertebrates with duplex retinae use colour-blind rod vision when noisy cone signals become unreliable, and their transition from cone- to rod-based vision is marked by the Purkinje shift. Rod-cone interactions have not been shown to improve colour vision in dim light, but may contribute to colour vision in mesopic light intensities. Frogs and toads that have two types of rods use opponent signals from these rods to control phototaxis even at their visual threshold. However, for tasks such as prey or mate choice, their colour discrimination abilities fail at brighter light intensities, similar to other vertebrates, probably limited by the dark noise in cones.This article is part of the themed issue 'Vision in dim light'. © 2017 The Author(s).

The BWR Hybrid 4 control rod

International Nuclear Information System (INIS)

Gross, H.; Fuchs, H.P.; Lippert, H.J.; Dambietz, W.

1988-01-01

The service life of BWR control rods designed in the past has been unsatisfactory. The main reason was irradiation assisted stress corrosion cracking of B 4 C rods caused by external swelling of the B 4 C powder. By this reason KWU developed an improved BWR control rod (Hybrid 4 control rod) with extended service life and increased control rod worth. It also allows the procedure for replacing and rearranging fuel assemblies to be considerably simplified. A complete set of Hydbrid 4 control rods is expected to last throughout the service life of a plant (assumption: ca. 40 years) if an appropriate control rod reshuffling management program is used. (orig.)

Characterization of multiple light damage paradigms reveals regional differences in photoreceptor loss.

Science.gov (United States)

Thomas, Jennifer L; Nelson, Craig M; Luo, Xixia; Hyde, David R; Thummel, Ryan

2012-04-01

Zebrafish provide an attractive model to study the retinal response to photoreceptor apoptosis due to its remarkable ability to spontaneously regenerate retinal neurons following damage. There are currently two widely-used light-induced retinal degeneration models to damage photoreceptors in the adult zebrafish. One model uses constant bright light, whereas the other uses a short exposure to extremely intense ultraviolet light. Although both models are currently used, it is unclear whether they differ in regard to the extent of photoreceptor damage or the subsequent regeneration response. Here we report a thorough analysis of the photoreceptor damage and subsequent proliferation response elicited by each individual treatment, as well as by the concomitant use of both treatments. We show a differential loss of rod and cone photoreceptors with each treatment. Additionally, we show that the extent of proliferation observed in the retina directly correlates with the severity of photoreceptor loss. We also demonstrate that both the ventral and posterior regions of the retina are partially protected from light damage. Finally, we show that combining a short ultraviolet exposure followed by a constant bright light treatment largely eliminates the neuroprotected regions, resulting in widespread loss of rod and cone photoreceptors and a robust regenerative response throughout the retina. Copyright © 2012 Elsevier Ltd. All rights reserved.

Early Events in Retinal Degeneration Caused by Rhodopsin Mutation or Pigment Epithelium Malfunction: Differences and Similarities

Science.gov (United States)

Di Pierdomenico, Johnny; García-Ayuso, Diego; Pinilla, Isabel; Cuenca, Nicolás; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Villegas-Pérez, María P.

2017-01-01

To study the course of photoreceptor cell death and macro and microglial reactivity in two rat models of retinal degeneration with different etiologies. Retinas from P23H-1 (rhodopsin mutation) and Royal College of Surgeon (RCS, pigment epithelium malfunction) rats and age-matched control animals (Sprague-Dawley and Pievald Viro Glaxo, respectively) were cross-sectioned at different postnatal ages (from P10 to P60) and rhodopsin, L/M- and S-opsin, ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acid protein (GFAP), and proliferating cell nuclear antigen (PCNA) proteins were immunodetected. Photoreceptor nuclei rows and microglial cells in the different retinal layers were quantified. Photoreceptor degeneration starts earlier and progresses quicker in P23H-1 than in RCS rats. In both models, microglial cell activation occurs simultaneously with the initiation of photoreceptor death while GFAP over-expression starts later. As degeneration progresses, the numbers of microglial cells increase in the retina, but decreasing in the inner retina and increasing in the outer retina, more markedly in RCS rats. Interestingly, and in contrast with healthy animals, microglial cells reach the outer nuclei and outer segment layers. The higher number of microglial cells in dystrophic retinas cannot be fully accounted by intraretinal migration and PCNA immunodetection revealed microglial proliferation in both models but more importantly in RCS rats. The etiology of retinal degeneration determines the initiation and pattern of photoreceptor cell death and simultaneously there is microglial activation and migration, while the macroglial response is delayed. The actions of microglial cells in the degeneration cannot be explained only in the basis of photoreceptor death because they participate more actively in the RCS model. Thus, the retinal degeneration caused by pigment epithelium malfunction is more inflammatory and would probably respond better to interventions

Burnable poison rod

International Nuclear Information System (INIS)

Natsume, Tomohiro.

1988-01-01

Purpose: To decrease the effect of water elimination and the effect of burn-up residue boron, thereby reduce the effect of burnable poison rods as the neutron poisons at the final stage of reactor core lifetime. Constitution: In a burnable poison rod according to the present invention, a hollow burnable poison material is filled in an external fuel can, an inner fuel can mounted with a carbon rod is inserted to the hollow portion of the burnable poison material and helium gases are charged in the outer fuel can. In such a burnable poison rod, the reactivity worths after the burning are reduced to one-half as compared with the conventional case. Accordingly, since the effect of the burnable poison as the neutron poisons is reduced at the final stage of the reactor core of lifetime, the excess reactivity of the reactor core is increased. (Horiuchi, T.)

