Science.gov

Sample records for 4-fold degenerate sites

  1. 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 ...

  2. 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.

  3. Is the subcallosal medial prefrontal cortex a common site of atrophy in Alzheimer's disease and frontotemporal lobar degeneration?

    PubMed Central

    Lindberg, Olof; Westman, Eric; Karlsson, Sari; Östberg, Per; Svensson, Leif A.; Simmons, Andrew; Wahlund, Lars-Olof

    2012-01-01

    Regions affected late in neurodegenerative disease are thought to be anatomically connected to regions affected earlier. The subcallosal medial prefrontal cortex (SMPC) has connections with the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and hippocampus (HC), which are regions that may become atrophic in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). We hypothesized that the SMPC is a common site of frontal atrophy in the FTLD subtypes and in AD. The volume of the SMPC, DLPFC, OFC, HC, and entorhinal cortex (EC) were manually delineated for 12 subjects with frontotemporal dementia (FTD), 13 with semantic dementia (SD), 9 with progressive nonfluent aphasia (PNFA), 10 AD cases, and 13 controls. Results revealed significant volume loss in the left SMPC in FTD, SD, and PNFA, while the right SMPC was also atrophied in SD and FTD. In AD a non significant tendency of volume loss in the left SMPC was found (p = 0.08), with no volume loss on the right side. Results indicated that volume loss reflected the degree of brain connectivity. In SD and AD temporal regions displayed most atrophy. Among the frontal regions, the SMPC (which receives the strongest temporal projections) demonstrated most volume loss, the OFC (which receives less temporal projections) less volume loss, while the DLPFC (which is at multisynaptic distance from the temporal regions) demonstrated no volume loss. In PNFA, the left SMPC was atrophic, possibly reflecting progression from the left anterior insula, while FTD patients may have had SMPC atrophy at the initial stages of the disease. Atrophy of the SMPC may thus be affected by either initial temporal or initial frontal atrophy, making it a common site of frontal atrophy in the dementia subtypes investigated. PMID:23189052

  4. Striatonigral Degeneration

    MedlinePLUS

    ... the disorder resemble some of those seen in Parkinson's disease, including rigidity, instability, impaired speech, and slow movements. ... the disorder have variable success. Treatments used for Parkinson's disease are recommended. However, unlike Parkinson's disease, striatonigral degeneration ...

  5. Crystalline structures of polymeric hydrocarbon with 3,4-fold helical chains

    PubMed Central

    Lian, Chao-Sheng; Li, Han-Dong; Wang, Jian-Tao

    2015-01-01

    Molecular hydrocarbons are well-known to polymerize under pressure to form covalently bonded frameworks. Here we predict by ab initio calculations two distinct three-dimensional hydrocarbon crystalline structures composed of 3-fold and 4-fold helical CH chains in rhombohedral () and tetragonal (I41/a) symmetry, respectively. Both structures with 1:1 stoichiometry are found to be energetically more favorable than solid acetylene and cubane, and even more stable than benzene II solid at high pressure. The calculations on vibrational, electronic, and optical properties reveal that the new chiral hydrocarbons are dynamically stable with large bulk moduli around 200?GPa, and exhibit a transparent insulating behavior with indirect band gaps of 5.9 ~ 6.7?eV and anisotropic adsorption spectra. Such forms of hydrocarbon, once synthesized, would have wide applications in mechanical, optoelectronic, and biological materials. PMID:25579707

  6. Lipoprotein(A) with An Intact Lysine Binding Site Protects the Retina From an Age-Related Macular Degeneration Phenotype in Mice (An American Ophthalmological Society Thesis)

    PubMed Central

    Handa, James T.; Tagami, Mizuki; Ebrahimi, Katayoon; Leibundgut, Gregor; Janiak, Anna; Witztum, Joseph L.; Tsimikas, Sotirios

    2015-01-01

    Purpose: To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is toxic to the retina unless neutralized by a variety of mechanisms, including binding by lipoprotein(a) [Lp(a)], which is composed of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB). Methods: Human maculas and eyes from two Lp(a) transgenic murine models were subjected to morphologic, ultrastructural, and immunohistochemical analysis. “Wild-type Lp(a)” mice, which express human apoB-100 and apo(a) that contains oxidized phospholipid, and “mutant LBS? Lp(a)” mice with a defective apo(a) lysine binding site (LBS) for oxidized phospholipid binding, were fed a chow or high-fat diet for 2 to 12 months. Oxidized phospholipid–containing lipoproteins were detected by immunoreactivity to E06, a murine monoclonal antibody binding to the phosphocholine headgroup of oxidized, but not native, phospholipids. Results: Oxidized phospholipids, apo(a), and apoB accumulate in maculas, including drusen, of age-related macular degeneration (AMD) samples and age-matched controls. Lp(a) mice fed a high-fat diet developed age-related changes. However, mutant LBS? Lp(a) mice fed a high-fat diet developed retinal pigment epithelial cell degeneration and drusen. These changes were associated with increased OxPL, decreased antioxidant defenses, increased complement, and decreased complement regulators. Conclusions: Human maculas accumulate Lp(a) and OxPL. Mutant LBS? Lp(a) mice, lacking the ability to bind E06-detectable oxidized phospholipid, develop AMD-like changes. The ability of Lp(a) to bind E06-detectable OxPL may play a protective role in AMD.

  7. Striatopallidonigral degeneration

    PubMed Central

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

    1971-01-01

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

  8. Corticobasal degeneration.

    PubMed

    Grijalvo-Perez, Ana M; Litvan, Irene

    2014-04-01

    Among the atypical parkinsonian syndromes, corticobasal degeneration (CBD) is probably the most challenging disorder to diagnose antemortem. It can present with multiple phenotypes, none of them specific enough to lead to an unequivocal diagnosis. Alternatively, multiple other neurodegenerative disorders with a different underlying pathology, such as Alzheimer disease (AD), can mimic its clinical course. The ultimate etiology of CBD is unknown; however, current neuropathological and genetic evidence support a role for microtubule-associated protein tau. The classic clinical presentation is corticobasal syndrome, which typically presents as an asymmetric parkinsonism with a variable combination of ideomotor apraxia, rigidity, myoclonus, and dystonia, often associated with the presence of an alien limb phenomenon. Recently, a new set of diagnostic criteria has been developed, but still definite diagnosis requires autopsy confirmation. At the present time, no disease modifying therapies are available, but extensive research is being conducted. PMID:24963675

  9. 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 ...

  10. 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.…

  11. 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

  12. 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.

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

    ClinicalTrials.gov

    2015-05-15

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

  14. American Macular Degeneration Foundation

    MedlinePLUS

    ... recipes, and eye health tips. AMD Treatment and Management Helpful Free Materials Take part in the IMRF Study Thrive You can thrive with Macular Degeneration! Witness how artists, actors, and others with AMD live full lives. AMDF Vision and Art Project Ed Asner Video Clip An Inspiring Her-story ...

  15. 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

  16. Quantum degenerate systems

    SciTech Connect

    Micheli, Fiorenza de; Zanelli, Jorge

    2012-10-15

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

  17. 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 genetics and molecular pathology make the prospect of biologically driven, disease-specific therapies for FTLD seem closer than ever. PMID:20369906

  18. Retinal remodeling triggered by photoreceptor degenerations.

    PubMed

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

    2003-09-01

    Many photoreceptor degenerations initially affect rods, secondarily leading to cone death. It has long been assumed that the surviving neural retina is largely resistant to this sensory deafferentation. New evidence from fast retinal degenerations reveals that subtle plasticities in neuronal form and connectivity emerge early in disease. By screening mature natural, transgenic, and knockout retinal degeneration models with computational molecular phenotyping, we have found an extended late phase of negative remodeling that radically changes retinal structure. Three major transformations emerge: 1) Müller cell hypertrophy and elaboration of a distal glial seal between retina and the choroid/retinal pigmented epithelium; 2) apparent neuronal migration along glial surfaces to ectopic sites; and 3) rewiring through evolution of complex neurite fascicles, new synaptic foci in the remnant inner nuclear layer, and new connections throughout the retina. Although some neurons die, survivors express molecular signatures characteristic of normal bipolar, amacrine, and ganglion cells. Remodeling in human and rodent retinas is independent of the initial molecular targets of retinal degenerations, including defects in the retinal pigmented epithelium, rhodopsin, or downstream phototransduction elements. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, it suggests that the neural retina may be more plastic than previously believed. PMID:12866125

  19. STUDIES UPON CALCAREOUS DEGENERATION

    PubMed Central

    Klotz, Oskar

    1905-01-01

    It will be seen from the above that we have studied the conditions associated with the deposit of calcareous salts: (I) in connection with normal and pathological ossification, and (2) in pathological calcification as exhibited in (a) atheroma of the vessels; (b) calcification of caseating tubercular lesions; (c) calcification of inflammatory new growth, and (d) degenerating tumors; and we have induced experimentally deposits of calcareous salts in the lower animals: (a) within celloidin capsules containing fats and soaps; (b) in the kidney, and (c) in connection with fat necrosis. I. We have found that bone formation and pathological calcareous infiltration are wholly distinct processes. In the former there is no evidence of associated fatty change, and the cells associated with the process of deposition of calcium are functionally active. In the latter there is an antecedent fatty change in the affected areas, and the cells involved present constant evidences of degeneration. The view that would seem to account best for the changes observed in the latter case is that with lowered vitality the cells are unable to utilize the products brought to them by the blood, or which they continue to absorb, so that the normal series of decompositions associated with their metabolism fails to take place and hence they interact among themselves in the cytoplasm with the result that insoluble compounds replace soluble ones. II. Besides the fact that calcification is always preceded by fatty change within the cells, another fact should be emphasized. namely: that combination of the fats present with calcium salts to form calcium soaps tends to occur. The stages immediately preceding these are difficult to follow with anything approaching certainty, perhaps because the earlier stages vary under different conditions. In fat necrosis, for instance, the cells affected are normally storehouses for neutral fats, and as long as they remain healthy neutral fats alone are present in them. When they are subjected to the action of the pancreatic juice with its fat-splitting ferment the cells are killed and coincidently the neutral fats are decomposed, fatty acids being deposited. The fatty acids now slowly combine with the calcium salts. In degenerating lipomata the process would seem to be similar. But in other cases the cells are not obviously fat-containing in the normal state; nevertheless prior to calcification they undergo so-called fatty degeneration, which is really a form of cell degeneration accompanied by fat infiltration. As regards the source of the cell fats in general we may safely accept: 1. That fats are transported in the blood as diffusible soaps. 2. That taken up by the cells these soaps may either— (a) Be reconverted into neutral fats and become stored in the cytoplasm as such, or (b) undergo assimilation proper, becoming part and parcel of the cell substance, in which case they are not recognizable by the ordinary microchemical tests. 3. If these two possibilities be accepted it follows that the appearance of fats and soaps in the degenerating cell may be due to either— (a) Absorption or infiltration of soaps from the surrounding medium, the degenerating cell retaining the power of splitting off the fat but being unable to utilize this in metabolism. (b) Cytoplasmic disintegration with dissociation of the soap-albumen combination or, more broadly, liberation of the fats from their combination with the cytoplasm. The appearances seen in the cells of atheromatous areas indicate that the first of these does occur. III. In areas undergoing calcareous infiltration we have demonstrated. the presence of soaps, and this often in such quantities that they can be isolated and estimated by gross chemical methods. By microchemical methods also we have been able to show that after removing all the neutral fats and fatty acids by petroleum ether there remains behind a substance giving with Sudan III the reaction we associate with the presence of soap. And experimentally we have produced these soaps within the organism, more

  20. Intervertebral disc degeneration.

    PubMed

    Fraser, R D; Osti, O L; Vernon-Roberts, B

    1993-03-01

    Disc degeneration in the human spine is a complex phenomenon characterised by biochemical change in the nucleus pulposus and inner annulus and the formation of clefts and fissures radiating from the central area of the disc towards the periphery. In addition, and probably independent of these phenomena, discrete defects in the outer annular attachement are seen which are likely to be due to mechanical stress and failure. The presence of stress tears in disc tissue and their failure to heal can initiate or accelerate the degeneration of the central component of the intervertebral disc. We postulate that discogenic pain may be linked to damage to the outer portion of the annulus fibrosus. Although it would seem logical to assume that discs with sustained high intradiscal pressure would be more prone to pain referred in the outer annular layers because of higher tensile strain, analysis of prospective studies has failed to confirm a relationship between typical pain reproduction at discography and high pressure values. It is concluded that, at present, the only consistent morphological changes present in patients with pain reproduction at discography are the presence of various annular defects involving the outer layers. Whether nerve ingrowth during attempts at repair of these defects is a consistent feature remains to be established. PMID:20054919

  1. Degenerate Extensions of General Relativity

    E-print Network

    Ted Jacobson; Joseph D. Romano

    1992-07-23

    General relativity has previously been extended to incorporate degenerate metrics using Ashtekar's hamiltonian formulation of the theory. In this letter, we show that a natural alternative choice for the form of the hamiltonian constraints leads to a theory which agrees with GR for non-degenerate metrics, but differs in the degenerate sector from Ashtekar's original degenerate extension. The Poisson bracket algebra of the alternative constraints closes in the non-degenerate sector, with structure functions that involve the {\\it inverse} of the spatial triad. Thus, the algebra does {\\it not} close in the degenerate sector. We find that it must be supplemented by an infinite number ofsecondary constraints, which are shown to be first class (although their explicit form is not worked out in detail). All of the constraints taken together are implied by, but do not imply, Ashtekar's original form of constraints. Thus, the alternative constraints give rise to a different degenerate extension of GR. In the corresponding quantum theory, the single loop and intersecting loop holonomy states found in the connection representation satisfy {\\it all} of the constraints. These states are therefore exact (formal) solutions to this alternative degenerate extension of quantum gravity, even though they are {\\it not} solutions to the usual vector constraint.

  2. Epidermal cells are the primary phagocytes in the fragmentation and clearance of degenerating dendrites in Drosophila

    PubMed Central

    Xiao, Hui; Wang, Denan; Franc, Nathalie C.; Jan, Lily Yeh; Jan, Yuh-Nung

    2014-01-01

    SUMMARY During developmental remodeling, neurites destined for pruning often degenerate on-site. Physical injury also induces degeneration of neurites distal to the injury site. Prompt clearance of degenerating neurites is important for maintaining tissue homeostasis and preventing inflammatory responses. Here we show that in both dendrite pruning and dendrite injury of Drosophila sensory neurons, epidermal cells rather than hemocytes are the primary phagocytes in clearing degenerating dendrites. Epidermal cells act via Draper-mediated recognition to facilitate dendrite degeneration and to engulf and degrade degenerating dendrites. Using multiple dendritic membrane markers to trace phagocytosis, we show that two members of the CD36 family, croquemort (crq) and debris buster (dsb), act at distinct stages of phagosome maturation for dendrite clearance. Our finding reveals the physiological importance of coordination between neurons and their surrounding epidermis, for both dendrite fragmentation and clearance. PMID:24412417

  3. GENERAL: Double Degenerate Stars

    NASA Astrophysics Data System (ADS)

    Luo, Xin-Lian; Bai, Hua; Zhao, Lei

    2008-07-01

    Regardless of the formation mechanism, an exotic object, the double degenerate star (DDS), is introduced and investigated, which is composed of baryonic matter and some unknown fermion dark matter. Different from the simple white dwarfs (WDs), there is additional gravitational force provided by the unknown fermion component inside DDSs, which may strongly affect the structure and the stability of such kind of objects. Many possible and strange observational phenomena connecting with them are concisely discussed. Similar to the normal WD, this object can also experience thermonuclear explosion as type Ia supernova explosion when DDS's mass exceeds the maximum mass that can be supported by electron degeneracy pressure. However, since the total mass of baryonic matter can be much lower than that of WD at Chandrasekhar mass limit, the peak luminosity should be much dimmer than what we expect before, which may throw a slight shadow on the standard candle of SN Ia in the research of cosmology.

  4. Double Degenerate Stars

    E-print Network

    Xin-Lian, Luo; Lei, Zhao

    2009-01-01

    Regardless of the formation mechanism, an exotic object, Double Degenerate Star (DDS), is introduced and investigated, which is composed of baryonic matter and some unknown fermion dark matter. Different from the simple White Dwarfs (WDs), there are additional gravitational force provided by the unknown fermion component inside DDSs, which may strongly affect the structure and the stability of such kind of objects. Many possible and strange observational phenomena connecting with them are concisely discussed. Similar to the normal WD, this object can also experience thermonuclear explosion as type Ia supernova explosion when DDS's mass exceeds the maximum mass that can be supported by electron degeneracy pressure. However, since the total mass of baryonic matter can be much lower than that of WD at Chandrasekhar mass limit, the peak luminosity should be much dimmer than what we expect before, which may throw a slight shadow on the standard candle of SNIa in the research of cosmology.

  5. 4-fold enhancement in the critical current density of YBa{sub 2}Cu{sub 3}O{sub 7} films by practical ion irradiation

    SciTech Connect

    Matsui, H.; Ogiso, H.; Yamasaki, H.; Kumagai, T.; Sohma, M.; Yamaguchi, I.; Manabe, T.

    2012-12-03

    We report an up-to-4-fold enhancement in the in-magnetic-field critical current density at 77 K of epitaxial YBa{sub 2}Cu{sub 3}O{sub 7} films on CeO{sub 2}-buffered SrTiO{sub 3} substrates by 3-MeV Au{sup 2+} irradiation. This indicates that irradiation using an industrially practical ion beam, which generally has kinetic energy less than 5 MeV, can provide a substantial increase in the in-field current performance of high-temperature superconductor films. Transmission electron microscopy results show that point-like defects smaller than 6 nm in diameter were created in the films by the irradiation.

  6. [Age related macular degeneration].

    PubMed

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

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support. PMID:21618758

  7. Degenerate quantum gases of strontium

    E-print Network

    Stellmer, Simon; Killian, Thomas C

    2013-01-01

    Degenerate quantum gases of alkaline-earth-like elements open new opportunities in research areas ranging from molecular physics to the study of strongly correlated systems. These experiments exploit the rich electronic structure of these elements, which is markedly different from the one of other species for which quantum degeneracy has been attained. Specifically, alkaline-earth-like atoms, such as strontium, feature metastable triplet states, narrow intercombination lines, and a non-magnetic, closed-shell ground state. This review covers the creation of quantum degenerate gases of strontium and the first experiments performed with this new system. It focuses on laser-cooling and evaporation schemes, which enable the creation of Bose-Einstein condensates and degenerate Fermi gases of all strontium isotopes, and shows how they are used for the investigation of optical Feshbach resonances, the study of degenerate gases loaded into an optical lattice, as well as the coherent creation of Sr_2 molecules.

  8. Counting Patterns in Degenerated Sequences

    NASA Astrophysics Data System (ADS)

    Nuel, Grégory

    Biological sequences like DNA or proteins, are always obtained through a sequencing process which might produce some uncertainty. As a result, such sequences are usually written in a degenerated alphabet where some symbols may correspond to several possible letters (ex: IUPAC DNA alphabet). When counting patterns in such degenerated sequences, the question that naturally arises is: how to deal with degenerated positions ? Since most (usually 99%) of the positions are not degenerated, it is considered harmless to discard the degenerated positions in order to get an observation, but the exact consequences of such a practice are unclear. In this paper, we introduce a rigorous method to take into account the uncertainty of sequencing for biological sequences (DNA, Proteins). We first introduce a Forward-Backward approach to compute the marginal distribution of the constrained sequence and use it both to perform a Expectation-Maximization estimation of parameters, as well as deriving a heterogeneous Markov distribution for the constrained sequence. This distribution is hence used along with known DFA-based pattern approaches to obtain the exact distribution of the pattern count under the constraints. As an illustration, we consider a EST dataset from the EMBL database. Despite the fact that only 1% of the positions in this dataset are degenerated, we show that not taking into account these positions might lead to erroneous observations, further proving the interest of our approach.

  9. 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

  10. [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

  11. Quantum degenerate dipolar Fermi gas.

    PubMed

    Lu, Mingwu; Burdick, Nathaniel Q; Lev, Benjamin L

    2012-05-25

    We report the first quantum degenerate dipolar Fermi gas, the realization of which opens a new frontier for exploring strongly correlated physics and, in particular, quantum liquid crystalline phases. A quantum degenerate Fermi gas of the most magnetic atom 161Dy is produced by laser cooling to 10 ?K before sympathetically cooling with ultracold, bosonic 162Dy. The temperature of the spin-polarized 161Dy is a factor T/T(F)=0.2 below the Fermi temperature T(F)=300 nK. The cotrapped 162Dy concomitantly cools to approximately T(c) for Bose-Einstein condensation, thus realizing a novel, nearly quantum degenerate dipolar Bose-Fermi gas mixture. Additionally, we achieve the forced evaporative cooling of spin-polarized 161Dy without 162Dy to T/T(F)=0.7. That such a low temperature ratio is achieved may be a first signature of universal dipolar scattering. PMID:23003275

  12. Quantum Degenerate Gases of Strontium

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  13. Degenerate neutrino mass models revisited

    E-print Network

    Singh, N Nimai; Borah, Abhijit; Singh, S Somorendro

    2009-01-01

    A parametrisation of the degenerate neutrino mass matrix obeying $\\mu -\\tau$ symmetry, is introduced for detailed numerical analysis. As a continuation of our earlier work on normal and inverted hierarchical models, the present parametrisation for degenerate models has the ability to lower the solar mixing angle below the tri-bimaximal value $\\tan^{2}\\theta_{12}=0.5$, while maintaining the condition of maximal atmospheric mixing angle and zero reactor angle. The combined data on the mass-squared differences derived from various oscillation experiments, and also from the bounds on absolute neutrino masses in $0\

  14. 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 ...

  15. Glial Vascular Degeneration in CADASIL

    PubMed Central

    Brennan-Krohn, Thea; Salloway, Stephen; Correia, Stephen; Dong, Matthew; de la Monte, Suzanne M.

    2010-01-01

    Background CADASIL is a genetic vascular dementia caused by mutations in the Notch 3 gene on Chromosome 19. However, little is known about the mechanisms of vascular degeneration. Methods We characterized upstream components of Notch signaling pathways that may be disrupted in CADASIL, by measuring expression of insulin, IGF-1, and IGF-2 receptors, Notch 1, Notch 3, and aspartyl-(asparaginyl)-?-hydroxylase (AAH) in cortex and white matter from 3 CADASIL and 6 control brains. We assessed CADASIL-associated cell loss by measuring mRNA corresponding to neurons, oligodendroglia, and astrocytes, and indices of vascular degeneration by measuring smooth muscle actin (SMA) and endothelin-1 (ET-1) expression in isolated vessels. Immunohistochemical staining was used to assess SMA degeneration. Results Significant abnormalities including reduced cerebral white matter mRNA levels of Notch 1, Notch 3, AAH, SMA, IGF receptors, myelin-associated glycoproteins, and glial fibrillary acidic protein, and reduced vascular expression of SMA, IGF receptors, Notch 1 and Notch 3 were detected in CADASIL-lesioned brains. In addition, we found CADASIL-associated reductions in SMA, and increases in ubiquitin immunoreactivity in the media of white matter and meningeal vessels. No abnormalities in gene expression or immunoreactivity were observed in CADASIL cerebral cortex. Conclusions Molecular abnormalities in CADASIL are largely restricted to white matter and white matter vessels, corresponding to the distribution of neuropathological lesions. These preliminary findings suggest that CADASIL is mediated by both glial and vascular degeneration with reduced expression of IGF receptors and AAH, which regulate Notch expression and function. PMID:21504125

  16. Neurosyphilis masquerading as corticobasal degeneration.

    PubMed

    Benito-León, J; Alvarez-Linera, J; Louis, E D

    2004-11-01

    We report on a patient with a syndrome resembling corticobasal ganglionic degeneration (CBD), including slight cognitive impairment, asymmetric akinesia, rigidity with myoclonus, and arm levitation, which can be one of the features of alien limb phenomenon; however, further diagnostic testing was consistent with neurosyphilis. Syphilis, "the great imitator," may also masquerade as CBD. Because neurosyphilis is treatable, it should be considered in the workup of patients with cognitive impairment and motor signs of CBD. PMID:15389980

  17. RP cone-rod degeneration.

    PubMed Central

    Heckenlively, J R

    1987-01-01

    A group of patients with progressive retinal degeneration and visual field loss, who meet the basic definition of RP were investigated to better define the relationship of the findings on the ERG with clinical characteristics such as visual field size, presence or absence of scotomata or pseudo-altitudinal defects on visual field, amount of night blindness; and presence or absence of macular or optic nerve changes. These studies suggest that cone-rod degeneration patients of the RP type go through the following stages; early, the ERG has a definite cone-rod pattern where the rod ERG is larger than the cone ERG while both are abnormal. As the disease advances, there is more of a reduction in the scotopic ERG such that both the rod and cone ERGs become nearly equal. As the disease further progresses the ERG becomes non-recordable on single-flash technique, but there is good residual rod function and the final rod threshold remains good until the visual field is reduced, typically less than 10 degrees with the IV-4 isopter. Finally with advanced disease the patient becomes night blind and generally becomes very difficult to distinguished from patients who have advanced rod-cone degeneration. While it may seem logical to find that visual field size correlates with various ERG parameters; this has not been as consistent a finding in patients with rod-cone degeneration in the author's experience. The analysis shows several new pieces of information about visual field changes in cone-rod degeneration; enlarged blind spots are seen earlier in cases which have recordable cone-rod patterns (group I), and pseudo-altitudinal changes are more likely to occur in autosomal recessive patients. Patients with macular lesions and central scotomata had larger amplitudes than patients with normal appearing maculae and no central scotomata. Patients with temporal optic atrophy had an earlier onset of symptoms and significant correlation with both photopic a- and b-waves and bright flash dark-adapted b-wave implicit times. Macular edema was present in patients with smaller amplitudes and longer implicit times which suggest that these patients have greater panretinal dysfunction which correlates with the macular alterations. Pigment changes within the classes of none, mild, and moderate deposition correlated with ERG parameters; there was more pigment in cases where ERG parameters were worse. However, cases with heavy pigmentation did not correlate with the ERG degree of severity, suggesting that independent factors influence the amount of pigmentation that occurs in these cases. PMID:3447340

  18. Genetics, Pregnancy, and Aortic Degeneration.

    PubMed

    Crawford, Jeffrey D; Hsieh, Cindy M; Schenning, Ryan C; Slater, Matthew S; Landry, Gregory J; Moneta, Gregory L; Mitchell, Erica L

    2016-01-01

    We present a case of familial thoracic aortic aneurysm and dissection (FTAAD) in a pregnant female. FTAAD is an inherited, nonsyndromic aortopathy resulting from several genetic mutations critical to aortic wall integrity have been identified. One such mutation is the myosin heavy chain gene (MYH11) which is responsible for 1-2% of all FTAAD cases. This mutation results in aortic medial degeneration, loss of elastin, and reticulin fiber fragmentation predisposing to TAAD. Aortic disease is more aggressive during pregnancy as a result of increased wall stress from hyperdynamic cardiovascular changes and estrogen-induced aortic media degeneration. Our patient was a 29-year-old G2P1 woman at 26 weeks gestation presenting with abdominal and back pain. Work-up revealed a 6.4-cm ascending aortic aneurysm with a type A dissection extending into all arch vessels, aortic coarctation at the isthmus, and a separate focal type B aortic dissection with visceral involvement. Surgical management included concomitant cesarean section with delivery of a live premature infant, tubal ligation, ascending aortic replacement with reconstruction of the arch vessels, and aortic valve resuspension. The type B dissection was managed medically without complication. This is the first reported case of aortic dissection in a patient with FTAAD/MYH11 mutation and pregnancy. This case highlights that FTAAD and pregnancy cause aortic degeneration via distinct mechanisms and that hyperdynamics of pregnancy increase aortic wall stress. Management of pregnancy associated with aortopathy requires early transfer to a tertiary center, careful investigation to identify familial aortopathy, fetal monitoring, and a multidisciplinary team approach. PMID:26381327

  19. 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.

  20. 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.

  1. 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.

  2. On the Constraint Algebra of Degenerate Relativity

    E-print Network

    Joseph D. Romano

    1993-06-28

    As shown by Ashtekar in the mid 80's, general relativity can be extended to incorporate degenerate metrics. This extension is not unique, however, as one can change the form of the hamiltonian constraints and obtain an {\\it alternative} degenerate extension of general relativity that disagrees with Ashtekar's original theory when the triads vectors are degenerate. In this paper, the constraint algebra of a particular alternative theory is explicitly evaluated and compared with that of Ashtekar's original degenerate extension. A generic classification of the difference between the two theories is given in terms of the degeneracy and surface-forming properties of the triad vectors. (This classification is valid when the degeneracy and surface-forming properties of the triad vectors is the same everywhere in an open set about a point in space.) If the triad vectors are degenerate and surface-forming, then all the secondary constraints of the alternative degenerate extension are satisfied as a consequence of the primary constraints, and the constraints of this theory are weaker than those of Ashtekar's. If the degenerate triad vectors are not surface-forming, then the first secondary constraint of the alternative theory already implies equivalence with Ashtekar's degenerate extension. What happens when the degeneracy and surface-forming properties of the triad vectors change from point to point is an open question.

  3. Laser therapy and macular degeneration

    NASA Astrophysics Data System (ADS)

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

    2001-10-01

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

  4. Genetics of Frontotemporal Lobar Degeneration

    PubMed Central

    Galimberti, Daniela; Scarpini, Elio

    2012-01-01

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

  5. Naturalness of nearly degenerate neutrinos

    E-print Network

    J. A. Casas; J. R. Espinosa; A. Ibarra; I. Navarro

    1999-05-03

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate. We study whether radiative corrections can or cannot be responsible for the small mass splittings, in agreement with all the available experimental data. We perform an exhaustive exploration of the bimaximal mixing scenario, finding that (i) the vacuum oscillations solution to the solar neutrino problem is always excluded; (ii) if the mass matrix is produced by a see-saw mechanism, there are large regions of the parameter space consistent with the large angle MSW solution, providing a natural origin for the $\\Delta m^2_{sol} << \\Delta m^2_{atm}$ hierarchy; (iii) the bimaximal structure becomes then stable under radiative corrections. We also provide analytical expressions for the mass splittings and mixing angles and present a particularly simple see-saw ansatz consistent with all observations.

  6. 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.

  7. Pegaptanib for wet macular degeneration.

    PubMed

    Fraunfelder, Frederick W

    2005-11-01

    Pegaptanib sodium injection (Macugen, Eyetech Pharmaceuticals, Pfizer, New York, NY, USA) is a relatively new medication intended to treat the so-called wet (neovascular ) form of age-related macular degeneration (AMD). This form of AMD is characterized by the growth of unwanted new blood vessels into the macula (angiogenesis). The aqueous solution containing pegaptanib is injected into the vitreous of the eye, where it binds to the 165 amino acid isoform of vascular endothelial growth factor (VEGF), a secreted protein that is thought to play a major role in the pathologic angiogenesis that occurs in wet AMD. Neovascular AMD is the leading cause of severe vision loss in people over age 60 in the United States and other industrialized countries (1). Pegaptanib acts as a selective VEGF antagonist through its molecular structure as an aptamer, a pegylated modified oligonucleotide that adopts a three-dimensional configuration, enabling it to bind to extracellular VEGF (Fig. 1). Aptamers are macromolecules composed of chemically synthesized single-stranded nucleic acids (either RNA or DNA) that bind with a high degree of selectivity and affinity when exposed to target proteins. Pegaptanib binds VEGF165, and bound VEGF165 is not able to bind to the VEGF receptor, thereby negating its ability to cause angiogenesis and vascular permeability. Other aptamers exist, as do other forms of treatment for AMD. To date, however, no treatment for AMD has allowed for better vision after treatment, with most surgical treatments leading to almost immediate loss of some vision in the expectation of preventing more severe loss. Research in the field of macular degeneration is advancing rapidly, and treatment with an aptamer such as pegaptanib is a viable option despite the possibility of adverse events. PMID:16395411

  8. Hunting Quasi-Degenerate Higgsinos

    E-print Network

    Zhenyu Han; Graham D. Kribs; Adam Martin; Arjun Menon

    2014-01-06

    We present a new strategy to uncover light, quasi-degenerate Higgsinos, a likely ingredient in a natural supersymmetric model. Our strategy focuses on Higgsinos with inter-state splittings of O(5-50) GeV that are produced in association with a hard, initial state jet and decay via off-shell gauge bosons to two or more leptons and missing energy, $pp \\to j + \\text{MET}\\, + 2^+\\, \\ell$. The additional jet is used for triggering, allowing us to significantly loosen the lepton requirements and gain sensitivity to small inter-Higgsino splittings. Focusing on the two-lepton signal, we find the seemingly large backgrounds from diboson plus jet, $\\bar tt$ and $Z/\\gamma^* + j$ can be reduced with careful cuts, and that fake backgrounds appear minor. For Higgsino masses $m_{\\chi}$ just above the current LEP II bound ($\\mu \\simeq 110\\,$) GeV we find the significance can be as high as 3 sigma at the LHC using the existing 20 fb$^{-1}$ of 8 TeV data. Extrapolating to LHC at 14 TeV with 100 fb$^{-1}$ data, and as one example $M_1 = M_2 = 500$ GeV, we find 5 sigma evidence for $m_{\\chi} \\lesssim\\, 140\\,$ GeV and 2 sigma evidence for $m_{\\chi} \\lesssim\\, 200\\,$ GeV . We also present a reinterpretation of ATLAS/CMS monojet bounds in terms of degenerate Higgsino ($\\delta m_{\\chi} \\ll 5\\,$) GeV plus jet production. We find the current monojet bounds on $m_{\\chi}$ are no better than the chargino bounds from LEP II.

  9. 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.

  10. 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

  11. 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.

  12. Perceptual timing in cerebellar degeneration.

    PubMed

    Nichelli, P; Alway, D; Grafman, J

    1996-09-01

    This study examined time perception in 12 patients with cerebellar degeneration (CD) and in 13 normal controls (NC). We used a time bisection procedure with four interval conditions (100-900 msec; 8-32 sec; 100-600 msec; 100-325 msec). Each subject's bisection point, discrimination ability (the Weber ratio) and precision (the inverse of the proportion of unexplained variance) was calculated for each condition. CD patients' performance on the 100-900 msec time bisection condition suggested a possible time discrimination deficit, which was confirmed with intervals in the range of 100-600 msec. Time discrimination was normal on the 100-325 msec condition and impaired on the 8-32 sec bisection task. However, when discriminating long intervals, CD patients also showed a precision deficit, which points to impaired sustained attention and/or decision processes. Our findings corroborate the view that cerebellar timing processes are not limited to the motor system but are also used in perceptual computations. PMID:8822733

  13. Degeneration of Biogenic Superparamagnetic Magnetite

    SciTech Connect

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

    2009-01-01

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

  14. EXCEPTIONAL BUNDLES ASSOCIATED TO DEGENERATIONS OF SURFACES

    E-print Network

    Hacking, Paul

    EXCEPTIONAL BUNDLES ASSOCIATED TO DEGENERATIONS OF SURFACES PAUL HACKING 1. Introduction In 1981 J HACKING F deforms in a unique way to a family of exceptional bundles on the fibers of Y/(0 S). Theorem 1

  15. I-degenerate pseudo-Riemannian metrics

    NASA Astrophysics Data System (ADS)

    Hervik, Sigbjørn; Haarr, Anders; Yamamoto, Kei

    2015-12-01

    In this paper we study pseudo-Riemannian spaces with a degenerate curvature structure i.e. there exists a continuous family of metrics having identical polynomial curvature invariants. We approach this problem by utilising an idea coming from invariant theory. This involves the existence of a boost which is assumed to extend to a neighbourhood. This approach proves to be very fruitful: It produces a class of metrics containing all known examples of I-degenerate metrics. To date, only Kundt and Walker metrics have been given, however, our study gives a plethora of examples showing that I-degenerate metrics extend beyond the Kundt and Walker examples. The approach also gives a useful criterion for a metric to be I-degenerate. Specifically, we use this to study the subclass of VSI and CSI metrics (i.e., spaces where polynomial curvature invariants are all vanishing or constants, respectively).

  16. A new degenerate Fermi gas apparatus

    E-print Network

    Setiawan, Widagdo

    2007-01-01

    In the summer of 2004, the BEC 2 lab of Wolfgang Ketterle's group at MIT started a new research direction of studying degenerate fermionic Lithium atoms in optical lattices. The major contributions to the new experimental ...

  17. Genetics Home Reference: Stargardt macular degeneration

    MedlinePLUS

    ... people with Stargardt macular degeneration, a fatty yellow pigment (lipofuscin) builds up in cells underlying the macula. ... acids ; gene ; inheritance ; inherited ; juvenile ; lipofuscin ; macula ; photoreceptor ; pigment ; prevalence ; protein ; recessive ; retina ; tissue ; toxic You may ...

  18. What Is Age-Related Macular Degeneration?

    MedlinePLUS

    ... Guidelines Home Remedies for Simple Eye Problems Medical Marijuana for Glaucoma Pregnancy Preventing Eye Injuries Smokers Sports ... treatment for dry macular degeneration , some people may benefit from a vitamin therapy regimen for dry macular ...

  19. Parkinson's Drug Shows Promise Against Macular Degeneration

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_155695.html Parkinson's Drug Shows Promise Against Macular Degeneration But more ... THURSDAY, Nov. 12, 2015 (HealthDay News) -- A common Parkinson's disease medication might hold potential for preventing or ...

  20. Degenerate primer design for highly variable genomes.

    PubMed

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

    2015-01-01

    The application of degenerate PCR primers towards target amplification and sequencing is a useful technique when a population of organisms under investigation is evolving rapidly, or is highly diverse. Degenerate bases in these primers are specified with ambiguity codes that represent alternative nucleotide configurations. Degenerate PCR primers allow the simultaneous amplification of a heterogeneous population by providing a mixture of PCR primers each of which anneal to an alternative genotype found in the isolated sample. However, as the number of degenerate bases specified in a pair of primers rises, the likelihood of amplifying unwanted alternative products also increases. These alternative products may confound downstream data analyses if their levels begin to obfuscate the desired PCR products. This chapter describes a set of computational methodologies that may be used to minimize the degeneracy of designed primers, while still maximizing the proportion of genotypes assayed in the targeted population. PMID:25697654

  1. Shear viscosity of degenerate electron matter

    E-print Network

    P. S. Shternin

    2008-03-27

    We calculate the partial electron shear viscosity $\\eta_{ee}$ limited by electron-electron collisions in a strongly degenerate electron gas taking into account the Landau damping of transverse plasmons. The Landau damping strongly suppresses $\\eta_{ee}$ in the domain of ultrarelativistic degenerate electrons and modifies its %asymptotic temperature behavior. The efficiency of the electron shear viscosity in the cores of white dwarfs and envelopes of neutron stars is analyzed.

  2. Protection of Retina by ?B Crystallin in Sodium Iodate Induced Retinal Degeneration

    PubMed Central

    Zhou, Peng; Kannan, Ram; Spee, Christine; Sreekumar, Parameswaran G.; Dou, Guorui; Hinton, David R.

    2014-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD and ?B crystallin expression is increased in RPE and associated drusen in AMD. The purpose of this study was to investigate the role of ?B crystallin in sodium iodate (NaIO3)-induced retinal degeneration, a model of AMD in which the primary site of pathology is the RPE. Dose dependent effects of intravenous NaIO3 (20-70 mg/kg) on development of retinal degeneration (fundus photography) and RPE and retinal neuronal loss (histology) were determined in wild type and ?B crystallin knockout mice. Absence of ?B crystallin augmented retinal degeneration in low dose (20 mg/kg) NaIO3-treated mice and increased retinal cell apoptosis which was mainly localized to the RPE layer. Generation of reactive oxygen species (ROS) was observed with NaIO3 in mouse and human RPE which increased further after ?B crystallin knockout or siRNA knockdown, respectively. NaIO3 upregulated AKT phosphorylation and peroxisome proliferator–activator receptor–? (PPAR?) which was suppressed after ?B crystallin siRNA knockdown. Further, PPAR? ligand inhibited NaIO3-induced ROS generation. Our data suggest that ?B crystallin plays a critical role in protection of NaIO3-induced oxidative stress and retinal degeneration in part through upregulation of AKT phosphorylation and PPAR? expression. PMID:24874187

  3. Neural remodeling in retinal degeneration.

    PubMed

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

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in phase 1 or 2 in some animal models, but depletion of all neuronal classes is evident in phase 3. As remodeling progresses over months and years, more neurons are lost and patches of the ganglion cell layer can become depleted. Some survivor neurons of all classes elaborate new neurites, many of which form fascicles that travel hundreds of microns through the retina, often beneath the distal glial seal. These and other processes form new synaptic microneuromas in the remnant inner nuclear layer as well as cryptic connections throughout the retina. Remodeling activity peaks at mid-phase 3, where neuronal somas actively migrate on glial surfaces. Some amacrine and bipolar cells move into the former ganglion cell layer while other amacrine cells are everted through the inner nuclear layer to the glial seal. Remodeled retinas engage in anomalous self-signaling via rewired circuits that might not support vision even if they could be driven anew by cellular or bionic agents. We propose that survivor neurons actively seek excitation as sources of homeostatic Ca(2+) fluxes. In late phase 3, neuron loss continues and the retina becomes increasingly glial in composition. Retinal remodeling is not plasticity, but represents the invocation of mechanisms resembling developmental and CNS plasticities. Together, neuronal remodeling and the formation of the glial seal may abrogate many cellular and bionic rescue strategies. However, survivor neurons appear to be stable, healthy, active cells and given the evidence of their reactivity to deafferentation, it may be possible to influence their emergent rewiring and migration habits. PMID:12892644

  4. Age-related macular degeneration.

    PubMed

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and ?-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. PMID:23580402

  5. Mechanism of All-trans-retinal Toxicity with Implications for Stargardt Disease and Age-related Macular Degeneration*S

    E-print Network

    Palczewski, Krzysztof

    -related Macular Degeneration*S Received for publication,October 19, 2011, and in revised form, December 17, 2011-related macular degeneration. To sustain vision, all-trans-retinal (atRAL),2 released from light-activated visual of aberrant atRAL metabolism (15). Patients affected by retinal degeneration in age-related macular

  6. The periodic table of n-categories for low dimensions I: degenerate categories and degenerate bicategories

    E-print Network

    Cheng, Eugenia

    The periodic table of n-categories for low dimensions I: degenerate categories and degenerate bicategories Eugenia Cheng and Nick Gurski Abstract. We examine the periodic table of weak n the first few entries in the "Periodic Table" of n- categories. This table was first described by Baez

  7. Prospectives for Gene Therapy of Retinal Degenerations

    PubMed Central

    Thumann, Gabriele

    2012-01-01

    Retinal degenerations encompass a large number of diseases in which the retina and associated retinal pigment epithelial (RPE) cells progressively degenerate leading to severe visual disorders or blindness. Retinal degenerations can be divided into two groups, a group in which the defect has been linked to a specific gene and a second group that has a complex etiology that includes environmental and genetic influences. The first group encompasses a number of relatively rare diseases with the most prevalent being Retinitis pigmentosa that affects approximately 1 million individuals worldwide. Attempts have been made to correct the defective gene by transfecting the appropriate cells with the wild-type gene and while these attempts have been successful in animal models, human gene therapy for these inherited retinal degenerations has only begun recently and the results are promising. To the second group belong glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). These retinal degenerations have a genetic component since they occur more often in families with affected probands but they are also linked to environmental factors, specifically elevated intraocular pressure, age and high blood sugar levels respectively. The economic and medical impact of these three diseases can be assessed by the number of individuals affected; AMD affects over 30 million, DR over 40 million and glaucoma over 65 million individuals worldwide. The basic defect in these diseases appears to be the relative lack of a neurogenic environment; the neovascularization that often accompanies these diseases has suggested that a decrease in pigment epithelium-derived factor (PEDF), at least in part, may be responsible for the neurodegeneration since PEDF is not only an effective neurogenic and neuroprotective agent but also a potent inhibitor of neovascularization. In the last few years inhibitors of vascularization, especially antibodies against vascular endothelial cell 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

  8. 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)-1? 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-1?-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-1?. 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

  9. Antioxidative nanofullerol prevents intervertebral disk degeneration.

    PubMed

    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)-1? 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-1?-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-1?. 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

  10. Ill-posedness of degenerate dispersive equations

    NASA Astrophysics Data System (ADS)

    Ambrose, David M.; Simpson, Gideon; Wright, J. Douglas; Yang, Dennis G.

    2012-09-01

    In this paper we provide numerical and analytical evidence that some degenerate dispersive partial differential equations are ill-posed. Specifically we study the K (2, 2) equation ut = (u2)xxx + (u2)x and the ‘degenerate Airy’ equation ut = 2uuxxx. For K (2, 2) our results are computational in nature: we conduct a series of numerical simulations which demonstrate that data which is very small in H2 can be of unit size at a fixed time which is independent of the data's size. For the degenerate Airy equation, our results are fully rigorous: we prove the existence of a compactly supported self-similar solution which, when combined with certain scaling invariances, implies ill-posedness (also in H2).

  11. THE CELL STRESS MACHINERY AND RETINAL DEGENERATION

    PubMed Central

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

    2015-01-01

    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

  12. Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration.

    PubMed Central

    Li, T; Franson, W K; Gordon, J W; Berson, E L; Dryja, T P

    1995-01-01

    The missense mutation Lys-296-->Glu (K296E) in the rhodopsin gene produces an opsin with no chromophore binding site and therefore is not activated by light. Nevertheless, the mutant opsin constitutively activates transducin in vitro and causes photoreceptor degeneration in vivo, possibly by continuously activating the phototransduction cascade, analogous to constant exposure to environmental light. We studied the K296E mutation in eight lines of transgenic mice. Each line developed photoreceptor degeneration with the rate of degeneration increasing monotonically as the ratio of mutant:wild-type opsin mRNA increased. At no time in the course of degeneration was there endogenous light adaptation in the retina as measured by the electroretinogram. The mutant opsin was found to be invariably phosphorylated and stably bound to arrestin. Light-independent activation of transducin was demonstrated only after the removal of arrestin and dephosphorylation of K296E opsin. Thus, K296E opsin in vivo does not activate the phototransduction cascade because it is shut off by photoreceptor inactivation mechanisms. Our data show that the K296E mutation does not cause photoreceptor degeneration by continuous activation of phototransduction. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7724596

  13. Degeneration under the microscope at the fin de siècle.

    PubMed

    Lawrence, Christopher

    2009-10-01

    Theories of familial, racial, and national degeneration in the late nineteenth and early twentieth centuries have been explored by historians in the context of social and moral pathology. At the same time nerve degeneration was studied in the post mortem room and in the laboratory but links to the broader ideology of degeneration have not been investigated by scholars. This paper joins these domains by examining the concept of Wallerian degeneration. It argues that various discourses--including those of the laboratory scientist, the clinician, and the social theorist--employed the term degeneration, and these discourses frequently overlapped demonstrating that degeneration was a ubiquitous fact of Victorian and Edwardian nature. PMID:20506746

  14. 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

  15. 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.

