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Sample records for degeneration slow rds

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

    SciTech Connect

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

    1995-07-20

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

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

    PubMed

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

    2015-11-13

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

  19. 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

  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. 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.

  4. [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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  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. 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.

  14. [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

  15. 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%.

  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. 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

  3. 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.

  4. 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.

  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. 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.

  14. 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.

  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. 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

  13. 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

  14. 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

  15. 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

  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 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

  18. 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

  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. 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

  5. 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.

  6. 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.

  7. 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

  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

    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,…

  15. 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…

  16. 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).

  17. 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.

  18. 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

  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. 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

  10. 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.

  11. 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…

  12. 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.

  13. 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.

  14. 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

  15. 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

  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. 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

  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. 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

  2. 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

  3. 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.

  4. 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.

  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. 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.

  7. 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

  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. 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

  10. 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.

  11. 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.

  12. 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).

  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. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  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. 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

  13. 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

  14. Metabolic anatomy of paraneoplastic cerebellar degeneration

    SciTech Connect

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

    1988-06-01

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

  15. Degenerate parametric oscillation in quantum membrane optomechanics

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  16. 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

  17. 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

  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. 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.

  3. 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

  4. 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

  5. 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.

  6. [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

  7. MicroRNA in intervertebral disc degeneration.

    PubMed

    Li, Zheng; Yu, Xin; Shen, Jianxiong; Chan, Matthew T V; Wu, William Ka Kei

    2015-06-01

    Aetiology of intervertebral disc degeneration (IDD) is complex, with genetic, developmental, biochemical and biomechanical factors contributing to the disease process. It is becoming obvious that epigenetic processes influence evolution of IDD as strongly as the genetic background. Deregulated phenotypes of nucleus pulposus cells, including differentiation, migration, proliferation and apoptosis, are involved in all stages of progression of human IDD. Non-coding RNAs, including microRNAs, have recently been recognized as important regulators of gene expression. Research into roles of microRNAs in IDD has been very active over the past 5 years. Our review summarizes current research enlightenment towards understanding roles of microRNAs in regulating nucleus pulposus cell functions in IDD. These exciting findings support the notion that specific modulation of microRNAs may represent an attractive approach for management of IDD. PMID:25736871

  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. Subwavelength total acoustic absorption with degenerate resonators

    NASA Astrophysics Data System (ADS)

    Yang, Min; Meng, Chong; Fu, Caixing; Li, Yong; Yang, Zhiyu; Sheng, Ping

    2015-09-01

    We report the experimental realization of perfect sound absorption by sub-wavelength monopole and dipole resonators that exhibit degenerate resonant frequencies. This is achieved through the destructive interference of two resonators' transmission responses, while the matching of their averaged impedances to that of air implies no backscattering, thereby leading to total absorption. Two examples, both using decorated membrane resonators (DMRs) as the basic units, are presented. The first is a flat panel comprising a DMR and a pair of coupled DMRs, while the second one is a ventilated short tube containing a DMR in conjunction with a sidewall DMR backed by a cavity. In both examples, near perfect absorption, up to 99.7%, has been observed with the airborne wavelength up to 1.2 m, which is at least an order of magnitude larger than the composite absorber. Excellent agreement between theory and experiment is obtained.

  11. 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

  12. Degenerate R-S perturbation theory

    NASA Technical Reports Server (NTRS)

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

    1973-01-01

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

  13. 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.

  14. Age-related macular degeneration: current treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

  15. Topological superradiance in a degenerate Fermi gas

    NASA Astrophysics Data System (ADS)

    Pan, Jian-Song; Liu, Xiong-Jun; Zhang, Wei; Yi, Wei; Guo, Guang-Can; Yi's Group Team; Liu's Group Team; Zhang's Group Team

    2015-05-01

    We predict the existence of a topological superradiant state in a two-component degenerate Fermi gas in a cavity. The superradiant light generation in the transversely driven cavity mode induces a cavity-assisted spin-orbit coupling in the system and opens a bulk gap at half filling. This mechanism can simultaneously drive a topological phase transition in the system, yielding a topological superradiant state. We map out the steady-state phase diagram of the system in the presence of an effective Zeeman field, and identify a critical tetracritical point beyond which the topological and the conventional superraidiant phase boundaries separate. We propose to detect the topological phase transition based on its signatures in either the momentum distribution of the atoms or in the cavity photon occupation.

  16. Retinas in a Dish Peek into Inherited Retinal Degeneration.

    PubMed

    Duong, Thu T; Vasireddy, Vidyullatha; Mills, Jason A; Bennett, Jean

    2016-06-01

    Human retinal degeneration can cause blindness, and the lack of relevant model systems has made identifying underlying mechanisms challenging. Parfitt et al. (2016) generate three-dimensional retinal tissue from patient-derived induced pluripotent stem cells to identify how CEP290 mutations cause retinal degeneration, and show an antisense approach can correct disease-associated phenotypes. PMID:27257755

  17. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  18. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

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

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. PMID:26572116

  20. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  1. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  2. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  3. Does lumbar facet arthrosis precede disc degeneration? A postmortem study.

    PubMed

    Eubanks, Jason David; Lee, Michael J; Cassinelli, Ezequiel; Ahn, Nicholas U

    2007-11-01

    It is believed lumbar degeneration begins in the disc, where desiccation and collapse lead to instability and compensatory facet arthrosis. We explored the contrary contention that facet degeneration precedes disc degeneration by examining 647 skeletal lumbar spines. Using facet osteophytosis as a measure of facet degeneration and vertebral rim osteophytosis as a measure of disc degeneration, we assumed bone degeneration in both locations equally reflected the progression of those in the soft tissues. We graded arthrosis Grade 0 to 4 on a continuum from no arthritis to ankylosis. The data were analyzed for different age groups to examine patterns of degeneration with age. Specimens younger than 30 years of age had a higher prevalence of facet osteophytosis compared with vertebral rim osteophotosis at L1-L2 and L2-L3. Specimens aged 30 to 39 years showed more facet osteophytosis than vertebral rim osteophytosis at L4-L5. Specimens older than 40 years, however, showed more vertebral rim osteophytosis compared with facet osteophytosis at all levels except L4-L5 and L5-S1. This skeletal study suggests facet osteophytosis appears early in the degenerative process, preceding vertebral rim osteophytosis of degenerating intervertebral discs. However, once facets begin deteriorating with age, vertebral rim osteophytosis overtakes continued facet osteophytosis. These data challenge the belief that facet osteophytosis follows vertebral rim osteophytosis; rather, it appears vertebral rim osteophytosis progresses more rapidly in later years, but facet osteophotosis occurs early, predominating in younger individuals. PMID:17767079

  4. Ouabain-induced cochlear degeneration in rat

    PubMed Central

    Fu, Yong; Ding, Dalian; Jiang, Haiyan; Salvi, Richard

    2012-01-01

    Ouabain, an potent inhibitor of the Na+/K+-ATPase pump, selectively destroys spiral ganglion neurons (SGNs) in gerbils and mice whereas in guinea pigs it preferentially damages cochlear hair cells. To elucidate the effects of ouabain on the rat inner ear, a species widely used in research, 5 µl of 1 mM or 10 mM ouabain was applied to the round window membrane. Distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) were used identify functional deficits in hair cells and neurons respectively and histological techniques were used to characterize cochlear pathologies. High-frequency ABR thresholds were elevated after treatment with 1 mM ouabain whereas DPOAEs remained normal. In contrast, 10 mM ouabain increased ABR thresholds and reduced DPOAE amplitudes. Consistent with the physiological changes, 1 mM ouabain only damaged the SGNs and auditory nerve fibers in the basal turn of the cochlea whereas 10 mM ouabain destroyed both SGNs and cochlear hair cells; damage was greatest near the base and decreased toward the apex. The nuclei of degenerating SGNs and hair cells were condensed and fragmented and many cells were TUNEL-positive, morphological features of apoptotic cell death. Thus, ouabain-induced cochlear degeneration in rats is apoptotic and concentration dependent; low concentrations preferentially damage SGNs in the base of the cochlea, producing an animal model of partial auditory neuropathy, whereas high concentrations damage both hair cells and SGNs with damage decreasing from the base towards the apex. PMID:22476946

  5. Crystallization and collapse in relativistically degenerate matter

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2013-04-15

    In this paper, it is shown that a mass density limit exists beyond which the relativistically degenerate matter would crystallize. The mass density limit, found here, is quite analogous to the mass limit predicted by Chandrasekhar for a type of compact stars called white dwarfs (M{sub Ch} Asymptotically-Equal-To 1.43 Solar Mass). In this study, the old problem of white dwarf core collapse, which has been previously investigated by Chandrasekhar using hydrostatic stability criteria, is revisited in the framework of the quantum hydrodynamics model by inspection of the charge screening at atomic scales in the relativistic degeneracy plasma regime taking into account the relativistic Fermi-Dirac statistics and electron interaction features such as the quantum statistical pressure, Coulomb attraction, electron exchange-correlation, and quantum recoil effects. It is revealed that the existence of ion correlation and crystallization of matter in the relativistically degenerate plasma puts a critical mass density limit on white dwarf core region. It is shown that a white dwarf star with a core mass density beyond this critical limit can undergo the spontaneous core collapse (SCC). The SCC phenomenon, which is dominantly caused by the electron quantum recoil effect (interference and localization of the electron wave function), leads to a new exotic state of matter. In such exotic state, the relativistic electron degeneracy can lead the white dwarf crystallized core to undergo the nuclear fusion and an ultimate supernova by means of the volume reduction (due to the enhanced compressibility) and huge energy release (due to the increase in cohesive energy), under the stars huge inward gravitational pressure. Moreover, it is found that the SCC phenomenon is significantly affected by the core composition (it is more probable for heavier plasmas). The critical mass density found here is consistent with the values calculated for core density of typical white dwarf stars.

  6. Ouabain-induced cochlear degeneration in rat.

    PubMed

    Fu, Yong; Ding, Dalian; Jiang, Haiyan; Salvi, Richard

    2012-08-01

    Ouabain, a potent inhibitor of the Na+/K+-ATPase pump, selectively destroys spiral ganglion neurons (SGNs) in gerbils and mice, whereas in guinea pigs it preferentially damages cochlear hair cells. To elucidate the effects of ouabain on the rat inner ear, a species widely used in research, 5 μl of 1 or 10 mM ouabain was applied to the round window membrane. Distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) were used to identify functional deficits in hair cells and neurons, respectively, and histological techniques were used to characterize cochlear pathologies. High-frequency ABR thresholds were elevated after treatment with 1 mM ouabain, whereas DPOAEs remained normal. In contrast, 10 mM ouabain increased ABR thresholds and reduced DPOAE amplitudes. Consistent with the physiological changes, 1 mM ouabain only damaged the SGNs and auditory nerve fibers in the basal turn of the cochlea whereas 10 mM ouabain destroyed both SGNs and cochlear hair cells; damage was greatest near the base and decreased toward the apex. The nuclei of degenerating SGNs and hair cells were condensed and fragmented and many cells were TUNEL-positive, morphological features of apoptotic cell death. Thus, ouabain-induced cochlear degeneration in rats is apoptotic and concentration dependent; low concentrations preferentially damage SGNs in the base of the cochlea, producing an animal model of partial auditory neuropathy, whereas high concentrations damage both hair cells and SGNs with damage decreasing from the base toward the apex. PMID:22476946

  7. Retrograde Axonal Degeneration in Parkinson Disease

    PubMed Central

    Tagliaferro, Patricia; Burke, Robert E.

    2016-01-01

    In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson’s disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics. PMID:27003783

  8. Preservation of retinotopic map in retinal degeneration.

    PubMed

    Xie, John; Wang, Gene-Jack; Yow, Lindy; Humayun, Mark S; Weiland, James D; Cela, Carlos J; Jadvar, Hossein; Lazzi, Gianluca; Dhrami-Gavazi, Elona; Tsang, Stephen H

    2012-05-01

    Retinal degenerations trigger the loss of photoreceptors and cause the remaining de-afferented neural retina to undergo remodeling. Concerns over this potential retinal synaptic reorganization following visual loss have raised questions regarding the usefulness of visual restoration via retinal electrical stimulation. We have used quantitative positron emission tomography (PET) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) to objectively evaluate the connection between the retina and the primary visual cortex under both light and transcorneal electrical stimulation (TcES) in five subjects with retinal degeneration (RD) who have had more than ten years of light-perception-only best visual acuity and five age-matched normal-sighted controls. All subjects underwent quantitative PET with FDG as the metabolic tracer during stimulation of the right eye under both light stimulation condition and transcorneal electrical stimulation (TcES) using ERG-Jet contact lens electrode. Cortical activation maps from each stimulation condition were obtained using statistical parametric mapping. TcES phosphene threshold current and qualitative visual cortex activation from both stimulation conditions were compared between the two subject groups. Average phosphene threshold current was 0.72 ± 0.18 mA for the five normal-sighted controls and 3.08 ± 2.01 mA for the retinal degenerative subjects. Phosphene threshold current was significantly higher in retinal degenerative subjects compared to normal-sighted controls (p < 0.05). We found both light stimulation and TcES resulted in retinotopically mapped primary visual cortex activation in both groups. In addition, the patterns of early visual area activation between the two subject groups are more similar during TcES than light stimulation. Our findings suggest primary visual cortex continues to maintain its retinotopy in RD subjects despite prolonged visual loss. PMID:22685713

  9. Transurethral resection and degeneration of bladder tumour

    PubMed Central

    Li, Aihua; Fang, Wei; Zhang, Feng; Li, Weiwu; Lu, Honghai; Liu, Sikuan; Wang, Hui; Zhang, Binghui

    2013-01-01

    Introduction: We evaluate the efficacy and safety of transurethral resection and degeneration of bladder tumour (TURD-Bt). Methods: In total, 56 patients with bladder tumour were treated by TURD-Bt. The results in these patients were compared with 32 patients treated by current transurethral resection of bladder tumour (TUR-Bt). Patients with or without disease progressive factors were respectively compared between the 2 groups. The factors included recurrent tumour, multiple tumours, tumour ≥3 cm in diameter, clinical stage T2, histological grade 3, adenocarcinoma, and ureteral obstruction or hydronephrosis. Results: Follow-up time was 48.55 ± 23.74 months in TURD-Bt group and 56.28 ± 17.61 months in the TUR-Bt group (p > 0.05). In patients without progressive factors, no tumour recurrence was found and overall survival was 14 (100%) in the TURD-Bt group; 3 (37.50%) patients had recurrence and overall survival was 5 (62.5%) in the TUR-Bt group. In patients with progressive factors, 8 (19.05%) patients had tumour recurrence, overall survival was 32 (76.19%) and cancer death was 3 (7.14%) in TURD-Bt group; 18 (75.00%) patients had tumour recurrence (p < 0.05), overall survival was 12 (50.00%) (p < 0.01) and cancer death was 8 (33.33%) (p < 0.05) in TUR-Bt group. No significant complication was found in TURD-Bt group. Conclusion: This study suggests that complete resection and degeneration of bladder tumour can be expected by TURD-Bt. The surgical procedure is safe and efficacious, and could be predictable and controllable before and during surgery. We would conclude that for bladder cancers without lymph node metastasis and distal metastasis, TURD-Bt could be performed to replace radical TUR-Bt and preserve the bladder. PMID:24475002

  10. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration

    PubMed Central

    Le Maitre, Christine Lyn; Freemont, Anthony John; Hoyland, Judith Alison

    2007-01-01

    Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

  11. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration.

    PubMed

    Le Maitre, Christine Lyn; Freemont, Anthony John; Hoyland, Judith Alison

    2007-01-01

    Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated beta-galactosidase (SA-beta-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-beta-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

  12. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    NASA Astrophysics Data System (ADS)

    Abbas, G.; Sarfraz, M.; Shah, H. A.

    2014-09-01

    Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

  13. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  14. Versal unfolding of planar Hamiltonian systems at fully degenerate equilibrium

    NASA Astrophysics Data System (ADS)

    Tang, Yilei; Zhang, Weinian

    2016-07-01

    In this paper we study bifurcations of a planar Hamiltonian system at a fully degenerate equilibrium, which has a zero linearization. Since the Poincaré normal form theory is not applicable to such a degenerate system, we investigate its restrictive normal forms in the class of Hamiltonian fields and prove that such a degenerate system is of codimension 3 degeneracy in the class, so that we introduce three parameters to versally unfold the degenerate system in the class. In order to discuss further the qualitative properties of the versal unfolding, we use the Poincaré index to determine the number and distribution of hyperbolic sectors near the degenerate equilibrium. We display its all bifurcations such as pitchfork bifurcation, saddle-center bifurcation and the Bogdanov-Takens bifurcation within Hamiltonian systems.

  15. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    SciTech Connect

    Abbas, G. Sarfraz, M.; Shah, H. A.

    2014-09-15

    Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

  16. Comet Borrelly Slows Solar Wind

    NASA Technical Reports Server (NTRS)

    2001-01-01

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

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

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

  17. Synchronization Properties of Slow Cortical Oscillations

    NASA Astrophysics Data System (ADS)

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

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

  18. Dietary Supplement Enriched in Antioxidants and Omega-3 Protects from Progressive Light-Induced Retinal Degeneration

    PubMed Central

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

    2015-01-01

    In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG) followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD). For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA), 142% for docosapentaenoic acid (DPA) and 19% for docosahexaenoic acid (DHA) and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration. PMID:26042773

  19. Molecular signatures of age-associated chronic degeneration of shoulder muscles

    PubMed Central

    Raz, Yotam; Henseler, Jan Ferdinand; Kolk, Arjen; Tatum, Zuotian; Groosjohan, Niels Kuipers; Verwey, Nisha E.; Arindrarto, Wibowo; Kielbasa, Szymon M.; Nagels, Jochem; Hoen, Peter A. C. 't; Nelissen, Rob G. H. H.; Raz, Vered

    2016-01-01

    Chronic muscle diseases are highly prevalent in the elderly causing severe mobility limitations, pain and frailty. The intrinsic molecular mechanisms are poorly understood due to multifactorial causes, slow progression with age and variations between individuals. Understanding the underlying molecular mechanisms could lead to new treatment options which are currently limited. Shoulder complaints are highly common in the elderly, and therefore, muscles of the shoulder's rotator cuff could be considered as a model for chronic age-associated muscle degeneration. Diseased shoulder muscles were characterized by muscle atrophy and fatty infiltration compared with unaffected shoulder muscles. We confirmed fatty infiltration using histochemical analysis. Additionally, fibrosis and loss of contractile myosin expression were found in diseased muscles. Most cellular features, including proliferation rate, apoptosis and cell senescence, remained unchanged and genome-wide molecular signatures were predominantly similar between diseased and intact muscles. However, we found down-regulation of a small subset of muscle function genes, and up-regulation of extracellular region genes. Myogenesis was defected in muscle cell culture from diseased muscles but was restored by elevating MyoD levels. We suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration. PMID:26885755

  20. Molecular signatures of age-associated chronic degeneration of shoulder muscles.

    PubMed

    Raz, Yotam; Henseler, Jan Ferdinand; Kolk, Arjen; Tatum, Zuotian; Groosjohan, Niels Kuipers; Verwey, Nisha E; Arindrarto, Wibowo; Kielbasa, Szymon M; Nagels, Jochem; 't Hoen, Peter A C; Nelissen, Rob G H H; Raz, Vered

    2016-02-23

    Chronic muscle diseases are highly prevalent in the elderly causing severe mobility limitations, pain and frailty. The intrinsic molecular mechanisms are poorly understood due to multifactorial causes, slow progression with age and variations between individuals. Understanding the underlying molecular mechanisms could lead to new treatment options which are currently limited. Shoulder complaints are highly common in the elderly, and therefore, muscles of the shoulder's rotator cuff could be considered as a model for chronic age-associated muscle degeneration. Diseased shoulder muscles were characterized by muscle atrophy and fatty infiltration compared with unaffected shoulder muscles. We confirmed fatty infiltration using histochemical analysis. Additionally, fibrosis and loss of contractile myosin expression were found in diseased muscles. Most cellular features, including proliferation rate, apoptosis and cell senescence, remained unchanged and genome-wide molecular signatures were predominantly similar between diseased and intact muscles. However, we found down-regulation of a small subset of muscle function genes, and up-regulation of extracellular region genes. Myogenesis was defected in muscle cell culture from diseased muscles but was restored by elevating MyoD levels. We suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration. PMID:26885755

  1. Slow stick slip of antigorite serpentinite under hydrothermal conditions as a possible mechanism for slow earthquakes

    NASA Astrophysics Data System (ADS)

    Okazaki, Keishi; Katayama, Ikuo

    2015-02-01

    Slow earthquakes, characterized by a different scaling law to regular earthquakes, have been detected at the hydrated plate interface in the subduction zones, but the generating mechanism of them remains almost unexplored. Frictional experiments on antigorite serpentinite under hydrothermal conditions are conducted to assess the distinct scaling law of slow earthquakes. Slow stick-slip was observed at temperatures that were close to the dehydration temperature of antigorite, which is resulted by the localized dehydration of serpentine in the shear zone. The occurrence of slow stick-slip is consistent with the temperature range found in the corner of the mantle wedge in SW Japan and Cascadia, where slow earthquakes occur. The laboratory slow stick-slip shows a similar scaling law of slow earthquakes, but distinct from that of regular earthquakes. We propose that the shear-induced dehydration of the serpentine play an important role for the generation of slow earthquakes.

  2. Obsessional Slowness in College Students: Case Studies

    ERIC Educational Resources Information Center

    Johnson, Aleta

    2014-01-01

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

  3. Simple Phenomena, Slow Motion, Surprising Physics

    ERIC Educational Resources Information Center

    Koupil, Jan; Vicha, Vladimir

    2011-01-01

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

  4. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  5. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  6. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  7. Can Fast and Slow Intelligence Be Differentiated?

    ERIC Educational Resources Information Center

    Partchev, Ivailo; De Boeck, Paul

    2012-01-01

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

  8. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  9. 49 CFR 236.813 - Speed, slow.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

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

    PubMed

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

    2016-01-13

    We propose a new mechanism to achieve light localization and slow light. Through the study on the coupling of two magnetic surface modes, we find a special convex band that takes on a negative refraction effect. The negative refraction results in an energy flow concellation effect from two degenerated modes on the convex band. The energy flow concellation effect leads to forming of the self-trapped and slow light bands. In the self-trapped band light is localized around the source without reflection wall in the waveguide direction, whereas in the slow light band, light becomes the standing-waves and moving standing-waves at the center and the two sides of the waveguide, respectively. PMID:26647772

  11. Slow Movements of Bio-Inspired Limbs

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  12. Exponential estimates of symplectic slow manifolds

    NASA Astrophysics Data System (ADS)

    Kristiansen, K. U.; Wulff, C.

    2016-07-01

    In this paper we prove the existence of an almost invariant symplectic slow manifold for analytic Hamiltonian slow-fast systems with finitely many slow degrees of freedom for which the error field is exponentially small. We allow for infinitely many fast degrees of freedom. The method we use is motivated by a paper of MacKay from 2004. The method does not notice resonances, and therefore we do not pose any restrictions on the motion normal to the slow manifold other than it being fast and analytic. We also present a stability result and obtain a generalization of a result of Gelfreich and Lerman on an invariant slow manifold to (finitely) many fast degrees of freedom.

  13. Connecting slow earthquakes to huge earthquakes

    NASA Astrophysics Data System (ADS)

    Obara, Kazushige; Kato, Aitaro

    2016-07-01

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

  14. Computing Slow Manifolds of Saddle Type

    NASA Astrophysics Data System (ADS)

    Guckenheimer, John; Kuehn, Christian

    2009-01-01

    Slow manifolds are important geometric structures in the state spaces of dynamical systems with multiple time scales. This paper introduces an algorithm for computing trajectories on slow manifolds that are normally hyperbolic with both stable and unstable fast manifolds. We present two examples of bifurcation problems where these manifolds play a key role and a third example in which saddle-type slow manifolds are part of a traveling wave profile of a partial differential equation. Initial value solvers are incapable of computing trajectories on saddle-type slow manifolds, so the slow manifold of saddle type (SMST) algorithm presented here is formulated as a boundary value method. We take an empirical approach here to assessing the accuracy and effectiveness of the algorithm.

  15. Connecting slow earthquakes to huge earthquakes.

    PubMed

    Obara, Kazushige; Kato, Aitaro

    2016-07-15

    Slow earthquakes are characterized by a wide spectrum of fault slip behaviors and seismic radiation patterns that differ from those of traditional earthquakes. However, slow earthquakes and huge megathrust earthquakes can have common slip mechanisms and are located in neighboring regions of the seismogenic zone. The frequent occurrence of slow earthquakes may help to reveal the physics underlying megathrust events as useful analogs. Slow earthquakes may function as stress meters because of their high sensitivity to stress changes in the seismogenic zone. Episodic stress transfer to megathrust source faults leads to an increased probability of triggering huge earthquakes if the adjacent locked region is critically loaded. Careful and precise monitoring of slow earthquakes may provide new information on the likelihood of impending huge earthquakes. PMID:27418504

  16. Anomalously slow relaxation of interacting liquid nanoclusters confined in a porous medium

    NASA Astrophysics Data System (ADS)

    Borman, V. D.; Belogorlov, A. A.; Tronin, V. N.

    2016-02-01

    Anomalously slow relaxation of clusters of a liquid confined in a disordered system of pores has been studied for the (water-L23 nanoporous medium) system. The evolution of the system of confined liquid clusters consists of a fast formation stage followed by slow relaxation of the system and its decay. The characteristic time for the formation of the initial state is τp˜10 s after the reduction of excess pressure after complete filling. Anomalously slow relaxation has been observed for times of 101- 105 s, and decay has been observed at times of >105 s. The time dependence of the volume fraction θ of pores filled with the confined liquid is described by a power law θ ˜t-α with the exponent α <0.15 . The exponent α and temperature dependence α (T ) are qualitatively described theoretically for the case of a slightly polydisperse medium in a mean-field approximation with the inclusion of the interaction of liquid clusters and averaging over various degenerate local configurations of clusters. In this approximation, slow relaxation is represented as a continuous transition through a sequence of metastable states of the system of clusters with a decreasing barrier.

  17. [Criteria for the diagnosis of corticobasal degeneration].

