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Sample records for degeneration slow rds

  1. Retinal degeneration slow (rds) in mouse results from simple insertion of a t haplotype-specific element into protein-coding exon II

    SciTech Connect

    Ma, J.; Norton, J.C.; Allen, A.C.; Burns, J.L.; Travis, G.H.

    1995-07-20

    Retinal degeneration slow (rds) is a semidominant mutation of mice that causes dysplasia and degeneration of rod and cone photoreceptors. Mutations in RDS, the human ortholog of the rds gene, are responsible for several inherited retinal dystrophies including a subset of retinitis pigmentosa. The normal rds locus encodes rds/peripherin, an integral membrane glycoprotein present in outer segment discs. Genomic libraries form wildtype and rds/rds mice were screened with an rds cDNA, and phage {lambda} clones that span the normal and mutant loci were mapped. We show that in mice, rds is caused by the insertion into exon II of a 9.2-kb repetitive genomic element that is very similar to the t haplotype-specific element in the H-2 complex. The entire element is included in the RNA products of the mutant locus. We present evidence that rds in mice represents a null allele. 40 refs., 4 figs.

  2. Retinal Degeneration Slow (RDS) Glycosylation Plays a Role in Cone Function and in the Regulation of RDS·ROM-1 Protein Complex Formation.

    PubMed

    Stuck, Michael W; Conley, Shannon M; Naash, Muna I

    2015-11-13

    The photoreceptor-specific glycoprotein retinal degeneration slow (RDS, also called PRPH2) is necessary for the formation of rod and cone outer segments. Mutations in RDS cause rod and cone-dominant retinal disease, and it is well established that both cell types have different requirements for RDS. However, the molecular mechanisms for this difference remain unclear. Although RDS glycosylation is highly conserved, previous studies have revealed no apparent function for the glycan in rods. In light of the highly conserved nature of RDS glycosylation, we hypothesized that it is important for RDS function in cones and could underlie part of the differential requirement for RDS in the two photoreceptor subtypes. We generated a knockin mouse expressing RDS without the N-glycosylation site (N229S). Normal levels of RDS and the unglycosylated RDS binding partner rod outer segment membrane protein 1 (ROM-1) were found in N229S retinas. However, cone electroretinogram responses were decreased by 40% at 6 months of age. Because cones make up only 3-5% of photoreceptors in the wild-type background, N229S mice were crossed into the nrl(-/-) background (in which all rods are converted to cone-like cells) for biochemical analysis. In N229S/nrl(-/-) retinas, RDS and ROM-1 levels were decreased by ~60% each. These data suggest that glycosylation of RDS is required for RDS function or stability in cones, a difference that may be due to extracellular versus intradiscal localization of the RDS glycan in cones versus rods. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Gene Therapy in the Retinal Degeneration Slow Model of Retinitis Pigmentosa

    PubMed Central

    Cai, Xue; Conley, Shannon M.; Naash, Muna I.

    2011-01-01

    Human blinding disorders are often initiated by hereditary mutations that insult rod and/or cone photoreceptors and cause subsequent cellular death. Generally, the disease phenotype can be predicted from the specific mutation as many photoreceptor genes are specific to rods or cones; however certain genes, such as Retinal Degeneration Slow (RDS), are expressed in both cell types and cause different forms of retinal disease affecting rods, cones, or both photoreceptors. RDS is a transmembrane glycoprotein critical for photoreceptor outer segment disc morphogenesis, structural maintenance, and renewal. Studies using animal models with Rds mutations provide valuable insight into Rds gene function and regulation; and a better understanding of the physiology, pathology, and underlying degenerative mechanisms of inherited retinal disease. Furthermore, these models are an excellent tool in the process of developing therapeutic interventions for the treatment of inherited retinal degenerations. In this paper, we review these topics with particular focus on the use of rds models in gene therapy. PMID:20238065

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

    PubMed Central

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

    2011-01-01

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

  5. Neuroprotection of photoreceptors by direct delivery of erythropoietin to the retina of the retinal degeneration slow mouse.

    PubMed

    Rex, Tonia S; Wong, Ying; Kodali, Kishore; Merry, Shayla

    2009-11-01

    The primary objectives of this study were to determine if erythropoietin (EPO) is neuroprotective to the photoreceptors in the retinal degeneration slow (rds) mouse in the absence of an increase in hematocrit and to determine if deglycosylated EPO (DEPO) is less neuroprotective. We performed subretinal injections of 10U EPO, DEPO or hyperglycosylated EPO (HEPO) in postnatal day 7 rds mice. Whole eye EPO levels were quantified by ELISA at specified time points post-injection. TUNEL analysis, hematocrit, and immunohistochemistry were performed at postnatal day 20. Half of the amount of EPO measured immediately after injection was detected less than 1 h later. Twenty four hours later, EPO levels were 1000 times lower than the amount originally detected. Uninjected rds mice contained 36 +/- 2 TUNEL-positive cells/mm retina and PBS injected mice contained 17 +/- 3 TUNEL-positive cells/mm retina. EPO, DEPO, and HEPO treated rds retinas contained 5 +/- 2, 9 +/- 2, and 3 +/- 1 TUNEL-positive cells/mm retina, respectively. The hematocrit was 43% in control and 41% in treated rds mice Previous studies have shown neuroprotection of the retina by treatment with as little as 24-39 mU EPO/mg total protein in the eye. In this study, we detected 40 mU/mg EPO in the eye 11 h after injection of 10 U EPO. Treatment with all forms of EPO tested was neuroprotective to the photoreceptors without a concomitant increase in hematocrit.

  6. PRPH2/RDS and ROM-1: Historical context, current views and future considerations.

    PubMed

    Stuck, Michael W; Conley, Shannon M; Naash, Muna I

    2016-05-01

    Peripherin 2 (PRPH2), also known as RDS (retinal degeneration slow) is a photoreceptor specific glycoprotein which is essential for normal photoreceptor health and vision. PRPH2/RDS is necessary for the proper formation of both rod and cone photoreceptor outer segments, the organelle specialized for visual transduction. When PRPH2/RDS is defective or absent, outer segments become disorganized or fail to form entirely and the photoreceptors subsequently degenerate. Multiple PRPH2/RDS disease-causing mutations have been found in humans, and they are associated with various blinding diseases of the retina such as macular degeneration and retinitis pigmentosa, the vast majority of which are inherited dominantly, though recessive LCA and digenic RP have also been associated with RDS mutations. Since its initial discovery, the scientific community has dedicated a considerable amount of effort to understanding the molecular function and disease mechanisms of PRPH2/RDS. This work has led to an understanding of how the PRPH2/RDS molecule assembles into complexes and functions as a necessary part of the machinery that forms new outer segment discs, as well as leading to fundamental discoveries about the mechanisms that underlie OS biogenesis. Here we discuss PRPH2/RDS-associated research and how experimental results have driven the understanding of the PRPH2/RDS protein and its role in human disease.

  7. A 350 bp region of the proximal promoter of Rds drives cell-type specific gene expression

    PubMed Central

    Cai, Xue; Conley, Shannon M.; Cheng, Tong; Al-Ubaidi, Muayyad R.; Naash, Muna I.

    2010-01-01

    RDS (retinal degeneration slow) is a photoreceptor-specific tetraspanin protein required for the biogenesis and maintenance of rod and cone outer segments. Mutations in the Rds gene are associated with multiple forms of rod- and cone-dominant retinal degeneration. To gain more insight into the mechanisms underlying the regulation of this gene the identification of regulatory sequences within the promoter of Rds was undertaken. A 3.5kb fragment of the 5′ flanking region of the mouse Rds gene was isolated and binding sites for Crx, Otx2, Nr2e3, RXR family members, Mef2C, Esrrb, NF1, AP1, and SP1 in addition to several E-boxes, GC-boxes and GAGA-boxes were identified. Crx binding sequences were conserved in all mammalian species examined. Truncation expression analysis of the Rds promoter region in Y-79 retinoblastoma cells showed maximal activity in the 350bp proximal promoter region. We also show that inclusion of more distal fragments reduced promoter activity to the basal level, and that the promoter activities are cell-type and direction specific. Co-transfection with Nrl increased promoter activity, suggesting that this gene positively regulates Rds expression. Based on these findings, a relatively small fragment of the Rds promoter may be useful in future gene transfer studies to drive gene expression in photoreceptors. PMID:20447394

  8. Giant amplification in degenerate band edge slow-wave structures interacting with an electron beam

    SciTech Connect

    Othman, Mohamed A. K.; Veysi, Mehdi; Capolino, Filippo; Figotin, Alexander

    2016-03-15

    We propose a new amplification regime based on a synchronous operation of four degenerate electromagnetic (EM) modes in a slow-wave structure and the electron beam, referred to as super synchronization. These four EM modes arise in a Fabry-Pérot cavity when degenerate band edge (DBE) condition is satisfied. The modes interact constructively with the electron beam resulting in superior amplification. In particular, much larger gains are achieved for smaller beam currents compared to conventional structures based on synchronization with only a single EM mode. We demonstrate giant gain scaling with respect to the length of the slow-wave structure compared to conventional Pierce type single mode traveling wave tube amplifiers. We construct a coupled transmission line model for a loaded waveguide slow-wave structure exhibiting a DBE, and investigate the phenomenon of giant gain via super synchronization using the Pierce model generalized to multimode interaction.

  9. Giant amplification in degenerate band edge slow-wave structures interacting with an electron beam

    NASA Astrophysics Data System (ADS)

    Othman, Mohamed A. K.; Veysi, Mehdi; Figotin, Alexander; Capolino, Filippo

    2016-03-01

    We propose a new amplification regime based on a synchronous operation of four degenerate electromagnetic (EM) modes in a slow-wave structure and the electron beam, referred to as super synchronization. These four EM modes arise in a Fabry-Pérot cavity when degenerate band edge (DBE) condition is satisfied. The modes interact constructively with the electron beam resulting in superior amplification. In particular, much larger gains are achieved for smaller beam currents compared to conventional structures based on synchronization with only a single EM mode. We demonstrate giant gain scaling with respect to the length of the slow-wave structure compared to conventional Pierce type single mode traveling wave tube amplifiers. We construct a coupled transmission line model for a loaded waveguide slow-wave structure exhibiting a DBE, and investigate the phenomenon of giant gain via super synchronization using the Pierce model generalized to multimode interaction.

  10. Multiple scattering of slow ions in a partially degenerate electron fluid

    SciTech Connect

    Popoff, Romain; Maynard, Gilles; Deutsch, Claude

    2009-10-15

    We extend former investigation to a partially degenerate electron fluid at any temperature of multiple slow ion scattering at T=0. We implement an analytic and mean-field interpolation of the target electron dielectric function between T=0 (Lindhard) and T{yields}{infinity} (Fried-Conte). A specific attention is given to multiple scattering of proton projectiles in the keV energy range, stopped in a hot-electron plasma at solid density.

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

    PubMed

    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.

  12. Modulating Expression of Peripherin/rds in Transgenic Mice: Critical Levels and the Effect of Overexpression

    PubMed Central

    Nour, May; Ding, Xi-Qin; Stricker, Heidi; Fliesler, Steven J.; Naash, Muna I.

    2010-01-01

    PURPOSE Mutations in the photoreceptor-specific protein peripherin/rds are associated with multiple retinal diseases. To date, attempts to achieve complete structural and functional rescue in animal models of peripherin/rds-induced retinal degeneration have not been successful. Gene therapy – directed approaches have been hindered by the haploinsufficiency phenotype, which dictates well-regulated expression of peripherin/rds protein levels. METHODS Using a transgenic mouse line expressing wild-type peripherin/rds (NMP), the authors evaluated the critical in vivo level of peripherin/rds needed to maintain photoreceptor structure and ERG function and assessed the consequences of peripherin/rds overexpression in both rods and cones by Western blot and immunoprecipitation analyses, immunohistochemistry, electron microscopy, and electroretinography. The NMP transgene included a C-terminal modification (P341Q) to facilitate detection of the transgenic protein in the presence of wild-type peripherin/rds, using the monoclonal antibody 3B6. RESULTS Peripherin/rds protein levels in NMP homozygotes were ~60% of wild-type levels. Western blot and immunoprecipitation analyses confirmed normal biochemical properties of the NMP protein when compared with wild-type peripherin/rds. Immunohistochemistry demonstrated appropriate localization of transgenic peripherin/rds protein to the disc rim region of photoreceptor outer segments. Total peripherin/rds levels in the retina were modulated by crossing NMP transgenic mice into different rds genetic backgrounds. A positive correlation was observed between peripherin/rds expression levels and the structural and functional integrity of photoreceptor outer segments. Overexpression of peripherin/rds caused no detectable adverse effects on rod or cone structure and function. CONCLUSIONS These findings may have significant implications regarding therapeutic intervention in peripherin/rds-associated retinal diseases. PMID:15277471

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

    PubMed Central

    Ramirez, Grisela

    2016-01-01

    Abstract 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. PMID:27699209

  14. Simultaneous degeneration of myenteric plexuses and pelvic parasympathetic colonic nerve in slow transit constipation

    PubMed Central

    Cheng, Zhiqiang; Zhao, Kun; Bi, Dongsong

    2017-01-01

    Abstract Rationale: Slow transit constipation (STC) is a common disease of which the etiology is still not clear. Multiple hypotheses have been proposed to explain STC, including autonomic neuropathy, disorders of the enteric nervous system and so forth. Morphological abnormalities of the enteric nerves of the colon in patients with STC have been extensively reported, while there have been no morphological reports focusing on extrinsic extramural fibers from the pelvic plexus to the distal colon (i.e., pelvic parasympathetic colonic nerve) in patients with STC. Patient concerns: Whether morphological changes of pelvic parasympathetic colonic nerve coexist with abnormalities of the enteric nerves of the colon in the patient with STC. Diagnosis: Slow transit constipation (STC). Interventions: The patient with STC underwent a partial colectomy (sigmoid colon and partial descending colon). The fibers of the myenteric plexuses within the removed colon and the myelinated fibers of the pelvic parasympathetic colonic nerve were observed under optical and electron-microscope. Outcomes: The fibers of the myenteric plexuses showed vacuolated degeneration between the muscularis propria layer under optical microscope. Myelinated fibers of the pelvic parasympathetic colonic nerve showed obvious vacuolated degeneration under electron-microscopic examination. Lessons: Such a simultaneous neuropathy in both myenteric plexuses and extrinsic extramural nerves has not been documented previously. Our finding supports the notion that neuropathy remains the most plausible explanation for STC, in which nerve dysfunction might occur by way of a degenerative process. PMID:28296784

  15. Allele-Specific Inhibition of Rhodopsin With an Antisense Oligonucleotide Slows Photoreceptor Cell Degeneration

    PubMed Central

    Murray, Susan F.; Jazayeri, Ali; Matthes, Michael T.; Yasumura, Douglas; Yang, Haidong; Peralta, Raechel; Watt, Andy; Freier, Sue; Hung, Gene; Adamson, Peter S.; Guo, Shuling; Monia, Brett P.; LaVail, Matthew M.; McCaleb, Michael L.

    2015-01-01

    Purpose To preserve photoreceptor cell structure and function in a rodent model of retinitis pigmentosa with P23H rhodopsin by selective inhibition of the mutant rhodopsin allele using a second generation antisense oligonucleotide (ASO). Methods Wild-type mice and rats were treated with ASO by intravitreal (IVT) injection and rhodopsin mRNA and protein expression were measured. Transgenic rats expressing the murine P23H rhodopsin gene (P23H transgenic rat Line 1) were administered either a mouse-specific P23H ASO or a control ASO. The contralateral eye was injected with PBS and used as a comparator control. Electroretinography (ERG) measurements and analyses of the retinal outer nuclear layer were conducted and correlated with rhodopsin mRNA levels. Results Rhodopsin mRNA and protein expression was reduced after a single ASO injection in wild-type mice with a rhodopsin-specific ASO. Transgenic rat eyes that express a murine P23H rhodopsin gene injected with a murine P23H ASO had a 181 ± 39% better maximum amplitude response (scotopic a-wave) as compared with contralateral PBS-injected eyes; the response in control ASO eyes was not significantly different from comparator contralateral eyes. Morphometric analysis of the outer nuclear layer showed a significantly thicker nuclear layer in eyes injected with murine P23H ASO (18%) versus contralateral PBS-injected eyes. Conclusions Allele-specific ASO-mediated knockdown of mutant P23H rhodopsin expression slowed the rate of photoreceptor degeneration and preserved the function of photoreceptor cells in eyes of the P23H rhodopsin transgenic rat. Our data indicate that ASO treatment is a potentially effective therapy for the treatment of retinitis pigmentosa. PMID:26436889

  16. AAV Mediated GDNF Secretion From Retinal Glia Slows Down Retinal Degeneration in a Rat Model of Retinitis Pigmentosa

    PubMed Central

    Dalkara, Deniz; Kolstad, Kathleen D; Guerin, Karen I; Hoffmann, Natalie V; Visel, Meike; Klimczak, Ryan R; Schaffer, David V; Flannery, John G

    2011-01-01

    Mutations in over 80 identified genes can induce apoptosis in photoreceptors, resulting in blindness with a prevalence of 1 in 3,000 individuals. This broad genetic heterogeneity of disease impacting a wide range of photoreceptor functions renders the design of gene-specific therapies for photoreceptor degeneration impractical and necessitates the development of mutation-independent treatments to slow photoreceptor cell death. One promising strategy for photoreceptor neuroprotection is neurotrophin secretion from Müller cells, the primary retinal glia. Müller glia are excellent targets for secreting neurotrophins as they span the entire tissue, ensheath all neuronal populations, are numerous, and persist through retinal degeneration. We previously engineered an adeno-associated virus (AAV) variant (ShH10) capable of efficient and selective glial cell transduction through intravitreal injection. ShH10-mediated glial-derived neurotrophic factor (GDNF) secretion from glia, generates high GDNF levels in treated retinas, leading to sustained functional rescue for over 5 months. This GDNF secretion from glia following intravitreal vector administration is a safe and effective means to slow the progression of retinal degeneration in a rat model of retinitis pigmentosa (RP) and shows significant promise as a gene therapy to treat human retinal degenerations. These findings also demonstrate for the first time that glia-mediated secretion of neurotrophins is a promising treatment that may be applicable to other neurodegenerative conditions. PMID:21522134

  17. Retinal degeneration mutants in the mouse.

    PubMed

    Chang, B; Hawes, N L; Hurd, R E; Davisson, M T; Nusinowitz, S; Heckenlively, J R

    2002-02-01

    The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to look for genetically determined eye variations and disorders. Through ophthalmoscopy, electroretinography and histology, we have discovered disorders affecting all aspects of the eye including the lid, cornea, iris, lens and retina, resulting in corneal disorders, cataracts, glaucoma and retinal degenerations. Mouse models of retinal degeneration have been investigated for many years in the hope of understanding the causes of photoreceptor cell death. Sixteen naturally occurring mouse mutants that manifest degeneration of photoreceptors in the retina with preservation of all other retinal cell types have been found: retinal degeneration (formerly rd, identical with rodless retina, r, now Pde6b(rd1)); Purkinje cell degeneration (pcd); nervous (nr); retinal degeneration slow (rds, now Prph(Rd2)); retinal degeneration 3 (rd3); motor neuron degeneration (mnd); retinal degeneration 4 (Rd4); retinal degeneration 5 (rd5, now tub); vitiligo (vit, now Mitf(mi-vit)); retinal degeneration 6 (rd6); retinal degeneration 7 (rd7, now Nr2e3(rd7)); neuronal ceroid lipofuscinosis (nclf); retinal degeneration 8 (rd8); retinal degeneration 9 (Rd9); retinal degeneration 10 (rd10, now Pde6b(rd10)); and cone photoreceptor function loss (cpfl1). In this report, we first review the genotypes and phenotypes of these mutants and second, list the mouse strains that carry each mutation. We will also provide detailed information about the cpfl1 mutation. The phenotypic characteristics of cpfl1 mice are similar to those observed in patients with complete achromatopsia (ACHM2, OMIM 216900) and the cpfl1 mutation is the first naturally-arising mutation in mice to cause cone-specific photoreceptor function loss. cpfl1 mice may provide a model for congenital achromatopsia in humans.

  18. Trans-synaptic Retrograde Degeneration in the Human Visual System: Slow, Silent, and Real.

    PubMed

    Dinkin, Marc

    2017-02-01

    Degeneration of neuron and axons following injury to cells with which they synapse is termed trans-synaptic degeneration. This phenomenon may be seen in postsynaptic neurons (anterograde) or in presynaptic neurons (retrograde). Retrograde trans-synaptic degeneration (RTSD) of the retinal ganglion cells and retinal nerve fiber layer following injury to the occipital lobe has been well documented histologically in animal studies, but its occurrence in the human retina was, for many years, felt to be limited to cases of neonatal injury during a critical period of neuronal development. Over the last decade, imaging techniques such as MRI and optical coherence tomography have allowed us to visualize and quantify RTSD and analyze its time course and relationship to degree of vision loss and age of cortical injury. A deeper understanding of RTSD in the human visual system may allow us to interfere with its occurrence, potentially allowing for greater recovery following visual cortex injury.

  19. Muscle Fibers Secrete FGFBP1 to Slow Degeneration of Neuromuscular Synapses during Aging and Progression of ALS.

    PubMed

    Taetzsch, Thomas; Tenga, Milagros J; Valdez, Gregorio

    2017-01-04

    The identity of muscle secreted factors critical for the development and maintenance of neuromuscular junctions (NMJs) remains largely unknown. Here, we show that muscle fibers secrete and concentrate the fibroblast growth factor binding protein 1 (FGFBP1) at NMJs. Although FGFBP1 expression increases during development, its expression decreases before NMJ degeneration during aging and in SOD1(G93A) mice, a mouse model for amyotrophic lateral sclerosis (ALS). Based on these findings, we examined the impact of deleting FGFBP1 on NMJs. In the absence of FGFBP1, NMJs exhibit structural abnormalities in developing and middle age mice. Deletion of FGFBP1 from SOD1(G93A) mice also accelerates NMJ degeneration and death. Based on these findings, we sought to identify the mechanism responsible for decreased FGFBP1 in stressed skeletal muscles. We show that FGFBP1 expression is inhibited by increased accumulation of the transforming growth factor-β1 (TGF-β1) in skeletal muscles and at their NMJs. These findings suggest that targeting the FGFBP1 and TGF-β1 signaling axis holds promise for slowing age- and disease-related degeneration of NMJs. The neuromuscular junction (NMJ) is critical for all voluntary movement. Its malformation during development and degeneration in adulthood impairs motor function. Therefore, it is important to identify factors that function to maintain the structural integrity of NMJs. We show that muscle fibers secrete and concentrate the fibroblast growth factor binding protein 1 (FGFBP1) at NMJs. However, FGFBP1 expression decreases in skeletal muscles during aging and before NMJ degeneration in SOD1(G93A) mice, a mouse model for amyotrophic lateral sclerosis. We show that transforming growth factor-β1 is responsible for the decreased levels of FGFBP1. Importantly, we demonstrate critical roles for FGFBP1 at NMJs in developing, aging and SOD1(G93A) mice. Copyright © 2017 the authors 0270-6474/17/370070-13$15.00/0.

  20. Old but not (so) degenerated--slow evolution of largely homomorphic sex chromosomes in ratites.

    PubMed

    Yazdi, Homa Papoli; Ellegren, Hans

    2014-06-01

    Degeneration of the nonrecombining chromosome is a common feature of sex chromosome evolution, readily evident by the presence of a pair of largely heteromorphic chromosomes, like in eutherian mammals and birds. However, in ratites (order Palaeognathae, including, e.g., ostrich), the Z and W chromosomes are similar in size and largely undifferentiated, despite avian sex chromosome evolution was initiated > 130 Ma. To better understand what may limit sex chromosome evolution, we performed ostrich transcriptome sequencing and studied genes from the nonrecombining region of the W chromosome. Fourteen gametologous gene pairs present on the W chromosome and Z chromosome were identified, with synonymous sequence divergence of 0.027-0.177. The location of these genes on the Z chromosome was consistent with a sequential increase in divergence, starting 110-157 and ending 24-30 Ma. On the basis of the occurrence of Z-linked genes hemizygous in females, we estimate that about one-third of the Z chromosome does not recombine with the W chromosome in female meiosis. Pairwise d(N)/d(S) between gametologs decreased with age, suggesting strong evolutionary constraint in old gametologs. Lineage-specific d(N)/d(S) was consistently higher in W-linked genes, in accordance with the lower efficacy of selection expected in nonrecombining chromosomes. A higher ratio of GC > AT:AT > GC substitutions in W-linked genes supports a role for GC-biased gene conversion in differentially driving base composition on the two sex chromosomes. A male-to-female (M:F) expression ratio of close to one for recombining genes and close to two for Z-linked genes lacking a W copy show that dosage compensation is essentially absent. Some gametologous genes have retained active expression of the W copy in females (giving a M:F ratio of 1 for the gametologous gene pair), whereas for others W expression has become severely reduced resulting in a M:F ratio of close to 2. These observations resemble the patterns

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

    PubMed

    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

  2. A novel Cys-214-Ser mutation in the peripherin/RDS gene in a Japanese family with autosomal dominant retinitis pigmentosa.

    PubMed

    Saga, M; Mashima, Y; Akeo, K; Oguchi, Y; Kudoh, J; Shimizu, N

    1993-11-01

    We have screened for possible disease-causing mutations in the peripherin/retinal degeneration slow (RDS) gene in 13 Japanese families with autosomal dominant retinitis pigmentosa (ADRP). Using polymerase chain reaction-single strand conformation polymorphism analysis, a novel mutation at codon 214 was found in which the highly conserved cysteine was replaced with a serine in one family. The mutation at codon 214 was found in all three affected siblings of this family, but none of the 40 normal control individuals had this mutation. These results strongly suggest that the mutation is pathogenic for RP in this family. The clinical phenotype for this family is a late-onset form of ADRP.

  3. C20-D3-vitamin A Slows Lipofuscin Accumulation and Electrophysiological Retinal Degeneration in a Mouse Model of Stargardt Disease*

    PubMed Central

    Ma, Li; Kaufman, Yardana; Zhang, Junhua; Washington, Ilyas

    2011-01-01

    Stargardt disease, also known as juvenile macular degeneration, occurs in approximately one in 10,000 people and results from genetic defects in the ABCA4 gene. The disease is characterized by premature accumulation of lipofuscin in the retinal pigment epithelium (RPE) of the eye and by vision loss. No cure or treatment is available. Although lipofuscin is considered a hallmark of Stargardt disease, its mechanism of formation and its role in disease pathogenesis are poorly understood. In this work we investigated the effects of long-term administration of deuterium-enriched vitamin A, C20-D3-vitamin A, on RPE lipofuscin deposition and eye function in a mouse model of Stargardt's disease. Results support the notion that lipofuscin forms partly as a result of the aberrant reactivity of vitamin A through the formation of vitamin A dimers, provide evidence that preventing vitamin A dimerization may slow disease related, retinal physiological changes and perhaps vision loss and suggest that administration of C20-D3-vitamin A may be a potential clinical strategy to ameliorate clinical symptoms resulting from ABCA4 genetic defects. PMID:21156790

  4. Targeted inactivation of synaptic HRG4(UNC119) causes dysfunction in the distal photoreceptor and slow retinal degeneration, revealing a new function

    PubMed Central

    Ishiba, Yasutsugu; Higashide, Tomomi; Mori, Naoki; Kobayashi, Akira; Kutobta, Shinya; McLaren, Margaret J.; Satoh, Hiromasa; Wong, Fulton; Inana, George

    2007-01-01

    photoreceptors, i.e., the distal inner/outer segments and proximal synapses, respectively, indicating a second function of MRG4 in the distal photoreceptor and dual functionality of MRG4. Thus, inactivation of MRG4 by gene targeting resulted in a retinal degeneration phenotype quite different from that previously seen in the TG, attesting to the multiplicity of MRG4 function, in addition to the importance of this protein for normal retinal function. These models will be useful in elucidating the functions of HRG4/MRG4 and the mechanism of slow retinal degeneration. PMID:17174953

  5. Screening for mutations in rhodopsin and peripherin/RDS in patients with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Rodriguez, J.A.; Gannon, A.M.; Daiger, S.P.

    1994-09-01

    Mutations in rhodopsin account for approximately 30% of all cases of autosomal dominant retinits pigmentosa (adRP) and mutations in peripherin/RDS account for an additional 5% of cases. Also, mutations in rhodopsin can cause autosomal recessive retinitis pigmentosa and mutations in peripherin/RDS can cause dominant macular degeneration. Most disease-causing mutations in rhodopsin and peripherin/RDS are unique to one family or, at most, to a few families within a limited geographic region, though a few mutations are found in multiple, unrelated families. To further determine the spectrum of genetic variation in these genes, we screened DNA samples from 134 unrelated patients with retinitis pigmentosa for mutations in both rhodopsin and peripherin/RDS using SSCP followed by genomic sequencing. Of the 134 patients, 86 were from families with apparent adRP and 48 were either isolated cases or were from families with an equivocal mode of inheritance. Among these patients we found 14 distinct rhodopsin mutations which are likely to cause retinal disease. Eleven of these mutations were found in one individual or one family only, whereas the Pro23His mutation was found in 14 {open_quotes}unrelated{close_quotes}individuals. The splice-site mutation produces dominant disease though with highly variable expression. Among the remaining patients were found 6 distinct peripherin/RDS mutations which are likely to cause retinal disease. These mutations were also found in one patient or family only, except the Gly266Asp mutation which was found in two unrelated patients. These results confirm the expected frequency and broad spectrum of mutations causing adRP.

  6. Sustained Delivery of NT-3 from Lens Fiber Cells in Transgenic Mice Reveals Specificity of Neuroprotection in Retinal Degenerations

    PubMed Central

    LaVail, Matthew M.; Nishikawa, Shimpei; Duncan, Jacque L.; Yang, Haidong; Matthes, Michael T.; Yasumura, Douglas; Vollrath, Douglas; Overbeek, Paul A.; Ash, John D.; Robinson, Michael L.

    2009-01-01

    Several neurotrophic factors (NTFs) are effective in protecting retinal photoreceptor cells from the damaging effects of constant light and slowing the rate of inherited photoreceptor degenerations. It is currently unclear whether, if continuously available, all NTFs can be protective for many or most retinal degenerations (RDs). We have used transgenic mice that continuously overexpress the neurotrophin, NT-3, from lens fibers under the control of the αA-crystallin promoter to test for neuroprotection in light-damage experiments and in four naturally occurring or transgenically induced RDs in mice. Lens-specific expression of NT-3 mRNA was demonstrated both by in situ hybridization in embryos and by RT-PCR in adult mice. Furthermore, NT-3 protein was found in abundance in the lens, ocular fluids and retina by ELISA and immunocytochemistry. Overexpression of NT-3 had no adverse effects on the structure or function of the retina for up to at least 14 months of age. Mice expressing the NT-3 transgene were protected from the damaging effects of constant light to a much greater degree than those receiving bolus injections of NT-3. When the NT-3 transgene was transferred into rd/rd, Rds/+, Q344ter mutant rhodopsin or Mertk knockout mice, overexpression of NT-3 had no protective effect on the RDs in these mice. Thus, specificity of the neuroprotective effect of NT-3 is clearly demonstrated, and different molecular mechanisms are inferred to mediate the protective effect in light-induced and inherited RDs. PMID:18925574

  7. Non-Nutritive Suck Parameter in Preterm Infants with RDS

    PubMed Central

    Estep, Meredith; Barlow, Steven M.; Vantipalli, Rajesh; Finan, Donald; Lee, Jaehoon

    2008-01-01

    Objective To characterize the integrity of non-nutritive suck (NNS) parameters among three groups of preterm infants ranging from normal to those with progressive degrees of respiratory distress syndrome (RDS). Study Design NNS compression waveforms were sampled from 55 infants in the neonatal intensive care unit using a silicone pacifier electronically instrumented for intraluminal pressure. Seven select NNS parameters were measured at two different sessions, and statistically analyzed using a General Linear Model Analysis of Covariance. Results and Conclusions Preterm infants with a more extensive history of RDS and oxygen therapy manifest significantly (p≤0.001) degraded performance on six of the seven NNS measures. This trend was disproportionately amplified in preterm infants with moderate-to-severe RDS. Prolonged periods of RDS requiring oxygen therapy may cause maladaptive orosensory experiences, and restrict oral movements which may contribute to delayed NNS development. PMID:19190723

  8. P2Y2 Receptor Agonist INS37217 Enhances Functional Recovery after Detachment Caused by Subretinal Injection in Normal and rds Mice

    PubMed Central

    Nour, May; Quiambao, Alexander B.; Peterson, Ward M.; Al-Ubaidi, Muayyad R.; Naash, Muna I.

    2010-01-01

    Purpose To evaluate the effects of INS37217 on the recovery of retinal function after experimental retinal detachment induced by subretinal injection. Methods Subretinal injections of 1 μL of fluorescent microbeads, saline, or INS37217 (1–200 μM) were made by the transvitreal method in normal (C57BL/6) mice and in mice heterozygous for the retinal degeneration slow (rds) gene. Control, mock-injected animals underwent corneal puncture without injection. Histologic and ERG evaluations were made at 0 to 1 and 8 hours, and 1, 3, 7, 10, 14, and 60 days post injection (PI). DNA fragmentation was evaluated by terminal deoxynucleotidyl transferase–mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL). Results A single subretinal injection of saline solution containing fluorescent beads caused a histologically evident retinal detachment and distributed the microbeads to almost all the subretinal space. Spontaneous reattachment occurred within 24 hours after injection and was accompanied by evident retinal folding that appeared largely resolved by 6 days later. Relative to controls, injection of saline resulted in approximately 40% recovery of dark-adapted a-wave amplitude at 24 hours PI and gradually improved to approximately 90% of controls at 2 months PI. Subretinal injection of saline containing INS37217 (10 μM) significantly increased rod and cone ERG of normal and rds+/− mice at 1 and 10 days PI, when compared with injection of saline alone. Additionally, INS37217 reduced the number of TUNEL-positive photoreceptors and the enhanced rate of reattachment. Conclusions Enhancement of ERG recovery by INS37217 is likely due to reduced retinal folding and cell death associated with detachment. These results support the use of INS37217 to help restore function after therapies that involve subretinal administration of drugs in animal models of retinal diseases. PMID:14507899

  9. Replacement Gene Therapy with a Human RPGRIP1 Sequence Slows Photoreceptor Degeneration in a Murine Model of Leber Congenital Amaurosis

    PubMed Central

    Pawlyk, Basil S.; Bulgakov, Oleg V.; Liu, Xiaoqing; Xu, Xiaoyun; Adamian, Michael; Sun, Xun; Khani, Shahrokh C.; Berson, Eliot L.; Sandberg, Michael A.

    2010-01-01

    Abstract RPGR-interacting protein-1 (RPGRIP1) is localized in the photoreceptor-connecting cilium, where it anchors the RPGR (retinitis pigmentosa GTPase regulator) protein, and its function is essential for photoreceptor maintenance. Genetic defect in RPGRIP1 is a known cause of Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. We evaluated the efficacy of replacement gene therapy in a murine model of LCA carrying a targeted disruption of RPGRIP1. The replacement construct, packaged in an adeno-associated virus serotype 8 (AAV8) vector, used a rhodopsin kinase gene promoter to drive RPGRIP1 expression. Both promoter and transgene were of human origin. After subretinal delivery of the replacement gene in the mutant mice, human RPGRIP1 was expressed specifically in photoreceptors, localized correctly in the connecting cilia, and restored the normal localization of RPGR. Electroretinogram and histological examinations showed better preservation of rod and cone photoreceptor function and improved photoreceptor survival in the treated eyes. This study demonstrates the efficacy of human gene replacement therapy and validates a gene therapy design for future clinical trials in patients afflicted with this condition. Our results also have therapeutic implications for other forms of retinal degenerations attributable to a ciliary defect. PMID:20384479

  10. Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype.

    PubMed

    Schubert, Timm; Gleiser, Corinna; Heiduschka, Peter; Franz, Christoph; Nagel-Wolfrum, Kerstin; Sahaboglu, Ayse; Weisschuh, Nicole; Eske, Gordon; Rohbock, Karin; Rieger, Norman; Paquet-Durand, François; Wissinger, Bernd; Wolfrum, Uwe; Hirt, Bernhard; Singer, Wibke; Rüttiger, Lukas; Zimmermann, Ulrike; Knipper, Marlies

    2015-10-01

    The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell's Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms.

  11. Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.

    PubMed

    Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J; Cuenca, Nicolás

    2012-12-01

    Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi-) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.

  12. Proinsulin Slows Retinal Degeneration and Vision Loss in the P23H Rat Model of Retinitis Pigmentosa

    PubMed Central

    Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M.; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J.

    2012-01-01

    Abstract Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi−) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa. PMID:23017108

  13. Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs.

    PubMed

    Zhu, Jun; Tang, Haoyu; Zhang, Zhenhua; Zhang, Yong; Qiu, Chengfeng; Zhang, Ling; Huang, Pinge; Li, Feng

    2017-02-01

    Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration.

  14. Controlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats.

    PubMed

    Fernández-Sánchez, Laura; Bravo-Osuna, Irene; Lax, Pedro; Arranz-Romera, Alicia; Maneu, Victoria; Esteban-Pérez, Sergio; Pinilla, Isabel; Puebla-González, María Del Mar; Herrero-Vanrell, Rocío; Cuenca, Nicolás

    2017-01-01

    Successful drug therapies for treating ocular diseases require effective concentrations of neuroprotective compounds maintained over time at the site of action. The purpose of this work was to assess the efficacy of intravitreal controlled delivery of tauroursodeoxycholic acid (TUDCA) encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres for the treatment of the retina in a rat model of retinitis pigmentosa. PLGA microspheres (MSs) containing TUDCA were produced by the O/W emulsion-solvent evaporation technique. Particle size and morphology were assessed by light scattering and scanning electronic microscopy, respectively. Homozygous P23H line 3 rats received a treatment of intravitreal injections of TUDCA-PLGA MSs. Retinal function was assessed by electroretinography at P30, P60, P90 and P120. The density, structure and synaptic contacts of retinal neurons were analyzed using immunofluorescence and confocal microscopy at P90 and P120. TUDCA-loaded PLGA MSs were spherical, with a smooth surface. The production yield was 78%, the MSs mean particle size was 23 μm and the drug loading resulted 12.5 ± 0.8 μg TUDCA/mg MSs. MSs were able to deliver the loaded active compound in a gradual and progressive manner over the 28-day in vitro release study. Scotopic electroretinografic responses showed increased ERG a- and b-wave amplitudes in TUDCA-PLGA-MSs-treated eyes as compared to those injected with unloaded PLGA particles. TUDCA-PLGA-MSs-treated eyes showed more photoreceptor rows than controls. The synaptic contacts of photoreceptors with bipolar and horizontal cells were also preserved in P23H rats treated with TUDCA-PLGA MSs. This work indicates that the slow and continuous delivery of TUDCA from PLGA-MSs has potential neuroprotective effects that could constitute a suitable therapy to prevent neurodegeneration and visual loss in retinitis pigmentosa.

  15. Controlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats

    PubMed Central

    Lax, Pedro; Arranz-Romera, Alicia; Maneu, Victoria; Esteban-Pérez, Sergio; Pinilla, Isabel; Puebla-González, María del Mar; Herrero-Vanrell, Rocío

    2017-01-01

    Successful drug therapies for treating ocular diseases require effective concentrations of neuroprotective compounds maintained over time at the site of action. The purpose of this work was to assess the efficacy of intravitreal controlled delivery of tauroursodeoxycholic acid (TUDCA) encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres for the treatment of the retina in a rat model of retinitis pigmentosa. PLGA microspheres (MSs) containing TUDCA were produced by the O/W emulsion-solvent evaporation technique. Particle size and morphology were assessed by light scattering and scanning electronic microscopy, respectively. Homozygous P23H line 3 rats received a treatment of intravitreal injections of TUDCA-PLGA MSs. Retinal function was assessed by electroretinography at P30, P60, P90 and P120. The density, structure and synaptic contacts of retinal neurons were analyzed using immunofluorescence and confocal microscopy at P90 and P120. TUDCA-loaded PLGA MSs were spherical, with a smooth surface. The production yield was 78%, the MSs mean particle size was 23 μm and the drug loading resulted 12.5 ± 0.8 μg TUDCA/mg MSs. MSs were able to deliver the loaded active compound in a gradual and progressive manner over the 28-day in vitro release study. Scotopic electroretinografic responses showed increased ERG a- and b-wave amplitudes in TUDCA-PLGA-MSs-treated eyes as compared to those injected with unloaded PLGA particles. TUDCA-PLGA-MSs-treated eyes showed more photoreceptor rows than controls. The synaptic contacts of photoreceptors with bipolar and horizontal cells were also preserved in P23H rats treated with TUDCA-PLGA MSs. This work indicates that the slow and continuous delivery of TUDCA from PLGA-MSs has potential neuroprotective effects that could constitute a suitable therapy to prevent neurodegeneration and visual loss in retinitis pigmentosa. PMID:28542454

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

    PubMed

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

    2016-11-18

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

  17. New mouse primary retinal degeneration (rd-3)

    SciTech Connect

    Chang, B.; Hawes, N.L.; Roderick, T.H. ); Heckenlively, J.R. )

    1993-04-01

    A new mouse retinal degeneration that appears to be an excellent candidate for modeling human retinitis pigmentosa is reported. In this degeneration, called rd-3, differentiation proceeds postnatally through 2 weeks, and photoreceptor degeneration starts by 3 weeks. The rod photoreceptor loss is essentially complete by 5 weeks, whereas remnant cone cells are seen through 7 weeks. This is the only mouse homozygous retinal degeneration reported to date in which photoreceptors are initially normal. Crosses with known mouse retinal degenerations rd, Rds, nr, and pcd are negative for retinal degeneration in offspring, and linkage analysis places rd-3 on mouse chromosome 1 at 10 [+-]2.5 cM distal to Akp-1. Homology mapping suggests that the homologous human locus should be on chromosome 1q. 32 refs., 3 figs., 3 tabs.

  18. TUDCA Slows Retinal Degeneration in Two Different Mouse Models of Retinitis Pigmentosa and Prevents Obesity in Bardet-Biedl Syndrome Type 1 Mice

    PubMed Central

    Drack, Arlene V.; Dumitrescu, Alina V.; Bhattarai, Sajag; Gratie, Daniel; Stone, Edwin M.; Mullins, Robert

    2012-01-01

    Purpose. To evaluate and compare the protective effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration in different models of retinal degeneration (RD) in mice. Methods. BbsM390R/M390R mice were injected subcutaneously twice a week, from P40 to P120, and rd10 mice were injected every 3 days from P6 to P38 with TUDCA or vehicle (0.15 M NaHCO3). Rd1 and rd16 mice were injected daily from P6 to P30 with TUDCA or vehicle. Retinal structure and function were determined at multiple time points by electroretinography (ERG), optical coherence tomography (OCT), and histology. Results. The amplitude of ERG b-waves was significantly higher in TUDCA-treated Bbs1 and rd10 animals than in controls. Retinal thickness on OCT was slightly greater in treated Bbs1 animals than in the controls. Histologically, outer segments were preserved, and the outer nuclear layer was significantly thicker in the treated Bbs1 and rd10 mice than in the controls. Bbs1M390R/M390R mice developed less obesity than the control Bbs1M390R/M390R while receiving TUDCA. The Rd1 and rd16 mice showed no improvement with TUDCA treatment, and the rd1 mice did not have normal weight gain during treatment. Conclusions. TUDCA treatment preserved ERG b-waves and the outer nuclear layer in Bbs1M390R/M390R mice, and prevented obesity assessed at P120. TUDCA treatment preserved ERG b-waves and the outer nuclear layer in the rd10 mice to P30. TUDCA is a prime candidate for treatment of humans with retinal degeneration, especially those with Bardet-Biedl syndrome, whom it may help not only with the vision loss, but with the debilitating obesity as well. PMID:22110077

  19. Brief Potentially Ictal Rhythmic Discharges [B(I)RDs] in Non-critically Ill Adults.

    PubMed

    Yoo, Ji Yeoun; Marcuse, Lara V; Fields, Madeline C; Rosengard, Jillian; Traversa, Maria Vittoria; Gaspard, Nicolas; Hirsch, Lawrence J

    2016-10-19

    Brief potentially ictal rhythmic discharges (B(I)RDs) have been described in neonates and critically ill adults, and their association with seizures has been demonstrated. Their significance in non-critically ill adults remains unclear. We aimed to investigate their prevalence, electrographic characteristics and clinical significance. We identified adult patients with B(I)RDs who received long term EEG recordings either in the epilepsy monitoring unit or in the ambulatory setting. Patients with acute findings on imaging or status epilepticus were excluded. B(I)RDs were defined as very brief (<10 seconds) runs of focal or generalized sharply contoured rhythmic activity greater than 4 Hz, with or without evolution, that were not consistent with any known normal or benign pattern. The clinical history, EEG and imaging results were retrieved. Each patient with B(I)RDs was matched by age and etiology to a control group with epileptiform discharges but without B(I)RDs in a 1:2 ratio. We identified B(I)RDs in 15 patients out of 1230 EEGs (1.2%). The pattern typically consisted of 0.5-4 second runs of sharply contoured alpha activity without evolution. All patients with B(I)RDs had epilepsy, and, when compared to controls with epilepsy but without BIRDs, were more likely to be medically refractory (10 of 15 [67%] vs. 5 of 30 [17%]; p<0.01). All seizure onsets co-localized to the B(I)RDs, and most were morphologically similar. In non-critically ill patients, B(I)RDs are associated with refractory epilepsy and their location is correlated with the seizure onset area.

  20. Brief Potentially Ictal Rhythmic Discharges [B(I)RDs] in Noncritically Ill Adults.

    PubMed

    Yoo, Ji Yeoun; Marcuse, Lara V; Fields, Madeline C; Rosengard, Jillian L; Traversa, Maria Vittoria; Gaspard, Nicolas; Hirsch, Lawrence J

    2017-05-01

    Brief potentially ictal rhythmic discharges (B(I)RDs) have been described in neonates and critically ill adults, and their association with seizures has been demonstrated. Their significance in noncritically ill adults remains unclear. We aimed to investigate their prevalence, electrographic characteristics, and clinical significance. We identified adult patients with B(I)RDs who received long-term EEG recordings either in the epilepsy monitoring unit or in the ambulatory setting. Patients with acute findings on imaging or status epilepticus were excluded. B(I)RDs were defined as very brief (<10 seconds) runs of focal or generalized sharply contoured rhythmic activity greater than 4 Hz, with or without evolution, that were not consistent with any known normal or benign pattern. The clinical history, EEG, and imaging results were retrieved. Each patient with B(I)RDs was matched by age and etiology to a control group with epileptiform discharges but without B(I)RDs in a 1:2 ratio. We identified B(I)RDs in 15 patients of 1,230 EEGs (1.2%). The pattern typically consisted of 0.5 to 4 second runs of sharply contoured alpha activity without evolution. All patients with B(I)RDs had epilepsy, and, when compared with controls with epilepsy but without BIRDs, were more likely to be medically refractory (10 of 15 [67%] vs. 5 of 30 [17%]; P < 0.01). All seizure onsets colocalized to the B(I)RDs, and most were morphologically similar. In noncritically ill patients, B(I)RDs are associated with refractory epilepsy and their location is correlated with the seizure onset area.

  1. A novel mutation (ASn244Lys) in the peripherin/RDS gene causing autosomal dominant retinitis pigmentosa associated with bull's eye maculopathy detected by nonradioisotopic SSCP

    SciTech Connect

    Kikawa, Emi; Nakazawa, Mitsuru; Chida, Yasushi; Shiono, Takashi; Tamai, Makota )

    1994-03-01

    Retinitis pigmentosa (RP) is characterized by night blindness, an eventual loss of visual field, a diminished response on the electroretinogram, and pigmentary retinal degeneration. These features are primarily explained by the degeneration of photoreceptors. The recent development of the molecular genetic approach has enabled the identification of genes responsible for parts of autosomal dominant RP (ADRP). Rhodopsin and peripherin/RDS genes, in particular, have been successfully shown to cosegregate with ADRP. The authors, therefore, screened 42 unrelated Japanese patients with ADRP to search for mutations in the peripherin/RDS gene. The method we employed for screening was a nonradioisotopic modification of single-strand conformation polymorphism. Among 42 unrelated patients with ADRP, the DNA from one patient (SY) showed an abnormal pattern in exon 2 on SSCP. The DNA fragments were then amplified from affected and nonaffected members of the same family as SY. The alteration in the DNA sequence that was commonly found in the affected members of the family was identified as a heterozygous transversional change of C to A at the third nucleotide in codon 244, resulting in the amino acid replacement of asparagine residue with lysine residue. None of unaffected family members or 30 normal control individuals had this alteration.

  2. Can HMG Co-A reductase inhibitors (“statins”) slow the progression of age-related macular degeneration? The Age-Related Maculopathy Statin Study (ARMSS)

    PubMed Central

    Guymer, Robyn H; Dimitrov, Peter N; Varsamidis, Mary; Lim, Lyndell L; Baird, Paul N; Vingrys, Algis J; Robman, Luba

    2008-01-01

    Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. The role of cholesterol-lowering medications, HMG Co-A reductase inhibitors or statins, in reducing the risk of AMD or of delaying its progression has not been fully investigated. A 3-year prospective randomized controlled trial of 40 mg simvastatin per day compared to placebo in subjects at high risk of AMD progression is described. This paper outlines the primary aims of the Age-Related Maculopathy Statin Study (ARMSS), and the methodology involved. Standardized clinical grading of macular photographs and comparison of serial macular digital photographs, using the International grading scheme, form the basis for assessment of primary study outcomes. In addition, macular function is assessed at each visit with detailed psychophysical measurements of rod and cone function. Information collected in this study will assist in the assessment of the potential value of HMG Co-A reductase inhibitors (statins) in reducing the risk of AMD progression. PMID:18982929

  3. Simulation, Design, and Testing of a High Power Collimator for the RDS-112 Cyclotron

    PubMed Central

    Peeples, Johanna L.; Stokely, Matthew H.; Poorman, Michael C.; Bida, Gerald T.; Wieland, Bruce W.

    2015-01-01

    A high power [F-18]fluoride target package for the RDS-112 cyclotron has been designed, tested, and commercially deployed. The upgrade includes the CF-1000 target, a 1.3 kW water target with an established commercial history on RDS-111/Eclipse cyclotrons, and a redesigned collimator with improved heat rejection capabilities. Conjugate heat transfer analyses were employed to both evaluate the existing collimator capabilities and design a suitable high current replacement. PMID:25562677

  4. Macular degeneration

    MedlinePlus Videos and Cool Tools

    ... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

  5. Genetic Addiction Risk Score (GARS): molecular neurogenetic evidence for predisposition to Reward Deficiency Syndrome (RDS).

    PubMed

    Blum, Kenneth; Oscar-Berman, Marlene; Demetrovics, Zsolt; Barh, Debmalya; Gold, Mark S

    2014-12-01

    We have published extensively on the neurogenetics of brain reward systems with reference to the genes related to dopaminergic function in particular. In 1996, we coined "Reward Deficiency Syndrome" (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function. RDS as a useful concept has been embraced in many subsequent studies, to increase our understanding of Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and impulsive behaviors. Interestingly, albeit others, in one published study, we were able to describe lifetime RDS behaviors in a recovering addict (17 years sober) blindly by assessing resultant Genetic Addiction Risk Score (GARS™) data only. We hypothesize that genetic testing at an early age may be an effective preventive strategy to reduce or eliminate pathological substance and behavioral seeking activity. Here, we consider a select number of genes, their polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is evidence for convergence to reward candidate genes. The evidence presented serves as a plausible brain-print providing relevant genetic information that will reinforce targeted therapies, to improve recovery and prevent relapse on an individualized basis. The primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction medicine that embraces the neuroscience of addiction and RDS as a pathological condition in brain reward circuitry that calls for appropriate evidence-based therapy and early genetic diagnosis and that requires further intensive investigation.

  6. Molecular Genetic Testing in Reward Deficiency Syndrome (RDS): Facts and Fiction.

    PubMed

    Blum, Kenneth; Badgaiyan, Rajendra D; Agan, Gozde; Fratantonio, James; Simpatico, Thomas; Febo, Marcelo; Haberstick, Brett C; Smolen, Andrew; Gold, Mark S

    The Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors or RDS, which was coined to define addictive behaviors and their genetic components. To carry out this review we searched a number of important databases including: Filtered: Cochrane Systematic reviews; DARE; Pubmed Central Clinical Quaries; National Guideline Clearinghouse and unfiltered resources: PsychINFO; ACP PIER; PsychSage; Pubmed/Medline. The major search terms included: dopamine agonist therapy for Addiction; dopamine agonist therapy for Reward dependence; dopamine antagonistic therapy for addiction; dopamine antagonistic therapy for reward dependence and neurogenetics of RDS. While there are many studies claiming a genetic association with RDS behavior, not all are scientifically accurate. Albeit our bias, this Clinical Pearl discusses the facts and fictions behind molecular genetic testing in RDS and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™), the first test to accurately predict one's genetic risk for RDS.

  7. Molecular Genetic Testing in Reward Deficiency Syndrome (RDS): Facts and Fiction

    PubMed Central

    Blum, Kenneth; Badgaiyan, Rajendra D.; Agan, Gozde; Fratantonio, James; Simpatico, Thomas; Febo, Marcelo; Haberstick, Brett C.; Smolen, Andrew; Gold, Mark S.

    2015-01-01

    Background The Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors or RDS, which was coined to define addictive behaviors and their genetic components. Methods To carry out this review we searched a number of important databases including: Filtered: Cochrane Systematic reviews; DARE; Pubmed Central Clinical Quaries; National Guideline Clearinghouse and unfiltered resources: PsychINFO; ACP PIER; PsychSage; Pubmed/Medline. The major search terms included: dopamine agonist therapy for Addiction; dopamine agonist therapy for Reward dependence; dopamine antagonistic therapy for addiction; dopamine antagonistic therapy for reward dependence and neurogenetics of RDS. Results While there are many studies claiming a genetic association with RDS behavior, not all are scientifically accurate. Conclusion Albeit our bias, this Clinical Pearl discusses the facts and fictions behind molecular genetic testing in RDS and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™), the first test to accurately predict one’s genetic risk for RDS. PMID:26052557

  8. Sorting photons of different rotational Doppler shifts (RDS) by orbital angular momentum of single-photon with spin-orbit-RDS entanglement.

    PubMed

    Chen, Lixiang; She, Weilong

    2008-09-15

    We demonstrate that single photons from a rotating q-plate exhibit an entanglement in three degrees of freedom of spin, orbital angular momentum, and the rotational Doppler shift (RDS) due to the nonconservation of total spin and orbital angular momenta. We find that the rotational Doppler shift deltaomega = Omega((delta)s + deltal) , where s, l and Omega are quantum numbers of spin, orbital angular momentum, and rotating velocity of the q-plate, respectively. Of interest is that the rotational Doppler shift directly reflects the rotational symmetry of q-plates and can be also expressed as deltaomega = (Omega)n , where n = 2(q-1) denotes the fold number of rotational symmetry. Besides, based on this single-photon spin-orbit-RDS entanglement, we propose an experimental scheme to sort photons of different frequency shifts according to individual orbital angular momentum.

  9. Relationship between the cortisol levels in umbilical cord blood and neonatal RDS/TTN in twin pregnancies.

    PubMed

    Tsuda, Hiroyuki; Kotani, Tomomi; Sumigama, Seiji; Mano, Yukio; Nakano, Tomoko; Hua, Li; Kikkawa, Fumitaka

    2016-01-01

    Twin neonates have a higher risk of respiratory complications, such as respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), than singleton neonates. The purpose of this study was to evaluate the relationship between the cortisol levels in the umbilical cord and neonatal RDS/TTN in twin pregnancies. We analyzed data obtained from 106 neonates (53 twin pairs), comprising 33 dichorionic twin (DCT) and 20 monochorionic twin (MCT) gestations. All infants were delivered via scheduled cesarean section without labor. We measured the cortisol levels in umbilical vein blood using enzyme-linked immunosorbent assay. The cortisol levels in the umbilical vein were significantly lower in the RDS/TTN group than in the no RDS/TTN group (p = 0.004). The umbilical cortisol levels in the TTN group were between the values observed in the RDS group and no RDS/TTN group. We subsequently analyzed the cut-off cortisol values for RDS/TTN and observed higher accuracy in the DCTs than in the MCTs. Neonates who develop RDS/TTN have significantly lower cortisol levels in the umbilical cord at birth than no RDS/TTN neonates in twin pregnancies. When applying these data in clinical practice, physicians should pay attention to differences based on chorionicity.