  16. Histone Deacetylase: Therapeutic Targets in Retinal Degeneration.

    PubMed

    Daly, Conor; Yin, Jun; Kennedy, Breandán N

    2016-01-01

    Previous studies report that retinitis pigmentosa (RP) patients treated with the histone deacetylase inhibitor (HDACi) valproic acid (VPA) present with improved visual fields and delayed vision loss. However, other studies report poor efficacy and safety of HDACi in other cohorts of retinal degeneration patients. Furthermore, the molecular mechanisms by which HDACi can improve visual function is unknown, albeit HDACi can attenuate pro-apoptotic stimuli and induce expression of neuroprotective factors. Thus, further analysis of HDACi is warranted in pre-clinical models of retinal degeneration including zebrafish. Analysis of HDAC expression in developing zebrafish reveals diverse temporal expression patterns during development and maturation of visual function. PMID:26427446

  17. Experiments with Quantum Degenerate Atomic Strontium

    NASA Astrophysics Data System (ADS)

    Yan, Mi; Desalvo, Brian; Huang, Ying; Balasubramanian, Ramachand; Pu, Han; Killian, Thomas

    2012-06-01

    We will describe experiments with quantum degenerate gases of atomic strontium. We are able to produce Bose-Einstein condensates of ^84Sr and quantum degenerate mixtures of ^87Sr (fermion) and ^88Sr (boson). With ^88Sr we have demonstrated control over condensate dynamics with an optical Feshbach resonance and have developed tools to model the dynamics after a rapid change in scattering length. We will describe photoassociative spectroscopy near the ^1S0-^3P1 atomic asymptote for various isotopes and the calculation of parameters for optical Feshbach resonances. We will also discuss our recent progress loading condensates into optical lattices.

  18. Pollen Tube Discharge Completes the Process of Synergid Degeneration That Is Initiated by Pollen Tube-Synergid Interaction in Arabidopsis1[OPEN

    PubMed Central

    Leydon, Alexander R.; Tsukamoto, Tatsuya; Dunatunga, Damayanthi; Qin, Yuan; Johnson, Mark A.; Palanivelu, Ravishankar

    2015-01-01

    In flowering plant reproduction, pollen tube reception is the signaling system that results in pollen tube discharge, synergid degeneration, and successful delivery of male gametes (two sperm cells) to the site where they can fuse with female gametes (egg cell and central cell). Some molecules required for this complex and essential signaling exchange have been identified; however, fundamental questions about the nature of the interactions between the pollen tube and the synergid cells remain to be clarified. Here, we monitor pollen tube arrival, pollen tube discharge, and synergid degeneration in Arabidopsis (Arabidopsis thaliana) wild type and in male and female gametophytic mutants that disrupt development and function of the gametophytes. By combining assays used previously to study these interactions and an assay that facilitates simultaneous analysis of pollen tube discharge and synergid degeneration, we find that synergid degeneration could be initiated without pollen tube discharge. Our data support the hypothesis that pollen tube-synergid contact, or signaling via secreted molecules, initiates receptive synergid degeneration. We also find that when pollen tubes successfully burst, they always discharge into a degenerated synergid. In addition to this pollen tube-dependent promotion of synergid degeneration, we also show that a basal developmental pathway mediates synergid degeneration in the absence of pollination. Our results are consistent with the model that a complex set of interactions between the pollen tube and synergid cells promote receptive synergid degeneration. PMID:26229050

  19. 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

  20. Correlation between rotator cuff tear and glenohumeral degeneration.

    PubMed

    Hsu, Horng-Chaung; Luo, Zong-Ping; Stone, James J; Huang, Tze-Hsi; An, Kai-Nan

    2003-02-01

    We studied the occurrence and correlation between a rotator cuff tear and glenohumeral degeneration. 44 cadaveric shoulders (22 right) were obtained from 32 subjects (18 females), mean age 73 (62-86) years and without a history of systemic diseases. Rotator cuffs were exposed and tear size (14 shoulders) was measured after removal of soft tissue and deltoid. Articular cartilage damage of the glenoid and humeral head was recorded by photography. A grading system of 1 (intact), 2 (mild) and 3 (severe) was used to determine the severity of cartilage damage. The area of articular cartilage damage was calculated using the Sonic Digitizer Analyzing System. The area of articular cartilage damage to the glenoid and the humeral head in the rotator cuff tear group was 32% and 36%, respectively. It was greater than that in the groups without a tear, which was 6% in the glenoid and 7% in the humeral head. However, it was not correlated with the size of the tear. Most of the articular cartilage damage in massive and large rotator cuff tears was located in the anterior-inferior portion of the glenoid and in the posterior portion of the humeral head. The articular cartilage damage area of the glenoid was correlated with that of the humeral head. In conclusion, the area of glenohumeral degeneration was greater in the rotator cuff tear group and was located in a specific site. PMID:12635800

  1. Retinal Remodeling Triggered by Photoreceptor Degenerations

    E-print Network

    Marc, Robert E.

    . Neurol. 464:1­16, 2003. © 2003 Wiley-Liss, Inc. Indexing terms: retinitis pigmentosa; animal models such as retinitis pigmentosa (RP) affect the sensory retina, and the resultant loss of photo- receptor inputRetinal Remodeling Triggered by Photoreceptor Degenerations BRYAN W. JONES,1* CARL B. WATT,1 JEANNE

  2. Retinal remodeling in inherited photoreceptor degenerations.

    PubMed

    Marc, Robert E; Jones, Bryan W

    2003-10-01

    Photoreceptor degenerations initiated in rods or the retinal pigmented epithelium usually evoke secondary cone death and sensory deafferentation of the surviving neural retina. In the mature central nervous system, deafferentation evokes atrophy and connective re-patterning. It has been assumed that the neural retina does not remodel, and that it is a passive survivor. Screening of advanced stages of human and rodent retinal degenerations with computational molecular phenotyping has exposed a prolonged period of aggressive negative remodeling in which neurons migrate along aberrant glial columns and seals, restructuring the adult neural retina (1). Many neurons die, but survivors rewire the remnant inner plexiform layer (IPL), forming thousands of novel ectopic microneuromas in the remnant inner nuclear layer (INL). Bipolar and amacrine cells engage in new circuits that are most likely corruptive. Remodeling in human and rodent retinas emerges regardless of the molecular defects that initially trigger retinal degenerations. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, the exposure of intrinsic retinal remodeling by the removal of sensory control in retinal degenerations suggests that neuronal organization in the normal retina may be more plastic than previously believed. PMID:14576452

  3. 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…

  4. 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,…

  5. Ecological transition predictably associated with gene degeneration.

    PubMed

    Wessinger, Carolyn A; Rausher, Mark D

    2015-02-01

    Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories. PMID:25371436

  6. Reorganization of Visual Processing in Age-Related Macular Degeneration

    E-print Network

    Peli, Eli

    Reorganization of Visual Processing in Age-Related Macular Degeneration Depends on Foveal Loss with central vision loss due to macular degeneration (MD) view stimuli in the periphery, most of them activate of bottom-up input to ``foveal'' cortex owing to macular degeneration (MD), the deprived region of cortex

  7. Identifying Age-related Macular Degeneration In Volumetric Retinal Images

    E-print Network

    Coenen, Frans

    Identifying Age-related Macular Degeneration In Volumetric Retinal Images Abdulrahman Albarrak a Age-related Macular Degeneration (AMD) is a retina disorder, which is currently on the increase. Age-related Macular Degeneration(AMD) is one of these disorders. OCT images indicate clearly different

  8. 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.

  9. Bohmian Mechanics for a Degenerate Time Foliation

    E-print Network

    Ward Struyve; Roderich Tumulka

    2015-05-12

    The version of Bohmian mechanics in relativistic space-time that works best, the hypersurface Bohm--Dirac model, assumes a preferred foliation of space-time into spacelike hypersurfaces (called the time foliation) as given. We consider here a degenerate case in which, contrary to the usual definition of a foliation, several leaves of the time foliation have a region in common. That is, if we think of the time foliation as a 1-parameter family of hypersurfaces, with the hypersurfaces moving towards the future as we increase the parameter, a degenerate time foliation is one for which a part of the hypersurface does not move as we increase the parameter. We show that the hypersurface Bohm--Dirac model still works in this situation; that is, we show that a Bohm-type law of motion can still be defined, and that the appropriate $|\\psi|^2$ distribution is still equivariant with respect to this law.

  10. 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

  11. Ultracompact quantum splitter of degenerate photon pairs

    E-print Network

    He, Jiakun; Casas-Bedoya, Alvaro; Zhang, Yanbing; Xiong, Chunle; Eggleton, Benjamin J

    2015-01-01

    Integrated sources of indistinguishable photons have attracted a lot of attention because of their applications in quantum communication and optical quantum computing. Here, we demonstrate an ultra-compact quantum splitter for degenerate single photons based on a monolithic chip incorporating Sagnac loop and a micro-ring resonator with a footprint of 0.011 mm2, generating and deterministically splitting indistinguishable photon pairs using time-reversed Hong-Ou-Mandel interference. The ring resonator provides enhanced photon generation rate, and the Sagnac loop ensures the photons travel through equal path lengths and interfere with the correct phase to enable the reversed HOM effect to take place. In the experiment, we observed a HOM dip visibility of 94.5 +- 3.3 %, indicating the photons generated by the degenerate single photon source are in a suitable state for further integration with other components for quantum applications, such as controlled-NOT gates.

  12. 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.

  13. Discovery of supersymmetry with degenerated mass spectrum

    E-print Network

    Kiyotomo Kawagoe; Mihoko M. Nojiri

    2006-06-09

    Discovery of supersymmetric (SUSY) particles at the Large Hadron Collider(LHC) has been studied for the models where squarks and gluino are much heavier than the lightest supersymetric particle (LSP). In this paper, we investigate the SUSY discovery in the models with degenerated mass spectrum up to m_LSP~0.7 m_sq. Such mass spectrum is predicted in certain parameter region of the mixed modulas anomaly mediation (MMAM) model. We find that the effective transverse mass of the signal for the degenerated parameters shows the distribution similar to that of the background. Experimental sensitivity of the SUSY particles at the LHC therefore depends on the uncertainty of the background in this class of model. We also find that SUSY signal shows an interesting correlation between M_eff and ETmiss which may be used to determine the signal region properly to enhance the S/N ratio even if the sparticle masses are rather degenerated. The structure is universal for the models with new heavy colored particles decaying into visible particles and a stable neutral particle, dark matter.

  14. Production of quantum-degenerate strontium gases

    NASA Astrophysics Data System (ADS)

    Stellmer, Simon; Grimm, Rudolf; Schreck, Florian

    2013-01-01

    We report on an improved scheme to generate Bose-Einstein condensates (BECs) and degenerate Fermi gases of strontium. This scheme allows us to create quantum gases with higher atom number, a shorter time of the experimental cycle, or deeper quantum degeneracy than before. We create a BEC of 84Sr exceeding 107 atoms, which is a 30-fold improvement over previously reported experiments. We increase the atom number of 86Sr BECs to 2.5×104 (a fivefold improvement) and refine the generation of attractively interacting 88Sr BECs. We present a scheme to generate 84Sr BECs with a cycle time of 2 s. We create deeply degenerate 87Sr Fermi gases with T/TF as low as 0.10(1), where the number of populated nuclear spin states can be set to any value between one and ten. Furthermore, we report on a total of five different double-degenerate Bose-Bose and Bose-Fermi mixtures. These studies prepare an excellent starting point for applications of strontium quantum gases anticipated in the near future.

  15. [New drug therapy for retinal degeneration].

    PubMed

    Ohguro, Hiroshi

    2008-01-01

    Retinitis pigmentosa (RP) is an inherited retinal degeneration characterized by nyctalopia, ring scotoma, and bone-spicule pigmentation of the retina. So far, no effective therapy has been found for RP. As a possible molecular etiology of RP, retina-specific gene deficits are most likely involved, but little has been identified in terms of intracellular mechanisms leading to retinal photoreceptor cell death at post-translational levels. In order to find an effective therapy for RP, we must look for underlying common mechanisms that are responsible for the development of RP, instead of designing a specific therapy for each of the RP types with different causes. Therefore, in the present study, several animal models with different causes of RP were studied, including (1)Royal College of Surgeons (RCS) rats with a deficit of retinal pigment epithelium (RPE) function caused by rhodopsin mutation; (2) P23H rats, (3) S334ter rats, (4) photo stress rats, (5) retinal degeneration (rd) mice with a deficit of phosphodiesterase(PDE) function; and (6) cancer-associated retinopathy (CAR) model rats with a deficit of recoverin-dependent photoreceptor adaptation function. In each of these models, the following assessments were made in order to elucidate common pathological mechanisms among the models: (1) retinal function assessed by electroretinogram (ERG), (2) retinal morphology, (3) retinoid analysis, (4) rhodopsin regeneration, (5) rhodopsin phosphorylation and dephosphorylation, and (6) cytosolic cGMP levels. We found that unregulated photoreceptor adaptation processes caused by an imbalance of rhodopsin phosphorylation and dephosphorylation caused retinal dysfunction leading to photoreceptor cell death. As possible candidate drugs for normalizing these retinal dysfunctions and stopping further retinal degeneration, nilvadipine, a Ca channel blocker, retinoid derivatives, and anthocyanine were chosen and tested to determine their effect on the above animal models with retinal degeneration. Nilvadipine showed beneficial effects against retinal degeneration in all models tested, but retinoid derivatives and anthocyanine showed these beneficial effects in only some models. Thus our present data allowed us to test the effectiveness of nilvadipine in the treatment of human RP patients. PMID:18240599

  16. 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 ?u - n (x)u?. An important characteristic of this work is that the region where the logistic term n (?) vanishes, that is K0 = { x : n (x) = 0 }, may be non-smooth. We analyze conditions on ?, ?, n (?) 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.

  17. Radiative Seesaw Mechanism and Degenerate Neutrinos

    SciTech Connect

    Bajc, Borut; Senjanovic, Goran

    2005-12-31

    The radiative seesaw mechanism of Witten generates the right-handed neutrino masses in SO(10) with the spinorial 16{sub H} Higgs field. We study here analytically the 2nd and 3rd generations for the minimal Yukawa structure containing 10{sub H} and 120{sub H} Higgs representations. In the approximation of small 2nd generation masses and gauge loop domination we find the following results: (1) b-{tau} unification (2) natural coexistence between large {theta}{sub l} and small {theta}{sub q}, and (3) degenerate neutrinos.

  18. Landau Diamagnetism of Degenerate Collisional Plasma

    E-print Network

    A. V. Latyshev; A. A. Yushkanov

    2010-07-05

    For the first time the kinetic description of Landau diamagnetism for degenerate collisional plasma is given. The correct expression for transverse electric conductivity of the quantum plasma, found by authors (see arXiv:1002.1017 [math-ph] 4 Feb 2010) is used. In work S. Dattagupta, A.M. Jayannavar and N. Kumar [Current science, V. 80, No. 7, 10 April, 2001] was discussed the important problem of dissipation (collisions) influence on Landau diamagnetism. The analysis of this problem is given with the use of exact expression for transverse conductivity of quantum plasma.

  19. Aneutronic Fusion in a Degenerate Plasma

    SciTech Connect

    S. Son; N.J. Fisch

    2004-09-03

    In a Fermi-degenerate plasma, the electronic stopping of a slow ion is smaller than that given by the classical formula, because some transitions between the electron states are forbidden. The bremsstrahlung losses are then smaller, so that the nuclear burning of an aneutronic fuel is more efficient. Consequently, there occurs a parameter regime in which self-burning is possible. Practical obstacles in this regime that must be overcome before net energy can be realized include the compression of the fuel to an ultra dense state and the creation of a hot spot.

  20. [Spotty fatty retinal degeneration (author's transl)].

    PubMed

    Daicker, B

    1978-04-01

    The author describes the macroscopical, microscopical and ultrastructural features of a peculiar form of snail track degeneration, which was found in 3 eyes with absolute glaucoma. The snowflakes are concentrated to scattered patches in an extensive frosted area of the peripheral retina. The glittering points consist of neutral fat in a gliotic and atrophic retina. Electron microscopy examination shows fat droplets within the astrocytes and Müller cells. These findings are believed to be the expression of a "in situ break down" of a very slowly atrophying retina by the macroglia. PMID:651237

  1. Age-related macular degeneration: what do patients find on the internet?

    PubMed Central

    Rennie, Christina A; Hannan, Shabeeba; Maycock, Nick; Kang, Chee

    2007-01-01

    Objective To assess the quality of information and readability of the top internet sites for age-related macular degeneration (AMD). Design An examination of the technical information provision, quality and readability of websites found during an internet search for ‘age-related macular degeneration’. Setting Six internet search engines were used to find 26 unique sites on AMD. Main outcome measures Technical information and quality were assessed using a simple grading system. Readability was assessed using a Simple Measure Of Gobbledygook (SMOG) rating. Results Twelve organizational, seven academic and seven commercial sites were identified. The average technical scores were 82.3%, 67.9% and 65.2% for each type of site, respectively (P=0.097, one way ANOVA). The average quality scores were 62.2%, 62.6%, and 49.5% for each type of site, respectively (P=0.356, one-way ANOVA). The average SMOG ratings were 16.3, 16.1, and 16.2 for each type of site, respectively (P=0.983, one-way ANOVA). Fifteen of the sites provided details of new and emerging treatments, with seven providing a detailed discussion. Conclusions Many websites are now meeting the challenge of providing comprehensive information about AMD and its new treatments. Quality scores were disappointing, with sites needing to provide more evidence of authorship and attribution of information. The majority of sites had SMOG scores above 10, making them difficult for the average person to understand. As physicians we need to help design and direct patients to sites that provide high quality, current information. PMID:17911131

  2. A finite volume scheme for nonlinear degenerate parabolic equations

    E-print Network

    Bessemoulin-Chatard, Marianne

    2011-01-01

    We propose a second order finite volume scheme for nonlinear degenerate parabolic equations. For some of these models (porous media equation, drift-diffusion system for semiconductors, ...) it has been proved that the transient solution converges to a steady-state when time goes to infinity. The present scheme preserves steady-states and provides a satisfying long-time behavior. Moreover, it remains valid and second-order accurate in space even in the degenerate case. After describing the numerical scheme, we present several numerical results which confirm the high-order accuracy in various regime degenerate and non degenerate cases and underline the efficiency to preserve the large-time asymptotic.

  3. Functional Rescue of Retinal Degeneration-Associated Mutant RPE65 Proteins.

    PubMed

    Jin, Minghao; Li, Songhua; Hu, Jane; Jin, Heather H; Jacobson, Samuel G; Bok, Dean

    2016-01-01

    More than 100 different mutations in the RPE65 gene are associated with inherited retinal degeneration. Although some missense mutations have been shown to abolish isomerase activity of RPE65, the molecular bases leading to loss of function and retinal degeneration remain incompletely understood. Here we show that several missense mutations resulted in significant decrease in expression level of RPE65 in the human retinal pigment epithelium cells. The 26S proteasome non-ATPase regulatory subunit 13, a newly identified negative regulator of RPE65, mediated degradation of mutant RPE65s, which were misfolded and formed aggregates in the cells. Many mutations, including L22P, T101I, and L408P, were mapped on nonactive sites of RPE65. Enzyme activities of these mutant RPE65s were significantly rescued at low temperature, whereas mutant RPE65s with a distinct active site mutation could not be rescued under the same conditions. 4-phenylbutyrate (PBA) displayed a significant synergistic effect on the low temperature-mediated rescue of the mutant RPE65s. Our results suggest that a low temperature eye mask and PBA, a FDA-approved oral medicine, may provide a promising "protein repair therapy" that can enhance the efficacy of gene therapy for delaying retinal degeneration caused by RPE65 mutations. PMID:26427455

  4. The formation of primordial degenerate protostars

    NASA Astrophysics Data System (ADS)

    Lenzuni, Paolo; Chernoff, David F.; Salpeter, Edwin E.

    1992-07-01

    Low rates of accretion (less than 10 exp -10 solar masses/yr) of metal-free gas onto a small (less than 0.15 solar masses) protostellar core allow efficient cooling of the settling gas and yield very degenerate interior conditions. The steady-state, spherically symmetric flow near such a protostar is modeled. The calculations include a shock which stands above the stellar surface, a cooling region in which bremsstrahlung is the dominant radiative mechanism, an absorption layer just above the protostellar surface in which ionizing radiation is reprocessed, and a settling region in which the newly accreted material cools and joins the hydrostatic atmosphere of the protostar. In addition, there exists an external H II-like region in the preshock region. The transition between degenerate and nondegenerate conditions is a strong function of both mass and accretion rate. Opacity in the outer layers is primarily due to collision-induced absorption. An extensive set of solutions is provided in which a given interior flux is carried by convection at large depths. Some astrophysical implications of accretion at the rates considered are briefly discussed.

  5. Degenerate parametric oscillation in quantum membrane optomechanics

    E-print Network

    Mónica Benito; Carlos Sánchez Muñoz; Carlos Navarrete-Benlloch

    2015-06-26

    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. The possibility of implementing it in nonlinear optical resonators was the main motivation for introducing such model in the eighties, which 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 multi-chromatic 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 studying spontaneous symmetry breaking and enhanced metrology in one of the cleanest dissipative phase transitions.

  6. 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.

  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. Getting superstring amplitudes by degenerating Riemann surfaces

    NASA Astrophysics Data System (ADS)

    Matone, Marco; Volpato, Roberto

    2010-11-01

    We explicitly show how the chiral superstring amplitudes can be obtained through factorisation of the higher genus chiral measure induced by suitable degenerations of Riemann surfaces. This powerful tool also allows to derive, at any genera, consistency relations involving the amplitudes and the measure. A key point concerns the choice of the local coordinate at the node on degenerate Riemann surfaces that greatly simplifies the computations. As a first application, starting from recent ansätze for the chiral measure up to genus five, we compute the chiral two-point function for massless Neveu-Schwarz states at genus two, three and four. For genus higher than three, these computations include some new corrections to the conjectural formulae appeared so far in the literature. After GSO projection, the two-point function vanishes at genus two and three, as expected from space-time supersymmetry arguments, but not at genus four. This suggests that the ansatz for the superstring measure should be corrected for genus higher than four.

  9. Quantum Degenerate Gases of Atomic Strontium

    NASA Astrophysics Data System (ADS)

    Killian, T. C.

    2010-03-01

    This talk will describe the production and properties of a Bose-Einstein condensate of ^84Sr and a quantum degenerate mixture of ^87Sr (fermion) and ^88Sr (boson). ^88Sr has a small negative scattering length leading to a maximum condensate size for our trapping conditions of about 10^4 atoms. ^87Sr is used to sympathetically cool ^88Sr, but it is also of interest for study of quantum degenerate Fermi gases because it has a large nuclear spin (I=9/2). Alkaline-earth metal atoms and atoms with similar electronic structure are of interest for quantum computing proposals, cold collision studies, and investigation of quantum fluids. There are a wealth of isotopes that allow mass-tuning of interactions and creation of various quantum mixtures. The two-valence electrons lead to a singlet ground state and narrow intercombination transitions to metastable triplet states, offering the promise of low-loss optical Feshbach resonances for manipulating scattering lengths. Fermions often have large nuclear spin, which is decoupled from electronic degrees of freedom and leads to a large degree of symmetry and degeneracy in the interaction Hamiltonian. Work done in collaboration with Y.N. Martinez de Escobar, P.G. Mickelson, M. Yan, B.J. DeSalvo, and S.B. Nagel, Rice University.

  10. Viscosity Solutions to Degenerate Complex Monge-Ampre Equations

    E-print Network

    Costantino, Francesco

    Viscosity Solutions to Degenerate Complex Monge-Ampère Equations PHILIPPE EYSSIDIEUX Institut of viscosity solutions and systematically compare viscosity concepts with pluripotential theoretic ones PDE approach to second-order degenerate elliptic equations is the method of viscosity solutions

  11. Degenerate R-S perturbation theory

    NASA Technical Reports Server (NTRS)

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

    1973-01-01

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

  12. 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

  13. 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.

  14. Nearly degenerate neutrinos, Supersymmetry and radiative corrections

    E-print Network

    J. A. Casas; J. R. Espinosa; A. Ibarra; I. Navarro

    1999-05-18

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate with a mass matrix of the bimaximal mixing type. We study this scenario in the MSSM framework, finding that if neutrino masses are produced by a see-saw mechanism, the radiative corrections give rise to mass splittings and mixing angles that can accommodate the atmospheric and the (large angle MSW) solar neutrino oscillations. This provides a natural origin for the $\\Delta m^2_{sol} << \\Delta m^2_{atm}$ hierarchy. On the other hand, the vacuum oscillation solution to the solar neutrino problem is always excluded. We discuss also in the SUSY scenario other possible effects of radiative corrections involving the new neutrino Yukawa couplings, including implications for triviality limits on the Majorana mass, the infrared fixed point value of the top Yukawa coupling, and gauge coupling and bottom-tau unification.

  15. 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.

  16. Prevention of age-related macular degeneration

    PubMed Central

    Koo, Simon Chi Yan; Chan, Clement Wai Nang

    2010-01-01

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

  17. Retinal degeneration following lead exposure - functional aspects.

    PubMed

    Sobieniecki, Andrzej; Gutowska, Izabela; Machali?ska, Anna; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-01-01

    Due to the prevalence of lead (Pb) in the environment, the neurotoxic effects on the human body have become an important clinical problem. Despite that Pb concentration in the environment decreased after banning its use in petrol, it is still a significant issue which can affect child development and vision. This paper focuses on the degeneration of the retina under exposure to lead. We present the most frequent sources of exposure to lead in the environment and the influence on vision, mechanisms leading to the apoptosis of photoreceptor cells, as well as strategies for blocking rod apoptosis. We also present Pb-induced disorders in the calcium metabolism of photoreceptor cells and Ca2+-dependent enzymes. PMID:26671916

  18. Polarization degenerate solid-state cavity QED

    E-print Network

    Morten P. Bakker; Ajit V. Barve; Thomas Ruytenberg; Wolfgang Loffler; Larry A. Coldren; Dirk Bouwmeester; Martin P. van Exter

    2015-03-27

    A polarization degenerate microcavity containing charge-controlled quantum dots (QDs) enables equal coupling of all polarization degrees of freedom of light to the cavity QED system, which we explore through resonant laser spectroscopy. We first measure interference of the two fine-split neutral QD transitions and find very good agreement of this V-type three-level system with a coherent polarization dependent cavity QED model. We also study a charged QD that suffers from decoherence, and find also in this case that availability of the full polarization degrees of freedom is crucial to reveal the dynamics of the QD transitions. Our results pave the way for postselection-free quantum devices based on electron spin-photon polarization entanglement.

  19. 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].

  20. 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].

  1. 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

  2. Single-Degenerate Type Ia Supernovae Are Preferentially Overluminous

    E-print Network

    Fisher, Robert

    2015-01-01

    Recent observational and theoretical progress has favored merging and helium-accreting sub-Chandrasekhar mass white dwarfs 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 white dwarfs 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 white dwarfs in the single-degenerate channel are buoyancy-driven, and consequently lack a vigorous deflagration phase. We thus infer that single-degenerate SNe Ia are gen...

  3. 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

  4. Nonlinear electromagnetic perturbations in a degenerate electron-positron plasma

    NASA Astrophysics Data System (ADS)

    El-Taibany, W. F.; Mamun, A. A.; El-Shorbagy, Kh. H.

    2012-07-01

    Nonlinear propagation of fast and slow magnetosonic perturbation modes in an ultra-cold, degenerate (extremely dense) electron-positron (EP) plasma (containing non-relativistic, ultra-cold, degenerate electron and positron fluids) has been investigated by the reductive perturbation method. It is shown that due to the property of being equal mass of the plasma species (me=mp, where me and mp are electron and positron mass, respectively), the degenerate EP plasma system supports the K-dV solitons which are associated with either fast or slow magnetosonic perturbation modes. It is also found 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 degenerate electron and positron pressures. The applications of the results in an EP plasma medium, which occurs in compact astrophysical objects, particularly in white dwarfs, have been briefly discussed.

  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. Crystallization and collapse in relativistically degenerate matter

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2013-04-01

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

  7. Age related macular degeneration and visual disability.

    PubMed

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of substantial benefit in people with age-related macular degeneration. Prescription filters are one of the most beneficial visual aids that people with macular degeneration. In principle, one aims both at reducing short-wavelength light to reduce glare and at identifying light with specific wavelengths (colours) preferred by the patient for viewing. In both instances, such interventions result in apparent improved contrast sensitivity and better visual acuity. Although specific tests are performed to determine the best colour, tint, lens material, and type of frame for the patient's need, no scientific protocol has been developed so far to assist in prescribing tinted or selective transmission lenses . Magnifying optical lenses are available in a wide range of dioptric powers and are made from materials that correct for weight (plastic), thickness (high index), spherical aberrations (aspherical), and variable light intensities (photochromatic). These lenses can be used as loose lenses, mounted on optical frames, or used with a wide variety of attachments. As the dioptric power of plus lenses increases, the viewing distance of the target decreases, hence their usefulness mainly for tasks requiring near resolution acuity, like reading. Magnification can also be achieved with the use of telescopic devices that are built of two or more plus and (or) minus (minifying) optical lenses. Normal resolution acuity levels can be achieved with these devices for all viewing distances. Therefore, all telescopic devices are useful only for stationary patient tasks that do not require mobility and orientation. Electronic magnification has the great advantage over plus lenses of producing an acuity reserve enabling reading skills for almost all levels of visual acuity. The additional benefit provided is preservation of binocularity, even at high levels of visual disparity between the two eyes. Vision rehabilitation can help patients to maximize their remaining vision and adapt to activities of daily living. The support of the patient's social network is critical to patient's well-bei

  8. Weakly dissipative solitons in dense relativistic-degenerate plasma

    NASA Astrophysics Data System (ADS)

    Ahmad, Saeed; Ata-ur-Rahman; Khan, S. A.

    2015-07-01

    We investigate the features of weakly nonlinear waves in a collisional dense plasma consisting of ultra-relativistic degenerate electrons and non-relativistic degenerate ions. In weak dissipation limit, the dynamics of low frequency nonlinear ion (solitary) wave is described by solving a damped Korteweg-deVries equation. The analytical and numerical analysis shows the existence of weakly dissipative solitons evolving with time. The characteristics of soliton evolution with plasma number density and slow ion-neutral collision rate are discussed with some detail. The relevance of the study with degenerate plasmas in ultra-dense astrophysical objects, particularly white dwarf stars is also pointed out.

  9. From hidden symmetry to extra dimensions: A five-dimensional formulation of the degenerate BESS model

    NASA Astrophysics Data System (ADS)

    Coradeschi, Francesco; de Curtis, Stefania; Dominici, Daniele

    2010-07-01

    We consider the continuum limit of a moose model corresponding to a generalization to N sites of the degenerate BESS model. The five-dimensional formulation emerging in this limit is a realization of a RS1 type model with SU(2)L?SU(2)R in the bulk, broken by boundary conditions and a vacuum expectation value on the infrared brane. A low-energy effective Lagrangian is derived by means of the holographic technique and corresponding bounds on the model parameters are obtained.

  10. From hidden symmetry to extra dimensions: A five-dimensional formulation of the degenerate BESS model

    SciTech Connect

    Coradeschi, Francesco; De Curtis, Stefania; Dominici, Daniele

    2010-07-01

    We consider the continuum limit of a moose model corresponding to a generalization to N sites of the degenerate BESS model. The five-dimensional formulation emerging in this limit is a realization of a RS1 type model with SU(2){sub L} x SU(2){sub R} in the bulk, broken by boundary conditions and a vacuum expectation value on the infrared brane. A low-energy effective Lagrangian is derived by means of the holographic technique and corresponding bounds on the model parameters are obtained.

  11. Nonneovascular Age-Related Macular Degeneration.

    PubMed

    Michels, Stephan; Garhöfer, Gerhard

    2016-01-01

    The discovery of several genetic variants associated with an increased risk for age-related macular degeneration (AMD) has led to a completely new understanding of AMD. In addition to the known modifiable risk factors, genetic risk factors may also help to assess the risk to progress to nonneovascular AMD. Recently published primary studies have indicated that genetic risk analysis may be valuable in the selection of the currently available antioxidant therapy. So far, the best evidence for preventing progression to nonneovascular AMD comes from the Age-Related Eye Disease Studies (AREDS) I and II. These studies indicate that high doses of antioxidants can reduce the risk of progression to the advanced form of the disease. However, the recent evaluation of the addition of either lutein and zeaxanthin, or x03C9;-3 long-chain polyunsaturated fatty acids, or both, to the established AREDS I formulation did not significantly reduce the risk of developing advanced AMD. There is clearly a large unmet medical need for new therapeutic options for nonneovascular AMD. The modulation of the complement cascade is - despite initially disappointing outcomes obtained with blocking complement factor 5 - currently the most promising approach to the treatment of nonneovascular AMD. PMID:26502209

  12. Animal models of age related macular degeneration.

    PubMed

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

    2012-08-01

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

  13. Producing Quantum Degenerate Gases of Strontium

    NASA Astrophysics Data System (ADS)

    Camargo, Francisco; Ding, Roger; Whalen, Joseph; Woehl, Germano; Dunning, Barry; Killian, Thomas

    2015-05-01

    We present our progress towards producing quantum degenerate gases of all four stable isotopes of strontium (84Sr, 86Sr, 87Sr, 88Sr) and isotopic mixtures. We characterize the performance of our broad-line (461 nm, 30.5 MHz), narrow-line (689 nm, 7.5 kHz) magneto-optical traps, and examine evaporative cooling for all four isotopes. The new apparatus will be used to create and study tunable long-range interactions by dressing with strongly-interacting Rydberg states. The ability to trap the four different isotopes allows a measure of control of these interactions through access to a range of attractive and repulsive interactions. Simultaneous trapping of different isotopes provides opportunities for novel laser cooling schemes for studying Bose-Bose and Bose-Fermi mixtures. Research supported by the AFOSR under grant no. FA9550-12-1-0267, the NSF under grants nos. 1301773 and 1205946, and the Robert A. Welch Foundation under grant no. C-0734.

  14. 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].

  15. Degenerate crystals from colloidal dimers under confinement.

    PubMed

    Muangnapoh, Kullachate; Avendaño, Carlos; Escobedo, Fernando A; Liddell Watson, Chekesha M

    2014-12-28

    Colloidal aperiodic phases (i.e., entropy stabilized degenerate crystals, DCs) are realized via self-assembly of hollow fluorescent silica dimers under wedge-cell confinement. The dimer building blocks approximate two tangent spheres and their arrangements are studied via laser scanning confocal microscopy. In the DCs, the individual lobes tile a lattice and five distinct DC arrangements with square, triangular or rectangular layer symmetry are determined as a function of confinement height. Moreover, Monte Carlo simulations are used to construct the phase diagram for DCs up to two layer confinements and to analyze structural order in detail. Just as for spheres, the DC structural transitions under confinement are attributed to the ability or frustration to accommodate an integral number of particle layers between hard walls. Unlike spheres, dimers can also experience transitions involving changes in orientation. DCs are among the unconventional structures (e.g., semi-regular tilings, quasicrystals, plastic crystals) expected to enhance the properties of photonic solids. PMID:25366128

  16. Degenerate intracavity parametric processes with injected signal

    NASA Astrophysics Data System (ADS)

    Olsen, M. K.; Dechoum, K.; Plimak, L. I.

    2003-07-01

    A common way of increasing the efficiency of optical frequency conversion processes is by the injection of a coherent signal at the desired frequency. We study the efficiency of this method and its effect on the quantum statistics of the fields by performing theoretical analyses of the intracavity parametric ?(2) processes of second harmonic generation and degenerate optical parametric oscillation with injected signal fields. We find that the threshold behaviour of the optical parametric oscillator with an injected signal field gives further insight into the normal threshold behaviour, considered as a limiting case as the signal field goes to zero. An injected signal is also shown to change the critical points of the systems, which define the region where the maximum of noise suppression and other quantum effects may be expected. We also investigate the self-pulsing behaviour of second harmonic generation, showing how an injected signal can affect the oscillations. We show the process of second harmonic generation can be blocked by an injected signal of the appropriate intensity, effectively removing the crystal from the cavity.

  17. 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

  18. Nodular Bilateral Amygdala Degeneration in Demented Individuals

    PubMed Central

    Lain, Aurelio Hernandez; Lieberman, Andrew P.; Pfannl, Rolf; Hedley-Whyte, E. Tessa

    2011-01-01

    Among more than 2050 brains in our Alzheimer disease brain banks we came across three brains with well demarcated indurated white-yellow nodules in the amygdalas. Microscopically, these nodules were composed of numerous lipid-laden macrophages located in the central region surrounded by an eosinophilic hyaline-like material with minimal reactive gliosis in the periphery. Neurons within these lesions had a normal appearance but were moderately decreased in number. Beta-amyloid, tau and alpha-synuclein immunostaining revealed no abnormal deposits within the nodules. The three patients had long histories of dementia (one linked to a presenilin-1 mutation). The neuropathological diagnoses were Alzheimer disease in two of them and an unclassified tauopathy with argyrophilic grains in the third. Conclusion The pathogenesis of these lesions is uncertain. We favor that the degeneration has some relationship to the underlying dementing disease, either secondary to deafferentation or an alteration in metabolic demand, perhaps related to the bi-directional anatomical and functional connections that exist between the amygdala and the hippocampus or less likely as a primary event. PMID:20838797

  19. Age-related macular degeneration: a complementopathy?

    PubMed

    Kijlstra, Aize; Berendschot, Tos T J M

    2015-01-01

    Age-related macular degeneration (AMD) is a progressive eye disease affecting many elderly individuals. It has a multifactorial pathogenesis and is associated with numerous environmental (e.g. smoking, light and nutrition) and genetic risk factors. A breakthrough in the mechanisms causing AMD is emerging; the involvement of the alternative pathway of the complement system appears to play a pivotal role. This has led to the statement that AMD is a disease caused by a hyperactive complement system, allowing the term 'complementopathy' to define it more precisely. Abundant evidence includes: the identification of drusen components as activators of complement, immunohistochemical data showing the presence of many species of the complement system in the retinal pigment epithelium-Bruch's membrane-choroidocapillary region of AMD eyes, a strong association of AMD with certain genetic complement protein variants, raised complement levels in blood from AMD patients and the preliminary successful treatments of geographic atrophy with complement factor D (FD) inhibitors. FD is the rate-limiting enzyme of the alternative complement pathway, and is produced by adipose tissue. Recent findings suggest that nutrition may play a role in controlling the level of FD in the circulation. Addressing modifiable risk factors such as smoking and nutrition may thus offer opportunities for the prevention of AMD. PMID:26159686

  20. Degenerating Synaptic Boutons in Prion Disease

    PubMed Central

    Šišková, Zuzana; Page, Anton; O’Connor, Vincent; Perry, Victor Hugh

    2009-01-01

    A growing body of evidence suggests that the loss of synapses is an early and major component of a number of neurodegenerative diseases. Murine prion disease offers a tractable preparation in which to study synaptic loss in a chronic neurodegenerative disease and to explore the underlying mechanisms. We have previously shown that synaptic loss in the hippocampus underpins the first behavioral changes and that there is a selective loss of presynaptic elements. The microglia have an activated morphology at this stage but they have an anti-inflammatory phenotype. We reasoned that the microglia might be involved in synaptic stripping, removing synapses undergoing a degenerative process, and that this gives rise to the anti-inflammatory phenotype. Analysis of synaptic density revealed a progressive loss from 12 weeks post disease initiation. The loss of synapses was not associated with microglia processes; instead, we found that the postsynaptic density of the dendritic spine was progressively wrapped around the degenerating presynaptic element with loss of subcellular components. Three-dimensional reconstructions of these structures from Dual Beam electron microscopy support the conclusion that the synaptic loss in prion disease is a neuron autonomous event facilitated without direct involvement of glial cells. Previous studies described synapse engulfment by developing and injured neurons, and we suggest that this mechanism may contribute to developmental and pathological changes in synapse numbers. PMID:19779137

  1. Neovascular Age-Related Macular Degeneration.

    PubMed

    Shao, Jack; Choudhary, Maria M; Schachat, Andrew P

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe vision loss in individuals over the age of 50 years. Choroidal neovascularization (CNV) is the hallmark of 'wet' or 'exudative' AMD, and is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) is a key component in the development and progression of wet AMD. Since the approval of ranibizumab in 2006, VEGF inhibitors have rapidly altered the treatment and standard of care for wet AMD. Ranibizumab, bevacizumab, and aflibercept are now the most widely used anti-VEGF agents for the treatment of wet AMD. This chapter discusses the pharmacologic properties, pharmacokinetics, safety, and efficacy of these medications, as well as revisits landmark clinical trials that establish these drugs as gold standards in care. While these medications have greatly and positively altered the way we treat AMD, there are still many economic and therapeutic limitations with our current therapy regimens. There continue to be advancements and innovations in exploring alternative and new treatment modalities, as well as combining existing treatment options to improve efficacy, and reduce cost and patient burden. PMID:26501146

  2. 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.

  3. Genetic aspects of intervertebral disc degeneration.

    PubMed

    Hanaei, Sara; Abdollahzade, Sina; Khoshnevisan, Alireza; Kepler, Christopher K; Rezaei, Nima

    2015-10-01

    Intervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD. PMID:25996483

  4. [The macular fatty degeneration of the peripheral retina a variety of the snail track degeneration (author's transl)].

    PubMed

    Daicker, B

    1978-02-22

    A previously undescribed form of snail-track degeneration with scattered flecks was found in three eyes with absolute glaucoma. Light- and electron-microscopic examination of these lesions in the retinal periphery revealed atrophy and gliosis with massive accumulation of fat within the astrocytes and Müller's cells. It was not possible to explain the patchy distribution of the lesions. The fatty change in the macroglia is believed to indicate 'in situ breakdown' of slowly atrophying retina. Morphologic and pathogenetic similarities suggest that all forms of snail-track degeneration with snowflakes represent nonspecific fatty degeneration of the retina. PMID:305729

  5. Meromorphic differentials with imaginary periods on degenerating hyperelliptic curves

    NASA Astrophysics Data System (ADS)

    Bertola, M.; Tovbis, A.

    2015-03-01

    We provide a direct and explicit proof that imaginary (real) normalized differentials of the second kind with prescribed polar part do not develop additional singularities as the underlying hyperelliptic Riemann surface degenerates in an arbitrary way.

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

    E-print Network

    Sanner, Christian Burkhard

    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 ...

  7. Genetics Home Reference: Age-related macular degeneration

    MedlinePLUS

    ... form. The dry form is much more common, accounting for 85 to 90 percent of all cases ... Where can I find information about diagnosis or management of age-related macular degeneration? These resources address ...

  8. Intervertebral disc degeneration: evidence for two distinct phenotypes

    PubMed Central

    Adams, Michael A; Dolan, Patricia

    2012-01-01

    We review the evidence that there are two types of disc degeneration. ‘Endplate-driven’ disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. ‘Annulus-driven’ disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct. PMID:22881295

  9. Many-Body Green Function of Degenerate Systems

    SciTech Connect

    Brouder, Christian; Panati, Gianluca; Stoltz, Gabriel

    2009-12-04

    A rigorous nonperturbative adiabatic approximation of the evolution operator in the many-body physics of degenerate systems is derived. This approximation is used to solve the long-standing problem of the choice of the initial states of H{sub 0} leading to eigenstates of H{sub 0}+V for degenerate systems. These initial states are eigenstates of P{sub 0}VP{sub 0}, where P{sub 0} is the projection onto a degenerate eigenspace of H{sub 0}. This result is used to give the proper definition of the Green function, the statistical Green function and the nonequilibrium Green function of degenerate systems. The convergence of these Green functions is established.

  10. 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.

  11. Singular Fibers in Barking Families of Degenerations of Elliptic Curves

    E-print Network

    Okuda, Takayuki

    2012-01-01

    Takamura established a theory on splitting families of degenerations of complex curves. He introduced a powerful method for constructing a splitting family, called a barking family, in which there appear not only a singular fiber over the origin but also singular fibers over other points, called subordinate fibers. In this paper, for the case of degenerations of elliptic curves, we determine the types of these subordinate fibers.

  12. Generalized degeneracy, dynamic monopolies and maximum degenerate subgraphs

    E-print Network

    Zaker, Manouchehr

    2012-01-01

    A graph $G$ is said to be a $k$-degenerate graph if any subgraph of $G$ contains a vertex of degree at most $k$. Let $\\kappa$ be any non-negative function on the vertex set of $G$. We first define a $\\kappa$-degenerate graph. Next we give an efficient algorithm to determine whether a graph is $\\kappa$-degenerate. We revisit the concept of dynamic monopolies in graphs. The latter notion is used in formulation and analysis of spread of influence such as disease or opinion in social networks. We consider dynamic monopolies with (not necessarily positive) but integral threshold assignments. We obtain a sufficient and necessary relationship between dynamic monopolies and generalized degeneracy. As applications of the previous results we consider the problem of determining the maximum size of $\\kappa$-degenerate (or $k$-degenerate) induced subgraphs in any graph. We obtain some upper and lower bounds for the maximum size of any $\\kappa$-degenerate induced subgraph in general and regular graphs. All of our bounds ar...

  13. Perceptual learning in patients with macular degeneration

    PubMed Central

    Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Rühle, Sabine; Greenlee, Mark W.

