Science.gov

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. PMID:26420485

  3. Atypical gliosis in Müller cells of the slowly degenerating rds mutant mouse retina.

    PubMed

    Iandiev, Ianors; Biedermann, Bernd; Bringmann, Andreas; Reichel, Martin B; Reichenbach, Andreas; Pannicke, Thomas

    2006-03-01

    Retinal Müller glial cells are known to undergo reactive changes (gliosis) in various retinal diseases. In virtually all cases studied, an upregulation of glial fibrillary acidic protein (GFAP) and a hypertrophy can be observed. Physiological alterations, such as a strong downregulation of inwardly rectifying K+ (Kir) currents, were found after retinal detachment (man, rabbit) and after ischemia/reperfusion (rat) but not in more slowly progressing retinal degenerations (Borna Disease Virus-infected rats, RCS rats). This led us to hypothesize that Müller cells respond with 'typical' reactive gliosis only to rapid but not to slow retinal degeneration. To test this hypothesis, we studied Müller cells from rds mutant mice (PrphRd2), which show a retinal degeneration of early onset and slow progression, resulting in a complete loss of photoreceptors after 9-12 months. In Müller cells of rds mice, we found immunoreactivity for GFAP, a marker of gliosis in Müller cells, from postnatal day 21 on, accompanied by a moderately increased membrane capacitance (taken as an indicator of hypertrophy), whereas no change in the expression of the Kir4.1 protein occurred in adult rds mice. We failed to observe significant changes in the membrane resistance and the membrane potential of cells from rds mice from first week after birth until 1 year of age. Current densities were decreased in cells from 3- and 5-week old rds mice. Furthermore, as in control cells from wildtype animals, these cells displayed dominant Kir currents, voltage-dependent Na+ currents, and glutamate uptake currents. These data support the idea that in mice as well as previously shown in rats, slow retinal degeneration induces an atypical gliosis of Müller cells. PMID:16154566

  4. 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. PMID:26773759

  5. Varying the GARP2-to-RDS Ratio Leads to Defects in Rim Formation and Rod and Cone Function

    PubMed Central

    Chakraborty, Dibyendu; Conley, Shannon M.; DeRamus, Marci L.; Pittler, Steven J.; Naash, Muna I.

    2015-01-01

    Purpose The beta subunit of the rod cyclic nucleotide gated channel B1 (CNGB1) contains a proline/glutamic acid-rich N-terminal domain (GARP), which is also present in rods as a non–membrane-bound protein (GARP1/2). GARP2 and CNGB1 bind to retinal degeneration slow (RDS), which is present in the rims of rod and cone outer segment (OS) layers. Here we focus on the importance of RDS/GARP complexes in OS morphogenesis and stability. Methods Retinal structure, function, and biochemistry were assessed in GARP2-Tg transgenic mice crossed onto rds+/+, rds+/−, and rds−/− genetic backgrounds. Results GARP2 expression decreased in animals with reduced RDS levels. Overexpression of GARP2 led to abnormalities in disc stacking in GARP2-Tg/rds+/+ and the accumulation of abnormal vesicular structures in GARP2-Tg/rds+/− OS, as well as alterations in RDS-ROM-1 complex formation. These abnormalities were associated with diminished scotopic a- and b-wave amplitudes in GARP2-Tg mice on both the rds+/+ and rds+/− backgrounds. In addition, severe defects in cone function were observed in GARP2-Tg mice on all RDS backgrounds. Conclusions Our results indicate that overexpression of GARP2 significantly exacerbates the defects in rod function associated with RDS haploinsufficiency and leads to further abnormalities in OS ultrastructure. These data also suggest that GARP2 expression in cones can be detrimental to cones. RDS/GARP interactions remain under investigation but are critical for both OS structure and function. PMID:26720471

  6. SNAREs Interact with Retinal Degeneration Slow and Rod Outer Segment Membrane Protein-1 during Conventional and Unconventional Outer Segment Targeting

    PubMed Central

    Zulliger, Rahel; Conley, Shannon M.; Mwoyosvi, Maggie L.; Stuck, Michael W.; Azadi, Seifollah; Naash, Muna I.

    2015-01-01

    Mutations in the photoreceptor protein peripherin-2 (also known as RDS) cause severe retinal degeneration. RDS and its homolog ROM-1 (rod outer segment protein 1) are synthesized in the inner segment and then trafficked into the outer segment where they function in tetramers and covalently linked larger complexes. Our goal is to identify binding partners of RDS and ROM-1 that may be involved in their biosynthetic pathway or in their function in the photoreceptor outer segment (OS). Here we utilize several methods including mass spectrometry after affinity purification, in vitro co-expression followed by pull-down, in vivo pull-down from mouse retinas, and proximity ligation assay to identify and confirm the SNARE proteins Syntaxin 3B and SNAP-25 as novel binding partners of RDS and ROM-1. We show that both covalently linked and non-covalently linked RDS complexes interact with Syntaxin 3B. RDS in the mouse is trafficked from the inner segment to the outer segment by both conventional (i.e., Golgi dependent) and unconventional secretory pathways, and RDS from both pathways interacts with Syntaxin3B. Syntaxin 3B and SNAP-25 are enriched in the inner segment (compared to the outer segment) suggesting that the interaction with RDS/ROM-1 occurs in the inner segment. Syntaxin 3B and SNAP-25 are involved in mediating fusion of vesicles carrying other outer segment proteins during outer segment targeting, so could be involved in the trafficking of RDS/ROM-1. PMID:26406599

  7. Structural characterization of the second intra-discal loop of the photoreceptor tetraspanin RDS.

    PubMed

    Chakraborty, Dibyendu; Rodgers, Karla K; Conley, Shannon M; Naash, Muna I

    2013-01-01

    Vertebrate photoreceptors contain a unique tetraspanin protein known as 'retinal degeneration slow' (RDS). Mutations in the RDS gene have been identified in a variety of human retinal degenerative diseases, and more than 70% of these mutations are located in the second intra-discal (D2) loop, highlighting the importance of this region. Here we examined the conformational and thermal stability properties of the D2 loop of RDS, as well as interactions with ROM-1, a non-glycosylated homolog of RDS. The RDS D2 loop was expressed in Escherichia coli as a fusion protein with maltose binding protein (MBP). The fusion protein, referred to as MBP-D2, was purified to homogeneity. Circular dichroism spectroscopy showed that the wild-type (WT) D2 loop consists of approximately 21% α-helix, approximately 20% β-sheet and approximately 59% random coil. D2 loop fusion proteins carrying disease-causing mutations in RDS (e.g. R172W, C214S, N244H/K) were also examined, and conformational changes were observed (compared to wild-type D2). In particular, the C150S, C214S and N244H proteins showed significant reductions in α-helicity. However, the thermal stability of the mutants was unchanged compared to wild-type, and all the mutants were capable of interacting with ROM-1, indicating that this functional aspect of the isolated D2 loop remained intact in the mutants despite the observed conformational changes. An I-TASSER model of the RDS D2 loop predicted a structure consistent with the circular dichroism experiments and the structure of the conserved region of the D2 loop of other tetraspanin family members. These results provide significant insight into the mechanism of RDS complex formation and the disease process underlying RDS-associated retinal degeneration. PMID:23121719

  8. The Y141C knockin mutation in RDS leads to complex phenotypes in the mouse.

    PubMed

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

    2014-12-01

    Mutations in the photoreceptor-specific gene peripherin-2 (PRPH-2, also known as retinal degeneration slow/RDS) cause incurable retinal degeneration with a high degree of phenotypic variability. Patient phenotypes range from retinitis pigmentosa to various forms of macular and pattern dystrophy. Macular and pattern dystrophy in particular are associated with complex, poorly understood disease mechanisms, as severe vision loss is often associated both with defects in the photoreceptors, as well as the choroid and retinal pigment epithelium (RPE). Since there is currently no satisfactory model to study pattern dystrophy disease mechanisms, we generated a knockin mouse model expressing an RDS pattern dystrophy mutation, Y141C. Y141C mice exhibited clinical signs similar to those in patients including late-onset fundus abnormalities characteristic of RPE and choroidal defects and electroretinogram defects. Ultrastructural examination indicated that disc formation was initiated by the Y141C protein, but proper sizing and alignment of discs required wild-type RDS. The biochemical mechanism underlying these abnormalities was tied to defects in the normal process of RDS oligomerization which is required for proper RDS function. Y141C-RDS formed strikingly abnormal disulfide-linked complexes which were localized to the outer segment (OS) where they impaired the formation of proper OS structure. These data support a model of pattern dystrophy wherein a primary molecular defect occurring in all photoreceptors leads to secondary sequellae in adjacent tissues, an outcome which leads to macular vision loss. An understanding of the role of RDS in the interplay between these tissues significantly enhances our understanding of RDS-associated pathobiology and our ability to design rational treatment strategies. PMID:25001182

  9. The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves

    PubMed Central

    Beirowski, Bogdan; Adalbert, Robert; Wagner, Diana; Grumme, Daniela S; Addicks, Klaus; Ribchester, Richard R; Coleman, Michael P

    2005-01-01

    Background The progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons. We recently validated the study of Wallerian degeneration using yellow fluorescent protein (YFP) in a small, representative population of axons, which greatly improves longitudinal imaging. Here, we apply this method to study the progressive nature of Wallerian degeneration in both wild-type and slow Wallerian degeneration (WldS) mutant mice. Results In wild-type nerves, we directly observed partially fragmented axons (average 5.3%) among a majority of fully intact or degenerated axons 37–42 h after transection and 40–44 h after crush injury. Axons exist in this state only transiently, probably for less than one hour. Surprisingly, axons degenerated anterogradely after transection but retrogradely after a crush, but in both cases a sharp boundary separated intact and fragmented regions of individual axons, indicating that Wallerian degeneration progresses as a wave sequentially affecting adjacent regions of the axon. In contrast, most or all WldS axons were partially fragmented 15–25 days after nerve lesion, WldS axons degenerated anterogradely independent of lesion type, and signs of degeneration increased gradually along the nerve instead of abruptly. Furthermore, the first signs of degeneration were short constrictions, not complete breaks. Conclusions We conclude that Wallerian degeneration progresses rapidly along individual wild-type axons after a heterogeneous latent phase. The speed of progression and its ability to travel in either direction challenges earlier models in which clearance of

  10. 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.

  11. 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.

  12. High prevalence of mutations in peripherin/RDS in autosomal dominant macular dystrophies in a Spanish population

    PubMed Central

    Gamundi, María José; Hernan, Imma; Muntanyola, Marta; Trujillo, María José; García-Sandoval, Blanca; Ayuso, Carmen; Baiget, Montserrat

    2007-01-01

    Purpose Mutations in the peripherin/retinal degeneration slow (RDS) gene are a known cause of various types of central retinal dystrophies. The purpose of this study was to determine the prevalence of mutations in the peripherin/RDS gene in Spanish patients with different types of autosomal dominant macular dystrophy. Methods Ophthalmic and electrophysiological examination was performed in patients from 61 unrelated autosomal dominant macular dystrophy (adMD) Spanish families. Screening for mutations in the peripherin/RDS gene by denaturing gradient gel electrophoresis (DGGE) and direct genomic sequencing was performed in index patients and extended to the family when positive. Results We report four novel mutations in peripherin/RDS and a relatively high frequency (23%) of mutations in this gene in families with adMD. Thirteen different mutations were found in fifteen adMD families. Three novel missense, four nonsense and a cis-acting splicing mutation IVS2+2T>C, were found in a Spanish population while five more missense mutations were also reported in other populations. The Arg142Trp and Arg172Trp mutations, present in several populations, were both detected in two independent Spanish families. All the missense mutations produce an amino acid substitution in the second intradiscal loop of the peripherin, while the nonsense mutations presumably generate a truncated protein. Conclusions A high frequency (23%) of mutations in the peripherin/RDS gene was found in a cohort of 61 unrelated patients with various types of autosomal dominant central retinal dystrophies as compared with a low prevalence (1.3%) of mutations in this gene causing retinitis pigmentosa in a Spanish population. Different macular dystrophy phenotypes according to the mutations in peripherin/RDS are shown. However, a limited phenotype variation was observed for these mutations within the family. PMID:17653047

  13. A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses.

    PubMed

    Adalbert, Robert; Gillingwater, Thomas H; Haley, Jane E; Bridge, Katherine; Beirowski, Bogdan; Berek, Livia; Wagner, Diana; Grumme, Daniela; Thomson, Derek; Celik, Arzu; Addicks, Klaus; Ribchester, Richard R; Coleman, Michael P

    2005-01-01

    The slow Wallerian degeneration phenotype, Wld(S), which delays Wallerian degeneration and axon pathology for several weeks, has so far been studied only in mice. A rat model would have several advantages. First, rats model some human disorders better than mice. Second, the larger body size of rats facilitates more complex surgical manipulations. Third, rats provide a greater yield of tissue for primary culture and biochemical investigations. We generated transgenic Wld(S) rats expressing the Ube4b/Nmnat1 chimeric gene in the central and peripheral nervous system. As in Wld(S) mice, their axons survive up to 3 weeks after transection and remain functional for at least 1 week. Protection of axotomized nerve terminals is stronger than in mice, particularly in one line, where 95-100% of neuromuscular junctions remained intact and functional after 5 days. Furthermore, the loss of synaptic phenotype with age was much less in rats than in mice. Thus, the slow Wallerian degeneration phenotype can be transferred to another mammalian species and synapses may be more effectively preserved after axotomy in species with longer axons. PMID:15654865

  14. Intra-axonal calcium changes after axotomy in wild-type and slow Wallerian degeneration axons.

    PubMed

    Adalbert, R; Morreale, G; Paizs, M; Conforti, L; Walker, S A; Roderick, H L; Bootman, M D; Siklós, L; Coleman, M P

    2012-12-01

    Calcium accumulation induces the breakdown of cytoskeleton and axonal fragmentation in the late stages of Wallerian degeneration. In the early stages there is no evidence for any long-lasting, extensive increase in intra-axonal calcium but there does appear to be some redistribution. We hypothesized that changes in calcium distribution could have an early regulatory role in axonal degeneration in addition to the late executionary role of calcium. Schmidt-Lanterman clefts (SLCs), which allow exchange of metabolites and ions between the periaxonal and extracellular space, are likely to have an increased role when axon segments are separated from the cell body, so we used the oxalate-pyroantimonate method to study calcium at SLCs in distal stumps of transected wild-type and slow Wallerian degeneration (Wld(S)) mutant sciatic nerves, in which Wallerian degeneration is greatly delayed. In wild-type nerves most SLCs show a step gradient of calcium distribution, which is lost at around 20% of SLCs within 3mm of the lesion site by 4-24h after nerve transection. To investigate further the association with Wallerian degeneration, we studied nerves from Wld(S) rats. The step gradient of calcium distribution in Wld(S) is absent in around 20% of the intact nerves beneath SLCs but 4-24h following injury, calcium distribution in transected axons remained similar to that in uninjured nerves. We then used calcium indicators to study influx and buffering of calcium in injured neurites in primary culture. Calcium penetration and the early calcium increase in this system were indistinguishable between Wld(S) and wild-type axons. However, a significant difference was observed during the following hours, when calcium increased in wild-type neurites but not in Wld(S) neurites. We conclude that there is little relationship between calcium distribution and the early stages of Wallerian degeneration at the time points studied in vivo or in vitro but that Wld(S) neurites fail to show a later

  15. Modified cell cycle status in a mouse model of altered neuronal vulnerability (slow Wallerian degeneration; Wlds)

    PubMed Central

    Wishart, Thomas M; Pemberton, Helen N; James, Sally R; McCabe, Chris J; Gillingwater, Thomas H

    2008-01-01

    Background Altered neuronal vulnerability underlies many diseases of the human nervous system, resulting in degeneration and loss of neurons. The neuroprotective slow Wallerian degeneration (Wlds) mutation delays degeneration in axonal and synaptic compartments of neurons following a wide range of traumatic and disease-inducing stimuli, providing a powerful experimental tool with which to investigate modulation of neuronal vulnerability. Although the mechanisms through which Wlds confers neuroprotection remain unclear, a diverse range of downstream modifications, incorporating several genes/pathways, have been implicated. These include the following: elevated nicotinamide adenine dinucleotide (NAD) levels associated with nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1; a part of the chimeric Wlds gene); altered mRNA expression levels of genes such as pituitary tumor transforming gene 1 (Pttg1); changes in the location/activity of the ubiquitin-proteasome machinery via binding to valosin-containing protein (VCP/p97); and modified synaptic expression of proteins such as ubiquitin-activating enzyme E1 (Ube1). Results Wlds expression in mouse cerebellum and HEK293 cells induced robust increases in a broad spectrum of cell cycle-related genes. Both NAD-dependent and Pttg1-dependent pathways were responsible for mediating different subsets of these alterations, also incorporating changes in VCP/p97 localization and Ube1 expression. Cell proliferation rates were not modified by Wlds, suggesting that later mitotic phases of the cell cycle remained unaltered. We also demonstrate that Wlds concurrently altered endogenous cell stress pathways. Conclusion We report a novel cellular phenotype in cells with altered neuronal vulnerability. We show that previous reports of diverse changes occurring downstream from Wlds expression converge upon modifications in cell cycle status. These data suggest a strong correlation between modified cell cycle pathways and altered

  16. VCP binding influences intracellular distribution of the slow Wallerian degeneration protein, Wld(S).

    PubMed

    Wilbrey, Anna L; Haley, Jane E; Wishart, Thomas M; Conforti, Laura; Morreale, Giacomo; Beirowski, Bogdan; Babetto, Elisabetta; Adalbert, Robert; Gillingwater, Thomas H; Smith, Trevor; Wyllie, David J A; Ribchester, Richard R; Coleman, Michael P

    2008-07-01

    Wallerian degeneration slow (Wld(S)) mice express a chimeric protein that delays axonal degeneration. The N-terminal domain (N70), which is essential for axonal protection in vivo, binds valosin-containing protein (VCP) and targets both Wld(S) and VCP to discrete nuclear foci. We characterized the formation, composition and localization of these potentially important foci. Missense mutations show that the N-terminal sixteen residues (N16) of Wld(S) are essential for both VCP binding and targeting Wld(S) to nuclear foci. Removing N16 abolishes foci, and VCP binding sequences from ataxin-3 or HrdI restore them. In vitro, these puncta co-localize with proteasome subunits. In vivo, Wld(S) assumes a range of nuclear distribution patterns, including puncta, and its neuronal expression and intranuclear distribution is region-specific and varies between spontaneous and transgenic Wld(S) models. We conclude that VCP influences Wld(S) intracellular distribution, and thus potentially its function, by binding within the N70 domain required for axon protection. PMID:18468455

  17. 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

  18. An ENU-Induced Mutation in the Mertk Gene (Mertknmf12) Leads to a Slow Form of Retinal Degeneration

    PubMed Central

    Maddox, Dennis M.; Hicks, Wanda L.; Vollrath, Douglas; LaVail, Matthew M.; Naggert, Jürgen K.