  10. Lipid profile of children suffering from pediatric rheumatic diseases (pRDS).

    PubMed

    Rashid, A K M Mamunur; Sultana, Habiba; Islam, Tasnuva

    2017-08-21

    Aim of this study is to assess the lipid status of the patients of pediatric rheumatologic diseases (pRDS) This observational study is carried out in the department of pediatrics, Khulna medical college hospital, Bangladesh for a period of one year. Total 23 patients are included in this study. These new cases are diagnosed according to the ILAR, ACR, and EULAR criteria. Early morning blood samples are sent to the laboratory for the assessment of lipid status (TC, TG, HDL, and LDL). These values are collected and statistically recorded. Total new cases of pRDS are 23. Among them JIA is 15, SLE 4, and Vasculitis 4 in number. HSP is in 3 and KD in 1 cases of vasculitis group. Male/ Female ratio is 1.6:1. Mean age of the diseases are 8.54 years.TC, and TG is found in significant level in 4(17.4%), and 12(52.8%) pRDS cases respectively. HDL is observed of risk level in 4(17.3%) patients. LDL is observed normal in all the patients.TG is found of significant level in 7(46.7%) JIA, 3(75%) SLE and 2 (50%) vasculitis patients. TG is the lipid observed in significant level in majority of the new pRDS cases. Elevated TG may be considered as an index of disease activity in all cases of pRDS. Measures can be adopted in all pRDS to control the lipid status from the beginning of illness to reduce the complications from dyslipidemia like atherosclerosis and cardiovascular morbidity and mortality in future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Cerebellar Degeneration

    MedlinePlus

    ... is a process in which neurons in the cerebellum - the area of the brain that controls coordination ... body, can cause neurons to die in the cerebellum. Neurological diseases that feature cerebellar degeneration include: ischemic ...

  12. VEGF levels in humans and animal models with RDS and BPD: temporal relationships.

    PubMed

    Meller, Stephanie; Bhandari, Vineet

    2012-05-01

    Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) contribute significantly to neonatal morbidity and mortality. Pulmonary function depends on the interaction between alveolar microvasculature and airspace development. While it has been shown in various animal models that vascular endothelial growth factor (VEGF) and its receptors increase in normal animal lung development, its pathophysiological role in neonatal respiratory failure is not yet entirely clear. Current animal and human studies exhibit controversial results. Though animal models are invaluable tools in the study of human lung disease, inherent differences in physiology mandate clarification of the timing of these studies to ensure that they appropriately correlate with the human stages of lung development. The purpose of this review article is to highlight the importance of considering the temporal relationship of VEGF and lung development in human neonates and developmentally-appropriate animal models with RDS and BPD.

  13. Comparison of Complications and Efficacy of NIPPV and Nasal CPAP in Preterm Infants With RDS

    PubMed Central

    Esmaeilnia, Tahereh; Nayeri, Fatemeh; Taheritafti, Roya; Shariat, Mamak; Moghimpour-Bijani, Faezeh

    2016-01-01

    Background: Respiratory distress syndrome (RDS) is one of the most common diseases in neonates admitted to NICU. For this important cause of morbidity and mortality in preterm neonates, several treatment methods have been used. To date, non-invasive methods are preferred due to fewer complications. Objectives: Herein, two non-invasive methods of ventilation support are compared: NCPAP vs. NIPPV. Patients and Methods: This is a randomized clinical trial. Premature neonates with less than 34 weeks gestation, suffering from RDS entered the study, including 151 newborns admitted to Vali-Asr NICU during 2012-2013. Most of these patients received surfactant as early rescue via INSURE method and then randomly divided into two NCPAP (73 neonates) and NIPPV (78 neonates) groups. Both early and late complications are compared including extubation failure, hospital length of stay, GI perforation, apnea, intraventricular hemorrhage (IVH) and mortality rate. Results: The need for re-intubation was 6% in NIPPV vs. 17.6% in NCPAP group, which was statistically significant (P = 0.031). The length of hospital stay was 23.92 ± 13.5 vs. 32.61 ± 21.07 days in NIPPV and NCPAP groups, respectively (P = 0.002). Chronic lung disease (CLD) was reported to be 4% in NCPAP and 0% in NIPPV groups (P = 0.035). The most common complication occurred in both groups was traumatization of nasal skin and mucosa, all of which fully recovered. Gastrointestinal perforation was not reported in either group. Conclusions: This study reveals the hospital length of stay, re-intubation and BPD rates are significantly declined in neonates receiving NIPPV as the treatment for RDS. PMID:27307960

  14. Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci

    SciTech Connect

    Kajiwara, K.; Berson, E.L.; Dryja, T.P. )

    1994-06-10

    In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM 1 and peripherin/RDS, in which only double heterozygotes develop retinitis pigmentosa (RP). These findings indicate that the allelic and nonallelic heterogeneity known to be a feature of monogenic RP is complicated further by interactions between unlinked mutations causing digenic RP. Recognition of the inheritance pattern exemplified by these three families might facilitate the identification of other examples of digenic inheritance in human disease.

  15. Striatopallidonigral degeneration

    PubMed Central

    Bell, W. E.; McCormick, W. F.

    1971-01-01

    A 15-year-old girl is described with a sporadic, progressive illness manifested by unilateral limb rigidity and dystonia. Obvious dysarthria and some intellectual decline also were noted. Neuropathological findings included gross discoloration and shrinkage of the pallida and, microscopically, profound neuronal loss and gliosis of the caudata and putamena, with less severe neuronal loss from the pallida and substantia nigra. The disease bears some similarities to striatonigral degeneration, but certain clinical and morphological differences justify its consideration as a separate syndrome. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:5565467

  16. Community understanding of Respondent-Driven Sampling in a medical research setting in Uganda: importance for the use of RDS for public health research

    PubMed Central

    McCreesh, Nicky; Tarsh, Matilda Nadagire; Seeley, Janet; Katongole, Joseph; White, Richard G

    2013-01-01

    Respondent-driven sampling (RDS) is a widely-used variant of snowball sampling. Respondents are selected not from a sampling frame, but from a social network of existing members of the sample. Incentives are provided for participation and for the recruitment of others. Ethical and methodological criticisms have been raised about RDS. Our purpose was to evaluate whether these criticisms were justified. In this study RDS was used to recruit male household heads in rural Uganda. We investigated community members’ understanding and experience of the method, and explored how these may have affected the quality of the RDS survey data. Our findings suggest that because participants recruit participants, the use of RDS in medical research may result in increased difficulties in gaining informed consent, and data collected using RDS may be particularly susceptible to bias due to differences in the understanding of key concepts between researchers and members of the community. PMID:24273435

  17. Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes

    PubMed Central

    Liu, Haitao; Tang, Jie; Du, Yunpeng; Saadane, Aicha; Tonade, Deoye; Samuels, Ivy; Veenstra, Alex; Palczewski, Krzysztof; Kern, Timothy S.

    2016-01-01

    Purpose Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin−/− and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. Methods Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. Results Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. Conclusions Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration. PMID:27548901

  18. Age-related macular degeneration.

    PubMed

    Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y

    2012-05-05

    Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.

  19. Dry Macular Degeneration

    MedlinePlus

    ... delay vision loss due to dry macular degeneration. Symptoms Dry macular degeneration symptoms usually develop gradually and without pain. They may ... of printed words Decreased intensity or brightness of ... causes total blindness. Dry macular degeneration is one of two types ...

  20. Macular degeneration (image)

    MedlinePlus

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  1. Surfactant therapy in preterm infants with respiratory distress syndrome and in near-term or term newborns with acute RDS.

    PubMed

    Ramanathan, R

    2006-05-01

    Many different surfactant preparations derived from animal sources, as well as synthetic surfactants, are available for the treatment of preterm infants with respiratory distress syndrome (RDS). Natural, modified surfactants containing surfactant-associated proteins appear to be more effective than non-protein-containing synthetic surfactants. Comparative trials with poractant alfa at a higher initial dose of 200 mg/kg appear to be associated with rapid weaning of FiO2, less need for additional doses, and decreased mortality in infants <32 weeks gestation when compared with beractant. Early rescue (<30 min of age) surfactant therapy is an effective method to minimize over treatment of some preterm infants who may not develop RDS. Surfactant therapy followed by rapid extubation to nasal ventilation appears to be more beneficial than continued mechanical ventilation. In near-term or term newborns with acute RDS, surfactant therapy has been shown to be 70% effective in improving respiratory failure.

  2. An Empirical Analysis of the Impact of Recruitment Patterns on RDS Estimates among a Socially Ordered Population of Female Sex Workers in China

    PubMed Central

    Yamanis, Thespina J.; Merli, M. Giovanna; Neely, William Whipple; Tian, Felicia Feng; Moody, James; Tu, Xiaowen; Gao, Ersheng

    2013-01-01

    Respondent-driven sampling (RDS) is a method for recruiting “hidden” populations through a network-based, chain and peer referral process. RDS recruits hidden populations more effectively than other sampling methods and promises to generate unbiased estimates of their characteristics. RDS’s faithful representation of hidden populations relies on the validity of core assumptions regarding the unobserved referral process. With empirical recruitment data from an RDS study of female sex workers (FSWs) in Shanghai, we assess the RDS assumption that participants recruit nonpreferentially from among their network alters. We also present a bootstrap method for constructing the confidence intervals around RDS estimates. This approach uniquely incorporates real-world features of the population under study (e.g., the sample’s observed branching structure). We then extend this approach to approximate the distribution of RDS estimates under various peer recruitment scenarios consistent with the data as a means to quantify the impact of recruitment bias and of rejection bias on the RDS estimates. We find that the hierarchical social organization of FSWs leads to recruitment biases by constraining RDS recruitment across social classes and introducing bias in the RDS estimates. PMID:24288418

  3. Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

    PubMed Central

    Blum, Kenneth; Chen, Amanda L. C.; Oscar-Berman, Marlene; Chen, Thomas J. H.; Lubar, Joel; White, Nancy; Lubar, Judith; Bowirrat, Abdalla; Braverman, Eric; Schoolfield, John; Waite, Roger L.; Downs, Bernard W.; Madigan, Margaret; Comings, David E.; Davis, Caroline; Kerner, Mallory M.; Knopf, Jennifer; Palomo, Tomas; Giordano, John J.; Morse, Siobhan A.; Fornari, Frank; Barh, Debmalya; Femino, John; Bailey, John A.

    2011-01-01

    Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may

  4. Degenerate metric phase boundaries

    NASA Astrophysics Data System (ADS)

    Bengtsson, I.; Jacobson, T.

    1997-11-01

    The structure of boundaries between degenerate and non-degenerate solutions of Ashtekar's canonical reformulation of Einstein's equations is studied. Several examples are given of such `phase boundaries' in which the metric is degenerate on one side of a null hypersurface and non-degenerate on the other side. These include portions of flat space, Schwarzschild and plane-wave solutions joined to degenerate regions. In the last case, the wave collides with a planar phase boundary and continues on with the same curvature but degenerate triad, while the phase boundary continues in the opposite direction. We conjecture that degenerate phase boundaries are always null.

  5. Insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) expression in human lung in RDS and BPD.

    PubMed

    Chetty, Anne; Andersson, Sture; Lassus, Patrik; Nielsen, Heber C

    2004-02-01

    We hypothesize that IGF-1 and IGF-1R proteins are upregulated in lung epithelia and fibroblasts in RDS compared to normal development, and are further upregulated in BPD. We used immunohistochemistry to evaluate IGF-1 and IGF-R expression in lungs from autopsies of human stillbirths and RDS and BPD patients. IGF-1 and IGF-R immunostaining were present in fetal, RDS, and BPD lungs. In RDS, IGF-1 was present in alveolar epithelium and prominent in columnar and cuboidal airway epithelia. In BPD lungs, immunostaining was intensely increased in both airway and alveolar epithelia and in mesenchyme. The immunostaining index in bronchial epithelial cells and peribronchial myofibroblasts was significantly higher in BPD compared to RDS. IGF-1R expression was minimal in fetal lung and found mainly in mesenchyme. IGF-1R was increased in mesenchyme in RDS. In BPD it was especially increased in peribronchial and perialveolar mesenchyme. Immunostaining index for IGF-1R in epithelial cells and peribronchial myofibroblasts was increased in BPD compared to RDS. IGF-1 and IGF-R expression is low during fetal development, but is acutely upregulated in RDS, and persists with further upregulation in BPD. Copyright 2004 Wiley-Liss, Inc.

  6. Reproducibility of Respondent-Driven Sampling (RDS) in Repeat Surveys of Men Who have Sex with Men, Unguja, Zanzibar.

    PubMed

    Khatib, Ahmed; Haji, Shaaban; Khamis, Maryam; Said, Christen; Khalid, Farhat; Dahoma, Mohammed; Ali, Ameir; Othman, Asha; Welty, Susie; McFarland, Willi

    2017-07-01

    To assess the reproducibility of respondent-driven sampling (RDS) in obtaining comparable samples across two survey rounds, we conducted integrated bio-behavioral surveillance surveys (IBBSS) using RDS in 2007 and 2011 among men who have sex with men (MSM) on Unguja island in Zanzibar. Differences in the two rounds were assessed by comparing RDS-adjusted population estimates, stratified estimates, and bottleneck plots. Participants in the 2011 survey round were younger (31.4 vs. 9.9% under 19 years old, p < 0.001), more likely to have tested for HIV in the last year (53.7 vs. 10.6%, p < 0.001), and less likely to have injected drugs in the last 3 months (1.0 vs. 23.2%, p < 0.001) compared to participants in the 2007 round. HIV prevalence was 12.3% in 2007 compared to 2.6% in 2011 (p < 0.001). The difference in HIV prevalence persisted after stratifying and adjusting for known differences in the two surveys rounds. Bottleneck plots suggest that recruitment chains were "trapped" in the social networks of MSM who injected drugs to a greater extent in 2007 than in 2011. We conclude that the two rounds of RDS sampled different subsets of the MSM population on Unguja, particularly with respect to inclusion of MSM within the social networks of people who inject drugs. Findings underscore the need to evaluate the reproducibility of RDS in repeated rounds of IBBSS and to develop new sampling methods for key populations at high risk for HIV in order to track the epidemic, develop evidence-based prevention and care programs, and assess their impact.

  7. RDS - A systematic approach towards system thermal hydraulics input code development for a comprehensive deterministic safety analysis

    SciTech Connect

    Salim, Mohd Faiz; Roslan, Ridha; Ibrahim, Mohd Rizal Mamat

    2014-02-12

    Deterministic Safety Analysis (DSA) is one of the mandatory requirements conducted for Nuclear Power Plant licensing process, with the aim of ensuring safety compliance with relevant regulatory acceptance criteria. DSA is a technique whereby a set of conservative deterministic rules and requirements are applied for the design and operation of facilities or activities. Computer codes are normally used to assist in performing all required analysis under DSA. To ensure a comprehensive analysis, the conduct of DSA should follow a systematic approach. One of the methodologies proposed is the Standardized and Consolidated Reference Experimental (and Calculated) Database (SCRED) developed by University of Pisa. Based on this methodology, the use of Reference Data Set (RDS) as a pre-requisite reference document for developing input nodalization was proposed. This paper shall describe the application of RDS with the purpose of assessing its effectiveness. Two RDS documents were developed for an Integral Test Facility of LOBI-MOD2 and associated Test A1-83. Data and information from various reports and drawings were referred in preparing the RDS. The results showed that by developing RDS, it has made possible to consolidate all relevant information in one single document. This is beneficial as it enables preservation of information, promotes quality assurance, allows traceability, facilitates continuous improvement, promotes solving of contradictions and finally assisting in developing thermal hydraulic input regardless of whichever code selected. However, some disadvantages were also recognized such as the need for experience in making engineering judgments, language barrier in accessing foreign information and limitation of resources. Some possible improvements are suggested to overcome these challenges.

  8. RDS - A systematic approach towards system thermal hydraulics input code development for a comprehensive deterministic safety analysis

    NASA Astrophysics Data System (ADS)

    Salim, Mohd Faiz; Roslan, Ridha; Ibrahim, Mohd Rizal Mamat @

    2014-02-01

    Deterministic Safety Analysis (DSA) is one of the mandatory requirements conducted for Nuclear Power Plant licensing process, with the aim of ensuring safety compliance with relevant regulatory acceptance criteria. DSA is a technique whereby a set of conservative deterministic rules and requirements are applied for the design and operation of facilities or activities. Computer codes are normally used to assist in performing all required analysis under DSA. To ensure a comprehensive analysis, the conduct of DSA should follow a systematic approach. One of the methodologies proposed is the Standardized and Consolidated Reference Experimental (and Calculated) Database (SCRED) developed by University of Pisa. Based on this methodology, the use of Reference Data Set (RDS) as a pre-requisite reference document for developing input nodalization was proposed. This paper shall describe the application of RDS with the purpose of assessing its effectiveness. Two RDS documents were developed for an Integral Test Facility of LOBI-MOD2 and associated Test A1-83. Data and information from various reports and drawings were referred in preparing the RDS. The results showed that by developing RDS, it has made possible to consolidate all relevant information in one single document. This is beneficial as it enables preservation of information, promotes quality assurance, allows traceability, facilitates continuous improvement, promotes solving of contradictions and finally assisting in developing thermal hydraulic input regardless of whichever code selected. However, some disadvantages were also recognized such as the need for experience in making engineering judgments, language barrier in accessing foreign information and limitation of resources. Some possible improvements are suggested to overcome these challenges.

  9. EDITORIAL: Slow light Slow light

    NASA Astrophysics Data System (ADS)

    Boyd, Robert; Hess, Ortwin; Denz, Cornelia; Paspalakis, Emmanuel

    2010-10-01

    Research into slow light began theoretically in 1880 with the paper [1] of H A Lorentz, who is best known for his work on relativity and the speed of light. Experimental work started some 60 years later with the work of S L McCall and E L Hahn [2] who explored non-linear self-induced transparency in ruby. This field of research has burgeoned in the last 10 years, starting with the work of L Vestergaard Hau and coworkers on slow light via electromagnetically induced transparency in a Bose-Einstein condensate [3]. Many groups are now able to slow light down to a few metres per second or even stop the motion of light entirely [4]. Today, slow light - or more often `slow and fast light' - has become its own vibrant field with a strongly increasing number of publications. In broad scope, slow light research can be categorized in terms of the sort of physical mechanism used to slow down the light. One sort of slow light makes use of material dispersion. This dispersion can be the natural dispersion of the ordinary refractive index or can be the frequency dependence of some nonlinear optical process, such as electromagnetically induced transparency, coherent population oscillations, stimulated light scattering, or four-wave mixing processes. The second sort of slow light makes use of the wavelength dependence of artificially structured materials, such as photonic crystals, optical waveguides, and collections of microresonators. Material systems in which slow light has been observed include metal vapours, rare-earth-doped materials, Raman and Brillioun gain media, photonic crystals, microresonators and, more recently, metamaterials. A common feature of all of these schemes is the presence of a sharp single resonance or multiple resonances produced by an atomic transition, a resonance in a photonic structure, or in a nonlinear optical process. Current applications of slow light include a series of attractive topics in optical information processing, such as optical data

  10. Study of objective evaluation indicators of 3D visual fatigue based on RDS related tasks

    NASA Astrophysics Data System (ADS)

    Huang, Yi; Liu, Yue; Zou, Bochao; Wang, Yongtian; Cheng, Dewen

    2015-03-01

    Three dimensional (3D) displays have witnessed rapid progress in recent years because of its highly realistic sensation and sense of presence to humanist users. However, the comfort issues of 3D display are often reported and thus restrict its wide applications. In order to study the objective evaluation indicators associated with 3D visual fatigue, an experiment is designed in which subjects are required to accomplish a task realized with random dot stereogram (RDS). The aim of designing the task is to induce 3D visual fatigue of subjects and exclude the impacts of monocular depth cues. The visual acuity, critical flicker frequency (CFF), reaction time and correct rate of subjects during the experiment are recorded and analyzed. Correlation of the experimental data with the subjective evaluation scores is studied to find which indicator is closely related to 3D visual fatigue. Analysis of the experimental data shows that the trends of the correct rate are in line with the result of subjective evaluation.

  11. Macular Degeneration Partnership

    MedlinePlus

    ... Age Related Macular Degeneration) Partnership Listen AMD Month Public Service Announcement To raise awareness of AMD, the Macular Degeneration Partnership (MDP) is distributing a public service announcement (PSA) nationwide. Seen through the eyes of a ...

  12. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  13. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  14. Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS

    PubMed Central

    Wolfson, Marla R.; Wu, Jichuan; Hubert, Terrence L.; Gregory, Timothy J.; Mazela, Jan; Shaffer, Thomas H.

    2013-01-01

    Background Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants. Methods Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination. Results SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or beractant. Conclusion These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant. PMID:22821059

  15. The genetics of age-related macular degeneration.

    PubMed

    Gorin, M B; Breitner, J C; De Jong, P T; Hageman, G S; Klaver, C C; Kuehn, M H; Seddon, J M

    1999-11-03

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  16. A Qualitative Examination of Respondent-Driven Sampling (RDS) Peer Referral Challenges Among Young Transwomen in the San Francisco Bay Area

    PubMed Central

    Cai, Xiang; Wilson, Erin C

    2015-01-01

    Background Efforts have focused on developing innovative recruitment strategies to engage the most marginalized of populations in public health research. Respondent-driven sampling (RDS) has been found to be an effective sampling strategy for hard-to-reach, hidden populations. Though studies have documented RDS peer referral as challenging, literature contextualizing these challenges is scant and rarely do they discuss the role of Internet technologies. Objective The objective of the study was to explore reasons for peer referral challenges in a human immunodeficiency virus (HIV) risk and resilience study among a hidden population of youth, specifically, young transwomen. These findings amplify the unique opportunities Internet technologies bring to public health research and methodology. Methods We conducted focused, semistructured, qualitative interviews with 16 young transwomen to investigate the reasons why youth did or did not refer peers to an RDS study for transwomen ages 16-24 in the San Francisco Bay Area. Qualitative interview data were coded and analyzed using grounded theory. Results Participants discussed specific barriers and facilitators related to four factors that include study design, study implementation, community characteristics, and individual characteristics, which contributed to RDS peer referral challenges. Conclusions Our grounded theory analysis identifies important considerations for future RDS studies with hidden youth populations. Exploring research participants’ experiences is integral in strengthening future epidemiologic research efforts that plan to use RDS to sample and estimate the hidden epidemics among at-risk youth and transgender women. Additionally, Internet technologies and Web-based adaptations offer solutions to traditional RDS peer referral challenges, having the potential to increase accessibility and use among hidden youth populations. PMID:27227143

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

    PubMed

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

    2013-10-15

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

  18. Genome-wide location analysis reveals an important overlap between the targets of the yeast transcriptional regulators Rds2 and Adr1.

    PubMed

    Soontorngun, Nitnipa; Baramee, Sirilak; Tangsombatvichit, Chalinee; Thepnok, Piyasuda; Cheevadhanarak, Supapon; Robert, François; Turcotte, Bernard

    2012-07-13

    Upon glucose depletion, a massive reprogramming of gene expression occurs in the yeast Saccharomyces cerevisiae for the use of alternate carbon sources such as the nonfermentable compounds ethanol and glycerol. This process is mediated by the master kinase Snf1 that controls the activity of various targets including the transcriptional regulators Cat8, Sip4 and Adr1. We have recently identified Rds2 as an additional player in this pathway. Here, we have performed genome-wide location analysis of Rds2 in cells grown in the presence of glycerol. We show that Rds2 binds to promoters of genes involved in gluconeogenesis, the glyoxylate shunt, and the TCA cycle as well as some genes encoding mitochondrial components or some involved in the stress response. Interestingly, we also detected Rds2 at the promoters of SIP4, ADR1 and HAP4 which encodes the limiting subunit of the Hap2/3/4/5 complex, a regulator of respiration. Strikingly, we observed an important overlap between the targets of Rds2 and Adr1. Finally, we provide a model to account for the complex interplay among these transcriptional regulators.

  19. Potent anorexic-like effects of RDS-127 (2-di-n-propylamino-4,7-dimethoxyindane) in the rat: a comparison with other dopamine-receptor agonists.

    PubMed

    Arnerić, S P; Roetker, A; Long, J P

    1982-09-01

    Modification of food intake and motor activity was investigated following administration of amphetamine (AMP), apomorphine (APO) and three novel 2-aminoindanes (2-AI): 2-di-n-propylaminoindane (JPC-60-36), 2-di-n-propylamino-5,6-dimethoxyindane (JPC-211) and 2-di-n-propylamine-4,7-dimethoxyindane (RDS-127). These compounds demonstrated dose- and time-related inhibition of food intake in male rats which were habituated to eating 4 hr each day. The ranked potencies were as follows: RDS-127 greater than AMP = APO greater than JPC-60-36 and JPC-211 was inactive. 2-di-n-Propylamine-4,7-dimethoxyindane (RDS-127) did not increase motor activity in a dose range that Significantly inhibited food intake (66% of control intake with 0.08 mumol/kg). Food intake inhibition was blocked by pimozide, but not by propranolol or phentolamine. The anorectic-like actions of RDS-127 were long-lasting (greater than 4 hr) and RDS-127 was approximately 3-fold more potent than amphetamine or apomorphine in producing increased locomotor activity; the other 2-aminoindanes were less potent in producing hyperactivity. Hyperactivity responses were blocked by pimozide, but not by alpha-methyl-p-tyrosine. These results suggest that 2-aminoindanes may modify motor behaviors, at least in part, via direct stimulation of dopamine receptors. The structure-activity relationships of 2-aminoindanes on locomotor activity and inhibition of food intake are discussed.

  20. Slow Pseudotachylites

    NASA Astrophysics Data System (ADS)

    Pec, M.; Stunitz, H.; Heilbronner, R.

    2011-12-01

    Tectonic pseudotachylites as solidified, friction induced melts are believed to be the only unequivocal evidence for paleo-earthquakes. Earthquakes occur when fast slip (1 - 3 m/s) propagates on a localized failure plane and are always related with stress drops. The mechanical work expended, together with the rock composition and the efficiency of thermal dissipation, controls whether the temperature increase on a localized slip plane will be sufficient to induce fusion. We report the formation of pseudotachylites during steady-state plastic flow at slow bulk shear strain rates (~10^-3 to ~10^-5 /s corresponding to slip rates of ~10^-6 to ~10^-8 m/s) in experiments performed at high confining pressures (500 MPa) and temperatures (300°C) corresponding to a depth of ~15 km. Crushed granitioid rock (Verzasca gneiss), grain size ≤ 200 μm, with 0.2 wt% water added was placed between alumina forcing blocks pre-cut at 45°, weld-sealed in platinum jackets and deformed with a constant displacement rate in a solid medium deformation apparatus (modified Griggs rig). Microstructural observations show the development of a S-C-C' fabric with C' slip zones being the dominant feature. Strain hardening in the beginning of the experiment is accompanied with compaction which is achieved by closely spaced R1 shears pervasively cutting the whole gouge zone and containing fine-grained material (d < 100 nm). The peak strength is achieved at γ ~ 2 at shear stress levels of 1350-1450 MPa when compaction ceases. During further deformation, large local displacements (γ > 10) are localized in less densely spaced, ~10 μm thick C'-C slip zones which develop predominantly in feldspars and often contain micas. In TEM, they appear to have no porosity consisting of partly amorphous material and small crystalline fragments with the average grain size of 20 nm. After the peak strength, the samples weaken by ~20 MPa and continue deforming up to γ ~ 4 without any stress drops. Strain

  1. Pellucid marginal corneal degeneration.

    PubMed

    Krachmer, J H

    1978-07-01

    Pellucid marginal degeneration of the cornea is a bilateral, clear, inferior, peripheral corneal-thinning disorder. Protrusion of the cornea occurs above a band of thinning, which is located 1 to 2 mm from the limbus and measures 1 to 2 mm in width. American ophthalmologists are generally not familiar with the condition because most of the literature concerning pellucid degeneration is European. Four cases are described. This condition is differentiated from other noninflammatory cornel-thinning disorders such as keratoconus, keratoglobus, keratotorus, and posterior keratoconus. It is also differentiated from peripheral corneal disorders associated with inflammation such as Terrien's peripheral corneal degeneration, Mooren's ulcers, and ulcers from connective tissue disease.

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

    SciTech Connect

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

    1995-05-20

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

  3. Double Degenerate Binary Systems

    SciTech Connect

    Yakut, K.

    2011-09-21

    In this study, angular momentum loss via gravitational radiation in double degenerate binary (DDB)systems (NS + NS, NS + WD, WD + WD, and AM CVn) is studied. Energy loss by gravitational waves has been estimated for each type of systems.

  4. Biomechanics of Disc Degeneration

    PubMed Central

    Palepu, V.; Kodigudla, M.; Goel, V. K.

    2012-01-01

    Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the “gold standard” in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population. PMID:22745914

  5. Wet Macular Degeneration

    MedlinePlus

    ... has a hereditary component. Researchers have identified several genes related to developing the condition. Smoking. Smoking cigarettes or being regularly exposed to smoke significantly increases your risk of macular degeneration. Obesity. Research indicates that being obese increases the chance ...

  6. Use of Respondent Driven Sampling (RDS) Generates a Very Diverse Sample of Men Who Have Sex with Men (MSM) in Buenos Aires, Argentina

    PubMed Central

    Carballo-Diéguez, Alex; Balan, Ivan; Marone, Rubén; Pando, María A.; Dolezal, Curtis; Barreda, Victoria; Leu, Cheng-Shiun; Ávila, María Mercedes

    2011-01-01

    Background Prior research focusing on men who have sex with men (MSM) conducted in Buenos Aires, Argentina, used convenience samples that included mainly gay identified men. To increase MSM sample representativeness, we used Respondent Driven Sampling (RDS) for the first time in Argentina. Using RDS, under certain specified conditions, the observed estimates for the percentage of the population with a specific trait are asymptotically unbiased. We describe, the diversity of the recruited sample, from the point of view of sexual orientation, and contrast the different subgroups in terms of their HIV sexual risk behavior. Methodology 500 MSM were recruited using RDS. Behavioral data were collected through face-to-face interviews and Web-based CASI. Conclusion In contrast with prior studies, RDS generated a very diverse sample of MSM from a sexual identity perspective. Only 24.5% of participants identified as gay; 36.2% identified as bisexual, 21.9% as heterosexual, and 17.4% were grouped as “other.” Gay and non-gay identified MSM differed significantly in their sexual behavior, the former having higher numbers of partners, more frequent sexual contacts and less frequency of condom use. One third of the men (gay, 3%; bisexual, 34%, heterosexual, 51%; other, 49%) reported having had sex with men, women and transvestites in the two months prior to the interview. This population requires further study and, potentially, HIV prevention strategies tailored to such diversity of partnerships. Our results highlight the potential effectiveness of using RDS to reach non-gay identified MSM. They also present lessons learned in the implementation of RDS to recruit MSM concerning both the importance and limitations of formative work, the need to tailor incentives to circumstances of the less affluent potential participants, the need to prevent masking, and the challenge of assessing network size. PMID:22102896

  7. Use of respondent driven sampling (RDS) generates a very diverse sample of men who have sex with men (MSM) in Buenos Aires, Argentina.

    PubMed

    Carballo-Diéguez, Alex; Balan, Ivan; Marone, Rubén; Pando, María A; Dolezal, Curtis; Barreda, Victoria; Leu, Cheng-Shiun; Avila, María Mercedes

    2011-01-01

    Prior research focusing on men who have sex with men (MSM) conducted in Buenos Aires, Argentina, used convenience samples that included mainly gay identified men. To increase MSM sample representativeness, we used Respondent Driven Sampling (RDS) for the first time in Argentina. Using RDS, under certain specified conditions, the observed estimates for the percentage of the population with a specific trait are asymptotically unbiased. We describe, the diversity of the recruited sample, from the point of view of sexual orientation, and contrast the different subgroups in terms of their HIV sexual risk behavior. 500 MSM were recruited using RDS. Behavioral data were collected through face-to-face interviews and Web-based CASI. In contrast with prior studies, RDS generated a very diverse sample of MSM from a sexual identity perspective. Only 24.5% of participants identified as gay; 36.2% identified as bisexual, 21.9% as heterosexual, and 17.4% were grouped as "other." Gay and non-gay identified MSM differed significantly in their sexual behavior, the former having higher numbers of partners, more frequent sexual contacts and less frequency of condom use. One third of the men (gay, 3%; bisexual, 34%, heterosexual, 51%; other, 49%) reported having had sex with men, women and transvestites in the two months prior to the interview. This population requires further study and, potentially, HIV prevention strategies tailored to such diversity of partnerships. Our results highlight the potential effectiveness of using RDS to reach non-gay identified MSM. They also present lessons learned in the implementation of RDS to recruit MSM concerning both the importance and limitations of formative work, the need to tailor incentives to circumstances of the less affluent potential participants, the need to prevent masking, and the challenge of assessing network size.

  8. Prospectives for gene therapy of retinal degenerations.

    PubMed

    Thumann, Gabriele

    2012-08-01

    growth factors (VEGF), have been used to prevent the neovascularization that accompanies AMD and DR resulting in the amelioration of vision in a significant number of patients. In animal models it has been shown that transfection of RPE cells with the gene for PEDF and other growth factors can prevent or slow degeneration. A limited number of studies in humans have also shown that transfection of RPE cells in vivo with the gene for PEDF is effective in preventing degeneration and restore vision. Most of these studies have used virally mediated gene delivery with all its accompanying side effects and have not been widely used. New techniques using non-viral protocols that allow efficient delivery and permanent integration of the transgene into the host cell genome offer novel opportunities for effective treatment of retinal degenerations.

  9. Prospectives for Gene Therapy of Retinal Degenerations

    PubMed Central

    Thumann, Gabriele

    2012-01-01

    growth factors (VEGF), have been used to prevent the neovascularization that accompanies AMD and DR resulting in the amelioration of vision in a significant number of patients. In animal models it has been shown that transfection of RPE cells with the gene for PEDF and other growth factors can prevent or slow degeneration. A limited number of studies in humans have also shown that transfection of RPE cells in vivo with the gene for PEDF is effective in preventing degeneration and restore vision. Most of these studies have used virally mediated gene delivery with all its accompanying side effects and have not been widely used. New techniques using non-viral protocols that allow efficient delivery and permanent integration of the transgene into the host cell genome offer novel opportunities for effective treatment of retinal degenerations. PMID:23372421

  10. High-speed real-time animated displays on the ADAGE (trademark) RDS 3000 raster graphics system

    NASA Technical Reports Server (NTRS)

    Kahlbaum, William M., Jr.; Ownbey, Katrina L.

    1989-01-01

    Techniques which may be used to increase the animation update rate of real-time computer raster graphic displays are discussed. They were developed on the ADAGE RDS 3000 graphic system in support of the Advanced Concepts Simulator at the NASA Langley Research Center. These techniques involve the use of a special purpose parallel processor, for high-speed character generation. The description of the parallel processor includes the Barrel Shifter which is part of the hardware and is the key to the high-speed character rendition. The final result of this total effort was a fourfold increase in the update rate of an existing primary flight display from 4 to 16 frames per second.

  11. Involvement of lysosomes in the early stages of axon degeneration.

    PubMed

    Zheng, Jin; Yan, Tingting; Feng, Yan; Zhai, Qiwei

    2010-02-01

    Axon degeneration is a common hallmark of many neurodegenerative diseases, and the underlying mechanism remains largely unknown. Lysosomes are involved in some neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Whether lysosomes are involved in axon degeneration is yet to be elucidated. In this study, we found only about 10% lysosomes remained in axons of cultured superior cervical ganglia (SCGs) after transection for 4h when stained with LysoTracker. Furthermore, we found that lysosomal disruption occurred earlier than morphological changes and loss of mitochondrial membrane potential. In addition, the well-known axon-protective protein Wld(S) delayed injury-induced axon degeneration from both morphological changes and lysosomal disruption. Lysosomal inhibitors including chloroquine and ammonium chloride induced axon degeneration in cultured SCGs, and Wld(S) also slowed down the axon degeneration induced by lysosomal inhibitors. All these data suggest that lysosomal disruption is an early marker of axon degeneration, and inhibition of lysosome induces axon degeneration in a Wld(S)-protectable way. Thus, maintenance of normal lysosomal function might be an important approach to delay axon degeneration in neurodegenerative diseases.

  12. Movement - uncontrolled or slow

    MedlinePlus

    Dystonia; Involuntary slow and twisting movements; Choreoathetosis; Leg and arm movements - uncontrollable; Arm and leg movements - uncontrollable; Slow involuntary movements of large muscle groups; Athetoid movements

  13. Molecular Heterogeneity Within the Clinical Diagnosis of Pericentral Retinal Degeneration

    PubMed Central

    Matsui, Rodrigo; Cideciyan, Artur V.; Schwartz, Sharon B.; Sumaroka, Alexander; Roman, Alejandro J.; Swider, Malgorzata; Huang, Wei Chieh; Sheplock, Rebecca; Jacobson, Samuel G.

    2015-01-01

    Purpose To characterize in detail the phenotype and genotype of patients with pericentral retinal degeneration (PRD). Methods Patients were screened for an annular ring scotoma ranging from 3° to 40° (n = 28, ages 24–71) with kinetic perimetry. All patients had pigmentary retinopathy in the region of the dysfunction. Further studies included cross-sectional and en face imaging, static chromatic perimetry, and electroretinography. Molecular screening was performed. Results Genotypes of 14 of 28 PRD patients were identified: There were mutations in eight different genes previously associated with autosomal dominant or autosomal recessive RDs. Kinetic fields monitored in some patients over years to more than a decade could be stable or show increased extent of the scotoma. Electroretinograms were recordable but with different severities of dysfunction. Patterns of photoreceptor outer nuclear layer (ONL) loss corresponded to the distribution of visual dysfunction. Outer nuclear layer thickness topography and en face imaging indicated that the greatest disease expression was in the area of known highest rod photoreceptor density. Conclusions Molecular heterogeneity was a feature of the PRD phenotype. Many of the molecular causes were also associated with other phenotypes, such as maculopathies, typical retinitis pigmentosa (RP) and cone–rod dystrophy. The pericentral pattern of retinal degeneration is thus confirmed to be an uncommon phenotype of many different genotypes rather than a distinct disease entity. PMID:26393467

  14. Coherent perfect absorption and reflection in slow-light waveguides.

    PubMed

    Gutman, Nadav; Sukhorukov, Andrey A; Chong, Y D; de Sterke, C Martijn

    2013-12-01

    We identify a family of unusual slow-light modes occurring in lossy multimode grating waveguides, for which either the forward or backward mode components, or both, are degenerate. In the fully degenerate case, the response can be modulated between coherent perfect absorption (zero reflection) and perfect reflection by varying the wave amplitudes in a uniform input waveguide. The perfectly absorbed wave has anomalously short absorption length, scaling as the inverse one-third power of the absorptivity.

  15. Neuro-Genetics of Reward Deficiency Syndrome (RDS) as the Root Cause of "Addiction Transfer": A New Phenomenon Common after Bariatric Surgery.

    PubMed

    Blum, Kenneth; Bailey, John; Gonzalez, Anthony M; Oscar-Berman, Marlene; Liu, Yijun; Giordano, John; Braverman, Eric; Gold, Mark

    2011-12-23

    Now after many years of successful bariatric (weight-loss) surgeries directed at the obesity epidemic clinicians are reporting that some patients are replacing compulsive overeating with newly acquired compulsive disorders such as alcoholism, gambling, drugs, and other addictions like compulsive shopping and exercise. This review article explores evidence from psychiatric genetic animal and human studies that link compulsive overeating and other compulsive disorders to explain the phenomenon of addiction transfer. Possibly due to neurochemical similarities, overeating and obesity may act as protective factors reducing drug reward and addictive behaviors. In animal models of addiction withdrawal from sugar induces imbalances in the neurotransmitters, acetylcholine and dopamine, similar to opiate withdrawal. Many human neuroimaging studies have supported the concept of linking food craving to drug craving behavior. Previously our laboratory coined the term Reward Deficiency Syndrome (RDS) for common genetic determinants in predicting addictive disorders and reported that the predictive value for future RDS behaviors in subjects carrying the DRD2 Taq A1 allele was 74%. While poly genes play a role in RDS, we have also inferred that disruptions in dopamine function may predispose certain individuals to addictive behaviors and obesity. It is now known that family history of alcoholism is a significant obesity risk factor. Therefore, we hypothesize here that RDS is the root cause of substituting food addiction for other dependencies and potentially explains this recently described Phenomenon (addiction transfer) common after bariatric surgery.

  16. Neuro-Genetics of Reward Deficiency Syndrome (RDS) as the Root Cause of “Addiction Transfer”: A New Phenomenon Common after Bariatric Surgery

    PubMed Central

    Blum, Kenneth; Bailey, John; Gonzalez, Anthony M; Oscar-Berman, Marlene; Liu, Yijun; Giordano, John; Braverman, Eric; Gold, Mark

    2012-01-01

    Now after many years of successful bariatric (weight-loss) surgeries directed at the obesity epidemic clinicians are reporting that some patients are replacing compulsive overeating with newly acquired compulsive disorders such as alcoholism, gambling, drugs, and other addictions like compulsive shopping and exercise. This review article explores evidence from psychiatric genetic animal and human studies that link compulsive overeating and other compulsive disorders to explain the phenomenon of addiction transfer. Possibly due to neurochemical similarities, overeating and obesity may act as protective factors reducing drug reward and addictive behaviors. In animal models of addiction withdrawal from sugar induces imbalances in the neurotransmitters, acetylcholine and dopamine, similar to opiate withdrawal. Many human neuroimaging studies have supported the concept of linking food craving to drug craving behavior. Previously our laboratory coined the term Reward Deficiency Syndrome (RDS) for common genetic determinants in predicting addictive disorders and reported that the predictive value for future RDS behaviors in subjects carrying the DRD2 Taq A1 allele was 74%. While poly genes play a role in RDS, we have also inferred that disruptions in dopamine function may predispose certain individuals to addictive behaviors and obesity. It is now known that family history of alcoholism is a significant obesity risk factor. Therefore, we hypothesize here that RDS is the root cause of substituting food addiction for other dependencies and potentially explains this recently described Phenomenon (addiction transfer) common after bariatric surgery. PMID:23483116

  17. The Cerebellum and Language: Evidence from Patients with Cerebellar Degeneration

    ERIC Educational Resources Information Center

    Stoodley, Catherine J.; Schmahmann, Jeremy D.

    2009-01-01

    Clinical and imaging studies suggest that the cerebellum is involved in language tasks, but the extent to which slowed language production in cerebellar patients contributes to their poor performance on these tasks is not clear. We explored this relationship in 18 patients with cerebellar degeneration and 16 healthy controls who completed measures…

  18. The Cerebellum and Language: Evidence from Patients with Cerebellar Degeneration

    ERIC Educational Resources Information Center

    Stoodley, Catherine J.; Schmahmann, Jeremy D.

    2009-01-01

    Clinical and imaging studies suggest that the cerebellum is involved in language tasks, but the extent to which slowed language production in cerebellar patients contributes to their poor performance on these tasks is not clear. We explored this relationship in 18 patients with cerebellar degeneration and 16 healthy controls who completed measures…

  19. Striatal degeneration in childhood.

    PubMed Central

    Erdohazi, M; Marshall, P

    1979-01-01

    The clinical features, and the radiological and neuropathological findings of 3 unrelated children with striatal degeneration are presented. In one case the father had recently developed choreiform movements while in the other two the family history was negative for neurological disorders. Two patients had juvenile onset of psychiatric symptoms, seizures, and rigidity. The 3rd child presented with focal seizures at 9 weeks of age. The neuropathological findings are virtually identical in all 3 cases. The classification of striatal degeneration in childhood is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:434899

  20. Constitutive opsin signaling: night blindness or retinal degeneration?

    PubMed

    Lem, Janis; Fain, Gordon L

    2004-04-01

    A subset of genetic mutations in photoreceptor-specific genes results in abnormally prolonged activation of transducin-mediated photosignaling in rod cells. In humans and animal models, these mutations cause visual dysfunctions ranging from a mild stationary night blindness to severe, early-onset retinal degeneration. There are mechanistic differences between mutations causing night blindness and those causing retinal degeneration. Here, we hypothesize that mutations causing continuous activation of the visual cascade as the result, for example, of the inability of the photoreceptor to regenerate rhodopsin, lead to retinal degeneration; those mutations that can terminate signaling, even if only partially and intermittently, slow the rate of degeneration sufficiently to give rise to stationary night blindness. Furthermore, we hypothesize that a prolonged decrease in intracellular calcium concentration resulting from persistent activation is responsible for triggering apoptotic rod-cell death.

  1. [Age-related macular degeneration (AMD)].

    PubMed

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  2. Kraepelin and degeneration theory.

    PubMed

    Hoff, Paul

    2008-06-01

    Emil Kraepelin's contribution to the clinical and scientific field of psychiatry is recognized world-wide. In recent years, however, there have been a number of critical remarks on his acceptance of degeneration theory in particular and on his political opinion in general, which was said to have carried "overtones of proto-fascism" by Michael Shepherd [28]. The present paper discusses the theoretical cornerstones of Kraepelinian psychiatry with regard to their relevance for Kraepelin's attitude towards degeneration theory. This theory had gained wide influence not only in scientific, but also in philosophical and political circles in the last decades of the nineteenth century. There is no doubt that Kraepelin, on the one hand, accepted and implemented degeneration theory into the debate on etiology and pathogenesis of mental disorders. On the other hand, it is not appropriate to draw a simple and direct line from early versions of degeneration theory to the crimes of psychiatrists and politicians during the rule of national socialism. What we need, is a differentiated view, since this will be the only scientific one. Much research needs to be done here in the future, and such research will surely have a significant impact not only on the historical field, but also on the continuous debate about psychiatry, neuroscience and neurophilosophy.

  3. Frontotemporal Lobar Degeneration

    PubMed Central

    Josephs, Keith A.

    2009-01-01

    Synopsis Frontotemporal lobar degeneration (FTLD) is a syndromic diagnosis that encompasses at least three different variants. Imaging modalities are clinically useful in FTLD while pathology remains the gold standard for definitive diagnosis. To date three different genes have been identified that account for FTLD. PMID:17659185

  4. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  5. Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

    PubMed Central

    Cashman, Christopher R.; Höke, Ahmet

    2015-01-01

    Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

  6. Quantum degenerate systems

    SciTech Connect

    Micheli, Fiorenza de; Zanelli, Jorge

    2012-10-15

    A degenerate dynamical system is characterized by a symplectic structure whose rank is not constant throughout phase space. Its phase space is divided into causally disconnected, nonoverlapping regions in each of which the rank of the symplectic matrix is constant, and there are no classical orbits connecting two different regions. Here the question of whether this classical disconnectedness survives quantization is addressed. Our conclusion is that in irreducible degenerate systems-in which the degeneracy cannot be eliminated by redefining variables in the action-the disconnectedness is maintained in the quantum theory: there is no quantum tunnelling across degeneracy surfaces. This shows that the degeneracy surfaces are boundaries separating distinct physical systems, not only classically, but in the quantum realm as well. The relevance of this feature for gravitation and Chern-Simons theories in higher dimensions cannot be overstated.

  7. Frontotemporal Lobar Degeneration

    PubMed Central

    Rabinovici, Gil D.; Miller, Bruce L.

    2010-01-01

    Frontotemporal lobar degeneration (FTLD) is a clinically and pathologically heterogeneous syndrome, characterized by progressive decline in behaviour or language associated with degeneration of the frontal and anterior temporal lobes. While the seminal cases were described at the turn of the 20th century, FTLD has only recently been appreciated as a leading cause of dementia, particularly in patients presenting before the age of 65 years. Three distinct clinical variants of FTLD have been described: (i) behavioural-variant frontotemporal dementia, characterized by changes in behaviour and personality in association with frontal-predominant cortical degeneration; (ii) semantic dementia, a syndrome of progressive loss of knowledge about words and objects associated with anterior temporal neuronal loss; and (iii) progressive nonfluent aphasia, characterized by effortful language output, loss of grammar and motor speech deficits in the setting of left perisylvian cortical atrophy. The majority of pathologies associated with FTLD clinical syndromes include either tau-positive (FTLD-TAU) or TAR DNA-binding protein 43 (TDP-43)-positive (FTLD-TDP) inclusion bodies. FTLD overlaps clinically and pathologically with the atypical parkinsonian disorders corticobasal degeneration and progressive supranuclear palsy, and with amyotrophic lateral sclerosis. The majority of familial FTLD cases are caused by mutations in the genes encoding microtubule-associated protein tau (leading to FTLD-TAU) or progranulin (leading to FTLD-TDP). The clinical and pathologic heterogeneity of FTLD poses a significant diagnostic challenge, and in vivo prediction of underlying histopathology can be significantly improved by supplementing the clinical evaluation with genetic tests and emerging biological markers. Current pharmacotherapy for FTLD focuses on manipulating serotonergic or dopaminergic neurotransmitter systems to ameliorate behavioural or motor symptoms. However, recent advances in FTLD

  8. Cataracts and macular degeneration.

    PubMed

    Shoch, D

    1979-09-01

    The intraocular lens restores general vision and some degree of independence and mobility to patients with dense cataracts and macular degeneration. The patient, however, must be repeatedly warned that fine central vision, particularly reading, will not be possible after the surgery. An aphakic spectacle leaves such patients a narrow band of vision when superimposed over the macular lesion, and contact lenses are too small for the patient to manage insertion without help.

  9. Development of a Reference Data Set (RDS) for dental age estimation (DAE) and testing of this with a separate Validation Set (VS) in a southern Chinese population.

    PubMed

    Jayaraman, Jayakumar; Wong, Hai Ming; King, Nigel M; Roberts, Graham J

    2016-10-01

    Many countries have recently experienced a rapid increase in the demand for forensic age estimates of unaccompanied minors. Hong Kong is a major tourist and business center where there has been an increase in the number of people intercepted with false travel documents. An accurate estimation of age is only possible when a dataset for age estimation that has been derived from the corresponding ethnic population. Thus, the aim of this study was to develop and validate a Reference Data Set (RDS) for dental age estimation for southern Chinese. A total of 2306 subjects were selected from the patient archives of a large dental hospital and the chronological age for each subject was recorded. This age was assigned to each specific stage of dental development for each tooth to create a RDS. To validate this RDS, a further 484 subjects were randomly chosen from the patient archives and their dental age was assessed based on the scores from the RDS. Dental age was estimated using meta-analysis command corresponding to random effects statistical model. Chronological age (CA) and Dental Age (DA) were compared using the paired t-test. The overall difference between the chronological and dental age (CA-DA) was 0.05 years (2.6 weeks) for males and 0.03 years (1.6 weeks) for females. The paired t-test indicated that there was no statistically significant difference between the chronological and dental age (p > 0.05). The validated southern Chinese reference dataset based on dental maturation accurately estimated the chronological age. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  10. Dental age assessment (DAA) of Afro-Trinidadian children and adolescents. Development of a Reference Dataset (RDS) and comparison with Caucasians resident in London, UK.

    PubMed

    Moze, Kevin; Roberts, Graham

    2012-07-01

    The large number of extant Dental Panoramic Tomographs of Afro-Trinidadian subjects were collected and Tooth Development Stages (TDSs) were assessed for each of the 878 radiographs to provide a Reference Dataset (RDS) of Afro-Trinidadian children and adolescents. The values for each of the 256 TDSs present were statistically significantly different from the values for the same TDSs in the UK Caucasian RDS. A validation study of 50 radiographs of Afro-Trinidadian subjects from 24 boys and 26 girls were assessed to enable calculation of the Dental Age (DA). The DA calculated using the UK Caucasian RDS was statistically significantly different from the chronological age. The same radiographs were used to calculate the Age of Attainment of the individual Tooth Development Stages for females and males in both the UK Caucasian subjects, and the Afro-Trinidadians. The majority of these comparisons showed the TDSs in Afro-Trinidadian subjects to develop earlier than the UK Caucasian subjects by approximately 8 months.

  11. Two Ultracool Degenerate Companions

    NASA Astrophysics Data System (ADS)

    Farihi, J.

    2005-07-01

    In the course of an extensive survey for low mass stellar and substellar companions to nearby white dwarfs, two extrememly cool degenerate objects have been discovered. GD 392B is one of only a few known white dwarfs with Teff⪉4000 K and exhibits collision induced absorption in the near infrared tep{far04}. GD 1400B is the second known L dwarf companion to a white dwarf and a possible brown dwarf (Farihi & Christopher 2004). Interested readers should consult the references for a complete description of these two cool objects.

  12. FROM THE HISTORY OF PHYSICS: The extraordinarily beautiful physical principle of thermonuclear charge design (on the occasion of the 50th anniversary of the test of RDS-37 — the first Soviet two-stage thermonuclear charge)

    NASA Astrophysics Data System (ADS)

    Goncharov, German A.

    2005-11-01

    On 22 November 1955, the Semipalatinsk test site saw the test of the first domestic two-stage thermonuclear RDS-37 charge. The charge operation was based on the principle of radiation implosion. The kernel of the principle consists in the radiation generated in a primary A-bomb explosion and confined by the radiation-opaque casing propagating throughout the interior casing volume and flowing around the secondary thermonuclear unit. The secondary unit experiences a strong compression under the irradiation, with a resulting nuclear and thermonuclear explosion. The RDS-37 explosion was the strongest of all those ever realized at the Semipalatinsk test site. It produced an indelible impression on the participants in the test. This document-based paper describes the genesis of the ideas underlying the RDS-37 design and reflects the critical moments in its development. The advent of RDS-37 was an outstanding accomplishment of the scientists and engineers of our country.

  13. AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Gheorghe, Andreea; Mahdi, Labib; Musat, Ovidiu

    2015-01-01

    The objective of our study was to review the current knowledge on Age- Related Macular Degeneration, including pathogenesis, ocular manifestations, diagnosis and ancillary testing. Relevant publications on Age-Related Macular Degeneration that were published until 2014. Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterized by the appearance of drusen in the macula, accompanied by choroidal neovascularization (CNV) or geographic atrophy.

  14. What can we learn about age-related macular degeneration from other retinal diseases?

    PubMed

    Zack, D J; Dean, M; Molday, R S; Nathans, J; Redmond, T M; Stone, E M; Swaroop, A; Valle, D; Weber, B H

    1999-11-03

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  15. Slow and Fast Light

    DTIC Science & Technology

    2001-09-24

    25) where λ is the vacuum wavelength of the radiation. Recent demonstrations of slow light have been enabled by nonlinear optical techniques which can...typical procedure for producing slow light is to make use of electromagnetically induced transparency (EIT), a technique introduced by Harris, Field and... Slow ” and “Fast” Light Robert W. Boyd The Institute of Optics University of Rochester Rochester, New York 14627 USA Daniel J. Gauthier Department of

  16. Apoptosis in human retinal degenerations.

    PubMed

    Xu, G Z; Li, W W; Tso, M O

    1996-01-01

    This paper examined the role of apoptosis in human retinal degenerations including pathologic myopia, age-related macular degeneration, serous retinal detachment, retinal lattice, and paving stone degenerations. Thirty-seven enucleated human eyes with 1 of the above-mentioned retinal degenerations were studied by histopathology and by TdT-mediated biotin-dUTP nicked-end labelling (TUNEL) technique. Tunnel labelling characteristic DNA fragmentation of apoptosis was observed in photoreceptor cells in 2 of the 4 eyes with pathologic myopia and in 4 of 16 eyes with age-related macular degeneration, 2 of which were exudative and 2 of which were atrophic. However, only a few scattered photoreceptor cells were labelled in 4 of 8 eyes with serous retinal detachment secondary to malignant melanoma of the choroid. Moreover, none of the photoreceptors cells in the 4 eyes with retinal lattice degeneration and 6 eyes with retinal paving stone degeneration were labelled. Apoptosis is 1 of the important pathways of photoreceptor cell degeneration in pathologic myopia and age-related macular degeneration.

  17. Electromagnetic wave equations for relativistically degenerate quantum magnetoplasmas.

    PubMed

    Masood, Waqas; Eliasson, Bengt; Shukla, Padma K

    2010-06-01

    A generalized set of nonlinear electromagnetic quantum hydrodynamic (QHD) equations is derived for a magnetized quantum plasma, including collisional, electron spin- 1/2, and relativistically degenerate electron pressure effects that are relevant for dense astrophysical systems, such as white dwarfs. For illustrative purposes, linear dispersion relations are derived for one-dimensional magnetoacoustic waves for a collisionless nonrelativistic degenerate gas in the presence of the electron spin- 1/2 contribution and for magnetoacoustic waves in a plasma containing relativistically degenerate electrons. It is found that both the spin and relativistic degeneracy at high densities tend to slow down the magnetoacoustic wave due to the Pauli paramagnetic effect and relativistic electron mass increase. The present study outlines the theoretical framework for the investigation of linear and nonlinear behaviors of electromagnetic waves in dense astrophysical systems. The results are applied to calculate the magnetoacoustic speeds for both the nonrelativistic and relativistic electron degeneracy cases typical for white dwarf stars.

  18. Electromagnetic wave equations for relativistically degenerate quantum magnetoplasmas

    SciTech Connect

    Masood, Waqas; Eliasson, Bengt; Shukla, Padma K.

    2010-06-15

    A generalized set of nonlinear electromagnetic quantum hydrodynamic (QHD) equations is derived for a magnetized quantum plasma, including collisional, electron spin-(1/2), and relativistically degenerate electron pressure effects that are relevant for dense astrophysical systems, such as white dwarfs. For illustrative purposes, linear dispersion relations are derived for one-dimensional magnetoacoustic waves for a collisionless nonrelativistic degenerate gas in the presence of the electron spin-(1/2) contribution and for magnetoacoustic waves in a plasma containing relativistically degenerate electrons. It is found that both the spin and relativistic degeneracy at high densities tend to slow down the magnetoacoustic wave due to the Pauli paramagnetic effect and relativistic electron mass increase. The present study outlines the theoretical framework for the investigation of linear and nonlinear behaviors of electromagnetic waves in dense astrophysical systems. The results are applied to calculate the magnetoacoustic speeds for both the nonrelativistic and relativistic electron degeneracy cases typical for white dwarf stars.