Multimodal Imaging of Photoreceptor Structure in Choroideremia.

Science.gov (United States)

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

2016-01-01

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

New developments in age-related macular degeneration

Directory of Open Access Journals (Sweden)

Lyndon da Cruz

2008-09-01

Full Text Available The World Health Organization (WHO estimates that over 3 million people (9% of global blindness are blinded by age-related macular degeneration (AMD. AMD affects people over the age of 55. There are two main types of AMD, dry and wet. In dry AMD, patients slowly lose vision through progressive atrophy of the macular tissue. Wet, or exudative, AMD, is associated with new blood vessels called subretinal neovascular membranes (or SRNVM and affected patients lose vision more rapidly due to fluid leakage and haemorrhage at the macula.

Degeneration and height of cervical discs classified from MRI compared with precise height measurements from radiographs

International Nuclear Information System (INIS)

Kolstad, Frode; Myhr, Gunnar; Kvistad, Kjell Arne; Nygaard, Oystein P.; Leivseth, Gunnar

2005-01-01

Study design: Descriptive study comparing MRI classifications with measurements from radiographs. Objectives: 1.Define the relationship between MRI classified cervical disc degeneration and objectively measured disc height. 2.Assess the level of inter- and intra-observer errors using MRI in defining cervical disc degeneration. Summary of background data: Cervical spine degeneration has been defined radiologically by loss of disc height, decreased disc and bone marrow signal intensity and disc protrusion/herniation on MRI. The intra- and inter-observer error using MRI in defining cervical degeneration influences data interpretation. Few previous studies have addressed this source of error. The relation and time sequence between cervical disc degeneration classified by MRI and cervical disc height decrease measured from radiographs is unclear. Methods: The MRI classification of degeneration was based on nucleus signal, prolaps identification and bone marrow signal. Two neuro-radiologists evaluated the MR-images independently in a blinded fashion. The radiographic disc height measurements were done by a new computer-assisted method compensating for image distortion and permitting comparison with normal level-, age- and gender-appropriate disc height. Results/conclusions: 1.Progressing disc degeneration classified from MRI is on average significantly associated with a decrease of disc height as measured from radiographs. Within each MRI defined category of degeneration measured disc heights, however, scatter in a wide range. 2.The inter-observer agreement between two neuro-radiologists in both defining degeneration and disc height by MRI was only moderate. Studies addressing questions related to cervical disc degeneration should take this into consideration

Degeneration and height of cervical discs classified from MRI compared with precise height measurements from radiographs

Energy Technology Data Exchange (ETDEWEB)

Kolstad, Frode [National Centre of Spinal Disorders, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway)]. E-mail: frode.kolstad@medisin.ntnu.no; Myhr, Gunnar [Department of Radiology, University Hospital of Trondheim, 7006 Trondheim (Norway); Kvistad, Kjell Arne [Department of Radiology, University Hospital of Trondheim, 7006 Trondheim (Norway); Nygaard, Oystein P. [National Centre of Spinal Disorders, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway); Leivseth, Gunnar [Department of Neuromedicine, Faculty of Medicine, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway)

2005-09-01

Study design: Descriptive study comparing MRI classifications with measurements from radiographs. Objectives: 1.Define the relationship between MRI classified cervical disc degeneration and objectively measured disc height. 2.Assess the level of inter- and intra-observer errors using MRI in defining cervical disc degeneration. Summary of background data: Cervical spine degeneration has been defined radiologically by loss of disc height, decreased disc and bone marrow signal intensity and disc protrusion/herniation on MRI. The intra- and inter-observer error using MRI in defining cervical degeneration influences data interpretation. Few previous studies have addressed this source of error. The relation and time sequence between cervical disc degeneration classified by MRI and cervical disc height decrease measured from radiographs is unclear. Methods: The MRI classification of degeneration was based on nucleus signal, prolaps identification and bone marrow signal. Two neuro-radiologists evaluated the MR-images independently in a blinded fashion. The radiographic disc height measurements were done by a new computer-assisted method compensating for image distortion and permitting comparison with normal level-, age- and gender-appropriate disc height. Results/conclusions: 1.Progressing disc degeneration classified from MRI is on average significantly associated with a decrease of disc height as measured from radiographs. Within each MRI defined category of degeneration measured disc heights, however, scatter in a wide range. 2.The inter-observer agreement between two neuro-radiologists in both defining degeneration and disc height by MRI was only moderate. Studies addressing questions related to cervical disc degeneration should take this into consideration.

Biomechanics of lumbar cortical screw-rod fixation versus pedicle screw-rod fixation with and without interbody support.