    2011-01-01

    Purpose. To determine the basis and to characterize the phenotype of a chemically induced mutation in a mouse model of retinal degeneration. Methods. Screening by indirect ophthalmoscopy identified a line of N-ethyl-N-nitrosourea (ENU) mutagenized mice demonstrating retinal patches. Longitudinal studies of retinal histologic sections showed photoreceptors in the peripheral retina undergoing slow, progressive degeneration. The mutation was named neuroscience mutagenesis facility 12 (nmf12), and mapping localized the critical region to Chromosome 2. Results. Sequencing of nmf12 DNA revealed a point mutation in the c-mer tyrosine kinase gene, designated Mertknmf12. We detected elevated levels of tumor necrosis factor (Tnf, previously Tnfa) in retinas of Mertknmf12 homozygotes relative to wild-type controls and investigated whether the increase of TNF, an inflammatory cytokine produced by macrophages/monocytes that signals intracellularly to cause necrosis or apoptosis, could underlie the retinal degeneration observed in Mertknmf12 homozygotes. Mertknmf12 homozygous mice were mated to mice lacking the entire Tnf gene and partial coding sequences of the Lta (Tnfb) and Ltb (Tnfc) genes.2 B6.129P2-Ltb/Tnf/Ltatm1Dvk/J homozygotes did not exhibit a retinal degeneration phenotype and will, hereafter, be referred to as Tnfabc−/− mice. Surprisingly, mice homozygous for both the Mertknmf12 and the Ltb/Tnf/Ltatm1Dvk allele (Tnfabc−/−) demonstrated an increase in the rate of retinal degeneration. Conclusions. These findings illustrate that a mutation in the Mertk gene leads to a significantly slower progressive retinal degeneration compared with other alleles of Mertk. These results demonstrate that TNF family members play a role in protecting photoreceptors of Mertknmf12 homozygotes from cell death. PMID:21436282

  19. The slow Wallerian degeneration gene, WldS, inhibits axonal spheroid pathology in gracile axonal dystrophy mice.

    PubMed

    Mi, Weiqian; Beirowski, Bogdan; Gillingwater, Thomas H; Adalbert, Robert; Wagner, Diana; Grumme, Daniela; Osaka, Hitoshi; Conforti, Laura; Arnhold, Stefan; Addicks, Klaus; Wada, Keiji; Ribchester, Richard R; Coleman, Michael P

    2005-02-01

    Axonal dystrophy is the hallmark of axon pathology in many neurodegenerative disorders of the CNS, including Alzheimer's disease, Parkinson's disease and stroke. Axons can also form larger swellings, or spheroids, as in multiple sclerosis and traumatic brain injury. Some spheroids are terminal endbulbs of axon stumps, but swellings may also occur on unbroken axons and their role in axon loss remains uncertain. Similarly, it is not known whether spheroids and axonal dystrophy in so many different CNS disorders arise by a common mechanism. These surprising gaps in current knowledge result largely from the lack of experimental methods to manipulate axon pathology. The slow Wallerian degeneration gene, Wld(S), delays Wallerian degeneration after injury, and also delays 'dying-back' in peripheral nervous system disorders, revealing a mechanistic link between two forms of axon degeneration traditionally considered distinct. We now report that Wld(S) also inhibits axonal spheroid pathology in gracile axonal dystrophy (gad) mice. Both gracile nucleus (P < 0.001) and cervical gracile fascicle (P = 0.001) contained significantly fewer spheroids in gad/Wld(S) mice, and secondary signs of axon pathology such as myelin loss were also reduced. Motor nerve terminals at neuromuscular junctions continued to degenerate in gad/Wld(S) mice, consistent with previous observations that Wld(S) has a weaker effect on synapses than on axons, and probably contributing to the fact that Wld(S) did not alleviate gad symptoms. Wld(S) acts downstream of the initial pathogenic events to block gad pathology, suggesting that its effect on axonal swelling need not be specific to this disease. We conclude that axon degeneration mechanisms are more closely related than previously thought and that a link exists in gad between spheroid pathology and Wallerian degeneration that could hold for other disorders. PMID:15644421

  20. Synaptic plasticity in the rod terminals after partial photoreceptor cell loss in the heterozygous rds mutant mouse.

    PubMed

    Jansen, H G; Sanyal, S

    1992-02-01

    In the retina of mice heterozygous for the retinal degeneration slow gene (rds/+) the photoreceptor cells, both rods and cones, develop abnormal outer segments but establish normal synaptic contacts. The other retinal layers also show normal structural organization. Starting from the age of 2 months, a very slow loss of photoreceptor cells progresses throughout life. As a result, the photoreceptor cell population in the retina of the affected mice is reduced to less than half at the age of 9-18 months. In some of the surviving rod terminals during this period, an increase in the number of synaptic ribbons is recorded. At the same time, the profiles of processes originating from the second order neurons and participating in these synapses are also increased in number so that the multiple ribbons appear as centres of multiple synaptic sites. Morphometric measurements of the perimeter of the synaptic profiles in rod terminals show a significant increase in the rds/+ retina over that of the control retina. Observations based on serial electron microscopy indicate that multiple synaptic sites are developed while the number of the second order neuronal processes, entering the terminals, remains unchanged. The frequency of terminals with multiple synapses in the rds/+ retina increases with progressive photoreceptor cell loss. Similar changes do not occur in the terminals of the cones. It is postulated that loss of some rod photoreceptor cells within a group that is presynaptic to common bipolars or horizontal cells results in partial deafferentation which in turn stimulates the growth of the remaining synaptic elements. The possible compensatory effect and functional significance of such synaptic growth are discussed. PMID:1573048

  1. Formation of Degenerating Clusters in the α+8He Slow Scattering

    NASA Astrophysics Data System (ADS)

    Ito, Makoto

    2009-08-01

    The generalized two-center cluster model (GTCM), which can treat various single particle configurations in general two center systems, is applied to the light neutron-rich system, 12Be = α+α+4N. We discuss the change of the neutrons' configuration around two α-cores as a variation of an excitation energy. We found that the covalent, ionic and atomic configurations appear with a prominent degenerating feature above the α+8Heg.s. particle-decay threshold.

  2. Serotonin 2B receptor slows disease progression and prevents degeneration of spinal cord mononuclear phagocytes in amyotrophic lateral sclerosis.

    PubMed

    El Oussini, Hajer; Bayer, Hanna; Scekic-Zahirovic, Jelena; Vercruysse, Pauline; Sinniger, Jérôme; Dirrig-Grosch, Sylvie; Dieterlé, Stéphane; Echaniz-Laguna, Andoni; Larmet, Yves; Müller, Kathrin; Weishaupt, Jochen H; Thal, Dietmar R; van Rheenen, Wouter; van Eijk, Kristel; Lawson, Roland; Monassier, Laurent; Maroteaux, Luc; Roumier, Anne; Wong, Philip C; van den Berg, Leonard H; Ludolph, Albert C; Veldink, Jan H; Witting, Anke; Dupuis, Luc

    2016-03-01

    Microglia are the resident mononuclear phagocytes of the central nervous system and have been implicated in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). During neurodegeneration, microglial activation is accompanied by infiltration of circulating monocytes, leading to production of multiple inflammatory mediators in the spinal cord. Degenerative alterations in mononuclear phagocytes are commonly observed during neurodegenerative diseases, yet little is known concerning the mechanisms leading to their degeneration, or the consequences on disease progression. Here we observed that the serotonin 2B receptor (5-HT2B), a serotonin receptor expressed in microglia, is upregulated in the spinal cord of three different transgenic mouse models of ALS. In mutant SOD1 mice, this upregulation was restricted to cells positive for CD11b, a marker of mononuclear phagocytes. Ablation of 5-HT2B receptor in transgenic ALS mice expressing mutant SOD1 resulted in increased degeneration of mononuclear phagocytes, as evidenced by fragmentation of Iba1-positive cellular processes. This was accompanied by decreased expression of key neuroinflammatory genes but also loss of expression of homeostatic microglial genes. Importantly, the dramatic effect of 5-HT2B receptor ablation on mononuclear phagocytes was associated with acceleration of disease progression. To determine the translational relevance of these results, we studied polymorphisms in the human HTR2B gene, which encodes the 5-HT2B receptor, in a large cohort of ALS patients. In this cohort, the C allele of SNP rs10199752 in HTR2B was associated with longer survival. Moreover, patients carrying one copy of the C allele of SNP rs10199752 showed increased 5-HT2B mRNA in spinal cord and displayed less pronounced degeneration of Iba1 positive cells than patients carrying two copies of the more common A allele. Thus, the 5-HT2B receptor limits degeneration of spinal cord mononuclear

  3. The slow Wallerian degeneration gene in vivo protects motor axons but not their cell bodies after avulsion and neonatal axotomy.

    PubMed

    Adalbert, Robert; Nógrádi, Antal; Szabó, András; Coleman, Michael P

    2006-10-01

    The slow Wallerian degeneration gene (Wld(S)) delays Wallerian degeneration and axon pathology for several weeks in mice and rats. Interestingly, neuronal cell death is also delayed in some in vivo models, most strikingly in the progressive motoneuronopathy mouse. Here, we tested the hypothesis that Wld(S) has a direct protective effect on motoneurone cell bodies in vivo. Cell death was induced in rat L4 motoneurones by intravertebral avulsion of the corresponding ventral roots. This simultaneously removed most of the motor axon, minimizing the possibility that the protective effect toward axons could rescue cell bodies secondarily. There was no significant difference between the survival of motoneurones in control and Wld(S) rats, suggesting that the Wld(S) gene has no direct protective effect on cell bodies. We also tested for any delay in apoptotic motoneurone death following neonatal nerve injury in Wld(S) rats and found that, unlike Wld(S) mice, Wld(S) rats show no delay in cell death. However, the corresponding distal axons were preserved, confirming that motoneurone cell bodies and motor axons die by different mechanisms. Thus, Wld(S) does not directly prevent death of motoneurone cell bodies. It follows that the protection of neuronal cell bodies observed in several disease and injury models where axons or significant axonal stumps remain is most probably secondary to axonal protection. PMID:17074042

  4. RDS-SL VS Communication System

    Energy Science and Technology Software Center (ESTSC)

    2012-09-12

    The RDS-SL VS Communication System is a component of the Radiation Detection System for Strategic, Low-Volume Seaports. Its purpose is to acquire real-time data from radiation portal monitors and cameras, record that data in a database, and make it available to system operators and administrators via a web interface. The software system contains two components: a standalone data acquisition and storage component and an ASP.NETweb application that implements the web interface.

  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. A Single Valine Residue Plays an Essential Role in Peripherin/rds Targeting to Photoreceptor Outer Segments

    PubMed Central

    Salinas, Raquel Y.; Baker, Sheila A.; Gospe, Sidney M.; Arshavsky, Vadim Y.

    2013-01-01

    Peripherin/retinal degeneration slow (rds) is an integral membrane protein specifically localized to the light-sensing organelle of the photoreceptor cell, the outer segment. Within the outer segment, peripherin is found at the edges of photoreceptor discs, where it plays a critical role in disc morphogenesis and maintenance. Peripherin loss or mutations are often associated with severe forms of visual impairments. Like all other resident outer segment proteins, peripherin is synthesized in the photoreceptor cell body and subsequently transported to the outer segment. In an effort to further examine peripherin’s delivery to outer segments, we undertook a careful examination of its targeting sequence. Using a fluorescently labeled reporter expressed in the rods of transgenic tadpoles, we narrowed peripherin’s targeting sequence to ten amino acids within its C-terminal tail. This small stretch of amino acid residues is both necessary and sufficient for outer segment targeting. We also conducted alanine scanning of all residues within this sequence and found that only a single residue, valine at position 332, is essential for outer segment targeting. This valine is conserved in all species and its mutation is sufficient to completely abrogate the targeting of full-length peripherin in mouse rods. PMID:23342122

  7. Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene

    PubMed Central

    Wishart, Thomas M.; Paterson, Janet M.; Short, Duncan M.; Meredith, Sara; Robertson, Kevin A.; Sutherland, Calum; Cousin, Michael A.; Dutia, Mayank B.; Gillingwater, Thomas H.

    2007-01-01

    SUMMARY Non-somatic synaptic and axonal compartments of neurons are primary pathological targets in many neurodegenerative conditions, ranging from Alzheimer's disease through to motor neuron disease. Axons and synapses are protected from degeneration by the slow Wallerian degeneration (Wlds) gene. Significantly, the molecular mechanisms through which this spontaneous genetic mutation delays degeneration remain controversial and the downstream protein targets of Wlds resident in non-somatic compartments remain unknown. Here we have used differential proteomic analysis to identify proteins whose expression levels were significantly altered in isolated synaptic preparations from the striatum of Wlds mice. 8 of the 16 proteins we identified as having modified expression levels in Wlds synapses are known regulators of mitochondrial stability and degeneration (including VDAC1, Aralar1 and mitofilin). Subsequent analyses demonstrated that other key mitochondrial proteins, not identified in our initial screen, are also modified in Wlds synapses. Of the non-mitochondrial proteins identified, several have been implicated in neurodegenerative diseases where synapses and axons are primary pathological targets (including DRP-2 and Rab GDI beta). In addition, we show that downstream protein changes can be identified in pathways corresponding to both Ube4b (including UBE1) and Nmnat1 (including VDAC1 and Aralar1) components of the chimeric Wlds gene, suggesting that full-length Wlds protein is required to elicit maximal changes in synaptic proteins. We conclude that altered mitochondrial responses to degenerative stimuli are likely to play an important role in the neuroprotective Wlds phenotype and that targeting proteins identified in the current study may lead to novel therapies for the treatment of neurodegenerative diseases in humans. PMID:17470424

  8. Design of a novel quantitative PCR (QPCR)-based protocol for genotyping mice carrying the neuroprotective Wallerian degeneration slow (Wlds) gene

    PubMed Central

    Wishart, Thomas M; MacDonald, Stephen HF; Chen, Philip E; Shipston, Michael J; Coleman, Michael P; Gillingwater, Thomas H; Ribchester, Richard R

    2007-01-01

    Background Mice carrying the spontaneous genetic mutation known as Wallerian degeneration slow (Wlds) have a unique neuroprotective phenotype, where axonal and synaptic compartments of neurons are protected from degeneration following a wide variety of physical, toxic and inherited disease-inducing stimuli. This remarkable phenotype has been shown to delay onset and progression in several mouse models of neurodegenerative disease, suggesting that Wlds-mediated neuroprotection may assist in the identification of novel therapeutic targets. As a result, cross-breeding of Wlds mice with mouse models of neurodegenerative diseases is used increasingly to understand the roles of axon and synapse degeneration in disease. However, the phenotype shows strong gene-dose dependence so it is important to distinguish offspring that are homozygous or heterozygous for the mutation. Since the Wlds mutation comprises a triplication of a region already present in the mouse genome, the most stringent way to quantify the number of mutant Wlds alleles is using copy number. Current approaches to genotype Wlds mice are based on either Southern blots or pulsed field gel electrophoresis, neither of which are as rapid or efficient as quantitative PCR (QPCR). Results We have developed a rapid, robust and efficient genotyping method for Wlds using QPCR. This approach differentiates, based on copy number, homozygous and heterozygous Wlds mice from wild-type mice and each other. We show that this approach can be used to genotype mice carrying the spontaneous Wlds mutation as well as animals expressing the Wlds transgene. Conclusion We have developed a QPCR genotyping method that permits rapid and effective genotyping of Wlds copy number. This technique will be of particular benefit in studies where Wlds mice are cross-bred with other mouse models of neurodegenerative disease in order to understand the neuroprotective processes conferred by the Wlds mutation. PMID:17971231

  9. 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. PMID:25939269

  10. The slow Wallerian degeneration protein, WldS, binds directly to VCP/p97 and partially redistributes it within the nucleus.