    2014-01-01

    Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex. PMID:25368597

  14. Degenerate nucleophilic substitution in phosphonium salts.

    PubMed

    Jennings, Elizabeth V; Nikitin, Kirill; Ortin, Yannick; Gilheany, Declan G

    2014-11-19

    Rates and energy barriers of degenerate halide substitution on tetracoordinate halophosphonium cations have been measured by NMR techniques (VT and EXSY) using a novel experimental design whereby a chiral substituent ((s)Bu) lifts the degeneracy of the resultant salts. Concomitantly, a viable computational approach to the system was developed to gain mechanistic insights into the structure and relative stabilities of the species involved. Both approaches strongly suggest a two-step mechanism of formation of a pentacoordinate dihalophosphorane via backside attack followed by dissociation, resulting in inversion of configuration at phosphorus. The experimentally determined barriers range from <9 kcal mol(-1) to nearly 20 kcal mol(-1), ruling out a mechansm via Berry pseudorotation involving equatorial halides. In all cases studied, epimerization of chlorophosphonium chlorides has a lower energy barrier (by 2 kcal mol(-1)) than the analogous bromo salts. Calculations determined that this was due to the easier accessibility in solution of pentacoordinate dichlorophosphoranes when compared to analogous dibromophosphoranes. In line with the proposed associative mechanism, bulky substituents slow the reaction in the order Me < Et < (i)Pr < (t)Bu. Bulky substituents affect the shape of the reaction energy profile so that the pentacoordinate intermediate is destabilized eventually becoming a transition state. The magnitude of the steric effects is comparable to that of the same substituents on substitution at primary alkyl halides, which can be rationalized by the relatively longer P-C bonds. The reaction displays first-order kinetics due to the prevalence of tight- or solvent-separated ion pairs in solution. Three-dimensional reaction potential energy profiles (More O'Ferrall-Jencks plots) indicated a relatively shallow potential well corresponding to the trigonal bipyramid intermediate flanked by two transition states. PMID:25384344

  15. 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.

  16. Perceptual learning in patients with macular degeneration.

    PubMed

    Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Rühle, Sabine; Greenlee, Mark W

    2014-01-01

    Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex. PMID:25368597

  17. Criteria for the diagnosis of corticobasal degeneration

    PubMed Central

    Armstrong, Melissa J.; Lang, Anthony E.; Bak, Thomas H.; Bhatia, Kailash P.; Borroni, Barbara; Boxer, Adam L.; Dickson, Dennis W.; Grossman, Murray; Hallett, Mark; Josephs, Keith A.; Kertesz, Andrew; Lee, Suzee E.; Miller, Bruce L.; Reich, Stephen G.; Riley, David E.; Tolosa, Eduardo; Tröster, Alexander I.; Vidailhet, Marie; Weiner, William J.

    2013-01-01

    Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ?50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed. PMID:23359374

  18. 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.

  19. Effects of bone cement on intervertebral disc degeneration.

    PubMed

    Zhao, Hui; Ni, Cai-Fang; Huang, Jian; Zhao, Su-Ming; Gu, Wei-Wei; Jiang, Hao; Chen, Long; Tan, Tian-Si

    2014-04-01

    Percutaneous vertebroplasty (PVP) is popular for the treatment of intractable pain due to vertebral collapse from various lesions, intervertebral disk leakage of cement is a frequent complication. The aim of this study was to determine whether bone cement causes disc degeneration, and to evaluate the degree of intervertebral disc degeneration (IDD) according to the time period following cement injection, and the type and volume of cement injected. Sixteen dogs were randomly divided into two groups that were sacrificed at 12 or 24 weeks following cement injection. Five intervertebral discs in each dog were studied, including one control untreated disc and four discs randomly injected with polymethylmethacrylate (PMMA) or calcium phosphate cement (CPC) in two quantities. Radiographic and magnetic resonance imaging (MRI) studies were performed prior to animal sacrifice. T2-weighted mid-sagittal images of the discs were qualitatively analyzed for evidence of degeneration by calculating the MRI index, and all harvested discs were studied histopathologically. IDD was not evident in control discs. Univariate analysis revealed significant differences in the MRI index and the histological grade of disc degeneration in terms of the time period following cement injection, as well as the type and volume of cement injected. Result indicate that direct contact with PMMA and CPC can lead to IDD. However, IDD induced by PMMA was more severe than that induced by CPC. The extent of IDD was found to correlate with the time period post-cement injection and the volume of cement injected into the disc. PMMA and CPC may lead to intervertebral disc degeneration. Intervertebral disc degeneration induced by PMMA is more serious than that of CPC. The degree of intervertebral disc degeneration is correlative to the time after operation and the doses of bone cement. PMID:24669259

  20. Genetic Association Studies in Lumbar Disc Degeneration: A Systematic Review

    PubMed Central

    Eskola, Pasi J.; Lemmelä, Susanna; Kjaer, Per; Solovieva, Svetlana; Männikkö, Minna; Tommerup, Niels; Lind-Thomsen, Allan; Husgafvel-Pursiainen, Kirsti; Cheung, Kenneth M. C.; Chan, Danny

    2012-01-01

    Objective Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans. Methods A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990–2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. Results Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat), COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2 (rs9406328) and MMP9 (rs17576). Conclusions Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration. PMID:23185509

  1. 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 that an eQTL can modify a recessive IPD. PMID:26656104

  2. 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

  3. Rapid Y degeneration and dosage compensation in plant sex chromosomes

    PubMed Central

    Papadopulos, Alexander S. T.; Chester, Michael; Ridout, Kate; Filatov, Dmitry A.

    2015-01-01

    The nonrecombining regions of animal Y chromosomes are known to undergo genetic degeneration, but previous work has failed to reveal large-scale gene degeneration on plant Y chromosomes. Here, we uncover rapid and extensive degeneration of Y-linked genes in a plant species, Silene latifolia, that evolved sex chromosomes de novo in the last 10 million years. Previous transcriptome-based studies of this species missed unexpressed, degenerate Y-linked genes. To identify sex-linked genes, regardless of their expression, we sequenced male and female genomes of S. latifolia and integrated the genomic contigs with a high-density genetic map. This revealed that 45% of Y-linked genes are not expressed, and 23% are interrupted by premature stop codons. This contrasts with X-linked genes, in which only 1.3% of genes contained stop codons and 4.3% of genes were not expressed in males. Loss of functional Y-linked genes is partly compensated for by gene-specific up-regulation of X-linked genes. Our results demonstrate that the rate of genetic degeneration of Y-linked genes in S. latifolia is as fast as in animals, and that the evolutionary trajectories of sex chromosomes are similar in the two kingdoms. PMID:26438872

  4. Electrostatic Solitary Structures in a Relativistic Degenerate Multispecies Plasma

    NASA Astrophysics Data System (ADS)

    Hossen, M. R.; Mamun, A. A.

    2014-08-01

    The nonlinear propagation of cylindrical and spherical modified ion-acoustic (mIA) waves in an unmagnetized, collisionless, relativistic, degenerate multispecies plasma has been investigated theoretically. This plasma system is assumed to contain both relativistic degenerate electron and positron fluids, nonrelativistic degenerate positive and negative ions, and positively charged static heavy ions. The restoring force is provided by the degenerate pressures of the electrons and positrons, whereas the inertia is provided by the mass of positive and negative ions. The positively charged static heavy ions participate only in maintaining the quasi-neutrality condition at equilibrium. The nonplanar K-dV and mK-dV equations are derived by using reductive perturbation technique and numerically analyzed to identify the basic features (speed, amplitude, width, etc.) of mIA solitary structures. The basic characteristics of mIA solitary waves are found to be significantly modified by the effects of degenerate pressures of electron, positron, and ion fluids, their number densities, and various charge states of heavy ions. The implications of our results to dense plasmas in astrophysical compact objects (e.g., nonrotating white dwarfs, neutron stars, etc.) are briefly mentioned.

  5. Electrostatic Solitary Structures in a Relativistic Degenerate Multispecies Plasma

    NASA Astrophysics Data System (ADS)

    Hossen, M. R.; Mamun, A. A.

    2014-12-01

    The nonlinear propagation of cylindrical and spherical modified ion-acoustic (mIA) waves in an unmagnetized, collisionless, relativistic, degenerate multispecies plasma has been investigated theoretically. This plasma system is assumed to contain both relativistic degenerate electron and positron fluids, nonrelativistic degenerate positive and negative ions, and positively charged static heavy ions. The restoring force is provided by the degenerate pressures of the electrons and positrons, whereas the inertia is provided by the mass of positive and negative ions. The positively charged static heavy ions participate only in maintaining the quasi-neutrality condition at equilibrium. The nonplanar K-dV and mK-dV equations are derived by using reductive perturbation technique and numerically analyzed to identify the basic features (speed, amplitude, width, etc.) of mIA solitary structures. The basic characteristics of mIA solitary waves are found to be significantly modified by the effects of degenerate pressures of electron, positron, and ion fluids, their number densities, and various charge states of heavy ions. The implications of our results to dense plasmas in astrophysical compact objects (e.g., nonrotating white dwarfs, neutron stars, etc.) are briefly mentioned.

  6. Review: Retinal degeneration: Focus on the unfolded protein response

    PubMed Central

    Gorbatyuk, Oleg

    2013-01-01

    Recently published literature has provided evidence that the unfolded protein response (UPR) is involved in the development of retinal degeneration. The scope of these studies encompassed diabetic retinopathy, retinopathy of prematurity, glaucoma, retinal detachment, light-induced retinal degeneration, age-related macular degeneration, and inherited retinal degeneration. Subsequent studies investigating the role of individual UPR markers in retinal pathogenesis and examining the therapeutic potential of reprogramming the UPR as a method for modulating the rate of retinal degeneration have been initiated. Manipulation of UPR markers has been made possible by the use of knockout mice, pharmacological agents, and viral vector-mediated augmentation of gene expression. Future research will aim at identifying specific inhibitors and/or inducers of UPR regulatory markers as well as expand the list of UPR-related animal models. Additionally, adeno-associated virus-mediated gene delivery is a safe and effective method for modulating gene expression, and thus is a useful research tool for manipulating individual UPR markers in affected retinas and a promising delivery vector for gene therapy in retinal degenerative disorders. PMID:24068865

  7. 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

  8. 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

  9. Triaxial degenerate dwarfs and pulsing X-ray sources

    NASA Technical Reports Server (NTRS)

    Durisen, R. H.

    1975-01-01

    It is shown that triaxial configurations for rotating degenerate dwarfs consisting entirely of fluid are not limited to forms analogous to the Jacobi ellipsoids. Arguments are presented which rule out only the specialized class of uniformly rotating analogs of the Jacobi ellipsoid for some degenerate dwarfs. Several ways of forming triaxial degenerate dwarfs are examined along with the characteristic lifetimes of such objects. Noting that some of the alternative forms may exist in mass-transfer binary systems, consideration is given to the secondaries in Her X-1 and Cen X-3. It is suggested that the secondary in Her X-1 must be close to an analog of a Dedekind ellipsoid, and plausible triaxial white-dwarf configurations are proposed for the secondary in Cen X-3.

  10. Hot degenerate dwarfs in a two-phase model

    NASA Astrophysics Data System (ADS)

    Vavrukh, M. V.; Smerechinskii, S. V.

    2013-12-01

    The characteristics of degenerate dwarfs-core radius, mass, and energy, thickness of their outer layers-are calculated based on a mechanical-equilibrium equation in a five-parameter, two-phase compositemodel with an isothermal core and a non-degenerate outer region. An accurate equation of state for the partially degenerate, ideal, relativistic electron gas of the core is used together with a polytropic approximation for the outer layers. The model parameters are determined using the known masses, radii, and luminosities of observed DA white dwarfs. A region where dwarfs can exist is identified in a plot of core temperature vs. the relativity parameter at the center of the star, and the dependence of the core temperature on the effective temperature of the photosphere is constructed.

  11. Nonplanar solitons in a degenerate multi-species plasma

    NASA Astrophysics Data System (ADS)

    Shah, M. G.; Mamun, A. A.; Hossen, M. R.

    2015-04-01

    The nonlinear propagation of cylindrical and spherical positron-acoustic solitary waves (PASWs) in an unmagnetized, collisionless, relativistic, degenerate plasma system that consists of nonrelativistic inertial cold positrons, relativistic degenerate electron and hot positron fluids, and positively-charged immobile ions has been investigated theoretically. By using a reductive perturbation technique, we derive the Korteweg-de Vries (K-dV) equation. The solitary wave solution has been numerically analyzed to comprehend the localized electrostatic disturbances. We observed that the effects of the degenerate pressure, relativity, and the number densities of inertial cold positrons, hot positrons, electrons, and positively-charged static ions notably modify the fundamental features of the cylindrical and the spherical PASWs. The implications of our results for dense plasmas in astrophysical compact objects ( e.g., non-rotating white dwarfs, neutron stars, etc.) are briefly discussed.

  12. Exact Nonlinear Excitations in Double-Degenerate Plasmas

    E-print Network

    Akbari-Moghanjoughi, M

    2012-01-01

    In this work we use the conventional hydrodynamics (HD) formalism and incorporate the Chew-Goldberger-Low (CGL) 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 quantums plasma with different equations of state (EoS). 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 the dense astrophysical magnetized plasm...

  13. Electromagnetic wave equations for relativistically degenerate quantum magnetoplasmas

    SciTech Connect

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

    2010-06-15

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

  14. Trick for passing degenerate points in the Ashtekar formulation

    NASA Astrophysics Data System (ADS)

    Yoneda, Gen; Shinkai, Hisa-Aki; Nakamichi, Akika

    1997-08-01

    We examine one of the advantages of Ashtekar's formulation of general relativity: a tractability of degenerate points from the point of view of following the dynamics of classical spacetime. Assuming that all dynamical variables are finite, we conclude that an essential trick for such a continuous evolution is in complexifying variables. In order to restrict the complex region locally, we propose some ``reality recovering'' conditions on spacetime. Using a degenerate solution derived by a pullback technique, and integrating the dynamical equations numerically, we show that this idea works in an actual dynamical problem. We also discuss some features of these applications.

  15. Intramuscular iron therapy and tapetoretinal degeneration. A case report.

    PubMed

    Syversen, K

    1979-06-01

    A 63-years-old male with pernicious anemia had been treated for 20 years with weekly injections of iron-dextran and cyanocobalamine. Ophthalmological examination revealed the ophthalmoscopic picture of a tapetoretinal degeneration, reduced visual acuity and narrow visual fields. ERG and dark-adaptation test were normal. Hematological examination including liver and bone marrow biopsies gave no support for the existence of systemic siderosis. It is proposed that the retinal degeneration is due to the extensive parenteral iron treatment with a total dose of approximately 100 grams of iron. This theory is supported by a previous experimental report. PMID:474082

  16. Construction site Construction site

    E-print Network

    Frean, Marcus

    Construction site no access Construction site no access North RT49 Student Union (SU) Memorial Footpath to cable car Te Puni Village Adams Tce Bridge Staff parking only a b c d e f g h i j k l m a b c d

  17. Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

    PubMed Central

    Santos, Laura M.; Mattiace, Linda A.; Costa, Manoel L.; Ferreira, Luciano C.; Benabou, Kelly; Kim, Ana H.; Abrahams, John; Bennett, Michael V. L.; Rozental, Renato

    2012-01-01

    Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide. PMID:22308470

  18. 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

  19. 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

  20. Neural Reprogramming in Retinal Degeneration Robert E. Marc,1

    E-print Network

    Marc, Robert E.

    visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased diseases such as retinitis pigmentosa (RP) may arise from phased tissue remodeling and functionalNeural Reprogramming in Retinal Degeneration Robert E. Marc,1 Bryan W. Jones,1 James R. Anderson,1

  1. RESEARCH REPORT Limbic and Frontal Cortical Degeneration Is Associated

    E-print Network

    Gaser, Christian

    RESEARCH REPORT Limbic and Frontal Cortical Degeneration Is Associated with Psychiatric Symptoms, and Ferdinand Binkofski Background: Mutations in the PINK1 gene can cause Parkinson's disease and are frequently associated with psychiatric symptoms that might even precede motor signs. Methods: To determine whether

  2. 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.

  3. NUTRITIONAL SUPPLEMENTATION, CATARACTS AND AGE-RELATED MACULAR DEGENERATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related cataract and age-related macular degeneration (AMD) are the major causes of visual impairment and blindness in the aging population. Specific nutrients in the diet that are thought to be important in the prevention of these diseases are vitamins C and E, the carotenoids, lutein and zeaxa...

  4. 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…

  5. SCOTOMAS OF AGE-RELATED MACULAR DEGENERATION DETECTED AND

    E-print Network

    Arizona, University of

    SCOTOMAS OF AGE-RELATED MACULAR DEGENERATION DETECTED AND CHARACTERIZED BY MEANS OF A NOVEL THREE with large soft confluent drusen with retinal pigment epithelium mottling, there is a risk for conversion With several treat- ment possibilities for neovascular AMD, early detection and diagnosis may improve treatment

  6. Electron-ion relaxation time in moderately degenerate plasma

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

    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.

  7. DISCRETE DUALITY FINITE VOLUME SCHEMES FOR DOUBLY NONLINEAR DEGENERATE

    E-print Network

    DISCRETE DUALITY FINITE VOLUME SCHEMES FOR DOUBLY NONLINEAR DEGENERATE HYPERBOLIC of discrete duality finite volume schemes (in the spirit of Domelevo and Omn`es [41]) for these problems, and prove that sequences of approximate solutions generated by the discrete duality finite volume schemes

  8. Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.

    PubMed

    Berner, Andre K; 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

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

    ClinicalTrials.gov

    2015-12-01

    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)

  10. Rothe's method for parabolic problems with nonlinear degenerating coefficient

    E-print Network

    Rothe's method for parabolic problems with nonlinear degenerating coefficient Volker Pluschke on the solution u. We approximate the problem by semidiscretization in time (Rothe's method) and prove uniform in time (Rothe's method). Here G ae R N , N â?? 2, denotes a simply connected, bounded domain with boundary

  11. Exact null controllability of degenerate evolution equations with scalar control

    SciTech Connect

    Fedorov, Vladimir E; Shklyar, Benzion

    2012-12-31

    Necessary and sufficient conditions for the exact null controllability of a degenerate linear evolution equation with scalar control are obtained. These general results are used to examine the exact null controllability of the Dzektser equation in the theory of seepage. Bibliography: 13 titles.

  12. 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...

  13. 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…

  14. 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…

  15. Properties of Degenerated Fermi-Gas in Astrophysics

    E-print Network

    Rosner, Jonathan L.

    -gas is a dominated component in a highly dense re- gion in Astronomy, such as the center of a white dwarf of degenerated gas and its application on Astronomy. Part I Degeneracy of Electrons The density of electrons of a white dwarf, e 106 and T 106 , so this condition is satis...ed. As we knew, the center of a white dwarf

  16. Prolonged prevention of retinal degeneration with retinylamine loaded nanoparticles

    E-print Network

    Palczewski, Krzysztof

    to the eye for about a week and resulted in effective prolonged prevention of light-induced retinal configuration [1e3]. Continuous recycling of the retinoids is essential for the regeneration of light-sensitive to effectively pre- vent light-induced retinal degeneration in DKO mice. Controlled and sustained delivery

  17. Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

    E-print Network

    Palanker, Daniel

    (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed by Elsevier Ltd. 1. Introduction Retinitis pigmentosa (RP) and age-related macular degeneration (AMDInner retinal preservation in rat models of retinal degeneration implanted with subretinal

  18. Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation of

    E-print Network

    Sulzer, David

    Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation and Physiology, University of California, San Francisco, California 94143 Methamphetamine (METH) selectively producing oxyradical stress, autophagy, and neurite degeneration. Key words: methamphetamine; VMAT2

  19. EXISTENCE OF GLOBAL WEAK SOLUTIONS FOR 2D SHALLOW WATER EQUATIONS WITH ITS DEGENERATE VISCOSITY

    E-print Network

    Vasseur, Alexis

    EXISTENCE OF GLOBAL WEAK SOLUTIONS FOR 2D SHALLOW WATER EQUATIONS WITH ITS DEGENERATE VISCOSITY for 2D shallow water equations with degenerate viscosity. The method is based on the Bresch. Introduction The existence of global weak solutions of 2D shallow water equations with degenerate viscosity has

  20. Genetic degeneration of old and young Y chromosomes in the flowering plant Rumex hastatulus

    E-print Network

    Barrett, Spencer C.H.

    Genetic degeneration of old and young Y chromosomes in the flowering plant Rumex hastatulus Josh, and a common feature of their evolution is the degeneration of the Y chromosome, characterized by a loss evolution, the genetic changes that occur during the early stages of Y-chromosome degeneration are poorly

  1. In vivo imaging of retinal pigment epithelium cells in age related macular degeneration

    E-print Network

    In vivo imaging of retinal pigment epithelium cells in age related macular degeneration Ethan A-related macular degeneration (AMD). In this work, we improve Morgan's method by accounting for chromatic pigment epithelium. A manifestation of senile macular degeneration," Arch. Ophthalmol. 93(1), 19­25 (1975

  2. Author's personal copy The macular degeneration-linked C1QTNF5 (S163) mutation causes

    E-print Network

    Palczewski, Krzysztof

    Author's personal copy The macular degeneration-linked C1QTNF5 (S163) mutation causes higher Keywords: L-ORMD L-ORD Age-related macular degeneration Cellular adhesion CTRP5 C1QTNF5 a b s t r a c macular degeneration (L-ORMD). Here we also found that C1QTNF5 monomers can multimerize into a bouquet

  3. Retinal Image Classification for the Screening of Age-related Macular Degeneration

    E-print Network

    Coenen, Frans

    Retinal Image Classification for the Screening of Age-related Macular Degeneration Mohd Hanafi Ahmad Hijazi, Frans Coenen and Yalin Zheng Abstract Age-related Macular Degeneration (AMD) is the most-mail: yzheng@liverpool.ac.uk #12;Hijazi et al. 1 Introduction Age-related Macular Degeneration (AMD

  4. Multifunctional PEG Retinylamine Conjugate Provides Prolonged Protection against Retinal Degeneration in Mice

    E-print Network

    Palczewski, Krzysztof

    ) and age-related macular degeneration (AMD). The peptide spacer was introduced for sustained release Degeneration in Mice Guanping Yu,, Xueming Wu,, Nadia Ayat, Akiko Maeda,§, Song-Qi Gao,§ Marcin Golczak against light-induced retinal degeneration for 3 days after oral administration, as revealed by OCT retina

  5. Residual abilities in age-related macular degeneration to process spatial frequencies during natural scene

    E-print Network

    Alleysson, David

    Residual abilities in age-related macular degeneration to process spatial frequencies during) Abstract Age-related macular degeneration (AMD) is characterized by a central vision loss. We explored-related macular degeneration (AMD) is the first cause of central vision loss in the elderly population

  6. Data Mining Techniques for The Screening of Age-Related Macular Degeneration

    E-print Network

    Coenen, Frans

    Data Mining Techniques for The Screening of Age-Related Macular Degeneration Mohd Hanafi Ahmad, Malaysia Abstract Age related Macular Degeneration (AMD) is the primary cause of adult blindness. Currently-graph mining 1. Introduction Age-related Macular Degeneration (AMD) is the leading cause of blind- ness

  7. Severe atrophy and fatty degeneration of the infraspinatus muscle due to isolated infraspinatus tendon tear.

    PubMed

    Kolbe, Amy B; Collins, Mark S; Sperling, John W

    2012-01-01

    Atrophy of both the supraspinatus and infraspinatus muscles is usually caused by chronic rotator cuff tear, but may also derive from suprascapular nerve entrapment at the spinoglenoid notch. Isolated infraspinatus muscle atrophy is uncommon, and typically associates with suprascapular nerve entrapment occurring distal to the spinoglenoid notch. However, isolated atrophy of the infraspinatus muscle due to insertional tear of the infraspinatus tendon may also occur. We present a case of a 43-year-old male with isolated infraspinatus muscle atrophy and fatty degeneration following an isolated full-thickness infraspinatus tendon tear at the insertion site on the humerus. While it is important to rule out other causes of infraspinatus muscle atrophy, such as concomitant rotator cuff tendon/muscle pathology or suprascapular nerve palsy, we present this case to increase awareness of this uncommon clinical presentation and the potential implications for treatment. PMID:21918868

  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. 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.

  10. Type I seesaw mechanism for quasi degenerate neutrinos

    E-print Network

    Joshipura, Anjan S; Vempati, Sudhir K

    2009-01-01

    We discuss symmetries and scenarios leading to quasi-degenerate neutrinos in type-I seesaw models. The existence of degeneracy in the present approach is not linked to any specific structure for the Dirac neutrino Yukawa coupling matrix $y_D$ and holds in general. Basic input is the application of the minimal flavour violation principle to the leptonic sector. Generalizing this principle, we assume that the structure of the right handed neutrino mass matrix is determined by $y_D$ and the charged lepton Yukawa coupling matrix $y_l$ in an effective theory invariant under specific groups ${\\cal G}_F$ contained in the full symmetry group of the kinetic energy terms. ${\\cal G}_F$ invariance also leads to specific structure for the departure from degeneracy. The neutrino mass matrix (with degenerate mass $m_0$) resulting after seesaw mechanism has a simple form ${\\cal M}_\

  11. Type I seesaw mechanism for quasi degenerate neutrinos

    E-print Network

    Anjan S. Joshipura; Ketan M. Patel; Sudhir K. Vempati

    2009-11-30

    We discuss symmetries and scenarios leading to quasi-degenerate neutrinos in type-I seesaw models. The existence of degeneracy in the present approach is not linked to any specific structure for the Dirac neutrino Yukawa coupling matrix $y_D$ and holds in general. Basic input is the application of the minimal flavour violation principle to the leptonic sector. Generalizing this principle, we assume that the structure of the right handed neutrino mass matrix is determined by $y_D$ and the charged lepton Yukawa coupling matrix $y_l$ in an effective theory invariant under specific groups ${\\cal G}_F$ contained in the full symmetry group of the kinetic energy terms. ${\\cal G}_F$ invariance also leads to specific structure for the departure from degeneracy. The neutrino mass matrix (with degenerate mass $m_0$) resulting after seesaw mechanism has a simple form ${\\cal M}_\

  12. Degenerate stars and gravitational collapse in AdS/CFT

    NASA Astrophysics Data System (ADS)

    Arsiwalla, Xerxes; de Boer, Jan; Papadodimas, Kyriakos; Verlinde, Erik

    2011-01-01

    We construct composite CFT operators from a large number of fermionic primary fields corresponding to states that are holographically dual to a zero temperature Fermi gas in AdS space. We identify a large N regime in which the fermions behave as free particles. In the hydrodynamic limit the Fermi gas forms a degenerate star with a radius determined by the Fermi level, and a mass and angular momentum that exactly matches the boundary calculations. Next we consider an interacting regime, and calculate the effect of the gravitational back-reaction on the radius and the mass of the star using the Tolman-Oppenheimer-Volkoff equations. Ignoring other interactions, we determine the "Chandrasekhar limit" beyond which the degenerate star (presumably) undergoes gravitational collapse towards a black hole. This is interpreted on the boundary as a high density phase transition from a cold baryonic phase to a hot deconfined phase.

  13. Clinical diagnostic criteria and classification controversies in frontotemporal lobar degeneration

    PubMed Central

    RASCOVSKY, KATYA; GROSSMAN, MURRAY

    2014-01-01

    Frontotemporal lobar degeneration (FTLD) can manifest as a spectrum of clinical syndromes, ranging from behavioural impairment to language or motor dysfunction. Recently, revised diagnostic criteria have been proposed for the behavioural and progressive aphasia syndromes associated with frontotemporal degeneration. The present review will summarize these diagnostic guidelines and highlight some lingering controversies in the classification of FTLD clinical syndromes. We will discuss common tools and methods used to identify the insidious changes of behavioural variant frontotemporal dementia (bvFTD), the value of new, patient-based tasks of orbitofrontal function, and the issue of a benign or ‘phenocopy’ variant of bvFTD. With regard to primary progressive aphasia (PPA), we will discuss the scope of the semantic disorder in semantic-variant PPA, the nature of the speech disorder in non-fluent, agrammatic PPA, and the preliminary utility of a logopenic PPA classification. PMID:23611345

  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. Nonlinear Electromagnetic Waves in a Degenerate Electron-Positron Plasma

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  16. Nonplanar Electrostatic Solitary Waves in a Relativistic Degenerate Dense Plasma

    NASA Astrophysics Data System (ADS)

    Ata-ur-Rahman; Mushtaq, A.; S., Ali; Qamar, A.

    2013-04-01

    By employing the reductive perturbation technique, the propagation of cylindrical and spherical ion acoustic solitary waves is studied in an unmagnetized dense relativistic plasma, consisting of relativistically degenerate electrons and cold fluid ions. A modified Korteweg-de-Vries equation is derived and its numerical solutions have been analyzed to identify the basic features of electrostatic solitary structures that may form in such a degenerate Fermi plasma. Different degrees of relativistic electron degeneracy are discussed and compared. It is found that increasing number density leads to decrease the amplitude the width of the ion acoustic solitary wave in both the cylindrical and spherical geometries. The relevance of the work to the compact astrophysical objects, particularly white dwarfs is pointed out.

  17. On modular transformations of non-degenerate toric conformal blocks

    E-print Network

    Nikita Nemkov

    2015-04-27

    We derive and solve the difference equations on the toric modular kernel following from the consistency relations in the fusion algebra. The result is explicit and simple series expansion for the toric modular kernel of non-degenerate Virasoro conformal blocks. We show that this expansion is equivalent to the celebrated integral representation due to B. Ponsot and J. Teschner. We also interpret obtained series representation as a non-perturbative expansion and note that this raises further questions.

  18. Effects of degenerate sterile neutrinos on the supernova neutrino flux

    E-print Network

    P. Keranen; J. Maalampi; M. Myyrylainen; J. Riittinen

    2004-08-11

    We consider the possibility that there exist sterile neutrinos which are closely degenerate in mass with the active neutrinos and mixed with them. We investigate the effects of this kind of active-sterile neutrino mixing on the composition of supernova neutrino flux at the Earth. If an adiabatic MSW-transition between active and sterile neutrinos takes place, it could dramatically diminish the electron neutrino flux.

  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. Ultrafast Degenerate Transient Lens Spectroscopy in Semiconductor Nanosctructures

    NASA Astrophysics Data System (ADS)

    Leontyev, A. V.; Zharkov, D. K.; Shmelev, A. G.; Nikiforov, V. G.; Lobkov, V. S.

    2015-09-01

    We report the non-resonant excitation and probing of the nonlinear refractive index change in bulk semiconductors and semiconductor quantum dots through degenerate transient lens spectroscopy. The signal oscillates at the center laser field frequency, and the envelope of the former in quantum dots is distinctly different from the one in bulk sample. We discuss the applicability of this technique for polarization state probing in semiconductor media with femtosecond temporal resolution.

  1. Degenerate sterile neutrino dark matter in the cores of galaxies

    E-print Network

    Faustin Munyaneza; Peter L. Biermann

    2006-09-14

    We study the distribution of fermionic dark matter at the center of galaxies using NFW, Moore and isothermal density profiles and show that dark matter becomes degenerate for particle masses of a few {\\rm keV} and for distances less than a few parsec from the center of our galaxy. A compact degenerate core forms after galaxy merging and boosts the growth of supermassive black holes at the center of galaxies. To explain the galactic center black hole of mass of $\\sim 3.5 \\times 10^{6}M_{\\odot}$ and a supermassive black hole of $\\sim 3 \\times 10^{9}M_{\\odot}$ at a redshift of 6.41 in SDSS quasars, we require a degenerate core of mass between $3 \\times 10^{3} M_{\\odot}$ and $3.5 \\times 10^{6}M_{\\odot}$. This constrains the mass of the dark matter particle between $0.6 {\\rm keV}$ and $82 {\\rm keV}$. The lower limit on the dark matter mass is improved to {\\rm 7 keV} if exact solutions of Poisson's equation are used in the isothermal power law case. We argue that the constrained particle could be the long sought dark matter of the Universe that is interpreted here as a sterile neutrino.

  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. Quantum degenerate mixture of ytterbium and lithium atoms

    NASA Astrophysics Data System (ADS)

    Hansen, Anders H.; Khramov, Alexander; Dowd, William H.; Jamison, Alan O.; Ivanov, Vladyslav V.; Gupta, Subhadeep

    2011-07-01

    We have produced a quantum degenerate mixture of fermionic alkali-metal 6Li and bosonic spin-singlet 174Yb gases. This was achieved using sympathetic cooling of lithium atoms by evaporatively cooled ytterbium atoms in a far-off-resonant optical dipole trap. We observe the coexistence of Bose-condensed (T/Tc?0.8) 174Yb with 2.3×104 atoms and Fermi degenerate (T/TF?0.3) 6Li with 1.2×104 atoms. Quasipure Bose-Einstein condensates of up to 3×104 174Yb atoms can be produced in single-species experiments. Our results mark a significant step toward studies of few- and many-body physics with mixtures of alkali-metal and alkaline-earth-metal-like atoms, and for the production of paramagnetic polar molecules in the quantum regime. Our methods also establish a convenient scheme for producing quantum degenerate ytterbium atoms in a 1064 nm optical dipole trap.

  4. Production of quantum degenerate strontium gases: Larger, better, faster, colder

    E-print Network

    Stellmer, Simon; Schreck, Florian

    2012-01-01

    We report on an improved scheme to generate Bose-Einstein condensates (BECs) and degenerate Fermi gases of strontium. This scheme allows us to create quantum gases with higher atom number, a shorter time of the experimental cycle, or deeper quantum degeneracy than before. We create a BEC of 84-Sr exceeding 10^7 atoms, which is a 30-fold improvement over previously reported experiments. We increase the atom number of 86-Sr BECs to 2.5x10^4 (a fivefold improvement), and refine the generation of attractively interacting 88-Sr BECs. We present a scheme to generate 84-Sr BECs with a cycle time of 2s, which, to the best of our knowledge, is the shortest cycle time of BEC experiments ever reported. We create deeply-degenerate 87-Sr Fermi gases with T/T_F as low as 0.10(1), where the number of populated nuclear spin states can be set to any value between one and ten. Furthermore, we report on a total of five different double-degenerate Bose-Bose and Bose-Fermi mixtures. These studies prepare an excellent starting poi...

  5. 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.

  6. 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.

  7. Exact nonlinear excitations in double-degenerate plasmas

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2012-06-01

    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.

  8. 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

  9. The Local Type Ia Supernova Progenitors: One Double-Degenerate, No Symbiotics

    NASA Astrophysics Data System (ADS)

    Pagnotta, Ashley; Schaefer, B. E.

    2012-01-01

    Although the basic mechanism responsible for Type Ia supernovae appears to be well understood (thermonuclear explosion of a carbon-oxygen white dwarf that has reached the Chandrasekhar mass limit), the identity of the progenitor system(s) remains a mystery. With implications from stellar evolution to frontline cosmology, it is critical to attack this problem from every possible angle. We present results from our study of three known historical Ia supernovae in the Large Magellanic Cloud (LMC) which allow us to eliminate possible progenitor candidates for at least the local population. We used archival Hubble Space Telescope images of SNR 0509-67.5, SNR 0509-68.7, and SNR 0519-69.0 to determine the site of each explosion and then search the surrounding area for potential ex-companion stars that were left behind. The search was carried out within an error ellipse that accounts for measurement error on the geometric center of the remnant, the orbital velocity of the pre-supernova binary system, and kicks from the actual explosion. For SNR 0509-67.5, the error ellipse is empty to the HST 5? limiting magnitude of V=26.9. Using an LMC distance modulus of 18.5, this implies that any single degenerate ex-companion must be fainter than MV=+8.4 (corresponding approximately to a K9 main sequence star), which eliminates all currently-published single-degenerate models and leads us to conclude that this system had a double-degenerate (double white dwarf) progenitor. For SNR 0509-68.7 and SNR 0519-69.0, we can eliminate the possibility of red giant and subgiant ex-companions. It has been shown that the two confident galactic Ia supernovae (Tycho's SN 1572 and SN 1006) also do not have red giant ex-companion stars. Combined with our three systems, this eliminates the symbiotic progenitor channel for all of the nearby Ia supernovae. This work was supported by the National Science Foundation (AST-1109420).

  10. 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. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1776-1783, 2015. PMID:26135031

  11. Application of Degenerately Doped Metal Oxides in the Study of Photoinduced Interfacial Electron Transfer.

    PubMed

    Farnum, Byron H; Morseth, Zachary A; Brennaman, M Kyle; Papanikolas, John M; Meyer, Thomas J

    2015-06-18

    Degenerately doped In2O3:Sn semiconductor nanoparticles (nanoITO) have been used to study the photoinduced interfacial electron-transfer reactivity of surface-bound [Ru(II)(bpy)2(4,4'-(PO3H2)2-bpy)](2+) (RuP(2+)) molecules as a function of driving force over a range of 1.8 eV. The metallic properties of the ITO nanoparticles, present within an interconnected mesoporous film, allowed for the driving force to be tuned by controlling their Fermi level with an external bias while their optical transparency allowed for transient absorption spectroscopy to be used to monitor electron-transfer kinetics. Photoinduced electron transfer from excited-state -RuP(2+*) molecules to nanoITO was found to be dependent on applied bias and competitive with nonradiative energy transfer to nanoITO. Back electron transfer from nanoITO to oxidized -RuP(3+) was also dependent on the applied bias but without complication from inter- or intraparticle electron diffusion in the oxide nanoparticles. Analysis of the electron injection kinetics as a function of driving force using Marcus-Gerischer theory resulted in an experimental estimate of the reorganization energy for the excited-state -RuP(3+/2+*) redox couple of ?* = 0.83 eV and an electronic coupling matrix element, arising from electronic wave function overlap between the donor orbital in the molecule and the acceptor orbital(s) in the nanoITO electrode, of Hab = 20-45 cm(-1). Similar analysis of the back electron-transfer kinetics yielded ? = 0.56 eV for the ground-state -RuP(3+/2+) redox couple and Hab = 2-4 cm(-1). The use of these wide band gap, degenerately doped materials provides a unique experimental approach for investigating single-site electron transfer at the surface of oxide nanoparticles. PMID:25668488

  12. Structural Basis for Degenerate Recognition of Natural HIV Peptide Variants by Cytotoxic Lymphocytes

    SciTech Connect

    Martinez-Hackert,E.; Anikeeva, N.; Kalams, S.; Walker, B.; Hendrickson, W.; Sykulev, Y.

    2006-01-01

    It is well established that even small changes in amino acid side chains of antigenic peptide bound to MHC protein may completely abrogate recognition of the peptide-MHC (pMHC) complex by the T-cell receptor (TCR). Often, however, several non-conservative substitutions in the peptide antigen are accommodated and do not impair its recognition by TCR. For example, a preponderance of natural sequence variants of the HIV p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes (CTL), which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR. Here we study the molecular basis for this degenerate recognition of SL9 variants. We show that several SL9 variants bind comparably well to soluble HLA-A2 and to a particular soluble TCR and that these variants are active in the cognate cytotoxicity assay. Natural SL9 variation is restricted by its context in the HIV p17 matrix protein, and we have used synthetic variants to explore the wider spectrum of recognition. High-resolution crystal structures of seven selected SL9 variants bound to HLA-A2 all have remarkably similar peptide conformations and side-chain dispositions outside sites of substitution. This preservation of the peptide conformation despite epitope variations suggests a mechanism for the observed degeneracy in pMHC recognition by TCR, and may contribute to the persistence of SL9-mediated immune responses in chronically infected individuals.

  13. Inhibition of polyisoprenylated methylated protein methyl esterase by synthetic musks induces cell degeneration.

    PubMed

    Ayuk-Takem, Lambert; Amissah, Felix; Aguilar, Byron J; Lamango, Nazarius S

    2014-04-01

    Synthetic fragrances are persistent environmental pollutants that tend to bioaccumulate in animal tissues. They are widely used in personal care products and cleaning agents. Worldwide production of Galaxolide and Tonalide are in excess of 4500 tons annually. Because of their widespread production and use, they have been detected in surface waters and fish in the US and Europe. Consumption of contaminated water and fish from such sources leads to bioaccumulation and eventual toxicity. Since fragrances and flavors bear structural similarities to polyisoprenes, it was of interest to determine whether toxicity by Galaxolide and Tonalide may be linked with polyisoprenylated methylated protein methyl esterase (PMPMEase) inhibition. A concentration-dependent study of PMPMEase inhibition by Galaxolide and Tonalide as well as their effects on the degeneration of cultured cells were conducted. Galaxolide and Tonalide inhibited purified porcine liver PMPMEase with Ki values of 11 and 14 ?M, respectively. Galaxolide and Tonalide also induced human cancer cell degeneration with EC50 values of 26 and 98 ?M (neuroblastoma SH-SY5Y cells) and 58 and 14 ?M (lung cancer A549 cells), respectively. The effects on cell viability correlate well with the inhibition of PMPMEase activity in the cultured cells. Molecular docking analysis revealed that the binding interactions are most likely between the fragrance molecules and hydrophobic amino acids in the active site of the enzyme. These results appear to suggest that the reported neurotoxicity of these compounds may be associated with their inhibition of PMPMEase. Exposure to fragrances may pose a significant risk to individuals predisposed to developing degenerative disorders. PMID:22489002

  14. Attenuation of neuronal degeneration in thioredoxin-1 overexpressing mice after mild focal ischemia.

    PubMed

    Zhou, Feng; Gomi, Masanori; Fujimoto, Motoaki; Hayase, Makoto; Marumo, Takeshi; Masutani, Hiroshi; Yodoi, Junji; Hashimoto, Nobuo; Nozaki, Kazuhiko; Takagi, Yasushi

    2009-05-26

    Thioredoxin (Trx) is a 12-kDa protein ubiquitously expressed in all living cells that fulfills a variety of biological functions related to cell proliferation and apoptosis. It is characterized by the highly conserved reduction/oxidation (redox)-active site sequence Trp-Cys-Gly-Pro-Cys-Lys. Trx acts as a powerful antioxidant and plays an important role in maintaining critical protein thiols in the reduced state. Moreover, it has been shown to scavenge reactive oxygen species (ROS) and to protect against oxidative stress. We have reported that Trx-1 protects against neuronal damage during focal ischemia. However, the mechanisms underlying this protective effect and the effect of Trx-1 on neuronal apoptosis during ischemia have not been fully clarified. In this study, we analyzed the effect of Trx-1 overexpression against neuronal degeneration after a short duration of transient brain ischemia. Mild focal ischemia was reported to induce neuronal death through apoptosis. We employed Fluorojade-B staining to detect neuronal degeneration. In Trx transgenic mice, a smaller number of Fluorojade-B-positive neurons were detected after ischemia-reperfusion than in wild-type mice. In addition, we detected cleaved caspase-3- and TUNEL-positive cells, which indicated caspase-dependent apoptosis. Fewer caspase-3- and TUNEL-positive neurons were detected after ischemia-reperfusion in Trx transgenic mice than in wild-type mice. Furthermore, Akt signaling was reported to play a role in neuronal survival in Trx-1 overexpressing mice. After ischemia-reperfusion, Western blot and immunohistochemical analysis indicated that phosphorylation of Akt was enhanced in Trx transgenic mice after ischemia-reperfusion. Intraventricular injection of LY294002,which is a phosphoinositide 3-kinase (PI3K), vanished the neuroprotective effect in Trx-1 transgenic mice. These results indicate that Trx-1 overexpression protects neurons from apoptosis after ischemia-reperfusion. PMID:19328186

  15. ATF6 Is Mutated in Early Onset Photoreceptor Degeneration With Macular Involvement

    PubMed Central

    Xu, Mingchu; Gelowani, Violet; Eblimit, Aiden; Wang, Feng; Young, Marielle P.; Sawyer, Briana L.; Zhao, Li; Jenkins, Glen; Creel, Donnell J.; Wang, Keqing; Ge, Zhongqi; Wang, Hui; Li, Yumei; Hartnett, M. Elizabeth; Chen, Rui

    2015-01-01

    Purpose. Photoreceptor degeneration (PRD) is a genetically heterogeneous retinal disorder. Although a number of genes involved in PRD have been identified, their genetic basis remains unknown in a significant number of patients. In this study, we aimed to identify novel disease-causing genes of PRD. Methods. Comprehensive ocular examinations were performed in a 2-year-old patient diagnosed with early onset PRD. Retinal capture sequencing was performed to screen causative mutations in known retinal disease-causing loci. Whole-exome sequencing (WES) and a series of variant-filtering strategies were applied for identifying novel disease-causing genes. Retina ATF6 expression was confirmed by immunohistochemistry. RT-PCR was performed to identify ATF6 mRNA in the patient. Results. The patient showed typical PRD features, with macular involvement and ellipsoid zone irregularities. Results of retinal capture sequencing were negative. WES data led to identification of biallelic loss-of-function mutations in the ATF6 gene. The first variant generates a premature stop codon (NCBI accession no. NM_007348: c.1126C>T, p.R376*) and the second variant affects a splicing donor site (NM_007348: c.1533+1G>C). Sanger sequencing confirmed the 2 alleles are from 1 parent each. Both of the variants are extremely rare in the population. The splicing variant causes either intron inclusion or exon skipping in the patient, thus severely disrupting ATF6 functional domains. ATF6 is expressed in three neuronal cell layers of mouse retina. Conclusions. Our results support ATF6 as a novel disease-causing gene for PRD and suggest that disrupted protein quality control mechanisms may be a novel pathological mechanism underlying human retinal degeneration. PMID:26070061

  16. Lack of Acid Sphingomyelinase Induces Age-Related Retinal Degeneration

    PubMed Central

    Wu, Bill X.; Fan, Jie; Boyer, Nicholas P.; Jenkins, Russell W.; Koutalos, Yiannis; Hannun, Yusuf A.; Crosson, Craig E.