  19. Current-Drive Efficiency in a Degenerate Plasma

    SciTech Connect

    S. Son and N.J. Fisch

    2005-11-01

    a degenerate plasma, the rates of electron processes are much smaller than the classical model would predict, affecting the efficiencies of current generation by external non-inductive means, such as by electromagnetic radiation or intense ion beams. For electron-based mechanisms, the current-drive efficiency is higher than the classical prediction by more than a factor of 6 in a degenerate hydrogen plasma, mainly because the electron-electron collisions do not quickly slow down fast electrons. Moreover, electrons much faster than thermal speeds are more readily excited without exciting thermal electrons. In ion-based mechanisms of current drive, the efficiency is likewise enhanced due to the degeneracy effects, since the electron stopping power on slow ion beams is significantly reduced.

  20. The Slow Learner.

    ERIC Educational Resources Information Center

    Roucek, Joseph S., Ed.

    Papers on the slow learner treat physical defects and learning abilities, social and economic background as an obstacle to learning, the causes of dropouts and lapses in study, and the limitations and potential of the ungifted. The contribution interest in the slow learner has made to education is discussed; also discussed are problems of the…

  1. Genetics Home Reference: Stargardt macular degeneration

    MedlinePlus

    ... Genetics Home Health Conditions Stargardt macular degeneration Stargardt macular degeneration Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Stargardt macular degeneration is a genetic eye disorder that causes progressive ...

  2. Using the Neuroadaptagen KB200z™ to Ameliorate Terrifying, Lucid Nightmares in RDS Patients: the Role of Enhanced, Brain-Reward, Functional Connectivity and Dopaminergic Homeostasis

    PubMed Central

    McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene; Febo, Marcelo; Demetrovics, Zsolt; Agan, Gozde; Fratantonio, James; Gold, Mark S.

    2015-01-01

    Background Lucid Dreams are a form of dream life, during which the dreamer may be aware that he/she is dreaming, can stop/re-start the dreams, depending on the pleasantness or unpleasant nature of the dream, and experiences the dream as if he/she were fully awake. Depending on their content, they may be pleasant, un-pleasant or terrifying, at least in the context of patients, who also exhibit characteristics of Reward Deficiency Syndrome (RDS) and Posttraumatic Stress Disorder (PTSD). Case Series We present eight clinical cases, with known substance abuse, childhood abuse and diagnosed PTSD/RDS. The administration of a putative dopamine agonist, KB200Z™, was associated with the elimination of unpleasant and/or terrifying, lucid dreams in 87.5% of the cases presented, whereas one very heavy cocaine abuser showed a minimal response. These results required the continuous use of this nutraceutical. The lucid dreams themselves were distinguishable from typical, PTSD nightmares insofar as their content did not appear to reflect a symbolic rendition of an originally-experienced, historical trauma. Each of the cases was diagnosed with a form of RDS, i.e., ADHD, ADD, and/or Tourette’s syndrome. They all also suffered from some form of Post-Traumatic-Stress-Disorder (PTSD) and other psychiatric diagnoses as well. Conclusion The reduction or elimination of terrifying Lucid Dreams seemed to be dependent on KB220Z, whereby voluntary stopping of the agent results in reinstatement of the terrifying non-pleasant nature of the dreams. Following more required research on a much larger population we anticipate confirmation of these seemingly interesting observations. If these results in a small number of patients are indeed confirmed we may have found a frontline solution to a very perplexing and complicated symptom known as lucid dreams. PMID:26065033

  3. Using the Neuroadaptagen KB200z™ to Ameliorate Terrifying, Lucid Nightmares in RDS Patients: the Role of Enhanced, Brain-Reward, Functional Connectivity and Dopaminergic Homeostasis.

    PubMed

    McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene; Febo, Marcelo; Demetrovics, Zsolt; Agan, Gozde; Fratantonio, James; Gold, Mark S

    Lucid Dreams are a form of dream life, during which the dreamer may be aware that he/she is dreaming, can stop/re-start the dreams, depending on the pleasantness or unpleasant nature of the dream, and experiences the dream as if he/she were fully awake. Depending on their content, they may be pleasant, un-pleasant or terrifying, at least in the context of patients, who also exhibit characteristics of Reward Deficiency Syndrome (RDS) and Posttraumatic Stress Disorder (PTSD). We present eight clinical cases, with known substance abuse, childhood abuse and diagnosed PTSD/RDS. The administration of a putative dopamine agonist, KB200Z™, was associated with the elimination of unpleasant and/or terrifying, lucid dreams in 87.5% of the cases presented, whereas one very heavy cocaine abuser showed a minimal response. These results required the continuous use of this nutraceutical. The lucid dreams themselves were distinguishable from typical, PTSD nightmares insofar as their content did not appear to reflect a symbolic rendition of an originally-experienced, historical trauma. Each of the cases was diagnosed with a form of RDS, i.e., ADHD, ADD, and/or Tourette's syndrome. They all also suffered from some form of Post-Traumatic-Stress-Disorder (PTSD) and other psychiatric diagnoses as well. The reduction or elimination of terrifying Lucid Dreams seemed to be dependent on KB220Z, whereby voluntary stopping of the agent results in reinstatement of the terrifying non-pleasant nature of the dreams. Following more required research on a much larger population we anticipate confirmation of these seemingly interesting observations. If these results in a small number of patients are indeed confirmed we may have found a frontline solution to a very perplexing and complicated symptom known as lucid dreams.

  4. Analysis of data collected by RDS among sex workers in 10 Brazilian cities, 2009: estimation of the prevalence of HIV, variance, and design effect.

    PubMed

    Szwarcwald, Célia Landmann; de Souza Júnior, Paulo Roberto Borges; Damacena, Giseli Nogueira; Junior, Aristides Barbosa; Kendall, Carl

    2011-08-01

    Respondent-driven sampling (RDS) is a chain-referral method that is being widely used to recruit most at-risk populations. Because the method is respondent driven, observations are dependent. However, few publications have focused on methodological challenges in the analysis of data collected by RDS. In this article, we propose a method for estimating the variance of the HIV prevalence rate, based on the Markov transition probabilities and within recruitment cluster variation. The method was applied to a female commercial sex workers study carried out in 10 Brazilian cities in 2008. Both the inverse of network size and the size of the city were considered in the estimation of overall sampling weights. The study included a behavior questionnaire and rapid tests for HIV and syphilis. About 2523 interviews were conducted successfully, excluding the seeds. Results show a positive homophily between recruits for those HIV+; HIV- recruiters selected HIV+ recruits 4% of the time; HIV+ recruiters selected other HIV+ recruits 19.6% of the time, about 5 times higher. The prevalence rate was estimated at 4.8% (95% confidence interval: 3.4 to 6.1), and a design effect of 2.63. Using statistical methods for complex sample designs, it was possible to estimate HIV prevalence, standard error, and the design effect analytically. Additionally, the proposed analysis lends itself to logistic regression, permitting multivariate models. The stratification in cities has proved suitable for reducing the effect of design and can be adopted in other RDS studies, provided the weights of the strata are known.

  5. Progressive retinal degeneration in ranch mink.

    PubMed

    Hadlow, W J

    1984-01-01

    Retinal degeneration was prevalent in a large group of sapphire and pastel mink (Mustela vison) kept for studies on slow viral diseases. Nearly 78% of those two to eight years old were affected. The retinopathy was equally common in both sexes but more frequent in sapphires (85%) than in pastels (63%), and it was severe more often in sapphires than in pastels. By light microscopy, the primary change appeared to be progressive degeneration of fully developed photoreceptors, beginning in their outer segments. In many mink, including some younger ones, the rods and cones and outer nuclear layer had disappeared from all but the far periphery of the fundus. The inner retinal layers were spared until late in the disease, and the pigment epithelium remained essentially unchanged. The cause of the retinopathy was not established. It may represent an abiotrophy in which the structural integrity of the photoreceptors began to wane in many mink after they reached two years of age. Apart from reducing visual acuity, the retinopathy has implications for the photoperiodic control of fur growth and reproduction in this highly light-sensitive carnivore.

  6. SARM1 activation triggers axon degeneration locally via NAD⁺ destruction.

    PubMed

    Gerdts, Josiah; Brace, E J; Sasaki, Yo; DiAntonio, Aaron; Milbrandt, Jeffrey

    2015-04-24

    Axon degeneration is an intrinsic self-destruction program that underlies axon loss during injury and disease. Sterile alpha and TIR motif-containing 1 (SARM1) protein is an essential mediator of axon degeneration. We report that SARM1 initiates a local destruction program involving rapid breakdown of nicotinamide adenine dinucleotide (NAD(+)) after injury. We used an engineered protease-sensitized SARM1 to demonstrate that SARM1 activity is required after axon injury to induce axon degeneration. Dimerization of the Toll-interleukin receptor (TIR) domain of SARM1 alone was sufficient to induce locally mediated axon degeneration. Formation of the SARM1 TIR dimer triggered rapid breakdown of NAD(+), whereas SARM1-induced axon destruction could be counteracted by increased NAD(+) synthesis. SARM1-induced depletion of NAD(+) may explain the potent axon protection in Wallerian degeneration slow (Wld(s)) mutant mice. Copyright © 2015, American Association for the Advancement of Science.

  7. Do dopaminergic gene polymorphisms affect mesolimbic reward activation of music listening response? Therapeutic impact on Reward Deficiency Syndrome (RDS).

    PubMed

    Blum, Kenneth; Chen, Thomas J H; Chen, Amanda L H; Madigan, Margaret; Downs, B William; Waite, Roger L; Braverman, Eric R; Kerner, Mallory; Bowirrat, Abdalla; Giordano, John; Henshaw, Harry; Gold, Mark S

    2010-03-01

    affected by an individual's D2 density in the VTA mediated interaction of the NAc. It is therefore hypothesized that carriers of DRD2 A1 allele may respond significantly differently to carriers of the DRD2 A2 genotype. In this regard, carriers of the D2 A1 allele have a blunted response to glucose and monetary rewards. In contrast powerful D2 agonists like bromocryptine show a heightened activation of the reward circuitry only in DRD2 A1 allele carriers. If music causes a powerful activation in spite of the DRD2 A1 allele due to a strong DA neuronal release which subsequently impinges on existing D2 receptors, then it is reasonable to assume that music is a strong indirect D2 agonist (by virtue of DA neuronal release in the NAc) and may have important therapeutic applicability in Reward Deficiency Syndrome (RDS) related behaviors including Substance Use Disorder (SUD). Ross et al. [18] found that music therapy appears to be a novel motivational tool in a severely impaired inpatient sample of patients with co-occurring mental illness and addiction.

  8. Transformer Industry Productivity Slows.

    ERIC Educational Resources Information Center

    Otto, Phyllis Flohr

    1981-01-01

    Annual productivity increases averaged 2.4 percent during 1963-79, slowing since 1972 to 1.5 percent; computer-assisted design and product standardization aided growth in output per employee-hour. (Author)

  9. Transformer Industry Productivity Slows.

    ERIC Educational Resources Information Center

    Otto, Phyllis Flohr

    1981-01-01

    Annual productivity increases averaged 2.4 percent during 1963-79, slowing since 1972 to 1.5 percent; computer-assisted design and product standardization aided growth in output per employee-hour. (Author)

  10. Slow medical education.

    PubMed

    Wear, Delese; Zarconi, Joseph; Kumagai, Arno; Cole-Kelly, Kathy

    2015-03-01

    Slow medical education borrows from other "slow" movements by offering a complementary orientation to medical education that emphasizes the value of slow and thoughtful reflection and interaction in medical education and clinical care. Such slow experiences, when systematically structured throughout the curriculum, offer ways for learners to engage in thoughtful reflection, dialogue, appreciation, and human understanding, with the hope that they will incorporate these practices throughout their lives as physicians. This Perspective offers several spaces in the medical curriculum where slowing down is possible: while reading and writing at various times in the curriculum and while providing clinical care, focusing particularly on conducting the physical exam and other dimensions of patient care. Time taken to slow down in these ways offers emerging physicians opportunities to more fully incorporate their experiences into a professional identity that embodies reflection, critical awareness, cultural humility, and empathy. The authors argue that these curricular spaces must be created in a very deliberate manner, even on busy ward services, throughout the education of physicians.

  11. Imaging frontotemporal lobar degeneration.

    PubMed

    Diehl-Schmid, Janine; Onur, Oezguer A; Kuhn, Jens; Gruppe, Traugott; Drzezga, Alexander

    2014-10-01

    The term frontotemporal lobar degeneration (FTLD) refers to a group of neurodegenerative disorders that target the frontal and temporal lobes. It accounts for approximately 10 % of pathologically confirmed dementias but has been demonstrated to be as prevalent as Alzheimer's disease in patients below the age of 65. The 3 major clinical syndromes associated with FTLD include behavioral variant frontotemporal dementia, semantic and nonfluent variants of primary progressive aphasia. The more recently introduced term logopenic variant appears to represent an atypical form of Alzheimer's disease in the majority of cases. The neuropathology underlying these clinical syndromes is very heterogeneous and does not correlate well with the clinical phenotype. This causes great difficulties in early and reliable diagnosis and treatment of FTLD. However, significant advances have been made in recent years via the application of magnetic resonance imaging and positron emission tomography imaging methods as biomarkers. The current review aims to provide a synopsis on the value of magnetic resonance imaging-based and molecular imaging procedures in FTLD.

  12. [Age related macular degeneration].

    PubMed

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  13. Degenerate Quantum Gases of Strontium

    NASA Astrophysics Data System (ADS)

    Stellmer, Simon; Schreck, Florian; Killian, Thomas C.

    2014-03-01

    Degenerate quantum gases of alkaline-earth-like elements open new opportunities in research areas ranging from molecular physics to the study of strongly correlated systems. These experiments exploit the rich electronic structure of these elements, which is markedly different from the one of other species for which quantum degeneracy has been attained. Specifically, alkaline-earth-like atoms, such as strontium, feature metastable triplet states, narrow intercombination lines, and a nonmagnetic, closed-shell ground state. This review covers the creation of quantum degenerate gases of strontium and the first experiments performed with this new system. It focuses on laser-cooling and evaporation schemes, which enable the creation of Bose-Einstein condensates and degenerate Fermi gases of all strontium isotopes, and shows how they are used for the investigation of optical Feshbach resonances, the study of degenerate gases loaded into an optical lattice, as well as the coherent creation of Sr2 molecules.

  14. Age-Related Macular Degeneration

    MedlinePlus

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  15. Slow light beam splitter.

    PubMed

    Xiao, Yanhong; Klein, Mason; Hohensee, Michael; Jiang, Liang; Phillips, David F; Lukin, Mikhail D; Walsworth, Ronald L

    2008-07-25

    We demonstrate a slow light beam splitter using rapid coherence transport in a wall-coated atomic vapor cell. We show that particles undergoing random and undirected classical motion can mediate coherent interactions between two or more optical modes. Coherence, written into atoms via electromagnetically induced transparency using an input optical signal at one transverse position, spreads out via ballistic atomic motion, is preserved by an antirelaxation wall coating, and is then retrieved in outgoing slow light signals in both the input channel and a spatially-separated second channel. The splitting ratio between the two output channels can be tuned by adjusting the laser power. The slow light beam splitter may improve quantum repeater performance and be useful as an all-optical dynamically reconfigurable router.

  16. [Pathogenesis and treatment of slow transit constipation].

    PubMed

    Zhang, Dongxu; Zhu, Anlong

    2016-12-25

    Slow transit constipation (STC) is generally considered as a complex idiopathic disease affected by multiple factors synergistically. Primarily caused by the condition of gut dysmotility, the transit of intestinal contents turned so slow that the moisture absorption increases, defecation frequency decreases, bowel movement is weakened or even disappeared with or without abdominal distension, dry and hard stool. Its etiology and pathogenesis remains unclear.Recently some researches reported the pathogenesis may be associated with the changes of the enteric nervous system (ENS), such as the change or degeneration of intestinal nerve cells, gut glial cell damage and neurotransmitter changes. Besides, intestinal myopathy, ICC reduction, immune factors, endocrine factors, laxative, mental psychological factors, diet and exercise habits may also be associated with the occurrence and aggravation of STC. The current understanding of STC mechanism can not meet the needs of clinical diagnosis and treatment. Conservative treatment is the main treatment of STC nowadays. For those receiving normative medical treatment but with little effect, surgery is necessary. "Jingling procedure" and "antiperistaltic anastomosis" can both get good efficacy. Treatment aiming at causes of disease will be uncovered as the development of the researches on the pathogenesis and treatment of slow transit constipation.

  17. [Neurophysiology of corticobasal degeneration].

    PubMed

    Tyvaert, L; Cassim, F; Derambure, P; Defebvre, L

    2007-09-01

    Corticobasal degeneration (CBD) is a neurodegenerative disorder of mid- to late-adult life. From a clinical standpoint, CBD is characterized by (i) an insidious onset and a slowly progressing, unilateral, levodopa-unresponsive parkinsonian syndrome with dystonia or myoclonus and (ii) cerebral features such as apraxia, alien limb phenomena and cortical sensory loss. Decisive clinical diagnostic criteria are not available and thus a neuropathological study remains essential for accurate CBD diagnosis. Consequently, additional non-clinical criteria must be identified in order to improve diagnosis while patients are still alive. Electrophysiological exploration can yield functional information on a number of brain structures (both cortical and sub-cortical) involved in CBD. The disorder features a specific cortical (frontoparietal) alteration which could help with differential diagnoses for other extrapyramidal syndromes. Hence, exploration of a patient's myoclonus can provide some specific arguments for CBD. Indeed, myoclonus displays a number of clinical and electromyographical characteristics which are consistent with a cortical origin (a shorter latency of the cortical C response, for example). However, some typical cortical features are missing (giant somesthesic evoked potentials, and cortical potentials preceding myoclonus in jerk-locked back-averaging studies). Some authors explain these abnormalities in terms of a sub-cortical origin for the myoclonus. The frontoparietal alteration in CBD has also been explored in studies of oculomotor movement. Indeed, asymmetric lengthening of the lateral ocular saccade latency argues more in favour of CBD than progressive supranuclear palsy. Moreover, cognitive function is also compromised in the early stages of CBD, although it is sometimes difficult to distinguish between CBD, PSP and frontotemporal dementia. Studying cognitive potentials enables one to confirm subcorticofrontal abnormalities and to dissociate CBD

  18. Psychomotor Slowing in Schizophrenia

    PubMed Central

    Morrens, Manuel; Hulstijn, Wouter; Sabbe, Bernard

    2007-01-01

    Psychomotor slowing (PS) is a cluster of symptoms that was already recognized in schizophrenia by its earliest investigators. Nevertheless, few studies have been dedicated to the clarification of the nature and the role of the phenomenon in this illness. Moreover, slowed psychomotor functioning is often not clearly delineated from reduced processing speed. The current, first review of all existing literature on the subject discusses the key findings. Firstly, PS is a clinically observable feature that is most frequently established by neuropsychological measures assessing speed of fine movements such as writing or tasks that require rapid fingertip manipulations or the maintenance of maximal speed over brief periods of time in manual activities. Moreover, the slowed performance on the various psychomotor measures has been demonstrated independent of medication and has also been found to be associated with negative symptoms and, to a lesser extent, with positive and depressive symptoms. Importantly, performance on the psychomotor tasks proved related to the patients' social, clinical, and functional outcomes. Several imaging studies showed slowed performance to coincide with dopaminergic striatal activity. Finally, conventional neuroleptics do not improve the patients' PS symptoms, in contrast to the atypical agents that do seem to produce modestly improving effects. PMID:17093141

  19. Age-related macular degeneration

    PubMed Central

    Coleman, Hanna R; Chan, Chi-Chao; Ferris, Frederick L; Chew, Emily Y

    2008-01-01

    Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration. PMID:19027484

  20. Nonlinear Electromagnetic Waves in a Degenerate Electron-Positron Plasma

    NASA Astrophysics Data System (ADS)

    El-Labany, S. K.; El-Taibany, W. F.; El-Samahy, A. E.; Hafez, A. M.; Atteya, A.

    2015-08-01

    Using the reductive perturbation technique (RPT), the nonlinear propagation of magnetosonic solitary waves in an ultracold, degenerate (extremely dense) electron-positron (EP) plasma (containing ultracold, degenerate electron, and positron fluids) is investigated. The set of basic equations is reduced to a Korteweg-de Vries (KdV) equation for the lowest-order perturbed magnetic field and to a KdV type equation for the higher-order perturbed magnetic field. The solutions of these evolution equations are obtained. For better accuracy and searching on new features, the new solutions are analyzed numerically based on compact objects (white dwarf) parameters. It is found that including the higher-order corrections results as a reduction (increment) of the fast (slow) electromagnetic wave amplitude but the wave width is increased in both cases. The ranges where the RPT can describe adequately the total magnetic field including different conditions are discussed.

  1. [Cell Transplantation in Age-related Macular Degeneration].

    PubMed

    Kirchhof, Bernd

    2017-09-01

    Robert Machemer offers a surgical approach to age-related macular degeneration with his retinal rotation. There is already considerable experimental and clinical knowledge available in Europe and the US on transplantation techniques for age-related macular degeneration. On average, initial visual acuity can be preserved. When photodynamic therapy was standard for exudative AMD, transplantation was superior. Photodynamic therapy could not stop, but was instead able to slow down visual loss. Currently, VEGF-blocker therapy has priority, because the visual acuity can be improved. However, this advantage does not last much longer than two years. Therefore, in the future, transplantation with new cells and less surgical risk may be reconsidered. At present, homologous RPE stem cells show promising results. They may be delivered as "sheets" or as single cells. For dry AMD only, a prophylactic approach seems reasonable, because, thus far, we are unable to reverse the atrophy on the retinal side. Georg Thieme Verlag KG Stuttgart · New York.

  2. Genotrim, a DNA-customized nutrigenomic product, targets genetic factors of obesity: hypothesizing a dopamine-glucose correlation demonstrating reward deficiency syndrome (RDS).

    PubMed

    Blum, Kenneth; Chen, Thomas J H; Meshkin, Brian; Downs, B William; Gordon, Cory A; Blum, Seth; Mangucci, Julie F; Braverman, Eric R; Arcuri, Vanessa; Deutsch, Roger; Pons, Manuel-Martinez-

    2007-01-01

    Obesity is the second largest cause of preventable death in the United States. Historically, obesity was considered a behavioral problem that could be simply addressed with behavioral modifications in diet and exercise. As scientific advancements have demonstrated in other neurological healthcare conditions such as alcoholism, there are important biological and genetic components that limit the efficacy of behavioral adjustments alone. In light of data suggesting frequent co-morbidities to obesity, including diabetes mellitus, atherosclerosis, osteoporosis, and potentially others, we hypothesize that the biologic and genetic factors, synergistically with behavioral modifications, must be addressed to adequately treat this disease. We hypothesize that one such genetic factor that influences behavior and thus obesity is a predisposition to glucose craving and the overall effect of dopaminergic activity in the reward center of the brain. This defect drives individuals to engage in activities of behavioral excess, which will increase brain dopamine function, for which we have created the term reward deficiency syndrome (RDS) to categorize such biological influences on behavior. Consuming large quantities of alcohol or carbohydrates (carbohydrate bingeing) stimulates the brain's production of and utilization of dopamine. So too does the intake of crack/cocaine and the abuse of nicotine. We are proposing that a novel approach to nutritional supplementation may be required to target the RDS role in obesity. In this regard, Genotrim, a DNA based customized nutraceutical has been designed and is currently under investigation in several clinical studies. This is the first hypothesis paper whereby this new paradigm shift in thinking about obesity is presented.

  3. Nonlinear electromagnetic perturbations in a degenerate ultrarelativistic electron-positron plasma.

    PubMed

    El-Taibany, W F; Mamun, A A

    2012-02-01

    Nonlinear propagation of fast and slow magnetosonic perturbation modes in an ultrarelativistic, ultracold, degenerate (extremely dense) electron positron (EP) plasma (containing ultrarelativistic, ultracold, degenerate electron and positron fluids) has been investigated by the reductive perturbation method. The Alfvén wave velocity is modified due to the presence of the enthalpy correction in the fluid equations of motion. The degenerate EP plasma system (under consideration) supports the Korteweg-de Vries (KdV) solitons, which are associated with either fast or slow magnetosonic perturbation modes. It is found that the ultrarelativistic model leads to compressive (rarefactive) electromagnetic solitons corresponding to the fast (slow) wave mode. There are certain critical angles, θ(c), at which no soliton solution is found corresponding to the fast wave mode. For the slow mode, the magnetic-field intensity affects both the soliton amplitude and width. It is also illustrated that the basic features of the electromagnetic solitary structures, which are found to exist in such a degenerate EP plasma, are significantly modified by the effects of enthalpy correction, electron and positron degeneracy, magnetic-field strength, and the relativistic effect. The applications of the results in a pair-plasma medium, which occurs in many astrophysical objects (e.g., pulsars, white dwarfs, and neutron stars) are briefly discussed.

  4. Ion acoustic solitons in dense magnetized plasmas with nonrelativistic and ultrarelativistic degenerate electrons and positrons

    SciTech Connect

    Sadiq, Safeer; Mahmood, S.; Haque, Q.; Ali, Munazza Zulfiqar

    2014-09-20

    The propagation of electrostatic waves in a dense magnetized electron-positron-ion (EPI) plasma with nonrelativistic and ultrarelativistic degenerate electrons and positrons is investigated. The linear dispersion relation is obtained for slow and fast electrostatic waves in the EPI plasma. The limiting cases for ion acoustic wave (slow) and ion cyclotron wave (fast) are also discussed. Using the reductive perturbation method, two-dimensional propagation of ion acoustic solitons is found for both the nonrelativistic and ultrarelativistic degenerate electrons and positrons. The effects of positron concentration, magnetic field, and mass of ions on ion acoustic solitons are shown in numerical plots. The proper form of Fermi temperature for nonrelativistic and ultrarelativistic degenerate electrons and positrons is employed, which has not been used in earlier published work. The present investigation is useful for the understanding of linear and nonlinear electrostatic wave propagation in the dense magnetized EPI plasma of compact stars. For illustration purposes, we have applied our results to a pulsar magnetosphere.

  5. Quantum Degenerate Gases of Strontium

    NASA Astrophysics Data System (ADS)

    Desalvo, Brian; Martinez de Escobar, Natali; Mickelson, Pacal; Yan, Mi; Killian, Thomas

    2010-03-01

    We have produced quantum degenerate gases of three of the four stable isotopes of strontium. Using two-stage laser trapping and cooling followed by direct evaporative cooling in a far-off- resonance optical dipole trap (ODT), a stable Bose-Einstein Condensate (BEC) of ^84Sr is formed. Via dual species trapping and sympathetic cooling in an ODT, an attractive BEC of ^88Sr is created, as well as a degenerate Fermi gas of ^87Sr. Differences in the evaporation scheme used to reach degeneracy for each isotope will be presented as well as the varied dynamics of the gases.

  6. Imaging geographic atrophy in age-related macular degeneration.

    PubMed

    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.

  7. A gene affecting Wallerian nerve degeneration maps distally on mouse chromosome 4.

    PubMed Central

    Lyon, M F; Ogunkolade, B W; Brown, M C; Atherton, D J; Perry, V H

    1993-01-01

    When a nerve axon is cut or crushed, the nerve fibers in the distal part of the axon, separated from the cell body, undergo a form of spontaneous degeneration, known as Wallerian degeneration. A substrain of the mouse inbred strain C57BL, known as C57BL/Ola, carries a mutant form of a gene involved in Wallerian degeneration in the peripheral and central nervous systems, and in retrograde degeneration of retinal ganglion cells. Wallerian degeneration in this substrain is abnormally slow. Previously the defect had been shown to be due to an autosomal dominant gene. The locus has been given the name and symbol Wallerian degeneration Wld, with the mutant allele Wlds (Wallerian degeneration-slow). The Wld locus has now been mapped, by using conventional and molecular markers, to the distal end of chromosome 4, near the locus of pronatriodilatin (Pnd). The order of loci (with recombination distances in centimorgans, cM) is cen-D4Mit11-8.9 +/- 1.7 cM-Fuca-2.5 +/- 0.93 cM-Akp-2-3.2 +/- 1.1 cM-D4Mit48-3.5 +/- 1.1 cM-(Wld, Pnd, D4Mit49)-0.71 +/- 0.50 cM-(Eno-1, D4Mit33)-1.4 +/- 0.70 cM-D4Mit42-2.5 +/- 0.93 cM-D4Smh6b. The information on the position of the Wld locus should be valuable in further characterization of this gene involved in nerve degeneration and regeneration. PMID:8415768

  8. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Ataxias and Cerebellar or Spinocerebellar Degeneration

    MedlinePlus

    ... underlying cause of the degeneration. Many ataxias are hereditary and are classified by chromosomal location and pattern ... underlying cause of the degeneration. Many ataxias are hereditary and are classified by chromosomal location and pattern ...

  10. Quantum gravity slows inflation

    SciTech Connect

    Tsamis, N.C. |; Woodard, R.P.

    1996-02-01

    We consider the quantum gravitational back-reaction on an initially inflating, homogeneous and isotropic universe whose topology is T{sup 3} {times} {Re}. Although there is no secular effect at one loop, an explicit calculation shows that two-loop processes act to slow the rate of expansion by an amount which becomes non-pertubatively large at late times. By exploiting Feynman`s tree theorem we show that all higher loops act in the same sense. 18 refs., 1 fig.

  11. Go, Slow, and Whoa Foods

    MedlinePlus

    ... quick tips for seasonal health, safety and fun Go, Slow, and Whoa Foods Past Issues / Summer 2007 ... of California and Flaghouse, Inc. 2002 Food Group GO Almost anytime foods SLOW Sometimes foods WHOA Once ...

  12. Slow Transit Constipation.

    PubMed

    Wald, Arnold

    2002-08-01

    The diagnosis of slow transit functional constipation is based upon diagnostic testing of patients with idiopathic constipation who responded poorly to conservative measures such as fiber supplements, fluids, and stimulant laxatives. These tests include barium enema or colonoscopy, colonic transit of radio-opaque markers, anorectal manometry, and expulsion of a water-filled balloon. Plain abdominal films can identify megacolon, which can be further characterized by barium or gastrografin studies. Colonic transit of radio-opaque markers identifies patients with slow transit with stasis of markers in the proximal colon. However, anorectal function should be characterized to exclude outlet dysfunction, which may coexist with colonic inertia. Because slow colonic transit is defined by studies during which patients consume a high-fiber diet, fiber supplements are generally not effective, nor are osmotic laxatives that consist of unabsorbed sugars. Stimulant laxatives are considered first-line therapy, although studies often show a diminished colonic motor response to such agents. There is no evidence to suggest that chronic use of such laxatives is harmful if they are used two to three times per week. Polyethylene glycol with or without electrolytes may be useful in a minority of patients, often combined with misoprostol. I prefer to start with misoprostol 200 mg every other morning and increase to tolerance or efficacy. I see no advantage in prescribing misoprostol on a TID or QID basis or even daily because it increases cramping unnecessarily. This drug is not acceptable in young women who wish to become pregnant. An alternative may be colchicine, which is reported to be effective when given as 0.6 mg TID. Long-term efficacy has not been studied. Finally, biofeedback is a risk-free approach that has been reported as effective in approximately 60% of patients with slow transit constipation in the absence of outlet dysfunction. Although difficult to understand

  13. Phenotypic variety in the presentation of frontotemporal lobar degeneration.

    PubMed

    Shinagawa, Shunichiro

    2013-04-01

    Frontotemporal lobar degeneration (FTLD) is a heterogeneous syndrome characterized by a progressive decline in behaviour or language associated with degeneration of the frontal and anterior temporal lobes. FTLD can be classified into three clinical syndromes based on the early and predominant symptoms: behavioural variant frontotemporal dementia (bvFTD); semantic dementia (SD); and progressive non-fluent aphasia (PNFA). Patients with bvFTD present with marked changes in personality and behaviour such as disinhibition, apathy, loss of sympathy, compulsive behaviours, hyperorality. Neuroimaging studies have highlighted frontal atrophy, hypometabolism and hypoperfusion. SD is characterized by a fluent anomic aphasia and behavioural changes with degeneration of the anterior temporal lobes. Patients with left-sided SD present with progressive loss of word knowledge and meaning about words, objects and concepts. Patients with PNFA present slow, effortful speech, impaired production and comprehension of grammar. PNFA is associated with atrophy, hypometabolism and hypoperfusion of the left perisylvian area. However, overlap between the syndromes can occur, particularly later in the course. In the absence of definitive biomarkers, the diagnosis is dependent on clinical symptoms. A new diagnostic criterion of bvFTD was published in 2011. Identification of the syndrome's core symptoms is important in clinical diagnosis.

  14. Light scattering of degenerate fermions

    NASA Astrophysics Data System (ADS)

    Aubin, S.; Leblanc, L. J.; Myrskog, S.; Extavour, M. H. T.; McKay, D.; Stummer, A.; Thywissen, J. H.

    2006-05-01

    We report on progress in measuring the suppression of resonant light scattering in a gas of degenerate fermions. A gas of trapped degenerate fermions is expected to exhibit narrower optical linewidths and longer excited state lifetimes than single atoms when the Fermi energy is larger than the photon recoil energy [1-3]. In this case, the number of available states into which a scattered atom can recoil is significantly reduced due to the filling of the Fermi sea. We produce a degenerate gas of 4x10^4 ultra-cold fermionic ^40K atoms by sympathetic cooling with bosonic ^87Rb in a micro-magnetic chip trap. The atoms can then be loaded into a tight dipole trap just above the surface of the chip and probed with a near resonance laser pulse. [1] Th. Busch, J. R. Anglin, J. I. Cirac, and P. Zoller, Europhys. Lett. 44, 1 (1998). [2] B. DeMarco and D. S. Jin, Phys. Rev. A 58, R4267 (1998). [3] J. Javanainen and J. Ruostekosky, Phys. Rev. A 52, 3033 (1995). Work supported by NSERC, CFI, OIT, Research Corporation, and PRO.

  15. General Pathophysiology in Retinal Degeneration

    PubMed Central

    Wert, Katherine J.; Lin, Jonathan H.; Tsang, Stephen H.

    2015-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  16. Radial keratotomy associated endothelial degeneration

    PubMed Central

    Moshirfar, Majid; Ollerton, Andrew; Semnani, Rodmehr T; Hsu, Maylon

    2012-01-01

    Purpose To describe the presentation and clinical course of eyes with a history of radial keratotomy (RK) and varying degrees of endothelial degeneration. Methods Retrospective case series were used. Results Thirteen eyes (seven patients) were identified with clinical findings of significant guttata and a prior history of RK. The mean age of presentation for cornea evaluation was 54.3 years (range: 38–72 years), averaging 18.7 years (range: 11–33 years) after RK. The presentation of guttata varied in degree from moderate to severe. Best corrected visual acuity (BCVA) ranged from 20/25 to 20/80. All patients had a history of bilateral RK, except one patient who did not develop any guttata in the eye without prior RK. No patients reported a family history of Fuch’s Dystrophy. One patient underwent a penetrating keratoplasty in one eye and a Descemet’s stripping automated endothelial keratoplasty (DSAEK) in the other eye. Conclusions RK may induce a spectrum of endothelial degeneration. In elderly patients, the findings of guttata may signify comorbid Fuch’s dystrophy in which RK incisions could potentially hasten endothelial decomposition. In these select patients with stable cornea topography and prior RK, DSAEK may successfully treat RK endothelial degeneration. PMID:22347792

  17. Radial keratotomy associated endothelial degeneration.

    PubMed

    Moshirfar, Majid; Ollerton, Andrew; Semnani, Rodmehr T; Hsu, Maylon

    2012-01-01

    To describe the presentation and clinical course of eyes with a history of radial keratotomy (RK) and varying degrees of endothelial degeneration. Retrospective case series were used. Thirteen eyes (seven patients) were identified with clinical findings of significant guttata and a prior history of RK. The mean age of presentation for cornea evaluation was 54.3 years (range: 38-72 years), averaging 18.7 years (range: 11-33 years) after RK. The presentation of guttata varied in degree from moderate to severe. Best corrected visual acuity (BCVA) ranged from 20/25 to 20/80. All patients had a history of bilateral RK, except one patient who did not develop any guttata in the eye without prior RK. No patients reported a family history of Fuch's Dystrophy. One patient underwent a penetrating keratoplasty in one eye and a Descemet's stripping automated endothelial keratoplasty (DSAEK) in the other eye. RK may induce a spectrum of endothelial degeneration. In elderly patients, the findings of guttata may signify comorbid Fuch's dystrophy in which RK incisions could potentially hasten endothelial decomposition. In these select patients with stable cornea topography and prior RK, DSAEK may successfully treat RK endothelial degeneration.

  18. Slow Scan Telemedicine

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Originally developed under contract for NASA by Ball Bros. Research Corporation for acquiring visual information from lunar and planetary spacecraft, system uses standard closed circuit camera connected to a device called a scan converter, which slows the stream of images to match an audio circuit, such as a telephone line. Transmitted to its destination, the image is reconverted by another scan converter and displayed on a monitor. In addition to assist scans, technique allows transmission of x-rays, nuclear scans, ultrasonic imagery, thermograms, electrocardiograms or live views of patient. Also allows conferencing and consultation among medical centers, general practitioners, specialists and disease control centers. Commercialized by Colorado Video, Inc., major employment is in business and industry for teleconferencing, cable TV news, transmission of scientific/engineering data, security, information retrieval, insurance claim adjustment, instructional programs, and remote viewing of advertising layouts, real estate, construction sites or products.

  19. Slowing of Vortex Rings

    NASA Astrophysics Data System (ADS)

    Donnelly, Russell; Bolster, Diogo; Hershberger, Robert

    2008-11-01

    We have investigated the slowing of vortex rings in water which are created with very thin cores. We find that these rings propagate with no measurable change in diameter or core size. The drag appears to be the result of viscous forces on the core. A simple model for this drag describes experimental data in terms of a drag coefficient, which depends only on Reynolds number. Barenghi's group at Newcastle found that the translational velocity of a ring in an inviscid fluid perturbed by Kelvin waves decreases with increasing amplitude of Kelvin waves. This suggests that the velocity of vortex rings in a viscous fluid may well depend on the amplitude of Kelvin waves at the time of formation. Rings with substantial amplitude of Kelvin waves will be expected to move more slowly than rings with little or no Kelvin wave amplitude. We present experimental data confirming this suggestion.

  20. Slow-walking inflation

    SciTech Connect

    Erdmenger, Johanna; Halter, Sebastian; Núñez, Carlos; Tasinato, Gianmassimo E-mail: s.halter@physik.uni-muenchen.de E-mail: gianmassimo.tasinato@port.ac.uk

    2013-01-01

    We propose a new model of slow-roll inflation in string cosmology, based on warped throat supergravity solutions displaying 'walking' dynamics, i.e. the coupling constant of the dual gauge theory slowly varies over a range of energy scales. The features of the throat geometry are sourced by a rich field content, given by the dilaton and RR and NS fluxes. By considering the motion of a D3-brane probe in this geometry, we are able to analytically calculate the brane potential in a physically interesting regime. This potential has an inflection point: in its proximity we realize a model of inflation lasting sixty e-foldings, and whose robust predictions are in agreement with current observations. We are also able to interpret some of the most interesting aspects of this scenario in terms of the properties of the QFT dual theory.

  1. Slow change deafness.

    PubMed

    Neuhoff, John G; Wayand, Joseph; Ndiaye, Mamoudou C; Berkow, Ann B; Bertacchi, Breanna R; Benton, Catherine A

    2015-05-01

    In four experiments, we demonstrated a new phenomenon called "slow-change deafness." In Experiment 1 we presented listeners with continuous speech that changed three semitones in pitch over time, and we found that nearly 50 % failed to notice the change. Experiments 2 and 3 replicated the finding, demonstrated that the changes in the stimuli were well above threshold, and showed that when listeners were alerted to the possibility of a change, detection rates improved dramatically. Experiment 4 showed that increasing the magnitude of the change that occurred in the stimulus decreased the rate of change deafness. Our results are consistent with previous work that had shown that cueing listeners to potential auditory changes can significantly reduce change deafness. These findings support an account of change deafness that is dependent on both the magnitude of a stimulus change and listener expectations.

  2. Axonal Degeneration in Retinal Ganglion Cells Is Associated with a Membrane Polarity-Sensitive Redox Process

    PubMed Central

    Catrinescu, Maria-Magdalena; Binan, Loïc; Costantino, Santiago

    2017-01-01

    Axonal degeneration is a pathophysiological mechanism common to several neurodegenerative diseases. The slow Wallerian degeneration (WldS) mutation, which results in reduced axonal degeneration in the central and peripheral nervous systems, has provided insight into a redox-dependent mechanism by which axons undergo self-destruction. We studied early molecular events in axonal degeneration with single-axon laser axotomy and time-lapse imaging, monitoring the initial changes in transected axons of purified retinal ganglion cells (RGCs) from wild-type and WldS rat retinas using a polarity-sensitive annexin-based biosensor (annexin B12-Cys101,Cys260-N,N′-dimethyl-N-(iodoacetyl)-N′-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) ethylenediamine). Transected axons demonstrated a rapid and progressive change in membrane phospholipid polarity, manifested as phosphatidylserine externalization, which was significantly delayed and propagated more slowly in axotomized WldS RGCs compared with wild-type axons. Delivery of bis(3-propionic acid methyl ester)phenylphosphine borane complex, a cell-permeable intracellular disulfide-reducing drug, slowed the onset and velocity of phosphatidylserine externalization in wild-type axons significantly, replicating the WldS phenotype, whereas extracellular redox modulation reversed the WldS phenotype. These findings are consistent with an intra-axonal redox mechanism for axonal degeneration associated with the initiation and propagation of phosphatidylserine externalization after axotomy. SIGNIFICANCE STATEMENT Axonal degeneration is a neuronal process independent of somal apoptosis, the propagation of which is unclear. We combined single-cell laser axotomy with time-lapse imaging to study the dynamics of phosphatidylserine externalization immediately after axonal injury in purified retinal ganglion cells. The extension of phosphatidylserine externalization was slowed and delayed in Wallerian degeneration slow (WldS) axons and this phenotype could

  3. Can ageing be slowed?

    PubMed Central

    Gaman, L; Stoian, I; Atanasiu, V

    2011-01-01

    Redox metabolism has long been considered to play important roles in aging and the development of age-related diseases. Both dietary and pharmacological manipulations of redox metabolism have been associated with the extension of lifespan. Increasing new evidence s also suggests that the process of aging may derive from imperfect clearance of oxidatively damaged material. The accumulation of this molecular “garbage”, relatively indigestible, further hinders cellular functions, induces progressive failure of maintenance and repair and increases the probability of death. One important trend in anti–aging strategy is, therefore, to prevent or even revert the accumulation of these oxidatively altered molecules by stimulating the maintenance and repair systems through hormesis. A promising approach for slowing down ageing and achieving a healthy senescence is represented by repeated exposure to various mild stresses (caloric restriction, moderate exercise, nutritional or pharmacological hormetins). This article reviews the potential therapeutic tools available to date for increasing longevity and obtaining and successful ageing from the redox and hormetic perspective. PMID:22514565

  4. Slowing Ocean Acidification

    NASA Astrophysics Data System (ADS)

    Bravo, A.

    2016-12-01

    Currently our ocean's pH is 8.1, a decrease from 8.2 in the past 200 years since the beginning of the industrial revolution. The ocean absorbs about a third of the carbon dioxide (CO2) from the atmosphere, which is helpful to us, since reducing the amount of CO2 in the atmosphere shows global warming. However, what is the impact of all that CO2 on the ocean? I evaluated the effect of acidic water on bivalves, and found that the shells were broken down with exposure to increased acidity. I am concerned that continued ocean acidification will impact organisms that are unable to adapt to the changing ocean chemistry. While the US currently invests in alternative forms of energy including solar and wind, approximately 66% of our energy comes from sources that are releasing CO2 into the atmosphere. I want to explore the potential of wave energy as another form of renewable energy. When wind blows over the surface of the ocean, it creates a wave. Could this wave energy be a consistent clean energy source? Could a strategy to slow and reverse ocean acidification be found in the ocean?

  5. Slow wave sleep dreaming.

    PubMed

    Cavallero, C; Cicogna, P; Natale, V; Occhionero, M; Zito, A

    1992-12-01

    Fifty volunteers slept two nonconsecutive nights in a sleep laboratory under electropolygraphic control. They were awakened for one report per night. Awakenings were made, in counterbalanced order, from slow wave sleep (SWS--stage 3-4 and stage 4) and rapid eye movement (REM) sleep. Following dream reporting, subjects were asked to identify memory sources of their dream imagery. Two independent judges reliably rated mentation reports for temporal units and for several content and structural dimensions. The same judges also categorized memory sources as autobiographical episodes, abstract self-references, or semantic knowledge. We found that REM reports were significantly longer than SWS reports. Minor content SWS-REM differences were also detected. Moreover, semantic knowledge was more frequently mentioned as a dream source for REM than for SWS dream reports. These findings are interpreted as supporting the hypothesis that dreaming is a continuous process that is not unique to REM sleep. Different levels of engagement of the cognitive system are responsible for the few SWS-REM differences that have been detected.

  6. Slow frictional waves

    NASA Astrophysics Data System (ADS)

    Viswanathan, Koushik; Sundaram, Narayan; Chandrasekar, Srinivasan

    Stick-slip, manifest as intermittent tangential motion between two dry solid surfaces, is a friction instability that governs diverse phenomena from automobile brake squeals to earthquakes. We show, using high-speed in situ imaging of an adhesive polymer interface, that low velocity stick-slip is fundamentally of three kinds, corresponding to passage of three different surface waves -- separation pulses, slip pulses and the well-known Schallamach waves. These waves, traveling much slower than elastic waves, have clear distinguishing properties. Separation pulses and Schallamach waves involve local interface separation, and propagate in opposite directions while slip pulses are characterized by a sharp stress front and do not display any interface detachment. A change in the stick-slip mode from separation to slip pulse is effected simply by increasing the normal force. Together, these three waves constitute all possible stick-slip modes in adhesive friction and are shown to have direct analogues in muscular locomotory waves in soft bodied invertebrates. A theory for slow wave propagation is also presented which is capable of explaining the attendant interface displacements, velocities and stresses.

  7. Gravity slows light

    NASA Astrophysics Data System (ADS)

    O'Sullivan, Ian

    2014-03-01

    The speed of light is measured as a constant number of metres per second. However, a meter is a measure of how far light travels in a second. That is, light always travels as far as it does in a second every second. This is a circular definition. When measured against other things, light speed must change. Gravity is usually described as a consequence of a curve in spacetime. The word ``space'' has two distinct meanings. In geometry, space is a continuous area. In relativity, ``space'' refers exclusively to geometric spaces measured with light. ``Time'' in a relativistic sense also refers exclusively to the passage of time as measured against light. So a curve in spacetime (a relativistic concept) is a gradual deviation in the thing we use to measure geometric spaces and the passage of time, i.e. the speed of light. I show how Newtonian gravity can explain observable phenomena if the speed of light is inversely proportional to the strength of the gravitational field. For example, we would also expect light to refract as it changes speed passing near massive bodies. Boundary conditions are also discussed, for example, very high gravity will slow light to a stop, making it impossible to measure anything against light, giving a gravitational singularity.

  8. EPA Slow in Controlling PCBs.

    DTIC Science & Technology

    1981-12-30

    SIANOARDS- 1963 A BY THE U.S. GENERAL ACCOUNTING OFFICE SReport To The Administrator ~Environmental Protection Agency EPA Slow In Controlling PC;s In 1976 the...Congress required that the Envi- ronmental Protection Agency control the wide- ly used chemicals, polychlorinated biphenyls D T IC (PCBs). Slow in...parties. Sincerely yours, Henry Eschwege Director I I " V . I GENERAL ACCOUNTING OFFICE EPA SLOW IN CONTROLLING PCBs REPORT TO TME ADMINISTRATOR

  9. Slow Speed Machining of Titanium

    DTIC Science & Technology

    1981-10-01

    MRL-R-833 SLOW SPEED MACHINING OF TITANIUM D.M. Turley Approved for Public Release I -J C) COMMONWEALTH OF AUSTRALIA 1981 OCTOBER, 1981 82ോ 20 059...DEPARTMENT OF DEFENCE MATERIALS RESEARCH LABORATORIES REPORT MRL-R-833 SLOW SPEED MACHINING OF TITANIUM D.M. Turley ABSTRACT Catastrophic-shear type...MRL-R-833 b. Title in isolation: UNCLASSIFIED c. Report Number: MRL-R-833 c. Abstract in isolation: UNCLASSIFIED 3. TITLE: SLOW SPEED MACHINING OF

  10. Age-related macular degeneration

    PubMed Central

    Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

    2011-01-01

    Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

  11. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.

  12. Degeneration of a Nonrecombining Chromosome

    NASA Astrophysics Data System (ADS)

    Rice, William R.

    1994-01-01

    Comparative studies suggest that sex chromosomes begin as ordinary autosomes that happen to carry a major sex determining locus. Over evolutionary time the Y chromosome is selected to stop recombining with the X chromosome, perhaps in response to accumulation of alleles beneficial to the heterogametic but harmful to the homogametic sex. Population genetic theory predicts that a nonrecombining Y chromosome should degenerate. Here this prediction is tested by application of specific selection pressures to Drosophila melanogaster populations. Results demonstrate the decay of a nonrecombining, nascent Y chromosome and the capacity for recombination to ameliorate such decay.

  13. Mathematical glimpse on the Y chromosome degeneration

    NASA Astrophysics Data System (ADS)

    Lobo, M. P.

    2006-04-01

    The Y chromosomes are genetically degenerate and do not recombine with their matching partners X. Non-recombination of XY pairs has been pointed out as the key factor for the degeneration of the Y chromosome. The aim here is to show that there is a mathematical asymmetry in sex chromosomes which leads to the degeneration of Y chromosomes even in the absence of XX and XY recombination. A model for sex-chromosome evolution in a stationary regime is proposed. The consequences of their asymmetry are analyzed and lead us to a couple of conclusions. First, Y chromosome degeneration shows up sqrt{2} more often than X chromosome degeneration. Second, if nature prohibits female mortalities from beeing exactly 50%, then Y chromosome degeneration is inevitable.

  14. Slow light and slow acoustic phonons in optophononic resonators

    NASA Astrophysics Data System (ADS)

    Villafañe, V.; Soubelet, P.; Bruchhausen, A. E.; Lanzillotti-Kimura, N. D.; Jusserand, B.; Lemaître, A.; Fainstein, A.

    2016-11-01

    Slow and confined light have been exploited in optoelectronics to enhance light-matter interactions. Here we describe the GaAs/AlAs semiconductor microcavity as a device that, depending on the excitation conditions, either confines or slows down both light and optically generated acoustic phonons. The localization of photons and phonons in the same place of space amplifies optomechanical processes. Picosecond laser pulses are used to study through time-resolved reflectivity experiments the coupling between photons and both confined and slow acoustic phonons when the laser is tuned either with the cavity (confined) optical mode or with the stop-band edge (slow) optical modes. A model that fully takes into account the modified propagation of the acoustic phonons and light in these resonant structures is used to describe the laser detuning dependence of the coherently generated phonon spectra and amplitude under these different modes of laser excitation. We observe that confined light couples only to confined mechanical vibrations, while slow light can generate both confined and slow coherent vibrations. A strong enhancement of the optomechanical coupling using confined photons and vibrations, and also with properly designed slow photon and phonon modes, is demonstrated. The prospects for the use of these optoelectronic devices in confined and slow optomechanics are addressed.

  15. [Pathogenesis of age-related macular degeneration].

    PubMed

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  16. Safranal, a Saffron Constituent, Attenuates Retinal Degeneration in P23H Rats

    PubMed Central

    Esquiva, Gema; Martín-Nieto, José; Pinilla, Isabel; Cuenca, Nicolás

    2012-01-01

    Saffron, an extract from Crocus sativus, has been largely used in traditional medicine for its antiapoptotic and anticarcinogenic properties. In this work, we investigate the effects of safranal, a component of saffron stigmas, in attenuating retinal degeneration in the P23H rat model of autosomal dominant retinitis pigmentosa. We demonstrate that administration of safranal to homozygous P23H line-3 rats preserves both photoreceptor morphology and number. Electroretinographic recordings showed higher a- and b-wave amplitudes under both photopic and scotopic conditions in safranal-treated versus non-treated animals. Furthermore, the capillary network in safranal-treated animals was preserved, unlike that found in untreated animals. Our findings indicate that dietary supplementation with safranal slows photoreceptor cell degeneration and ameliorates the loss of retinal function and vascular network disruption in P23H rats. This work also suggests that safranal could be potentially useful to retard retinal degeneration in patients with retinitis pigmentosa. PMID:22900092

  17. Safranal, a saffron constituent, attenuates retinal degeneration in P23H rats.

    PubMed

    Fernández-Sánchez, Laura; Lax, Pedro; Esquiva, Gema; Martín-Nieto, José; Pinilla, Isabel; Cuenca, Nicolás

    2012-01-01

    Saffron, an extract from Crocus sativus, has been largely used in traditional medicine for its antiapoptotic and anticarcinogenic properties. In this work, we investigate the effects of safranal, a component of saffron stigmas, in attenuating retinal degeneration in the P23H rat model of autosomal dominant retinitis pigmentosa. We demonstrate that administration of safranal to homozygous P23H line-3 rats preserves both photoreceptor morphology and number. Electroretinographic recordings showed higher a- and b-wave amplitudes under both photopic and scotopic conditions in safranal-treated versus non-treated animals. Furthermore, the capillary network in safranal-treated animals was preserved, unlike that found in untreated animals. Our findings indicate that dietary supplementation with safranal slows photoreceptor cell degeneration and ameliorates the loss of retinal function and vascular network disruption in P23H rats. This work also suggests that safranal could be potentially useful to retard retinal degeneration in patients with retinitis pigmentosa.

  18. A comparison of two interventions for HHHFNC in preterm infants weighing 1,000 to 1,500 g in the recovery period of newborn RDS

    PubMed Central

    Sadeghnia, Alireza; Badiei, Zohre; Talakesh, Hassan

    2014-01-01

    Background: Nasal cannula, beside administering low-flow therapy, showed the capability for the administration of continuous positive airway pressure (CPAP) through high-flow nasal cannula (HFNC). Meeting specific physical criteria of 100% relative humidity (RH) and temperature of 37°C are the basic interventional requirements to administer oxygen for the newborns through a nasal cannula. Recently, two systems, MR850 and PMH7000, received the Food and Drug Administration (FDA) approval to administer heated, humidified HFNC (HHHFNC). These systems are evaluated in this study based on their humidifying and heating capabilities. Materials and Methods: This study was done as an RCT on newborns weighing 1,000 to 1,500 g recovering from respiratory distress syndrome (RDS) while nCPAP was administered at CDP = 4 cmH2O, Fio2 <30%. Patients were randomized to two groups of 35 receiving HHHFNC after treatment with nCPAP, with one group using MR850 humidifier and the other PMH7000. The patients were compared according to the duration of HHHFNC administration, repeated need for nCPAP respiratory support, the need for invasive ventilation, apnea, chronic lung disease (CLD), nasal trauma, RH, and temperature of the gases. Results: The average time of support with HHHNFC did not show any significant difference in the two groups. There was no significant difference between the groups in the need for nCPAP, invasive ventilation, apnea, nasal trauma, and CLD. The difference in the levels of average temperature and humidity was significant (P value <0.001). Conclusion: Although the records of temperature and RH in the PMH7000 system was lower than the records from the MR850 system, no clinical priority was observed for respiratory support with HHHNFC in the two systems. PMID:25250286

  19. Slow-release fertilizers 101

    Treesearch

    Robin Rose

    2002-01-01

    Slow release fertilizers have been in common use within the horticultural industry for decades. Probably the mostly commonly heard of product is Scott's Osmocote which has been around for a quite a long time. However, some time ago slow release fertilizers moved out of the potted greenhouse environment and onto golf courses, suburban lawns and bushes, and orchards...

  20. Stepwise relaxation and stochastic precession in degenerate oscillators dispersively coupled to particles

    NASA Astrophysics Data System (ADS)

    Rhén, Christin; Isacsson, Andreas

    2017-09-01

    By numerical integration, we study the relaxation dynamics of degenerate harmonic oscillator modes dispersively coupled to particle positions. Depending on whether the effective inertial potential induced by the oscillators keeps the particles confined or if the particle trajectories traverse the system, the local oscillator energy dissipation rate changes drastically. The inertial trapping, release, and retrapping of particles result in a characteristic stepwise relaxation process, with alternating regions of fast and slow dissipation. To demonstrate this phenomenon we consider first a one-dimensional minimal prototype model which displays these characteristics. We then treat the effect of dispersive interaction in a model corresponding to an adsorbate diffusing on a circular membrane interacting with its three lowest vibrational modes. In the latter model, stepwise relaxation appears only in the presence of thermal noise, which also causes a slow-in-time stochastic precession of the mixing angle between the degenerate eigenmodes.

  1. Inflammatory profiles in canine intervertebral disc degeneration.

    PubMed

    Willems, Nicole; Tellegen, Anna R; Bergknut, Niklas; Creemers, Laura B; Wolfswinkel, Jeannette; Freudigmann, Christian; Benz, Karin; Grinwis, Guy C M; Tryfonidou, Marianna A; Meij, Björn P

    2016-01-13

    Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs. PGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples. PGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the

  2. Exact propagators for some degenerate hyperbolic operators

    NASA Astrophysics Data System (ADS)

    Beals, Richard; Kannai, Yakar

    2006-10-01

    Exact propagators are obtained for the degenerate second order hyperbolic operators ∂2 t - t 2 l Δ x , l=1,2,..., by analytic continuation from the degenerate elliptic operators ∂2 t + t 2 l Δ x . The partial Fourier transforms are also obtained in closed form, leading to integral transform formulas for certain combinations of Bessel functions and modified Bessel functions.