    PubMed

    Laser, Heike; Conforti, Laura; Morreale, Giacomo; Mack, Till G M; Heyer, Molly; Haley, Jane E; Wishart, Thomas M; Beirowski, Bogdan; Walker, Simon A; Haase, Georg; Celik, Arzu; Adalbert, Robert; Wagner, Diana; Grumme, Daniela; Ribchester, Richard R; Plomann, Markus; Coleman, Michael P

    2006-03-01

    Slow Wallerian degeneration (Wld(S)) mutant mice express a chimeric nuclear protein that protects sick or injured axons from degeneration. The C-terminal region, derived from NAD(+) synthesizing enzyme Nmnat1, is reported to confer neuroprotection in vitro. However, an additional role for the N-terminal 70 amino acids (N70), derived from multiubiquitination factor Ube4b, has not been excluded. In wild-type Ube4b, N70 is part of a sequence essential for ubiquitination activity but its role is not understood. We report direct binding of N70 to valosin-containing protein (VCP; p97/Cdc48), a protein with diverse cellular roles including a pivotal role in the ubiquitin proteasome system. Interaction with Wld(S) targets VCP to discrete intranuclear foci where ubiquitin epitopes can also accumulate. Wld(S) lacking its N-terminal 16 amino acids (N16) neither binds nor redistributes VCP, but continues to accumulate in intranuclear foci, targeting its intrinsic NAD(+) synthesis activity to these same foci. Wild-type Ube4b also requires N16 to bind VCP, despite a more C-terminal binding site in invertebrate orthologues. We conclude that N-terminal sequences of Wld(S) protein influence the intranuclear location of both ubiquitin proteasome and NAD(+) synthesis machinery and that an evolutionary recent sequence mediates binding of mammalian Ube4b to VCP. PMID:16371511

  11. The Slow Wallerian Degeneration Protein, WldS, Binds Directly to VCP/p97 and Partially Redistributes It within the NucleusD⃞

    PubMed Central

    Laser, Heike; Conforti, Laura; Morreale, Giacomo; Mack, Till G.M.; Heyer, Molly; Haley, Jane E.; Wishart, Thomas M.; Beirowski, Bogdan; Walker, Simon A.; Haase, Georg; Celik, Arzu; Adalbert, Robert; Wagner, Diana; Grumme, Daniela; Ribchester, Richard R.; Plomann, Markus; Coleman, Michael P.

    2006-01-01

    Slow Wallerian degeneration (WldS) mutant mice express a chimeric nuclear protein that protects sick or injured axons from degeneration. The C-terminal region, derived from NAD+ synthesizing enzyme Nmnat1, is reported to confer neuroprotection in vitro. However, an additional role for the N-terminal 70 amino acids (N70), derived from multiubiquitination factor Ube4b, has not been excluded. In wild-type Ube4b, N70 is part of a sequence essential for ubiquitination activity but its role is not understood. We report direct binding of N70 to valosin-containing protein (VCP; p97/Cdc48), a protein with diverse cellular roles including a pivotal role in the ubiquitin proteasome system. Interaction with WldS targets VCP to discrete intranuclear foci where ubiquitin epitopes can also accumulate. WldS lacking its N-terminal 16 amino acids (N16) neither binds nor redistributes VCP, but continues to accumulate in intranuclear foci, targeting its intrinsic NAD+ synthesis activity to these same foci. Wild-type Ube4b also requires N16 to bind VCP, despite a more C-terminal binding site in invertebrate orthologues. We conclude that N-terminal sequences of WldS protein influence the intranuclear location of both ubiquitin proteasome and NAD+ synthesis machinery and that an evolutionary recent sequence mediates binding of mammalian Ube4b to VCP. PMID:16371511

  12. 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.

  13. Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model

    PubMed Central

    Leckie, Steven K.; Bechara, Bernard P.; Hartman, Robert A.; Sowa, Gwendolyn A.; Woods, Barrett I.; Coelho, Joao P.; Witt, William T.; Dong, Qing D.; Bowman, Brent W.; Bell, Kevin M.; Vo, Nam V.; Wang, Bing; Kang, James D.

    2016-01-01

    BACKGROUND CONTEXT Intervertebral disc degeneration (IDD) is a common cause of back pain. Patients who fail conservative management may face the morbidity of surgery. Alternative treatment modalities could have a significant impact on disease progression and patients’ quality of life. PURPOSE To determine if the injection of a virus vector carrying a therapeutic gene directly into the nucleus pulposus improves the course of IDD. STUDY DESIGN Prospective randomized controlled animal study. METHODS Thirty-four skeletally mature New Zealand white rabbits were used. In the treatment group, L2–L3, L3–L4, and L4–L5 discs were punctured in accordance with a previously validated rabbit annulotomy model for IDD and then subsequently treated with adeno-associated virus serotype 2 (AAV2) vector carrying genes for either bone morphogenetic protein 2 (BMP2) or tissue inhibitor of metalloproteinase 1 (TIMP1). A nonoperative control group, nonpunctured sham surgical group, and punctured control group were also evaluated. Serial magnetic resonance imaging (MRI) studies at 0, 6, and 12 weeks were obtained, and a validated MRI analysis program was used to quantify degeneration. The rabbits were sacrificed at 12 weeks, and L4–L5 discs were analyzed histologically. Viscoelastic properties of the L3–L4 discs were analyzed using uniaxial load normalized displacement testing. Creep curves were mathematically modeled according to a previously validated two-phase exponential model. Serum samples obtained at 0, 6, and 12 weeks were assayed for biochemical evidence of degeneration. RESULTS The punctured group demonstrated MRI and histologic evidence of degeneration as expected. The treatment groups demonstrated less MRI and histologic evidence of degeneration than the punctured group. The serum biochemical marker C-telopeptide of collagen type II increased rapidly in the punctured group, but the treated groups returned to control values by 12 weeks. The treatment groups

  14. 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.

  15. Cerebellar Degeneration

    MedlinePlus

    ... Degeneration? Cerebellar degeneration is a process in which neurons in the cerebellum - the area of the brain ... proteins that are necessary for the survival of neurons. Associated diseases: Diseases that are specific to the ...

  16. Extensive intrafamilial and interfamilial phenotypic variation among patients with autosomal dominant retinal dystrophy and mutations in the human RDS/peripherin gene.

    PubMed Central

    Apfelstedt-Sylla, E; Theischen, M; Rüther, K; Wedemann, H; Gal, A; Zrenner, E

    1995-01-01

    Clinical phenotypes of patients with mutations in the human RDS/peripherin gene are described. A 67-year-old woman, who carried a 1 base pair deletion in codon 307, presented with typical late onset autosomal dominant retinitis pigmentosa (RP). In another autosomal dominant pedigree, a nonsense mutation at codon 46 caused 'inverse' retinitis pigmentosa-like fundus changes associated with progressive cone-rod degeneration in a 58-year-old man, whereas his 40-year-old son presented with yellow deposits in the retinal pigment epithelial layer resembling a pattern dystrophy, and with moderately reduced rod and cone function, as determined by two colour dark adapted threshold perimetry and electroretinography. It is suggested that both clinical pictures within this latter family may represent manifestations of fundus flavimaculatus. The clinical data of the three patients provide further evidence for the remarkable variety of disease expression within and between families with mutations in the RDS/peripherin gene. Currently, the most comprehensive statement could be that RDS/peripherin mutations are associated either with typical RP or with various forms of flecked retinal disease. Images PMID:7880786

  17. 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.

  18. 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

  19. The use of canine models of inherited retinal degeneration to test novel therapeutic approaches

    PubMed Central

    Beltran, William A.

    2011-01-01

    Inherited retinal degenerations (RDs) are a common cause of blindness in dogs and in humans. Over the past two decades numerous genes causally associated with these diseases have been identified and several canine models have been used to improve our understanding of the molecular mechanisms of RDs, as well as to test the proof of principle and safety of novel therapies. This review briefly summarizes the drug delivery approaches and therapeutic strategies that have been and are currently tested in dogs, with a particular emphasis on corrective gene therapy, and retinal neuroprotection. PMID:19392879

  20. 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

  1. Human surfactant protein-C: Genetic homogeneity and expression in RDS; comparison with other species

    SciTech Connect

    Hatzis, D.; Deiter, G.; deMello, D.E.; Floros, J. Harvard Medical School, Boston, MA Cardinal Glennon Children's Hospital, St. Louis, MO )

    1994-01-01

    Human surfactant protein C (SP-C) mRNA is detected early during fetal lung development before the differentiation of the type II cell and the need for surfactant. Later in life SP-C contributes to the surface-lowering properties of surfactant, as shown by several investigators. In this study the authors sequenced both coding and noncoding regions of 12 genomic SP-C clones from several human groups including RDS (respiratory distress syndrome), whites, and black Nigerians, and examined the expression of SP-C in tissues from RDS and from non-RDS. The data showed that all clones had identical DNA sequences, not only within coding regions, consistent with previous observations, but also within intervening, 5[prime] flanking, and 3[prime] untranslated regions. Some differences from the previously published sequence were noted. The expression of SP-C in tissues from RDS and non-RDS as determined by tissue in situ hybridization was comparable between the two groups, suggesting that altered SP-C expression, the result of pretranslational regulatory abnormalities, is an unlikely contributor to the pathogenesis of RDS. In addition the results show, using genomic blot analysis, that a remarkable conservation within coding and 5[prime] flanking but not within 3[prime] untranslated sequences exists in all mammalian species examined. These data taken together suggest that strong evolutionary pressures have been exerted on SP-C to maintain conservation, not only among humans but also among species, which may underscore important roles of SP-C in as yet unknown developmental/functional lung processes. 38 refs., 5 figs., 2 tabs.

  2. Macular Degeneration

    MedlinePlus

    ... common early symptom. Dry AMD happens when the light-sensitive cells in the macula slowly break down. Your gradually lose your central vision. A common early symptom is that straight lines appear crooked. Regular comprehensive eye exams can detect macular degeneration before the disease ...

  3. Corticobasal degeneration.

    PubMed

    Gibb, W R; Luthert, P J; Marsden, C D

    1989-10-01

    Three patients with clinical and pathological features of corticobasal degeneration are described. They presented with a progressive disease bearing some clinical resemblance to Steele-Richardson-Olszewski syndrome and displaying some pathological features of Pick's disease. Their illness began at the age of 59 to 66 yrs with focal dystonia and myoclonus of an arm, the 'alien hand' sign, or an akinetic-rigid syndrome. They developed a supranuclear gaze palsy, parkinsonian features and mild cerebellar signs. Two patients showed constructional dyspraxia when using the arms. The duration of disease to death was 4 to 6 yrs. Pathological examination showed frontoparietal atrophy with cortical cell loss, gliosis and Pick cells, but there was no significant hippocampal disease or Pick bodies in this region. There was nerve cell loss and gliosis in the thalamus, lentiform nucleus, subthalamic nucleus, red nucleus, midbrain tegmentum, substantia nigra and locus coeruleus. Neuronal inclusions in the substantia nigra, termed corticobasal inclusions, were reminiscent of the globose neurofibrillary tangle of Steele-Richardson-Olszewski syndrome, and other pale inclusions resembled the pale body of Parkinson's disease, but Lewy bodies and neurofibrillary tangles were generally absent. Some nigral inclusions were similar to those in Pick's disease. Despite some pathological similarities to Pick's disease we suggest that the distribution of nerve cell loss and the corticobasal inclusion are unique to corticobasal degeneration. PMID:2478251

  4. 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 ...

  5. 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

  6. 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

  7. 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.

  8. Nutritional supplements for macular degeneration.

    PubMed

    2006-02-01

    Age-related macular degeneration is the commonest cause of blindness in developed countries and the third most common worldwide. Each year in the UK, around 17,000 people become blind or partially sighted as a result of this condition, and its prevalence is likely to increase with an ageing population. Laser therapy and rarely surgery, can slow disease progression in a minority of patients but is unlikely to restore lost vision. A wide range of nutritional supplements are now on sale with promotional claims that they improve eye health. While some specialists recommend their use to patients with advanced disease, these supplements are also increasingly promoted to people with early or no signs of disease. Consequently, GPs come under pressure from patients to recommend, or even prescribe, a nutritional supplement. Here we examine the evidence for nutritional supplements in the management of age-related macular degeneration and consider which, if any, can be recommended. PMID:16550811

  9. 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

  10. 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. PMID:16625226

  11. 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

  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. "Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

    PubMed

    Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

    2012-01-01

    In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily selfadministered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions. PMID:22236117

  14. 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.

  15. 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.

  16. 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

  17. Estimating Vertex Measures in Social Networks by Sampling Completions of RDS Trees

    PubMed Central

    Khan, Bilal; Dombrowski, Kirk; Curtis, Ric; Wendel, Travis

    2015-01-01

    This paper presents a new method for obtaining network properties from incomplete data sets. Problems associated with missing data represent well-known stumbling blocks in Social Network Analysis. The method of “estimating connectivity from spanning tree completions” (ECSTC) is specifically designed to address situations where only spanning tree(s) of a network are known, such as those obtained through respondent driven sampling (RDS). Using repeated random completions derived from degree information, this method forgoes the usual step of trying to obtain final edge or vertex rosters, and instead aims to estimate network-centric properties of vertices probabilistically from the spanning trees themselves. In this paper, we discuss the problem of missing data and describe the protocols of our completion method, and finally the results of an experiment where ECSTC was used to estimate graph dependent vertex properties from spanning trees sampled from a graph whose characteristics were known ahead of time. The results show that ECSTC methods hold more promise for obtaining network-centric properties of individuals from a limited set of data than researchers may have previously assumed. Such an approach represents a break with past strategies of working with missing data which have mainly sought means to complete the graph, rather than ECSTC's approach, which is to estimate network properties themselves without deciding on the final edge set. PMID:25838988

  18. Intervertebral Disc Degeneration

    PubMed Central

    Rannou, François; Lee, Tzong-Shyuan; Zhou, Rui-Hai; Chin, Jennie; Lotz, Jeffrey C.; Mayoux-Benhamou, Marie-Anne; Barbet, Jacques Patrick; Chevrot, Alain; Shyy, John Y.-J.