Science.gov (United States)

Perez-Orribo, Luis; Kalb, Samuel; Reyes, Phillip M; Chang, Steve W; Crawford, Neil R

2013-04-15

Seven different combinations of posterior screw fixation, with or without interbody support, were compared in vitro using nondestructive flexibility tests. To study the biomechanical behavior of a new cortical screw (CS) fixation construct relative to the traditional pedicle screw (PS) construct. The CS is an alternative to the PS for posterior fixation of the lumbar spine. The CS trajectory is more sagittally and cranially oriented than the PS, being anchored in the pars interarticularis. Like PS fixation, CS fixation uses interconnecting rods fastened with top-locking connectors. Stability after bilateral CS fixation was compared with stability after bilateral PS fixation in the setting of intact disc and with direct lateral interbody fixation (DLIF) or transforaminal lateral interbody fixation (TLIF) support. Standard nondestructive flexibility tests were performed in cadaveric lumbar specimens, allowing non-paired comparisons of specific conditions from 28 specimens (4 groups of 7) within a larger experiment of multiple hardware configurations. Condition tested and group from which results originated were as follows: (1) intact (all groups); (2) with L3-L4 bilateral PS-rods (group 1); (3) with bilateral CS-rods (group 2); (4) with DLIF (group 3); (5) with DLIF + CS-rods (group 4); (6) with DLIF + PS-rods (group 3); (7) with TLIF + CS-rods (group 2), and (8) with TLIF + PS-rods (group 2). To assess spinal stability, the mean range of motion, lax zone, and stiff zone at L3-L4 were compared during flexion-extension, lateral bending, and axial rotation. With intact disc, stability was equivalent after PS-rod and CS-rod fixation, except that PS-rod fixation was stiffer during axial rotation. With DLIF support, there was no significant difference in stability between PS-rod and CS-rod fixation. With TLIF support, PS-rod fixation was stiffer than CS-rod fixation during lateral bending. Bilateral CS-rod fixation provided about the same stability in cadaveric specimens

Ontogenic retinal changes in three ecologically distinct elopomorph fishes (Elopomorpha:Teleostei) correlate with light environment and behavior.

Science.gov (United States)

Taylor, Scott M; Loew, Ellis R; Grace, Michael S

2015-01-01

Unlike the mammalian retina, the teleost fish retina undergoes persistent neurogenesis from intrinsic stem cells. In marine teleosts, most cone photoreceptor genesis occurs early in the embryonic and larval stages, and rods are added primarily during and after metamorphosis. This study demonstrates a developmental paradigm in elopomorph fishes in which retinas are rod-dominated in larvae, but undergo periods of later cone genesis. Retinal characteristics were compared at different developmental stages among three ecologically distinct elopomorph fishes-ladyfish (Elops saurus), bonefish (Albula vulpes), and speckled worm eel (Myrophis punctatus). The objectives were to improve our understanding of (1) the developmental strategy in the elopomorph retina, (2) the functional architecture of the retina as it relates to ecology, and (3) how the light environment influences photoreceptor genesis. Photoreceptor morphologies, distributions, and spectral absorption were studied at larval, juvenile, and adult stages. Premetamorphic retinas in all three species are rod-dominated, but the retinas of these species undergo dramatic change over the course of development, resulting in juvenile and adult retinal characteristics that correlate closely with ecology. Adult E. saurus has high rod densities, grouped photoreceptors, a reflective tapetum, and longer-wavelength photopigments, supporting vision in turbid, low-light conditions. Adult A. vulpes has high cone densities, low rod densities, and shorter-wavelength photopigments, supporting diurnal vision in shallow, clear water. M. punctatus loses cones during metamorphosis, develops new cones after settlement, and maintains high rod but low cone densities, supporting primarily nocturnal vision. M. punctatus secondary cone genesis occurs rapidly throughout the retina, suggesting a novel mechanism of vertebrate photoreceptor genesis. Finally, in postsettlement M. punctatus, the continuous presence or absence of visible light

A review on primary progressive aphasia

Directory of Open Access Journals (Sweden)

Gabriel C Léger

2007-01-01

Full Text Available Gabriel C Léger1,2, Nancy Johnson31Neurology Service, Hôtel-Dieu du Centre Hospitalier de l’Univertité de Montréal, Montréal, Québec, Canada; 2Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; 3Cognitive Neurology and Alzheimer’s Disease Center, Department of Psychiatry and Behavioral Science, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Primary progressive aphasia (PPA is a neurodegenerative disease of insidious onset presenting with progressive isolated loss of language function, without significant impairment in other cognitive domains. Current diagnostic criteria require the language dysfunction to remain isolated for at least two years, and to remain the salient feature as the disease progresses, usually to involve other domains such as behavior, executive functions, and judgment. Although PPA in its early stages can usually be differentiated from probable Alzheimer’s disease (PRAD and the behavioral variant of frontotemporal lobar degeneration by the absence of significant changes in memory and behavior, and the preservation of activities daily living, progression of the disease often leads to deficits more consistent with the latter. Underlying etiologies remain heterogeneous: the neuropathological characteristics associated with frontotemporal lobar degeneration, cortocobasal degeneration, and motor neuron disease are usually found. There is a strong genetic susceptibility with affliction of first-degree relatives with similar disease in up to 40 to 50% in some series. Pathogenic mutations in genes coding for the proteins tau and progranulin have been isolated. These are leading to a better understanding of the neuropathological mechanisms and hopefully targeted disease-modifying therapy. Current therapy is limited to improving mood symptoms and targeting behavior changes as they develop. Referral to specialized centers where speech therapy, counseling, and education

Freely suspended rod fall dampener, especially for control rod of liquid-cooled nuclear reactor

International Nuclear Information System (INIS)

Becvar, J.; Saroch, V.