  3. The molecular basis of intervertebral disc degeneration.

    PubMed

    Kepler, Christopher K; Ponnappan, Ravi K; Tannoury, Chadi A; Risbud, Marakand V; Anderson, David G

    2013-03-01

    Intervertebral disc (IVD) degeneration remains a clinically important condition for which treatment is costly and relatively ineffective. The molecular basis of degenerative disc disease has been an intense focus of research recently, which has greatly increased our understanding of the biology underlying this process. To review the current understanding of the molecular basis of disc degeneration. Review article. A literature review was performed to identify recent investigations and current knowledge regarding the molecular basis of IVD degeneration. The unique structural requirements and biochemical properties of the disc contribute to its propensity toward degeneration. Mounting evidence suggests that genetic factors account for up to 75% of individual susceptibility to IVD degeneration, far more than the environmental factors such as occupational exposure or smoking that were previously suspected to figure prominently in this process. Decreased extracellular matrix production, increased production of degradative enzymes, and increased expression of inflammatory cytokines contribute to the loss of structural integrity and accelerate IVD degeneration. Neurovascular ingrowth occurs, in part, because of the changing degenerative phenotype. A detailed understanding of the biology of IVD degeneration is essential to the design of therapeutic solutions to treat degenerative discs. Although significant advances have been made in explaining the biologic mediators of disc degeneration, the inhospitable biochemical environment of the IVD remains a challenging environment for biological therapies. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... To Protect Against Macular Degeneration Jan 27, 2016 Eye Exercises May Improve Vision Around Blind Spot Sep 29, 2015 Could Stem Cells Cure Blindness Caused by Macular Degeneration? Sep 29, 2015 Fighting the Signs of Aging? Don’t Forget the Eyes Sep 11, ... Follow The Academy Professionals: Education ...

  5. Kinetics of degenerate atomic gases

    NASA Astrophysics Data System (ADS)

    Geist, W.; You, L.; Kennedy, T. A. B.

    1998-05-01

    Using the Uehling-Uhlenbeck, or quantum Boltzmann equation, we discuss the kinetics and evaporative cooling of quantum degenerate gases confined in magnetic traps with cylindrical symmetry. We study the full nonergodic time evolution and compare with results obtained by making the ergodic or continuum energy approximation(C. W. Gardiner, P. Zoller, R. J. Ballagh, M. J. Davis, ``Quantum kinetic theory. Simulation of the quantum Boltzmann master equation'', Phys. Rev. A 56), 575 (1997).. We report evidence of strongly non-ergodic distribution functions, whose relaxation times do not coincide with other characteristic timescales, but depend on trap anisotropy. We also report our study of condensate growth which exhibits the same qualitative behaviour as observed in a recent experiment(H. J. Miesner, D. M. Stamper, M. R. Andrews, D. S. Durfee, S. Inouve, W. Ketterle, ``Bosonic stimulation in the formation of a Bose-Einstein condensate'', (preprint).). Preliminary results for sympathetic cooling of fermions by bosons will also be presented.

  6. Regularized degenerate multi-solitons

    NASA Astrophysics Data System (ADS)

    Correa, Francisco; Fring, Andreas

    2016-09-01

    We report complex {P}{T} -symmetric multi-soliton solutions to the Korteweg de-Vries equation that asymptotically contain one-soliton solutions, with each of them possessing the same amount of finite real energy. We demonstrate how these solutions originate from degenerate energy solutions of the Schrödinger equation. Technically this is achieved by the application of Darboux-Crum transformations involving Jordan states with suitable regularizing shifts. Alternatively they may be constructed from a limiting process within the context Hirota's direct method or on a nonlinear superposition obtained from multiple Bäcklund transformations. The proposed procedure is completely generic and also applicable to other types of nonlinear integrable systems.

  7. Degenerate doping of metallic anodes

    DOEpatents

    Friesen, Cody A; Zeller, Robert A; Johnson, Paul B; Switzer, Elise E

    2015-05-12

    Embodiments of the invention relate to an electrochemical cell comprising: (i) a fuel electrode comprising a metal fuel, (ii) a positive electrode, (iii) an ionically conductive medium, and (iv) a dopant; the electrodes being operable in a discharge mode wherein the metal fuel is oxidized at the fuel electrode and the dopant increases the conductivity of the metal fuel oxidation product. In an embodiment, the oxidation product comprises an oxide of the metal fuel which is doped degenerately. In an embodiment, the positive electrode is an air electrode that absorbs gaseous oxygen, wherein during discharge mode, oxygen is reduced at the air electrode. Embodiments of the invention also relate to methods of producing an electrode comprising a metal and a doped metal oxidation product.

  8. Neural reprogramming in retinal degenerations

    PubMed Central

    Marc, Robert E.; Jones, Bryan W.; Anderson, James R.; Kinard, Krista; Marshak, David W.; Wilson, John H.; Wensel, Theodore; Lucas, Robert J.

    2008-01-01

    Purpose Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. We sought to explore the functional expression of ionotropic (iGluR) and group III, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degenerations. Methods Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degenerations and a sample of human RP. Results After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, while amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the numbers of bipolar cells expressing functional iGluRs was double that of normal retina. Conclusions RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some non-glutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late-RP photoreceptor transplant attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function. PMID:17591910

  9. Clinicopathological correlations in corticobasal degeneration.

    PubMed

    Lee, Suzee E; Rabinovici, Gil D; Mayo, Mary Catherine; Wilson, Stephen M; Seeley, William W; DeArmond, Stephen J; Huang, Eric J; Trojanowski, John Q; Growdon, Matthew E; Jang, Jung Y; Sidhu, Manu; See, Tricia M; Karydas, Anna M; Gorno-Tempini, Maria-Luisa; Boxer, Adam L; Weiner, Michael W; Geschwind, Michael D; Rankin, Katherine P; Miller, Bruce L

    2011-08-01

    To characterize cognitive and behavioral features, physical findings, and brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS) with known histopathology. We reviewed clinical and magnetic resonance imaging data in all patients evaluated at our center with either an autopsy diagnosis of CBD (n = 18) or clinical CBS at first presentation with known histopathology (n = 40). Atrophy patterns were compared using voxel-based morphometry. CBD was associated with 4 clinical syndromes: progressive nonfluent aphasia (n = 5), behavioral variant frontotemporal dementia (n = 5), executive-motor (n = 7), and posterior cortical atrophy (n = 1). Behavioral or cognitive problems were the initial symptoms in 15 of 18 patients; less than half exhibited early motor findings. Compared to controls, CBD patients showed atrophy in dorsal prefrontal and perirolandic cortex, striatum, and brainstem (p < 0.001 uncorrected). The most common pathologic substrates for clinical CBS were CBD (35%), Alzheimer disease (AD, 23%), progressive supranuclear palsy (13%), and frontotemporal lobar degeneration (FTLD) with TDP inclusions (13%). CBS was associated with perirolandic atrophy irrespective of underlying pathology. In CBS due to FTLD (tau or TDP), atrophy extended into prefrontal cortex, striatum, and brainstem, whereas in CBS due to AD, atrophy extended into temporoparietal cortex and precuneus (p < 0.001 uncorrected). Frontal lobe involvement is characteristic of CBD, and in many patients frontal, not parietal or basal ganglia, symptoms dominate early stage disease. CBS is driven by medial perirolandic dysfunction, but this anatomy is not specific to a single underlying histopathology. Antemortem prediction of CBD will remain challenging until clinical features of CBD are redefined, and sensitive, specific biomarkers are identified. Copyright © 2011 American Neurological Association.

  10. Clinicopathological correlations in corticobasal degeneration

    PubMed Central

    Lee, Suzee E.; Rabinovici, Gil D.; Mayo, Mary Catherine; Wilson, Stephen M.; Seeley, William W.; DeArmond, Stephen J.; Huang, Eric J.; Trojanowski, John Q.; Growdon, Matthew E.; Jang, Jung Y.; Sidhu, Manu; See, Tricia M.; Karydas, Anna M.; Gorno-Tempini, Maria-Luisa; Boxer, Adam L.; Weiner, Michael W.; Geschwind, Michael D.; Rankin, Katherine P.; Miller, Bruce L.

    2011-01-01

    Objective To characterize cognitive and behavioral features, physical findings and brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS) with known histopathology. Methods We reviewed clinical and MRI data in all patients evaluated at our center with either an autopsy diagnosis of CBD (n=18) or clinical CBS at first presentation with known histopathology (n=40). Atrophy patterns were compared using voxel-based morphometry. Results CBD was associated with four clinical syndromes: progressive nonfluent aphasia (5), behavioral variant frontotemporal dementia (5), executive-motor (7), and posterior cortical atrophy (1). Behavioral or cognitive problems were the initial symptoms in 15/18 patients; less than half exhibited early motor findings. Compared to controls, CBD patients showed atrophy in dorsal prefrontal and peri-rolandic cortex, striatum and brainstem (p<0.001 uncorrected). The most common pathologic substrates for clinical CBS were CBD (35%), Alzheimer’s disease (AD, 23%), progressive supranuclear palsy (13%), and frontotemporal lobar degeneration (FTLD) with TDP inclusions (13%). CBS was associated with perirolandic atrophy irrespective of underlying pathology. In CBS due to FTLD (tau or TDP), atrophy extended into prefrontal cortex, striatum and brainstem, while in CBS due to AD, atrophy extended into temporoparietal cortex and precuneus (p<0.001 uncorrected). Interpretation Frontal lobe involvement is characteristic of CBD, and in many patients frontal, not parietal or basal ganglia symptoms, dominate early-stage disease. CBS is driven by medial peri-rolandic dysfunction, but this anatomy is not specific to one single underlying histopathology. Antemortem prediction of CBD will remain challenging until clinical features of CBD are redefined, and sensitive, specific biomarkers are identified. PMID:21823158

  11. Acute Axonal Degeneration Drives Development of Cognitive, Motor, and Visual Deficits after Blast-Mediated Traumatic Brain Injury in Mice.

    PubMed

    Yin, Terry C; Voorhees, Jaymie R; Genova, Rachel M; Davis, Kevin C; Madison, Ashley M; Britt, Jeremiah K; Cintrón-Pérez, Coral J; McDaniel, Latisha; Harper, Matthew M; Pieper, Andrew A

    2016-01-01

    Axonal degeneration is a prominent feature of many forms of neurodegeneration, and also an early event in blast-mediated traumatic brain injury (TBI), the signature injury of soldiers in Iraq and Afghanistan. It is not known, however, whether this axonal degeneration is what drives development of subsequent neurologic deficits after the injury. The Wallerian degeneration slow strain (WldS) of mice is resistant to some forms of axonal degeneration because of a triplicated fusion gene encoding the first 70 amino acids of Ufd2a, a ubiquitin-chain assembly factor, that is linked to the complete coding sequence of nicotinamide mononucleotide adenylyltransferase 1 (NMAT1). Here, we demonstrate that resistance of WldS mice to axonal degeneration after blast-mediated TBI is associated with preserved function in hippocampal-dependent spatial memory, cerebellar-dependent motor balance, and retinal and optic nerve-dependent visual function. Thus, early axonal degeneration is likely a critical driver of subsequent neurobehavioral complications of blast-mediated TBI. Future therapeutic strategies targeted specifically at mitigating axonal degeneration may provide a uniquely beneficial approach to treating patients suffering from the effects of blast-mediated TBI.

  12. Acute Axonal Degeneration Drives Development of Cognitive, Motor, and Visual Deficits after Blast-Mediated Traumatic Brain Injury in Mice

    PubMed Central

    Voorhees, Jaymie R.; Genova, Rachel M.; Britt, Jeremiah K.; McDaniel, Latisha; Harper, Matthew M.

    2016-01-01

    Abstract Axonal degeneration is a prominent feature of many forms of neurodegeneration, and also an early event in blast-mediated traumatic brain injury (TBI), the signature injury of soldiers in Iraq and Afghanistan. It is not known, however, whether this axonal degeneration is what drives development of subsequent neurologic deficits after the injury. The Wallerian degeneration slow strain (WldS) of mice is resistant to some forms of axonal degeneration because of a triplicated fusion gene encoding the first 70 amino acids of Ufd2a, a ubiquitin-chain assembly factor, that is linked to the complete coding sequence of nicotinamide mononucleotide adenylyltransferase 1 (NMAT1). Here, we demonstrate that resistance of WldS mice to axonal degeneration after blast-mediated TBI is associated with preserved function in hippocampal-dependent spatial memory, cerebellar-dependent motor balance, and retinal and optic nerve–dependent visual function. Thus, early axonal degeneration is likely a critical driver of subsequent neurobehavioral complications of blast-mediated TBI. Future therapeutic strategies targeted specifically at mitigating axonal degeneration may provide a uniquely beneficial approach to treating patients suffering from the effects of blast-mediated TBI. PMID:27822499

  13. Slow Earthquakes Triggered by Typhoons

    NASA Astrophysics Data System (ADS)

    Liu, C.; Linde, A. T.; Sacks, I. S.

    2006-12-01

    Taiwan experiences very high deformation rates, particularly along its eastern margins. To investigate this region, we have started (in 2003) to install several small networks of Sacks-Evertson strainmeters. The initial data from all sites show characteristics of good quality: tidal signals with very high signal to noise ratio and large (~10,000 counts on 24 bit ADC system) amplitudes; strains trending into contraction with rates that decrease exponentially with time and earthquakes clearly recorded. Additionally the instruments have recorded a number of slow strain changes with durations ranging from about an hour up to a few days; we interpret these signals in terms of slow earthquakes. All of the slow events identified to date occur at the times of typhoons passing over or very close to the study area, but not all typhoons are associated with slow strain events (9 typhoons in 2004 were accompanied by 5 slow events). Seismicity for the area deliniates a roughly north-south striking steeply dipping (to the west) zone with reverse slip; the shallowest extent of the zone is just inland. We look for source solutions consistent with that tectonic setting. The slow events exhibit a considerable range of amplitude and complexity; small, short amplitude events have a quite simple and smooth waveform; the longest (2 days) and largest (100 to 350 nanostrain at 3 sites) has waveforms with a lot of structure. The similarity among the stations (located in an ~isosceles triangular array with spacing ~10 km and 4 km) is indicative of rupture propagation of a slow slip source (equivalent magnitude about 5). We are able to match the essential character of the data with a very simple model of a downward propagating line source with uniform slip; the largest slow event appears to be comprised of 3 sub-events all starting at a depth of ~3 km with the final sub-event propagating to a depth ~10 km. Typhoon activity produces a large increase in short period (~sec) energy so it is not

  14. Active cortical innervation protects striatal neurons from slow degeneration in culture.

    PubMed

    Fishbein, Ianai; Segal, Menahem

    2011-03-01

    Spiny striatal GABAergic neurons receive most of their excitatory input from the neocortex. In culture, striatal neurons form inhibitory connections, but the lack of intrinsic excitatory afferents prevents the development of spontaneous network activity. Addition of cortical neurons to the striatal culture provides the necessary excitatory input to the striatal neurons, and in the presence of these neurons, striatal cultures do express spontaneous network activity. We have confirmed that cortical neurons provide excitatory drive to striatal neurons in culture using paired recording from cortical and striatal neurons. In the presence of tetrodotoxin (TTX), which blocks action potential discharges, the connections between cortical and striatal neurons are still formed, and in fact synaptic currents generated between them when TTX is removed are far larger than in control, undrugged cultures. Interestingly, the continuous presence of TTX in the co-culture caused striatal cell death. These observations indicate that the mere presence of cortical neurons is not sufficient to preserve striatal neurons in culture, but their synchronous activity, triggered by cortical excitatory synapses, is critical for the maintenance of viability of striatal neurons. These results have important implications for understanding the role of activity in neurodegenerative diseases of the striatum.

  15. Wallerian degeneration of zebrafish trigeminal axons in the skin is required for regeneration and developmental pruning

    PubMed Central

    Martin, Seanna M.; O'Brien, Georgeann S.; Portera-Cailliau, Carlos; Sagasti, Alvaro

    2010-01-01

    Fragments of injured axons that detach from their cell body break down by the molecularly regulated process of Wallerian degeneration (WD). Although WD resembles local axon degeneration, a common mechanism for refining neuronal structure, several previously examined instances of developmental pruning were unaffected by WD pathways. We used laser axotomy and time-lapse confocal imaging to characterize and compare peripheral sensory axon WD and developmental pruning in live zebrafish larvae. Detached fragments of single injured axon arbors underwent three stereotyped phases of WD: a lag phase, a fragmentation phase and clearance. The lag phase was developmentally regulated, becoming shorter as embryos aged, while the length of the clearance phase increased with the amount of axon debris. Both cell-specific inhibition of ubiquitylation and overexpression of the Wallerian degeneration slow protein (WldS) lengthened the lag phase dramatically, but neither affected fragmentation. Persistent WldS-expressing axon fragments directly repelled regenerating axon branches of their parent arbor, similar to self-repulsion among sister branches of intact arbors. Expression of WldS also disrupted naturally occurring local axon pruning and axon degeneration in spontaneously dying trigeminal neurons: although pieces of WldS-expressing axons were pruned, and some WldS-expressing cells still died during development, in both cases detached axon fragments failed to degenerate. We propose that spontaneously pruned fragments of peripheral sensory axons must be removed by a WD-like mechanism to permit efficient innervation of the epidermis. PMID:21041367

  16. Effect of disc degeneration on the muscle recruitment pattern in upright posture: a computational analysis.

    PubMed

    Kim, Young Eun; Choi, Hae Won

    2015-01-01

    Based on the sensor driving control mechanism model, the effect of disc degeneration on the trunk muscle recruitment (TMR) pattern was analysed in erect standing posture. A previously developed computational model was used for this analysis, with modifications incorporating the T12-L1 motion segment and additional muscle fascicles. To generate disc degeneration at three different levels (L3-L4, L4-L5, or L5-S1), the material properties of the ground matrix of the annulus and bulk modulus of the nucleus were reduced. The finite element method combined with an optimization technique was applied to calculate the muscle forces. Minimization of deviations in the averaged tensile stress in the annulus fibres at the outermost layer in the five discs was selected for muscle force calculations. The results indicated that the disc degeneration noticeably increased the activation of the superficial muscle (IT and R) even though there was no clear change in the longissimus thoracis. Unlike some of the superficial muscles, activation in the deep muscles (multifidus (ML, MS, MT), LL and Q) was decreased. The change in TMR pattern generated an intervertebral disc angle difference and nucleus pressure increased in the upper level. These differences are expected to be functional in that they reduce the stress at the degenerated disc by changing the muscle activation, which slows down the progress of disc degeneration.

  17. Genetics Home Reference: age-related macular degeneration

    MedlinePlus

    ... Health Conditions age-related macular degeneration age-related macular degeneration Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Age-related macular degeneration is an eye disease that is a leading ...

  18. Structure formation through self-gravitational instability in degenerate and non-degenerate anisotropic magnetized plasma

    NASA Astrophysics Data System (ADS)

    Sharma, Prerana

    2017-04-01

    The self-gravitational instability is examined for non-degenerate and degenerate magnetized plasma. In the case of non-degenerate collisionless magnetized plasma the pressure is considered as anisotropic while in the case of degenerate situations it is taken as isotropic. The effect of finite Larmor radius correction of non-degenerate ions and viscous dissipation is taken into account in both the cases. Firstly in non-degenerate anisotropic plasma the conventional magnetohydrodynamic model is used to construct basic set of equations within the framework of modified Chew-Goldberger and Low theory. Secondly, in the case of degenerate isotropic plasma, which is considered to be composed of degenerate electrons and non-degenerate ions, the model equations are constructed using quantum magneto hydrodynamic model. The dynamics of degenerate particles are governed by Bohm and exchange potentials. The general dispersion relations are derived for both degenerate and non-degenerate situations separately using linearized perturbation equations. The results are discussed analytically and numerically for various modes of propagation. In case of non degenerate strongly magnetized plasma the effects of stress tensor anisotropy dominate over the influence of FLR effects while the FLR effects prevail in the weak magnetic field region. In case of isotropic degenerate plasma the implications of exchange parameter on the Jeans mass have been estimated and it is found that the increase in exchange parameter increases the limit of Jeans mass. The Jeans length and Jeans mass have been estimated for the white dwarf stars as LJ ≈ 2.1 × 10^{11} m and MJ ≈ 5 × 10^{39} kg respectively assist the existence of super Chandrasekhar white dwarfs.

  19. Late onset cerebellar cortical degeneration in a koala.

    PubMed

    Kuwamura, M; Murai, F; Nishioka, S; Aoki, M; Ohashi, F; Yamate, J; Kotani, T; Summers, B A

    2009-08-01

    A 10-year-old male koala started to fall from the tree while sleeping. Subsequently, the koala often fell down while walking and showed a gait abnormality, abnormal nystagmus and hypersalivation. At 12 years of age, the koala became ataxic and seemed blind. At 13 years of age, the koala exhibited signs of dysstasia and was euthanased. Necropsy revealed marked symmetrical atrophy of the cerebellum. Histopathologically, a severe loss of Purkinje and granule cells was evident in the cerebellum, while the molecular layer was more cellular than normal with cells resembling small neurons, which were positively stained with parvalbumin immunohistochemistry. Reactive Bergmann glial cells (astrocytes) were present adjacent to the depleted Purkinje cell zone. The very late onset and slow progression of the cerebellar cortical degeneration in this case is particularly interesting and appears to be the first report in the koala.

  20. Type C botulinum toxin causes degeneration of motoneurons in vivo.

    PubMed

    Zhao, Li-Chun; Yang, Bo; Wang, Rengang; Lipton, Stuart A; Zhang, Dongxian

    2010-01-06

    All botulinum toxins (BoNTs, types A-G) inhibit synaptic transmitter release from motoneurons, and thus result in respiratory arrest and death. Rapid treatment with anti-BoNT antibodies can prevent progression, but recovery still requires weeks on a ventilator. Even after recovery, there is a potential for persistent fatigue in some cases of botulism even years after the insult, possibly because of motoneuron dropout for previously unknown reasons. Unique among BoNTs, the C-type (BoNT/C) cleaves two proteins involved in neurotransmitter release, syntaxin and SNAP-25, and induces apoptotic cell death in cultured cerebellar neurons. It is not clear, however, whether BoNT/C also affects neurons that encounter toxin in vivo, namely motoneurons. Here, we provide experimental evidence that BoNT/C causes a slow degeneration of motoneurons both in vitro and in vivo. This novel form of BoNT/C-induced cell death may require new treatment strategies.

  1. Direct intranigral injection of dopaminochrome causes degeneration of dopamine neurons

    PubMed Central

    Touchette, Jillienne C.; Breckenridge, Julie M.; Wilken, Gerald H.; Macarthur, Heather

    2016-01-01

    Parkinson's disease (PD) is characterized by progressive neurodegeneration of nigrastriatal dopaminergic neurons leading to clinical motor dysfunctions. Many animal models of PD have been developed using exogenous neurotoxins and pesticides. Evidence strongly indicates that the dopaminergic neurons of the substantia nigra pars compacta (SNpc) are highly susceptible to neurodegeneration due to a number of factors including oxidative stress and mitochondrial dysfunction. Oxidation of DA to a potential endogenous neurotoxin, dopaminochrome (DAC), may be a potential contributor to the vulnerability of the nigrostriatal tract to oxidative insult. In this study, we show that DAC causes slow and progressive degeneration of dopaminergic neurons in contrast to 1-methyl-4-phenylpyridinium (MPP+), which induces rapid lesions of the region. The DAC model may be more reflective of early stresses that initiate the progressive neurodegenerative process of PD, and may prove a useful model for future neurodegenerative studies. PMID:26704434

  2. Gene-Diet Interactions in Age-Related Macular Degeneration.

    PubMed

    Rowan, Sheldon; Taylor, Allen

    2016-01-01

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50 % of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation is the only available treatment option for the dry form of the disease known to slow progression of AMD. Despite an excellent understanding of genes and nutrition in AMD, there is remarkably little known about gene-diet interactions that may identify efficacious approaches to treat individuals. This review will summarize our current understanding of gene-diet interactions in AMD with a focus on animal models and human epidemiological studies.

  3. Coupling Neurogenetics (GARS™) and a Nutrigenomic Based Dopaminergic Agonist to Treat Reward Deficiency Syndrome (RDS): Targeting Polymorphic Reward Genes for Carbohydrate Addiction Algorithms.

    PubMed

    Blum, Kenneth; Simpatico, Thomas; Badgaiyan, Rajendra D; Demetrovics, Zsolt; Fratantonio, James; Agan, Gozde; Febo, Marcelo; Gold, Mark S

    Earlier work from our laboratory, showing anti-addiction activity of a nutraceutical consisting of amino-acid precursors and enkephalinase inhibition properties and our discovery of the first polymorphic gene (Dopamine D2 Receptor Gene [DRD2]) to associate with severe alcoholism serves as a blue-print for the development of "Personalized Medicine" in addiction. Prior to the later genetic finding, we developed the concept of Brain Reward Cascade, which continues to act as an important component for stratification of addiction risk through neurogenetics. In 1996 our laboratory also coined the term "Reward Deficiency Syndrome (RDS)" to define a common genetic rubric for both substance and non-substance related addictive behaviors. Following many reiterations we utilized polymorphic targets of a number of reward genes (serotonergic, Opioidergic, GABAergic and Dopaminergic) to customize KB220 [Neuroadaptogen- amino-acid therapy (NAAT)] by specific algorithms. Identifying 1,000 obese subjects in the Netherlands a subsequent small subset was administered various KB220Z formulae customized according to respective DNA polymorphisms individualized that translated to significant decreases in both Body Mass Index (BMI) and weight in pounds. Following these experiments, we have been successfully developing a panel of genes known as "Genetic Addiction Risk Score" (GARSpDX)™. Selection of 10 genes with appropriate variants, a statistically significant association between the ASI-Media Version-alcohol and drug severity scores and GARSpDx was found A variant of KB220Z in abstinent heroin addicts increased resting state functional connectivity in a putative network including: dorsal anterior cingulate, medial frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas, and cerebellum. In addition, we show that KB220Z significantly activates, above placebo, seed regions of interest including the left nucleus accumbens, cingulate gyrus, anterior thalamic nuclei

  4. Coupling Neurogenetics (GARS™) and a Nutrigenomic Based Dopaminergic Agonist to Treat Reward Deficiency Syndrome (RDS): Targeting Polymorphic Reward Genes for Carbohydrate Addiction Algorithms

    PubMed Central

    Blum, Kenneth; Simpatico, Thomas; Badgaiyan, Rajendra D.; Demetrovics, Zsolt; Fratantonio, James; Agan, Gozde; Febo, Marcelo; Gold, Mark S.

    2016-01-01

    Earlier work from our laboratory, showing anti-addiction activity of a nutraceutical consisting of amino-acid precursors and enkephalinase inhibition properties and our discovery of the first polymorphic gene (Dopamine D2 Receptor Gene [DRD2]) to associate with severe alcoholism serves as a blue-print for the development of “Personalized Medicine” in addiction. Prior to the later genetic finding, we developed the concept of Brain Reward Cascade, which continues to act as an important component for stratification of addiction risk through neurogenetics. In 1996 our laboratory also coined the term “Reward Deficiency Syndrome (RDS)” to define a common genetic rubric for both substance and non-substance related addictive behaviors. Following many reiterations we utilized polymorphic targets of a number of reward genes (serotonergic, Opioidergic, GABAergic and Dopaminergic) to customize KB220 [Neuroadaptogen- amino-acid therapy (NAAT)] by specific algorithms. Identifying 1,000 obese subjects in the Netherlands a subsequent small subset was administered various KB220Z formulae customized according to respective DNA polymorphisms individualized that translated to significant decreases in both Body Mass Index (BMI) and weight in pounds. Following these experiments, we have been successfully developing a panel of genes known as “Genetic Addiction Risk Score” (GARSpDX)™. Selection of 10 genes with appropriate variants, a statistically significant association between the ASI-Media Version-alcohol and drug severity scores and GARSpDx was found A variant of KB220Z in abstinent heroin addicts increased resting state functional connectivity in a putative network including: dorsal anterior cingulate, medial frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas, and cerebellum. In addition, we show that KB220Z significantly activates, above placebo, seed regions of interest including the left nucleus accumbens, cingulate gyrus, anterior

  5. Perovskite photovoltaics: Slow recombination unveiled

    NASA Astrophysics Data System (ADS)

    Moser, Jacques-E.

    2017-01-01

    One of the most salient features of hybrid lead halide perovskites is the extended lifetime of their photogenerated charge carriers. This property has now been shown experimentally to originate from a slow, thermally activated recombination process.

  6. Birth control - slow release methods

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007555.htm Birth control - slow release methods To use the sharing features on this page, please enable JavaScript. Certain birth control methods contain man-made forms of hormones. These ...

  7. Slow light in flight imaging

    NASA Astrophysics Data System (ADS)

    Wilson, Kali; Little, Bethany; Gariepy, Genevieve; Henderson, Robert; Howell, John; Faccio, Daniele

    2017-02-01

    Slow-light media are of interest in the context of quantum computing and enhanced measurement of quantum effects, with particular emphasis on using slow light with single photons. We use light-in-flight imaging with a single-photon avalanche diode camera array to image in situ pulse propagation through a slow-light medium consisting of heated rubidium vapor. Light-in-flight imaging of slow-light propagation enables direct visualization of a series of physical effects, including simultaneous observation of spatial pulse compression and temporal pulse dispersion. Additionally, the single-photon nature of the camera allows for observation of the group velocity of single photons with measured single-photon fractional delays greater than 1 over 1 cm of propagation.

  8. Slow shock and rotational discontinuity in MHD and Hall MHD models with anisotropic pressure

    NASA Astrophysics Data System (ADS)

    Hau, L.-N.; Wang, B.-J.

    2016-07-01

    Pressure anisotropy may modify the characteristics of magnetohydrodynamic (MHD) waves, in particular, the slow mode wave and the corresponding shocks and discontinuities. In this study the formation of slow shocks (SSs) in anisotropic plasmas is examined by solving the gyrotropic MHD and Hall MHD equations numerically for one-dimensional Riemann problem. The MHD shocks and discontinuities are generated by imposing a finite normal magnetic field on the Harris type current sheet with a guide magnetic By component. It is shown that anomalous SSs moving faster than the intermediate wave or with positive density-magnetic field correlation may be generated in gyrotropic MHD and Hall MHD models. Moreover, for some parameter values SSs may exhibit upstream wave trains with right-handed polarization in contrast with the earlier prediction that SSs shall possess downstream left-hand polarized wave trains based on the isotropic Hall MHD theory. For the cases of By ≠ 0, SSs with increased density and decreased magnetic field followed by noncoplanar intermediate mode or rotational discontinuity (RD)-like structures similar to the compound SS-RD structures observed in space plasma environments may possibly form in symmetric and asymmetric current layers. The Walén relation of these anomalous RDs without the correction of pressure anisotropy may significantly be violated.

  9. Low Starting Electron Beam Current in Degenerate Band Edge Oscillators

    NASA Astrophysics Data System (ADS)

    Othman, Mohamed A. K.; Veysi, Mehdi; Figotin, Alexander; Capolino, Filippo

    2016-06-01

    We propose a new principle of operation in vacuum electron-beam-based oscillators that leads to a low beam current for starting oscillations. The principle is based on super synchronous operation of an electron beam interacting with four degenerate electromagnetic modes in a slow-wave structure (SWS). The four mode super synchronous regime is associated with a very special degeneracy condition in the dispersion diagram of a cold periodic SWS called degenerate band edge (DBE). This regime features a giant group delay in the finitelength SWS and low starting-oscillation beam current. The starting beam current is at least an order of magnitude smaller compared to a conventional backward wave oscillator (BWO) of the same length. As a representative example we consider a SWS conceived by a periodically-loaded metallic waveguide supporting a DBE, and investigate starting-oscillation conditions using Pierce theory generalized to coupled transmission lines (CTL). The proposed super synchronism regime can be straightforwardly adapted to waveguide geometries others than the periodically-loaded waveguide considered here since DBE is a general property that can be realized in a variety of structures.

  10. Molecular pharmacodynamics of emixustat in protection against retinal degeneration

    PubMed Central

    Zhang, Jianye; Kiser, Philip D.; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P.; Palczewski, Krzysztof

    2015-01-01

    Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators. PMID:26075817

  11. Molecular pharmacodynamics of emixustat in protection against retinal degeneration.

    PubMed

    Zhang, Jianye; Kiser, Philip D; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P; Palczewski, Krzysztof

    2015-07-01

    Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators.

  12. Slow motion increases perceived intent

    PubMed Central

    Caruso, Eugene M.; Burns, Zachary C.; Converse, Benjamin A.

    2016-01-01

    To determine the appropriate punishment for a harmful action, people must often make inferences about the transgressor’s intent. In courtrooms and popular media, such inferences increasingly rely on video evidence, which is often played in “slow motion.” Four experiments (n = 1,610) involving real surveillance footage from a murder or broadcast replays of violent contact in professional football demonstrate that viewing an action in slow motion, compared with regular speed, can cause viewers to perceive an action as more intentional. This slow motion intentionality bias occurred, in part, because slow motion video caused participants to feel like the actor had more time to act, even when they knew how much clock time had actually elapsed. Four additional experiments (n = 2,737) reveal that allowing viewers to see both regular speed and slow motion replay mitigates the bias, but does not eliminate it. We conclude that an empirical understanding of the effect of slow motion on mental state attribution should inform the life-or-death decisions that are currently based on tacit assumptions about the objectivity of human perception. PMID:27482091

  13. Modified gravitational instability of degenerate and non-degenerate dusty plasma

    NASA Astrophysics Data System (ADS)

    Jain, Shweta; Sharma, Prerana

    2016-09-01

    The gravitational instability of strongly coupled dusty plasma (SCDP) is studied considering degenerate and non-degenerate dusty plasma situations. The SCDP system is assumed to be composed of the electrons, ions, neutrals, and strongly coupled dust grains. First, in the high density regime, due to small interparticle distance, the electrons are considered degenerate, whereas the neutrals, dust grains, and ions are treated non-degenerate. In this case, the dynamics of inertialess electrons are managed by Fermi pressure and Bohm potential, while the inertialess ions are by only thermal pressure. Second, in the non-degenerate regime, both the electrons and ions are governed by the thermal pressure. The generalized hydrodynamic model and the normal mode analysis technique are employed to examine the low frequency waves and gravitational instability in both degenerate and non-degenerate cases. The general dispersion relation is discussed for a characteristic timescale which provides two regimes of frequency, i.e., hydrodynamic regime and kinetic regime. Analytical solutions reveal that the collisions reduce the growth rate and have a strong impact on structure formation in both degenerate and non-degenerate circumstances. Numerical estimation on the basis of observed parameters for the degenerate and non-degenerate cases is presented to show the effects of dust-neutral collisions and dust effective velocity in the presence of polarization force. The values of Jeans length and Jeans mass have been estimated for degenerate white dwarfs as Jeans length L J = 1.3 × 10 5 cm and Jeans mass M J = 0.75 × 10 - 3 M⊙ and for non-degenerate laboratory plasma Jeans length L J = 6.86 × 10 16 cm and Jeans mass M J = 0.68 × 10 10 M⊙. The stability of the SCDP system is discussed using the Routh-Hurwitz criterion.

  14. Molecular Therapy for Disk Degeneration and Pain

    PubMed Central

    Mwale, Fackson

    2013-01-01

    The nucleus pulposus of the intervertebral disk contains high amounts of the proteoglycan aggrecan, which confers the disk with a remarkable ability to resist compression. Other molecules such as collagens and noncollagenous proteins in the extracellular matrix are also essential for function. During disk degeneration, aggrecan and other molecules are lost due to proteolysis. This can result in loss of disk height, which can ultimately lead to pain. Biological therapy of intervertebral disk degeneration aims at preventing or restoring primarily aggrecan content and other molecules using therapeutic molecules. The purpose of the article is to review recent advances in biological repair of degenerate disks and pain. PMID:24436869

  15. Total absorption by degenerate critical coupling

    SciTech Connect

    Piper, Jessica R. Liu, Victor; Fan, Shanhui

    2014-06-23

    We consider a mirror-symmetric resonator with two ports. We show that, when excited from a single port, complete absorption can be achieved through critical coupling to degenerate resonances with opposite symmetry. Moreover, any time two resonances with opposite symmetry are degenerate in frequency and absorption is always significantly enhanced. In contrast, when two resonances with the same symmetry are nearly degenerate, there is no absorption enhancement. We numerically demonstrate these effects using a graphene monolayer on top of a photonic crystal slab, illuminated from a single side in the near-infrared.

  16. Very Degenerate Higgsino Dark Matter

    DOE PAGES

    Chun, Eung Jin; Jung, Sunghoon; Park, Jong-Chul

    2017-01-03

    In this paper, we present a study of the Very Degenerate Higgsino Dark Matter (DM), whose mass splitting between the lightest neutral and charged components is O(1) MeV, much smaller than radiative splitting of 355 MeV. The scenario is realized in the minimal supersymmetric standard model by small gaugino mixings. In contrast to the pure Higgsino DM with the radiative splitting only, various observable signatures with distinct features are induced. First of all, the very small mass splitting makes (a) sizable Sommerfeld enhancement and Ramsauer-Townsend (RT) suppression relevant to ~1 TeV Higgsino DM, and (b) Sommerfeld-Ramsauer-Townsend effect saturate at lowermore » velocities v/c ≲ 10-3. As a result, annihilation signals can be large enough to be observed from the galactic center and/or dwarf galaxies, while the relative signal sizes can vary depending on the locations of Sommerfeld peaks and RT dips. In addition, at collider experiments, stable chargino signatures can be searched for to probe the model in the future. Finally, DM direct detection signals, however, depend on the Wino mass; even no detectable signals can be induced if the Wino is heavier than about 10 TeV.« less

  17. Very Degenerate Higgsino Dark Matter

    NASA Astrophysics Data System (ADS)

    Chun, Eung Jin; Jung, Sunghoon; Park, Jong-Chul

    2017-01-01

    We present a study of the Very Degenerate Higgsino Dark Matter (DM), whose mass splitting between the lightest neutral and charged components is O(1) MeV, much smaller than radiative splitting of 355 MeV. The scenario is realized in the minimal supersymmetric standard model by small gaugino mixings. In contrast to the pure Higgsino DM with the radiative splitting only, various observable signatures with distinct features are induced. First of all, the very small mass splitting makes (a) sizable Sommerfeld enhancement and Ramsauer-Townsend (RT) suppression relevant to ˜1 TeV Higgsino DM, and (b) Sommerfeld-Ramsauer-Townsend effect saturate at lower velocities v/c ≲ 10-3. As a result, annihilation signals can be large enough to be observed from the galactic center and/or dwarf galaxies, while the relative signal sizes can vary depending on the locations of Sommerfeld peaks and RT dips. In addition, at collider experiments, stable chargino signatures can be searched for to probe the model in the future. DM direct detection signals, however, depend on the Wino mass; even no detectable signals can be induced if the Wino is heavier than about 10 TeV.

  18. Degeneration of Biogenic Superparamagnetic Magnetite

    SciTech Connect

    Li, Dr. Yi-Liang; Pfiffner, Susan M.; Dyar, Dr. M Darby; Vali, Dr. Hojatolah; Konhauser, Dr, Kurt; Cole, David R; Rondinone, Adam Justin; Phelps, Tommy Joe

    2009-01-01

    ABSTRACT. Magnetite crystals precipitated as a consequence of Fe(III) reduction by Shewanella algae BrY after 265 hours incubation and 5-year storage were investigated with transmission electron microscopy, M ssbauer spectroscopy and X-ray diffraction. The magnetite crystals were typically superparamagnetic with an approximate size of 13 nm. The lattice constants of the 265 hour and 5-year crystals are 8.4164 and 8.3774 , respectively. The M ssbauer spectra indicated that the 265 hour magnetite had excess Fe(II) in its crystal-chemistry (Fe3+1.9901Fe2+ 1.0149O4) but the 5-year magnetite was Fe(II)-deficient in stoichiometry (Fe3+2.3875Fe2+0.4188O4). Such crystal-hemical changes may be indicative of the degeneration of superparamagnetic magnetite through the aqueous oxidization of Fe(II) anaerobically, and the concomitant oxidation of the organic phases(fatty acid methyl esters) that were present during the initial formation of the magnetite. The observation of a corona structure on the aged magnetite corroborates the oxidation of Fe(II) on the outer layers of magnetite crystals. These results suggest that there may be a possible link between the enzymatic activity of the bacteria and the stability of Fe(II)-excess magnetite, which may help explain why stable nano-magnetite grains are seldom preserved in natural environments.

  19. Activity-dependent degeneration of axotomized neuromuscular synapses in Wld S mice.

    PubMed

    Brown, R; Hynes-Allen, A; Swan, A J; Dissanayake, K N; Gillingwater, T H; Ribchester, R R

    2015-04-02

    Activity and disuse of synapses are thought to influence progression of several neurodegenerative diseases in which synaptic degeneration is an early sign. Here we tested whether stimulation or disuse renders neuromuscular synapses more or less vulnerable to degeneration, using axotomy as a robust trigger. We took advantage of the slow synaptic degeneration phenotype of axotomized neuromuscular junctions in flexor digitorum brevis (FDB) and deep lumbrical (DL) muscles of Wallerian degeneration-Slow (Wld(S)) mutant mice. First, we maintained ex vivo FDB and DL nerve-muscle explants at 32°C for up to 48 h. About 90% of fibers from Wld(S) mice remained innervated, compared with about 36% in wild-type muscles at the 24-h checkpoint. Periodic high-frequency nerve stimulation (100 Hz: 1s/100s) reduced synaptic protection in Wld(S) preparations by about 50%. This effect was abolished in reduced Ca(2+) solutions. Next, we assayed FDB and DL innervation after 7 days of complete tetrodotoxin (TTX)-block of sciatic nerve conduction in vivo, followed by tibial nerve axotomy. Five days later, only about 9% of motor endplates remained innervated in the paralyzed muscles, compared with about 50% in 5 day-axotomized muscles from saline-control-treated Wld(S) mice with no conditioning nerve block. Finally, we gave mice access to running wheels for up to 4 weeks prior to axotomy. Surprisingly, exercising Wld(S) mice ad libitum for 4 weeks increased about twofold the amount of subsequent axotomy-induced synaptic degeneration. Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity.

  20. Activity-dependent degeneration of axotomized neuromuscular synapses in WldS mice

    PubMed Central

    Brown, R.; Hynes-Allen, A.; Swan, A.J.; Dissanayake, K.N.; Gillingwater, T.H.; Ribchester, R.R.

    2015-01-01

    Activity and disuse of synapses are thought to influence progression of several neurodegenerative diseases in which synaptic degeneration is an early sign. Here we tested whether stimulation or disuse renders neuromuscular synapses more or less vulnerable to degeneration, using axotomy as a robust trigger. We took advantage of the slow synaptic degeneration phenotype of axotomized neuromuscular junctions in flexor digitorum brevis (FDB) and deep lumbrical (DL) muscles of Wallerian degeneration-Slow (WldS) mutant mice. First, we maintained ex vivo FDB and DL nerve-muscle explants at 32 °C for up to 48 h. About 90% of fibers from WldS mice remained innervated, compared with about 36% in wild-type muscles at the 24-h checkpoint. Periodic high-frequency nerve stimulation (100 Hz: 1 s/100 s) reduced synaptic protection in WldS preparations by about 50%. This effect was abolished in reduced Ca2+ solutions. Next, we assayed FDB and DL innervation after 7 days of complete tetrodotoxin (TTX)-block of sciatic nerve conduction in vivo, followed by tibial nerve axotomy. Five days later, only about 9% of motor endplates remained innervated in the paralyzed muscles, compared with about 50% in 5 day-axotomized muscles from saline-control-treated WldS mice with no conditioning nerve block. Finally, we gave mice access to running wheels for up to 4 weeks prior to axotomy. Surprisingly, exercising WldS mice ad libitum for 4 weeks increased about twofold the amount of subsequent axotomy-induced synaptic degeneration. Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity. PMID:25617654

  1. Slow earthquakes coincident with episodic tremors and slow slip events.

    PubMed

    Ito, Yoshihiro; Obara, Kazushige; Shiomi, Katsuhiko; Sekine, Shutaro; Hirose, Hitoshi

    2007-01-26

    We report on the very-low-frequency earthquakes occurring in the transition zone of the subducting plate interface along the Nankai subduction zone in southwest Japan. Seismic waves generated by very-low-frequency earthquakes with seismic moment magnitudes of 3.1 to 3.5 predominantly show a long period of about 20 seconds. The seismicity of very-low-frequency earthquakes accompanies and migrates with the activity of deep low-frequency tremors and slow slip events. The coincidence of these three phenomena improves the detection and characterization of slow earthquakes, which are thought to increase the stress on updip megathrust earthquake rupture zones.

  2. Characterizing Thalamocortical Disturbances in Cervical Spondylotic Myelopathy: Revealed by Functional Connectivity under Two Slow Frequency Bands

    PubMed Central

    Zhou, Fuqing; Wu, Lin; Liu, Xiaojia; Gong, Honghan; Luk, Keith Dip-Kei; Hu, Yong

    2015-01-01

    Background and Purpose Recent advanced MRI studies on cervical spondylotic myelopathy (CSM) revealed alterations of sensorimotor cortex, but the disturbances of large-scale thalamocortical systems remains elusive. The purpose of this study was to characterizing the CSM-related thalamocortical disturbances, which were associated with spinal cord structural injury, and clinical measures. Methods A total of 17 patients with degenerative CSM and well-matched control subjects participated. Thalamocortical disturbances were quantified using thalamus seed-based functional connectivity in two distinct low frequencies bands (slow-5 and slow-4), with different neural manifestations. The clinical measures were evaluated by Japanese Orthopaedic Association (JOA) score system and Neck Disability Index (NDI) questionnaires. Results Decreased functional connectivity was found in the thalamo-motor, -somatosensory, and -temporal circuits in the slow-5 band, indicating impairment of thalamo-cortical circuit degeneration or axon/synaptic impairment. By contrast, increased functional connectivity between thalami and the bilateral primary motor (M1), primary and secondary somatosensory (S1/S2), premotor cortex (PMC), and right temporal cortex was detected in the slow-4 band, and were associated with higher fractional anisotropy values in the cervical cord, corresponding to mild spinal cord structural injury. Conclusions These thalamocortical disturbances revealed by two slow frequency bands inform basic understanding and vital clues about the sensorimotor dysfunction in CSM. Further work is needed to evaluate its contribution in central functional reorganization during spinal cord degeneration. PMID:26053316

  3. Time Slows Down during Accidents.

    PubMed

    Arstila, Valtteri

    2012-01-01

    The experienced speed of the passage of time is not constant as time can seem to fly or slow down depending on the circumstances we are in. Anecdotally accidents and other frightening events are extreme examples of the latter; people who have survived accidents often report altered phenomenology including how everything appeared to happen in slow motion. While the experienced phenomenology has been investigated, there are no explanations about how one can have these experiences. Instead, the only recently discussed explanation suggests that the anecdotal phenomenology is due to memory effects and hence not really experienced during the accidents. The purpose of this article is (i) to reintroduce the currently forgotten comprehensively altered phenomenology that some people experience during the accidents, (ii) to explain why the recent experiments fail to address the issue at hand, and (iii) to suggest a new framework to explain what happens when people report having experiences of time slowing down in these cases. According to the suggested framework, our cognitive processes become rapidly enhanced. As a result, the relation between the temporal properties of events in the external world and in internal states becomes distorted with the consequence of external world appearing to slow down. That is, the presented solution is a realist one in a sense that it maintains that sometimes people really do have experiences of time slowing down.

  4. Transparency and tunable slow and fast light in a nonlinear optomechanical cavity

    NASA Astrophysics Data System (ADS)

    Li, Ling; Nie, Wenjie; Chen, Aixi

    2016-10-01

    We investigate theoretically the optical response of the output field and the tunable slow and fast light in a nonlinear optomechanical cavity with a degenerate optical parametric amplifier (OPA) and a higher order excited atomic ensemble. Studies show that the higher-order-excitation atom which is similar to the degenerate OPA that acts as a nonlinear medium, induces an additional dip in absorption spectrum of the probe field. The coherence of the mechanical oscillator leads to split the peak in absorption in the probe field spectrum so that the phenomenon of optomechanically induced transparency (OMIT) is generated from the output probe field. In particular, the presence of nonlinearities with the degenerate OPA and the higher order excited atoms can affect significantly the width of the transparency windows, providing an additional flexibility for controlling optical properties. Furthermore, in the presence of the degenerate OPA, the optical-response properties for the probe field become phase-sensitive so that a tunable switch from slow to fast light can be realized.

  5. Transparency and tunable slow and fast light in a nonlinear optomechanical cavity

    PubMed Central

    Li, Ling; Nie, Wenjie; Chen, Aixi

    2016-01-01

    We investigate theoretically the optical response of the output field and the tunable slow and fast light in a nonlinear optomechanical cavity with a degenerate optical parametric amplifier (OPA) and a higher order excited atomic ensemble. Studies show that the higher-order-excitation atom which is similar to the degenerate OPA that acts as a nonlinear medium, induces an additional dip in absorption spectrum of the probe field. The coherence of the mechanical oscillator leads to split the peak in absorption in the probe field spectrum so that the phenomenon of optomechanically induced transparency (OMIT) is generated from the output probe field. In particular, the presence of nonlinearities with the degenerate OPA and the higher order excited atoms can affect significantly the width of the transparency windows, providing an additional flexibility for controlling optical properties. Furthermore, in the presence of the degenerate OPA, the optical-response properties for the probe field become phase-sensitive so that a tunable switch from slow to fast light can be realized. PMID:27725763

  6. Hamiltonian structure for degenerate AKNS systems

    NASA Astrophysics Data System (ADS)

    Corona-Corona, Gulmaro

    1997-01-01

    There is a family of degenerate AKNS systems for which the full theory of generic AKNS systems does not directly extend. The linear space of potentials still has a natural Poisson structure, but the scattering method used by Beals and Sattinger to show complete integrability for the generic AKNS systems fails for the degenerate case. A Poisson structure is not induced on the scattering side as in the generic case. As a consequence, the problem of complete integrability for degenerate AKNS systems still is an open question. In addition, contrary to the generic case, the Lax pair gives flows for degenerate integrable systems that are nonlocal. In general, they do not exist, and they are no longer linear on the scattering side. Necessary conditions for their existence and for linear evolution in the scattering side are found.

  7. Hamiltonian Structure for Degenerate Akns Systems

    NASA Astrophysics Data System (ADS)

    Corona-Corona, Gulmaro

    1995-01-01

    There is a family of degenerate AKNS systems for which the full theory of generic AKNS systems does not directly extend. The linear space of potentials still has a natural Poisson structure. This is studied by the scattering method used by Richard Beals and D.H. Sattinger (Commun. Math. Phys. 138, 409-436, 1991) to show complete integrability for the generic AKNS systems. This method fails for the degenerate case since a Poisson structure is not induced on the scattering side as in the generic case. As a consequence, the problem of complete integrability for degenerate AKNS systems still is an open question. In addition, contrary to the generic case, the Lax pair gives flows for degenerate integrable systems that are nonlocal. In general they do not exist, and they are no longer linear on the scattering side. Necessary conditions for their existence and for linear evolution of the scattering side are found.

  8. Thermal Properties of Degenerate Relativistic Quantum Gases

    NASA Astrophysics Data System (ADS)

    Homorodean, Laurean

    We present the concentration-temperature phase diagram, characteristic functions, thermal equation of state and heat capacity at constant volume for degenerate ideal gases of relativistic fermions and bosons. The nonrelativistic and ultrarelativistic limits of these laws are also discussed.

  9. Degenerate primer design for highly variable genomes.

    PubMed

    Li, Kelvin; Shrivastava, Susmita; Stockwell, Timothy B

    2015-01-01

    The application of degenerate PCR primers towards target amplification and sequencing is a useful technique when a population of organisms under investigation is evolving rapidly, or is highly diverse. Degenerate bases in these primers are specified with ambiguity codes that represent alternative nucleotide configurations. Degenerate PCR primers allow the simultaneous amplification of a heterogeneous population by providing a mixture of PCR primers each of which anneal to an alternative genotype found in the isolated sample. However, as the number of degenerate bases specified in a pair of primers rises, the likelihood of amplifying unwanted alternative products also increases. These alternative products may confound downstream data analyses if their levels begin to obfuscate the desired PCR products. This chapter describes a set of computational methodologies that may be used to minimize the degeneracy of designed primers, while still maximizing the proportion of genotypes assayed in the targeted population.

  10. Quantitative Pfirrmann Disc Degeneration Grading System to Overcome the Limitation of Pfirrmann Disc Degeneration Grade.

    PubMed

    Rim, Dae Cheol

    2016-03-01

    Pfirrmann disc degeneration grade is one of morphologic disc degeneration grading system and it was reliable on routine T2-weighted magnetic resonance (MR) images. The purpose of this study was to evaluate the agreement of Pfirrmann disc degeneration grade, and check the alternative technique of disc degeneration grading system. Fifteen volunteers (4 medical doctors related to spinal disease, 2 medical doctors not related to spinal disease, 6 nurses in spinal hospital, and 3 para-medicines) were included in this study. Three different digitalized MR images were provided all volunteers, and they checked Pfirrmann disc degeneration grade of each disc levels after careful listening to explanation. Indeed, all volunteers checked the signal intensity of disc degeneration at the points of nucleus pulposus (NP), disc membrane, ligaments, fat, and air to modify the quantitative Pfirrmann disc degeneration grade. Total 225 grade results of Pfirrmann disc degeneration grade and 405 signal intensity results of quantitative Pfirrmann disc degeneration grade were analyzed. Average interobserver agreement was "moderate (mean±standard deviation, 0.575±0.251)" from poor to excellent. Completely agreed levels of Pfirrmann disc degeneration grade were only 4 levels (26.67%), and the disagreement levels were observed in 11 levels; two different grades in 8 levels (53.33%) and three different grades in 3 levels (20%). Quantitative Pfirrmann disc degeneration showed relatively cluster distribution with the interobserver deviations of 0.41-1.56 at the ratio of NP and disc membrane, and it showed relatively good cluster and distribution indicating that the proposed grading system has good discrimination ability. Pfirrmann disc degeneration grade showed the limitation of different interobserver results, but this limitation could be overcome by using quantitative techniques of MR signal intensity. Further evaluation is needed to access its advantage and reliabilities.

  11. [Presacral schwannoma with degenerated areas ("ancient schwannoma")].

    PubMed

    Netsch, C; Oberhagemann, K; Bach, T; Feyerabend, B; Gross, A J

    2010-10-01

    A presacral, degenerative schwannoma ("ancient schwannoma") is a rare entity. The clinical signs are nonspecific, and a reliable preoperative diagnosis is difficult. Tumor heterogeneity with calcifications may be seen in degenerated schwannomas on MRI or CT but not necessarily. First-line treatment is complete surgical excision. We present the case of a 44-year-old male who required surgery for a presacral mass. Histopathological examination revealed the diagnosis of a schwannoma with degenerated areas.

  12. Obsessional slowness: a case study.

    PubMed

    Lam, Wendy; Wong, Karen W; Fulks, Mary-Ann; Holsti, Liisa

    2008-10-01

    Obsessional slowness is a rare psychiatric disorder with few treatment options and limited research to date. Some suggest that targeted behavioural interventions may reduce the time taken for functional daily activities. To examine whether a behavioural intervention would reduce the amount of time taken for an adolescent with obsessional slowness to walk to class. A single-subject A-B-A withdrawal design was incorporated into this case study. The treatment involved one-to-one pacing and prompting during the subject's walk to gym class. Walking times to gym class were measured during a baseline phase, during a one-month treatment phase, and during a post-treatment follow-up phase. The subject's walking times decreased during the treatment phase. Post-treatment walking times suggested a carry-over effect. This study adds to the sparse evidence on treatments for obsessional slowness and suggests occupation-based treatment options.

  13. Dose from slow negative muons.

    PubMed

    Siiskonen, T

    2008-01-01

    Conversion coefficients from fluence to ambient dose equivalent, from fluence to maximum dose equivalent and quality factors for slow negative muons are examined in detail. Negative muons, when stopped, produce energetic photons, electrons and a variety of high-LET particles. Contribution from each particle type to the dose equivalent is calculated. The results show that for the high-LET particles the details of energy spectra and decay yields are important for accurate dose estimates. For slow negative muons the ambient dose equivalent does not always yield a conservative estimate for the protection quantities. Especially, the skin equivalent dose is strongly underestimated if the radiation-weighting factor of unity for slow muons is used. Comparisons to earlier studies are presented.

  14. FEL on slow cyclotron wave

    SciTech Connect

    Silivra, A.

    1995-12-31

    A physical mechanism of interaction of fast electromagnetic wave with slow cyclotron wave of relativistic electron beam in a FEL with helical wiggler field is described. It is shown that: (1) interaction is possible for both group of steady state electron trajectories (2) positive gain is achieved within certain interval of guide field strength (3) operation wavelength for group 1 trajectories ({Omega}{sub 0}/{gamma} < k{omega}{upsilon}{parallel}) is shorter than for the conventional FEL synchronism. A nonlinear analysis shows that efficiency of slow cyclotron FEL is restricted mainly by a breakdown of a single electron synchronism due to dependence of (modified) electron cyclotron frequency on an energy of electron. Nevertheless, as numerical simulation shows, typical efficiency of 15 % order is achieved in millimeter wavelength band for the midrelativistic ({gamma}= 3 {divided_by} 4) slow cyclotron wave FEL. Tapering of magnetic field results in a substantial increase of efficiency.