    2015-01-01

    Background Mutations of acid sphingomyelinase (ASMase) cause Niemann–Pick diseases type A and B, which are fatal inherited lipid lysosomal storage diseases, characterized with visceral organ abnormalities and neurodegeneration. However, the effects of suppressing retinal ASMase expression are not understood. The goal of this study was to determine if the disruption of ASMase expression impacts the retinal structure and function in the mouse, and begin to investigate the mechanisms underlying these abnormalities. Methods Acid sphingomyelinase knockout (ASMase KO) mice were utilized to study the roles of this sphingolipid metabolizing enzyme in the retina. Electroretinogram and morphometric analysis were used to assess the retinal function and structure at various ages. Sphingolipid profile was determined by liquid chromatography-mass spectrometry. Western blots evaluated the level of the autophagy marker LC3-II. Results When compared to control animals, ASMase KO mice exhibited significant age-dependent reduction in ERG a- and b-wave amplitudes. Associated with these functional deficits, morphometric analysis revealed progressive thinning of retinal layers; however, the most prominent degeneration was observed in the photoreceptor and outer nuclear layer. Additional analyses of ASMase KO mice revealed early reduction in ERG c-wave amplitudes and increased lipofuscin accumulation in the retinal pigment epithelium (RPE). Sphingolipid analyses showed abnormal accumulation of sphingomyelin and sphingosine in ASMase KO retinas. Western blot analyses showed a higher level of the autophagosome marker LC3-II. Conclusions These studies demonstrate that ASMase is necessary for the maintenance of normal retinal structure and function. The early outer retinal dysfunction, outer segment degeneration, accumulation of lipofuscin and autophagosome markers provide evidence that disruption of lysosomal function contributes to the age-dependent retinal degeneration exhibited by ASMase KO mice. PMID:26168297

  17. Mechanical overloading causes mitochondrial superoxide and SOD2 imbalance in chondrocytes resulting in cartilage degeneration

    PubMed Central

    Koike, Masato; Nojiri, Hidetoshi; Ozawa, Yusuke; Watanabe, Kenji; Muramatsu, Yuta; Kaneko, Haruka; Morikawa, Daichi; Kobayashi, Keiji; Saita, Yoshitomo; Sasho, Takahisa; Shirasawa, Takuji; Yokote, Koutaro; Kaneko, Kazuo; Shimizu, Takahiko

    2015-01-01

    Mechanical stress and aging are major risk factors of cartilage degeneration. Human studies have previously reported that oxidative damage increased, while SOD2 protein was reciprocally downregulated in osteoarthritic degenerated cartilage. However, it remains unclear whether mitochondrial superoxide imbalance in chondrocytes causes cartilage degeneration. We herein demonstrate that mechanical loading promoted mitochondrial superoxide generation and selective Sod2 downregulation in chondrocytes in vivo and that mitochondrial superoxide inducer also downregulated Sod2 expression in chondrocytes in vitro. A genetically manipulated model revealed that Sod2 deficiency in chondrocytes also resulted in mitochondrial superoxide overproduction and dysfunction, thus leading to cartilage degeneration. Intra-articular injection of a permeable antioxidant effectively suppressed the mechanical loading-induced mitochondrial superoxide generation and cartilage degeneration in mice. Our findings demonstrate that mitochondrial superoxide plays a pivotal role in the development and progression of osteoarthritis, and the mitochondrial superoxide balance may therefore be a promising target for the treatment of cartilage degeneration. PMID:26108578

  18. Future Therapies of Wet Age-Related Macular Degeneration

    PubMed Central

    Jin, Daisuke; Sawada, Yu; Abe, Sanae; Yoshitomi, Takeshi

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies. PMID:25802751

  19. Photon upconversion in degenerately sulfur doped InP nanowires.

    PubMed

    Mergenthaler, K; Lehmann, S; Wallentin, J; Zhang, W; Borgström, M T; Yartsev, A; Pistol, M-E

    2015-12-01

    Radiative recombination in degenerately n-doped InP nanowires is studied for excitation above and below the Fermi energy of the electron gas, using photoluminescence. Laser-induced electron heating is observed, which allows absorption below the Fermi energy. We observe photon upconversion where photo-excited holes recombine with high |k| electrons. This can be attributed to hole scattering to high |k|-values, and the temperature dependence of this process is measured. We show that hole relaxation via phonon scattering can be observed in continuous wave excitation luminescence measurements. PMID:26585229

  20. Stationary entanglement in N-atom subradiant degenerate cascade systems

    SciTech Connect

    Borrelli, Massimo; Piovella, Nicola; Paris, Matteo G. A.

    2011-01-15

    We address ultracold N-atom degenerate cascade systems and show that stationary subradiant states, already observed in the semiclassical regime, also exist in a fully quantum regime and for a small number of atoms. We explicitly evaluate the amount of stationary entanglement for the two-atom configuration and show full inseparability for the three-atom case. We also show that a continuous variable description of the systems is not suitable to detect entanglement due to the non-Gaussianity of subradiant states.

  1. [Diagnostic Criteria for Atrophic Age-related Macular Degeneration].

    PubMed

    Takahashi, Kanji; Shiraga, Fumio; Ishida, Susumu; Kamei, Motohiro; Yanagi, Yasuo; Yoshimura, Nagahisa

    2015-10-01

    Diagnostic criteria for dry age-related macular degeneration is described. Criteria include visual acuity, fundscopic findings, diagnostic image findings, exclusion criteria and classification of severity grades. Essential findings to make diagnosis as "geographic atrophy" are, 1) at least 250 ?m in diameter, 2) round/oval/cluster-like or geographic in shape, 3) sharp delineation, 4) hypopigmentation or depigmentation in retinal pigment epithelium, 5) choroidal vessels are more visible than in surrounding area. Severity grades were classified as mild, medium and severe by relation of geographic atrophy to the fovea and attendant findings. PMID:26571627

  2. Effects of Vitreomacular Adhesion on Age-Related Macular Degeneration

    PubMed Central

    Kang, Eui Chun; Koh, Hyoung Jun

    2015-01-01

    Herein, we review the association between vitreomacular adhesion (VMA) and neovascular age-related macular degeneration (AMD). Meta-analyses have shown that eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in neovascular AMD may induce inflammation, macular traction, decrease in oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other cytokines or may directly stimulate VEGF production. VMA may also interfere with the treatment effects of anti-VEGF therapy, which is the standard treatment for neovascular AMD, and releasing VMA can improve the treatment response to anti-VEGF treatment in neovascular AMD. We also reviewed currently available methods of relieving VMA. PMID:26425354

  3. Coherence switching of a degenerate VECSEL for multimodality imaging

    E-print Network

    Knitter, Sebastian; Redding, Brandon; Khokha, Mustafa K; Choma, Michael A; Cao, Hui

    2015-01-01

    We demonstrate a VECSEL (vertical external cavity surface emitting laser) based degenerate source with an adjustable degree of spatial coherence that is electrically pumped, mechanically compact and supports continuous-wave emission. The laser operation can be switched between a large number of mutually incoherent spatial modes and few-mode operation at little power loss. This technology allows multimodality imaging, where low spatial coherence illumination is used for traditional high-speed video-microscopy and high spatial coherence illumination is used to extract dynamic information of flow processes. The initial demonstration is performed on imaging embryo heart function in Xenopus, which is an important animal model for human heart disease.

  4. PCR Amplicon Prediction from Multiplex Degenerate Primer and Probe Sets

    SciTech Connect

    2013-08-08

    Assessing primer specificity and predicting both desired and off-target amplification products is an essential step for robust PCR assay design. Code is described to predict potential polymerase chain reaction (PCR) amplicons in a large sequence database such as NCBI nt from either singleplex or a large multiplexed set of primers, allowing degenerate primer and probe bases, with target mismatch annotates amplicons with gene information automatically downloaded from NCBI, and optionally it can predict whether there are also TaqMan/Luminex probe matches within predicted amplicons.

  5. PCR Amplicon Prediction from Multiplex Degenerate Primer and Probe Sets

    Energy Science and Technology Software Center (ESTSC)

    2013-08-08

    Assessing primer specificity and predicting both desired and off-target amplification products is an essential step for robust PCR assay design. Code is described to predict potential polymerase chain reaction (PCR) amplicons in a large sequence database such as NCBI nt from either singleplex or a large multiplexed set of primers, allowing degenerate primer and probe bases, with target mismatch annotates amplicons with gene information automatically downloaded from NCBI, and optionally it can predict whether theremore »are also TaqMan/Luminex probe matches within predicted amplicons.« less

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

    E-print Network

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

    2010-01-01

    We study density profiles of an ideal Fermi gas and observe Pauli suppression of density fluctuations for cold clouds deep in the quantum degenerate regime. Strong suppression of shot noise was observed for probe volumes containing more than 10,000 atoms. Atom noise provides sensitive thermometry at low temperatures. The Poissonian noise of a hot cloud provides a direct and accurate calibration of the optical resolution and absorption cross section. 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.

  7. Evidence for the degenerate dwarf nature of Cygnus X-2

    NASA Technical Reports Server (NTRS)

    Branduardi, G.; Kylafis, N. D.; Lamb, D. Q.; Mason, K. O.

    1980-01-01

    Observations of Cygnus X-2 using the Copernicus satellite have revealed a novel relationship between the spectral hardness and the intensity of this source in the 3-8 keV band. This behavior is very similar to that predicted for a spherically accreting nonmagnetic degenerate dwarf. The data, interpreted in terms of this model, determine solar mass, luminosity, and the distance for Cyg X-2; these parameters are at variance with the values derived from optical observations of the system. The implications of this discrepancy for the understanding of the source are examined.

  8. [Physical activity benefits patients with age-related macular degeneration.

    PubMed

    Subhi, Yousif; Munch, Inger Christine; Singh, Amardeep; Sørensen, Torben Lykke

    2014-09-01

    We have reviewed studies investigating the effect of physical activity on prevention of early age-related macular degeneration (AMD), progression to late AMD, and risk modulation of morbidity and mortality in patients with AMD. Regular physical activity may lower risk of developing early AMD and progression of early AMD to late AMD at a level comparable with smoking cessation or dietary supplements. Studies suggest that AMD itself is associated with physical inactivity which can result in higher morbidity levels. Patients with AMD may benefit from physical activity counselling at all stages of the disease. PMID:25294030

  9. [Physical activity benefits patients with age-related macular degeneration].

    PubMed

    Subhi, Yousif; Munch, Inger Christine; Singh, Amardeep; Sørensen, Torben Lykke

    2015-08-17

    We have reviewed studies investigating the effect of physical activity on prevention of early age-related macular degeneration (AMD), progression to late AMD, and risk modulation of morbidity and mortality in patients with AMD. Regular physical activity may lower risk of developing early AMD and progression of early AMD to late AMD at a level comparable with smoking cessation or dietary supplements. Studies suggest that AMD itself is associated with physical inactivity which can result in higher morbidity levels. Patients with AMD may benefit from physical activity counselling at all stages of the disease. PMID:26561660

  10. Hydrodynamics in a Degenerate, Strongly Attractive Fermi Gas

    NASA Technical Reports Server (NTRS)

    Thomas, John E.; Kinast, Joseph; Hemmer, Staci; Turlapov, Andrey; O'Hara, Ken; Gehm, Mike; Granade, Stephen

    2004-01-01

    In summary, we use all-optical methods with evaporative cooling near a Feshbach resonance to produce a strongly interacting degenerate Fermi gas. We observe hydrodynamic behavior in the expansion dynamics. At low temperatures, collisions may not explain the expansion dynamics. We observe hydrodynamics in the trapped gas. Our observations include collisionally-damped excitation spectra at high temperature which were not discussed above. In addition, we observe weakly damped breathing modes at low temperature. The observed temperature dependence of the damping time and hydrodynamic frequency are not consistent with collisional dynamics nor with collisionless mean field interactions. These observations constitute the first evidence for superfluid hydrodynamics in a Fermi gas.

  11. Electron thermal conductivity owing to collisions between degenerate electrons

    E-print Network

    P. S. Shternin; D. G. Yakovlev

    2006-08-17

    We calculate the thermal conductivity of electrons produced by electron-electron Coulomb scattering in a strongly degenerate electron gas taking into account the Landau damping of transverse plasmons. The Landau damping strongly reduces this conductivity in the domain of ultrarelativistic electrons at temperatures below the electron plasma temperature. In the inner crust of a neutron star at temperatures T electron conductivity due to electron-ion (electron-phonon) scattering and becomes competitive with the the electron conductivity due to scattering of electrons by impurity ions.

  12. Lhermitte's sign in subacute combined degeneration of the cord

    PubMed Central

    Gautier-Smith, P. C.

    1973-01-01

    Lhermitte's sign is a common early symptom of subacute combined degeneration of the cord occurring in 11 out of 44 patients admitted to the National Hospitals for Nervous Diseases during the decade 1962-71 with this diagnosis. Two patients, in both of whom it was the presenting complaint, are described in detail. It is concluded that, in these cases, Lhermitte's sign is due to stretching of demyelinated fibres in the posterior columns in the cervical cord, produced by neck flexion. The symptoms disappear after treatment with vitamin B12. The clinical importance of this symptom is emphasized. PMID:4753883

  13. Degenerate Bose-Fermi mixtures of rubidium and ytterbium

    NASA Astrophysics Data System (ADS)

    Vaidya, V. D.; Tiamsuphat, J.; Rolston, S. L.; Porto, J. V.

    2015-10-01

    We report the realization of a quantum degenerate mixture of bosonic 87Rb and fermionic 171Yb atoms in a hybrid optical dipole trap with a tunable, species-dependent trapping potential. 87Rb is shown to be a viable refrigerant for the noninteracting 171Yb atoms, cooling up to 2.4 ×105 Yb atoms to a temperature of T /TF=0.16 (2 ) while simultaneously forming a 87Rb Bose-Einstein condensate of 3.5 ×105 atoms. Furthermore we demonstrate our ability to independently tailor the potentials for each species, which paves the way for studying impurities immersed in a Bose gas.

  14. Degenerate quantum codes and the quantum Hamming bound

    SciTech Connect

    Sarvepalli, Pradeep; Klappenecker, Andreas

    2010-03-15

    The parameters of a nondegenerate quantum code must obey the Hamming bound. An important open problem in quantum coding theory is whether the parameters of a degenerate quantum code can violate this bound for nondegenerate quantum codes. In this article we show that Calderbank-Shor-Steane (CSS) codes, over a prime power alphabet q{>=}5, cannot beat the quantum Hamming bound. We prove a quantum version of the Griesmer bound for the CSS codes, which allows us to strengthen the Rains' bound that an [[n,k,d

  15. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  16. Degenerate nonlinear programming with a quadratic growth condition.

    SciTech Connect

    Anitescu, M.; Mathematics and Computer Science

    2000-01-01

    We show that the quadratic growth condition and the Mangasarian-Fromovitz constraint qualification (MFCQ) imply that local minima of nonlinear programs are isolated stationary points. As a result, when started sufficiently close to such points, an L1 exact penalty sequential quadratic programming algorithm will induce at least R-linear convergence of the iterates to such a local minimum. We construct an example of a degenerate nonlinear program with a unique local minimum satisfying the quadratic growth and the MFCQ but for which no positive semidefinite augmented Lagrangian exists. We present numerical results obtained using several nonlinear programming packages on this example and discuss its implications for some algorithms.

  17. Expansion of a quantum degenerate boson-fermion mixture

    SciTech Connect

    Hu, Hui; Liu, Xia-Ji; Modugno, Michele

    2003-06-01

    We study the expansion of an ultracold boson-fermion mixture released from an elongated magnetic trap, by using a scaling approach. We discuss in detail the role of the boson-fermion interaction on the evolution of the radial-to-axial aspect ratio of the condensate, and show that the latter depends crucially on the relative dynamics of the condensate and degenerate Fermi gas in the radial direction, which is characterized by the ratio between the trapping frequencies for fermions and bosons. The numerical solution of the scaling equations provides a reasonable agreement with the recent experiment [G. Roati et al., Phys. Rev. Lett. 89, 150403 (2002)].

  18. Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells

    PubMed Central

    Richardson, Stephen M.; Purmessur, Devina; Baird, Pauline; Probyn, Ben; Freemont, Anthony J.; Hoyland, Judith A.

    2012-01-01

    Innervation of nociceptive nerve fibres into the normally aneural nucleus pulposus (NP) of the intervertebral disc (IVD) occurs during degeneration resulting in discogenic back pain. The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which are associated with stimulation of axonal outgrowth and nociception by neuronal cells, are both expressed by NP cells, with BDNF levels increasing with disease severity. However the mechanism of interaction between human NP cells and neural cells has yet to be fully elucidated. Therefore the aim of this study was to determine whether non-degenerate or degenerate human NP cells inhibit or stimulate neural outgrowth and whether any outgrowth is mediated by NGF or BDNF. Human NP cells from non-degenerate and degenerate IVD were cultured in alginate beads then co-cultured for 48 hours with human SH-SY5Y neuroblastoma cells. Co-culture of non-degenerate NP cells with neural cells resulted in both an inhibition of neurite outgrowth and reduction in percentage of neurite expressing cells. Conversely co-culture with degenerate NP cells resulted in an increase in both neurite length and percentage of neurite expressing cells. Addition of anti-NGF to the co-culture with degenerate cells resulted in a decrease in percentage of neurite expressing cells, while addition of anti-BDNF resulted in a decrease in both neurite length and percentage of neurite expressing cells. Our findings show that while non-degenerate NP cells are capable of inhibiting neurite outgrowth from human neural cells, degenerate NP cells stimulate outgrowth. Neurotrophin blocking studies demonstrated that both NGF and BDNF, secreted by degenerate NP cells, may play a role in this stimulation with BDNF potentially playing the predominant role. These findings suggest that NP cells are capable of regulating nerve ingrowth and that neoinnervation occurring during IVD degeneration may be stimulated by the NP cells themselves. PMID:23091643

  19. 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.

  20. The condition of regular degeneration for singularly perturbed systems of linear differential-difference equations.

    NASA Technical Reports Server (NTRS)

    Cooke, K. L.; Meyer, K. R.

    1966-01-01

    Extension of problem of singular perturbation for linear scalar constant coefficient differential- difference equation with single retardation to several retardations, noting degenerate equation solution

  1. Growth Factors and Anticatabolic Substances for Prevention and Management of Intervertebral Disc Degeneration

    PubMed Central

    Longo, Umile Giuseppe; Petrillo, Stefano; Franceschetti, Edoardo; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Intervertebral disc (IVD) degeneration is frequent, appearing from the second decade of life and progressing with age. Conservative management often fails, and patients with IVD degeneration may need surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. Biological strategies aim to prevent and manage IVD degeneration, improving the function and anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells and inhibiting matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of growth factors and anticatabolic substances for prevention and management of intervertebral disc degeneration. PMID:25098367

  2. Three dimensional electrostatic solitary waves in a dense magnetoplasma with relativistically degenerate electrons

    NASA Astrophysics Data System (ADS)

    Ata-ur-Rahman; Masood, W.; Eliasson, B.; Qamar, A.

    2013-09-01

    In this paper, small but finite amplitude electrostatic solitary waves in a relativistic degenerate magnetoplasma, consisting of relativistically degenerate electrons and non-degenerate cold ions, are investigated. The Zakharov-Kuznetsov equation is derived employing the reductive perturbation technique and its solitary wave solution is analyzed. It is shown that only compressive electrostatic solitary structures can propagate in such a degenerate plasma system. The effects of plasma number density, ion cyclotron frequency, and direction cosines on the profiles of ion acoustic solitary waves are investigated and discussed at length. The relevance of the present investigation vis-a-vis pulsating white dwarfs is also pointed out.

  3. 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??g/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 mild IVD degeneration. The conjugated BMP-2 and BMP-2/7 appeared safe, but no disc regeneration was observed. Possible explanations include too low dosages, short follow-up time, and/or insufficient release of the conjugated BMPs. These aspects should be addressed in future studies. PMID:26543683

  4. Selective degeneration of oligodendrocytes mediated by reactive oxygen species.

    PubMed

    Griot, C; Vandevelde, M; Richard, A; Peterhans, E; Stocker, R

    1990-01-01

    The mechanism underlying demyelination in inflammatory canine distemper encephalitis is uncertain. Macrophages and their secretory products are thought to play an important effector role in this lesion. Recently, we have shown that anti-canine distemper virus antibodies, known to occur in chronic inflammatory lesions, stimulate macrophages leading to the secretion of reactive oxygen species (ROS). To investigate whether ROS could be involved in demyelination, dog glial cell cultures were exposed to xanthine/xanthine oxidase (X/XO), a system capable of generating O2-. This treatment resulted in a specific time-dependent degeneration and loss of oligodendrocytes, the myelin producing cells of the central nervous system. Initial degeneration was not associated with a decrease in viability of oligodendrocytes as judged by trypan blue and propidium iodide exclusion. Astrocytes and brain macrophages were not affected morphologically by this treatment. Further, an evaluation of the effect of several ROS scavengers, transition metal chelators and inhibitors of poly (ADP-ribose) polymerase suggests that a metal dependent formation of .OH or a similar highly oxidizing species could be responsible for the observed selective damage to oligodendrocytes. PMID:1965721

  5. Diffusion Tensor Imaging in a Child with Hypertrophic Olivary Degeneration

    PubMed Central

    Meoded, Avner; Poretti, Andrea; Ilica, A. Turan; Perez, Randall; Jallo, George; Burger, Peter C.; Huisman, Thierry A. G. M.

    2015-01-01

    Hypertrophic olivary degeneration (HOD) is caused by disruptive lesions affecting components of the Guillain–Mollaret triangle (GMT). We present conventional magnetic resonance and diffusion tensor imaging (DTI) findings in a 6-year-old girl with HOD after surgery for a midbrain pilocytic astrocytoma. To our knowledge, this is the first dedicated DTI analysis of GMT in a child with HOD in the literature. In our patient, we found higher fractional anisotropy (FA) and axial diffusivity values of the inferior olivary nucleus (ION) and lower FA, but higher radial diffusivity (RD) values of all other GMT components compared to age-matched controls. Increased FA values of the ION may be explained by increased packing of white matter fibers. However, associated hyperintense T2 signal is contradictory and the association between increased FA values and hyperintense T2 signal remains unclear. Low FA and high RD values of the other GMT components likely reflect demyelination with axonal degeneration and correlate well with histopathological findings. PMID:23307661

  6. Present and future treatment possibilities in macular degeneration

    NASA Astrophysics Data System (ADS)

    Fisher, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

    2005-11-01

    Purpose: To discuss present and future treatment possibilities in different types of choroidal neovascularisation. Methods: Presented are angiographic- and OCT-findings in patients with macular degeneration of different origin. Choroidal neovascularisations, which are not likely to respond positively to established procedures like thermal laser coagulation or photodynamic therapy will be discussed. Results and conclusions: Present study-guidelines and new methods of pharmacological intervention are analysed in different patterns of macular degeneration. Conventional laser coagulation in the treatment of classic, extrafoveal CNV and photodynamic therapy of predominantly classic subfoveal CNV still represent a gold standard. There are new recommendations, loosening the tight criteria of the TAP and VIP-guidelines, which cover, for instance, wider visual acuity ranges and the treatment of juxtafoveally located choroidal neovascularisations. Positive findings in literature confirm the role of PDT in pathologic myopia and other non-AMD CNV. Studies about surgical procedures, like macula- or RPE-translocation after surgical removal or thermal laser destruction of the CNV are in progress and are expected to show promising results. Phase II/III studies will soon point out the effect of anti-VEGF agents. The application of intravitreal (triamcinolone) or peribulbar (anecortave acetat) steroids could be useful. The combination with surgical or laser techniques could bring further benefit to the patient.

  7. Dwarf spheroidal galaxies as degenerate gas of free fermions

    NASA Astrophysics Data System (ADS)

    Domcke, Valerie; Urbano, Alfredo

    2015-01-01

    In this paper we analyze a simple scenario in which Dark Matter (DM) consists of free fermions with mass mf. We assume that on galactic scales these fermions are capable of forming a degenerate Fermi gas, in which stability against gravitational collapse is ensured by the Pauli exclusion principle. The mass density of the resulting con figuration is governed by a non-relativistic Lane-Emden equation, thus leading to a universal cored profile that depends only on one free parameter in addition to mf. After reviewing the basic formalism, we test this scenario against experimental data describing the velocity dispersion of the eight classical dwarf spheroidal galaxies of the Milky Way. We find that, despite its extreme simplicity, the model exhibits a good fit to the data and realistic predictions for the size of DM halos providing that mfsimeq 200 eV. Furthermore, we show that in this setup larger galaxies correspond to the non-degenerate limit of the gas. We propose a concrete realization of this model in which DM is produced non-thermally via inflaton decay. We show that imposing the correct relic abundance and the bound on the free-streaming length constrains the inflation model in terms of inflaton mass, its branching ratio into DM and the reheating temperature.

  8. [Indications for photodynamic therapy in age-related macular degeneration].

    PubMed

    Soubrane, G; Kuhn, D; Coscas, G

    2004-01-01

    Exudative age-related macular degeneration (ARMD) is now benefitting from new therapeutic approaches. Three international randomized clinical trials have demonstrated the efficacy of photodynamic therapy (PDT) in stabilizing visual acuity at 2 years. PDT is based on the activation of a photosensitizer with an adapted wavelength. In age-related macular degeneration, the photosensitizer used is verteporfin (Visudyne), which accumulates preferentially in choroidal new vessels. Functional results are obtained on the basis of a strict classification based on fluorescein angiography examining the type of the new vessels responsible for exudative ARMD. Thus, subfoveal lesions, either predominantly classic (>50%) or occult only, are the indication for PDT. Classic CNVs where laser photocoagulation thermal burns extend into the foveola may be an extrapolation of the indication for PDT. In addition, fluorescein angiography is essential for considering retreatment, usually necessary. Demonstrated growth and the persistence of leakage from the CNV is an absolute indication for a new session of PDT. A number of features still require assessment in order to define the responder group more accurately and to refine and possibly simplify the indications for retreatment. PMID:14968084

  9. Transverse phase shielding solitons in the degenerated optical parametric oscillator

    NASA Astrophysics Data System (ADS)

    Clerc, Marcel G.; Coulibaly, Saliya; Garcia-Ñustes, Mónica A.; Zárate, Yair

    2015-11-01

    Localized structures in optics have attracted attention for their potential applications in telecommunications and information storage. In the present work, localized structures with non-uniform phase structure in the degenerate optical parametrical oscillator are reported and elucidated. Dissipative solitons with non-uniform phase structures in parametrically driven systems have been already observed in prototype models being found in two typical shapes: symmetrical and asymmetrical. In contrast, the phase structure in degenerate optical parametrical oscillator is always symmetrical, showing a pronounced bell-shaped phase. We show that the nonlinear saturation present in this physical system is responsible of a relaxation dynamics and this symmetry. Probing that real physical systems exhibit always this unique type of localized structure with phase structure. An adequate analytical description for the phase, based on a simple model, is achieved showing that such structure is controlled by the interplay between the detuning, the external pump and the losses of the cavity. Numerical simulations present quite agreement with theoretical predictions.

  10. Type I seesaw mechanism for quasi-degenerate neutrinos

    NASA Astrophysics Data System (ADS)

    Joshipura, Anjan S.; Patel, Ketan M.; Vempati, Sudhir K.

    2010-06-01

    We discuss symmetries and scenarios leading to quasi-degenerate neutrinos in type I seesaw models. The existence of degeneracy in the present approach is not linked to any specific structure for the Dirac neutrino Yukawa coupling matrix yD and holds in general. Basic input is the application of the minimal flavour violation principle to the leptonic sector. Generalizing this principle, we assume that the structure of the right-handed neutrino mass matrix is determined by yD and the charged lepton Yukawa coupling matrix yl in an effective theory invariant under specific groups GF contained in the full symmetry group of the kinetic energy terms. GF invariance also leads to specific structure for the departure from degeneracy. The neutrino mass matrix (with degenerate mass m0) resulting after seesaw mechanism has a simple form M??m0(I-pylylT) in one particular scenario based on supersymmetry. This form is shown to lead to correct description of neutrino masses and mixing angles. The thermal leptogenesis after inclusion of flavour effects can account for the observed baryon asymmetry of the universe within the present scenario. Rates for lepton flavour violating processes can occur at observable levels in the supersymmetric version of the scenario.

  11. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides:

    NASA Astrophysics Data System (ADS)

    Chen, Junping; Patil, Swanand; Seal, Sudipta; McGinnis, James F.

    2006-11-01

    Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. These data indicate that the nanoceria particles may be effective in inhibiting the progression of ROI-induced cell death, which is thought to be involved in macular degeneration, retinitis pigmentosa and other blinding diseases, as well as the ROI-induced death of other cell types in diabetes, Alzheimer's disease, atherosclerosis, stroke and so on. The use of nanoceria particles as a direct therapy for multiple diseases represents a novel strategy and suggests that they may represent a unique platform technology.

  12. The Core-Degenerate Scenario for Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Soker, Noam

    2013-01-01

    In the core-degenerate (CD) scenario for the formation of Type Ia supernovae (SNe Ia) the Chandrasekhar or super-Chandrasekhar mass white dwarf (WD) is formed at the termination of the common envelope phase or during the planetary nebula phase, from a merger of a WD companion with the hot core of a massive asymptotic giant branch (AGB) star. The WD is destroyed and accreted onto the more massive core. In the CD scenario the rapidly rotating WD is formed shortly after the stellar formation episode, and the delay from stellar formation to explosion is basically determined by the spin-down time of the rapidly rotating merger remnant. The spin-down is due to the magneto-dipole radiation torque. Several properties of the CD scenario make it attractive compared with the double-degenerate (DD) scenario. (1) Off-center ignition of carbon during the merger process is not likely to occur. (2) No large envelope is formed. Hence avoiding too much mass loss that might bring the merger remnant below the critical mass. (3) This model explains the finding that more luminous SNe Ia occur preferentially in star forming galaxies.

  13. The core-degenerate scenario for type Ia supernovae

    E-print Network

    Soker, Noam

    2011-01-01

    In the core-degenerate (CD) scenario for the formation of Type Ia supernovae (SNe) the Chandrasekhar or super-Chandrasekhar mass white dwarf (WD) is formed at the termination of the common envelope phase or during the planetary nebula phase, from a merger of a WD companion with the hot core of a massive asymptotic giant branch (AGB) star. The WD is destructed and accreted onto the more massive core. In the CD scenario the rapidly rotating WD is formed shortly after the stellar formation episode, and the delay from stellar formation to explosion is basically determined by the spin-down time of the rapidly rotating merger remnant. The spin-down is due to the magneto-dipole radiation torque. Several properties of the CD scenario make it attractive compared with the double-degenerate (DD) scenario. (1) Off-center ignition of carbon during the merger process is not likely to occur. (2) No large envelope is formed. Hence avoiding too much mass loss that might bring the merger remnant below the critical mass. (3) Th...

  14. Mouse Models of Stargardt 3 Dominant Macular Degeneration.

    PubMed

    Barabas, Peter; Gorusupudi, Aruna; Bernstein, Paul S; Krizaj, David

    2016-01-01

    Stargardt type 3 macular degeneration is dependent on a dominant defect in a single gene, ELOVL4 (elongase of very long chain fatty acids 4). The encoded enzyme, ELOVL4, is required for the synthesis of very long chain polyunsaturated fatty acids (VLC-PUFAs), a rare class of > C24 lipids. In vitro expression studies suggest that mutated ELOVL4(STGD3) proteins fold improperly, resulting in ER stress and formation of cytosolic aggresomes of wild type and mutant ELOVL4. Although a number of mouse models have been developed to determine whether photoreceptor cell loss in STGD3 results from depletion of VLC-PUFAs, aggresome-dependent cell stress or a combination of these two factors, none of these models adequately recapitulates the disease phenotype in humans. Thus, the precise molecular mechanism by which ELOVL4 mutation causes photoreceptor degeneration in mice and in human patients remains to be characterized. This mini review compares and evaluates current STGD3 mouse models and determines what conclusions can be drawn from past work. PMID:26427404

  15. Prevalence and pattern of spinocerebellar degenerations in northeastern Libya.

    PubMed

    Sridharan, R; Radhakrishnan, K; Ashok, P P; Mousa, M E

    1985-12-01

    An intensive search over a two-year period for cases of cerebellar and spinocerebellar degenerations in Benghazi, Libya, made through polyclinics, university hospitals and a centre for the handicapped, revealed a total of 52 patients, among whom 30 were index cases; the remainder were detected on family study. Twenty-five patients lived in Benghazi, giving a crude prevalence of 4.8/100 000 population. There were 24 patients (10 families) with hereditary spastic paraplegia (HSP), 13 (9 families) with early onset cerebellar ataxia with retained tendon reflexes (EOCA), 3 with Friedreich's ataxia (FA), 5 (1 family) with late onset cerebellar ataxia (LOCA) with pigmentary retinal degeneration and autosomal dominant inheritance, 6 single cases of LOCA and 1 with ataxia telangiectasia. There were 14 families with definite autosomal recessive inheritance and only 2 with dominant transmission. The large family size (average of 6.2 children per married woman in the patient group) and the high rate of consanguineous marriages contribute to the high incidence of familial cases, especially those with autosomal recessive inheritance. Nerve conduction studies were normal in HSP and abnormal in EOCA and FA. Computed tomographic scans revealed atrophy of the brainstem and cerebellum in 3 cases of EOCA and 2 with LOCA. No indigenous forms of the disease were observed and the clinical features differed little from the descriptions in literature. However, the relative rarity of patients with FA, in comparison with other types of hereditary ataxias, is striking. PMID:4075075

  16. [Brain stem auditory evoked potentials in spinocerebellar degeneration].

    PubMed

    Illarioshkin, S N; Fedin, P A; Ivanova-smolenskaia, I A; Solov'ev, O I

    1992-01-01

    A study was made of brainstem auditory evoked potentials (BAEP) in 66 patients from 56 families with different forms of spinocerebellar degenerations (SCD). 27 patients with olivopontocerebellar degeneration (OPCD), 13 patients suffering from Friedreich's disease (FD), 10 patients with Pierre Marie's familial ataxia (PMFA), 6 patients with late onset cerebellar atrophy (LOCA), and 10 patients with other forms of SCD were examined. The changes in BAEP turned out extremely diverse which can be regarded as a manifestation of marked phenotypic pleomorphism common to SCD. The most considerable changes in BAEP were discovered in FD and OPCD, whereas the least marked ones in PMFA and LOCA. The character and degree of BAEP disorders reflect the spreading and gravity of degenerative alterations in the brain stem in different forms of SCD. The authors discuss the possibility of the use of BAEP for objective estimation of the gravity and spreading of the pathological process as well as of the electrophysiological control over its course in SCD patients. PMID:1333700

  17. Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice.

    PubMed

    Huang, Shanshan; Yang, Su; Guo, Jifeng; Yan, Sen; Gaertig, Marta A; Li, Shihua; Li, Xiao-Jiang

    2015-10-01

    In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA-box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP's interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases. PMID:26387956

  18. Testing the single degenerate channel for supernova Ia

    NASA Astrophysics Data System (ADS)

    Parsons, Steven

    2014-10-01

    The progenitors of supernova Ia are close binaries containing white dwarfs. Of crucial importance to the evolution of these systems is how much material the white dwarf can stably accrete and hence grow in mass. This occurs during a short-lived intense phase of mass transfer known as the super soft source (SSS) phase. The short duration of this phase and large extinction to soft X-rays means that only a handful are known in our Galaxy. Far more can be learned from the underlying SSS progenitor population of close white dwarf plus FGK type binaries. Unfortunately, these systems are hard to find since the main-sequence stars completely outshine the white dwarfs at optical wavelengths. Because of this, there are currently no known close white dwarf binaries with F, G or early K type companions, making it impossible to determine the contribution of the single degenerate channel towards supernova Ia. Using the GALEX and RAVE surveys we have now identified the first large sample of FGK stars with UV excesses, a fraction of which are these illusive, close systems. Following an intense ground based spectroscopic investigation of these systems, we have identified 5 definite close binaries, with periods of less than a few days. Here we apply for COS spectroscopic observations to measure the mass and temperature of the white dwarfs in order to determine the future evolution of these systems. This will provide a crucial test for the single degenerate channel towards supernova Ia.

  19. Dwarf spheroidal galaxies as degenerate gas of free fermions

    SciTech Connect

    Domcke, Valerie; Urbano, Alfredo E-mail: alfredo.urbano@sissa.it

    2015-01-01

    In this paper we analyze a simple scenario in which Dark Matter (DM) consists of free fermions with mass m{sub f}. We assume that on galactic scales these fermions are capable of forming a degenerate Fermi gas, in which stability against gravitational collapse is ensured by the Pauli exclusion principle. The mass density of the resulting con figuration is governed by a non-relativistic Lane-Emden equation, thus leading to a universal cored profile that depends only on one free parameter in addition to m{sub f}. After reviewing the basic formalism, we test this scenario against experimental data describing the velocity dispersion of the eight classical dwarf spheroidal galaxies of the Milky Way. We find that, despite its extreme simplicity, the model exhibits a good fit to the data and realistic predictions for the size of DM halos providing that m{sub f}? 200 eV. Furthermore, we show that in this setup larger galaxies correspond to the non-degenerate limit of the gas. We propose a concrete realization of this model in which DM is produced non-thermally via inflaton decay. We show that imposing the correct relic abundance and the bound on the free-streaming length constrains the inflation model in terms of inflaton mass, its branching ratio into DM and the reheating temperature.

  20. Quantitative Ultrasound Assessment of Cartilage Degeneration in Ovariectomized Rats with Low Estrogen Levels.

    PubMed

    Wang, Qing; Liu, Zhiwei; Wang, Yinong; Pan, Qingya; Feng, Qianjin; Huang, Qinghua; Chen, Wufan

    2016-01-01

    The aim of this study was to assess quantitatively the site-specific degeneration of articular cartilage in ovariectomized rats with low estrogen levels using a high-frequency ultrasound system. Fourteen female Sprague-Dawley rats were randomly divided into two groups (n = 7 per group): a sham group in which only the peri-ovarian fatty tissue was exteriorized and an ovariectomized group that underwent bilateral ovariectomy to create a menopause model with low estrogen levels. All animals were sacrificed at the end of the third week after ovariectomy. Hindlimbs were harvested. The articular cartilage from five anatomic sites (i.e., femoral caput [FC], medial femoral condyle [MFC], lateral femoral condyle [LFC], medial tibial plateau [MTP] and lateral tibial plateau [LTP]) was examined with ultrasound. Four parameters were extracted from the ultrasound radiofrequency data: reflection coefficient of the cartilage surface (RC1), reflection coefficient of the cartilage-bone interface (RC2), ultrasound roughness index (URI) and thickness of the cartilage tissue. The results indicated significant (p < 0.05) site dependence for cartilage thickness, URI and RC1 in the sham group. The 3-wk post-menopause ovariectomized rats exhibited significant increases (p < 0.05) in the URI at the LFC, MTP and LTP; significant decreases (p < 0.05) in RC1 at the FC, LFC and MTP; and significant decreases (p < 0.05) in cartilage thickness at the MFC, LFC, MTP and LTP. These results of this study suggest that post-menopausal estrogen reduction induces morphologic and acoustic alterations in the articular cartilage of the hip and knee joints in ovariectomized rats. PMID:26497769

  1. Appendix: Site codes ---all sites

    E-print Network

    Gold, Lois Swirsky

    ktu kidney tubule l/b lung, bronchus lar larynx lcg lacrimal gland leg leg lep leptomeninges lgi large mesenteric lymph node mls multiple sites mth mouth mul multiple organs mus muscle MXA more than one site

  2. Fluctuations and State Preparation in Quantum Degenerate Gases of Sodium and Lithium

    E-print Network

    Fluctuations and State Preparation in Quantum Degenerate Gases of Sodium and Lithium by Edward Su and State Preparation in Quantum Degenerate Gases of Sodium and Lithium by Edward Su Submitted- periments with sodium and lithium in optical lattices. We describe progress towards the implementation

  3. Degenerate nDoping of Few-Layer Transition Metal Dichalcogenides by Potassium

    E-print Network

    Javey, Ali

    Degenerate nDoping of Few-Layer Transition Metal Dichalcogenides by Potassium Hui Fang,,,§ Mahmut semiconductors by surface charge transfer using potassium. High-electron sheet densities of 1.0 × 1013 cm-2 and 2: Degenerate doping, few-layer, TMDCs, MoS2, WSe2, potassium, surface charge transfer The desire for enhanced

  4. Parkinson's disease (PD) is characterized by the rela-tively selective degeneration of dopaminergic neurons in

    E-print Network

    Feng, Jian

    Parkinson's disease (PD) is characterized by the rela- tively selective degeneration (Betarbet and others 2000), have demonstrated that PD-like symptoms and degeneration of dopaminergic (DA into a stiff, hollow tube. Each Microtubule: A Common Target for Parkin and Parkinson's Disease Toxins JIAN

  5. Fibroid degeneration in a postmenopausal woman presenting as an acute abdomen

    PubMed Central

    Shrestha, Rajesh; Khanal, Raju; Aryal, Madan Raj; Pathak, Ranjan; Karmacharya, Paras; Naqi, Muniba; Murukutla, Srujitha; Bhatt, Vijaya Raj; Gottesman, Aaron

    2015-01-01

    Uterine fibroid, one of the most common tumors in women, is estrogen dependent, which commonly regresses after menopause. Fibroid degeneration after menopause, therefore, is rare. Here the authors report a case of 56-year-old postmenopausal woman who presented with acute abdominal pain, low grade fever, and leukocytosis as a result of fibroid degeneration. PMID:25656665

  6. Association of Abdominal Obesity with Lumbar Disc Degeneration – A Magnetic Resonance Imaging Study

    PubMed Central

    Takatalo, Jani; Karppinen, Jaro; Taimela, Simo; Niinimäki, Jaakko; Laitinen, Jaana; Sequeiros, Roberto Blanco; Samartzis, Dino; Korpelainen, Raija; Näyhä, Simo; Remes, Jouko; Tervonen, Osmo

    2013-01-01

    Purpose To evaluate whether midsagittal (abdominal) obesity in magnetic resonance imaging (MRI), waist circumference (WC) and body fat percentage are associated with lumbar disc degeneration in early adulthood. Methods We obtained the lumbar MRI (1.5-T scanner) of 325 females and 233 males at a mean age of 21 years. Lumbar disc degeneration was evaluated using Pfirrmann classification. We analysed the associations of MRI measures of obesity (abdominal diameter (AD), sagittal diameter (SAD), ventral subcutaneous thickness (VST), and dorsal subcutaneous thickness (DST)), WC and body fat percentage with disc degeneration sum scores using ordinal logistic regression. Results A total of 155 (48%) females and 147 (63%) males had disc degeneration. AD and SAD were associated with a disc degeneration sum score of ?3 compared to disc degeneration sum score of 0–2 (OR 1.67; 95% confidence interval (CI) 1.20–2.33 and OR 1.40; 95% CI 1.12–1.75, respectively) among males, but we found no association among females. WC was also associated with disc degeneration among males (OR 1.03 per one cm; 95% CI 1.00–1.05), but not among females. Conclusion Measures of abdominal obesity in MRI and waist circumference were associated with disc degeneration among 21-year-old males. PMID:23418543

  7. Diet-Induced Obesity Exacerbates Auditory Degeneration via Hypoxia, Inflammation, and Apoptosis

    E-print Network

    Wu, Yih-Min

    Diet-Induced Obesity Exacerbates Auditory Degeneration via Hypoxia, Inflammation, and Apoptosis was to investigate the mechanisms of diet-induced obesity on hearing degeneration in CD/1 mice. Sixty 4-week-old male CD/1 mice were randomly and equally divided into 2 groups. For 16 weeks, the diet-induced obesity

  8. A Nonlinear Master Equation for a Degenerate Diffusion Model of Biofilm Growth

    E-print Network

    Hillen, Thomas

    A Nonlinear Master Equation for a Degenerate Diffusion Model of Biofilm Growth Hassan Khassehkhan1@math.ualberta.ca Abstract. We present a continuous time/discrete space model of biofilm growth, starting from the semi models of biofilms. Grid refinement leads formally to a degenerate parabolic equation. We show that a set

  9. The periodic table of n-categories for low dimensions I: degenerate categories and

    E-print Network

    Cheng, Eugenia

    The periodic table of n-categories for low dimensions I: degenerate categories and degenerate-mail: eugenia@math.uchicago.edu, gurski@math.uchicago.edu July 2005 Abstract We examine the periodic table the first few entries in the "Periodic Table" of n- categories. This table was first described by Baez

  10. The role of autophagy in axonal degeneration of the optic nerve.

    PubMed

    Koch, Jan Christoph; Lingor, Paul

    2016-03-01

    Different pathological conditions including glaucoma, optic neuritis, hereditary optic atrophy and traumatic injury lead to a degeneration of retinal ganglion cell axons in the optic nerve. Besides this clinical relevance, several experimental models employ the optic nerve as a model system to examine general mechanisms of axonal degeneration in the central nervous system. Several experimental studies have demonstrated that an activation of autophagy is a prominent feature of axonal degeneration in the optic nerve independent of the underlying pathological condition. However, the function of autophagy in axonal degeneration remains still unclear. Inhibition of autophagy was found to attenuate axonal degeneration within the first hours after optic nerve lesion. Other studies focusing on survival of retinal ganglion cells at later postlesional time points report contradicting results, where both inhibition and induction of autophagy were beneficial for survival, depending on the model system or examination time. Therefore, a more precise understanding of the role and the kinetics of autophagy in axonal degeneration is mandatory to develop new therapies for diseases of the optic nerve. Here, we review the literature on the pathophysiological role of autophagy in axonal degeneration in the optic nerve and discuss its implications for future therapeutic approaches in diseases of the eye and the central nervous system involving axonal degeneration. PMID:26315785

  11. Extreme retinal remodeling triggered by light damage: implications for age related macular degeneration

    E-print Network

    Marc, Robert E.

    closely mimics late-stage atrophic age relared macular degeneration (AMD). Methods: Sprague-Dawley (SD late stage atrophic age-related macular degenerations, it augurs poorly for simple molecularExtreme retinal remodeling triggered by light damage: implications for age related macular

  12. Image Classification for Age-related Macular Degeneration Screening using Hierarchical

    E-print Network

    Coenen, Frans

    Image Classification for Age-related Macular Degeneration Screening using Hierarchical Image-hijazi,c.jiang,coenen,yalin.zheng}@liverpool.ac.uk Abstract. Age-related Macular Degeneration (AMD) is the most com- mon cause of adult blindness 1 Introduction Vision loss and blindness may be caused by various factors; Age-related Macular

  13. Blow-up at the Boundary for Degenerate Semilinear Parabolic Equations

    E-print Network

    Floater, Michael S.

    Blow-up at the Boundary for Degenerate Semilinear Parabolic Equations M. S. Floater Department a superlinear parabolic equation, degenerate in the time derivative. It is shown that the solution may blow up in finite time. Moreover it is proved that for a large class of initial data blow-up occurs at the boundary

  14. The origin of the neural macrophage: a quantitative ultrastructural study of cell population changes during Wallerian degeneration.