    2004-01-01

    Degeneration of the intervertebral disk (IVD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Although mechanical stress is an important modulator of the degeneration, the underlying molecular mechanism remains unclear. The association of human IVD degeneration, assessed by magnetic resonance imaging, with annulus fibrosus cell apoptosis and anti-cytochrome c staining revealed that the activation of the mitochondria-dependent apoptosome was a major event in the degeneration process. Mouse models of IVD degeneration were used to investigate the role of the mechanical stress in this process. The application of mechanical overload (1.3 MPa) for 24 hours induced annulus fibrosus cell apoptosis and led to severe degeneration of the mouse disks. Immunostaining revealed cytochrome c release but not Fas-L generation. The role of the caspase-9-dependent mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload was investigated further with the use of cultured rabbit IVD cells in a stretch device. Mechanical overload (15% area change) induced apoptosis with increased caspase-9 activity and decreased mitochondrial membrane potential. Furthermore, Z-LEHD-FMK, a caspase-9 inhibitor, but not Z-IETD-FMK, a caspase-8 inhibitor, attenuated the overload-induced apoptosis. Our results from human samples, mouse models, and annulus fibrosus culture experiments demonstrate that the mechanical overload-induced IVD degeneration is mediated through the mitochondrial apoptotic pathway in IVD cells. PMID:14982845

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

    PubMed Central

    Gerdts, Josiah; Brace, E.J.; Sasaki, Yo; DiAntonio, Aaron

    2015-01-01

    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 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 (Wlds) mutant mice. PMID:25908823

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

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

    PubMed Central

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

    2013-01-01

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

  6. Degenerate astigmatic cavities

    NASA Astrophysics Data System (ADS)

    Courtois, Jérémie; Mohamed, Ajmal; Romanini, Daniele

    2013-10-01

    At the output of a high-finesse cavity a succession of Lissajous patterns may be observed as the cavity length is finely tuned inside a “degenerate region” around a reentrant spherical configuration. This behavior is ascribed to a small parasitic astigmatism of the cavity mirrors. Simple geometrical optics modeling confirms this hypothesis, and then a more realistic analysis using transverse Gaussian modes reveals that the Lissajous patterns correspond to an organization of the astigmatism-split modes into a finer substructure of degenerate modes relative to that of a reentrant spherical cavity. This provides a thorough understanding of the field patterns observed in the degenerate region, including an intriguing spatial symmetry of the patterns corresponding to opposite displacements with respect to a specific central cavity length. This investigation represents a generalization of the theory of reentrant spherical cavities to the astigmatic case.

  7. Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS): Potential Nutrigenomic Induced Dopaminergic Activation

    PubMed Central

    Blum, K; Oscar-Berman, M; Giordano, J; Downs, BW; Simpatico, T; Han, D; Femino, John

    2012-01-01

    Work from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)™ found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. This editorial focuses on the neurogenetics of brain reward systems with particular reference to genes related to dopaminergic function. The terminology “Reward Deficiency Syndrome” (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function, is a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. This editorial covers the neurological basis of pleasure and the role of natural and unnatural reward in motivating and reinforcing behaviors. Additionally, it briefly describes the concept of natural dopamine D2 receptor agonist therapy coupled with genetic testing of a panel of reward genes, the Genetic Addiction Risk Score (GARS). It serves as a spring-board for this combination of novel approaches to the prevention and treatment of RDS that was developed from fundamental genomic research. We encourage further required studies. PMID:23264886

  8. 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

  9. 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

  10. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

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

    ClinicalTrials.gov

    2016-08-16

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

  12. 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.

  13. 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

  14. 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

  15. Mechanisms of distal axonal degeneration in peripheral neuropathies.

    PubMed

    Cashman, Christopher R; Höke, Ahmet

    2015-06-01

    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 (Wld(S)) and Sarm knockout animal models. These studies have shown axonal degeneration to occur through a 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

  16. 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

  17. 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.

  18. “Liking” and “Wanting” Linked to Reward Deficiency Syndrome (RDS): Hypothesizing Differential Responsivity in Brain Reward Circuitry

    PubMed Central

    Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

    2013-01-01

    In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: “liking,” “learning,” and “wanting” [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or “wanting” hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily self-administered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens, and they stimulate the functioning of brain reward circuitry (producing the “high” that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions. PMID:22236117

  19. 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

  20. Cortical basal ganglionic degeneration.

    PubMed

    Scarmeas, N; Chin, S S; Marder, K

    2001-10-01

    In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms. PMID:14602941

  1. 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. PMID:20866534

  2. 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.

  3. Macular degeneration - age-related

    MedlinePlus

    Age-related macular degeneration (ARMD); AMD ... distorted and wavy. There may be a small dark spot in the center of your vision that ... leafy vegetables, may also decrease your risk of age-related macular degeneration. If you have wet AMD, ...

  4. Movement - uncontrolled or slow

    MedlinePlus

    ... leg movements - uncontrollable; Slow involuntary movements of large muscle groups; Athetoid movements ... The slow twisting movements of muscles (athetosis) or jerky muscle ... including: Cerebral palsy Drug side effects Encephalitis ...

  5. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... Degeneration Diagnosis: How is AMD diagnosed? Macular Degeneration Treatment: How is AMD Treated? Macular ... macular degeneration (AMD) is a deterioration or breakdown of the eye's macula. The macula is a small area in the ...

  6. In-situ monitoring of InP(100) and GaP(100) interfaces and characterization with RDS at 20 K

    NASA Astrophysics Data System (ADS)

    Hannappel, T.; Töben, L.; Möller, K.; Willig, F.

    2001-11-01

    MOVPE-preparation of highly ordered InP(100) and GaP(100) surfaces was monitored with in-situ reflectance difference spectroscopy (RDS). Specific ordered P-terminated and ordered cation-terminated surface reconstructions were identified with specific structured RD spectra with the highest peaks. After contamination-free transfer of the samples to UHV, RDS measurements were performed also at 20 K. The experimental RD spectrum for the In-terminated, (2×4) reconstructed InP(100) surface shows a remarkable similarity to a recently published theoretical spectrum, whereas there is only moderate similarity between the experimental RD spectrum for the (2×4) reconstructed Ga-terminated GaP(100) surface and a recently proposed theoretical spectrum.

  7. 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. PMID:6710807

  8. NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration.

    PubMed

    Conforti, L; Fang, G; Beirowski, B; Wang, M S; Sorci, L; Asress, S; Adalbert, R; Silva, A; Bridge, K; Huang, X P; Magni, G; Glass, J D; Coleman, M P

    2007-01-01

    The slow Wallerian degeneration protein (Wld(S)), a fusion protein incorporating full-length nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), delays axon degeneration caused by injury, toxins and genetic mutation. Nmnat1 overexpression is reported to protect axons in vitro, but its effect in vivo and its potency remain unclear. We generated Nmnat1-overexpressing transgenic mice whose Nmnat activities closely match that of Wld(S) mice. Nmnat1 overexpression in five lines of transgenic mice failed to delay Wallerian degeneration in transected sciatic nerves in contrast to Wld(S) mice where nearly all axons were protected. Transected neurites in Nmnat1 transgenic dorsal root ganglion explant cultures also degenerated rapidly. The delay in vincristine-induced neurite degeneration following lentiviral overexpression of Nmnat1 was significantly less potent than for Wld(S), and lentiviral overexpressed enzyme-dead Wld(S) still displayed residual neurite protection. Thus, Nmnat1 is significantly weaker than Wld(S) at protecting axons against traumatic or toxic injury in vitro, and has no detectable effect in vivo. The full protective effect of Wld(S) requires more N-terminal sequences of the protein. PMID:16645633

  9. Sphingolipid profile alters in retinal dystrophic P23H-1 rats and systemic FTY720 can delay retinal degeneration.

    PubMed

    Stiles, Megan; Qi, Hui; Sun, Eleanor; Tan, Jeremy; Porter, Hunter; Allegood, Jeremy; Chalfant, Charles E; Yasumura, Douglas; Matthes, Michael T; LaVail, Matthew M; Mandal, Nawajes A

    2016-05-01

    Retinal degeneration (RD) affects millions of people and is a major cause of ocular impairment and blindness. With a wide range of mutations and conditions leading to degeneration, targeting downstream processes is necessary for developing effective treatments. Ceramide and sphingosine-1-phosphate, a pair of bioactive sphingolipids, are involved in apoptosis and its prevention, respectively. Apoptotic cell death is a potential driver of RD, and in order to understand the mechanism of degeneration and potential treatments, we studied rhodopsin mutant RD model, P23H-1 rats. Investigating this genetic model of human RD allows us to investigate the association of sphingolipid metabolites with the degeneration of the retina in P23H-1 rats and the effects of a specific modulator of sphingolipid metabolism, FTY720. We found that P23H-1 rat retinas had altered sphingolipid profiles that, when treated with FTY720, were rebalanced closer to normal levels. FTY720-treated rats also showed protection from RD compared with their vehicle-treated littermates. Based on these data, we conclude that sphingolipid dysregulation plays a secondary role in retinal cell death, which may be common to many forms of RDs, and that the U.S. Food and Drug Administration-approved drug FTY720 or related compounds that modulate sphingolipid metabolism could potentially delay the cell death. PMID:26947037

  10. 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. PMID:25908823

  11. Salzmann's Nodular Degeneration.

    PubMed

    Maharana, Prafulla K; Sharma, Namrata; Das, Sujata; Agarwal, Tushar; Sen, Seema; Prakash, Gaurav; Vajpayee, Rasik B

    2016-01-01

    Salzmann's nodular degeneration (SND) is a rare, noninflammatory, slowly progressive degenerative disease of the cornea that is characterized by the appearance of nodular bluish gray opacities that vary in number and size. It is usually bilateral; most commonly occurring in people aged 50-60 years old, with a female preponderance; and often associated with a history of prior corneal inflammation. The clinical features usually depend on the location of the nodules. Generally, the nodules of SND are bluish white to gray in color, 1-2 mm in size, and round, conical or prismatic in shape. The overlying Bowman's layer is usually absent from the nodular areas and is partially replaced by granular Periodic Acid Schiff-positive eosinophilic material resembling the basement membrane. Diagnostic investigations include ultrasonic pachymetry, anterior segment optical coherence tomography, ultrasound biomicroscopy, and confocal microscopy. The majority of patients respond well to conservative management with topical lubricants; severe cases may require surgical intervention. The various surgical modalities described include superficial keratectomy, which may be combined with phototherapeutic keratectomy and keratoplasty. Various modifications of these procedures include the use of alcohol-assisted epithelial delamination, intraoperative mitomycin-C or amniotic membrane transplantation to make the procedure easy, reduce the risk of recurrence and improve postoperative comfort. Recurrences are rarely reported; overall, the visual prognosis following treatment is optimal. PMID:26462409

  12. Nutrition and retinal degenerations.

    PubMed

    Berson, E L

    2000-01-01

    Considerable progress has been made in the understanding and management of degenerative diseases of the retina involving photoreceptors. Nutritional approaches to treatment have proved successful in the case of the common forms of retinitis pigmentosa (supplementation with vitamin A), Bassen-Kornzweig disease (supplementation with vitamins A, E, and K), gyrate atrophy (low-protein, low-arginine diet and/or supplementation with vitamin B6), and Refsum disease (low-phytol, low-phytanic acid diet). The night blindness associated with Sorsby fundus dystrophy can be reversed over the short term with vitamin A. A significant trend for decreased risk for advanced or exudative ARMD has been reported among those whose diets contain a higher content of carotenoids, such as spinach and collard greens. A randomized trial is in progress to determine whether beta-carotene, vitamin C, and vitamin E as well as trace minerals, particularly zinc, will modify the course of ARMD. The difficulties that patients with retinal degenerations face as a result of their diminishing vision, sometimes over decades, cannot be underestimated. Nutritional therapy has proved effective in modifying the course of a number of these conditions; the therapeutic benefit of nutritional modification in diseases that have a genetic basis is of particular interest. Further research is warranted to determine the mechanisms by which these treatments provide their benefit as well as to identify other conditions that may yield to nutritional intervention. Risk-factor analyses of well-defined populations followed over time with food-frequency questionnaires in conjunction with careful assessments of visual function may reveal other dietary constituents that can modify the course of degenerative diseases of the retina. PMID:11064860

  13. Slow liner fusion

    SciTech Connect

    Shaffer, M.J.

    1997-08-01

    {open_quotes}Slow{close_quotes} liner fusion ({approximately}10 ms compression time) implosions are nondestructive and make repetitive ({approximately} 1 Hz) pulsed liner fusion reactors possible. This paper summarizes a General Atomics physics-based fusion reactor study that showed slow liner feasibility, even with conservative open-line axial magnetic field confinement and Bohm radial transport.

  14. [Neuropsychological exploration in frontotemporal degeneration].

    PubMed

    Peña-Casanova, J; Böhm, P

    2000-01-01

    The present paper discusses the neuropsychological assessment in fronto-temporal lobe degeneration. Having established the neuroanatomical and functional basis for the discussion the major syndromes included in the concept of frontotemporal degeneration are reviewed from a neuropsychological standpoint. With reference to fronto-temporal dementia the different frontal or executive function tests and their limitations are discussed. With reference to progressive aphasia and semantic dementia we differentiate the distinct language profiles as observed in aphasia batteries and general neuropsychological tests. Reference is made to especially useful tests for the differentiation of the two syndromes from each other, as well as from other primary progressive disorders. Concluding remarks postulate a series of axis of cognitive function in fronto-temporal lobe degenerations, which exist at the functional as well as the anatomical level and along which the different syndromes evolve. PMID:10723171

  15. 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

  16. Do recruitment patterns of young men who have sex with men (YMSM) recruited through respondent-driven sampling (RDS) violate assumptions?

    PubMed Central

    Phillips, Gregory; Kuhns, Lisa M.; Garofalo, Rob; Mustanski, Brian

    2014-01-01

    Background In order to generate unbiased estimates for data collected using respondent-driven sampling (RDS), a number of assumptions need to be met: individuals recruit randomly from their social network and people can accurately report their eligible network size. However, research has shown that these assumptions are often violated. Methods This study used baseline data from Crew 450, a longitudinal study of young men who have sex with men in Chicago who were recruited via a modified form of RDS, and its network substudy, in which a subset of 175 participants reported details on the composition and characteristics of their social network at either one or two years post-baseline. Results Nearly two-thirds of participants reported giving coupons to at least one alter (64.0%), and 56.3% believed their alter(s) used the coupons. Frequency of communication, closeness, and type of relationship played a major role in determining coupon distribution. Participants whose alters used coupons were significantly less likely to describe the strength of their relationship as “not at all close” (OR = 0.08; 95% CI: 0.02, 0.36) compared to “very close” and to communicate weekly (OR = 0.20; 95% CI: 0.08, 0.49) or 1–6 times in the last 6 months (OR = 0.18; 95% CI: 0.06, 0.59). Conclusion Contrary to RDS assumptions, we found that relationship characteristics played a significant role when individuals decided to whom they would give coupons. PMID:25086159

  17. 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)

  18. 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.

  19. 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. PMID:22463336

  20. 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. PMID:25426738

  1. Macular Degeneration - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Macular Degeneration URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Macular Degeneration - Multiple Languages To use the sharing features on ...

  2. Ataxias and Cerebellar or Spinocerebellar Degeneration

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page Synonym(s): ... Publications and Information Publicaciones en Español What are Ataxias and Cerebellar or Spinocerebellar Degeneration? Ataxia often occurs ...

  3. [Glaucoma and age-related macular degeneration intricacy].

    PubMed

    Valtot, F

    2008-07-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness among the elderly in Western nations. Age is also a well-known and well-evidenced risk factor for glaucoma. With increasing longevity and the rising prevalence of older people around the world, more and more patients will have glaucoma and AMD. Clinical evaluation of these patients still poses problems for clinicians. It is very important to order the right tests at the right time to distinguish glaucomatous defects from those caused by retinal lesions, because appropriate therapy has a beneficial effect on slowing or halting damage. PMID:18957915

  4. Two-photon interferences with degenerate and nondegenerate paired photons

    NASA Astrophysics Data System (ADS)

    Liu, Chang; Chen, J. F.; Zhang, Shanchao; Zhou, Shuyu; Kim, Yoon-Ho; Loy, M. M. T.; Wong, G. K. L.; Du, Shengwang

    2012-02-01

    We generate narrow-band frequency-tunable entangled photon pairs from spontaneous four-wave mixing in three-level cold atoms and study their two-photon quantum interference after a beam splitter. We find that the path-exchange symmetry plays a more important role in the Hong-Ou-Mandel interference than the temporal or frequency indistinguishability, and observe coalescence interference for both degenerate and nondegenerate photons. We also observe a quantum beat in the same experimental setup using either slow or fast detectors.

  5. The degeneration of Y chromosomes.

    PubMed

    Charlesworth, B; Charlesworth, D

    2000-11-29

    Y chromosomes are genetically degenerate, having lost most of the active genes that were present in their ancestors. The causes of this degeneration have attracted much attention from evolutionary theorists. Four major theories are reviewed here: Muller's ratchet, background selection, the Hill Robertson effect with weak selection, and the 'hitchhiking' of deleterious alleles by favourable mutations. All of these involve a reduction in effective population size as a result of selective events occurring in a non-recombining genome, and the consequent weakening of the efficacy of selection. We review the consequences of these processes for patterns of molecular evolution and variation at loci on Y chromosomes, and discuss the results of empirical studies of these patterns for some evolving Y-chromosome and neo-Y-chromosome systems. These results suggest that the effective population sizes of evolving Y or neo-Y chromosomes are severely reduced, as expected if some or all of the hypothesized processes leading to degeneration are operative. It is, however, currently unclear which of the various processes is most important; some directions for future work to help to resolve this question are discussed. PMID:11127901

  6. 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

  7. 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.