  15. Neural remodeling in retinal degeneration.

    PubMed

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  16. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary

    PubMed Central

    Blum, Kenneth; Chen, Amanda Lih Chuan; Chen, Thomas JH; Braverman, Eric R; Reinking, Jeffrey; Blum, Seth H; Cassel, Kimberly; Downs, Bernard W; Waite, Roger L; Williams, Lonna; Prihoda, Thomas J; Kerner, Mallory M; Palomo, Tomas; Comings, David E; Tung, Howard; Rhoades, Patrick; Oscar-Berman, Marlene

    2008-01-01

    . Proposal and conclusion The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine™, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system. PMID:19014506

  17. MALIGNANT DEGENERATION IN BURN SCARS

    PubMed Central

    Castañares, Salvador

    1961-01-01

    The malignant potential of burn scars has been recognized since Marjolin's classical description of cancer arising in several types of post-traumatic scars. With improved burn therapy since the last war, there has been a higher survival rate of severe burns with proportionate increase in cancer associated with burn scars. This will create increasing problems of permanent disability and compensation. The younger the patient at the time of the burn, the longer the time required for the cancer to develop. Acute cancer development in burn scars has been reported after a four-week interval. Cancer may develop from six weeks to fifty years or more. The etiology of cancer in burn scars is not known. The most important clinical finding is the fact that most of the burn cancers occur in areas which were not grafted. The most common type of cancer encountered in burn scars is squamous cell carcinoma, which forms in Marjolin ulcers. Basal cell carcinoma may develop in the most superficial of burn scars. Treatment should be directed primarily to prompt and adequate skin grafting in all deep burns in order to prevent malignant degeneration of the burn scars. Once it has developed the treatment is the same as for other malignancies which are not associated with burns. Wide surgical excision with block dissection of the regional lymph nodes when they are involved is the treatment of choice. The prognosis of burn scar cancer is poor, once the process has extended because of early and distant metastasis. ImagesFigure 1.Figure 2.Figure 2.Figure 3.Figure 3.Figure 4. PMID:13691372

  18. Frontotemporal lobar degeneration: current perspectives

    PubMed Central

    Riedl, Lina; Mackenzie, Ian R; Förstl, Hans; Kurz, Alexander; Diehl-Schmid, Janine

    2014-01-01

    The term frontotemporal lobar degeneration (FTLD) refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer’s disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT), the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN), and in the chromosome 9 open reading frame 72 (C9orf72) accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management. PMID:24600223

  19. Age-related macular degeneration.

    PubMed

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease.

  20. Slow Images and Entangled Photons

    SciTech Connect

    Swordy, Simon

    2007-06-20

    I will discuss some recent experiments using slow light and entangled photons. We recently showed that it was possible to map a two dimensional image onto very low light level signals, slow them down in a hot atomic vapor while preserving the amplitude and phase of the images. If time remains, I will discuss some of our recent work with time-energy entangled photons for quantum cryptography. We were able to show that we could have a measurable state space of over 1000 states for a single pair of entangled photons in fiber.

  1. Two slow meteors with spectra

    NASA Astrophysics Data System (ADS)

    Dubs, Martin; Sposetti, Stefano; Spinner, Roger; Booz, Beat

    2017-01-01

    On January 2, 2017 two peculiar meteors (M20170102_001216 and M20170102_015202) were observed by several stations in Switzerland. Both had a long duration, slow velocity, similar brightness and a very similar radiant. As they appeared in a time interval of 100 minutes, a satellite was suspected as a possible origin of these two observations. A closer inspection however showed that this interpretation was incorrect. The two objects were slow meteors. Spectra were taken from both objects, which were nearly identical. Together this points to a common origin of the two meteors.

  2. Slow shocks around the sun

    NASA Technical Reports Server (NTRS)

    Whang, Y. C.

    1982-01-01

    It is inferred from this study that magnetohydrodynamic slow shocks can exist in the vicinity of the sun. The study uses a two-hole corona model, the sub-Alfvenic streams originating from the edge of the polar open-field regions are forced to turn towards equator in coronal space following the curved boundary of the closed field region. When the streamlines from the opposite poles merge at a neutral point, their directions become parallel to the neutral sheet. An oblique slow shock can develop near or at the neutral point, the shock extends polewards to form a surface of discontinuity around the sun.

  3. Slow Crack Growth of Germanium

    NASA Technical Reports Server (NTRS)

    Salem, Jon

    2016-01-01

    The fracture toughness and slow crack growth parameters of germanium supplied as single crystal beams and coarse grain disks were measured. Although germanium is anisotropic (A=1.7), it is not as anisotropic as SiC, NiAl, or Cu, as evidence by consistent fracture toughness on the 100, 110, and 111 planes. Germanium does not exhibit significant slow crack growth in distilled water. (n=100). Practical values for engineering design are a fracture toughness of 0.7 MPam and a Weibull modulus of m=6+/-2. For well ground and reasonable handled coupons, fracture strength should be greater than 30 MPa.

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

    PubMed Central

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

    2016-01-01

    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 < 0.05; experiments vs. model), in which the rapid degeneration immediately after initiation of osteoarthritis (0–2 years, p < 0.001) was followed by a slow or negligible degeneration (2–4 years, p > 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis. PMID:26906749

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

    NASA Astrophysics Data System (ADS)

    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 < 0.05 experiments vs. model), in which the rapid degeneration immediately after initiation of osteoarthritis (0–2 years, p < 0.001) was followed by a slow or negligible degeneration (2–4 years, p > 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis.

  6. Microcurrent stimulation in the treatment of dry and wet macular degeneration

    PubMed Central

    Chaikin, Laurie; Kashiwa, Kellen; Bennet, Michael; Papastergiou, George; Gregory, Walter

    2015-01-01

    Purpose To determine the safety and efficacy of the application of transcutaneous (transpalpebral) microcurrent stimulation to slow progression of dry and wet macular degeneration or improve vision in dry and wet macular degeneration. Methods Seventeen patients aged between 67 and 95 years with an average age of 83 years were selected to participate in the study over a period of 3 months in two eye care centers. There were 25 eyes with dry age-related macular degeneration (DAMD) and six eyes with wet age-related macular degeneration (WAMD). Frequency-specific microcurrent stimulation was applied in a transpalpebral manner, using two programmable dual channel microcurrent units delivering pulsed microcurrent at 150 µA for 35 minutes once a week. The frequency pairs selected were based on targeting tissues, which are typically affected by the disease combined with frequencies that target disease processes. Early Treatment Diabetic Retinopathy Study or Snellen visual acuity (VA) was measured before and after each treatment session. All treatment was administered in a clinical setting. Results Significant increases were seen in VA in DAMD (P=0.012, Wilcoxon one-sample test), but in WAMD, improvements did not reach statistical significance (P=0.059). In DAMD eyes, twice as many patients showed increase in VA (52%) compared to those showing deterioration (26%), with improvements being often sizeable, whereas deteriorations were usually very slight. In WAMD eyes, five of six (83%) patients showed an increase and none showed deterioration. Conclusion The substantial changes observed over this period, combined with continued improvement for patients who continued treatment once a month, are encouraging for future studies. The changes observed indicate the potential efficacy of microcurrent to delay degeneration and possibly improve age-related macular degeneration, both wet and dry. However, this study has no control arm, so results should be treated with caution

  7. Microcurrent stimulation in the treatment of dry and wet macular degeneration.

    PubMed

    Chaikin, Laurie; Kashiwa, Kellen; Bennet, Michael; Papastergiou, George; Gregory, Walter

    2015-01-01

    To determine the safety and efficacy of the application of transcutaneous (transpalpebral) microcurrent stimulation to slow progression of dry and wet macular degeneration or improve vision in dry and wet macular degeneration. Seventeen patients aged between 67 and 95 years with an average age of 83 years were selected to participate in the study over a period of 3 months in two eye care centers. There were 25 eyes with dry age-related macular degeneration (DAMD) and six eyes with wet age-related macular degeneration (WAMD). Frequency-specific microcurrent stimulation was applied in a transpalpebral manner, using two programmable dual channel microcurrent units delivering pulsed microcurrent at 150 µA for 35 minutes once a week. The frequency pairs selected were based on targeting tissues, which are typically affected by the disease combined with frequencies that target disease processes. Early Treatment Diabetic Retinopathy Study or Snellen visual acuity (VA) was measured before and after each treatment session. All treatment was administered in a clinical setting. Significant increases were seen in VA in DAMD (P=0.012, Wilcoxon one-sample test), but in WAMD, improvements did not reach statistical significance (P=0.059). In DAMD eyes, twice as many patients showed increase in VA (52%) compared to those showing deterioration (26%), with improvements being often sizeable, whereas deteriorations were usually very slight. In WAMD eyes, five of six (83%) patients showed an increase and none showed deterioration. The substantial changes observed over this period, combined with continued improvement for patients who continued treatment once a month, are encouraging for future studies. The changes observed indicate the potential efficacy of microcurrent to delay degeneration and possibly improve age-related macular degeneration, both wet and dry. However, this study has no control arm, so results should be treated with caution. Randomized double-blind controlled studies

  8. The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration

    PubMed Central

    2013-01-01

    Most neurons are born with the potential to live for the entire lifespan of the organism. In addition, neurons are highly polarized cells with often long axons, extensively branched dendritic trees and many synaptic contacts. Longevity together with morphological complexity results in a formidable challenge to maintain synapses healthy and functional. This challenge is often evoked to explain adult-onset degeneration in numerous neurodegenerative disorders that result from otherwise divergent causes. However, comparably little is known about the basic cell biological mechanisms that keep normal synapses alive and functional in the first place. How the basic maintenance mechanisms are related to slow adult-onset degeneration in different diseasesis largely unclear. In this review we focus on two basic and interconnected cell biological mechanisms that are required for synaptic maintenance: endomembrane recycling and calcium (Ca2+) homeostasis. We propose that subtle defects in these homeostatic processes can lead to late onset synaptic degeneration. Moreover, the same basic mechanisms are hijacked, impaired or overstimulated in numerous neurodegenerative disorders. Understanding the pathogenesis of these disorders requires an understanding of both the initial cause of the disease and the on-going changes in basic maintenance mechanisms. Here we discuss the mechanisms that keep synapses functional over long periods of time with the emphasis on their role in slow adult-onset neurodegeneration. PMID:23829673

  9. Fast wandering of slow birds.

    PubMed

    Toner, John

    2011-12-01

    I study a single slow bird moving with a flock of birds of a different and faster (or slower) species. I find that every species of flocker has a characteristic speed γ ≠ v(0), where v(0) is the mean speed of the flock such that if the speed v(s) of the slow bird equals γ, it will randomly wander transverse to the mean direction of flock motion far faster than the other birds will: Its mean-squared transverse displacement will grow in d = 2 with time t like t(5/3), in contrast to t(4/3) for the other birds. In d = 3, the slow bird's mean-squared transverse displacement grows like t(5/4), in contrast to t for the other birds. If v(s) ≠ γ, the mean-squared displacement of the slow bird crosses over from t(5/3) to t(4/3) scaling in d = 2 and from t(5/4) to t scaling in d = 3 at a time t(c) that scales according to t(c) proportionally |v(s) - γ|(-2).

  10. Superconductive Microwave Slow Wave Structures.

    DTIC Science & Technology

    etching techniques , non-dispersive microstrip lines with storage times of several tens of microseconds and gigahertz bandwidths can be constructed. The...pulse compression study has shown that compression ratios of over 1,000 may be feasible using a superconductive slow wave structure in which radiation

  11. Supporting public involvement in research design and grant development: a case study of a public involvement award scheme managed by a National Institute for Health Research (NIHR) Research Design Service (RDS).

    PubMed

    Boote, Jonathan D; Twiddy, Maureen; Baird, Wendy; Birks, Yvonne; Clarke, Clare; Beever, Daniel

    2015-10-01

    It is good practice for the public to be involved in developing health research. Resources should be available for researchers to fund the involvement of the public in the development of their grants. To describe a funding award scheme to support public involvement in grant development, managed by an NIHR Research Design Service (RDS). Case examples of how the award contributed to successful grant applications and findings from a recent evaluation of the scheme are presented. A case study of resource provision to support public involvement activities in one region of England. University and NHS-based researchers, and members of the public. Between 2009 and 2012, the RDS approved 45 public involvement funding awards (totalling nearly £19,000). These awards contributed to 27 submitted applications at the time of writing, of which 11 were successful (totalling over £7.5 million). The evaluation revealed difficulties encountered by some researchers when involving the public in grant development, which led to suggestions about how the scheme could be improved. This award scheme represents an efficient method of providing researchers with resources to involve the public in grant development and would appear to represent good value for money. © 2013 John Wiley & Sons Ltd.

  12. Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis

    PubMed Central

    Leroy, Félix; Lamotte d'Incamps, Boris; Imhoff-Manuel, Rebecca D; Zytnicki, Daniel

    2014-01-01

    In amyotrophic lateral sclerosis (ALS) the large motoneurons that innervate the fast-contracting muscle fibers (F-type motoneurons) are vulnerable and degenerate in adulthood. In contrast, the small motoneurons that innervate the slow-contracting fibers (S-type motoneurons) are resistant and do not degenerate. Intrinsic hyperexcitability of F-type motoneurons during early postnatal development has long been hypothesized to contribute to neural degeneration in the adult. Here, we performed a critical test of this hypothesis by recording from identified F- and S-type motoneurons in the superoxide dismutase-1 mutant G93A (mSOD1), a mouse model of ALS at a neonatal age when early pathophysiological changes are observed. Contrary to the standard hypothesis, excitability of F-type motoneurons was unchanged in the mutant mice. Surprisingly, the S-type motoneurons of mSDO1 mice did display intrinsic hyperexcitability (lower rheobase, hyperpolarized spiking threshold). As S-type motoneurons are resistant in ALS, we conclude that early intrinsic hyperexcitability does not contribute to motoneuron degeneration. DOI: http://dx.doi.org/10.7554/eLife.04046.001 PMID:25313866

  13. Genetic deletion of S-opsin prevents rapid cone degeneration in a mouse model of Leber congenital amaurosis

    PubMed Central

    Zhang, Tao; Enemchukwu, Nduka O.; Jones, Alex; Wang, Shixian; Dennis, Emily; Watt, Carl B.; Pugh, Edward N.; Fu, Yingbin

    2015-01-01

    Mutations in RPE65 or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal synthesis and cause Leber congenital amaurosis (LCA), a severe hereditary blindness occurring in early childhood. The pathology is attributed to a combination of 11-cis-retinal deficiency and photoreceptor degeneration. The mistrafficking of cone membrane-associated proteins including cone opsins (M- and S-opsins), cone transducin (Gαt2), G-protein-coupled receptor kinase 1 (GRK1) and guanylate cyclase 1 (GC1) has been suggested to play a role in cone degeneration. However, their precise role in cone degeneration is unclear. Here we investigated the role of S-opsin (Opn1sw) in cone degeneration in Lrat−/−, a murine model for LCA, by genetic ablation of S-opsin. We show that deletion of just one allele of S-opsin from Lrat−/− mice is sufficient to prevent the rapid cone degeneration for at least 1 month. Deletion of both alleles of S-opsin prevents cone degeneration for an extended period (at least 12 months). This genetic prevention is accompanied by a reduction of endoplasmic reticulum (ER) stress in Lrat−/− photoreceptors. Despite cone survival in Opn1sw−/−Lrat−/− mice, cone membrane-associated proteins (e.g. Gαt2, GRK1 and GC1) continue to have trafficking problems. Our results suggest that cone opsins are the ‘culprit’ linking 11-cis-retinal deficiency to cone degeneration in LCA. This result has important implications for the current gene therapy strategy that emphasizes the need for a combinatorial therapy to both improve vision and slow photoreceptor degeneration. PMID:25416279

  14. Optic pathway degeneration in Japanese black cattle.

    PubMed

    Chiba, Shiori; Funato, Shingo; Horiuchi, Noriyuki; Matsumoto, Kotaro; Inokuma, Hisashi; Furuoka, Hidefumi; Kobayashi, Yoshiyasu

    2015-02-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy.

  15. Optic pathway degeneration in Japanese black cattle

    PubMed Central

    CHIBA, Shiori; FUNATO, Shingo; HORIUCHI, Noriyuki; MATSUMOTO, Kotaro; INOKUMA, Hisashi; FURUOKA, Hidefumi; KOBAYASHI, Yoshiyasu

    2014-01-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy. PMID:25421501

  16. Slow-roll thawing quintessence

    SciTech Connect

    Chiba, Takeshi

    2009-04-15

    We derive slow-roll conditions for thawing quintessence. We solve the equation of motion of {phi} for a Taylor expanded potential (up to the quadratic order) in the limit where the equation of state w is close to -1 to derive the equation of state as a function of the scale factor. We find that the evolution of {phi} and hence w are described by only two parameters. The expression for w(a), which can be applied to general thawing models, coincides precisely with that derived recently by Dutta and Scherrer for hilltop quintessence. The consistency conditions of |w+1|<<1 are derived. The slow-roll conditions for freezing quintessence are also derived.

  17. Slow-roll extended quintessence

    SciTech Connect

    Chiba, Takeshi; Siino, Masaru; Yamaguchi, Masahide

    2010-04-15

    We derive the slow-roll conditions for a nonminimally coupled scalar field (extended quintessence) during the radiation/matter dominated era extending our previous results for thawing quintessence. We find that the ratio {phi}e/3H{phi} becomes constant but negative, in sharp contrast to the ratio for the minimally coupled scalar field. We also find that the functional form of the equation of state of the scalar field asymptotically approaches that of the minimally coupled thawing quintessence.

  18. Slow extraction at the SSC

    SciTech Connect

    Colton, E.P.

    1985-01-01

    Resonant slow extraction at the SSC will permit fixed-target operation. Stochastic extraction appears to be a promising technique for achieving spill times of the order of 1000 s. However, systematic sextupole error fields in the SSC dipoles must be reduced a factor of twenty from the design values; otherwise the extraction process will be perturbed or suppressed. In addition, good regulation of the SSC power supplies is essential for smooth extraction over the spill period. 10 refs., 1 fig.

  19. Autophagy in axonal and dendritic degeneration.

    PubMed

    Yang, Yi; Coleman, Michael; Zhang, Lihui; Zheng, Xiaoxiang; Yue, Zhenyu

    2013-07-01

    Degeneration of axons and dendrites is a common and early pathological feature of many neurodegenerative disorders, and is thought to be regulated by mechanisms distinct from those determining death of the cell body. The unique structures of axons and dendrites (collectively neurites) may cause them to be particularly vulnerable to the accumulation of protein aggregates and damaged organelles. Autophagy is a catabolic mechanism in which cells clear protein aggregates and damaged organelles. Basal autophagy occurs continuously as a housekeeping function, and can be acutely expanded in response to stress or injury. Emerging evidence shows that insufficient or excessive autophagy contributes to neuritic degeneration. Here, we review the recent progress that has begun to reveal the role of autophagy in neurite function and degeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. The cell stress machinery and retinal degeneration.

    PubMed

    Athanasiou, Dimitra; Aguilà, Monica; Bevilacqua, Dalila; Novoselov, Sergey S; Parfitt, David A; Cheetham, Michael E

    2013-06-27

    Retinal degenerations are a group of clinically and genetically heterogeneous disorders characterised by progressive loss of vision due to neurodegeneration. The retina is a highly specialised tissue with a unique architecture and maintaining homeostasis in all the different retinal cell types is crucial for healthy vision. The retina can be exposed to a variety of environmental insults and stress, including light-induced damage, oxidative stress and inherited mutations that can lead to protein misfolding. Within retinal cells there are different mechanisms to cope with disturbances in proteostasis, such as the heat shock response, the unfolded protein response and autophagy. In this review, we discuss the multiple responses of the retina to different types of stress involved in retinal degenerations, such as retinitis pigmentosa, age-related macular degeneration and glaucoma. Understanding the mechanisms that maintain and re-establish proteostasis in the retina is important for developing new therapeutic approaches to fight blindness.

  1. Slow light and saturable absorption

    NASA Astrophysics Data System (ADS)

    Selden, A. C.

    2009-06-01

    Quantitative analysis of slow light experiments utilising coherent population oscillation (CPO) in a range of saturably absorbing media, including ruby and alexandrite, Er3+:Y2SiO5, bacteriorhodopsin, semiconductor quantum devices and erbium-doped optical fibres, shows that the observations may be more simply interpreted as saturable absorption phenomena. A basic two-level model of a saturable absorber displays all the effects normally associated with slow light, namely phase shift and modulation gain of the transmitted signal, hole burning in the modulation frequency spectrum and power broadening of the spectral hole, each arising from the finite response time of the non-linear absorption. Only where hole-burning in the optical spectrum is observed (using independent pump and probe beams), or pulse delays exceeding the limits set by saturable absorption are obtained, can reasonable confidence be placed in the observation of slow light in such experiments. Superluminal (“fast light”) phenomena in media with reverse saturable absorption (RSA) may be similarly explained.

  2. Potential Outcome Factors in Subacute Combined Degeneration

    PubMed Central

    Vasconcelos, Olavo M; Poehm, Erika H; McCarter, Robert J; Campbell, William W; Quezado, Zenaide M N

    2006-01-01

    BACKGROUND Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown; therefore, predicting complete recovery of neurologic deficits is challenging. PURPOSE To identify potential correlates of outcome and to generate hypotheses concerning predictors of complete resolution of neurologic deficits in subacute combined degeneration. DATA SOURCE We searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and references from identified reports. REPORTS SELECTION Reports of patients with subacute combined degeneration containing results of magnetic resonance imaging (MRI) and description of outcome and 1 patient treated by the authors. DATA EXTRACTION, SYNTHESIS We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms. RESULTS Eight patients (14%) achieved clinical resolution and 49 (86%) improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg, and Babinski signs were associated with a higher complete resolution rate. Patients with MRI lesions in ≤7 segments and age less than 50 also appear to have higher rates of complete resolution. CONCLUSIONS B12 therapy is reported to stop progression and improve neurologic deficits in most patients with subacute combined degeneration. However, complete resolution only occurs in a small percentage of patients and appears to be associated with factors suggestive of less severe disease at the time of diagnosis. PMID:16970556

  3. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), 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 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  4. Retinal degeneration associated with ectopia lentis.

    PubMed

    Simonelli, F; De Crecchio, G; Testa, F; Nunziata, G; Mazzeo, S; Romano, N; Cavaliere, L; Rinaldi, M M; Rinaldi, E

    1999-06-01

    Two brothers had retinal degeneration, lens subluxation, and myopia since early life. There was no evidence of Marfan syndrome, homocystinuria, or other systemic disease. They had nystagmus, myopia, inferior dislocation of the lens, and posterior subcapsular opacities in both eyes. Fundus examination showed attenuated retinal vessels, macular atrophy with occasional pigment accumulation as clumps, and perivascular sleeves. Electroretinography revealed decreased photopic and scotopic responses. The visual fields were constricted. We believe this to be the first report of retinal degeneration with bilateral lens subluxation in a family. It appears to be inherited in an autosomal recessive fashion.

  5. Retinal Cell Degeneration in Animal Models

    PubMed Central

    Niwa, Masayuki; Aoki, Hitomi; Hirata, Akihiro; Tomita, Hiroyuki; Green, Paul G.; Hara, Akira

    2016-01-01

    The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage. PMID:26784179

  6. Pathogenesis of tendinopathies: inflammation or degeneration?

    PubMed Central

    Abate, Michele; Gravare-Silbernagel, Karin; Siljeholm, Carl; Di Iorio, Angelo; De Amicis, Daniele; Salini, Vincenzo; Werner, Suzanne; Paganelli, Roberto

    2009-01-01

    The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies. PMID:19591655

  7. Visual system degeneration induced by blast overpressure.

    PubMed

    Petras, J M; Bauman, R A; Elsayed, N M

    1997-07-25

    The effect of blast overpressure on visual system pathology was studied in 14 male Sprague-Dawley rats weighing 360-432 g. Blast overpressure was simulated using a compressed-air driven shock tube, with the aim of studying a range of overpressures causing sublethal injury. Neither control (unexposed) rats nor rats exposed to 83 kiloPascals (kPa) overpressure showed evidence of visual system pathology. Neurological injury to brain visual pathways was observed in male rats surviving blast overpressure exposures of 104-110 kPa and 129-173 kPa. Optic nerve fiber degeneration was ipsilateral to the blast pressure wave. The optic chiasm contained small numbers of degenerated fibers. Optic tract fiber degeneration was present bilaterally, but was predominantly ipsilateral. Optic tract fiber degeneration was followed to nuclear groups at the level of the midbrain, midbrain-diencephalic junction, and the thalamus where degenerated fibers arborized among the neurons of: (i) the superior colliculus, (ii) pretectal region, and (iii) the lateral geniculate body. The superior colliculus contained fiber degeneration localized principally to two superficial layers (i) the stratum opticum (layer III) and (ii) stratum cinereum (layer II). The pretectal area contained degenerated fibers which were widespread in (i) the nucleus of the optic tract, (ii) olivary pretectal nucleus, (iii) anterior pretectal nucleus, and (iv) the posterior pretectal nucleus. Degenerated fibers in the lateral geniculate body were not universally distributed. They appeared to arborize among neurons of the dorsal and ventral nuclei: the ventral lateral geniculate nucleus (parvocellular and magnocellular parts); and the dorsal lateral geniculate nucleus. The axonopathy observed in the central visual pathways and nuclei of the rat brain are consistent with the presence of blast overpressure induced injury to the retina. The orbital cavities of the human skull contain frontally-directed eyeballs for binocular

  8. Kinematic control of robot with degenerate wrist

    NASA Technical Reports Server (NTRS)

    Barker, L. K.; Moore, M. C.

    1984-01-01

    Kinematic resolved rate equations allow an operator with visual feedback to dynamically control a robot hand. When the robot wrist is degenerate, the computed joint angle rates exceed operational limits, and unwanted hand movements can result. The generalized matrix inverse solution can also produce unwanted responses. A method is introduced to control the robot hand in the region of the degenerate robot wrist. The method uses a coordinated movement of the first and third joints of the robot wrist to locate the second wrist joint axis for movement of the robot hand in the commanded direction. The method does not entail infinite joint angle rates.

  9. CT of sarcomatous degeneration in neurofibromatosis

    SciTech Connect

    Coleman, B.G.; Arger, P.H.; Dalinka, M.K.; Obringer, A.C.; Raney, B.R.; Meadows, A.T.

    1983-02-01

    Neurofibromatosis is a relatively common disorder that often involves many organ systems. One of the least understood aspects of this malady is a well documented potential for sarcomatous degeneration of neurofibromas. The inability to identify patients at risk and the lack of noninvasive screening methods for symptomatic patients often leads to late diagnosis. In six of seven subsequently proven neurofibrosarcomas, CT demonstrated low-density areas that histopathologically appeared to be due to necrosis, hemorrhage, and/or cystic degeneration. The density differences within these sarcomas were enhanced by the intravenous adminstration of iodinated contrast agents.

  10. [New aspects in age related macular degeneration].

    PubMed

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  11. Modal theory of slow light enhanced third-order nonlinear effects in photonic crystal waveguides.

    PubMed

    Chen, Tao; Sun, Junqiang; Li, Linsen

    2012-08-27

    In this paper, we derive the couple-mode equations for third-order nonlinear effects in photonic crystal waveguides by employing the modal theory. These nonlinear interactions include self-phase modulation, cross-phase modulation and degenerate four-wave mixing. The equations similar to that in nonlinear fiber optics could be expanded and applied for third-order nonlinear processes in other periodic waveguides. Based on the equations, we systematically analyze the group-velocity dispersion, optical propagation loss, effective interaction area, slow light enhanced factor and phase mismatch for a slow light engineered silicon photonic crystal waveguide. Considering the two-photon and free-carrier absorptions, the wavelength conversion efficiencies in two low-dispersion regions are numerically simulated by utilizing finite difference method. Finally, we investigate the influence of slow light enhanced multiple four-wave-mixing process on the conversion efficiency.

  12. Axial Creep Loading and Unloaded Recovery of the Human Intervertebral Disc and the Effect of Degeneration

    PubMed Central

    O'Connell, Grace D.; Jacobs, Nathan T.; Sen, Sounok; Vresilovic, Edward J.; Elliott, Dawn M.

    2011-01-01

    The intervertebral disc maintains a balance between externally applied loads and internal osmotic pressure. Fluid flow plays a key role in this process, causing fluctuations in disc hydration and height. The objectives of this study were to quantify and model the axial creep and recovery responses of nondegenerate and degenerate human lumbar discs. Two experiments were performed. First, a slow compressive ramp was applied to 2000 N, unloaded to allow recovery for up to 24 hours, and re-applied. The linear-region stiffness and disc height were within 5% of the initial condition for recovery times greater than 8 hours. In the second experiment, a 1000 N creep load was applied for four hours, unloaded recovery monitored for 24 hours, and the creep load repeated. A viscoelastic model comprised of a “fast” and “slow” exponential response was used to describe the creep and recovery, where the fast response is associated with flow in the nucleus pulposus (NP) and endplate, while the slow response is associated with the annulus fibrosus (AF). The study demonstrated that recovery is 3-4X slower than loading. The fast response was correlated with degeneration, suggesting larger changes in the NP with degeneration compared to the AF. However, the fast response comprised only 10-15% of the total equilibrium displacement, with the AF-dominated slow response comprising 40-70%. Finally, the physiological loads and deformations and their associated long equilibrium times confirm that diurnal loading does not represent “equilibrium” in the disc, but that over time the disc is in steady-state. PMID:21783103

  13. Rod photoreceptors protect from cone degeneration-induced retinal remodeling and restore visual responses in zebrafish

    PubMed Central

    Saade, Carole J.; Alvarez-Delfin, Karen; Fadool, James M.

    2013-01-01

    Humans are largely dependent upon cone-mediated vision. However, death or dysfunction of rods, the predominant photoreceptor subtype, results in secondary loss of cones, remodeling of retinal circuitry and blindness. The changes in circuitry may contribute to the vision deficit and undermine attempts at restoring sight. We exploit zebrafish larvae as a genetic model to specifically characterize changes associated with photoreceptor degenerations in a cone-dominated retina. Photoreceptors form synapses with two types of second order neurons, bipolar cells and horizontal cells. Using cell-specific reporter gene expression and immunolabeling for postsynaptic glutamate receptors, significant remodeling is observed following cone degeneration in the pde6cw59 larval retina but not rod degeneration in the Xops:mCFPq13 line. In adults, rods and cones are present in approximately equal numbers, and in pde6cw59 mutants glutamate receptor expression and synaptic structures in the outer plexiform layer are preserved, and visual responses are gained in these once-blind fish. We propose that the abundance of rods in the adult protects the retina from cone degeneration-induced remodeling. We test this hypothesis by genetically manipulating the number of rods in larvae. We show that an increased number and uniform distribution of rods in lor/tbx2bp22bbtl or six7 morpholino-injected larvae protect from pde6cw59-induced secondary changes. The observations that remodeling is a common consequence of photoreceptor death across species, and that in zebrafish a small number of surviving photoreceptors afford protection from degeneration-induced changes provides a model for systematic analysis of factors that slow or even prevent the secondary deteriorations associated with neural degenerative disease. PMID:23365220

  14. Rod photoreceptors protect from cone degeneration-induced retinal remodeling and restore visual responses in zebrafish.

    PubMed

    Saade, Carole J; Alvarez-Delfin, Karen; Fadool, James M

    2013-01-30

    Humans are largely dependent upon cone-mediated vision. However, death or dysfunction of rods, the predominant photoreceptor subtype, results in secondary loss of cones, remodeling of retinal circuitry, and blindness. The changes in circuitry may contribute to the vision deficit and undermine attempts at restoring sight. We exploit zebrafish larvae as a genetic model to specifically characterize changes associated with photoreceptor degenerations in a cone-dominated retina. Photoreceptors form synapses with two types of second-order neurons, bipolar cells, and horizontal cells. Using cell-specific reporter gene expression and immunolabeling for postsynaptic glutamate receptors, significant remodeling is observed following cone degeneration in the pde6c(w59) larval retina but not rod degeneration in the Xops:mCFP(q13) line. In adults, rods and cones are present in approximately equal numbers, and in pde6c(w59) mutants glutamate receptor expression and synaptic structures in the outer plexiform layer are preserved, and visual responses are gained in these once blind fish. We propose that the abundance of rods in the adult protects the retina from cone degeneration-induced remodeling. We test this hypothesis by genetically manipulating the number of rods in larvae. We show that an increased number and uniform distribution of rods in lor/tbx2b(p25bbtl) or six7 morpholino-injected larvae protect from pde6c(w59)-induced secondary changes. The observations that remodeling is a common consequence of photoreceptor death across species, and that in zebrafish a small number of surviving photoreceptors afford protection from degeneration-induced changes, provides a model for systematic analysis of factors that slow or even prevent the secondary deteriorations associated with neural degenerative disease.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. [Progression of treatment and researches in dry age related macular degeneration].

    PubMed

    Zhang, Kaiyan; Tang, Shibo

    2015-03-01

    Age related macular degeneration (AMD) is the leading cause of blindness and visual disability among old patients in Europe and North America. AMD has been divided into two broad clinical categories depending on whether there is a presence of abnormal neovascularization: neovascular (exudative or wet) AMD and dry (or geographic atrophic) AMD. VEGF has been understood as a pathogenesis of wet AMD which allows us to get breakthroughs in treatment. While the progression of dry AMD treatment is very slow because the lack of pathogenesis, no acute loss of vision, and without appropriate standards for treatment. This review tries to introduce about the recent researches and progressions for dry AMD treatment.

  17. Bullous degeneration of the left lower lobe in a heroin addict.

    PubMed

    Smeenk, F W; Serlie, J; van der Jagt, E J; Postmus, P E

    1990-11-01

    A 34 yr old heroin addict was referred because of chest pain caused by air-trapping in a bulla in the left lower lobe. There was a marked difference between the functional residual capacity measured by body-plethysmography and helium dilution. A slow wash-in and wash-out were demonstrated by ventilation scintigraphy with Xenon133. Bullous degeneration is a known complication of intravenous drug abuse. Usually these bullae are found in the upper lobes. Possible causative mechanisms are discussed.

  18. Single Degenerate Progenitors of Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Bours, Madelon; Toonen, Silvia; Nelemans, Gijs

    2013-01-01

    There is a general agreement that Type Ia supernovae correspond to the thermonuclear runaway of a white dwarf (WD) in a compact binary. The details of these progenitor systems are still unclear. Using the population synthesis code SeBa and several assumption for the WD retention efficiency, we estimate the delay times and supernova rates for the single degenerate scenario.

  19. Superfluid regimes in degenerate atomic Fermi gases

    SciTech Connect

    Shlyapnikov, G.V.

    2005-05-05

    We give a brief overview of recent studies of quantum degenerate regimes in ultracold Fermi gases. The attention is focused on the regime of Bose-Einstein condensation of weakly bound molecules of fermionic atoms, formed at a large positive scattering length for the interspecies atom-atom interaction. We analyze remarkable collisional stability of these molecules and draw prospects for future studies.

  20. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  1. Ecological transition predictably associated with gene degeneration.

    PubMed

    Wessinger, Carolyn A; Rausher, Mark D

    2015-02-01

    Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories.

  2. Nonunital Spectral Triples Associated to Degenerate Metrics

    NASA Astrophysics Data System (ADS)

    Rennie, A.

    We show that one can define (p,∞)-summable spectral triples using degenerate metrics on smooth manifolds. Furthermore, these triples satisfy Connes-Moscovici's discrete and finite dimension spectrum hypothesis, allowing one to use the Local Index Theorem [1] to compute the pairing with K-theory. We demonstrate this with a concrete example.

  3. Intervertebral disk degeneration and emerging biologic treatments.

    PubMed

    Kepler, Christopher K; Anderson, D Greg; Tannoury, Chadi; Ponnappan, Ravi K

    2011-09-01

    Although understanding of the biologic basis of intervertebral disk (IVD) degeneration is rapidly advancing, the unique IVD environment presents challenges to the development and delivery of biologic treatments. Acceleration of cellular senescence and apoptosis in degenerative IVDs and the depletion of matrix proteins have prompted the development of treatments based on replacing IVD cells using various cell sources. However, this strategy has not been tested in animal models. IVD degeneration and associated pain have led to interest in pathologic innervation of the IVD and ultimately to the development of percutaneous devices to ablate afferent nerve endings in the posterior annulus. Degeneration leads to changes in the expression of matrix protein, cytokines, and proteinases. Injection of growth factors and mitogens may help overcome these degenerative changes in IVD phenotype, and these potential treatments are being explored in animal studies. Gene therapy is an elegant method to address changes in protein expression, but efforts to apply this technology to IVD degeneration are still at early stages.

  4. On abstract degenerate neutral differential equations

    NASA Astrophysics Data System (ADS)

    Hernández, Eduardo; O'Regan, Donal

    2016-10-01

    We introduce a new abstract model of functional differential equations, which we call abstract degenerate neutral differential equations, and we study the existence of strict solutions. The class of problems and the technical approach introduced in this paper allow us to generalize and extend recent results on abstract neutral differential equations. Some examples on nonlinear partial neutral differential equations are presented.

  5. The nature of apraxia in corticobasal degeneration.

    PubMed Central

    Leiguarda, R; Lees, A J; Merello, M; Starkstein, S; Marsden, C D

    1994-01-01

    Although apraxia is one of the most frequent signs in corticobasal degeneration, the phenomenology of this disorder has not been formally examined. Hence 10 patients with corticobasal degeneration were studied with a standardised evaluation for different types of apraxia. To minimise the confounding effects of the primary motor disorder, apraxia was assessed in the least affected limb. Whereas none of the patients showed buccofacial apraxia, seven showed deficits on tests of ideomotor apraxia and movement imitation, four on tests of sequential arm movements (all of whom had ideomotor apraxia), and three on tests of ideational apraxia (all of whom had ideomotor apraxia). Ideomotor apraxia significantly correlated with deficit in both the mini mental state examination and in a task sensitive to frontal lobe dysfunction (picture arrangement). Two of the three patients with ideomotor apraxia and ideational apraxia showed severe cognitive impairments. The alien limb behaviour was present only in patients with ideomotor apraxia. In conclusion, ideomotor apraxia is the most frequent type of apraxia in corticobasal degeneration, and may be due to dysfunction of the supplementary motor area. There is a subgroup of patients with corticobasal degeneration who have a severe apraxia (ideomotor and ideational apraxia), which correlates with global cognitive impairment, and may result from additional parietal or diffuse cortical damage. PMID:8163995

  6. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  7. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  8. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  9. Membrane trafficking in neuronal maintenance and degeneration.

    PubMed

    Wang, Dong; Chan, Chih-Chiang; Cherry, Smita; Hiesinger, P Robin

    2013-08-01

    Defects in membrane trafficking and degradation are hallmarks of most, and maybe all, neurodegenerative disorders. Such defects typically result in the accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal degradation, or autophagy. The genetic or environmental cause of a specific disease may directly affect these membrane trafficking processes. Alternatively, changes in intracellular sorting and degradation can occur as cellular responses of degenerating neurons to unrelated primary defects such as insoluble protein aggregates or other neurotoxic insults. Importantly, altered membrane trafficking may contribute to the pathogenesis or indeed protect the neuron. The observation of dramatic changes to membrane trafficking thus comes with the challenging need to distinguish pathological from protective alterations. Here, we will review our current knowledge about the protective and destructive roles of membrane trafficking in neuronal maintenance and degeneration. In particular, we will first focus on the question of what type of membrane trafficking keeps healthy neurons alive in the first place. Next, we will discuss what alterations of membrane trafficking are known to occur in Alzheimer's disease and other tauopathies, Parkinson's disease, polyQ diseases, peripheral neuropathies, and lysosomal storage disorders. Combining the maintenance and degeneration viewpoints may yield insight into how to distinguish when membrane trafficking functions protectively or contributes to degeneration.

  10. Central cornea involvement in Terrien's degeneration.

    PubMed

    Nirankari, V S; Kelman, S E; Richards, R D

    1983-03-01

    A 15-year-old female showed classical signs of Terrien's corneal degeneration including peripheral corneal thinning, vascularization, lipid deposition, and ectasia. She also showed episodes of conjunctival inflammation and perforation following minor trauma, all in the presence of an intact epithelium. She also showed progressive central corneal thinning and opacification, features not reported in the literature in the last 30 years.

  11. Retinal remodeling in inherited photoreceptor degenerations.

    PubMed

    Marc, Robert E; Jones, Bryan W

    2003-10-01

    Photoreceptor degenerations initiated in rods or the retinal pigmented epithelium usually evoke secondary cone death and sensory deafferentation of the surviving neural retina. In the mature central nervous system, deafferentation evokes atrophy and connective re-patterning. It has been assumed that the neural retina does not remodel, and that it is a passive survivor. Screening of advanced stages of human and rodent retinal degenerations with computational molecular phenotyping has exposed a prolonged period of aggressive negative remodeling in which neurons migrate along aberrant glial columns and seals, restructuring the adult neural retina (1). Many neurons die, but survivors rewire the remnant inner plexiform layer (IPL), forming thousands of novel ectopic microneuromas in the remnant inner nuclear layer (INL). Bipolar and amacrine cells engage in new circuits that are most likely corruptive. Remodeling in human and rodent retinas emerges regardless of the molecular defects that initially trigger retinal degenerations. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, the exposure of intrinsic retinal remodeling by the removal of sensory control in retinal degenerations suggests that neuronal organization in the normal retina may be more plastic than previously believed.

  12. Retinal remodeling triggered by photoreceptor degenerations.

    PubMed

    Jones, Bryan W; Watt, Carl B; Frederick, Jeanne M; Baehr, Wolfgang; Chen, Ching-Kang; Levine, Edward M; Milam, Ann H; Lavail, Matthew M; Marc, Robert E

    2003-09-08

    Many photoreceptor degenerations initially affect rods, secondarily leading to cone death. It has long been assumed that the surviving neural retina is largely resistant to this sensory deafferentation. New evidence from fast retinal degenerations reveals that subtle plasticities in neuronal form and connectivity emerge early in disease. By screening mature natural, transgenic, and knockout retinal degeneration models with computational molecular phenotyping, we have found an extended late phase of negative remodeling that radically changes retinal structure. Three major transformations emerge: 1) Müller cell hypertrophy and elaboration of a distal glial seal between retina and the choroid/retinal pigmented epithelium; 2) apparent neuronal migration along glial surfaces to ectopic sites; and 3) rewiring through evolution of complex neurite fascicles, new synaptic foci in the remnant inner nuclear layer, and new connections throughout the retina. Although some neurons die, survivors express molecular signatures characteristic of normal bipolar, amacrine, and ganglion cells. Remodeling in human and rodent retinas is independent of the initial molecular targets of retinal degenerations, including defects in the retinal pigmented epithelium, rhodopsin, or downstream phototransduction elements. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, it suggests that the neural retina may be more plastic than previously believed.

  13. Intense source of slow positrons

    NASA Astrophysics Data System (ADS)

    Perez, P.; Rosowsky, A.

    2004-10-01

    We describe a novel design for an intense source of slow positrons based on pair production with a beam of electrons from a 10 MeV accelerator hitting a thin target at a low incidence angle. The positrons are collected with a set of coils adapted to the large production angle. The collection system is designed to inject the positrons into a Greaves-Surko trap (Phys. Rev. A 46 (1992) 5696). Such a source could be the basis for a series of experiments in fundamental and applied research and would also be a prototype source for industrial applications, which concern the field of defect characterization in the nanometer scale.

  14. Slow Lévy flights

    NASA Astrophysics Data System (ADS)

    Boyer, Denis; Pineda, Inti

    2016-02-01

    Among Markovian processes, the hallmark of Lévy flights is superdiffusion, or faster-than-Brownian dynamics. Here we show that Lévy laws, as well as Gaussian distributions, can also be the limit distributions of processes with long-range memory that exhibit very slow diffusion, logarithmic in time. These processes are path dependent and anomalous motion emerges from frequent relocations to already visited sites. We show how the central limit theorem is modified in this context, keeping the usual distinction between analytic and nonanalytic characteristic functions. A fluctuation-dissipation relation is also derived. Our results may have important applications in the study of animal and human displacements.

  15. The CUORE slow monitoring systems

    DOE PAGES

    Gladstone, L.; Biare, D.; Cappelli, L.; ...

    2017-09-20

    CUORE is a cryogenic experiment searching primarily for neutrinoless double decay inmore » $$^{130}$$Te. It will begin data-taking operations in 2016. To monitor the cryostat and detector during commissioning and data taking, we have designed and developed Slow Monitoring systems. In addition to real-time systems using LabVIEW, we have an alarm, analysis, and archiving website that uses MongoDB, AngularJS, and Bootstrap software. These modern, state of the art software packages make the monitoring system transparent, easily maintainable, and accessible on many platforms including mobile devices.« less

  16. Slow rupture of polymer films

    NASA Astrophysics Data System (ADS)

    Kliakhandler, Igor

    2004-11-01

    Bursting of soap film is a fast and fascinating process. It turns out that certain polymer films rupture in a somewhat similar fashion, but much slower. The slowness of the process allows one to study the rupture of polymer films with details. The rupture process in Hele-Shaw-like fashion shows remarkable properties, and is a very simple system. It turns out that propagation speed of the rupture is a function of the film thickness, and rheologic properties of the polymer. Experimental results will be compared with theory, together with demonstration of the experiment.

  17. Glut, war slow Mideast activity

    SciTech Connect

    Not Available

    1984-07-20

    Oilpatch activity in the Middle East has been on the slow side recently, and with a heated-up war between Iran and Iraq throwing off violent sparks around the Arabian Gulf, it's difficult to keep one's mind on business-as-usual. The article deals with the rising cost of insurance for shipping because of the war and the effects on drilling, production and the environment (oil spills). The development and production of offshore oil and gas in Egypt, Saudi Arabia, and the United Arab Emirates is also discussed.

  18. The CUORE slow monitoring systems

    NASA Astrophysics Data System (ADS)

    Gladstone, L.; Biare, D.; Cappelli, L.; Cushman, J. S.; Del Corso, F.; Fujikawa, B. K.; Hickerson, K. P.; Moggi, N.; Pagliarone, C. E.; Schmidt, B.; Wagaarachchi, S. L.; Welliver, B.; Winslow, L. A.

    2017-09-01

    CUORE is a cryogenic experiment searching primarily for neutrinoless double decay in 130Te. It will begin data-taking operations in 2016. To monitor the cryostat and detector during commissioning and data taking, we have designed and developed Slow Monitoring systems. In addition to real-time systems using LabVIEW, we have an alarm, analysis, and archiving website that uses MongoDB, AngularJS, and Bootstrap software. These modern, state of the art software packages make the monitoring system transparent, easily maintainable, and accessible on many platforms including mobile devices.

  19. Comparison of vitrification and slow cooling for umbilical tissues.

    PubMed

    Da-Croce, Lilian; Gambarini-Paiva, Greicy Helen Ribeiro; Angelo, Patrícia Caroline; Bambirra, Eduardo Alves; Cabral, Antônio Carlos Vieira; Godard, Ana Lúcia Brunialti

    2013-03-01

    The tissue cryopreservation maintains the cellular metabolism in a quiescence state and makes the conservation possible for an indefinite period of time. The choice of an appropriate cryopreservation protocol is essential for maintenance of cryopreserved tissue banks. This study evaluated 10 samples of umbilical cord, from which small fragments of tissue (Wharton's jelly and cord lining membrane) were subjected to two protocols of cryopreservation: slow cooling and vitrification. The samples were frozen for a period of time ranging from 5 to 78 days. The efficiency of cryopreservation was evaluated by testing cell viability, histological analysis, cell culture, cytogenetic analysis and comparison with the results of the fresh samples. The results showed that the slow cooling protocol was more efficient than the vitrification for cryopreservation of umbilical cord tissue, because it has caused fewer changes in the structure of tissue (edema and degeneration of the epithelium) and, despite the significant decrease cell viability compared to fresh samples, the ability of cell proliferation in vitro was preserved in most samples. In conclusion, this study showed that it is possible to cryopreserve small fragments of tissue from the umbilical cord and, to obtain viable cells capable of proliferation in vitro after thawing, contributing to the creation of a frozen tissue bank.

  20. Cell therapy for the degenerating intervertebral disc.

    PubMed

    Tong, Wei; Lu, Zhouyu; Qin, Ling; Mauck, Robert L; Smith, Harvey E; Smith, Lachlan J; Malhotra, Neil R; Heyworth, Martin F; Caldera, Franklin; Enomoto-Iwamoto, Motomi; Zhang, Yejia

    2017-03-01

    Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy. The IVD progressively degenerates with age in humans, and strategies to repair the IVD depend on the stage of degeneration. Cell therapy and cell-based gene therapy aim to address moderate disc degeneration; advanced stage disease may require surgery. Studies involving autologous, allogeneic, and xenogeneic cells have all shown good survival of these cells in the IVD, confirming that the disc niche is an immunologically privileged site, permitting long-term survival of transplanted cells. All of the animal studies reviewed here reported some improvement in disc structure, and 2 studies showed attenuation of local inflammation. Among the 50 studies reviewed, 25 used some type of scaffold, and cell leakage is a consistently noted problem, though some studies showed reduced cell leakage. Hydrogel scaffolds may prevent cell leakage and provide biomechanical support until cells can become established matrix producers. However, these gels need to be optimized to prevent this leakage. Many animal models have been leveraged in this research space. Rabbit is the most frequently used model (28 of 50), followed by rat, pig, and dog. Sheep and goat IVDs resemble those of humans in size and in the absence of notochordal cells. Despite this advantage, there were only 2 sheep and 1 goat studies of 50 studies in this cohort. It is also unclear if a study in large animals is needed before clinical trials since

  1. Molecular mechanisms of retinal ganglion cell degeneration in glaucoma and future prospects for cell body and axonal protection

    PubMed Central

    Munemasa, Yasunari; Kitaoka, Yasushi

    2013-01-01

    Glaucoma, which affects more than 70 million people worldwide, is a heterogeneous group of disorders with a resultant common denominator; optic neuropathy, eventually leading to irreversible blindness. The clinical manifestations of primary open-angle glaucoma (POAG), the most common subtype of glaucoma, include excavation of the optic disc and progressive loss of visual field. Axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies are observed in glaucoma, in which the reduction of intraocular pressure (IOP) is known to slow progression of the disease. A pattern of localized retinal nerve fiber layer (RNFL) defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. The mechanisms of degeneration of neuronal cell bodies and their axons may differ. In this review, we addressed the molecular mechanisms of cell body death and axonal degeneration in glaucoma and proposed axonal protection in addition to cell body protection. The concept of axonal protection may become a new therapeutic strategy to prevent further axonal degeneration or revive dying axons in patients with preperimetric glaucoma. Further study will be needed to clarify whether the combination therapy of axonal protection and cell body protection will have greater protective effects in early or progressive glaucomatous optic neuropathy (GON). PMID:23316132

  2. Don't Forget the Slow Learner.

    ERIC Educational Resources Information Center

    Watson, Daniel L.; Rangel, Lyle

    1989-01-01

    Advocates cooperative learning as an effective tool for reaching slow learners, by bridging the gaps between the learning styles of slow learners and the teaching requirements of the classroom, resulting in improved academic performance for both slow learners and high achievers. (SR)

  3. Slow inactivation in human cardiac sodium channels.

    PubMed Central

    Richmond, J E; Featherstone, D E; Hartmann, H A; Ruben, P C

    1998-01-01

    The available pool of sodium channels, and thus cell excitability, is regulated by both fast and slow inactivation. In cardiac tissue, the requirement for sustained firing of long-duration action potentials suggests that slow inactivation in cardiac sodium channels may differ from slow inactivation in skeletal muscle sodium channels. To test this hypothesis, we used the macropatch technique to characterize slow inactivation in human cardiac sodium channels heterologously expressed in Xenopus oocytes. Slow inactivation was isolated from fast inactivation kinetically (by selectively recovering channels from fast inactivation before measurement of slow inactivation) and structurally (by modification of fast inactivation by mutation of IFM1488QQQ). Time constants of slow inactivation in cardiac sodium channels were larger than previously reported for skeletal muscle sodium channels. In addition, steady-state slow inactivation was only 40% complete in cardiac sodium channels, compared to 80% in skeletal muscle channels. These results suggest that cardiac sodium channel slow inactivation is adapted for the sustained depolarizations found in normally functioning cardiac tissue. Complete slow inactivation in the fast inactivation modified IFM1488QQQ cardiac channel mutant suggests that this impairment of slow inactivation may result from an interaction between fast and slow inactivation. PMID:9635748

  4. Slowing down bubbles with sound

    NASA Astrophysics Data System (ADS)

    Poulain, Cedric; Dangla, Remie; Guinard, Marion

    2009-11-01

    We present experimental evidence that a bubble moving in a fluid in which a well-chosen acoustic noise is superimposed can be significantly slowed down even for moderate acoustic pressure. Through mean velocity measurements, we show that a condition for this effect to occur is for the acoustic noise spectrum to match or overlap the bubble's fundamental resonant mode. We render the bubble's oscillations and translational movements using high speed video. We show that radial oscillations (Rayleigh-Plesset type) have no effect on the mean velocity, while above a critical pressure, a parametric type instability (Faraday waves) is triggered and gives rise to nonlinear surface oscillations. We evidence that these surface waves are subharmonic and responsible for the bubble's drag increase. When the acoustic intensity is increased, Faraday modes interact and the strongly nonlinear oscillations behave randomly, leading to a random behavior of the bubble's trajectory and consequently to a higher slow down. Our observations may suggest new strategies for bubbly flow control, or two-phase microfluidic devices. It might also be applicable to other elastic objects, such as globules, cells or vesicles, for medical applications such as elasticity-based sorting.

  5. Slow Monitoring Systems for CUORE

    NASA Astrophysics Data System (ADS)

    Dutta, Suryabrata; Cuore Collaboration

    2016-09-01

    The Cryogenic Underground Observatory for Rare Events (CUORE) is a ton-scale neutrinoless double-beta decay experiment under construction at the Laboratori Nazionali del Gran Sasso (LNGS). The experiment is comprised of 988 TeO2 bolometric crystals arranged into 19 towers and operated at a temperature of 10 mK. We have developed slow monitoring systems to monitor the cryostat during detector installation, commissioning, data taking, and other crucial phases of the experiment. Our systems use responsive LabVIEW virtual instruments and video streams of the cryostat. We built a website using the Angular, Bootstrap, and MongoDB frameworks to display this data in real-time. The website can also display archival data and send alarms. I will present how we constructed these slow monitoring systems to be robust, accurate, and secure, while maintaining reliable access for the entire collaboration from any platform in order to ensure efficient communications and fast diagnoses of all CUORE systems.

  6. Slow axoplasmic transport under scrutiny.

    PubMed

    Court, Felipe A; Alvarez, Jaime

    2011-01-01

    The origin of axoplasmic proteins is central for the biology of axons. For over fifty years axons have been considered unable to synthesize proteins and that cell bodies supply them with proteins by a slow transport mechanism. To allow for prolonged transport times, proteins were assumed to be stable, i.e., not degraded in axons. These are now textbook notions that configure the slow transport model (STM). The aim of this article is to cast doubts on the validity of STM, as a step toward gaining more understanding about the supply of axoplasmic proteins. First, the stability of axonal proteins claimed by STM has been disproved by experimental evidence. Moreover, the evidence for protein synthesis in axons indicates that the repertoire is extensive and the amount sizeable, which disproves the notion that axons are unable to synthesize proteins and that cell bodies supply most axonal proteins. In turn, axoplasmic protein synthesis gives rise to the metabolic model (MM). We point out a few inconsistencies in STM that MM redresses. Although both models address the supply of proteins to axons, so far they have had no crosstalk. Since proteins underlie every conceivable cellular function, it is necessary to re-evaluate in-depth the origin of axonal proteins. We hope this will shape a novel understanding of the biology of axons, with impact on development and maintenance of axons, nerve repair, axonopathies and plasticity, to mention a few fields.

  7. Slow wave sleep in crayfish.

    PubMed

    Ramón, Fidel; Hernández-Falcón, Jesús; Nguyen, Bao; Bullock, Theodore H

    2004-08-10

    Clear evidence of sleep in invertebrates is still meager. Defined as a distinct state of reduced activity, arousability, attention, and initiative, it is well established in mammals, birds, reptiles, and teleosts. It is commonly defined by additional electroencephalographic criteria that are only well established in mammals and to some extent in birds. Sleep states similar to those in mammals, except for electrical criteria, seem to occur in some invertebrates, based on behavior and some physiological observations. Currently the most compelling evidence for sleep in invertebrates (evidence that meets most standard criteria for sleep) has been obtained in the fruit fly Drosophila melanogaster. However, in mammals, sleep is also characterized by a brain state different from that at rest but awake. The electrophysiological slow wave criterion for this state is not seen in Drosophila or in honey bees. Here, we show that, in crayfish, a behavioral state with elevated threshold for vibratory stimulation is accompanied by a distinctive form of slow wave electrical activity of the brain, quite different from that during waking rest. Therefore, crayfish can attain a sleep state comparable to that of mammals.

  8. Exclusion Process with Slow Boundary

    NASA Astrophysics Data System (ADS)

    Baldasso, Rangel; Menezes, Otávio; Neumann, Adriana; Souza, Rafael R.