    PubMed

    Shimohata, Takayoshi; Aiba, Ikuko; Nishizawa, Masatoyo

    2015-04-01

    Corticobasal degeneration (CBD) is a distinct neurodegenerative disorder characterized by widespread neuronal and glial accumulation of abnormally phosphorylated tau protein. Patients with CBD often present with corticobasal syndrome (CBS) showing impairment of the motor system, cognition, or both. Several studies demonstrate that they may also present with progressive supranuclear palsy syndrome (PSPS), aphasia, Alzheimer disease-like dementia, or behavioral changes, suggesting that CBS is merely one of the presenting phenotypes of CBD. Accurate diagnosis is important for future clinical trials using drugs aimed at modifying the underlying tau pathology. Although previous CBD diagnostic criteria reflected only CBS, Armstrong et al. proposed new diagnostic criteria for CBD in 2013 (Armstrong's criteria). The new criteria include 4 CBD phenotypes, including CBS, frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and PSPS. These phenotypes were combined to create 2 sets of criteria: specific clinical research criteria for probable CBD (cr-CBD) and broader criteria for possible CBD that are more inclusive but have a higher probability of detecting other tau-based pathologies (p-CBD). However, two recent studies revealed that the sensitivity and specificity of these criteria were insufficient. Further refinement of the criteria is needed via biomarker research with prospective study designs. (Received August 19, 2014; Accepted December 26, 2014: Published April 1, 2015). PMID:25846600

  18. Diagnoses of corticobasal syndrome and corticobasal degeneration.

    PubMed

    Shimohata, Takayoshi; Aiba, Ikuko; Nishizawa, Masatoyo

    2016-03-30

    Experts use the term corticobasal syndrome (CBS) for patients with a clinical diagnosis of corticobasal degeneration (CBD), and reserve CBD for those whose conditions have been diagnosed on the basis of neuropathological analyses. Several studies demonstrated that patients with CBD may also present with progressive supranuclear syndrome (PSPS), aphasia, Alzheimer disease-like dementia or behavioral change, suggesting that CBS is merely one of the presenting phenotypes of CBD. Although previous CBD diagnostic criteria reflected only CBS, the international consortium proposed new diagnostic criteria for CBD in 2013 (Armstrong's criteria). The new criteria include 4 CBD subtypes; CBS, frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA),and PSPS. These subtypes were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD (cr-CBD) and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies (p-CBD). Two studies have already revealed that the sensitivity and specificity of the criteria were not high. Because therapeutic interventions that target abnormally-phosphorylated tau have started, further refinement of the criteria is needed via biomarker researches with prospective study designs. PMID:26876110

  19. Age-related macular degeneration: choroidal ischaemia?

    PubMed Central

    Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul

    2013-01-01

    Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784. PMID:23740965

  20. CERKL Knockdown Causes Retinal Degeneration in Zebrafish

    PubMed Central

    Riera, Marina; Burguera, Demian; Garcia-Fernàndez, Jordi; Gonzàlez-Duarte, Roser

    2013-01-01

    The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration. PMID:23671706

  1. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  2. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  3. [Multiple system atrophy - synuclein and neuronal degeneration].

    PubMed

    Yoshida, Mari

    2011-11-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome (SDS). The histopathological hallmarks are α-synuclein (AS) positive glial cytoplasmic inclusions (GCIs) in oligodendroglias. AS aggregation is also found in glial nuclear inclusions (GNIs), neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurties. Reviewing the pathological features of 102 MSA cases, OPCA-type was relatively more frequent and SND-type was less frequent in Japanese MSA cases, which suggested different phenotypic pattern of MSA might exist between races, compared to the relatively high frequency of SND-type in western countries. In early stage of MSA, NNIs, NCIs and diffuse homogenous stain of AS in neuronal nuclei and cytoplasm were observed in various vulnerable lesions including the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of thoracic cord, lower motor neurons and cortical pyramidal neurons, in additions to GCIs. These findings indicated that the primary nonfibrillar and fibrillar AS aggregation also occurred in neurons. Therefore both the direct involvement of neurons themselves and the oligodendroglia-myelin-axon mechanism may synergistically accelerate the degenerative process of MSA. PMID:22277386

  4. Linear stochastic degenerate Sobolev equations and applications†

    NASA Astrophysics Data System (ADS)

    Liaskos, Konstantinos B.; Pantelous, Athanasios A.; Stratis, Ioannis G.

    2015-12-01

    In this paper, a general class of linear stochastic degenerate Sobolev equations with additive noise is considered. This class of systems is the infinite-dimensional analogue of linear descriptor systems in finite dimensions. Under appropriate assumptions, the mild and strong well-posedness for the initial value problem are studied using elements of the semigroup theory and properties of the stochastic convolution. The final value problem is also examined and it is proved that this is uniquely strongly solvable and the solution is continuously dependent on the final data. Based on the results of the forward and backward problem, the conditions for the exact controllability are investigated for a special but important class of these equations. The abstract results are illustrated by applications in complex media electromagnetics, in the one-dimensional stochastic Dirac equation in the non-relativistic limit and in a potential application in input-output analysis in economics. Dedicated to Professor Grigoris Kalogeropoulos on the occasion of his seventieth birthday.

  5. An Interferometric Harvest of Double Degenerates

    NASA Astrophysics Data System (ADS)

    Nelan, Edmund

    2001-07-01

    The white dwarf {WD} mass and age distributions hold clues to the star formation history of our Galaxy and the age of the disk. To extract this information we need to carefully calibrate the WD mass-radius relation and the WD cooling curve. But to do so, we must directly determine the masses for a variety of WDs of different sub-types. The only direct method is through the orbital analysis of resolved WDs in non- interacting binary systems. Sadly, this has been done, with varying quality, for only 4 WDs {40 Eri B, Sirius B, Procyon B, and Stien 2051B}, mainly because it is extremely difficult to resolve WDs in binary systems with periods less than 50 years. We propose a high angular resolution Snapshot survey with FGS1r to observe cool WDs with the objective of discovering {resolving} double degenerate systems with modest separations and periods as short as 25 years, ideal binaries for follow up mass determinations. By carefully selecting our targets, about 10 such systems should be revealed. This will dramatically increase the number of WDs available for dynamical mass measurements {its 2 for 1.}, enabling a better calibration the WD mass-radius relation.

  6. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  7. Widespread cytoskeletal pathology characterizes corticobasal degeneration.

    PubMed Central

    Feany, M. B.; Dickson, D. W.

    1995-01-01

    Corticobasal degeneration (CBD) is a rare, progressive neurological disorder characterized by widespread neuronal and glial pathology. Using immunohistochemistry and laser confocal microscopy, we demonstrate that the nonamyloid cortical plaques of CBD are actually collections of abnormal tau in the distal processes of astrocytes. These glial cells express both vimentin and CD44, markers of astrocyte activation. Glial pathology also includes tau-positive cytoplasmic inclusions, here localized to Leu 7-expressing oligodendrocytes. In addition, a wide array of neuronal pathology is defined with tau-positive inclusions in multiple domains of a variety of cortical neurons. CBD thus exhibits widespread glial and neuronal cytoskeletal pathology, including a novel structure, the astrocytic plaque. CBD is a disease of generalized cytoskeletal disruption affecting several cell types and multiple domains of these cells. The further definition of CBD pathology refines the diagnosis and pathophysiological understanding of this unique disease and has important implications for other neurodegenerative diseases, like Alzheimer's disease, characterized by abnormal tau deposition. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7778678

  8. Disruption in dopaminergic innervation during photoreceptor degeneration.

    PubMed

    Ivanova, Elena; Yee, Christopher W; Sagdullaev, Botir T

    2016-04-15

    Dopaminergic amacrine cells (DACs) release dopamine in response to light-driven synaptic inputs, and are critical to retinal light adaptation. Retinal degeneration (RD) compromises the light responsiveness of the retina and, subsequently, dopamine metabolism is impaired. As RD progresses, retinal neurons exhibit aberrant activity, driven by AII amacrine cells, a primary target of the retinal dopaminergic network. Surprisingly, DACs are an exception to this physiological change; DACs exhibit rhythmic activity in healthy retina, but do not burst in RD. The underlying mechanism of this divergent behavior is not known. It is also unclear whether RD leads to structural changes in DACs, impairing functional regulation of AII amacrine cells. Here we examine the anatomical details of DACs in three mouse models of human RD to determine how changes to the dopaminergic network may underlie physiological changes in RD. By using rd10, rd1, and rd1/C57 mice we were able to dissect the impacts of genetic background and the degenerative process on DAC structure in RD retina. We found that DACs density, soma size, and primary dendrite length are all significantly reduced. Using a novel adeno-associated virus-mediated technique to label AII amacrine cells in mouse retina, we observed diminished dopaminergic contacts to AII amacrine cells in RD mice. This was accompanied by changes to the components responsible for dopamine synthesis and release. Together, these data suggest that structural alterations of the retinal dopaminergic network underlie physiological changes during RD. PMID:26356010

  9. [Multi-infarct disorder presenting as corticobasal degeneration (DCB): vascular pseudo-corticobasal degeneration?].

    PubMed

    Kreisler, A; Mastain, B; Tison, F; Fénelon, G; Destée, A

    2007-12-01

    We report on five patients with a clinical presentation of corticobasal degeneration (CBD), including gradually progressive, asymmetric, L-DOPA-resistant parkinsonism associated variously with apraxia, focal action myoclonus, focal dystonia, cortical sensory loss and alien limb phenomenon. Some patients also presented an atypical CBD clinical history or signs - notably sudden onset. The disease was however not suggestive of another diagnosis. Magnetic resonance imaging of the brain revealed extensive vascular lesions. Only five similar cases have been published to our knowledge. Although we cannot exclude underlying CBD pathology, our cases illustrate the fact that multi-infarct pathology can masquerade as CBD or alter the clinical phenotype of the disease. PMID:18355466

  10. Pyrroloquinoline Quinone Slows Down the Progression of Osteoarthritis by Inhibiting Nitric Oxide Production and Metalloproteinase Synthesis.

    PubMed

    Tao, Ran; Wang, Shitao; Xia, Xiaopeng; Wang, Youhua; Cao, Yi; Huang, Yuejiao; Xu, Xinbao; Liu, Zhongbing; Liu, Peichao; Tang, Xiaohang; Liu, Chun; Shen, Gan; Zhang, Dongmei

    2015-08-01

    Osteoarthritis (OA) is the most common arthritis and also one of the major causes of joint pain in elderly people. The aim of this study was to investigate the effects of pyrroloquinoline quinone (PQQ) on degenerated-related changes in osteoarthritis (OA). SW1353 cells were stimulated with IL-1β to establish the chondrocyte injury model in vitro. PQQ was administrated into SW1353 cultures 1 h before IL-1β treatment. Amounts of MMP-1, MMP-13, P65, IκBα, ERK, p-ERK, P38, and p-P38 were measured via western blot. The production of NO was determined by Griess reaction assay and reflected by the iNOS level. Meniscal-ligamentous injury (MLI) was performed on 8-week-old rats to establish the OA rat model. PQQ was injected intraperitoneally 3 days before MLI and consecutively until harvest, and the arthritis cartilage degeneration level was assessed. The expressions of MMP-1 and MMP-13 were significantly downregulated after PQQ treatment compared with that in IL-1β alone group. NO production and iNOS expression were decreased by PQQ treatment compared with control group. Amounts of nucleus P65 were upregulated in SW1353 after stimulated with IL-1β, while PQQ significantly inhibited the translocation. In rat OA model, treatment with PQQ markedly decelerated the degeneration of articular cartilage. These findings suggested that PQQ could inhibit OA-related catabolic proteins MMPs expression, NO production, and thus, slow down the articular cartilage degeneration and OA progression. Owing to its beneficial effects, PQQ is expected to be a novel pharmacological application in OA clinical prevention and treatment in the near future. PMID:25687637

  11. Delivery systems for the treatment of degenerated intervertebral discs.

    PubMed

    Blanquer, S B G; Grijpma, D W; Poot, A A

    2015-04-01

    The intervertebral disc (IVD) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production, abnormal enzyme activities and production of pro-inflammatory substances like cytokines. The established treatment strategy for IVD degeneration consists of physiotherapy, pain medication by drug therapy and if necessary surgery. This approach, however, has shown limited success. Alternative strategies to increase and prolong the effects of bioactive agents and to reverse the process of IVD degeneration include the use of delivery systems for drugs, proteins, cells and genes. In view of the specific anatomy and physiology of the IVD and depending on the strategy of the therapy, different delivery systems have been developed which are reviewed in this article. PMID:25451138

  12. Construction of nonregular pointwise degenerate delay-differential systems

    NASA Technical Reports Server (NTRS)

    Choudhury, A. K.

    1978-01-01

    Pointwise degenerate delay-differential systems (degeneracy at t = 2h) are reduced to Popov's construction under the regularity assumption. Necessary and sufficient conditions for the degeneracy are outlined.

  13. Degenerate higher derivative theories beyond Horndeski: evading the Ostrogradski instability

    NASA Astrophysics Data System (ADS)

    Langlois, David; Noui, Karim

    2016-02-01

    Theories with higher order time derivatives generically suffer from ghost-like instabilities, known as Ostrogradski instabilities. This fate can be avoided by considering ``degenerate'' Lagrangians, whose kinetic matrix cannot be inverted, thus leading to constraints between canonical variables and a reduced number of physical degrees of freedom. In this work, we derive in a systematic way the degeneracy conditions for scalar-tensor theories that depend quadratically on second order derivatives of a scalar field. We thus obtain a classification of all degenerate theories within this class of scalar-tensor theories. The quartic Horndeski Lagrangian and its extension beyond Horndeski belong to these degenerate cases. We also identify new families of scalar-tensor theories with the property that they are degenerate despite the nondegeneracy of the purely scalar part of their Lagrangian.

  14. An Unusual Case of Extensive Lattice Degeneration and Retinal Detachment

    PubMed Central

    Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V.

    2016-01-01

    Lattice degeneration of the retina is not infrequently encountered on a dilated retinal examination and many of them do not need any intervention. We report a case of atypical lattice degeneration variant with peripheral retinal detachment. An asymptomatic 35-year-old lady with minimal refractive error was found to have extensive lattice degeneration, peripheral retinal detachment and fibrotic changes peripherally with elevation of retinal vessels on dilated retinal examination. There were also areas of white without pressure, chorioretinal scarring and retinal breaks. All the changes were limited to beyond the equator but were found to span 360 degrees. She was treated with barrage laser all around to prevent extension of the retinal detachment posteriorly. She remained stable till her latest follow-up two years after the barrage laser. This case is reported for its rarity with a discussion of the probable differential diagnoses. To the best of our knowledge, this is the first report of such findings in lattice degeneration.

  15. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa

    PubMed Central

    Kijas, James W.; Cideciyan, Artur V.; Aleman, Tomas S.; Pianta, Michael J.; Pearce-Kelling, Susan E.; Miller, Brian J.; Jacobson, Samuel G.; Aguirre, Gustavo D.; Acland, Gregory M.

    2002-01-01

    Rhodopsin is the G protein-coupled receptor that is activated by light and initiates the transduction cascade leading to night (rod) vision. Naturally occurring pathogenic rhodopsin (RHO) mutations have been previously identified only in humans and are a common cause of dominantly inherited blindness from retinal degeneration. We identified English Mastiff dogs with a naturally occurring dominant retinal degeneration and determined the cause to be a point mutation in the RHO gene (Thr4Arg). Dogs with this mutant allele manifest a retinal phenotype that closely mimics that in humans with RHO mutations. The phenotypic features shared by dog and man include a dramatically slowed time course of recovery of rod photoreceptor function after light exposure and a distinctive topographic pattern to the retinal degeneration. The canine disease offers opportunities to explore the basis of prolonged photoreceptor recovery after light in RHO mutations and determine whether there are links between the dysfunction and apoptotic retinal cell death. The RHO mutant dog also becomes the large animal needed for preclinical trials of therapies for a major subset of human retinopathies. PMID:11972042

  16. Slow-Slip Propagation Speeds

    NASA Astrophysics Data System (ADS)

    Rubin, A. M.; Ampuero, J.

    2007-12-01

    Combined seismic and geodetic data from subduction zones and the Salton Trough have revealed slow slip events with reasonably well-defined propagation speeds. This in turn is suggestive of a more-or-less well- defined front separating nearly locked regions outside the slipping zone from interior regions that slide much more rapidly. Such crack-like nucleation fronts arise naturally in models of rate-and-state friction for lab-like values of a/b, where a and b are the coefficients of the velocity- and state-dependence of the frictional strength (with the surface being velocity-neutral for a/b=1). If the propagating front has a quasi-steady shape, the propagation and slip speeds are kinematically tied via the local slip gradient. Given a sufficiently sharp front, the slip gradient is given dimensionally by Δτp- r/μ', where Δτp-r is the peak-to-residual stress drop at the front and μ' the effective elastic shear modulus. Rate-and-state simulations indicate that Δτp-r is given reasonably accurately by bσ\\ln(Vmaxθi/Dc), where σ is the effective normal stress, Vmax is the maximum slip speed behind the propagating front, θi is the the value of "state" ahead of the propagating front, and Dc is the characteristic slip distance for state evolution. Except for a coefficient of order unity, Δτp-r is independent of the evolution law. This leads to Vprop/Vmax ~μ'/[bσ\\ln(Vmaxθi/Dc)]. For slip speeds a few orders of magnitude above background, \\ln(Vmaxθi/Dc) can with reasonable accuracy be assigned some representative value (~4-5, for example). Subduction zone transients propagate on the order of 10 km/day or 10-1 m/s. Geodetic data constrain the average slip speed to be a few times smaller than 1 cm/day or 10-7 m/s. However, numerical models indicate that the maximum slip speed at the front may be several times larger than the average, over a length scale that is probably too small to resolve geodetically, so a representative value of Vprop/Vmax may be ~106

  17. KEK-IMSS Slow Positron Facility

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

  18. Large Deviations in Fast-Slow Systems

    NASA Astrophysics Data System (ADS)

    Bouchet, Freddy; Grafke, Tobias; Tangarife, Tomás; Vanden-Eijnden, Eric

    2016-02-01

    The incidence of rare events in fast-slow systems is investigated via analysis of the large deviation principle (LDP) that characterizes the likelihood and pathway of large fluctuations of the slow variables away from their mean behavior—such fluctuations are rare on short time-scales but become ubiquitous eventually. Classical results prove that this LDP involves an Hamilton-Jacobi equation whose Hamiltonian is related to the leading eigenvalue of the generator of the fast process, and is typically non-quadratic in the momenta—in other words, the LDP for the slow variables in fast-slow systems is different in general from that of any stochastic differential equation (SDE) one would write for the slow variables alone. It is shown here that the eigenvalue problem for the Hamiltonian can be reduced to a simpler algebraic equation for this Hamiltonian for a specific class of systems in which the fast variables satisfy a linear equation whose coefficients depend nonlinearly on the slow variables, and the fast variables enter quadratically the equation for the slow variables. These results are illustrated via examples, inspired by kinetic theories of turbulent flows and plasma, in which the quasipotential characterizing the long time behavior of the system is calculated and shown again to be different from that of an SDE.

  19. Single-degenerate Type Ia Supernovae Are Preferentially Overluminous

    NASA Astrophysics Data System (ADS)

    Fisher, Robert; Jumper, Kevin

    2015-06-01

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

  20. Degenerations of generalized Krichever-Novikov algebras on tori

    NASA Astrophysics Data System (ADS)

    Schlichenmaier, Martin

    1993-08-01

    Degenerations of Lie algebras of meromorphic vector fields on elliptic curves (i.e., complex tori) which are holomorphic outside a certain set of points (markings) are studied. By an algebraic geometric degeneration process certain subalgebras of Lie algebras of meromorphic vector fields on P1, the Riemann sphere, are obtained. In case of some natural choices of the markings these subalgebras are explicitly determined. It is shown that the number of markings can change.

  1. Simulation of biological therapies for degenerated intervertebral discs.

    PubMed

    Zhu, Qiaoqiao; Gao, Xin; Temple, H Thomas; Brown, Mark D; Gu, Weiyong

    2016-04-01

    The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three-dimensional finite element model based on a cell-activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies-increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)-to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long-term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:699-708, 2016. PMID:26425965

  2. Distinct optical properties of relativistically degenerate matter

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2014-06-01

    In this paper, we use the collisional quantum magnetohydrodynamic (CQMHD) model to derive the transverse dielectric function of a relativistically degenerate electron fluid and investigate various optical parameters, such as the complex refractive index, the reflection and absorption coefficients, the skin-depth and optical conductivity. In this model we take into accounts effects of many parameters such as the atomic-number of the constituent ions, the electron exchange, electron diffraction effect and the electron-ion collisions. Study of the optical parameters in the solid-density, the warm-dense-matter, the big-planetary core, and the compact star number-density regimes reveals that there are distinct differences between optical characteristics of the latter and the former cases due to the fundamental effects of the relativistic degeneracy and other quantum mechanisms. It is found that in the relativistic degeneracy plasma regime, such as found in white-dwarfs and neutron star crusts, matter possess a much sharper and well-defined step-like reflection edge beyond the x-ray electromagnetic spectrum, including some part of gamma-ray frequencies. It is also remarked that the magnetic field intensity only significantly affects the plasma reflectivity in the lower number-density regime, rather than the high density limit. Current investigation confirms the profound effect of relativistic degeneracy on optical characteristics of matter and can provide an important plasma diagnostic tool for studying the physical processes within the wide scope of quantum plasma regimes be it the solid-density, inertial-confined, or astrophysical compact stars.

  3. Frontotemporal Lobar Degeneration and MicroRNAs

    PubMed Central

    Piscopo, Paola; Albani, Diego; Castellano, Anna E.; Forloni, Gianluigi; Confaloni, Annamaria

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) includes a spectrum of disorders characterized by changes of personality and social behavior and, often, a gradual and progressive language dysfunction. In the last years, several efforts have been fulfilled in identifying both genetic mutations and pathological proteins associated with FTLD. The molecular bases undergoing the onset and progression of the disease remain still unknown. Recent literature prompts an involvement of RNA metabolism in FTLD, particularly microRNAs (miRNAs). Dysregulation of miRNAs in several disorders, including neurodegenerative diseases, and increasing importance of circulating miRNAs in different pathologies has suggested to implement the study of their possible application as biological markers and new therapeutic targets; moreover, miRNA-based therapy is becoming a powerful tool to deepen the function of a gene, the mechanism of a disease, and validate therapeutic targets. Regarding FTLD, different studies showed that miRNAs are playing an important role. For example, several reports have evaluated miRNA regulation of the progranulin gene suggesting that it is under their control, as described for miR-29b, miR-107, and miR-659. More recently, it has been demonstrated that TMEM106B gene, which protein is elevated in FTLD-TDP brains, is repressed by miR-132/212 cluster; this post-transcriptional mechanism increases intracellular levels of progranulin, affecting its pathways. These findings if confirmed could suggest that these microRNAs have a role as potential targets for some related-FTLD genes. In this review, we focus on the emerging roles of the miRNAs in the pathogenesis of FTLD. PMID:26903860

  4. Distinct optical properties of relativistically degenerate matter

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2014-06-15

    In this paper, we use the collisional quantum magnetohydrodynamic (CQMHD) model to derive the transverse dielectric function of a relativistically degenerate electron fluid and investigate various optical parameters, such as the complex refractive index, the reflection and absorption coefficients, the skin-depth and optical conductivity. In this model we take into accounts effects of many parameters such as the atomic-number of the constituent ions, the electron exchange, electron diffraction effect and the electron-ion collisions. Study of the optical parameters in the solid-density, the warm-dense-matter, the big-planetary core, and the compact star number-density regimes reveals that there are distinct differences between optical characteristics of the latter and the former cases due to the fundamental effects of the relativistic degeneracy and other quantum mechanisms. It is found that in the relativistic degeneracy plasma regime, such as found in white-dwarfs and neutron star crusts, matter possess a much sharper and well-defined step-like reflection edge beyond the x-ray electromagnetic spectrum, including some part of gamma-ray frequencies. It is also remarked that the magnetic field intensity only significantly affects the plasma reflectivity in the lower number-density regime, rather than the high density limit. Current investigation confirms the profound effect of relativistic degeneracy on optical characteristics of matter and can provide an important plasma diagnostic tool for studying the physical processes within the wide scope of quantum plasma regimes be it the solid-density, inertial-confined, or astrophysical compact stars.

  5. Dystonia Associated with Idiopathic Slow Orthostatic Tremor

    PubMed Central

    Kobylecki, Christopher; Silverdale, Monty A.; Dick, Jeremy P. R.; Kellett, Mark W.; Marshall, Andrew G.

    2015-01-01

    Background We aimed to characterize the clinical and electrophysiological features of patients with slow orthostatic tremor. Case Report The clinical and neurophysiological data of patients referred for lower limb tremor on standing were reviewed. Patients with symptomatic or primary orthostatic tremor were excluded. Eight patients were identified with idiopathic slow 4–8 Hz orthostatic tremor, which was associated with tremor and dystonia in cervical and upper limb musculature. Coherence analysis in two patients showed findings different to those seen in primary orthostatic tremor. Discussion Slow orthostatic tremor may be associated with dystonia and dystonic tremor. PMID:26877891

  6. Gene expression profile analysis of human intervertebral disc degeneration

    PubMed Central

    Chen, Kai; Wu, Dajiang; Zhu, Xiaodong; Ni, Haijian; Wei, Xianzhao; Mao, Ningfang; Xie, Yang; Niu, Yunfei; Li, Ming

    2013-01-01

    In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were significantly overexpressed in more degenerated discs with a false discovery rate of < 3%. Functional annotation showed that these genes were significantly associated with membrane-bound vesicles, calcium ion binding and extracellular matrix. Protein-protein interaction analysis showed that these genes, including previously reported genes such as fibronectin, COL2A1 and β-catenin, may play key roles in disc degeneration. Unsupervised clustering indicated that the widely used morphology-based Thompson grading system was only marginally associated with the molecular classification of intervertebral disc degeneration. These findings indicate that detailed, systematic gene analysis may be a useful way of studying the biology of intervertebral disc degeneration. PMID:24130454

  7. N -methyl- N -nitrosourea-induced retinal degeneration in mice.

    PubMed

    Chen, Yuan-Yuan; Liu, Shi-Liang; Hu, Dan-Ping; Xing, Yi-Qiao; Shen, Yin

    2014-04-01

    Mouse retinal degeneration models have been investigated for many years in the hope of understanding the mechanism of photoreceptor cell death. N -methyl- N -nitrosourea (MNU) has been previously shown to induce outer retinal degeneration in mice. After MNU was intraperitoneally injected in C57/BL mice, we observed a gradual decrease in the outer nuclear layer (ONL) thickness associated with photoreceptor outer segment loss, bipolar cell dendritic retraction and reactive gliosis. Reactive gliosis was confirmed by increased GFAP protein levels. More serious damage to the central retina as opposed to the peripheral retina was found in the MNU-induced retinal degeneration model. Retinal ganglion cells (RGC) appear to be spared for at least two months after MNU treatment. Following retinal vessel labelling, we observed vascular complexes in the distal vessels, indicating retinal vessel damage. In the remnant retinal photoreceptor of the MNU-treated mouse, concentrated colouring nuclei were detected by electron microscopy, together with the loss of mitochondria and displaced remnant synaptic ribbons in the photoreceptor. We also observed decreased mitochondrial protein levels and increased amounts of nitrosylation/nitration in the photoreceptors. The mechanism of MNU-induced apoptosis may result from oxidative stress or the loss of retinal blood supply. MNU-induced mouse retinal degeneration in the outer retina is a useful animal model for photoreceptor degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). PMID:24509257

  8. Development of Animal Models of Local Retinal Degeneration

    PubMed Central

    Lorach, Henri; Kung, Jennifer; Beier, Corinne; Mandel, Yossi; Dalal, Roopa; Huie, Philip; Wang, Jenny; Lee, Seungjun; Sher, Alexander; Jones, Bryan William; Palanker, Daniel

    2015-01-01

    Purpose Development of nongenetic animal models of local retinal degeneration is essential for studies of retinal pathologies, such as chronic retinal detachment or age-related macular degeneration. We present two different methods to induce a highly localized retinal degeneration with precise onset time, that can be applied to a broad range of species in laboratory use. Methods A 30-μm thin polymer sheet was implanted subretinally in wild-type (WT) rats. The effects of chronic retinal separation from the RPE were studied using histology and immunohistochemistry. Another approach is applicable to species with avascular retina, such as rabbits, where the photoreceptors and RPE were thermally ablated over large areas, using a high power scanning laser. Results Photoreceptors above the subretinal implant in rats degenerated over time, with 80% of the outer nuclear layer disappearing within a month, and the rest by 3 months. Similar loss was obtained by selective photocoagulation with a scanning laser. Cells in the inner nuclear layer and ganglion cell layer were preserved in both cases. However, there were signs of rewiring and decrease in the size of the bipolar cell terminals in the damaged areas. Conclusions Both methods induce highly reproducible degeneration of photoreceptors over a defined area, with complete preservation of the inner retinal neurons during the 3-month follow-up. They provide a reliable platform for studies of local retinal degeneration and development of therapeutic strategies in a wide variety of species. PMID:26207299

  9. PILOT PLANT EXPLORATION OF SLOW RATE FILTRATION

    EPA Science Inventory

    Alternatives to conventional coagulation water filtration plants (those that utilize coagulation, flocculation, sedimentation and filtration) may be appropriate for some small water utilities. One such alternative is slow rate filtration. This paper describes pilot plant studies ...