  8. General pathophysiology in retinal degeneration.

    PubMed

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

    2014-01-01

    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

  9. 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

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

    PubMed

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

    2013-02-01

    Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5-11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term. PMID:23341635

  11. Targeting iron-mediated retinal degeneration by local delivery of transferrin.

    PubMed

    Picard, Emilie; Le Rouzic, Quentin; Oudar, Antonin; Berdugo, Marianne; El Sanharawi, Mohamed; Andrieu-Soler, Charlotte; Naud, Marie-Christine; Jonet, Laurent; Latour, Chloé; Klein, Christophe; Galiacy, Stéphane; Malecaze, François; Coppin, Hélène; Roth, Marie-Paule; Jeanny, Jean-Claude; Courtois, Yves; Behar-Cohen, Francine

    2015-12-01

    Iron is essential for retinal function but contributes to oxidative stress-mediated degeneration. Iron retinal homeostasis is highly regulated and transferrin (Tf), a potent iron chelator, is endogenously secreted by retinal cells. In this study, therapeutic potential of a local Tf delivery was evaluated in animal models of retinal degeneration. After intravitreal injection, Tf spread rapidly within the retina and accumulated in photoreceptors and retinal pigment epithelium, before reaching the blood circulation. Tf injected in the vitreous prior and, to a lesser extent, after light-induced retinal degeneration, efficiently protected the retina histology and function. We found an association between Tf treatment and the modulation of iron homeostasis resulting in a decrease of iron content and oxidative stress marker. The immunomodulation function of Tf could be seen through a reduction in macrophage/microglial activation as well as modulated inflammation responses. In a mouse model of hemochromatosis, Tf had the capacity to clear abnormal iron accumulation from retinas. And in the slow P23H rat model of retinal degeneration, a sustained release of Tf in the vitreous via non-viral gene therapy efficently slowed-down the photoreceptors death and preserved their function. These results clearly demonstrate the synergistic neuroprotective roles of Tf against retinal degeneration and allow identify Tf as an innovative and not toxic therapy for retinal diseases associated with oxidative stress. PMID:26454080

  12. RDS, LEED and STM of the P-rich and Ga-rich surfaces of GaP(1 0 0)

    NASA Astrophysics Data System (ADS)

    Töben, L.; Hannappel, T.; Möller, K.; Crawack, H.-J.; Pettenkofer, C.; Willig, F.

    2001-11-01

    Reflectance difference spectroscopy was measured in the metal organic chemical vapor deposition reactor and also in UHV at 20 K. It revealed a characteristic negative peak at the low energy side that was indicative of the specific surface reconstruction. This peak disappeared completely if the sample was kept within a narrow intermediate temperature range. At 20 K the negative peak appeared at 2.4 eV for the Ga-terminated (2×4)-reconstructed surface and at 2.6 eV for the P-terminated (2×1)/(2×2)-reconstructed surface. RDS for the two different surface reconstructions displayed strong structures also in the range of the bulk transitions. A characteristic zig-zag pattern was observed in the STM image of the P-terminated surface.

  13. Ultraviolet spectrophotometry of degenerate stars

    NASA Technical Reports Server (NTRS)

    Greenstein, J. L.; Oke, J. B.

    1979-01-01

    Observations of one helium- and three hydrogen-atmosphere degenerates made with the International Ultraviolet Explorer are discussed. Fluxes in the UV give temperatures in good accordance with those determined from the ground and from the ANS satellite data. Profiles of the strong L-alpha absorption in two DA's fit predictions for the expected temperatures. Gravity determination is vitiated by their steep temperature dependence. If one accepts that theoretical predictions should be correct, corrections to the absolute IUE calibration derived are an upward shift of 3-5%, with irregular residuals attaining + or - 7%.

  14. 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.

  15. [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. PMID:25715554

  16. 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.

  17. Axon degeneration: context defines distinct pathways.

    PubMed

    Geden, Matthew J; Deshmukh, Mohanish

    2016-08-01

    Axon degeneration is an essential part of development, plasticity, and injury response and has been primarily studied in mammalian models in three contexts: 1) Axotomy-induced Wallerian degeneration, 2) Apoptosis-induced axon degeneration (axon apoptosis), and 3) Axon pruning. These three contexts dictate engagement of distinct pathways for axon degeneration. Recent advances have identified the importance of SARM1, NMNATs, NAD+ depletion, and MAPK signaling in axotomy-induced Wallerian degeneration. Interestingly, apoptosis-induced axon degeneration and axon pruning have many shared mechanisms both in signaling (e.g. DLK, JNKs, GSK3α/β) and execution (e.g. Puma, Bax, caspase-9, caspase-3). However, the specific mechanisms by which caspases are activated during apoptosis versus pruning appear distinct, with apoptosis requiring Apaf-1 but not caspase-6 while pruning requires caspase-6 but not Apaf-1. PMID:27197022

  18. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients. PMID:10420956

  19. 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 ...

  20. 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

  1. Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx

    PubMed Central

    Yamagishi, Yuya; Tessier-Lavigne, Marc

    2015-01-01

    Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program. SIGNIFICANCE STATEMENT Axon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled

  2. Hot subdwarfs with degenerate companions

    NASA Astrophysics Data System (ADS)

    Mereghetti, Sandro

    2010-10-01

    Stellar evolutionary models predict that most of the hot sub-dwarfs in close binary systems have white dwarf companions. In a few cases even more massive compact objects (neutron stars or black holes) are suggested by the optical mass functions. The X-ray emission expected from accretion of the sub-dwarf's wind can reveal the nature of the compact companions and be used to derive other important information on these post-common envelope systems, as recently demonstrated by the discovery of a massive WD in HD 49798. We selected 3 promising targets from a sample of hot subdwarfs suspected to have degenerate companions. This proposal was accepted in AO9 with C priority.

  3. Laser therapy and macular degeneration

    NASA Astrophysics Data System (ADS)

    Menchini, Ugo; Virgili, Gianni; Giansanti, Fabrizio; Giacomelli, Giovanni; Cappelli, Stefania

    2001-10-01

    Among macular diseases, choroidal neovascularization (CNV) is one of the most common causes of visual loss, especially in the form associated with age-related macular degeneration and pathologic myopia. Research on these diseases has recently evaluated new treatment modalities that use laser light differently; among these, photodynamic therapy (PDT) has been introduced in the clinical practice, allowing us to expand the possibility of reducing visual loss in patients affected by CNV. With PDT, a photosensitizer (verteporfin, VisudyneTM) is injected intravenously, and it selectively binds to new vessels; low-power laser light exposure then activates the drug, leading to oxidative damage of the endothelium and new vessels thrombosis. Yet, other therapies, such as transpupillary termotherapy, or the use of photocoagulation to cause feeder-vessel occlusion, could proof effective, but they need further investigation.

  4. Genetics of Frontotemporal Lobar Degeneration

    PubMed Central

    Galimberti, Daniela; Scarpini, Elio

    2012-01-01

    Frontotemporal lobar degeneration (FTLD), the most frequent neurodegenerative disorder with a presenile onset, presents with a spectrum of clinical manifestations, ranging from behavioral and executive impairment to language disorders and motor dysfunction. Familial aggregation is frequently reported, and about 10% of cases have an autosomal dominant transmission. Microtubule associated protein tau (MAPT) gene mutations have been the first ones identified and are associated with early onset behavioral variant frontotemporal dementia phenotype. More recently, progranulin gene (GRN) mutations were recognized in association with familial form of FTLD. In addition, other genes are linked to rare cases of familial FTLD. Lastly, a number of genetic risk factors for sporadic forms have also been identified. In this review, current knowledge about mutations at the basis of familial FTLD will be described, together with genetic risk factors influencing the susceptibility to FTLD. PMID:22536193

  5. 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.

  6. Degenerate adiabatic perturbation theory: Foundations and applications

    NASA Astrophysics Data System (ADS)

    Rigolin, Gustavo; Ortiz, Gerardo

    2014-08-01

    We present details and expand on the framework leading to the recently introduced degenerate adiabatic perturbation theory [Phys. Rev. Lett. 104, 170406 (2010), 10.1103/PhysRevLett.104.170406], and on the formulation of the degenerate adiabatic theorem, along with its necessary and sufficient conditions [given in Phys. Rev. A 85, 062111 (2012), 10.1103/PhysRevA.85.062111]. We start with the adiabatic approximation for degenerate Hamiltonians that paves the way to a clear and rigorous statement of the associated degenerate adiabatic theorem, where the non-Abelian geometric phase (Wilczek-Zee phase) plays a central role to its quantitative formulation. We then describe the degenerate adiabatic perturbation theory, whose zeroth-order term is the degenerate adiabatic approximation, in its full generality. The parameter in the perturbative power-series expansion of the time-dependent wave function is directly associated to the inverse of the time it takes to drive the system from its initial to its final state. With the aid of the degenerate adiabatic perturbation theory we obtain rigorous necessary and sufficient conditions for the validity of the adiabatic theorem of quantum mechanics. Finally, to illustrate the power and wide scope of the methodology, we apply the framework to a degenerate Hamiltonian, whose closed-form time-dependent wave function is derived exactly, and also to other nonexactly solvable Hamiltonians whose solutions are numerically computed.

  7. 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.

  8. 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. PMID:25025614

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

    PubMed

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

    2016-01-26

    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

  10. 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. PMID:19673852

  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. PMID:26075817

  12. 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

  13. A Monte Carlo algorithm for degenerate plasmas

    SciTech Connect

    Turrell, A.E. Sherlock, M.; Rose, S.J.

    2013-09-15

    A procedure for performing Monte Carlo calculations of plasmas with an arbitrary level of degeneracy is outlined. It has possible applications in inertial confinement fusion and astrophysics. Degenerate particles are initialised according to the Fermi–Dirac distribution function, and scattering is via a Pauli blocked binary collision approximation. The algorithm is tested against degenerate electron–ion equilibration, and the degenerate resistivity transport coefficient from unmagnetised first order transport theory. The code is applied to the cold fuel shell and alpha particle equilibration problem of inertial confinement fusion.

  14. 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.

  15. Advances in the management of macular degeneration

    PubMed Central

    2014-01-01

    Current management of age-related macular degeneration (AMD) can be divided into two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection for wet macular degeneration; second, anti-oxidant vitamins for dry macular degeneration. New therapies are being developed for both of these diseases using novel technologies and different modes of administration. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition. PMID:24860651

  16. 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.

  17. Slow inactivation of Na(+) channels.

    PubMed

    Silva, Jonathan

    2014-01-01

    Prolonged depolarizing pulses that last seconds to minutes cause slow inactivation of Na(+) channels, which regulates neuron and myocyte excitability by reducing availability of inward current. In neurons, slow inactivation has been linked to memory of previous excitation and in skeletal muscle it ensures myocytes are able to contract when K(+) is elevated. The molecular mechanisms underlying slow inactivation are unclear even though it has been studied for 50+ years. This chapter reviews what is known to date regarding the definition, measurement, and mechanisms of voltage-gated Na(+) channel slow inactivation. PMID:24737231

  18. Carnosic acid slows photoreceptor degeneration in the Pde6brd10 mouse model of retinitis pigmentosa

    PubMed Central

    Kang, Kai; Tarchick, Matthew J.; Yu, Xiaoshan; Beight, Craig; Bu, Ping; Yu, Minzhong

    2016-01-01

    The photoreceptor cell death associated with the various genetic forms of retinitis pigmentosa (RP) is currently untreatable and leads to partial or complete vision loss. Carnosic acid (CA) upregulates endogenous antioxidant enzymes and has proven neuroprotective in studies of neurodegenerative models affecting the brain. In this study, we examined the potential effect of CA on photoreceptor death in the Pde6brd10 mouse model of RP. Our data shows that CA provided morphological and functional preservation of photoreceptors. CA appears to exert its neuroprotective effects through inhibition of oxidative stress and endoplasmic reticulum stress. PMID:26961159

  19. Dispersion relations in weakly degenerate plasmas

    NASA Astrophysics Data System (ADS)

    Rocchi, F.; Molinari, V. G.; Mostacci, D.; Sumini, M.

    2001-06-01

    From a quantum mechanical point of view, electrons in laser produced plasmas can be regarded as weakly degenerate. For instance, for a plasma with electron density of 10 22 cm -3 and electron temperature of 1 eV, Sommerfeld's parameter is between 1 and 2. Under these conditions the usual dispersion relations for waves in plasmas need be corrected to account for degeneracy. In the present work, starting from the transport equation with a simplified version of the Boltzmann-Uehling-Uhlenbeck collision kernel the propagation of waves impinging on a plasma with weakly degenerate electrons is investigated and dispersion relations accounting for degeneracy are derived. These dispersion relations give the classical ones in the limit for Sommerfeld's parameter approaching zero. A shift of the wavenumber value and a non-collisional damping due to degeneracy effects are predicted which render a weakly degenerate plasma more opaque to radiation than a non-degenerate one.

  20. Degenerate neuronal systems sustaining cognitive functions

    PubMed Central

    Noppeney, Uta; Friston, Karl J; Price, Cathy J

    2004-01-01

    The remarkable resilience of cognitive functions to focal brain damage suggests that multiple degenerate neuronal systems can sustain the same function either via similar mechanisms or by implementing different cognitive strategies. In degenerate functional neuroanatomy, multiple degenerate neuronal systems might be present in a single brain where they are either co-activated or remain latent during task performance. In degeneracy over subjects, a particular function may be sustained by only one neuronal system within a subject, but by different systems over subjects. Degeneracy over subjects might have arisen from (ab)normal variation in neurodevelopmental trajectories or long-term plastic changes following structural lesions. We discuss how degenerate neuronal systems can be revealed using (1) intersubject variability, (2) multiple lesion studies and (3) an iterative approach integrating information from lesion and functional imaging studies. PMID:15610392

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

    PubMed Central

    2016-01-01

    Objective 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. Methods 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. Results 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. Conclusion 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

  2. 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

  3. 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

  4. Source modeling sleep slow waves

    PubMed Central

    Murphy, Michael; Riedner, Brady A.; Huber, Reto; Massimini, Marcello; Ferrarelli, Fabio; Tononi, Giulio

    2009-01-01

    Slow waves are the most prominent electroencephalographic (EEG) feature of sleep. These waves arise from the synchronization of slow oscillations in the membrane potentials of millions of neurons. Scalp-level studies have indicated that slow waves are not instantaneous events, but rather they travel across the brain. Previous studies of EEG slow waves were limited by the poor spatial resolution of EEGs and by the difficulty of relating scalp potentials to the activity of the underlying cortex. Here we use high-density EEG (hd-EEG) source modeling to show that individual spontaneous slow waves have distinct cortical origins, propagate uniquely across the cortex, and involve unique subsets of cortical structures. However, when the waves are examined en masse, we find that there are diffuse hot spots of slow wave origins centered on the lateral sulci. Furthermore, slow wave propagation along the anterior−posterior axis of the brain is largely mediated by a cingulate highway. As a group, slow waves are associated with large currents in the medial frontal gyrus, the middle frontal gyrus, the inferior frontal gyrus, the anterior cingulate, the precuneus, and the posterior cingulate. These areas overlap with the major connectional backbone of the cortex and with many parts of the default network. PMID:19164756

  5. 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

  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. 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.

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

    PubMed

    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 (R(2) = 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

  9. 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

  10. Slow bars in spiral galaxies

    NASA Astrophysics Data System (ADS)

    Fridman, A. M.; Khoruzhii, O. V.

    2000-11-01

    Here we put forward some arguments in favour of the existence of slow bars. More then a half of spiral galaxies have in their central regions a bar - a structure in the form of triaxial ellipsoid. Historically two models of the bar were developed - those of the so called ``slow'' and ``fast'' bars. In both cases the bar is in some resonance with the galactic disc region near the bar ends - it is the corotation resonance for a fast bar and the inner Lindblad resonance for a slow bar. For the same angular velocity the fast bar would be larger then the slow bar. Alternatively, for the same size the fast bar would have much higher angular velocity, that being the reason for the terminology used. Up till now, the direct measurement of angular velocity of a bar has been an open problem. This is why all arguments on the nature of bar observed in some particular galaxy are inevitably indirect. Despite the fact that the model of slow bars was developed slightly earlier, the main part of attention was focused on the fast bars. Presently many researchers believe in the existence of the fast bars in real galaxies, while discussions on the existence of the slow bars continue so far. In this Letter we demonstrate that the bar detected in the grand design spiral galaxy NGC 157 is the slow bar.