    2017-06-01

    We study the hydrodynamic and the hydrostatic behavior of the simple symmetric exclusion process with slow boundary. The term slow boundary means that particles can be born or die at the boundary sites, at a rate proportional to N^{-θ }, where θ > 0 and N is the scaling parameter. In the bulk, the particles exchange rate is equal to 1. In the hydrostatic scenario, we obtain three different linear profiles, depending on the value of the parameter θ ; in the hydrodynamic scenario, we obtain that the time evolution of the spatial density of particles, in the diffusive scaling, is given by the weak solution of the heat equation, with boundary conditions that depend on θ . If θ \\in (0,1), we get Dirichlet boundary conditions, (which is the same behavior if θ =0, see Farfán in Hydrostatics, statical and dynamical large deviations of boundary driven gradient symmetric exclusion processes, 2008); if θ =1, we get Robin boundary conditions; and, if θ \\in (1,∞), we get Neumann boundary conditions.

  9. Anesthetic management of a patient with spinocerebellar degeneration

    PubMed Central

    Vadhanan, Prasanna; Kumar, Pramod

    2011-01-01

    Spinocerebellar degeneration or olivopontocerebellar degeneration denotes a group of disorders of various etiologies manifesting as degenerative changes of various part of the central nervous system. We describe the anesthetic management of a patient with severe olivopontocerebellar degeneration posted for vaginal hysterectomy. A combined spinal epidural technique was performed at the level of L2-L3. The anesthetic implications of the various aspects of spinocerebellar degeneration are discussed. PMID:21772692

  10. Treatment of age-related macular degeneration: focus on ranibizumab

    PubMed Central

    Spitzer, Martin S; Ziemssen, Focke; Bartz-Schmidt, Karl U; Gelisken, Faik; Szurman, Peter

    2008-01-01

    Ranibizumab, a humanized antigen-binding fragment (Fab) that binds all isoforms of VEGF-A, significantly slows down loss of vision and causes significant visual improvement in many patients with choroidal neovascularization (CNV) due to exudative age-related macular degeneration (AMD). These benefits of intravitreal ranibizumab apply to all angiographic subtypes of neovascular AMD and across all lesion sizes when the drug is injected at monthly intervals as shown in two pivotal phase III trials (ANCHOR and MARINA). The results from the PrONTO study suggest that less frequent treatment with ranibizumab through a variable dosing regimen dependent on optical coherence tomography (OCT) findings is a treatment option that results in comparably favorable visual outcomes. Currently, it is unclear whether combination therapy of ranibizumab with photodynamic therapy (PDT) provides any significant advantage over ranibizumab monotherapy (FOCUS trial); however, the combination of PDT and ranibizumab may decrease the need for frequent retreatment. This question will be addressed in the SUMMIT trial. Therapy with ranibizumab is generally very well tolerated with a low rate of seriously adverse ocular events or systemic side-effects. The advent of vascular endothelial growth factor (VEGF) inhibitors has revolutionized the therapy of neovascular AMD. Ranibizumab at the moment appears to be the most effective approved treatment for neovascular AMD. PMID:19668384

  11. Reconstruction of constant slow-roll inflation

    NASA Astrophysics Data System (ADS)

    Gao, Qing

    2017-09-01

    Using the relations between the slow-roll parameters and the power spectra for the single field slow-roll inflation, we derive the scalar spectral tilt n s and the tensor to scalar ratio r for the constant slow-roll inflation, and obtain the constraint on the slow-roll parameter η from the Planck 2015 results. The inflationary potential for the constant slow-roll inflation is then reconstructed in the framework of both general relativity and the scalar-tensor theory of gravity, and compared with the recently reconstructed E model potential. In the strong coupling limit, we show that the η attractor is reached.

  12. Slow Molecular Recognition by RNA.

    PubMed

    Gleitsman, Kristin R; Sengupta, Raghuvir N; Herschlag, Daniel

    2017-09-28

    Molecular recognition is central to biological processes, function, and specificity. Proteins associate with ligands with maximal rates that match the theoretical limit set by the rate of diffusional collision and with a wide range of observed values. As less is known about RNA association, we compiled association rate constants for all RNA/ligand complexes that we could find in the literature. Like proteins, RNAs exhibit a wide range of association rate constants. However, the fastest RNA association rates are considerably slower than those of the fastest protein associations and fall well below the diffusional limit. The apparently general observation of slow association with RNAs has implications for evolution and for modern-day biology. Our compilation highlights a quantitative molecular property that can contribute to biological understanding and underscores our limited physical understanding of molecular recognition events. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  13. Plant domestication slows pest evolution.

    PubMed

    Turcotte, Martin M; Lochab, Amaneet K; Turley, Nash E; Johnson, Marc T J

    2015-09-01

    Agricultural practices such as breeding resistant varieties and pesticide use can cause rapid evolution of pest species, but it remains unknown how plant domestication itself impacts pest contemporary evolution. Using experimental evolution on a comparative phylogenetic scale, we compared the evolutionary dynamics of a globally important economic pest - the green peach aphid (Myzus persicae) - growing on 34 plant taxa, represented by 17 crop species and their wild relatives. Domestication slowed aphid evolution by 13.5%, maintained 10.4% greater aphid genotypic diversity and 5.6% higher genotypic richness. The direction of evolution (i.e. which genotypes increased in frequency) differed among independent domestication events but was correlated with specific plant traits. Individual-based simulation models suggested that domestication affects aphid evolution directly by reducing the strength of selection and indirectly by increasing aphid density and thus weakening genetic drift. Our results suggest that phenotypic changes during domestication can alter pest evolutionary dynamics.

  14. Slow relaxation in granular compaction

    NASA Astrophysics Data System (ADS)

    Ben-Naim, E.; Knight, J. B.; Nowak, E. R.; Jaeger, H. M.; Nagel, S. R.

    1998-11-01

    Experimental studies show that the density of a vibrated granular material evolves from a low density initial state into a higher density final steady state. The relaxation towards the final density follows an inverse logarithmic law. As the system approaches its final state, a growing number of beads have to be rearranged to enable a local density increase. A free volume argument shows that this number grows as N = {ϱ}/{(1-ϱ)}. The time scale associated with such events increases exponentially ∼ e N, and as a result a logarithmically slow approach to the final state is found ϱ ∞ - ϱ(t) ∼ {1}/{lnt }. Furthermore, a one-dimensional toy model that captures this relaxation dynamics as well as the observed density fluctuations is discussed.

  15. Highly Alfvenic Slow Solar Wind

    NASA Technical Reports Server (NTRS)

    Roberts, D. Aaron

    2010-01-01

    It is commonly thought that fast solar wind tends to be highly Alfvenic, with strong correlations between velocity and magnetic fluctuations, but examples have been known for over 20 years in which slow wind is both Alfvenic and has many other properties more typically expected of fast solar wind. This paper will present a search for examples of such flows from more recent data, and will begin to characterize the general characteristics of them. A very preliminary search suggests that such intervals are more common in the rising phase of the solar cycle. These intervals are important for providing constraints on models of solar wind acceleration, and in particular the role waves might or might not play in that process.

  16. Is cosmic acceleration slowing down?

    SciTech Connect

    Shafieloo, Arman; Sahni, Varun; Starobinsky, Alexei A.

    2009-11-15

    We investigate the course of cosmic expansion in its recent past using the Constitution SN Ia sample, along with baryon acoustic oscillations (BAO) and cosmic microwave background (CMB) data. Allowing the equation of state of dark energy (DE) to vary, we find that a coasting model of the universe (q{sub 0}=0) fits the data about as well as Lambda cold dark matter. This effect, which is most clearly seen using the recently introduced Om diagnostic, corresponds to an increase of Om and q at redshifts z < or approx. 0.3. This suggests that cosmic acceleration may have already peaked and that we are currently witnessing its slowing down. The case for evolving DE strengthens if a subsample of the Constitution set consisting of SNLS+ESSENCE+CfA SN Ia data is analyzed in combination with BAO+CMB data. The effect we observe could correspond to DE decaying into dark matter (or something else)

  17. NEUTRINO PROCESSES IN PARTIALLY DEGENERATE NEUTRON MATTER

    SciTech Connect

    Bacca, S.; Hally, K.; Liebendoerfer, M.; Perego, A.; Pethick, C. J.; Schwenk, A.

    2012-10-10

    We investigate neutrino processes for conditions reached in simulations of core-collapse supernovae. In regions where neutrino-matter interactions play an important role, matter is partially degenerate, and we extend earlier work that addressed the degenerate regime. We derive expressions for the spin structure factor in neutron matter, which is a key quantity required for evaluating rates of neutrino processes. We show that, for essentially all conditions encountered in the post-bounce phase of core-collapse supernovae, it is a very good approximation to calculate the spin relaxation rates in the nondegenerate limit. We calculate spin relaxation rates based on chiral effective field theory interactions and find that they are typically a factor of two smaller than those obtained using the standard one-pion-exchange interaction alone.

  18. Macular degeneration in an arc welder.

    PubMed

    Kim, Eun A; Kim, Byung-Gyu; Yi, Cheol-Ho; Kim, Il Gon; Chae, Chang-Ho; Kang, Seong-Kyu

    2007-04-01

    A male welder who had been working in an industrial machine plant for more than 20 years experienced acute intense pain in his left eye with continuous lacrimation while performing arc welding in 1997. Later in 1997, at the age of 39 yr, macular edema was found in his left eye. He was diagnosed with macular degeneration (MD) of the left eye in 2002, and with right eye MD in 2004. Radiation in the visible and near infrared (IR) spectra penetrates the eye and is absorbed by the retina, possibly causing thermal or photochemical damage. Such retinal damage may be permanent and, therefore, sight-threatening. The young age and history of an acute painful eye injury are not consistent with age related macular degeneration (AMD) but rather is likely maculopathy caused by welding arc exposure.

  19. Equivalent multipole operators for degenerate Rydberg states

    SciTech Connect

    Ostrovsky, V. N.; Vrinceanu, D.; Flannery, M. R.

    2006-08-15

    As shown by Pauli, [Z. Phys. 36, 336 (1926)], the electric dipole operator r can be replaced by the Runge-Lenz vector A when operating within the n{sup 2} degenerate manifold of hydrogenic states of principal quantum number n. We seek to develop similar rules for higher multipole operators by expressing equivalent operators in terms only of the two vector constants of motion - the orbital angular momentum L and the Runge-Lenz vector A - appropriate to the degenerate hydrogenic shell. Equivalence of two operators means here that they yield identical matrix elements within a subspace of Hilbert space that corresponds to fixed n. Such equivalent-operator techniques permit direct algebraic calculation of perturbations of Rydberg atoms by external fields and often exact analytical results for transition probabilities. Explicit expressions for equivalent quadrupole and octupole operators are derived, examples are provided, and general aspects of the problem are discussed.

  20. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  1. Drugs in Phase II clinical trials for the treatment of age-related macular degeneration.

    PubMed

    Tolentino, Michael John; Dennrick, Abrahan; John, Elizabeth; Tolentino, Michael Steven

    2015-02-01

    The clinical development of anti-VEGF therapies for the treatment of exudative age-related macular degeneration (wet AMD) has revolutionized ophthalmology. Indeed, it has provided clinicians and patients with treatments that lessen visual loss from in a disease that once was uniformly blinding. Although blindness is yet to be eradicated from AMD, repeated intraocular anti-VEGF injections are required to preserve a patient's vision. Therefore, further advances in this field are necessary. This review provides an overview of the agents that are in mid-stage phase trials for both exudative (wet AMD) and nonexudative macular degeneration (dry AMD). For wet AMD, new agents intend to enhance efficacy, develop alternative delivery such as eye drops, investigate alternate targets and construct sustained release strategies. For advanced dry AMD, the goal is to develop a strategy to slow or stop progressive loss of retinal tissue seen in geographic atrophy, the hallmark of advanced dry AMD. It is important to develop better more sensitive biomarkers, validating different approvable clinical trial endpoints and stratifying patients on their genetic polymorphisms. These developments should help to progress the already rapidly developing field of macular degeneration therapy.

  2. Recombination-generation currents in degenerate semiconductors

    NASA Technical Reports Server (NTRS)

    Von Roos, O.

    1978-01-01

    The classical Shockley-Read-Hall theory of free carrier recombination and generation via traps is extended to degenerate semiconductors. A concise and simple expression is found which avoids completely the concept of a Fermi level, a concept which is alien to nonequilibrium situations. Assumptions made in deriving the recombination generation current are carefully delineated and are found to be basically identical to those made in the original theory applicable to nondegenerate semiconductors.

  3. Recombination-generation currents in degenerate semiconductors

    NASA Technical Reports Server (NTRS)

    Von Roos, O.

    1978-01-01

    The classical Shockley-Read-Hall theory of free carrier recombination and generation via traps is extended to degenerate semiconductors. A concise and simple expression is found which avoids completely the concept of a Fermi level, a concept which is alien to nonequilibrium situations. Assumptions made in deriving the recombination generation current are carefully delineated and are found to be basically identical to those made in the original theory applicable to nondegenerate semiconductors.

  4. Corticospinal tract degeneration in motor neuron disease.

    PubMed

    Mascalchi, M; Salvi, F; Valzania, F; Marcacci, G; Bartolozzi, C; Tassinari, C A

    1995-04-01

    Long-repetition-time spin-echo MR images showed symmetric hyperintensity of the intracerebral corticospinal tracts in two patients with clinical and neurophysiologic diagnosis of primary lateral sclerosis and amyotrophic lateral sclerosis. In both, axial low-flip-angle gradient-echo images of the cervical spine showed hyperintensity of the lateral columns of the cord consistent with antegrade degeneration of the crossed corticospinal tracts.

  5. Dichromatic Langmuir waves in degenerate quantum plasma

    SciTech Connect

    Dubinov, A. E. Kitayev, I. N.

    2015-06-15

    Langmuir waves in fully degenerate quantum plasma are considered. It is shown that, in the linear approximation, Langmuir waves are always dichromatic. The low-frequency component of the waves corresponds to classical Langmuir waves, while the high-frequency component, to free-electron quantum oscillations. The nonlinear problem on the profile of dichromatic Langmuir waves is solved. Solutions in the form of a superposition of waves and in the form of beatings of its components are obtained.

  6. Conceptual foundations of schizophrenia: I. Degeneration.

    PubMed

    Barrett, R J

    1998-10-01

    This is the first of two papers that aim to identify some of the institutional processes of 19th century European psychiatry, and some prevailing cultural themes of that era that played a role in shaping the development of schizophrenia as a disease concept. Three areas of psychiatric history are examined: the first is concerned with the key figures who coined the concept of dementia praecox; the second with the rise of the asylum; and the third is to do with the ideology of 19th century psychiatric science and its relationship to a broader intellectual milieu. These three literatures are examined for common themes. The theme of degeneration is evident in all three literatures, and denotes both a biological process (neuro-degeneration) and a moral state (degeneracy). The idea of degeneration, a pervasive cultural theme of the 19th century, dominated psychiatric thinking long before schizophrenia was developed as a diagnostic category. It contributed to the ideational form-work that gave foundation, structure and shape to the concept of schizophrenia.

  7. Spontaneous hepatocellular adenoma with marked cystic degeneration.

    PubMed

    Kobayashi, M; Enzan, H; Araki, K; Kawai, S; Kitagawa, N

    1999-01-01

    We report a case of spontaneous hepatocellular adenoma with marked cystic degeneration in the non-cirrhotic liver. A 36 year-old Japanese woman with neither history of liver diseases nor use of oral contraceptives and steroids, complained of a 6 kg weight loss over 6 months. Barium meal study revealed an extramural compression along the fornix of the stomach. Abdominal ultrasonography (UC) and computed tomography (CT) demonstrated a mass in the left lateral segment of the liver that measured 11.6x9.5 cm with cystic lesions. Laboratory data on admission showed no significant findings. Celiac angiography revealed a hyper-vascular mass. Surgical exploration revealed a soft mass arising and protruding from the left lateral segment of the liver. Partial resection of the left lateral segment was performed. Histologically, the tumor was surrounded by a thin fibrous pseudocapsule. The neoplastic cells resembling normal hepatocytes around the tumor were large, pale and arranged in thick, irregular cords. Neither mitotic figures nor foci of dysplasia were present. The central portions of the tumor showed marked cystic degeneration. The tumor was histologically diagnosed as hepatocellular adenoma (HCA). HCA with cystic degeneration has been rarely reported.

  8. Hypertrophic olivary degeneration secondary to pontine haemorrhage.

    PubMed

    Wein, Sara; Yan, Bernard; Gaillard, Frank

    2015-07-01

    We report a 58-year-old man who developed hyptertrophic olivary degeneration (HOD) after haemorrhage of a cavernous malformation in the pons. Lesions of the triangle of Guillain and Mollaret (the dentatorubro-olivary pathway) may lead to HOD, a secondary transsynaptic degeneration of the inferior olivary nucleus. HOD is considered unique because the degenerating olive initially becomes hypertrophic rather than atrophic. The primary lesion causing pathway interruption is often haemorrhage, either due to hypertension, trauma, surgery or, as in our patient, a vascular malformation such as a cavernoma. Ischaemia and demyelination can also occasionally be the inciting events. The classic clinical presentation of HOD is palatal myoclonus, although not all patients with HOD develop this symptom. The imaging features of HOD evolve through characteristic phases. The clue to the diagnosis of HOD is recognition of the distinct imaging stages and identification of a remote primary lesion in the triangle of Guillain and Mollaret. Familiarity with the classic imaging findings of this rare phenomenon is necessary in order to avoid misdiagnosis and prevent unnecessary intervention.

  9. Inertial fusion features in degenerate plasmas

    NASA Astrophysics Data System (ADS)

    León, Pablo T.; Eliezer, Shalom; Piera, Mireia; Martínez-Val, José M.

    2005-04-01

    Very high plasma densities can be obtained at the end of the implosion phase in inertial fusion targets, particularly in the so-called fast-ignition scheme (Tabak et al., 1994; Mulser & Bauer, 2004), where a central hot spark is not needed at all. By properly tailoring the fuel compression stage, degenerate states can be reached (Azechi et al., 1991; Nakai et al., 1991; McCory, 1998). In that case, most of the relevant energy transfer mechanisms involving electrons are affected (Honrubia & Tikhonchuk, 2004; Bibi & Matte, 2004; Bibi et al., 2004). For instance, bremsstrahlung emission is highly suppressed (Eliezer et al., 2003). In fact, a low ignition-temperature regime appears at very high plasma densities, due to radiation leakage reduction (León et al., 2001). Stopping power and ion-electron coulomb collisions are also changed in this case, which are important mechanisms to trigger ignition by the incoming fast jet, and to launch the fusion wave from the igniting region into the colder, degenerate plasma. All these points are reviewed in this paper. Although degenerate states would not be easy to obtain by target implosion, they present a very interesting upper limit that deserves more attention in order to complete the understanding on the different domains for inertial confinement fusion.

  10. Visual hallucinations in patients with macular degeneration.

    PubMed

    Holroyd, S; Rabins, P V; Finkelstein, D; Nicholson, M C; Chase, G A; Wisniewski, S C

    1992-12-01

    This study was undertaken to determine the prevalence of visual hallucinations in patients with macular degeneration, describe such hallucinations phenomenologically, and possibly determine factors predisposing to their development. Using a case-control design, the authors screened 100 consecutive patients with age-related macular degeneration for visual hallucinations. Each patient with visual hallucinations was matched to the next three patients without hallucinations. The patients and comparison subjects were compared in terms of scores on the Beck Depression Inventory, Eysenck Personality Questionnaire, Telephone Interview for Cognitive Status, and a structured questionnaire including demographic characteristics, family history, and medical and psychiatric history. Ophthalmologic data were obtained by chart review. Of the 100 patients, 13 experienced visual hallucinations. Four variables were significantly associated with having hallucinations: living alone, lower cognition score, history of stroke, and bilaterally worse visual acuity. Hallucinations were not associated with family or personal history of psychiatric disorder or with personality traits. In 11 (84.6%) of the 13 patients, the hallucinations had begun in association with an acute change in vision. These results indicate that visual hallucinations are prevalent among patients with macular degeneration. They appear unrelated to primary psychiatric disorder. The predisposing factors of bilaterally worse vision and living alone support an association with sensory deprivation, while history of stroke and worse cognition support a decreased cortical inhibition theory.

  11. Magnetic resonance imaging of hypertrophic olivary degeneration.

    PubMed

    Blanco Ulla, M; López Carballeira, A; Pumar Cebreiro, J M

    2015-01-01

    To review the pathophysiologic mechanisms involved in hypertrophic olivary degeneration, with attention to epidemiologic and clinical aspects and especially to imaging findings. We reviewed 5 patients diagnosed with hypertrophic olivary degeneration at our center from 2010 through 2013, analyzing relevant clinical, epidemiologic, and radiologic findings. In all cases, a hyperintensity was seen in the inferior olivary nuclei in FLAIR and T2-weighted sequences. No signal alterations were seen on T1-weighted sequences, and no enhancement was seen after intravenous injection of contrast material. In the cases studied by diffusion-weighted imaging, no significant alterations were seen in these sequences. Olivary hypertrophy was seen in all patients except in one, in whom presumably not enough time had elapsed for hypertrophy to occur. The alterations were bilateral in two of the five cases. Only one case exhibited the typical clinical manifestations. Given that patients may not present clinical manifestations that can be attributed to hypertrophic olivary degeneration, it is important to recognize the characteristic radiologic signs of this entity. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  12. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive, late-onset disorder of the macula affecting central vision. It is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown that AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2016), EMBASE (January 1980 to March 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2016), PubMed (January 1946 to March 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 5 June 2014), 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 31 March 2016. Selection criteria We included randomized controlled trials (RCTs) and quasi-randomized trials that compared statins with other treatments, no treatment, or placebo in people who were diagnosed as having the early stages of AMD. Data collection and analysis We used standard methodological procedures expected by Cochrane. Two review authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to

  13. Slow dynamics in proteins and polymer chains

    NASA Astrophysics Data System (ADS)

    Hu, Chin-Kun

    2013-02-01

    How a biological system can maintain in a non-equilibrium state for a very long time and why proteins aggregate are still not well understood. In this paper, we first review critical slow down of the Ising model and slow relaxation of a spin-glass model at low temperatures. The data indicate that relaxation of the spin glass model at low temperatures can be slower than the critical slowing down of the Ising model. We then review recent molecular dynamics results for the slow relaxation of polymer chains and experimental data for the glassy behavior of collagen fibrils. The slow dynamics in polymer chains and collagen fibrils can provide clues for understanding why a biological system can maintain in a non-equilibrium state for a very long time, and how to slow down protein aggregation related to neurodegenerative diseases.

  14. Comet Borrelly Slows Solar Wind

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Over 1300 energy spectra taken on September 22, 2001 from the ion and electron instruments on NASA's Deep Space 1 span a region of 1,400,000 kilometers (870,000 miles) centered on the closest approach to the nucleus of comet Borrelly. A very strong interaction occurs between the solar wind (horizontal red bands to left and right in figure) and the comet's surrounding cloud of dust and gas, the coma. Near Deep Space 1's closest approach to the nucleus, the solar wind picked up charged water molecules from the coma (upper green band near the center), slowing the wind sharply and creating the V-shaped energy structure at the center.

    Deep Space 1 completed its primary mission testing ion propulsion and 11 other advanced, high-risk technologies in September 1999. NASA extended the mission, taking advantage of the ion propulsion and other systems to undertake this chancy but exciting, and ultimately successful, encounter with the comet. More information can be found on the Deep Space 1 home page at http://nmp.jpl.nasa.gov/ds1/ .

    Deep Space 1 was launched in October 1998 as part of NASA's New Millennium Program, which is managed by JPL for NASA's Office of Space Science, Washington, D.C. The California Institute of Technology manages JPL for NASA.

  15. Slow cooling of protein crystals.

    PubMed

    Warkentin, Matthew; Thorne, Robert E

    2009-10-01

    Cryoprotectant-free thaumatin crystals have been cooled from 300 to 100 K at a rate of 0.1 K s(-1) - 10(3)-10(4) times slower than in conventional flash cooling - while continuously collecting X-ray diffraction data, so as to follow the evolution of protein lattice and solvent properties during cooling. Diffraction patterns show no evidence of crystalline ice at any temperature. This indicates that the lattice of protein molecules is itself an excellent cryoprotectant, and with sodium potassium tartrate incorporated from the 1.5 M mother liquor ice nucleation rates are at least as low as in a 70% glycerol solution. Crystal quality during slow cooling remains high, with an average mosaicity at 100 K of 0.2 degrees . Most of the mosaicity increase occurs above approximately 200 K, where the solvent is still liquid, and is concurrent with an anisotropic contraction of the unit cell. Near 180 K a crossover to solid-like solvent behavior occurs, and on further cooling there is no additional degradation of crystal order. The variation of B factor with temperature shows clear evidence of a protein dynamical transition near 210 K, and at lower temperatures the slope dB/dT is a factor of 3-6 smaller than has been reported for any other protein. These results establish the feasibility of fully temperature controlled studies of protein structure and dynamics between 300 and 100 K.

  16. Fast and slow ENSO modes

    NASA Astrophysics Data System (ADS)

    An, S.; Jin, F.

    2003-12-01

    Climate variability in the tropical Pacific has a rich frequency spectrum that partly results from coupled modes with different time scales. We examined the contributions of the thermocline feedback (the vertical advection of anomalous subsurface temperature by the mean upwelling) and zonal advective feedback (the zonal advection of mean sea surface temperature by anomalous current) in determining the time scales of the coupled modes. Firstly, using a dynamical ocean model, we study the dependence of maximum amplitudes and locations of equatorial zonal current and thermocline on the time scales of the wind forcing. Then we examine in a linearized intermediate air-sea coupled model the impacts of these feedbacks on the co-existence of leading coupled modes of different time scales. For slowly varying wind forcing, amplitudes of zonal currents are very weak and locate at western Pacific, whereas the thermocline response is strong. The zonal advective feedback thus tends but to be of secondly importance in a slow mode of interannual periodicity although it plays a dominating role in a fast coupled mode of near annual periodicity. The changes in the basic state of the coupled system can have significant impacts on the relative importance of the two main feedbacks and thus the periodicity and stability of the leading modes the coupled tropical Pacific climate system.

  17. Excitation of a slow wave structure

    SciTech Connect

    Zhang Peng; Lau, Y. Y.; Hoff, Brad; French, D. M.; Luginsland, J. W.

    2012-12-15

    The Green's function on a slow wave structure is constructed. The Green's function includes all radial modes, and for each radial mode, all space harmonics. We compare the analytic solution of the frequency response on the slow wave structure with that obtained from a particle-in-cell code. Favorable comparison is obtained when the first few lower order modes are resonantly excited. This gives some confidence in the prediction of converting a pulse train into radiation using a slow wave structure.

  18. Computational molecular phenotyping of retinal sheet transplants to rats with retinal degeneration

    PubMed Central

    Seiler, M.J.; Jones, B.W.; Aramant, R.B.; Yang, P.B.; Keirstead, H.S.; Marc, R.E.

    2012-01-01

    Retinal progenitor sheet transplants have been shown to extend neuronal processes into a degenerating host retina and to restore visual responses in the brain. The aim of this study was the first attempt to identify cells involved in transplant signals to retinal degenerate hosts using computational molecular phenotyping (CMP). - S334ter line 3 rats received fetal retinal sheet transplants at the age of 24-40d. Donor tissues were incubated with slow-releasing microspheres containing BDNF or GDNF. Up to 265 days after surgery, eyes of selected rats were vibratome sectioned through the transplant area (some slices stained for donor marker hPAP), dehydrated and embedded in Eponate, sectioned into serial ultrathin datasets and probed for rhodopsin, cone opsin, CRALBP, L-glutamate, L-glutamine, glutathione, glycine, taurine, GABA, and DAPI. - In large transplant areas, photoreceptor outer segments in contact with host RPE revealed rod and cone opsin immunoreactivity whereas no such staining was found in the degenerate host retina. Transplant photoreceptor layers contained high taurine levels. Glutamate levels in the transplants were higher than in the host retina whereas GABA levels were similar. The transplant inner nuclear layer showed some loss of neurons, but amacrine cells and horizontal cells were not reduced. In many areas, glial hypertrophy between the host and transplant was absent and host and transplant neuropil appeared to intermingle. CMP data indicate that horizontal cells and both glycinergic and GABAergic amacrine cells are involved in a novel circuit between transplant and host, generating alternative signal pathways between transplant and degenerating host retina. PMID:22594836

  19. Decreased Fixation Stability of the Preferred Retinal Location in Juvenile Macular Degeneration

    PubMed Central

    Bethlehem, Richard A. I.; Dumoulin, Serge O.; Dalmaijer, Edwin S.; Smit, Miranda; Berendschot, Tos T. J. M.; Nijboer, Tanja C. W.; Van der Stigchel, Stefan

    2014-01-01

    Macular degeneration is the main cause for diminished visual acuity in the elderly. The juvenile form of macular degeneration has equally detrimental consequences on foveal vision. To compensate for loss of foveal vision most patients with macular degeneration adopt an eccentric preferred retinal location that takes over tasks normally performed by the healthy fovea. It is unclear however, whether the preferred retinal locus also develops properties typical for foveal vision. Here, we investigated whether the fixation characteristics of the preferred retinal locus resemble those of the healthy fovea. For this purpose, we used the fixation-offset paradigm and tracked eye-position using a high spatial and temporal resolution infrared eye-tracker. The fixation-offset paradigm measures release from fixation under different fixation conditions and has been shown useful to distinguish between foveal and non-foveal fixation. We measured eye-movements in nine healthy age-matched controls and five patients with juvenile macular degeneration. In addition, we performed a simulation with the same task in a group of five healthy controls. Our results show that the preferred retinal locus does not adopt a foveal type of fixation but instead drifts further away from its original fixation and has overall increased fixation instability. Furthermore, the fixation instability is most pronounced in low frequency eye-movements representing a slow drift from fixation. We argue that the increased fixation instability cannot be attributed to fixation under an unnatural angle. Instead, diminished visual acuity in the periphery causes reduced oculomotor control and results in increased fixation instability. PMID:24937090

  20. Length-dependent axo-terminal degeneration at the neuromuscular synapses of type II muscle in SOD1 mice

    PubMed Central

    Tallon, Carolyn; Russell, Katelyn A.; Sakhalkar, Shilpa; Andrapallayal, Nirmal; Farah, Mohamed H.

    2015-01-01

    In motor neuron diseases, there is a prolonged period of time before any clinical symptoms begin to appear. During this time, distal axonal degeneration, or “dying back” axonopathy, begins to occur before the onset of clinical symptoms and motor neuron death. This preclinical degeneration is a hallmark of motor neuron diseases in both animal models and human patients. Generally, in muscles with mixed fiber types, distal degeneration occurs in fast-fatigable α–motor axons innervating type IIb muscle fibers before axons innervating slow, type I muscle fibers. We investigated whether the “dying back” axonopathy in a pure fast-fatigable α–motor axon nerve is a length dependent process. The lateral thoracic nerve (LTN) exclusively consists of motor nerves that innervate the very thin cutaneous maximus muscle (CMM) that solely contains type II neuromuscular synapses. We characterized the LTN and CMM synapses both morphologically and physiologically in the superoxide dismutase 1 (SOD1) mutant mouse model of amyotrophic lateral sclerosis (ALS). By 60 days of age, there was a significant “dying back” phenomenon at the caudal region while the rostral region remained intact. The longer axons innervating the caudal region appear to be more susceptible to degeneration in the SOD1 mouse indicating that the axonal degeneration of motor neurons innervating type II fibers is a length dependent process. Additionally, we identified how the simplicity of the LTN-CMM system offers a better method to investigate axon degeneration in an ALS mouse model and may be used to investigate possible therapeutic compounds for axon protection and regeneration. PMID:26592719

  1. Length-dependent axo-terminal degeneration at the neuromuscular synapses of type II muscle in SOD1 mice.

    PubMed

    Tallon, C; Russell, K A; Sakhalkar, S; Andrapallayal, N; Farah, M H

    2016-01-15

    In motor neuron diseases, there is a prolonged period of time before any clinical symptoms begin to appear. During this time, distal axonal degeneration, or "dying back" axonopathy, begins to occur before the onset of clinical symptoms and motor neuron death. This preclinical degeneration is a hallmark of motor neuron diseases in both animal models and human patients. Generally, in muscles with mixed fiber types, distal degeneration occurs in fast-fatigable α-motor axons innervating type IIb muscle fibers before axons innervating slow, type I muscle fibers. We investigated whether the "dying back" axonopathy in a pure fast-fatigable α-motor axon nerve is a length-dependent process. The lateral thoracic nerve (LTN) exclusively consists of motor nerves that innervate the very thin cutaneous maximus muscle (CMM) that solely contains type II neuromuscular synapses. We characterized the LTN and CMM synapses both morphologically and physiologically in the superoxide dismutase 1 (SOD1) mutant mouse model of amyotrophic lateral sclerosis (ALS). By 60days of age, there was a significant "dying back" phenomenon at the caudal region while the rostral region remained intact. The longer axons innervating the caudal region appear to be more susceptible to degeneration in the SOD1 mouse indicating that the axonal degeneration of motor neurons innervating type II fibers is a length-dependent process. Additionally, we identified how the simplicity of the LTN-CMM system offers a better method to investigate axon degeneration in an ALS mouse model and may be used to investigate possible therapeutic compounds for axon protection and regeneration. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Synchronization Properties of Slow Cortical Oscillations

    NASA Astrophysics Data System (ADS)

    Takekawa, T.; Aoyagi, T.; Fukai, T.

    During slow-wave sleep, the brain shows slow oscillatory activity with remarkable long-range synchrony. Intracellular recordings show that the slow oscillation consists of two phases: an textit{up} state and a textit{down} state. Deriving the phase-response function of simplified neuronal systems, we examine the synchronization properties on slow oscillations between the textit{up} state and the textit{down} state. As a result, the strange interaction functions are found in some parameter ranges. These functions indicate that the states with the smaller phase lag than a critical value are all stable.

  3. Delayed glial clearance of degenerating axons in aged Drosophila is due to reduced PI3K/Draper activity

    PubMed Central

    Purice, Maria D.; Speese, Sean D.; Logan, Mary A.

    2016-01-01

    Advanced age is the greatest risk factor for neurodegenerative disorders, but the mechanisms that render the senescent brain vulnerable to disease are unclear. Glial immune responses provide neuroprotection in a variety of contexts. Thus, we explored how glial responses to neurodegeneration are altered with age. Here we show that glia–axon phagocytic interactions change dramatically in the aged Drosophila brain. Aged glia clear degenerating axons slowly due to low phosphoinositide-3-kinase (PI3K) signalling and, subsequently, reduced expression of the conserved phagocytic receptor Draper/MEGF10. Importantly, boosting PI3K/Draper activity in aged glia significantly reverses slow phagocytic responses. Moreover, several hours post axotomy, early hallmarks of Wallerian degeneration (WD) are delayed in aged flies. We propose that slow clearance of degenerating axons is mechanistically twofold, resulting from deferred initiation of axonal WD and reduced PI3K/Draper-dependent glial phagocytic function. Interventions that boost glial engulfment activity, however, can substantially reverse delayed clearance of damaged neuronal debris. PMID:27647497

  4. Contraception. Slow train gathers speed.

    PubMed

    Hampton, N; Kubba, A

    The otherwise slow pace of contraceptive research developments has recently quickened, with new products developed, more on the way, and encouraging new data emerging about existing methods. While the 1995 UK pill scare called attention to a differential in the risk of venous thromboembolism (VTE) between pills containing levonorgestrel or norethisterone and those containing desogestrel or gestodene, there is only an extremely small level of excess mortality attributable to third-generation progestogens, less than 2 per million women per year. Tentative evidence suggests that pills with less anti-estrogenic progestogens are neutral with regard to coronary artery disease. The pill remains extremely safe for healthy young women, although additional research with larger numbers of participants is warranted. Salient research findings are that the combined oral contraceptive pill may protect against colon cancer, the pill appears to offer no protection against bone fractures, new products contain less estrogen and have a shortened pill-free interval, a WHO paper showed no significant association between cardiovascular disease and the use of oral or injectable progestogens, a UK study showed no correlation between bone density and plasma estrogen concentrations among long-term users of depot medroxyprogesterone acetate, and a WHO controlled trial found a progestogen-only method of emergency contraception to be considerably more effective in preventing expected pregnancies than the Yuzpe regimen. The T 380 copper IUD provides very high protection against intrauterine and extrauterine pregnancies for 10 years and is now available in an improved inserting mechanism, the Mirena levonorgestrel-releasing IUD system is now licensed for 5 years, and the GyneFIX IUD implant is a frameless device fixed during insertion to the fundal myometrium.

  5. Harmonicity in slow protein dynamics

    NASA Astrophysics Data System (ADS)

    Hinsen, Konrad; Petrescu, Andrei-Jose; Dellerue, Serge; Bellissent-Funel, Marie-Claire; Kneller, Gerald R.

    2000-11-01

    The slow dynamics of proteins around its native folded state is usually described by diffusion in a strongly anharmonic potential. In this paper, we try to understand the form and origin of the anharmonicities, with the principal aim of gaining a better understanding of the principal motion types, but also in order to develop more efficient numerical methods for simulating neutron scattering spectra of large proteins. First, we decompose a molecular dynamics (MD) trajectory of 1.5 ns for a C-phycocyanin dimer surrounded by a layer of water into three contributions that we expect to be independent: the global motion of the residues, the rigid-body motion of the sidechains relative to the backbone, and the internal deformations of the sidechains. We show that they are indeed almost independent by verifying the factorization of the incoherent intermediate scattering function. Then, we show that the global residue motions, which include all large-scale backbone motions, can be reproduced by a simple harmonic model which contains two contributions: a short-time vibrational term, described by a standard normal mode calculation in a local minimum, and a long-time diffusive term, described by Brownian motion in an effective harmonic potential. The potential and the friction constants were fitted to the MD data. The major anharmonic contribution to the incoherent intermediate scattering function comes from the rigid-body diffusion of the sidechains. This model can be used to calculate scattering functions for large proteins and for long-time scales very efficiently, and thus provides a useful complement to MD simulations, which are best suited for detailed studies on smaller systems or for shorter time scales.

  6. Sustained eye closure slows saccades

    PubMed Central

    Shaikh, Aasef G.; Wong, Aaron L.; Optican, Lance M.; Miura, Kenichiro; Solomon, David; Zee, David S.

    2010-01-01

    Saccadic eye movements rapidly orient the line of sight towards the object of interest. Pre-motor burst neurons (BNs) controlling saccades receive excitation from superior colliculus and cerebellum, but inhibition by omnipause neurons (OPNs) prevents saccades. When the OPNs pause, BNs begin to fire. It has been presumed that part of the BN burst comes from post-inhibitory rebound (PIR). We hypothesized that in the absence of prior inhibition from OPNs there would be no PIR, and thus the increase in initial firing rate of BNs would be reduced. Consequently, saccade acceleration would be reduced. We measured eye movements and showed that sustained eye closure, which inhibits the activity of OPNs and thus hypothetically should weaken PIR, reduced the peak velocity, acceleration, and deceleration of saccades in healthy human subjects. Saccades under closed eyelids also had irregular trajectories; the frequency of the oscillations underlying this irregularity was similar to that of high-frequency ocular flutter (back-to-back saccades) often seen in normal subjects during attempted fixation at straight ahead while eyes are closed. Saccades and quick phases of nystagmus are generated by the same pre-motor neurons, and we found that the quick-phase velocity of nystagmus was also reduced by lid closure. These changes were not due to a mechanical hindrance to the eyes, because lid closure did not affect the peak velocities or accelerations of the eyes in the “slow-phase” response to rapid head movements of comparable speeds to those of saccades. These results indicate a role for OPNs in generating the abrupt onset and high velocities of saccades. We hypothesize that the mechanism involved is PIR in pre-motor burst neurons. PMID:20573593

  7. Retinoid receptors trigger neuritogenesis in retinal degenerations

    PubMed Central

    Lin, Yanhua; Jones, Bryan W.; Liu, Aihua; Tucker, James F.; Rapp, Kevin; Luo, Ling; Baehr, Wolfgang; Bernstein, Paul S.; Watt, Carl B.; Yang, Jia-Hui; Shaw, Marguerite V.; Marc, Robert E.

    2012-01-01

    Anomalous neuritogenesis is a hallmark of neurodegenerative disorders, including retinal degenerations, epilepsy, and Alzheimer's disease. The neuritogenesis processes result in a partial reinnervation, new circuitry, and functional changes within the deafferented retina and brain regions. Using the light-induced retinal degeneration (LIRD) mouse model, which provides a unique platform for exploring the mechanisms underlying neuritogenesis, we found that retinoid X receptors (RXRs) control neuritogenesis. LIRD rapidly triggered retinal neuron neuritogenesis and up-regulated several key elements of retinoic acid (RA) signaling, including retinoid X receptors (RXRs). Exogenous RA initiated neuritogenesis in normal adult retinas and primary retinal cultures and exacerbated it in LIRD retinas. However, LIRD-induced neuritogenesis was partly attenuated in retinol dehydrogenase knockout (Rdh12−/−) mice and by aldehyde dehydrogenase inhibitors. We further found that LIRD rapidly increased the expression of glutamate receptor 2 and β Ca2+/calmodulin-dependent protein kinase II (βCaMKII). Pulldown assays demonstrated interaction between βCaMKII and RXRs, suggesting that CaMKII pathway regulates the activities of RXRs. RXR antagonists completely prevented and RXR agonists were more effective than RA in inducing neuritogenesis. Thus, RXRs are in the final common path and may be therapeutic targets to attenuate retinal remodeling and facilitate global intervention methods in blinding diseases and other neurodegenerative disorders.—Lin, Y., Jones, B. W., Liu, A., Tucker, J. F., Rapp, K., Luo, L., Baehr, W., Bernstein, P. S., Watt, C. B., Yang, J.-H., Shaw, M. V., Marc, R. E. Retinoid receptors trigger neuritogenesis in retinal degenerations. PMID:21940995

  8. Preserved retinotopic brain connectivity in macular degeneration.

    PubMed

    Haak, Koen V; Morland, Antony B; Rubin, Gary S; Cornelissen, Frans W

    2016-05-01

    The eye disease macular degeneration (MD) is a leading cause of blindness worldwide. There is no cure for MD, but several promising treatments aimed at restoring vision at the level of the retina are currently under investigation. These treatments assume that the patient's brain can still process appropriately the retinal input once it is restored, but whether this assumption is correct has yet to be determined. We used functional magnetic resonance imaging (fMRI) and connective field modelling to determine whether the functional connectivity between the input-deprived portions of primary visual cortex (V1) and early extrastriate areas (V2/3) is still retinotopically organised. Specifically, in both patients with juvenile macular degeneration and age-matched controls with simulated retinal lesions, we assessed the extent to which the V1-referred connective fields of extrastriate voxels, as estimated on the basis of spontaneous fMRI signal fluctuations, adhered to retinotopic organisation. We found that functional connectivity between the input-deprived portions of visual areas V1 and extrastriate cortex is still largely retinotopically organised in MD, although on average less so than in controls. Patients with stable fixation exhibited normal retinotopic connectivity, however, suggesting that for the patients with unstable fixation, eye-movements resulted in spurious, homogeneous signal modulations across the entire input-deprived cortex, which would have hampered our ability to assess their spatial structure of connectivity. Despite the prolonged loss of visual input due to MD, the cortico-cortical connections of input-deprived visual cortex remain largely intact. This suggests that the restoration of sight in macular degeneration can rely on a largely unchanged retinotopic representation in early visual cortex following loss of central retinal function. © 2016 The Authors Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of

  9. Target Positioning and Tracking in Degenerate Geometry

    DTIC Science & Technology

    2011-07-01

    estimation accuracy is to use the geometric dilution of precision ( GDOP ) [8]. In a poor geometry with not enough independent measurements and/or nearly...in GDOP may be significant, leading to degenerate cases. Indeed, when a target is close to or crosses the baseline, the 2D solution is no longer...7) is given by (8). The resulting position error is σx = √2/2σ, which is equivalent to having a GDOP of 0.707, the lowest of the 2D solution. A

  10. Degenerate Fermi Gas of Sr87

    NASA Astrophysics Data System (ADS)

    Desalvo, B. J.; Yan, M.; Mickelson, P. G.; Martinez de Escobar, Y. N.; Killian, T. C.

    2010-07-01

    We report quantum degeneracy in a gas of ultracold fermionic Sr87 atoms. By evaporatively cooling a mixture of spin states in an optical dipole trap for 10.5 s, we obtain samples well into the degenerate regime with T/TF=0.26-0.06+0.05. The main signature of degeneracy is a change in the momentum distribution as measured by time-of-flight imaging, and we also observe a decrease in evaporation efficiency below T/TF˜0.5.

  11. Relativistic Bernstein waves in a degenerate plasma

    SciTech Connect

    Ali, Muddasir; Hussain, Azhar; Murtaza, G.

    2011-09-15

    Bernstein mode for a relativistic degenerate electron plasma is investigated. Using relativistic Vlasov-Maxwell equations, a general expression for the conductivity tensor is derived and then employing Fermi-Dirac distribution function a generalized dispersion relation for the Bernstein mode is obtained. Two limiting cases, i.e., non-relativistic and ultra-relativistic are discussed. The dispersion relations obtained are also graphically presented for some specific values of the parameters depicting how the propagation characteristics of Bernstein waves as well as the Upper Hybrid oscillations are modified with the increase in plasma number density.

  12. Depression in Age-Related Macular Degeneration.

    PubMed

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depression, and summarizes interventions for preventing depression in this high-risk group.

  13. Can subretinal microphotodiodes successfully replace degenerated photoreceptors?

    PubMed

    Zrenner, E; Stett, A; Weiss, S; Aramant, R B; Guenther, E; Kohler, K; Miliczek, K D; Seiler, M J; Haemmerle, H

    1999-07-01

    The idea of implanting microphotodiode arrays as visual prostheses has aroused controversy on its feasibility from the moment it appeared in print. We now present results which basically support the concept of replacing damaged photoreceptors with subretinally implanted stimulation devices. Network activity in degenerated rat retinae could be modulated through local electrical stimulation in vitro. We also investigated the long term stability and biocompatibility of the subretinal implants and their impact on retinal physiology in rats. Ganzfeld electroretinograms and histology showed no significant side effect of subretinal implants on retinal function or the architecture of the inner retina.

  14. Envelope solitons in three-component degenerate relativistic quantum plasmas

    NASA Astrophysics Data System (ADS)

    Islam, S.; Sultana, S.; Mamun, A. A.

    2017-09-01

    The criteria for the formation of envelope solitons and their basic features in a three-component degenerate relativistic quantum plasma (DRQP) system (containing relativistically degenerate electrons, non-degenerate inertial light nuclei, and stationary heavy nuclei) are theoretically investigated. The nonlinear Schrödinger equation is derived by employing the multi-scale perturbation technique. The envelope solitons are found to be associated with the modified ion-acoustic waves in which the inertia (restoring force) is provided by the mass density of light nuclei (degenerate pressure of cold electrons). The basic features of these envelope solitons, which are found to formed in such a DRQP system, and their modulational instability criteria (on the basis of the plasma parameters associated with the degenerate pressure of electrons, number densities of degenerate electrons, inertial light nuclei, and stationary heavy nuclei) are identified. The numerical simulations are also performed to confirm the stability of the envelope solitons predicted here by analytical analysis.

  15. Mechanisms of secondary degeneration after partial optic nerve transection

    PubMed Central

    Li, Hong-Ying; Ruan, Yi-Wen; Ren, Chao-Ran; Cui, Qi; So, Kwok-Fai

    2014-01-01

    Secondary degeneration occurs commonly in the central nervous system after traumatic injuries and following acute and chronic diseases, including glaucoma. A constellation of mechanisms have been shown to be associated with secondary degeneration including apoptosis, necrosis, autophagy, oxidative stress, excitotoxicity, derangements in ionic homeostasis and calcium influx. Glial cells, such as microglia, astrocytes and oligodendrocytes, have also been demonstrated to take part in the process of secondary injury. Partial optic nerve transection is a useful model which was established about 13 years ago. The merit of this model compared with other optic nerve injury models used for glaucoma study, including complete optic nerve transection model and optic nerve crush model, is the possibility to separate primary degeneration from secondary degeneration in location. Therefore, it provides a good tool for the study of secondary degeneration. This review will focus on the research progress of the mechanisms of secondary degeneration using partial optic nerve transection model. PMID:25206855

  16. Obsessional Slowness in College Students: Case Studies

    ERIC Educational Resources Information Center

    Johnson, Aleta

    2014-01-01

    Cases of obsessional slowness, a variant of obsessive compulsive disorder, have been documented in case literature regarding relatively low functioning populations. However, obsessional slowness can also present in higher functioning populations, including college and graduate students, as illustrated here by three case examples from a competitive…

  17. Obsessional Slowness in College Students: Case Studies

    ERIC Educational Resources Information Center

    Johnson, Aleta

    2014-01-01

    Cases of obsessional slowness, a variant of obsessive compulsive disorder, have been documented in case literature regarding relatively low functioning populations. However, obsessional slowness can also present in higher functioning populations, including college and graduate students, as illustrated here by three case examples from a competitive…

  18. Simple Phenomena, Slow Motion, Surprising Physics

    ERIC Educational Resources Information Center

    Koupil, Jan; Vicha, Vladimir

    2011-01-01

    This article describes a few simple experiments that are worthwhile for slow motion recording and analysis either because of interesting phenomena that can be seen only when slowed down significantly or because of the ability to do precise time measurements. The experiments described in this article are quite commonly done in Czech schools. All…

  19. Simple Phenomena, Slow Motion, Surprising Physics

    ERIC Educational Resources Information Center

    Koupil, Jan; Vicha, Vladimir

    2011-01-01

    This article describes a few simple experiments that are worthwhile for slow motion recording and analysis either because of interesting phenomena that can be seen only when slowed down significantly or because of the ability to do precise time measurements. The experiments described in this article are quite commonly done in Czech schools. All…

  20. Slow shocks in coronal mass ejections

    NASA Technical Reports Server (NTRS)

    Steinolfson, R. S.

    1989-01-01

    The possibility that slow-mode shock compression may produce at least some of the increased brightness observed at the leading edge of coronal mass ejections is investigated. Among the reasons given for the possible existence of slow shocks are the following: (1) transient velocities are often greater than the upstream sound speed but less than the Alfven speed, (2) the presence of a slow shock is consistent with the flat top observed in some transients, and (3) the lateral extension of slow shocks may be responsible for distributing adjacent structures as also seen on the observations. It is shown that there may be some difficulties with this suggestion for transients originating inside the closed-field region at the base of a preexisting coronal streamer. First of all, slow mode characteristics have difficulty emerging from the closed-field region at the streamer base so they can merge to form a slow shock, unless a preceding, large-amplitude disturbance opens the field lines. In addition, a slow shock cannot exist at the center of the streamer current sheet. Finally, numerical simulations demonstrate that at least the last two (and possibly all) of the above reasons for slow shocks can be satisfied by a disturbance whose leading edge propagates at the local fast-mode speed without any shocks. The leading portion of the transient that would be seen in white-light coronagraphs propagates at a speed either less than or equal to the fast-mode speed.

  1. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Speed, slow. 236.813 Section 236.813 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Speed, slow. A speed not exceeding 20 miles per hour. ...

  2. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Speed, slow. 236.813 Section 236.813 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Speed, slow. A speed not exceeding 20 miles per hour. ...

  3. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Speed, slow. 236.813 Section 236.813 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Speed, slow. A speed not exceeding 20 miles per hour. ...

  4. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Speed, slow. 236.813 Section 236.813 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Speed, slow. A speed not exceeding 20 miles per hour. ...

  5. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Speed, slow. 236.813 Section 236.813 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Speed, slow. A speed not exceeding 20 miles per hour. ...

  6. Can Fast and Slow Intelligence Be Differentiated?

    ERIC Educational Resources Information Center

    Partchev, Ivailo; De Boeck, Paul

    2012-01-01

    Responses to items from an intelligence test may be fast or slow. The research issue dealt with in this paper is whether the intelligence involved in fast correct responses differs in nature from the intelligence involved in slow correct responses. There are two questions related to this issue: 1. Are the processes involved different? 2. Are the…

  7. Can Fast and Slow Intelligence Be Differentiated?

    ERIC Educational Resources Information Center

    Partchev, Ivailo; De Boeck, Paul

    2012-01-01

    Responses to items from an intelligence test may be fast or slow. The research issue dealt with in this paper is whether the intelligence involved in fast correct responses differs in nature from the intelligence involved in slow correct responses. There are two questions related to this issue: 1. Are the processes involved different? 2. Are the…

  8. Rim formation is not a prerequisite for distribution of cone photoreceptor outer segment proteins.

    PubMed

    Conley, Shannon M; Al-Ubaidi, Muayyad R; Han, Zongchao; Naash, Muna I

    2014-08-01

    Retinal degeneration slow (RDS/PRPH2) is critical for the formation of the disc/lamella rim in photoreceptor outer segments (OSs), but plays a different role in rods vs. cones. Without RDS, rods fail to form OSs, however, cones lacking RDS (in the rds(-/-)/Nrl(-/-)) exhibit balloon-like OSs devoid of lamellae. We show that distribution of most proteins in the lamella and PM domains is preserved even in the absence of RDS, rim, and lamella structures. However, the rim protein prominin-1 exhibits altered trafficking and OS localization, suggesting that proper targeting and distribution of rim proteins may require RDS. Our ultrastructural studies show that in cones, OS formation is initiated by the growth of opsin-containing membrane with RDS-mediated rim formation as a secondary step. This is directly opposite to rods and significantly advances our understanding of the role of the rim in cone OS morphogenesis. Furthermore, our results suggest that the unique folded lamella architecture of the cone OS may maximize density or proximity of phototransduction proteins, but is not required for OS function or for protein distribution and retention in different membrane domains. © FASEB.

  9. Connecting slow earthquakes to huge earthquakes

    NASA Astrophysics Data System (ADS)

    Obara, Kazushige; Kato, Aitaro

    2016-07-01

    Slow earthquakes are characterized by a wide spectrum of fault slip behaviors and seismic radiation patterns that differ from those of traditional earthquakes. However, slow earthquakes and huge megathrust earthquakes can have common slip mechanisms and are located in neighboring regions of the seismogenic zone. The frequent occurrence of slow earthquakes may help to reveal the physics underlying megathrust events as useful analogs. Slow earthquakes may function as stress meters because of their high sensitivity to stress changes in the seismogenic zone. Episodic stress transfer to megathrust source faults leads to an increased probability of triggering huge earthquakes if the adjacent locked region is critically loaded. Careful and precise monitoring of slow earthquakes may provide new information on the likelihood of impending huge earthquakes.

  10. Slow Movements of Bio-Inspired Limbs

    NASA Astrophysics Data System (ADS)

    Babikian, Sarine; Valero-Cuevas, Francisco J.; Kanso, Eva

    2016-10-01

    Slow and accurate finger and limb movements are essential to daily activities, but the underlying mechanics is relatively unexplored. Here, we develop a mathematical framework to examine slow movements of tendon-driven limbs that are produced by modulating the tendons' stiffness parameters. Slow limb movements are driftless in the sense that movement stops when actuations stop. We demonstrate, in the context of a planar tendon-driven system representing a finger, that the control of stiffness suffices to produce stable and accurate limb postures and quasi-static (slow) transitions among them. We prove, however, that stable postures are achievable only when tendons are pretensioned, i.e., they cannot become slack. Our results further indicate that a non-smoothness in slow movements arises because the precision with which individual stiffnesses need to be altered changes substantially throughout the limb's motion.

  11. Connecting slow earthquakes to huge earthquakes.

    PubMed

    Obara, Kazushige; Kato, Aitaro

    2016-07-15

    Slow earthquakes are characterized by a wide spectrum of fault slip behaviors and seismic radiation patterns that differ from those of traditional earthquakes. However, slow earthquakes and huge megathrust earthquakes can have common slip mechanisms and are located in neighboring regions of the seismogenic zone. The frequent occurrence of slow earthquakes may help to reveal the physics underlying megathrust events as useful analogs. Slow earthquakes may function as stress meters because of their high sensitivity to stress changes in the seismogenic zone. Episodic stress transfer to megathrust source faults leads to an increased probability of triggering huge earthquakes if the adjacent locked region is critically loaded. Careful and precise monitoring of slow earthquakes may provide new information on the likelihood of impending huge earthquakes.

  12. Frontotemporal Lobar Degeneration: Defining Phenotypic Diversity Through Personalized Medicine

    PubMed Central

    Irwin, David J; Cairns, Nigel J.; Grossman, Murray; McMillan, Corey T.; Lee, Edward B.; Van Deerlin, Vivianna M.; Lee, Virginia M.-Y.; Trojanowski, John Q.