  10. Should the "slow code" be resuscitated?

    PubMed

    Lantos, John D; Meadow, William L

    2011-11-01

    Most bioethicists and professional medical societies condemn the practice of "slow codes." The American College of Physicians ethics manual states, "Because it is deceptive, physicians or nurses should not perform half-hearted resuscitation efforts ('slow codes')." A leading textbook calls slow codes "dishonest, crass dissimulation, and unethical." A medical sociologist describes them as "deplorable, dishonest and inconsistent with established ethical principles." Nevertheless, we believe that slow codes may be appropriate and ethically defensible in situations in which cardiopulmonary resuscitation (CPR) is likely to be ineffective, the family decision makers understand and accept that death is inevitable, and those family members cannot bring themselves to consent or even assent to a do-not-resuscitate (DNR) order. In such cases, we argue, physicians may best serve both the patient and the family by having a carefully ambiguous discussion about end-of-life options and then providing resuscitation efforts that are less vigorous or prolonged than usual. PMID:22047113

  11. Teaching the Third World to Slow Learners.

    ERIC Educational Resources Information Center

    Clabrough, Peter

    1978-01-01

    Describes a simulation game about the third world which can be valuable to slow learners because it enables them to acquire abstract concepts using a concrete method (induction). For journal availability, see SO 507 289. (Author/CK)

  12. Experimental demonstration of spinor slow light

    NASA Astrophysics Data System (ADS)

    Lee, Meng-Jung; Ruseckas, Julius; Lee, Chin-Yuan; Kudriašov, Viačeslav; Chang, Kao-Fang; Cho, Hung-Wen; JuzeliÅ«nas, Gediminas; Yu, Ite A.

    2016-03-01

    Over the last decade there has been a continuing interest in slow and stored light based on the electromagnetically induced transparency (EIT) effect, because of their potential applications in quantum information manipulation. However, previous experimental works all dealt with the single-component slow light which cannot be employed as a qubit. In this work, we report the first experimental demonstration of two-component or spinor slow light (SSL) using a double tripod (DT) atom-light coupling scheme. The oscillations between the two components, similar to the Rabi oscillation of a two-level system or a qubit, were observed. Single-photon SSL can be considered as two-color qubits. We experimentally demonstrated a possible application of the DT scheme as quantum memory and quantum rotator for the two-color qubits. This work opens up a new direction in the slow light research.

  13. Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration.

    PubMed

    Karan, G; Lillo, C; Yang, Z; Cameron, D J; Locke, K G; Zhao, Y; Thirumalaichary, S; Li, C; Birch, D G; Vollmer-Snarr, H R; Williams, D S; Zhang, K

    2005-03-15

    Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness. PMID:15749821

  14. Tyro3 Modulates Mertk-Associated Retinal Degeneration

    PubMed Central

    Vollrath, Douglas; Yasumura, Douglas; Benchorin, Gillie; Matthes, Michael T.; Feng, Wei; Nguyen, Natalie M.; Sedano, Cecilia D.; Calton, Melissa A.; LaVail, Matthew M.

    2015-01-01

    Inherited photoreceptor degenerations (IPDs) are the most genetically heterogeneous of Mendelian diseases. Many IPDs exhibit substantial phenotypic variability, but the basis is usually unknown. Mutations in MERTK cause recessive IPD phenotypes associated with the RP38 locus. We have identified a murine genetic modifier of Mertk-associated photoreceptor degeneration, the C57BL/6 (B6) allele of which acts as a suppressor. Photoreceptors degenerate rapidly in Mertk-deficient animals homozygous for the 129P2/Ola (129) modifier allele, whereas animals heterozygous for B6 and 129 modifier alleles exhibit an unusual intermixing of degenerating and preserved retinal regions, with females more severely affected than males. Mertk-deficient mice homozygous for the B6 modifier allele display degeneration only in the far periphery, even at 8 months of age, and have improved retinal function compared to animals homozygous for the 129 allele. We genetically mapped the modifier to an approximately 2-megabase critical interval that includes Tyro3, a paralog of Mertk. Tyro3 expression in the outer retina varies with modifier genotype in a manner characteristic of a cis-acting expression quantitative trait locus (eQTL), with the B6 allele conferring an approximately three-fold higher expression level. Loss of Tyro3 function accelerates the pace of photoreceptor degeneration in Mertk knockout mice, and TYRO3 protein is more abundant in the retinal pigment epithelium (RPE) adjacent to preserved central retinal regions of Mertk knockout mice homozygous for the B6 modifier allele. Endogenous human TYRO3 protein co-localizes with nascent photoreceptor outer segment (POS) phagosomes in a primary RPE cell culture assay, and expression of murine Tyro3 in cultured cells stimulates phagocytic ingestion of POS. Our findings demonstrate that Tyro3 gene dosage modulates Mertk-associated retinal degeneration, provide strong evidence for a direct role for TYRO3 in RPE phagocytosis, and suggest

  15. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

    PubMed Central

    2014-01-01

    Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3–7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6–8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies. PMID:24387033

  16. BMP-2 and BMP-2/7 Heterodimers Conjugated to a Fibrin/Hyaluronic Acid Hydrogel in a Large Animal Model of Mild Intervertebral Disc Degeneration.

    PubMed

    Peeters, Mirte; Detiger, Suzanne E L; Karfeld-Sulzer, Lindsay S; Smit, Theo H; Yayon, Avner; Weber, Franz E; Helder, Marco N

    2015-01-01

    Intervertebral disc (IVD) degeneration is etiologically associated with low back pain and is currently only treated in severe cases with spinal fusion. Regenerative medicine attempts to restore degenerated tissue by means of cells, hydrogels, and/or growth factors and can therefore be used to slow, halt, or reverse the degeneration of the IVD in a minimally invasive manner. Previously, the growth factors bone morphogenetic proteins 2 and 7 (BMP-2, -7) were shown to enhance disc regeneration, in vitro and in vivo. Since BMPs have only a short in vivo half-life, and to prevent heterotopic ossification, we evaluated the use of a slow release system for BMP-2 homodimers and BMP-2/7 heterodimers for IVD regeneration. BMP growth factors were conjugated to a fibrin/hyaluronic acid (FB/HA) hydrogel and intradiscally injected in a goat model of mild IVD degeneration to study safety and efficacy. Mild degeneration was induced in five lumbar discs of seven adult Dutch milk goats, by injections with the enzyme chondroitinase ABC. After 12 weeks, discs were treated with either FB/HA-hydrogel only or supplemented with 1 or 5 μg/mL of BMP-2 or BMP-2/7. BMPs were linked to the FB/HA hydrogels using a transglutaminase moiety, to be released through an incorporated plasmin cleavage site. After another 12 weeks, goats were sacrificed and discs were assessed using radiography, MRI T2* mapping, and biochemical and histological analyses. All animals maintained weight throughout the study and no heterotopic bone formation or other adverse effects were noted during follow-up. Radiographs showed significant disc height loss upon induction of mild degeneration. MRI T2* mapping showed strong and significant correlations with biochemistry and histology as shown before. Surprisingly, no differences could be demonstrated in any parameter between intervention groups. To our knowledge, this is the first large animal study evaluating BMPs conjugated to an FB/HA-hydrogel for the treatment of

  17. BMP-2 and BMP-2/7 Heterodimers Conjugated to a Fibrin/Hyaluronic Acid Hydrogel in a Large Animal Model of Mild Intervertebral Disc Degeneration

    PubMed Central

    Peeters, Mirte; Detiger, Suzanne E.L.; Karfeld-Sulzer, Lindsay S.; Smit, Theo H.; Yayon, Avner; Weber, Franz E.; Helder, Marco N.

    2015-01-01

    Abstract Intervertebral disc (IVD) degeneration is etiologically associated with low back pain and is currently only treated in severe cases with spinal fusion. Regenerative medicine attempts to restore degenerated tissue by means of cells, hydrogels, and/or growth factors and can therefore be used to slow, halt, or reverse the degeneration of the IVD in a minimally invasive manner. Previously, the growth factors bone morphogenetic proteins 2 and 7 (BMP-2, -7) were shown to enhance disc regeneration, in vitro and in vivo. Since BMPs have only a short in vivo half-life, and to prevent heterotopic ossification, we evaluated the use of a slow release system for BMP-2 homodimers and BMP-2/7 heterodimers for IVD regeneration. BMP growth factors were conjugated to a fibrin/hyaluronic acid (FB/HA) hydrogel and intradiscally injected in a goat model of mild IVD degeneration to study safety and efficacy. Mild degeneration was induced in five lumbar discs of seven adult Dutch milk goats, by injections with the enzyme chondroitinase ABC. After 12 weeks, discs were treated with either FB/HA-hydrogel only or supplemented with 1 or 5 μg/mL of BMP-2 or BMP-2/7. BMPs were linked to the FB/HA hydrogels using a transglutaminase moiety, to be released through an incorporated plasmin cleavage site. After another 12 weeks, goats were sacrificed and discs were assessed using radiography, MRI T2* mapping, and biochemical and histological analyses. All animals maintained weight throughout the study and no heterotopic bone formation or other adverse effects were noted during follow-up. Radiographs showed significant disc height loss upon induction of mild degeneration. MRI T2* mapping showed strong and significant correlations with biochemistry and histology as shown before. Surprisingly, no differences could be demonstrated in any parameter between intervention groups. To our knowledge, this is the first large animal study evaluating BMPs conjugated to an FB/HA-hydrogel for the

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

    PubMed Central

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

    2014-01-01

    Retinal degeneration slow (RDS/PRPH2) is critical for the formation of the disc/lamella rim in photoreceptor outer segments (OSs), but plays a different role in rods vs. cones. Without RDS, rods fail to form OSs, however, cones lacking RDS (in the rds−/−/Nrl−/−) exhibit balloon-like OSs devoid of lamellae. We show that distribution of most proteins in the lamella and PM domains is preserved even in the absence of RDS, rim, and lamella structures. However, the rim protein prominin-1 exhibits altered trafficking and OS localization, suggesting that proper targeting and distribution of rim proteins may require RDS. Our ultrastructural studies show that in cones, OS formation is initiated by the growth of opsin-containing membrane with RDS-mediated rim formation as a secondary step. This is directly opposite to rods and significantly advances our understanding of the role of the rim in cone OS morphogenesis. Furthermore, our results suggest that the unique folded lamella architecture of the cone OS may maximize density or proximity of phototransduction proteins, but is not required for OS function or for protein distribution and retention in different membrane domains.—Conley, S. M., Al-Ubaidi, M. R., Han, Z., Naash, M. I. Rim formation is not a prerequisite for distribution of cone photoreceptor outer segment proteins. PMID:24736412

  19. Slow slip and the transition from fast to slow fronts in the rupture of frictional interfaces

    PubMed Central

    Trømborg, Jørgen Kjoshagen; Sveinsson, Henrik Andersen; Scheibert, Julien; Thøgersen, Kjetil; Amundsen, David Skålid; Malthe-Sørenssen, Anders

    2014-01-01

    The failure of the population of microjunctions forming the frictional interface between two solids is central to fields ranging from biomechanics to seismology. This failure is mediated by the propagation along the interface of various types of rupture fronts, covering a wide range of velocities. Among them are the so-called slow fronts, which are recently discovered fronts much slower than the materials’ sound speeds. Despite intense modeling activity, the mechanisms underlying slow fronts remain elusive. Here, we introduce a multiscale model capable of reproducing both the transition from fast to slow fronts in a single rupture event and the short-time slip dynamics observed in recent experiments. We identify slow slip immediately following the arrest of a fast front as a phenomenon sufficient for the front to propagate further at a much slower pace. Whether slow fronts are actually observed is controlled both by the interfacial stresses and by the width of the local distribution of forces among microjunctions. Our results show that slow fronts are qualitatively different from faster fronts. Because the transition from fast to slow fronts is potentially as generic as slow slip, we anticipate that it might occur in the wide range of systems in which slow slip has been reported, including seismic faults. PMID:24889640

  20. Slow slip and the transition from fast to slow fronts in the rupture of frictional interfaces.

    PubMed

    Trømborg, Jørgen Kjoshagen; Sveinsson, Henrik Andersen; Scheibert, Julien; Thøgersen, Kjetil; Amundsen, David Skålid; Malthe-Sørenssen, Anders

    2014-06-17

    The failure of the population of microjunctions forming the frictional interface between two solids is central to fields ranging from biomechanics to seismology. This failure is mediated by the propagation along the interface of various types of rupture fronts, covering a wide range of velocities. Among them are the so-called slow fronts, which are recently discovered fronts much slower than the materials' sound speeds. Despite intense modeling activity, the mechanisms underlying slow fronts remain elusive. Here, we introduce a multiscale model capable of reproducing both the transition from fast to slow fronts in a single rupture event and the short-time slip dynamics observed in recent experiments. We identify slow slip immediately following the arrest of a fast front as a phenomenon sufficient for the front to propagate further at a much slower pace. Whether slow fronts are actually observed is controlled both by the interfacial stresses and by the width of the local distribution of forces among microjunctions. Our results show that slow fronts are qualitatively different from faster fronts. Because the transition from fast to slow fronts is potentially as generic as slow slip, we anticipate that it might occur in the wide range of systems in which slow slip has been reported, including seismic faults. PMID:24889640

  1. Transplantation and Stem Cell Therapy for Cerebellar Degenerations.

    PubMed

    Cendelin, Jan

    2016-02-01

    Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration. PMID:26155762

  2. Human Annulus Fibrosus Dynamic Tensile Modulus Increases with Degeneration.

    PubMed

    Sen, Sounok; Jacobs, Nathan T; Boxberger, John I; Elliott, Dawn M

    2012-01-01

    The annulus fibrosus (AF) of the intervertebral disc experiences cyclic tensile loading in vivo at various states of mechanical equilibrium. Disc degeneration is associated with alterations in the biochemical composition of the AF including decreased water content, decreased proteoglycan concentration, and increased collagen deposition that affect mechanical function of the AF in compression and shear. Such changes may also affect the dynamic viscoelastic properties of the AF and thus alter the disc's ability to dissipate energy under physiologic loading. The objectives of this study were to quantify the dynamic viscoelastic properties of human AF in circumferential tension and to determine the effect of degeneration on these properties. Nondegenerated and degenerated human AF tensile samples were tested in uniaxial tension over a spectrum of loading frequencies spanning 0.01Hz to 2Hz at several states of equilibrium strain to determine the dynamic viscoelastic properties (dynamic modulus, phase angle) using a linear viscoelastic model. The AF dynamic modulus increased at higher equilibrium strain levels. The AF behaved more elastically at higher frequencies with a decreased phase angle. Degeneration resulted in a higher dynamic modulus at all strain levels but had no effect on phase angle. The findings from this study elucidate the effect of degeneration on the dynamic viscoelastic properties of human AF and lend insight into the mechanical role of the AF in cyclic loading conditions. PMID:22247579

  3. Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

    PubMed Central

    Vasiliadis, Elias S; Pneumaticos, Spyros G; Evangelopoulos, Demitrios S; Papavassiliou, Athanasios G

    2014-01-01

    Disc degeneration is the most common cause of back pain in adults and has enormous socioeconomic implications. Conservative management is ineffective in most cases, and results of surgical treatment have not yet reached desirable standards. Biologic treatment options are an alternative to the above conventional management and have become very attractive in recent years. The present review highlights the currently available biologic treatment options in mild and moderate disc degeneration, where a potential for regeneration still exists. Biologic treatment options include protein-based and cell-based therapies. Protein-based therapies involve administration of biologic factors into the intervertebral disc to enhance matrix synthesis, delay degeneration or impede inflammation. These factors can be delivered by an intradiscal injection, alone or in combination with cells or tissue scaffolds and by gene therapy. Cell-based therapies comprise treatment strategies that aim to either replace necrotic or apoptotic cells, or minimize cell death. Cell-based therapies are more appropriate in moderate stages of degenerated disc disease, when cell population is diminished; therefore, the effect of administration of growth factors would be insufficient. Although clinical application of biologic treatments is far from being an everyday practice, the existing studies demonstrate promising results that will allow the future design of more sophisticated methods of biologic intervention to treat intervertebral disc degeneration. PMID:25171110

  4. RADIOLOGICAL ANALYSIS OF EXPERIMENTAL DISC DEGENERATION IN RABBITS

    PubMed Central

    Vialle, Emiliano; Vialle, Luiz Roberto; Arruda, André de Oliveira; Riet, Ricardo Nascimento; Krieger, Antônio Bernardo de Queiroz

    2015-01-01

    Objective: To validate radiographic evaluation of a rabbit model for disc degeneration. Methods: Lumbar intervertebral discs of New Zealand rabbits were stabbed three times with a 18G needle at a limited depth of 5mm, through lateral approach. Serial radiographic images were taken on the early pre-and postoperative periods, and after four, eight and 12 weeks of the procedure, with subsequent analysis of disc height, osteophyte formation, endplate sclerosis, and presence of disc degeneration. The statistical analysis of data was validated by the Kappa coefficient, with a confidence interval (CI) of 95%. Results: A significant reduction of disc space was found on AP X-ray images after 12 postoperative weeks, with Kappa = 0.489 for CI 95% (0.25-0.72) with p < 0.001. X-ray signs of disc degeneration also presented Kappa = 0.63 for CI 95% (0.39-0.86) with p < 0.001. The remaining assessed criteria showed positive results, but with a lower Kappa value. Conclusion: The disc degeneration model using rabbits as proposed in this study was shown to be feasible, with positive X-ray correlation between pre- and postoperative images, validating the potential to induce disc degeneration in this animal model for future studies. PMID:27022512

  5. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  6. Global network of slow solar wind

    NASA Astrophysics Data System (ADS)

    Crooker, N. U.; Antiochos, S. K.; Zhao, X.; Neugebauer, M.

    2012-04-01

    The streamer belt region surrounding the heliospheric current sheet (HCS) is generally treated as the primary or sole source of the slow solar wind. Synoptic maps of solar wind speed predicted by the Wang-Sheeley-Arge model during selected periods of solar cycle 23, however, show many areas of slow wind displaced from the streamer belt. These areas commonly have the form of an arc that is connected to the streamer belt at both ends. The arcs mark the boundaries between fields emanating from different coronal holes of the same polarity and thus trace the paths of belts of pseudostreamers, i.e., unipolar streamers that form over double arcades and lack current sheets. The arc pattern is consistent with the predicted topological mapping of the narrow open corridor or singular separator line that must connect the holes and, thus, consistent with the separatrix-web model of the slow solar wind. Near solar maximum, pseudostreamer belts stray far from the HCS-associated streamer belt and, together with it, form a global-wide web of slow wind. Recognition of pseudostreamer belts as prominent sources of slow wind provides a new template for understanding solar wind stream structure, especially near solar maximum.

  7. Global Network of Slow Solar Wind

    NASA Technical Reports Server (NTRS)

    Crooker, N. U.; Antiochos, S. K.; Zhao, X.; Neugebauer, M.

    2012-01-01

    The streamer belt region surrounding the heliospheric current sheet (HCS) is generally treated as the primary or sole source of the slow solar wind. Synoptic maps of solar wind speed predicted by the Wang-Sheeley-Arge model during selected periods of solar cycle 23, however, show many areas of slow wind displaced from the streamer belt. These areas commonly have the form of an arc that is connected to the streamer belt at both ends. The arcs mark the boundaries between fields emanating from different coronal holes of the same polarity and thus trace the paths of belts of pseudostreamers, i.e., unipolar streamers that form over double arcades and lack current sheets. The arc pattern is consistent with the predicted topological mapping of the narrow open corridor or singular separator line that must connect the holes and, thus, consistent with the separatrix-web model of the slow solar wind. Near solar maximum, pseudostreamer belts stray far from the HCS-associated streamer belt and, together with it, form a global-wide web of slow wind. Recognition of pseudostreamer belts as prominent sources of slow wind provides a new template for understanding solar wind stream structure, especially near solar maximum.

  8. Topological Origins of the Slow Solar Wind

    NASA Technical Reports Server (NTRS)

    Antiochos, Spiro

    2008-01-01

    Although the slow solar wind has been studied for decades with both in situ and remote sensing observations, its origin is still a matter of intense debate. In the standard quasi-steady model, the slow wind is postulated to originate near coronal hole boundaries that define topologically well-behaved separatrices between open and closed field regions. In the interchange model, on the other hand, the slow wind is postulated to originate on open flux that is dynamically diffusing throughout the seemingly closed-field corona. We argue in favor of the quasi-steady scenario and propose that the slow wind is due to two effects: First, the open-closed boundary is highly complex due to the complexity of the photospheric flux distribution. Second, this boundary is continuously driven by the transport of magnetic helicity from the closed field region into the open. The implications of this model for the structure and dynamics of the corona and slow wind are discussed, and observational tests of the mode

  9. Slow phase hemolysis in hypotonic electrolyte solutions.

    PubMed

    Chan, T K; LaCelle, P L; Weed, R I

    1975-02-01

    When a population of erythrocytes is partially hemolyzed the time course of hemolysis can be divided into a fast phase and a slow phase. The slow phase occurs with both rapid and gradual addition of the hypotonic medium (rapid and gradual hemolysis). There is no difference in the osmotic fragility of erythrocytes remaining at 60 minutes after rapid or gradual hemolysis. Erythrocytes near their critical hemolytic volume have an equimolar ouabaininsensitive sodium-potassium exchange. Critical non-hemolytic swelling with resulting stress on the membrane appears requisite to slow phase hemolysis since more non-penetrant sucrose is required to prevent slow phase lysis rather than that which would be predicted from the intracellular colloid osmotic pressure due to hemoglobin. Sucrose protection from slow phase hemolysis thus depends not only on counter-balancing the colloid osmotic pressure, but also removal of sufficient intracellular water to prevent critical membrane strain. This model is consistent with that proposed by Katchalsky. Irreversible membrane changes associated with hypotonic stress manifested by persistent stomatocytic shape change and membrane wrinkling on return of cells to isotonicity appear to be due to critical changes in membrane components. Such cells, having normal indices and specific gravity are less deformable than control cells in 2.8 mum pore size polycarbonate filters. PMID:1110261

  10. Autophagy: A double-edged sword in intervertebral disk degeneration.

    PubMed

    Zhang, Shu-Jun; Yang, Wei; Wang, Cheng; He, Wen-Si; Deng, Hai-Yang; Yan, Yi-Guo; Zhang, Jian; Xiang, Yong-Xiao; Wang, Wen-Jun

    2016-06-01

    Autophagy is a homeostatic mechanism through which intracellular damaged organelles and proteins are degraded and recycled in response to increased metabolic demands or stresses. Although primarily cytoprotective, dysfunction of autophagy is often associated with many degenerative diseases, including intervertebral disc (IVD) degeneration (IDD). As a main contributing factor to low back pain, IDD is the pathological basis for various debilitating spinal diseases. Either higher or lower levels of autophagy are observed in degenerative IVD cells. Despite the precise role of autophagy in disc degeneration that is still controversial, with difference from protection to aggravation, targeting autophagy has shown promise for mitigating disc degeneration. In the current review, we summarize the changes of autophagy in degenerative IVD cells and mainly discuss the relationship between autophagy and IDD. With continued efforts, modulation of the autophagic process could be a potential and attractive therapeutic strategy for degenerative disc disease. PMID:27018178

  11. Reprogramming of adult rod photoreceptors prevents retinal degeneration

    PubMed Central

    Montana, Cynthia L.; Kolesnikov, Alexander V.; Shen, Susan Q.; Myers, Connie A.; Kefalov, Vladimir J.; Corbo, Joseph C.

    2013-01-01

    A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rod-specific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration. PMID:23319618

  12. Molecular mechanisms of cell death in intervertebral disc degeneration (Review)

    PubMed Central

    ZHANG, FAN; ZHAO, XUELING; SHEN, HONGXING; ZHANG, CAIGUO

    2016-01-01

    Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration. PMID:27121482

  13. Synaptic remodeling of neuronal circuits in early retinal degeneration

    PubMed Central

    Soto, Florentina; Kerschensteiner, Daniel

    2015-01-01

    Photoreceptor degenerations are a major cause of blindness and among the most common forms of neurodegeneration in humans. Studies of mouse models revealed that synaptic dysfunction often precedes photoreceptor degeneration, and that abnormal synaptic input from photoreceptors to bipolar cells causes circuits in the inner retina to become hyperactive. Here, we provide a brief overview of frequently used mouse models of photoreceptor degenerations. We then discuss insights into circuit remodeling triggered by early synaptic dysfunction in the outer and hyperactivity in the inner retina. We discuss these insights in the context of other experimental manipulations of synaptic function and activity. Knowledge of the plasticity and early remodeling of retinal circuits will be critical for the design of successful vision rescue strategies. PMID:26500497

  14. Molecular mechanisms of cell death in intervertebral disc degeneration (Review).

    PubMed

    Zhang, Fan; Zhao, Xueling; Shen, Hongxing; Zhang, Caiguo

    2016-06-01

    Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration. PMID:27121482

  15. Wallerian degeneration: an emerging axon death pathway linking injury and disease.

    PubMed

    Conforti, Laura; Gilley, Jonathan; Coleman, Michael P

    2014-06-01

    Axon degeneration is a prominent early feature of most neurodegenerative disorders and can also be induced directly by nerve injury in a process known as Wallerian degeneration. The discovery of genetic mutations that delay Wallerian degeneration has provided insight into mechanisms underlying axon degeneration in disease. Rapid Wallerian degeneration requires the pro-degenerative molecules SARM1 and PHR1. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is essential for axon growth and survival. Its loss from injured axons may activate Wallerian degeneration, whereas NMNAT overexpression rescues axons from degeneration. Here, we discuss the roles of these and other proposed regulators of Wallerian degeneration, new opportunities for understanding disease mechanisms and intriguing links between Wallerian degeneration, innate immunity, synaptic growth and cell death. PMID:24840802

  16. A novel mutation in Prph2, a gene regulated by Nr2e3, causes retinal degeneration and outer segment defects similar to Nr2e3rd7/rd7 retinas

    PubMed Central

    Nystuen, Arne M.; Sachs, Andrew J.; Yuan, Yang; Heuermann, Laura; Haider, Neena B.