    PubMed Central

    Gibson, J D

    1979-01-01

    The changes that follow a localised crush injury to the rat sural nerve have been used to study endoneurial populations during Wallerian degeneration. The removal of products of degeneration, and in particular myelin debris, is accomplished by globule-laden cells which appear in the endoneurium during the first few days of repair. The origin of these cells has been investigated using a quantitative ultrastructural technique. Serial planimetric measurements of all populations, identifiable in terms of criteria that did not pre-judge their true nature, were made at intervals over a period of 15 days. Cell counts obtained immediately below the site of injury and 1 and 3 cm distally were compared, and graphs of endoneurial population changes constructed from these measurements. Additional descriptive evidence was invoked to assist in establishing the actual identity of the extratubal vacuolated cells which had been classified and measured empirically. Comparing the changes in the number of these cells with that of the intratubal vascuolated cell population, and taking account of the presence of immature macrophages in both proximal and distal situations, lead to the conclusion that the extratubal vacuolated cells are mostly derived from the bloodstream, the rest being of local intratubal origin. There was no evidence to support the notion that Schwann cells transform into macrophages. Images Fig. 6 Fig. 7 Fig. 8 Figs. 9 and 10 PMID:511756

  15. Functional consequences of locus coeruleus degeneration in Alzheimer's disease.

    PubMed

    Weinshenker, David

    2008-06-01

    Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients, and its prevalence is expected to soar in coming decades. Neuropathologically, AD is characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, and cholinergic neuronal loss. In addition to the hallmark of memory loss, the disease is associated with other neuropsychiatric and behavioral abnormalities, including psychosis, aggression, and depression. Although cholinergic cell loss is clearly an important attribute of the pathological process, another well-described yet underappreciated early feature of AD pathogenesis is degeneration of the locus coeruleus (LC), which serves as the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The purpose of this review is to explore the extent to which LC loss contributes to AD neuropathology and cognitive deficits. PMID:18537547

  16. New Approaches for Producing Quantum Degenerate Gases of Strontium

    NASA Astrophysics Data System (ADS)

    Ding, Roger; Woehl, Germano, Jr.; Camargo, Francisco; Whalen, Joseph; Dunning, F. Barry; Killian, Thomas

    2015-05-01

    We investigate two novel methods for laser cooling strontium to quantum degeneracy. The first takes advantage of the isotope shifts and the narrow 1S0 -3P1 intercombination line (7.5 kHz at 689 nm) to produce an isotope selective optical dipole trap (ODT). We demonstrate this technique by sympathetically cooling 88Sr or 87Sr using 86Sr to produce quantum degenerate gases. The second uses an acousto-optic modulator driven with multiple RF frequencies to dynamically shape a far-off resonance ODT. This is easy to implement in existing traps and allows for optimized loading and evaporation tailored for each isotope. The simple setup has been applied in various atomic physics experiments, and we describe its application in strontium. Research supported by the AFOSR under grant no. FA9550-12-1-0267, the NSF under grants nos. 1301773 and 1205946, and the Robert A. Welch Foundation under grant no. C-0734.

  17. Age-Related Macular Degeneration: Insights into Inflammatory Genes

    PubMed Central

    Ragazzo, Michele; Missiroli, Filippo; Borgiani, Paola; Angelucci, Francesco; Marsella, Luigi Tonino; Cusumano, Andrea; Novelli, Giuseppe; Ricci, Federico; Giardina, Emiliano

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old). AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension). In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species) have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2) that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression. PMID:25478207

  18. Degenerate Bose-Fermi mixtures of rubidium and ytterbium

    E-print Network

    Vaidya, Varun D; Rolston, S L; Porto, J V

    2015-01-01

    We report the first realization of a quantum degenerate mixture of bosonic $^{87}$Rb and fermionic $^{171}$Yb atoms in a hybrid optical dipole trap with a tunable, species-dependent trapping potential. $^{87}$Rb is shown to be a viable refrigerant for the non-interacting $^{171}$Yb atoms, cooling up to $2.4 \\times 10^5$ $^{171}$Yb atoms to a temperature of $T/T_F = 0.16(2) $ while simultaneously forming a $^{87}$Rb BEC of $3.5 \\times 10^5$ atoms. Furthermore we demonstrate our ability to independently tailor the potentials for each species, which paves the way for studying impurities immersed in a Bose gas.

  19. Complement factor H polymorphism and age-related macular degeneration.

    PubMed

    Edwards, Albert O; Ritter, Robert; Abel, Kenneth J; Manning, Alisa; Panhuysen, Carolien; Farrer, Lindsay A

    2005-04-15

    Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (P = 4.95 x 10(-10)) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD. PMID:15761121

  20. [Visual fixation features after treatment of exudative age macular degeneration].

    PubMed

    Surguch, V K; Surnina, Z V; Sizova, M V

    2011-01-01

    Changes of visual fixation in patients with choroidal neovascularitation (CNV) associated with age macular degeneration (AMD) after bevacizumab are studied. 45 patients (45 eyes) with active CNV treated with intravitreal bevacizumab were enrolled into the study. Visual fixation was studied before and 3-6 months after treatment using original method that included fundus foto and fluorescein angiography. Fixation relative to fovea and lesion was evaluated. Foveal fixation beyond lesion was found in 9%, foveal fixation within lesion--in 47%, extrafoveal fixation beyond lesion--in 18%, extrafoveal fixation within lesion--in 26% of patients. Changes of fixation localization after treatment was found in 24% patients. Examination of visual fixation may be useful for prognosis of anti-VEGF treatment efficacy in patients with CNV. PMID:21721271

  1. Topological Superradiant States in a Degenerate Fermi Gas.

    PubMed

    Pan, Jian-Song; Liu, Xiong-Jun; Zhang, Wei; Yi, Wei; Guo, Guang-Can

    2015-07-24

    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 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 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. The topological phase transition can be detected from its signatures in either the momentum distribution of the atoms or the variation of the cavity photon occupation due to the nontrivial feedback of the atoms on the cavity field. PMID:26252692

  2. Radiation Therapy for Neovascular Age-related Macular Degeneration

    SciTech Connect

    Kishan, Amar U.; Modjtahedi, Bobeck S.; Morse, Lawrence S.; Lee, Percy

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  3. Experiments with Ultracold Quantum-degenerate Fermionic Lithium Atoms

    NASA Technical Reports Server (NTRS)

    Ketterle, Wolfgang

    2003-01-01

    Experimental methods of laser and evaporative cooling, used in the production of atomic Bose-Einstein condensates have recently been extended to realize quantum degeneracy in trapped Fermi gases. Fermi gases are a new rich system to explore the implications of Pauli exclusion on scattering properties of the system, and ultimately fermionic superfluidity. We have produced a new macroscopic quantum system, in which a degenerate Li-6 Fermi gas coexists with a large and stable Na-23 BEC. This was accomplished using inter-species sympathetic cooling of fermionic 6Li in a thermal bath of bosonic Na-23. We have achieved high numbers of both fermions (less than 10(exp 5) and bosons (less than 10(exp 6), and Li-6 quantum degeneracy corresponding to one half of the Fermi temperature. This is the first time that a Fermi sea was produced with a condensate as a "refrigerator".

  4. Age-related macular degeneration and the aging eye

    PubMed Central

    Ehrlich, Rita; Harris, Alon; Kheradiya, Nisha S; Winston, Diana M; Ciulla, Thomas A; Wirostko, Barbara

    2008-01-01

    Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch’s membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly. PMID:18982917

  5. New treatments for age-related macular degeneration.

    PubMed

    Mittra, Robert A

    2003-04-01

    The estimated increase in life expectancy of the U.S. population will result in a greater incidence of age-related macular degeneration (AMD) in the next few decades. Exudative AMD, which is characterized by choroidal neovascularization, carries a high risk of severe central vision loss and can compromise an individual's independence and quality of life. The increasing burden of AMD has created an acute need for more effective treatments. Results from a recent large-scale study have shown that supplementation with antioxidants and zinc reduces the risk of progression of dry to exudative AMD. Standard thermal laser photocoagulation can reduce the risk of central vision loss in exudative AMD in a limited number of patients. The recent advent of photodynamic laser therapy has increased the number of patients with exudative AMD who can benefit from treatment. This paper summarizes the clinical presentation of AMD and reviews treatments that are currently available, as well as treatments in development. PMID:12797657

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

    PubMed

    Rowan, Sheldon; Taylor, Allen

    2016-01-01

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50 % of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation is the only available treatment option for the dry form of the disease known to slow progression of AMD. Despite an excellent understanding of genes and nutrition in AMD, there is remarkably little known about gene-diet interactions that may identify efficacious approaches to treat individuals. This review will summarize our current understanding of gene-diet interactions in AMD with a focus on animal models and human epidemiological studies. PMID:26427399

  7. Topological Superradiant States in a Degenerate Fermi Gas

    NASA Astrophysics Data System (ADS)

    Pan, Jian-Song; Liu, Xiong-Jun; Zhang, Wei; Yi, Wei; Guo, Guang-Can

    2015-07-01

    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 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 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. The topological phase transition can be detected from its signatures in either the momentum distribution of the atoms or the variation of the cavity photon occupation due to the nontrivial feedback of the atoms on the cavity field.

  8. Today and Future of Age-Related Macular Degeneration

    PubMed Central

    Liu, Kang; Xie, Bolin

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 in developed countries. Understanding of the pathologic process, genetic mechanisms, and risk factors of this disease has the benefit of seeking newer and more effective treatment options. Current clinical therapy for AMD shows a dramatic change from a decade ago. Anti-VEGF drug therapy is regarded as the more effective treatment for neovascular AMD now, especially combining PDT therapy. In the future, the genetic and biochemical therapies may be the promising treatments for AMD. This paper will focus on the progress of pathology, candidate genes of AMD, risk factors, and the existing drugs or surgical therapies available, in order to present some new directions of care with the prospect of improved vision in many patients suffered from AMD. PMID:24558588

  9. Gene Therapy for MERTK-Associated Retinal Degenerations.

    PubMed

    LaVail, Matthew M; Yasumura, Douglas; Matthes, Michael T; Yang, Haidong; Hauswirth, William W; Deng, Wen-Tao; Vollrath, Douglas

    2016-01-01

    MERTK-associated retinal degenerations are thought to have defects in phagocytosis of shed outer segment membranes by the retinal pigment epithelium (RPE), as do the rodent models of these diseases. We have subretinally injected an RPE-specific AAV2 vector, AAV2-VMD2-hMERTK, to determine whether this would provide long-term photoreceptor rescue in the RCS rat, which it did for up to 6.5 months, the longest time point examined. Moreover, we found phagosomes in the RPE in the rescued regions of RCS retinas soon after the onset of light. The same vector also had a major protective effect in Mertk-null mice, with a concomitant increase in ERG response amplitudes in the vector-injected eyes. These findings suggest that planned clinical trials with this vector will have a favorable outcome. PMID:26427450

  10. Progress Toward Effective Treatments for Human Photoreceptor Degenerations

    PubMed Central

    Stone, Edwin M.

    2015-01-01

    Mutations in several dozen genes have been shown to cause inherited photoreceptor degeneration in humans and it is likely that mutations in several dozen more will eventually be identified. Careful study of these genes has provided insight into the cellular and molecular mechanisms of human photoreceptor disease and has accelerated the development of a number of different classes of therapy including: nutritional supplementation, toxin avoidance, small- and large-molecule drugs, gene replacement, cell replacement, and even retinal prostheses. The retina is a very favorable system for the development of novel treatments for neurodegenerative disease because of its optical and physical accessibility as well as its highly ordered structure. With several forms of treatment for inherited retinal disease in or near clinical trial, one of the greatest remaining challenges is to educate clinicians in the appropriate use of genetic testing for identifying the individuals who will be most likely to benefit from each specific modality. PMID:19414246

  11. Corneal Hydrops in Pellucid Marginal Degeneration: A Case Series

    PubMed Central

    Bhandari, Vipul; Ganesh, Sri

    2015-01-01

    Purpose To report an unusual presentation of pellucid marginal degeneration (PMD) and its management by using air injection and tension sutures. Case Report We report 2 cases with a history of acute pain and loss of vision. Examination revealed hydrops at the 6–9 o'clock meridian with Descemet's membrane detachment and tear at the same area and advanced PMD in the other eye. Discussion Air injection with suturing to treat the hydrops in PMD and crescentic excision with lamellar grafting instead of lamellar keratoplasty lead to better results than conservative management. Conclusion Corneal hydrops and perforation in patients with PMD is a rare presentation and can be managed by tension sutures and air injection. PMID:26265904

  12. The physical properties of double degenerate common proper motion binaries

    NASA Technical Reports Server (NTRS)

    Sion, Edward M.; Oswalt, Terry D.; Liebert, James; Hintzen, Paul

    1991-01-01

    Spectral types and spectrophotometry are presented for 21 double degenerate (DD) common proper motion binaries, along with estimates of their colors, absolute visual and bolometric magnitudes, and cooling ages. The oldest pairs in the sample are 9 x 10 to the 9th yr; the differential cooling ages range from 0.01 to 0.84. The median and mean separations of the DD pairs are 426 and 407 Au, respectively, both apparently smaller than the WD+MS values. The average UVW motions and velocity dispersions are significantly larger than the average velocities and dispersions associated with selected samples of single white dwarfs and MS+WD binaries when the latter are restricted to the same color/Mv range as the DD systems. This may be a result of the dynamical inflation of the velocity dispersion of DD systems due to their extremely ancient total stellar ages.

  13. Bietti's tapetoretinal degeneration with marginal corneal dystrophy crystalline retinopathy.

    PubMed Central

    Welch, R B

    1977-01-01

    In 1937 Bietti reported a tapetoretinal degeneration with associated corneal deposits at the limbus. The hallmark of the disease was the crystalline characteristics of the retinal spots as well as those at the corneal limbus. Bagolini and Ioli-Spade in 1968 presented a 30 year follow-up on Bietti's cases and presented six additional cases. The present report delas with this entity in Orientals, a Chinese woman and a Japanese man. Corneal and conjunctival biopsy from the female patient revelaed a lipid deposition in both fibroblasts and epithelium. The term "crystalline retinopathy" has been added to the description of this entity since it defines the most characteristic feature of the syndrome. Images FIGURE 7 A FIGURE 7 B FIGURE 1 A FIGURE 1 B FIGURE 1 C FIGURE 2 A FIGURE 2 B FIGURE 2 C FIGURE 3 FIGURE 4 A FIGURE 4 B FIGURE 5 FIGURE 6 A FIGURE 6 B FIGURE 6 C FIGURE 8 PMID:306693

  14. Lifespan maturation and degeneration of human brain white matter

    PubMed Central

    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 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

  15. Quantum degenerate mixtures of strontium and rubidium atoms

    E-print Network

    Pasquiou, Benjamin; Tzanova, Slava; Stellmer, Simon; Szczepkowski, Jacek; Parigger, Mark; Grimm, Rudolf; Schreck, Florian

    2013-01-01

    We report on the realization of quantum degenerate gas mixtures of the alkaline-earth element strontium with the alkali element rubidium. A key ingredient of our scheme is sympathetic cooling of Rb by Sr atoms that are continuously laser cooled on a narrow linewidth transition. This versatile technique allows us to produce ultracold gas mixtures with a phase-space density of up to 0.06 for both elements. By further evaporative cooling we create double Bose-Einstein condensates of 87Rb with either 88Sr or 84Sr, reaching more than 10^5 condensed atoms per element for the 84Sr-87Rb mixture. These quantum gas mixtures constitute an important step towards the production of a quantum gas of polar, open-shell RbSr molecules.

  16. Quantum degenerate mixtures of strontium and rubidium atoms

    NASA Astrophysics Data System (ADS)

    Pasquiou, Benjamin; Bayerle, Alex; Tzanova, Slava M.; Stellmer, Simon; Szczepkowski, Jacek; Parigger, Mark; Grimm, Rudolf; Schreck, Florian

    2013-08-01

    We report on the realization of quantum degenerate gas mixtures of the alkaline-earth-metal element strontium with the alkali-metal element rubidium. A key ingredient of our scheme is sympathetic cooling of Rb by Sr atoms that are continuously laser cooled on a narrow-linewidth transition. This versatile technique allows us to produce ultracold gas mixtures with a phase-space density of up to 0.06 for both elements. By further evaporative cooling we create double Bose-Einstein condensates of 87Rb with either 88Sr or 84Sr, reaching more than 1×105 condensed atoms per element for the 84Sr-87Rb mixture. These quantum gas mixtures constitute an important step towards the production of a quantum gas of polar, open-shell RbSr molecules.

  17. The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration.

    PubMed

    Washington, Ilyas; Saad, Leonide

    2016-01-01

    One of the earliest events preceding several forms of retinal degeneration is the formation and accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and underlying Bruch's membrane (BM). Such degenerations include Stargardt disease, Best disease, forms of retinitis pigmentosa, and age-related macular degeneration (AMD). Since their discovery in the 1990's, dimers of vitamin A, have been postulated as chemical triggers driving retinal senescence and degeneration. There is evidence to suggest that the rate at which vitamin A dimerizes and the eye's response to the dimerization products may dictate the retina's lifespan. Here, we present outstanding questions, finding the answers to which may help to elucidate the role of vitamin A dimerization in retinal degeneration. PMID:26427431

  18. Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy.

    PubMed

    Lee, Yun-Sil; Lehar, Adam; Sebald, Suzanne; Liu, Min; Swaggart, Kayleigh A; Talbot, C Conover; Pytel, Peter; Barton, Elisabeth R; McNally, Elizabeth M; Lee, Se-Jin

    2015-10-15

    Myostatin is a secreted signaling molecule that normally acts to limit muscle growth. As a result, there is extensive effort directed at developing drugs capable of targeting myostatin to treat patients with muscle loss. One potential concern with this therapeutic approach in patients with muscle degenerative diseases like muscular dystrophy is that inducing hypertrophy may increase stress on dystrophic fibers, thereby accelerating disease progression. To investigate this possibility, we examined the effect of blocking the myostatin pathway in dysferlin-deficient (Dysf(-/-)) mice, in which membrane repair is compromised, either by transgenic expression of follistatin in skeletal muscle or by systemic administration of the soluble form of the activin type IIB receptor (ACVR2B/Fc). Here, we show that myostatin inhibition by follistatin transgene expression in Dysf(-/-) mice results in early improvement in histopathology but ultimately exacerbates muscle degeneration; this effect was not observed in dystrophin-deficient (mdx) mice, suggesting that accelerated degeneration induced by follistatin transgene expression is specific to mice lacking dysferlin. Dysf(-/-) mice injected with ACVR2B/Fc showed significant increases in muscle mass and amelioration of fibrotic changes normally seen in 8-month-old Dysf(-/-) mice. Despite these potentially beneficial effects, ACVR2B/Fc treatment caused increases in serum CK levels in some Dysf(-/-) mice, indicating possible muscle damage induced by hypertrophy. These findings suggest that depending on the disease context, inducing muscle hypertrophy by myostatin blockade may have detrimental effects, which need to be weighed against the potential gains in muscle growth and decreased fibrosis. PMID:26206886

  19. Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy

    PubMed Central

    Lee, Yun-Sil; Lehar, Adam; Sebald, Suzanne; Liu, Min; Swaggart, Kayleigh A.; Talbot, C. Conover; Pytel, Peter; Barton, Elisabeth R.; McNally, Elizabeth M.; Lee, Se-Jin

    2015-01-01

    Myostatin is a secreted signaling molecule that normally acts to limit muscle growth. As a result, there is extensive effort directed at developing drugs capable of targeting myostatin to treat patients with muscle loss. One potential concern with this therapeutic approach in patients with muscle degenerative diseases like muscular dystrophy is that inducing hypertrophy may increase stress on dystrophic fibers, thereby accelerating disease progression. To investigate this possibility, we examined the effect of blocking the myostatin pathway in dysferlin-deficient (Dysf?/?) mice, in which membrane repair is compromised, either by transgenic expression of follistatin in skeletal muscle or by systemic administration of the soluble form of the activin type IIB receptor (ACVR2B/Fc). Here, we show that myostatin inhibition by follistatin transgene expression in Dysf?/? mice results in early improvement in histopathology but ultimately exacerbates muscle degeneration; this effect was not observed in dystrophin-deficient (mdx) mice, suggesting that accelerated degeneration induced by follistatin transgene expression is specific to mice lacking dysferlin. Dysf?/? mice injected with ACVR2B/Fc showed significant increases in muscle mass and amelioration of fibrotic changes normally seen in 8-month-old Dysf?/? mice. Despite these potentially beneficial effects, ACVR2B/Fc treatment caused increases in serum CK levels in some Dysf?/? mice, indicating possible muscle damage induced by hypertrophy. These findings suggest that depending on the disease context, inducing muscle hypertrophy by myostatin blockade may have detrimental effects, which need to be weighed against the potential gains in muscle growth and decreased fibrosis. PMID:26206886

  20. New Perspective on Parkinsonism in Frontotemporal Lobar Degeneration

    PubMed Central

    Park, Hee Kyung; Chung, Sun J.

    2013-01-01

    Frontotemporal dementia (FTD) is the second most common type of presenile dementia. Three clinical prototypes have been defined; behavioral variant FTD, semantic dementia, and progressive nonfluent aphasia. Progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease may possess clinical and pathological characteristics that overlap with FTD, and it is possible that they may all belong to the same clinicopathological spectrum. Frontotemporal lobar degeneration (FTLD) is a clinicopathological syndrome that encompasses a heterogenous group of neurodegenerative disorders. Owing to the advancement in the field of molecular genetics, diagnostic imaging, and pathology, FTLD has been the focus of great interest. Nevertheless, parkinsonism in FTLD has received relatively less attention. Parkinsonism is found in approximately 20–30% of patients in FTLD. Furthermore, parkinsonism can be seen in all FTLD subtypes, and some patients with familial and sporadic FTLD can present with prominent parkinsonism. Therefore, there is a need to understand parkinsonism in FTLD in order to obtain a better understanding of the disease. With regard to the clinical characteristics, the akinetic rigid type of parkinsonism has predominantly been described. Parkinsonism is frequently observed in familial FTD, more specifically, in FTD with parkinsonism linked to chromosome 17q (FTDP-17). The genes associated with parkinsonism are microtubule associated protein tau (MAPT), progranulin (GRN or PGRN), and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion. The neural substrate of parkinsonism remains to be unveiled. Dopamine transporter (DAT) imaging revealed decreased uptake of DAT, and imaging findings indicated atrophic changes of the basal ganglia. Parkinsonism can be an important feature in FTLD and, therefore, increased attention is needed on the subject. PMID:24868417

  1. Age-related macular degeneration: Evidence of a major gene

    SciTech Connect

    Bhatt, S.; Warren, C.; Yang, H.

    1994-09-01

    Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

  2. Simulating the Double-Degenerate Channel for Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Jumper, Kevin; Fisher, R. T.

    2013-01-01

    Type Ia Supernovae (SNe Ia) are the thermonuclear explosions of white dwarfs, and are of fundamental importance to the study of many phenomena, including the expansion of the universe and dark energy. For many years, it was suspected that that SNe Ia occur in binary systems, but the identity of the white dwarf’s companion could not be determined. A leading hypothesis, the single-degenerate (SD) channel, suggests that the companion is either on the main sequence or a red giant, and that the white dwarf accretes matter off of its companion until it nears the Chandrasekhar limit of 1.4 solar masses, causing the white dwarf to detonate shortly thereafter. Another hypothesis, the double-degenerate (DD) channel, proposes that both stars in the system are white dwarfs and that they merge together, resulting in a central, rapidly spinning white dwarf, surrounded by a thick disk of remnant material. Precisely how this triggers a detonation remains unclear; early spherically-symmetric models by Nomoto et al. indicated that merged white dwarfs would collapse to neutron stars instead of producing supernovae. Recent observations of two supernovae discovered last year by the Palomar Transient Factory (PTF), SN 2011 fe and SN PTF11k, have provided evidence that suggests that both the SD and DD channels coexist in nature. Consequently, it is important to develop simulations that can resolve the mystery of the DD channel’s detonation mechanism. To this end, we use a smoothed-particle hydrodynamics (SPH) code, GADGET-1, to model the rotating flows characteristic of merged DD systems and study how they evolve with time.

  3. Clinical Impact of Sagittal Spinopelvic Parameters on Disc Degeneration in Young Adults

    PubMed Central

    Oh, Young-Min; Eun, Jong-Pil

    2015-01-01

    Abstract The sagittal balance plays an important role in the determination of shear and compressive forces applied on the anterior (vertebral bodies and intervertebral discs) and posterior (facet joints) elements of the lumbar vertebral column. Many studies have also examined the effect of structural changes in the disc on the biomechanical characteristics of the spinal segment. Nevertheless, the relationship between sagittal balance and the degree of disc degeneration has not been extensively explored. Thus, here we investigated the relationships between various sagittal spinopelvic parameters and the degree of disc degeneration in young adults. A total of 278 young adult male patients were included in this study (age range: 18–24 years old). Multiple sagittal spinopelvic parameters, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), sacral inclination (SI), lumbosacral angle (LSA), and sacral table angle (STA), were measured from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. To assess the pain intensity of each patient, the visual analogue scale (VAS) score for low back pain (LBP) was obtained from all the patients. Finally, the relationships between these spinopelvic parameters and the degree of disc degeneration in young adults were analyzed. Also, we performed multiple logistic regression study. Out of all the spinopelvic parameters measured in this study, a low STA and a low SI were the only significant risk factors that were associated with disc degeneration in young adults. It means that patients with disc degeneration tend to have more severe sacral kyphosis and vertical sacrum. We found that patients with disc degeneration showed a lower SI and lower STA compared with patients without disc degeneration in young adults. Therefore, we suggest that the patients with disc degeneration tend to have more vertical sacrum, more sacral kyphosis, and more severe LBP, and that SI and STA measurements should be carefully considered to predict or prevent further disc degeneration and LBP. PMID:26496324

  4. Clinical Impact of Sagittal Spinopelvic Parameters on Disc Degeneration in Young Adults.

    PubMed

    Oh, Young-Min; Eun, Jong-Pil

    2015-10-01

    The sagittal balance plays an important role in the determination of shear and compressive forces applied on the anterior (vertebral bodies and intervertebral discs) and posterior (facet joints) elements of the lumbar vertebral column. Many studies have also examined the effect of structural changes in the disc on the biomechanical characteristics of the spinal segment. Nevertheless, the relationship between sagittal balance and the degree of disc degeneration has not been extensively explored. Thus, here we investigated the relationships between various sagittal spinopelvic parameters and the degree of disc degeneration in young adults.A total of 278 young adult male patients were included in this study (age range: 18-24 years old). Multiple sagittal spinopelvic parameters, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), sacral inclination (SI), lumbosacral angle (LSA), and sacral table angle (STA), were measured from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. To assess the pain intensity of each patient, the visual analogue scale (VAS) score for low back pain (LBP) was obtained from all the patients. Finally, the relationships between these spinopelvic parameters and the degree of disc degeneration in young adults were analyzed. Also, we performed multiple logistic regression study.Out of all the spinopelvic parameters measured in this study, a low STA and a low SI were the only significant risk factors that were associated with disc degeneration in young adults. It means that patients with disc degeneration tend to have more severe sacral kyphosis and vertical sacrum.We found that patients with disc degeneration showed a lower SI and lower STA compared with patients without disc degeneration in young adults. Therefore, we suggest that the patients with disc degeneration tend to have more vertical sacrum, more sacral kyphosis, and more severe LBP, and that SI and STA measurements should be carefully considered to predict or prevent further disc degeneration and LBP. PMID:26496324

  5. Regulation of age-related macular degeneration-like pathology by complement factor H.

    PubMed

    Toomey, Christopher B; Kelly, Una; Saban, Daniel R; Bowes Rickman, Catherine

    2015-06-01

    Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh(+/-) and Cfh(-/-) mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch's membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh(+/-) and Cfh(-/-) mice, RPE damage accompanied by loss of vision occurred only in old Cfh(+/-) mice. We demonstrate that such pathology is a function of excess complement activation in Cfh(+/-) mice versus complement deficiency in Cfh(-/-) animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch's membrane lipoprotein binding and show, using human Bruch's membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD. PMID:25991857

  6. Degenerate Connective Polypeptide 1 (CP1) Domain from Human Mitochondrial Leucyl-tRNA Synthetase.

    PubMed

    Ye, Qing; Wang, Meng; Fang, Zhi-Peng; Ruan, Zhi-Rong; Ji, Quan-Quan; Zhou, Xiao-Long; Wang, En-Duo

    2015-10-01

    The connective polypeptide 1 (CP1) editing domain of leucyl-tRNA synthetase (LeuRS) from various species either harbors a conserved active site to exclude tRNA mis-charging with noncognate amino acids or is evolutionarily truncated or lost because there is no requirement for high translational fidelity. However, human mitochondrial LeuRS (hmtLeuRS) contains a full-length but degenerate CP1 domain that has mutations in some residues important for post-transfer editing. The significance of such an inactive CP1 domain and a translational accuracy mechanism with different noncognate amino acids are not completely understood. Here, we identified the essential role of the evolutionarily divergent CP1 domain in facilitating hmtLeuRS's catalytic efficiency and endowing enzyme with resistance to AN2690, a broad-spectrum drug acting on LeuRSs. In addition, the canonical core of hmtLeuRS is not stringent for noncognate norvaline (Nva) and valine (Val). hmtLeuRS has a very weak tRNA-independent pre-transfer editing activity for Nva, which is insufficient to remove mis-activated Nva. Moreover, hmtLeuRS chimeras fused with a functional CP1 domain from LeuRSs of other species, regardless of origin, showed restored post-transfer editing activity and acquired fidelity during aminoacylation. This work offers a novel perspective on the role of the CP1 domain in optimizing aminoacylation efficiency. PMID:26272616

  7. Recent Patents on Emerging Therapeutics for the Treatment of Glaucoma, Age Related Macular Degeneration and Uveitis

    PubMed Central

    Vadlapudi, Aswani Dutt; Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K.

    2014-01-01

    Advancements in the field and rising interest among pharmaceutical researchers have led to the development of new molecules with enhanced therapeutic activity. Design of new drugs which can target a particular pathway and/or explore novel targets is of immense interest to ocular pharmacologists worldwide. Delivery of suitable pharmacologically active agents at proper dose (within the therapeutic window) to the target tissues without any toxicity to the healthy ocular tissues still remain an elusive task. Moreover, the presence of static and dynamic barriers to drug absorption including the corneal epithelium (lipophilic), corneal and scleral stroma (hydrophilic), conjunctival lymphatics, choroidal vasculature and the blood-ocular barriers also pose a significant challenge for achieving therapeutic drug concentrations at the target site. Although many agents are currently available, new compounds are being introduced for treating various ocular diseases. Deeper understanding of the etiology and complex mechanisms associated with the disease condition would aid in the development of potential therapeutic candidates. Novel small molecules as well as complex biotechnology derived macromolecules with superior efficacy, safety and tolerability are being developed. Therefore, this review article provides an overview of existing drugs, treatment options, advances in emerging therapeutics and related recent patents for the treatment of ocular disorders such as glaucoma, age related macular degeneration (AMD) and uveitis. PMID:25414810

  8. Investigating Mitochondria as a Target for Treating Age-Related Macular Degeneration

    PubMed Central

    Terluk, Marcia R.; Kapphahn, Rebecca J.; Soukup, Lauren M.; Gong, Hwee; Gallardo, Christopher; Montezuma, Sandra R.

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. Although the pathological mechanisms have not been definitively elucidated, evidence suggests a key role for mitochondrial (mt) dysfunction. The current study used our unique collection of human retinal samples graded for the donor's stage of AMD to address fundamental questions about mtDNA damage in the retina. To evaluate the distribution of mtDNA damage in the diseased retina, damage in the retinal pigment epithelium (RPE) and neural retina from individual donors were compared. To directly test a long-held belief that the macula is selectively damaged with AMD, RPE mtDNA damage was measured in the macula and peripheral sections from individual donors. Small segments of the entire mt genome were examined to determine whether specific regions are preferentially damaged. Our results show that mtDNA damage is limited to the RPE, equivalent mtDNA damage is found in the macular and peripheral RPE, and sites of damage are localized to regions of the mt genome that may impact mt function. These results provide a scientific basis for targeting the RPE mitochondria with therapies that protect and enhance mt function as a strategy for combating AMD. PMID:25948278

  9. Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study

    E-print Network

    2013-01-01

    smoking influence the risk of age-related macular degenerationsmoking and obesity [62,64]. Conclusions Age-related macular degeneration (smoking, body mass index, environmental associations with advanced age-related macular degeneration.

  10. Models of collective cell spreading with variable cell aspect ratio: A motivation for degenerate diffusion models

    NASA Astrophysics Data System (ADS)

    Simpson, Matthew J.; Baker, Ruth E.; McCue, Scott W.

    2011-02-01

    Continuum diffusion models are often used to represent the collective motion of cell populations. Most previous studies have simply used linear diffusion to represent collective cell spreading, while others found that degenerate nonlinear diffusion provides a better match to experimental cell density profiles. In the cell modeling literature there is no guidance available with regard to which approach is more appropriate for representing the spreading of cell populations. Furthermore, there is no knowledge of particular experimental measurements that can be made to distinguish between situations where these two models are appropriate. Here we provide a link between individual-based and continuum models using a multiscale approach in which we analyze the collective motion of a population of interacting agents in a generalized lattice-based exclusion process. For round agents that occupy a single lattice site, we find that the relevant continuum description of the system is a linear diffusion equation, whereas for elongated rod-shaped agents that occupy L adjacent lattice sites we find that the relevant continuum description is connected to the porous media equation (PME). The exponent in the nonlinear diffusivity function is related to the aspect ratio of the agents. Our work provides a physical connection between modeling collective cell spreading and the use of either the linear diffusion equation or the PME to represent cell density profiles. Results suggest that when using continuum models to represent cell population spreading, we should take care to account for variations in the cell aspect ratio because different aspect ratios lead to different continuum models.

  11. Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

    ClinicalTrials.gov

    2016-01-05

    Macular Degeneration; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; Maculopathy, Age-Related; Retinal Degeneration; Retinal Neovascularization; Gene Therapy; Therapy, Gene; Eye Diseases

  12. Can Intra-Y Gene Conversion Oppose the Degeneration of the Human Y Chromosome? A Simulation Study

    E-print Network

    Gordo, Isabel

    Can Intra-Y Gene Conversion Oppose the Degeneration of the Human Y Chromosome? A Simulation Study@biomserv.univ-lyon1.fr. Accepted: 11 May 2010 Abstract The human Y is a genetically degenerate chromosome, which has otherwise. Here, we tested this idea by simulating the evolution of degenerating Y chromosomes

  13. Am. J. Hum. Genet. 73:540550, 2003 Age-Related Macular Degeneration--a Genome Scan in Extended Families

    E-print Network

    Majewski, Jacek

    Am. J. Hum. Genet. 73:540­550, 2003 540 Age-Related Macular Degeneration--a Genome Scan in Extended Genetics, Rockefeller University, New York; 2 Macular Degeneration Center, Casey Eye Institute, Department and genetic linkage analysis, to identify loci associated with age-related macular degeneration (AMD). We

  14. Reorganization of visual processing in macular degeneration: Replication and clues about the role of foveal loss q

    E-print Network

    Kanwisher, Nancy

    Reorganization of visual processing in macular degeneration: Replication and clues about the role individuals with loss of foveal input from macular degeneration [Baker, C.I., Peli, E., Knouf, N., & Kanwisher, N. G. (2005). Reorganization of visual processing in macular degeneration. Journal of Neuroscience

  15. Mechanism of All-trans-retinal Toxicity: Implications for Stargardt's Disease and Age-related Macular Degeneration

    E-print Network

    Palczewski, Krzysztof

    -related Macular Degeneration Yu Chen1 , Kiichiro Okano1 , Tadao Maeda1,2 , Vishal Chauhan1,2 , Marcin Golczak1;4 Supplemental Figure 3. Abca4--/-- Rdh8--/-- mouse photoreceptors exhibit light-induced degeneration in vivo. Four- to 5-week old Abca4--/-- Rdh8--/-- mice develop severe light-induced photoreceptor degeneration

  16. Evaluation of Potential Therapies for a Mouse Model of Human Age-Related Macular Degeneration Caused by

    E-print Network

    Palczewski, Krzysztof

    Evaluation of Potential Therapies for a Mouse Model of Human Age-Related Macular Degeneration of potential therapeutics in Rdh8 / Abca4 / mice, a rodent model of human age-related macular degeneration (AMD Vis Sci. 2009;50:4917­4925) DOI:10.1167/iovs.09-3581 Age-related macular degeneration (AMD), a leading

  17. Am. J. Hum. Genet. 74:482494, 2004 Age-Related Macular Degeneration: A High-Resolution Genome Scan

    E-print Network

    Abecasis, Goncalo

    Am. J. Hum. Genet. 74:482­494, 2004 482 Age-Related Macular Degeneration: A High-Resolution Genome, Philadelphia Age-related macular degeneration (AMD) is a complex multifactorial disease that affects for disease-associated sequence variants. Introduction Age-related macular degeneration (AMD [MIM 603075

  18. Reorganization of visual processing in macular degeneration: Replication and clues about the role of foveal loss q

    E-print Network

    Peli, Eli

    Reorganization of visual processing in macular degeneration: Replication and clues about the role of foveal input from macular degeneration [Baker, C.I., Peli, E., Knouf, N., & Kanwisher, N. G. (2005). Reorganization of visual processing in macular degeneration. Journal of Neuroscience, 25(3), 614­618]. Here, we

  19. Value siting

    SciTech Connect

    Ferrar, T.A.; Howes, J.A.

    1995-02-01

    Finding an appropriate site is becoming an increasing challenge in building new power projects. One of the first orders of business in project development is identifying a site that offers the maximum spread between the cost of fuel and net power price. The collection of sites that exhibit an adequate spread - presenting a first-order, acceptable economic expectation - must now be subjected to an ever increasing number of political, societal, technical, and economic exclusion screens. The barriers can include cooling water constraints, community resistance, visual incompatibility, archaeological concerns and endangered species preservation issues. Most power siting difficulties can be substantially mitigated by gaining access to developed, but under-used sites, whose current owners are bound by circumstances - political or financial - that prevent them from using such locations. There are two such categories of sites: Utilities that have sites on which depreciated power production assets rest; and, The federal government, with numerous sites throughout the country, particularly military bases subject to closure under the Base Realignment and Closure (BRAC) proceedings. It is in the interests of developers, as well as consumers, investors and taxpayers, ti undertake a thorough examination of these overlooked pearls of opportunities and develop their potential.

  20. Adipose-derived stem cells improve the viability of nucleus pulposus cells in degenerated intervertebral discs.

    PubMed

    Song, Keran; Gu, Tao; Shuang, Feng; Tang, Jiaguang; Ren, Dongfeng; Qin, Jiang; Hou, Shuxun

    2015-09-01

    Patients with degenerative disc disease (DDD) experience serious clinical symptoms, including chronic low back pain. A series of therapies have been developed to treat DDD, including physical therapy and surgical treatment. However, the therapeutic effect of such treatments has remained insufficient. Recently, stem cell?based therapy, in which stem cells are injected into the nucleus pulposus in degenerated intervertebral disc tissue, has appeared to be effective in the treatment of DDD. In the present study, the effect of adipose?derived stem cells on degenerated nucleus pulposus cells was investigated using a co?culture system to evaluate the biological activity of degenerated nucleus pulposus cells. Human degenerated nucleus pulposus tissue was obtained from surgical specimens and the adipose?derived stem cells were derived from adipose tissue. The degenerated nucleus pulposus cells were cultured in a mono?culture or in a co?culture with adipose?derived stem cells using 0.4?µm Transwell inserts. The results indicated that adipose?derived stem cells were able to stimulate matrix synthesis and the cell proliferation of degenerated nucleus pulposus cells, promoting the restoration of nucleus pulposus cells in the degenerated intervertebral disc. PMID:26059030

  1. Alterations in Kainate Receptor and TRPM1 Localization in Bipolar Cells after Retinal Photoreceptor Degeneration

    PubMed Central

    Gayet-Primo, Jacqueline; Puthussery, Theresa

    2015-01-01

    Photoreceptor degeneration differentially impacts glutamatergic signaling in downstream On and Off bipolar cells. In rodent models, photoreceptor degeneration leads to loss of glutamatergic signaling in On bipolar cells, whereas Off bipolar cells appear to retain glutamate sensitivity, even after extensive photoreceptor loss. The localization and identity of the receptors that mediate these residual glutamate responses in Off bipolar cells have not been determined. Recent studies show that macaque and mouse Off bipolar cells receive glutamatergic input primarily through kainate-type glutamate receptors. Here, we studied the impact of photoreceptor degeneration on glutamate receptor and their associated proteins in Off and On bipolar cells. We show that the kainate receptor subunit, GluK1, persists in remodeled Off bipolar cell dendrites of the rd10 mouse retina. However, the pattern of expression is altered and the intensity of staining is reduced compared to wild-type retina. The kainate receptor auxiliary subunit, Neto1, also remains in Off bipolar cell dendrites after extensive photoreceptor degeneration. Similar preservation of kainate receptor subunits was evident in human retina in which photoreceptors had degenerated due to serous retinal detachment. In contrast, photoreceptor degeneration leads to loss of synaptic expression of TRPM1 in mouse and human On bipolar cells, but strong somatic expression remains. These findings demonstrate that Off bipolar cells retain dendritic glutamate receptors during retinal degeneration and could thus serve as a conduit for signal transmission from transplanted or optogenetically restored photoreceptors.

  2. Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors

    PubMed Central

    Krock, Emerson; Rosenzweig, Derek H; Chabot-Doré, Anne-Julie; Jarzem, Peter; Weber, Michael H; Ouellet, Jean A; Stone, Laura S; Haglund, Lisbet

    2014-01-01

    Intervertebral disc degeneration (IVD) can result in chronic low back pain, a common cause of morbidity and disability. Inflammation has been associated with IVD degeneration, however the relationship between inflammatory factors and chronic low back pain remains unclear. Furthermore, increased levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are both associated with inflammation and chronic low back pain, but whether degenerating discs release sufficient concentrations of factors that induce nociceptor plasticity remains unclear. Degenerating IVDs from low back pain patients and healthy, painless IVDs from human organ donors were cultured ex vivo. Inflammatory and nociceptive factors released by IVDs into culture media were quantified by enzyme-linked immunosorbent assays and protein arrays. The ability of factors released to induce neurite growth and nociceptive neuropeptide production was investigated. Degenerating discs release increased levels of tumour necrosis factor-?, interleukin-1?, NGF and BDNF. Factors released by degenerating IVDs increased neurite growth and calcitonin gene-related peptide expression, both of which were blocked by anti-NGF treatment. Furthermore, protein arrays found increased levels of 20 inflammatory factors, many of which have nociceptive effects. Our results demonstrate that degenerating and painful human IVDs release increased levels of NGF, inflammatory and nociceptive factors ex vivo that induce neuronal plasticity and may actively diffuse to induce neo-innervation and pain in vivo. PMID:24650225

  3. Evaluation of the Effect of Mega MSM on Improving Joint Function in Populations Experiencing Joint Degeneration

    PubMed Central

    Xu, Gang; Zhou, Tian; Gu, Yaqin; Wang, Qinping; Shariff, Mina; Gu, Pingping; Nguyen, Tuong; Shi, Rong; Rao, Jianyu

    2015-01-01

    Joint degeneration has become a commonplace problem in aging populations. The main clinical manifestations include joint pain, joint stiffness and joint swelling with functional disorder. Mega MSM is a nutritional supplement that may provide potential relief for joint problems associated with joint degeneration. The current experiment performed was a 12-week, randomized, double-blind, controlled study conducted on populations in China experiencing joint degeneration. The objective of the study was to determine whether the daily use of Mega MSM capsules could improve joint function, relieve symptoms of joint degeneration and improve the quality of life in aging populations. A total of 100 male and female participants over 50 years old who had at least one of the related symptoms of joint degeneration (joint pain, joint stiffness, joint swelling, difficulty walking, difficulty getting up from bed and difficulty going down stairs) were recruited and their symptoms of joint degeneration before and after the intervention were recorded. In this study, Mega MSM shows positive effects in improving joint function, relieving symptoms associated with joint degeneration and improving the quality of life in aging populations. PMID:26199577

  4. Exploring the potential of quantum degenerate gases in microgravity

    NASA Astrophysics Data System (ADS)

    Ertmer, Wolfgang

    Microgravity is expected to be a decisive ingredient for the next leap in tests in fundamental physics of gravity, relativity and theories beyond the standard model. A promising technique for fundamental tests in the quantum domain are matter-wave sensors based on cold atoms or atom lasers, which use atoms as unperturbed microscopic test bodies for measuring inertial forces or as frequency references. Microgravity is of high relevance for matter-wave interferometers and experiments with quantum matter (Bose-Einstein Condensates or degenerate Fermi gases) as it permits the extension the unperturbed free fall of these test particles in a low-noise environment. Microgravity will also help to establish a new scientific avenue in the research on degenerate quantum gases. Cold quantum gases and, in particular, Bose-Einstein condensates represent a new state of matter which is nowadays established in many laboratories. They offer unique insights into a broad range of fundamental physics as well as prospects for novel quantum sensors. Microgravity will substantially extend the science of quantum gases towards nowadays inaccessible regimes at lowest temperatures, to macroscopic dimensions, and to unequalled durations of unperturbed evolution of these distinguished quantum objects. With the launch of the development of a mobile BEC platform project for microgravity experiments in the drop tower and during parabolic flights within a pilot project, running since January 2004, the DLR took a major first step to establish this field of research in Germany. The group joins the scientific expertise of leading German groups working on various aspects of cold quantum gases with the unique possibilities and technological knowledge offered by the drop tower group at ZARM, University Bremen, to introduce and explore the new field of quantum gases under microgravity. The pilot projects aims for a first technological demonstration of the feasibility of such experiments at the drop tower. The prospects of such an experiment, however, cover the study of quantum gases in the regime of unperturbed evolution with extremely large correlation length and longest unperturbed time of flight. The research will be performed with regard to scientific and technological aspects, from fundamental physical questions with low energy quantum phase transitions and the establishment of quantum correlations to measurements of highest precision in atom interferometric set-ups.

  5. Multiple Independent Oscillatory Networks in the Degenerating Retina

    PubMed Central

    Euler, Thomas; Schubert, Timm

    2015-01-01

    During neuronal degenerative diseases, microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. This can be particularly well observed in the retina, where photoreceptor degeneration triggers rewiring of connections in the retina’s first synaptic layer (e.g., Strettoi et al., 2003; Haq et al., 2014), while the synaptic organization of inner retinal circuits appears to be little affected (O’Brien et al., 2014; Figures 1A,B). Remodeling of (outer) retinal circuits and diminishing light-driven activity due to the loss of functional photoreceptors lead to spontaneous activity that can be observed at different retinal levels (Figure 1C), including the retinal ganglion cells, which display rhythmic spiking activity in the degenerative retina (Margolis et al., 2008; Stasheff, 2008; Menzler and Zeck, 2011; Stasheff et al., 2011). Two networks have been suggested to drive the oscillatory activity in the degenerating retina: a network of remnant cone photoreceptors, rod bipolar cells (RBCs) and horizontal cells in the outer retina (Haq et al., 2014), and the AII amacrine cell-cone bipolar cell network in the inner retina (Borowska et al., 2011). Notably, spontaneous rhythmic activity in the inner retinal network can be triggered in the absence of synaptic remodeling in the outer retina, for example, in the healthy retina after photo-bleaching (Menzler et al., 2014). In addition, the two networks show remarkable differences in their dominant oscillation frequency range as well as in the types and numbers of involved cells (Menzler and Zeck, 2011; Haq et al., 2014). Taken together this suggests that the two networks are self-sustained and can be active independently from each other. However, it is not known if and how they modulate each other. In this mini review, we will discuss: (i) commonalities and differences between these two oscillatory networks as well as possible interaction pathways; (ii) how multiple self-sustained networks may hamper visual restoration strategies employing, for example, microelectronic implants, optogenetics or stem cells, and briefly; and (iii) how the finding of diverse (independent) networks in the degenerative retina may relate to other parts of the neurodegenerative central nervous system. PMID:26617491

  6. Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs.