    2015-01-01

    Frontotemporal lobar degeneration (FTLD) comprises two main classes of neurodegenerative diseases characterized by neuronal/glial proteinaceous inclusions (ie. proteinopathies) including tauopathies (i.e. FTLD-Tau) and TDP-43 proteinopathies (i.e. FTLD-TDP) while other very rare forms of FTLD are known such as FTLD with FUS pathology (FTLD-FUS). This review focuses mainly on FTLD-Tau and FLTD-TDP, which may present as several clinical syndromes: a behavioral/dysexecutive syndrome (behavioral-variant frontotemporal dementia); language disorders (primary progressive aphasia variants); and motor disorders (amyotrophic lateral sclerosis, corticobasal syndrome, progressive supranuclear palsy syndrome). There is considerable heterogeneity in clinical presentations of underlying neuropathology and current clinical criteria do not reliably predict underlying proteinopathies ante-mortem. In contrast, molecular etiologies of hereditary FTLD are consistently associated with specific proteinopathies. These include MAPT mutations with FTLD-Tau and GRN, C9orf72, VCP and TARDBP with FTLD-TDP. The last decade has seen a rapid expansion in our knowledge of the molecular pathologies associated with this clinically and neuropathologically heterogeneous group of FTLD diseases. Moreover, in view of current limitations to reliably diagnose specific FTLD neuropathologies prior to autopsy, we summarize the current state of the science in FTLD biomarker research including neuroimaging, biofluid and genetic analyses. We propose that combining several of these biomarker modalities will improve diagnostic specificity in FTLD through a personalized medicine approach. The goals of these efforts are to enhance power for clinical trials focused on slowing or preventing progression of spread of tau, TDP-43 and other FTLD-associated pathologies and work towards the goal of defining clinical endophenotypes of FTD. PMID:25549971

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

    NASA Astrophysics Data System (ADS)

    Sharif, Ali Sakawa

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

  14. Metabolic anatomy of paraneoplastic cerebellar degeneration

    SciTech Connect

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-06-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis.

  15. Degenerate parametric oscillation in quantum membrane optomechanics

    NASA Astrophysics Data System (ADS)

    Benito, Mónica; Sánchez Muñoz, Carlos; Navarrete-Benlloch, Carlos

    2016-02-01

    The promise of innovative applications has triggered the development of many modern technologies capable of exploiting quantum effects. But in addition to future applications, such quantum technologies have already provided us with the possibility of accessing quantum-mechanical scenarios that seemed unreachable just a few decades ago. With this spirit, in this work we show that modern optomechanical setups are mature enough to implement one of the most elusive models in the field of open system dynamics: degenerate parametric oscillation. Introduced in the eighties and motivated by its alleged implementability in nonlinear optical resonators, it rapidly became a paradigm for the study of dissipative phase transitions whose corresponding spontaneously broken symmetry is discrete. However, it was found that the intrinsic multimode nature of optical cavities makes it impossible to experimentally study the model all the way through its phase transition. In contrast, here we show that this long-awaited model can be implemented in the motion of a mechanical object dispersively coupled to the light contained in a cavity, when the latter is properly driven with multichromatic laser light. We focus on membranes as the mechanical element, showing that the main signatures of the degenerate parametric oscillation model can be studied in state-of-the-art setups, thus opening the possibility of analyzing spontaneous symmetry breaking and enhanced metrology in one of the cleanest dissipative phase transitions. In addition, the ideas put forward in this work would allow for the dissipative preparation of squeezed mechanical states.

  16. Disc degeneration-related clinical phenotypes.

    PubMed

    Battié, Michele C; Lazáry, Aron; Fairbank, Jeremy; Eisenstein, Stephen; Heywood, Chris; Brayda-Bruno, Marco; Varga, Péter Pál; McCall, Iain

    2014-06-01

    The phenotype, or observable trait of interest, is at the core of studies identifying associated genetic variants and their functional pathways, as well as diagnostics. Yet, despite remarkable technological developments in genotyping and progress in genetic research, relatively little attention has been paid to the equally important issue of phenotype. This is especially true for disc degeneration-related disorders, and the concept of degenerative disc disease, in particular, where there is little consensus or uniformity of definition. Greater attention and rigour are clearly needed in the development of disc degeneration-related clinical phenotypes if we are to see more rapid advancements in knowledge of this area. When selecting phenotypes, a basic decision is whether to focus directly on the complex clinical phenotype (e.g. the clinical syndrome of spinal stenosis), which is ultimately of interest, or an intermediate phenotype (e.g. dural sac cross-sectional area). While both have advantages, it cannot be assumed that associated gene variants will be similarly relevant to both. Among other considerations are factors influencing phenotype identification, comorbidities that are often present, and measurement issues. Genodisc, the European research consortium project on disc-related clinical pathologies has adopted a strategy that will allow for the careful characterisation and examination of both the complex clinical phenotypes of interest and their components.

  17. Wallerian degeneration in ICAM-1-deficient mice.

    PubMed Central

    Vougioukas, V. I.; Roeske, S.; Michel, U.; Brück, W.

    1998-01-01

    Wallerian degeneration of the peripheral nervous system was studied in ICAM-1-deficient mice and compared with the phenomena observed in C57BL wild-type animals. There was a decrease in myelin density in both mice strains 4 and 6 days after transection of the sciatic nerve. The degenerating nerves were invaded by Mac-1-, LFA-1-, and F4/80-positive macrophages; significantly lower numbers of macrophages were present in ICAM-1-deficient nerves. Myelin loss decreased after nerve transection with a more prominent loss in ICAM-1-deficient animals. Schwann cells revealed a much higher myelin load in these animals when compared with wild-type nerves, and there was an increased proliferation of endoneurial cells in ICAM-1-deficient mice. These data indicate that ICAM-1 is involved in macrophage recruitment to injured peripheral nerves as well as in the proliferative and phagocytic response of Schwann cells after peripheral nerve transection. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9422541

  18. Hyaline cartilage degenerates after autologous osteochondral transplantation.

    PubMed

    Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

    2004-11-01

    Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

  19. Changes in ganglion cells during retinal degeneration.

    PubMed

    Saha, Susmita; Greferath, Ursula; Vessey, Kirstan A; Grayden, David B; Burkitt, Anthony N; Fletcher, Erica L

    2016-08-04

    Inherited retinal degeneration such as retinitis pigmentosa (RP) is associated with photoreceptor loss and concomitant morphological and functional changes in the inner retina. It is not known whether these changes are associated with changes in the density and distribution of synaptic inputs to retinal ganglion cells (RGCs). We quantified changes in ganglion cell density in rd1 and age-matched C57BL/6J-(wildtype, WT) mice using the immunocytochemical marker, RBPMS. Our data revealed that following complete loss of photoreceptors, (∼3months of age), there was a reduction in ganglion cell density in the peripheral retina. We next examined changes in synaptic inputs to A type ganglion cells by performing double labeling experiments in mice with the ganglion cell reporter lines, rd1-Thy1 and age-matched wildtype-Thy1. Ribbon synapses were identified by co-labelling with CtBP2 (RIBEYE) and conventional synapses with the clustering molecule, gephyrin. ON RGCs showed a significant reduction in RIBEYE-immunoreactive synapse density while OFF RGCs showed a significant reduction in the gephyrin-immmunoreactive synapse density. Distribution patterns of both synaptic markers across the dendritic trees of RGCs were unchanged. The change in synaptic inputs to RGCs was associated with a reduction in the number of immunolabeled rod bipolar and ON cone bipolar cells. These results suggest that functional changes reported in ganglion cells during retinal degeneration could be attributed to loss of synaptic inputs. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Calculation of ρ R-parameter and Energy Gain for Aneutronic Fusion in Degenerate P-11 B Plasma

    NASA Astrophysics Data System (ADS)

    Hosseini Motlagh, S. N.; Mohamadi, Sh. S.; Shamsi, R.

    2008-09-01

    Aneutronic fusion reactions are more safe and clean than the other reactions. One of the important candidate for these reactions is P-11 B. This reaction in characteristic conditions creates degenerate plasma. In a Fermi-degenerate plasma, the electronic stopping of a slow ion is smaller than given by the classical formula, because some transitions between the electron states are forbidden. The bremsstrahlung losses are then smaller, so that the nuclear burning of an aneutronic fuel is more efficient. Practical obstacles in this regime that must be overcome before net energy can be realized include the compression of the fuel to an ultra dense state and the creation of a hot spot. In this paper, ρ R parameter (Lawson's criterion) and energy gain for P-11 B are given.

  1. A hypothetic aging pathway from skin to hypothalamic suprachiasmatic nucleus via slow wave sleep.

    PubMed

    Cai, Zi-Jian

    2016-01-01

    Many observations have demonstrated that the hypothalamic neuroendocrine change determines the chronological sequence of aging in mammals. However, it remains uncertain on the mechanism to account for the hypothalamic aging manifestations. In this article, it is pointed out that, as constantly exposed to sunshine and oxygen, the skin would undergo both telomere-shortening and oxidative senescent processes. The senescent alterations of skin, such as attenuation in electrodermal activities, would in turn reduce the emotional responses and memories. Whereas previously I demonstrated that the slow wave sleep just functioned to adjust the emotional balance disrupted by accumulated emotional memories, especially capable of ameliorating the symptoms of depressed patients. Therefore, the reduction in emotional responses and memories from skin senescence would reduce the requirement for slow wave sleep in many senescent observations. The decrement in slow wave sleep would in further cause functional but not chronological degeneration of suprachiasmatic nucleus rather than paraventricular nucleus in hypothalamus. In these respects, from skin senescence to slow wave sleep, there forms a new degenerative aging pathway able to account for the hypothalamic chronological sequence of aging, specifically addressed to the suprachiasmatic nucleus.

  2. Caloric Restriction Mimetics Slow Aging of Neuromuscular Synapses and Muscle Fibers.

    PubMed

    Stockinger, Jessica; Maxwell, Nicholas; Shapiro, Dillon; deCabo, Rafael; Valdez, Gregorio

    2017-03-07

    Resveratrol and metformin have been shown to mimic some aspects of caloric restriction and exercise. However, it remains unknown if these molecules also slow age-related synaptic degeneration, as previously shown for caloric restriction and exercise. In this study, we examined the structural integrity of neuromuscular junctions (NMJs) in 2-year-old mice treated with resveratrol and metformin starting at 1 year of age. We found that resveratrol significantly slows aging of NMJs in the extensor digitorum longus muscle of 2-year-old mice. Resveratrol also preserved the morphology of muscle fibers in old mice. Although metformin slowed the rate of muscle fiber aging, it did not significantly affect aging of NMJs. Based on these findings, we sought to determine if resveratrol directly affects NMJs. For this, we examined postsynaptic sites, the NMJ region located on the muscle peripheral membrane, on cultured myotubes derived from C2C12 cells. We discovered that resveratrol increases the number of postsynaptic sites on myotubes exhibiting a youthful architecture, suggesting that resveratrol directly affects the NMJ. Altogether, we provide compelling evidence indicating that resveratrol slows aging of NMJs and muscle fibers. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Broad self-trapped and slow light bands based on negative refraction and interference of magnetic coupled modes.

    PubMed

    Fang, Yun-Tuan; Ni, Zhi-Yao; Zhu, Na; Zhou, Jun

    2016-01-13

    We propose a new mechanism to achieve light localization and slow light. Through the study on the coupling of two magnetic surface modes, we find a special convex band that takes on a negative refraction effect. The negative refraction results in an energy flow concellation effect from two degenerated modes on the convex band. The energy flow concellation effect leads to forming of the self-trapped and slow light bands. In the self-trapped band light is localized around the source without reflection wall in the waveguide direction, whereas in the slow light band, light becomes the standing-waves and moving standing-waves at the center and the two sides of the waveguide, respectively.

  4. Neuropathological characterization of spinal motor neuron degeneration processes induced by acute and chronic excitotoxic stimulus in vivo.

    PubMed

    Ramírez-Jarquín, Uri Nimrod; Tapia, Ricardo

    2016-09-07

    Motor neuron (MN) diseases are characterized by progressive cell degeneration, and excitotoxicity has been postulated as a causal factor. Using two experimental procedures for inducing excitotoxic spinal MN degeneration in vivo, by acute and chronic overactivation of α-amino-3-hydroxy-5-methyl-4-isoxazoleacetic acid (AMPA) receptors, we characterized the time course of the neuropathological changes. Electron transmission microscopy showed that acute AMPA perfusion by microdialysis caused MN swelling 1.5h after surgery and lysis with membrane rupture as early as 3h; no cleaved caspase 3 was detected by immunochemistry. Chronic AMPA infusion by osmotic minipumps induced a slow degeneration process along 5days, characterized by progressive changes: endoplasmic reticulum swelling, vacuolization of cytoplasm, vacuole fusion and cell membrane rupture. Quantification of these ultrastructural alterations showed that the increase of vacuolated area was at the expense of the nuclear area. Caspase 3 cleavage was observed since the first day of AMPA infusion. We conclude that acute AMPA-induced excitotoxicity induces MN loss by necrosis, while the progress of degeneration induced by chronic infusion is slow, starting with an early apoptotic process followed by necrosis. In both the acute and chronic procedures a correlation could be established between the loss of MN by necrosis, but not by caspase 3-linked apoptosis, and severe motor deficits and hindlimb paralysis. Our findings are relevant for understanding the mechanisms of neuron death in degenerative diseases and thus for the design of pharmacological therapeutic strategies. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Linking Sleep Slow Oscillations with consciousness theories: new vistas on Slow Wave Sleep unconsciousness.

    PubMed

    Gemignani, Angelo; Menicucci, Danilo; Laurino, Marco; Piarulli, Andrea; Mastorci, Francesca; Sebastiani, Laura; Allegrini, Paolo

    2015-01-01

    We review current models of consciousness in the context of wakefulness and sleep. We show that recent results on Slow Wave Sleep, including our own works, naturally fit within consciousness models. In particular, Sleep Slow Oscillations, namely low-frequency (<1Hz) oscillations, contain electrophysiological properties (up and down states) able to elicit and quench neural integration during Slow Wave Sleep. The physiological unconsciousness related to the Sleep Slow Oscillation derives from the interplay between spontaneous or evoked wake-like activities (up states) and half-a-second's electrical silences (down states). Sleep Slow Oscillation induces unconsciousness via the formation of parallel and segregated neural activities.

  6. KEK-IMSS Slow Positron Facility

    NASA Astrophysics Data System (ADS)

    Hyodo, T.; Wada, K.; Yagishita, A.; Kosuge, T.; Saito, Y.; Kurihara, T.; Kikuchi, T.; Shirakawa, A.; Sanami, T.; Ikeda, M.; Ohsawa, S.; Kakihara, K.; Shidara, T.

    2011-12-01

    The Slow Positron Facility at the Institute of Material Structure Science (IMSS) of High Energy Accelerator Research Organization (KEK) is a user dedicated facility with an energy tunable (0.1 - 35 keV) slow positron beam produced by a dedicated 55MeV linac. The present beam line branches have been used for the positronium time-of-flight (Ps-TOF) measurements, the transmission positron microscope (TPM) and the photo-detachment of Ps negative ions (Ps-). During the year 2010, a reflection high-energy positron diffraction (RHEPD) measurement station is going to be installed. The slow positron generator (converter/ moderator) system will be modified to get a higher slow positron intensity, and a new user-friendly beam line power-supply control and vacuum monitoring system is being developed. Another plan for this year is the transfer of a 22Na-based slow positron beam from RIKEN. This machine will be used for the continuous slow positron beam applications and for the orientation training of those who are interested in beginning researches with a slow positron beam.

  7. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  8. Early degeneration of the cerebellar cortex, particularly the granular cells.

    PubMed

    Bugiani, O; Berio, A; Di Stefano, A; Mangiante, G; Mancardi, G L; Leonardi, A

    1978-12-07

    An 8 month old infant, who died of severe gastroenteritis, presented a degeneration of the cerebellar cortex involving cells arising from the outer granular layer as well as Purkinje and Golgi II cells. Residual Purkinje cells showed vacuolar change of the cell body and dendritic abnormalities. Related lesions were atrophy of the inferior olives and degeneration of the mossy fibers.

  9. ELECTRON MICROSCOPIC AND HISTOCHEMICAL OBSERVATIONS OF MUSCLE DEGENERATION AFTER TOURNIQUET

    PubMed Central

    Moore, Dan H.; Ruska, Helmut; Copenhaver, Wilfred M.

    1956-01-01

    As an experimental model for the different forms of muscle degeneration, injury caused by 2 hours' ischemia has been studied from 20 minutes to 16 hours after release of the tourniquet. Discoid degeneration developed in stretched fibers by dissolution of the I bands (Z substances and actin). The discs represented the Q bands (A-H-A). In fibers which passively maintained contraction lengths during degeneration, the Z substances were dissolved, but the continuity of the fibrils was preserved, since the filaments are continuous over all sarcomeres under these conditions. Mitochondria and the tubules of the endoplasmic reticulum swelled, ruptured, and disintegrated. Granular degeneration developed in fibers where mitochondria were abundant. Unstretched degenerating fibers with few mitochondria gave a homogeneous or hyaline appearance. The different forms of degeneration therefore were dependent on the status of stretch and the fiber type. The extent of degeneration was not a function of time after ischemia, there being both nearly normal and severely damaged fibers at 20 minutes and 16 hours after the release of tourniquets. When degeneration occurred, however, the basic alterations were the same in all fibers; there was mitochondrial and reticular swelling, dissolution of the Z substances, and finally disintegration of the contractile material. Some damage developed in the sarcolemmas and capillaries. The mitochondrial disintegration was not linked with inactivation of the succinic dehydrogenase system. PMID:13398442

  10. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index.

  11. Degenerate R-S perturbation theory

    NASA Technical Reports Server (NTRS)

    Hirschfelder, J. O.; Certain, P. R.

    1973-01-01

    A concise, systematic procedure is given for determining the Rayleigh-Schrodinger energies and wave functions of degenerate states to arbitrarily high orders even when the degeneracies of the various states are resolved in arbitrary orders. The procedure is expressed in terms of an iterative cycle in which the energy through the (2n+1)st order is expressed in terms of the partially determined wave function through the n-th order. Both a direct and an operator derivation are given. The two approaches are equivalent and can be transcribed into each other. The direct approach deals with the wave functions (without the use of formal operators) and has the advantage that it resembles the usual treatment of nondegenerate perturbations and maintains close contact with the basic physics. In the operator approach, the wave functions are expressed in terms of infinite order operators which are determined by the successive resolution of the space of the zeroth order functions.

  12. Odour Identification in Frontotemporal Lobar Degeneration

    PubMed Central

    Rami, Lorena; Loy, Clement T.; Hailstone, Julia; Warren, Jason D.

    2008-01-01

    Little information is available concerning olfactory processing in frontotemporal lobar degeneration (FTLD). We undertook a case-control study of olfactory processing in three male patients fulfilling clinical criteria for FTLD. Odour identification (semantic analysis) and odour discrimination (perceptual analysis) were investigated using tests adapted from the University of Pennsylvania Smell Identification Test. General neuropsychometry and structural volumetric brain magnetic resonance imaging (MRI) were also performed. The three patients with FTLD exhibited a disorder of olfactory processing with the characteristics of a predominantly semantic (odour identification) deficit. This olfactory deficit was more prominent in patients with greater involvement of the temporal lobes on MRI. Central deficits of odour identification may be more common in FTLD than previously recognised, and these deficits may assist in clinical characterisation. PMID:17380245

  13. Generalized sheath criterion for arbitrary degenerate plasmas

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2017-01-01

    In this research, we study the generalized sheath criterion for plasmas with an arbitrary degree of electron degeneracy and temperature, ranging from the classical dilute regime to the fully degenerate quantum plasmas. The latter may be relevant to warm dense matter and/or laboratory high energy density matter or even astrophysical stellar plasmas. The hydrostatic one dimensional model is used to establish the generalized Bohm's criterion for sheath entrance ion speed limits, and the small amplitude theory of the sheath problem, which accurately describes the sheath parameters for lower ion acoustic Mach numbers, is developed. Our results indicate that the sheath characteristic parameters such as electrostatic potential and density profiles, as well as the wall potential and the sheath length, are significantly affected by plasma parameters such as the ion and electron temperature and number densities in the plasma region. In particular, there are fundamental differences between sheath structures of the dilute classical plasmas and those of dense quantum ones.

  14. A computational model of motor neuron degeneration.

    PubMed

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L F

    2014-08-20

    To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    PubMed Central

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

    2014-01-01

    SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

  16. CEMAsuite: open source degenerate PCR primer design.

    PubMed

    Lane, Courtney E; Hulgan, Daniel; O'Quinn, Kelly; Benton, Michael G

    2015-11-15

    The codon-equivalent multiple alignment suite begins conservational analysis for polymerase chain reaction primer design at the protein level, allowing the user to design consensus primers capable of detecting homologous coding sequences even when low-to-moderate sequence information is available. This package also condenses the wealth of information associated with multiple sequence alignments and presents them in an intuitive manner, allowing the user to quickly and effectively address degenerate primer design considerations. https://sourceforge.net/projects/cemasuite/. benton@lsu.edu or cemasuite@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Prevention of age-related macular degeneration

    PubMed Central

    Koo, Simon Chi Yan; Chan, Clement Wai Nang

    2010-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

  18. Odor identification in frontotemporal lobar degeneration subtypes.

    PubMed

    Magerova, Hana; Vyhnalek, Martin; Laczo, Jan; Andel, Ross; Rektorova, Irena; Kadlecova, Alexandra; Bojar, Martin; Hort, Jakub

    2014-12-01

    Odor identification impairment is a feature of several neurodegenerative disorders. Although neurodegenerative changes in the frontotemporal lobar degeneration (FTLD) subtypes involve areas important for olfactory processing, data on olfactory function in these patients are limited. An 18-item, multiple-choice odor identification test developed at our memory clinic, the Motol Hospital smell test, was administered to 9 patients with behavioral variant frontotemporal dementia, 13 patients with the language variants, primary nonfluent aphasia (n = 7) and semantic dementia (n = 6), and 8 patients with progressive supranuclear palsy. Compared to the control group (n = 15), all FTLD subgroups showed significant impairment of odor identification (P < .05). The differences between the FTLD subgroups were not significant. No correlation between odor identification and neuropsychological tests results was found. Our data suggest that odor identification impairment is a symptom common to FTLD syndromes, and it seems to be based on olfactory structure damage rather than cognitive decline.

  19. Degenerate polygonal tilings in simple animal tissues

    NASA Astrophysics Data System (ADS)

    Hočevar, A.; Ziherl, P.

    2009-07-01

    The salient feature of one-cell-thick epithelia is their en face view, which reveals the polygonal cross section of the close-packed prismatic cells. The physical mechanisms that shape these tissues were hitherto explored using theories based on cell proliferation, which were either entirely topological or included certain morphogenetic forces. But mitosis itself may not be instrumental in molding the tissue. We show that the structure of simple epithelia can be explained by an equilibrium model where energy-degenerate polygons in an entropy-maximizing tiling are described by a single geometric parameter encoding their inflatedness. The two types of tilings found numerically—ordered and disordered—closely reproduce the patterns observed in Drosophila, Hydra, and Xenopus and they generalize earlier theoretical results. Free of a specific cell self-energy, cell-cell interaction, and cell division kinetics, our model provides an insight into the universality of living and inanimate two-dimensional cellular structures.

  20. Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium

    PubMed Central

    Uhl, Patrizia B.; Amann, Barbara; Hauck, Stefanie M.; Deeg, Cornelia A.

    2015-01-01

    Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, equine recurrent uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectable in healthy RPE due to both phagocytosis and the expression by the RPE cells themselves. Our novel findings are very promising for better understanding the molecular mechanisms taking place on RPE in uveitis. PMID:25629227

  1. Novel localization of peripherin 2, the photoreceptor-specific retinal degeneration slow protein, in retinal pigment epithelium.

    PubMed

    Uhl, Patrizia B; Amann, Barbara; Hauck, Stefanie M; Deeg, Cornelia A

    2015-01-26

    Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, equine recurrent uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectable in healthy RPE due to both phagocytosis and the expression by the RPE cells themselves. Our novel findings are very promising for better understanding the molecular mechanisms taking place on RPE in uveitis.

  2. Crystallization and collapse in relativistically degenerate matter

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2013-04-01

    In this paper, it is shown that a mass density limit exists beyond which the relativistically degenerate matter would crystallize. The mass density limit, found here, is quite analogous to the mass limit predicted by Chandrasekhar for a type of compact stars called white dwarfs (MCh≃1.43 Solar Mass). In this study, the old problem of white dwarf core collapse, which has been previously investigated by Chandrasekhar using hydrostatic stability criteria, is revisited in the framework of the quantum hydrodynamics model by inspection of the charge screening at atomic scales in the relativistic degeneracy plasma regime taking into account the relativistic Fermi-Dirac statistics and electron interaction features such as the quantum statistical pressure, Coulomb attraction, electron exchange-correlation, and quantum recoil effects. It is revealed that the existence of ion correlation and crystallization of matter in the relativistically degenerate plasma puts a critical mass density limit on white dwarf core region. It is shown that a white dwarf star with a core mass density beyond this critical limit can undergo the spontaneous core collapse (SCC). The SCC phenomenon, which is dominantly caused by the electron quantum recoil effect (interference and localization of the electron wave function), leads to a new exotic state of matter. In such exotic state, the relativistic electron degeneracy can lead the white dwarf crystallized core to undergo the nuclear fusion and an ultimate supernova by means of the volume reduction (due to the enhanced compressibility) and huge energy release (due to the increase in cohesive energy), under the stars huge inward gravitational pressure. Moreover, it is found that the SCC phenomenon is significantly affected by the core composition (it is more probable for heavier plasmas). The critical mass density found here is consistent with the values calculated for core density of typical white dwarf stars.

  3. Crystallization and collapse in relativistically degenerate matter

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2013-04-15

    In this paper, it is shown that a mass density limit exists beyond which the relativistically degenerate matter would crystallize. The mass density limit, found here, is quite analogous to the mass limit predicted by Chandrasekhar for a type of compact stars called white dwarfs (M{sub Ch} Asymptotically-Equal-To 1.43 Solar Mass). In this study, the old problem of white dwarf core collapse, which has been previously investigated by Chandrasekhar using hydrostatic stability criteria, is revisited in the framework of the quantum hydrodynamics model by inspection of the charge screening at atomic scales in the relativistic degeneracy plasma regime taking into account the relativistic Fermi-Dirac statistics and electron interaction features such as the quantum statistical pressure, Coulomb attraction, electron exchange-correlation, and quantum recoil effects. It is revealed that the existence of ion correlation and crystallization of matter in the relativistically degenerate plasma puts a critical mass density limit on white dwarf core region. It is shown that a white dwarf star with a core mass density beyond this critical limit can undergo the spontaneous core collapse (SCC). The SCC phenomenon, which is dominantly caused by the electron quantum recoil effect (interference and localization of the electron wave function), leads to a new exotic state of matter. In such exotic state, the relativistic electron degeneracy can lead the white dwarf crystallized core to undergo the nuclear fusion and an ultimate supernova by means of the volume reduction (due to the enhanced compressibility) and huge energy release (due to the increase in cohesive energy), under the stars huge inward gravitational pressure. Moreover, it is found that the SCC phenomenon is significantly affected by the core composition (it is more probable for heavier plasmas). The critical mass density found here is consistent with the values calculated for core density of typical white dwarf stars.

  4. Retrograde Axonal Degeneration in Parkinson Disease

    PubMed Central

    Tagliaferro, Patricia; Burke, Robert E.

    2016-01-01

    In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson’s disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics. PMID:27003783

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

    PubMed

    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.

  6. Depression Can Slow Hospital Patients' Recovery

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_166427.html Depression Can Slow Hospital Patients' Recovery: Study Screening for ... 9, 2017 FRIDAY, June 9, 2017 (HealthDay News) -- Depression affects about one-third of hospital patients and ...

  7. Multi-band slow light metamaterial.

    PubMed

    Zhu, Lei; Meng, Fan-Yi; Fu, Jia-Hui; Wu, Qun; Hua, Jun

    2012-02-13

    In this paper, a multi-band slow light metamaterial is presented and investigated. The metamaterial unit cell is composed of three cut wires of different sizes and parallel to each other. Two transparency windows induced by two-two overlaps of absorption bands of three cut wires are observed. The multi-band transmission characteristics and the slow light properties of metamaterial are verified by numerical simulation, which is in a good agreement with theoretical predictions. The impacts of structure parameters on transparency windows are also investigated. Simulation results show the spectral properties can be tuned by adjusting structure parameters of metamaterial. The equivalent circuit model and the synthesis method of the multi-band slow light metamaterial are presented. It is seen from simulation results that the synthesis method accurately predicts the center frequency of the multi-band metamaterial, which opens a door to a quick and accurate construction for multi-band slow light metamaterial.

  8. Nurses' and doctors' perspectives on slow codes.

    PubMed

    Kelly, Jacinta

    2008-01-01

    The aim of this study was to ascertain nurses' and doctors' perspectives on the practice of slow codes, which are cardiopulmonary resuscitative efforts that are intentionally performed too slowly for resuscitation to occur. A Heideggerian phenomenological study was conducted in 2005, during which data were gathered in the Republic of Ireland from three nurses and two doctors (via unstructured interviews) and analysed using Colaizzi's reductive procedure. Slow codes do occur in Ireland and are intended as beneficent acts. However, slow codes were identified as pointless and undignified when intrusive measures were employed. There is a need for discussion on the topic of slow codes in Ireland, and for aids to cardiopulmonary resuscitation decision making to be developed, such as advance directives, communication training, clinical guidelines and an explanatory leaflet for patients and families.

  9. Structural processes at slow-spreading ridges.

    PubMed

    Mutter, J C; Karson, J A

    1992-07-31

    Slow-spreading (<35 millimeters per year) mid-ocean ridges are dominated by segmented, asymmetric, rifted depressions like continental rifts. Fast-spreading ridges display symmetric, elevated volcanic edifices that vary in shape and size along axis. Deep earthquakes, major normal faults, and exposures of lower crustal rocks are common only along slow-spreading ridges. These contrasting features suggest that mechanical deformation is far more important in crustal formation at slow-spreading ridges than at fast-spreading ridges. New seismic images suggest that the nature and scale of segmentation of slow-spreading ridges is integral to the deformational process and not to magmatic processes that may control segmentation on fast-spreading ridges.

  10. Slow positron beam generator for lifetime studies

    NASA Technical Reports Server (NTRS)

    Singh, Jag J. (Inventor); Eftekhari, Abe (Inventor); St.clair, Terry L. (Inventor)

    1991-01-01

    A slow positron beam generator uses a conductive source residing between two test films. Moderator pieces are placed next to the test film on the opposite side of the conductive source. A voltage potential is applied between the moderator pieces and the conductive source. Incident energetic positrons: (1) are emitted from the conductive source; (2) are passed through test film; and (3) isotropically strike moderator pieces before diffusing out of the moderator pieces as slow positrons, respectively. The slow positrons diffusing out of moderator pieces are attracted to the conductive source which is held at an appropriate potential below the moderator pieces. The slow positrons have to pass through the test films before reaching the conductive source. A voltage is adjusted so that the potential difference between the moderator pieces and the conductive source forces the positrons to stop in the test films. Measurable annihilation radiation is emitted from the test film when positrons annihilate (combine) with electrons in the test film.

  11. Slow Electron Cooling in Colloidal Quantum Dots

    NASA Astrophysics Data System (ADS)

    Pandey, Anshu; Guyot-Sionnest, Philippe

    2008-11-01

    Hot electrons in semiconductors lose their energy very quickly (within picoseconds) to lattice vibrations. Slowing this energy loss could prove useful for more efficient photovoltaic or infrared devices. With their well-separated electronic states, quantum dots should display slow relaxation, but other mechanisms have made it difficult to observe. We report slow intraband relaxation (>1 nanosecond) in colloidal quantum dots. The small cadmium selenide (CdSe) dots, with an intraband energy separation of ~0.25 electron volts, are capped by an epitaxial zinc selenide (ZnSe) shell. The shell is terminated by a CdSe passivating layer to remove electron traps and is covered by ligands of low infrared absorbance (alkane thiols) at the intraband energy. We found that relaxation is markedly slowed with increasing ZnSe shell thickness.

  12. Should the "slow code" be resuscitated?

    PubMed

    Lantos, John D; Meadow, William L

    2011-11-01

    Most bioethicists and professional medical societies condemn the practice of "slow codes." The American College of Physicians ethics manual states, "Because it is deceptive, physicians or nurses should not perform half-hearted resuscitation efforts ('slow codes')." A leading textbook calls slow codes "dishonest, crass dissimulation, and unethical." A medical sociologist describes them as "deplorable, dishonest and inconsistent with established ethical principles." Nevertheless, we believe that slow codes may be appropriate and ethically defensible in situations in which cardiopulmonary resuscitation (CPR) is likely to be ineffective, the family decision makers understand and accept that death is inevitable, and those family members cannot bring themselves to consent or even assent to a do-not-resuscitate (DNR) order. In such cases, we argue, physicians may best serve both the patient and the family by having a carefully ambiguous discussion about end-of-life options and then providing resuscitation efforts that are less vigorous or prolonged than usual.

  13. New developments in slow sand filtration

    SciTech Connect

    Fox, K.R.

    1993-01-01

    Recent regulations promulgated by the U.S. Environmental Protection Agency (EPA), including the Surface Water Treatment Rule, have helped to renew the interest in the use of slow sand filtration (SSF) for treating surface waters for small communities. Slow sand filtration is not a new process, but is one that has been used to treat water effectively since the early 1800's. Interest in slow sand filtration in the United States has increased dramatically in the past thirteen years. New analytical techniques, such as particle counting, improved turbidity, improved growth media for microbiological analysis, and advanced techniques for measuring organic constituents allowed for more detailed studies than were possible in the early 1900's. The new work led to the publication of design manuals and task committee reports describing slow sand filtration in detail.

  14. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    NASA Astrophysics Data System (ADS)

    Abbas, G.; Sarfraz, M.; Shah, H. A.

    2014-09-01

    Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

  15. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    SciTech Connect

    Abbas, G. Sarfraz, M.; Shah, H. A.

    2014-09-15

    Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

  16. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  17. The effect of kyphoscoliosis on intervertebral disc degeneration in dogs.

    PubMed

    Faller, Kiterie; Penderis, Jacques; Stalin, Catherine; Guevar, Julien; Yeamans, Carmen; Gutierrez-Quintana, Rodrigo

    2014-06-01

    In people, abnormalities in vertebral column conformation, such as kyphoscoliosis, induce degenerative changes in adjacent intervertebral disc (IVD) structure and composition. It was hypothesised that canine IVDs adjacent to a vertebral malformation undergo early degeneration. In a blinded retrospective study, thoracic IVD degeneration was evaluated in 14 dogs on magnetic resonance images using Pfirrmann's grade. IVDs adjacent to a vertebral malformation had higher grades of degeneration than non-adjacent IVDs (P < 0.0001). There was an age-dependency, with dogs between 1 and 4 years showing higher grade of degeneration in adjacent than non-adjacent IVDs (P < 0.0001). Conversely, in older dogs, all IVDs - including the non-adjacents - showed degenerative signs, possibly due to normal aging. These results suggest that congenital vertebral malformation results in early degeneration of adjacent IVDs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Formation of Degenerate Band Gaps in Layered Systems

    PubMed Central

    Ignatov, Anton I.; Merzlikin, Alexander M.; Levy, Miguel; Vinogradov, Alexey P.

    2012-01-01

    In the review, peculiarities of spectra of one-dimensional photonic crystals made of anisotropic and/or magnetooptic materials are considered. The attention is focused on band gaps of a special type—the so called degenerate band gaps which are degenerate with respect to polarization. Mechanisms of formation and properties of these band gaps are analyzed. Peculiarities of spectra of photonic crystals that arise due to the linkage between band gaps are discussed. Particularly, it is shown that formation of a frozen mode is caused by linkage between Brillouin and degenerate band gaps. Also, existence of the optical Borrmann effect at the boundaries of degenerate band gaps and optical Tamm states at the frequencies of degenerate band gaps are analyzed. PMID:28817024

  19. The quiescent corona and slow solar wind

    NASA Technical Reports Server (NTRS)

    Noci, G.; Kohl, J. L.; Antonucci, E.; Tondello, G.; Huber, M. C. E.; Fineschi, S.; Gardner, L. D.; Korendyke, C. M.; Nicolosi, P.; Romoli, M.; hide

    1997-01-01

    The observations of the ultraviolet coronagraph spectrometer (UVCS), operating onboard the Solar and Heliospheric Observatory (SOHO) spacecraft, are discussed. The purpose of the UVCS is the study of the quiescent coronal streamer and the slow solar wind. The observations started in January 1996. Polarized radiance data in the visible continuum were obtained. Some characteristics of the coronal streamer from the UVCS recorded data are discussed. A model for the source of the slow solar wind in the inner corona is proposed.

  20. Ultrabroad Bandwidth Slow Light in Semiconductor Nanostructures

    DTIC Science & Technology

    2008-12-31

    REPORT DATE (DDAfM-YYYV? 31-12-2008 2. REPORT DATE Report Type - Final Technical 3L DATES COVERED (From-To) 6/9/06-9/30/08 4. TITLE AMD SUBTITLE...AVAILABIUTY STATEMENT DISTRIBUTION STATEMENT A: UNLIMITED 1i SUPPLEMENTARY NOTES 20100426209 14 .AB8TRACT Slow and fast light enables key functionality in...Connie Chang-Hasnain, "Experimental Demonstration of Slow and Superluminal Light in Semiconductor Optical Amplifiers", Vol. 14 , No. 26, OPTICS EXPRESS

  1. The quiescent corona and slow solar wind

    NASA Technical Reports Server (NTRS)

    Noci, G.; Kohl, J. L.; Antonucci, E.; Tondello, G.; Huber, M. C. E.; Fineschi, S.; Gardner, L. D.; Korendyke, C. M.; Nicolosi, P.; Romoli, M.; Spadaro, D.; Maccari, L.; Raymond, J. C.; Siegmund, O. H. W.; Benna, C.; Ciaravella, A.; Giordano, S.; Michels, J.; Modigliani, A.; Naletto, G.

    1997-01-01

    The observations of the ultraviolet coronagraph spectrometer (UVCS), operating onboard the Solar and Heliospheric Observatory (SOHO) spacecraft, are discussed. The purpose of the UVCS is the study of the quiescent coronal streamer and the slow solar wind. The observations started in January 1996. Polarized radiance data in the visible continuum were obtained. Some characteristics of the coronal streamer from the UVCS recorded data are discussed. A model for the source of the slow solar wind in the inner corona is proposed.

  2. Ultra slow-roll G inflation

    NASA Astrophysics Data System (ADS)

    Hirano, Shin'ichi; Kobayashi, Tsutomu; Yokoyama, Shuichiro

    2016-11-01

    The conventional slow-roll approximation is broken in the so-called "ultra slow-roll" models of inflation, for which the inflaton potential is exactly (or extremely) flat. The interesting nature of (canonical) ultra slow-roll inflation is that the curvature perturbation grows on superhorizon scales, but has a scale-invariant power spectrum. We study the ultra slow-roll inflationary dynamics in the presence of noncanonical kinetic terms of the scalar field, namely ultra slow-roll G inflation. We compute the evolution of the curvature perturbation and show that the primordial power spectrum follows a broken power law with an oscillation feature. It is demonstrated that this could explain the lack of large-scale power in the cosmic microwave background temperature anisotropies. We also point out that the violation of the null energy condition is prohibited in ultra slow-roll G inflation, and hence a blue tensor tilt is impossible as long as inflation is driven by the potential. This statement is, however, not true if the energy density is dominated by the kinetic energy of the scalar field.

  3. A novel rat model with obesity-associated retinal degeneration.

    PubMed

    Reddy, Geereddy Bhanuprakash; Vasireddy, Vidyullatha; Mandal, Md Nawajes A; Tiruvalluru, Mrudula; Wang, Xiaofei F; Jablonski, Monica M; Nappanveettil, Giridharan; Ayyagari, Radha

    2009-07-01

    A strong association between retinal degeneration and obesity has been shown in humans. However, the molecular basis of increased risk for retinal degeneration in obesity is unknown. Thus, an animal model with obesity and retinal degeneration would greatly aid the understanding of obesity-associated retinal degeneration. The retinal abnormalities in a novel rat model (WNIN-Ob) with spontaneously developed obesity are described. Histologic and immunohistochemical examination were performed on retinal sections of 2- to 12-month-old WNIN-Ob rats, and findings were compared with those of lean littermate controls. RNA from retinas of 12-month-old WNIN-Ob and lean littermate rats was used for microarray and qRT-PCR analysis. The WNIN-Ob rats developed severe obesity, with an onset at approximately 35 days. Evaluation of retinal morphology in 2- to 12-month-old WNIN-Ob and age-matched lean littermate controls revealed progressive retinal degeneration, with an onset between 4 to 6 months of age. Immunohistochemical analysis with anti-rhodopsin, anti-cone opsin, and PSD-95 antibodies further confirmed retinal degeneration, particularly rod cell loss and thinner outer plexiform layer, in the obese rat retina. Gene expression by microarray analysis and qRT-PCR established activation of stress response, tissue remodeling, impaired phototransduction, and photoreceptor degeneration in WNIN-Ob rat retina. WNIN-Ob rats develop increased stress in retinal tissue and progressive retinal degeneration after the onset of severe obesity. The WNIN-Ob rat is the first rat model to develop retinal degeneration after the onset of obesity. This novel rat model may be a valuable tool for investigating retinal degeneration associated with obesity in humans.

  4. Cyclin-dependent kinase 5 immunoreactivity for granulovacuolar degeneration.

    PubMed

    Nakamori, Masahiro; Takahashi, Tetsuya; Yamazaki, Yuu; Kurashige, Takashi; Yamawaki, Takemori; Matsumoto, Masayasu

    2012-10-24

    In addition to senile plaque and neurofibrillary tangles, granulovacuolar degeneration is a hallmark of Alzheimer's disease. A number of tau kinases, such as c-jun N-terminal kinase (JNK), glycogen-synthase kinase-3β (GSK3β), and casein kinase 1 (CK1), have been reported to be markers of granulovacuolar degeneration. In addition, cyclin-dependent kinase 5 (CDK5), which phosphorylates tau, has been shown to be abundantly expressed in neurofibrillary tangles in the hippocampus. CDK5 has a unique staining pattern, and therefore, has the potential to be a novel marker for granulovacuolar degeneration. In this study, we investigated the ability of CDK5 to be a marker for granulovacuolar degeneration using immunohistochemical analysis. Four Alzheimer's disease cases, three myotonic dystrophy (MyD) cases, and three control cases were subjected to immunohistochemistry and immunofluorescent techniques using anti-CDK5, anti-charged multivesicular body protein 2B (CHMP2B), anti-pSmad2/3, anti-ubiquitin (Ub), anti-phospho-TDP-43 and AT8 antibodies. Some CDK5-positive granules were morphologically similar to granulovacuolar degeneration intraluminal granules, and these granules overlapped with those immunopositive for pSmad2/3, Ub and phospho-TDP-43 established granulovacuolar degeneration markers. Moreover, CDK5-positive granulovacuolar degeneration and phosphorylated tau colocalized in pyramidal neurons in Alzheimer's disease and MyD cases. The numbers of CDK5-positive granules showed an inverse relationship with the degree of mature neurofibrillary tangles in each cell, as was the case with CHMP2B-positive granulovacuolar degeneration granules and neurofibrillary tangles. The presence of tau kinases including CDK5 in granulovacuolar degeneration might implicate that granulovacuolar degeneration is structurally involved in tau modification.

  5. Degenerate photon-pair generation in an ultracompact silicon photonic crystal waveguide.

    PubMed

    He, Jiakun; Clark, Alex S; Collins, Matthew J; Li, Juntao; Krauss, Thomas F; Eggleton, Benjamin J; Xiong, Chunle

    2014-06-15

    We demonstrate degenerate, correlated photon-pair generation via slow-light-enhanced spontaneous four-wave mixing in a 96 μm long silicon photonic crystal waveguide. Our device represents a more than 50 times smaller footprint than silicon nanowires. We have achieved a coincidence-to-accidental ratio as high as 47 at a photon generation rate of 0.001 pairs per pulse and 14 at a photon generation rate of 0.023 pairs per pulse, which are both higher than the useful level of 10. This demonstration provides a path to generate indistinguishable photons in an ultracompact platform for future quantum photonic technologies.

  6. Age-related macular degeneration: a guide for the primary care physician.

    PubMed

    Hazin, Ribhi; Freeman, P David; Kahook, Malik Y

    2009-02-01

    Age-related macular degeneration (AMD) is the leading cause of visual loss in Americans over the age of 50 years. AMD often results in profound disability due to the disease destroying the macula, the part of the retina responsible for central visual acuity and color vision. Risk factors for AMD include age greater than 50, female gender, Caucasian race, cigarette smoking, and family history of AMD. African Americans and other racial or ethnic groups can be affected by AMD. Although there is no cure for AMD, early diagnosis and treatment may slow disease progression and minimize irreversible visual dysfunction. Individuals suffering from central vision loss from AMD often retain peripheral vision. These affected individuals can benefit from low vision therapy, visual rehabilitation, or both to maintain or enhance activities of daily living.

  7. Visual-function tests for self-monitoring of age-related macular degeneration.

    PubMed

    Liu, Lei; Wang, Yi-Zhong; Bedell, Harold E

    2014-08-01

    Age-related macular degeneration (AMD) is one of the leading causes of severe visual impairment in the United States. Changes in lifestyle can slow the progression of AMD, and new therapies that arrest choroidal neovascularization can preserve vision in patients who progress to the neovascular form of advanced AMD. Appropriate timing is required for these interventions to be optimally effective, which, in turn, depends critically on early diagnosis. Because annual or semiannual eye examinations may not be sufficient to ensure an early diagnosis, the preferred practice for AMD management must include self-monitoring by patients for disease onset or progression. In this review, we discuss a number of visual functions that have been shown to be impaired in eyes with AMD and specify desirable characteristics of visual-function tests that can be used for self-monitoring by populations at risk for AMD.

  8. The astroglial response to Wallerian degeneration after spinal cord injury in humans.

    PubMed

    Puckett, W R; Hiester, E D; Norenberg, M D; Marcillo, A E; Bunge, R P

    1997-12-01

    We describe the changes exhibited by astrocytes in areas of Wallerian degeneration after spinal cord injury in humans using glial fibrillary acidic protein immunohistochemistry correlated to standard histology at time points ranging from 8 days to 23 years after injury. Astrocytes were slow to react; a slight increase in immunoreactivity was observed at 4 months. Over time they began to lose immunoreactivity in both the somata and the processes as the debris from the degenerative process was cleared. By 1 year after injury the staining intensity had decreased to levels which were lower than in normal areas of the cord. This hypointense staining persisted for at least 23 years after injury. These findings are significantly different from those observed in animal studies and emphasize the need for additional pathological studies of human spinal cord injury. Copyright 1997 Academic Press.

  9. Remodeling of cone photoreceptor cells after rod degeneration in rd mice.

    PubMed

    Lin, Bin; Masland, Richard H; Strettoi, Enrica

    2009-03-01

    We studied the survival of cone photoreceptors following the degeneration of rods in the rd mouse. Cones were visualized by selective expression of green fluorescent protein (GFP) following transduction with an adeno-associated virus (AAV) vector. As previously reported, many cones survive after the initial degeneration of the rods. Soon after the initial degeneration, they lose their outer segments and all but a vestigial inner segment; and they partially retract or lose their axon and synaptic pedicle. However, they retain many fundamental features of the cone phenotype, and for many weeks show a polarized morphology indicative of substantial regrowth of processes. The cells retain their laminar position, forming a cell row just distal to a much thinned outer plexiform layer. The somata subsequently enlarge. Most of the cells extend bipolar processes, recreating the original bipolar morphology of a photoreceptor cell--though now turned on its side relative to the native position. The cells express short- or middle-wavelength opsins, recoverin and connexin36. One or more of the polarized processes could often be shown to contain synaptic ribbons, as visualized by antibodies against RIBEYE. The cones do not express protein kinase C alpha, Go alpha, ChX10 or calbindin, markers of bipolar or horizontal cells. The partially differentiated cone morphology persists for at least several months, after which the processes begin to retract and there is slow loss of the cells. Thus, during the time following the loss of their rod-dominated microenvironment, the cones achieve a semi-stable state in which much of their normal phenotype is preserved. Cone photoreceptors in retinas of human RP donors appear from their morphology to undergo a similar progression. The therapeutic window for rescue of cone photoreceptors may be longer than would have been thought.

  10. Dietary Supplement Enriched in Antioxidants and Omega-3 Protects from Progressive Light-Induced Retinal Degeneration

    PubMed Central

    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. PMID:26042773

  11. Slow Earthquakes and Typhoons in Taiwan

    NASA Astrophysics Data System (ADS)

    Liu, C.; Linde, A. T.; Sacks, I. S.

    2006-05-01

    As part of a cooperative program between Academica Sinica, Taiwan, and Carnegie Institution of Washington a small network of Sacks-Evertson strainmeters has been installed in eastern Taiwan, starting in 2003. The program focuses on providing data that will complement GPS data sets in aiding improved understanding of the rapid and complex tectonic deformation of the area. The initial data from all sites show the standard characteristics of good quality: tidal signals with very high signal to noise ratio and large (~10,000 counts on 24 bit ADC system) amplitudes; strains trending into conpression with rates that decrease exponentially with time and earthquakes clearly recorded. Additionally the instruments have recorded a number of slow strain changes with durations ranging from about an hour up to a few days; we interpret these signals in terms of slow earthquakes. All of the slow events identified to date occur at the times of typhoons passing over or very close to the study area, but not all typhoons are associated with slow strain events (e.g. 9 typhoons in 2004 were accompanied by 5 slow events). Seismicity for the area deliniates a roughly north-south striking steeply dipping (to the west) zone with reverse slip; the shallowest extent of the zone is approximately 10 km inland. We look for source solutions consistent with that tectonic setting. The slow events exhibit a considerable range of amplitude and complexity; small, short amplitude events have a quite simple and smooth waveform; the longest (2 days) and largest (100 to 350 nanostrain at 3 sites) has waveforms with a lot of structure. The similarity among the stations (located in an isosceles triangular array with spacing ~10 km and 4 km) is indicative of rupture propagation of a slow slip source (equivalent magnitude about 5), propagating up dip and from south to north. Typhoon activity produces a large increase in short period (~ sec) energy so it is not possible to determine whether these slow events

  12. Molecular signatures of age-associated chronic degeneration of shoulder muscles.

    PubMed

    Raz, Yotam; Henseler, Jan Ferdinand; Kolk, Arjen; Tatum, Zuotian; Groosjohan, Niels Kuipers; Verwey, Nisha E; Arindrarto, Wibowo; Kielbasa, Szymon M; Nagels, Jochem; 't Hoen, Peter A C; Nelissen, Rob G H H; Raz, Vered

    2016-02-23

    Chronic muscle diseases are highly prevalent in the elderly causing severe mobility limitations, pain and frailty. The intrinsic molecular mechanisms are poorly understood due to multifactorial causes, slow progression with age and variations between individuals. Understanding the underlying molecular mechanisms could lead to new treatment options which are currently limited. Shoulder complaints are highly common in the elderly, and therefore, muscles of the shoulder's rotator cuff could be considered as a model for chronic age-associated muscle degeneration. Diseased shoulder muscles were characterized by muscle atrophy and fatty infiltration compared with unaffected shoulder muscles. We confirmed fatty infiltration using histochemical analysis. Additionally, fibrosis and loss of contractile myosin expression were found in diseased muscles. Most cellular features, including proliferation rate, apoptosis and cell senescence, remained unchanged and genome-wide molecular signatures were predominantly similar between diseased and intact muscles. However, we found down-regulation of a small subset of muscle function genes, and up-regulation of extracellular region genes. Myogenesis was defected in muscle cell culture from diseased muscles but was restored by elevating MyoD levels. We suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration.

  13. Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

    PubMed Central

    Santos, Laura M.; Mattiace, Linda A.; Costa, Manoel L.; Ferreira, Luciano C.; Benabou, Kelly; Kim, Ana H.; Abrahams, John; Bennett, Michael V. L.; Rozental, Renato

    2012-01-01

    Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide. PMID:22308470

  14. Molecular signatures of age-associated chronic degeneration of shoulder muscles

    PubMed Central

    Raz, Yotam; Henseler, Jan Ferdinand; Kolk, Arjen; Tatum, Zuotian; Groosjohan, Niels Kuipers; Verwey, Nisha E.; Arindrarto, Wibowo; Kielbasa, Szymon M.; Nagels, Jochem; Hoen, Peter A. C. 't; Nelissen, Rob G. H. H.; Raz, Vered

    2016-01-01

    Chronic muscle diseases are highly prevalent in the elderly causing severe mobility limitations, pain and frailty. The intrinsic molecular mechanisms are poorly understood due to multifactorial causes, slow progression with age and variations between individuals. Understanding the underlying molecular mechanisms could lead to new treatment options which are currently limited. Shoulder complaints are highly common in the elderly, and therefore, muscles of the shoulder's rotator cuff could be considered as a model for chronic age-associated muscle degeneration. Diseased shoulder muscles were characterized by muscle atrophy and fatty infiltration compared with unaffected shoulder muscles. We confirmed fatty infiltration using histochemical analysis. Additionally, fibrosis and loss of contractile myosin expression were found in diseased muscles. Most cellular features, including proliferation rate, apoptosis and cell senescence, remained unchanged and genome-wide molecular signatures were predominantly similar between diseased and intact muscles. However, we found down-regulation of a small subset of muscle function genes, and up-regulation of extracellular region genes. Myogenesis was defected in muscle cell culture from diseased muscles but was restored by elevating MyoD levels. We suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration. PMID:26885755

  15. Slow slip and the transition from fast to slow fronts in the rupture of frictional interfaces

    PubMed Central

    Trømborg, Jørgen Kjoshagen; Sveinsson, Henrik Andersen; Scheibert, Julien; Thøgersen, Kjetil; Amundsen, David Skålid; Malthe-Sørenssen, Anders

    2014-01-01

    The failure of the population of microjunctions forming the frictional interface between two solids is central to fields ranging from biomechanics to seismology. This failure is mediated by the propagation along the interface of various types of rupture fronts, covering a wide range of velocities. Among them are the so-called slow fronts, which are recently discovered fronts much slower than the materials’ sound speeds. Despite intense modeling activity, the mechanisms underlying slow fronts remain elusive. Here, we introduce a multiscale model capable of reproducing both the transition from fast to slow fronts in a single rupture event and the short-time slip dynamics observed in recent experiments. We identify slow slip immediately following the arrest of a fast front as a phenomenon sufficient for the front to propagate further at a much slower pace. Whether slow fronts are actually observed is controlled both by the interfacial stresses and by the width of the local distribution of forces among microjunctions. Our results show that slow fronts are qualitatively different from faster fronts. Because the transition from fast to slow fronts is potentially as generic as slow slip, we anticipate that it might occur in the wide range of systems in which slow slip has been reported, including seismic faults. PMID:24889640

  16. Age related macular degeneration and visual disability.

    PubMed

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  17. Neural Responses to Multielectrode Stimulation of Healthy and Degenerate Retina.

    PubMed

    Halupka, Kerry J; Abbott, Carla J; Wong, Yan T; Cloherty, Shaun L; Grayden, David B; Burkitt, Anthony N; Sergeev, Evgeni N; Luu, Chi D; Brandli, Alice; Allen, Penelope J; Meffin, Hamish; Shivdasani, Mohit N

    2017-07-01

    Simultaneous stimulation of multiple retinal electrodes in normally sighted animals shows promise in improving the resolution of retinal prostheses. However, the effects of simultaneous stimulation on degenerate retinae remain unknown. Therefore, we investigated the characteristics of cortical responses to multielectrode stimulation of the degenerate retina. Four adult cats were bilaterally implanted with retinal electrode arrays in the suprachoroidal space after unilateral adenosine triphosphate (ATP)-induced retinal photoreceptor degeneration. Functional and structural changes were characterized by using electroretinogram a-wave amplitude and optical coherence tomography. Multiunit activity was recorded from both hemispheres of the visual cortex. Responses to single- and multielectrode stimulation of the ATP-injected and fellow control eyes were characterized and compared. The retinae of ATP-injected eyes displayed structural and functional changes consistent with mid- to late-stage photoreceptor degeneration and remodeling. Responses to multielectrode stimulation of the ATP-injected eyes exhibited shortened latencies, lower saturated spike counts, and higher thresholds, compared to stimulation of the fellow control eyes. Electrical receptive field sizes were significantly larger in the ATP-injected eye than in the control eye, and positively correlated with the extent of degeneration. Significant differences exist between cortical responses to stimulation of healthy and degenerate retinae. Our results highlight the importance of using a retinal degeneration model when evaluating the efficacy of novel stimulation paradigms.

  18. Can vertebral density changes be explained by intervertebral disc degeneration?

    PubMed

    Homminga, Jasper; Aquarius, Rene; Bulsink, Vera E; Jansen, Christiaan T J; Verdonschot, Nico

    2012-05-01

    One of the major problems facing the elderly spine is the occurrence of vertebral fractures due to low bone mass. Although typically attributed to osteoporosis, disc degeneration has also been suggested to play a role in vertebral fractures. Existing bone adaptation theories and simulations may explain the biomechanical pathway from a degenerated disc to an increased fracture risk. A finite element model of a lumbar segment was created and calibrated. Subsequently the disc properties were varied to represent either a healthy or degenerated disc and the resulting bone adaptation was simulated. Disc degeneration resulted in a shift of load from the nucleus to the annulus. The resulting bone adaptation led to a dramatically reduced density of the trabecular core and to an increased density in the vertebral walls. Degeneration of just the nucleus, and in particular the dehydration of the nucleus, resulted in most of this bone density change. Additional annulus degeneration had much less of an effect on the density values. The density decrease in the trabecular core as seen in this study matches clinical observations. Therefore, bone remodeling theories can assists in explaining the potential synergistic effects of disc degeneration and osteoporotis in the occurrence of vertebral fractures. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

  19. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2014-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search strategy We searched CENTRAL in The Cochrane Library, MEDLINE, EMBASE and LILACS on 30 April 2009 and the WHO International Clinical Trials Registry Platform on 11 May 2009. We searched reference lists and the Science Citation Index. There were no language or date restrictions in the search for trials. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the analyses of 30 participants did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity at three months of treatment (decimal visual acuity 0.21± 0.56 in simvastatin and 0.19± 0.40 in placebo arm) or 45 days after the completion of treatment (decimal visual acuity 0.20± 0.50 in simvastatin and 0.19± 0.48 in placebo arm). The lens and

  20. Magnon inflation: slow roll with steep potentials

    SciTech Connect

    Adshead, Peter; Blas, Diego; Burgess, C.P.; Hayman, Peter; Patil, Subodh P.