    2014-01-01

    The nmf193 mutant was generated by a large-scale ENU mutagenesis screen and originally described as having a dominantly inherited phenotype characterized by fundus abnormalities. We determined that nmf193 mice exhibit outer segment defects and progressive retinal degeneration. Clinical examination revealed retinal spotting apparent at 6 weeks of age. Histological analysis of homozygous mutant mice at 6 weeks indicated an absence of outer segments (OS) and a 50% reduction of photoreceptor cells which progressed to complete loss of photoreceptors by 10 months. Mice heterozygous for the nmf193 mutation had a less severe phenotype of shortened outer segments at 2 months with progressive loss of photoreceptor cells to 50% by 10 months. A positional cloning approach using a DNA pooling strategy was performed to identify the causative mutation in nmf193 mice. The nmf193 mutation linked to chromosome 17 and fine mapped to an interval containing the peripherin/rds (Prph2) gene. Mutation analysis identified a single base change in Prph2 that causes aberrant splicing between exon 1 and 2. Interestingly, a comparative histological analysis demonstrated that Prph2nmf193/+ mutants have similar photoreceptor degeneration to that of Nr2e3rd7/rd7. We show that Prph2 mRNA and protein levels are reduced in the Nr2e3rd7/rd7 mutant compared to control littermates. Further, chromatin immunoprecipitation analysis shows that Prph2 is a direct target of NR2E3. In addition, the down-regulation of Prph2 gene expression is similar in both the Nr2e3rd7/rd7 and Prph2nmf193/+ mutants suggesting that the reduction of Prph2 may contribute to the degenerative pathology seen in Nr2e3rd7/rd7. PMID:18763016

  17. Slowing presentation speed increases illusions of knowledge.

    PubMed

    Fazio, Lisa K; Marsh, Elizabeth J

    2008-02-01

    Prior research on false memories has shown that suggestibility is often reduced when the presentation rate is slowed enough to allow monitoring. We examined whether slowing presentation speed would reduce factual errors learned from fictional stories. Would subjects use the extra time to detect the errors in the stories, reducing reproduction of these errors on a later test? Surprisingly, slowing presentation speed increased the production of story errors on a later general knowledge test. Instructing the reader to mark whether each sentence contained an error, however, did decrease suggestibility. Readers appear to passively accept information presented in stories and need a constant reminder to monitor for errors. These results highlight differences between typical episodic false memories and illusions of knowledge (such as learning from fiction). Manipulations that reduce suggestibility for episodic false memories do not always reduce suggestibility for illusions of knowledge. PMID:18605500

  18. OBSERVED DAMPING OF THE SLOW MAGNETOACOUSTIC MODE

    SciTech Connect

    Marsh, M. S.; Walsh, R. W.; De Moortel, I. E-mail: mmarsh@uclan.ac.uk

    2011-06-20

    Spectroscopic and stereoscopic imaging observations of slow magnetoacoustic wave propagation within a coronal loop are investigated to determine the decay length scale of the slow magnetoacoustic mode in three dimensions and the density profile within the loop system. The slow wave is found to have an e-folding decay length scale of 20,000{sup +4000}{sub -3000} km with a uniform density profile along the loop base. These observations place quantitative constraints on the modeling of wave propagation within coronal loops. Theoretical forward modeling suggests that magnetic field line divergence is the dominant damping factor and thermal conduction is insufficient, given the observed parameters of the coronal loop temperature, density, and wave mode period.

  19. Slow and fast light switching in ruby

    NASA Astrophysics Data System (ADS)

    Rajan, Rajitha P.; Riesen, Hans

    2015-05-01

    Studies about light propagation have been undertaken for more than a century. It is now well established that any material that has normal or anomalous dispersion generates slow or fast light. In this paper, we demonstrate an experimental technique to rapidly switch between slow and fast light in ruby. The experiment utilizes transient holeburning to create drastic variation in refractive index of ruby to produce slow as well as fast light. Transient hole-burning involves the depletion of the ground state leading to a highly populated excited state by single frequency laser excitation. This leads to a hole in the absorption spectrum when readout by a laser. We observed a delay of 29 ns and advancement of -11 ns in an external magnetic field of B║c = 12 mT corresponding to a group velocity of c/961 and negative group velocity of -c/365 respectively.

  20. Lumbar intervertebral disc degeneration and related factors in Korean firefighters

    PubMed Central

    Jang, Tae-Won; Ahn, Yeon-Soon; Byun, Junsu; Lee, Jong-In; Kim, Kun-Hyung; Kim, Youngki; Song, Han-Soo; Lee, Chul-Gab; Kwon, Young-Jun; Yoon, Jin-Ha; Jeong, Kyoungsook

    2016-01-01

    Objectives The job of firefighting can cause lumbar burden and low back pain. This study aimed to identify the association between age and lumbar intervertebral disc degeneration and whether the association differs between field and administrative (non-field) firefighters. Methods Subjects were selected using a stratified random sampling method. Firefighters were stratified by geographic area, gender, age and type of job. First, 25 fire stations were randomly sampled considering regional distribution. Then firefighters were stratified by gender, age and their job and randomly selected among the strata. A questionnaire survey and MRI scans were performed, and then four radiologists used Pfirrmann classification methods to determine the grade of lumbar intervertebral disc degeneration. Results Pfirrmann grade increased with lumbar intervertebral disc level. Analysis of covariance showed that age was significantly associated with lumbar intervertebral disc degeneration (p<0.05). The value of β (parameter estimate) was positive at all lumbar intervertebral disc levels and was higher in the field group than in the administrative group at each level. In logistic regression analysis, type of job was statistically significant only with regard to the L4–5 intervertebral disc (OR 3.498, 95% CI 1.241 to 9.860). Conclusions Lumbar intervertebral disc degeneration is associated with age, and field work such as firefighting, emergency and rescue may accelerate degeneration in the L4–5 intervertebral disc. The effects of field work on lumbar intervertebral disc degeneration were not clear in discs other than at the level L4–5. PMID:27354080

  1. Automated diagnosis of Age-related Macular Degeneration using greyscale features from digital fundus images.

    PubMed

    Mookiah, Muthu Rama Krishnan; Acharya, U Rajendra; Koh, Joel E W; Chandran, Vinod; Chua, Chua Kuang; Tan, Jen Hong; Lim, Choo Min; Ng, E Y K; Noronha, Kevin; Tong, Louis; Laude, Augustinus

    2014-10-01

    Age-related Macular Degeneration (AMD) is one of the major causes of vision loss and blindness in ageing population. Currently, there is no cure for AMD, however early detection and subsequent treatment may prevent the severe vision loss or slow the progression of the disease. AMD can be classified into two types: dry and wet AMDs. The people with macular degeneration are mostly affected by dry AMD. Early symptoms of AMD are formation of drusen and yellow pigmentation. These lesions are identified by manual inspection of fundus images by the ophthalmologists. It is a time consuming, tiresome process, and hence an automated diagnosis of AMD screening tool can aid clinicians in their diagnosis significantly. This study proposes an automated dry AMD detection system using various entropies (Shannon, Kapur, Renyi and Yager), Higher Order Spectra (HOS) bispectra features, Fractional Dimension (FD), and Gabor wavelet features extracted from greyscale fundus images. The features are ranked using t-test, Kullback-Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance (CBBD), Receiver Operating Characteristics (ROC) curve-based and Wilcoxon ranking methods in order to select optimum features and classified into normal and AMD classes using Naive Bayes (NB), k-Nearest Neighbour (k-NN), Probabilistic Neural Network (PNN), Decision Tree (DT) and Support Vector Machine (SVM) classifiers. The performance of the proposed system is evaluated using private (Kasturba Medical Hospital, Manipal, India), Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) datasets. The proposed system yielded the highest average classification accuracies of 90.19%, 95.07% and 95% with 42, 54 and 38 optimal ranked features using SVM classifier for private, ARIA and STARE datasets respectively. This automated AMD detection system can be used for mass fundus image screening and aid clinicians by making better use of their expertise on selected images that

  2. Cone survival and preservation of visual acuity in an animal model of retinal degeneration.

    PubMed

    Piano, Ilaria; Novelli, Elena; Gasco, Paolo; Ghidoni, Riccardo; Strettoi, Enrica; Gargini, Claudia

    2013-06-01

    The prevention of cone loss during retinal degeneration is a major goal of most therapeutic strategies in retinal degenerative diseases. An intriguing issue in the current research in this field is to understand why a genetic mutation that affects rods eventually leads to cone death. The main objective of the present study was to investigate to what extent rescuing rods from degeneration affects the survival of cones and prevents functional impairment of the visual performance. To this purpose, we compared rod and cone viabilities by both ex vivo and in vivo determinations in the rd10 mutant mouse, a validated model of human retinitis pigmentosa. The ex vivo experiments included morphological and biochemical tests, whereas in vivo studies compared the rod-mediated scotopic with the cone-mediated photopic electroretinogram. We also determined the overall visual performance by behaviorally testing the visual acuity (VA). The electroretinogram measurements showed that the kinetics of the photopic response in rd10 mice was slowed down with respect to the age-paired wild-type at a very early stage of the disease, when rods were still present and responsive. We then tested cone viability and function under a pharmacological scheme previously shown to prolong rod survival. The treatment consisted of eye drop administration of myriocin, an inhibitor of the biosynthesis of ceramide, a powerful proapoptotic messenger. The results of biochemical, morphological and functional assays converged to show that, in treated rd10 mice cone photoreceptors, the inner retina and overall visual performance were preserved well after rod death. PMID:23551187

  3. WHITE DWARF/M DWARF BINARIES AS SINGLE DEGENERATE PROGENITORS OF TYPE Ia SUPERNOVAE

    SciTech Connect

    Wheeler, J. Craig

    2012-10-20

    Limits on the companions of white dwarfs in the single-degenerate scenario for the origin of Type Ia supernovae (SNe Ia) have gotten increasingly tight, yet igniting a nearly Chandrasekhar mass C/O white dwarf from a condition of near hydrostatic equilibrium provides compelling agreement with observed spectral evolution. The only type of non-degenerate stars that survive the tight limits, M{sub V} {approx}> 8.4 on the SN Ia in SNR 0509-67.5 and M{sub V} {approx}> 9.5 in the remnant of SN 1572, are M dwarfs. While M dwarfs are observed in cataclysmic variables, they have special properties that have not been considered in most work on the progenitors of SNe Ia: they have small but finite magnetic fields and they flare frequently. These properties are explored in the context of SN Ia progenitors. White dwarf/M dwarf pairs may be sufficiently plentiful to provide, in principle, an adequate rate of explosions even with slow orbital evolution due to magnetic braking or gravitational radiation. Even modest magnetic fields on the white dwarf and M dwarf will yield adequate torques to lock the two stars together, resulting in a slowly rotating white dwarf, with the magnetic poles pointing at one another in the orbital plane. The mass loss will be channeled by a 'magnetic bottle' connecting the two stars, landing on a concentrated polar area on the white dwarf. This enhances the effective rate of accretion compared to spherical accretion. Luminosity from accretion and hydrogen burning on the surface of the white dwarf may induce self-excited mass transfer. The combined effects of self-excited mass loss, polar accretion, and magnetic inhibition of mixing of accretion layers give possible means to beat the 'nova limit' and grow the white dwarf to the Chandrasekhar mass even at rather moderate mass accretion rates.

  4. White Dwarf/M Dwarf Binaries as Single Degenerate Progenitors of Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Wheeler, J. Craig

    2012-10-01

    Limits on the companions of white dwarfs in the single-degenerate scenario for the origin of Type Ia supernovae (SNe Ia) have gotten increasingly tight, yet igniting a nearly Chandrasekhar mass C/O white dwarf from a condition of near hydrostatic equilibrium provides compelling agreement with observed spectral evolution. The only type of non-degenerate stars that survive the tight limits, MV >~ 8.4 on the SN Ia in SNR 0509-67.5 and MV >~ 9.5 in the remnant of SN 1572, are M dwarfs. While M dwarfs are observed in cataclysmic variables, they have special properties that have not been considered in most work on the progenitors of SNe Ia: they have small but finite magnetic fields and they flare frequently. These properties are explored in the context of SN Ia progenitors. White dwarf/M dwarf pairs may be sufficiently plentiful to provide, in principle, an adequate rate of explosions even with slow orbital evolution due to magnetic braking or gravitational radiation. Even modest magnetic fields on the white dwarf and M dwarf will yield adequate torques to lock the two stars together, resulting in a slowly rotating white dwarf, with the magnetic poles pointing at one another in the orbital plane. The mass loss will be channeled by a "magnetic bottle" connecting the two stars, landing on a concentrated polar area on the white dwarf. This enhances the effective rate of accretion compared to spherical accretion. Luminosity from accretion and hydrogen burning on the surface of the white dwarf may induce self-excited mass transfer. The combined effects of self-excited mass loss, polar accretion, and magnetic inhibition of mixing of accretion layers give possible means to beat the "nova limit" and grow the white dwarf to the Chandrasekhar mass even at rather moderate mass accretion rates.

  5. Inducing Chronic Excitotoxicity in the Mouse Spinal Cord to Investigate Lower Motor Neuron Degeneration

    PubMed Central

    Blizzard, Catherine A.; Lee, K. M.; Dickson, Tracey C.

    2016-01-01

    We report the methodology for the chronic delivery of an excitotoxin to the mouse spinal cord via surgically implanted osmotic mini-pumps. Previous studies have investigated the effect of chronic application of excitotoxins in the rat, however there has been little translation of this model to the mouse. Using mice that express yellow fluorescent protein (YFP), motor neuron and neuromuscular junction alterations can be investigate following targeted, long-term (28 days) exposure to the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor excitotoxin, kainic acid. By targeting the L3-4 region of the lumbar spinal cord, with insertion of an intrathecal catheter into the subarachnoid space at L5, chronic application of the kainic acid results in slow excitotoxic death in the anterior ventral horn, with a significant (P < 0.05) reduction in the number of SMI-32 immunopositive neurons present after 28 days infusion. Use of the Thy1-YFP mice provides unrivaled visualization of the neuromuscular junction and enables the resultant distal degeneration in skeletal muscle to be observed. Both neuromuscular junction retraction at the gastrocnemius muscle and axonal fragmentation in the sciatic nerve were observed after chronic infusion of kainic acid for 28 days. Lower motor neuron, and distal neuromuscular junction, degeneration are pathological hallmarks of the devastating neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). This mouse model will be advantageous for increasing our understanding of how the pathophysiological phenomena associated with this disease can lead to lower motor neuron loss and distal pathology, as well as providing a robust in vivo platform to test therapeutic interventions directed at excitotoxic mechanisms. PMID:26973454

  6. Degenerate approach to the mean field Bose-Hubbard Hamiltonian

    NASA Astrophysics Data System (ADS)

    Belemuk, Alexander M.; Ryzhov, Valentin N.

    2016-04-01

    A degenerate variant of mean field perturbation theory for the on-site Bose-Hubbard Hamiltonian is presented. We split the perturbation into two terms and perform exact diagonalization in the two-dimensional subspace corresponding to the degenerate states. The final relations for the second order ground state energy and first order wave function do not contain singularities at integer values of the chemical potentials. The resulting equation for the phase boundary between superfluid and Mott states coincides with the prediction from the conventional mean field perturbation approach.

  7. Key emerging issues in progressive supranuclear palsy and corticobasal degeneration.

    PubMed

    Josephs, Keith A

    2015-03-01

    It has been approximately 50 years since neurologists were introduced to the entities, "progressive supranuclear palsy" and "corticobasal degeneration". Since the two seminal publications, there have been significant advancements in our understanding of these two neurodegenerative diseases, particularly the fact that both are associated with tau. Recent advances over the past 3 years that are notable to the field are discussed in this review that covers clinical diagnosis, pathological features, neuroimaging and CSF biomarkers, genetic associations and clinical trials related to progressive supranuclear palsy and corticobasal degeneration. PMID:25701010

  8. Extended Hellmann-Feynman theorem for degenerate eigenstates

    NASA Astrophysics Data System (ADS)

    Zhang, G. P.; George, Thomas F.

    2004-04-01

    In a previous paper, we reported a failure of the traditional Hellmann-Feynman theorem (HFT) for degenerate eigenstates. This has generated enormous interest among different groups. In four independent papers by Fernandez, by Balawender, Hola, and March, by Vatsya, and by Alon and Cederbaum, an elegant method to solve the problem was devised. The main idea is that one has to construct and diagonalize the force matrix for the degenerate case, and only the eigenforces are well defined. We believe this is an important extension to HFT. Using our previous example for an energy level of fivefold degeneracy, we find that those eigenforces correctly reflect the symmetry of the molecule.

  9. Geodynamic environments of ultra-slow spreading

    NASA Astrophysics Data System (ADS)

    Kokhan, Andrey; Dubinin, Evgeny

    2015-04-01

    Ultra-slow spreading is clearly distinguished as an outstanding type of crustal accretion by recent studies. Spreading ridges with ultra-slow velocities of extension are studied rather well. But ultra-slow spreading is characteristic feature of not only spreading ridges, it can be observed also on convergent and transform plate boundaries. Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on divergent plate boundaries: 1. On spreading ridges with ultra-slow spreading, both modern (f.e. Gakkel, South-West Indian, Aden spreading center) and ceased (Labrador spreading center, Aegir ridge); 2. During transition from continental rifting to early stages of oceanic spreading (all spreading ridges during incipient stages of their formation); 3. During incipient stages of formation of spreading ridges on oceanic crust as a result of ridge jumps and reorganization of plate boundaries (f.e. Mathematicians rise and East Pacific rise); 4. During propagation of spreading ridge into the continental crust under influence of hotspot (Aden spreading center and Afar triple junction), under presence of strike-slip faults preceding propagation (possibly, rift zone of California Bay). Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on transform plate boundaries: 1. In transit zones between two "typical" spreading ridges (f.e. Knipovich ridge); 2. In semi strike-slip/extension zones on the oceanic crust (f.e. American-Antarctic ridge); 3. In the zones of local extension in regional strike-slip areas in pull-apart basins along transform boundaries (Cayman trough, pull-apart basins of the southern border of Scotia plate). Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on convergent plate boundaries: 1. During back-arc rifting on the stage of transition into back-arc spreading (central

  10. Synchronized Ion Acceleration by Ultraintense Slow Light.

    PubMed

    Brantov, A V; Govras, E A; Kovalev, V F; Bychenkov, V Yu

    2016-02-26

    An effective scheme of synchronized laser-triggered ion acceleration and the corresponding theoretical model are proposed for a slow light pulse of relativistic intensity, which penetrates into a near-critical-density plasma, strongly slows, and then increases its group velocity during propagation within a target. The 3D particle-in-cell simulations confirm this concept for proton acceleration by a femtosecond petawatt-class laser pulse experiencing relativistic self-focusing, quantify the characteristics of the generated protons, and demonstrate a significant increase of their energy compared with the proton energy generated from optimized ultrathin solid dense foils. PMID:26967421

  11. Optimized slow light and beam profiles

    NASA Astrophysics Data System (ADS)

    Kalra, Rita; Klein, Mason; Xiao, Yanhong; Hohensee, Michael; Phillips, David F.; Walsworth, Ronald L.

    2008-05-01

    We will present an overview of Electromagnetically Induced Transparency (EIT) and slow light dependence on transverse laser field profile. Idealized treatments typically assume a uniform optical field profile while experiments are typically performed with gaussian beam profiles. Here we present a comparison of EIT lineshapes measured with flat top and gaussian transverse profiles and compare slow light delays observed under such circumstances with those derived from measured EIT line shapes in simple models. Additionally we study the effects of differential AC Stark shifts due to transverse beam profiles and their effect on light storage.

  12. Synchronized Ion Acceleration by Ultraintense Slow Light

    NASA Astrophysics Data System (ADS)

    Brantov, A. V.; Govras, E. A.; Kovalev, V. F.; Bychenkov, V. Yu.

    2016-02-01

    An effective scheme of synchronized laser-triggered ion acceleration and the corresponding theoretical model are proposed for a slow light pulse of relativistic intensity, which penetrates into a near-critical-density plasma, strongly slows, and then increases its group velocity during propagation within a target. The 3D particle-in-cell simulations confirm this concept for proton acceleration by a femtosecond petawatt-class laser pulse experiencing relativistic self-focusing, quantify the characteristics of the generated protons, and demonstrate a significant increase of their energy compared with the proton energy generated from optimized ultrathin solid dense foils.

  13. Slow crack growth in spinel in water

    NASA Technical Reports Server (NTRS)

    Schwantes, S.; Elber, W.

    1983-01-01

    Magnesium aluminate spinel was tested in a water environment at room temperature to establish its slow crack-growth behavior. Ring specimens with artificial flaws on the outside surface were loaded hydraulically on the inside surface. The time to failure was measured. Various precracking techniques were evaluated and multiple precracks were used to minimize the scatter in the static fatigue tests. Statistical analysis techniques were developed to determine the strength and crack velocities for a single flaw. Slow crack-growth rupture was observed at stress intensities as low as 70 percent of K sub c. A strengthening effect was observed in specimens that had survived long-time static fatigue tests.

  14. Slow breathing influences cardiac autonomic responses to postural maneuver: Slow breathing and HRV.

    PubMed

    Vidigal, Giovanna Ana de Paula; Tavares, Bruna S; Garner, David M; Porto, Andrey A; Carlos de Abreu, Luiz; Ferreira, Celso; Valenti, Vitor E

    2016-05-01

    Chronic slow breathing has been reported to improve Heart Rate Variability (HRV) in patients with cardiovascular disorders. However, it is not clear regarding its acute effects on HRV responses on autonomic analysis. We evaluated the acute effects of slow breathing on cardiac autonomic responses to postural change manoeuvre (PCM). The study was conducted on 21 healthy male students aged between 18 and 35 years old. In the control protocol, the volunteer remained at rest seated for 15 min under spontaneous breathing and quickly stood up within 3 s and remained standing for 15 min. In the slow breathing protocol, the volunteer remained at rest seated for 10 min under spontaneous breath, then performed slow breathing for 5 min and rapidly stood up within 3 s and remained standing for 15 min. Slow breathing intensified cardiac autonomic responses to postural maneuver. PMID:27157952

  15. Polymorphism and disorder in natural active ingredients. Low and high-temperature phases of anhydrous caffeine: Spectroscopic ((1)H-(14)N NMR-NQR/(14)N NQR) and solid-state computational modelling (DFT/QTAIM/RDS) study.

    PubMed

    Seliger, Janez; Žagar, Veselko; Apih, Tomaž; Gregorovič, Alan; Latosińska, Magdalena; Olejniczak, Grzegorz Andrzej; Latosińska, Jolanta Natalia

    2016-03-31

    The polymorphism of anhydrous caffeine (1,3,7-trimethylxanthine; 1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione) has been studied by (1)H-(14)N NMR-NQR (Nuclear Magnetic Resonance-Nuclear Quadrupole Resonance) double resonance and pure (14)N NQR (Nuclear Quadrupole Resonance) followed by computational modelling (Density Functional Theory, supplemented Quantum Theory of Atoms in Molecules with Reduced Density Gradient) in solid state. For two stable (phase II, form β) and metastable (phase I, form α) polymorphs the complete NQR spectra consisting of 12 lines were recorded. The assignment of signals detected in experiment to particular nitrogen sites was verified with the help of DFT. The shifts of the NQR frequencies, quadrupole coupling constants and asymmetry parameters at each nitrogen site due to polymorphic transition were evaluated. The strongest shifts were observed at N(3) site, while the smallest at N(9) site. The commercial pharmaceutical sample was found to contain approximately 20-25% of phase I and 75-80% of phase II. The orientational disorder in phase II with a local molecular arrangement mimics that in phase I. Substantial differences in the intermolecular interaction phases I and II of caffeine were analysed using computational (DFT/QTAIM/RDS) approach. The analysis of local environment of each nitrogen nucleus permitted drawing some conclusions on the topology of interactions in both polymorphs. For the most stable orientations in phase I and phase II the maps of the principal component qz of EFG tensor and its asymmetry parameter at each point of the molecular system were calculated and visualized. The relevant maps calculated for both phases I and II indicates small variation in electrostatic potential upon phase change. Small differences between packings in phases slightly disturb the neighbourhood of the N(1) and N(7) nitrogens, thus are meaningless from the biological point of view. The composition of two phases in pharmaceutical material

  16. Slow viscous flow in a syringe.

    PubMed

    Watson, L T; Billups, S C; Wang, C Y; Everett, E A

    1986-11-01

    The slow viscous flow in a syringe is modeled by the quasi-steady axisymmetric Stokes equation with a point sink for the needle hole. The governing equations are approximated using nonstandard finite difference formulas optimized for the boundary conditions, and solved numerically using a SOR technique. Streamlines and pressure profiles are computed for a variety of syringe configurations. PMID:3795876

  17. Slow Reading: Reading along "Lectio" Lines

    ERIC Educational Resources Information Center

    Badley, K. Jo-Ann; Badley, Ken

    2011-01-01

    The medieval monastic movement preserved and developed reading practices--lectio--from ancient Greek pedagogy as a slow, mindful approach to reading for formation. This ancient way of reading, now better known as lectio divina, challenges the fast, pragmatic reading so characteristic of our time. We propose that the present moment may be ripe for…

  18. States Slow to Embrace Online Testing

    ERIC Educational Resources Information Center

    Ash, Katie

    2008-01-01

    Although most assessment experts agree that in the future, state tests will routinely be administered by computer, progress toward that goal has been slow, expensive, and fraught with logistical challenges. Stuart R. Kahl, the president and chief executive officer of Measured Progress, a Dover, N.H.-based nonprofit organization that provides…

  19. Slowed ageing, welfare, and population problems.

    PubMed

    Wareham, Christopher

    2015-10-01

    Biological studies have demonstrated that it is possible to slow the ageing process and extend lifespan in a wide variety of organisms, perhaps including humans. Making use of the findings of these studies, this article examines two problems concerning the effect of life extension on population size and welfare. The first--the problem of overpopulation--is that as a result of life extension too many people will co-exist at the same time, resulting in decreases in average welfare. The second--the problem of underpopulation--is that life extension will result in too few people existing across time, resulting in decreases in total welfare. I argue that overpopulation is highly unlikely to result from technologies that slow ageing. Moreover, I claim that the problem of underpopulation relies on claims about life extension that are false in the case of life extension by slowed ageing. The upshot of these arguments is that the population problems discussed provide scant reason to oppose life extension by slowed ageing. PMID:26246312

  20. Experimental demonstration of spinor slow light

    PubMed Central

    Lee, Meng-Jung; Ruseckas, Julius; Lee, Chin-Yuan; Kudriašov, Viačeslav; Chang, Kao-Fang; Cho, Hung-Wen; Juzeliānas, Gediminas; Yu, Ite A.