1977-01-01

A shock absorber is described whose advantage is that the space required for the movement of the shock absorber in the operating travel of the system suspension rod-control rod bundle may be reduced. The design allows the automatic disconnection of the system and the removal of the suspension rod from the reactor without dismantling. The braking force reaction is transmitted to the structure above the core. The system fall energy is absorbed on the side of the suspension rod which has a bigger mass. (J.B.)

RodPilot{sup R} - The Innovative and Cost-Effective Digital Control Rod Drive Control System for PWRs

Energy Technology Data Exchange (ETDEWEB)

Baron, Clemens [AREVA NP GmbH, NLEE-G, Postfach 1199, 91001 Erlangen (Germany)

2008-07-01

With RodPilot, AREVA NP offers an innovative and cost-effective system for controlling control rods in Pressurized Water Reactors. RodPilot controls the three operating coils of the control rod drive mechanism (lift, moveable gripper and stationary gripper coil). The rods are inserted into or withdrawn from the core as required by the Reactor Control System. The system combines modern components, state-of-the-art logic and a proven electronic control rod drive control principle to provide enhanced reliability and lower maintenance costs. (author)

Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration.

Science.gov (United States)

Folgar, Francisco A; Yuan, Eric L; Sevilla, Monica B; Chiu, Stephanie J; Farsiu, Sina; Chew, Emily Y; Toth, Cynthia A

2016-01-01

To analyze the value of novel measures of retinal pigment epithelium-drusen complex (RPEDC) volume to predict 2-year disease progression of intermediate age-related macular degeneration (AMD). Prospective, observational study. Three hundred forty-five AMD and 122 non-AMD participants enrolled in the Age Related Eye Disease Study 2 Ancillary Spectral-Domain (SD) Optical Coherence Tomography (OCT) study. High-density SD OCT macular volumes were obtained at yearly study visits. The RPEDC abnormal thickening (henceforth, OCT drusen) and RPEDC abnormal thinning (RAT) volumes were generated by semiautomated segmentation of total RPEDC within a 5-mm-diameter macular field. Volume change and odds ratio (OR) with 95% confidence intervals (CI) for progression to advanced AMD with choroidal neovascularization (CNV) or central geographic atrophy (GA). Complete volumes were obtained in 265 and 266 AMD eyes and in 115 and 97 control eyes at baseline and at year 2, respectively. In AMD eyes, mean (standard deviation) OCT drusen volume increased from 0.08 mm(3) (0.16 mm(3)) to 0.10 mm(3) (0.23 mm(3); P < 0.001), and RAT volume increased from 8.3 × 10(-4) mm(3) (20.8 × 10(-4) mm(3)) to 18.4 × 10(-4) mm(3) (46.6 × 10(-4) mm(3); P < 0.001). Greater baseline OCT drusen volume was associated with 2-year progression to CNV (P = 0.002). Odds of developing CNV increased by 31% for every 0.1-mm(3) increase in baseline OCT drusen volume (OR, 1.31; 95% CI, 1.06-1.63; P = 0.013). Greater baseline RAT volume was associated with significant 2-year increase in RAT volume (P < 0.001), noncentral GA (P < 0.001), and progression to central GA (P < 0.001). Odds of developing central GA increased by 32% for every 0.001-mm(3) increase in baseline RAT volume (OR, 1.32; 95% CI, 1.14-1.53; P < 0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change. Macular OCT drusen and RAT volumes increased significantly in AMD eyes over 2 years

Analysis of the RPE sheet in the rd10 retinal degeneration model

Energy Technology Data Exchange (ETDEWEB)

Jiang, Yi [Los Alamos National Laboratory

2011-01-04

The normal RPE sheet in the C57Bl/6J mouse is subclassified into two major tiling patterns: A regular generally hexagonal array covering most of the surface and a 'soft network' near the ciliary body made of irregularly shaped cells. Physics models predict these two patterns based on contractility and elasticity of the RPE cell, and strength of cellular adhesion between cells. We hypothesized and identified major changes in RPE regular hexagonal tiling pattern in rdl0 compared to C57BL/6J mice. RPE sheet damage was extensive but occurred in rd10 later than expected, after most retinal degeneration. RPE sheet changes occur in zones with a bullseye pattern. In the posterior zone around the optic nerve RPE cells take on larger irregular and varied shapes to form an intact monolayer. In mid periphery, there is a higher than normal density of cells that progress into involuted layers of RPE under the retina. The periphery remains mostly normal until late stages of degeneration. The number of neighboring cells varies widely depending on zone and progression. RPE morphology continues to deteriorate long after the photoreceptors have degenerated. The RPE cells are bystanders to the rd10 degeneration within photo receptors, and the collateral damage to the RPE sheet resembles stimulation of migration or chemotaxis. Quantitative measures of the tiling patterns and histopathology detected here, scripted in a pipeline written in Perl and Cell Profiler (an open source Matlab plugin), are directly applicable to RPE sheet images from noninvasive fundus autofluorescence (FAF), adaptive optics confocal scanning laser ophthalmoscope (AO-cSLO), and spectral domain optical coherence tomography (SD-OCT) of patients with early stage AMD or RP.

Control-rod driving mechanism

International Nuclear Information System (INIS)

Jodoi, Takashi.

1976-01-01

Purpose: To prevent falling of control rods due to malfunction. Constitution: The device of the present invention has a scram function in particular, and uses principally a fluid pressure as a scram accelerating means. The control rod is held by upper and lower holding devices, which are connected by a connecting mechanism. This connecting mechanism is designed to be detachable only at the lower limit of driving stroke of the control rod so that there occurs no erroneous scram resulting from careless disconnection of the connecting mechanism. Further, scramming operation due to own weight of the scram operating portion such as control rod driving shaft may be effected to increase freedom. (Kamimura, M.)