    2016-11-04

    We find multi-scalar effective field theories (EFTs) that can achieve a slow inflationary roll despite having a scalar potential that does not satisfy G{sup ab}∂{sub a}V∂{sub b}V≪V{sup 2}/M{sub p}{sup 2} (where G{sub ab} is the target-space metric). They evade the usual slow-roll conditions on V because their kinetic energies are dominated by single-derivative terms rather than the usual two-derivative terms. Single derivatives dominate during slow roll and so do not require a breakdown of the usual derivative expansion that underpins calculational control in much of cosmology. The presence of such terms requires some sort of UV Lorentz-symmetry breaking during inflation (besides the usual cosmological breaking). Chromo-natural inflation provides one particular example of a UV theory that can generate the multi-field single-derivative terms we consider, and we argue that the EFT we find indeed captures the slow-roll conditions for its background evolution. We also show that our EFT can be understood as a multi-field generalization of the single-field Cuscuton models. The multi-field case introduces a new feature, however: the scalar kinetic terms define a target-space 2-form, F{sub ab}, whose antisymmetry gives new ways for slow roll to be achieved.

  1. Slow wave propagation in soft adhesive interfaces.

    PubMed

    Viswanathan, Koushik; Sundaram, Narayan K; Chandrasekar, Srinivasan

    2016-11-16

    Stick-slip in sliding of soft adhesive surfaces has long been associated with the propagation of Schallamach waves, a type of slow surface wave. Recently it was demonstrated using in situ experiments that two other kinds of slow waves-separation pulses and slip pulses-also mediate stick-slip (Viswanathan et al., Soft Matter, 2016, 12, 5265-5275). While separation pulses, like Schallamach waves, involve local interface detachment, slip pulses are moving stress fronts with no detachment. Here, we present a theoretical analysis of the propagation of these three waves in a linear elastodynamics framework. Different boundary conditions apply depending on whether or not local interface detachment occurs. It is shown that the interface dynamics accompanying slow waves is governed by a system of integral equations. Closed-form analytical expressions are obtained for the interfacial pressure, shear stress, displacements and velocities. Separation pulses and Schallamach waves emerge naturally as wave solutions of the integral equations, with oppositely oriented directions of propagation. Wave propagation is found to be stable in the stress regime where linearized elasticity is a physically valid approximation. Interestingly, the analysis reveals that slow traveling wave solutions are not possible in a Coulomb friction framework for slip pulses. The theory provides a unified picture of stick-slip dynamics and slow wave propagation in adhesive contacts, consistent with experimental observations.

  2. Global Network of Slow Solar Wind

    NASA Technical Reports Server (NTRS)

    Crooker, N. U.; Antiochos, S. K.; Zhao, X.; Neugebauer, M.

    2012-01-01

    The streamer belt region surrounding the heliospheric current sheet (HCS) is generally treated as the primary or sole source of the slow solar wind. Synoptic maps of solar wind speed predicted by the Wang-Sheeley-Arge model during selected periods of solar cycle 23, however, show many areas of slow wind displaced from the streamer belt. These areas commonly have the form of an arc that is connected to the streamer belt at both ends. The arcs mark the boundaries between fields emanating from different coronal holes of the same polarity and thus trace the paths of belts of pseudostreamers, i.e., unipolar streamers that form over double arcades and lack current sheets. The arc pattern is consistent with the predicted topological mapping of the narrow open corridor or singular separator line that must connect the holes and, thus, consistent with the separatrix-web model of the slow solar wind. Near solar maximum, pseudostreamer belts stray far from the HCS-associated streamer belt and, together with it, form a global-wide web of slow wind. Recognition of pseudostreamer belts as prominent sources of slow wind provides a new template for understanding solar wind stream structure, especially near solar maximum.

  3. Topological Origins of the Slow Solar Wind

    NASA Astrophysics Data System (ADS)

    Antiochos, S.

    2008-12-01

    Although the slow solar wind has been studied for decades with both in situ and remote sensing observations, its origin is still a matter of intense debate. In the standard quasi-steady model, the slow wind is postulated to originate near coronal hole boundaries that define topologically well-behaved separatrices between open and closed field regions. In the interchange model, on the other hand, the slow wind is postulated to originate on open flux that is dynamically diffusing throughout the seemingly closed-field corona. We argue in favor of the quasi-steady scenario and propose that the slow wind is due to two effects: First, the open-closed boundary is highly complex due to the complexity of the photospheric flux distribution. Second, this boundary is continuously driven by the transport of magnetic helicity from the closed field region into the open. The implications of this model for the structure and dynamics of the corona and slow wind are discussed, and observational tests of the model are presented. This work has been supported, in part, by the NASA LWS, HTP, and SR&T programs.

  4. Magnon inflation: slow roll with steep potentials

    NASA Astrophysics Data System (ADS)

    Adshead, Peter; Blas, Diego; Burgess, C. P.; Hayman, Peter; Patil, Subodh P.

    2016-11-01

    We find multi-scalar effective field theories (EFTs) that can achieve a slow inflationary roll despite having a scalar potential that does not satisfy Script Gab ∂a V ∂b V ll V2/Mp2 (where Script Gab is the target-space metric). They evade the usual slow-roll conditions on V because their kinetic energies are dominated by single-derivative terms rather than the usual two-derivative terms. Single derivatives dominate during slow roll and so do not require a breakdown of the usual derivative expansion that underpins calculational control in much of cosmology. The presence of such terms requires some sort of UV Lorentz-symmetry breaking during inflation (besides the usual cosmological breaking). Chromo-natural inflation provides one particular example of a UV theory that can generate the multi-field single-derivative terms we consider, and we argue that the EFT we find indeed captures the slow-roll conditions for its background evolution. We also show that our EFT can be understood as a multi-field generalization of the single-field Cuscuton models. The multi-field case introduces a new feature, however: the scalar kinetic terms define a target-space 2-form, ℱab, whose antisymmetry gives new ways for slow roll to be achieved.

  5. Topological Origins of the Slow Solar Wind

    NASA Technical Reports Server (NTRS)

    Antiochos, Spiro

    2008-01-01

    Although the slow solar wind has been studied for decades with both in situ and remote sensing observations, its origin is still a matter of intense debate. In the standard quasi-steady model, the slow wind is postulated to originate near coronal hole boundaries that define topologically well-behaved separatrices between open and closed field regions. In the interchange model, on the other hand, the slow wind is postulated to originate on open flux that is dynamically diffusing throughout the seemingly closed-field corona. We argue in favor of the quasi-steady scenario and propose that the slow wind is due to two effects: First, the open-closed boundary is highly complex due to the complexity of the photospheric flux distribution. Second, this boundary is continuously driven by the transport of magnetic helicity from the closed field region into the open. The implications of this model for the structure and dynamics of the corona and slow wind are discussed, and observational tests of the mode

  6. Properties of the very slow solar wind

    NASA Astrophysics Data System (ADS)

    Sanchez-Diaz, Eduardo; Segura, Kevin; Rouillard, Alexis P.; Lavraud, Benoit

    2015-04-01

    Solar wind plasma data taken between 0.29-0.9 AU by the twin HELIOS spacecraft reveals the frequent occurrence of very low radial wind speeds (200 < V < 300 km/s), very rarely measured near 1 AU. By analysing the occurrence as a function of heliocentric distance and time, we show that it is primarly measured inside 0.5 AU and mostly during solar maximum, although some very slow wind events were also measured during short periods at solar minimum. We show that the very slow wind is frequently measured during the passage of the solar wind plasma sheet usually detected in the vicinity of the heliospheric current sheet. By tracing these slow events back to the Sun and using a potential field reconstruction of the coronal magnetic field based on magnetograms taken by Mount Wilson Observatory, we compare the speed of the very slow wind with the geometry of the magnetic flux tube at its source. We discuss theoretical mechanisms that could explain the abundance and origin of this very slow wind, we also stress the importance of these findings for our understanding of solar wind structure. This study was carried out as part of the HELCATS FP7 project.

  7. [Current concepts in pathogenesis of age-related macular degeneration].

    PubMed

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Bożena

    2014-01-01

    Age-related macular degeneration is the leading cause of central blindness in elderly population of the western world. The pathogenesis of this disease, likely multifactorial, is not well known, although a number of theories have been put forward, including oxidative stress, genetic interactions, hemodynamic imbalance, immune and inflammatory processes. The understanding of age-related macular degeneration pathogenesis will give rise to new approaches in prevention and treatment of the early and late stages of both atrophic and neovascular age-related macular degeneration.

  8. Pathophysiological basis of lumbar disc degeneration: imaging analysis.

    PubMed

    Ostrum, B J; Romy, M; Swartz, J D

    1993-12-01

    This article provides a brief synopsis of the pathoanatomic basis of disc degeneration. An attempt is made to correlate CT, MR and CT discographic findings. The T2-weighted sagittal images are the most sensitive for evaluating disc degeneration. The contour changes on axial CT and MR scans are sensitive for abnormalities but not always specific. The CT discogram adds information unavailable by other imaging methods pertaining to the internal architecture of the disc. It additionally defines focal nuclear herniations and also is helpful in evaluating the stage of disc degeneration.

  9. Degenerate Fermi gas perturbations at standard background cosmology

    SciTech Connect

    Bernardini, A.E.; Perico, E.L.D. E-mail: elduarte@ifi.unicamp.br

    2011-01-01

    The hypothesis of a tiny fraction of the cosmic inventory evolving cosmologically as a degenerate Fermi gas test fluid at some dominant cosmological background is investigated. Our analytical results allow for performing preliminary computations to the evolution of perturbations for relativistic and non-relativistic test fluids. The density fluctuation, δ, the fluid velocity divergence, θ, and an explicit expression for the dynamics of the shear stress, σ, are obtained for a degenerate Fermi gas in the background regime of radiation. Extensions to the dominance of matter and to the ΛCDM cosmological background are also investigated and lessons concerning the formation of large structures of degenerate Fermi gas are depicted.

  10. Indirect searches of the degenerate MSSM

    NASA Astrophysics Data System (ADS)

    Chowdhury, Debtosh; Patel, Ketan M.; Tata, Xerxes; Vempati, Sudhir K.

    2017-04-01

    A degenerate sfermionic particle spectrum can escape constraints from flavor physics, and at the same time evade the limits from the direct searches if the degeneracy extends to the gaugino-Higgsino sector. Inspired by this, we consider a scenario where all the soft terms have an approximately common mass scale at MSUSY , with splittings ≲O (10 %). As a result, the third generation sfermions have large to maximal (left-right) mixing, the same being the case with charginos and some sectors of the neutralino mass matrix. We study this scenario in the light of discovery of the Higgs boson with mass ˜125 GeV . We consider constraints from B physics, the anomalous magnetic moment of the muon and the dark matter relic density. We find that a supersymmetric spectrum as light as 600 GeV could be consistent with all current data and also account for the observed anomalous magnetic moment of the muon within 2 σ . The neutralino relic density is generally too small to saturate the measured cold dark matter relic density. Direct detection limits from XENON100 and LUX put severe constraints on this scenario which will be conclusively probed by the XENONnT experiment.

  11. Disruption in dopaminergic innervation during photoreceptor degeneration.

    PubMed

    Ivanova, Elena; Yee, Christopher W; Sagdullaev, Botir T

    2016-04-15

    Dopaminergic amacrine cells (DACs) release dopamine in response to light-driven synaptic inputs, and are critical to retinal light adaptation. Retinal degeneration (RD) compromises the light responsiveness of the retina and, subsequently, dopamine metabolism is impaired. As RD progresses, retinal neurons exhibit aberrant activity, driven by AII amacrine cells, a primary target of the retinal dopaminergic network. Surprisingly, DACs are an exception to this physiological change; DACs exhibit rhythmic activity in healthy retina, but do not burst in RD. The underlying mechanism of this divergent behavior is not known. It is also unclear whether RD leads to structural changes in DACs, impairing functional regulation of AII amacrine cells. Here we examine the anatomical details of DACs in three mouse models of human RD to determine how changes to the dopaminergic network may underlie physiological changes in RD. By using rd10, rd1, and rd1/C57 mice we were able to dissect the impacts of genetic background and the degenerative process on DAC structure in RD retina. We found that DACs density, soma size, and primary dendrite length are all significantly reduced. Using a novel adeno-associated virus-mediated technique to label AII amacrine cells in mouse retina, we observed diminished dopaminergic contacts to AII amacrine cells in RD mice. This was accompanied by changes to the components responsible for dopamine synthesis and release. Together, these data suggest that structural alterations of the retinal dopaminergic network underlie physiological changes during RD.

  12. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  13. Genetic Factors in Intervertebral Disc Degeneration

    PubMed Central

    Feng, Yi; Egan, Brian; Wang, Jinxi

    2016-01-01

    Low back pain (LBP) is a major cause of disability and imposes huge economic burdens on human society worldwide. Among many factors responsible for LBP, intervertebral disc degeneration (IDD) is the most common disorder and is a target for intervention. The etiology of IDD is complex and its mechanism is still not completely understood. Many factors such as aging, spine deformities and diseases, spine injuries, and genetic factors are involved in the pathogenesis of IDD. In this review, we will focus on the recent advances in studies on the most promising and extensively examined genetic factors associated with IDD in humans. A number of genetic defects have been correlated with structural and functional changes within the intervertebral disc (IVD), which may compromise the disc’s mechanical properties and metabolic activities. These genetic and proteomic studies have begun to shed light on the molecular basis of IDD, suggesting that genetic factors are important contributors to the onset and progression of IDD. By continuing to improve our understanding of the molecular mechanisms of IDD, specific early diagnosis and more effective treatments for this disabling disease will be possible in the future. PMID:27617275

  14. Frontotemporal lobar degeneration: diversity of FTLD lesions.

    PubMed

    Seilhean, D; Bielle, F; Plu, I; Duyckaerts, C

    2013-10-01

    Frontotemporal lobar degeneration (FTLD) is a heterogeneous group including both sporadic and familial diseases, characterized by a macroscopic alteration. It may correspond to various cognitive syndromes: behavioral variant of frontotemporal dementia (bvFTD), progressive nonfluent aphasia, and semantic dementia. The neuropathologic classification is now based on identification of the protein that accumulates in neurons and glia: Tau, TAR DNA Binding Protein 43 (TDP-43), and FUsed in Sarcoma (FUS). The disorders in which the corresponding proteins accumulate have been named FTLD-Tau, FTLD-TDP, and FTLD-FUS. FTLD-Tau includes sporadic cases (e.g. Pick's disease) and Tau mutations. FTLD-TDP are subdivided within four types (A, B, C, D) according to the shape and distribution of TDP-43 positive lesions within the associative frontal cortex. The FTLD-FUS group includes atypical FTLD with ubiquitinated lesions (FTLD-U), Neuronal Intermediate Filament Inclusion Disease (NIFID) and Basophilic Inclusion Body Disease (BIBD). Copyright © 2013. Published by Elsevier Masson SAS.

  15. Quantum kinetic theories in degenerate plasmas

    NASA Astrophysics Data System (ADS)

    Brodin, Gert; Ekman, Robin; Zamanian, Jens

    2017-01-01

    In this review we give an overview of the recent work on quantum kinetic theories of plasmas. We focus, in particular, on the case where the electrons are fully degenerate. For such systems, perturbation methods using the distribution function can be problematic. Instead we present a model that considers the dynamics of the Fermi surface. The advantage of this model is that, even though the value of the distribution function can be greatly perturbed outside the equilibrium Fermi surface, deformation of the Fermi surface is small up to very large amplitudes. Next, we investigate the short-scale dynamics for which the Wigner-Moyal equation replaces the Vlasov equation. In particular, we study wave-particle interaction, and deduce that new types of wave damping can occur due to the simultaneous absorption (or emission) of multiple wave quanta. Finally, we consider exchange effects within a quantum kinetic formalism to find a model that is more accurate than those using exchange potentials from density functional theory. We deduce the exchange corrections to the dispersion relations for Langmuir and ion-acoustic waves. In comparison to results based on exchange potentials deduced from density functional theory we find that the latter models are reasonably accurate for Langmuir waves, but rather inaccurate for ion acoustic waves.

  16. Animal models of age related macular degeneration.

    PubMed

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  17. Evidence for degenerate tetraploidy in bdelloid rotifers.

    PubMed

    Mark Welch, David B; Mark Welch, Jessica L; Meselson, Matthew

    2008-04-01

    Rotifers of class Bdelloidea have evolved for millions of years apparently without sexual reproduction. We have sequenced 45- to 70-kb regions surrounding the four copies of the hsp82 gene of the bdelloid rotifer Philodina roseola, each of which is on a separate chromosome. The four regions comprise two colinear gene-rich pairs with gene content, order, and orientation conserved within each pair. Only a minority of genes are common to both pairs, also in the same orientation and order, but separated by gene-rich segments present in only one or the other pair. The pattern is consistent with degenerate tetraploidy with numerous segmental deletions, some in one pair of colinear chromosomes and some in the other. Divergence in 1,000-bp windows varies along an alignment of a colinear pair, from zero to as much as 20% in a pattern consistent with gene conversion associated with recombinational repair of DNA double-strand breaks. Although pairs of colinear chromosomes are a characteristic of sexually reproducing diploids and polyploids, a quite different explanation for their presence in bdelloids is suggested by the recent finding that bdelloid rotifers can recover and resume reproduction after suffering hundreds of radiation-induced DNA double-strand breaks per oocyte nucleus. Because bdelloid primary oocytes are in G(1) and therefore lack sister chromatids, we propose that bdelloid colinear chromosome pairs are maintained as templates for the repair of DNA double-strand breaks caused by the frequent desiccation and rehydration characteristic of bdelloid habitats.

  18. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  19. Making the Diagnosis of Frontotemporal Lobar Degeneration

    PubMed Central

    Bigio, Eileen H.

    2013-01-01

    Context Autopsy evaluation of the brain of a patient with frontotemporal dementia (FTD) can be daunting to the general pathologist. At some point in their training, most pathologists learn about Pick disease, and can recognize Pick bodies, the morphologic hallmark of Pick disease. Pick disease is a type of frontotemporal lobar degeneration (FTLD), the general category of pathologic process underlying most cases of FTD. The 2 major categories of pathologic FTLD are tauopathies (FTLD-tau) and ubiquitinopathies (FTLD-U). Pick disease is one of the FTLD-tau subtypes and is termed FTLD-tau (PiD). Objective To “demystify” FTLDs, and to demonstrate that subtypes of FTLD-tau and FTLD-U can be easily determined by following a logical, stepwise, histochemical, and immunohistochemical investigation of the FTD autopsy brain. Data Sources Previously published peer-reviewed articles. Conclusions The hope is that this article will be a useful reference for the general pathologist faced with performing a brain autopsy on a decedent with frontotemporal dementia. PMID:23451743

  20. Linear stochastic degenerate Sobolev equations and applications†

    NASA Astrophysics Data System (ADS)

    Liaskos, Konstantinos B.; Pantelous, Athanasios A.; Stratis, Ioannis G.

    2015-12-01

    In this paper, a general class of linear stochastic degenerate Sobolev equations with additive noise is considered. This class of systems is the infinite-dimensional analogue of linear descriptor systems in finite dimensions. Under appropriate assumptions, the mild and strong well-posedness for the initial value problem are studied using elements of the semigroup theory and properties of the stochastic convolution. The final value problem is also examined and it is proved that this is uniquely strongly solvable and the solution is continuously dependent on the final data. Based on the results of the forward and backward problem, the conditions for the exact controllability are investigated for a special but important class of these equations. The abstract results are illustrated by applications in complex media electromagnetics, in the one-dimensional stochastic Dirac equation in the non-relativistic limit and in a potential application in input-output analysis in economics. Dedicated to Professor Grigoris Kalogeropoulos on the occasion of his seventieth birthday.

  1. Case report 872. "Ancient" schwannoma (degenerated neurilemoma).

    PubMed

    Schultz, E; Sapan, M R; McHeffey-Atkinson, B; Naidich, J B; Arlen, M

    1994-10-01

    A case of an ancient schwannoma was presented. The rare occurrence of this tumor has resulted in only a few reported cases with descriptions of its features on imaging. Our patient's tumor, like one previously reported case, demonstrated calcification on the plain film - a finding not associated with other histologic types of schwannomas. Angiography revealed the tumor to be hypervascular. Evaluation by MRI demonstrated a lobulated, encapsulated soft tissue mass containing several cystic areas that corresponded histologically to areas of necrosis. Hypertrophied blood vessels were seen in the periphery of the tumoral mass. Too few ancient schwannomas have been reported to conclude whether or not radiographic evidence of soft tissue calcification is characteristic of this histologically distinctive subtype of schwannoma. However, since calcification is seen histologically as part of the degenerating process, its presence on plain films could be a feature of this tumor. Furthermore, the presence of cystic areas on MRI is not surprising given the pathological changes that occur in this tumor. We suggest that a diagnosis of ancient schwannoma be considered when a patient presents with a hypervascular soft tissue mass containing amorphous calcification on plain films and cystic areas on MRI. Despite the nonspecificity of these imaging findings, this point is relevant because each of these features suggests the presence of a malignant mass. Awareness of the possibility of a benign ancient schwannoma could obviate unnecessary radical surgery.

  2. Cytokines in rotator cuff degeneration and repair.

    PubMed

    Bedi, Asheesh; Maak, Travis; Walsh, Christopher; Rodeo, Scott A; Grande, Dan; Dines, David M; Dines, Joshua S

    2012-02-01

    The pathogenesis of rotator cuff degeneration remains poorly defined, and the incidence of degenerative tears is increasing in the aging population. Rates of recurrent tear and incomplete tendon-to-bone healing after repair remain significant for large and massive tears. Previous studies have documented a disorganized, fibrous junction at the tendon-to-bone interface after rotator cuff healing that does not recapitulate the organization of the native enthesis. Many biologic factors have been implicated in coordinating tendon-to-bone healing and maintenance of the enthesis after rotator cuff repair, including the expression and activation of transforming growth factor-β, basic fibroblast growth factor, platelet-derived growth factor-β, matrix metalloproteinases, and tissue inhibitors of metalloproteinases. Future techniques to treat tendinopathy and enhance tendon-to-bone healing will be driven by our understanding of the biology of this healing process after rotator cuff repair surgery. The use of cytokines to provide important signals for tissue formation and differentiation, the use of gene therapy techniques to provide sustained cytokine delivery, the use of stem cells, and the use of transcription factors to modulate endogenous gene expression represent some of these possibilities. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  3. Neurophysiology of central retinal degeneration in cat.

    PubMed

    Levick, W R; Thibos, L N

    1993-01-01

    Receptive fields of ganglion cells have been studied in cats possessing a chronic, arrested lesion of central retinal degeneration. Lesions were characterized by an ophthalmoscopically sharp border separating apparently normal retina from the region of the lesion. Under direct ophthalmoscopic guidance, a succession of recordings was obtained from ganglion cells having cell bodies at various positions relative to the lesion. Cells located more than 1 deg outside the ophthalmoscopic border had normal visual sensitivity as assessed by area-threshold experiments. Inside the lesion cells within 1 deg of the border had reduced sensitivity which often precluded functional classification by the usual visual tests. Ganglion cells located more than 1 deg inside the border of large lesions were blind and some had abnormal patterns of maintained discharge of action potentials. Nevertheless, the antidromic latencies of these blind cells fell into the familiar conduction groups (T1/T2/T3). Receptive-field maps of cells near the border of the lesion often appeared truncated, with the missing portion of the field covered by the lesion. These observations were consistent with the abnormal form of area-threshold curves. Although the responsiveness of cells near the lesion was abnormally low for grating stimuli, cutoff spatial frequency and orientation bias of these cells were within normal limits.

  4. An Interferometric Harvest of Double Degenerates

    NASA Astrophysics Data System (ADS)

    Nelan, Edmund

    2001-07-01

    The white dwarf {WD} mass and age distributions hold clues to the star formation history of our Galaxy and the age of the disk. To extract this information we need to carefully calibrate the WD mass-radius relation and the WD cooling curve. But to do so, we must directly determine the masses for a variety of WDs of different sub-types. The only direct method is through the orbital analysis of resolved WDs in non- interacting binary systems. Sadly, this has been done, with varying quality, for only 4 WDs {40 Eri B, Sirius B, Procyon B, and Stien 2051B}, mainly because it is extremely difficult to resolve WDs in binary systems with periods less than 50 years. We propose a high angular resolution Snapshot survey with FGS1r to observe cool WDs with the objective of discovering {resolving} double degenerate systems with modest separations and periods as short as 25 years, ideal binaries for follow up mass determinations. By carefully selecting our targets, about 10 such systems should be revealed. This will dramatically increase the number of WDs available for dynamical mass measurements {its 2 for 1.}, enabling a better calibration the WD mass-radius relation.

  5. Producing Quantum Degenerate Gases of Strontium

    NASA Astrophysics Data System (ADS)

    Camargo, Francisco; Ding, Roger; Whalen, Joseph; Woehl, Germano; Dunning, Barry; Killian, Thomas

    2015-05-01

    We present our progress towards producing quantum degenerate gases of all four stable isotopes of strontium (84Sr, 86Sr, 87Sr, 88Sr) and isotopic mixtures. We characterize the performance of our broad-line (461 nm, 30.5 MHz), narrow-line (689 nm, 7.5 kHz) magneto-optical traps, and examine evaporative cooling for all four isotopes. The new apparatus will be used to create and study tunable long-range interactions by dressing with strongly-interacting Rydberg states. The ability to trap the four different isotopes allows a measure of control of these interactions through access to a range of attractive and repulsive interactions. Simultaneous trapping of different isotopes provides opportunities for novel laser cooling schemes for studying Bose-Bose and Bose-Fermi mixtures. Research supported by the AFOSR under grant no. FA9550-12-1-0267, the NSF under grants nos. 1301773 and 1205946, and the Robert A. Welch Foundation under grant no. C-0734.

  6. Degenerate interfaces in antigen-antibody complexes.

    PubMed

    Decanniere, K; Transue, T R; Desmyter, A; Maes, D; Muyldermans, S; Wyns, L

    2001-10-26

    In most of the work dealing with the analysis of protein-protein interfaces, a single X-ray structure is available or selected, and implicitly it is assumed that this structure corresponds to the optimal complex for this pair of proteins. However, we have found a degenerate interface in a high-affinity antibody-antigen complex: the two independent complexes of the camel variable domain antibody fragment cAb-Lys3 and its antigen hen egg white lysozyme present in the asymmetric unit of our crystals show a difference in relative orientation between antibody and antigen, leading to important differences at the protein-protein interface. A third cAb-Lys3-hen lysozyme complex in a different crystal form adopts yet another relative orientation. Our results show that protein-protein interface characteristics can vary significantly between different specimens of the same high-affinity antibody-protein antigen complex. Consideration should be given to this type of observation when trying to establish general protein-protein interface characteristics.

  7. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  8. Slow and Fast Light in Coupled Microresonators

    NASA Technical Reports Server (NTRS)

    Chang, Hongrok; Smith, David D.; Fuller, Kirk A.; Dimmock, John O.; Gregory, Don A.; Frazier, Donald O.

    2005-01-01

    We predict the propagation of slow and fast light in two co-resonant coupled optical resonators. In coupled resonators, slow light can propagate without attenuation by a cancellation of absorption as a result of mode splitting and destructive interference, whereas transparent fast light propagation can be achieved by the assistance of gain and splitting of the intracavity resonances, which consequently change the dispersion from normal to anomalous. The effective steady-state response of coupled-resonators is derived using the temporal coupled-mode formalism, and the absorptive and dispersive responses are described. Specifically, the occurrence of slow light via coupled-resonator-induced transparency and gain-assisted fast light are discussed.

  9. Slow and fast light switching in ruby

    NASA Astrophysics Data System (ADS)

    Rajan, Rajitha P.; Riesen, Hans

    2015-05-01

    Studies about light propagation have been undertaken for more than a century. It is now well established that any material that has normal or anomalous dispersion generates slow or fast light. In this paper, we demonstrate an experimental technique to rapidly switch between slow and fast light in ruby. The experiment utilizes transient holeburning to create drastic variation in refractive index of ruby to produce slow as well as fast light. Transient hole-burning involves the depletion of the ground state leading to a highly populated excited state by single frequency laser excitation. This leads to a hole in the absorption spectrum when readout by a laser. We observed a delay of 29 ns and advancement of -11 ns in an external magnetic field of B║c = 12 mT corresponding to a group velocity of c/961 and negative group velocity of -c/365 respectively.

  10. Particle acceleration by slow magnetosonic wave turbulence

    SciTech Connect

    Gallegos-Cruz, A.

    1997-06-01

    An important alternative for particle acceleration in a turbulent plasma is through magnetohydrodynamic (MHD) wave modes. However, particle acceleration by slow magnetosonic mode has been systematically disregarded for some nonquantitative considerations. Slow magnetosonic waves interchange energy with the medium through two basic processes: resonant (Landau and gyroresonant) and nonresonant (as viscosity and thermal conduction). The energized particles lose energy mainly through Coulombian collisions with the plasma particles. In this work, a quantitative study of the time scales involved in several energetic transfer wave{endash}particle processes is done. Comparison of all these time scales allows one to determine the possibilities that particle acceleration by slow magnetosonic wave mode may occur within the solar corona. It is shown that physical conditions can hardly exist within the solar corona, where thermal particles can be energized and form an acceleration spectrum after crossing the collisional barrier. {copyright} {ital 1997 American Institute of Physics.}

  11. Slow and Fast Light in Coupled Microresonators

    NASA Technical Reports Server (NTRS)

    Chang, Hongrok; Smith, David D.; Fuller, Kirk A.; Dimmock, John O.; Gregory, Don A.; Frazier, Donald O.

    2005-01-01

    We predict the propagation of slow and fast light in two co-resonant coupled optical resonators. In coupled resonators, slow light can propagate without attenuation by a cancellation of absorption as a result of mode splitting and destructive interference, whereas transparent fast light propagation can be achieved by the assistance of gain and splitting of the intracavity resonances, which consequently change the dispersion from normal to anomalous. The effective steady-state response of coupled-resonators is derived using the temporal coupled-mode formalism, and the absorptive and dispersive responses are described. Specifically, the occurrence of slow light via coupled-resonator-induced transparency and gain-assisted fast light are discussed.

  12. Belief Propagation for Probabilistic Slow Feature Analysis

    NASA Astrophysics Data System (ADS)

    Omori, Toshiaki; Sekiguchi, Tomoki; Okada, Masato

    2017-08-01

    Slow feature analysis (SFA) is a time-series analysis method for extracting slowly-varying latent features from multi-dimensional data. A recent study proposed a probabilistic framework of SFA using the Bayesian statistical framework. However, the conventional probabilistic framework of SFA can not accurately extract the slow feature in noisy environments since its marginal likelihood function was approximately derived under the assumption that there exists no observation noise. In this paper, we propose a probabilistic framework of SFA with rigorously derived marginal likelihood function. Here, we rigorously derive the marginal likelihood function of the probabilistic framework of SFA by using belief propagation. We show using numerical data that the proposed probabilistic framework of SFA can accurately extract the slow feature and underlying parameters for the latent dynamics simultaneously even under noisy environments.

  13. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa.

    PubMed

    Kijas, James W; Cideciyan, Artur V; Aleman, Tomas S; Pianta, Michael J; Pearce-Kelling, Susan E; Miller, Brian J; Jacobson, Samuel G; Aguirre, Gustavo D; Acland, Gregory M

    2002-04-30

    Rhodopsin is the G protein-coupled receptor that is activated by light and initiates the transduction cascade leading to night (rod) vision. Naturally occurring pathogenic rhodopsin (RHO) mutations have been previously identified only in humans and are a common cause of dominantly inherited blindness from retinal degeneration. We identified English Mastiff dogs with a naturally occurring dominant retinal degeneration and determined the cause to be a point mutation in the RHO gene (Thr4Arg). Dogs with this mutant allele manifest a retinal phenotype that closely mimics that in humans with RHO mutations. The phenotypic features shared by dog and man include a dramatically slowed time course of recovery of rod photoreceptor function after light exposure and a distinctive topographic pattern to the retinal degeneration. The canine disease offers opportunities to explore the basis of prolonged photoreceptor recovery after light in RHO mutations and determine whether there are links between the dysfunction and apoptotic retinal cell death. The RHO mutant dog also becomes the large animal needed for preclinical trials of therapies for a major subset of human retinopathies.

  14. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa

    PubMed Central

    Kijas, James W.; Cideciyan, Artur V.; Aleman, Tomas S.; Pianta, Michael J.; Pearce-Kelling, Susan E.; Miller, Brian J.; Jacobson, Samuel G.; Aguirre, Gustavo D.; Acland, Gregory M.

    2002-01-01

    Rhodopsin is the G protein-coupled receptor that is activated by light and initiates the transduction cascade leading to night (rod) vision. Naturally occurring pathogenic rhodopsin (RHO) mutations have been previously identified only in humans and are a common cause of dominantly inherited blindness from retinal degeneration. We identified English Mastiff dogs with a naturally occurring dominant retinal degeneration and determined the cause to be a point mutation in the RHO gene (Thr4Arg). Dogs with this mutant allele manifest a retinal phenotype that closely mimics that in humans with RHO mutations. The phenotypic features shared by dog and man include a dramatically slowed time course of recovery of rod photoreceptor function after light exposure and a distinctive topographic pattern to the retinal degeneration. The canine disease offers opportunities to explore the basis of prolonged photoreceptor recovery after light in RHO mutations and determine whether there are links between the dysfunction and apoptotic retinal cell death. The RHO mutant dog also becomes the large animal needed for preclinical trials of therapies for a major subset of human retinopathies. PMID:11972042

  15. Coupled Transmission Line Based Slow Wave Structures for Traveling Wave Tubes Applications

    NASA Astrophysics Data System (ADS)

    Zuboraj, Md. Rashedul Alam

    High power microwave devices especially Traveling Wave Tubes (TWTs) and Backward Wave Oscillators (BWOs) are largely dependent on Slow Wave Structures for efficient beam to RF coupling. In this work, a novel approach of analyzing SWSs is proposed and investigated. Specifically, a rigorous study of helical geometries is carried out and a novel SWS "Half-Ring-Helix" is designed. This Half-Ring-Helix circuit achieves 27% miniaturization and delivers 10dB more gain than conventional helices. A generalization of the helix structures is also proposed in the form of Coupled Transmission Line (CTL). It is demonstrated that control of coupling among the CTLs leads to new propagation properties. With this in mind, a novel geometry referred to as "Curved Ring-Bar" is introduced. This geometry is shown to deliver 1MW power across a 33% bandwidth. Notably, this is the first demonstration of MW power TWT across large bandwidth. The CTL is further expanded to enable engineered propagation characteristics. This is done by introducing CTLs having non-identical transmission lines and CTLs with as many as four transmission lines in the same slow wave structure circuit. These non-identical CTLs are demonstrated to generate fourth order dispersion curves. Building on the property of CTLs, a `butterfly' slow wave structure is developed and demonstrated to provide degenerate band edge (DBE) mode. This mode are known to provide large feld enhancement that can be exploited to design high power backward wave oscillators.

  16. Ultrafast Faraday Rotation of Slow Light

    NASA Astrophysics Data System (ADS)

    Musorin, A. I.; Sharipova, M. I.; Dolgova, T. V.; Inoue, M.; Fedyanin, A. A.

    2016-08-01

    The active control of optical signals in the time domain is what science and technology demand in fast all-optical information processing. Nanostructured materials can modify the group velocity and slow the light down, as the artificial light dispersion emerges. We observe the ultrafast temporal behavior of the Faraday rotation within a single femtosecond laser pulse under conditions of slow light in a one-dimensional magnetophotonic crystal. The Faraday effect changes by 20% over the time of 150 fs. This might be applicable to the fast control of light in high-capacity photonic devices.

  17. Slow light by coherent hole burnings

    NASA Astrophysics Data System (ADS)

    He, Qiong-Yi; Zhang, Bing; Wei, Xiao-Gang; Wu, Jin-Hui; Kuang, Shang-Qi; Gao, Jin-Yue

    2008-06-01

    We show that the simultaneous application of a copropagating saturating pump and a counterpropagating coherent beam can be used to burn a narrow spectral hole within the absorption line of the optical transition in a Doppler-broadened medium. The large index of refraction of this hole slows down a light pulse by a factor of about 104 . In addition, we propose a method to create two-color slow light pulses with simultaneous gain by employing a bichromatic field to saturate the medium.

  18. Slow crack growth in spinel in water

    NASA Technical Reports Server (NTRS)

    Schwantes, S.; Elber, W.

    1983-01-01

    Magnesium aluminate spinel was tested in a water environment at room temperature to establish its slow crack-growth behavior. Ring specimens with artificial flaws on the outside surface were loaded hydraulically on the inside surface. The time to failure was measured. Various precracking techniques were evaluated and multiple precracks were used to minimize the scatter in the static fatigue tests. Statistical analysis techniques were developed to determine the strength and crack velocities for a single flaw. Slow crack-growth rupture was observed at stress intensities as low as 70 percent of K sub c. A strengthening effect was observed in specimens that had survived long-time static fatigue tests.

  19. Geodynamic environments of ultra-slow spreading

    NASA Astrophysics Data System (ADS)

    Kokhan, Andrey; Dubinin, Evgeny

    2015-04-01

    Ultra-slow spreading is clearly distinguished as an outstanding type of crustal accretion by recent studies. Spreading ridges with ultra-slow velocities of extension are studied rather well. But ultra-slow spreading is characteristic feature of not only spreading ridges, it can be observed also on convergent and transform plate boundaries. Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on divergent plate boundaries: 1. On spreading ridges with ultra-slow spreading, both modern (f.e. Gakkel, South-West Indian, Aden spreading center) and ceased (Labrador spreading center, Aegir ridge); 2. During transition from continental rifting to early stages of oceanic spreading (all spreading ridges during incipient stages of their formation); 3. During incipient stages of formation of spreading ridges on oceanic crust as a result of ridge jumps and reorganization of plate boundaries (f.e. Mathematicians rise and East Pacific rise); 4. During propagation of spreading ridge into the continental crust under influence of hotspot (Aden spreading center and Afar triple junction), under presence of strike-slip faults preceding propagation (possibly, rift zone of California Bay). Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on transform plate boundaries: 1. In transit zones between two "typical" spreading ridges (f.e. Knipovich ridge); 2. In semi strike-slip/extension zones on the oceanic crust (f.e. American-Antarctic ridge); 3. In the zones of local extension in regional strike-slip areas in pull-apart basins along transform boundaries (Cayman trough, pull-apart basins of the southern border of Scotia plate). Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on convergent plate boundaries: 1. During back-arc rifting on the stage of transition into back-arc spreading (central

  20. Polymorphism and disorder in natural active ingredients. Low and high-temperature phases of anhydrous caffeine: Spectroscopic ((1)H-(14)N NMR-NQR/(14)N NQR) and solid-state computational modelling (DFT/QTAIM/RDS) study.

    PubMed

    Seliger, Janez; Žagar, Veselko; Apih, Tomaž; Gregorovič, Alan; Latosińska, Magdalena; Olejniczak, Grzegorz Andrzej; Latosińska, Jolanta Natalia

    2016-03-31

    The polymorphism of anhydrous caffeine (1,3,7-trimethylxanthine; 1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione) has been studied by (1)H-(14)N NMR-NQR (Nuclear Magnetic Resonance-Nuclear Quadrupole Resonance) double resonance and pure (14)N NQR (Nuclear Quadrupole Resonance) followed by computational modelling (Density Functional Theory, supplemented Quantum Theory of Atoms in Molecules with Reduced Density Gradient) in solid state. For two stable (phase II, form β) and metastable (phase I, form α) polymorphs the complete NQR spectra consisting of 12 lines were recorded. The assignment of signals detected in experiment to particular nitrogen sites was verified with the help of DFT. The shifts of the NQR frequencies, quadrupole coupling constants and asymmetry parameters at each nitrogen site due to polymorphic transition were evaluated. The strongest shifts were observed at N(3) site, while the smallest at N(9) site. The commercial pharmaceutical sample was found to contain approximately 20-25% of phase I and 75-80% of phase II. The orientational disorder in phase II with a local molecular arrangement mimics that in phase I. Substantial differences in the intermolecular interaction phases I and II of caffeine were analysed using computational (DFT/QTAIM/RDS) approach. The analysis of local environment of each nitrogen nucleus permitted drawing some conclusions on the topology of interactions in both polymorphs. For the most stable orientations in phase I and phase II the maps of the principal component qz of EFG tensor and its asymmetry parameter at each point of the molecular system were calculated and visualized. The relevant maps calculated for both phases I and II indicates small variation in electrostatic potential upon phase change. Small differences between packings in phases slightly disturb the neighbourhood of the N(1) and N(7) nitrogens, thus are meaningless from the biological point of view. The composition of two phases in pharmaceutical material

  1. Slow breathing influences cardiac autonomic responses to postural maneuver: Slow breathing and HRV.

    PubMed

    Vidigal, Giovanna Ana de Paula; Tavares, Bruna S; Garner, David M; Porto, Andrey A; Carlos de Abreu, Luiz; Ferreira, Celso; Valenti, Vitor E

    2016-05-01

    Chronic slow breathing has been reported to improve Heart Rate Variability (HRV) in patients with cardiovascular disorders. However, it is not clear regarding its acute effects on HRV responses on autonomic analysis. We evaluated the acute effects of slow breathing on cardiac autonomic responses to postural change manoeuvre (PCM). The study was conducted on 21 healthy male students aged between 18 and 35 years old. In the control protocol, the volunteer remained at rest seated for 15 min under spontaneous breathing and quickly stood up within 3 s and remained standing for 15 min. In the slow breathing protocol, the volunteer remained at rest seated for 10 min under spontaneous breath, then performed slow breathing for 5 min and rapidly stood up within 3 s and remained standing for 15 min. Slow breathing intensified cardiac autonomic responses to postural maneuver.

  2. [Progress on the degeneration mechanism of cave fishes' eyes].

    PubMed

    Gu, Xian; Ning, Tiao; Xiao, Heng

    2012-08-01

    Attempts to understand the degeneration of the eyes in cave fish has largely been explained by either various extents of gradual degeneration, ranging from partial to total loss, observed in various species or by acceleration of loss caused by dark environments. However, neither the theory of biological evolution developed by Charles Darwin nor the neutral theory of molecular evolution formulated by Kimura Motoo adequately explains these phenomena. Recent trends in utilizing multidisciplinary research, however, have yielded better results, helping reveal a more complex picture of the mechanisms of degeneration. Here, we summarize the current progress of the research via morphology and anatomy, development biology, animal behavior science and molecular genetics, and offer some perspectives on the ongoing research into the development and degeneration of eyes in cave fish.

  3. Construction of nonregular pointwise degenerate delay-differential systems

    NASA Technical Reports Server (NTRS)

    Choudhury, A. K.

    1978-01-01

    Pointwise degenerate delay-differential systems (degeneracy at t = 2h) are reduced to Popov's construction under the regularity assumption. Necessary and sufficient conditions for the degeneracy are outlined.

  4. Neuronal degeneration in subacute necrotizing encephalomyelopathy (Leigh's disease). Case report.

    PubMed

    Lindboe, C F; Lie, A K; Aase, S T; Schjetne, O B; Haave, I

    1995-01-01

    We report clinical, radiological and pathological findings in a 5-year-old girl who died of subacute necrotizing encephalomyelopathy (SNE) after 4 weeks of illness. Autopsy revealed endothelial swelling and vacuolar degeneration of the neuropil in the brain, brain stem and cerebellum. In addition, the affected areas showed degeneration of the neurons which was different from anoxic nerve cell damage both with regard to morphological picture and topographical distribution. This neuronal degeneration was probably due to the underlying metabolic defect in SNE per se and resembled in several aspects the nerve cell changes seen in the thalami and inferior olives in active Wernicke's encephalopathy. It is our opinion that more attention should be paid to the nerve cell degeneration in SNE rather than focusing on the relative preservation of these cells.

  5. [Research advances in animal models of intervertebral disc degeneration].

    PubMed

    Zhang, Wenli; Liu, Hao; Li, Tanzhu

    2007-11-01

    To review the research advances in animal models of human disc degeneration. The relative articles in recent years were extensively reviewed. Studies both at home and abroad were analyzed and classified. The advantages and disadvantages of each method were compared. Studies were classified as either experimentally induced models or spontaneous models. The induced models were subdivided as mechanical (alteration of forces on the normal disc), structural (injury or chemical alteration) and genetically induced models. Spontaneous models included those animals that naturally developed degenerative disc disease. Animal model of intervertebral disc degeneration is an important path for revealing the pathogenesis of human disc degeneration, and play an important role in testing novel interventions. With recent advances in the relevance of animal models and humans, it has a great prospect in study of human disc degeneration.

  6. Arbitrary electron acoustic waves in degenerate dense plasmas

    NASA Astrophysics Data System (ADS)

    Rahman, Ata-ur; Mushtaq, A.; Qamar, A.; Neelam, S.

    2017-05-01

    A theoretical investigation is carried out of the nonlinear dynamics of electron-acoustic waves in a collisionless and unmagnetized plasma whose constituents are non-degenerate cold electrons, ultra-relativistic degenerate electrons, and stationary ions. A dispersion relation is derived for linear EAWs. An energy integral equation involving the Sagdeev potential is derived, and basic properties of the large amplitude solitary structures are investigated in such a degenerate dense plasma. It is shown that only negative large amplitude EA solitary waves can exist in such a plasma system. The present analysis may be important to understand the collective interactions in degenerate dense plasmas, occurring in dense astrophysical environments as well as in laser-solid density plasma interaction experiments.

  7. Age-related macular degeneration: current treatment and future options.

    PubMed

    Moutray, Tanya; Chakravarthy, Usha

    2011-09-01

    Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.

  8. Arbitrary electron acoustic waves in degenerate dense plasmas

    NASA Astrophysics Data System (ADS)

    Rahman, Ata-ur; Mushtaq, A.; Qamar, A.; Neelam, S.

    2016-12-01

    A theoretical investigation is carried out of the nonlinear dynamics of electron-acoustic waves in a collisionless and unmagnetized plasma whose constituents are non-degenerate cold electrons, ultra-relativistic degenerate electrons, and stationary ions. A dispersion relation is derived for linear EAWs. An energy integral equation involving the Sagdeev potential is derived, and basic properties of the large amplitude solitary structures are investigated in such a degenerate dense plasma. It is shown that only negative large amplitude EA solitary waves can exist in such a plasma system. The present analysis may be important to understand the collective interactions in degenerate dense plasmas, occurring in dense astrophysical environments as well as in laser-solid density plasma interaction experiments.

  9. Secondary orthostatic tremor in the setting of cerebellar degeneration.

    PubMed

    Sarva, Harini; Severt, William Lawrence; Jacoby, Nuri; Pullman, Seth L; Saunders-Pullman, Rachel

    2016-05-01

    Orthostatic tremor (OT) and cerebellar ataxia are uncommon and difficult to treat. We present two patients with OT and cerebellar degeneration, one of whom had spinocerebellar ataxia type 2 and a good treatment response.

  10. Degenerate higher derivative theories beyond Horndeski: evading the Ostrogradski instability

    SciTech Connect

    Langlois, David; Noui, Karim E-mail: karim.noui@lmpt.univ-tours.fr

    2016-02-01

    Theories with higher order time derivatives generically suffer from ghost-like instabilities, known as Ostrogradski instabilities. This fate can be avoided by considering ''degenerate'' Lagrangians, whose kinetic matrix cannot be inverted, thus leading to constraints between canonical variables and a reduced number of physical degrees of freedom. In this work, we derive in a systematic way the degeneracy conditions for scalar-tensor theories that depend quadratically on second order derivatives of a scalar field. We thus obtain a classification of all degenerate theories within this class of scalar-tensor theories. The quartic Horndeski Lagrangian and its extension beyond Horndeski belong to these degenerate cases. We also identify new families of scalar-tensor theories with the property that they are degenerate despite the nondegeneracy of the purely scalar part of their Lagrangian.

  11. Melange a Six Ondes Degenere dans les Absorbants Saturables

    NASA Astrophysics Data System (ADS)

    Blouin, Alain

    Issus d'une generalisation du melange a quatre ondes degenere, les melanges a n ondes degeneres sont utiles pour la mesure des divers ordres de la susceptibilite nonlineaire. Nous avons procede a l'etude theorique et experimentale du melange a six ondes degenere dans des absorbants isotropes et anisotropes. Pour l'analyse theorique, nous avons developpe une methode de calcul basee sur une approche holographique. Cette methode fut utilisee pour l'etude du melange a six ondes en regimes stationnaire et transitoire sous des conditions de faibles et de fortes saturations. Des experiences realisees a l'aide d'impulsions excitatrices de courte duree, soit 33 picosecondes, dans des verres dopes aux semi-conducteurs et dans la Rhodamine 6G en solution ont permis de verifier la validite de notre modele theorique. Nous avons aussi etudie les oscillateurs auto-pompes par melange a six ondes degenere.

  12. Intervertebral disc degeneration: evidence for two distinct phenotypes

    PubMed Central

    Adams, Michael A; Dolan, Patricia

    2012-01-01

    We review the evidence that there are two types of disc degeneration. ‘Endplate-driven’ disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. ‘Annulus-driven’ disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct. PMID:22881295

  13. Drosophila melanogaster as a Model of Muscle Degeneration Disorders.

    PubMed

    Kreipke, R E; Kwon, Y V; Shcherbata, H R; Ruohola-Baker, H

    2017-01-01

    Drosophila melanogaster provides a powerful platform with which researchers can dissect complex genetic questions and biochemical pathways relevant to a vast array of human diseases and disorders. Of particular interest, much work has been done with flies to elucidate the molecular mechanisms underlying muscle degeneration diseases. The fly is particularly useful for modeling muscle degeneration disorders because there are no identified satellite muscle cells to repair adult muscle following injury. This allows for the identification of endogenous processes of muscle degeneration as discrete events, distinguishable from phenotypes due to the lack of stem cell-based regeneration. In this review, we will discuss the ways in which the fruit fly provides a powerful platform with which to study human muscle degeneration disorders.

  14. Purifying Greenberger-Horne-Zeilinger states using degenerate quantum codes

    NASA Astrophysics Data System (ADS)

    Ho, K. H.; Chau, H. F.

    2008-10-01

    Degenerate quantum codes are codes that do not reveal the complete error syndrome. Their ability to conceal the complete error syndrome makes them powerful resources in certain quantum-information processing tasks. In particular, the most error-tolerant way to purify depolarized Bell states using one-way communication known to date involves degenerate quantum codes. Here we study three closely related purification schemes for depolarized Greenberger-Horne-Zeilinger states shared among m⩾3 players by means of degenerate quantum codes and one-way classical communications. We find that our schemes tolerate more noise than all other one-way schemes known to date, further demonstrating the effectiveness of degenerate quantum codes in quantum-information processing.

  15. Fast and Slow Spindles during the Sleep Slow Oscillation: Disparate Coalescence and Engagement in Memory Processing

    PubMed Central

    Mölle, Matthias; Bergmann, Til O.; Marshall, Lisa; Born, Jan

    2011-01-01

    Study Objectives: Thalamo-cortical spindles driven by the up-state of neocortical slow (< 1 Hz) oscillations (SOs) represent a candidate mechanism of memory consolidation during sleep. We examined interactions between SOs and spindles in human slow wave sleep, focusing on the presumed existence of 2 kinds of spindles, i.e., slow frontocortical and fast centro-parietal spindles. Design: Two experiments were performed in healthy humans (24.5 ± 0.9 y) investigating undisturbed sleep (Experiment I) and the effects of prior learning (word paired associates) vs. non-learning (Experiment II) on multichannel EEG recordings during sleep. Measurements and Results: Only fast spindles (12-15 Hz) were synchronized to the depolarizing SO up-state. Slow spindles (9-12 Hz) occurred preferentially at the transition into the SO down-state, i.e., during waning depolarization. Slow spindles also revealed a higher probability to follow rather than precede fast spindles. For sequences of individual SOs, fast spindle activity was largest for “initial” SOs, whereas SO amplitude and slow spindle activity were largest for succeeding SOs. Prior learning enhanced this pattern. Conclusions: The finding that fast and slow spindles occur at different times of the SO cycle points to disparate generating mechanisms for the 2 kinds of spindles. The reported temporal relationships during SO sequences suggest that fast spindles, driven by the SO up-state feed back to enhance the likelihood of succeeding SOs together with slow spindles. By enforcing such SO-spindle cycles, particularly after prior learning, fast spindles possibly play a key role in sleep-dependent memory processing. Citation: Mölle M; Bergmann TO; Marshall L; Born J. Fast and slow spindles during the sleep slow oscillation: disparate coalescence and engagement in memory processing. SLEEP 2011;34(10):1411–1421. PMID:21966073

  16. SINGLE-DEGENERATE TYPE Ia SUPERNOVAE ARE PREFERENTIALLY OVERLUMINOUS

    SciTech Connect

    Fisher, Robert; Jumper, Kevin

    2015-06-01

    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.

  17. First and second sounds in a degenerate Bose gas

    NASA Astrophysics Data System (ADS)

    Dmytruk, I.; Svidzynskiy, A.; Shygorin, P.

    2017-06-01

    In this work the propagation of sound waves in a degenerate quantum gas is considered. We modify the Wang Chang and Uhlenbeck method for description of the sounds in a Maxwell gas for the case of a degenerate quantum gas. Using this approach, we constructed a dispersion relation for sound waves in a condensed Bose gas at finite temperatures, and calculate the velocities of first and second sounds in the first approximation. The possibility of the theoretical investigation for sound damping is discussed.

  18. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2013-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to September 2011), EMBASE (January 1980 to September 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 16 September 2011. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the

  19. Treatment of macular degeneration, according to Bangerter.

    PubMed

    Teichmann, K D

    1997-10-30

    Age-related macular degeneration (AMD) is a common cause of visual loss among elderly patients. Although some risk factors have been determined, the ultimate cause of the disease is not known. For a long time, therapeutic nihilism has been the rule among ophthalmologists confronted with such patients. Bangerter has not shared this attitude, especially since the time that he incidentally discovered, more than 40 years ago, the beneficial effects of radiotherapy, in discouraging the growth of new vessels at the posterior pole of the eye. A variety of approaches are combined and used by Bangerter in the treatment of the different types of AMD, including retrobulbar injections of either vasodilating medications (in the dry - or atrophic - type) or corticosteroids (in the wet - or exudative - type), general medical measures aimed at improving metabolic and vascular functions such as supplementation with trace elements, antioxidants, and vitamins; ozone therapy; advice to increase physical fitness, improve nutrition, and abstain from smoking; and protection from excessive light exposure. Being convinced of the usefulness of his type of combination treatment, he has always rejected undertaking controlled clinical trials, of only single aspects of the therapy, as unethical and invalid. For this reason, scientific journals have not proven cooperative in several attempts at publishing his results, as collected in retrospective surveys. Recently, however, some of the several approaches combined by Bangerter in treating AMD have been pronounced effective by other investigators. We present here an overview of his treatment approaches, as few people are aware of them, to clear up misconceptions and to set records straight.

  20. Symmetric corticobasal degeneration (S-CBD).

    PubMed

    Hassan, Anhar; Whitwell, Jennifer L; Boeve, Bradley F; Jack, Clifford R; Parisi, Joseph E; Dickson, Dennis W; Josephs, Keith A

    2010-03-01

    Corticobasal degeneration (CBD) is a neurodegenerative disease characterized pathologically by neuronal loss, gliosis and tau deposition in neocortex, basal ganglia and brainstem. Typical clinical presentation is known as corticobasal syndrome (CBS) and involves the core features of progressive asymmetric rigidity and apraxia, accompanied by other signs of cortical and extrapyramidal dysfunction. Asymmetry is also emphasized on neuroimaging. To describe a series of cases of CBD with symmetric clinical features and to compare clinical and imaging features of these symmetric CBD cases (S-CBD) to typical cases of CBS with CBD pathology. All cases of pathologically confirmed CBD from the Mayo Clinic Rochester database were identified. Clinical records were reviewed and quantitative volumetric analysis of symmetric atrophy on head MRI using atlas based parcellation was performed. Subjects were classified as S-CBD if no differences had been observed between right- and left-sided cortical or extrapyramidal signs or symptoms. S-CBD cases were compared to 10 randomly selected typical CBS cases. Five cases (2 female) met criteria for S-CBD. None had limb dystonia, myoclonus, apraxia or alien limb phenomena. S-CBD cases had significantly less asymmetric atrophy when compared with CBS cases (p=0.009); they were also younger at onset (median 61 versus 66 years, p<0.05) and death (67 versus 73 years, p<0.05). Family history was present in 40% of S-CBD cases. CBD can have a symmetric presentation, clinically and radiologically, in which typical features of CBS, such as limb apraxia, myoclonus, dystonia and alien limb phenomenon, may be absent. Copyright (c) 2009 Elsevier Ltd. All rights reserved.