    2014-01-01

    Slow light based on the effect of electromagnetically induced transparency is of great interest due to its applications in low-light-level nonlinear optics and quantum information manipulation. The previous experiments all dealt with the single-component slow light. Here, we report the experimental demonstration of two-component or spinor slow light using a double-tripod atom–light coupling scheme. The scheme involves three atomic ground states coupled to two excited states by six light fields. The oscillation due to the interaction between the two components was observed. On the basis of the stored light, our data showed that the double-tripod scheme behaves like the two outcomes of an interferometer enabling precision measurements of frequency detuning. We experimentally demonstrated a possible application of the double-tripod scheme as quantum memory/rotator for the two-colour qubit. Our study also suggests that the spinor slow light is a better method than a widely used scheme in the nonlinear frequency conversion. PMID:25417851

  1. Rescuing Students from the Slow Learner Trap

    ERIC Educational Resources Information Center

    Shaw, Steven R.

    2010-01-01

    Slow learners, such as students with borderline intellectual functioning, represent one of the most challenging student populations for administrators and teachers. Standard systems and supports are often ineffective--even counterproductive--because they fail to meet students' specific learning needs and instead create a cycle of failure. This…

  2. Experimental demonstration of spinor slow light

    NASA Astrophysics Data System (ADS)

    Lee, Meng-Jung; Ruseckas, Julius; Lee, Chin-Yuan; Kudriašov, Viačeslav; Chang, Kao-Fang; Cho, Hung-Wen; Juzeliānas, Gediminas; Yu, Ite A.

    2014-11-01

    Slow light based on the effect of electromagnetically induced transparency is of great interest due to its applications in low-light-level nonlinear optics and quantum information manipulation. The previous experiments all dealt with the single-component slow light. Here, we report the experimental demonstration of two-component or spinor slow light using a double-tripod atom-light coupling scheme. The scheme involves three atomic ground states coupled to two excited states by six light fields. The oscillation due to the interaction between the two components was observed. On the basis of the stored light, our data showed that the double-tripod scheme behaves like the two outcomes of an interferometer enabling precision measurements of frequency detuning. We experimentally demonstrated a possible application of the double-tripod scheme as quantum memory/rotator for the two-colour qubit. Our study also suggests that the spinor slow light is a better method than a widely used scheme in the nonlinear frequency conversion.

  3. Slow extraction from the Fermilab Main Injector

    SciTech Connect

    Craig D. Moore et al.

    2001-07-20

    Slow resonant extraction from the Fermilab Main Injector through the extraction channel was achieved in February, 2000, with a spill length of 0.3 sec. Beam losses were small. Excellent wire chamber profiles were obtained and analyzed. The duty factor was not very good and needs to be improved.

  4. Zero-frequency and slow elastic modes in phononic monolayer granular membranes.

    PubMed

    Zheng, Li-Yang; Pichard, Hélène; Tournat, Vincent; Theocharis, Georgios; Gusev, Vitalyi

    2016-07-01

    We theoretically study the dispersion properties of elastic waves in hexagonal and honeycomb monolayer granular membranes with either out-of-plane or in-plane particle motion. The particles interact predominantly via normal and transverse contact rigidities. When rotational degrees of freedom are taken into account, the bending and torsional rigidities of the intergrain contacts can control some of the phononic modes. The existence of zero-frequency modes, zero-group-velocity modes and their transformation into slow propagating phononic modes due to weak bending and torsional intergrain interactions are investigated. We also study the formation and manipulation of Dirac cones and multiple degenerated modes. This could motivate variety of potential applications in elastic waves control by manipulating the contact rigidities in granular phononic crystals. PMID:26607105

  5. Slow-light probe of Fermi pairing through an atom-molecule dark state

    SciTech Connect

    Jing, H.; Deng, Y.; Meystre, P.

    2011-06-15

    We consider the two-color photoassociation of a quantum degenerate atomic gas into ground-state diatomic molecules via a molecular dark state. This process can be described in terms of a {Lambda} level scheme that is formally analogous to the situation in electromagnetically induced transparency in atomic systems and therefore can result in slow-light propagation. We show that the group velocity of the light field depends explicitly on whether the atoms are bosons or fermions, as well as on the existence or absence of a pairing gap in the case of fermions, so that the measurement of the group velocity realizes a nondestructive diagnosis of the atomic state and the pairing gap.

  6. Oocyte Degeneration Associated with Follicle Cells in Female Mactra chinensis (Bivalvia: Mactridae)

    PubMed Central

    Kim, Sung Han; Chung, Ee-Yung; Lee, Ki-Young

    2014-01-01

    Ultrastructural studies of oocyte degeneration in the oocyte, and the functions of follicle cells during oocyte degeneration are described to clarify the reproductive mechanism on oocyte degeneration of Mactra chinensis using cytological methods. Commonly, the follicle cells are attached to the oocyte. Follicle cells play an important role in oocyte degeneration. In particular, the functions of follicle cells during oocyte degeneration are associated with phagocytosis and the intracellular digestion of products. In this study, morphologically similar degenerated phagosomes (various lysosomes), which were observed in the degenerated oocytes, appeared in the follicle cells. After the spawning of the oocytes, the follicle cells were involved in oocyte degeneration through phagocytosis by phagolysosomes. Therefore, it can be assumed that follicle cells reabsorb phagosomes from degenerated oocytes. In this study, the presence of lipid granules, which occurred from degenerating yolk granules, gradually increased in degenerating oocytes. The function of follicle cells can accumulate reserves of lipid granules and glycogen in the cytoplasm, which can be employed by the vitellogenic oocyte. Based on observations of follicle cells attached to degenerating oocytes after spawning, the follicle cells of this species are involved in the lysosomal induction of oocyte degeneration for the reabsorption of phagosomes (phagolysosomes) in the cytoplasm for nutrient storage, as seen in other bivalves. PMID:25949203

  7. Human Gamma Oscillations during Slow Wave Sleep

    PubMed Central

    Valderrama, Mario; Crépon, Benoît; Botella-Soler, Vicente; Martinerie, Jacques; Hasboun, Dominique; Alvarado-Rojas, Catalina; Baulac, Michel; Adam, Claude; Navarro, Vincent; Le Van Quyen, Michel

    2012-01-01

    Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30–50 Hz) and high (60–120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves (“IN-phase” pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave (“ANTI-phase” pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks. PMID:22496749

  8. The Experience of Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  9. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  10. Emerging monochromatic fluxes and colors of red degenerate stars

    NASA Technical Reports Server (NTRS)

    Kapranidis, S.

    1985-01-01

    The emerging monochromatic fluxes and the B-V, V-I, J-H, and V-K color indices are presented for red degenerate stars with helium atmospheres which were calculated using an equation of state and opacities based on a hot Thomas-Fermi model of the helium gas. The effective temperature range is 4500-2500 K. It is found that although the emerging fluxes resemble blackbody curves, red degenerates emit more radiation than blackbodies in the short wavelength range and less in the long wavelength range. Thus, red degenerates appear bluer than blackbodies of the same temperature. The calculated colors of these models are compared to the colors of some of the coolest known non-DA degenerate stars. In particular it is found that the B-V and V-I colors of the cool white dwarf VB 11, whose temperature had been previously estimated to be higher than 4000 K, suggest a temperature of 3750 K. If this result is correct, then VB 11 is probably the coolest known white dwarf.

  11. Gestural Imitation and Limb Apraxia in Corticobasal Degeneration

    ERIC Educational Resources Information Center

    Salter, Jennifer E.; Roy, Eric A.; Black, Sandra E.; Joshi, Anish; Almeida, Quincy

    2004-01-01

    Limb apraxia is a common symptom of corticobasal degeneration (CBD). While previous research has shown that individuals with CBD have difficulty imitating transitive (tool-use actions) and intransitive non-representational gestures (nonsense actions), intransitive representational gestures (actions without a tool) have not been examined. In the…

  12. Microsphere embolization of nerve capillaries and fiber degeneration.

    PubMed Central

    Nukada, H.; Dyck, P. J.

    1984-01-01

    Polystyrene microspheres, the size chosen to plug capillaries and precapillaries, were injected into the arterial supply of rat sciatic nerves. They produced widespread segmental occlusion of capillaries in lower limb nerves. The clinical and pathologic effect was dose-related. One million microspheres produced selective capillary occlusion but no nerve fiber degeneration; approximately 6 million microspheres also produced selective capillary occlusion and associated foot and leg weakness, sensory loss, and fiber degeneration, beginning in a central core of the distal sciatic nerve; 30 million microspheres caused both capillary and arterial occlusion and a greater neuropathologic deficit. From these observations it is inferred that 1) occlusion of isolated precapillaries and capillaries does not produce ischemic fiber degeneration; 2) occlusion of many microvessels results in central fascicular fiber degeneration, indicating that these cores are watershed regions of poor perfusion; and 3) stereotyped pathologic alterations of nerve fibers and Schwann cells are related to dose, anatomic site, and time elapsed since injection. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:6326580

  13. Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

    ClinicalTrials.gov

    2016-04-29

    FTLD; Progressive Supranuclear Palsy (PSP); Frontotemporal Dementia (FTD); Corticobasal Degeneration (CBD); PPA Syndrome; Behavioral Variant Frontotemporal Dementia (bvFTD); Semantic Variant Primary Progressive Aphasia (svPPA); Nonfluent Variant Primary Progressive Aphasia (nfvPPA); FTD With Amyotrophic Lateral Sclerosis (FTD/ALS); Amyotrophic Lateral Sclerosis (ALS); Oligosymptomatic PSP (oPSP); Corticobasal Syndrome (CBS)

  14. Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration

    PubMed Central

    Kleinman, Mark E.

    2016-01-01

    Recent data have revealed epigenetic derangements and subsequent chromatin remodeling as a potent biologic switch for chronic inflammation and cell survival which are important therapeutic targets in the pathogenesis of several retinal degenerations. Histone deacetylases (HDACs) are a major component of this system and serve as a unique control of the chromatin remodeling process. With a multitude of targeted HDAC inhibitors now available, their use in both basic science and clinical studies has widened substantially. In the field of ocular biology, there are data to suggest that HDAC inhibition may suppress neovascularization and may be a possible treatment for retinitis pigmentosa and dry age-related macular degeneration (AMD). However, the effects of these inhibitors on cell survival and chemokine expression in the chorioretinal tissues remain very unclear. Here, we review the multifaceted biology of HDAC activity and pharmacologic inhibition while offering further insight into the importance of this epigenetic pathway in retinal degenerations. Our laboratory investigations aim to open translational avenues to advance dry AMD therapeutics while exploring the role of acetylation on inflammatory gene expression in the aging and degenerating retina. PMID:26427391

  15. The Effects of Simulated Microgravity on Intervertebral Disc Degeneration

    PubMed Central

    Jin, Li; Feng, Gang; Reames, Davis L; Shimer, Adam L; Shen, Francis H; Li, Xudong

    2012-01-01

    BACKGROUND CONTEXT Astronauts experience back pain, particularly low back pain, during and after spaceflight. Recent studies have described histological and biochemical changes in rat intervertebral discs after space travel, but there is still no in vitro model to investigate the effects of microgravity on disc metabolism. PURPOSE To study the effects of microgravity on disc degeneration and to establish an in vitro simulated microgravity study model STUDY DESIGN Discs were cultured in static and rotating conditions in bioreactor, and the characteristics of disc degeneration were evaluated METHODS The mice discs were cultured in a rotating wall vessel bioreactor where the microgravity condition was simulated. Intervertebral discs were cultured in static and microgravity condition. Histology, biochemistry, and immunohistochemical assays were performed to evaluate the characteristics of the discs in microgravity condition. RESULTS Intervertebral discs cultured in rotating bioreactors were found to develop changes of disc degeneration manifested by reduced red Safranin-o staining within the annulus fibrosus, downregulated GAG content and GAG/Hypro ratio, increased MMP-3 expression, and upregulated apoptosis. CONCLUSIONS We conclude that simulated microgravity induces the molecular changes of disc degeneration. The rotating bioreactor model will provide a foundation to investigate the effects of microgravity on disc metabolism. PMID:23537452

  16. Anisotropic uniqueness classes for a degenerate parabolic equation

    SciTech Connect

    Vil'danova, V F; Mukminov, F Kh

    2013-11-30

    Anisotropic uniqueness classes of Tacklind type are identified for a degenerate linear parabolic equation of the second order in an unbounded domain. The Cauchy problem and mixed problems with boundary conditions of the first and third type are considered. Bibliography: 18 titles.

  17. Dystonia and Cerebellar Degeneration in the Leaner Mouse Mutant

    PubMed Central

    Raike, Robert S.; Hess, Ellen J.; Jinnah, H.A.

    2015-01-01

    Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons were lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences. PMID:25791619

  18. Electron–ion relaxation time in moderately degenerate plasma

    SciTech Connect

    Vronskii, M. A. Koryakina, Yu. V.

    2015-09-15

    A formula is derived for the electron–ion relaxation time in a partially degenerate plasma with electron-ion interaction via a central field. The resulting expression in the form of an integral of the transport cross section generalizes the well-known Landau and Brysk approximations.

  19. Cesare Lombroso: an anthropologist between evolution and degeneration

    PubMed Central

    Mazzarello, Paolo

    Summary Cesare Lombroso (1835–1909) was a prominent Italian medical doctor and intellectual in the second half of the nineteenth century. He became world famous for his theory that criminality, madness and genius were all sides of the same psychobiological condition: an expression of degeneration , a sort of regression along the phylogenetic scale, and an arrest at an early stage of evolution. Degeneration affected criminals especially, in particular the “born delinquent” whose development had stopped at an early stage, making them the most “atavistic” types of human being. Lombroso also advocated the theory that genius was closely linked with madness. A man of genius was a degenerate, an example of retrograde evolution in whom madness was a form of “biological compensation” for excessive intellectual development. To confirm this theory, in August 1897, Lombroso, while attending the Twelfth International Medical Congress in Moscow, decided to meet the great Russian writer Lev Tolstoy in order to directly verify, in him, his theory of degeneration in the genius. Lombroso’s anthropological ideas fuelled a heated debate on the biological determinism of human behaviour. PMID:21729591

  20. Nutritional modulation of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  1. Speech and Language Findings Associated with Paraneoplastic Cerebellar Degeneration

    ERIC Educational Resources Information Center

    Paslawski, Teresa; Duffy, Joseph R.; Vernino, Steven

    2005-01-01

    Paraneoplastic cerebellar degeneration (PCD) is an autoimmune disease that can be associated with cancer of the breast, lung, and ovary. The clinical presentation of PCD commonly includes ataxia, visual disturbances, and dysarthria. The speech disturbances associated with PCD have not been well characterized, despite general acceptance that…

  2. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins.

    PubMed

    Capossela, S; Schläfli, P; Bertolo, A; Janner, T; Stadler, B M; Pötzel, T; Baur, M; Stoyanov, J V

    2014-01-01

    Degeneration of intervertebral discs (IVDs) is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP) to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases. PMID:24706108

  3. Nonlinear isothermal waves in a degenerate electron plasma

    SciTech Connect

    Dubinov, A. E.; Dubinova, A. A.

    2008-05-15

    A nonlinear differential equation describing oscillations of the chemical potential in a one-dimensional steady-state wave propagating in a degenerate electron gas against an immobile neutralizing ion background is derived, investigated, and solved exactly. It is found that the wave phase velocity is bounded below by a critical velocity, whose exact value is obtained.

  4. MicroRNAs: New players in intervertebral disc degeneration.

    PubMed

    Wang, Cheng; Wang, Wen-Jun; Yan, Yi-Guo; Xiang, Yong-Xiao; Zhang, Jian; Tang, Zhi-Han; Jiang, Zhi-Sheng

    2015-10-23

    Chronic low back pain is generally attributed to intervertebral disc (IVD) degeneration (IDD), which is closely associated with apoptosis, extracellular matrix (ECM) disruption, cell proliferation and inflammatory response. Currently, there is no clinical therapy targeting the pathophysiology of disc degeneration. microRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression at the post-transcriptional levels. miRNAs not only regulate many normal physiological processes, but also play an important role in the development of most disorders, including degenerative disc disease. A variety of miRNAs are differentially expressed in degenerative human IVD tissues and cells. Among these, some of the miRNAs have been shown to be involved in multiple pathological processes during disc degeneration, including apoptosis, ECM degradation, cell proliferation and inflammatory response. This review will mainly focus on the expression profiles, roles, and therapeutic implications of miRNAs in IDD. With continued efforts, restoration of dysregulated miRNA expression may represent a promising biological treatment approach for mitigating or reversing IVD degeneration. PMID:26368266

  5. Inflammatory Mediators in Intervertebral Disk Degeneration and Discogenic Pain

    PubMed Central

    Wuertz, Karin; Haglund, Lisbet

    2013-01-01

    Although degeneration of the intervertebral disk has historically been described as a misbalance between anabolic and catabolic factors, the role of inflammatory mediators has long been neglected. However, past research clearly indicates that inflammatory mediators such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α are expressed at higher levels in “diseased” intervertebral disks. Both disk cells as well as invading macrophages can be the source of the detected cytokines. Importantly, occurrence of inflammatory mediators in the disk can worsen the progress of degeneration by inducing the expression of matrix degrading enzymes as well as by inhibiting extracellular matrix synthesis. In addition, inflammatory mediators play a crucial role in pain development during intervertebral disk herniation (i.e., sciatica) and disk degeneration (i.e., discogenic pain). This review provides information on the most relevant inflammatory mediators during different types of disk diseases and explains how these factors can induce disk degeneration and the development of discogenic and sciatic/radiculopathic pain. PMID:24436868

  6. Cesare Lombroso: an anthropologist between evolution and degeneration.

    PubMed

    Mazzarello, Paolo

    2011-01-01

    Cesare Lombroso (1835-1909) was a prominent Italian medical doctor and intellectual in the second half of the nineteenth century. He became world famous for his theory that criminality, madness and genius were all sides of the same psychobiological condition: an expression of degeneration, a sort of regression along the phylogenetic scale, and an arrest at an early stage of evolution. Degeneration affected criminals especially, in particular the "born delinquent" whose development had stopped at an early stage, making them the most "atavistic" types of human being. Lombroso also advocated the theory that genius was closely linked with madness. A man of genius was a degenerate, an example of retrograde evolution in whom madness was a form of "biological compensation" for excessive intellectual development. To confirm this theory, in August 1897, Lombroso, while attending the Twelfth International Medical Congress in Moscow, decided to meet the great Russian writer Lev Tolstoy in order to directly verify, in him, his theory of degeneration in the genius. Lombroso's anthropological ideas fuelled a heated debate on the biological determinism of human behaviour. PMID:21729591

  7. Biological treatment strategies for disc degeneration: potentials and shortcomings

    PubMed Central

    Nerlich, Andreas G.; Boos, Norbert

    2006-01-01

    Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

  8. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. PMID:26292978

  9. Slow Earthquakes and The Mechanics of Slow Frictional Stick-Slip

    NASA Astrophysics Data System (ADS)

    Marone, Chris; Scuderi, Marco; Leeman, John; Saffer, Demian; Collettini, Cristiano; Johnson, Paul

    2015-04-01

    Slow earthquakes represent one mode of the spectrum of fault slip behaviors ranging from steady aseismic slip to normal earthquakes. Like normal earthquakes, slow earthquakes can occur repetitively, such that a fault fails in a form of stick-slip failure defined by interseismic strain accumulation and slow, quasidynamic slip. The mechanics of frictional stick-slip and seismogenic faulting appear to apply to slow earthquakes, however, the mechanisms that limit dynamic slip velocity, rupture propagation speed, and the scaling between moment and duration of slow earthquakes are poorly understood. Here, we describe laboratory experiments that explore the mechanics of repetitive, slow frictional stick-slip failure. We document the role of loading stiffness and friction constitutive behavior in dictating the properties of repetitive, frictional stick-slip. Our results show that a spectrum of dynamic and quasidynamic slip velocities can occur in stick-slip events depending on the relation between loading stiffness k and the rheologic critical stiffness kc given, in the context of rate and state friction, by the ratio of the friction rate parameter (b-a) divided by the critical friction distance Dc. Slow slip is favored by conditions for which k is ~ equal to kc, whereas normal, fast stick slip occurs when k/kc < 1. We explore the role of elastic coupling and spatially extended slip propagation by comparing slow slip results for shear in a layer driven by forcing blocks of varying stiffness. We evaluate our data in the framework of rate and state friction laws and focus on the frictional mechanics of slow stick-slip failure with special attention paid to the connections between quasidynamic failure and mechanisms of the brittle-ductile transition in fault rocks.

  10. Properties of slow oscillation during slow-wave sleep and anesthesia in cats.

    PubMed

    Chauvette, Sylvain; Crochet, Sylvain; Volgushev, Maxim; Timofeev, Igor

    2011-10-19

    Deep anesthesia is commonly used as a model of slow-wave sleep (SWS). Ketamine-xylazine anesthesia reproduces the main features of sleep slow oscillation: slow, large-amplitude waves in field potential, which are generated by the alternation of hyperpolarized and depolarized states of cortical neurons. However, direct quantitative comparison of field potential and membrane potential fluctuations during natural sleep and anesthesia is lacking, so it remains unclear how well the properties of sleep slow oscillation are reproduced by the ketamine-xylazine anesthesia model. Here, we used field potential and intracellular recordings in different cortical areas in the cat to directly compare properties of slow oscillation during natural sleep and ketamine-xylazine anesthesia. During SWS cortical activity showed higher power in the slow/delta (0.1-4 Hz) and spindle (8-14 Hz) frequency range, whereas under anesthesia the power in the gamma band (30-100 Hz) was higher. During anesthesia, slow waves were more rhythmic and more synchronous across the cortex. Intracellular recordings revealed that silent states were longer and the amplitude of membrane potential around transition between active and silent states was bigger under anesthesia. Slow waves were mostly uniform across cortical areas under anesthesia, but in SWS, they were most pronounced in associative and visual areas but smaller and less regular in somatosensory and motor cortices. We conclude that, although the main features of the slow oscillation in sleep and anesthesia appear similar, multiple cellular and network features are differently expressed during natural SWS compared with ketamine-xylazine anesthesia. PMID:22016533

  11. A novel platform for minimally invasive delivery of cellular therapy as a thin layer across the subretina for treatment of retinal degeneration

    NASA Astrophysics Data System (ADS)

    Rotenstreich, Ygal; Tzameret, Adi; Kalish, Sapir E.; Belkin, Michael; Meir, Amilia; Treves, Avraham J.; Nagler, Arnon; Sher, Ifat

    2015-03-01

    Incurable retinal degenerations affect millions worldwide. Stem cell transplantation rescued visual functions in animal models of retinal degeneration. In those studies cells were transplanted in subretinal "blebs", limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection sites. We developed a minimally-invasive surgical platform for drug and cell delivery in a thin layer across the subretina and extravascular spaces of the choroid. The novel system is comprised of a syringe with a blunt-tipped needle and an adjustable separator. Human bone marrow mesenchymal stem cells (hBM-MSCs) were transplanted in eyes of RCS rats and NZW rabbits through a longitudinal triangular scleral incision. No immunosuppressants were used. Retinal function was determined by electroretinogram analysis and retinal structure was determined by histological analysis and OCT. Transplanted cells were identified as a thin layer across the subretina and extravascular spaces of the choroid. In RCS rats, cell transplantation delayed photoreceptor degeneration across the entire retina and significantly enhanced retinal functions. No retinal detachment or choroidal hemorrhages were observed in rabbits following transplantation. This novel platform opens a new avenue for drug and cell delivery, placing the transplanted cells in close proximity to the damaged RPE and retina as a thin layer, across the subretina and thereby slowing down cell death and photoreceptor degeneration, without retinal detachment or choroidal hemorrhage. This new transplantation system may increase the therapeutic effect of other cell-based therapies and therapeutic agents. This study is expected to directly lead to phase I/II clinical trials for autologous hBM-MSCs transplantation in retinal degeneration patients.

  12. Decreased Expression of DREAM Promotes the Degeneration of Retinal Neurons

    PubMed Central

    Chintala, Shravan; Cheng, Mei; Zhang, Xiao

    2015-01-01

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

  13. Repair of the degenerate retina by photoreceptor transplantation

    PubMed Central

    Barber, Amanda C.; Hippert, Claire; Duran, Yanai; West, Emma L.; Bainbridge, James W. B.; Warre-Cornish, Katherine; Luhmann, Ulrich F. O.; Lakowski, Jorn; Sowden, Jane C.; Ali, Robin R.; Pearson, Rachael A.

    2013-01-01

    Despite different aetiologies, age-related macular degeneration and most inherited retinal disorders culminate in the same final common pathway, the loss of photoreceptors. There are few treatments and none reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. Recently, we demonstrated restoration of vision following rod-photoreceptor transplantation into a mouse model of stationary night-blindness, raising the critical question of whether photoreceptor replacement is equally effective in different types and stages of degeneration. We present a comprehensive assessment of rod-photoreceptor transplantation across six murine models of inherited photoreceptor degeneration. Transplantation is feasible in all models examined but disease type has a major impact on outcome, as assessed both by the morphology and number of integrated rod-photoreceptors. Integration can increase (Prph2+/Δ307), decrease (Crb1rd8/rd8, Gnat1−/−, Rho−/−), or remain constant (PDE6βrd1/rd1, Prph2rd2/rd2) with disease progression, depending upon the gene defect, with no correlation with severity. Robust integration is possible even in late-stage disease. Glial scarring and outer limiting membrane integrity, features that change with degeneration, significantly affect transplanted photoreceptor integration. Combined breakdown of these barriers markedly increases integration in a model with an intact outer limiting membrane, strong gliotic response, and otherwise poor transplantation outcome (Rho−/−), leading to an eightfold increase in integration and restoration of visual function. Thus, it is possible to achieve robust integration across a broad range of inherited retinopathies. Moreover, transplantation outcome can be improved by administering appropriate, tailored manipulations of the recipient environment. PMID:23248312

  14. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    MedlinePlus

    ... macular degeneration Three studies point to same risk gene for age-related macular degeneration NIH-funded research ... in Nature Genetics have converged on the same gene as a rare, but powerful risk factor for ...