  11. Neural factors influence the degeneration of muscle fibers in the chelae of snapping shrimps.

    PubMed

    Young, R E; Wong, A; Pearce, J; Govind, C K

    1996-01-01

    The asymmetric pincer and snapper claws in the snapping shrimp differ in external morphology and musculature. The snapper is a massive claw used for displays and defense; the pincer is small and slender, used for feeding and burrowing. The snapper has only slow muscle fibers; the pincer has both slow and fast. Removal or denervation of the snapper claw induces transformation of the contralateral pincer to a snapper type of claw at the subsequent molt. A removed claw regenerates as a pincer type, as long as the innervation of the remaining claw is intact. Fast muscle fibers, found exclusively in the pincer claw, normally degenerate completely within 10 d after the moult, which transforms the pincer to a snapper. Morphological transformation of the pincer following removal of the snapper claw can occur even if the pincer claw is denervated. Denervation of the pincer, however, delays degeneration of the fast fibers, increasing the estimated half-time of muscle degeneration, for 4.4 +/- 0.2 to 19.5 +/- 0.8. d after the transforming moult. Neural influences therefore are involved both in the determination of the morphology of the claw and in the induction of degenerative changes during the remodeling of an existing claw. PMID:8871972

  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. 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

  14. Antioxidative nanofullerol prevents intervertebral disk degeneration

    PubMed Central

    Yang, Xinlin; Jin, Li; Yao, Lu; Shen, Francis H; Shimer, Adam L; Li, Xudong

    2014-01-01

    Compelling evidence suggests that reactive oxygen species (ROS) play a pivotal role in disk degeneration. Fullerol nanoparticles prepared in aqueous solution have been demonstrated to have outstanding ability to scavenge ROS. In this report, in vitro and in vivo models were used to study the efficacy of fullerol in preventing disk degeneration. For in vitro experiments, a pro-oxidant H2O2 or an inflammatory cytokine interleukin (IL)-1β was employed to induce degenerated phenotypes in human nucleus pulposus cells encapsulated in alginate beads, and fullerol was added in the culture medium. For the animal study, an annulus-puncture model with rabbit was created, and fullerol was injected into disks. It was shown that cytotoxicity and cellular ROS level induced by H2O2 were significantly diminished by fullerol. IL-1β-induced nitric oxide generation in culture medium was suppressed by fullerol as well. Gene-profile and biochemical assays showed that fullerol effectively reversed the matrix degradation caused by either H2O2 or IL-1β. The animal study delineated that intradiskal injection of fullerol prevented disk degeneration, increasing water and proteoglycan content and inhibiting ectopic bone formation. These results suggest that antioxidative fullerol may have a potential therapeutic application for disk degeneration. PMID:24876775

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

    PubMed

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

    2015-03-15

    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

  17. Slow earthquakes triggered by typhoons.

    PubMed

    Liu, ChiChing; Linde, Alan T; Sacks, I Selwyn

    2009-06-11

    The first reports on a slow earthquake were for an event in the Izu peninsula, Japan, on an intraplate, seismically active fault. Since then, many slow earthquakes have been detected. It has been suggested that the slow events may trigger ordinary earthquakes (in a context supported by numerical modelling), but their broader significance in terms of earthquake occurrence remains unclear. Triggering of earthquakes has received much attention: strain diffusion from large regional earthquakes has been shown to influence large earthquake activity, and earthquakes may be triggered during the passage of teleseismic waves, a phenomenon now recognized as being common. Here we show that, in eastern Taiwan, slow earthquakes can be triggered by typhoons. We model the largest of these earthquakes as repeated episodes of slow slip on a reverse fault just under land and dipping to the west; the characteristics of all events are sufficiently similar that they can be modelled with minor variations of the model parameters. Lower pressure results in a very small unclamping of the fault that must be close to the failure condition for the typhoon to act as a trigger. This area experiences very high compressional deformation but has a paucity of large earthquakes; repeating slow events may be segmenting the stressed area and thus inhibiting large earthquakes, which require a long, continuous seismic rupture. PMID:19516339

  18. Slow motion increases perceived intent.

    PubMed

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

    2016-08-16

    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

  19. 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

  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. PMID:23684651

  1. Resonance charge exchange between excited states in slow proton-hydrogen collisions

    SciTech Connect

    Tolstikhina, Inga Yu.; Kato, Daiji

    2010-09-15

    The theory of resonance charge exchange in slow collisions of a proton with a hydrogen atom in the excited state is developed. It extends the Firsov-Demkov theory of resonance charge exchange to the case of degenerate initial and final states. The theory is illustrated by semiclassical and quantum calculations of charge exchange cross sections between states with n=2 in parabolic and spherical coordinates. The results are compared with existing close-coupling calculations.

  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. 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

  4. 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

  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. Ion acoustic shock waves in degenerate plasmas

    SciTech Connect

    Akhtar, N.; Hussain, S.

    2011-07-15

    Korteweg de Vries Burgers equation for negative ion degenerate dissipative plasma has been derived using reductive perturbation technique. The quantum hydrodynamic model is used to study the quantum ion acoustic shock waves. The effects of different parameters on quantum ion acoustic shock waves are studied. It is found that quantum parameter, electrons Fermi temperature, temperature of positive and negative ions, mass ratio of positive to negative ions, viscosity, and density ratio have significant impact on the shock wave structure in negative ion degenerate plasma.

  7. 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.

  8. 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.

  9. 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

  10. 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. PMID:17138867

  11. Time Slows Down during Accidents

    PubMed Central

    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. PMID:22754544

  12. 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. PMID:22754544

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

    PubMed

    Ramírez-Jarquín, Uri Nimrod; Tapia, Ricardo

    2016-09-01

    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. PMID:27320208

  14. Driving and Age-Related Macular Degeneration

    PubMed Central

    Owsley, Cynthia; McGwin, Gerald

    2009-01-01

    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, and considers directions for future research. PMID:20046818

  15. A family of degenerate Lie algebras

    NASA Astrophysics Data System (ADS)

    Cruz, I.

    1999-08-01

    We show that almost all the real Lie algebras with only zero- and two-dimensional coadjoint orbits are degenerate in both the smooth and analytic category. The only exceptions are the already known cases (studied for example by Dufour and Weinstein).

  16. 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,…

  17. 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…

  18. Spectroscopic observations of cool degenerate star candidates

    NASA Technical Reports Server (NTRS)

    Hintzen, P.

    1986-01-01

    Spectroscopic observations are reported for 23 Luyten Half-Second degenerate star candidates and for 13 Luyten-Palomar common proper-motion pairs containing possible degenerate star components. Twenty-five degenerate stars are identified, 20 of which lack previous spectroscopy. Most of these stars are cool - Luyten color class g or later. One star, LP 77-57, shows broad continuum depressions similar to those in LHS 1126, which Liebert and Dahn attributed to pressure-shifted C2. A second degenerate star, LHS 290, exhibits apparent strong Swan bands which are blueshifted about 75 A. Further observations, including polarimetry and photometry, are required to appraise the spectroscopic peculiarities of these stars. Finally, five cool, sharp-lined DA white dwarfs have been observed to detect lines of metals and to determine line strengths. None of these DAs show signs of Mg b or the G band, and four show no evidence of Ca II K. The attempt to detect Ca MI in the fifth star, G199-71, was inconclusive.

  19. Tenascin-C and human tendon degeneration.

    PubMed Central

    Riley, G. P.; Harrall, R. L.; Cawston, T. E.; Hazleman, B. L.; Mackie, E. J.

    1996-01-01

    We investigated the distribution of tenascin in supraspinatus tendons to determine whether an alteration in tenascin expression was associated with human tendon degeneration. Tenascin was present in all of the tendons studied, although with two distinct patterns of expression. First, tenascin was associated with organized, fibrous regions of the tendon matrix that were typical of the normal tendon structure. This distribution is consistent with a role for tenascin in collagen fibril organization, perhaps maintaining the interface between fibrils and adjacent structures. Second, although tenascin was generally absent from poorly organized matrix in degenerate tendons, it was strongly associated with some rounded cells in disorganized fibrocartilaginous regions that were more abundant in pathological specimens. Tenascin was also found around infiltrating blood vessels, with more intense staining associated with a mononuclear cell infiltrate. Western blotting of tendon extracts showed differences in tenascin isoform expression, with only the small (200-kd) tenascin isoform found in normal tendons. Degenerate tendons also expressed the 300-kd isoform, consistent with a role for the larger tenascin isoform in tendon disease, potentially stimulating tenocyte proliferation, cell rounding, and fibrocartilaginous change. Proteolytic fragments of tenascin were detected but only in ruptured tendons, an indication of matrix remodeling in degenerate tendons, with fragment sizes consistent with the activity of matrix metalloproteinase enzymes. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8780397

  20. 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

  1. 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.

  2. Excessive activation of cyclic nucleotide-gated channels contributes to neuronal degeneration of photoreceptors.

    PubMed

    Vallazza-Deschamps, Géraldine; Cia, David; Gong, Jie; Jellali, Abdeljelil; Duboc, Agnès; Forster, Valérie; Sahel, Jose A; Tessier, Luc-Henri; Picaud, Serge

    2005-09-01

    In different animal models, photoreceptor degeneration was correlated to an abnormal increase in cGMP concentration. The cGMP-induced photoreceptor toxicity was demonstrated by applying the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine on retinal explants. To assess the role of cGMP-gated channels in this cGMP toxicity, the Ca(2+) channel blockers verapamil and L- and D-diltiazem, which block cGMP-gated channels with different efficacies, were applied to in vitro animal models of photoreceptor degeneration. These models included: (i) adult rat retinal explants incubated with zaprinast, a more specific inhibitor of the rod phosphodiesterase than 3-isobutyl-1-methylxanthine and (ii) rd mouse retinal explants. Photoreceptor apoptosis was assessed by terminal dUTP nick end labelling and caspase 3 activation. Effects of the blockers on the synaptic rod Ca(2+) channels were measured by patch-clamp recording. In the zaprinast-induced photoreceptor degeneration model, both diltiazem isomers rescued photoreceptors whereas verapamil had no influence. Their neuroprotective efficacy was correlated to their inhibition of cGMP-gated channels (l-diltiazem>d-diltiazem>verapamil=0). In contrast, all three Ca(2+) channel blockers suppressed rod Ca(2+) channel currents similarly. This suppression of the currents by the diltiazem isomers was very weak (16.5%) at the neuroprotective concentration (10 microm). In rd retinal explants, both diltiazem isomers also slowed down rod degeneration in contrast to verapamil. L-diltiazem exhibited this effect at concentrations ranging from 1 to 20 microm. This study further supports the photoreceptor neuroprotection by diltiazem particularly in the rd mouse retina, whereas the absence of neuroprotection by verapamil further suggests the role of cGMP-gated channel activation in the induction of photoreceptor degeneration. PMID:16176343

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Purinergic signaling in retinal degeneration and regeneration.

    PubMed

    Reichenbach, Andreas; Bringmann, Andreas

    2016-05-01

    Purinergic signaling is centrally involved in mediating the degeneration of the injured and diseased retina, the induction of retinal gliosis, and the protection of the retinal tissue from degeneration. Dysregulated calcium signaling triggered by overactivation of P2X7 receptors is a crucial step in the induction of neuronal and microvascular cell death under pathogenic conditions like ischemia-hypoxia, elevated intraocular pressure, and diabetes, respectively. Overactivation of P2X7 plays also a pathogenic role in inherited and age-related photoreceptor cell death and in the age-related dysfunction and degeneration of the retinal pigment epithelium. Gliosis of micro- and macroglial cells, which is induced and/or modulated by purinergic signaling and associated with an impaired homeostatic support to neurons, and the ATP-mediated propagation of retinal gliosis from a focal injury into the surrounding noninjured tissue are involved in inducing secondary cell death in the retina. On the other hand, alterations in the glial metabolism of extracellular nucleotides, resulting in a decreased level of ATP and an increased level of adenosine, may be neuroprotective in the diseased retina. Purinergic signals stimulate the proliferation of retinal glial cells which contributes to glial scarring which has protective effects on retinal degeneration and adverse effects on retinal regeneration. Pharmacological modulation of purinergic receptors, e.g., inhibition of P2X and activation of adenosine receptors, may have clinical importance for the prevention of photoreceptor, neuronal, and microvascular cell death in diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration, and glaucoma, respectively, for the clearance of retinal edema, and the inhibition of dysregulated cell proliferation in proliferative retinopathies. This article is part of a Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:25998275

  8. 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.

  9. Fluoxetine is neuroprotective in slow-channel congenital myasthenic syndrome.

    PubMed

    Zhu, Haipeng; Grajales-Reyes, Gary E; Alicea-Vázquez, Vivianette; Grajales-Reyes, Jose G; Robinson, KaReisha; Pytel, Peter; Báez-Pagán, Carlos A; Lasalde-Dominicci, Jose A; Gomez, Christopher M

    2015-08-01

    The slow-channel congenital myasthenic syndrome (SCS) is an inherited neurodegenerative disease that caused mutations in the acetylcholine receptor (AChR) affecting neuromuscular transmission. Leaky AChRs lead to Ca(2+) overload and degeneration of the neuromuscular junction (NMJ) attributed to activation of cysteine proteases and apoptotic changes of synaptic nuclei. Here we use transgenic mouse models expressing two different mutations found in SCS to demonstrate that inhibition of prolonged opening of mutant AChRs using fluoxetine not only improves motor performance and neuromuscular transmission but also prevents Ca(2+) overload, the activation of cysteine proteases, calpain, caspase-3 and 9 at endplates, and as a consequence, reduces subsynaptic DNA damage at endplates, suggesting a long term benefit to therapy. These studies suggest that prolonged treatment of SCS patients with open ion channel blockers that preferentially block mutant AChRs is neuroprotective. PMID:25448156

  10. Slow extraction at LAMPF II

    SciTech Connect

    Colton, E.P.

    1985-10-01

    Half-integer resonant extraction will be used to slow extract the 45 GeV proton beam from the LAMPF II main ring during a time spread of 1/6 sec. High extraction efficiency is obtained by performing the extraction in a high-beta long straight section and by utilizing an electrostatic wire septum and iron septum.

  11. Slow extraction at LAMPF II

    SciTech Connect

    Colton, E.P.

    1985-01-01

    Half-integer resonant extraction will be used to slow extract the 45 GeV proton beam from the LAMPF II main ring during a time spread of 1/6 sec. High extration efficiency is obtained by performing the extraction in a high-beta long straight section and by utilizing an electrostatic wire septum and iron septum. 3 refs., 4 figs.

  12. Reading and the Slow Learner.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Advocates of high standards and expectations usually believe that gaps in reading achievement can be eliminated with good teaching, but slow readers need a specially designed reading curriculum. The teacher first needs to use an informal reading inventory to determine the student's reading level. Functioning generally on a higher level than…

  13. Fast wandering of slow birds

    NASA Astrophysics Data System (ADS)

    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≠v0, where v0 is the mean speed of the flock such that if the speed vs 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 t5/3, in contrast to t4/3 for the other birds. In d=3, the slow bird's mean-squared transverse displacement grows like t5/4, in contrast to t for the other birds. If vs≠γ, the mean-squared displacement of the slow bird crosses over from t5/3 to t4/3 scaling in d=2 and from t5/4 to t scaling in d=3 at a time tc that scales according to tc∝|vs-γ|-2.

  14. 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

  15. Current Therapeutic Development for Atrophic Age-related Macular Degeneration

    PubMed Central

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation which has been demonstrated to slow down the progression of dry AMD. This review summarizes recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem-cell based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  16. Modifiable risk factors for age-related macular degeneration.

    PubMed

    Guymer, Robyn H; Chong, Elaine Wei-Tinn

    2006-05-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in Australia and other Western countries. As there is no cure for AMD, and treatments to stop its progression have met with limited success, there is an interest in identifying modifiable risk factors to prevent or slow disease progression. To date, smoking is the only proven modifiable risk factor for AMD. Other factors under study include (i) cardiovascular risk factors such as hypertension, body mass index, and atherosclerosis; and (ii) dietary risk factors including fat and antioxidant intake, but so far these studies have produced conflicting results. Dietary fat in relation to AMD has recently attracted media attention. Despite very limited work supporting an association between vegetable fat and AMD, widespread publicity advocating margarine as a cause of AMD and encouraging use of butter instead has caused confusion and anxiety among sufferers of AMD and the general public, as well as concern among health professionals. The antioxidant carotenoids--lutein and zeaxanthin--found in dark green or yellow vegetables exist in high concentrations in the macula and are hypothesised to play a protective role. Of nine controlled trials of supplementation with carotenoids and other antioxidants, three suggested that various combinations of antioxidants and carotenoids were protective. While a low-fat diet rich in dark green and yellow vegetables is advocated in general, any specific recommendations regarding certain fats or antioxidant supplementation and AMD are not based on consistent findings at this stage. PMID:16646746

  17. Current therapeutic developments in atrophic age-related macular degeneration.

    PubMed

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age-Related Eye Disease Study (AREDS) formulation, which has been demonstrated to slow down the progression of dry AMD. This review summarises recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem cell-based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  18. Lifespan maturation and degeneration of human brain white matter.