What Is Age-Related Macular Degeneration?

Science.gov (United States)

... Eye Health / Eye Health A-Z Age-Related Macular Degeneration Sections What Is Macular Degeneration? How is AMD ... What Does Macular Degeneration Look Like? What Is Macular Degeneration? Leer en Español: ¿Qué es la degeneración macular ...

Assessment of the suitability of biodegradable rods for use in posterior lumbar fusion: An in-vitro biomechanical evaluation and finite element analysis.

Directory of Open Access Journals (Sweden)

Fon-Yih Tsuang

Full Text Available Interbody fusion with posterior instrumentation is a common method for treating lumbar degenerative disc diseases. However, the high rigidity of the fusion construct may produce abnormal stresses at the adjacent segment and lead to adjacent segment degeneration (ASD. As such, biodegradable implants are becoming more popular for use in orthopaedic surgery. These implants offer sufficient stability for fusion but at a reduced stiffness. Tailored to degrade over a specific timeframe, biodegradable implants could potentially mitigate the drawbacks of conventional stiff constructs and reduce the loading on adjacent segments. Six finite element models were developed in this study to simulate a spine with and without fixators. The spinal fixators used both titanium rods and biodegradable rods. The models were subjected to axial loading and pure moments. The range of motion (ROM, disc stresses, and contact forces of facet joints at adjacent segments were recorded. A 3-point bending test was performed on the biodegradable rods and a dynamic bending test was performed on the spinal fixators according to ASTM F1717-11a. The finite element simulation showed that lumbar spinal fusion using biodegradable implants had a similar ROM at the fusion level as at adjacent levels. As the rods degraded over time, this produced a decrease in the contact force at adjacent facet joints, less stress in the adjacent disc and greater loading on the anterior bone graft region. The mechanical tests showed the initial average fatigue strength of the biodegradable rods was 145 N, but this decreased to 115N and 55N after 6 months and 12 months of soaking in solution. Also, both the spinal fixator with biodegradable rods and with titanium rods was strong enough to withstand 5,000,000 dynamic compression cycles under a 145 N axial load. The results of this study demonstrated that biodegradable rods may present more favourable clinical outcomes for lumbar fusion. These polymer rods

Upper motor neuron predominant degeneration with frontal and temporal lobe atrophy.

Science.gov (United States)

Konagaya, M; Sakai, M; Matsuoka, Y; Konagaya, Y; Hashizume, Y

1998-11-01

The autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. He showed slowly progressive spasticity, pseudobulbar palsy and character change, and died 32 months after the onset of symptoms. Autopsy revealed severe atrophy of the frontal and temporal lobes, remarkable neuronal loss and gliosis in the precentral gyrus, left temporal lobe pole and amygdala, mild degeneration of the Ammon's horn, degeneration of the corticospinal tract, and very mild involvement of the lower motor neurons. The anterior horn cells only occasionally demonstrated Bunina body by cystatin-C staining, and skein-like inclusions by ubiquitin staining. This is a peculiar case with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease predominantly affecting the upper motor neuron.

REACTOR CONTROL ROD OPERATING SYSTEM

Science.gov (United States)

Miller, G.

1961-12-12

A nuclear reactor control rod mechanism is designed which mechanically moves the control rods into and out of the core under normal conditions but rapidly forces the control rods into the core by catapultic action in the event of an emergency. (AEC)

Mach cones in space and laboratory dusty magnetoplasmas

International Nuclear Information System (INIS)

Mamun, A.A.; Shukla, P.K

2004-07-01

We present a rigorous theoretical investigation on the possibility for the formation of Mach cones in both space and laboratory dusty magnetoplasmas. We find the parametric regimes for which different types of Mach cones, such as dust acoustic Mach cones, dust magneto-acoustic Mach cones, oscillonic Mach cones, etc. are formed in space and laboratory dusty magnetoplasmas. We also identify the basic features of such different classes of Mach cones (viz. dust- acoustic, dust magneto-acoustic, oscillonic Mach cones, etc.), and clearly explain how they are relevant to space and laboratory dusty manetoplasmas. (author)

Association between menopause and lumbar disc degeneration: an MRI study of 1,566 women and 1,382 men.

Science.gov (United States)

Lou, Chao; Chen, Hongliang; Mei, Liangwei; Yu, Weiyang; Zhu, Kejun; Liu, Feijun; Chen, Zhenzhong; Xiang, Guangheng; Chen, Minjiang; Weng, Qiaoyou; He, Dengwei

2017-10-01

The aim of this study was to revisit and further investigate the association between menopause and disc degeneration in the lumbar spine using a magnetic resonance imaging-based eight-level grading system. This study cohort comprised of 1,566 women and 1,382 age-matched men who were admitted for low back pain from June 2013 to October 2016. Data on age, weight, height, body mass index, age at natural menopause, and years since menopause (YSM) were obtained. Lumbar disc degeneration was assessed using a magnetic resonance imaging-based eight-level grading system. After adjustment for the confounding factors of age, height, and weight, young age-matched men were more susceptible to disc degeneration than premenopausal women (P menopause, postmenopausal women had a significant tendency to develop more severe disc degeneration than their age-matched men (P  0.05). Menopause is associated with lumbar disc degeneration. The association occurred in the first 15 YSM, suggesting estrogen deficiency might be a risk factor of disc degeneration of the lumbar spine. Further studies need to be carried out for deciding whether age or menopause plays a more important role in the progression of disc degeneration in the lumbar spine.