  15. Slow and fast light in semiconductors

    NASA Astrophysics Data System (ADS)

    Sedgwick, Forrest Grant

    Slow and fast light are the propagation of optical signals at group velocities below and above the speed of light in a given medium. There has been great interest in the use of nonlinear optics to engineer slow and fast light dispersion for applications in optical communications and radio-frequency or microwave photonics. Early results in this field were primarily confined to dilute atomic systems. While these results were impressive, they had two major barriers to practical application. First, the wavelengths were not compatible with fiber optic telecommunications. More importantly, the bandwidth obtainable in these experiments was inherently low; 100 kHz or less. Within the last five years slow and fast light effects have been observed and engineered in a much wider variety of systems. In this work, we detail our efforts to realize slow and fast light in semiconductor systems. There are three primary advantages of semiconductor systems: fiber-compatible wavelengths, larger bandwidth, and simplification of integration with other optical components. In this work we will explore three different types of physical mechanisms for implementing slow and fast light. The first is electromagnetically induced transparency (EIT). In transporting this process to semiconductors, we initially turn our attention to quantum dots or "artificial atoms". We present simulations of a quantum dot EIT-based device within the context of an optical communications link and we derive results which are generally applicable to a broad class of slow light devices. We then present experimental results realizing EIT in quantum wells by using long-lived electron spin coherence. The second mechanism we will explore is coherent population oscillations (CPO), also known as carrier density pulsations (CDP). We examine for the first time how both slow and fast light may be achieved in a quantum well semiconductor optical amplifier (SOA) while operating in the gain regime. Again, we simulate the device

  16. Your Premature Baby

    MedlinePlus

    ... It may happen together with a slow heart rate. Respiratory distress syndrome (RDS) . This is a breathing problem ... It may happen together with a slow heart rate. Respiratory distress syndrome (RDS) . This is a breathing problem ...

  17. Current status of vascular endothelial growth factor inhibition in age-related macular degeneration.

    PubMed

    Mousa, Shaker A; Mousa, Shaymaa S

    2010-06-01

    Angiogenesis, the process by which new vessels are created from pre-existing vasculature, has become the subject of intense research in recent years. Increased rates of angiogenesis are associated with several disease states, including cancer, age-related macular degeneration (AMD), psoriasis, rheumatoid arthritis, and diabetic retinopathy. Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including AMD, diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress to involve both eyes. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay of treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Several therapies have been or are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, the VEGF receptor decoy aflibercept, small interfering RNA-based therapies bevasiranib and AGN 211745, sirolimus, and tyrosine kinase inhibitors, including vatalanib, pazopanib, TG 100801, TG 101095, AG 013958, and AL 39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still under investigation offer the potential for further advances. In AMD patients, these therapies slow the rate of vision loss and in some cases increase visual acuity. Although VEGF-inhibitor therapies are a milestone in the treatment of these disease states, several concerns need to be addressed before their impact can be fully realized. PMID:20210371

  18. The Slow Learner in Mathematics: Characteristics and Needs of the Slow Learner

    ERIC Educational Resources Information Center

    Schulz, Richard W.

    1973-01-01

    Strengths and weaknesses of students classified as slow learners'' are presented with emphasis on affective concerns. The teacher, as strategic change-agent, is given suggestions for managing instruction. (LS)

  19. Tricyclic antidepressant treatment evokes regional changes in neurotrophic factors over time within the intact and degenerating nigrostriatal system

    PubMed Central

    Paumier, Katrina L.; Sortwell, Caryl E.; Madhavan, Lalitha; Terpstra, Brian; Daley, Brian F.; Collier, Timothy J.

    2015-01-01

    In addition to alleviating depression, trophic responses produced by antidepressants may regulate neural plasticity in the diseased brain, providing not only symptomatic benefit but potentially slowing the rate of disease progression in Parkinson’s disease (PD). Recent in vitro and in vivo data provide evidence that neurotrophic factors such as brain derived-neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) may be key mediators of the therapeutic response to antidepressants. As such, we conducted a cross-sectional time-course study to determine whether antidepressant-mediated changes in neurotrophic factors occur in relevant brain regions in response to amitriptyline (AMI) treatment before and after intrastriatal 6-hydroxydopamine (6OHDA). Adult male Wistar rats were divided into seven cohorts and given daily injections (i.p.) of AMI (5mg/kg) or saline throughout the duration of the study. In parallel, various cohorts of intact or parkinsonian animals were sacrificed at specific time points to determine the impact of AMI treatment on trophic factor levels in the intact and degenerating nigrostriatal system. The left and right hemispheres of the substantia nigra, striatum, frontal cortex, piriform cortex, hippocampus and anterior cingulate cortex were dissected and BDNF and GDNF levels were measured with ELISA. Results show that chronic AMI treatment elicits effects in multiple brain regions and differentially regulates levels of BDNF and GDNF depending on the region. Additionally, AMI halts the progressive degeneration of dopamine (DA) neurons elicited by an intrastriatal 6-OHDA lesion. Taken together, these results suggest that AMI treatment elicits significant trophic changes important to DA neuron survival within both the intact and degenerating nigrostriatal system. PMID:25681575

  20. Vascular-targeted photodynamic therapy in the treatment of neovascular age-related macular degeneration: Clinical perspectives.

    PubMed

    Kawczyk-Krupka, A; Bugaj, A M; Potempa, M; Wasilewska, K; Latos, W; Sieroń, A

    2015-06-01

    Vascular targeted photodynamic therapy (VTP), with use of verteporfin as a photosensitizer is one of the few therapies, which has been shown to effectively slow the progression of the "wet" form of age-related macular degeneration (AMD), and even to stabilize visual acuity over many years. Although, due to considerable advance of AMD treatment, it is currently not recommended in monotherapy of AMD, however, its combination with steroids and anti-angiogenic biologic drugs may reveal high therapeutic potential in the treatment of neovascular AMD. The future of VTP as a method of AMD treatment is development of new selective and targeted photosensitizer and combination of this method with other therapeutic strategies targeting cellular structures or pathways involved in AMD progression. PMID:25843911

  1. Recurrent slow slip event reveals the interaction with seismic slow earthquakes and disruption from large earthquake

    NASA Astrophysics Data System (ADS)

    Liu, Zhen; Moore, Angelyn W.; Owen, Susan

    2015-09-01

    It remains enigmatic how slow slip events (SSEs) interact with other slow seismic events and large distant earthquakes at many subduction zones. Here we model the spatiotemporal slip evolution of the most recent long-term SSE in 2009-2011 in the Bungo Channel region, southwest Japan using GEONET GPS position time-series and a Kalman filter-based, time-dependent slip inversion method. We examine the space-time relationship between the geodetically determined slow slip transient and seismically observed low frequency earthquakes (LFEs) and very-low frequency earthquakes (V-LFEs) near the Nankai trough. We find a strong but distinct temporal correlation between transient slip and LFEs and V-LFEs, suggesting a different relationship to the SSE. We also find the great Tohoku-Oki earthquake appears to disrupt the normal source process of the SSE, probably reflecting large-scale stress redistribution caused by the earthquake. Comparison of the 2009-2011 SSE with others in the same region shows much similarity in slip and moment release, confirming its recurrent nature. Comparison of transient slip with plate coupling shows that slip transients mainly concentrate on the transition zone from strong coupling region to downdip LFEs with transient slip relieving elastic strain accumulation at transitional depth. The less consistent spatial correlation between the long-term SSE and seismic slow earthquakes, and susceptibility of these slow earthquakes to various triggering sources including long-term slow slip, suggests caution in using the seismically determined slow earthquakes as a proxy for slow slip.

  2. Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples.

    PubMed

    Gillespie, Anna K; Jones, Emily A; Lin, Yuan-Hung; Karlsson, Mattias P; Kay, Kenneth; Yoon, Seo Yeon; Tong, Leslie M; Nova, Philip; Carr, Jessie S; Frank, Loren M; Huang, Yadong

    2016-05-18

    Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD), but the mechanism by which it causes cognitive decline is unclear. In knockin (KI) mice, human apoE4 causes age-dependent learning and memory impairments and degeneration of GABAergic interneurons in the hippocampal dentate gyrus. Here we report two functional apoE4-KI phenotypes involving sharp-wave ripples (SWRs), hippocampal network events critical for memory processes. Aged apoE4-KI mice had fewer SWRs than apoE3-KI mice and significantly reduced slow gamma activity during SWRs. Elimination of apoE4 in GABAergic interneurons, which prevents learning and memory impairments, rescued SWR-associated slow gamma activity but not SWR abundance in aged mice. SWR abundance was reduced similarly in young and aged apoE4-KI mice; however, the full SWR-associated slow gamma deficit emerged only in aged apoE4-KI mice. These results suggest that progressive decline of interneuron-enabled slow gamma activity during SWRs critically contributes to apoE4-mediated learning and memory impairments. VIDEO ABSTRACT. PMID:27161522

  3. Slow Microbial Life in the Seabed

    NASA Astrophysics Data System (ADS)

    Jørgensen, Bo Barker; Marshall, Ian P. G.

    2016-01-01

    Global microbial cell numbers in the seabed exceed those in the overlying water column, yet these organisms receive less than 1% of the energy fixed as organic matter in the ocean. The microorganisms of this marine deep biosphere subsist as stable and diverse communities with extremely low energy availability. Growth is exceedingly slow, possibly regulated by virus-induced mortality, and the mean generation times are tens to thousands of years. Intermediate substrates such as acetate are maintained at low micromolar concentrations, yet their turnover time may be several hundred years. Owing to slow growth, a cell community may go through only 10,000 generations from the time it is buried beneath the mixed surface layer until it reaches a depth of tens of meters several million years later. We discuss the efficiency of the energy-conserving machinery of subsurface microorganisms and how they may minimize energy consumption through necessary maintenance, repair, and growth.

  4. Slow microwaves in left-handed materials

    NASA Astrophysics Data System (ADS)

    di Gennaro, E.; Parimi, P. V.; Lu, W. T.; Sridhar, S.; Derov, J. S.; Turchinetz, B.

    2005-07-01

    Remarkably slow propagation of microwaves in two different classes of left-handed materials (LHM’s) is reported from microwave-pulse and continuous-wave transmission measurements. Microwave dispersion in a composite LHM made of split-ring resonators and wire strips reveals group velocity vg˜c/50 , where c is the free-space light velocity. Photonic crystals (PhC’s) made of dielectric Al2O3 rods reveal vg˜c/10 . Group delay dispersion of both the composite LHM and PhC’s determined from the experiment is in complete agreement with that obtained from theory. The slow group velocities are quantitatively described by the strong dispersion observed in these materials.

  5. Is slow slip in Cascadia tidally modulated?

    NASA Astrophysics Data System (ADS)

    Hawthorne, J. C.; Rubin, A. M.

    2009-12-01

    Several studies have shown that the seismic tremor in episodic tremor and slip is tidally modulated, suggesting a strong sensitivity to the rather small tidal stresses. We address whether the slip is also tidally modulated by examining data from six borehole strainmeters in northwest Washington and southern Vancouver Island. We use the processed data provided by Plate Boundary Observatory (PBO), which is resampled to 5-minute intervals. However, we recompute empirical corrections for tides, a long-term linear trend, and barometric pressure in the 50 days surrounding each slow slip event. We then fit sinusoids at the tidal periods to the processed data as proxies for the tidally modulated component of slip, along with a linear trend as a proxy for the net strain in the slow slip. The data are too noisy to allow detection any tidal modulation using only a single event and station. We therefore simultaneously fit data from multiple stations and from three slow slip events since 2007. This assumes that the phase of the tides at the slipping regions detected by all stations is the same and that the phase of the fault response to the tidal stress is constant. Combining the stations and events both reduces the noise at the tidal periods and creates a longer time series, which allows us to separate energy at the different tidal frequencies. We find significant tidal signals at the 12.4 and 25.8-hour periods which differ from zero at the 1.5 to 2-sigma level. Errors are estimated by bootstrapping the slow slip strain and by considering the tidal signal at times before the slow slip event. The 12.4 and 25.8-hour sinusoids have amplitudes of 23 (10-40 at 2-sigma) and 15 (0-30 at 2-sigma) percent of the maximum amplitude that does not allow the slow slip strain signal to change sign, where the mean strain rate is estimated from the linear trends fit to the slow slip data. In terms of slip rate, the sinusoids at each period could then modulate the slip rate 23 and 15 percent

  6. Critical slowing down in a dynamic duopoly

    NASA Astrophysics Data System (ADS)

    Escobido, M. G. O.; Hatano, N.

    2015-01-01

    Anticipating critical transitions is very important in economic systems as it can mean survival or demise of firms under stressful competition. As such identifying indicators that can provide early warning to these transitions are very crucial. In other complex systems, critical slowing down has been shown to anticipate critical transitions. In this paper, we investigate the applicability of the concept in the heterogeneous quantity competition between two firms. We develop a dynamic model where the duopoly can adjust their production in a logistic process. We show that the resulting dynamics is formally equivalent to a competitive Lotka-Volterra system. We investigate the behavior of the dominant eigenvalues and identify conditions that critical slowing down can provide early warning to the critical transitions in the dynamic duopoly.

  7. Slowing progression of chronic kidney disease.

    PubMed

    Drawz, Paul E; Rosenberg, Mark E

    2013-12-01

    Early identification of chronic kidney disease (CKD) provides an opportunity to implement therapies to improve kidney function and slow progression. The goal of this article is to review established and developing clinical therapies directed at slowing progression. The importance of controlling blood pressure will be discussed along with the target blood pressure that should be achieved in CKD patients. Therapy directed at inhibiting the renin-angiotensin-aldosterone system remains the mainstay of treatment with single-agent inhibition of this system being as good as dual blockade with fewer adverse effects. Other therapies that may be used include correction of metabolic acidosis, dietary protein restriction, and new models for delivering care to patients with CKD. Emerging therapies targeting endothelin, uric acid, kidney fibrosis, and oxidant stress hold promise for the future. PMID:25019022

  8. Slow Microbial Life in the Seabed.

    PubMed

    Jørgensen, Bo Barker; Marshall, Ian P G

    2016-01-01

    Global microbial cell numbers in the seabed exceed those in the overlying water column, yet these organisms receive less than 1% of the energy fixed as organic matter in the ocean. The microorganisms of this marine deep biosphere subsist as stable and diverse communities with extremely low energy availability. Growth is exceedingly slow, possibly regulated by virus-induced mortality, and the mean generation times are tens to thousands of years. Intermediate substrates such as acetate are maintained at low micromolar concentrations, yet their turnover time may be several hundred years. Owing to slow growth, a cell community may go through only 10,000 generations from the time it is buried beneath the mixed surface layer until it reaches a depth of tens of meters several million years later. We discuss the efficiency of the energy-conserving machinery of subsurface microorganisms and how they may minimize energy consumption through necessary maintenance, repair, and growth. PMID:26209150

  9. Techniques for slow cryopreservation of embryos.

    PubMed

    Gosden, Lucinda Veeck

    2014-01-01

    The slow cryopreservation of embryos has been used for nearly three decades as a means of storing surplus conceptuses from single IVF (in vitro fertilization) cycles. Doing so has allowed caregivers to maximize pregnancy rates without wastage of precious biological materials. Very detailed methods are described here using a popular biological freezing unit manufactured by Planer PLC (Middlesex, UK). Culture media preparation and tranfer protocols, including replacement in both natural and stimulated cycles, are included. PMID:24782021

  10. Slowed demand ushers in summer season

    SciTech Connect

    1996-07-01

    This article is the June 1996 market summary in uranium market. During this reporting period, there were six deals in the U3O8 spot market and three long-term deals for U3O8. There were four deals for UF6 conversion, and the spot market for uranium separation services had no transactions. This was little change from the previous month`s activities, and this slowness was reflected in the price trends of little or no increase.

  11. Slow-moving vehicles in Swedish traffic.

    PubMed

    Pinzke, S; Lundqvist, P

    2004-05-01

    The objective of this study was to reach a better understanding of accidents on Swedish roads involving slow-moving vehicles and to suggest ways of preventing such accidents. We analyzed accident data from a 5-year period (1992-1996) involving all types of farm vehicles as well as horses and horse-drawn vehicles. During each year of the period under investigation, slow-moving vehicles were involved in more than 250 traffic accidents on Swedish roads, and an average of 10 people were killed, 66 sustained serious injuries, and 192 sustained slight injuries. This was about 1.3% of all persons injured in traffic accidents in Sweden. The deaths and injuries mostly involved car drivers and passengers. Tractor drivers and unprotected road users (people walking or traveling by motorcycle, moped, or bicycle) also sustained serious injuries and deaths. Vehicles overtaking slow-moving vehicles from behind were the most common type of accident (30%), followed by turning accidents (27%), accidents at crossroads (26%), and with oncoming vehicles (17%). To strengthen the suggestions for improvement, a questionnaire was sent out to driving school teachers in Sweden. Subjects were asked about their experiences with farm vehicles on the roads and their suggestions for ways to increase traffic safety. Based on the accident data and the questionnaire responses, we developed several suggestions for reducing road accidents, including measures for making farm vehicles more visible, improvement of the training provided at driving schools, and information campaigns directed at drivers of farm vehicles and other road users. Further in-depth research is needed to analyze road accidents involving slow-moving vehicles and to test different intervention measures. PMID:15216651

  12. Single-electron tunneling with slow insulators

    NASA Astrophysics Data System (ADS)

    Fedorov, S. A.; Chtchelkatchev, N. M.; Udalov, O. G.; Beloborodov, I. S.

    2015-09-01

    The usual paradigm in the theory of electron transport is related to the fact that the dielectric permittivity of the insulator is assumed to be constant, with no time dispersion. We take into account the "slow" polarization dynamics of the dielectric layers in the tunnel barriers in the fluctuating electric fields induced by single-electron tunneling events and study transport in the single-electron transistor (SET). Here "slow" dielectric implies a time scale that is slow compared to the characteristic time scales of the SET charging-discharging effects. We show that for strong enough polarizability, such that the induced charge on the island is comparable to the elementary charge, the transport properties of the SET substantially deviate from the known results of transport theory of the SET. In particular, the Coulomb blockade is more pronounced at finite temperature, the conductance peaks change their shape, and the current-voltage characteristics show the memory effect (hysteresis). However, in contrast to SETs with ferroelectric tunnel junctions, here the periodicity of the conductance in the gate voltage is not broken; instead, the period strongly depends on the polarizability of the gate dielectric. We uncover the fine structure of the hysteresis effect where the "large" hysteresis loop may include a number of "smaller" loops. Also we predict the memory effect in the current-voltage characteristics I (V ) , with I (V )≠-I (-V ) .

  13. The Magnetic Topology of Slow Wind Sources

    NASA Astrophysics Data System (ADS)

    Antiochos, S. K.

    2012-12-01

    Due to its observed location in the heliosphere, plasma composition, and variability, most models for the origins of the slow wind postulate that it is a result of the release of closed-field plasma onto open field lines. In particular, in the S-Web model the slow wind originates at a dynamic boundary region between open and closed flux in the solar corona. Consequently, the detailed topology of the open-closed magnetic boundary is critically important for determining the properties of the slow wind. We discuss the possible magnetic topologies for the open-closed boundary. There are three main topologies corresponding to three types of observed coronal structures: helmet streamers, plumes/coronal jets, and plasma sheets (also known as pseudostreamers). I present models for each of these topologies and show that each is very different at the Sun. I also argue that each will have very different consequences for the observed properties of the wind in the heliosphere. This work was funded in part by the NASA TR&T and SR&T Programs.

  14. New slow-releasing molybdenum fertilizer.

    PubMed

    Bandyopadhyay, Siladitya; Bhattacharya, Ishita; Ghosh, Kunal; Varadachari, Chandrika

    2008-02-27

    This paper describes a new water-insoluble molybdenum compound that has been developed as a slow-release fertilizer. The compound is an inorganic polymer formed by inclusion of molybdenum within a long-chain polyphosphate structure. It was designed by a process of "reverse engineering" of the molecule. Synthesis involved reaction of phosphoric acid with magnesium oxide, molybdenum trioxide, and sodium carbonate at 275 degrees C. Kinetics of reaction revealed complex multistage processes. X-ray diffraction patterns showed a crystalline nature with short-range as well as long-range ordering. The magnesium sodium polymolybdophosphate had ideal slow-release characteristics; it had low water solubility and high citrate solubility and was powdery, free flowing, and nonhygroscopic. Field testing showed an 80% increase in yield of green gram at a low dose of 0.04 kg/ha Mo. Nodulation increased by over 161%, and N content of gram increased by 20%. The slow-release fertilizer would provide an effective, low-cost, and environmentaly friendly alternative to Mo fertilization. PMID:18247562

  15. Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging.

    PubMed

    Mader, Kerstin T; Peeters, Mirte; Detiger, Suzanne E L; Helder, Marco N; Smit, Theo H; Le Maitre, Christine L; Sammon, Chris

    2016-06-23

    Traditionally tissue samples are analysed using protein or enzyme specific stains on serial sections to build up a picture of the distribution of components contained within them. In this study we investigated the potential of multivariate curve resolution-alternating least squares (MCR-ALS) to deconvolute 2nd derivative spectra of Fourier transform infrared (FTIR) microscopic images measured in transflectance mode of goat and human paraffin embedded intervertebral disc (IVD) tissue sections, to see if this methodology can provide analogous information to that provided by immunohistochemical stains and bioassays but from a single section. MCR-ALS analysis of non-degenerate and enzymatically in vivo degenerated goat IVDs reveals five matrix components displaying distribution maps matching histological stains for collagen, elastin and proteoglycan (PG), as well as immunohistochemical stains for collagen type I and II. Interestingly, two components exhibiting characteristic spectral and distribution profiles of proteoglycans were found, and relative component/tissue maps of these components (labelled PG1 and PG2) showed distinct distributions in non-degenerate versus mildly degenerate goat samples. MCR-ALS analysis of human IVD sections resulted in comparable spectral profiles to those observed in the goat samples, highlighting the inter species transferability of the presented methodology. Multivariate FTIR image analysis of a set of 43 goat IVD sections allowed the extraction of semi-quantitative information from component/tissue gradients taken across the IVD width of collagen type I, collagen type II, PG1 and PG2. Regional component/tissue parameters were calculated and significant correlations were found between histological grades of degeneration and PG parameters (PG1: p = 0.0003, PG2: p < 0.0001); glycosaminoglycan (GAG) content and PGs (PG1: p = 0.0055, PG2: p = 0.0001); and MRI T2* measurements and PGs (PG1: p = 0.0021, PG2: p < 0.0001). Additionally

  16. Nekhoroshev stability in quasi-integrable degenerate Hamiltonian systems.

    NASA Astrophysics Data System (ADS)

    Guzzo, M.

    A perturbation of a degenerate integrable Hamiltonian system has the form H(I,φ ,p,q)=h(I)+ɛ f(I,φ ,p,q) with (I,φ )in Rn x Tn, (p,q) in B subseteq R2m and the two-form is dI wedge dφ + dp wedge dq. In the case h is convex, Nekhoroshev theorem provides the usual bound to the motion of the actions I, but only for a time which is the smaller between the usual exponentially-long time and the escape time of (p,q) from B. Furthermore, the theorem does not provide any estimate for the `degenerate' variables (p,q) better than the a priori one dot p,dot q ~ ɛ, and actually in the literature there are examples of degenerate systems with degenerate variables that perform large chaotic motions in short times. Therefore, there is the problem of individuating which assumptions on the perturbation and on the initial data allows one to produce stability bounds for the degenerate variables over long times, thus preventing chaotic motions and escape. The problem is relevant to understand the long time stability of several systems, like the three body problem, the asteroid belt dynamical system and the fast rotations of the rigid body. In this work we show that if the `secular' hamiltonian of H, i.e the average of H with respect to the fast angles φ, is integrable (or quasi-integrable) and if it satisfies a suitable convexity condition, then a Nekhoroshev-like bound also holds for the degenerate variables (p,q) (actually for the actions of the secular integrable system) for all initial data except those with initial action I(0) in a small neighborhood of the resonant manifolds of order lower than ln 1 ɛ. It is worthwhile to note that even if the secular hamiltonian of H is integrable, strong chaotic motions can take place in short times near such low order resonant manifolds, as it can be shown on examples. This result was proved for the first time in connection with the problem of the long-time stability in the asteroid belt.

  17. Slow movement execution in event-related potentials (P300).

    PubMed

    Naruse, Kumi; Sakuma, Haruo; Hirai, Takane

    2002-02-01

    We examined whether slow movement execution has an effect on cognitive and information processing by measuring the P300 component. 8 subjects performed a continuous slow forearm rotational movement using 2 task speeds. Slow (a 30-50% decrease from the subject's Preferred speed) and Very Slow (a 60-80% decrease). The mean coefficient of variation for rotation speed under Very Slow was higher than that under Slow, showing that the subjects found it difficult to perform the Very Slow task smoothly. The EEG score of alpha-1 (8-10 Hz) under Slow Condition was increased significantly more than under the Preferred Condition; however, the increase under Very Slow was small when compared with Preferred. After performing the task. P300 latency under Very Slow increased significantly as compared to that at pretask. Further, P300 amplitude decreased tinder both speed conditions when compared to that at pretask, and a significant decrease was seen under the Slow Condition at Fz, whereas the decrease under the Very Slow Condition was small. These differences indicated that a more complicated neural composition and an increase in subjects' attention might have been involved when the task was performed under the Very Slow Condition. We concluded that slow movement execution may have an influence on cognitive function and may depend on the percentage of decrease from the Preferred speed of the individual. PMID:11883570

  18. Challenges in the Development of Therapy for Dry Age-Related Macular Degeneration.

    PubMed

    Wei, Cynthia X; Sun, Aixu; Yu, Ying; Liu, Qianyong; Tan, Yue-Qing; Tachibana, Isamu; Zeng, Hong; Wei, Ji-Ye

    2016-01-01

    Dry age-related macular degeneration (AMD), a multifactorial progressive degenerative disease of the retinal photoreceptors, pigmented epithelium and Bruch's membrane/choroid in central retina, causes visual impairment in millions of elderly people worldwide. The only available therapy for this disease is the over-the-counter (OTC) multi-vitamins plus macular xanthophyll (lutein/zeaxanthin) which attempts to block the damages of oxidative stress and ionizing blue light. Therefore development of dry AMD prescribed treatment is a pressing unmet medical need. However, this effort is currently hindered by many challenges, including an incomplete understanding of the mechanism of pathogenesis that leads to uncertain targets, confounded by not yet validated preclinical models and the difficulty to deliver the drugs to the posterior segment of the eye. Additionally, with slow disease progression and a less than ideal endpoint measurement method, clinical trials are necessarily large, lengthy and expensive. Increased commitment to research and development is an essential foundation for dealing with these problems. Innovations in clinical trials with novel endpoints, nontraditional study designs and the use of surrogate diseases might shorten the study time, reduce the patient sample size and consequently lower the budget for the development of the new therapies for the dry AMD. PMID:26427400

  19. Nutrient Supplementation for Age-related Macular Degeneration, Cataract, and Dry Eye

    PubMed Central

    Hobbs, Ronald P.; Bernstein, Paul S.