    PubMed

    Kortz, G D; Meier, W A; Higgins, R J; French, R A; McKiernan, B C; Fatzer, R; Zachary, J F

    1997-07-01

    With the recent epizootic of bovine spongiform encephalopathy in Europe, the differential diagnosis of neuronal vacuolation and spongiform change in other species has become critically important. Four Rottweiler puppies of both sexes, presented at 3-8 months of age, had clinical signs of generalized weakness and ataxia that started at 6 weeks of age. In all pups, neurologic examination detected an ataxia and tetraparesis, most severe in the pelvic limbs, and slowed proprioceptive placing reactions. Subsequently, there was rapid progressive neurologic deterioration, with severe placing deficits, knuckling, severe ataxia, and quadraparesis by 8 months of age. At necropsy, no gross lesions were observed. Microscopic lesions were restricted to the nervous system. The major lesion in all dogs was an intracytoplasmic neuronal vacuolation that was most prominent in the cerebellar roof nuclei and in nuclei of the extrapyramidal system. Similar vacuolation was found in neurons in both dorsal nerve root ganglia, myenteric plexus, and other ganglia of the autonomic nervous system. The single or multiple empty vacuoles were between 1 and 45 microm in diameter. A mild spongiform change was seen in the adjacent neuropil. Purkinje cell vacuolation and degeneration with segmental cell loss was seen in the oldest dog. In ventromedial and dorsolateral areas of the spinal cord white matter, there was mild bilaterally symmetrical axonal degeneration. Immunoblotting and immunocytochemical staining of the brain for protease-resistant scrapie prion protein was negative. All forms of vacuoles were negative for immunohistochemical staining with a variety of lectins. Ultrastructurally, the vacuoles were bound by a single membrane and contained granular material and sometimes membranous profiles. There was mild distension of the cytocavitary network but no unequivocal connection with the vacuoles was found. Axosomatic and axodendritic synapses in affected neurons were intact both ultrastructurally and with synaptophysin immunostaining. The clinicopathologic findings were different from those seen in the other neurologic diseases of Rottweilers. The age of the dogs, distribution and type of the lesions, ultrastructural findings, and negative immunoblotting most likely rule out the possibility of a scrapie agent-associated spongiform encephalopathy. However, the etiology of this new disease was not determined. PMID:9240838

  7. Subacute combined degeneration of the cord due to folate deficiency: response to methyl folate treatment.

    PubMed Central

    Lever, E G; Elwes, R D; Williams, A; Reynolds, E H

    1986-01-01

    Subacute combined degeneration of the cord is a rare complication of folate deficiency. Disturbance of methylation reactions in nervous tissue probably underlie subacute combined degeneration of the cord arising from folate as well as vitamin B12 deficiency. Methyl tetrahydrofolate is the form in which folic acid is transported into the CNS. Therefore methyl tetrahydrofolate treatment of the neurological and psychiatric manifestations of folate deficiency would seem to be theoretically advantageous. A case of subacute combined degeneration of the cord due to dietary folate deficiency and associated with an organic brain syndrome is reported. There was striking haematological, neurological and psychiatric response to methyl folate treatment. PMID:3783183

  8. Dual-pumped degenerate Kerr oscillator in a silicon nitride microresonator.

    PubMed

    Okawachi, Yoshitomo; Yu, Mengjie; Luke, Kevin; Carvalho, Daniel O; Ramelow, Sven; Farsi, Alessandro; Lipson, Michal; Gaeta, Alexander L

    2015-11-15

    We demonstrate a degenerate parametric oscillator in a silicon nitride microresonator. We use two frequency-detuned pump waves to perform parametric four-wave mixing and operate in the normal group-velocity dispersion regime to produce signal and idler fields that are frequency degenerate. Our theoretical modeling shows that this regime enables generation of bimodal phase states, analogous to the ?(2)-based degenerate OPO. Our system offers potential for realization of CMOS-chip-based coherent optical computing and an all-optical quantum random number generator. PMID:26565851

  9. Low frequency collective modes in dense relativistic-degenerate strongly coupled plasma

    NASA Astrophysics Data System (ADS)

    Khan, S. A.

    2012-07-01

    It is shown that low frequency electrostatic ion mode couples with electromagnetic shear Alfven mode in a dense plasma containing strongly coupled non-degenerate ion and relativistic degenerate electron fluids. By employing the appropriate fluid equations, a linear dispersion equation is obtained which shows modifications due to ion correlations and electron relativistic degeneracy. The results are discussed in the ultra-relativistic and weak-relativistic limits and implications of the results in dense degenerate plasmas of astrophysical origin (e.g., white dwarf stars) are pointed out with possible consequences.

  10. Degenerate Quasicrystal of Hard Triangular Bipyramids Stabilized by Entropic Forces

    NASA Astrophysics Data System (ADS)

    Haji-Akbari, Amir; Engel, Michael; Glotzer, Sharon

    2012-02-01

    The assembly of hard polyhedra into novel ordered structures has recently received much attention. Here we focus on triangular bipyramids (TBPs)- i.e. dimers of hard tetrahedra- which pack densely in a simple triclinic crystal with two particles per unit cell [1]. This packing is referred to as the TBP crystal. We show that hard TBPs do not form this densest packing in simulation. Instead, they assemble into a different, far more complicated structure, a dodecagonal quasicrystal, which, in the level of monomers, is identical to the quasicrystal recently discovered in the hard tetrahedron system [2], but the way that tetrahedra pair into TBPs in the nearest neighbor network is random, making it the first degenerate quasicrystal reported in the literature [3]. This notion of degeneracy is in the level of decorating individual tiles and is different from the degeneracy of a quasiperiodic random tiling arising from phason flips [4]. The (3.4.3^2.4) approximant of the quasicrystal is shown to be more stable than the TBP crystal at densities below 79.7%.[4pt] [1] Chen ER, Engel M, Sharon SC, Disc. Comp. Geom. 44:253 (2010).[0pt] [2] Haji-Akbari A, Engel M, et al. Nature 462:773 (2009).[0pt] [3] Haji-Akbari A, Engel M, Glotzer SC, arXiv:1106.5561 [PRL, in press].[0pt] [4] Elser V, PRL 54: 1730 (1985)

  11. The ELM Survey. VI. Eleven New Double Degenerates

    NASA Astrophysics Data System (ADS)

    Gianninas, A.; Kilic, Mukremin; Brown, Warren R.; Canton, Paul; Kenyon, Scott J.

    2015-10-01

    We present the discovery of 11 new double degenerate systems containing extremely low-mass white dwarfs (ELM WDs). Our radial velocity observations confirm that all of the targets have orbital periods ?slant 1 day. We perform spectroscopic fits and provide a complete set of physical and binary parameters. We review and compare recent evolutionary calculations and estimate that the systematic uncertainty in our mass determinations due to differences in the evolutionary models is small (? 0.01 M?). Five of the new systems will merge due to gravitational wave radiation within a Hubble time, bringing the total number of merger systems found in the ELM Survey to 38. We examine the ensemble properties of the current sample of ELM WD binaries, including the period distribution as a function of effective temperature, and the implications for the future evolution of these systems. We also revisit the empirical boundaries of instability strip of ELM WDs and identify new pulsating ELM WD candidates. Finally, we consider the kinematic properties of our sample of ELM WDs and estimate that a significant fraction of the WDs from the ELM Survey are members of the Galactic halo. Based on observations obtained at the MMT Observatory, a joint facility of the Smithsonian Institution and the University of Arizona.

  12. Pachychoroid neovasculopathy and age-related macular degeneration.

    PubMed

    Miyake, Masahiro; Ooto, Sotaro; Yamashiro, Kenji; Takahashi, Ayako; Yoshikawa, Munemitsu; Akagi-Kurashige, Yumiko; Ueda-Arakawa, Naoko; Oishi, Akio; Nakanishi, Hideo; Tamura, Hiroshi; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2015-01-01

    Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p?=?5.1?×?10(-5)) and showed a greater subfoveal choroidal thickness (p?=?3.4?×?10(-14)). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p?=?0.029), CFH rs800292 (p?=?0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p?=?3.8?×?10(-3)). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies. PMID:26542071

  13. Ocular Surface Temperature in Age-Related Macular Degeneration

    PubMed Central

    Sodi, Andrea; Giacomelli, Giovanni; Corvi, Andrea; Menchini, Ugo

    2014-01-01

    Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value?>0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD. PMID:25436140

  14. Selective mitochondrial degeneration in renal tubules following hyperbaric oxygen exposure.

    PubMed Central

    Greene, W. B.; Balentine, J. D.; Hennigar, G. R.

    1979-01-01

    To study the ultrastructural effects of hyperoxia on the kidney, young adult Sprague Dawley rats were exposed to 3 atmospheres absolute (ATAs) of pure oxygen for 5 hours and were killed in a time sequence varying from immediately to 30 days after exposure. Their renal cortices were processed for electron microscopy. Selective mitochondrial changes were observed within sublethally and transiently altered proximal tubular epithelial cells. The most consistent finding was the accumulation of 0.08 mu to 0.5 mu round to ovoid homogeneous matrical inclusions which frequently formed larger confluent amorphous masses. The inclusions stained intensely with lead and uranium but appeared homogeneously electron-lucent in unstained sections. Energy-dispersive x-ray analysis revealed that they did not contain calcium or phosphorus. The inclusions were different from the innately electron-opaque flocculent densities commonly found in pathologically altered mitochondria. Since the mitochondria containing them were removed by autophagocytosis, it is suggested that the inclusions were associated with selective mitochondrial degeneration induced by hyperoxia. No glomerular lesions were found. Images Figure 5 Figure 6 Figure 7 Figure 8 Figure 1 Figure 2 Figure 3 Figure 10 Figure 11 Figure 9 Figure 4 PMID:224708

  15. Axonal Degeneration in Dental Pulp Precedes Human Primary Teeth Exfoliation.

    PubMed

    Suzuki, K; Lovera, M; Schmachtenberg, O; Couve, E

    2015-10-01

    The dental pulp in human primary teeth is densely innervated by a plethora of nerve endings at the coronal pulp-dentin interface. This study analyzed how the physiological root resorption (PRR) process affects dental pulp innervation before exfoliation of primary teeth. Forty-four primary canine teeth, classified into 3 defined PRR stages (early, middle, and advanced) were fixed and demineralized. Longitudinal cryosections of each tooth were stained for immunohistochemical and quantitative analysis of dental pulp nerve fibers and associated components with confocal and electron microscopy. During PRR, axonal degeneration was prominent and progressive in a Wallerian-like scheme, comprising nerve fiber bundles and nerve endings within the coronal and root pulp. Neurofilament fragmentation increased significantly during PRR progression and was accompanied by myelin degradation and a progressive loss of myelinated axons. Myelin sheath degradation involved activation of autophagic activity by Schwann cells to remove myelin debris. These cells expressed a sequence of responses comprising dedifferentiation, proliferative activity, GAP-43 overexpression, and Büngner band formation. During the advanced PRR stage, increased immune cell recruitment within the dental pulp and major histocompatibility complex (MHC) class II upregulation by Schwann cells characterized an inflammatory condition associated with the denervation process in preexfoliative primary teeth. The ensuing loss of dental pulp axons is likely to be responsible for the progressive reduction of sensory function of the dental pulp during preexfoliative stages. PMID:26149320

  16. Pachychoroid neovasculopathy and age-related macular degeneration

    PubMed Central

    Miyake, Masahiro; Ooto, Sotaro; Yamashiro, Kenji; Takahashi, Ayako; Yoshikawa, Munemitsu; Akagi-Kurashige, Yumiko; Ueda-Arakawa, Naoko; Oishi, Akio; Nakanishi, Hideo; Tamura, Hiroshi; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2015-01-01

    Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p?=?5.1?×?10?5) and showed a greater subfoveal choroidal thickness (p?=?3.4?×?10?14). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p?=?0.029), CFH rs800292 (p?=?0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p?=?3.8?×?10?3). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies. PMID:26542071

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

    PubMed

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

    2008-03-01

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

  18. Epidemiology of Frontotemporal Lobar Degeneration in Northern Finland

    PubMed Central

    Luukkainen, Laura; Bloigu, Risto; Moilanen, Virpi; Remes, Anne Marja

    2015-01-01

    Background Frontotemporal lobar degeneration (FTLD) is responsible for as many as every fifth case of early-onset dementia. Very few epidemiological studies of FTLD have been conducted; there are no published epidemiological data of FTLD from Finland or the other Nordic countries. The C9ORF72 expansion-associated FTLD is common in Finland; thus, the prevalence of FTLD is expected to be high in this population. Methods We retrospectively evaluated the incidence and prevalence of FTLD in university hospital settings in Northern Finland. Results The mean 1-year incidence of FTLD was 5.54/100,000 (range 1.9-11.3/100,000) in the population aged 45-65 years. The prevalence of FTLD in the same age group was 20.5/100,000. Conclusion The incidence and prevalence of FTLD in Finland seem to be the highest in Europe. However, studies from different countries may not be directly mutually comparable due to methodological issues. PMID:26675285

  19. Quantum correlation in degenerate optical parametric oscillators with mutual injections

    NASA Astrophysics Data System (ADS)

    Takata, Kenta; Marandi, Alireza; Yamamoto, Yoshihisa

    2015-10-01

    We theoretically and numerically study the quantum dynamics of two degenerate optical parametric oscillators with mutual injections. The cavity mode in the optical coupling path between the two oscillator facets is explicitly considered. Stochastic equations for the oscillators and mutual injection path based on the positive P representation are derived. The system of two gradually pumped oscillators with out-of-phase mutual injections is simulated, and its quantum state is investigated. When the incoherent loss of the oscillators other than the mutual injections is small, the squeezed quadratic amplitudes p ? in the oscillators are positively correlated near the oscillation threshold. It indicates finite quantum correlation, estimated via Gaussian quantum discord, and the entanglement between the intracavity subharmonic fields. When the loss in the injection path is low, each oscillator around the phase transition point forms macroscopic superposition even under a small pump noise. It suggests that the squeezed field stored in the low-loss injection path weakens the decoherence in the oscillators.

  20. Age-related macular degeneration: linking clinical presentation to pathology.

    PubMed

    Nivison-Smith, Lisa; Milston, Rebecca; Madigan, Michele; Kalloniatis, Michael

    2014-08-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide in the elderly population. Optometrists, as primary eye health care providers, require the skills and knowledge to accurately diagnose and manage AMD patients. There is an overwhelming body of research related to the clinical presentation, etiology, epidemiology, and pathology of this disease. Additionally, the evolution of new imaging modalities creates new opportunities to clinically detect and analyze previously uncharacterized and earlier changes in the retina. The challenge for optometrists is to combine all this information into an applicable knowledge base for use in everyday clinical assessment of AMD so that timely and accurate referrals can be made to retinal specialists. This review attempts to address this issue by linking the clinical presentation of AMD with the underlying disease biology. We emphasize the contribution of recent noninvasive imaging technologies to the clinical assessment of early and more advanced AMD including optical coherence tomography, fundus autofluorescence, and infrared reflectance. PMID:24879089

  1. Clinical characteristics and current therapies for inherited retinal degenerations.

    PubMed

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

    2015-02-01

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

  2. Donor and acceptor concentrations in degenerate InN

    SciTech Connect

    Look, D.C.; Lu, H.; Schaff, W.J.; Jasinski, J.; Liliental-Weber, Z.

    2002-01-28

    A formalism is presented to determine donor (N{sub D}) and acceptor (N{sub A}) concentrations in wurtzitic InN characterized by degenerate carrier concentration (n) and mobility ({mu}). The theory includes scattering not only by charged point defects and impurities, but also by charged threading dislocations, of concentration N{sub dis}. For an 0.45-{micro}m-thick InN layer grown on Al{sub 2}O{sub 3} by molecular beam epitaxy, having N{sub dis} = 5 x 10{sup 10} cm{sup -2}, determined by transmission electron microscopy, n(20 K) = 3.5 x 10{sup 18} cm{sup -3}, and {mu}(20 K) = 1055 cm{sup 2}/V-s, determined by Hall-effect measurements, the fitted values are N{sub D} = 4.7 x 10{sup 18} cm{sup -3} and N{sub A} = 1.2 x 10{sup 18} cm{sup -3}. The identities of the donors and acceptors are not known, although a comparison of N{sub D} with analytical data, and also with calculations of defect formation energies, suggests that a potential candidate for the dominant donor is H.

  3. The ELM Survey. VI. Eleven New Double Degenerates

    E-print Network

    Gianninas, A; Brown, Warren R; Canton, Paul; Kenyon, Scott J

    2015-01-01

    We present the discovery of 11 new double degenerate systems containing extremely low-mass white dwarfs (ELM WDs). Our radial velocity observations confirm that all of the targets have orbital periods $\\leq$ 1 day. We perform spectroscopic fits and provide a complete set of physical and binary parameters. We review and compare recent evolutionary calculations and estimate that the systematic uncertainty in our mass determinations due to differences in the evolutionary models is small ($\\approx$ 0.01 M$_{\\odot}$). Five of the new systems will merge due to gravitational wave radiation within a Hubble time, bringing the total number of merger systems found in the ELM Survey to 38. We examine the ensemble properties of the current sample of ELM WD binaries, including the period distribution as a function of effective temperature, and the implications for the future evolution of these systems. We also revisit the empirical boundaries of instability strip of ELM WDs and identify new pulsating ELM WD candidates. Fin...

  4. Mechanism of Inflammation in Age-Related Macular Degeneration

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  5. Prevalence of age-related macular degeneration among the elderly

    PubMed Central

    Rasoulinejad, Seyed Ahmad; Zarghami, Amin; Hosseini, Seyed Reza; Rajaee, Neda; Rasoulinejad, Seyed Elahe; Mikaniki, Ebrahim

    2015-01-01

    Background: Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in elderly population in the developing countries. Previous epidemiological studies revealed various potential modifiable risk factors for this disease. The purpose of this study was to evaluate the prevalence of AMD among elderly living in Babol, North of Iran. Methods: The study population of this cross-sectional study came from the Amirkola Health and Ageing Project (AHAP), the first comprehensive cohort study of the health of people aged 60 years and over in Amirkola, North of Iran. The prevalence of AMD was estimated and its risk was determined using logistic regression analysis (LRA) with regard to variables such as smoking, hyperlipidemia, hypertension and diabetes. Results: Five hundred and five participants with mean age of 71.55±5.9 (ranged 60-89) years entered the study. The prevalence of AMD was 17.6%. There was a significant association between AMD and smoking (P<0.001) but no association was seen with AMD and age, level of education, history of hyperlipidemia, hypertension and diabetes. Multiple LRAs revealed that smoking increased AMD by odds ratio of 5.03 (95% confidence interval 2.47-10.23 p<0.001) as compared to nonsmokers Conclusion: According to our findings, the prevalence of AMD was relatively high and smoking increased the risk of AMD in the elderly population.

  6. Age-Related Macular Degeneration: A Scientometric Analysis

    PubMed Central

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993–2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic’s structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  7. Omega-3 Fatty Acids and Age-Related Macular Degeneration.

    PubMed

    Souied, Eric H; Aslam, Tariq; Garcia-Layana, Alfredo; Holz, Frank G; Leys, Anita; Silva, Rufino; Delcourt, Cécile

    2015-12-01

    Against a background of considerable epidemiological and other evidence implicating omega-3 fatty acids in the prevention of age-related macular degeneration (AMD), the negative results of the Age-Related Disease Study 2 (AREDS2) were unexpected. The possibility that the design, setting, intake or subjects of AREDS2 may not have permitted the prophylactic potential of omega-3 to be adequately demonstrated is considered. Epidemiological studies had indicated potential preventative effects of omega-3, and an earlier randomised prospective study (NAT2) showed that patients who achieved high red blood cell membrane EPA/DHA (eicosapentaenoic acid/docosahexaenoic acid) levels were significantly protected against AMD compared with those with permanently low EPA/DHA levels. Various methodological differences between these studies are considered. NAT2 included a true placebo group, whereas control subjects in AREDS2 received a nutritional formula already found to be effective in AREDS1, but no placebo for DHA/EPA supplementation. Differences in the handling of non-compliant subjects and the formulation of the test formulations are considered. Given these considerations, and other lines of evidence from laboratory and clinical studies, closing the chapter on omega-3 in AMD prevention may be premature. PMID:26610051

  8. 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

  9. Detecting Superlight Dark Matter with Fermi-Degenerate Materials

    E-print Network

    Yonit Hochberg; Matt Pyle; Yue Zhao; Kathryn M. Zurek

    2015-12-14

    We examine in greater detail the recent proposal of using superconductors for detecting dark matter as light as the warm dark matter limit of O(keV). Detection of such light dark matter is possible if the entire kinetic energy of the dark matter is extracted in the scattering, and if the experiment is sensitive to O(meV) energy depositions. This is the case for Fermi-degenerate materials in which the Fermi velocity exceeds the dark matter velocity dispersion in the Milky Way of ~10^-3. We focus on a concrete experimental proposal using a superconducting target with a transition edge sensor in order to detect the small energy deposits from the dark matter scatterings. Considering a wide variety of constraints, from dark matter self-interactions to the cosmic microwave background, we show that models consistent with cosmological/astrophysical and terrestrial constraints are observable with such detectors. We also show that metal targets pay a strong in-medium suppression for kinetically mixed mediators; this suppression is alleviated with insulating targets.

  10. Detecting Superlight Dark Matter with Fermi-Degenerate Materials

    E-print Network

    Hochberg, Yonit; Zhao, Yue; Zurek, Kathryn M

    2015-01-01

    We examine in greater detail the recent proposal of using superconductors for detecting dark matter as light as the warm dark matter limit of O(keV). Detection of such light dark matter is possible if the entire kinetic energy of the dark matter is extracted in the scattering, and if the experiment is sensitive to O(meV) energy depositions. This is the case for Fermi-degenerate materials in which the Fermi velocity exceeds the dark matter velocity dispersion in the Milky Way of ~10^-3. We focus on a concrete experimental proposal using a superconducting target with a transition edge sensor in order to detect the small energy deposits from the dark matter scatterings. Considering a wide variety of constraints, from dark matter self-interactions to the cosmic microwave background, we show that models consistent with cosmological/astrophysical and terrestrial constraints are observable with such detectors. We also show that metal targets pay a strong in-medium suppression for kinetically mixed mediators; this su...

  11. Biomarkers in Frontotemporal Lobar Degenerations – Progress and Challenges

    PubMed Central

    Hu, William T.; Trojanowski, John Q.; Shaw, Leslie M.

    2011-01-01

    Neuronal and glial changes associated with tau, TAR DNA binding protein of ~43 kD (TDP-43), and fused in sarcoma (FUS) together constitute the pathologic spectrum of frontotemporal lobar degeneration (FTLD). Most patients with FTLD present with prominent behavior or language changes, sometimes accompanied by extrapyramidal symptoms or motor neuron disease. Identification of FTLD patients with mutations in genes for tau, TDP-43, and FUS lends strong support for their pathogenic roles in FTLD, and elucidation of their dysfunction will pave the way for development of substrate specific therapy. However, there remains no reliable biomarker for early detection of FTLD or prediction of underlying FTLD pathologic change. Clinical syndromes usually reflects the earliest affected brain regions where atrophy can be visualized on structural MRI, but neither clinical nor structural imaging-based biomarkers has been accurately correlated with underlying pathology on the individual patient level. Biochemical markers in the cerebrospinal fluid (CSF) have also been investigated in FTLD and related disorders, including amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP). However, their accuracy and pathologic significance need to be confirmed in future multi-center studies. Here we review the progress made in FTLD biomarkers, including clinical phenotype/feature characterization, neuropsychological analysis, CSF and plasma analytes, and patterns of brain atrophy and network dysfunction detectable on brain imaging. Given the pathologic overlap of FTLD with ALS and PSP, collaboration with specialists in those fields will be essential in the translation of promising FTLD biomarkers into clinical practice. PMID:21554923

  12. Nitroxide pharmaceutical development for age-related degeneration and disease

    PubMed Central

    Zarling, Jacob A.; Brunt, Vienna E.; Vallerga, Anne K.; Li, Weixing; Tao, Albert; Zarling, David A.; Minson, Christopher T.

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed. PMID:26594225

  13. Nutritional Risk Factors for Age-Related Macular Degeneration

    PubMed Central

    Ersoy, Lebriz; Lechanteur, Yara T.; Hoyng, Carel B.; Kirchhof, Bernd; den Hollander, Anneke I.

    2014-01-01

    Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). Results. In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 × 10?6; 2–6x/week: OR: 1.67, P = 7.98 × 10?5) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2–6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. Conclusion. Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD. PMID:25101280

  14. Cellular models and therapies for age-related macular degeneration

    PubMed Central

    Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

    2015-01-01

    ABSTRACT Age-related macular degeneration (AMD) is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE) cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD). A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease. PMID:26035859

  15. Resonant scattering and recombination of pseudo-degenerate WIMPs

    E-print Network

    Maxim Pospelov; Adam Ritz

    2008-08-27

    We consider the direct and indirect detection signatures of WIMPs \\chi^0 in kinematic regimes with a heavier, but nearly degenerate, charged state \\chi^{+-}. For small splittings of O(10) MeV, the scattering of WIMPs off nuclei may be dominated by inelastic recombination processes mediated by the formation of (\\chi^- N) bound states, leading to a distinct signature for direct detection. These cross-sections are bound primarily by limits on the abundance of heavy isotopes, and may be considerably larger than the elastic scattering cross section in more conventional models. If the mass splitting is too large for recombination to occur, there may still be a significant resonant enhancement of loop-induced electromagnetic form-factors of the WIMP, which can enhance the elastic scattering cross-section. We also discuss how this regime affects the annihilation cross-section and indirect detection signatures, and note the possibility of a significant mono-energetic \\gamma-signal, mediated by resonant processes near the (\\chi^+\\chi^-) bound state threshold.

  16. Genetic & Neuronanatomic Associations in Sporadic Frontotemporal Lobar Degeneration

    PubMed Central

    McMillan, Corey T.; Toledo, Jon B.; Avants, Brian B.; Cook, Philip A.; Wood, Elisabeth M.; Suh, Eunran; Irwin, David J.; Powers, John; Olm, Christopher; Elman, Lauren; McCluskey, Leo; Schellenberg, Gerard D.; Lee, Virginia M.-Y.; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Grossman, Murray

    2014-01-01

    Genome-wide association studies have identified SNPs that are sensitive for tau or TDP-43 pathology in frontotemporal lobar degeneration (FTLD). Neuroimaging analyses have revealed distinct distributions of disease in FTLD patients with genetic mutations. However, genetic influences on neuroanatomical structure in sporadic FTLD have not been assessed. In this report we use novel multivariate tools, eigenanatomy and sparse canonical correlation analysis (SCCAN), to identify associations between SNPs and neuroanatomical structure in sporadic FTLD. MRI analyses revealed that rs8070723 (MAPT) was associated with grey matter variance in the temporal cortex. DTI analyses revealed that rs1768208 (MOBP), rs646776 (near SORT1) and rs5848 (PGRN) were associated with white matter variance in the midbrain and superior longitudinal fasciculus. In an independent autopsy series we observed that rs8070723 and rs1768208 conferred significant risk of tau pathology relative to TDP-43, and rs646776 conferred increased risk of TDP-43 pathology relative to tau. Identified brain regions and SNPs may help provide an in vivo screen for underlying pathology in FTLD and contribute to our understanding of sporadic FTLD. PMID:24373676

  17. Anterior temporal lobe degeneration produces widespread network-driven dysfunction

    PubMed Central

    Guo, Christine C.; Gorno-Tempini, Maria Luisa; Gesierich, Benno; Henry, Maya; Trujillo, Andrew; Shany-Ur, Tal; Jovicich, Jorge; Robinson, Simon D.; Kramer, Joel H.; Rankin, Katherine P.; Miller, Bruce L.

    2013-01-01

    The neural organization of semantic memory remains much debated. A ‘distributed-only’ view contends that semantic knowledge is represented within spatially distant, modality-selective primary and association cortices. Observations in semantic variant primary progressive aphasia have inspired an alternative model featuring the anterior temporal lobe as an amodal hub that supports semantic knowledge by linking distributed modality-selective regions. Direct evidence has been lacking, however, to support intrinsic functional interactions between an anterior temporal lobe hub and upstream sensory regions in humans. Here, we examined the neural networks supporting semantic knowledge by performing a multimodal brain imaging study in healthy subjects and patients with semantic variant primary progressive aphasia. In healthy subjects, the anterior temporal lobe showed intrinsic connectivity to an array of modality-selective primary and association cortices. Patients showed focal anterior temporal lobe degeneration but also reduced physiological integrity throughout distributed modality-selective regions connected with the anterior temporal lobe in healthy controls. Physiological deficits outside the anterior temporal lobe correlated with scores on semantic tasks and with anterior temporal subregion atrophy, following domain-specific and connectivity-based predictions. The findings provide a neurophysiological basis for the theory that semantic processing is orchestrated through interactions between a critical anterior temporal lobe hub and modality-selective processing nodes. PMID:24072486

  18. Age-Related Macular Degeneration: Genetics and Biology Coming Together

    PubMed Central

    Fritsche, Lars G.; Fariss, Robert N.; Stambolian, Dwight; Abecasis, Gonçalo R.; Curcio, Christine A.

    2014-01-01

    Genetic and genomic studies have enhanced our understanding of complex neurodegenerative diseases that exert a devastating impact on individuals and society. One such disease, age-related macular degeneration (AMD), is a major cause of progressive and debilitating visual impairment. Since the pioneering discovery in 2005 of complement factor H (CFH) as a major AMD susceptibility gene, extensive investigations have confirmed 19 additional genetic risk loci, and more are anticipated. In addition to common variants identified by now-conventional genome-wide association studies, targeted genomic sequencing and exome-chip analyses are uncovering rare variant alleles of high impact. Here, we provide a critical review of the ongoing genetic studies and of common and rare risk variants at a total of 20 susceptibility loci, which together explain 40–60% of the disease heritability but provide limited power for diagnostic testing of disease risk. Identification of these susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment. PMID:24773320

  19. White matter degeneration in schizophrenia: a comparative diffusion tensor analysis

    NASA Astrophysics Data System (ADS)

    Ingalhalikar, Madhura A.; Andreasen, Nancy C.; Kim, Jinsuh; Alexander, Andrew L.; Magnotta, Vincent A.

    2010-03-01

    Schizophrenia is a serious and disabling mental disorder. Diffusion tensor imaging (DTI) studies performed on schizophrenia have demonstrated white matter degeneration either due to loss of myelination or deterioration of fiber tracts although the areas where the changes occur are variable across studies. Most of the population based studies analyze the changes in schizophrenia using scalar indices computed from the diffusion tensor such as fractional anisotropy (FA) and relative anisotropy (RA). The scalar measures may not capture the complete information from the diffusion tensor. In this paper we have applied the RADTI method on a group of 9 controls and 9 patients with schizophrenia. The RADTI method converts the tensors to log-Euclidean space where a linear regression model is applied and hypothesis testing is performed between the control and patient groups. Results show that there is a significant difference in the anisotropy between patients and controls especially in the parts of forceps minor, superior corona radiata, anterior limb of internal capsule and genu of corpus callosum. To check if the tensor analysis gives a better idea of the changes in anisotropy, we compared the results with voxelwise FA analysis as well as voxelwise geodesic anisotropy (GA) analysis.

  20. Automatic age-related macular degeneration detection and staging

    NASA Astrophysics Data System (ADS)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  1. Age-Related Macular Degeneration: A Scientometric Analysis.

    PubMed

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993-2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic's structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  2. [Age-related macular degeneration - biology and treatment].

    PubMed

    Klettner, Alexa

    2015-07-01

    Age-related macular degeneration (AMD) is the main cause for legal blindness of the elderly in the industrialized world and due to the demographic changes of the Western societies the prevalence is expected to increase strongly. The late forms of this disease are differentiated into geographic atrophy and exsudative (wet) AMD, where vessels grow from the choroid into the retina. On a biological level, the most important structure ofAMD pathogenesis in the photoreceptor/retinal pigment epithelium (RPE)/choroid complex. The interaction of the components of this structure enables the photoreceptors to function. Age-related alterations of this complex play an important role in the development of AMD. The exact triggers for AMD onset, however, are not known. There are no available therapies for the early forms of AMD or for geographic atrophy. However, the exsudative form can be treated by inhibiting vascular endothelial growth factor (VEGF). The currently available therapeutics (ranibizumab, aflibercept, bevacizumab) show good results in the clinic, however, in order to uphold the therapeutic effect they have to be regularly injected into the vitreous body. The inhibitors differ on a molecular level as well as on a biological level concerning their interaction with retinal pigment epithelial cells. PMID:26364363

  3. SINGLE-DEGENERATE TYPE Ia SUPERNOVAE WITHOUT HYDROGEN CONTAMINATION

    SciTech Connect

    Justham, Stephen

    2011-04-01

    The lack of hydrogen in spectra of type Ia supernovae (SNe Ia) is often seen as troublesome for single-degenerate (SD) progenitor models. We argue that, since continued accretion of angular momentum can prevent explosion of the white dwarf, it may be natural for the donor stars in SD progenitors of SNe Ia to exhaust their envelopes and shrink rapidly before the explosion. This outcome seems most likely for SD SN Ia progenitors where mass transfer begins from a giant donor star and might extend to other SD systems. Not only is the amount of hydrogen left in such a system below the current detection limit, but the donor star is typically orders of magnitude smaller than its Roche lobe by the point when an SD SN Ia occurs, in which case attempts to observe collisions between SN shocks and giant donor stars seem unlikely to succeed. We consider the constraints on this model from the circumstellar structures seen in spectra of SN 2006X and suggest a novel explanation for the origin of this material.

  4. Detection of genetic alterations in Korean ovarian carcinomas by degenerate oligonucleotide primed polymerase chain reaction-comparative genomic hybridization.

    PubMed

    Kim, Gi-Jin; Kim, Joo-Oh; Hong, Eun-Kyung; Kim, Hyun; Chun, Yong-Hyuck; Park, Sun-Hwa

    2003-11-01

    Chromosomal aberrations in 22 Koreans with ovarian carcinomas were investigated by degenerate oligonucleotide primed-polymerase chain reaction comparative genomic hybridization. The common sites of copy number increases were 20q (90%), 17q23 approximately qter (86%), 8q22 approximately qter (68%), 3q25 approximately qter (59%), 6p21 (59%), 11q13 (54%), 16p (40%), 2q31 approximately qter (36%), 7q (36%), 14q31 (36%), 15q24 approximately qter (36%), and 1q32 approximately qter (31%). DNA amplification was identified in 18 carcinomas (82%). The frequent sites of amplification were 20q13.2 approximately qter, 8q24.1, 17q23 approximately qter, 3q25 approximately qter, and 6p21. The most frequent sites of copy number decreases were 4q21 approximately q31 (54%), 5q13 approximately q21 (50%), and 13q14 approximately q21 (45%). The recurrent gains and losses of chromosomal regions identified in this study provide candidate regions that may contain oncogenes or tumor suppressor genes, respectively. PMID:14580767

  5. Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis.

    PubMed

    Sun, Fang; Lin, Chien-Liang Glenn; McTigue, Dana; Shan, Xiu; Tovar, C Amy; Bresnahan, Jacqueline C; Beattie, Michael S

    2010-08-15

    Wallerian degeneration in the dorsal columns (DC) after spinal cord injury (SCI) is associated with microglial activation and prolonged oligodendrocyte (OL) apoptosis that may contribute to demyelination and dysfunction after SCI. But, there is an increase in OL lineage cells after SCI that may represent a reparative response, and there is evidence for remyelination after SCI. To assess the role of axonal degeneration per se in OL apoptosis and proliferation, we cut the L2-S2 dorsal roots producing massive axonal degeneration and microglial activation in the DC, and found no evidence of OL loss or apoptosis. Rather, the numbers of OL-lineage cells positive for NG2 and APC (CC1) increased, and BrdU studies suggested new OL formation. We then tested contusion SCI (cSCI) that results in comparable degeneration in the DC rostral to the injury, microglial activation, and apoptosis of DC OLs by eight days. NG2+ cell proliferation and oligodendrogenesis was seen as after rhizotomy. The net result of this combination of proliferation and apoptosis was a reduction in DC OLs, confirming earlier studies. Using an antibody to oxidized nucleic acids, we found rapid and prolonged RNA oxidation in OLs rostral to cSCI, but no evidence of oxidative stress in DC OLs after rhizotomy. These results suggest that signals associated with axonal degeneration are sufficient to induce OL proliferation, and that secondary injury processes associated with the central SCI, including oxidative stress, rather than axonal degeneration per se, are responsible for OL apoptosis. PMID:20607865

  6. Transapical implantation of an Edwards SAPIEN XT in a degenerated mitral bioprosthesis without fluoroscopic landmarks.

    PubMed

    Salizzoni, Stefano; Barbero, Cristina; Grosso Marra, Walter; Moretti, Claudio; Rinaldi, Mauro

    2014-09-01

    An 84-year-old male with degeneration of a radiolucent mitral bioprosthesis was successfully treated with transapical valve-in-valve implantation exclusively guided by transesophageal echocardiography. The techniques involved in performing this procedure are reviewed. PMID:24641319

  7. Creating a quantum degenerate gas of stable molecules via weak photoassociation

    SciTech Connect

    Mackie, Matt; Phou, Pierre

    2010-07-15

    Quantum degenerate molecules represent a new paradigm for fundamental studies and practical applications. Association of already quantum degenerate atoms into molecules provides a crucial shortcut around the difficulty of cooling molecules to ultracold temperatures. Whereas association can be induced with either laser or magnetic fields, photoassociation requires impractical laser intensity to overcome poor overlap between the atom pair and molecular wave functions, and experiments are currently restricted to magnetoassociation. Here we model realistic production of a quantum degenerate gas of stable molecules via two-photon photoassociation of Bose-condensed atoms. An adiabatic change of the laser frequency converts the initial atomic condensate almost entirely into stable molecular condensate, even for low-intensity lasers. Results for dipolar LiNa provide an upper bound on the necessary photoassociation laser intensity for alkali-metal atoms {approx}30 W/cm{sup 2}, indicating a feasible path to quantum degenerate molecules beyond magnetoassociation.

  8. Cell Signaling Pathways Related to Pain Receptors in the Degenerated Disk

    PubMed Central

    Hiyama, Akihiko; Sakai, Daisuke; Mochida, Joji

    2013-01-01

    Many of the causes of low back pain are still unknown; sufficient evidence indicates that both degenerative and mechanical change within the intervertebral disk (IVD) is a relevant factor. This article reviews intracellular signaling pathways related to pain receptors in the degenerated IVD. Several reports have demonstrated the number of nerve fibers in the IVD was increased in degenerated disks. In recent years, some groups have reported that an increase in nerve fibers is associated with the presence of inflammatory mediators and/or neurotrophins in the IVD. Cell signaling events, which are regulated by inflammatory mediators and neurotrophins, must be identified to clarify the mechanism underlying low back pain. Major intracellular signaling pathways (nuclear factor kappa ?, mitogen-activated protein kinases, and Wnts) potentially play vital roles in mediating the molecular events responsible for the initiation and progression of IVD degeneration. These signaling pathways may represent therapeutic targets for the treatment of IVD degeneration and its associated back pain. PMID:24436867

  9. The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration

    PubMed Central

    Wang, Shiuan; Tan, Kai Li; Agosto, Melina A.; Xiong, Bo; Yamamoto, Shinya; Sandoval, Hector; Jaiswal, Manish; Bayat, Vafa; Zhang, Ke; Charng, Wu-Lin; David, Gabriela; Duraine, Lita; Venkatachalam, Kartik; Wensel, Theodore G.; Bellen, Hugo J.

    2014-01-01

    Rhodopsin mistrafficking can cause photoreceptor (PR) degeneration. Upon light exposure, activated rhodopsin 1 (Rh1) in Drosophila PRs is internalized via endocytosis and degraded in lysosomes. Whether internalized Rh1 can be recycled is unknown. Here, we show that the retromer complex is expressed in PRs where it is required for recycling endocytosed Rh1 upon light stimulation. In the absence of subunits of the retromer, Rh1 is processed in the endolysosomal pathway, leading to a dramatic increase in late endosomes, lysosomes, and light-dependent PR degeneration. Reducing Rh1 endocytosis or Rh1 levels in retromer mutants alleviates PR degeneration. In addition, increasing retromer abundance suppresses degenerative phenotypes of mutations that affect the endolysosomal system. Finally, expressing human Vps26 suppresses PR degeneration in Vps26 mutant PRs. We propose that the retromer plays a conserved role in recycling rhodopsins to maintain PR function and integrity. PMID:24781186

  10. Creating a quantum degenerate gas of stable molecules via weak photoassociation

    NASA Astrophysics Data System (ADS)

    Mackie, Matt; Phou, Pierre

    2010-07-01

    Quantum degenerate molecules represent a new paradigm for fundamental studies and practical applications. Association of already quantum degenerate atoms into molecules provides a crucial shortcut around the difficulty of cooling molecules to ultracold temperatures. Whereas association can be induced with either laser or magnetic fields, photoassociation requires impractical laser intensity to overcome poor overlap between the atom pair and molecular wave functions, and experiments are currently restricted to magnetoassociation. Here we model realistic production of a quantum degenerate gas of stable molecules via two-photon photoassociation of Bose-condensed atoms. An adiabatic change of the laser frequency converts the initial atomic condensate almost entirely into stable molecular condensate, even for low-intensity lasers. Results for dipolar LiNa provide an upper bound on the necessary photoassociation laser intensity for alkali-metal atoms ~30 W/cm2, indicating a feasible path to quantum degenerate molecules beyond magnetoassociation.

  11. Axons Degenerate in the Absence of Mitochondria in C. elegans

    E-print Network

    Rawson, Randi L.

    Many neurodegenerative disorders are associated with mitochondrial defects [1, 2 and 3]. Mitochondria can play an active role in degeneration by releasing reactive oxygen species and apoptotic factors [4, 5, 6 and 7]. ...

  12. Reorganization of Visual Processing in Macular Degeneration Is Not Specific to the "Preferred Retinal Locus"

    E-print Network

    Baker, Chris I.

    Recent work has shown that foveal cortex, deprived of its normal bottom-up input as a result of macular degeneration (MD), begins responding to stimuli presented to a peripheral retinal location. However, these studies ...

  13. Natural guardians of the race: heredity, hygiene, alcohol, and degeneration in Scottish Psychiatry, c. 1860 – 1920 

    E-print Network

    Wood, James Anthony

    2012-06-29

    This thesis investigates the ways in which hereditary degeneration was discussed by Scottish psychiatrists in the late nineteenth and early twentieth centuries with particular reference to the anti-alcohol debate. I ...

  14. Nonnegative global weak solutions for a degenerate parabolic system modeling thin films driven by capillarity

    E-print Network

    Matioc, Bogdan-Vasile

    2011-01-01

    We prove global existence of nonnegative weak solutions for a strongly coupled, fourth order degenerate parabolic system governing the motion of two thin fluid layers in a porous medium when capillarity is the sole driving mechanism.

  15. Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice

    PubMed Central

    Galli, Soledad; Lopes, Douglas M.; Ammari, Rachida; Kopra, Jaakko; Millar, Sarah E.; Gibb, Alasdair; Salinas, Patricia C.

    2014-01-01

    Synapse degeneration is an early and invariant feature of neurodegenerative diseases. Indeed, synapse loss occurs prior to neuronal degeneration and correlates with the symptom severity of these diseases. However, the molecular mechanisms that trigger synaptic loss remain poorly understood. Here we demonstrate that deficient Wnt signalling elicits synaptic degeneration in the adult striatum. Inducible expression of the secreted Wnt antagonist Dickkopf1 (Dkk1) in adult mice (iDkk1) decreases the number of cortico-striatal glutamatergic synapses and of D1 and D2 dopamine receptor clusters. Synapse loss occurs in the absence of axon retraction or cell death. The remaining excitatory terminals contain fewer synaptic vesicles and have a reduced probability of evoked transmitter release. IDkk1 mice show impaired motor coordination and are irresponsive to amphetamine. These studies identify Wnts as key endogenous regulators of synaptic maintenance and suggest that dysfunction in Wnt signalling contributes to synaptic degeneration at early stages in neurodegenerative diseases. PMID:25318560

  16. Exponential Mixing of the 3D Stochastic Navier-Stokes Equations Driven by Mildly Degenerate Noises

    SciTech Connect

    Albeverio, Sergio; Debussche, Arnaud; Xu Lihu

    2012-10-15

    We prove the strong Feller property and exponential mixing for 3D stochastic Navier-Stokes equation driven by mildly degenerate noises (i.e. all but finitely many Fourier modes being forced) via a Kolmogorov equation approach.

  17. Primary neuronal degeneration in the guinea pig effects on spontaneous rate-type

    E-print Network

    Furman, Adam C. (Adam Charles)

    2013-01-01

    Acoustic overexposure can cause death of cochlear nerve fibers, even if elevations in cochlear sensitivity are reversible and even if there is no hair cell loss. We hypothesized that this primary neural degeneration does ...

  18. Investigating the genetic and molecular basis of age-related macular degeneration 

    E-print Network

    Stanton, Chloe May

    2012-06-30

    Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years. Environmental and genetic risk-factors contribute to the development ...

  19. Alpha-Synuclein Disrupted Dopamine Homeostasis Leads to Dopaminergic Neuron Degeneration in Caenorhabditis elegans

    E-print Network

    Cao, Pengxiu; Yuan, Yiyuan; Pehek, Elizabeth A.; Moise, Alexander R.; Huang, Ying; Palczewski, Krzysztof; Feng, Zhaoyang

    2010-02-19

    Disruption of dopamine homeostasis may lead to dopaminergic neuron degeneration, a proposed explanation for the specific vulnerability of dopaminergic neurons in Parkinson's disease. While expression of human ?-synuclein in C. elegans results...