A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration.

Science.gov (United States)

Carrigan, Matthew; Duignan, Emma; Humphries, Pete; Palfi, Arpad; Kenna, Paul F; Farrar, G Jane

2016-04-01

The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa. A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies. Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function. These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Splitting deformations of degenerations of complex curves towards the classification of atoms of degenerations

CERN Document Server

2006-01-01

The author develops a deformation theory for degenerations of complex curves; specifically, he treats deformations which induce splittings of the singular fiber of a degeneration. He constructs a deformation of the degeneration in such a way that a subdivisor is "barked" (peeled) off from the singular fiber. These "barking deformations" are related to deformations of surface singularities (in particular, cyclic quotient singularities) as well as the mapping class groups of Riemann surfaces (complex curves) via monodromies. Important applications, such as the classification of atomic degenerations, are also explained.

Degenerate pressure driven modified nucleus-acoustic waves in degenerate plasmas

Science.gov (United States)

Mamun, A. A.

2018-02-01

The existence of degenerate pressure driven modified nucleus-acoustic (DPDMNA) waves propagating in a cold degenerate quantum plasma (DQP) system [containing cold inertialess degenerate electron species (DES), cold inertial non-degenerate light nucleus species (LNS), and stationary heavy nucleus species (HNS)] is predicted for the first time. The DPDMNA waves (in which the mass density of the cold LNS provides the inertia and the cold inertialess DES gives rise to the restoring force) are new since they completely disappear if the degenerate pressure of the cold DES is neglected. It is found that the phase speed (Vp) of the DPDMNA waves decreases with the rise of the charge number density of the stationary HNS for both non-relativistic and ultra-relativistic DES, and that the ultra-relativistic DES does not have any effect on Vp when β = 1, where β = Λc/Λe with Λ e = ne 0 - 1 / 3 being the average inter-electron distance in the DQP system and Λc being the constant (˜10-10 cm) for the DES. However, the ultra-relativistic DES does have quite a significant effect on Vp for β ≫ 1 and β ≪ 1, and the ultra-relativistic effect significantly enhances (reduces) Vp for β ≫ 1 (β ≪ 1). The DPDMNA waves and their dispersion properties are expected to be useful in understanding the basic features of the electrostatic perturbation mode in space and laboratory DQP systems.

Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina.

Science.gov (United States)

Mollick, Tanzina; Mohlin, Camilla; Johansson, Kjell

2016-09-01

Retinal neurodegenerative disorders like retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and retinal detachment decrease retinal functionality leading to visual impairment. The pathological events are characterized by photoreceptor degeneration, synaptic disassembly, remodeling of postsynaptic neurons and activation of glial cells. Despite intense research, no effective treatment has been found for these disorders. The current study explores the potential of human neural progenitor cell (hNPC) derived factors to slow the degenerative processes in adult porcine retinal explants. Retinas were cultured for 3 days with or without hNPCs as a feeder layer and investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, western blot and quantitative real time-polymerase chain reaction (qRT-PCR) techniques. TUNEL showed that hNPCs had the capacity to limit photoreceptor cell death. Among cone photoreceptors, hNPC coculture resulted in better maintenance of cone outer segments and reduced opsin mislocalization. Additionally, maintained synaptic structural integrity and preservation of second order calbindin positive horizontal cells was also observed. However, Müller cell gliosis only seemed to be alleviated in terms of reduced Müller cell density. Our observations indicate that at 3 days of coculture, hNPC derived factors had the capacity to protect photoreceptors, maintain synaptic integrity and support horizontal cell survival. Human neural progenitor cell applied treatment modalities may be an effective strategy to help maintain retinal functionality in neurodegenerative pathologies. Whether hNPCs can independently hinder Müller cell gliosis by utilizing higher concentrations or by combination with other pharmacological agents still needs to be determined. Copyright © 2016 Elsevier B.V. All rights reserved.

Iron in hereditary retinal degeneration: PIXE microanalysis Preliminary results

International Nuclear Information System (INIS)

Sergeant, C.; Gouget, B.; Llabador, Y.; Simonoff, M.; Yefimova, M.; Courtois, Y.; Jeanny, J.C.

1999-01-01

Several types of hereditary retinal degeneration with progressive alteration of photoreceptors exist in men and animals. Recent immunohistochemical results have shown strong degradation of transferrin, the protein responsible for iron transport, in retinas of rats with hereditary retinal degeneration. Freeze-dried thin sections of rat retinas from different stages of the disease, and respective coeval control sections, have been analyzed using nuclear microprobe. In this first part of the study, the rat retinas at post-natal stages of 35 and 45 days have been analyzed. The sample preparation and the post-irradiation staining to determine precisely the retinal layers involved are described. Preliminary results of element distributions (K, Ca, Fe) in the rat retina layers are discussed. A very high content of calcium in the choriocapillaris of dystrophic rat retinas was observed. Preliminary results on iron distribution in the rat retina layers are presented

The Preliminary Study for Numerical Computation of 37 Rod Bundle in CANDU Reactor