    2014-01-01

    There have been enormous advances in the past decade for the treatment of age-related macular degeneration (AMD); however, these treatments are expensive and require frequent follow-up and injections which place a tremendous burden on both the healthcare system and patients. Consequently, there remains considerable interest in preventing or slowing the progression of AMD requiring treatment. Epidemiological studies have shown that diet is a modifiable AMD risk factor, and nutrient modification is a particularly appealing treatment for AMD due to the perceived universal benefit and relatively low expense. Recently, the age-related eye disease study part two (AREDS2) was concluded and demonstrated further benefit with the addition of lutein and zeaxanthin as a replacement for the β-carotene of the previous generation formulation. The addition of omega-3 essential fatty acids did not show an added benefit. This review aims to highlight some of the evidenced based body of knowledge that has been accumulated from recent studies regarding the use of nutritional supplements and their effect on AMD, cataracts, and dry eyes. PMID:25709776

  20. Electrostatic soliton and double layer structures in unmagnetized degenerate pair plasmas

    SciTech Connect

    Mahmood, S.; Khan, S. A.; Ur-Rehman, H.

    2010-11-15

    The acoustic solitons and double layers are studied in unmagnetized quantum electron-positron plasmas in the presence of stationary ions. The quantum hydrodynamic model is employed and reductive perturbation method is used to derive the Korteweg-de Vries (KdV) and extended KdV equations for solitons and double layers, respectively. It is found that in the linear limit both slow acoustic and fast Langmuir waves can propagate in such type of quantum plasmas like in classical pair-ion or pair plasmas. The amplitude and width of the electrostatic solitons are found to be decreasing with the increase in concentration of positrons (or decrease in the concentration of ions) in degenerate electron-positron-ion plasmas. It is found that only rarefactive double layer can exist in such plasmas which depend on various parameters. The dependence of double layer structure on ion concentration and quantum diffraction effects of electrons and positrons are also discussed. The results are also elaborated graphically by considering dense plasma parameters in the outer layers of astrophysical objects such as white dwarfs and neutron stars.

  1. Use of Hydrogen as a Novel Therapeutic Strategy Against Photoreceptor Degeneration in Retinitis Pigmentosa Patients

    PubMed Central

    Tao, Ye; Geng, Lei; Wang, Liqiang; Xu, Weiwei; Qin, Limin; Peng, Guanghua; Huang, Yi Fei; Yang, Ji xue

    2016-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterized by progressive photoreceptor apoptosis. Reactive oxygen species (ROS) have been recognized as critical initiators of the photoreceptor apoptosis in RP. Photoreceptor survival in RP mutants will not only require the inhibition of effectors of apoptotic machinery, but also the elimination of the initiating upstream signals, such as ROS. These cytotoxic ROS should be neutralized by the antioxidant defense system, otherwise they would interact with the macromolecules essential for photoreceptor survival. Hydrogen is a promising gaseous agent that has come to the forefront of therapeutic research over the last few years. It has been verified that hydrogen is capable of neutralizing the cytotoxic ROS selectively, rectifying abnormities in the apoptotic cascades, and attenuating the related inflammatory response. Hydrogen is so mild that it does not disturb the metabolic oxidation-reduction reactions or disrupt the physiologic ROS involved in cell signaling. Based on these findings, we hypothesize that hydrogen might be an effective therapeutic agent to slow or prevent photoreceptor degeneration in RP retinas. It is a logical step to test hydrogen for therapeutic use in multiple RP animal models, and ultimately in human RP patients. PMID:26952558

  2. Combination of memantine and vitamin D prevents axon degeneration induced by amyloid-beta and glutamate.

    PubMed

    Annweiler, Cédric; Brugg, Bernard; Peyrin, Jean-Michel; Bartha, Robert; Beauchet, Olivier

    2014-02-01

    The currently available drugs for treatment of Alzheimer's disease are symptomatic and only temporarily slow down the natural history of the disease process. Recently, its has been proposed that the combination of memantine with vitamin D, a neurosteroid hormone, may prevent amyloid-beta and glutamate neurotoxicity. Here, our purpose was to examine the potential protective effects of memantine and vitamin D against amyloid-beta peptide and glutamate toxicity in cortical neuronal cultures. We provide the first evidence that cortical axons degenerate less after exposure to amyloid-beta peptide or glutamate in microfluidic neuronal cultures enriched with memantine plus vitamin D compared to control medium and cultures enriched with only memantine or only vitamin D. The reported synergistic neuroprotective effect of memantine plus vitamin D -the combination originating an effect stronger than the sum- corroborate previous clinical finding that Alzheimer's disease patients using this drug combination have improved cognition. This finding reinforces the pharmacological potential of a new drug combining memantine plus vitamin D for the treatment or the prevention of Alzheimer's disease. PMID:24011542

  3. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?

    PubMed

    Saad, Leonide; Washington, Ilyas

    2016-01-01

    We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway. PMID:26427432

  4. Nonlinear dynamical triggering of slow slip

    SciTech Connect

    Johnson, Paul A; Knuth, Matthew W; Kaproth, Bryan M; Carpenter, Brett; Guyer, Robert A; Le Bas, Pierre - Yves; Daub, Eric G; Marone, Chris

    2010-12-10

    Among the most fascinating, recent discoveries in seismology have been the phenomena of triggered slip, including triggered earthquakes and triggered-tremor, as well as triggered slow, silent-slip during which no seismic energy is radiated. Because fault nucleation depths cannot be probed directly, the physical regimes in which these phenomena occur are poorly understood. Thus determining physical properties that control diverse types of triggered fault sliding and what frictional constitutive laws govern triggered faulting variability is challenging. We are characterizing the physical controls of triggered faulting with the goal of developing constitutive relations by conducting laboratory and numerical modeling experiments in sheared granular media at varying load conditions. In order to simulate granular fault zone gouge in the laboratory, glass beads are sheared in a double-direct configuration under constant normal stress, while subject to transient perturbation by acoustic waves. We find that triggered, slow, silent-slip occurs at very small confining loads ({approx}1-3 MPa) that are smaller than those where dynamic earthquake triggering takes place (4-7 MPa), and that triggered slow-slip is associated with bursts of LFE-like acoustic emission. Experimental evidence suggests that the nonlinear dynamical response of the gouge material induced by dynamic waves may be responsible for the triggered slip behavior: the slip-duration, stress-drop and along-strike slip displacement are proportional to the triggering wave amplitude. Further, we observe a shear-modulus decrease corresponding to dynamic-wave triggering relative to the shear modulus of stick-slips. Modulus decrease in response to dynamical wave amplitudes of roughly a microstrain and above is a hallmark of elastic nonlinear behavior. We believe that the dynamical waves increase the material non-affine elastic deformation during shearing, simultaneously leading to instability and slow-slip. The inferred

  5. Intervertebral disc degeneration in the dog. Part 1: Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration.

    PubMed

    Bergknut, Niklas; Smolders, Lucas A; Grinwis, Guy C M; Hagman, Ragnvi; Lagerstedt, Anne-Sofie; Hazewinkel, Herman A W; Tryfonidou, Marianna A; Meij, Björn P

    2013-03-01

    Intervertebral disc (IVD) degeneration is common in dogs and can give rise to a number of diseases, such as IVD herniation, cervical spondylomyelopathy, and degenerative lumbosacral stenosis. Although there have been many reports and reviews on the clinical aspects of canine IVD disease, few reports have discussed and reviewed the process of IVD degeneration. In this first part of a two-part review, the anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are described. In Part 2, the aspects of IVD degeneration in chondrodystrophic and non-chondrodystrophic dog breeds are discussed in depth. PMID:23177522

  6. A role of Heat Shock Protein 70 in Photoreceptor Cell Death: Potential as a Novel Therapeutic Target in Retinal Degeneration.

    PubMed

    Furukawa, Ayako; Koriyama, Yoshiki

    2016-01-01

    Retinal degenerative diseases (RDs) such as retinitis pigmentosa (RP) are a genetically heterogeneous group of disorders characterized by night blindness and peripheral vision loss, which caused by the dysfunction and death of photoreceptor cells. Although many causative gene mutations have been reported, the final common end stage is photoreceptor cell death. Unfortunately, no effective treatments or therapeutic agents have been discovered. Heat shock protein 70 (HSP70) is highly conserved and has antiapoptotic activities. A few reports have shown that HSP70 plays a role in RDs. Thus, we focused on the role of HSP70 in photoreceptor cell death. Using the N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death model in mice, we could examine two stages of the novel cell death mechanism; the early stage, including HSP70 cleavage through protein carbonylation by production of reactive oxygen species, lipid peroxidation and Ca(2+) influx/calpain activation, and the late stage of cathepsin and/or caspase activation. The upregulation of intact HSP70 expression by its inducer is likely to protect photoreceptor cells. In this review, we focus on the role of HSP70 and the novel cell death signaling process in RDs. We also describe candidate therapeutic agents for RDs. PMID:26507240

  7. Histology of spheroidal degeneration of the cornea in Labrador.

    PubMed Central

    Johnson, G. J.; Overall, M.

    1978-01-01

    Nine specimens of the corneas of patients from Labrador and Northern Newfoundland affected by spheroidal degeneration (climatic droplet keratopathy) have been examined microscopically. Histochemical stains confirmed studies of similar corneal degenerations from other geographical areas that the droplets contain a protein which does not have all the characteristic properties of elastic tissue. Staining compatible in some instances with fibrin and "fibrinoid" was found. By immunoperoxidase techniques the droplets were located in the zones of greatest concentration of various plasma constituents, especially albumin and immunoglobulins G and A. Reasons are given why the abnormal deposits are not thought to be derived directly from corneal collagen. It is suggested that some of the plasma proteins, which are known to be diffusing through the cornea from the limbal vessels under normal conditions are acted upon by the ultraviolet light reflected from the ice of Labrador and degraded so that they accumulate in the superficial stroma. Images PMID:629911

  8. Molecular pathology of age-related macular degeneration

    PubMed Central

    Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

    2009-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

  9. C1,1 regularity for degenerate elliptic obstacle problems

    NASA Astrophysics Data System (ADS)

    Daskalopoulos, Panagiota; Feehan, Paul M. N.

    2016-03-01

    The Heston stochastic volatility process is a degenerate diffusion process where the degeneracy in the diffusion coefficient is proportional to the square root of the distance to the boundary of the half-plane. The generator of this process with killing, called the elliptic Heston operator, is a second-order, degenerate-elliptic partial differential operator, where the degeneracy in the operator symbol is proportional to the distance to the boundary of the half-plane. In mathematical finance, solutions to the obstacle problem for the elliptic Heston operator correspond to value functions for perpetual American-style options on the underlying asset. With the aid of weighted Sobolev spaces and weighted Hölder spaces, we establish the optimal C 1 , 1 regularity (up to the boundary of the half-plane) for solutions to obstacle problems for the elliptic Heston operator when the obstacle functions are sufficiently smooth.

  10. Doppel Induces Degeneration of Cerebellar Purkinje Cells Independently of Bax

    PubMed Central

    Dong, Jiaxin; Li, Aimin; Yamaguchi, Naohiro; Sakaguchi, Suehiro; Harris, David A.

    2007-01-01

    Doppel (Dpl) is a prion protein paralog that causes neurodegeneration when expressed ectopically in the brain. To investigate the cellular mechanism underlying this effect, we analyzed Dpl-expressing transgenic mice in which the gene for the proapoptotic protein Bax had been deleted. We found that Bax deletion does not alter either clinical symptoms or Purkinje cell degeneration in Dpl transgenic mice. In addition, we observed that degenerating Purkinje cells in these animals do not display DNA fragmentation or caspase-3 activation. Our results suggest that non-Bax-dependent pathways mediate the toxic effects of Dpl in Purkinje cells, highlighting a possible role for nonapoptotic mechanisms in the death of these neurons. PMID:17569776

  11. Visual prosthetic device for bilateral end-stage macular degeneration.

    PubMed

    Chun, Dal W; Heier, Jeffrey S; Raizman, Michael B

    2005-11-01

    Age-related macular degeneration is the leading cause of blindness in the USA. For the 1.8 million patients in the most advanced stages, there are currently no available treatments to improve vision. A visual prosthetic device that provides one eye with an enlarged retinal image of the central visual field has been developed with the goal of improving central vision in patients with bilateral end-stage macular degeneration. The other eye is left unimplanted to provide peripheral vision. This device is designed for implantation in the posterior chamber of the eye during an outpatient surgical procedure. In US Food and Drug Administration clinical trials, 72% of patients experienced an improvement in their level of visual impairment (profound or severe, to severe or moderate). This was accompanied by a clinically significant improvement in quality of life. PMID:16293092

  12. Juvenile-Onset Macular Degeneration and Allied Disorders

    PubMed Central

    North, Victoria; Gelman, Rony; Tsang, Stephen H.

    2015-01-01

    While age-related macular degeneration (AMD) is a leading cause of central vision loss among the elderly, many inherited diseases that present earlier in life share features of AMD. These diseases of juvenile-onset macular degeneration include Stargardt disease, Best disease, retinitis pigmentosa, X-linked retinoschisis, and other allied disorders. In particular, they can be accompanied by the appearance of drusen, geographic atrophy, macular hyperpigmentation, choroidal neovascularization, and disciform scarring just as in AMD, and often may be confused for the adult form of the disease. Diagnosis based on funduscopic findings alone can be challenging. However, the use of diagnostic studies such as electroretinography, electrooculography, optical coherence tomography, and fundus autofluorescence in conjunction with genetic testing can lead to an accurate diagnosis. PMID:24732760

  13. Oral and silent reading performance with macular degeneration.

    PubMed

    Lovie-Kitchin, J E; Bowers, A R; Woods, R L

    2000-09-01

    Previous studies have shown that reading rate for very large print (6 degrees, 1.86 logMAR character size) is a strong predictor of oral reading rate with low vision devices (LVDs). We investigated whether this would apply using large print sizes more readily available in clinical situations (e.g. 2 degrees, 1.4 logMAR), for subjects with macular degeneration. We assessed rauding rates--reading for understanding. A combination of near word visual acuity and large print reading rate (without LVDs) provided the best prediction of oral rauding rates (with LVDs). However, near word visual acuity alone was almost as good. Similarly, silent rauding rate was predicted best by near word visual acuity alone. We give near visual acuity limits as a clinical guide to expected oral and silent reading performance with LVDs for patients with macular degeneration. PMID:11045244

  14. Degenerate band edge resonances in periodic silicon ridge waveguides.

    PubMed

    Wood, Michael G; Burr, Justin R; Reano, Ronald M

    2015-06-01

    We experimentally demonstrate degenerate band edge resonances in periodic Si ridge waveguides that are compatible with carrier injection modulation for active electro-optical devices. The resonant cavities are designed using a combination of the plane-wave expansion method and the finite difference time domain technique. Measured and simulated quality factors of the first band edge resonances scale to the fifth power of the number of periods. Quality factor scaling is determined to be limited by fabrication imperfections. Compared to resonators based on a regular transmission band edge, degenerate band edge devices can achieve significantly larger quality factors in the same number of periods. Applications include compact electro-optical switches, modulators, and sensors that benefit from high-quality factors and large distributed electric fields. PMID:26030540

  15. Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

    PubMed Central

    Yamada, Jun; Abula, Kahaer; Inoue, Makiko; Sekiya, Ichiro; Muneta, Takeshi

    2014-01-01

    Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration. PMID:25574420

  16. Smoking and Age-Related Macular Degeneration: Review and Update

    PubMed Central

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  17. Degenerate perturbative treatment of the hydrogenic Zeeman effect

    SciTech Connect

    Chen, A.C.

    1983-07-01

    Degenerate perturbation theory is applied to study the first 14 energy levels of the hydrogen atom in a uniform magnetic field up to the second order. The twofold degeneracy of all the levels among them in terms of the oscillator or parabolic states is completely removed. The results obtained with the use of the Pade approximant are compared with those found in the literature. Level crossings are discussed.

  18. Cardiac valve degeneration in a patient with Sneddon syndrome.

    PubMed

    Diosteanu, Raluca; Schuler, Gerhard; Müller, Ulrike

    2015-06-01

    Sneddon syndrome--a rare cause of aortic and mitral valve stenosis. Sneddon syndrome is a rare disorder that leads to repeated occurrence of cerebrovascular disease and skin manifestation, defined as livedo racemosa generalisata. The authors report the occurrence of multiple valve degenerations in a 49-year-old patient with Sneddon syndrome, which seemed to have been asymptomatic through a long period of time and was diagnosed as it needed a complex surgical intervention. PMID:25479820

  19. Suppression of Density Fluctuations in a Quantum Degenerate Fermi Gas

    SciTech Connect

    Sanner, Christian; Su, Edward J.; Keshet, Aviv; Gommers, Ralf; Shin, Yong-il; Huang Wujie; Ketterle, Wolfgang

    2010-07-23

    We study density profiles of an ideal Fermi gas and observe Pauli suppression of density fluctuations (atom shot noise) for cold clouds deep in the quantum degenerate regime. Strong suppression is observed for probe volumes containing more than 10 000 atoms. Measuring the level of suppression provides sensitive thermometry at low temperatures. After this method of sensitive noise measurements has been validated with an ideal Fermi gas, it can now be applied to characterize phase transitions in strongly correlated many-body systems.

  20. Degeneration of the Y chromosome in evolutionary aging models

    NASA Astrophysics Data System (ADS)

    Lobo, M. P.; Onody, R. N.

    2005-06-01

    The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

  1. Electrostatic rogue-waves in relativistically degenerate plasmas

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2014-10-15

    In this paper, we investigate the modulational instability and the possibility of electrostatic rogue-wave propagations in a completely degenerate plasma with arbitrary degree of degeneracy, i.e., relativistically degenerate plasma, ranging from solid density to the astrophysical compact stars. The hydrodynamic approach along with the perturbation method is used to reduce the governing equations to the nonlinear Schrödinger equation from which the modulational instability, the growth rate of envelope excitations and the occurrence of rogue as well as super-rogue waves in the plasma, is evaluated. It is observed that the modulational instability in a fully degenerate plasma can be quite sensitive to the plasma number-density and the wavenumber of envelop excitations. It is further revealed that the relativistically degeneracy plasmas (R{sub 0} > 1) are almost always modulationally unstable. It is found, however, that the highly energetic sharply localized electrostatic rogue as well as super-rogue waves can exist in the astrophysical compact objects like white dwarfs and neutron star crusts. The later may provide a link to understand many physical processes in such stars and it may lead us to the origin of the random-localized intense short gamma-ray bursts, which “appear from nowhere and disappear without a trace” quite similar to oceanic rogue structures.

  2. Exact nonlinear excitations in double-degenerate plasmas

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2012-06-15

    In this work, we use the conventional hydrodynamics formalism and incorporate the Chew-Goldberger-Low double-adiabatic theory to evaluate the nonlinear electrostatic ion excitations in double-degenerate (electron spin-orbit degenerate) magnetized quantum plasmas. Based on the Sagdeev pseudopotential method, an exact general pseudopotential is calculated which leads to the allowed Mach-number range criteria for such localized density structures in an anisotropic magnetized plasma. We employ the criteria on the Mach-number range for diverse magnetized quantum plasma with different equations of state. It is remarked that various plasma fractional parameters such as the system dimensionality, ion-temperature, relativistic-degeneracy, Zeeman-energy, and plasma composition are involved in the stability of an obliquely propagating nonlinear ion-acoustic wave in a double-degenerate quantum plasma. Current study is most appropriate for nonlinear wave analysis in dense astrophysical magnetized plasma environments such as white-dwarfs and neutron-star crusts where the strong magnetic fields can be present.

  3. Advances in repairing the degenerate retina by rod photoreceptor transplantation☆

    PubMed Central

    Pearson, Rachael A.

    2014-01-01

    Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application. PMID:24412415

  4. Accretion of gas and comets onto a nearby degenerate star

    NASA Astrophysics Data System (ADS)

    Pineault, S.

    1987-04-01

    Conditions under which accretion onto a nearby degenerate star, i.e., a white dwarf (WD) or neutron star (NS), could produce a sufficient flux of high-energy radiation to threaten the Earth's protective ozone layer are investigated. Both the case of a field star making a brief encounter with the Solar System and that of a degenerate solar companion ("Nemesis") are considered. For steady accretion from the interstellar medium (ISM), no significant flux is expected from a WD or a low-mass NS. A 1 M_sun; NS could deplete the ozone layer but only if either its closest approach is on the order of 1000 AU or the local ISM density is somewhat higher than average. A field star has a probability of about 2% of making such a close encounter over the lifetime of the Solar System. In the Nemesis case, an ellipticity of 0.99 is implied for a canonical period of 26 myr. In both cases, accretion of comets from the Oort cloud could result in γ-ray bursts, whose fluence could reach a significant level if the star came near the inner edge of the comet cloud. A degenerate Nemesis, if now at the aphelion of its proposed orbit, could be potentially observable as an X-ray or γ-ray source.

  5. Ultra-long-ranged dispersion interaction between degenerate molecules

    NASA Astrophysics Data System (ADS)

    Dobson, John; Savin, Andreas

    2015-03-01

    It is known (see e.g.) that extended nano-systems with zero electronic gaps can exhibit dispersion interactions that fall off with unexpected powers of distance D. We seek to find a similar phenomenon between finite molecules that have a strictly degenerate many-electron groundstate (zero gap). As a toy model we take H3 with the atoms constrained to lie on an equilateral triangle of side a, using a minimal (s) basis set, and with spin-orbit coupling omitted. Rotational symmetry at fixed spins guarantees a degenerate time-reversed pair of three-electron states. For sufficiently small atomic spacing a where inter-atomic hopping kinetic energy dominates the electron-electron repulsion, these degenerate time-reversed pairs of states are many-electron groundstates. We confirm this groundstate degeneracy via limited-basis CI calculations. We show that the resulting dispersion energy between two such constrained H3 molecules falls off as D**(-3)instead of the usual D**(-6). Within the classification scheme proposed in ref, this effect can be interpreted as a ``type C non-additivity'' of the dispersion interaction. This model may be relevant to metal atom clusters. JFD acknowledges Australian Research Council Grant DP1096240. We benefited from discussions with Prof. Janos Angyan and Dr. Ru-Fen Liu.

  6. Humor and laughter in patients with cerebellar degeneration.

    PubMed

    Frank, B; Propson, B; Göricke, S; Jacobi, H; Wild, B; Timmann, D

    2012-06-01

    Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation. PMID:22012411

  7. Decellularized allogeneic intervertebral disc: natural biomaterials for regenerating disc degeneration

    PubMed Central

    Hu, Zhijun; Chen, Kai; Shan, Zhi; Chen, Shuai; Wang, Jiying; Mo, Jian; Ma, Jianjun; Xu, Wenbing; Qin, An; Fan, Shunwu

    2016-01-01

    Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo. Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro. Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro. Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo. In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases. PMID:26933821

  8. Coherent pulsed excitation of degenerate multistate systems: Exact analytic solutions

    SciTech Connect

    Kyoseva, E. S.; Vitanov, N. V.

    2006-02-15

    We show that the solution of a multistate system composed of N degenerate lower (ground) states and one upper (excited) state can be reduced by using the Morris-Shore transformation to the solution of a two-state system involving only the excited state and a (bright) superposition of ground states. In addition, there are N-1 dark states composed of ground states. We use this decomposition to derive analytical solutions for degenerate extensions of the most popular exactly soluble models: the resonance solution, the Rabi, Landau-Zener, Rosen-Zener, Allen-Eberly, and Demkov-Kunike models. We suggest various applications of the multistate solutions, for example, as tools for creating multistate coherent superpositions by generalized resonant {pi} pulses. We show that such generalized {pi} pulses can occur even when the upper state is far off resonance, at specific detunings, which makes it possible to operate in the degenerate ground-state manifold without populating the (possibly lossy) upper state, even transiently.

  9. Synapse loss and axon retraction in response to local muscle degeneration.

    PubMed

    Hegstrom, C D; Truman, J W

    1996-10-01

    During metamorphosis in the moth, Manduca sexta, the abdominal body-wall muscle DEO1 is remodeled to form the adult muscle DE5. As the larval muscle degenerates, its motoneuron loses its end plates and retracts axon branches from the degenerating muscle. Muscle degeneration is under the control of the insect hormones, the ecdysteroids. Topical application of an ecdysteroid mimic resulted in animals that produced a localized patch of pupal cuticle. Muscle fibers underlying the patch showed a gradient of degeneration. The motoneuron showed end-plate loss and axon retraction from degenerating regions of a given fiber but maintained its fine terminal branches and end plates on intact regions. The results suggest that local steroid treatments that result in local muscle degeneration bring about a loss of synaptic contacts from regions of muscle degeneration. PMID:8885199

  10. Slow Wave Sleep and Long Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Whitmire, Alexandra; Orr, Martin; Arias, Diana; Rueger, Melanie; Johnston, Smith; Leveton, Lauren

    2012-01-01

    While ground research has clearly shown that preserving adequate quantities of sleep is essential for optimal health and performance, changes in the progression, order and /or duration of specific stages of sleep is also associated with deleterious outcomes. As seen in Figure 1, in healthy individuals, REM and Non-REM sleep alternate cyclically, with stages of Non-REM sleep structured chronologically. In the early parts of the night, for instance, Non-REM stages 3 and 4 (Slow Wave Sleep, or SWS) last longer while REM sleep spans shorter; as night progresses, the length of SWS is reduced as REM sleep lengthens. This process allows for SWS to establish precedence , with increases in SWS seen when recovering from sleep deprivation. SWS is indeed regarded as the most restorative portion of sleep. During SWS, physiological activities such as hormone secretion, muscle recovery, and immune responses are underway, while neurological processes required for long term learning and memory consolidation, also occur. The structure and duration of specific sleep stages may vary independent of total sleep duration, and changes in the structure and duration have been shown to be associated with deleterious outcomes. Individuals with narcolepsy enter sleep through REM as opposed to stage 1 of NREM. Disrupting slow wave sleep for several consecutive nights without reducing total sleep duration or sleep efficiency is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. Depression has been shown to be associated with a reduction of slow wave sleep and increased REM sleep. Given research that shows deleterious outcomes are associated with changes in sleep structure, it is essential to characterize and mitigate not only total sleep duration, but also changes in sleep stages.

  11. Detecting slow moving targets in SAR images

    NASA Astrophysics Data System (ADS)

    Linnehan, Robert; Perlovsky, Leonid; Mutz, Chris W.; Schindler, John

    2004-08-01

    Ground moving target indication (GMTI) radars can detect slow-moving targets if their velocities are high enough to produce distinguishable Doppler frequencies. However, no reliable technique is currently available to detect targets that fall below the minimum detectable velocity (MDV) of GMTI radars. In synthetic aperture radar (SAR) images, detection of moving targets is difficult because of target smear due to motion, which could make low-RCS targets fall below stationary ground clutter. Several techniques for SAR imaging of moving targets have been discussed in the literature. These techniques require sufficient signal-to-clutter ratio (SCR) and adequate MDV for pre-detection. Other techniques require complex changes in hardware. Extracting the maximum information from SAR image data is possible using adaptive, model-based approaches. However, these approaches lead to computational complexity, which exceeds current processing power for more than a single object in an image. This combinatorial complexity is due to the need for having to consider a large number of combinations between multiple target models and the data, while estimating unknown parameters of the target models. We are developing a technique for detecting slow-moving targets in SAR images with low signal-to-clutter ratio, without minimal velocity requirements, and without combinatorial complexity. This paper briefly summarizes the difficulties related to current model-based detection algorithms. A new concept, dynamic logic, is introduced along with an algorithm suitable for the detection of very slow-moving targets in SAR images. This new mathematical technique is inspired by the analysis of biological systems, like the human brain, which combines conceptual understanding with emotional evaluation and overcomes the combinatorial complexity of model-based techniques.