    PubMed

    Yeatman, Jason D; Wandell, Brian A; Mezer, Aviv A

    2014-01-01

    Properties of human brain tissue change across the lifespan. Here we model these changes in the living human brain by combining quantitative magnetic resonance imaging (MRI) measurements of R1 (1/T1) with diffusion MRI and tractography (N=102, ages 7-85). The amount of R1 change during development differs between white-matter fascicles, but in each fascicle the rate of development and decline are mirror-symmetric; the rate of R1 development as the brain approaches maturity predicts the rate of R1 degeneration in aging. Quantitative measurements of macromolecule tissue volume (MTV) confirm that R1 is an accurate index of the growth of new brain tissue. In contrast to R1, diffusion development follows an asymmetric time-course with rapid childhood changes but a slow rate of decline in old age. Together, the time-courses of R1 and diffusion changes demonstrate that multiple biological processes drive changes in white-matter tissue properties over the lifespan. PMID:25230200

  19. 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.

  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. Shell nuclear explosions in degenerate dwarfs

    NASA Astrophysics Data System (ADS)

    Kuznetsov, O. A.; Tutukov, A. V.; Chechetkin, V. M.

    1989-08-01

    Numerical gas dynamics simulations are used to study shell nuclear explosions of degenerate carbon-oxygen dwarfs with masses of 1.17, 1.36, and 1.42 solar masses. It is assumed that the calorific capacity of the burning shell matter is between 5 X 10 to the 17th and 5 X 10 to the 18th erg/g. It is shown that, at a low calorific capacity, a remnant may form if the mass of the shell is less than 90 percent of the mass of the degenerate dwarf. In the case of high calorific capacity, a remnant may form only if the mass of the shell is less than half of the dwarf's mass.

  2. Degeneration and regeneration of ganglion cell axons.

    PubMed

    Weise, J; Ankerhold, R; Bähr, M

    2000-01-15

    The retino-tectal system has been used to study developmental aspects of axon growth, synapse formation and the establishment of a precise topographic order as well as degeneration and regeneration of adult retinal ganglion cell (RGC) axons after axonal lesion. This paper reviews some novel findings that provide new insights into the mechanisms of developmental RGC axon growth, pathfinding, and target formation. It also focuses on the cellular and molecular cascades that underlie RGC degeneration following an axonal lesion and on some therapeutic strategies to enhance survival of axotomized RGCs in vivo. In addition, this review deals with problems related to the induction of regeneration after axonal lesion in the adult CNS using the retino-tectal system as model. Different therapeutic approaches to promote RGC regeneration and requirements for specific target formation of regenerating RGCs in vitro and in vivo are discussed. PMID:10649506

  3. 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. PMID:17485886

  4. Calabi-Yau manifolds and their degenerations.

    PubMed

    Tosatti, Valentino

    2012-07-01

    Calabi-Yau manifolds are geometric objects of central importance in several branches of mathematics, including differential geometry, algebraic geometry, and mathematical physics. In this paper, we give a brief introduction to the subject aimed at a general mathematical audience and present some of our results that shed some light on the possible ways in which families of Calabi-Yau manifolds can degenerate. PMID:22257362

  5. Degenerate Bose gases with uniform loss

    NASA Astrophysics Data System (ADS)

    Grišins, Pjotrs; Rauer, Bernhard; Langen, Tim; Schmiedmayer, Jörg; Mazets, Igor E.

    2016-03-01

    We theoretically investigate a weakly interacting degenerate Bose gas coupled to an empty Markovian bath. We show that in the universal phononic limit the system evolves towards an asymptotic state where an emergent temperature is set by the quantum noise of the outcoupling process. For situations typically encountered in experiments, this mechanism leads to significant cooling. Such dissipative cooling supplements conventional evaporative cooling and dominates in settings where thermalization is highly suppressed, such as in a one-dimensional quasicondensate.

  6. Effect of trapping in degenerate quantum plasmas

    SciTech Connect

    Shah, H. A.; Qureshi, M. N. S.; Tsintsadze, N.

    2010-03-15

    In the present work we consider the effect of trapping as a microscopic process in a plasma consisting of quantum electrons and nondegenerate ions. The formation of solitary structures is investigated in two cases: first when the electrons are fully degenerate and second when small temperature effects are taken into account. It is seen that not only rarefactive but coupled rarefactive and compressive solitons are obtained under different temperature conditions.

  7. 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.

  8. 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.

  9. Equilibrium configurations of degenerate fluid spheres

    SciTech Connect

    Whitman, P.G.

    1985-04-01

    Equilibrium configurations of degenerate fluid spheres which assume a polytropic form in the ultrahigh-density regime are considered. We show that analytic solutions more general than those of Misner and Zapolsky exist which possess the asymptotic equation of state. Simple expressions are derived which indicate this nature of the fluids in the extreme relativistic limit, and the stability of these interiors is considered in the asymptotic region.

  10. Asymmetrical alien hands in corticobasal degeneration.

    PubMed

    Fitzgerald, David B; Drago, Valeria; Jeong, Yong; Chang, Yu-Ling; White, Keith D; Heilman, Kenneth M

    2007-03-15

    There are several forms of alien limb, but alien limb in corticobasal degeneration (CBD) is not well understood. We studied a patient with CBD who demonstrated two different types of alien limb. With his right hand he demonstrated a tactile avoidance response with levitation. With his left hand, he demonstrated continuous tactile pursuit of the examiner's hand ("tactile mitgehen"). Mitgehen is often associated with frontal dysfunction, but avoidance response and levitation are often associated with parietal dysfunction. PMID:17230447

  11. Buoyancy instabilities in degenerate, collisional, magnetized plasmas

    NASA Astrophysics Data System (ADS)

    Chang, Philip; Quataert, Eliot

    2010-03-01

    In low-collisionality plasmas, anisotropic heat conduction due to a magnetic field leads to buoyancy instabilities for any non-zero temperature gradient. We study analogous instabilities in degenerate collisional plasmas, i.e. when the electron collision frequency is large compared to the electron cyclotron frequency. Although heat conduction is nearly isotropic in this limit, the small residual anisotropy ensures that collisional degenerate plasmas are also convectively unstable independent of the sign of the temperature gradient. We show that the range of wavelengths that are unstable is independent of the magnetic field strength, while the growth time increases with decreasing magnetic field strength. We discuss the application of these collisional buoyancy instabilities to white dwarfs and neutron stars. Magnetic tension and the low specific heat of a degenerate plasma significantly limit their effectiveness; the most promising venues for growth are in the liquid oceans of young, weakly magnetized neutron stars (B <~ 109 G) and in the cores of young, high magnetic field white dwarfs (B ~ 109 G).

  12. 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.

  13. Propagation of disturbances in degenerate quantum systems

    NASA Astrophysics Data System (ADS)

    Chancellor, Nicholas; Haas, Stephan

    2011-07-01

    Disturbances in gapless quantum many-body models are known to travel an unlimited distance throughout the system. Here, we explore this phenomenon in finite clusters with degenerate ground states. The specific model studied here is the one-dimensional J1-J2 Heisenberg Hamiltonian at and close to the Majumdar-Ghosh point. Both open and periodic boundary conditions are considered. Quenches are performed using a local magnetic field. The degenerate Majumdar-Ghosh ground state allows disturbances which carry quantum entanglement to propagate throughout the system and thus dephase the entire system within the degenerate subspace. These disturbances can also carry polarization, but not energy, as all energy is stored locally. The local evolution of the part of the system where energy is stored drives the rest of the system through long-range entanglement. We also examine approximations for the ground state of this Hamiltonian in the strong field limit and study how couplings away from the Majumdar-Ghosh point affect the propagation of disturbances. We find that even in the case of approximate degeneracy, a disturbance can be propagated throughout a finite system.

  14. Lack of Degeneration of Loci on the Neo-Y Chromosome of Drosophila Americana Americana

    PubMed Central

    Charlesworth, B.; Charlesworth, D.; Hnilicka, J.; Yu, A.; Guttman, D. S.

    1997-01-01

    The extent of genetic degeneration of the neo-Y chromosome of Drosophila americana americana has been investigated. Three loci, coding for the enzymes enolase, phosphoglycerate kinase and alcohol dehydrogenase, have been localized to chromosome 4 of D. a. americana, which forms the neo-Y and neo-X chromosomes. Crosses between D. a. americana and D. virilis or D. montana showed that the loci coding for these enzymes carry active alleles on the neo-Y chromosome in all wild-derived strains of americana that were tested. Intercrosses between a genetically marked stock of virilis and strains of americana were carried out, creating F(3) males that were homozygous for sections of the neo-Y chromosome. The sex ratios in the F(3) generation of the intercrosses showed that no lethal alleles have accumulated on any of the neo-Y chromosomes tested. There was evidence for more minor reductions in fitness, but this seems to be mainly caused by deleterious alleles that are specific to each strain. A similar picture was provided by examination of the segregation ratios of two marker genes among the F(3) progeny. Overall, the data suggest that the neo-Y chromosome has undergone very little degeneration, certainly not to the extent of having lost the functions of vital genes. This is consistent with the recent origin of the neo-Y and neo-X chromosomes, and the slow rates at which the forces that cause Y chromosome degeneration are likely to work. PMID:9093852

  15. Slow Conduction in Cardiac Muscle

    PubMed Central

    Lieberman, Melvyn; Kootsey, J. Mailen; Johnson, Edward A.; Sawanobori, Tohru

    1973-01-01

    Mechanisms of slow conduction in cardiac muscle are categorized and the most likely identified. Propagating action potentials were obtained experimentally from a synthetically grown strand of cardiac muscle (around 50 μm by 30 mm) and theoretically from a one-dimensional cable model that incorporated varying axial resistance and membrane properties along its length. Action potentials propagated at about 0.3 m/s, but in some synthetic strands there were regions (approximately 100 μm in length) where the velocity decreased to 0.002 m/s. The electrophysiological behavior associated with this slow conduction was similar to that associated with slow conduction in naturally occurring cardiac muscle (notches, Wenckebach phenomena, and block). Theoretically, reasonable changes in specific membrane capacitance, membrane activity, and various changes in geometry were insufficient to account for the observed slow conduction velocities. Conduction velocities as low as 0.009 m/s, however, could be obtained by increasing the resistance (ri) of connections between the cells in the cable; velocities as low as 0.0005 m/s could be obtained by a further increase in ri made possible by a reduction in membrane activity by one-fourth, which in itself decreased conduction velocity by only a factor of 1/1.4. As a result of these findings, several of the mechanisms that have been postulated, previously, are shown to be incapable of accounting for delays such as those which occur in the synthetic strand as well as in the atrioventricular (VA) node. ImagesFIGURE 1FIGURE 2FIGURE 3FIGURE 4 PMID:4709519

  16. 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.

  17. Slow-light polaritons in Rydberg gases

    NASA Astrophysics Data System (ADS)

    Fleischhauer, Michael

    2012-02-01

    Slow-light polaritons are quasi-particles generated in the interaction of photons with laser-driven atoms with a λ- or ladder-type coupling scheme under conditions of electromagnetically induced transparency (EIT). They are a superposition of electromagnetic and collective spin excitations. If one of the states making up the atomic spin is a high lying Rydberg level, the polaritons are subject to a strong and non-local interaction mediated by a dipole-dipole or van-der Waals coupling between excited Rydberg atoms. I will present and discuss an effective many-body model for these Rydberg polaritons. Depending on the detuning of the control laser the interaction potential between the polaritons can be repulsive or attractive and can have a large imaginary component for distances less than the so-called blockade radius. The non-local effective interaction gives rize to interesting many-body phenomena such as the generation of photons with an avoided volume, visible in stronlgy suppressed two-particle correlations inside the blockade volume. Moreover the long-range, power-law scaling of the interaction can in the repulsive case give rize to the formation of quasi-crystalline structures of photons. In a one dimensional system the low-energy dynamics of the polaritons can be described in terms of a Luttinger liquid. Using DMRG simulations the Luttinger K parameter is calculated and conditions for the formation of a quasi-crystal are derived. When confined to a two-dimensional geometry, e.g. using a resonator with quasi-degenerate transversal mode spectrum, Rydberg polaritons are an interesting candidate to study the bosonic fractional quantum Hall effect. I will argue that the formation of photons with an avoided volume is essential for explaining recent experiments on stationary EIT in Rydberg gases [1,2].[4pt] [1] J.D. Pritchard et al., Phys. Rev. Lett. 105, 193603 (2010). [0pt] [2] D. Petrosyan, J. Otterbach, and M. Fleischhauer, arXiv:1106.1360

  18. 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.

  19. 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.

  20. 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.

  1. Asymptotic behavior of degenerate logistic equations

    NASA Astrophysics Data System (ADS)

    Arrieta, José M.; Pardo, Rosa; Rodríguez-Bernal, Aníbal

    2015-12-01

    We analyze the asymptotic behavior of positive solutions of parabolic equations with a class of degenerate logistic nonlinearities of the type λu - n (x)uρ. An important characteristic of this work is that the region where the logistic term n (ṡ) vanishes, that is K0 = { x : n (x) = 0 }, may be non-smooth. We analyze conditions on λ, ρ, n (ṡ) and K0 guaranteeing that the solution starting at a positive initial condition remains bounded or blows up as time goes to infinity. The asymptotic behavior may not be the same in different parts of K0.

  2. Vector polarons in a degenerate electron system

    NASA Astrophysics Data System (ADS)

    Clougherty, Dennis P.; Foell, Charles A.

    2004-08-01

    We consider a one-dimensional model of an electron in a doubly (or nearly) degenerate band that interacts with elastic distortions. We show that the electron equations of motion reduce to a set of coupled nonlinear Schrödinger equations. For the case of interband electron-phonon coupling stemming from local Jahn-Teller interactions, multicomponent self-localized polaron solutions-vector polarons- are described and classified. The phase diagram for the different types of vector polarons in this model is presented. By interpreting the components of the orbital doublet as those of spin- (1)/(2) , our results can also be used to describe bound magnetic polarons.

  3. Degenerate Fermi Gas of {sup 87}Sr

    SciTech Connect

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

    2010-07-16

    We report quantum degeneracy in a gas of ultracold fermionic {sup 87}Sr 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/T{sub F}=0.26{sub -0.06}{sup +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/T{sub F{approx}}0.5.

  4. Pharmacogenetics and age-related macular degeneration.

    PubMed

    Schwartz, Stephen G; Brantley, Milam A

    2011-01-01

    Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent. PMID:22046503

  5. 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.