  20. Malignant degeneration of perineal endometriosis in episiotomy scar, case report and review of the literature.

    PubMed

    Chene, G; Darcha, C; Dechelotte, P; Mage, G; Canis, M

    2007-01-01

    Although malignant degeneration of cutaneous endometriosis is rare at only 0.3-1% in endometriosis surgical scars, diagnosis and management need to be defined. A case of malignant degeneration of perineal endometriosis is reported, with a review of literature. Physiopathology, epidemiological data, diagnostic and therapeutic methods are discussed for malignant degeneration of cutaneous endometriosis. Any scar lesion that evolves in response to the menstrual cycle should be considered endometriosis until proven otherwise, and thus could require surgical resection, with histological analysis. A history of cutaneous endometriosis with frequent recurrences can indicate malignant degeneration. All cases require long-term clinical follow-up because, despite the rarity of this diagnosis, the delay between benign endometriosis and malignant transformation can vary from a few months to over 40 years. PMID:17300680

  1. Computation of angle averaged cross sections in a degenerate Compton scattering medium

    SciTech Connect

    Nickel, G.H.; Pochkowski, M.; Bailey, W.F.

    1985-01-01

    An accurate yet simple analytic method is developed for calculating Compton scattering cross sections for monoenergetic photons interacting with an isotropic and degenerate distribution of relativistic electrons. 4 refs., 2 figs.

  2. Exploring the Origin of Nearly Degenerate Doublet Bands in Ag106

    NASA Astrophysics Data System (ADS)

    Rather, N.; Datta, P.; Chattopadhyay, S.; Rajbanshi, S.; Goswami, A.; Bhat, G. H.; Sheikh, J. A.; Roy, S.; Palit, R.; Pal, S.; Saha, S.; Sethi, J.; Biswas, S.; Singh, P.; Jain, H. C.

    2014-05-01

    The lifetimes of the excited levels for the two nearly degenerate bands of Ag106 have been measured using the Doppler-shift attenuation method. The deduced B(E2) and B(M1) rates in the two bands are found to be similar, except around the band crossing spin, while their moments of inertia are quite different. This is a novel observation for a nearly degenerate doublet band.

  3. Temperature jump in degenerate quantum gases in the presence of a Bose - Einstein condensate

    E-print Network

    A. V. Latyshev; A. A. Yushkanov

    2010-01-04

    We construct a kinetic equation modeling the behavior of degenerate quantum Bose gases whose collision rate depends on the momentum of elementary excitations. We consider the case where the phonon component is the decisive factor in the elementary excitations. We analytically solve the half-space boundary value problem of the temperature jump at the boundary of the degenerate Bose gas in the presence of a Bose -- Einstein condensate.

  4. Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration[S

    PubMed Central

    Chen, Hui; Tran, Julie-Thu A.; Eckerd, Annette; Huynh, Tuan-Phat; Elliott, Michael H.; Brush, Richard S.; Mandal, Nawajes A.

    2013-01-01

    Light-induced retinal degeneration (LIRD) in albino rats causes apoptotic photoreceptor cell death. Ceramide is a second messenger for apoptosis. We tested whether increases in ceramide mediate photoreceptor apoptosis in LIRD and if inhibition of ceramide synthesis protects the retina. Sprague-Dawley rats were exposed to 2,700 lux white light for 6 h, and the retinal levels of ceramide and its intermediary metabolites were measured by GC-MS or electrospray ionization tandem mass spectrometry. Enzymes of the de novo biosynthetic and sphingomyelinase pathways of ceramide generation were assayed, and gene expression was measured. The dosage and temporal effect of the ceramide synthase inhibitor FTY720 on the LIRD retina were measured by histological and functional analyses. Retinal ceramide levels increased coincident with the increase of dihydroceramide at various time points after light stress. Light stress in retina induces ceramide generation predominantly through the de novo pathway, which was prevented by systemic administration of FTY720 (10 mg/kg) leading to the protection of retinal structure and function. The neuroprotection of FTY720 was independent of its immunosuppressive action. We conclude that ceramide increase by de novo biosynthesis mediates photoreceptor apoptosis in the LIRD model and that inhibition of ceramide production protects the retina against light stress. PMID:23468130

  5. Cartilage Degeneration, Subchondral Mineral and Meniscal Mineral Densities in Hartley and Strain 13 Guinea Pigs

    PubMed Central

    Sun, Yubo; Scannell, Brian P; Honeycutt, Patrick R; Mauerhan, David R; H, James Norton; Hanley Jr, Edward N

    2015-01-01

    Osteoarthritis is a joint disease involved in articular cartilage, subchondral bone, meniscus and synovial membrane. This study sought to examine cartilage degeneration, subchondral bone mineral density (BMD) and meniscal mineral density (MD) in male Hartley, female Hartley and female strain 13 guinea pigs to determine the association of cartilage degeneration with subchondral BMD and meniscal MD. Cartilage degeneration, subchondral BMD and meniscal MD in 12 months old guinea pigs were examined with histochemistry, X-ray densitometry and calcium analysis. We found that male Hartley guinea pigs had more severe cartilage degeneration, subchondral BMD and meniscal MD than female Hartley guinea pigs, but not female strain 13 guinea pigs. Female strain 13 guinea pigs had more severe cartilage degeneration and higher subchondral BMD, but not meniscal MD, than female Hartley guinea pigs. These findings indicate that higher subchondral BMD, not meniscal MD, is associated with more severe cartilage degeneration in the guinea pigs and suggest that abnormal subchondral BMD may be a therapeutic target for OA treatment. These findings also indicate that the pathogenesis of OA in the male guinea pigs and female guinea pigs are different. Female strain 13 guinea pig may be used to study female gender-specific pathogenesis of OA. PMID:26401159

  6. Linkage of Oxidative Stress and Mitochondrial Dysfunctions to Spontaneous Culture Degeneration in Aspergillus nidulans*

    PubMed Central

    Li, Lin; Hu, Xiao; Xia, Yongliang; Xiao, Guohua; Zheng, Peng; Wang, Chengshu

    2014-01-01

    Filamentous fungi including mushrooms frequently and spontaneously degenerate during subsequent culture maintenance on artificial media, which shows the loss or reduction abilities of asexual sporulation, sexuality, fruiting, and production of secondary metabolites, thus leading to economic losses during mass production. To better understand the underlying mechanisms of fungal degeneration, the model fungus Aspergillus nidulans was employed in this study for comprehensive analyses. First, linkage of oxidative stress to culture degeneration was evident in A. nidulans. Taken together with the verifications of cell biology and biochemical data, a comparative mitochondrial proteome analysis revealed that, unlike the healthy wild type, a spontaneous fluffy sector culture of A. nidulans demonstrated the characteristics of mitochondrial dysfunctions. Relative to the wild type, the features of cytochrome c release, calcium overload and up-regulation of apoptosis inducing factors evident in sector mitochondria suggested a linkage of fungal degeneration to cell apoptosis. However, the sector culture could still be maintained for generations without the signs of growth arrest. Up-regulation of the heat shock protein chaperones, anti-apoptotic factors and DNA repair proteins in the sector could account for the compromise in cell death. The results of this study not only shed new lights on the mechanisms of spontaneous degeneration of fungal cultures but will also provide alternative biomarkers to monitor fungal culture degeneration. PMID:24345786

  7. Identification and mapping of nucleotide binding site-leucine rich repeat resistance gene analogs in bermudagrass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Thirty-one bermudagrass (Cynodon spp.) disease resistance gene homologs (BRGH) were cloned and sequenced from diploid, triploid, and hexaploid bermudagrass using degenerate primers to target the nucleotide binding site (NBS) of the NBS- leucine rich repeat (LRR) resistance gene family. Alignment of ...

  8. VAGINAL DEGENERATION FOLLOWING IMPLANTATION OF SYNTHETIC MESH WITH INCREASED STIFFNESS

    PubMed Central

    Liang, Rui; Abramowitch, Steven; Knight, Katrina; Palcsey, Stacy; Nolfi, Alexis; Feola, Andrew; Stein, Susan; Moalli, Pamela A.

    2012-01-01

    Objective To compare the impact of the prototype prolapse mesh Gynemesh PS to that of two new generation lower stiffness meshes, UltraPro and SmartMesh, on vaginal morphology and structural composition. Design A mechanistic study employing a non-human primate (NHP) model. Setting Magee-Womens Research Institute at the University of Pittsburgh. Population Parous rhesus macaques, with similar age, weight, parity and POP-Q scores. Methods Following IACUC approval, 50 rhesus macaques were implanted with Gynemesh PS (n=12), UltraPro with its blue line perpendicular to the longitudinal axis of vagina (n=10), UltraPro with its blue line parallel to the longitudinal axis of vagina (n=8) and SmartMesh (n=8) via sacrocolpopexy following hysterectomy. Sham operated animals (n=12) served as controls. Main Outcome Measures The mesh-vagina complex (MVC) was removed after 12 weeks and analyzed for histomorphology, in situ cell apoptosis, total collagen, elastin, glycosaminoglycan content and total collagenase activity. Appropriate statistics and correlation analyses were performed accordingly. Results Relative to sham and the two lower stiffness meshes, Gynemesh PS had the greatest negative impact on vaginal histomorphology and composition. Compared to sham, implantation with Gynemesh PS caused substantial thinning of the smooth muscle layer (1557 ± 499?m vs 866 ± 210 ?m, P=0.02), increased apoptosis particularly in the area of the mesh fibers (P=0.01), decreased collagen and elastin content (20% (P=0.03) and 43% (P=0.02), respectively) and increased total collagenase activity (135% (P=0.01)). GAG (glycosaminoglycan), a marker of tissue injury, was the highest with Gynemesh PS compared to sham and other meshes (P=0.01). Conclusion Mesh implantation with the stiffer mesh Gynemesh PS induced a maladaptive remodeling response consistent with vaginal degeneration. PMID:23240802

  9. Compositional MRI techniques for evaluation of cartilage degeneration in osteoarthritis.

    PubMed

    Guermazi, A; Alizai, H; Crema, M D; Trattnig, S; Regatte, R R; Roemer, F W

    2015-10-01

    Osteoarthritis (OA), a leading cause of disability, affects 27 million people in the United States and its prevalence is rising along with the rise in obesity. So far, biomechanical or behavioral interventions as well as attempts to develop disease-modifying OA drugs have been unsuccessful. This may be partly due to antiquated imaging outcome measures such as radiography, which are still endorsed by regulatory agencies such as the United States Food and Drug Administration (FDA) for use in clinical trials. Morphological magnetic resonance imaging (MRI) allows unparalleled multi-feature assessment of the OA joint. Furthermore, advanced MRI techniques also enable evaluation of the biochemical or ultrastructural composition of articular cartilage relevant to OA research. These compositional MRI techniques have the potential to supplement clinical MRI sequences in identifying cartilage degeneration at an earlier stage than is possible today using morphologic sequences only. The purpose of this narrative review is to describe compositional MRI techniques for cartilage evaluation, which include T2 mapping, T2* Mapping, T1 rho, dGEMRIC, gagCEST, sodium imaging and diffusion weighted imaging (DWI). We also reviewed relevant clinical studies that have utilized these techniques for the study of OA. The different techniques are complementary. Some focus on isotropy or the collagen network (e.g., T2 mapping) and others are more specific in regard to tissue composition, e.g., gagCEST or dGEMRIC that convey information on the GAG concentration. The application and feasibility of these techniques is also discussed, as they will play an important role in implementation in larger clinical trials and eventually clinical practice. PMID:26050864

  10. Memory deficits in a demented patient with probable corticobasal degeneration.

    PubMed

    Beatty, W W; Scott, J G; Wilson, D A; Prince, J R; Williamson, D J

    1995-04-01

    Anterograde and retrograde amnesia in a patient with probable corticobasal degeneration (pCBD) and dementia were studied in a university medical center setting. The patient with pCBD and four comparison patients of comparable global mental status (Mini-Mental State Exam) who met NINCDS-ADRDA criteria for Alzheimer's disease (AD) were included. Standard neuropsychological tests of naming, intelligence, achievement, verbal fluency, anterograde and remote verbal and visuospatial memory, and motor skill learning were given. The pCBD patient exhibited a progressive asymmetric akinetic-rigid syndrome, which was unresponsive to Sinemet. His initially mild, intellectual deficits consisted of apraxia, slowed speech, and word-finding and memory difficulties. Over a 2-year period, a dementia syndrome developed, which involved more-serious deficits in praxis and naming, as well as impairments in spelling, calculation, verbal fluency, IQ, anterograde verbal and visuospatial memory, and motor skill learning. When tested by recall methods, the pCBD patient exhibited marked deficits on several tests of remote memory; however, on recognition testing, he performed normally on the Famous Faces Test and on a test of geographical knowledge, which measures remote visuospatial memory. By contrast, the four AD patients, who showed equivalent naming difficulties, less-severe fluency deficits, and normal motor skill learning, showed severe impairments in recalling and recognizing the names of famous people from photographs. A magnetic resonance imaging (MRI) scan of the pCBD patient showed marked frontal and parietal lobe atrophy and central atrophy, with ventriculomegaly that was greater on the left side of the brain. The temporal lobes were relatively spared, and the amygdalae, hippocampi, and temporal horns were of normal size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7794479

  11. OBSERVATIONAL CONSTRAINTS ON THE DEGENERATE MASS-RADIUS RELATION

    SciTech Connect

    Holberg, J. B.; Oswalt, T. D.; Barstow, M. A. E-mail: toswalt@fit.edu

    2012-03-15

    The white dwarf mass-radius relationship is fundamental to modern astrophysics. It is central to routine estimation of DA white dwarf masses derived from spectroscopic temperatures and gravities. It is also the basis for observational determinations of the white dwarf initial-final-mass relation. Nevertheless, definitive and detailed observational confirmations of the mass-radius relation (MRR) remain elusive owing to a lack of sufficiently accurate white dwarf masses and radii. Current best estimates of masses and radii allow only broad conclusions about the expected inverse relation between masses and radii in degenerate stars. In this paper, we examine a restricted set of 12 DA white dwarf binary systems for which accurate (1) trigonometric parallaxes, (2) spectroscopic effective temperatures and gravities, and (3) gravitational redshifts are available. We consider these three independent constraints on mass and radius in comparison with an appropriate evolved MRR for each star. For the best-determined systems it is found that the DA white dwarfs conform to evolve theoretical MRRs at the 1{sigma} to 2{sigma} level. For the white dwarf 40 Eri B (WD 0413-077) we find strong evidence for the existence of a 'thin' hydrogen envelope. For other stars improved parallaxes will be necessary before meaningful comparisons are possible. For several systems current parallaxes approach the precision required for the state-of-the-art mass and radius determinations that will be obtained routinely from the Gaia mission. It is demonstrated here how these anticipated results can be used to firmly constrain details of theoretical mass-radius determinations.

  12. Observational Constraints on the Degenerate Mass-Radius Relation

    NASA Astrophysics Data System (ADS)

    Holberg, J. B.; Oswalt, T. D.; Barstow, M. A.

    2012-03-01

    The white dwarf mass-radius relationship is fundamental to modern astrophysics. It is central to routine estimation of DA white dwarf masses derived from spectroscopic temperatures and gravities. It is also the basis for observational determinations of the white dwarf initial-final-mass relation. Nevertheless, definitive and detailed observational confirmations of the mass-radius relation (MRR) remain elusive owing to a lack of sufficiently accurate white dwarf masses and radii. Current best estimates of masses and radii allow only broad conclusions about the expected inverse relation between masses and radii in degenerate stars. In this paper, we examine a restricted set of 12 DA white dwarf binary systems for which accurate (1) trigonometric parallaxes, (2) spectroscopic effective temperatures and gravities, and (3) gravitational redshifts are available. We consider these three independent constraints on mass and radius in comparison with an appropriate evolved MRR for each star. For the best-determined systems it is found that the DA white dwarfs conform to evolve theoretical MRRs at the 1? to 2? level. For the white dwarf 40 Eri B (WD 0413-077) we find strong evidence for the existence of a "thin'' hydrogen envelope. For other stars improved parallaxes will be necessary before meaningful comparisons are possible. For several systems current parallaxes approach the precision required for the state-of-the-art mass and radius determinations that will be obtained routinely from the Gaia mission. It is demonstrated here how these anticipated results can be used to firmly constrain details of theoretical mass-radius determinations.

  13. Delayed Neural Network Degeneration after Neonatal Hypoxia-Ischemia

    PubMed Central

    Stone, Brian S.; Zhang, Jiangyang; Mack, Devin W.; Mori, Susumu; Martin, Lee J.; Northington, Frances J.

    2008-01-01

    Objective Clinical MR studies show delayed and ongoing neurodegeneration following neonatal hypoxia-ischemia (HI), but the mechanisms and timing of this neurodegeneration remain unclear. We use ex vivo Diffusion Tensor Imaging (DTI) and brain neuropathology to determine if selective injury to white matter tracts occurs following neonatal HI in mice resulting in neural system associated attrition in remote regions and at delayed time points. Methods The Rice Vannucci model (unilateral carotid ligation + 45 minutes of hypoxia FIO2=0.08) was used to cause brain injury in postnatal (p)7 C57BL6 mice and ex vivo DTI and correlative neuropathology were performed at p8,p11,p15,p21,p28, and p42. Results DTI provides excellent contrast visualization of unmyelinated white matter in the immature mouse brain. Acute severe ipsilateral injury to the hippocampus is seen with both histopathology and diffusion-weighted MRI 24 hours post injury. Injury to axons is evident 24 hours after HI in the hippocampal alveus. By p11 and continuing until p28, the ipsilateral fimbria fornix degenerates. Beginning at p15, there is injury and loss of axons entering the ipsilateral septal nucleus followed by ipsilateral septal atrophy. Volume loss in the hippocampus is rapid and severe but is subacute and significantly slower in the ipsilateral septum. Neonatal HIE, also interrupts the normal developmental increase in fractional anisotropy in the ipsilateral fimbria but not in the contralateral fimbria from p8 to p42. Interpretation In the neonatal brain there is a progressive systems-preferential injury following HI. DTI allows unparalleled visualization of this neural-network associated attrition so that it can be followed longitudinally in the developing brain. PMID:19067347

  14. Nutritional Modulation of Age-Related Macular Degeneration

    PubMed Central

    Weikel, Karen A; Taylor, Allen

    2012-01-01

    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 with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/wk of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available. PMID:22503690

  15. TYPE Ia SINGLE DEGENERATE SURVIVORS MUST BE OVERLUMINOUS

    SciTech Connect

    Shappee, Benjamin J.; Kochanek, C. S.; Stanek, K. Z. E-mail: ckochanek@astronomy.ohio-state.edu

    2013-03-10

    In the single-degenerate (SD) channel of a Type Ia supernovae (SNe Ia) explosion, a main-sequence (MS) donor star survives the explosion but it is stripped of mass and shock heated. An essentially unavoidable consequence of mass loss during the explosion is that the companion must have an overextended envelope after the explosion. While this has been noted previously, it has not been strongly emphasized as an inevitable consequence. We calculate the future evolution of the companion by injecting 2-6 Multiplication-Sign 10{sup 47} erg into the stellar evolution model of a 1 M{sub Sun} donor star based on the post-explosion progenitors seen in simulations. We find that, due to the Kelvin-Helmholtz collapse of the envelope, the companion must become significantly more luminous (10-10{sup 3} L{sub Sun }) for a long period of time (10{sup 3}-10{sup 4} yr). The lack of such a luminous ''leftover'' star in the LMC supernova remnant SNR 0609-67.5 provides another piece of evidence against the SD scenario. We also show that none of the stars proposed as the survivors of the Tycho supernova, including Tycho G, could plausibly be the donor star. Additionally, luminous donors closer than {approx}10 Mpc should be observable with the Hubble Space Telescope starting {approx}2 yr post-peak. Such systems include SN 1937C, SN 1972E, SN 1986G, and SN 2011fe. Thus, the SD channel is already ruled out for at least two nearby SNe Ia and can easily be tested for a number of additional ones. We also discuss similar implications for the companions of core-collapse SNe.

  16. Regulation of age-related macular degeneration-like pathology by complement factor H

    PubMed Central

    Toomey, Christopher B.; Kelly, Una; Saban, Daniel R.; Bowes Rickman, Catherine

    2015-01-01

    Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/? and Cfh?/? mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/? and Cfh?/? mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/? mice. We demonstrate that such pathology is a function of excess complement activation in Cfh+/? mice versus complement deficiency in Cfh?/? animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD. PMID:25991857

  17. Magnetotransport in epitaxial films of the degenerate semiconductor Zn1-xCoxO

    NASA Astrophysics Data System (ADS)

    Budhani, R. C.; Pant, Prita; Rakshit, R. K.; Senapati, K.; Mandal, S.; Pandey, N. K.; Kumar, Jitendra

    2005-01-01

    Magnetotransport measurements are performed over a broad range of temperature (T) and magnetic field (H) on highly degenerate n-type Zn1-xCoxO (0 \\le x \\le 0.30) epitaxial films. The cobalt-free samples are characterized by a metallic resistivity ?(T) down to 2 K, a negative and predominantly isotropic magnetoresistance (MR) and optical transmission above 85% in the visible range of the electromagnetic spectrum. X-ray diffraction measurements show that while for x \\le 0.20 , all cobalt atoms occupy the tetrahedral sites of the wurtzite structure of ZnO, a phase separation into CoO is seen for x>0.2. In the solution phase, we do not observe any signatures of a spontaneous ordering of the cobalt spins despite a large concentration of mobile electrons (>1020 cm-3). The absence of anomalous Hall resistance is consistent with this observation. The carrier concentration (n) over the entire range of x remains above the Mott limit for the insulator-to-metal transition in a doped semiconductor. However, while the Co-free samples are metallic (T>2 K), we see a resistivity (?) minimum followed by lnT divergence of ?(T) at low temperatures with increasing x. The magnetoresistance of these samples is negative and predominantly isotropic. Moreover, the MR tends to follow a logH behaviour at high fields. These observations, including the Kondo-like minimum in the resistivity, suggest s-d exchange dominated transport in these dilute magnetic semiconductors.

  18. [Pharmacological therapy of age-related macular degeneration based on the etiopathogenesis].

    PubMed

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration. PMID:26548469

  19. The generation of stationary ?-electron rotations in chiral aromatic ring molecules possessing non-degenerate excited states.

    PubMed

    Yamaki, Masahiro; Teranishi, Yoshiaki; Nakamura, Hiroki; Lin, Sheng Hsien; Fujimura, Yuichi

    2016-01-21

    The electron angular momentum is a fundamental quantity of high-symmetry aromatic ring molecules and finds many applications in chemistry such as molecular spectroscopy. The stationary angular momentum or unidirectional rotation of ? electrons is generated by the excitation of a degenerated electronic excited state by a circularly-polarized photon. For low-symmetry aromatic ring molecules having non-degenerate states, such as chiral aromatic ring molecules, on the other hand, whether stationary angular momentum can be generated or not is uncertain and has not been clarified so far. We have found by both theoretical treatments and quantum optimal control (QOC) simulations that a stationary angular momentum can be generated even from a low-symmetry aromatic ring molecule. The generation mechanism can be explained in terms of the creation of a dressed-state, and the maximum angular momentum is generated by the dressed state with an equal contribution from the relevant two excited states in a simple three-electronic state model. The dressed state is formed by inducing selective nonresonant transitions between the ground and each excited state by two lasers with the same frequency but having different polarization directions. The selective excitation can be carried out by arranging each photon-polarization vector orthogonal to the electronic transition moment of the other transition. We have successfully analyzed the results of the QOC simulations of (P)-2,2'-biphenol of axial chirality in terms of the analytically determined optimal laser fields. The present findings may open up new types of chemical dynamics and spectroscopy by utilizing strong stationary ring currents and current-induced magnetic fields, which are created at a local site of large compounds such as biomolecules. PMID:26670839

  20. Transcriptional regulation of bone morphogenetic protein 4 by tumor necrosis factor and its relationship with age-related macular degeneration

    PubMed Central

    Xu, Jing; Zhu, Danhong; He, Shikun; Spee, Christine; Ryan, Stephen J.; Hinton, David R.

    2011-01-01

    Bone morphogenetic protein-4 (BMP4) may be involved in the molecular switch that determines which late form of age-related macular degeneration (AMD) an individual develops. BMP4 expression is high in retinal pigment epithelium (RPE) cells in late, dry AMD patients, while BMP4 expression is low in the wet form of the disease, characterized by choroidal neovascularization (CNV). Here, we sought to determine the mechanism by which BMP4 is down-regulated in CNV. BMP4 expression was decreased within laser-induced CNV lesions in mice at a time when tumor necrosis factor (TNF) expression was high (7 d postlaser) and was reexpressed in RPE when TNF levels declined (14 d postlaser). We found that TNF, an important angiogenic stimulus, significantly down-regulates BMP4 expression in cultured human fetal RPE cells, ARPE-19 cells, and RPE cells in murine posterior eye cup explants. We identified two specificity protein 1 (Sp1) binding sites in the BMP4 promoter that are required for basal expression of BMP4 and its down-regulation by TNF. Through c-Jun NH2-terminal kinase (JNK) activation, TNF modulates Sp1 phosphorylation, thus decreasing its affinity to the BMP4 promoter. The down-regulation of BMP4 expression by TNF in CNV and mechanisms established might be useful for defining novel targets for AMD therapy.—Xu, J., Zhu, D., He, S., Spee, C., Ryan, S. J., Hinton, D. R. Transcriptional regulation of bone morphogenetic protein 4 by tumor necrosis factor and its relationship with age-related macular degeneration. PMID:21411747

  1. Lipids, Lipid Genes and Incident Age-Related Macular Degeneration: The Three Continent Age-Related Macular Degeneration Consortium

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T. V. M.; Sivakumaran, Theru A.; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K.; Lee, Kristine E.; Stricker, Bruno H.; Vingerling, Johannes R.; Mitchell, Paul; Klein, Barbara E. K.; Klaver, Caroline C. W.; Wang, Jie Jin

    2014-01-01

    Purpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods Setting Three population-based cohorts. Population 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). Observation Procedures Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios (HRs) associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. Main Outcome Measures Incidence of AMD. Results The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the three studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. Conclusion In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. PMID:24879949

  2. Site Accessibility

    Cancer.gov

    The National Institutes of Health, NIH is making every effort to ensure that the information available on our website is accessible to all. If you use special adaptive equipment to access the Web and encounter problems when using our site, please let us know.

  3. Site Construction.

    ERIC Educational Resources Information Center

    Richardson, Eric C.

    1996-01-01

    Presents a guide to planning and building a Web site, with an emphasis on setting up a Web server. Discussion includes hiring a consultant, contracts and payment, assembly of teams, training, development of a business plan, registration of domain name, purchase of hardware and software, local area networks, and types of Internet connection. (JKP)

  4. Effect of Lycium barbarum (Wolfberry) on alleviating axonal degeneration after partial optic nerve transection.

    PubMed

    Li, Hong-Ying; Ruan, Yi-Wen; Kau, Phillis Wan-Foon; Chiu, Kin; Chang, Raymond Chuen-Chung; Chan, Henry H L; So, Kwok-Fai

    2015-01-01

    Our previous results showed that the polysaccharides extracted from Lycium barbarum (LBP) could delay secondary degeneration of retinal ganglion cell bodies and improve the function of the retinas after partial optic nerve transection (PONT). Although the common degeneration mechanisms were believed to be shared by both neuronal bodies and axons, recently published data from slow Wallerian degeneration mutant (Wld(s)) mice supported the divergence in the mechanisms of them. Therefore, we want to determine if LBP could also delay the degeneration of axons after PONT. Microglia/macrophages were thought to be a source of reactive oxygen species after central nervous system (CNS) injury. After PONT, however, oxidative stress was believed to occur prior to the activation of microglia/macrophages in the areas vulnerable to secondary degeneration both in the optic nerves (ONs) and the retinas. But the results did not take into account the morphological changes of microglia/macrophages after their activation. So we examined the morphology in addition to the response magnitude of microglia/macrophages to determine their time point of activation. In addition, the effects of LBP on the activation of microglia/macrophages were investigated. The results showed that (1) LBP reduced the loss of axons in the central ONs and preserved the g-ratio (axon diameter/fiber diameter) in the ventral ONs although no significant effect was detected in the dorsal ONs; (2) microglia/macrophages were activated in the ONs by 12 h after PONT; (3) LBP decreased the response magnitude of microglia/macrophages 4 weeks after PONT. In conclusion, our results showed that LBP could delay secondary degeneration of the axons, and LBP could also inhibit the activation of microglia/macrophages. Therefore, LBP could be a promising herbal medicine to delay secondary degeneration in the CNS via modulating the function of microglia/macrophages. PMID:25622224

  5. Sarm1-mediated axon degeneration requires both SAM and TIR interactions.

    PubMed

    Gerdts, Josiah; Summers, Daniel W; Sasaki, Yo; DiAntonio, Aaron; Milbrandt, Jeffrey

    2013-08-14

    Axon degeneration is an evolutionarily conserved pathway that eliminates damaged or unneeded axons. Manipulation of this poorly understood pathway may allow treatment of a wide range of neurological disorders. In an RNAi-based screen performed in cultured mouse DRG neurons, we observed strong suppression of injury-induced axon degeneration upon knockdown of Sarm1 [SARM (sterile ?-motif-containing and armadillo-motif containing protein)]. We find that a SARM-dependent degeneration program is engaged by disparate neuronal insults: SARM ablation blocks axon degeneration induced by axotomy or vincristine treatment, while SARM acts in parallel with a soma-derived caspase-dependent pathway following trophic withdrawal. SARM is a multidomain protein that associates with neuronal mitochondria. Deletion of the N-terminal mitochondrial localization sequence disrupts SARM mitochondrial localization in neurons but does not alter its ability to promote axon degeneration. In contrast, mutation of either the SAM (sterile ? motif) or TIR (Toll-interleukin-1 receptor) domains abolishes the ability of SARM to promote axonal degeneration, while a SARM mutant containing only these domains elicits axon degeneration and nonapoptotic neuronal death even in the absence of injury. Protein-protein interaction studies demonstrate that the SAM domains are necessary and sufficient to mediate SARM-SARM binding. SARM mutants lacking a TIR domain bind full-length SARM and exhibit strong dominant-negative activity. These results indicate that SARM plays an integral role in the dismantling of injured axons and support a model in which SAM-mediated multimerization is necessary for TIR-dependent engagement of a downstream destruction pathway. These findings suggest that inhibitors of SAM and TIR interactions represent therapeutic candidates for blocking pathological axon loss and neuronal cell death. PMID:23946415

  6. The Role of Activity in Synaptic Degeneration in a Protein Misfolding Disease, Prion Disease

    PubMed Central

    Vannini, Eleonora; Siskova, Zuzana; Al-Malki, Hussain; Morgan, Ruth; O'Connor, Vincent; Perry, V. Hugh

    2012-01-01

    In chronic neurodegenerative diseases associated with aggregates of misfolded proteins (such as Alzheimer's, Parkinson's and prion disease), there is an early degeneration of presynaptic terminals prior to the loss of the neuronal somata. Identifying the mechanisms that govern synapse degeneration is of paramount importance, as cognitive decline is strongly correlated with loss of presynaptic terminals in these disorders. However, very little is known about the processes that link the presence of a misfolded protein to the degeneration of synapses. It has been suggested that the process follows a simple linear sequence in which terminals that become dysfunctional are targeted for death, but there is also evidence that high levels of activity can speed up degeneration. To dissect the role of activity in synapse degeneration, we infused the synaptic blocker botulinum neurotoxin A (BoNT/A) into the hippocampus of mice with prion disease and assessed synapse loss at the electron microscopy level. We found that injection of BoNT/A in naïve mice caused a significant enlargement of excitatory presynaptic terminals in the hippocampus, indicating transmission impairment. Long-lasting blockade of activity by BoNT/A caused only minimal synaptic pathology and no significant activation of microglia. In mice with prion disease infused with BoNT/A, rates of synaptic degeneration were indistinguishable from those observed in control diseased mice. We conclude that silencing synaptic activity neither prevents nor enhances the degree of synapse degeneration in prion disease. These results challenge the idea that dysfunction of synaptic terminals dictates their elimination during prion-induced neurodegeneration. PMID:22815961

  7. eEF1A2 and neuronal degeneration.

    PubMed

    Abbott, Catherine M; Newbery, Helen J; Squires, Charlotte E; Brownstein, David; Griffiths, Lowri A; Soares, Dinesh C

    2009-12-01

    Translation elongation factor eEF1A (eukaryotic elongation factor 1A) exists as two individually encoded variants in mammals, which are 98% similar and 92% identical at the amino acid level. One variant, eEF1A1, is almost ubiquitously expressed, the other variant, eEF1A2, shows a very restricted pattern of expression. A spontaneous mutation was described in 1972, which gives rise to the wasted phenotype: homozygous wst/wst mice develop normally until shortly after weaning, but then lose muscle bulk, acquire tremors and gait abnormalities and die by 4 weeks. This mutation has been shown to be a deletion of 15 kb that removes the promoter and first exon of the gene encoding eEF1A2. The reciprocal pattern of expression of eEF1A1 and eEF1A2 in muscle fits well with the timing of onset of the phenotype of wasted mice: eEF1A1 declines after birth until it is undetectable by 3 weeks, whereas eEF1A2 expression increases over this time. No other gene is present in the wasted deletion, and transgenic studies have shown that the phenotype is due to loss of eEF1A2. We have shown that eEF1A2, but not eEF1A1, is also expressed at high levels in motor neurons in the spinal cord. Wasted mice develop many pathological features of motor neuron degeneration and may represent a good model for early onset of motor neuron disease. Molecular modelling of the eEF1A1 and eEF1A2 protein structures highlights differences between the two variants that may be critical for functional differences. Interactions between eEF1A2 and ZPR1 (zinc-finger protein 1), which interacts with the SMN (survival motor neuron) protein, may be important in motor neuron biology. PMID:19909265

  8. Crystallization of dense magnetic polarons in degenerate magnetic semiconductors

    NASA Astrophysics Data System (ADS)

    Umehara, Masakatsu

    1987-07-01

    Crystallization of dense magnetic polarons (CDM) is studied on the basis of the density-functional method with parametrized variational electron densities at zero and finite temperatures. In the present paper, the case for antiferromagnetic semiconductors is studied in detail, in relation to heavily doped EuTe and Gd3-x?xS4 (x~(1/3), where ? stands for vacancies. For relatively low electron concentrations, dense magnetic polarons may be crystallized; in this case, the electron densities are extremely concentrated in the central part of each crystallization unit cell so that the ferromagnetic domain with (nearly) saturated magnetization, that is, the magnetic polaron, is established in the central part of the cell, while in the remaining part of the cell, the electron densities are extremely small with a nearly antiferromagnetic ordering of localized spins. By this process, the interaction energy between electrons and localized spins is almost fully gained at the cost of the kinetic energy, the Coulomb interaction energy of electrons, and the energy of localized spins. When this state is energetically favorable compared with the homogeneous state studied previously by Umehara and Kasuya [J. Phys. Soc. Jpn. 40, 13 (1976)], CDM is stabilized. For larger electron concentrations, a different type of crystallization occurs: In the central part of the cell, the electron densities become extremely small with nearly antiferromagnetic ordering of localized spins, while in the remaining part of the cell, the electron densities are larger than the average density with ferromagnetic ordering of localized spins, which is the reverse CDM and is called the crystallization of dense bubbles (CDB). With further increasing electron concentration, CDB melts into the homogeneous state. The temperature dependence of both crystallization states is very weak except in the vicinity of the critical temperature for the transition to the homogeneous state. The result obtained from the present study is compared with experimental data, which shows that the present mechanism is a convincing one for degenerate EuTe and Gd3-x?xS4, at least at low temperatures.

  9. An update on cystic ovarian degeneration in cattle.

    PubMed

    Peter, A T

    2004-02-01

    Cystic ovarian degeneration (COD) is considered to be one of the most important causes of reproductive failure in cattle. There is a severe economic loss to dairy industry because COD increases days-open in the postpartum period and the culling rates. The disease process is a consequence of a mature follicle that fails to ovulate at the appointed time of ovulation in the oestrous cycle. This anovulatory follicular structure either regresses or persists as a follicular or luteal cyst depending upon its structural/functional characteristics. The cells lining the follicular cyst synthesize oestrogen that, in certain instances, forces the animal to exhibit clinical signs of nymphomania. Besides oestrogen production, as per recent findings, they are also capable of secreting varying amount of progesterone which may dictate their fate. The animals that carry a luteal cyst may tend to be in anoestrus as the higher amount of progesterone secreted by this luteinized structure may change the pattern of gonadotrophins' secretion. Present findings suggest that perturbation of the hypothalamo-hypophyseal-ovarian (HHO) axis, due to many exogenous and endogenous factors, as the cause for anovulation. For example, it has been suggested that lack of hypothalamic or hypophyseal response to the positive feedback effect of oestrogens that are secreted by the dominant follicle as one of the many causes. The non-physiological changes that occur in the receptor expression of the HHO axis for the hormones involved in maturation, deviation, dominance and ovulation of the follicle may be yet another cause. The changes that occur at the cellular and molecular level in the ovary (in response to the factors mentioned above) that contribute to anovulation remain to be documented. This approach would allow us to completely understand the disease process. Hitherto, hormonal preparations that release luteinizing hormone from the anterior pituitary or have luteinizing hormone-like action are used to treat follicular cysts. GnRH belongs to the former group and human chorionic gonadotrophin (hCG) hormone forms the latter group. Treatment with a luteolytic agent, prostaglandin F2alpha (PGF2alpha), is successful if a luteal cyst is diagnosed properly. Many agents may be developed in the future if the cellular and molecular pathways of the disease process are delineated. This article will review recent advances in our understanding of the pathogenesis of COD and suggest direction for future studies to completely understand the disease mechanism. This review will also discuss the existing method of treatments for cysts and methods proposed for treatment of cysts that tend to be refractory in nature. PMID:15129913

  10. Self-conscious emotion deficits in frontotemporal lobar degeneration.

    PubMed

    Sturm, Virginia E; Rosen, Howard J; Allison, Stephen; Miller, Bruce L; Levenson, Robert W

    2006-09-01

    Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease associated with dramatic changes in emotion. The precise nature of these changes is not fully understood; however, we believe that the most salient losses relate to self-relevant processing. Thus, FTLD patients exhibit emotional changes that are consistent with a reduction in self-monitoring, self-awareness and the ability to place the self in a social context. In contrast, other more primitive aspects of the emotional system may remain relatively intact. The startle response is a useful way to examine the precise nature of emotional deficits in neurological patients. In addition to a stereotyped defensive response (characterized by negative emotional facial behaviour and physiological activation), in many individuals it also evokes embarrassment, a self-conscious emotional response. Embarrassment seems to occur as the person becomes aware that the reaction to the startle was excessive and was observed by others. Because the self-conscious response depends on certain regions in frontal cortex, we expected that FTLD patients would have specific deficits in their self-conscious response. To test this notion, we examined the response of 30 FTLD patients and 23 cognitively normal controls to a loud, unexpected acoustic startle stimulus (115-dB burst of white noise). Emotional behaviours were measured along with an assessment of somatic, electrodermal, cardiovascular and respiratory responses. Results indicated that FTLD patients and controls were similar in terms of physiological responses and negative emotional facial behaviour to the startle, indicating that the defensive aspect of the startle was preserved. However, there were profound differences in the self-conscious response. FTLD patients showed significantly fewer facial signs of embarrassment than controls. This deficit in self-conscious response could not be explained by sex, cognitive status, age, education, medication, or differences in the negative emotional behaviour or physiological response. Thus, the emotional deficit in FTLD patients' response to the startle suggests a reduction in self-consciousness. These findings suggest that the emotional deficit in FTLD may be most profound in higher-order processes akin to those involved in the generation of embarrassment. These deficits are consistent with neural loss in the medial prefrontal cortex, which may play an important role in the production of self-conscious emotions. Disrupted self-conscious emotions in FTLD patients may have clinical importance because these deficits may underlie some of the socially inappropriate behaviours that are common in these patients. PMID:16844714

  11. The Use of T1 Sagittal Angle in Predicting Cervical Disc Degeneration

    PubMed Central

    Yang, Bong-Seok; Lee, Su-Keon; Song, Kyung-Sub; Yoon, Sang-Pil; Jang, Geun; Lee, Chae-Chul; Moon, Seong-Hwan; Lee, Hwan-Mo

    2015-01-01

    Study Design Retrospective evaluation. Purpose To analyze the effect of T1 slope on degree of degeneration in patients with cervical disc degeneration. Overview of Literature The T1 slope is well known parameter that may be very useful in evaluating sagittal balance. There are no reports on the analysis of the relationship between T1 slope and cervical disc degeneration. We hypothesized that T1 slope has an effect on the degree of cervical degeneration. Methods Sixty patients who had cervical spine magnetic resonance imaging (MRI) in our orthopedic clinic were enrolled. Patients were divided into two groups according to T1 slope. Radiologic parameters obtained from radiography and cervical spine MRI were compared between low T1 slope group (?25) and high T1 slope group (>25). Results Among low T1 slope group, average degeneration grade of each cervical segment was 2.65 in C2-3, 2.50 in C3-4, 2.62 in C4-5, 3.23 in C5-6, and 2.81 in C6-7. And that of high T1 group was 2.35 in C2-3, 2.32 in C3-4, 2.59 in C4-5, 2.79 in C5-6, and 2.32 in C6-7. Grade of degeneration of low T1 group was significantly higher, as compared with high T1 group in C5-6 (p=0.028) and C6-7 (p=0.009). Percentage of high grade degeneration of more than grand III was 65.4% in low T1 group and 32.4% in high T1 group (p=0.018). Risk of high grade degeneration of C6-7 was significantly higher in low T1 group (odds ratio, 5.63; 95% confidence interval, 1.665-19.057; p=0.005). Conclusions Patients with low T1 slope had higher grade of degeneration regardless of age and gender. Low T1 slope is a potential risk factor of cervical spondylosis especially in the C6-7 cervical segment. PMID:26435795

  12. Oxidative stress-dependent phosphorylation activates ZNRF1 to induce neuronal/axonal degeneration.

    PubMed

    Wakatsuki, Shuji; Furuno, Akiko; Ohshima, Makiko; Araki, Toshiyuki

    2015-11-23

    Oxidative stress is a well-known inducer of neuronal apoptosis and axonal degeneration. We previously showed that the E3 ubiquitin ligase ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B activation. We now demonstrate that oxidative stress serves as an activator of the ubiquitin ligase activity of ZNRF1 by inducing epidermal growth factor receptor (EGFR)-mediated phosphorylation at the 103rd tyrosine residue and that the up-regulation of ZNRF1 activity by oxidative stress leads to neuronal apoptosis and Wallerian degeneration. We also show that nicotinamide adenine dinucleotide phosphate-reduced oxidase activity is required for the EGFR-dependent phosphorylation-induced activation of ZNRF1 and resultant AKT degradation via the ubiquitin proteasome system to induce Wallerian degeneration. These results indicate the pathophysiological significance of the EGFR-ZNRF1 pathway induced by oxidative stress in the regulation of neuronal apoptosis and Wallerian degeneration. A deeper understanding of the regulatory mechanism for ZNRF1 catalytic activity via phosphorylation will provide a potential therapeutic avenue for neurodegeneration. PMID:26572622

  13. Epoxiconazole-induced degeneration in rat placenta and the effects of estradiol supplementation.

    PubMed

    Rey Moreno, Maria Cecilia; Fussell, Karma C; Gröters, Sibylle; Schneider, Steffen; Strauss, Volker; Stinchcombe, Stefan; Fegert, Ivana; Veras, Mariana; van Ravenzwaay, Bennard

    2013-06-01

    Epoxiconazole (CAS-No. 133855-98-8) was recently shown to cause both a marked depletion of maternal estradiol blood levels and a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (GD 7-18 or 21); estradiol supplementation prevented this epoxiconazole effect in rats (Stinchcombe et al., 2013), indicating that epoxiconazole-mediated estradiol depletion is a critical key event for induction of late fetal resorptions in rats. For further elucidation of the mode of action, the placentas from these modified prenatal developmental toxicity experiments with 23 and 50 mg/kg bw/d epoxiconazole were subjected to a detailed histopathological examination. This revealed dose-dependent placental degeneration characterized by cystic dilation of maternal sinuses in the labyrinth, leading to rupture of the interhemal membrane. Concomitant degeneration occurred in the trophospongium. Both placentas supporting live fetuses and late fetal resorptions were affected; the highest degree of severity was observed in placentas with late resorptions. Placental degeneration correlated with a severe decline in maternal serum estradiol concentration. Supplementation with 0.5 and 1.0 ?g of the synthetic estrogen estradiol cyclopentylpropionate per day reduced the severity of the degeneration in placentas with live fetuses. The present study demonstrates that both the placental degeneration and the increased incidence of late fetal resorptions are due to decreased levels of estrogen, since estrogen supplementation ameliorates the former and abolishes the latter. PMID:23749492

  14. Morphological and physiological retinal degeneration induced by intravenous delivery of vitamin A dimers in rabbits

    PubMed Central

    Penn, Jackie; Mihai, Doina M.; Washington, Ilyas

    2015-01-01

    The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD) and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE) and Bruch’s membrane (BM). However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina’s response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness. PMID:25504631

  15. Axonal degeneration in Alzheimer's disease: when signaling abnormalities meet the axonal transport system.

    PubMed

    Kanaan, Nicholas M; Pigino, Gustavo F; Brady, Scott T; Lazarov, Orly; Binder, Lester I; Morfini, Gerardo A

    2013-08-01

    Alzheimer's disease (AD) is characterized by progressive, age-dependent degeneration of neurons in the central nervous system. A large body of evidence indicates that neurons affected in AD follow a dying-back pattern of degeneration, where abnormalities in synaptic function and axonal connectivity long precede somatic cell death. Mechanisms underlying dying-back degeneration of neurons in AD remain elusive but several have been proposed, including deficits in fast axonal transport (FAT). Accordingly, genetic evidence linked alterations in FAT to dying-back degeneration of neurons, and FAT defects have been widely documented in various AD models. In light of these findings, we discuss experimental evidence linking several AD-related pathogenic polypeptides to aberrant activation of signaling pathways involved in the phosphoregulation of microtubule-based motor proteins. While each pathway appears to affect FAT in a unique manner, in the context of AD, many of these pathways might work synergistically to compromise the delivery of molecular components critical for the maintenance and function of synapses and axons. Therapeutic approaches aimed at preventing FAT deficits by normalizing the activity of specific protein kinases may help prevent degeneration of vulnerable neurons in AD. PMID:22721767

  16. 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

  17. Disc in flames: Roles of TNF-? and IL-1? in intervertebral disc degeneration.

    PubMed

    Johnson, Z I; Schoepflin, Z R; Choi, H; Shapiro, I M; Risbud, M V

    2015-01-01

    The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc--incited by aging, traumatic insult, genetic predisposition, or other factors--is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, as well as compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current therapies are limited and often focused on symptomatic pain relief rather than curtailing the progression of the disease. Inflammatory processes exacerbated by cytokines tumour necrosis factor-? (TNF-?) and interleukin-1? (IL-1?) are believed to be key mediators of disc degeneration and low back pain. In this review, we describe the contributions of TNF-? and IL-1? to changes seen during disc degeneration at both cellular and tissue level, as well as new evidence suggesting a link between infection of the spine and low back pain, and the emerging therapeutic modalities aimed at combating these processes. PMID:26388614

  18. Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress

    PubMed Central

    Jaiswal, Manish; Haelterman, Nele A.; Sandoval, Hector; Xiong, Bo; Donti, Taraka; Kalsotra, Auinash; Yamamoto, Shinya; Cooper, Thomas A.; Graham, Brett H.; Bellen, Hugo J.