  12. BLAISDELL SLOW SAND FILTER WASHING MACHINE. VIEW LOOKING SOUTHWEST. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BLAISDELL SLOW SAND FILTER WASHING MACHINE. VIEW LOOKING SOUTHWEST. - Yuma Main Street Water Treatment Plant, Blaisdell Slow Sand Filter Washing Machine, Jones Street at foot of Main Street, Yuma, Yuma County, AZ

  13. Improved Slow Light Capacity In Graphene-based Waveguide

    PubMed Central

    Hao, Ran; Peng, Xi-Liang; Li, Er-Ping; Xu, Yang; Jin, Jia-Min; Zhang, Xian-Min; Chen, Hong-Sheng

    2015-01-01

    We have systematically investigated the wideband slow light in two-dimensional material graphene, revealing that graphene exhibits much larger slow light capability than other materials. The slow light performances including material dispersion, bandwidth, dynamic control ability, delay-bandwidth product, propagation loss, and group-velocity dispersion are studied, proving graphene exhibits significant advantages in these performances. A large delay-bandwidth product has been obtained in a simple yet functional grating waveguide with slow down factor c/vg at 163 and slow light bandwidth Δω at 94.4 nm centered at 10.38 μm, which is several orders of magnitude larger than previous results. Physical explanation of the enhanced slow light in graphene is given. Our results indicate graphene is an excellent platform for slow light applications, promoting various future slow light devices based on graphene. PMID:26478563

  14. Slow-wave synchronous pick-up and kicker

    SciTech Connect

    DiMassa, G.

    1988-01-01

    Slow-wave synchronous pick-up (PU) and Kicker (K) are proposed for the stochastic cooling of bunched beams in RHIC. A corrugated waveguide is used to support a slow wave that is synchronous with the beam.

  15. Slowing after Observed Error Transfers across Tasks

    PubMed Central

    Wang, Lijun; Pan, Weigang; Tan, Jinfeng; Liu, Congcong; Chen, Antao

    2016-01-01

    After committing an error, participants tend to perform more slowly. This phenomenon is called post-error slowing (PES). Although previous studies have explored the PES effect in the context of observed errors, the issue as to whether the slowing effect generalizes across tasksets remains unclear. Further, the generation mechanisms of PES following observed errors must be examined. To address the above issues, we employed an observation-execution task in three experiments. During each trial, participants were required to mentally observe the outcomes of their partners in the observation task and then to perform their own key-press according to the mapping rules in the execution task. In Experiment 1, the same tasksets were utilized in the observation task and the execution task, and three error rate conditions (20%, 50% and 80%) were established in the observation task. The results revealed that the PES effect after observed errors was obtained in all three error rate conditions, replicating and extending previous studies. In Experiment 2, distinct stimuli and response rules were utilized in the observation task and the execution task. The result pattern was the same as that in Experiment 1, suggesting that the PES effect after observed errors was a generic adjustment process. In Experiment 3, the response deadline was shortened in the execution task to rule out the ceiling effect, and two error rate conditions (50% and 80%) were established in the observation task. The PES effect after observed errors was still obtained in the 50% and 80% error rate conditions. However, the accuracy in the post-observed error trials was comparable to that in the post-observed correct trials, suggesting that the slowing effect and improved accuracy did not rely on the same underlying mechanism. Current findings indicate that the occurrence of PES after observed errors is not dependent on the probability of observed errors, consistent with the assumption of cognitive control account

  16. Slow relaxation in structure-forming ferrofluids

    NASA Astrophysics Data System (ADS)

    Sreekumari, Aparna; Ilg, Patrick

    2013-10-01

    We study the behavior of colloidal magnetic fluids at low density for various dipolar interaction strengths by performing extensive Langevin dynamics simulations with model parameters that mimic cobalt-based ferrofluids used in experiments. Our study mainly focuses on the structural and dynamical properties of dipolar fluids and the influence of structural changes on their dynamics. Drastic changes from chainlike to networklike structures in the absence of an external magnetic field are observed. This crossover plays an important role in the slowing down of dynamics that is reflected in various dynamical properties including the tracer diffusion and the viscosity and also in the structural relaxation.

  17. Slow Wave Sleep and Long Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Orr, M.; Whitmire, A.; Arias, D.; Leveton, L.

    2011-01-01

    To review the literature on slow wave sleep (SWS) in long duration space flight, and place this within the context of the broader literature on SWS particularly with respect to analogous environments such as the Antarctic. Explore how SWS could be measured within the International Space Station (ISS) context with the aim to utilize the ISS as an analog for future extra-orbital long duration missions. Discuss the potential use of emergent minimally intrusive wireless technologies like ZEO for integrated prelaunch, flight, and return to Earth analysis and optimization of SWS (and general quality of sleep).

  18. Counting graphene layers with very slow electrons

    SciTech Connect

    Frank, Ludĕk; Mikmeková, Eliška; Müllerová, Ilona; Lejeune, Michaël

    2015-01-05

    The study aimed at collection of data regarding the transmissivity of freestanding graphene for electrons across their full energy scale down to the lowest energies. Here, we show that the electron transmissivity of graphene drops with the decreasing energy of the electrons and remains below 10% for energies below 30 eV, and that the slow electron transmissivity value is suitable for reliable determination of the number of graphene layers. Moreover, electrons incident below 50 eV release adsorbed hydrocarbon molecules and effectively clean graphene in contrast to faster electrons that decompose these molecules and create carbonaceous contamination.

  19. Scattering of slow neutrons by bound nuclei

    NASA Astrophysics Data System (ADS)

    Nowak, Ernst

    1982-09-01

    The T-operator for scattering of slow neutrons by a system of bound nuclei is calculated up to quadratic terms in the scattering length. Binding effects as well as effects of multiple scattering have to be included in order to avoid inconsistencies. For the discussion of binding effects one can adopt methods developed by Dietze and Nowak [1] for treating scattering by an elastically bound nucleus. In particular the case of coherent elastic scattering is discussed: we show how the corrections can be expressed in terms of correlation functions and that binding effects are most important for scattering by light nuclei.

  20. Lead Slowing Down Spectrometer Status Report

    SciTech Connect

    Warren, Glen A.; Anderson, Kevin K.; Bonebrake, Eric; Casella, Andrew M.; Danon, Yaron; Devlin, M.; Gavron, Victor A.; Haight, R. C.; Imel, G. R.; Kulisek, Jonathan A.; O'Donnell, J. M.; Weltz, Adam

    2012-06-07

    This report documents the progress that has been completed in the first half of FY2012 in the MPACT-funded Lead Slowing Down Spectrometer project. Significant progress has been made on the algorithm development. We have an improve understanding of the experimental responses in LSDS for fuel-related material. The calibration of the ultra-depleted uranium foils was completed, but the results are inconsistent from measurement to measurement. Future work includes developing a conceptual model of an LSDS system to assay plutonium in used fuel, improving agreement between simulations and measurement, design of a thorium fission chamber, and evaluation of additional detector techniques.

  1. Slow relaxation in structure-forming ferrofluids.

    PubMed

    Sreekumari, Aparna; Ilg, Patrick

    2013-10-01

    We study the behavior of colloidal magnetic fluids at low density for various dipolar interaction strengths by performing extensive Langevin dynamics simulations with model parameters that mimic cobalt-based ferrofluids used in experiments. Our study mainly focuses on the structural and dynamical properties of dipolar fluids and the influence of structural changes on their dynamics. Drastic changes from chainlike to networklike structures in the absence of an external magnetic field are observed. This crossover plays an important role in the slowing down of dynamics that is reflected in various dynamical properties including the tracer diffusion and the viscosity and also in the structural relaxation. PMID:24229180

  2. Counting graphene layers with very slow electrons

    NASA Astrophysics Data System (ADS)

    Frank, Luděk; Mikmeková, Eliška; Müllerová, Ilona; Lejeune, Michaël

    2015-01-01

    The study aimed at collection of data regarding the transmissivity of freestanding graphene for electrons across their full energy scale down to the lowest energies. Here, we show that the electron transmissivity of graphene drops with the decreasing energy of the electrons and remains below 10% for energies below 30 eV, and that the slow electron transmissivity value is suitable for reliable determination of the number of graphene layers. Moreover, electrons incident below 50 eV release adsorbed hydrocarbon molecules and effectively clean graphene in contrast to faster electrons that decompose these molecules and create carbonaceous contamination.

  3. Slow earthquakes, preseismic velocity changes, and the origin of slow frictional stick-slip.

    PubMed

    Kaproth, Bryan M; Marone, C

    2013-09-13

    Earthquakes normally occur as frictional stick-slip instabilities, resulting in catastrophic failure and seismic rupture. Tectonic faults also fail in slow earthquakes with rupture durations of months or more, yet their origin is poorly understood. Here, we present laboratory observations of repetitive, slow stick-slip in serpentinite fault zones and mechanical evidence for their origin. We document a transition from unstable to stable frictional behavior with increasing slip velocity, providing a mechanism to limit the speed of slow earthquakes. We also document reduction of P-wave speed within the active shear zone before stick-slip events. If similar mechanisms operate in nature, our results suggest that higher-resolution studies of elastic properties in tectonic fault zones may aid in the search for reliable earthquake precursors. PMID:23950495

  4. Proteomic analysis to elucidate degeneration of Clostridium beijerinckii NCIMB 8052 and role of Ca(2+) in strain recovery from degeneration.

    PubMed

    Lv, Jia; Jiao, Shengyin; Du, Renjia; Zhang, Ruijuan; Zhang, Yan; Han, Bei

    2016-06-01

    Degeneration of solventogenic Clostridium strains is one of the major barriers in bio-butanol production. A degenerated Clostridium beijerinckii NCIMB 8052 strain (DG-8052) was obtained without any genetic manipulation. Supplementation of CaCO3 to fermentation medium could partially recover metabolism of DG-8052 by more than 50 % increase of cell growth and solvent production. This study investigated the protein expression profile of DG-8052 and its response to CaCO3 treatment. Compared with WT-8052, the lower expressed proteins were responsible for disruption of RNA secondary structures and DNA repair, sporulation, signal transduction, transcription regulation, and membrane transport in DG-8052. Interestingly, accompanied with the decreased glucose utilization and lower solvent production, there was a decreased level of sigma-54 modulation protein which may indicate that the level of sigma-54 activity may be associated with the observed strain degeneration. For the addition of CaCO3, proteomic and biochemical study results revealed that besides buffer capacity, Ca(2+) could stabilize heat shock proteins, increase DNA synthesis and replication, and enhance expression of solventogenic enzymes in DG-8052, which has a similar contribution in WT-8052. PMID:27021843

  5. Good, Clean, Fair: The Rhetoric of the Slow Food Movement

    ERIC Educational Resources Information Center

    Schneider, Stephen

    2008-01-01

    This article outlines the origins of the Slow Food movement before examining the ways in which Slow Food rhetoric seeks to redefine gastronomy and combat the more deleterious effects of globalization. In articulating a new gastronomy, Slow Food founder Carlo Petrini attempts to reconstruct the gastronomy of Jean Anthelme Brillat-Savarin, at once…

  6. Instructional Approaches to Slow Learning. Practical Suggestions for Teaching Series.

    ERIC Educational Resources Information Center

    Younie, William J.

    Designed for teachers, the text distinguishes types of slow learners and suggests practical approaches for their educational problems. Slow learning and its types are defined; the slow learner is characterized; stages of educational evaluation and aspects of administration are outlined. Curriculum considerations for different levels are described,…

  7. Small but slow world: How network topology and burstiness slow down spreading

    NASA Astrophysics Data System (ADS)

    Karsai, M.; Kivelä, M.; Pan, R. K.; Kaski, K.; Kertész, J.; Barabási, A.-L.; Saramäki, J.

    2011-02-01

    While communication networks show the small-world property of short paths, the spreading dynamics in them turns out slow. Here, the time evolution of information propagation is followed through communication networks by using empirical data on contact sequences and the susceptible-infected model. Introducing null models where event sequences are appropriately shuffled, we are able to distinguish between the contributions of different impeding effects. The slowing down of spreading is found to be caused mainly by weight-topology correlations and the bursty activity patterns of individuals.

  8. Slow Solar Wind: Observations and Modeling

    NASA Astrophysics Data System (ADS)

    Abbo, L.; Ofman, L.; Antiochos, S. K.; Hansteen, V. H.; Harra, L.; Ko, Y.-K.; Lapenta, G.; Li, B.; Riley, P.; Strachan, L.; von Steiger, R.; Wang, Y.-M.

    2016-06-01

    While it is certain that the fast solar wind originates from coronal holes, where and how the slow solar wind (SSW) is formed remains an outstanding question in solar physics even in the post-SOHO era. The quest for the SSW origin forms a major objective for the planned future missions such as the Solar Orbiter and Solar Probe Plus. Nonetheless, results from spacecraft data, combined with theoretical modeling, have helped to investigate many aspects of the SSW. Fundamental physical properties of the coronal plasma have been derived from spectroscopic and imaging remote-sensing data and in situ data, and these results have provided crucial insights for a deeper understanding of the origin and acceleration of the SSW. Advanced models of the SSW in coronal streamers and other structures have been developed using 3D MHD and multi-fluid equations. However, the following questions remain open: What are the source regions and their contributions to the SSW? What is the role of the magnetic topology in the corona for the origin, acceleration and energy deposition of the SSW? What are the possible acceleration and heating mechanisms for the SSW? The aim of this review is to present insights on the SSW origin and formation gathered from the discussions at the International Space Science Institute (ISSI) by the Team entitled "Slow solar wind sources and acceleration mechanisms in the corona" held in Bern (Switzerland) in March 2014 and 2015.

  9. Slow waves in mutually inhibitory neuronal networks

    NASA Astrophysics Data System (ADS)

    Jalics, Jozsi

    2004-05-01

    A variety of experimental and modeling studies have been performed to investigate wave propagation in networks of thalamic neurons and their relationship to spindle sleep rhythms. It is believed that spindle oscillations result from the reciprocal interaction between thalamocortical (TC) and thalamic reticular (RE) neurons. We consider a network of TC and RE cells reduced to a one-layer network model and represented by a system of singularly perturbed integral-differential equations. Geometric singular perturbation methods are used to prove the existence of a locally unique slow wave pulse that propagates along the network. By seeking a slow pulse solution, we reformulate the problem to finding a heteroclinic orbit in a 3D system of ODEs with two additional constraints on the location of the orbit at two distinct points in time. In proving the persistence of the singular heteroclinic orbit, difficulties arising from the solution passing near points where normal hyperbolicity is lost on a 2D critical manifold are overcome by employing results by Wechselberger [Singularly perturbed folds and canards in R3, Thesis, TU-Wien, 1998].

  10. Sheet beam slow-wave amplifiers

    SciTech Connect

    Kirolous, H.; Joe, J.; Basten, M.A.; Booske, J.H.; Scharer, J.E.; Anderson, J.; True, R.; Scheitrum, G.

    1994-12-31

    Sheet electron beams used in conjunction with slow-wave (Cerenkov) structures are a promising way to realize higher average power millimeter-wave amplifiers. For example, a sheet beam with a meander line structure is proposed to obtain a 100 watt W-band power booster amplifier. A sheet beam with a tapered grating structure is also being considered as a wideband ({approximately} 10--20% instantaneous bandwidth) Ka-band amplifier with approximately 10 kW of average output power. The authors describe results of research that examine critical technological issues relevant to the realization of the proposed devices. The method of forming a sheet beam using magnetic quadrupole lenses and focusing it using periodically-cusped magnetic (PCM) fields are discussed. A pencil beam from a 10 kV, 0.25 A Pierce electron source is used for the initial investigations. The EGUN simulations with the measured magnetic field indicates that a thin (2 mm dia.) beam is available at the interaction region. Beam characterization has been performed using current density probes and an electrostatic velocity spread analyzer. Numerical modeling and cold test measurements of a tapered slow-wave structure together with the simulations and measurements of small-signal gain and bandwidth are also presented.

  11. Slow internal protein dynamics in solution.

    PubMed

    Biehl, R; Richter, D

    2014-12-17

    Large-scale domain dynamics in proteins are found when flexible linkers or hinges connect domains. The related conformational changes are often related to the function of the protein,for example by arranging the active center after substrate binding or allowing transport and release of products. The adaptation of a specific active structure is referred to as ‘induced fit’ and is challenged by models such as ‘conformational sampling’. Newer models about protein unction include some flexibility within the protein structure or even internal dynamics of the protein. As larger domains contribute to the configurational changes, the timescale of the involved motions is slowed down. The role of slow domain dynamics is being increasingly recognized as essential to understanding the function of proteins. Neutron spin echospectroscopy (NSE) is a technique that is able to access the related timescales from 0.1 up to several hundred nanoseconds and simultaneously covers the length scale relevant for protein domain movements of several nanometers distance between domains. Here we focus on these large-scale domain fluctuations and show how the structure and dynamics of proteins can be assessed by small-angle neutron scattering and NSE. PMID:25419898

  12. Maxwell Equations for Slow-Moving Media

    NASA Astrophysics Data System (ADS)

    Rozov, Andrey

    2015-12-01

    In the present work, the Minkowski equations obtained on the basis of theory of relativity are used to describe electromagnetic fields in moving media. But important electromagnetic processes run under non-relativistic conditions of slow-moving media. Therefore, one should carry out its description in terms of classical mechanics. Hertz derived electrodynamic equations for moving media within the frame of classical mechanics on the basis of the Maxwell theory. His equations disagree with the experimental data concerned with the moving dielectrics. In the paper, a way of description of electromagnetic fields in slow-moving media on the basis of the Maxwell theory within the frame of classical mechanics is offered by combining the Hertz approach and the experimental data concerned with the movement of dielectrics in electromagnetic fields. Received Maxwell equations lack asymmetry in the description of the reciprocal electrodynamic action of a magnet and a conductor and conform to known experimental data. Comparative analysis of the Minkowski and Maxwell models is carried out.

  13. Arbitrarily slow, non-quasistatic, isothermal transformations

    NASA Astrophysics Data System (ADS)

    Gavrilov, Momčilo; Bechhoefer, John

    2016-06-01

    For an overdamped colloidal particle diffusing in a fluid in a controllable, virtual potential, we show that arbitrarily slow transformations, produced by smooth deformations of a double-well potential, need not be reversible. The arbitrarily slow transformations do need to be fast compared to the barrier crossing time, but that time can be extremely long. We consider two types of cyclic, isothermal transformations of a double-well potential. Both start and end in the same equilibrium state, and both use the same basic operations —but in different order. By measuring the work for finite cycle times and extrapolating to infinite times, we found that one transformation required no work, while the other required a finite amount of work, no matter how slowly it was carried out. The difference traces back to the observation that when time is reversed, the two protocols have different outcomes, when carried out arbitrarily slowly. A recently derived formula relating work production to the relative entropy of forward and backward path probabilities predicts the observed work average.

  14. Deuterium Enrichment of Vitamin A at the C20 Position Slows the Formation of Detrimental Vitamin A Dimers in Wild-type Rodents*

    PubMed Central

    Kaufman, Yardana; Ma, Li; Washington, Ilyas

    2011-01-01

    Degenerative eye diseases are the most common causes of untreatable blindness. Accumulation of lipofuscin (granular deposits) in the retinal pigment epithelium (RPE) is a hallmark of major degenerative eye diseases such as Stargardt disease, Best disease, and age-related macular degeneration. The intrinsic reactivity of vitamin A leads to its dimerization and to the formation of pigments such as A2E, and is believed to play a key role in the formation of ocular lipofuscin. We sought a clinically pragmatic method to slow vitamin A dimerization as a means to elucidate the pathogenesis of macular degenerations and to develop a therapeutic intervention. We prepared vitamin A enriched with the stable isotope deuterium at carbon twenty (C20-D3-vitamin A). Results showed that dimerization of deuterium-enriched vitamin A was considerably slower than that of vitamin A at natural abundance as measured in vitro. Administration of C20-D3-vitamin A to wild-type rodents with no obvious genetic defects in vitamin A processing, slowed A2E biosynthesis. This study elucidates the mechanism of A2E biosynthesis and suggests that administration of C20-D3-vitamin A may be a viable, long-term approach to retard vitamin A dimerization and by extension, may slow lipofuscin deposition and the progression of common degenerative eye diseases. PMID:21075840

  15. Degeneration of retinal ganglion cells in diabetic dogs and mice: Relationship to glycemic control and retinal capillary degeneration

    PubMed Central

    Howell, Scott J.; Mekhail, Mena N.; Azem, Rami; Ward, Nicole L.

    2013-01-01

    Purpose The purpose of this study was to investigate (i) the effect of diabetes on retinal ganglion cell death in diabetic dogs and mice, (ii) the effect of prolonged glycemic control on diabetes-induced death of retinal ganglion cells, (iii) whether retinal ganglion cell death in diabetes is associated with degeneration of retinal capillaries, and (iv) the effect of diet on diabetes-induced degeneration of retinal ganglion cells in mice. Methods Diabetes was induced in dogs using streptozotocin, and levels of glycemic control (good, moderate, and poor) were maintained for 5 years. Diabetes was studied in two mouse models (diabetes induced in C57Bl/6J mice using streptozotocin and spontaneously diabetic Ins2Akita mice). Retinal ganglion cell death was investigated by counting the number of axons from the ganglion cells in the optic nerve and with terminal transferase deoxyuridine triphosphate nick-end labeling and annexin V staining in mice. Results As reported previously, the development and severity of vascular lesions of diabetic retinopathy in diabetic dogs were strongly associated with glycemic control. Loss of retinal ganglion cells was extensive in dogs kept in poor glycemic control, and was essentially prevented in diabetic dogs kept in good glycemic control for the 5 years of study. In contrast, “moderate” glycemic control (intermediate between poor and good glycemic control) caused a significant increase in vascular pathology, but did not cause loss of retinal axons in the optic nerve. Using this validated optic nerve axon counting method, the two mouse models of diabetic retinopathy were studied to assess ganglion cell death. Despite 10 months of diabetes (a duration that has been shown to cause retinal capillary degeneration in both models), neither mouse model showed loss of optic nerve axons (thus suggesting no loss of retinal ganglion cells). Likewise, other parameters of cell death (terminal transferase deoxyuridine triphosphate nick

  16. MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine.

    PubMed

    Stolworthy, Dean K; Bowden, Anton E; Roeder, Beverly L; Robinson, Todd F; Holland, Jacob G; Christensen, S Loyd; Beatty, Amanda M; Bridgewater, Laura C; Eggett, Dennis L; Wendel, John D; Stieger-Vanegas, Susanne M; Taylor, Meredith D

    2015-12-01

    Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2-6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann-grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration. PMID:26135031

  17. Threshold Characteristics of Slow-Light Photonic Crystal Lasers

    NASA Astrophysics Data System (ADS)

    Xue, Weiqi; Yu, Yi; Ottaviano, Luisa; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mork, Jesper

    2016-02-01

    The threshold properties of photonic crystal quantum dot lasers operating in the slow-light regime are investigated experimentally and theoretically. Measurements show that, in contrast to conventional lasers, the threshold gain attains a minimum value for a specific cavity length. The experimental results are explained by an analytical theory for the laser threshold that takes into account the effects of slow light and random disorder due to unavoidable fabrication imperfections. Longer lasers are found to operate deeper into the slow-light region, leading to a trade-off between slow-light induced reduction of the mirror loss and slow-light enhancement of disorder-induced losses.

  18. What is the evidence for stress resistance and slowed aging?

    PubMed

    Hamilton, Karyn L; Miller, Benjamin F

    2016-09-01

    Stress resistance is thought to contribute to slowed-aging, although cause and effect between the two is controversial. On October 30, 2015 researchers gathered at the Front Range Consortium on Stress Resistance and Slowed Aging in Fort Collins, CO, to discuss what the current evidence is that stress resistance imparts slowed aging. Included in that discussion was defining stress resistance, distinguishing if there are key stresses to which resistance imparts slowed aging, what models aid in our understanding of stress resistance and aging, and how to translate that knowledge into slowed aging treatment. The following article is a brief summary of that discussion and recommendations for moving forward. PMID:27268049

  19. Threshold Characteristics of Slow-Light Photonic Crystal Lasers.

    PubMed

    Xue, Weiqi; Yu, Yi; Ottaviano, Luisa; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mork, Jesper

    2016-02-12

    The threshold properties of photonic crystal quantum dot lasers operating in the slow-light regime are investigated experimentally and theoretically. Measurements show that, in contrast to conventional lasers, the threshold gain attains a minimum value for a specific cavity length. The experimental results are explained by an analytical theory for the laser threshold that takes into account the effects of slow light and random disorder due to unavoidable fabrication imperfections. Longer lasers are found to operate deeper into the slow-light region, leading to a trade-off between slow-light induced reduction of the mirror loss and slow-light enhancement of disorder-induced losses. PMID:26918991

  20. Impact of PICALM and CLU on hippocampal degeneration.

    PubMed

    Yang, Xianfeng; Li, Jin; Liu, Bing; Li, Yonghui; Jiang, Tianzi

    2016-07-01

    PICALM and CLU are two major risk genes of late-onset Alzheimer's disease (LOAD), and there is strong molecular evidence suggesting their interaction on amyloid-beta deposition, hence finding functional dependency between their risk genotypes may lead to better understanding of their roles in LOAD development and greater clinical utility. In this study, we mainly investigated interaction effects of risk loci PICALM rs3581179 and CLU rs11136000 on hippocampal degeneration in both young and elderly adults in order to understand their neural mechanism on aging process, which may help identify robust biomarkers for early diagnosis and intervention. Besides volume we also assessed hippocampal shape phenotypes derived from diffeomorphic metric mapping and nonlinear dimensionality reduction. In elderly individuals (75.6 ± 6.7 years) significant interaction effects existed on hippocampal volume (P < 0.001), whereas in young healthy adults (19.4 ± 1.1 years) such effects existed on a shape phenotype (P = 0.01) indicating significant variation at hippocampal head and tail that mirror most AD vulnerable regions. Voxel-wise analysis also pointed to the same regions but lacked statistical power. In both cohorts, PICALM protective genotype AA only exhibited protective effects on hippocampal degeneration and cognitive performance when combined with CLU protective T allele, but adverse effects with CLU risk CC. This study revealed novel PICALM and CLU interaction effects on hippocampal degeneration along aging, and validated effectiveness of diffeomorphometry in imaging genetics study. Hum Brain Mapp 37:2419-2430, 2016. © 2016 Wiley Periodicals, Inc. PMID:27017968