International Nuclear Information System (INIS)

Jeon, Yu Mi; Park, Joo Hwan

2010-09-01

A typical CANDU 6 fuel bundle consists of 37 fuel rods supported by two endplates and separated by spacer pads at various locations. In addition, the bearing pads are brazed to each outer fuel rod with the aim of reducing the contact area between the fuel bundle and the pressure tube. Although the recent progress of CFD methods has provided opportunities for computing the thermal-hydraulic phenomena inside of a fuel channel, it is yet impossible to reflect numerical computations on the detailed shape of rod bundle due to challenges with computing mesh and memory capacity. Hence, the previous studies conducted a numerical computation for smooth channels without considering spacers and bearing pads. But, it is well known that these components are an important factor to predict the pressure drop and heat transfer rate in a channel. In this study, the new computational method is proposed to solve complex geometry such as a fuel rod bundle. Before applying a solution to the problem of the 37 rod bundle, the validity and the accuracy of the method are tested by applying the method to simple geometry. The split channel method has been proposed with the aim of computing the fully shaped CANDU fuel channel with detailed components. The validity was tested by applying the method to the single channel problem. The average temperature have similar values for the considered two methods, while the local temperature shows a slight difference by the effect of conduction heat transfer in the solid region of a rod. Based on the present result, the calculation for the fully shaped 37-rod bundle is scheduled for future work

Control rod velocity limiter

International Nuclear Information System (INIS)

Cearley, J.E.; Carruth, J.C.; Dixon, R.C.; Spencer, S.S.; Zuloaga, J.A. Jr.

1986-01-01

This patent describes a velocity control arrangement for a reciprocable, vertically oriented control rod for use in a nuclear reactor in a fluid medium, the control rod including a drive hub secured to and extending from one end therefrom. The control device comprises: a toroidally shaped control member spaced from and coaxially positioned around the hub and secured thereto by a plurality of spaced radial webs thereby providing an annular passage for fluid intermediate the hub and the toroidal member spaced therefrom in coaxial position. The side of the control member toward the control rod has a smooth generally conical surface. The side of the control member away from the control rod is formed with a concave surface constituting a single annular groove. The device also comprises inner and outer annular vanes radially spaced from one another and spaced from the side of the control member away from the control rod and positioned coaxially around and spaced from the hub and secured thereto by spaced radial webs thereby providing an annular passage for fluid intermediate the hub and the vanes. The vanes are angled toward the control member, the outer edge of the inner vane being closer to the control member and the inner edge of the outer vane being closer to the control member. When the control rod moves in the fluid in the direction toward the drive hub the vanes direct a flow of fluid turbulence which provides greater resistance to movement of the control rod in the direction toward the drive hub than in the other direction

Control rod position control device

International Nuclear Information System (INIS)

Ubukata, Shinji.

1997-01-01

The present invention provides a control rod position control device which stores data such as of position signals and driving control rod instruction before and after occurrence of abnormality in control for the control rod position for controlling reactor power and utilized the data effectively for investigating the cause of abnormality. Namely, a plurality of individual control devices have an operation mismatching detection circuit for outputting signals when difference is caused between a driving instruction given to the control rod position control device and the control rod driving means and signals from a detection means for detecting an actual moving amount. A general control device collectively controls the individual control devices. In addition, there is also disposed a position storing circuit for storing position signals at least before and after the occurrence of the control rod operation mismatching. With such procedures, the cause of the abnormality can be determined based on the position signals before and after the occurrence of control rod mismatching operation stored in the position storing circuit. Accordingly, the abnormality cause can be determined to conduct restoration in an early stage. (I.S.)

Centralization of extruded medial meniscus delays cartilage degeneration in rats.

Science.gov (United States)

Ozeki, Nobutake; Muneta, Takeshi; Kawabata, Kenichi; Koga, Hideyuki; Nakagawa, Yusuke; Saito, Ryusuke; Udo, Mio; Yanagisawa, Katsuaki; Ohara, Toshiyuki; Mochizuki, Tomoyuki; Tsuji, Kunikazu; Saito, Tomoyuki; Sekiya, Ichiro

2017-05-01

Meniscus extrusion often observed in knee osteoarthritis has a strong correlation with the progression of cartilage degeneration and symptom in the patients. We recently reported a novel procedure "arthroscopic centralization" in which the capsule was sutured to the edge of the tibial plateau to reduce meniscus extrusion in the human knee. However, there is no animal model to study the efficacy of this procedure. The purposes of this study were [1] to establish a model of centralization for the extruded medial meniscus in a rat model; and [2] to investigate the chondroprotective effect of this procedure. Medial meniscus extrusion was induced by the release of the anterior synovial capsule and the transection of the meniscotibial ligament. Centralization was performed by the pulled-out suture technique. Alternatively, control rats had only the medial meniscus extrusion surgery. Medial meniscus extrusion was evaluated by micro-CT and macroscopic findings. Cartilage degeneration of the medial tibial plateau was evaluated macroscopically and histologically. By micro-CT analysis, the medial meniscus extrusion was significantly improved in the centralization group in comparison to the extrusion group throughout the study. Both macroscopically and histologically, the cartilage lesion of the medial tibial plateau was prevented in the centralization group but was apparent in the control group. We developed medial meniscus extrusion in a rat model, and centralization of the extruded medial meniscus by the pull-out suture technique improved the medial meniscus extrusion and delayed cartilage degeneration, though the effect was limited. Centralization is a promising treatment to prevent the progression of osteoarthritis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Control rod selecting and driving device

International Nuclear Information System (INIS)

Isobe, Hideo.