    2015-01-01

    Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration—defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that cause photoreceptor degeneration, we identified mutations in a nuclear-encoded mitochondrial gene, ppr, a homolog of human LRPPRC. We found that ppr is required for protection against light-induced degeneration. Its function is essential to maintain membrane depolarization of the photoreceptors upon repetitive light exposure, and an impaired phototransduction cascade in ppr mutants results in excessive Rhodopsin1 endocytosis. Moreover, loss of ppr results in a reduction in mitochondrial RNAs, reduced electron transport chain activity, and reduced ATP levels. Oxidative stress, however, is not induced. We propose that the reduced ATP level in ppr mutants underlies the phototransduction defect, leading to increased Rhodopsin1 endocytosis during light exposure, causing photoreceptor degeneration independent of oxidative stress. This hypothesis is bolstered by characterization of two other genes isolated in the screen, pyruvate dehydrogenase and citrate synthase. Their loss also causes a light-induced degeneration, excessive Rhodopsin1 endocytosis and reduced ATP without concurrent oxidative stress, unlike many other mutations in mitochondrial genes that are associated with elevated oxidative stress and light-independent photoreceptor demise. PMID:26176594

  19. Nonplanar Shock Structures in a Relativistic Degenerate Multi-Species Plasma

    NASA Astrophysics Data System (ADS)

    M. R., Hossen; S. A., Ema; A. A., Mamun

    2014-12-01

    A nonlinear propagation of cylindrical and spherical modified ion-acoustic (mIA) waves in an unmagnetized, collisionless, relativistic, degenerate multi-species plasma has been investigated theoretically. This plasma system is assumed to contain non-relativistic degenerate light ions, both non-relativistic and ultra-relativistic degenerate electron and positron fluids, and arbitrarily charged static heavy ions. The restoring force is provided by the degenerate pressures of the electrons and positrons, whereas the inertia is provided by the mass of ions. The arbitrarily charged static heavy ions participate only in maintaining the quasi-neutrality condition at equilibrium. The modified Burgers (mB) equation is derived by using reductive perturbation technique and numerically analyzed to identify the basic features of mIA shock structures. The basic characteristics of mIA shock waves are found to be significantly modified by the effects of degenerate pressures of electron, positron, and ion fluids, their number densities, and various charge state of heavy ions. The implications of our results to dense plasmas in astrophysical compact objects (e.g., non-rotating white dwarfs, neutron stars, etc.) are briefly discussed.

  20. Incorporation of fucose and leucine into PNS myelin proteins in nerves undergoing early Wallerian degeneration

    SciTech Connect

    Peterson, R.G.; Baughman, S.; Scheidler, D.M.

    1981-02-01

    The simultaneous incorporation of (/sup 3/H)fucose and (1-/sup 14/C)leucine into normal rat sciatic nerve was examined using an in vitro incubation model. A linear rate of protein precursor uptake was found in purified myelin protein over 1/2-6 hr of incubation utilizing a supplemented medium containing amino acids. This model was then used to examine myelin protein synthesis in nerves undergoing degeneration at 1-4 days following a crush injury. Data showed a statistically significant decrease in the ratio of fucose to leucine at 2, 3, and 4 days of degeneration, which was the consequence of a significant increase in leucine uptake. These results, plus substantial protein recovery in axotomized nerves, are indicative of active synthesis of proteins that purify with myelin during early Wallerian degeneration.

  1. Nearly degenerate heavy sterile neutrinos in cascade decay: Mixing and oscillations

    NASA Astrophysics Data System (ADS)

    Boyanovsky, Daniel

    2014-11-01

    Some extensions beyond the Standard Model propose the existence of nearly degenerate heavy sterile neutrinos. If kinematically allowed these can be resonantly produced and decay in a cascade to common final states. The common decay channels lead to mixing of the heavy sterile neutrino states and interference effects. We implement nonperturbative methods to study the dynamics of the cascade decay to common final states, which features similarities but also noteworthy differences with the case of neutral meson mixing. We show that mixing and oscillations among the nearly degenerate sterile neutrinos can be detected as quantum beats in the distribution of final states produced from their decay. These oscillations would be a telltale signal of mixing between heavy sterile neutrinos. We study in detail the case of two nearly degenerate sterile neutrinos produced in the decay of pseudoscalar mesons and decaying into a purely leptonic "visible" channel: ?h?e+e-?a. Possible cosmological implications for the effective number of neutrinos Neff are discussed.

  2. Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells

    PubMed Central

    Duregotti, Elisa; Negro, Samuele; Scorzeto, Michele; Zornetta, Irene; Dickinson, Bryan C.; Chang, Christopher J.; Montecucco, Cesare; Rigoni, Michela

    2015-01-01

    An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases. PMID:25605902

  3. Effective cubic nonlinearity and cnoidal waves in the degenerate parametric frequency conversion

    SciTech Connect

    Petnikova, V M; Shuvalov, Vladimir V

    2010-05-26

    It is shown that under the degenerate conditions (SHG and type-I degenerate parametric generation), the increase in the order of a system of truncated wave equations reduces the initial problem to the solution of two independent nonlinear Schroedinger equations, which allows one to write down the analytic solutions of the corresponding problems by using the standard methods for constructing the searched-for solutions in the form of cnoidal waves. It is established that in realising of cascade processes (quasi-synchronism), one of which is degenerate, this approach based on the introduction of the concept of the effective cascade cubic nonlinearity is not very convenient because the latter in the general case is no longer the Kerr one.

  4. Analytic approximations for degenerate accumulation layers in semiconductors, with applications to barrier lowering in isotype heterojunctions

    NASA Astrophysics Data System (ADS)

    Kroemer, Herbert

    1981-02-01

    The Joyce-Dixon approximation for the Fermi energy in a degenerate semiconductor is used to obtain rapidly converging series expansions for both the potential and the electric field for degenerate accumulation layers in semiconductors, as functions of the electron concentration. The expressions are valid for electron concentrations up to about 20 times the effective density of states. The approximation is applied to Schottky barriers on degenerate semiconductors, where it leads to an increase in the value of the Gummel-Scharfetter correction in the C-V relation for Schottky barriers. A detailed quantitative treatment is given for the barrier lowering in abrupt n-N heterojunctions with increased reverse bias. Both barrier lowering and reverse bias are given as closed-form parametric expressions, with the electron concentration at the bottom of the heterojunction notch as the independent variable.

  5. 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.

  6. ANT: Software for Generating and Evaluating Degenerate Codons for Natural and Expanded Genetic Codes.

    PubMed

    Engqvist, Martin K M; Nielsen, Jens

    2015-08-21

    The Ambiguous Nucleotide Tool (ANT) is a desktop application that generates and evaluates degenerate codons. Degenerate codons are used to represent DNA positions that have multiple possible nucleotide alternatives. This is useful for protein engineering and directed evolution, where primers specified with degenerate codons are used as a basis for generating libraries of protein sequences. ANT is intuitive and can be used in a graphical user interface or by interacting with the code through a defined application programming interface. ANT comes with full support for nonstandard, user-defined, or expanded genetic codes (translation tables), which is important because synthetic biology is being applied to an ever widening range of natural and engineered organisms. The Python source code for ANT is freely distributed so that it may be used without restriction, modified, and incorporated in other software or custom data pipelines. PMID:25901796

  7. Second-order nonlinear Schrödinger equation breather solutions in the degenerate and rogue wave limits

    NASA Astrophysics Data System (ADS)

    Kedziora, David J.; Ankiewicz, Adrian; Akhmediev, Nail

    2012-06-01

    We present an explicit analytic form for the two-breather solution of the nonlinear Schrödinger equation with imaginary eigenvalues. It describes various nonlinear combinations of Akhmediev breathers and Kuznetsov-Ma solitons. The degenerate case, when the two eigenvalues coincide, is quite involved. The standard inverse scattering technique does not generally provide an answer to this scenario. We show here that the solution can still be found as a special limit of the general second-order expression and appears as a mixture of polynomials with trigonometric and hyperbolic functions. A further restriction of this particular case, where the two eigenvalues are equal to i, produces the second-order rogue wave with two free parameters considered as differential shifts. The illustrations reveal a precarious dependence of wave profile on the degenerate eigenvalues and differential shifts. Thus we establish a hierarchy of second-order solutions, revealing the interrelated nature of the general case, the rogue wave, and the degenerate breathers.

  8. Quantum Degenerate Two-Species Fermi-Fermi Mixture Coexisting with a Bose-Einstein Condensate

    SciTech Connect

    Taglieber, M.; Voigt, A.-C.; Aoki, T.; Haensch, T. W.; Dieckmann, K.

    2008-01-11

    We report on the generation of a quantum degenerate Fermi-Fermi mixture of two different atomic species. The quantum degenerate mixture is realized employing sympathetic cooling of fermionic {sup 6}Li and {sup 40}K gases by an evaporatively cooled bosonic {sup 87}Rb gas. We describe the combination of trapping and cooling methods that proved crucial to successfully cool the mixture. In particular, we study the last part of the cooling process and show that the efficiency of sympathetic cooling of the {sup 6}Li gas by {sup 87}Rb is increased by the presence of {sup 40}K through catalytic cooling. Because of the differing physical properties of the two components, the quantum degenerate {sup 6}Li-{sup 40}K Fermi-Fermi mixture is an excellent candidate for a stable, heteronuclear system allowing the study of several so far unexplored types of quantum matter.

  9. Differential scanning calorimetric studies of superficial digital flexor tendon degeneration in the horse.

    PubMed

    Miles, C A; Wardale, R J; Birch, H L; Bailey, A J

    1994-07-01

    Differential scanning calorimetry (DSC) of equine superficial digital flexor tendons revealed the presence of a small exothermic peak at 23 degrees C of unknown origin, and a large endothermic peak at 70 degrees C due to denaturation of cross-linked collagen fibres. In the central degenerated core of damaged tendons the denaturation temperature remained at 70 degrees C but the enthalpy decreased in relation to the extent of degeneration of the tendon. We suggest that this reduction in enthalpy is due to depolymerisation and denaturation of the collagen fibres. This contention is supported by the observed increased activity of the degradative enzyme cathepsin B secreted by the fibroblasts. DSC analysis of cultured porcine tendon fibroblasts revealed a multicomponent endotherm, denaturation beginning at 46 degrees C, a temperature capable of being achieved within the tendon during intensive exercise. DSC clearly has considerable potential in complementing morphological and biochemical studies to determine the aetiology and progress of equine tendon degeneration. PMID:8575396

  10. Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells.

    PubMed

    Duregotti, Elisa; Negro, Samuele; Scorzeto, Michele; Zornetta, Irene; Dickinson, Bryan C; Chang, Christopher J; Montecucco, Cesare; Rigoni, Michela

    2015-02-01

    An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases. PMID:25605902

  11. Nonlinear ion-acoustic waves in a degenerate plasma with nuclei of heavy elements

    NASA Astrophysics Data System (ADS)

    Hossen, M. A.; Mamun, A. A.

    2015-10-01

    The ion-acoustic (IA) solitary waves propagating in a fully relativistic degenerate dense plasma (containing relativistic degenerate electron and ion fluids, and immobile nuclei of heavy elements) have been theoretically investigated. The relativistic hydrodynamic model is used to derive the Korteweg-de Vries (K-dV) equation by the reductive perturbation method. The stationary solitary wave solution of this K-dV equation is obtained to characterize the basic features of the IA solitary structures that are found to exist in such a degenerate plasma. It is found that the effects of electron dynamics, relativistic degeneracy of the plasma fluids, stationary nuclei of heavy elements, etc., significantly modify the basic properties of the IA solitary structures. The implications of this results in astrophysical compact objects like white dwarfs are briefly discussed.

  12. Nonlinear ion acoustic excitations in relativistic degenerate, astrophysical electron-positron-ion plasmas

    NASA Astrophysics Data System (ADS)

    Rahman, Ata-Ur; Ali, S.; Mushtaq, A.; Qamar, A.; Qamar

    2013-10-01

    The dynamics and propagation of ion acoustic (IA) waves are considered in an unmagnetized collisionless plasma, whose constituents are the relativistically degenerate electrons and positrons as well as the inertial cold ions. At a first step, a linear dispersion relation for IA waves is derived and analysed numerically. For nonlinear analysis, the reductive perturbation technique is used to derive a Korteweg-deVries equation, which admits a localized wave solution in the presence of relativistic degenerate electrons and positrons. It is shown that only compressive IA solitary waves can propagate, whose amplitude, width and phase velocity are significantly modified due to the positron concentration. The latter also strongly influences all the relativistic plasma parameters. Our present analysis is aimed to understand collective interactions in dense astrophysical objects, e.g. white dwarfs, where the lighter species electrons and positrons are taken as relativistically degenerate.

  13. Solitary structures in a spatially nonuniform degenerate plasma in the presence of quantizing magnetic field

    NASA Astrophysics Data System (ADS)

    Masood, W.; Shaukat, Muzzamal I.; Shah, H. A.; Mirza, Arshad M.

    2015-03-01

    In the present investigation, linear and nonlinear propagation of low frequency ( ???ci ) electrostatic waves have been studied in a spatially inhomogeneous degenerate plasma with one dimensional electron trapping in the presence of a quantizing magnetic field and finite temperature effects. Using the drift approximation, formation of 1 and 2D drift ion solitary structures have been studied both for fully and partially degenerate plasmas. The theoretical results obtained have been analyzed numerically for the parameters typically found in white dwarfs for illustrative purpose. It is observed that the inclusion of Landau quantization significantly changes the expression of the electron number density of a dense degenerate plasma which affects the linear and nonlinear propagation of drift acoustic solitary waves in such a system. The present work may be beneficial to understand the propagation of drift solitary structures with weak transverse perturbation in a variety of physical situations, such as white dwarfs and laser-induced plasmas, where the quantum effects are expected to dominate.

  14. Compressive and rarefactive dust ion-acoustic solitary waves with degenerate electron-positron-ion plasma

    NASA Astrophysics Data System (ADS)

    Mukta, K. N.; Zobaer, M. S.; Roy, N.; Mamun, A. A.

    2015-06-01

    The nonlinear propagation of dust ion-acoustic (DIA) waves in a unmagnetized collisionless degenerate dense plasma (containing degenerate electron and positron, and classical ion fluids) has been theoretically investigated. The K-dV equation has been derived by employing the reductive perturbation method and by taking into account the effect of different plasma parameters in plasma fluid. The stationary solitary wave solution of K-dV equation is obtained, and numerically analyzed to identify the basic properties of DIA solitary structures. It has been shown that depending on plasma parametric values, the degenerate plasma under consideration supports compressive or rarefactive solitary structures. It has been also found that the effect of pressures on electrons, ions, and positrons significantly modify the basic features of solitary waves that are found to exist in such a plasma system. The relevance of our results in astrophysical objects such as white dwarfs and neutron stars, which are of scientific interest, is discussed briefly.

  15. Intrastriatal injection of pre-formed mouse ?-synuclein fibrils into rats triggers ?-synuclein pathology and bilateral nigrostriatal degeneration.

    PubMed

    Paumier, Katrina L; Luk, Kelvin C; Manfredsson, Fredric P; Kanaan, Nicholas M; Lipton, Jack W; Collier, Timothy J; Steece-Collier, Kathy; Kemp, Christopher J; Celano, Stephanie; Schulz, Emily; Sandoval, Ivette M; Fleming, Sheila; Dirr, Elliott; Polinski, Nicole K; Trojanowski, John Q; Lee, Virginia M; Sortwell, Caryl E

    2015-10-01

    Previous studies demonstrate that intrastriatal injections of fibrillar alpha-synuclein (?-syn) into mice induce Parkinson's disease (PD)-like Lewy body (LB) pathology formed by aggregated ?-syn in anatomically interconnected regions and significant nigrostriatal degeneration. The aim of the current study was to evaluate whether exogenous mouse ?-syn pre-formed fibrils (PFF) injected into the striatum of rats would result in accumulation of LB-like intracellular inclusions and nigrostriatal degeneration. Sprague-Dawley rats received unilateral intrastriatal injections of either non-fibrillized recombinant ?-syn or PFF mouse ?-syn in 1- or 2- sites and were euthanized at 30, 60 or 180days post-injection (pi). Both non-fibrillized recombinant ?-syn and PFF ?-syn injections resulted in phosphorylated ?-syn intraneuronal accumulations (i.e., diffuse Lewy neurite (LN)- and LB-like inclusions) with significantly greater accumulations following PFF injection. LB-like inclusions were observed in several areas that innervate the striatum, most prominently the frontal and insular cortices, the amygdala, and the substantia nigra pars compacta (SNpc). ?-Syn accumulations co-localized with ubiquitin, p62, and were thioflavin-S-positive and proteinase-k resistant, suggesting that PFF-induced pathology exhibits properties similar to human LBs. Although ?-syn inclusions within the SNpc remained ipsilateral to striatal injection, we observed bilateral reductions in nigral dopamine neurons at the 180-day time-point in both the 1- and 2-site PFF injection paradigms. PFF injected rats exhibited bilateral reductions in striatal dopaminergic innervation at 60 and 180days and bilateral decreases in homovanillic acid; however, dopamine reduction was observed only in the striatum ipsilateral to PFF injection. Although the level of dopamine asymmetry in PFF injected rats at 180days was insufficient to elicit motor deficits in amphetamine-induced rotations or forelimb use in the cylinder task, significant disruption of ultrasonic vocalizations was observed. Taken together, our findings demonstrate that ?-syn PFF are sufficient to seed the pathological conversion and propagation of endogenous ?-syn to induce a progressive, neurodegenerative model of ?-synucleinopathy in rats. PMID:26093169

  16. ELECTROMAGNETISM, OPTICS, ACOUSTICS, HEAT TRANSFER, CLASSICAL MECHANICS, AND FLUID DYNAMICS: Time Evolution and Squeezing of Degenerate and Non-degenerate Coupled Parametric Down-Conversion with Driving Term

    NASA Astrophysics Data System (ADS)

    Li, Jiang-Fan; Fang, Jia-Yuan; Xiao, Fu-Liang; Liu, Xin-Hai; Wang, Cheng-Zhi

    2009-03-01

    By properly selecting the time-dependent unitary transformation for the linear combination of the number operators, we construct a time-dependent invariant and derive the corresponding auxiliary equations for the degenerate and non-degenerate coupled parametric down-conversion system with driving term. By means of this invariant and the Lewis-Riesenfeld quantum invariant theory, we obtain closed formulae of the quantum state and the evolution operator of the system. We show that the time evolution of the quantum system directly leads to production of various generalized one- and two-mode combination squeezed states, and the squeezed effect is independent of the driving term of the Hamiltonian. In some special cases, the current solution can reduce to the results of the previous works.

  17. 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. Randomized double-blind controlled studies are needed to determine long-term effects. PMID:26719667

  18. Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process

    PubMed Central

    1977-01-01

    Two genes in Drosophila, rdgA and rdgB, which when defective cause retinal degeneration, were discovered by Hotta and Benzer (Hotta, Y., and S. Benzer. 1970. Proc. Natl, Acad. Sci. U. S, A. 67:1156-1163). These mutants have photoreceptor cells that are histologically normal upon eclosion but subsequently degenerate. The defects in the rdgA and rdgB mutants were localized by the study of genetic mosaics to the photoreceptor cells. In rdgB mutants retinal degeneration is light induced. It can be prevented by rearing the flies in the dark or by blocking the receptor potential with a no-receptor-potential mutation, norpA. Vitamin A deprivation and genetic elimination of the lysosomal enzyme acid phosphatase alsoprotect the photoreceptors of rdgB flies against light-induced damage. The photopigment kinetics of dark-reared rdgB flies appear normal in vitro by spectrophotometric measurements, and in vivo by measurements of the M potential. In normal Drosophila, a 1-s exposure to intense 470-nm light produces a prolonged depolarizing afterpotential (PDA) which can last for several hours. In dark-reared rdgB mutants the PDA lasts less than 2 min;; it appears to initiate the degeneration process, since the photoreceptors become permanently unresponsive after a single such exposure. Another mutant was isolated which prevents degeneration in rdgB flies but which has a normal receptor potential. This suppressor of degeneration is an allele of norpA. It is proposed that the normal norpA gene codes for a product which, when activated, leads to the receptor potential, and which is inactivated by the product of the normal rdgB gene. PMID:139462

  19. THE PROGENITORS OF TYPE Ia SUPERNOVAE. II. ARE THEY DOUBLE-DEGENERATE BINARIES? THE SYMBIOTIC CHANNEL

    SciTech Connect

    Di Stefano, R.

    2010-08-10

    In order for a white dwarf (WD) to achieve the Chandrasekhar mass, M{sub C} , and explode as a Type Ia supernova (SNIa), it must interact with another star, either accreting matter from or merging with it. The failure to identify the class or classes of binaries which produce SNeIa is the long-standing 'progenitor problem'. Its solution is required if we are to utilize the full potential of SNeIa to elucidate basic cosmological and physical principles. In single-degenerate models, a WD accretes and burns matter at high rates. Nuclear-burning white dwarfs (NBWDs) with mass close to M{sub C} are hot and luminous, potentially detectable as supersoft X-ray sources (SSSs). In previous work, we showed that >90%-99% of the required number of progenitors do not appear as SSSs during most of the crucial phase of mass increase. The obvious implication might be that double-degenerate binaries form the main class of progenitors. We show in this paper, however, that many binaries that later become double degenerates must pass through a long-lived NBWD phase during which they are potentially detectable as SSSs. The paucity of SSSs is therefore not a strong argument in favor of double-degenerate models. Those NBWDs that are the progenitors of double-degenerate binaries are likely to appear as symbiotic binaries for intervals >10{sup 6} years. In fact, symbiotic pre-double-degenerates should be common, whether or not the WDs eventually produce SNeIa. The key to solving the Type Ia progenitor problem lies in understanding the appearance of NBWDs. Most of them do not appear as SSSs most of the time. We therefore consider the evolution of NBWDs to address the question of what their appearance may be and how we can hope to detect them.

  20. Multiply Degenerate Exceptional Points and Quantum Phase Transitions

    E-print Network

    Denis I. Borisov; Frantisek Ruzicka; Miloslav Znojil

    2014-12-20

    The realization of a genuine phase transition in quantum mechanics requires that at least one of the Kato's exceptional-point parameters becomes real. A new family of finite-dimensional and time-parametrized quantum-lattice models with such a property is proposed and studied. All of them exhibit, at a real exceptional-point time $t=0$, the Jordan-block spectral degeneracy structure of some of their observables sampled by Hamiltonian $H(t)$ and site-position $Q(t)$. The passes through the critical instant $t=0$ are interpreted as schematic simulations of non-equivalent versions of the Big-Bang-like quantum catastrophes.

  1. Multiply Degenerate Exceptional Points and Quantum Phase Transitions

    NASA Astrophysics Data System (ADS)

    Borisov, Denis I.; Ruži?ka, František; Znojil, Miloslav

    2015-12-01

    The realization of a genuine phase transition in quantum mechanics requires that at least one of the Kato's exceptional-point parameters becomes real. A new family of finite-dimensional and time-parametrized quantum-lattice models with such a property is proposed and studied. All of them exhibit, at a real exceptional-point time t = 0, the Jordan-block spectral degeneracy structure of some of their observables sampled by Hamiltonian H( t) and site-position Q( t). The passes through the critical instant t = 0 are interpreted as schematic simulations of non-equivalent versions of the Big-Bang-like quantum catastrophes.

  2. Clinical characteristics and current treatment of age-related macular degeneration.

    PubMed

    Yonekawa, Yoshihiro; Kim, Ivana K

    2015-01-01

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

  3. Blow-up properties for a degenerate parabolic system with nonlinear localized sources

    NASA Astrophysics Data System (ADS)

    Wang, Minxing; Wei, Yunfeng

    2008-07-01

    This paper deals with blow-up properties for a degenerate parabolic system with nonlinear localized sources subject to the homogeneous Dirichlet boundary conditions. The main aim of this paper is to study the blow-up rate estimate and the uniform blow-up profile of the blow-up solution. Our conclusions extend the results of [L.L. Du, Blow-up for a degenerate reaction-diffusion system with nonlinear localized sources, J. Math. Anal. Appl. 324 (2006) 304-320]. At the end, the blow-up set and blow up rate with respect to the radial variable is considered when the domain [Omega] is a ball.

  4. On the Properties of Time-Dependent, Force-Free, Degenerate Electrodynamics

    E-print Network

    S. S. Komissarov

    2002-02-25

    This paper formulates time-dependent, force-free, degenerate electrodynamics as a hyperbolic system of conservation laws. It is shown that this system has four characteristic modes, a pair of fast waves propagating with the speed of light and a pair of Alfven waves. All these modes are linearly degenerate. The results of this analytic study can be used in developing upwind numerical schemes for the electrodynamics of black holes and pulsar magnetospheres. As an example, this paper describes a simple one-dimensional numerical scheme based on linear and exact Riemann solvers.

  5. Smoking and age-related macular degeneration: biochemical mechanisms and patient support.

    PubMed

    Willeford, Kevin T; Rapp, Jerry

    2012-11-01

    A small percentage of the population associates smoking with ocular disease. Most optometrists do not stress the importance of smoking cessation to their patients, and the centrality of smoking regarding the risk for ocular disease is not emphasized in optometric education. Age-related macular degeneration has strong epidemiological associations with smoking, and so serves as an appropriate model for the adverse effects of cigarette smoke on the eye. This article aims to provide basic scientific information to optometrists and optometry students so that they can better understand the pathogenesis of age-related macular degeneration and provide education and support to their patients wishing to stop smoking. PMID:23034338

  6. My father's experience with macular degeneration: implications for the home healthcare nurse.

    PubMed

    Schexnaydre, Mary; Carruth, Ann K

    2008-01-01

    Macular degeneration has become a problem of substantial proportions for older adults. This article can help the home health nurse gain a greater understanding of macular degeneration and therefore be more effective in the home setting. The addition of vision rehabilitation also can prolong older adults' independent years and enhance their satisfaction with life. Using Parse's human-becoming theory as a theoretical framework, the home health nurse can coparticipate in the older adult's experience of living and thus enhance the probability that the last years will be a rewarding time of life. PMID:18158486

  7. Classification of nondegenerate equilibria and degenerate 1-dimensional orbits of the Kovalevskaya-Yehia integrable system

    SciTech Connect

    Logacheva, Nina S

    2012-01-31

    The paper is devoted to a topological analysis of the Kovalevskaya-Yehia integrable case in rigid body dynamics. It is proved that the integral has the Bott property on isoenergy surfaces of the system; the topology of the Liouville foliation in a neighbourhood of degenerate 1-dimensional orbits and equilibria (points of rank 0) is also described. In particular, marked loop molecules are constructed for degenerate 1-dimensional orbits, and a representation in the form of an almost direct product is found for nondegenerate singularities of rank 0. Bibliography: 17 titles.

  8. Area law in one dimension: Degenerate ground states and Renyi entanglement entropy

    E-print Network

    Yichen Huang

    2015-01-07

    An area law is proved for the Renyi entanglement entropy of possibly degenerate ground states in one-dimensional gapped quantum systems. Suppose in a chain of $n$ spins the ground states of a local Hamiltonian with energy gap $\\epsilon$ are constant-fold degenerate. Then, the Renyi entanglement entropy $R_\\alpha(0<\\alpha<1)$ of any ground state across any cut is upper bounded by $\\tilde O(\\alpha^{-3}/\\epsilon)$, and any ground state can be well approximated by a matrix product state of subpolynomial bond dimension $2^{\\tilde O(\\epsilon^{-1/4}\\log^{3/4}n)}$.

  9. Longitudinal permeability of collisional plasmas under arbitrary degree of degeneration of electron gas

    E-print Network

    A. V. Latyshev; A. A. Yushkanov

    2010-03-04

    Electric conductivity and dielectric permeability of the non-degenerate electronic gas for the collisional plasmas under arbitrary degree of degeneration of electron gas is found. The kinetic equation of Wigner - Vlasov - Boltzmann with collision integral in relaxation form BGK (Bhatnagar, Gross and Krook) in coordinate space is used. Dielectric permeability with using of the relaxation equation in the momentum space has been received by Mermin. Comparison with Mermin's formula has been realized. It is shown, that in the limit when Planck's constant tends to zero expression for dielectric permeability passes in the classical.

  10. Genetic testing for age-related macular degeneration: not indicated now.

    PubMed

    Stone, Edwin M

    2015-05-01

    Age-related macular degeneration is a very common condition that is caused by a complex interplay of genetic and environmental factors. It is likely that, in the future, genetic testing will allow physicians to achieve better clinical outcomes by administering specific treatments to patients based on their genotypes. However, improved outcomes for genotyped patients have not yet been demonstrated in a prospective clinical trial, and as a result, the costs and risks of routine genetic testing currently outweigh the benefits for patients with age-related macular degeneration. PMID:25789813

  11. Propagation of arbitrary-amplitude ion waves in relativistically degenerate electron-ion plasmas

    E-print Network

    Akbari-Moghanjoughi, M

    2010-01-01

    We employ the Sagdeev pseudo-potential method to investigate the propagation of nonlinear ion waves in a relativistically degenerate electron-ion plasmas. The matching criteria for existence of such nonlinear excitations are numerically investigated in terms of the relativity measure (relativistic degeneracy parameter) of electrons and the allowed Mach-number range for propagation of such waves is evaluated. It is shown that the electron relativistic degeneracy parameter has significant effects on nonlinear wave dynamics in superdense degenerate plasmas such as that encountered in white dwarfs and the cores of massive planets.

  12. Reverse evolution leads to genotypic incompatibility despite functional and active site convergence.

    PubMed

    Kaltenbach, Miriam; Jackson, Colin J; Campbell, Eleanor C; Hollfelder, Florian; Tokuriki, Nobuhiko

    2015-01-01

    Understanding the extent to which enzyme evolution is reversible can shed light on the fundamental relationship between protein sequence, structure, and function. Here, we perform an experimental test of evolutionary reversibility using directed evolution from a phosphotriesterase to an arylesterase, and back, and examine the underlying molecular basis. We find that wild-type phosphotriesterase function could be restored (>10(4)-fold activity increase), but via an alternative set of mutations. The enzyme active site converged towards its original state, indicating evolutionary constraints imposed by catalytic requirements. We reveal that extensive epistasis prevents reversions and necessitates fixation of new mutations, leading to a functionally identical sequence. Many amino acid exchanges between the new and original enzyme are not tolerated, implying sequence incompatibility. Therefore, the evolution was phenotypically reversible but genotypically irreversible. Our study illustrates that the enzyme's adaptive landscape is highly rugged, and different functional sequences may constitute separate fitness peaks. PMID:26274563

  13. Brain-derived neurotrophic factor in patients with advanced age-related macular degeneration

    PubMed Central

    Afarid, Mehrdad; Torabi-Nami, Mohammad; Nemati, Alijan; Khosravi, Amir; Malekzadeh, Mahyar

    2015-01-01

    AIM To investigate the serum level of the brain-derived neurotrophic factor (BDNF) in age-related macular degeneration (AMD) and healthy control subjects. The disruption in the tight balance of neuroinflammatory and neuroprotective processes in an immune-privileged site like retina is proposed to contribute to the pathogenesis of AMD. One of the main neuroprotective mediators in the central nervous system is BDNF with its serum level notably affected in several neurodegenerative disorders. METHODS Thirty-six patients with AMD and 36 age-matched controls were enrolled in this study. The serum level of BDNF was measured using the enzyme-linked immunosorbent assay method. Results were analyzed to compare case and control values. Comparisons were also made between the BDNF level of wet- vs dry-AMD, and male vs female patients and controls. Analysis of variance (ANOVA) and Student's t-test were employed to analyze the data. RESULTS The mean BDNF levels in AMD group were significantly higher than the control group. Furthermore, our analysis revealed greater BDNF values in all AMD subgroups compared to controls (P=0.004, 0.005, 0.001 and 0.02 for male wet-AMD, male dry-AMD, female wet-AMD and female dry-AMD vs controls, respectively). The BDNF level however did not vary between wet- and dry-AMD patients (P=0.74). While within-group comparisons in males and females of AMD and control groups did not show any difference in BDNF (P=0.16, 0.64 and 0.85 for wet-AMD, dry-AMD and control groups, respectively), between-group data showed a higher mean BDNF in both male and female AMD subjects than their peer controls. CONCLUSION This study demonstrated that the serum BDNF level is different in patients with AMD as compared to subjects without AMD. Future attempts should be done to unravel beneficial or deleterious effect of this neurotrophin in the pathogenesis of AMD. PMID:26558215

  14. Barrier Trees of Degenerate Landscapes 1 Christoph Flamm a,# , Ivo L. Hofacker a , Peter F. Stadler a,b ,

    E-print Network

    Stadler, Peter F.

    Barrier Trees of Degenerate Landscapes 1 Christoph Flamm a,# , Ivo L. Hofacker a , Peter F. Stadler for estimating transition frequencies. In non­degenerate landscapes the decom­ position of a landscape examples of landscapes. Keywords: Fitness landscape, Potential energy surface, energy barrier, saddle

  15. Observation of the splitting of degenerate surface plasmon polariton modes in a two-dimensional metallic nanohole array

    E-print Network

    Fainman, Yeshaiahu

    Observation of the splitting of degenerate surface plasmon polariton modes in a two the experimental observation of the splitting of the degenerate 0, ±1 surface plasmon polariton modes excited plasmon polaritons SPPs i.e., surface confinement, maximum amplitude value on the surface of the interface

  16. Ultra-low power, Zeno effect based optical modulation in a degenerate V-system with a

    E-print Network

    Shahriar, Selim

    Ultra-low power, Zeno effect based optical modulation in a degenerate V-system with a tapered nano, leading to a degenerate V-system involving coherent superpositions of Zeeman sublevels. The modulation is due primarily to the quantum Zeno effect for the signal beam induced by the control beam

  17. Improvements in Limb Kinetic Apraxia by Repetition of a Newly Designed Facilitation Exercise in a Patient with Corticobasal Degeneration

    ERIC Educational Resources Information Center

    Kawahira, Kazumi; Noma, Tomokazu; Iiyama, Junichi; Etoh, Seiji; Ogata, Atsuko; Shimodozono, Megumi

    2009-01-01

    Corticobasal degeneration is a progressive neurological disorder characterized by a combination of parkinsonism and cortical dysfunction such as limb kinetic apraxia, alien limb phenomenon, and dementia. To study the effect of repetitive facilitation exercise (RFE) in a patient with corticobasal degeneration, we used a newly designed facilitation…

  18. Current Biology 24, 760765, March 31, 2014 2014 Elsevier Ltd All rights reserved http://dx.doi.org/10.1016/j.cub.2014.02.025 Axons Degenerate in the Absence

    E-print Network

    Horvitz, H. Robert

    to the kinesin-1/unc-116 mutant. When axons lacking mito- chondria are cut with a laser, they rapidly degenerate. Some neurons even spontaneously degenerate in ric-7 mutants. Degeneration can be suppressed by forcing

  19. Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration

    PubMed Central

    Silveira, João W.; Issy, Ana Carolina; Castania, Vitor A.; Salmon, Carlos E. G.; Nogueira-Barbosa, Marcello H.; Guimarães, Francisco S.; Defino, Helton L. A.; Bel, Elaine Del

    2014-01-01

    Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol) injected immediately after lesion were analyzed acutely (2 days) by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration. PMID:25517414

  20. Degenerate U-and V -statistics under weak dependence: Asymptotic theory and bootstrap consistency

    E-print Network

    - and V -statistics 2.1. Survey of literature. Let (Xn)nN be a sequence of Rd -valued random vari- ablesDegenerate U- and V -statistics under weak dependence: Asymptotic theory and bootstrap consistency of model-based bootstrap methods for U- and V -statistics under easily verifiable conditions

  1. The Psychosocial Impact of Closed-Circuit Televisions on Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Huber, Jessica G.; Jutai, Jeffrey W.; Strong, J. Graham; Plotkin, Ann D.

    2008-01-01

    Closed-circuit televisions (CCTVs) are used by many elderly people who have age-related macular degeneration (AMD). The functional vision of 68 participants, which was measured immediately after they adopted CCTVs, suggested successful outcomes, but the psychosocial impact of the use of CCTVs did not peak until a month later. The findings help…

  2. PHYSICAL REVIEW A 83, 033834 (2011) Degenerate four-wave mixing in triply resonant Kerr cavities

    E-print Network

    2011-01-01

    PHYSICAL REVIEW A 83, 033834 (2011) Degenerate four-wave mixing in triply resonant Kerr cavities four-wave mixing in triply resonant nonlinear (Kerr) cavities. We employ a general and accurate the critical powers in the order of 10 mW, assuming very conservative cavity parameters (modal volumes 10 cubic

  3. Desert Hedgehog-Patched 2 Expression in Peripheral Nerves during Wallerian Degeneration and

    E-print Network

    Jessen, Kristjan R

    Desert Hedgehog-Patched 2 Expression in Peripheral Nerves during Wallerian Degeneration. As Desert hedgehog (Dhh) is involved in the development of peripheral nerves and is expressed in adult to injury. ' 2005 Wiley Periodicals, Inc. J Neurobiol 66: 243­255, 2006 Keywords: Desert hedgehog (Dhh

  4. A systematic review on zinc for the prevention and treatment of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zinc is a potential candidate for the prevention and treatment of age-related macular degeneration (AMD) due to its high concentration in the retina and role as a cofactor for antioxidant enzymes. The objective of this work was to conduct a systematic review of studies that investigated dietary inta...

  5. Deafness and Retinal Degeneration in a Novel USH1C Knock-In Mouse Model

    E-print Network

    Rubel, Edwin

    of deafness and retinitis pigmentosa (RP) as well as the presence or absence of vestibular function. Usher IDeafness and Retinal Degeneration in a Novel USH1C Knock-In Mouse Model Jennifer J. Lentz,1 is characterized by profound congenital hearing loss, vestibular dysfunc- tion, and progressive retinitis

  6. Photoreceptor Proteins Initiate Microglial Activation via Toll-like Receptor 4 in Retinal Degeneration Mediated by

    E-print Network

    Palczewski, Krzysztof

    degeneration and retinitis pigmentosa. Although several genetic and biochemical factors are associ- ated from the retina, and in a retinitis pigmentosa mouse model with impaired retinal pigment epithe- lium disease, and retinitis pigmentosa (RP). AMD is the leading cause of legal blindness in industrialized

  7. Time-series Spectroscopy of Two Candidate Double Degenerates in the Open Cluster NGC 6633

    NASA Astrophysics Data System (ADS)

    Williams, Kurtis A.; Serna-Grey, Donald; Chakraborty, Subho; Gianninas, A.; Canton, Paul A.

    2015-12-01

    SNe Ia are heavily used tools in precision cosmology, yet we still are not certain what the progenitor systems are. General plausibility arguments suggest there is potential for identifying double degenerate SN Ia progenitors in intermediate-age open star clusters. We present time-resolved high-resolution spectroscopy of two white dwarfs (WDs) in the field of the open cluster NGC 6633 that had previously been identified as candidate double degenerates in the cluster. However, three hours of continuous observations of each candidate failed to detect any significant radial velocity variations at the ?10 km s?1 level, making it highly unlikely that either WD is a double degenerate that will merge within a Hubble Time. The WD LAWDS NGC 6633 4 has a radial velocity inconsistent with cluster membership at the 2.5? level, while the radial velocity of LAWDS NGC 6633 7 is consistent with cluster membership. We conservatively conclude that LAWDS 7 is a viable massive double degenerate candidate, though unlikely to be a Type Ia progenitor. Astrometric data from GAIA will likely be needed to determine if either WD is truly a cluster member. The data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

  8. Self-similar intermediate asymptotics for a degenerate parabolic filtration-absorption equation

    E-print Network

    Chertock, Alina

    Self-similar intermediate asymptotics for a degenerate parabolic filtration-absorption equation G as a model of the groundwater flow in a water-absorbing fissurized porous rock; therefore, we refer to this equation as a filtration-absorption equation. A family of self-similar solutions to this equation

  9. Oculomotor Function in Frontotemporal Lobar Degeneration, Related Disorders and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Garbutt, Siobhan; Matlin, Alisa; Hellmuth, Joanna; Schenk, Ana K.; Johnson, Julene K.; Rosen, Howard; Dean, David; Kramer, Joel; Neuhaus, John; Miller, Bruce L.; Lisberger, Stephen G.; Boxer, Adam L.

    2008-01-01

    Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were…

  10. A generalized Jaynes-Cummings model and the relativistic degenerate parametric amplifier

    E-print Network

    D. Ojeda-Guillén; R. D. Mota; V. D. Granados

    2014-11-07

    We introduce a generalization of the Jaynes-Cummings model and study some of its properties. We obtain the energy spectrum and eigenfunctions of this model by using the tilting transformation and the squeezed number states of the one-dimensional harmonic oscillator. We show that in the non-relativistic limit, this model can be mapped onto the degenerate parametric amplifier

  11. Lighting Needs and Lighting Comfort During Reading with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Fosse, Per; Valberg, Arne

    2004-01-01

    This study investigated the effects of changes in luminance on the oral reading speeds of 13 participants with age-related macular degeneration (AMD) and a control group of six age-matched persons with typical vision. For the AMD participants, self-reports of light preferences were also recorded. In the AMD group, reading rates depended on light…

  12. Introduction to the issue regarding research regarding age related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blindness is the second greatest fear among the elderly. Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly in most industrialized nations. AMD first compromises central high acuity vision. Subsequently, all vision may be lost. AMD is a progressive retinal d...

  13. Cerebellar granuloprival degeneration in an Australian kelpie and a Labrador retriever dog.

    PubMed

    Huska, Jonathan; Gaitero, Luis; Snyman, Heindrich N; Foster, Robert A; Pumarola, Marti; Rodenas, Sergio

    2013-01-01

    A 7-month-old Australian kelpie dog and a 14-month-old Labrador retriever dog were diagnosed with an uncommon form of cerebellar abiotrophy called cerebellar granuloprival degeneration. This was characterized by a loss of the granular neurons with relative sparing of the Purkinje neurons. PMID:23814302

  14. Cerebellar granuloprival degeneration in an Australian kelpie and a Labrador retriever dog

    PubMed Central

    Huska, Jonathan; Gaitero, Luis; Snyman, Heindrich N.; Foster, Robert A.; Pumarola, Marti; Rodenas, Sergio

    2013-01-01

    A 7-month-old Australian kelpie dog and a 14-month-old Labrador retriever dog were diagnosed with an uncommon form of cerebellar abiotrophy called cerebellar granuloprival degeneration. This was characterized by a loss of the granular neurons with relative sparing of the Purkinje neurons. PMID:23814302

  15. Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration

    E-print Network

    Shadmehr, Reza

    Modulation of error-sensitivity during a prism adaptation task in people with cerebellar of error-sensi- tivity during a prism adaptation task in people with cerebellar degeneration. J to reach to a target while viewing the scene through wedge prisms. The prisms were computer controlled

  16. Intact Ability to Learn Internal Models of Arm Dynamics in Huntington's Disease But Not Cerebellar Degeneration

    E-print Network

    Shadmehr, Reza

    Intact Ability to Learn Internal Models of Arm Dynamics in Huntington's Disease But Not Cerebellar internal models of arm dynamics in Huntington's disease but not cerebellar degeneration. J Neurophysiol 93 reported that while on-line error correction was disturbed in patients with Huntington's disease (HD

  17. Investigating the role of eEF1A2 in motor neuron degeneration 

    E-print Network

    Griffiths, Lowri Ann

    2011-11-25

    Abnormal expression of the eukaryotic translation elongation factor 1A (eEF1A) has been implicated in disease states such as motor neuron degeneration and cancer. Two variants of eEF1A are found in mammals, named eEF1A1 ...

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

    NASA Astrophysics Data System (ADS)

    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, ?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.

  19. Psychosocial Intervention for Age-Related Macular Degeneration: A Pilot Project

    ERIC Educational Resources Information Center

    Wahl, Hans-Werner; Kammerer, Annette; Holz, Frank; Miller, Daniel; Becker, Stefanie; Kaspar, Roman; Himmelsbach, Ines

    2006-01-01

    This study evaluated an emotion-focused and a problem-focused intervention designed for patients with age-related macular degeneration. It found a limited decrease in depression in the emotion-focused group and an increase in active problem orientation and in adaptation to vision loss in the problem-focused group.

  20. Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc

    PubMed Central

    Binch, Abbie L. A.; Cole, Ashley A.; Breakwell, Lee M.; Michael, Anthony L. R.; Chiverton, Neil; Creemers, Laura B.; Cross, Alison K.; Le Maitre, Christine L.

    2015-01-01

    Nerve and blood vessel ingrowth during intervertebral disc degeneration, is thought to be a major cause of low back pain, however the regulation of this process is poorly understood. Here, we investigated the expression and regulation of a subclass of axonal guidance molecules known as the class 3 semaphorins, and their receptors; plexins and neuropilins within human NP tissue and their regulation by pro-inflammatory cytokines. Importantly this determined whether semaphorin expression was associated with the presence of nerves and blood vessels in tissues from human intervertebral discs. The study demonstrated that semaphorin3A, 3C, 3D, 3E and 3F and their receptors were expressed by native NP cells and further demonstrated their expression was regulated by IL-1? but to a lesser extent by IL-6 and TNF?. This is the first study to identify sema3C, sema3D and their receptors within the nucleus pulposus of intervertebral discs. Immunopositivity shows significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. Therefore data presented here suggests that semaphorin3C may have a role in promoting innervation and vascularisation during degeneration, which may go on to cause low back pain. PMID:26286962