  6. Slow Learners: Are Educators Leaving Them Behind?

    ERIC Educational Resources Information Center

    Kaznowski, Kimberly

    2004-01-01

    This study compared the school performance of a sample of slow learners who qualified for special education as learning disabled with a sample of slow learners who did not qualify for special education. The intent of the study was to determine which group of slow learners was more successful in school in order to know if special education or…

  7. Double Chooz Slow Monitoring System

    NASA Astrophysics Data System (ADS)

    Chang, Pi-Jung; Horton-Smith, Glenn; McKee, David; Shrestha, Deepak; Winslow, Lindley; Conrad, Janet

    2010-02-01

    The Double Chooz experiment aims to measure neutrino flux from two nearly identical detectors with an uncertainty less than 0.6%. The Double Chooz slow monitoring system records conditions of the experiment's environment which can impact the experiment's goals. The slow monitoring system includes temperatures and voltages in electronics, experimental hall environmental conditions, line voltages, liquid temperatures, PMT's magnetic field, radon concentrations, and photo-tube high voltages. This system scans all channels automatically, stores data in a common database, and warns of changes in the two detectors' physical environments. Most functions in this system can be accomplished by 1-Wire products from Dallas Semiconductor. We can use a single master for several functions' controls and operations and the power is derived from a signal bus. Every device has a unique unalterable ID. The sensors monitoring the liquid system, such as liquid thermal meters, are covered by epoxy in order to isolate in the liquid. Their radioactivity can be ignored and will not affect the uncertainty in the system. )

  8. Family-Specific Degenerate Primer Design: A Tool to Design Consensus Degenerated Oligonucleotides

    PubMed Central

    Goñi, Sandra Elizabeth; Lozano, Mario Enrique

    2013-01-01

    Designing degenerate PCR primers for templates of unknown nucleotide sequence may be a very difficult task. In this paper, we present a new method to design degenerate primers, implemented in family-specific degenerate primer design (FAS-DPD) computer software, for which the starting point is a multiple alignment of related amino acids or nucleotide sequences. To assess their efficiency, four different genome collections were used, covering a wide range of genomic lengths: Arenavirus (10 × 104 nucleotides), Baculovirus (0.9 × 105 to 1.8 × 105 bp), Lactobacillus sp. (1 × 106 to 2 × 106 bp), and Pseudomonas sp. (4 × 106 to 7 × 106 bp). In each case, FAS-DPD designed primers were tested computationally to measure specificity. Designed primers for Arenavirus and Baculovirus were tested experimentally. The method presented here is useful for designing degenerate primers on collections of related protein sequences, allowing detection of new family members. PMID:23533783

  9. MRI and MR tractography in bilateral hypertrophic olivary degeneration

    PubMed Central

    Sen, Debraj; Gulati, Yoginder S.; Malik, Virender; Mohimen, Aneesh; Sibi, Eranki; Reddy, Deepak Chandra

    2014-01-01

    Hypertrophic olivary degeneration is a trans-synaptic neuronal degeneration associated with hypertrophy of the inferior olivary nucleus due to a lesion in the triangle of Guillain-Mollaret. Familiarity with this entity on magnetic resonance imaging (MRI) is essential to avoid other erroneous ominous diagnoses. We present a case of bilateral hypertrophic olivary degeneration and discuss the etiopathogenesis and MRI findings in this entity. The contributory role of MR tractography in the diagnosis is also highlighted. PMID:25489133

  10. Predicting Progression of ABCA4-Associated Retinal Degenerations Based on Longitudinal Measurements of the Leading Disease Front

    PubMed Central

    Cideciyan, Artur V.; Swider, Malgorzata; Schwartz, Sharon B.; Stone, Edwin M.; Jacobson, Samuel G.

    2015-01-01

    Purpose To evaluate the progression of the earliest stage of disease in ABCA4-associated retinal degenerations (RDs). Methods Near-infrared excited reduced-illuminance autofluorescence imaging was acquired across the retina up to 80 degrees eccentricity in 44 patients with two ABCA4 alleles. The eccentricity of the leading disease front (LDF) corresponding to the earliest stage of disease was measured along the four meridians. A mathematical model describing the expansion of the LDF was developed based on 6 years of longitudinal follow-up. Results The extent of LDF along the superior, inferior, and temporal meridians showed a wide spectrum from 3.5 to 70 degrees. In patients with longitudinal data, the average centrifugal expansion rate was 2 degrees per year. The nasal extent of LDF between the fovea and ONH ranged from 4.3 to 16.5 degrees and expanded at 0.35 degrees per year. The extent of LDF beyond ONH ranged from 19 to 75 degrees and expanded on average at 2 degrees per year. A mathematical model fit well to the longitudinal data describing the expansion of the LDF. Conclusions The eccentricity of the LDF in ABCA4-RD shows a continuum from parafovea to far periphery along all four meridians consistent with a wide spectrum of severity observed clinically. The model of progression may provide a quantitative prediction of the LDF expansion based on the age and eccentricity of the LDF at a baseline visit, and thus contribute significantly to the enrollment of candidates appropriate for clinical trials planning specific interventions, efficacy outcomes, and durations. PMID:26377081

  11. Fast and slow flexural waves in a deviated borehole in homogeneous and layered anisotropic formations

    NASA Astrophysics Data System (ADS)

    He, Xiao; Hu, Hengshan; Guan, Wei

    2010-04-01

    Dipole acoustic fields in an arbitrarily deviated well penetrating a homogeneous as well as a stratified transversely isotropic formation are simulated using a 3-D finite-difference time-domain algorithm in cylindrical coordinates. The modelling results show that a dipole source can excite a fast- and a slow-flexural mode due to the shear wave anisotropy when the borehole is inclined with respect to the symmetry axis of transverse isotropy. Both flexural slownesses change with the wellbore deviation angle. The splitting of flexural modes is prominent in full wave arrays when the shear anisotropy is strong enough. It is revealed that the dipole orientation influences the relative amplitudes of the fast- and slow-flexural waves but it has no effect on their slownesses or phases. In a vertical well parallel to the symmetry axis, the two flexural waves degenerate and propagate at the same speed. The degenerated flexural wave travels approximately at the shear speed along the borehole wall except in a few formations. Our study shows, for example, that it is about 10 per cent slower than the shear wave in Mesaverde clayshale 5501. Even in that kind of formations, however, extraction of the fast- and slow-shear velocities from the flexural modes is still possible if the borehole deviation is large enough. To examine the effect of layering, we modelled the full waves in a formation with a sandwich. When the well is perpendicular to the layer interfaces, reflection is obvious and can be recognized. It becomes weaker or even invisible as the deviation angle increases, so it is difficult to detect a thin layer embedded in a formation directly from reflected waves. The sandwich can, instead, be recognized from the irregularity in the spectra of the full waveforms displayed versus depth. [Correction added after online publication 25th February 2009; the original spelling of `homogenous' in the title has been corrected to `homogeneous'.[

  12. Changes in ganglion cells during retinal degeneration.

    PubMed

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

    2016-08-01

    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. PMID:27132232

  13. Nodular fasciitis with degeneration and regression.

    PubMed

    Yanagisawa, Akihiro; Okada, Hideki

    2008-07-01

    Nodular fasciitis is a benign reactive proliferation that is frequently misdiagnosed as a sarcoma. This article describes a case of nodular fasciitis of 6-month duration located in the cheek, which degenerated and spontaneously regressed after biopsy. The nodule was fixed to the zygoma but was free from the overlying skin. The mass was 3.0 cm in diameter and demonstrated high signal intensity on T2-weighted magnetic resonance imaging. A small part of the lesion was biopsied. Pathological and immunohistochemical examinations identified the nodule as nodular fasciitis with myxoid histology. One month after the biopsy, the mass showed decreased signal intensity on T2-weighted images and measured 2.2 cm in size. The signal on T2-weighted images showed time-dependent decreases, and the mass continued to reduce in size throughout the follow-up period. The lesion presented as hypointense to the surrounding muscles on T2-weighted images and was 0.4 cm in size at 2 years of follow-up. This case demonstrates that nodular fasciitis with myxoid histology can change to that with fibrous appearance gradually with time, thus bringing about spontaneous regression. Degeneration may be involved in the spontaneous regression of nodular fasciitis with myxoid appearance. The mechanism of regression, unclarified at present, should be further studied. PMID:18650753

  14. 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.

  15. 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.

  16. 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

  17. Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine.

    PubMed

    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

    2015-04-01

    Frontotemporal lobar degeneration (FTLD) comprises two main classes of neurodegenerative diseases characterized by neuronal/glial proteinaceous inclusions (i.e., 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 toward the goal of defining clinical endophenotypes of FTD. PMID:25549971

  18. 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)

  19. 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.

  20. Jumps of adiabatic invariant at the separatrix of a degenerate saddle point.

    PubMed

    Artemyev, A V; Neishtadt, A I; Zelenyi, L M

    2011-12-01

    We consider a slow-fast Hamiltonian system with two degrees of freedom. One degree of freedom corresponds to slow variables, and the other one corresponds to fast variables. A characteristic ratio of the rates of change of slow and fast variables is a small parameter κ. For every fixed value of the slow variables, in the phase portrait of the fast variables there are a saddle point and separatrices passing through it. When the slow variables change, phase points may cross the separatrices. The action variable of the fast motion is an adiabatic invariant of the full system as long as a trajectory is far from the separatrices: value of the adiabatic invariant is conserved with an accuracy of order of κ on time intervals of order of 1/κ. A passage through a narrow neighborhood of the separatrices results in a jump of the adiabatic invariant. We consider a case when the saddle point is degenerate. We derive an asymptotic formula for the jump of the adiabatic invariant which turns out to be a value of order of κ(3/4) (in the case of a non-degenarate saddle point a similar jump is known to be a value of order of κ). Accumulation of these jumps after many consecutive separatrix crossings leads to the "diffusion" of the adiabatic invariant and chaotic dynamics. We verify the analytical expression for the jump of the adiabatic invariant by numerical simulations. We discuss application of the obtained results to the description of charged particle dynamics in the Earth magnetosphere. PMID:22225357

  1. Rapid loss of motor nerve terminals following hypoxia–reperfusion injury occurs via mechanisms distinct from classic Wallerian degeneration

    PubMed Central

    Baxter, Becki; Gillingwater, Thomas H; Parson, Simon H

    2008-01-01

    Motor nerve terminals are known to be vulnerable to a wide range of pathological stimuli. To further characterize this vulnerability, we have developed a novel model system to examine the response of mouse motor nerve terminals in ex vivo nerve/muscle preparations to 2 h hypoxia followed by 2 h reperfusion. This insult induced a rapid loss of neurofilament and synaptic vesicle protein immunoreactivity at pre-synaptic motor nerve terminals but did not appear to affect post-synaptic endplates or muscle fibres. The severity of nerve terminal loss was dependent on the age of the mouse and muscle type: in 8–12-week-old mice the predominantly fast-twitch lumbrical muscles showed an 82.5% loss, whereas the predominantly slow-twitch muscles transversus abdominis and triangularis sterni showed a 57.8% and 27.2% loss, respectively. This was contrasted with a > 97% loss in the predominantly slow-twitch muscles from 5–6-week-old mice. We have also demonstrated that nerve terminal loss occurs by a mechanism distinct from Wallerian degeneration, as the slow Wallerian degeneration (Wlds) gene did not modify the extent of nerve terminal pathology. Together, these data show that our new model of hypoxia–reperfusion injury is robust and repeatable, that it induces rapid, quantitative changes in motor nerve terminals and that it can be used to further examine the mechanisms regulating nerve terminal vulnerability in response to hypoxia–reperfusion injury. PMID:18510509

  2. 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

  3. Hypocoercivity of linear degenerately dissipative kinetic equations

    NASA Astrophysics Data System (ADS)

    Duan, Renjun

    2011-08-01

    In this paper we develop a general approach of studying the hypocoercivity for a class of linear kinetic equations with both transport and degenerately dissipative terms. As concrete examples, the relaxation operator, Fokker-Planck operator and linearized Boltzmann operator are considered when the spatial domain takes the whole space or torus and when there is a confining force or not. The key part of the developed approach is to construct some equivalent temporal energy functionals for obtaining time rates of the solution trending towards equilibrium in some Hilbert spaces. The result in the case of the linear Boltzmann equation with confining forces is new. The proof mainly makes use of the macro-micro decomposition combined with Kawashima's argument on dissipation of the hyperbolic-parabolic system. At the end, a Korn-type inequality with probability measure is provided to deal with dissipation of momentum components.

  4. [Epidemiology of age-related macular degeneration].

    PubMed

    Brandl, C; Stark, K J; Wintergerst, M; Heinemann, M; Heid, I M; Finger, R P

    2016-09-01

    Age-related macular degeneration (AMD) is the main cause of blindness in industrialized societies. Population-based epidemiological investigations generate important data on prevalence, incidence, risk factors, and future trends. This review summarizes the most important epidemiological studies on AMD with a focus on their transferability to Germany including existing evidence for the main risk factors for AMD development and progression. Future tasks, such as the standardization of grading systems and the use of recent retinal imaging technology in epidemiological studies are discussed. In Germany, epidemiological data on AMD are scarce. However, the need for epidemiological research in ophthalmology is currently being addressed by several recently started population-based studies. PMID:27541733

  5. Solitons in Degenerate Electron-Phonon Systems

    NASA Astrophysics Data System (ADS)

    Foell, Charles; Clougherty, Dennis

    2004-03-01

    We consider a 1øplus 1-dimensional model describing the coupling between degenerate electron states under local Jahn-Teller interactions. In the adiabatic approximation, the equations of motion are shown to reduce to a set of coupled non-linear Schrödinger equations in the electron fields. We demonstrate that in the continuum limit solitary waves of the wave-daughter wave type are stable for sufficiently strong on-site Coulomb repulsion. Our results may have relevance to describing the electronic and optical properties of quasi-one-dimensional systems such as halogen-bridged mixed-valence transition-metal linear-chain complexes (MX chains) and polymeric fullerides.

  6. Therapeutic interventions in parkinsonism: Corticobasal degeneration.

    PubMed

    Marsili, Luca; Suppa, Antonio; Berardelli, Alfredo; Colosimo, Carlo

    2016-01-01

    Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder resulting from pathological accumulation of tau protein and is included in the spectrum of Atypical Parkinsonism. The typical clinical phenotype of CBD is characterized by the Corticobasal syndrome (CBS). In recent years it has become clear that the clinical picture of CBS may be caused by different pathological conditions, resulting in frequent misdiagnosis. CBD has high morbidity and poor prognosis with no effective therapies. In this review, we will discuss the symptomatic treatment, the palliative care and the disease modifying strategies currently in use. Symptomatic treatment in patients with CBD may sometimes be useful for improving motor (parkinsonism, dystonia and myoclonus) and non-motor (cognitive-behavioral) symptoms, but the effects are often unsatisfactory. In addition, non-pharmacological strategies and palliative care are useful integrating components of the multidisciplinary therapeutic approach for patients with CBD. Despite many efforts, a disease-modifying treatment is still unavailable for CBD. PMID:26382843

  7. Cartilage degeneration in different human joints.

    PubMed

    Kuettner, K E; Cole, A A

    2005-02-01

    Variations among joints in the initiation and progression of degeneration may be explained, in part, by metabolic, biochemical and biomechanical differences. Compared to the cartilage in the knee joint, ankle cartilage has a higher content of proteoglycans and water, as well as an increased rate of proteoglycan turnover and synthesis, all of which are responsible for its increased stiffness and reduced permeability. Chondrocytes within ankle cartilage have a decreased response to catabolic factors such as interleukin-1 and fibronectin fragments, compared to the chondrocytes of knee cartilage. Moreover, in response to damage, ankle chondrocytes synthesize proteoglycans at a higher rate than that found in knee cartilage chondrocytes, which suggests a greater capacity for repair. In addition to the cartilages of the two joints, the underlying bones also respond differently to degenerative changes. Taken together, these metabolic, biochemical and biomechanical differences may provide protection to the ankle. PMID:15694570

  8. The muon g - 2 and degenerate supersymmetry

    NASA Astrophysics Data System (ADS)

    Chowdhury, Debtosh; Patel, Ketan M.; Tata, Xerxes; Vempati, Sudhir K.

    2016-04-01

    A degenerate supersymmetric particle spectrum can escape constraints from flavor physics and at the same time evade limits from the direct searches. If such a spectrum is light enough, it can also account for the observed value of the anomalous magnetic moment of the muon. Inspired by this, we consider a scenario where all the soft terms have approximately a common mass scale while allowing for small splittings. We study this scenario considering the constraints from Higgs mass, various B meson decays and the dark matter relic density. We find that, with superpartners ~ 800 - 1000 GeV, it is still possible to escape the present limits from the first run of LHC and flavor physics and can account for muon g - 2 within 2σ.

  9. Quantum Walk in Degenerate Spin Environments

    NASA Astrophysics Data System (ADS)

    Carlström, Johan; Prokof'ev, Nikolay; Svistunov, Boris

    2016-06-01

    We study the propagation of a hole in degenerate (paramagnetic) spin environments. This canonical problem has important connections to a number of physical systems, and is perfectly suited for experimental realization with ultracold atoms in an optical lattice. At the short-to-intermediate time scale that we can access using a stochastic-series-type numeric scheme, the propagation turns out to be distinctly nondiffusive with the probability distribution featuring minima in both space and time due to quantum interference, yet the motion is not ballistic, except at the beginning. We discuss possible scenarios for long-term evolution that could be explored with an unprecedented degree of detail in experiments with single-atom resolved imaging.

  10. Spectroscopic temperature determination of degenerate Fermi gases

    SciTech Connect

    Kostrun, Marijan; Cote, Robin

    2003-12-01

    We suggest a simple method for measuring the temperature of ultracold gases made of fermions. We show that by using a two-photon Raman probe, it is possible to obtain line shapes which reveal properties of the degenerate sample, notably its temperature T. The proposed method could be used with identical fermions in different hyperfine states interacting via s-wave scattering or identical fermions in the same hyperfine state via p-wave scattering. We illustrate the applicability of the method in realistic conditions for {sup 6}Li prepared in two different hyperfine states. We find that temperatures down to 0.05T{sub F} can be determined by this in situ method.