1981-01-01

Purpose: To simultaneously drive a predetermined number of control rods in a predetermined mode by the control of addresses for predetermined number of control rods and read or write of driving codified data to and from the memory by way of a memory controller. Constitution: The system comprises a control rod information selection device for selecting predetermined control rods from a plurality of control rods disposed in a reactor and outputting information for driving them in a predetermined mode, a control rod information output device for codifying the information outputted from the above device and outputting the addresses to the predetermined control rods and driving mode coded data, and a driving device for driving said predetermined control rods in a predetermined mode in accordance with the codified data outputted from the above device, said control rod infromation output device comprising a memory device capable of storing a predetermined number of the codified data and a memory control device for storing the predetermined number of data into the above memory device at a predetermined timing while successively outputting the thus stored predetermined number of data at a predetermined timing. (Seki, T.)

NEUTRONIC REACTOR CONTROL ROD DRIVE APPARATUS

Science.gov (United States)

Oakes, L.C.; Walker, C.S.

1959-12-15

ABS>A suspension mechanism between a vertically movable nuclear reactor control rod and a rod extension, which also provides information for the operator or an automatic control signal, is described. A spring connects the rod extension to a drive shift. The extension of the spring indicates whether (1) the rod is at rest on the reactor, (2) the rod and extension are suspended, or (3) the extension alone is suspended, the spring controlling a 3-position electrical switch.

Design of a trichromatic cone array.

Directory of Open Access Journals (Sweden)

Patrick Garrigan

2010-02-01

Full Text Available Cones with peak sensitivity to light at long (L, medium (M and short (S wavelengths are unequal in number on the human retina: S cones are rare (<10% while increasing in fraction from center to periphery, and the L/M cone proportions are highly variable between individuals. What optical properties of the eye, and statistical properties of natural scenes, might drive this organization? We found that the spatial-chromatic structure of natural scenes was largely symmetric between the L, M and S sensitivity bands. Given this symmetry, short wavelength attenuation by ocular media gave L/M cones a modest signal-to-noise advantage, which was amplified, especially in the denser central retina, by long-wavelength accommodation of the lens. Meanwhile, total information represented by the cone mosaic remained relatively insensitive to L/M proportions. Thus, the observed cone array design along with a long-wavelength accommodated lens provides a selective advantage: it is maximally informative.

Cartilage Degeneration and Alignment in Severe Varus Knee Osteoarthritis.

Science.gov (United States)

Nakagawa, Yasuaki; Mukai, Shogo; Yabumoto, Hiromitsu; Tarumi, Eri; Nakamura, Takashi

2015-10-01

The aim of this study was to examine the relationship between cartilage, ligament, and meniscus degeneration and radiographic alignment in severe varus knee osteoarthritis in order to understand the development of varus knee osteoarthritis. Fifty-three patients (71 knees) with primary varus knee osteoarthritis and who underwent total knee arthroplasty were selected for this study. There were 6 men and 47 women, with 40 right knees and 31 left knees studied; their mean age at operation was 73.5 years. The ligament, meniscus, degeneration of joint cartilage, and radiographic alignments were examined visually. The tibial plateau-tibial shaft angle was larger if the condition of the cartilage in the lateral femoral condyle was worse. The femorotibial angle and tibial plateau-tibial shaft angle were larger if the conditions of the lateral meniscus or the cartilage in the lateral tibial plateau were worse. Based on the results of this study, progression of varus knee osteoarthritis may occur in the following manner: medial knee osteoarthritis starts in the central portion of the medial tibial plateau, and accompanied by medial meniscal extrusion and anterior cruciate ligament rupture, cartilage degeneration expands from the anterior to the posterior in the medial tibial plateau. Bone attrition occurs in the medial tibial plateau, and the femoro-tibial angle and tibial plateau-tibial shaft angle increase. Therefore, the lateral intercondylar eminence injures the cartilage of the lateral femoral condyle in the longitudinal fissure type. Thereafter, the cartilage degeneration expands in the whole of the knee joints.

Cone and Seed Maturation of Southern Pines

Science.gov (United States)

James P. Barnett

1976-01-01

If slightly reduced yields and viability are acceptable, loblolly and slash cone collections can begin 2 to 3 weeks before maturity if the cones are stored before processing. Longleaf(P. palestris Mill.) pine cones should be collected only when mature, as storage decreased germination of seeds from immature cones. Biochemical analyses to determine reducing sugar...

RODDRP - A FORTRAN program for use in control rod calibration by the rod drop method

International Nuclear Information System (INIS)

Wilson, W.E.

1972-01-01

The different methods to measure reactivity which are applicable to control rod calibration are discussed. They include: 1) the positive period method, 2) the rod drop method, 3) the source-jerk method, 4) the rod oscillation method, and 5) the pulsed neutron method. The instrument setup used at WSU for rod drop measurements is presented. To speed up the analysis of power fall-off trace, a FORTRAN IV program called RODDRP was written to simultaneously solve the in-hour equation and relative neutron flux. The procedure for calculating the worth of the rod that produced the power trace is given. The reactivity for each time relative flux point is obtained. Conclusions about the status of the equipment are made